United States PesticidesAnd EPA 560/2-91-001
Environmental Protection Toxic Substances July 1991
Agency (TS778)
Preliminary Evaluations
Of Initial TSCA
Section 8(e)
Substantial Risk Notices
January 1989 - September 1990
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NOTICE TO ADMINISTRATOR OF SUBSTANTIAL RISKS. Any person who
manufactures, [imports,] processes, or distributes in commerce a
chemical substance or mixture and who obtains information which
reasonably supports the conclusion that such substance or mixture
presents a substantial risk of injury to health or the environment
shall immediately inform the [EPA] Administrator of such
information unless such person has actual knowledge that the
Administrator has been adequately informed of such information.
Section 8(e), Toxic Substances Control Act (1976)
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EPA 560/2-91-
JULY 1991
PRELIMINARY EVALUATIONS OF INITIAL
T8CA SECTION 8(e) SUBSTANTIAL RISK NOTICES
JANUARY 1, 1989 TO SEPTEMBER 30, 1990
Office of Toxic Substances
Office of Pesticides and Toxic Substances
Washington, D.C. 20460
U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF PESTICIDES AND TOXIC SUBSTANCES
WASHINGTON/ D.C. 20460
Printed on Recycled Paper
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Disclaimer
This volume has been reviewed by the Office of Pesticides and Toxic
Substances (OPTS), U.S. Environmental Protection Agency (EPA), and
approved for publication. The "status reports" contained in this
volume present EPA's preliminary evaluations of the submitted
information and do not represent final Agency policy/intent with
respect to the subject chemical substances. The mention of company
names, trade names, or commercial products does not constitute an
EPA endorsement or recommendation either for or against use.
ii
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Foreword
This volume contains, in ascending submission number order, "status
reports" (i.e., preliminary evaluations) prepared by staff of the
Office of Toxic Substances (OTS) in the Office of Pesticides and
Toxic Substances (OPTS) for initial submissions received by EPA
from chemical manufacturers, importers, processors, distributors
and others between January 1, 1989, and September 30, 1990, under
Section 8(e), the substantial risk information reporting provision
of the Toxic Substances Control Act (TSCA; 90 Stat. 2029, 15 U.S.C.
2607(e)). It should be noted that the status reports contained in
this compendium reflect only part of the initial phase of the OTS
evaluation process for such information.
This volume is being distributed publicly through the Environmental
Assistance Division (EAD) in OTS/OPTS. Any person who wishes to
obtain a copy of this volume of TSCA Section 8(e) status reports
should write to:
Environmental Assistance Division (TS-799)
Office of Toxic Substances/OPTS
U.S. Environmental Protection Agency
401 "M" street, S.W.
Washington, D.C. 20460
EPA plans to print a limited number of copies of this volume.
After the Agency's supply is exhausted, copies can be purchased
through the National Technical Information Service (NTIS), 5285
Port Royal Road, Springfield, Virginia 22161. Copies of the six
(6) previously published TSCA Section 8(e) status report volumes
(PB# 80-221609, PB# 81-145732, PB# 83-187815, PB# 87-129409, PB#
87-176004 and PB# 89-182687) are currently available through NTIS.
The Agency welcomes the submission of additional information for,
or comments on, the evaluations presented in this volume. The
submission of unpublished information relating to biological or
environmental effects, production/importation volumes, use(s), and
worker, consumer and environmental exposure to the subject chemical
substances and mixtures would be especially valuable to EPA. Such
information will be considered at subsequent steps in the overall
OTS chemical assessment processes. All submissions of additional
information for, or comments pertaining to, the evaluations that
are contained in this volume should be directed to:
Mr. Frank D. Kover (TS-778)
Chief, Chemical Screening Branch
Existing Chemical Assessment Division
Office of Toxic Substances/OPTS
U.S. Environmental Protection Agency
401 "M" Street, S.W.
Washington, D.C. 20460
iii
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Non-confidential Section 8(e) submissions and EPA status reports
can be viewed and copied in the OTS public files located at EPA
Headquarters, Room G-004 Northeast Mall, 401 "M" Street S.W.,
Washington, D.C. Non-confidential TSCA Section 8(e) submissions
and status reports can be ordered by writing to EPA's Freedom of
Information Office at the following address:
This and previous status report volumes have been published for two
reasons. First, volumes of status reports will make Section 8(e)
data even more accessible. Second, such volumes may, by providing
specific examples of submitted information and EPA's evaluation of
that information, help subject persons understand better the types
of information that should be submitted under Section 8(e) of TSCA.
It is important to note that EPA's overall implementation of TSCA
Section 8(e) has resulted in heightened chemical industry awareness
of potential risks posed by chemical substances. This heightened
corporate awareness has led, in many cases, to voluntary pollution
prevention/risk reduction activities designed primarily to protect
human health or the environment. For example, many companies have
reported that in direct response to submitted TSCA Section 8 (e)
data, the following types of health and environmental protection
measures were initiated on a voluntary basis:
0 formal notification of others (e.g., workers, customers)
about reported data by way of letters and/or modifications
to product labels and Material Safety Data Sheets;
0 changes made in manufacturing, processing and handling
procedures to reduce or eliminate chemical exposure;
0 use or production of chemicals halted temporarily or
discontinued altogether; and
0 additional toxicologic and monitoring studies undertaken
to improve understanding of chemical toxicity or exposure.
The chemical industry's increased awareness of potential risks is
evidenced further by the Agency's receipt to date of approximately
800 voluntary "For Your Information" (FYI) submissions containing
valuable toxicologic, exposure and voluntary pollution prevention/
risk reduction information.
Freedom of Information Office (A-101)
U.S. Environmental Protection Agency
401 "M" Street, S.W.
Washington, D.C. 20460
Charles M. Auer, Director
Existing Chemical Assessment Division/OTS
iv
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Acknowledgment
In preparing the status reports contained in this compendium, EPA's
Office of Toxic Substances (OTS) frequently found it necessary to
seek additional information about, or clarification of, submitted
data. OTS appreciates the efforts and cooperation of the companies
and organizations (listed on this and the following page) that have
submitted the information reflected in this volume:
3M Company
Air Products and Chemicals, Inc.
Akzo Chemicals Inc.
Albright & Wilson Company, LTD.
Allied-Signal Inc.
Aluminum Company of America (ALCOA)
American Cyanamid Company
American Telephone and Telegraph Company (AT&T)
Antimony Oxide Industry Association
Amoco Chemical Company
Amoco Oil Company
Arco Chemical Company
Atochem North America, Inc.
Baker Performance Chemicals, Inc.
BASF Corporation
B. F. Goodrich Company
Chemical Manufacturers Association
ChemRex Inc.
Chevron Chemical Company
Chevron International Oil Company, Inc.
CIBA-GEIGY Corporation
Crompton & Knowles Corporation, U.S.A.
Dixie Chemical Company
Dow Chemical Company
Dow Corning Corporation
Eastman Kodak Company
E. I. DuPont de Nemours & Company, Inc.
Eli Lilly and Company
EM Industries, Inc.
Enimont America Inc.
ETAD - U.S. Operating Committee
Exxon Chemical Americas
FMC corporation
GAF Chemicals Corporation
General Electric Company
Givaudan Corporation
Goodyear Tire & Rubber Company
Great Lakes Chemical Corporation
Halocarbon Products Corporation
Hercules Incorporated
Hi-Tek Polymers, Inc.
Hoechst Celanese Corporation
Huls America Inc.
v
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ICI Americas Inc.
Industrial Health Foundation, Inc.
International Isocyanate Institute, Inc.
Mead Corporation
Methyl Bromide Idustry Panel
Methyl Tertiary Butyl Ether Task Force
Mitsubishi Gas chemical America, Inc.
Mitsubishi Yuka America, Inc.
Mitsui Petrochemicals (America), LTD.
Mobay Corporation
Mobil Research and Development Corporation
Monsanto Company
Morton International, Inc.
Motorola Inc.
Nalco Chemical Company
NOR-AM Chemical Company
Occidental Chemical Corporation
01in Corporation
Pfister Chemical, Inc.
PPG Industries, Inc.
PQ Corporation
Procter & Gamble Company
Rhone-Poulenc Inc.
Ricoh Electronics Inc.
Rohm and Haas Company
R. T. Vanderbilt Company, Inc.
Shell Oil Company
Texaco Inc.
Union Carbide Chemicals and Plastics Company Inc.
Upjohn Company
Vista Chemical Company
Witco corporation
vi
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Contents
Foreword . ... iii
Acknowledgment v
Introduction 1
Status Reports 8EHQ-0189-0779 through 8EHQ-0990-1084 5
Appendix A. Section 8(e) Policy Statement (43 FR 11110) .... 800
Technical Amendment Citation (52 FR 20083) 807
Appendix B. Status Reports Listed by CAS Number 808
Appendix C. Status Reports Listed by Chemical Name 843
Appendix D. Status Reports Listed by Information Type 898
Appendix E. status Reports Listed by Submission Number 914
Report Documentation Page 957
vii
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Introduction
Section 8(e) of the Toxic Substances Control Act (TSCA? the Act)
states that "any person who manufactures, [imports,] processes, or
distributes in commerce a chemical substance or mixture and who
obtains information which reasonably supports the conclusion that
such substance or mixture presents a substantial risk of injury to
health or the environment shall immediately inform the [EPA]
Administrator of such information unless such person has actual
knowledge that the Administrator has been adequately informed of
such information."
In view of the fact that Section 8(e) was self-implementing (i.e.,
required no implementing rules), chemical manufacturers, importers,
processors and distributors became subject to the Section 8(e)
reporting provision as of January 1, 1977, the effective date of
TSCA. In order to clarify the types of information to be submitted
and the procedures for doing so, the Agency (following receipt and
review of public comments) published its TSCA Section 8(e) policy
statement ("Statement of Interpretation and Enforcement Policy;
Notification of Substantial Risk" 43 FR 11110; March 16, 1978). For
easy referral when using this volume, the TSCA Section 8(e) policy
statement appears as Appendix A in the back of this volume.
EPA's March 16, 1978 TSCA Section 8(e) policy statement expresses
the Agency's policy that the information subject to Section 8(e)
reporting is information that "reasonably supports" a conclusion
that a chemical substance or mixture presents a "substantial risk"
of injury to health or the environment.1 Such information need
not, and typically does not, indicate conclusively that such a risk
exists. The determination to report "substantial risk" information
to EPA should not include an evaluation of either the economic or
social benefits of the use of the subject chemical substance or
mixture. Therefore, the term "substantial risk" is not synonymous
with the term "unreasonable risk" found in other sections of TSCA.
Although EPA's receipt of information under Section 8(e) does not
necessarily trigger immediate regulatory action, the information
that is submitted pursuant to Section 8(e) does receive priority
review and evaluation by EPA in order to determine an appropriate
course of Agency action.
"Substantial risk" information must be reported to EPA
unless the subject person has actual knowledge that EPA has been
adequately informed already about the information. Part VII of
the March 16, 1978 TSCA Section 8(e) policy statement as well as
the TSCA Section 8(e) "reporting guide" (discussed later in this
Introduction to this status report volume) address the types of,
and circumstances under which, information need not be reported
to EPA under Section 8(e) of TSCA.
1
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Thus far, EPA and the chemical industry have devoted significant
efforts in fulfilling their respective responsibilities under
Section 8(e) of TSCA. Since January 1, 1977, over 1250 initial
TSCA Section 8(e) submissions covering a broad range of toxicity
and exposure-related information on a wide variety of chemicals
have been received and given priority evaluation and follow-up
attention by the staff of the Office of Toxic Substances (OTS) in
EPA's Office of Pesticides and Toxic Substances (OPTS). In general,
each initial TSCA Section 8(e) submission is promptly reviewed and
evaluated by OTS scientific staff to determine both the degree of
concern that should be attached to the submitted information and
the initial course of any warranted OTS follow-up action(s). A
"status report" is prepared which contains a brief description of
the submitted information, the results of the OTS preliminary
evaluation, a statement with respect to the production and use of
the. subject chemical(s), and the recommendations for appropriate
follow-up actions. Upon approval of the status report, recommended
follow-up actions are initiated. A letter containing the status
report and any EPA requests for additional information is sent to
the submitting company. In addition, copies of all status reports
are transmitted to the OPTS public files, other designated EPA
Program Offices and Federal Agencies, and to the Environmental
Assistance Division/OTS (formerly the OTS TSCA Assistance Office)
for further distribution. Other OTS follow-up actions include
consideration of further, more in-depth assessment of the reported
chemical hazard or risk. It should be noted also that OTS staff
immediately reviews, evaluates, and initiates appropriate follow-up
actions for information contained in "follow-up" and "supplemental"
Section 8(e) submissions. By definition, a follow-up submission
contains information submitted directly in response to a specific
EPA request, whereas a supplemental submission is one that contains
information not specifically requested by EPA.
A Document Control Number is used by EPA to identify Section 8(e)
submissions? this number takes the following form: 8EHQ-0000-0000.
Starting at the left, the first four symbols identify the informa-
tion as a Section 8(e) submission received by EPA Headquarters; the
next four digits identify the month and year (e.g., -0591-) of the
Agency's receipt of the information; the final four digits identify
the submission's chronological number. In addition to the basic
numerical sequence, additional characters may be added to the right
of the Document Control Number to convey other information. These
additional characters and their specific meanings are as follows:
S: indicates the submission was sanitized to delete information
claimed by the submitting organization to be TSCA Confidential
Business Information (TSCA CBI);
P: indicates the notice contained an individual's name or other
identifier (e.g., Social Security Number) the release of which
may violate the Privacy Act (such documents are sanitized to
remove an individual's name or other identifiers); and
2
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*: indicates that, based on a preliminary evaluation, either
1) the submission was considered by EPA to be unwarranted
for reporting under Section 8(e) , or 2) it was unclear to
the Agency that the submission was warranted and further
clarifying information was requested from the submitting
organization.
When reviewing the status reports contained in this volume, the
reader should realize that the main purpose of the OTS preliminary
evaluation is to determine quickly the significance of submitted
information in terms of a need for possible follow-up action by the
Agency. This determination involves a critical analysis of the
submitted data to assess the extent that the reported hazard or
risk is supported by the provided information. The scope of this
initial evaluation, however, is generally limited to the submitted
documents and to any closely related information known by the OTS
reviewer. Neither a literature search to identify other reported
effects nor an in-depth analysis of possible sources of exposure to
subject chemicals is part of the evaluation process. Therefore, a
status report should be viewed only as a preliminary evaluation of
the submitted information and not as a comprehensive assessment of
the chemical substance or mixture for which a TSCA Section 8(e)
notice has been filed.
It is important to note that as of October 1, 1990, OTS staff began
to prepare and issue "summaries" rather than "status reports" for
incoming initial section 8(e) submissions. These summaries contain
a detailed accounting of toxicological data and other information
(e.g., voluntary action information, exposure data) presented in
the initial submission. The summaries do not reflect, however, the
Agency's preliminary evaluation or disposition of the reported
information. Copies of Section 8(e) submission summaries can be
obtained in the same manner used to obtain copies of Section 8(e)
status reports.
It should be noted also that in June 1991, EPA published a TSCA
Section 8(e) "reporting guide" designed for use in conjunction with
EPA's March 16, 1978 Section 8(e) policy statement. Most of the
guide is presented in a question and answer (Q&A) format reflecting
primarily the questions most frequently asked about Section 8(e).
In addition, the "reporting guide" contains EPA's comments about
the Section 8(e)-applicability/reportability of data from a number
of generic toxicological "case studies" submitted to EPA by the
Chemical Manufacturers Assocation (CMA). The "guide" also contains
a cumulative index of the vast majority of those status reports
that reflect specific and/or general TSCA Section 8(e) reporting
guidance, as well as an index of all status reports prepared by EPA
to date arranged by submitted information type. Any person who
wishes to obtain a copy of this TSCA Section 8(e) "reporting guide"
should write to the Environmental Assistance Division (EAD/OTS) at
the address provided on the first page (iii) of the "Foreword" to
this volume.
3
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Finally, it is important to point out that on February 1, 1991 (see
56 FR 4128), EPA announced a one-time, voluntary TSCA Section 8(e)
"Compliance Audit Program" (CAP). The TSCA Section 8(e) CAP, which
incorporated stipulated monetary penalties and an overall monetary
penalty ceiling, was designed primarily to 1) achieve EPA's goal of
obtaining outstanding TSCA Section 8(e) information, and 2) provide
maximum encouragement to companies to voluntarily audit their files
for TSCA Section 8(e)-reportable information.
On April 26, 1991 (see 56 FR 19514), EPA announced the following
Section 8(e) CAP modifications: 1) extensions of the registration
and termination dates, 2) addition of an opportunity to petition
EPA on a case-by-case basis for an extension of the CAP termination
date, 3) modification of the CAP "Agreement" provision involving an
admission of a Section 8(e) violation, and 4) an announcement of
the Agency's intention to prepare and disseminate a Section 8(e)
"reporting guide."
Additional and final modifications to the TSCA Section 8(e) CAP
were announced by EPA on June 20, 1991 (see 56 FR 28458). These
modifications included 1) an extension of the CAP registration
deadline; 2) announcement of the availability of the Section 8(e)
reporting guide; 3) addition of a "listing" provision and reduced
stipulated penalties for certain types of Section 8(e)-reportable
information already in EPA's possession as the result of either i)
formal submission under a mandatory reporting provision of TSCA or
other statute administered by EPA, or ii) submission to EPA and
filing within the EPA's Office of Toxic Substances' formal "For
Your Information" (FYI) submission filing system; and 4) suspension
of Parts V(b) (1) and V(c) of EPA's March 16, 1978 TSCA Section 8(e)
policy statement for the purposes of judging the reportability of
information concerning "widespread and previously unsuspected
distribution in environmental media" and "emergency incidents of
environmental contamination" under the CAP and Section 8(e) in
general. Specifically, with regard to Parts V(b)(1) and V(c) of
the TSCA Section 8(e) policy statement, the June 20, 1991 Federal
Register announcement informed the regulated community that until
such time as EPA can provide more specific quidance on the types of
environmental monitoring, environmental release and environmental
contamination information should be submitted under Section 8(e),
subject persons should focus on statutory language of Section 8(e)
itself in determining the reportability of such information for the
purposes of the Section 8(e) CAP as well as ongoing compliance with
Section 8(e).
4
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Page 1 of 4
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
¦*<
Office of
Pesticides and Toxic Substances
date: MAR -8 1989
APPROVED
SUBJECT: status Report1 8EHQ-0189-0779
FROM: James F. Darr, Section Head
Chemical Risk Identification Section/CSB
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
The Eastman Kodak Company provided the final report from an acute
oral toxicity study of N-formyl-N'-p-aminophenylhydrazide (CAS No.
63402-26-6) in rats. Eastman Kodak's cover letter presents the
following summary information regarding the conduct and preliminary
results of this study:
"In an acute oral toxicity study [involving single doses
of 10, 20, 39 or 5000 mg/kg], estimated oral LD50 values
of 21 mg/kg and 14 mg/kg were obtained in male and female
rats, respectively. All animals receiving doses of 39
mg/kg or more died before scheduled study termination.
A dose of 20 mg/kg was also lethal to all females and to
2/5 males.
"Microscopic kidney lesions seen in one or more animals
at the 39 and 20 mg/kg dose levels included diffuse
necrosis of the proximal convoluted tubule epithelium
with granular and epithelial cast formation in the
proximal and distal renal tubules, and mineralized casts
in the proximal convoluted tubules. The only treatment-
related change in the 10 mg/kg dose group consisted of
This status report is the result of a preliminary evaluation of
information that has been submitted to EPA under Section 8(e), the "substantial
risk" information reporting provision of the Toxic Substances Control Act (TSCA) .
The statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Any
review of this status report should take into account that the report may be
based on incomplete information.
5
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8EHQ-0189-0779
Page 2 of 4
enlarged, pale kidneys in one female. Microscopic
examination revealed epithelial regeneration in the
proximal convoluted tubules. All animals at this dose
level survived the 14-day observation period "
Eastman Kodak also provided the final results of an acute dermal
toxicity study of the subject chemical in guinea pigs. The cover
letter provides the following summary information regarding the
conduct and results of this study:
"When applied to the skin [of guinea pigs at a single
dose of 0.5 g], the test article was, at most, a slight
skin irritant. Based on survival and weight gain, there
was no evidence of percutaneous absorption."
Eastman Kodak also submitted a copy of the subject chemical's
Material Safety Data Sheet (MSDS) that had been revised to reflect
the toxicologic findings reported in this Section 8(e) notice.
Finally, Eastman Kodak reported that the company is "not aware of
any health problems associated with . . . [the subject chemical's]
manufacture or use ..."
SUBMISSION EVALUATION
While the reported results of the acute dermal toxicity study in
guinea pigs indicate that the subject chemical is only slightly
irritating to the skin, the LD50 values (21 mg/kg in male rats and
14 mg/kg in female rats) estimated from the acute oral toxicity
study indicate that the chemical is "extremely toxic" according to
some acute toxicity classification systems. All of the rats that
received 39 mg/kg or more died before scheduled study termination,
while the 20 mg/kg dose level was lethal to all of the females and
2/5 males. As described in the submitted acute rat oral toxicity
study final report, microscopic kidney lesions were observed at the
2 0 mg/kg and 39 mg/kg dose levels. These kidney lesions were
reported to include diffuse necrosis of the proximal convoluted
tubule epithelium with granular and epithelial cast formation in
the proximal and distal convoluted tubules, and mineralized casts
in the proximal convoluted tubules. One female rat at the lowest
dose level tested (i.e., 10 mg/kg) exhibited enlarged, pale kidneys
characterized further histologically by epithelial regeneration in
the proximal convoluted tubules. In addition to the observed renal
effects, histopathologic examination of some of the tissues from
some of the rats receiving 2 0 mg/kg or 3 9 mg/kg reportedly revealed
a number of effects, including but not limited to: hemorrhage in
the glandular and non-glandular gastric mucosa; focal necrosis of
the hepatocytes; and hyperplasia and congestion or hemorrhage of
the zona fasciculata of the adrenal glands; the testes showed
interstitial hemorrhage and spermatid degeneration; the splenic
lesions included atrophy and congestion of the red pulp and atrophy
of the white pulp. Finally, hemorrhage was observed in the wall
of the urinary bladder of one male rat in the 39 mg/kg dose group.
6
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8EHQ-0189-0779
Page 3 of 4
The adverse effects described previously are consistent to some
degree with those seen as the result of exposure to hydrazine and
phenylhydrazine. The primary effects of phenylhydrazine in man and
animals are contact dermatitis, hemolytic anemia and liver/kidney
injury. Hydrazine itself is a strong skin and mucous membrane
irritant, convulsant, liver toxin and a moderate hemolytic agent.
Hydrazine can be absorbed via the lungs, gastrointestinal tract,
parenteral injection sites and intact skin. Airborne exposure to
hydrazine can result in eye and respiratory tract irritation with
lung congestion, bronchitis and pulmonary edema in some animals.
While adverse nervous system effects ending with convulsions can
occur via any route of hydrazine exposure, such neurotoxic effects
were not plainly evident in Eastman Kodak's acute rat oral toxicity
study of N-formyl-N'-p-aminophenylhydrazide.
CURRENT PRODUCTION AND DSE
A review of the production range (includes importation volumes)
statistics for CAS No. 63402-26-6, which is listed in the Agency's
initial TSCA Chemical Substance Inventory, showed that no 1977
manufacture/importation was reported or that all of the manufacture
and/or importation data reported were claimed as TSCA Confidential
Business Information (TSCA CBI) by the person(s) reporting for the
initial TSCA Inventory and cannot be disclosed (Section 14(a) of
TSCA; U.S.C. 2613(a)). All of the information reported for the
initial TSCA Inventory, including the production range information,
is subject to the limitations that are contained in the Agency's
TSCA Inventory Reporting Regulations (40 CFR 710).
In its submission, Eastman Kodak provided the following information
regarding the company's use of and the potential for exposure to
the subject chemical:
"This chemical is a low volume, site-limited intermediate
used to manufacture a photographic chemical. None of the
intermediate appears in the final product The
[subject intermediate chemical] was originally evaluated
as health hazards unknown - avoid all contact. The inter-
mediate is generally handled in a semi-liquid or wet cake
form. Based on the acute toxicity testing, employees
will be required to wear company-supplied clothing and
gloves, in addition, employees will be required to wear
respiratory protection when a potential for inhalation
exposure exists."
COMMENTS/RECO»fMy!MpiTTONff
In addition to modifying the MSDS and general handling procedures
for N-formyl-N'-p-aminophenylhydrazide, Eastman Kodak stated that
the company is currently considering the need to conduct additional
toxicologic studies of the subject chemical substance.
7
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8EHQ-0189-0779
Page 4 of 4
a) in view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity or exposure information, Eastman Kodak will be
asked to describe the nature and results, if available,
of all studies (other than those submitted already to EPA
or those cited in the open scientific literature) about
which Eastman Kodak is aware or that the company has
conducted, is conducting or plans to conduct that are
designed to determine the toxicity of N-formyl-N'-p-
aminophenylhydraz ide.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of the subject chemical.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be provided to the TSCA
Assistance Office (TAO/OTS) for further distribution.
8
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o^OSr«v„ Pa.ee 1 of 7
1^32 ^ united states environmental protection agency
\ -
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8EHQ-0389-0780
Page 2 of 7
Dnsft Mortalities r/No.
Dyina/No. Dosed)1
Time to Death
(Days)
fml /ka}
Male
Female
4.00
4/5
ND*
1-2
2.00
1/5
5/5
2-4
1.41
ND*
1/5
1
1. 00
0/5
0/5
ND* Not dosed
Union Carbide stated that the preceding dose-mortality data allowed
calculation of undiluted Silane A-1100 acute peroral LD50s of 2.83
ml/kg in the male rats and 1.57 ml/kg in the female rats. Further,
Union Carbide reported the following information regarding clinical
signs and the results of gross and histopathological examinations:
"Signs of toxicity, seen principally at doses of 1.41
ml/kg and above, included sluggishness, diarrhea, red
perinasal and periocular encrustation, and red-brown
stains in the perineal area. [The] survivors recovered
from these effects at 2-9 days, and gained weight over
the 2-week post-dosing observation period.
"Gross pathology seen in animals that died included dark
or bright red lungs, dark red glandular portion of the
stomach, and distended liquid-filled intestine. [The]
survivors showed no gross pathology at necropsy, carried
out immediately after sacrifice at the end of the [14-
day] observation period.
"Light microscopical examination was undertaken on [the]
kidneys from 7 rats dosed perorally with Silane A-1100
(2 males at 4.0 ml/kg; 2 males and 3 females at 2.0 ml/
kg) and urinary bladders from all animals except one
male of the 4.0 ml/kg group. Kidneys from males of the
4.0 ml/kg group and females of the 2.0 ml/kg group
showed acute cortical tubular necrosis, with mineraliza-
tion of the tubular epithelium in several animals. One
male rat (survivor) showed no significant renal histo-
pathology. Only one rat ([a male?] 4.0 ml/kg) showed
a urinary bladder lesion, which took the form of focal
epithelial necrosis."
Union Carbide submitted the following summary information regarding
the company's acute dermal toxicity study of silane A-1100 in
rabbits:
"Undiluted Silane A-1100 was applied to the shaven trunk
skin of groups of 5 male and 5 female New Zealand White
rabbits at the doses shown in the . . . [following
Table]. Material was held in contact with the skin for
24 hr by means of an occlusive dressing. Following
removal of the dressing, animals were observed for signs
10
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8EHQ-0389-0780
Page 3 of 7
of local and/or systemic toxic or pharmacologic effects
over a 2-week period. Mortalities were as follows over
the observation period:
Dose Mortalities r (No. Dvincr/No. Dosed! 1 Time to Death
(ml/kg) Male Female (Davs)
8.0
5/5
5/5
1-2
4 . 0
2/5
2/5
2-3
2.0
0/5
0/5
-
1.0
0/5
0/5
"
According to Union Carbide, the preceding dose-mortality data
allowed calculation of acute percutaneous LD50s of 4.29 ml/kg for
both the male and female rabbits. In addition, Union Carbide
provided the following information regarding clinical signs and the
results of gross and histopathological examinations of the rabbits:
"Signs of toxicity, seen principally at applied doses
of 2 ml/kg and above, included sluggishness and prostra-
tion, and the presence of blood (confirmed by HemastixR)
in the urogenital area and floor of the cage. [The]
survivors recovered from these effects by 2 to 4 days
after dosing. On removal of the occlusive dressing,
local skin lesions included erythema, edema, necrosis,
and ecchymoses, persisting for 7 to 14 days. After 7
days, there was the development of fissures, desquama-
tion and scab formation. Survivors lost weight over the
first post-application week, with partial (4 ml/kg) or
full (l and 2 ml/kg) recovery of weight during the
second week.
"Necropsy of animals that died revealed lungs that were
mottled dark red or pink, red liquid or clots in the
urinary bladder, and tan-colored kidneys. Histological
examination . . . was conducted on [the] kidneys from
a few animals at all doses, with the following results.
In [the] rabbits that died at 8.0 and 4.0 ml/kg, there
was marked acute tubular nephrosis, characterized by
swelling and necrosis of cortical proximal convoluted
tubules with sloughing of cells and evidence of tubular
proteinosis. In one male [rabbit] sacrificed at 2.0
ml/kg, there were acute tubular changes similar to those
seen at 8.0 and 4.0 ml/kg. At 1.0 ml/kg (males and
females) and 2.0 and 4.0 ml/kg (females), the survivors
had little acute nephrotic change, although the 4.0
ml/kg survivor [(the sex was not specified)] did show
regenerative changes."
Union Carbide also presented the following conclusions that the
company has drawn from these and other studies conducted to date
with Organofunctional Silane A-llOO:
li
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Page 4 of 7
"Silane A-1100 can produce nephrotoxic effects, seen as
renal cortical tubular necrosis at lethal doses absorbed
perorally (rat) or percutaneously (rabbit), indicating
that renal failure and its attendant biochemical aberra-
tions may be the cause of death. At sublethal doses,
either no kidney injury, or injuring with healing,
occurs. Acute exposure to vapor from Silane A-1100 did
not produce any signs of systemic toxicity or gross
pathology suggestive of nephrotoxicity. In these latter
studies, 5 male and 5 female rats were exposed for 6 hr.
to a vapor-saturated atmosphere generated statically at
25°C.
"The LD50 data and degrees of primary irritancy accord
with previously conducted 'range-finding' studies (with-
out histology) on Silane A-1100 over a period of 34
years. A further relevant study, which is nearing
completion, has involved the recurrent application to
rabbits of Silane A-1100 at doses of 17 and 84 mg/kg/day
for 6 hr/day for 9 days. This procedure produced local
skin inflammation, which was marginal at 17 mg/kg/day
and moderate to severe at 84 mg/kg/day. There were no
clinical, biochemical, or morphological indications of
systemic toxicity (including kidney injury). Also,
Organofunctional Silane A-1100 has been shown not to be
genotoxic in the following studies:
(1) An Ames bacterial mutagenicity assay using five
strains of Salmonella typhimuriuro.
(2) An in vitro forward gene mutation test (HGPRT-locus)
in Chinese Hamster ovary cells.
(3) An in vitro cytogenetics (clastogenicity) study in
Chinese Hamster ovary cells.
(4) An in vivo micronucleus study in mice
"The acute renal cortical tubular necrosis described
above for Organofunctional Silane A-1100 has not been
observed to date with other trialkoxysilanes, and
therefore ... it would not be appropriate to ascribe
these unusual effects to an entire chemical class."
Union Carbide stated that the final reports from the acute rabbit
dermal and rat oral toxicity studies, as well as the ongoing 9-day
repeated dermal contact study in rabbits, will be sent to EPA as
soon as those reports are completed.
SUBMISSION EVALtlftT'Tnil
Over the past several years, EPA has evaluated a number of studies
of the toxicity of silane compounds. For the most part, these
previous studies have focussed primarily on toxicities resulting
12
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8EHQ-0389-0780
Page 5 of 7
from inhalation exposure. In general, the studies have highlighted
respiratory effects, specifically petechial hemorrhages, focal
reddening of the lungs and failure of the lungs to collapse upon
opening the thoracic cavity (i.e., a condition described as "fixed
lungs"). In the current submission, however, the kidney has also
projected as a target organ.
According to the present submission, the gross observations for rats
given undiluted Silane A-1100 at oral dose levels of 1.41 mg/kg and
above included dark or bright red lungs, dark red glandular portions
of the stomach and distended liquid-filled intestines. Histopatho-
logic examination of the kidneys from 7 rats revealed acute cortical
tubular necrosis, with mineralization of the tubular epithelium of
the kidneys in several of the animals; only one animal showed no
significant renal histopathology. In addition, one animal exhibited
a urinary bladder lesion (which was in the form of focal epithelial
necrosis). The oral LD50s were found to be 2.83 ml/kg (males) and
1.57 ml/kg (females).
In the dermal toxicity study of undiluted Silane A-1100, 24-hour
contact with rabbit skin resulted in erythema, edema and ecchymoses
that persisted for 7 to 14 days. After 7 days, there were dermal
fissures, desquamation and scab formation. The dermal LD50 was
found to be 4.29 ml/kg. The gross effects noted in the animals that
died included dark, mottled dark red or pink lungs, red liquid or
clots in the urinary bladder and tan colored kidneys. The animals
that died at the 4.0 ml/kg and 8.0 ml/kg dose levels showed acute
tubular nephrosis characterized by swelling and necrosis of the
cortical proximal convoluted tubules with sloughing of cells and
tubular proteinosis, it should be noted also that Union Carbides's
statement that rabbits in the 1.0 ml/kg and 2.0 ml/kg groups "had
little acute nephrotic change" implies that adverse kidney effects
of an unstated magnitude may have been seen at the lower doses.
While the Agency agrees that the observed nephrotoxic effects may
be chemical-specific and not characteristic of the entire class of
trialkoxysilanes, in the absence of more definitive information, a
concern for nephrotoxicity should be included with the already pre-
sent concern for respiratory toxicity when assessing the potential
toxicity of these types of chemicals.
CURRENT PRODUCTION AND Ufilfl
A review of the production range (includes importation volumes)
statistics for CAS No. 919-30-2, which is listed in EPA's initial
TSCA Chemical Substance Inventory, showed that between 10 thousand
and 101 thousand pounds were reported as being manufactured and/or
imported in 1977. This production range information does not
include any data that were claimed to be TSCA Confidential Business
Information (TSCA CBI) by the person(s) who reported for the TSCA
Inventory, nor does it include any information that would compromise
TSCA CBI. All of the data reported for the initial TSCA Inventory,
including the production range data, are subject to the limitations
contained in the TSCA Inventory Reporting Regulations (40 CFR 710) .
13
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8EHQ-0389-0780
Page 6 of 7
Union Carbide did not submit any information on current production
or specific use(s) of Silane A-1100 nor was such information found
in the secondary scientific literature sources that were consulted
by the Agency.
COMMENTS/RECOMMENDATIONS
Union Carbide reported that the Organofunctional Silane A-1100
Material Safety Data Sheet is being updated to reflect the reported
toxicologic findings. Union Carbide also stated that the reported
information is being communicated to the company's Silane A-1100
customers and those employees involved in the production/handling
of Silane A-1100. Union Carbide reported further that "additional
acute studies are being conducted to more precisely define the
nephrotoxic potential of Silane A-1100." Finally, Union Carbide
stated that the company is conducting acute toxicologic studies
using a "valid sample of Organofunctional silane A-189."
It should be noted that EPA has received a number of Section 8(e)
and "For Your Information" (FYI) notices containing information on
organosilane chemicals, including Silane A-lioo. In addition, the
Chemical Screening Branch has prepared a Chemical Hazard Information
Profile (CHIP) that covers a number of chemicals within this class.
Finally, the Risk Analysis Branch (RAB/ECAD/OTS) is now evaluating
available toxicologic/exposure data on organosilanes.
a) The Chemical Screening Branch will ask Union Carbide to
ensure that EPA receives a full copy of the final report
(including the actual experimental protocol, results of
gross and histopathological examinations, results of any
statistical analyses, etc.) from each study (including
the acute vapor inhalation and genotoxicity studies)
cited in the company's submission.
In view of EPA's general interest in company actions
that are taken on a voluntary basis in response to
chemical toxicity/exposure data, Union Carbide will be
asked to describe the nature and results, if available,
of all studies (other than those submitted already to
EPA or those cited in the open scientific literature)
about which Union Carbide is aware or that the company
has conducted, is conducting or plans to conduct that
are designed to determine the toxicity of or exposure
to Silane A-1100. Further, Union Carbide will be asked
to keep the Agency apprised about the results of the
company's toxicologic studies using "valid" samples of
Organofunctional Silane A-189.
b) As was the case with the initial Section 8(e) notice,
the Chemical Screening Branch will immediately provide
copies of all reported information to the Risk Analysis
Branch for inclusion in their ongoing organosilanes
review.
14
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8EHQ-0389-0780
Page 7 of 7
c) The Chemical Screening Branch will send copies of this
Status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be sent to the TSCA
Assistance Office (TAO/OTS) for further distribution.
15
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Page 1 of 4
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
Office of
Pesticides and Toxic Substances
MAR -9 1989 approved:
Status Report1 8EHQ-0189-0781 8
James F. Darr, Section Head
Chemical Risk Identification Section/CSB
Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Hi-Tek Polymers, Inc. has claimed certain information in its TSCA
Section 8(e) notice to be Confidential Business Information (CBI).
Staff of the Information Management Division (IMD/OTS) will review
all incoming correspondence related to this TSCA CBI claim.
SUBMISSION DESCRIPTION
Hi-Tek Polymers, Inc. submitted preliminary findings from a 1-week
rat oral feeding study of the ethylidenebis-4,1-phenylene ester of
cyanic acid. The company's cover letter presents the following
summary information regarding the conduct and preliminary results
of this acute toxicity study:
"This study was conducted to establish dose levels for
a 4-week oral toxicity test. The chemical, [which was]
coded as HTP-103 for this study, was fed [by gavage]
daily [to male and female rats] for seven days at doses
of 0, 10, 50, 250 and 1000 mg/kg/day. At the 1000 mg/kg
dose level, all [of] the rats (5 male and 5 female) died
within two days. At the 250 mg/kg dose level, one of 10
rats [(a female)] died [on] the sixth day. Most of the
DATE:
SUBJECT:
PROM:
TO:
NOTE
This status report is the result of a preliminary evaluation of
information that has been submitted to EPA under Section 8(e), the "substantial
risk" information reporting provision of the Toxic Substances Control Act (TSCA).
The statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Any
review of this status report should take into account that the report may be
based on incomplete information.
16
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8EHQ-0189-0781 S
Page 2 of 4
rats that died prematurely had depressed foci on the
stomach and two had a ruptured duodenum. Salivation and
brown staining around the mouth was found among all
groups receiving HTP-103. Organ weight analysis of male
rats receiving 250 mg/kg showed an increase in liver and
spleen weights »
Hi-Tek reported that previously conducted acute rabbit studies
using a "less pure form" of the subject chemical showed that the
chemical was "practically non-toxic" following dermal application
and "essentially non-irritating" to the skin and eyes. Hi-Tek
reported also that "acute studies conducted on similar compounds
showed no evidence of toxicity." In addition, Hi-Tek reported that
the methylenebis(2,6-dimethyl-4,1-phenylene) ester of cyanic acid
(CAS No. 101657-77-6) "underwent the same range finding test at the
same time as HTP-103 and was found to be non-toxic at the 1000
mg/kg/day dose level.11
SUBMISSION EVALUATION
According to the submitted information, the ethylidenebis-4,1-
phenylene ester of cyanic acid was administered in an aqueous
solution to groups of Sprague-Dawley rats (5/sex/group) by gavage
at dose levels of 10, 50, 250 or 1000 mg/kg/day for 7 consecutive
days. The control animals received distilled water.
All rats at the highest dose (1000 mg/kg/day) exhibited salivation,
hunched posture, piloerection, pale extremities, hypothermia and
labored breathing on days 1-2. The high dose animals were either
killed in extremis on day 1 or day 2 or were found dead on day 2.
The necropsy findings for 3/5 males and 3/5 females were dark red
stomach and ruptured duodenum.
One female rat in the 250 mg/kg/day dose group displayed signs of
toxicity similar to those seen in the 1000 mg/kg/day dose group
animals (i.e., labored breathing, pale extremities, hypothermia).
This particular animal was killed in extremis on day 6. [The] other
rats in the 250 mg/kg/day dose group survived the 7-day study
period and exhibited only salivation and brown staining around the
mouth; their body weights and food consumption, however, were
reported to be slightly reduced. Organ weight analyses for rats
in the 250 mg/kg/day dose group showed a statistically significant
increase in liver weight in males and in both liver and spleen
weights in females when compared to the control animals. Although
depressed foci in the stomach were noted in one female in the 250
mg/kg/day dose group, no other gross morphological abnormalities
were detected in the other animals in this dose group.
The 7-day administration of the two lowest doses (i.e., 10 and 50
mg/kg/day) did not appear to result in any significant toxicities.
Overall, the provided data indicate that prolonged exposure to the
ethyl idenebis-4, l-phenylene ester of cyanic acid may cause toxicity
to the stomach, intestines, liver and spleen.
17
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8EHQ-0189-0781 S
Page 3 of 4
CURRENT PRODUCTION AND USE
In its Section 8(e) submission, Hi-Tek stated non-confidentially
that the ethylidenebis-4,1-phenylene ester of cyanic acid is an
experimental research and development (R&D) product that is not on
the Agency's TSCA Chemical Substance Inventory. Hi-Tek stated also
non-confidentially that "commercial manufacture [of the chemical]
has not commenced." In addition, Hi-Tek submitted the following
non-confidential information regarding the use of and the potential
for exposure to the ethylidenebis-4,1-phenylene ester of cyanic
acid:
"This [chemical] substance is being evaluated for use as
a polymerizable monomer component in thermoset fiber
reinforced structures. These [reinforced structures]
are manufactured under controlled conditions which make
direct contact or ingestion very unlikely. No consumer
use of the unpolymerized substance is anticipated. The
Material Safety Data Sheet [(MSDS)] for this substance
has been revised to reflect these [reported] results and
is being distributed to people currently evaluating this
product "
Hi-Tek included a copy of the updated MSDS in its TSCA Section 8(e)
notice. It should be noted, however, that the "INGESTION" section
of the submitted MSDS states simply that "a feeding study indicates
[that the] LD50 may be <1000 mg/kg for rats."
It should be noted also that the other chemical substance (i.e.,
the methylenebis(2,6-dimethyl-4,1-phenylene) ester of cyanic acid;
CAS No. 101657-77-6) cited in Hi-Tek's TSCA Section 8(e) submission
was not located on the currently available non-confidential printed
or computerized versions of the Agency's TSCA Chemical Substance
Inventory.
COMMENTS/RECOMMENDATIONS
In its TSCA Section 8(e) submission, Hi-Tek stated that a number
of other studies have been initiated or are planned to further
define the potential toxicity of the ethylidenebis-4,1-phenylene
ester of cyanic acid. These initiated/planned studies include a
4-week oral toxicity study, acute oral and inhalation toxicity
studies, a skin sensitization study, genotoxicity studies and
aquatic toxicity studies.
a) The Chemical Screening Branch will ask Hi-Tek to ensure
that EPA receives a complete copy of the final report
(including the actual experimental protocol, results of
gross and histopathological examinations, results of any
statistical analyses conducted, etc.) from each study
cited in the company's Section 8(e) submission, including
the 1-week oral toxicity study of the methylenebis(2,6-
dimethy1-4,1-phenylene) ester of cyanic acid (CAS No.
101657-77-6).
18
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8EHQ-0189-0781 S
Page 4 of 4
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity or exposure data, Hi-Tek will be requested to
describe the nature and results, if/when available, of
all studies (other than those submitted already to EPA
or those cited in the published scientific literature)
about which Hi-Tek is aware or that the company has
conducted, is conducting or plans to conduct that are
designed to determine the toxicity of or the exposure to
the ethylidenebis-4,1-phenylene ester of cyanic acid and
the methylenebis(2,6-dimethyl-4,1-phenylene) ester of
cyanic acid.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of the cited cyanic acid derivatives.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be provided to the TSCA
Assistance Office (TAO/OTS) for further distribution.
19
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w
*> . \
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
Office of
Pesticides and Toxic Substances
DATE: mar 2 0 1989
approved:
SUBJECT! status Repprt1 8EHQ-0289-0782 S
FROM: James F. Darr, Section Head
Chemical Risk Identificatio
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
The Dow Chemical Company has claimed the exact identity of the
subject chemical to be TSCA Confidential Business Information
(CBI). The Information Management Division (IMD/OTS) will review
all incoming correspondence related to the company's CBI claims.
In the "sanitized" version of its TSCA Section 8(e) notice, Dow
reported non-confidentially that the subject chemical substance is
a "substituted aromatic sulfonamide."
SUBMISSION DESCRIPTION
The Dow chemical Company provided the following summary information
regarding the conduct and preliminary results of a dietary probe
study of the substituted aromatic sulfonamide in Beagle dogs:
"This dietary probe study was conducted to assess the
palatability of the test material when administered to
commercially supplied laboratory bred Beagle dogs. The
study consisted of two experiments, Phase A and Phase B.
In Phase A, groups of 2 female dogs were administered the
test material at targeted dose levels of 0, 250, 500 or
1000 mg/kg body weight (BW)/day. After 14 days on test,
one dog given 0, 250 or 1000 mg/kgBW/day was humanely
This status report is the result of a preliminary evaluation of
information t^hat has been submitted to EPA under Section 8(e), the "substantial
risk" information reporting provision of the Toxic Substances Control Act (TSCA) .
The statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Any
review of this status report should take into account that the report may be
based on incomplete information.
20
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8EHQ-0289-0782 S
Page 2 of 4
euthanatized and examined for gross pathologic effects.
The remaining female dogs that survived 14 days of
exposure (one each at dose levels of 0, 250 or 500
mg/kgBW/day) were maintained on control canine chow for
2 weeks and then humanely euthanatized prior to gross
pathologic examination. In Phase B, groups of male, as
well as female dogs, were administered the test material
at targeted dose levels of 0, 25, 100 or 250 mg/kgBW/day
(2 [dogs]/sex/dose level). Following 14 days of dietary
exposure, all [of the] surviving animals were humanely
euthanatized and a gross necropsy was performed. [The]
parameters measured in both [the Phase A and Phase B]
experiments included: physical examination, body weights,
feed consumption," gross pathology, and histopathologic
examination of selected tissues.
"Dietary administration of the test material [to Beagle
dogs] at targeted dose levels of 100«, 250, 500 or 1000
mg/kgBW/day produced treatment-related effects in the eye
and kidney. [The] ocular effects consisted of retinal
degeneration, retinal necrosis, and retinal detachment
secondary to degeneration. Peripheral nerve tissue,
optic nerve/chiasma, and sciatic nerve were unaffected
by treatment. [The] renal effects were localized to the
distal convoluted tubules and collecting ducts and con-
sisted of degeneration of these structures at dose levels
of 100 mg/kgBW/day and above, and focal necrosis of these
structures at dose levels of 2 50 mg/kgBW/day and above.
Significant decreases in body weight and feed consumption
suggested an unpalatability of diets at dose levels > 100
mg/kgBW/day; however, the extent of target organ effects
noted at these doses may have also affected the animals'
dietary intake. Increases in mortality also occurred in
[the] female dogs given dose levels of 250, 500 or 1000
mg/kgBW/day (one animal fed each of these dose levels
died prior to scheduled necropsy).
"No ocular or renal lesions, or effects on any other
study parameters, were noted among male or female dogs
administered the bottom dose level of 25 mg/kgBW/day,
establishing this dose as the No-Observed-Effect level."
SUBMISSION EVA^i.Tr»M
The dietary administration of this substituted aromatic sulfonamide
to Beagle dogs for 14 days at dose levels of 100, 250, 500 or 1000
mg/kg/ctay resulted in adverse ocular and kidney effects. Although
Dow stated that retinal degeneration, retinal necrosis and retinal
detachment were observed, the company did not report in how many
of the dogs per dose group these effects were found. The renal
effects were reported to be localized in the distal convoluted
tubules and collecting ducts; the effects consisted of degeneration
of these structures at 100 mg/kg/day and above. At dose levels of
250 mg/kg/day and above, there was focal necrosis of these renal
21
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8EHQ-0289-0782 S
Page 3 of 4
structures. As with the ocular effects, the frequency of the renal
effects was not reported. In the female dogs receiving the test
material at doses of 2 50 mg/kg/day and higher, there were increases
in mortality (i.e., 1 animal/dose level died prior to the scheduled
necropsy). According to the provided summary information, there
were no adverse ocular or renal effects or "effects on any other
study parameters" observed at 25 mg/kg/day, the lowest dose level
that was tested.
It is important to point out that sulfonamides, when administered
as drugs, exist in the blood in three forms: free, conjugated and
protein-bound; the free form is the active form. According to the
general scientific literature, sulfonamides are noted for their
ability to cause phototoxic dermal reactions involving swelling,
redness, blistering and possibly hyperpigmentation (which is
associated with long-term morphologic changes in the melanosomes).
Ocular effects such as periorbital edema, keratoconjunctivitis or
corneal or lens opacities are also attributed to the administration
of sulfonamides. Photoallergenicity is also a consequence as are
blood dyscrasias (e.g., agranulocytosis, aplastic anemia, purpura
(small hemorrhages) and methemoglobinemia). In the kidney, when
there are high concentrations of sulfonamides in the tubular urine,
the solubilities of the sulfonamides can be exceeded and crystals
will form. These crystals may be eliminated from the kidney or
deposited in the collecting system leading to formation of larger
crystals or stones. These stones can mechanically obstruct the
kidney tubules resulting in an increase in intratubular pressure
followed by diminished glomerular filtration rate and renal blood
flow; the diminished filtration rate and blood flow can result in
tissue ischemia and subsequent loss of renal tissue. Finally, it
should be noted that sulfonamides are also known for their ability
to potentiate hepatotoxicity.
A full copy of the final report of Dow's 14-day study (including
the actual experimental protocol, results of gross/histopathologic
examinations, etc.) is expected to provide a more definitive
profile of the toxic effects of the subject substituted aromatic
sulfonamide when administered to dogs.
CURRENT PRODUCTION AND USE
In view of Dow's TSCA CBI claim, no information regarding the TSCA
Chemical Substance Inventory status of the subject chemical will
appear in this status report.
According to the sanitized version of Dow's TSCA Section 8(e)
submission, this substituted aromatic sulfonamide "is at the
research stage and is being evaluated for use as a pesticide."
ffOMMENTS/RECQMMENDATIONfl
Dow reported that in accordance with longstanding company practice,
all relevant Dow employees are being notified about the submitted
toxicologic findings.
22
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8EHQ-0289-0782 S
Page 4 of 4
a) The Chemical Screening Branch will ask Dow to ensure that
EPA receives a full copy of the final report (including
the actual experimental protocol, results of gross and
histopathological examinations, results of statistical
analyses, etc.) from the company's 14-day dietary probe
study of this substituted aromatic sulfonamide in Beagle
dogs.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, Dow will be asked to describe the
nature and results, if available, of all studies (other
than those submitted already to EPA or those cited in the
published scientific literature) about which Dow is aware
or that the company has conducted, is conducting or plans
to conduct that are designed to determine the toxicity
of this substituted aromatic sulfonamide.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of the subject chemical.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be provided to the TSCA
Assistance Office (TAO/OTS) for further distribution.
23
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Page 1 of 4
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
MAR 2 I 1989
APPROVED:
SUBJECT: Status Report1 8EHQ-0289-0783 8
FROM: James F. Darr, Section Head Unna-j / . U^nrx—
Chemical Risk Identification/Section/CSB
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
The submitting company claimed its name and the exact identity of
the subject chemical to be TSCA Confidential Business Information
(CBI). The Information Management Division (IMD/OTS) will review
all incoming correspondence related to these CBI claims. In the
"sanitized" version of the Section 8(e) notice, the company stated
non-confidentially that the subject chemical is a "heterocyclic
pyrazolyl amide."
SUBMISSION DESCRIPTION
The submitting company provided the following summary information
regarding the conduct and preliminary results of a teratology study
of the subject heterocyclic pyrazolyl amide in rats:
"Preliminary results obtained from a pilot rat teratology
study indicates that [this heterocyclic pyrazolyl amide]
produces significant maternal and developmental toxicity
when administered [by gavage] to pregnant rats at 400
mg/kg/day. Slight maternal toxicity and equivocal embryo-
toxic ity were noted at 125 mg/kg/day. In this study,
[the subject chemical] was administered to 3 groups of
mated female rats [(25 rats/group)] at dose levels of 0,
125, and 400 mg/kg/day during gestation days 6 through
18. Surviving dams were sacrificed on gestation day 20.
Fetuses were removed, weighed and examined for external
malformations.
1 This status report is the result of a preliminary evaluation of
information that has been submitted to EPA under Section 8(e), the "substantial
risk" information reporting provision of the Toxic Substances Control Act (TSCA) .
The statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Any
review of this status report should take Into account that the report may be
based on incomplete Information.
24
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8EHQ-0289-0783 S
Page 2 of 4
"One rat at 125 mg/kg/day and 3 rats at 4 00 mg/kg/day
died prior to the scheduled sacrifice. Clinical signs
of toxicity (primarily urogenital staining) were noted
at 400 mg/kg/day and, to a much lesser degree, at 125
mg/kg/day. Body weight effects were most apparent during
gestation days 6-9. Mean weight gains for this interval
were 7, 0, and -18 grams, respectively, in the 0, 125 and
400 mg/kg/day groups. Weight gain in the treated groups
appeared to recover during the remainder of the gestation
period. [The] food consumption was decreased in a similar
manner. Post-implantation loss was increased at 4 00
mg/kg/day and possibly at 125 mg/kg/day but mean fetal
weights were apparently unaffected. No external malfor-
mations were noted at 125 mg/kg/day but 5 fetuses from
3 litters at 400 mg/kg/day exhibited umbilical hernias
and facial defects (cleft palate, cleft lip, etc.).
Three of the fetuses with external malformations (2 with
umbilical hernias and 1 with facial defects) came from
the same dam. This dam produced 10 live fetuses (with
a mean weight of 2.2 g) and 7 resorptions.
"The no-effect level of 12 5 mg/kg was determined from the
data for external malformations. For post-implantation
loss, a no-effect level of approximately 38 mg/kg was
plotted from the available data."
In its Section 8(e) submission, the company reported further that
a previously conducted teratology study "did not show evidence of
treatment related effects." A submitted summary presents the
following information with regard to the conduct and results of
this previous study:
"[The heterocyclic pyrazolyl amide] was administered by
gavage to 6 groups of mated female rats [(8 rats/group)]
at dose levels of 0, 50, 125, 250, 500 and 1000 mg/kg/day
during gestation days 6-15. [The] surviving dams were
sacrificed on gestation day 20 [and the] fetuses were
removed, weighed, sexed and examined for possible
external malformations.
"One of 8 females from both the 500 and 1000 mg/kg/day
groups died during the study. Weight loss or reduced
weight gain was noted at >250 mg/kg/day, primarily during
the first 3 days of dosing. Post-implantation loss and
fetal body weights did not appear to be affected at any
[dose] level. The only malformations observed were a
single fetus with a kinky tail at 50 mg/kg/day and one
fetus with omphalocele (an umbilical cord defect) at 125
mg/kg/day. Because tail defects and omphalocele are
sometimes observed in control animals, and because no
malformations were observed in the higher dose groups,
the defects seen in this study do not appear to be
treatment related."
25
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8EHQ-0289-0783 S
Page 3 of 4
SUBMISSION EVALUATION
This Section 8(e) notice provides evidence regarding the potential
developmental and maternal toxicity of this heterocyclic pyrazolyl
amide. The pilot teratology study showed maternal toxicity (e.g.,
maternal death, urogenital staining, reduced body weight gain)
following exposure to 125 mg/kg/day and 400 mg/kg/day; the degree
of toxicity was dose-dependent. Fetal toxicity was also evident
at 125 mg/kg/day and 400 mg/kg/day. The administration of 400
mg/kg/day lesulted in a significant increase in post-implantation
loss (i.e., total and early resorptions), a significant decrease
in litter size, an increase pre-implantation loss, and an increase
in the number of fetuses with malformations (umbilical hernias and
cleft palate or lip); exposure to 125 mg/kg/day resulted in an
increase in post-implantation loss and a decrease in litter size.
Considering that 125 mg/kg/day was the lowest dose tested in the
pilot teratology study and an increase in post-implantation loss
was observed at this dose level, the study findings do not allow
the establishment of a "no-observable-adverse-effect-level" (NOAEL)
for the developmental toxicity of the heterocyclic pyrazolyl amide.
CURRENT PRODUCTION AND USE
In view of the submitting company's TSCA CBI claims, no information
with regard to the TSCA Chemical Substance Inventory status of this
heterocyclic pyrazolyl amide will appear in this status report.
The submitting company reported non-confidentially that the subject
chemical "is currently being manufactured exclusively for [research
and development (R&D)] purposes."
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will ask the submitter to
ensure that EPA receives full copies of the final reports
(including the actual experimental protocols, results of
gross and histopathological examinations, results of any
statistical analyses, etc.) from the pilot and range-
finding teratology studies cited in the submission.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, the submitting company will be
requested to describe the actions that the company has
taken or plans to take 1) to notify workers and others
about the reported information, and 2) to reduce or
eliminate exposure to this heterocyclic pyrazolyl amide.
In addition, the company will be asked to describe the
nature and results, if available, of all studies (other
than those submitted already to EPA or those cited in the
published scientific literature) about which the company
is aware or that the company has conducted, is conducting
or plans to conduct that are designed to determine the
toxicity of the subject heterocyclic pyrazolyl amide.
26
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8E-1Q-0 289-0783 S
Page 4 of 4
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of this heterocyclic pyrazolyl amide.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be provided to the TSCA
Assistance Office (TAO/OTS) for further distribution.
27
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Page 1 of 4
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
«t PflQl
Office of
Pesticides and Toxic Substances
date: MAR 2 2 1989
APPROVED:
7JlL ^
SUBJECT; Status Report1 8EHQ-0289-0784
FROM: James F. Darr, Section Head
Chemical Risk Identificatio
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
The Dow Chemical Company provided summary information about Dow's
development and validation of "methods for monitoring workplace air
for methylene bisphenyl isocyanate (MDI)." According to Dow, these
monitoring studies were performed because "discrepancies in methods
were noted by other researchers in laboratory and field studies and
were to date unexplained." Dow's Section 8(e) submission presents
the following information regarding the conduct and results of the
company's studies:
"One of the major steps in these studies was to generate
an MDI atmosphere containing both vapors and aerosols of
MDI. MDI is used in the work environment in heating and
spray operations, and because of its extremely low vapor
pressure, has the potential to exist as both a vapor and
aerosol. The MDI atmospheres were generated by passing
heated, dried air through a J-tube packed with glass
beads coated with [Dow's] ISONATER 125M (98% 4,4'-MDI and
2% 2,4'-MDI). MDI prepolymer and polymeric MDI were also
tested. This air stream was then blended with a make-up
air stream to give a total flow of approximately 75 L/min
going in the 117 liter stainless steel testing chamber.
Hot MDI vapors condense and form aerosols. The instru-
ments and sampling devices were placed directly in the
chamber for testing.
1 This status report is the result of a preliminary evaluation of
information that has been submitted to EPA under Section 8(e), the "substantial
risk" information reporting provision of the Toxic Substances Control Act (TSCA).
The statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Any
review of this status report should take into account that the report may be
based on incomplete information.
28
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8EHQ-0289-0784
Page 2 of 4
"The [generated] atmosphere was characterized using a
parallel stage impactor. This device contains an array
of 6 impactor stages in parallel, with particle cut-off
stages ranging from 0.3 [microns] to 7.5 microns; one
stage collects the total particulates. The flow rate
through each stage was controlled at 700 mL/min. At the
base of each stage is a 25-mm glass fiber filter which
can be analyzed to determine the particle size distri-
bution. The 25-mm glass fiber filters were coated with
1 mg of l-(2-pyridyl)piperazine and analyzed by high
performance liquid chromatography (HPLC) to determine the
mass of MDI The results suggest that a small
proportion of the [generated] particles are vapor, with
a larger percentage represented by particles in the range
from 3 [microns] to 4 microns.
"Several monitoring methods [(including OSHA Method 47
and NIOSH P & CAM 142) ] were tested. ... It was
evident from early experience that an impinger method
utilizing l-(2-pyridyl)piperazine as a derivatization
reagent followed by analysis by HPLC consistently gave
the highest reading.
"Based on these data, the impinger method was chosen
initially as the reference method to which the other
methods were compared. Later in the study, after some
understanding was reached as to why these differences
were occurring, another method showed equivalency to the
reference impinger method. This method used a 13-mm
glass fiber filter coated with 1 mg of 1-(2-pyridyl)-
piperazine and 5% (by volume) diethyl phthalate for the
collection medium followed by analysis by HPLC. This
method was also then used as a reference method. . . .
"The [obtained] data for OSHA Method 47 . . . show that
at MDI concentrations greater than approximately 25 ppb
MDI, the coated filter method can significantly under-
estimate the MDI concentration. A possible explanation
for these results is the poor inlet capture velocity of
this method, it is important to note that these filters
were analyzed in less than 1 day. A preliminary storage
study conducted with these filters after sampling this
aerosol atmosphere showed a loss in recovery after 7 days
of storage.
h. . . [The NIOSH P & CAM 142 monitoring data] indicated
a mean recovery of 78% and have a significant amount of
variability, as indicated by the high standard deviation.
•»»... [MDHS 49, a monitoring method used by the Health
and Safety Executive (HSE), London, England, gave very
precise data but] "gave an average recovery for MDI of
34%, underestimating the MDI level."
29
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8EHQ-0289-0784
Page 3 of 4
"Some evaluations were also conducted with commercially
available paper tape instrumentation. After testing the
various filter methods and realizing that paper tapes
would behave quite similarly to [the] filters, it was
felt early in the study that the current commercially
available instruments would likely underestimate MDI air
concentrations."
Dow reported that one commercial paper tape monitoring device, sold
for analysis of toluene diisocyanate (TDI), "underestimated the MDI
levels when placed in an atmosphere containing both MDI vapors and
aerosols." Dow also stated, however, that modifications made by
the manufacturer produced an instrument "specifically for MDI which
could accurately sample vapors and aerosols, at least those of the
size described in this study . . . The [modified] instrument was
shown to be equivalent to the reference 13-mm filter method."
Dow also reported that another paper tape instrument (sold by its
manufacturer for MDI analysis) "consistently provided significantly
low readings" when compared to those obtained via the 13-mm filter
method or the modified commercial monitoring device cited above.
According to Dow, these results were duplicated in the field at a
facility of one of Dow's customers.
Finally, Dow provided the following information with regard to the
overall significance of the company's comparative air monitoring
studies:
"It is quite evident from the data presented that many
of the monitoring methods currently being used for MDI
are deficient when aerosols of the particle size range
used in this [Dow] study are present. The MDI atmosphere
that was generated in this study does not represent all
field situations but does represent at least a potential
workplace atmosphere. There are other areas such as
spraying operations and wood product plants which could
potentially pose [MDI] sampling problems which were not
addressed in this study. While . . . [Dow has] no data
for larger particle size aerosols, it is . . . [Dow's]
belief that the methods found to be deficient in . . .
[Dow's] study might yield even worse results under such
conditions. This study in . . . [Dow's] estimation
represents very ideal conditions and emphasizes the
importance of determining what is actually present in the
workplace. [Air] monitoring for MDI is much more complex
than most people have realized, probably leading them to
believe they are meeting established exposure limits when
in fact they may not be."
SUBMISSION EVALUATION
Immediately upon receipt, the Chemical Screening Branch transmitted
copies of this TSCA Section 8(e) submission to OSHA, NIOSH and the
American Conference of Governmental Industrial Hygienists (ACGIH).
30
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8EHQ-0289-0784
Page 4 of 4
In addition, copies of this submission were provided immediately
to the Risk Analysis Branch (RAB/ECAD/OTS) for inclusion in their
ongoing review of available toxicity and exposure information on
diisocyanates (e.g., MDI, polymeric MDI and TDI). It should be
noted that EPA has received a number of TSCA Section 8(e) and "For
Your Information" (FYI) submissions on diisocyanates. Further,
EPA prepared (in 1984) Chemical Hazard Information Profiles (CHIPS)
on MDI (including polymeric MDI) and TDI. TDI and MDI (including
polymeric MDI) are also the subject of TSCA Section 8(d) and 8(c)
information gathering rules. Finally, it should be noted that the
Interagency Testing Committee (ITC) has designated hexamethylene
diisocyanate (HDI) for testing pursuant to Section 4 of TSCA; HDI
is the subject of TSCA Section 8(d) and 8(a) information gathering
rules.
COMMENTS/RECOMMENDATIONS
In its submission, Dow stated that the company is notifying its
MDI customers and competitors about the reported findings.
a) The Chemical Screening Branch will ask Dow to ensure that
EPA receives a full copy of the final report (including
the actual experimental protocols, data, etc.) from the
MDI monitoring studies cited in the submission.
b) As in the case of the initial submission, the Chemical
Screening Branch will immediately provide the reported
information to the Risk Analysis Branch (RAB/ECAD/OTS)
for inclusion in the ongoing diisocyanates assessment.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, ACGIH, CPSC, FDA, NTP,
OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and
RAB/ECAD/OTS; copies of this status report will be sent
also to the TSCA Assistance Office (TAO/OTS) for further
distribution.
31
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Page 1 of 4
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATES
MAR 30 1989
APPROVED:
SUBJECT: Status Report1 8EHQ-0289-0785 S
FROM: James F. Darr, Section Heai
Chemical Risk Identificati
TO: Frank D. Kover, Branch Chief
Chemical Screening, Branch/ECAD/OTS/OPTS
NOTE
The submitting company has claimed its company name and the exact
identity of the subject chemical to be TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. In the "sanitized" version of its Section 8(e)
notice, the company reported non-confidentially that the subject
chemical substance is an "acylamino pyrimidine."
SUBMISSION DESCRIPTION
The submitting company provided the following summary information
about the conduct and preliminary results of a teratologic study
of this acylamino pyrimidine in rats:
"... [The data] obtained from a rat teratology study
indicates that acylamino pyrimidine produces maternal and
developmental toxicity when administered to rats at 750
mg/kg/day. Equivocal soft tissue and skeletal malforma-
tions were observed at a dose of 250 mg/kg/day. In this
study, acylamino pyrimidine was administered to 3 groups
of mated female rats at dose levels of 0, 75, 250 and 750
mg/kg/day during gestation days 6 through 15. Dams were
sacrificed on gestation day 20. [The] fetuses were
removed, weighed and examined for external soft tissue
and skeletal malformations.
This status report is the result of a preliminary evaluation of
information that has been submitted to EPA under Section 8(e), the "substantial
risk" information reporting provision of the Toxic Substances Control Act (TSCA) .
The statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s), Any
review of this status report should take into account that the report may be
based on incomplete information.
32
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8EHQ-0289-0785 S
Page 2 of 4
"Clinical signs of [maternal] toxicity (alopecia and
urogenital staining) were seen at 750 mg/kg/day. A body
weight gain deficit when compared to controls of 33%
during the treatment period and 14.6% for gestation days
0-20 was observed at 750 mg/kg/day. Weight gain in this
group did begin to recover following treatment. Two [of
the] females at 750 mg/kg/day had no viable fetuses. The
mean number of early resorptions was apparently increased
at 750 mg/kg/day with 2.2 vs. 1.0 in controls. Fetal body
weight was decreased an average of 23% for males and
females at 750 mg/kg/day.
"External malformations were observed at 750 mg/kg/day
which were not seen in controls including malrotated
hindlimbs, filamentous tail and rudimentary tail. [The]
external malformations occurred in a total of 4 fetuses
from 3 litters. Several soft tissue variations were
observed at increased frequencies at 750 mg/kg/day. Two
of these, dilatation of the lateral ventricle and
increased renal pelvic cavitation, were equivocally
increased at 250 mg/kg/day. Four soft tissue malforma-
tions (spinal cord agenesis, heart and/or great vessel
malformation, ectopic kidneys and adrenal agenesis) were
observed at the high dose which were not observed at
other dose levels or the control. Eighteen separate
skeletal variations were significantly increased at the
high dose. Two of these, less than four caudal vertebrae
ossified and 5th/6th sternebrae incompletely ossified,
were equivocally increased at 2 50 mg/kg/day. Four
skeletal malformations (filamentous tail, rudimentary
tail, forked/fused ribs and vertebral anomaly) were
observed at 750 mg/kg/day which were not seen at other
dose levels. The skeletal malformations were observed
in a total of 4.1% of the fetuses in 18% of the litters."
The submitting company also provided the following information with
regard to the conduct and preliminary findings of a teratologic
study of this acylamino pyrimidine in rabbits:
"In this study, acylamino pyrimidine was administered to
3 groups of pregnant female rabbits at dose levels of 0,
15, 50 and 150 mg/kg/day during gestation days 7 through
19. Does were sacrificed on gestation day 29. Fetuses
were removed, weighed and examined for external soft
tissue and skeletal malformations.
"Maternal body weight gain at 150 mg/kg/day was decreased
73% during the treatment period of days 7-20, however the
animals did gain weight following treatment (days 20-29).
Total mean resorptions were apparently increased at 150
mg/kg/day with 2.6 (29.9%) vs. 1.0 (11.7%) in controls.
There was an equivocal increase [found] in the incidence
of unossified hyoid (skeletal variation) at 50 and 150
mg/kg/day with an incidence of 2 fetuses from one litter
33
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8EHQ-0289-0785 S
Page 3 of 4
vs. none in the controls. The skeletal variation,
sternebrae asymmetrically ossified with minor fusion, was
also equivocally increased at 150 mg/kg/day with an
incidence of 2 fetuses from one litter vs. none in the
control. There were no treatment related malformations
observed in the study."
SUBMISSION EVALUATION
The submitted summary information indicates that both maternal and
developmental toxicity occurred in rats and rabbits after exposure
to the subject acylamino pyrimidine. In the rat study, maternal
toxicity was seen at the high dose level and adverse developmental
effects were seen at the high and mid-dose levels. In the rabbit
study, maternal weight gain appears to have been affected at the
high dose level, it should be noted, however, that maternal weight
gain in the rabbit is known to be quite variable. Adverse develop-
mental effects were observed at the high and mid-dose levels in the
rabbit study.
In order to evaluate the overall significance of the observed
toxicological findings, the submitting company should be asked to
ensure that EPA receives complete copies of the final reports
(including the actual experimental protocols, results of gross and
histopathological examinations, results of statistical analyses,
etc.) from the rat and rabbit teratology studies that were cited
in this TSCA Section 8(e) submission.
CURRENT PRODUCTION AND USE
In light of the submitter's CBI claims, no information about the
TSCA Chemical Substance Inventory status or use of the acylamino
pyrimidine will appear in this report. The submitter stated non-
confidentially that the chemical "is currently being manufactured
exclusively for . . . [research and development (R&D)] purposes."
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will ask the submitter to
ensure that EPA receives full copies of the final reports
(including the actual experimental protocols, results of
gross and histopathological examinations, results of any
statistical analyses, etc.) from the rat and rabbit
teratology studies that were cited in the company's TSCA
Section 8(e) the submission.
Considering the Agency's general interest in company
actions taken on a voluntary basis in response to
chemical toxicity/exposure data, the submitter will be
asked to describe the actions that the company has taken
or plans to take 1) to notify workers and others about
the reported information, and 2) to reduce or eliminate
exposure to this acylamino pyrimidine. In addition, the
submitter will be requested to describe the nature and
34
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8EHQ-0289-0785 S
Page 4 of 4
results, if available, of all studies (other than those
submitted already to EPA or those cited in the published
scientific literature) about which the company is aware
or that the company has conducted, is conducting or plans
to conduct that are designed to determine the toxicity
of or the exposure to the subject chemical substance.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of this acylamino pyrimidine.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be provided to the TSCA
Assistance Office (TAO/OTS) for further distribution.
35
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^to srAf. Page 1 of 3
/ A \
1222 Z« united states environmental protection agency
% WASHINGTON, D.C. 20460
' Office of
Pesticides and Toxic Substances
DATES _ J iggg APPROVED: MI°fa
SUBJECT: Status Report1 8EHQ-0389-0786 S
FROM: James F. Darr, Section Head.
Chemical Risk Identificatiofrv/Section/CSB
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
The submitting company claimed its company name and certain other
information in its section 8(e) submission to be TSCA Confidential
Business Information (CBI). Staff of the Information Management
Division (IMD/OTS) will review all incoming correspondence related
to the company's TSCA CBI claims.
SUBMISSION DESCRIPTION
The submitting company provided the following summary information
regarding the conduct and preliminary results of a pilot teratology
study of 3-methyl pyrazole (CAS No. 1453-58-3) in rats:
"Preliminary results suggest that this material produces
maternal and developmental toxicity when administered to
pregnant rats at > 100 mg/kg/day. In this study, 3-methyl
pyrazole was administered by gavage to 6 groups of 8
mated female rats at dose levels of 0, 25, 100, 175 and
225 mg/kg/day during gestation days 6-18. [The] surviving
dams were sacrificed on gestation day 20. [The] fetuses
were removed, weighed, sexed and examined for possible
external malformations.
1 This status report is the result of a preliminary evaluation of
information that has been submitted to EPA under Section 8(e), the "substantial
risk" information reporting provision of the Toxic Substances Control Act (TSCA) .
The statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Any
review of this status report should take into account that the report may be
based on incomplete information.
36
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8EHQ-0389-0786 S
Page 2 of 3
"Six of eight animals at 175 mg/kg/day and all 8 animals
at 225 mg/kg/day died or were sacrificed in extremis. No
body weight effects were apparent at 25 mg/kg/day, but
moderate to severe body weight losses were noted during
gestation days 6-12 at 100 mg/kg/day. An increase in
resorptions was noted at 100 mg/kg/day and no fetuses
were produced by the 2 survivors at 175 mg/kg/day. Fetal
weights were substantially reduced at 100 mg/kg/day but
appeared to be normal or close to normal weight at 25
mg/kg/day. One fetus in the 100 mg/kg/day [dose] group
exhibited external malformations (cleft palate and lip) .
However, these findings are not unusual since this fetus
weighed only 1.2 grams."
SUBMISSION EVALUATION
This submission provides evidence for adverse developmental and
maternal effects resulting from exposure to 3-methyl pyrazole at
doses greater than 25 mg/kg/day.
The maternal toxicity consisted of lethality (6/8 and 8/8 dams died
or were killed in extremis at 175 and 225 mg/kg/day, respectively)
and moderate to severe body weight losses (over gestation days 6-
12 for dams receiving 100 mg/kg/day) . Further, no fetuses were
produced by the 2 surviving dams in the 175 mg/kg/day dose group.
In addition, it is not clear from the provided summary information
if any of the dead or moribund dams in the 175 or 225 mg/kg/day
dose groups were pregnant.
The adverse developmental effects consisted primarily of increased
resorptions in, and "substantially reduced" body weight of the live
fetuses from, the dams receiving 100 mg/kg/day. It should be noted
also that one fetus from the 100 mg/kg/day group was found to have
a cleft lip and palate. Further, all fetuses from the 25 mg/kg/day
group were reported to appear "normal or close to normal weight."
It should be noted that while the submitted summary indicates that
6 groups of rats were involved in the study, the summary provides
information relating to only 5 groups (i.e., a control group and
4 exposed groups). It is not clear whether this discrepancy is
due to a typographical error or the existence of an additional but
uncited control or exposed group.
An evaluation of the overall significance of the reported findings
should be possible upon EPA's receipt of a full copy of the final
report from this pilot teratology study of 3-methyl pyrazole.
pTTRRENT PRODUCTION AND USE
3-Methyl pyrazole (which is known also as 5-methyl pyrazole) was
not found in the non-confidential printed or computerized versions
of EPA's initial TSCA Chemical Substance Inventory.
37
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8EHQ-0389-0786 S
Page 3 of 3
The information obtained from publicly available computerized
scientific literature sources cites or alludes to the following
uses for 3-methyl pyrazole: drug/therapeutic agent, plant growth
stimulator and biocide.
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will ask the submitter to
ensure that EPA receives a full copy of the final report
(including the actual experimental protocol, results of
gross and histopathological examinations, results of
statistical analyses, etc.) from the pilot teratology
study that was cited in the submission.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, the submitting company will be
requested to describe the actions that the company has
taken or plans to take 1) to notify workers and others
about the reported data, and 2) to reduce or eliminate
exposure to the subject chemical substance. In addition,
the company will be requested to describe the nature and
results, if available, of all studies (other than those
submitted already to EPA or those cited in the published
scientific literature) about which the company is aware
or that the company has conducted, is conducting or plans
to conduct that are designed to determine the toxicity
of or the exposure to 3-methyl pyrazole.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of 3-methyl pyrazole.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be provided to the TSCA
Assistance Office (TAO/OTS) for further distribution.
38
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
date: MAR 3 0 1989
APPROVED:
£
SUBJECT: Status Report1 8EHQ-0389-0787 8
FROM: James F. Darr, Section Head (/'Can/
Chemical Risk Identificatio ion/CSB
7-i3C
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
The submitting company has claimed its company name and the exact
identity of the subject chemical to be TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review . ^ incoming correspondence related to the company's
TSCA CBI claims. In the "sanitized" version of its Section 8(e)
notice, the company reported non-confidentially that the subject
chemical is an "alkyl heterocycle."
SUBMISSION DESCRIPTION
The submitting company provided the final results of several acute
toxicity studies of the subject alkyl heterocycle. The company's
cover letter presents the following non-confidential information
regarding the conduct and results of these studies:
"When [the] undiluted alkyl heterocycle was administered
to fasted albino rats of both sexes, the acute oral LD50
was estimated to be greater than 50 but less than 500
milligrams per kilogram (mg/kg). The dermal LD50 was
estimated to be less than 50 mg/kg when albino rabbits
received a continuous 24-hour application of undiluted
alkyl heterocycle on intact skin. Thus, [the] alkyl
heterocycle is considered to be moderately toxic by
ingestion m single doses and highly toxic by single
dermal applications. '
f ^ s^aJ~us _ reP°rt^ is the result of a preliminary evaluation of
" ?f*f eef submitted to EPA under Section 8(e), the "substantial
°f the ToXic Substances Control Act (TSCA)
f ll^ Aeencv nolicv nr i t- Statuf ,rePort should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Any
review of this status report should take into account that the report may be
based on Incomplete information, y
39
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Page 2 of 3
"When 0.1 ml of undiluted alkyl heterocycle was placed
into the conjunctival sac of the rabbit eye, moderate
irritation resulted. Two of six animals died by 72 hours
post-exposure. The eyes of the remaining four animals
were clear by day 7 post-exposure.
"When 0.5 ml of undiluted alkyl heterocycle was held in
continuous 4-hour contact with rabbit skin, no irritation
was observed."
SUBMISSION EVALUATION
In the acute oral study, the chemical was found to have an LD50 of
greater than 50 mg/kg but lower than 500 mg/kg in fasted albino
rats. The animals that received 500 mg/kg exhibited lethargy,
progressive weakness and collapse, followed by death. Gross
necropsy revealed hemorrhagic lungs and livers, kidney and spleen
discoloration and gastrointestinal inflammation. Of the 5 male
rats receiving 500 mg/kg, 4 died between 7 hours to 1 day post-
dosing; all 5 females died between 1 to 3 days post-dosing. The
animals receiving 50 mg/kg did not display any toxic signs.
When the test chemical was applied to the intact skin of albino
rabbits for a continuous 24 hour exposure period, the dermal LD50
was found to be less than 50 mg/kg. Progressive weakness, collapse
and death were observed amongst the 2 animals/sex that were tested
at the 50 mg/kg dose level. Only 1 male rabbit survived the 14-
day post-application observation period? the mortalities occurred
between 1 and 3 days post-dosing. Gross necropsy revealed liver
and spleen discoloration, hemorrhagic areas of the lung and gastro-
intestinal inflammation.
Moderate irritation was observed following instillation of 0.1 ml
of this alkyl heterocycle into the conjunctival sac of rabbits'
eyes. By 72 hours post-instillation, 2/6 animals were dead. It
was reported that the eyes of the remaining 4 animals were clear
by day 7 post-exposure.
When tested for dermal irritation, no irritation was seen following
a 4-hour continuous contact with 0.5 ml of the test material to the
skin of rabbits.
Overall, the submitted information shows that the subject alkyl
heterocycle is highly acutely toxic in animals when administered
via the oral, dermal or ocular routes of exposure.
CURRENT PRODUCTION AND USE
In view of the submitting company's TSCA CBI claims, no information
regarding the TSCA Chemical Substance Inventory status or use of
the subject chemical will appear in this status report. In the
Section 8(e) submission, the company provided the following non-
confidential information regarding the potential for exposure to
this alkyl heterocycle:
40
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Page 3 of 3
[The] alkyl heterocycle is currently being manufactured
exclusively for . . . [research and development (R&D)]
purposes and is handled only by technically qualified
workers. The material is handled in the laboratory using
prudent laboratory practices. Appropriate personal pro-
tective measures, engineering controls and waste disposal
procedures are utilized by the researchers in order to
effectively control and minimize human and environmental
exposure to this chemical. This information is being
incorporated in a research and development Material
Safety Data Sheet (MSDS). The MSDS will be provided to
all potentially exposed workers in compliance with the
TSCA Section 5 R&D exemption requirements and the OSHA
Hazard Communication requirements."
COMMENTS/recommendations
a) Considering EPA's general interest in company actions
taken on a voluntary basis in response to chemical
toxicity/exposure data, the submitter will be asked to
describe the nature and results, if available, of all
studies (other than those submitted already to the Agency
or those cited in the published scientific literature)
about which the company is aware or that the company has
conducted, is conducting or plans to conduct that are
designed to determine the toxicity of the subject alkyl
heterocycle.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of this alkyl heterocycle.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA? in addition,
copies of this status report will be provided to the TSCA
Assistance Office (TAO/OTS) for further distribution.
41
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§
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE
MAR 2 3 1989
approved:
7&L if&fa
SUBJECT: status Report1 8EHQ-0389-0788 8
FROM: James F.
Chemical
Darr, Section Head
Risk Identificatio
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
The submitting company has claimed its company name and the exact
identity of the subject chemical to be TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. In the "sanitized" version of its Section 8(e)
notice, the company reported non-confidentially that the subject
chemical is a "halo alkyl hydroxy heterocycle."
SUBMISSION DESCRIPTION
The submitting company reported simply that the subject chemical
"is highly toxic to rats after acute inhalation and repeated
dietary exposure, and has substantial anticoagulant properties."
SUBMISSION EVALUATION
An evaluation of the significance of the reported toxicological
findings should be possible upon EPA's receipt of full copies of
the final reports from the acute inhalation and repeated dietary
exposure studies cited in the company's submission.
This status report is the result of a preliminary evaluation of
information that has been submitted to EPA under Section 8(e), the "substantial
risk" information reporting provision of the Toxic Substances Control Act (TSCA) .
The statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Any
review of this status report should take into account that the report may be
based on incomplete information.
42
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Page 2 of 2
CURRENT PRODUCTION AND USE
In view of the submitting company's TSCA CBI claims, no information
regarding the TSCA Chemical Substance Inventory status or use of
the subject chemical will appear in this status report.
In its submission, the company reported non-confidentially that the
subject chemical "is currently being manufactured exclusively for
[research and development (R&D)] purposes."
COMMENTS/RECOMMENDATIONS
The submitting company stated non-confidentially that the reported
toxicological findings "have been communicated to all individuals
who may potentially be exposed to this chemical." In addition,
the company reported non-confidentially that further studies of
this halo alkyl hydroxy heterocycle are underway.
a) The Chemical Screening Branch will ask the submitter to
ensure that EPA receives full copies of the final reports
(including the actual experimental protocols, results of
gross and histopathological examinations, results of any
statistical analyses, etc.) from the acute inhalation and
repeated dietary exposure studies cited in the company's
TSCA Section 8(e) submission.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, the submitting company will be
asked to describe the nature and results, if available,
of all studies (other than those submitted already to EPA
or those cited in the published scientific literature)
about which the company is aware or that the company has
conducted, is conducting or plans to conduct that are
designed to determine the toxicity of or the exposure to
this halo alkyl hydroxy heterocycle.
k) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of the subject chemical.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be provided to the TSCA
Assistance Office (TAO/OTS) for further distribution.
43
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Page 1 of 4
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
Office of
Pesticides and Toxic Substances
date: APR I 8 1989
APPROVED
SUBJECT: status Report1 8EHQ-0389-0789
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
The BASF Corporation submitted the following summary information
with regard to the conduct and preliminary results of an ongoing
inhalation study of Pigment Yellow 184 (mixture of bismuth vanadate
(CAS No. 14059-33-7) and bismuth molybdate (CAS No. 13565-96-3))
in rats:
"Groups of Wistar rats were exposed in head-nose inhala-
tion units to concentrations of 0, 2.0, 8.0 and 80 mg/m3
of test material [for] 6 hours/day, 5 days/week for 4
weeks. Particle sizes of the test material were in the
respirable range. Increased lung weights and pulmonary
lesions (alveolar proteinosis and multifocal re-epitheli-
alization) were observed in all dose groups after the end
of exposure and a one-month recovery period. After a
six-month recovery period, alveolar proteinosis was
observed only at the two highest doses. A No-Observed-
Effect-Level (NOEL) was not established in the study."
According to BASF, this ongoing study (which is being conducted by
the parent company,BASF Aktiengesellschaft, West Germany) includes
a 12-month recovery group.
This status report is the result of a preliminary evaluation of
information that has been submitted to EPA under Section 8(e), the "substantial
risk" information reporting provision of the Toxic Substances Control Act (TSCA) .
The statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Any
review of this status report should take into account that the report may be
based on incomplete information.
44
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8EUQ-0389-0789
Page 2 of 4
SUBMISSION EVALUATION
The preliminary findings from this study suggest a potential health
hazard posed by chronic inhalation exposure to Pigment Yellow 184.
The observed lung toxicities (alveolar proteinosis and multifocal
re-epithelialization) were observed in rats of all dose groups at
the end of the 4-week exposure period and at the end of the 4-week
post-exposure recovery period. After a 6-month recovery period,
alveolar proteinosis was still seen in animals from the two highest
dose groups (8 and 80 mg/m3) . It should be noted that the provided
summary does not indicate whether the effects were dose-related.
Considering that lung toxicity was observed following such a short
duration of exposure to such relatively low dust concentrations
(i.e., 2 and 8 mg/m3), it would be prudent to exercise caution
during handling of the tested material. Further, it is apparent
that additional studies are needed to determine a No-Observable-
Adverse-Effect-Level (NOAEL) for this pigment.
gURRENT PRODUCTION AND USE
A review of the production range (includes importation volumes)
statistics for bismuth molybdate (CAS No. 13565-96-3), which is
listed in the initial TSCA chemical Substance Inventory, has shown
that between 10 thousand and 100 thousand pounds of this chemical
were reported as manufactured and/or imported in 1977.
A review of the production range (includes importation volumes)
statistics for bismuth vanadate (CAS No. 14059-33-7) , which is also
listed in the initial TSCA Chemical Substance Inventory, has shown
that no 1977 manufacture/importation was reported or that all of
the manufacture and/or importation data reported were claimed as
TSCA Confidential Business Information (TSCA CBI) by the person(s)
reporting for the initial TSCA Inventory and cannot be disclosed
(Section 14(a) of TSCA; U.S.C. 2613(a)).
The above production range information does not include any data
that were claimed to be TSCA Confidential Business Information
(TSCA CBI) by the person(s) who reported for the TSCA Inventory,
nor does it include any information that would compromise TSCA CBI.
All of the data reported for the initial TSCA Inventory, including
production range data, are subject to the limitations contained in
the TSCA Inventory Reporting Regulations (40 CFR 710).
BASF reported the company imports and sells Pigment Yellow 184 for
use "as a colorant in paints and varnishes." in addition, BASF
provided the following information regarding the potential for
exposure to Pigment Yellow 184:
"Exposure to the pigment is anticipated to be low for
several reasons: the density of the product is high,
causing dusts to settle rapidly? the product as sold
contains a relatively small amount of particles of
45
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8EHQ-0 389-0789
Page 3 of 4
respirable size; and agglomerates in the product increase
particle size and reduce dust formation. The supplier
of this preliminary information indicates that exposures
to the pigment during manufacturing are at or below 0.1
mg/m3 The supplier of the pigment indicates
that the powder form is being changed to a free-flowing
granular form with average particle sizes of 80-200 jum
to further reduce its dusting potential "
No further information regarding the use of Pigment Yellow 184 or
its constituents was located in the secondary literature sources
consulted by EPA.
COMMENTS/RECOMMENDATIONS
BASF provided the following information regarding the company's
actions to notify workers/others about the submitted toxicologic
findings:
"Although [workplace] exposures [to Pigment Yellow 184]
are anticipated to be low, BASF Corporation will notify
all customers ['via a customer letter and Material Safety
Data Sheet' (MSDS)] of these preliminary findings. The
importance of reducing dusting to the extent feasible and
the use of appropriate respiratory protection will be
stressed. This information will also be supplied to any
BASF Corporation personnel handling the product. ..."
In addition, BASF reported that "additional studies are planned in
order to determine a NOEL and suitable [workplace] exposure limits
[for Pigment Yellow 184]."
a) The Chemical Screening Branch will ask BASF to ensure
that EPA receives a complete copy of the final report
(including the actual experimental protocol, results of
gross and histopathological examinations, results of
statistical analyses, etc.) from the ongoing inhalation
study cited in the company's submission.
In view of EPA's general interest in company actions that
are tfken on a voluntary basis in response to chemical
toxicity/exposure data, BASF will be asked to describe
the nature and results, if available, of all studies
(other than those submitted already to EPA or those cited
in the published scientific literature) about which BASF
is aware or that BASF has conducted, is conducting or
plans to conduct that are designed to determine the
toxicity of Pigment Yellow 184 or its constituents.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of Pigment Yellow 184, bismuth vanadate
and bismuth molybdate.
46
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8EH0-0389-0789
Page 4 of 4
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be provided to the TSCA
Assistance Office (TAO/OTS) for further distribution.
47
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
date:
APR - 7 1989
APPROVED.*
SUBJECT: Status Report1 8EHQ-0389-0790 S
FROM: James F. Darr, Section Head
Chemical Risk Identificatio
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
The submitting company has claimed its company name and the exact
identity of the subject chemical to be TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
(IMD/OTS) will review all incoming correspondence related to the
company's TSCA CBI claim(s). In the "sanitized" version of the
Section 8(e) notice, the company reported non-confidentially that
the subject chemical is a "diheterocyclic ketone."
SUBMISSION DESCRIPTION
The submitting company provided the following summary information
regarding the conduct and preliminary results of a pilot teratology
study of this diheterocyclic ketone in rats:
"In this [teratologic] study, the diheterocyclic ketone
was administered by gavage to 5 groups of 8 mated female
rats at dose levels of 0, 50, 125, 250 and 500 mg/kg/day
during gestation days 6-18. [The] surviving dams were
sacrificed on gestation day 20. Fetuses were removed,
weighed, sexed and examined for possible external
malformations.
This status report is the result of a preliminary evaluation of
information that has been submitted to EPA under Section 8(e), the "substantial
risk" information reporting provision of the Toxic Substances Control Act (TSCA).
The statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Any
review of this status report should take into account that the report may be
based on incomplete information.
48
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Page 2 of 3
"Mortality occurred in 2/8 animals at 250 mg/kg/day and
5/8 animals at 500 mg/kg/day. Weight losses and/or
substantially decreased weight gains were noted at > 125
mg/kg/day. slightly decreased weight gain was observed
at 50 mg/kg/day during gestation days 6-9 but overall
weight gain at this level appeared normal. Abnormal
clinical signs and a dose-related increase in liver
weights (-22 to 51%) were noted at all dose levels. No
fetuses were produced by the survivors at 250 and 500
mg/kg/day and only 6 light-weight fetuses were produced
at 125 mg/kg/day. A slight increase in post-implantation
loss and a possible slight decrease in fetal weight were
noted at 50 mg/kg/day. The only external fetal abnormal-
ity observed was a single fetus at 50 mg/kg/day with
omphalocele."
SUBMIBflTON EVALUATION
The submitted information (which included several data tables)
provides evidence of the potential developmental and maternal
toxicity of this diheterocyclic ketone. In addition, it should be
noted that the submitted data tables indicate that a 750 mg/kg/day
dose group was included in this study.
Maternal toxicity was observed in all treatment groups. No dams
survived in the 750 mg/kg/day dose group; exposure to 250 and 500
m9/kg/day resulted in death for 2/8 and 5/8 animals, respectively.
The 125, 250 and 500 mg/kg dose group dams exhibited a significant
reduction in body weight. Although no specific supporting data
were included in the submission, the submission does state that
"abnormal clinical signs and a dose-related increase in liver
weights . . . were noted at all dose levels." Given these reported
observations, a "no-observable-adverse-effect-level" (NOAEL) for
maternal toxicity was not established in this study.
With regard to developmental toxicity, embryotoxicity/fetotoxicity
was observed at all exposure levels. The dams that survived the
exposure to 250 and 500 mg/kg/day did not produce any live pups.
The 6 gravid dams from the 125 mg/kg/day dose group produced a
total of 6 pups, all of which were classified as being "light-
weight." The exposure to 50 mg/kg/day resulted in a significant
decrease in mean fetal body weight, an increase in total and early
resorptions, and a decrease in litter size. Further, omphalocele
was reportedly seen in one fetus from the 50 mg/kg/day dose group.
As was the case for maternal toxicity, a NOAEL for developmental
toxicity was not established in this study.
CURRENT PRODUCTION AND USE
In view of the submitter's CBI claims, no information about the
TSCA Chemical Substance Inventory status or use of the dihetero-
cyclic ketone will appear in this report. In the sanitized version
49
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8EHQ-0389-0790 S
BEt-°NGr. TO* Page 3 of 3
US EPA TOXiCS Li"¦'
401 W ST Sia'/to
^S«f4(1^ey^ubroission, the company provided the following information
with regard to the potential for exposure to the subject chemical
substance:
"The . . . diheterocyclic ketone is a new . . . [research
and development (R&D)] compound which is handled only by
technically qualified workers. Manufacturing of this R&D
material has been carried out in compliance with [the]
TSCA Section 5 R&D exemption requirements. Appropriate
personal protective measures, engineering controls and
waste disposal procedures are utilized by the researchers
in order to effectively control and minimize human and
environmental exposure to this chemical."
COMMENTS/RECOMMENDATIONS
The company stated non-confidentially that the reported toxicologic
findings are "being provided to all potentially exposed workers in
compliance with the TSCA Section 5 R&D exemption requirements.11
a) The Chemical Screening Branch will ask the submitting
company to ensure that EPA receives a full copy of the
final report (including the actual experimental protocol,
results of gross/histopathological examinations, results
of statistical analyses, etc.) from the pilot teratology
study cited in the company's Section 8(e) submission.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, the submitter will be requested
to describe the nature and results, if available, of all
studies (other than those submitted already to the Agency
or those cited in the published scientific literature)
about which the company is aware or that the company has
conducted, is conducting or plans to conduct that are
designed to determine the toxicity of this diheterocyclic
ketone.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of this diheterocyclic ketone.
c) The Chemical screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA? in addition,
copies of this status report will be provided to the TSCA
Assistance Office (TAO/OTS) for further distribution.
50
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
MAR 3 0 1989
APPROVED
SUBJECT: Status Report1 8EHQ-0389-0791 S
MATERIAL BELONGS 1
US EPA TOXICS LI3CA
401 M STCW/T3-70'
WASHINGTON, DC 20*
FROM: James F. Darr, Section Head
Chemical Risk Identificatio:
(JSection/CSB;
(202) 260-3944
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
NQ2E
Eli Lilly and Company has claimed the exact identity of the subject
chemical to be TSCA Confidential Business Information (CBI). Staff
of the Information Management Division (IMD/OTS) will review all
incoming correspondence related to the company's TSCA CBI claim.
In the "sanitized" version of its Section 8(e) notice, Eli Lilly
reported non-confidentially that the subject chemical substance is
an "unsaturated sulfone" that "has not yet been patented."
SUBMISSION DESCRIPTION
Eli Lilly and Company provided the following summary information
regarding the conduct and preliminary results of several in vitro
genotoxicity studies of this unsaturated sulfone:
"The compound was evaluated in the gradient plate assay,
a modification of the Ames assay, used to screen com-
pounds for the induction of mutations in bacteria. A
positive response was obtained in JLl coli strain WP2uvrA-
both in the presence and in the absence of metabolic
activation; and in Salmonella tvphimurium strain TA100
without activation only. Positive responses were observed
in E. coli exposed to the compound at concentrations that
ranged between 5 and 10 fig/ml and between 5 and 40 ng/ml
in the assays without and with activation, respectively.
The response in TA100 occurred between 0.1 and 1 ng/ml.
1 This status report is the result of a preliminary evaluation of
information that has been submitted to EPA under Section 8(e), the "substantial
risk" information reporting provision of the Toxic Substances Control Act (TSCA).
The statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical (s). Any
review of this status report should take into account that the report may be
based on incomplete information.
51
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Page 2 of 3
"The [subject] compound was also evaluated for the
ability to induce chromosome aberrations in cultured
Chinese hamster ovary cells. A positive dose response
was obtained in the assay conducted without metabolic
activation. The compound at concentrations of 1, 2 and
4 fxg/ml yielded aberration frequencies of 4, 8 and 17
percent, respectively. The solvent control aberration
frequency was 4 percent. The compound was also tested
for aberration induction with activation; however, the
microscope slides have not yet been evaluated."
SUBMISSION EVALUATION
The submitted information indicates that this unsaturated sulfone
possesses some degree of genotoxic activity. An EPA evaluation of
the overall significance of the reported in vitro results should
be possible upon the Agency's receipt of full copies of the final
reports from the performed studies.
CURRENT PRODUCTIOK AND USE
In view of the submitter's TSCA CBI claim, no information about the
TSCA Chemical Substance Inventory status of the unsaturated sulfone
will appear in this report.
In the sanitized version of the Section 8(e) submission, Eli Lilly
provided the following non-confidential information with regard to
the manufacture/use of and the potential for worker exposure to the
subject chemical:
"Lilly has manufactured less than 10 kilograms of the
compound, which is utilized in controlled field trials
for pesticidal effectiveness in Lilly test plots and
selected university test plots in the United States and
in selected university test plots and government test
plots outside of the United States. The compound is
labelled as hazardous and all personnel who work with it
are notified of the compound's properties and of the
appropriate safety precautions. Field applications are
being limited to those allowed under . . . [the Federal
Insecticide, Fungicide and Rodenticide (FIFRA)] pre-
Experimental Use Permit ('EUP') guidelines. The total
number of people working with this compound is approxi-
mately 25. The exposure time averages 16 hours per year
each. If the field trials indicate that the compound may
be suitable for commercial use, Lilly will apply for an
EUP, at which time all required toxicological information
about the compound will be submitted to the EPA."
COMMENTB/RECQMMENDATTmig
Although a positive in vitro genotoxicity test, when considered
alone, may not be sufficient to offer reasonable support for a
conclusion of substantial risk (as that term is defined in EPA's
52
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Page 3 of 3
TSCA Section 8(e) policy statement ("Statement of Interpretation
and Enforcement Policy; Notification of Substantial Risk" 43 FR
11110; March 16, 1978)), EPA does believe that such information is
of value in assessing the possible risk(s) posed by exposure to the
tested chemical or mixture. Further, EPA believes that a positive
genotoxicity test result, in combination with other information
(e.g., knowledge of actual/potential exposure to and/or high pro-
duction of the tested chemical or mixture), would suggest the need,
in many cases, to conduct further studies designed to determine
the toxicity of or the exposure to that chemical substance or
mixture. EPA expects the results of such additional studies to be
considered also for submission under Section 8(e) of TSCA.
a) The Chemical Screening Branch will request Eli Lilly to
ensure that EPA receives full copies of the final reports
(including actual experimental protocols, data, results
of statistical analyses, etc.) from all jjj vitro studies
cited in the company's TSCA Section 8(e) submission.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, Eli Lilly will be requested to
describe the nature and results, if available, of all
studies (other than those submitted already to EPA or
those cited in the published scientific literature) about
which Eli Lilly is aware or that Eli Lilly has conducted,
is conducting or plans to conduct that are designed to
determine the toxicity of this unsaturated sulfone.
k) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of the subject chemical.
°) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be provided to the TSCA
Assistance Office (TA0/0TS) for further distribution.
53
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
Office of
Pesticides and Toxic Substances
DATE: APR I 7 1989
APPROVED:
sm. 4<*h
SUBJECT: Status Report1 8EHQ-0489-0792
PROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
The Mobay Corporation provided complete copies of the final reports
(written in German) from two teratology studies of 1,2,4-triazole
(CAS No. 288-88-0) in rats. According to Mobay, these teratology
studies, which were performed by Mobay's parent company (Bayer AG
located in West Germany), present "new findings for 1,2,4-triazole."
Mobay's Section 8(e) cover letter contains the following informa-
tion with regard to the conduct and results of the studies:
"The first study . . . was conducted at [oral] dose
levels of 100 and 200 mg/kg/day on days 6-15 of gesta-
tion. Effects seen in this study at 200 mg/kg included
decreased body weight gain in the dams, decreased numbers
of fetuses, increased fetal loss, decreased fetal weights
and an increase of fetal malformations and runts. Effects
seen in the 100 mg/kg group included decreased fetal
weights, increased skeletal deviations and increased
numbers of runts. No No-Observed-Effect-Level [(NOEL)]
was achieved in this study, so a second study was
performed.
This status report is the result of a preliminary evaluation of
information that has been submitted to EPA under Section 8(e), the "substantial
risk" information reporting provision of the Toxic Substances Control Act (TSCA).
The statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Any
review of this status report should take into account that the report may be
based on incomplete information.
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Page 2 of 3
"The second study . . . was conducted at dose levels of
10, 30 and 100 mg/kg/day. Effects seen in this study
were limited to the high dose of 100 mg/kg and included
decreased body weight gain in the dams, decreased numbers
of fetuses, decreased fetal weights and an increased
number of runts."
In its TSCA Section 8(e) cover letter, Mobay stated that, upon
completion, English translations of the two study reports would be
submitted to the Agency. Mobay reported by phone on April 7, 1989
that the company expects to receive those translations within the
next two months.
SUBMISSION EVALUATION
According to the submitted summary information,
causes maternal as well as developmental toxicity. . ld b
of the overall significance of the reported fmdi:ngs sh
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8EHQ-0489-0792
Page 3 of 3
COMMENTS/RECOMMENDATIONS
Mobay stated that the company will advise its employees and those
customers to whom Mobay has distributed 1,2,4-triazole about the
reported toxicologic findings.
a) The Chemical Screening Branch will ask Mobay to ensure
that full copies of the translations of the submitted
German final reports are sent to the Agency immediately
upon the company's receipt of those translations.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity and exposure data, Mobay will be requested to
describe the nature and results, if available, of all
studies (other than those submitted already to EPA or
those cited in the open scientific literature) about
which Mobay is aware or that the company has conducted,
is conducting or plans to conduct that are designed to
determine the toxicity of 1,2,4-triazole.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of 1,2,4-triazole.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be provided to the TSCA
Assistance Office (TAO/OTS) for further distribution.
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
U -0
WASHINGTON, D.C. 20460
Office of
Pesticides and Toxic Substances
date: may-3 1989
APPROVED:
SUBJECTS Status Report1 8EHQ-0489-0793
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
The IBM Corporation provided an interim summary report concerning
a 13-week oral toxicity study of 5-methyl-3-heptanone (ethyl sec-
amyl ketone (EAK) ; CAS No. 541-85-5) in male rats. According to
IBM, this study (which was conducted by the Eastman Kodak Company
for IBM) was "designed to evaluate the potential neurotoxicity" of
EAK. IBM's cover letter presents the following information about
the conduct and preliminary results of this 13-week study:
"The solvent [(EAK)] was administered by gavage [5 days
per week for 13 weeks] to groups of five adult male rats
at doses of 0, 100, 500 and 1,000 rag/kg. [The control
animals received distilled water in a volume equal (on
a per kilogram basis) to that received by the high dose
group animals.] . . . . Acute neurotoxic effects
observed during the course of exposure included reduced
activity, ataxia, and sialorrhea. Symptoms indicative
of peripheral neuropathy were also noted, primarily in
the high-dose group. A marked reduction in body weight
gain was observed in the high-dose animals, Histopatho-
logical evaluation of sciatic and tibial nerves from the
high-dose animals indicated lesions characteristic of
those produced by gamma-diketones
1 This status report is the result of a preliminary evaluation of
information that has been submitted to EPA under Section 8(e), the "substantial
risk" information reporting provision of the Toxic Substances Control Act (TSCA).
The statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to tfhe subject chemical(s). Any
review of this status report should take into account that the report may be
based on incomplete information.
57
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8EHQ-0489-O793
Page 2 of 3
"Histopathology of mid- and low-dose animals will be
conducted to determine a no effect level for EAK-induced
gamma-diketone neuropathy. Based on Kodak's experience
with this class of solvents, EAK appears to be somewhat
more potent on a mg/kg basis than 3-heptanone (ethyl n-
butyl ketone, EnBK) in producing experimental neuropathy.
3-Heptanone is neurotoxic following oral exposure only;
it is not neurotoxic by inhalation."
According to the provided interim report, the EAK dose levels used
in the 13-week study "were based on results of a two-week probe
study in which animals were administered EAK doses of 0, 150, 500,
750, or 1500 mg/kg/day."
SUBMISSION EVALUATION
Observations made at the 1000 mg/kg/day dose level in the 13-week
oral study of EAK in male rats included sialorrhea, depression of
activity, pink urine, unkempt hair coats, gait abnormalities
(stumbling), decreased food consumption, decreased body weight,
some changes in the functional observational battery (FOB; e.g.,
impairment of limb motion, righting difficulties), decreased hind-
limb grip strength (day 91) , decreased aminotransferase levels,
and giant axonal neuropathy (i*e., paranodal axonal swelling with
organelle accumulation).
Observations made among the animals at the 500 mg/kg/day dose level
included sialorrhea, general depression of activity, pink urine,
unkempt hair coats, slight body weight decreases, changes in the
FOB (similar but less intense effects than those found at the 1000
mg/kg/day dose level), and decreased aminotransferase levels.
At the 100 mg/kg/day dose level, decreased forelimb grip strength
was seen (day 7 and day 63); however, it should be noted that this
effect was not observed in the 500 or 1000 mg/kg/day dose groups.
In general, the submitted data indicate that EAK can produce a
peripheral neuropathy similar to that caused by gamma-diketones.
Further EPA evaluation of the reported findings should be possible
upon the Agency's receipt of a complete copy.of the final report
(which should include results of the histopathological examination
of animals from the 100 and 500 mg/kg/day dose groups). In order
to supplement EPA's evaluation of the reported findings, IBM should
be asked to submit a full copy of the cited 2-week probe study of
EAK administered at doses of 0, 150, 500, 750 and 1500 mg/kg/day.
CURRENT PRODUCTION AND USE
EAK (CAS No. 541-85-5) was not located on the current printed or
computerized versions of the non-confidential initial TSCA Chemical
Substance Inventory. According to the Information Management
Division (IMD/OTS), however, EAK (CAS No. 541-85-5) was recently
added to the unpublished, non-confidential initial TSCA Inventory
based on a formal correction request made by a reporting company.
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Page 3 of 3
The submitted interim report from the 13-week study states that
EAK is a ketone solvent that can be synthesized or obtained from
natural products. The report also states that EAK "has been used
as a solvent for nitrocellulose-alkyd, nitrocellulose-maleic and
vinyl resins." According to the Condensed Chemical Dictionary
(10th Edition), EAK is used also in perfumery.
IBM stated that EAK "exposure at IBM is currently controlled to a
level of l ppm." IBM stated also that under the current conditions
of EAK use within IBM, EAK "does not present a health risk to IBM
employees."
COMMENTfl/RECOMMENDATIONS
a) The Chemical Screening Branch will ask IBM to ensure that
EPA receives full copies of the final reports (including
the actual experimental protocols, results of gross and
histopathological examinations, results of statistical
analyses, etc.) from the 13-week and 2-week studies that
were cited in the submission.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, IBM will be requested to describe
the actions that the company has taken or plans to take
to notify workers and others about the reported findings
for EAK. In addition, IBM will be asked to describe the
nature and results, if available, of all studies (other
than those submitted already to EPA or those cited in the
open scientific literature) about which IBM is aware or
that IBM has conducted, is conducting or plans to conduct
that are designed to determine the toxicity of EAK.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of EAK,
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be provided to the TSCA
Assistance Office (TAO/OTS) for further distribution.
59
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Page 1 of 4
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
date: MAY -8 1989
approved:
ru rkb
SUBJECT: status Report1 8EHQ-0489-0794 S
,"^4 irf r ^
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
The submitting company has claimed its company name and the exact
identity of the subject chemical to be TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
CBI claims. In a "sanitized" addendum to its Section 8(e) notice,
the company reported non-confidentially that the subject chemical
is an alkali metal salt of a substituted aryl sulfonic acid.
SUBMISSION DESCRIPTION
The submitting company provided the final report from an oral
teratology study of the subject chemical substance (coded as P-15)
in rats. The submitter's cover letter presents the following
summary information regarding the conduct and results of the study:
"The test article, P-15, was evaluated in a conventional
teratology study in which a control and three treatment
groups of 25 Charles River rats each were used. Dosage
levels of 160, 800, and 4000 mg/kg/day were administered
orally by gavage as a single daily dose on days 6 through
15 of gestation at a volume of 16 ml/kg. The control
group received the vehicle only, 0.7% carboxymethylcellu-
lose, on a comparable regimen. Cesarean sections were
performed on all surviving dams on gestation day 20 and
the fetuses were removed for teratologic evaluation.
1 This status report is the result of a preliminary evaluation of
information that has been submitted to EPA under Section 8(e), the "substantial
risk" information reporting provision of the Toxic Substances Control Act (TSCA) .
The statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical (s). Any
review of this status report should take into account that the report may be
based on incomplete information.
NOTE
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8EHQ-0489-0794 S
Page 2 of 4
"Maternal toxicity was not detectable in the control, low
(160 mg/kg/day), or intermediate (800 mg/kg/day) - dose
animals. Furthermore, no significant developmental toxi-
city of any kind was evident in the low and intermediate
groups as compared to the control group.
"In the high dose group, maternal toxicity was observed,
which included labored breathing, tremors, loss of [the]
righting reflex, hypothermia, moribundity, emaciation,
yellow staining in the anogenital region, and piloerec-
tion. There also was a significant reduction in the
group mean maternal body weight gain, and a persistent
depression in motor activity in all the test subjects.
In a few animals, depressed motor activity persisted up
to the time of [the] scheduled sacrifice. Moreover,
three dams succumbed during the treatment period and one
additional animal in extremis was sacrificed before term.
Fetal toxicity exhibited as lowering of mean fetal body
weight and a reduction in fetal viability was observed.
In addition, a slight, but statistically insignificant,
increase in microphthalmia and in a vertebral anomaly was
noted in the fetuses examined."
In its cover letter, the submitting company stated that based on
the observations made exclusively in the high dose group, the
company has "arrived at the conclusion that [the] developmental
toxicity encountered was probably secondary to the maternal stress
resulting from the distinctive maternal toxicity." The submitter
provided several stress-related literature citations believed by
the company to support its position. The submitter also reported
that "no attempt [will be made] to establish the high dose group
as an overall no observable effect level because maternal and fetal
toxicity were unmistakenly present." The company reported, however,
that "the data obtained clearly support the intermediate dose, 800
ro9/kg/day, being an overall no observable effect level, fetal or
maternal, which represents at least 4 to 5 orders of magnitude, in
terms of the daily dose, higher than the worst situation where
humans are likely to be exposed to this substance." According to
the "TEST ARTICLE ADMINISTRATION" section of the teratology study
final report, "the selected route of administration was oral since
this was considered the most closely equivalent to the typical
human exposure [to the chemical]."
submission evaluation
This Section 8(e) notice presents evidence regarding the maternal
and developmental toxicity of the subject chemical substance. The
maternal toxicity was clearly evident only at the high dose (4000
m<3/kg) . Three dams in this group died (2 on gestation day 9 and
1 on gestation day 10). In addition, 1 female was sacrificed An
extrepjy on gestation day 8. During necropsy of the 4 dead and
early sacrifice dams, a thick and irregular non-glandular stomach
was noted in 1 dam? no gross lesions were seen in the pther 3 dams.
The cause of death was not determined for any of these animals.
61
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Page 3 of 4
The mean body weight of the 4000 rag/kg group dams was reduced on
gestation days 6-20; the differences were significant on gestation
days 9, 16 and 20. Clinical signs of toxicity in the high dose
dams included reduced motor activity of all the dams early in the
treatment period (exact days not specified) and reduced motor
activity of some of the dams (number not specified) for the entire
treatment period. In addition, 1 or more of the 4 animals that
died or were sacrificed early exhibited labored breathing, tremors,
loss of the righting reflex, hypothermia, moribundity, emaciation,
yellow staining in the urogenital region and piloerection. Although
some of these clinical observations suggest neurotoxicity, it is
not possible to ascertain (solely on the submitted information)
whether the symptoms are actually due directly to a neurotoxic
effect of the chemical or result from some other type of toxicity.
Developmental toxicity was clearly evident in the 4000 mg/kg dose
group. There was a significant increase in post-implantation loss
and a corresponding decrease in litter size. In addition, there
was a significant reduction in the mean fetal body weight. There
was also an increase in the total number of fetuses and litters
with malformations; the increase was principally in the incidence
of microphthalmia (3% of the fetuses) and a vertebral anomaly with
or without an associated rib anomaly (4.5% of the fetuses). The
number of fetuses with skeletal variations was also increased (89%
versus 36% in the controls) ; this was due primarily to an increased
incidence of delayed ossification (unossified hyoid, reduced skull
ossification and unossified sternebrae) and 2 rib variations (bent
ribs and 7th cervical ribs). There was no strong evidence found
for developmental toxicity in either the 160 mg/kg or 800 mg/kg
dose groups.
For this study, the lowest-observable-adverse-effect-level (LOAEL)
and no-observable-adverse-effect-level (NOAEL) for both maternal
and developmental toxicity of the subject chemical is 4000 mg/kg
(LOAEL) and 800 mg/kg (NOAEL).
Considering the very large spread between the 4000 mg/kg (LOAEL)
and 800 mg/kg (NOAEL) dose levels, the submitting company should
be asked if it is planning to conduct a study to determine more
precisely the maternal and developmental effects of the subject
chemical substance at doses between 800 mg/kg and 4000 mg/kg. In
addition, it would be of interest to know if the submitting company
plans to conduct a repeated dose study (e.g., a 28-day oral gavage
or feeding study) to determine if the subject chemical substance
is neurotoxic.
CURRENT PRODUCTION AND URf.
In the sanitized version of the Section 8(e) notice cover letter,
the submitting company reported non-confidentially that the subject
chemical substance "is an experimental research material not listed
on . • • [EPA's TSCA Chemical Substance Inventory]." The submitter
also reported that the company is in full compliance with the TSCA
research and development (R&D) conditions.
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Page 4 of 4
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will ask the submitting
company to provide a complete copy of the final report
(including the actual experimental protocol, results of
gross and histopathological examinations, etc.) from the
acute oral toxicity study mentioned in the "TEST ARTICLE
ADMINISTRATION" section of the submitted final report of
the oral teratology study in rats.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, the submitter will be asked to
describe the nature and results, if available, of all
studies (other than those sent already to EPA or those
cited in the open scientific literature) about which the
company is aware or that the company has conducted that
are designed to determine the toxicity of this chemical.
The submitting company will be informed that the Agency
is interested especially in knowing if the company plans
to conduct 1) a rat teratology study using oral doses
between 800 mg/kg and 4000 mg/kg, and 2) a repeated dose
study in rats (e.g., a 28-day oral gavage or feeding
study) to determine if the subject chemical substance is
neurotoxic.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of this alkali metal salt of a substituted
aryl sulfonic acid.
c) The Chemical Screening Branch will send copies of this
status report to NI0SH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and 0PP/0PTS/EPA; in addition,
copies of this status report will be provided to the TSCA
Assistance Office (TAO/OTS) for further distribution.
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 5
DATES JUN I 2 1989 APPROVED
TOXIC SUBSTANCES
PESTICIDES AND
OFFICE OF
SUBJECT: Status Report1 8EHQ-0489-0795
8EHQ-0589-0796
a/fits**^
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
In 8EHQ-0489-0795, the Amoco Chemical Company (an affiliate of the
Amoco Corporation) submitted the final report of a respiratory
sensitization study of 4,41-sulfonylbis(phthalic anhydride) (SPAN;
CAS No. 2540-99-0) in rats. (The CAS No. for the subject chemical
was reported by the Amoco Chemical Company non-confidentially by
phone on May 5, 1989.) The company's TSCA Section 8(e) notice cover
letter provides the following information regarding the conduct and
results of this study:
"Three groups of 10 male and 10 female Sprague-Dawley
rats were used to study SPAN. One group was exposed to
SPAN as a particulate aerosol at a target concentration
of 50 iiq/w, 6 hours/day for 5 days. The remaining two
groups were exposed to filtered air only. Following a
3-week rest period, the SPAN-exposed group along with one
filtered air-exposed group were challenged with the same
[SPAN] concentration [(50 M9/m )] f°r 6 hours. The second
filtered air-exposed group served as a non-challenged
control.
"The analytical time weighted averages for the five
[SPAN] exposures and challenge were 45.9 and 43.6 /zg/m3,
respectively.
This status report is the result of a preliminary evaluation of
information that has been submitted to EPA under Section 8(e), the "subvtanriVi
risk" information reporting provision of the Toxic S^stancLc^lZ'^A)
The statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s) Ant
review of this status report should take into account that the renort ma h
based on incomplete information. 6p°rt ^ be
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8EHQ-0589-0796
Page 2 of 5
"This [respiratory sensitization] study indicated a
statistically significant increase in lung foci in the
SPAN-exposed rats when compared to the challenged and
non-challenged control rats. Lung foci counts ranging
from 12 to 55 were present in 7 of 20 SPAN-exposed rats.
Serum IgG antibody levels were significantly elevated in
the SPAN-exposed males compared to the challenged and
non-challenged controls. There were no statistically sig-
nificant effects of treatment on body weight and absolute
and relative lung weight and volume."
In 8EHQ-0589-0796, Amoco provided the final report of a respiratory
sensitization study of benzophenone tetracarboxylic dianhydride
(BTDA; CAS No. 2421-28-5) in rats. The company's TSCA Section 8(e)
submission cover letter provides the following information with
regard to the conduct and results of this respiratory sensitization
study:
"The study consisted of three groups of 10 male and 10
female Sprague-Dawley rats each. One group was exposed
to BTDA as a particulate aerosol at a target concentra-
tion of 50 (xg/m3, 6 hours/day for 5 days. The remaining
two groups were exposed to filtered air only. Following
a 3-week rest period, the BTDA-exposed rats along with
one filtered air-exposed group were challenged with the
same concentration of BTDA for 6 hours. The second
filtered air-exposed group served as a non-challenged
control.
[•The analytical time-weighted averages for the five
[BTDA] exposures and challenge were 47.0 and 43.2 /zg/m3,
respectively.1]
"The results [of this respiratory sensitization study]
indicated that [the] serum IgG antibody levels were sig-
nificantly elevated in the BTDA-exposed male rats [when]
compared to the challenged and non-challenged controls.
No other statistically significant effects of treatment
were associated with the increased serum IgG antibody
levels. Body weight, absolute and relative lung weight
and volume, and lung foci [(<10 'observed in the majority
of [the] rats from all groups')] were not significantly
different in BTDA-treated animals compared to controls.
None of the rats died and no significant clinical signs
were noted in any rat during the study."
In the cover letters accompanying these two TSCA Section 8(e)
submissions, Amoco stated that the submitted toxicological findings
"indicate that there is evidence to support the conclusion that
SPAN . . . [and BTDA are] potential respiratory sensitizer^] at
particulate aerosol concentrations of 50 ng/xa2 for 6 hours/day for
5 days."
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8EHQ-0589-0796
Page 3 of 5
SUBMISSION EVALUATION
In the SPAN study, sex specific elevations in serum IgG antibody
levels were observed in the SPAN-exposed/challenged rats (5/10
males, 1/10 females). In both sexes of SPAN-exposed/challenged and
SPAN-challenged-only rats, there was a statistically significant
(although widely variable) increase in the number of lung foci/lung
but not in the number of rats that exhibited lung foci. The number
of lung foci/rat ranged from 12-55 in 7/20 SPAN-exposed/challenged
rats versus less than 10 foci/rat in the SPAN-challenged-only and
filtered-air/unchallenged rats. The number of rats with lung foci
were 9/10 males and 6/10 females in the SPAN-challenged-only group,
10/10 males and 6/10 females in the SPAN-exposed/challenged group
and 6/10 males and 2/10 females in the filtered-air/unchallenged
control group. In general, the study did not provide a correlation
between the increase in lung foci and the increase in serum IgG
levels.
In the BTDA study, although elevations in serum IgG antibody levels
were seen in both sexes of BTDA-exposed and BTDA-challenged-only
rats, the significance of these elevations is unclear considering
the wide variation that was found for IgG levels in the filtered-
air/unchallenged control animals. For example, 3 female rats in
the filtered air/unchallenged control group had serum IgG levels
higher than any values found in rats from the BTDA-challenged-only
group. In contrast to the SPAN study, the BTDA study does not
indicate any sex-related differences for elevated serum IgG levels.
Although several rats from each group in the BTDA study had lung
foci, there were no statistically significant differences in the
number of foci-bearing rats from any group. There was, however, a
slight elevation found in the number of lung foci/rat in the BTDA-
exposed and BTDA-challenged-only groups. As in the SPAN study, the
occurrence of lung foci did not correlate with the elevated serum
IgG levels.
Overall, the evidence that BTDA is a potential pulmonary sensitizer
is not as persuasive as that obtained for SPAN. Further, the low
doses tested (i.e., ~50 ^.g/m ), the lack of good histopathological
characterization of the foci and the lack of proper physiological
measurements precludes any firm judgements about the ability of
SPAN or BTDA to cause respiratory sensitization. It is important
to point out, however, that 1) both BTDA and SPAN contain two
phthalic anhydride moieties, and 2) phthalic anhydride itself has
been shown to cause respiratory sensitization in humans at airborne
concentrations that range (according to one published scientific
literature source) from 3000 to 13 000 M<3/m • It is also important
to note that although the submitted studies on SPAN and BTDA use
serum IgG antibody levels as an indicator of sensitization, asthma
and other allergen responses occur most often in direct relation
to IgE, another class of immunoglobulin. Therefore, a study to
determine the ability of a chemical substance to cause respiratory
sensitization should include measurements of serum IgE antibody
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SEIIQ - 0 5 89 - 0 79 6
Page 4 of 5
levels (both pre- and post-exposure) , as well as measurements of
bronchoconstriction, respiratory rate or some other physiological
parameters of pulmonary function. Finally, and in view also of the
fact that anhydrides can be irritating to skin, the conduct of such
studies should include consideration of the need for 1) oronasal
or head-only exposure as opposed to whole-body exposure, and 2)
higher airborne concentrations of the test article.
CURRENT PRODUCTION AND USE
4,4'-Sulfonylbis(phthalic anhydride) was not located on the current
printed or computerized versions of the Agency's non-confidential
TSCA Chemical Substance Inventory.
Amoco did not provide any information with regard to the use(s) of
4, 4 1-sulfonylbis (phthalic anhydride) nor was such information found
in the secondary literature sources consulted by EPA.
A review of the production range (includes importation volumes)
statistics for BTDA (CAS No. 2421-28-5) , which is listed in the
initial TSCA Chemical Substance Inventory, has shown that between
0 and 2,000 pounds of this chemical were reported as manufactured
and/or imported in 1977. This production range information does
not include any information claimed as TSCA Confidential Business
Information (TSCA CBI) by the person(s) who reported for the TSCA
Inventory, nor does it include any information that would compro-
mise TSCA CBI. All data reported for the initial TSCA Inventory,
including the production range data, are subject to the limitations
contained in the TSCA Inventory Reporting Regulations (40 CFR 710) .
According to the Condensed Chemical Dictionary (10th Edition), the
uses of BTDA include: "Epoxy curing agent; heat-resistant polymers,
specialty alkyd resins; polyesters and plasticizers."
COMMENTS/RECOMMENDATIONS
Amoco stated that the SPAN and BTDA Material Safety Data Sheets and
product labels will be updated to reflect the reported findings.
a) In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, the Amoco Chemical Company will
be requested to describe the actions that the company has
taken or. plans to take to reduce or eliminate exposure
to SPAN and BTDA. In addition, Amoco will be asked to
describe the nature and results, if available, of all
studies (other than those submitted already to EPA or
those cited in the published scientific literature) about
which Amoco is aware or that the company has conducted,
is conducting or plans to conduct that are designed to
determine the toxicity of or the exposure to SPAN and/or
BTDA.
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8EHQ-0589-0796
Page 5 of 5
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of SPAN and BTDA.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be provided to the TSCA
Assistance Office (TAO/OTS) for further distribution.
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<¦ mm. mi J
I sy? I UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
Office of
Pesticides and Toxic Substances
DATES JUN - I 1989
APPROVED
. bN W
SUBJECTS Status Report1 8EHQ-0589-0797
^y>4i^4«i 4' .
FROHs David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TOs Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
On behalf of the Antimony Oxide Industry Association (AOIA) member
companies (AMSPEC Chemical? ANZON, Inc.; ASARCO Incorporated?
Laurel Industries, Inc.; and M&T Chemicals), an outside counsel
submitted the following summary information about the conduct of
and preliminary ophthalmologic findings from a two-year inhalation
study of antimony trioxide (Sb203; CAS No. 1309-64-4) in rats.
"AOIA is currently sponsoring a two-year inhalation study
of antimony trioxide in Fischer 344 rats as part of a
voluntary test program with EPA [pursuant to Section 4
of TSCA]. 48 Fed. Reg. 39979 (September 2, 1983). The
rats were exposed to airborne concentrations of 0.05, 0.5
or 5.0 mg/m3 for a period of one year followed by a one-
year recovery period. The recovery period [has] ended
and the 24-month sacrifice occurred in February, 1989.
A final report of the study will be available later this
year.
"... [According to the ophthalmologist's report,] there
is an indication of dose-related cataracts. The incidence
of all types of cataracts is reported as follows:
1 This status report is the result of a preliminary evaluation of
information that has been submitted to EPA under Section 8(e), the "substantial
risk" information reporting provision of the Toxic Substances Control Act (TSCA).
The statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Any
review of this status report should take into account that the report may be
based on incomplete information.
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Low Dose
Mid Dose
High Dose
Control Group
6/55 (11%)
12/49 (24%)
18/64 (28%)
19/60 (32%)
"The ophthalmologist's report also states that there
appears to be a compound relationship in the incidence
of chromodacryorrhea. The incidence of chromodacryorrhea
was reported as follows:
Control Group
2
6
14
7
Low Dose
Mid Dose
High Dose
"The cataracts and chromodacryorrhea do not appear to be
related; for the most part, the effects were not seen in
the same test animals.
"The ophthalmologist does not consider the [observed]
chromodacryorrhea to be indicative of a human hazard. No
decrease in function of the tear glands was noted. At
most, there may be evidence of a slight over-production
of tears.
"When evaluating the ophthalmologist's report, it should
be noted that the rats received additional exposure to
antimony trioxide via the oral route from normal grooming
and preening. To the extent the reported cataracts are
dose-related, [. . . the ophthalmologist] has stated that
he considers it unlikely that the effects were caused by
[direct] eye exposure to airborne antimony trioxide. A
preliminary survey indicates that cataracts have not been
observed in the workplace by AOIA members. Further
analysis may be aided by the pathologist's final report,
which will be included in the chronic inhalation study
final report."
According to a provided summary report, the historical incidence
of cataracts "in the control animals from three other recently
completed 24-month oncogenicity studies using Fischer 344 rats were
11, 14 and 15%." The provided summary report states further that
the 32% incidence of cataracts observed in the highest antimony
trioxide exposure group in the present inhalation study "is well
beyond [the] normal variation." Finally, the summary report states
that an "association with cataracts and antimony exposure has not
previously been reported."
SUBMISSION
Immediately upon receipt, the Chemical Screening Branch transmitted
a full copy of this TSCA Section 8(e) submission to the Test Rules
Development Branch (TRDB/ECAD/OTS) for inclusion in their ongoing
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Page 3 of 4
review of toxicity/exposure data on antimony trioxide. Antimony
trioxide, antimony metal (Sb metal) and antimony sulfide (Sb2S3)
were designated by the Interagency Testing Committee (ITC) for
testing consideration under Section 4 of TSCA. On January 6, 1983,
the Agency published a proposed Negotiated Testing Agreement (NTA;
48 Fed. Reg. 716) covering these chemicals. EPA's acceptance of
the Negotiated Testing Agreement was published on September 2, 1983
(48 Fed. Reg. 39979).
It should be noted that EPA's Office of Toxic Substances (OTS) has
published TSCA Section 8(a) and Section 8(d) information gathering
rules covering antimony trioxide. In addition, OTS has received
a number of TSCA Section 8(e) and "For Your Information" (FYI)
notices on antimony trioxide, as well as other antimony compounds.
In 1981, the Chemical Screening Branch prepared a "Chemical Hazard
Information Profile" (CHIP) on antimony trioxide.
CURRENT PRODUCTION AND QBE
Information with regard to the manufacture/importation and uses of,
as well as the potential for exposure to, antimony trioxide can be
found in the Agency's January 6, 1983 proposed Negotiated Testing
Agreement (48 Fed. Reg. 716).
COMMENTS/RECOMMENDATIONS
It is important to point out that the TSCA Section 8(e) reporting
requirement applies to any substantial risk information2 obtained
during a study conducted under Section 4 of TSCA unless such
information, when obtained, is otherwise required to be submitted
to EPA under Section 4 of TSCA. To date, EPA has received a number
of TSCA Section 8(e) notices containing interim results of studies
conducted under Section 4 of TSCA. The Section 8(e) reporting that
takes place in such instances occurs typically before reporting of
the information is required under Section 4. If required reporting
under Section 4 occurs before or coincidental with an obligation
to report under Section 8(e), the information does not need to be
submitted also under Section 8(e). The purpose of this exemption
is not to change substantially the TSCA Section 8(e) reporting
obligation, but is merely to avoid duplicative reporting except in
those cases where timeliness of reporting is paramount.
2 As defined in the Agency's March 16, 1978 TSCA Section 8(e) policy
statement ("Statement of Interpretation and Enforcement Policy; Notification of
Substantial Risk" 43 FR 11110), the term "substantial risk information" is any
new information that offers reasonable support for a conclusion that a subject
chemical or mixture presents a substantial risk of injury to health or the
environment; new information is that information about which EPA is not already
adequately informed.
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Page 4 of 4
a) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and TRDB/ECAD/OTS;
copies of this report will be provided also to the TSCA
Assistance Office (TAO/OTS) for further distribution.
b) The Chemical Screening Branch will send a copy of this
status report to AOIA and ask AOIA to transmit copies of
the report to their member companies.
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* UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
58ZZ/
• J? WASHINGTON, DC 20460
"«< P„0^°
date: JUN I 2 1989
APPROVED:
gmL
SUBJECT: Status Report1 8EHQ-0589-0798 8
^n«
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
The submitting company has claimed its company name and the exact
identity and use of the subject chemical to be TSCA Confidential
Business Information (CBI) . Staff of the Information Management
Division will review all incoming correspondence related to the
company's TSCA CBI claims. In the "sanitized" version of its
Section 8(e) submission, the company reported non-confidentially
that the subject chemical substance is "an isolatable process
intermediate" and identified the chemical generically as a
"chlorinated aliphatic ketone."
SUBMISSION DESCRIPTION
The submitting company provided the final report from an Ames
Salmonella tvphimurium (bacteria) mutagenicity assay of the subject
chlorinated aliphatic ketone. According to the company's cover
letter, the results of the test "indicate that this chemical caused
a positive increase in the numbers of histidine revertants per
plate with Salmonella tester strain TA-100 in the presence of
[exogenous] microsomal enzymes." The cover letter reports also
that "positive increases were not induced in any of the other
tester strains, either with or without the metabolic activation
system."
This status report is the result of a preliminary evaluation of
information that has been submitted to EPA under Section 8(e), the "substantial
risk" information reporting provision of the Toxic Substances Control Act (TSCA).
The statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Any
review of this status report should take into account that the report may be
based on incomplete information.
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Page 2 of 3
According to the provided final report, this chlorinated aliphatic
ketone was tested for its ability to induce gene mutations in
Salmonella typhimurium strains TA-1535, TA-1537, TA-1538, TA-98 and
TA-100 both with and without exogenous metabolic activation. (The
S-9 fraction from livers of rats treated prior to sacrifice with
Aroclor 1254 for the non-specific induction of liver enzymes served
as the source of metabolic activation.) The chlorinated aliphatic
ketone was dissolved in dimethylsulfoxide (DMSO) and tested over
a dose range of 66.6 to 3,330 ul/plate using 3 plates for each test
concentration.
SUBMISSION EVALUATION
The highest chlorinated aliphatic ketone concentration tested
(i.e., 3,330 ul/plate) was toxic to all bacterial strains in the
study. All of the tests performed without exogenous metabolic
activation in strains TA-1535, TA-1537, TA-1538, TA-98 and TA-100
were found to be uniformly negative. In the tests conducted with
metabolic activation, the subject chemical induced mutations only
in strain TA-100. In strain TA-100 with activation, there was a
dose-related increase in the number of revertant colonies that
reached a maximum of 4.7 times background (control) reversion rate
at a test article concentration of 666 ul/plate. Based on these
data, this chlorinated aliphatic ketone is mutagenic in the Ames
assay. The positive response observed with strain TA-100 in the
presence of exogenous metabolic activation is not mitigated in any
way by 1) the negative responses that were obtained with TA-100
without activation, or 2) the negative responses obtained in the
other strains tested with and without activation.
CURRENT PRODUCTION AND USE
In view of the submitter's TSCA CBI claims, no information about
the TSCA Chemical Substance Inventory status or use of this
chlorinated aliphatic ketone will appear in this status report.
The submitter provided the following non-confidential information
with regard to the potential for exposure to the subject chemical
substance:
"Due to process conditions, [the] potential fcjr exposure
is low. As an added precaution, personnel with possible
exposure wear personal protective equipment, including
full face air-purifying respirators approved for organic
vapors and gloves. The glove material has been tested
and found to be impermeable for periods up to twelve (12)
hours.» '
The submitting company stated further non-confidentially that its
"employees have been informed of . . . [the submitted genotoxicity
findings] in keeping with an extensive hazard communication
program."
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8EHQ-0589-0 798 S
Page 3 of 3
COMMENTS/RECOMMENDATIONS
Although a positive in vitro genotoxicity test, when considered
alone, may not be sufficient to offer reasonable support for a
conclusion of substantial risk (as that term is defined in EPA's
TSCA Section 8(e) policy statement ("Statement of Interpretation
and Enforcement Policy; Notification of Substantial Risk" 43 FR
11110; March 16, 1978)), EPA does believe that such information is
of value in assessing the possible risks posed by exposure to the
tested chemical or mixture. Further, EPA believes that a positive
genotoxicity test result, in combination with other information
(e.g., knowledge of actual/potential exposure to and/or high pro-
duction of the tested chemical or mixture), would suggest the need,
in many cases, to conduct further studies designed to determine
the toxicity of or the exposure to that chemical substance or mix-
ture. The Agency expects the results of such additional studies
to be considered also for submission under Section 8(e) of TSCA.
a) In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, the Chemical Screening Branch
will ask the submitting company to describe the nature
and results, if available, of all studies (other than
those submitted already to EPA or those cited in the
published scientific literature) about which the company
is aware or that the company has conducted, is conducting
or plans to conduct that are designed to determine the
toxicity of this chlorinated aliphatic ketone.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of the subject chemical.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and 0PP/0PTS/EPA; in addition,
copies of this status report will be provided to the TSCA
Assistance Office (TA0/0TS) for further distribution.
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tubes, four in all, were put into an oven at 200°C for 2
days. The analysis was done using a method developed by
the OSHA Analytical Laboratory of Salt Lake City.
"The results after one week indicated that the 300 g
sample in the one gallon cylinder contained 430 ppb of
chloromethyl methyl ether [(CAS No. 107-30-2)] and 2.29
ppb bis-chloromethyl ether [(BCME; CAS No. 542-88-1),
both highly toxic materials (BCME has been found to be
a human carcinogen). [The] analysis of the sealed tubes
was complicated. Many products seem to be formed and
reacted with the derivatizing agent used (sodium salt of
2,4, 6-trichlorophenol). The analysis of these tubes was
therefore indeterminate.
"The probability exists that these decomposition products
may build up in concentration after extended exposure.
Since bis-chloromethyl ether and chloromethyl methyl
ether were clearly detected when R12 and DME were heated
for 1 week at 200°C in the presence of steel, aluminum
and copper, . . . [Allied-Signal believes that] this
blend may pose a health risk under foreseeable use condi-
tions in an automotive air conditioner system, especially
for service people who change the refrigerant after many
months or years of the refrigerant's use. If this blend
were to be used, . . . [Allied-Signal believes that] ad-
ditional risk assessment related studies would be needed
to more accurately characterize and quantify the health
risk to both the public and automotive service people."
SUBMISSION EVALUATION
Immediately upon receipt, the Chemical Screening Branch sent a copy
of this TSCA Section 8(e) notice to the Chemical Control Division
(CCD/OTS) for inclusion in its ongoing review of CFC substitutes/
reduction.
COMMENTS/RECOMMENDATIONS
Allied-Signal reported that the company is notifying the patent
holder and other CFC producers about the submitted findings.
a) The Chemical Screening Branch will ask Allied-Signal to
ensure that the Agency receives a full copy of the final
report (including the actual experimental protocol, data,
etc.) from the simulated automotive air conditioning
application study that was cited in the submission.
b) As was the case with the initial Section 8(e) notice, the
Chemical Screening Branch will immediately forward full
copies of all incoming data to CCD/OTS.
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c) The Chemical Screening Branch will transmit copies of
this status report to NIOSH, OSHA, CPSC, FDA, NTP,
OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and
CCD/OTS/OPTS/EPA; in addition, copies of this status
report will be provided to the TSCA Assistance Office
(TAO/OTS) for further distribution.
78
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 4
DATE: JW 29 1989
TOXIC SUBSTANCES
APPROVED:
SUBJECT: Status Report1 8EHQ-0589-0800
^ /f h
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
The American Cyanamid Company reported that based on recently
conducted 4-hour nose-only inhalation tests in rats, the LC50 for
dimethyl-lfl,l-trifluoro-2,4-pentanedionato gold (CAS No. 63470-
53-1) "is approximately 30 ppm or somewhat greater than one-half
the saturated vapor concentration." American Cyanamid reported
further that "exposure at one-third the saturated vapor pressure
(approximately 17 ppm) produced no mortality nor other toxic
findings." In addition, American Cyanamid stated that "prior
studies, which have been submitted [already] to the EPA, indicated
that the material is a moderate skin irritant in rabbits and is not
a dermal sensitizer in guinea pigs."
According to American Cyanamid, the tested chemical substance is
the subject of a TSCA Section 5 "Low Volume Exemption" (LVE No.
L89-032). American Cyanamid stated further that 1) the preliminary
results of the acute nose-only inhalation studies had been received
orally from the IBM Materials Toxicology Laboratory, and 2) the
studies are being conducted for IBM at a contract laboratory.
A "COMPANY SANITIZED" (i.e., non-confidential) American Cyanamid
document retrieved from EPA's public LVE No. L89-032 file states
that the subject chemical, identified therein as dimethylgold
trifluoroacetylacetonate (DMGTF), when applied at a dose of 0.5 g
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
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Page 2 o£ 4
for 4 to 4.5 hours to the shaved, intact skin of rabbits, 1) caused
moderate irritation, 2) caused "initially, a blackish discoloration
to the skin which appears to fade to a yellow to brownish color"
and 3) did not cause any observable clinical signs or mortality.
In addition, this non-confidential document states that despite the
fact that "many gold compounds will produce an allergic response
upon repeated contact," the subject chemical did not cause dermal
sensitization in guinea pigs.
SUBMISSION EVALUATION
Immediately upon receipt, the Chemical Screening Branch transmitted
a complete copy of the incoming TSCA Section 8(e) submission to the
Chemical Control Division (CCD/OTS) which is responsible for EPA's
"New Chemicals Program" (NCP) under Section 5 of TSCA.
Based on the 4-hour 30 ppm LC50 value reported in this Section 8(e)
notice, the subject chemical substance could be classified as being
extremely toxic via inhalation. EPA's evaluation of the overall
significance of the reported findings should be possible upon the
Agency's receipt of the final report from this study.
CURRENT PRODUCTION AND USE
The non-confidential document that was obtained from EPA's public
LVE No. L89-032 file stated that American Cyanamid was planning to
import the subject chemical. This non-confidential document, which
contains copies of a technical bulletin and a draft Material Safety
Data Sheet (MSDS), also provides the following information about
the use of and potential for exposure to the chemical:
"Dimethylgold trifluoroacetylacetonate (DMGTF) is an
electronic grade crystalline solid product used in the
fabrication of electronic components. Specifically,
DMGTF is used to deposit gold on various substrates, such
as, for example, silicon wafers, in order to fabricate,
repair, or modify circuits. The deposition of gold is
accomplished by the vapor phase decomposition of DMGTF
which is induced by any suitable means, such as a laser
or a focused ion or electron beam,
"Risk of exposure during use at the customer's site is
minimal due to the low usage volume and the special self-
contained equipment designed to prevent leakage of the
organo-gold complex Customer facilities are
in most cases either laboratories or highly specialized
manufacturing sites having skilled operators, technicians
and engineers especially trained to handle materials of
this type. Many customer applications require specially
constructed and equipped clean-room operations, where
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[the] operators and technicians are also required to wear
special over-clothing and gear. The purpose here is to
protect the processes from deleterious trace contamina-
tion. The protective clothing and gear usually worn in
typical chemical plant operations are not necessarily
used in all electronic chemicals applications. This is
because of the stringent containment and exposure control
measures employed."
In its TSCA Section 8(e) submission, American Cyanamid provided the
following additional information with regard to the potential for
exposure to the subject chemical:
". . . .A normal shipment of this material to customers
is 5-10 grams. If the entire shipment were to be spilled
in a typical laboratory (15 X 30 X 8 ft.) and allowed to
come to equilibrium, the concentrations obtained are not
likely to exceed the levels which produced no mortality
or toxic effects in animals after exposure for 4 hours.
Since this material has a very unpleasant and pungent,
musky odor, any spills are readily detected."
COMMENTS/RECOMMENDATIONS
In its Section 8(e) submission, American Cyanamid reported that the
final report of the 4-hour nose-only inhalation study would be sub-
mitted to the Agency "in compliance with the requirements of the
low volume exemption granted . . . [for the subject chemical under
Section 5 of TSCA]."
It should be noted that Part VII of EPA's Section 8(e) policy
statement ("Statement of Interpretation and Enforcement Policy;
Notification of Substantial Risk" 43 FR 11110; March 16, 1978)
describes the kinds of information that do not need to be submitted
to EPA under Section 8(e) of TSCA. For example, Part VII(b) of the
policy statement explains that information need not be submitted
under Section 8(e) if the information has been submitted already
to EPA pursuant to mandatory reporting requirements under TSCA
(e.g., Section 5 of TSCA) or any other authority administered by
EPA. In other words, if the required reporting of information to
the Agency under Section 5 of TSCA, for example, occurs prior to
or coincidental with a respondent's obligation to report that same
information under Section 8(e) of TSCA, the information need not
be reported also under Section 8(e). The overall purpose of this
exemption is not to change substantially the TSCA Section 8(e)
reporting obligation, but is designed merely to avoid duplicative
submission except in those cases where the timeliness of reporting
is critical. Therefore, to the extent that American Cyanamid was
required under Section 5 of TSCA to submit their preliminary acute
inhalation test results and had already done so within 15 working
days of obtaining the results, the company's reporting of those
results additionally under Section 8(e) of TSCA was not required.
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a) The Chemical Screening Branch will ask American Cyanamid
to ensure that EPA receives a complete copy of the final
report (including the actual experimental protocol, the
results of any gross and histopathological examinations,
the results of statistical analyses, etc.) from the acute
nose-only inhalation tests cited in the company's TSCA
Section 8(e) submission.
In view of EPA's general interest in company actions that
are taken (especially on a voluntary basis) in response
to chemical toxicity/exposure data, American Cyanamid
will be asked to describe the actions the company has
taken or plans to take 1) to notify workers and others
about the reported data, and 2) to reduce or eliminate
exposure to the subject chemical substance. In addition,
American Cyanamid will be asked to describe the nature
and results, if available, of all studies (other than
those submitted already to EPA or those cited in the
published scientific literature) about which the company
is aware or that the company has conducted, is conducting
or plans to conduct that are designed to determine the
toxicity of or the exposure to the subject chemical.
b) As was the case for the initial Section 8(e) submission,
the Chemical Screening Branch will forward all additional
incoming information received on the subject chemical to
staff of the Chemical Control Division for review and
appropriate followup attention.
c) The Chemical Screening Branch will send copies of this
report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA, OW/EPA,
ORD/EPA, OAR/EPA, OPP/OPTS/EPA and CCD/OTS/OPTS/EPA; in
addition, copies of this status will be sent to the TSCA
Assistance Office (TAO/OTS) for further distribution.
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JQL \ UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
DATE: JUfiJ 3Q [Qgg APPROVED
. sm ->/sh
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECTS Status Report1 8EHQ-0589-0801
ZyX-. f/ & O
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
The Union Carbide Corporation submitted summary results of the
company's attempts "to develop and validate workplace monitoring
methods for ethylenediamine" (EDA; CAS No. 107-15-3). Union Carbide
stated that its research efforts "indicate that industrial hygiene
methods in current use for EDA may be seriously deficient where
particulates of EDA or its compounds are present." Union Carbide
provided the following information to substantiate this assertion:
"[In order] to monitor the presence of EDA in the work-
place, Union Carbide formerly used a small bore (4-6mm
[inner diameter (ID)]) glass' sampling tube containing
XAD-2 ion exchange resin adsorbent as the sampling
device. The sampling rate used was limited to 100 ml/min.
NIOSH method 276 uses a similarly small bore (6 mm ID)
glass sample tube containing silica gel and a sampling
rate of 1000 ml/min. OSHA method 60 uses a small bore
(4 mm ID) glass sample tube containing a coated XAD-2
resin adsorbent and a sampling rate of 100 ml/min.
"EDA forms EDA-carbamate (a fine particulate) when
exposed to [the] carbon dioxide present in humid air.
Union Carbide's recent research indicates that use of
current industrial hygiene methods may result in poor
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
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Page 2 of 4
detection of this particulate. The reason appears to be
the low effective capture rate of the small bore sampling
tube. [Union Carbide's] tests have demonstrated that in
the absence of EDA-carbamate, the former Union Carbide
sampling method obtains acceptable recovery of EDA in the
test chamber. When moist air containing carbon dioxide
is used, poor results are achieved by the sampler but an
independent analysis of the test air monitored by the
sampler indicates that EDA is present (most likely in the
EDA-carbamate form).
"When EDA-carbamate is placed on the adsorbent in the
sample tube, the recommended desorption and analytical
procedure results in acceptable recovery of the EDA-
carbamate as EDA. This finding demonstrates that if [the]
EDA-carbamate is collected on the sampling tube, it will
be desorbed and analyzed by the recommended procedure.
"Union Carbide has concluded that the source of the
problem is the small effective source sectional area (13-
26 mm ) of the sample tube inlet and the low sampling
rates. Field experience has demonstrated that for fine
particulates, a minimum sampling rate of 300-500 ml/min
is suggested for effective capture of particulates. The
former Union Carbide and OSHA methods for EDA are limited
to 100 ml/min whereas the NIOSH method has a recommended
1000 ml/min sampling rate. Although the NIOSH method has
the suggested sampling rate to capture the finely dis-
persed EDA-carbamate effectively, NIOSH reports that its
method suffers adversely from ammonia interference, and
is not well suited for many applications where amines are
used.
"It is evident from the information presented that many
of the monitoring methods [that are] currently being used
for EDA are seriously deficient when particulates of EDA-
based compounds are present. Consequently, Union Carbide
has developed a new recommended sampling and analytical
method for EDA. The new [Union Carbide] method employs
a liquid sampler containing a pH buffer solution. The
buffer solution is reacted with a fluorogenic reagent to
form a characteristic fluorophor and is analyzed using
UV spectrophotometry techniques. Sampling is done at
800-1000 ml/min. Laboratory and field validation studies
have demonstrated that the new Union Carbide method has
overcome the sampling deficiency of the small bore-low
sampling rate method, and provides more realistic moni-
toring data because it samples both the free EDA and its
carbamate form.
"Early field results to date indicate that airborne con-
centrations of EDA in Union Carbide workplaces are well
below the OSHA PEL and ACGIH TLV of 10 ppm (8-hour TWA)
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SUBMISSION EVALUATION
Immediately upon receipt of this TSCA Section 8(e) submission, the
Chemical Screening Branch sent full copies of the submission to
NIOSH, OSHA, ACGIH and the Exposure Evaluation Division (EED/OTS).
According to secondary literature, EDA is a colorless alkaline
liquid with an ammonia-like odor that is irritating (in some cases
severely irritating) to skin, eyes and respiratory tract; some
individuals are reportedly hypersensitive to EDA. Based on an
inhalation LC50 value of 0.3 mg/1 in mice, EDA is listed as an
"Extremely Hazardous Substance" (EHS) under Section 302 of the
Superfund Amendments and Reauthorization Act (SARA) and is subject
to certain SARA requirements (e.g., EDA has a "Threshold Planning
Quantity" (TPQ) of 10,000 pounds). Further, EDA is subject to the
Superfund chemical substance release reporting requirements (EDA
has a "Reportable Quantity" (RQ) of 5,000 pounds).
CURRENT PRODUCTION AND D8E
A review of the production range (includes importation volumes)
statistics for ethylenediamine (CAS No. 107-15-3), which is listed
in the initial TSCA Chemical Substance Inventory, shows that about
11-61 million pounds were reported as manufactured and/or imported
in 1977. This production range information does not include any
data that were claimed to be TSCA Confidential Business Information
(TSCA CBI) by the person(s) who reported for the TSCA Inventory,
nor does it include any data that would compromise TSCA CBI. All
data reported for the initial TSCA Inventory, including production
range data, are subject to the limitations in the TSCA Inventory
Reporting Regulations (40 CFR 710).
According to the Condensed Chemical Dictionary (10th Edition), EDA
uses include: "Fungicides; manufacture of chelating agents (EDTA) ;
dimethylolethylene-urea resins; chemical intermediate; solvent;
emulsifying agent; textile lubricants; antifreeze inhibitor."
COMMENTS/RECOMMENDATIONS
In its submission, Union Carbide reported that the company plans
to conduct further sampling and analysis. Union Carbide stated
also that the company is notifying its EDA customers and other
domestic EDA suppliers about the reported information.
a) The Chemical Screening Branch will ask Union Carbide to
ensure that EPA receives full copies of the final reports
(including the actual experimental protocols, data, etc.)
from the monitoring studies cited in the submission.
b) The Chemical Screening Branch will review the submitted
information to determine the need for further OTS
assessment of the reported findings.
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c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, ACGIH,
OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA, OPP/EPA and EED/OTS;
copies of this report will be provided also to the TSCA
Assistance Office (TAO/OTS) for further distribution.
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jmj
\ c*
Page 1 of 3
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
DATE:
JUL -3 1989 APPROVED: f/5{/^
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0689-0802
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
The 01in Corporation reported the findings from a guinea pig skin
sensitization study of octadecyl isocyanate (CAS No. 112-96-9).
01 in provided the following summary information regarding the
conduct and results of this study:
". . . . Ten male Hartley albino guinea pigs received
nine topical applications of the test material over a
three-week period. Subsequent to the induction phase,
the animals were challenged on two separate occasions
beginning two weeks following the last induction
application. Each animal was challenged at two sites,
at the original site used for induction and at a virgin
site. In the challenge phase, 7/10 and 8/10 animals
developed a positive reaction during the first and second
challenges, respectively. This reaction consisted of
moderate erythema indicative of skin sensitization. The
results of this test reveal that octadecyl isocyanate
causes allergic skin sensitization of mild-to-moderate
potency."
1 This status report is the result of a preliminary evaluation of
information that has been submitted to EPA under Section 8(e), the "substantial
risk" information reporting provision of the Toxic Substances Control Act (TSCA).
The statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Any
review of this status report should take into account that the report may be
based on incomplete information.
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8EHQ-0689-080 2
Page 2 of 3
SUBMISSION EVALUATION
Although Olin's Section 8(e) letter stated that a copy of the final
report of the skin sensitization study of octadecyl isocyanate was
attached, the final report did not accompany the letter. Therefore,
in order for the Agency to evaluate the overall significance of the
reported findings, Olin should be asked to submit a full copy of
the final report (including the actual.experimental protocol, data,
etc.) from the cited skin sensitization study.
Immediately upon receipt of Olin's incoming Section 8(e) letter,
the Chemical Screening Branch provided a complete copy of the
letter to the Risk Analysis Branch (RAB/ECAD/OTS); RAB staff are
currently reviewing toxicologic/exposure data on several monomeric
diisocyanates (e.g., toluene diisocyanate).
CURRENT PRODUCTION AND USE
A review of the production range (includes importation volumes)
statistics for octadecyl isocyanate (CAS No. 112-96-9), which is
listed in the initial TSCA Chemical Substance Inventory, has shown
that no 1977 manufacture/importation was reported or that all of
the manufacture and/or importation data reported were claimed as
TSCA Confidential Business Information (TSCA CBI) by the person(s)
reporting for the initial TSCA Inventory and cannot be disclosed
(Section 14(a) of TSCA; U.S.C. 2613(a)). All of the data reported
for the initial TSCA Inventory, including production range data,
are subject to the limitations contained in the TSCA Inventory
Reporting Regulations (40 CFR 710).
Olin reported that the company "manufactures very small amounts
(less than 3,000 pounds . . . [as of about June, 1989]) of this
material at its Lake Charles, Louisiana plant and sells such
quantities to . . . [Olin's] only customer, 3M Company, St. Paul,
Minnesota, as a raw material in the manufacture of a product used
for adhesive-type applications.11
According to the Condensed Chemical Dictionary (10th Edition), the
uses of octadecyl isocyanate include: "Intermediate in synthesis;
water-repellent textiles, paper, and other surfaces."
COMMENTS/RECOMMENDATIONS
Olin reported that although the company does not plan to conduct
any further evaluations of octadecyl isocyanate, the company is
informing its Lake Charles, Louisiana plant-site employees about
the submitted skin sensitization results and "confirm with such
employees previously furnished data and information concerning the
appropriate precautions and worker protection equipment which must
be worn when handling this material." In addition, Olin stated
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8EHQ-0689-0802
Page 3 of 3
that the octadecyl isocyanate Material Safety Data Sheet (MSDS) is
being updated to reflect the reported findings. Finally, Olin
stated that a copy of the revised MSDS for octadecyl isocyanate
will be provided to the 3M Company.
a) The Chemical Screening Branch will ask Olin to submit a
complete copy of the final report (including the actual
experimental protocol, data, etc.) from the guinea pig
skin sensitization study of octadecyl isocyanate cited
in the company's TSCA Section 8(e) submission.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure information, Olin will be requested to
describe the nature and results of all studies (other
than those submitted already to EPA or those cited in the
published scientific literature) about which Olin is
aware or that Olin has conducted that are designed to
determine the toxicity of or the exposure to octadecyl
isocyanate.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of octadecyl isocyanate.
c) The Chemical Screening Branch will send copies of this
report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA, OW/EPA,
ORD/EPA, OAR/EPA, OPP/OPTS/EPA and RAB/ECAD/OTS/OPTS/EPA;
in addition, copies of this report will be provided to
the TSCA Assistance Office (TAO/OTS/OPTS/EPA) for further
distribution.
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4> f<
Page 1 of 5
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
DATE:
SUBJECT:
FROM:
TO:
APPROVED:
rm,
JUL 24 1989
Status Report1 8EKQ-0689-0803
David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBMISSION DESCRIPTION
The Union Carbide Corporation submitted 1) a full copy of the final
report from a 1-hour inhalation LC50 study of Chlorosilane A-199
(dichlorosilane; CAS No. 4109-96-0) in rats, and 2) preliminary
results from a 9-day repeated inhalation exposure study of this
chemical substance in rats. Union Carbide's TSCA Section 8(e)
cover letter presents the following summary information about the
conduct and results of these studies:
"An acute exposure study with dichlorosilane vapor [in
Sprague-Dawley rats] allowed the determination of a 1-hr
LC50 (with 95% confidence limits) of 314 (211-466) ppm
calculated as nominal dichlorosilane vapor. . . In view
of the moderately high acute inhalation toxicity of the
vapor, a short-term repeated exposure of Sprague-Dawley
rats to dichlorosilane vapor was conducted. Target con-
centrations were 15, 7 and 3 ppm dichlorosilane vapor,
using 10 male and 10 female rats per exposure group.
Additionally, there was an air-alone (0 ppm) control and
a hydrogen chloride [ (HC1).] gas control because of the
hydrolysis of dichlorosilane to hydrogen chloride* After
This status report is the result of a preliminary evaluation of
information that has been submitted to EPA under Section 8(e), the "substantial
risk" information reporting provision of the Toxic Substances Control Act (TSCA).
The statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Any
review of this status report should take into account that the report may be
based on incomplete Information.
90
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8EHQ-0689-0803
Page 2 of S
a 14-day post-exposure period, survivors were sacrificed
for necropsy examination and removal of various tissues
and organs for weighing and histological examination.
Major findings were as follows:
1) "The nominal (metered) chamber concentrations
of dichlorosilane were, respectively, 15.0,
6.9, and 2.7 ppm for the target high, inter-
mediate and low concentration groups. However,
[the] dichlorosilane could not be analytically
detected in the [exposure] chambers by gas
chromatography. The hydrogen chloride concen-
trations, as mean + SD [(Standard Deviation)],
were 28+5.4, 19+5.8 and 8+0.9 ppm for
the target dichlorosilane concentrations of
15, 7 and 3 ppm. The concentration in the
hydrogen chloride control was 34+6.3 ppm.
2) "There were no mortalities during [the 9-day]
exposure or over the 14-day post-exposure
observation period.
3) "[The] signs of toxicity, occurring principally
in the 15 ppm dichlorosilane group, included
blepharitis [(inflammation of the eyelids)]
and audible breathing.
4) "Body weight decreases, both absolute weight
and weight gains, were measured in the 13 ppm
group. Males of the 7 and 3 ppm group showed
reduced body weight gain. There were no
effects on body weight gain of the HC1 group.
5) "Food and water consumption were reduced for
the 15 ppm dichlorosilane group.
6) "Hematology for the 15 ppm dichlorosilane group
showed slight increase in erythrocyte count
and hematocrit, and decrease in mean corpus-
cular hemoglobin, for males. Females of this
group had slightly increased total leucocyte
count.
"For the males and females of the HC1-alone
group, there was an increase in leucocyte
count. Males showed slight increase in
erythrocyte count, hematocrit and mean
corpuscular volume; the mean corpuscular
hemoglobin and mean corpuscular hemoglobin
concentration were decreased.
7) "At necropsy, the lungs of [rats from] the high
concentration dichlorosilane group appeared red
or dark pink.
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Page 3 of 5
8) "Lung weights were increased (60-70%) above
control weights in the highest dichlorosilane
group. Also, the lung weight relative to body
weight was increased for the intermediate
group, but with males only.
9a) "Abnormal histological effects were seen in the
upper respiratory tract of all dichlorosilane
exposed animals. [The] principal effects were
rhinitis [(inflammation of the nasal mucosa)],
epithelial hyperplasia, and squamous metaplasia
of the nasal mucosa; metaplasia was present
mainly in the anterior regions. Also, with
the high and intermediate dichlorosilane
groups, there was epithelial hyperplasia of the
trachea.
b) "Rats of the high dichlorosilane group had lung
lesions, consisting of inflammation, alveolar
histiocytosis, and interstitial fibrosis.
c) "There were no abnormal histological findings
in the respiratory tract of rats from the
control or hydrogen chloride groups.
"The above findings indicate that a 9-day repeated
[inhalation] exposure of rats to low nominal [vapor]
concentrations of dichlorosilane (range 2.7 to 15.0 ppm)
caused inflammatory, hyperplastic, and metaplastic
lesions in the respiratory tract. These were produced
at concentrations where the equivalent hydrolytically-
generated hydrogen chloride [(HC1)] concentrations are
ineffective in producing such lesions, and in the absence
of analytically detectable dichlorosilane in the chamber
atmosphere. The causative molecule(s) and mechanisms are
unknown."
SUBMISSION EVALUATION
An EPA evaluation of the overall significance of the reported
toxicologic findings should be possible upon the Agency's receipt
of a full copy of the final report from the cited 9*-day repeated
dichlorosilane vapor inhalation study in rats.
CURRENT PRODUCTION AND QBE
A review of the production range (includes importation volumes)
statistics for dichlorosilane (CAS No. 4109-96-0), which is listed
in the initial TSCA Chemical Substance Inventory, has shown that
between 11,000 and 110,000 pounds of this chemical were reported
as manufactured and/or imported in 1977. This production range
information does not include any data that were claimed to be TSCA
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Page 4 of 5
Confidential Business Information (TSCA CBI) by the person(s) who
reported for the TSCA Inventory, nor does it include any data that
would compromise TSCA CBI. All data reported for the initial TSCA
Inventory, including the production range data, are subject to the
limitations contained in the TSCA Inventory Reporting Regulations
(40 CFR 710).
Union Carbide did not provide any specific information about the
use(s) of dichlorosilane, nor was such information located in the
secondary literature sources consulted by EPA. According to the
American Chemical Society (ACS) CHEMCYCLOPEDIA (Volume 6? 1988),
dichlorosilane is available in "electronic" and "semiconductor"
grades.
COMMENTS/RECOMMENDATIONS
Union Carbide stated that the dichlorosilane Material Safety Data
Sheet (MSDS) is being revised to reflect the reported toxicological
findings. In addition, Union Carbide stated that its employees and
customers are being advised about the reported findings.
It should be noted that the Agency has received a number of TSCA
Section 8(e) and "For Your Information" (FYI) notices containing
toxicologic and/or exposure data on organosilanes. In addition,
the Chemical Screening Branch prepared (in 1986) a Chemical Hazard
Information Profile (CHIP) covering several organosilanes. Finally,
the Risk Analysis Branch (RAB/ECAD/OTS) is currently evaluating
available toxicologic and exposure information on organosilanes.
a) The Chemical Screening Branch will ask Union Carbide to
ensure that EPA receives a complete copy of the final
report (including the actual experimental protocol,
results of gross and histopathological examinations,
results of statistical analyses, etc.) from the 9-day
inhalation study cited in the company's submission.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure information, Union Carbide will be
requested to describe the actions that the company has
taken or plans to take to reduce or eliminate exposure
to dichlorosilane. In addition, Union Carbide will be
asked to describe the nature and results, if available,
of all studies (other than those submitted already to EPA
or those cited in the published scientific literature)
about which the company is aware or that the company has
conducted, is conducting or plans to conduct that are
designed to determine the toxicity of or the exposure to
dichlorosilane.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of dichlorosilane.
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Page 5 of 5
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS and RAB/ECAD/OTS; in
addition, copies of this status report will be sent to
the TSCA Assistance Office (TAO/OTS/OPTS) for further
distribution.
94
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 3
OFFICE OF
m-
PESTICIDES AND
date: JUL I T 1989
TOXIC SUBSTANCES
APPROVED:
SUBJECT: Status Report1 8EHQ-0689-0804
8EHQ-0689-0804 S SUPP.
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
Technical Assessment Systems, Inc. submitted the following summary
information on behalf of Albright & Wilson Company, Ltd., which is
located in England:
"Tetrakis(hydroxymethyl)phosphonium chloride (THPC; CAS
No. 124-64-1) and tetrakis(hydroxymethyl)phosphonium
sulfate (THPS; CAS No. 55566-30-8) have been produced for
approximately 35 years using the same chemical processes.
No reported incidents of adverse health effects have been
encountered by Albright & Wilson [Company], Ltd. during
this time interval.
"New analytical data regarding the composition of THPC
and THPS have recently become available to Albright &
Wilson [Company], Ltd
"Using a more sophisticated analytical procedure than
available originally, the presence of previously unknown
equilibrium moieties have been detected in THPC and THPS
which led [the company] to suspect the presence of pre-
viously undetected formaldehyde [(CAS No. 50-00-0)].
Preliminary indications are that formaldehyde is present
at levels between 0.1% and 1.0%. . . .
1 This status report is the result of a preliminary evaluation of
information that has been submitted to EPA under Section8(e), the "substantial
risk" information reporting provision of the Toxic Substances Control Act (TSCA).
The abatements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Any
review of this status report should take into account that the report may be
based on incomplete information.
95
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The initial submission notes that no evidence of carcinogenicity
was seen in the National Toxicology Program (NTP) 2-year gavage
studies of THPC and THPS in Fischer 344/N rats and B6C3F1 mice (NTP
Technical Report No. 296).
Albright & Wilson's supplemental submission contains analytical
information on which the company's initial submission was based.
SUBMISSION EVALUATION
Immediately upon receipt, the Chemical Screening Branch sent copies
of the initial and supplemental TSCA Section 8(e) submissions to
staff of the Risk Analysis Branch (RAB/ECAD/OTS) for inclusion in
the Agency's review of formaldehyde.
CURRENT PRODUCTION AND USE
A review of the production range (includes importation volumes)
statistics for THPC (CAS No. 124-64-1) , which is listed in the
initial TSCA Chemical Substance Inventory, has shown that between
100 thousand and 1 million pounds of this chemical were reported
as manufactured and/or imported in 1977. A review of the production
range statistics for THPS (CAS No. 55566-30-8), which is listed
also in the initial TSCA Chemical Substance Inventory, has shown
that between 1.1 million and 11 million pounds of this chemical
were reported as manufactured and/or imported in 1977.
The above production range information does not include any data
that were claimed to be TSCA Confidential Business Information
(TSCA CBI) by the person(s) who reported for the TSCA Inventory,
nor does it include any data that would compromise TSCA CBI. All
of the data reported for the initial TSCA Inventory, including the
production range data, are subject to the limitations contained in
the TSCA Inventory Reporting Regulations (40 CFR 710).
According to information presented in the "1. Manufacture." section
of Albright & Wilson's supplemental TSCA Section 8(e) submission,
THPC and THPS are "used as feedstocks for the manufacture of flame
retardant treatments for textiles" and have recently been "found
to have a number of end applications as biocides."
COMMENTS/RECOMMENDATIONS
According to Technical Assessment Systems, Inc., Albright & Wilson
has further analytical work underway to quantify the formaldehyde
concentrations in THPC and THPS. In addition, Albright & Wilson is
reportedly advising its customers (via updated product labels and
Material Safety Data Sheets (MSDSs)) about the company's detection
of formaldehyde in THPC and THPS.
It should be noted that EPA has received other TSCA Section 8(e)
and "For Your Information" (FYI) submissions on THPC and THPS; the
reader's attention is directed to the "Status Reports" that EPA
prepared in response to 8EHQ-1080-0369 et seq..
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a) In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, Albright & Wilson will be asked
to describe the actions that the company has taken or
plans to take to 1) notify its THPC and THPS production
workers about the reported detection of formaldehyde in
THPC and THPS, and 2) reduce or eliminate formaldehyde
in those chemicals.
b) The Chemical Screening Branch will forward any further
reported information to staff of the Risk Analysis Branch
for inclusion in the ongoing EPA review of formaldehyde.
c) The Chemical Screening Branch will send copies of this
status repprt to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS and RAB/ECAD/OTS/OPTS;
copies of this report will be provided also to the TSCA
Assistance Office (TAO/OTS) for further distribution.
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° V Page 1 of 3
s JEL \ UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
153TZl
WASHINGTON, DC 20460
date : JUL I 2 1989
APPROVED
: &L jKt W
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECTS Status Report1 8EHQ-0789-0805 S
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
Eli Lilly and Company has claimed the exact identity of the subject
chemical to be TSCA Confidential Business Information (TSCA CBI).
The Information Management Division will review all of the incoming
correspondence related to the company's TSCA CBI claim. In the
"sanitized" version of this TSCA Section 8(e) submission, Eli Lilly
reported non-confidentially that the subject chemical substance is
an "unsaturated sulfone."
SUBMISSION DESCRIPTION
Eli Lilly provided the following summary information regarding the
conduct and results of genotoxicologic testing of this unsaturated
sulfone:
"The compound was evaluated in the gradient plate assay,
a modification of the Ames assay, used to screen com-
pounds for the induction of mutations in bacteria. A
positive response was obtained in E*. coli strain WP2uvrA-
both in the presence and the absence of metabolic
activation, and in Salmonella tvphimurium strain TA100
with metabolic activation only. Positive responses were
This status report is the result of a preliminary evaluation of
information that has been submitted to EPA under Section 8(e), the "substantial
risk" information reporting provision of the Toxic Substances Control Act (TSCA) .
The statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Any
review of this status report should take into account that the report may be
based on incomplete information.
98
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8EHQ-0789-0805 S
Page 2 of 3
observed in coli between 1 and 2 ug/ml and 1 and 10
ug/ml in the assays without activation and with activa-
tion, respectively. The response in TA100 occurred
between 1 and 10 ug/ml.
"The compound was also evaluated for the ability to
induce chromosome aberrations in cultured Chinese hamster
ovary [(CHO)] cells. A positive response was obtained
at the mid-dose only in the assay conducted without
activation. Compound concentrations of 1, 2, and 3 ug/ml
yielded 3, 8, and 4 percent cells with aberrations,
respectively. The solvent control yielded 1 percent
cells with aberrations. A positive response was also
obtained at the high dose only in the assay conducted
with activation. Compound concentrations of 25, 37.5, and
50 ug/ml yielded 3, 2 and 19 percent cells with aberra-
tions, respectively. The solvent control yielded 1
percent cells with aberrations."
SUBMISSION EVALUATION
The submitted information indicates that this unsaturated sulfone
does possess some degree of genotoxic activity. An evaluation of
the overall significance of the reported findings should be
possible upon EPA's receipt of full copies of the final reports
from the cited studies.
It should be noted that genotoxicological findings for another
unsaturated sulfone were reported previously by Eli Lilly to the
Agency under Section 8(e) of TSCA (8EHQ-0389-0791 S). The reader's
attention is directed to the "Status Report" prepared by EPA for
that previous Section 8(e) submission.
CURRENT PRODUCTION AND USE
In view of Eli Lilly's TSCA CBI claim, no information regarding
the TSCA Chemical Substance Inventory status of this unsaturated
sulfone will appear in this status report.
Eli Lilly provided the following non-confidential information about
the manufacture and use of, as well as the future plans for this
unsaturated sulfone:
"Lilly has manufactured less than 5 kilograms of this
[research] compound for use in controlled field studies
for pesticidal effectiveness in Lilly test plots in the
United States. Of the 5 kilograms [made], approximately
250 grams were actually applied in 1988 and 1989. Lilly
does not plan to do further work on this compound. The
remainder of the compound, except for a reference
standard, will be incinerated."
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8EHQ-0789-0805 S
Page 3 of 3
COMMENTS/RECOMMENDATION8
Although a positive in vitro genotoxicity test, when considered
alone, may not be sufficient to offer reasonable support for a
conclusion of substantial risk (as that term is defined in EPA's
TSCA Section 8(e) policy statement ("Statement of Interpretation
and Enforcement Policy; Notification of Substantial Risk" 43 FR
11110; March 16, 1978)), EPA does believe that such information is
of value in assessing the possible risk(s) posed by exposure to the
tested chemical or mixture. Further, EPA believes that a positive
genotoxicity test result, in combination with other information
(e.g., knowledge of actual/potential exposure to and/or high pro-
duction of the tested chemical or mixture), would suggest the need,
in many cases, to conduct further studies designed to determine
the toxicity of or the exposure to that chemical substance or
mixture. EPA expects the results of such additional studies to be
considered also for submission under Section 8(e) of TSCA.
a) The Chemical Screening Branch will request Eli Lilly to
ensure that EPA receives a complete copy of the final
report (including the actual experimental protocol, data,
etc.) from each study cited in the company's submission.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity or exposure data, Eli Lilly will be asked to
describe the nature and results, if available, of all
studies (other than those submitted already to the Agency
or those cited in the published scientific literature)
about which Eli Lilly is aware or that the company has
conducted that are designed to determine the toxicity of
this unsaturated sulfone.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of the subject chemical.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be provided to the TSCA
Assistance Office (TAO/OTS) for further distribution.
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 3
-71*1
PESTICIDES AND
TOXIC SUBSTANCES
dates JUL I 2 1989
APPROVED:
SUBJECT: Status Report1 8EHQ-0789-0806 8
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Eli Lilly and Company has claimed the exact identity of the subject
chemical to be TSCA Confidential Business Information (CBI). Staff
of the Information Management Division will review all incoming
correspondence related to the company's TSCA CBI claim. In the
"sanitized" version of its TSCA Section 8(e) submission, Eli Lilly
stated non-confidentially that the subject chemical substance is
a "substituted quinazoline."
SUBMISSION DESCRIPTION
Eli Lilly provided the following summary information regarding the
conduct and results of an acute toxicity study of this substituted
quinazoline in mice:
"Preliminary testing of this research compound has
resulted in a mouse oral toxicity study with a median
lethal dose [of] less than 50 mg/kg.
"The acute toxicity of the compound administered orally
to female CD-I mice was evaluated. There were three ani-
mals in each of the three dose groups, and the animals
1 This status report is the result of a preliminary evaluation of
information that has been submitted to EPA under Section 8(e), the "substantial
risk" information reporting provision of the Toxic Substances Control Act (TSCA).
The statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s), Any
review of this status report should take into account that the report may be
based on incomplete information.
NOTE
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8EHQ-0789-0806 S
Page 2 of 3
received either 50, 500, or 2 000 mg/kg of the compound.
There were no survivors following a single oral dose of
this compound. All of the deaths occurred by test day
three. Antemortem signs of toxicity included ataxia,
coma, hypoactivity, lethargy, piloerection, and tremors."
SUBMISSION EVALUATION
The submitted summary information indicates that this substituted
quinazoline is extremely toxic via oral administration. An EPA
evaluation of the overall significance of the reported findings
should be possible upon the Agency's receipt of a full copy of the
final report of the cited acute toxicity study in mice.
CURRENT PRODUCTION AND USE
In view of the submitter's TSCA CBI claim, no information regarding
the TSCA Chemical Substance Inventory status or use of the subject
chemical will appear in this status report. In its Section 8(e)
notice, Eli Lilly stated non-confidentially that the company has
manufactured only 2 grams of this substituted quinazoline thus far
and is in the process of producing an additional 50 to 100 grams
of the chemical.
COMMENTS/RECOMMENDATIONS
Eli Lilly stated that this substituted quinazoline is now labelled
as "hazardous."
a) The Chemical Screening Branch will ask Eli Lilly to
ensure that EPA receives a complete copy of the final
report (including the actual experimental protocol,
results of gross and histopathological examinations,
results of statistical analyses, etc.) from the acute
oral toxicity study cited in the company's Section 8(e)
submission.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, Eli Lilly will be requested to
describe any additional actions the company has taken or
plans to take l) to notify workers and others about the
reported toxicologic information, and 2) to reduce or
eliminate exposure to the subject chemical. In addition,
Eli Lilly will be requested to describe the nature and
results, if available, of all studies (other than those
submitted already to EPA or those cited in the published
scientific literature) about which Eli Lilly is aware or
that Eli Lilly has conducted, is conducting or plans to
conduct that are designed to determine the toxicity of
or the exposure to this substituted quinazoline.
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8EHQ-0789-0806 S
Page 3 of 3
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of the subject chemical.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be provided to the TSCA
Assistance Office (TAO/OTS) for further distribution.
103
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^ *v!>
%
'«t p«0^°
J
Page 1 of 7
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
DATE:
AUG 2 5 1989
APPROVED
: (
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report
NOTE
8EHQ-0789-0807 S and
FYI-OTS-0389-0677 S
Q
FROM: Frank D. Kover, Chief
Chemical Screening Branch/ECAD
TO: Joseph J. Merenda, Director
Existing Chemical Assessment Division/OTS
This status report pertains to an initial Section 8(e) submission
(8EHQ-0789-0807 S) and an initial "For Your Information" (FYI)
submission (FYI-OTS-0389-0677 S) on pyrazole (CAS No. 288-13-1).
The submitting companies have claimed their company names to be
TSCA Confidential Business Information (TSCA CBI); the Information
Management Division will review all incoming correspondence related
to these CBI claims.
SUBMISSION DESCRIPTIONS
The submitter of 8EHQ-0789-0807 S provided the following summary
information about the conduct and preliminary results of a pilot
oral teratology study of pyrazole in rats:
"Preliminary unaudited results . . . [from this study]
suggest that pyrazole causes developmental as well as
maternal toxicity in rats at dose levels > 10 mg/kg/day.
In this study, pyrazole was administered by gavage to 6
groups of 8 mated female rats at dose levels of 0, 1, 5,
10, 15 and 20 mg/kg/day during gestation days 6-18. Sur-
viving dams were sacrificed on gestation day 20. Fetuses
were removed, weighed, sexed and examined for possible
external malformations.
This status report is the result of a preliminary evaluation of data
submitted to the Agency on a "For Your Information" (FYI) basis and under Section
8(e), the "substantial risk" information reporting provision of the Toxic
Substances Control Act (TSCA). Statements made in this status report should not
be regarded as expressing final EPA policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the
report may be based on incomplete information.
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"No mortality occurred at any [pyrazole] dose level.
However, substantial body weight losses were noted at 15
and 20 mg/kg/day. Slight to moderate mean body weight
effects occurred at 10 and possibly 5 mg/Jcg/day,
primarily during the first 3 days of dosing. A dose
related decrease in mean fetal weights was apparent at
> 10 mg/ kg/day. Implantation loss may have been
marginally increased at 20 mg/kg/day. The only external
malformations observed were cleft palate in 6 fetuses
from 2 litters at 20 mg/kg/day."
The submitter of FYI-OTS-0389-0677 S Initial provided the following
summary information with regard to two published and one company-
conducted developmental toxicity studies of pyrazole:
"Pyrazole . . . previously has been reported to induce
developmental toxicity in rats and mice. Varma and
Presaud (Res. Communic. Chem. Path. Pharm. 26:65-73,
1979) reported a 'high incidence of ocular and urinary
bladder anomalies in the offspring of [Sprague-Dawley]
rats following [oral] treatment on gestational day 9.'
'Embryocidal effects' and 'infrequent minor structural
abnormalities' were reported in [Swiss Webster] mice
injected [intraperitoneally on gestation days 8, 10, 12
and 14] with pyrazole (Giknis and Damjanov, Teratology
25:43A, 1982).
"To further evaluate . . . [the] potential to produce
developmental toxicity, pyrazole was administered to
pregnant female rats [ (strain not specified)] at dose
levels ranging from 25 to 225 mg/kg/day during gestation
days 6-18. Fetuses were weighed and evaluated for
external malformations. Unfortunately, substantial
maternal toxicity (substantial weight loss and/or death)
was noted at all dose levels. No fetuses were produced
at > 100 mg/kg/day. Fetuses were produced at 25 mg/kg/day
but these fetuses weighed about one-half that of [the]
controls. These fetuses also exhibited a high incidence
of external malformations (primarily cleft palate) but
that was not unusual considering the low fetal weights.
"Because of the excessive maternal toxicity, this study
is judged to be inadequate to assess the developmental
toxicity of pyrazole."
SUBMISSION EVALUATIONS
The information presented in the published studies cited in the
FYI submission indicates that pyrazole can cause developmentally
toxic effects following intraperitoneal injection in mice and oral
administration to rats. Giknis and Damjanov (1982) found that
intraperitoneal injections of pyrazole at a dose of 6 mg/kg/day to
pregnant Swiss Webster mice on days 8, 10, 12 and 14 of gestation
resulted in reduced litter size and reduced fetal weight. Further,
105
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Varma and Persaud (1979) observed a significant increase in the
incidence of maXformations, primarily ocular and urinary bladder
anomalies following administration of a single oral dose of 100
mg/kg to pregnant Sprague-Dawley rats on gestation day 9; single
oral adminstration of this dose on gestation day 6 or 12 was not
found to produce an increase in the incidence of malformations.
No maternal toxicity was noted by the investigators. It should be
noted that no other published developmental toxicity information
on pyrazole was located by the Agency during an initial search of
several publicly available computerized data bases and a variety
of secondary literature sources.
The FY I submission states that the company-conducted study involved
administration of pyrazole to pregnant rats at doses ranging from
25 to 225 mg/kg on gestational days 6-15; the rat strain, route of
administration, exact dose levels administered and group sizes were
not reported in the submitted summary. Maternal toxicity, evidenced
by death and/or "substantial" weight loss, reportedly occurred at
all dose levels; however, the number of deaths and the degree of
weight loss was not reported. According to the summary, dams that
received > 100 mg/kg failed to produce offspring. Further, fetuses
from the 25 mg/kg dose group were reported to have 1) "reduced body
weight (about one-half that of controls)," and 2) a "high incidence
of external malformations (primarily cleft palate) ." The submitter
asserts that these malformations were "not unusual considering the
low fetal weights." The submitter stated also that "because of the
excessive maternal toxicity, this "is judged to be inadequate for
establishing the developmental toxicity of pyrazole." Although it
may be true that this study may not be adequate for establishing
the limits for exposure to pyrazole, the study does provide further
and more precise information than that contained in the published
literature about the developmental toxicity of this chemical. EPA
should request a complete copy of the final report (including the
actual experimental protocol, results of gross/histopathological
examinations, results of any statistical analyses, etc.) from the
developmental toxicity study cited in FY1-OTS-0389-0677 S Initial.
The Section 8(e) submission provides still further and even more
precise information with regard to the maternal and developmental
toxicity of pyrazole. In this study, 6 groups, each containing 8
pregnant rats (strain not given), received pyrazole via gavage at
dose levels of 0, 1/ 5, 10, 15 or 20 mg/kg on gestation days 6-18.
Maternal toxicity (significantly decreased weight gain) was evident
in the dams from the 15 and 20 mg/kg/day groups. A slight reduction
in body weight gain was seen in the dams in the 5 and 10 mg/kg/day
groups during the first 3 days of dosing? thereafter, however, the
body weight gains for these groups were comparable to the controls.
Developmental toxicity was apparent at pyrazole dose levels of 10
mg/kg/day and greater. Fetuses from the 10, 15 and 20 mg/kg/day
dose groups had significantly reduced body weights. In addition,
there was an increased incidence of cleft palate among fetuses from
20 "»g/kg/day dose group (6 fetuses from 2 litters) ; no other
malformations were reportedly seen in the fetuses from the control
or any of the other pyrazole-exposed groups. An interpretation of
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the litter size and post-implantation loss data from this study is
somewhat very difficult due to the fact that the litter size in the
control group appears to be relatively small. The mean litter size
for the control was 13.3, while the mean litter sizes for the 1,
5, 10, 15 and 20 mg/kg/day pyrazole dose groups were 15.6, 15.4,
15.3, 13.9 and 13.4, respectively. It appears that the litter
sizes from the 15 and 20 mg/kg/day dose groups were reduced when
compared to the other treated groups, but not when compared to the
control. It is not clear whether this reduction is of biological
relevance or it is a sampling error due in part to the small number
of litters/group (i.e., 8 litters as opposed to the 20 litters used
normally in a full teratology study. It must be noted that there
also appears to have been an increase in post-implantation loss in
the 20 mg/kg/day dose group (1.5 vs 0.9 in the control); again, a
larger sample size would aid resolution. The submitter of this
Section 8(e) notice should be asked to ensure that EPA receives a
complete copy of the final report from this teratological study.
It should be noted that EPA also received a previous Section 8(e)
notice (8EHQ-0389-0786 S) containing summary results from a pilot
rat teratology study of 3-methyl pyrazole administered orally at
doses of 0, 25, 100, 175 or 225 mg/kg/day on gestation days 6-18.
This previous TSCA Section 8(e) submission provides evidence for
adverse developmental and maternal effects resulting from exposure
to 3-methyl pyrazole. The maternal toxicity consisted of lethality
(6/8 and 8/8 dams died or were killed in extremis at 175 and 225
mg/kg/day, respectively) and moderate to severe body weight losses
over gestation days 6-12 for dams receiving 100 mg/kg/day. Further,
no fetuses were produced by the 2 dams that survived in the 175
mg/kg/day dose group. Also, it was not clear from the provided
summary information if any of the dead or moribund dams in the 175
or 225 mg/kg/day dose groups were pregnant. The serious adverse
developmental effects consisted primarily of increased resorptions
and "substantially reduced" body weight of the live fetuses in the
dams receiving 100 mg/kg/day. It should be noted also that a fetus
from the 100 mg/kg/day dose group was found to have a cleft lip and
palate. Further, all of the fetuses from the 25 mg/kg/day group
were reported to appear "normal or close to normal weight." For
further information about this teratological study of 3-methyl
pyrazole, the reader's attention is directed to the status report
that was prepared by the Agency in response to 8EHQ-0389-0786 S.
CURRENT PRODUCTION AND USE
A review of the production range (includes importation volumes)
statistics for pyrazole (CAS No. 288-13-1), which is listed in the
initial TSCA Chemical Substance Inventory, has shown that no 1977
manufacture/importation was reported or that all of the manufacture
and/or importation data reported were claimed as TSCA Confidential
Business Information (TSCA CBI) by the person(s) reporting for the
initial TSCA Inventory and cannot be disclosed (Section 14(a) of
TSCA; U.S.C. 2613(a)). All data reported for the initial Inventory,
including production range data, are subject to the limitations
contained in the TSCA Inventory Reporting Regulations (40 CFR 710).
107
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In 8EHQ-0789-0807 S, the submitting company reported that pyrazole
"was previously utilized exclusively for . . # [research and
development (R&D)] purposes, but is no longer under active R&D."
The submitter of FYI-OTS-0389-0677 S did not provide any informa-
tion with regard to pyrazole use(s).
The 10th Edition of the Condensed Chemical Dictionary states that
pyrazole has the following uses: "Chemical intermediate; stabilizer
for halogenated solvents and lubricating oils."
COMMENTS/RECOMMENDATIONS
Following review of FYI-OTS-0389-0677 S Initial, EPA believes that
the summary developmental toxicity information presented therein
should have been submitted pursuant to section 8(e) of TSCA. The
following discussion provides the basis for the Agency's position:
TSCA Section 8(e) states, "Any person who manufactures,
[imports,] processes or distributes in commerce a chemi-
cal substance or mixture and who obtains information
which reasonably supports the conclusion that such
substance or mixture presents a substantial risk of
injury to health or the environment shall immediately
inform the [EPA] Administrator of such information unless
such person has actual knowledge that the Administrator
has been adequately informed of such information."
The preface to Part V of EPA's TSCA Section 8(e) policy
statement ("statement of Interpretation and Enforcement
Policy; Notification of Substantial Risk" 43 FR 11110;
March 16, 1978) explains that a "substantial risk of
injury to health ... is a risk of considerable concern
because of (a) the seriousness of the effect . . . and
(b) the fact or probability of its occurrence." With
regard to the seriousness of the effect, Part V explains
that the types of serious health effects for which
substantial risk information must be reported include,
for example, "any pattern of effects or evidence that the
subject chemical or mixture can produce . . . birth
defects ...» The information concerning such serious
toxic effects can be obtained directly or inferred from
designed studies (e.g., studies conducted in animals) as
described in Part VI of the TSCA Section 8(e) policy
statement. Part VI explains further that a subject
"person is not to delay reporting until he obtains
conclusive evidence that a substantial risk exists, but
is to immediately report any evidence that reasonably
supports that conclusion."
With regard to "the fact or probability of its [(i.e.,
the serious effect's)] occurrence criterion, Part V of
the Section 8(e) policy statement explains that certain
types of adverse health effects (e.g., birth defects)
are considered by EPA to be so serious that relatively
108
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little or no weight should be attached to the subject
chemical1s exposure in determining whether a risk is
substantial. Further, EPA's response to Comment 31 in
Appendix B of the TSCA Section 8(e) policy statement as
it pertains to a question on research and development
(R&D) substance, states that the mere occurrence of
serious toxic effects such as those that are described
in Part V(a) of the Section 8(e) policy statement pre-
suppose exposure to the subject chemical or mixture and
must be reported to EPA immediately under Section 8(e).
With regard to the kinds of information that do not need
to be reported to EPA under Section 8(e) , Part VII of the
policy statement explains that "information need not be
reported if it ... is corroborative of well established
adverse effects already documented in the scientific
literature. . It is important to point out, however,
that the Agency does not consider new-found information
to corroborate previously available information regarding
a serious adverse effect if, for example, the new-found
information differs in terms of parameters such as, but
not limited to, route of exposure, dose, time to onset
of the effect, severity of the effect, species and/or
strain of animal in which the effect was observed.
Considering the preceding discussion and EPA's evaluation of the
information contained in FYI-OTS-0389-0677 S Initial, EPA believes
that the provided information meets the reporting criteria set
forth in EPA's 1978 TSCA Section 8(e) policy statement. Further,
the Agency believes that 1) the developmental toxicity of pyrazole
cannot be considered in any way to have been "well established,"
and 2) the provided information does not corroborate previously
available information on pyrazole (i.e., the Information contained
in this FYI submission differs in terms of the dose levels, the
dosing regimen and the nature of the observed developmental effects
from the information previously available to the Agency on this
chemical substance). It is EPA's initial position, therefore, that
the data presented in FYI-OTS-0389-0677 S Initial should have been
submitted to the Agency under Section 8(e) of TSCA.
- a) The Existing Chemical Assessment Division will provide
the submitter of FYI-OTS-0389-0677 S an ample opportunity
(i.e., 20 working days) to rebut EPA's initial position
on the TSCA Section 8(e)-applicability/reportability of
the summary developmental toxicity information that was
presented in the company's FYI submission.
b) The submitter of FYI-OTS-0389-0677 S and the submitter
of 8EHQ-0789-0807 S will be requested to ensure that EPA
receives complete copies of the final reports (including
the actual experimental protocols, results of gross and
histopathological examinations, results of statistical
analyses, etc.) from the unpublished developmental
toxicity studies that were cited in those submissions.
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c) In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity and/or exposure data, the FYI and Section 8(e)
submitters will be requested to describe the actions
taken or planned to notify workers and others about the
reported information. The FYI and Section 8(e) submitters
will be asked also to describe the nature and results,
if available, of all studies (other than those submitted
already to the Agency or those cited in the published
scientific literature) about which the submitters are
aware or that the submitters have conducted that are
designed to determine the toxicity of pyrazole.
d) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of pyrazole.
e) The Chemical Screening Branch will send copies of this
Status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; copies of this
status report will be provided also to the Environmental
Assistance Division/OTS (formerly the TSCA Assistance
Office/OTS) for further distribution.
110
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Page 1 of 3
I \ UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
\ ^ WASHINGTON, DC 20460
% net*
DATES JUL 2 4 1989 APPROVED: /Jt&~
SUBJECTS Status Report1 8EHQ-0789-0808 8
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
NOTE
Lilly Research Laboratories (a division of Eli Lilly and Company)
has claimed the exact identity of the subject chemical substance
to be TSCA Confidential Business Information (CBX); Information
Management Division staff will review all incoming correspondence
related to the company's CBI claim. In the "sanitized" version of
this TSCA Section 8(e) notice, Lilly stated non-confidentially that
the subject chemical is a "substituted quinazoline."
SUBMISSION DESCRIPTION
Lilly provided the following summary information regarding the
conduct and preliminary results of an acute oral toxicity study of
this substituted quinazoline in mice:
"Preliminary testing of this research compound has
resulted in a mouse oral toxicity study with a median
lethal dose [of] less than 50 mg/kg.
"The acute toxicity of the compound administered orally
to female Cti-l mice was evaluated. There were three
animals in each of the three dose groups, and the animals
This status report is the result of a preliminary evaluation of
information that has been submitted to EPA under Section 8(e), the "substantial
risk" information reporting provision of the Toxic Substances Control Act (TSCA).
The statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Any
review of this status report should take into account that the report may be
based on Incomplete Information.
Ill
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8EHQ-0789-0808 S
Page 2 of 3
received either 50, 500, or 2000 mg/kg of the compound.
There were no survivors following a single oral dose of
this compound. All of the deaths occurred by test day
three. Antemortem signs of toxicity included ataxia,
coma, hypoactivity, lethargy, piloerection, soft stools,
exophthalmos, and tremors."
BUBMI88ION EVALUATION
The submitted summary information indicates that this substituted
quinazoline is extremely toxic via oral administration. An EPA
evaluation of the overall significance of the reported findings
should be possible upon the Agency's receipt of a full copy of the
final report of the cited acute toxicity study in mice.
It should be noted that EPA recently received a TSCA Section 8(e)
notice from Eli Lilly and Company in which the company reported
that another "substituted quinazoline" was found to be extremely
toxic (LD50 of less than 50 mg/kg) in an acute oral toxicity study
in mice. The reader's attention is directed to the "Status Report"
prepared by the Agency in response to this previous Section 8(e)
submission (8EHQ-0689-0806 S).
CURRENT PRODUCTION AND P8E
In view of the submitter's TSCA CBI claim, no information regarding
the TSCA Chemical Substance Inventory status or use of the subject
chemical will appear in this status report. In its Section 8(e)
submission, Lilly stated non-confidentially that the company "has
manufactured only 5.6 grams" of this substituted quinazoline.
COMMENT 8/RECOMMENDATIONS
Lilly reported that this substituted quinazoline is labelled as
being "hazardous."
a) The Chemical Screening Branch will ask Lilly to ensure
that EPA receives a complete copy of the final report
(including the actual experimental protocol, results of
gross and histopathological examinations, results of
statistical analyses, etc.) from the acute oral toxicity
study cited in the company's Section 8(e) submission.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, Lilly will be asked to describe
any additional actions the company has taken or plans to
take 1) to notify workers and others about the reported
toxicologic information, and 2) to reduce or eliminate
exposure to the subject chemical. In addition, Lilly
will be requested to describe the nature and results, if
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8EHQ-0789-0808 S
Page 3 of 3
available, of all studies (other than those submitted
already to EPA or those cited in the published scientific
literature) about which Lilly is aware or that Lilly has
conducted, is conducting or plans to conduct that are
designed to determine the toxicity of or the exposure to
this substituted quinazoline.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of the subject chemical.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be provided to the TSCA
Assistance Office (TAO/OTS) for further distribution.
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 3
OFFICE OF
PESTICIDES AND
date: JUL 2 4 1989
APPROVED:
TOXIC SUBSTANCES
SUBJECTS Status Report1 8EHQ-0789-0809
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
Dixie Chemical Company, Inc. submitted the following summarized
information from a draft National Toxicology Program (NTP) report
concerning NTP chronic studies of glycidol (CAS No. 556-52-5) in
mice and rats:
"Under the conditions of these 2-year gavage studies,
there was clear evidence of carcinogenic activity of
glycidol for male and female F344/N rats and male and
female B6C3Fi mice, based on increased incidences of a
variety of neoplasms at numerous tissue sites."
SUBMISSION EVALUATION
Immediately upon receipt, the chemical Screening Branch sent a full
copy of this Section 8(e) submission to the Test Rule Development
Branch (TRDB/ECAD/OTS) and the Risk Analysis Branch (RAB/ECAD/OTS)
for inclusion in ongoing reviews of glycidol and certain glycidol
derivatives. Glycidol and its derivatives were recommended by the
Interagency Testing Committee (ITC) for testing consideration by
EPA pursuant to Section 4 of TSCA. In addition, EPA fias published
TSCA Section 8(a) and 8(d) information gathering rules on glycidol
and certain glycidol derivatives.
This status report is the result of a preliminary evaluation of
information that has been submitted to EPA under Section 8(e), the "substantial
risk" information reporting provision of the Toxic Substances Control Act (TSCA).
The statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Any
review of this status report should take into account that the report may be
based on incomplete information.
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CURRENT PRODOCTION AND USE
Information relating to production and uses of glycidol as well as
the potential for exposure to glycidol can be found in an "Advance
Notice of Proposed Rulemaking" (ANPR) published by the Agency on
December 30, 1983 (see 48 FR 57562-57571). Additional information
on glycidol can be found in the "Third Report of the Interagency
Testing Committee" (see 43 FR 50630-50635 and 44 FR 18733).
COMMENTS/RECOMMENDATIONS
It should be noted that Part VII of EPA's TSCA Section 8(e) policy
statement ("Statement of Interpretation and Enforcement Policy;
Notification of Substantial Risk" 43 FR 11110; March 16, 1978)
provides a number of examples of the types of information that need
not be reported under Section 8(e) (i.e., information about which
subject persons can automatically assume EPA to be "adequately
informed"). In addition to the examples that are cited specifically
in Part VII, subject persons can automatically assume, for the
purposes of TSCA Section 8(e) reporting, that the Agency has been
adequately informed about substantial risk information contained
in a formal publication or report released to the general public
by another agency of the U.S. Government. It should be noted also
that EPA's position on the Section 8(e)-reportability of results
of NTP bioassays has been described previously; the reader's
attention is directed to the "Status Report" prepared by EPA in
response to TSCA Section 8(e) submission number 8EHQ-1282-0467.
In summary, EPA's position on the TSCA Section 8(e)-reportability
of results of NTP bioassays is as follows:
A subject person can assume automatically that the Agency
has been "adequately informed" about the results of an
NTP carcinogenesis bioassay once the NTP has formally
released copies of the draft technical report from that
study for peer review by the Technical Report Peer Review
Subcommittee of NTP's Board of Scientific Counselors.
This assumption can be made because EPA's Office of Toxic
Substances (OTS) routinely receives complete copies of
all draft NTP carcinogenesis bioassay technical reports
formally released by NTP for peer review.
Therefore, if a subject company obtains (i.e., knows of
or possesses) toxicologic information concerning an NTP
bioassay and there has not been a formal public release
of those findings by NTP (e.g., formal release of the
draft technical report for peer review), the subject
company should immediately consider the need to report
the information to EPA under Section 8(e) of TSCA.
It should be noted that EPA has correctly received a
number of Section 8(e) submissions (usually comprised of
1 to 2 typed pages) filed by companies that obtained
toxicologic data from studies conducted by/for agencies
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Page 3 of 3
of the U.S. Government that have not been published or
released formally to the general public. In each of
these cases, OTS has immediately initiated appropriate
followup activities directly with the other Federal
agency in order to minimize and, in most cases, eliminate
further TSCA Section 8(e) reporting obligations on the
part of the submitting company to provide such items as
complete copies of supporting data or actual technical
reports.
Considering the preceding discussion and in view of the fact that
the source of the oncogenicity findings reported in the present
submission by Dixie was a draft NTP glycidol bioassay technical
report that had been released formally by the NTP for peer review
by the Technical Report Peer Review Subcommittee of NTP's Board of
Scientific Counselors, Dixie's submission of those findings to EPA
under Section 8(e) was not warranted.
a) Despite the fact that Dixie was not required to report
in this instance under Section 8(e) of TSCA, EPA does
have a general interest in corporate actions taken on a
voluntary basis in response to chemical toxicity/exposure
data. Therefore, Dixie will be requested to describe the
actions the company has taken or is planning to take l)
to notify workers/others about the reported information,
and 2) to reduce or eliminate exposure to glycidol. In
addition, Dixie will be asked to describe the nature and
results, if available, of all studies (other than those
submitted already to EPA or those cited in the published
scientific literature) about which Dixie is aware or that
Dixie has conducted, is conducting or plans to conduct
that are designed to determine the toxicity of or the
exposure to glycidol.
b) As was the case for the initial submission, the Chemical
Screening Branch will immediately send a complete copy
of all reported information to the Test Rules Development
Branch and the Risk Analysis Branch.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA, TRDB/ECAD7OTS and
RAB/ECAD/OTS? in addition, copies of this status report
will be sent also to the TSCA Assistance Office (TAO/OTS)
for further distribution.
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\ UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
k WASHINGTON, DC 20460
DATE: AUG 30 1989
APPROVED:
office op
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report 8EKQ-0889-0810 8
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
The submitting company has claimed its company name to be TSCA
Confidential Business Information (CBI) . Staff of the Information
Management Division will review all incoming correspondence related
to the company's TSCA CBI claim.
SUBMISSION DESCRIPTION
The submitting company provided the following summary information
with regard to the conduct and preliminary results of an acute oral
(with 28-day followup) toxicity study of methyl vinyl oximino
silane (MVOS; CAS No. 73160-32-4) in rats:
"The results of the Study indicate that, unlike other
oximino silanes tested, MVOS had an adverse effect on the
reproductive system in male rats [(strain not specified) ]
following a single oral (gastric intubation) exposure at
dose levels of 0.2, 1.0 and 2.0 ml/kg. Although these
dose levels are significantly higher than potential human
exposure, and the oral route is not considered [to be]
a potential route of exposure as a result of foreseeable
uses for MVOS, these results raise some concerns about
MVOS as a potential male reproductive toxin. Exposure to
MVOS via the inhalation route would also be limited since
1 This status report is the result of a preliminary evaluation of
information that has been submitted to EPA under Section 8(e), the "substantial
risk" information reporting provision of the Toxic Substances Control Act (TSCA).
The statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemLcal(s). Any
review of this status report should take into account that the report may be
based on incomplete information.
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Page 2 of 4
MVOS has a very low vapor pressure (1.2 mm Hg at 7 5°C)
and readily disassociates when exposed to atmospheric
moisture.
"Specifically, microscopic examination of the testes and
epididymides from rats sacrificed at various times during
the study revealed bilateral degeneration of the germinal
epithelium of the testes with associated intratubular
formation of spermatocytic-spermatidic giant cells. The
lesions occurred in a dose-related manner. The germinal
epithelium degeneration was observed from day 1 through
day 28 in the high-dose group (2.0 ml/kg), day 1 through
day 21 in the mid-dose group (1.0 ml/kg), and on day 7
and day 14 in the low-dose group (0.2 ml/kg) . Exfoliation
of the germinal epithelium of the testes was felt to
account for increased bilateral accumulation of cellular
debris observed in epididymal ducts during the study.
"The pathologist believed that the test compound damaged
the primary spermatocytes, secondary spermatocytes and
spermatids such that these cells were absent from tissue
sections of the testes observed as early as 24 hours
after exposure to MVOS. Nearly all of the animals on
study showed this effect. The loss of these spermatogenic
cells resulted in a disappearance of mature sperm during
the second week following exposure. Recovery was dose-
related with sperm reappearing in the testes of the low-
dose group rats by 21 days following exposure and by 28
days following exposure in mid-dose rats. Only partial
recovery was observed in high-dose rats at 28 days.
"Based on the above microscopic findings, the pathologist
concluded that reproductive capacity would be reduced 14
days after exposure in rats from the low-, mid- and high-
dose groups, 21 days after exposure in rats from the mid-
and high-dose groups, and 28 days after exposure in rats
from the high-dose group. In addition, repeated breeding
of rats from the mid- and high-dose groups from 1 to 7
days after exposure would be expected to result in poor
reproductive performance. Of particular concern was the
loss of spermatogonia observed in one rat from the high-
dose group 7 days after exposure.
"Other microscopic effects were noted in the spleen and
bone marrow, but these were generally consistent with
hemolytic anemia and compensatory hematopoiesis."
The company reported also that this particular study was conducted
"to confirm the results of an acute oral toxicity study that was
submitted . . . [Previously to the Agency with a TSCA Section 5
"Pre-Manufacture Notification" (PMN)]." Further information with
regard to the submitter's manufacture and use of MVOS can be found
in the CURRENT PRODUCTION AND USE section of this status report.
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Page 3 of 4
SUBMISSION EVALUATION
The summary information contained in this Section 8(e) submission
provides strong evidence for the ability of MVOS to cause serious
adverse reproductive system effects in male rats. Further, the
finding of adverse spleen and bone marrow effects "consistent with
hemolytic anemia and compensatory hematopoiesis" is of concern in
light of EPA's lack of parallel information on a number of other
silane-based chemicals; it is possible that these spleen and bone
marrow effects may be due, however, to the non-silane MVOS moieties
or may be specific to MVOS itself. In order for EPA to evaluate
the overall significance of the reported adverse reproductive and
hematopoietic system effects, the submitter should be asked to
ensure that the Agency receives a full copy of the final report
from the company's acute/28-day followup oral toxicity study of
MVOS in male rats. It would also be of interest to know if the
company is performing any studies designed to allow evaluation of
the potential for MVOS to produce adverse effects on the female
reproductive system.
CURRENT PRODUCTION AMD USE
In the "sanitized" (i.e., non-confidential) version of this TSCA
Section 8(e) notice, the submitting company provided the following
information with regard to MVOS:
"A . . . [Section 5 PMN] was submitted for this material
on July 10, 1985, and [was] subsequently withdrawn on
November 25, 1987, due to lack of commercial viability
at that time. . . % . Currently, MVOS is used solely
as . . . [a research and development (R&D)] compound."
The sanitized version of the company's TSCA Section 8(e) submission
did not contain any information with regard to the specific use(s)
of MVOS.
COMMENTS/RECOMMENDATIONS
In its Section 8(e) notice, the submitting company stated that the
results of the acute/28-day followup oral toxicity study of MVOS
"have been communicated to those [employees] in R&D studying the
possible development of this material." In addition, the company
reported that labels on research samples of MVOS are being revised
to include a warning about the potential for MVOS to cause adverse
male reproductive system effects.
a) The Chemical Screening Branch will ask the submitting
company to ensure that the Agency receives a full copy
of the final report (including the actual experimental
protocol, results of gross/histopathologic examinations,
results of any statistical analyses performed, etc.) from
the acute/28-day followup rat oral toxicity study that
was cited in the company's TSCA Section 8(e) submission
on MVOS.
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Page 4 of 4
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, the company will be requested to
describe the nature and results, if available, of all
studies (other than those submitted already to the Agency
or those cited in the published scientific literature)
about which the company is aware or that the company has
conducted, is conducting or plans to conduct that are
designed to determine the toxicity of MVOS.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of MVOS. In addition, and as was the case
for the initial Section 8(e) submission, the Chemical
Screening Branch will immediately send a complete copy
of any submitted information on MVOS to the Chemical
Control Division (CCD/OTS); CCD is responsible for the
administration of EPA's TSCA Section 5 "New Chemicals
Program" (NCP).
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and CCD/OTS; in
addition, copies of this report will be provided to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
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cr
^ y| UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
% P„0*°
DATES SEP 18 1989 APPROVED:
H
OFFICE OF
PESTICIDES AND
r? TOXIC substances
SUBJECT: Status Report1 8EHQ-0889-0811 S
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
The submitting company has claimed its company name and the exact
identity of the subject chemical to be TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. In the "sanitized" version of its Section 8(e)
notice, the company reported non-confidentially that the subject
chemical is an "aryl propyl ether."
SUBMISSION DESCRIPTION
The submitting company provided summary information about the
conduct and preliminary results of developmental toxicity studies
of this aryl propyl ether in rats and rabbits. The following
information was presented with regard to the rat study:
"Aryl propyl ether was administered daily by gavage [to
pregnant rats (strain not specified)] at doses of 0, 3,
10 and 30 mg/kg/day from Day 6 up to and including Day
15 of pregnancy.
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
121
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Page 2 of 5
"Clinical signs associated with treatment with aryl
propyl ether were confined to 3 0 mg/kg/day. Following
the first administration, all animals at this dosage
showed general twitching and occasional flicking of paws.
After a second administration, all animals became hyper-
sensitive, showing extreme response to touch and sound,
and were biting their forepaws; these signs continued and
after the last administration (on Day 15) all animals at
30 mg/kg/day had marked body tremors.
"At 30 mg/kg/day, reduced [maternal body] weight gain to
Day 8 was apparent following the initiation of treatment;
thereafter, weight gains compared well with controls
although parity with the control group had not been fully
restored by Day 20. At 10 mg/kg/day, a slightly reduced
weight gain was seen between Days 12 - 14 and 16 - 18;
otherwise, gains were comparable with [the] controls. At
3 mg/kg/day, gains were essentially similar to controls
throughout.
"At [the] terminal autopsy of the adults, there were no
findings which were considered to be related to [aryl
propyl ether] treatment.
"Litter parameters of the pre- and post-implantation loss
and total live young were similar among all the groups
including the controls. At 10 mg/kg/day, slightly reduced
litter and mean fetal weights were seen; however, con-
sidering no similar effects were seen at 30 mg/kg/day,
the effect at 10 mg/kg/day is thought to be coincidental
and not related to treatment.
"At gross examination, there were two malformations both
at 30 mg/kg/day. At this stage, it is not clear whether
these are treatment related."
The submission presents the following summary information with
regard to the conduct and preliminary results of the developmental
toxicity study in rabbits:
"Aryl propyl ether was administered [to pregnant rabbits
(strain not specified)] by gavage at doses of 0, 1, 3 and
9 mg/kg/day from Day 7 to Day 19 of pregnancy inclusive.
On Day 29, animals were sacrificed and litter values
determined.
"Clinical signs were apparent at varying degrees in all
treated groups and mainly consisted of flicking and
chewing of [the] paws post dosing. At 9 mg/kg/day, these
signs were generally observed throughout the treatment
period, occurring immediately after dosing and persisting
through to the initial examination on the next day. At
3 mg/kg/day, signs were generally observed throughout the
treatment period occurring about 1 hour after dosing and
122
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Page 3 of 5
were, very occasionally, apparent at the initial examina-
tion the next day; there were also 2 occasions where 2
animals recovered 2-3 hours after dosing. At 1 mg/kg/day,
signs were observed for no more than 10 days during the
treatment and [were] generally observed to occur 1-3
hours after dosing; they were never observed at the
initial examination the next day. On 6 occasions, 4
animals [in the 1 mg/kg/day group] recovered 1-3 days
after dosing. Another sign related to treatment was
scabbing, seen in 2/6 animals at both 3 and 9 mg/kg/day,
which appeared to be directly correlated with the history
of chewing seen during the dosing period.
"One control animal showed marked anorexia until Day 9
of pregnancy and appeared to be unduly influencing the
group mean body weight gain. Excluding this animal, the
following summarizes the findings.
"Following initiation of treatment, an apparent dose
related reduction in [the] food intake was seen with
respect to the control value. Evidence of recovery is
seen throughout the remainder of the treatment period,
although parity with controls is not achieved until Days
24 - 28.
"Weight loss at 9 mg/kg/day was apparent from initiation
of treatment to Day 9, thereafter weight gain comparable
with controls was seen to Day 15; reduced weight gain is
seen to Day 20 with [the] gains comparing favorably with
controls to termination. At 3 mg/kg/day, slight weight
loss from Day 9 to Day 11 was seen along with reduced
weight gain from Day 15 to Day 20; other gains compared
favorably with controls. At 1 mg/kg/day, there was no
conclusive evidence that the slightly reduced weight gain
following initiation of dosing was related to treatment.
"At terminal autopsy, 1 and 2 animals at 3 and 9 mg/kg/
day [respectively] had scabbing with associated fur loss;
a further 1, 1, l and 2 [animals] at 0, 1, 3 and 9 mg/kg/
day [respectively] had fur loss alone. None of the other
findings were considered to be related to treatment with
aryl propyl ether.
"Total litter sizes generally reflected the number of
implantations and post-implantation losses, upon which
there was no clear dosage related effect. Litter weights
similarly reflected litter size, although at this stage,
there appeared to be a slight reduction in mean fetal
weight at 9 mg/kg/day. The sex ratios were generally
comparable among all the groups.
"There were three fetuses with gross morphological
changes, one each at 0, 1 and 9 mg/kg/day. None were
judged to be related to treatment."
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SUBMISSION EVALUATION
With regard to the rat study, there was evidence of maternal
toxicity after exposure to 10 mg/kg/day and 3 0 mg/kg/day. There
was reduced maternal body weight gain at 30 mg/kg/day on gestation
days 7-8, and at 10 mg/kg/day on gestation days 12-14 and 16-18.
The dams in the 30 mg/kg/day group exhibited clear clinical signs
of neurotoxicity. The clinical signs seen following the first
administration of aryl propyl ether included general twitching and
occasional flicking of the paws. On the subsequent 30 mg/kg dosing
days, the dams showed sensory hypersensitivity and were found to
be biting their paws. These neurotoxicological signs, which con-
tinued through and beyond the last day of dosing (i.e., gestation
day 15), were accompanied by marked whole body tremors; the actual
duration of these effects is not clear from the submitted summary
information. The terminal autopsy was reported to show no findings
related to treatment; however, without a full copy of the actual
necropsy protocol, the overall adequacy of the neurotoxicological
methods used in the study is unknown.
With regard to the rabbit study, maternal toxicity was reported to
be evident at all dose levels administered (1, 3 and 9 mg/kg/day).
The provided summary reports that there was a dose-related decrease
in food consumption. Further, a reduction in body weight gain was
reportedly seen on gestation days 7-9 and 15-20 for dams receiving
9 mg/kg/day and on gestation days 9-11 and 15-20 for dams receiving
3 mg/kg/day. Clinical signs of neurotoxicity, including flicking
and chewing of paws, were reportedly observed at all dose levels.
As in the rat teratology study, the provided necropsy information
is not sufficient to permit a full neurotoxicological evaluation.
The clinical signs that were observed in rats and rabbits following
daily oral administration of amyl propyl ether are associated with
polyneuritis. Chemicals that have been shown to induce central or
peripheral nervous system polyneuritis, characterized by an initial
hypersensitivity, include alkyl and aryl phosphates, kepone, DDT
acrylamide and n-hexane. Although no supporting data were located
on aryl propyl ether, the submitted data suggest strongly that this
chemical can produce a similar neurological syndrome. It would be
of interest to know if the company is conducting or plans to con-
duct a neurotoxicity battery (that would include a full functional
observational battery (FOB), motor activity evaluation and complete
neuropathology). If so, special attention should be given to the
neuropathological protocol to ensure proper tissue preparation,
storage, handling and evaluation.
With regard to developmental effects, reduced litter/body weight
was seen only for the 10 mg/kg/day rat fetuses and reduced mean
body weights was found only for the 9 mg/kg/day rabbit fetuses.
Further, two 30 mg/kg/day rat fetuses had "malformations" and 3
rabbit fetuses (1 each from the 0, 1 and 9 mg/kg/day dose groups)
were to have "gross morphological changes." Based solely on the
submitted summary information, however, a developmental toxicity
evaluation for this aryl propyl ether is not possible at this time.
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Page 5 of 5
CURRENT PRODUCTION AND USE
In view of the submitter's TSCA CBI claims, no information about
the TSCA Chemical Substance Inventory status or specific use of the
subject chemical will appear in this report. According to the
"sanitized" (i.e., non-confidential) version of the Section 8(e)
notice, this aryl propyl ether is being used by the submitting
company solely for research and development (R&D) purposes.
COMMENTS/RECOMMENDATIONS
The submitting company stated that all of the company's R&D
personnel who might be exposed to this aryl propyl ether were
informed about the reported toxicological findings.
a) The Chemical Screening Branch will ask the submitter to
ensure that EPA receives complete copies of the final
reports (including the actual experimental protocols,
results of gross and histopathological examinations,
results of any statistical analyses, etc.) from the rat
and rabbit developmental toxicity studies cited in the
company's submission. In addition, the submitter will
be asked to provide, to the fullest extent possible, a
detailed chemical characterization of this aryl propyl
ether.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, the submitter will be requested
to describe the nature and results, if available, of all
studies (other than those submitted already to the Agency
or those cited in the published scientific literature)
about which the company is aware or that the company has
conducted, is conducting or plans to conduct that are
designed to determine the toxicity of this aryl propyl
ether.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of the subject chemical.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be provided to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
125
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%
Page 1 of 4
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
DATE: SEP 22 1989 APPROVED
: Oi f/^
Oh F ICE Of
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT; Status Report1 8EHQ-0889-0812
Zbu**i
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
Hercules Incorporated provided the first 38 pages of "PART I" of
a February 24, 1986 report from a chronic (2-year) toxicity and
oncogenicity study of 1,3-dichloropropan-2-ol (CAS No. 96-23-1)
administered in the drinking water to Wistar rats. The "SUMMARY"
portion of the submitted document gives the following information
regarding the conduct of this 2-year bioassay:
"In this chronic toxicity and oncogenicity study, 1,3-
dichloropropan-2-ol was administered [at daily doses of
0, 27, 80 or 240 mg/1] in the drinking water to Wistar
rats for 104 weeks. The study was comprised of four
groups, each containing 80 male and 80 female rats."
The "ASSESSMENT" section of the submitted document contains the
following information about the results of this study:
". . . . The pathomorphologic findings in this study
strongly suggest an oncogenic effect of 1,3-dichloro-
propan-2-ol on [the] liver (hepatocellular adenomas and
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
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carcinomas, hemangiosarcomas), kidney (tubular adenomas
and carcinomas), oral epithelial/tongue (papillomas and
carcinomas) and thyroid gland (follicular adenomas and
carcinomas) in rats at dose levels of 80 and 240 mg/1
water."
"It cannot be decided from this study, whether or not
the single papilloma observed in the tongue of one male
in group 2 [(27 mg/1)] reflects an oncogenic effect of
the test article or whether it is a spontaneous finding.
Historical data reveal that papillomas and carcinomas in
the tongue have rarely occurred spontaneously in the
Wistar rat strain used by RCC. The same holds true for
the papilloma observed in the forestomach of one of ten
females examined in group 4 [(240 mg/1)] after 78 weeks
of treatment.
"The increased incidence of slight to moderate hepatic
fatty change [observed] in groups 3 and 4 [(80 and 240
mg/1, respectively)], and the increased incidence of
hemosiderin-storing Kupffer cells in the liver in animals
of groups 3 and 4 may reflect a metabolic disturbance of
the liver caused by the test article.
"The significance of the sinusoidal peliosis observed in
all treated groups is not clear. However, peliosis may
represent a preneoplastic stage of vascular hepatic
neoplasia, such as hemangiosarcoma . . .
"The other neoplastic and non-neoplastic lesions noted
in this study are considered to be incidental since they
are commonly encountered in rats of this strain and age."
According to the portion of PART I that was submitted by Hercules,
the subject study was conducted from 1983 to 1985 by the Research
and Consulting Company AG (RCC; Switzerland) for the tyerband der
Suppenindustrie e.V. (roughly translated to be the Association of
Soup Producers). Hercules stated that the company is contacting
the European sponsor in an attempt to obtain a full copy of the
final report of this 2-year drinking water study for supplemental
submission to the Agency.
It should be noted that in previous TSCA Section 8(e) submissions
(8EHQ-1280-0401 et seq.), the Stauffer Chemical Company reported
that tris(l,3-dichloropropan-2-ol)phosphate (CAS No. 13674-87-8)
caused a statistically significant increase in malignant liver
tumors (hepatocellular carcinomas) at 80 mg/kg/day, the highest
dose level tested in a 2-year feeding study in rats. For further
information with regard to tris(l,3-dichloropropan-2-ol)phosphate,
the reader's attention is directed to the status report that was
prepared by the Agency in response to these previous Section 8(e)
submissions. The reader's attention is also directed to a "Chemical
Hazard Information Profile" (CHIP) that was prepared by EPA in 1981
on tris(l,3-dichloropropan-2-ol)phosphate.
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Page 3 of 4
SUBMISSION EVALUATION
Based on a preliminary review of the submitted information only,
this 2-year study appears to be well designed, well conducted, and
thorough. The provided information indicates clearly that at the
two highest doses administered (80 and 240 mg/1), 1,3-dichloro-
propan-2-ol induced a wide variety of benign and malignant tumors.
Further, the reported pre-neoplastic pathomorphologic observations
are consistent fully with the observed oncogenic effects.
A complete evaluation of the findings from this chronic drinking
water study should be possible if a full copy of the final report
can be obtained by Hercules and sent to the Agency. If Hercules
is not successful in its attempt, however, other avenues should be
explored immediately by the Agency in order to obtain the complete
final report of this study.
CURRENT PRODUCTION AND USE
A review of the production range (includes importation volumes)
statistics for 1,3-dichloropropan-2-ol (CAS No. 96-23-1), which is
listed in the initial TSCA Chemical Substance Inventory, has shown
that between 2,000 and 20,000 pounds of this chemical were reported
as manufactured and/or imported in 1977. This production range
information does not include any data that were claimed to be TSCA
Confidential Business Information (TSCA CBI) by the person(s) who
reported for the TSCA Inventory, nor does it include any informa-
tion that would compromise TSCA CBI.
All of the data that were reported for the initial TSCA Inventory,
including the above cited production range data, are subject to the
limitations contained in the TSCA Inventory Reporting Regulations
(see 40 CFR 710).
The Condensed Chemical Dictionary (10th Edition) states that the
uses of 1,3-dichloropropan-2-ol include: "General solvent; inter-
mediate in organic synthesis; paints, varnishes, lacquers; water
colors' binder; photographic lacquers."
It must be noted that in a previous "For Your Information" (FYI)
submission (FYI-OTS-0586-0493), Exxon Chemical Americas stated that
l/3-dichloropropan-2-ol was detected (along with several other by-
products and impurities) in polyamine/epichlorohydrin polymers that
had been approved for drinking water treatment. The other reported
impurities were epichlorohydrin (CAS No. 106-89-8), 3-chloro-l,2-
propanediol (CAS No. 96-24-2) and glycidol (CAS No. 556-52-5). In
this FYI notice, Exxon stated that the "sum of the concentration
of such compounds [including l,3-dichloropropan-2-ol] was sometimes
found to exceed the 500 ppm level, the concentration generally
recognized as the acceptable level for residual monomers such as
epichlorohydrin, acrylamide, and monomethyl amine." Exxon reported
also that the concentrations of these contaminants "are variable,
and highly dependent on the manufacturing process." Exxon reported
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Page 4 of 4
further that as the result of its evaluation and despite the fact
that the company's polyamine/epichlorohydrin polymer drinking water
treatment products had been approved by EPA's Office of Drinking
Water (ODW/OW), Exxon decided not to provide for potable drinking
water treatment any polyamine/epichlorohydrin polymer products
"where the combined concentrations of these contaminants exeeds 500
ppm." Finally, Exxon stated that the reported findings were being
provided to other manufacturers and to the Chemical Manufacturers
Association (CMA) Potable Water Additives Panel. Immediately upon
receipt of Exxon's FYI submission, the Chemical Screening Branch
sent full copies of that notice to a number of other EPA offices
including ODW/OW.
COMMENTS/RECOMMENDATIONS
On June 15, 1988, the Test Rules Development Branch (TRDB/ECAD/OTS)
published a TSCA Section 4 "Test Rule" (53 FR 22300) that requires
subchronic toxicity and soil adsorption testing on 1,3-dichloro-
propan-2-ol. The testing of this chemical, as well as more than
3 0 other chemical substances, was requested by the Office of Solid
Waste (OSW) in the Office of Solid Waste and Emergency Response
(OSWER) to support EPA's Hazardous Waste Regulatory Program under
the Resource Conservation and Recovery Act (RCRA).
a) In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity and/or exposure data, Hercules will be asked to
describe the actions that the company has taken or plans
to take 1) to notify workers/others about the reported
information, and 2) to reduce or eliminate exposure to
the subject chemical. In addition, Hercules will be
asked to describe the nature and results, if available,
of all studies (other than those submitted already to EPA
or those cited in the published scientific literature)
about which the company is aware or that the company has
conducted, is conducting or plans to conduct that are
designed to determine the toxicity of or the exposure to
1,3-dichloropropan-2-ol.
b) As was the case for the initial Section 8(e) submission,
the Chemical Screening Branch will immediately transmit
full copies of all reported information to TRDB/ECAD/OTS,
OW/EPA and OSW/OSWER/EPA. The Chemical Screening Branch
will continue to review all reported information in order
to determine the need for further OTS assessment of 1,3-
dichloropropan-2-ol.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and TRDB/ECAD/OTS ?
copies of this status report will be sent to staff of the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
129
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Page 1 of 3
OFFtCfe OF
PESTICIDES AND
TOXIC SUBSTANCES
This TSCA Section 8(e) notice was submitted to EPA by the Chemical
Manufacturers Association (CMA) Rubber Additives Panel on behalf
of companies who are members of the MBT (2-mercaptobenzothiazole)
Task Group. A list of these member companies, who manufacture or
distribute MBT, or import MBT-containing rubber articles, can be
found on the last page (page 3) of this status report.
SUBMISSION DESCRIPTION
In its Section 8(e) submission, CMA presented preliminary results
from a developmental toxicity study of MBT (CAS No. 149-30-4)
administered by gavage at doses of 0, 300, 1200 or 1800 mg/kg/day
to pregnant rats. According to CMA, preliminary results of this
developmental toxicity study, conducted in response to a final TSCA
Section 4 Test Rule (September 7, 1989; 53 FR 34514), "show an
increase in postimplantation loss." According to the submission,
the increase in postimplantation loss, which was "almost entirely
dependent upon early resorptions," was statistically significant
(when compared to concurrent controls) at 300 and 1800 mg/kg/day
but not at 1200 mg/kg/day. In addition, CMA presented an in-depth
discussion to support CMA's belief that the reported findings may
not be toxicologically or biologically significant.
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
cr
ssi
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON. DC 20460
date: SEP 2 2 1989
APPROVED
= rfM, yMf
SUBJECT: Status Report1 8EHQ-0889-0813
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
130
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8EHQ-0889-0813
Page 2 of 3
SUBMISSION EVALUATION
Immediately upon receipt, the Chemical Screening Branch transmitted
full copies of this TSCA Section 8(e) submission to the Test Rules
Development Branch (TRDB/ECAD/OTS) for inclusion in their ongoing
evaluation of available toxicological and exposure information on
MBT, a chemical recommended for testing by the Interagency Testing
Committee (ITC). In addition, EPA has published TSCA Section 8(a)
and 8(d) information gathering rules for MBT,
CURRENT PRODUCTION AND USE
Information about the production and use of, as well as information
on the potential exposure to, MBT can be found in the final TSCA
Section 4 Test Rule on MBT (53 FR 34514; September 7, 1988).
COMMENT8/RECOMMENDATIONS
To date, EPA has received a number of TSCA Section 8(e) submissions
from trade associations on behalf of their member companies. The
Agency reiterated its position regarding the Section 8(e) reporting
obligations of trade associations and their member companies in the
COMMENTS/RECOMMENDATIONS section of the status report prepared for
Section 8(e) submission 8EHQ-0186-0587. The reader's attention is
directed to this previous status report for further information.
It is important to point out also that the Section 8(e) reporting
requirement applies to any substantial risk information2 obtained
during a study conducted pursuant to Section 4 of TSCA unless such
information, when obtained, is otherwise required to be submitted
to EPA under Section 4 of TSCA. To date, EPA has received a number
of TSCA Section 8(e) notices containing interim results of studies
conducted under Section 4 of TSCA. The Section 8(e) reporting that
takes place in such instances occurs typically before reporting of
the information is required under Section 4. If required reporting
under Section 4 occurs before or coincidental with an obligation
to report under Section 8(e), however, the information does not
need to be submitted also under Section 8(e). The purpose of this
exemption is not to change substantially the TSCA Section 8(e)
reporting obligation, but is merely to avoid duplicative reporting
except in those cases where timeliness of reporting is paramount.
2 As defined in the Agency's March 16, 1978 TSCA Section 8(e) policy statement
("Statement of Interpretation and Enforcement Policy; Notification of Substantial Risk" 43 FR
11110), the term "substantial risk information" is any new information that offers reasonable
support for a conclusion that a subject chemical or mixture presents a substantial risk of injury
to health or the environment; new information is that information about which EPA is not
already adequately informed.
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8EHQ-0889-0813
Page 3 of 3
a) The Chemical Screening Branch will ask CMA to ensure that
the Agency receives a complete copy of the final report
(including the actual experimental protocol, results of
gross and histopathological examinations, results of any
statistical analyses, etc.) from the developmental
toxicity study of MBT in rats cited in the submission.
b) The Chemical Screening Branch will ensure that full
copies of all submitted documents on MBT are forwarded
immediately to TRDB/ECAD/OTS for review.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and TRDB/ECAD/OTS;
in addition, copies of this status report will be sent
to the Environmental Assistance Division/OTS (formerly
the TSCA Assistance Office/OTS) for further distribution.
The Chemical Screening Branch will ask CMA to send full
copies of this status report to each of the companies
listed below.
CMA Rubber Additives Panel/MBT Task Group Member Companiea
Akzo Chemicals Inc.
BF Goodrich Company - Chemical Group
Firestone Tire and Rubber Company
Goodyear Tire and Rubber Company
Mobay Corporation
Monsanto Company
Quimica Organica De Mexico, S.A. de C.V.*
R.T. Vanderbilt Company, Inc.
Uniroyal Chemical Company. Inc.
* on behalf of the Albis Corporation, Lyons
Associates and the Vivion Chemical Company
132
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 3
OFFICE OF
date: SEP 2 5 1989
APPROVED:
TOXIC SUBSTANCES
PESTICIDES AND
SUBJECT: status Report 8EHQ-0889-0814
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
The CIBA-GEIGY Corporation submitted final reports from 6 jjj vitro
genotoxicity studies of bis-trimethylolpropane tetraglycidyl ether
(LMB-4075; no CAS Registry Number as yet). According to CIBA-GEIGY,
LMB-4075 was found to be positive 1) in the presence of exogenous
metabolic activation in an Ames Salm
-------
8EHQ-0889-0814
Page 2 of 3
this claim are illegible. In the absence of more readable copies
of the data tables, therefore, this particular study is considered
to be an "unconfirmed" negative. Overall, however, the obtained
negative findings do not outweigh a cause for concern that LMB-4075
may be a potential germ cell mutagen and carcinogen; this concern
is based on the positive results from gene mutation and chromosomal
aberration assays.
CURRENT PRODUCTION AND DSE
According to CIBA-GEIGY, "LMB-4075 is a new developmental epoxy
resin intended for coating applications." CIBA-GEIGY reported also
that only small quantities have been imported thus far into the
U.S. for research and development (R&D) purposes. In addition,
the company stated that 2 potential customers have received samples
of LMB-4 075 to date. CIBA-GEIGY reported further that the LMB-4075
exposure should be "minimal or nil" when the chemical is handled
in accordance with the current Material Safety Data Sheet (MSDS)
which carries the following precautionary information:
"Wear impervious gloves. Wear splash-proof chemical
goggles. Use NIOSH approved organic vapor cartridge
respirator when vapor/mist exposure is likely. Wear
appropriate protective equipment to avoid personal
contact and exposure."
CIBA-GEIGY reported that once LMB-4075 "is used in its intended
application, it becomes a highly crosslinked, high molecular
weight, insoluble and inert material.1' Finally, CIBA-GEIGY stated
that there is no consumer exposure to LMB-4075.
COMMENTS/RECOMMENDATIONS
Although a positive iB vitro genotoxicity test, when considered
alone, may not be sufficient to offer reasonable support for a
conclusion of substantial risk (as that term is defined in EPA's
TSCA Section 8(e) policy statement ("Statement of Interpretation
and Enforcement Policy? Notification of Substantial Risk" 43 FR
11110; March 16, 1978)), EPA does believe that such information is
of value in assessing the possible risk(s) posed by exposure to the
tested chemical or mixture. Further, EPA believes that a positive
genotoxicity test result, in combination with other * information
(e.g., knowledge of actual/potential exposure to and/or high pro-
duction of the tested chemical or mixture), would suggest the need,
in many cases, to conduct further studies designed to determine
the toxicity of or the exposure to that chemical or mixture. EPA
expects the results of such additional studies to be considered
also for submission under Section 8(e) of TSCA.
In its submission, CIBA-GEIGY stated that the company is revising
the current LMB-4075 MSDS to reflect the reported positive and
negative genotoxicologic findings. CIBA-GEIGY reported also that
the company is informing its workers and the 2 potential LMB-4075
customers about the submitted findings.
134
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8EHQ-0889-0814
Page 3 of 3
Immediately upon receipt of this TSCA Section 8(e) notice, staff
of the Chemical Screening Branch transmitted full copies of the
notice to the Test Rules Development Branch (TRDB/ECAD/OTS) and
the Risk Analysis Branch (RAB/ECAD/OTS) for inclusion in their
ongoing reviews of glycidyl ethers and epoxy resins, respectively.
a) The Chemical Screening Branch will request CIBA-GEIGY to
submit, if available, readable copies of all data tables
from the cell transformation assay of LMB-4075.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, CIBA-GEIGY will be requested to
describe the nature and results, if available, of all
studies (other than those submitted already to the Agency
or those cited in the published scientific literature)
about which CIBA-GEIGY is aware or that the company has
conducted, is conducting or plans to conduct that are
designed to determine the toxicity of LMB-4075.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of the subject chemical substance.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA, and TRDB and
RAB/ECAD/OTS; in addition, copies of this status report
will be provided to staff of the Environmental Assistance
Division/OTS (formerly the TSCA Assistance Office/OTS)
for further distribution.
135
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Page 1 of 10
W
'%r/
PoO^
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
DATE: AUG I 6 1989 APPROVEDaUxtToseph ST. Merenda
OFFICE O
PESTICIDES AND
toxic surstances
SUBJECT: status Report1 8EHQ-0886-0815 INIT
8EHQ-0487-0815 FLWP
FROM: Frank D. Kover, Chief
Chemical Screening Branch/ECAD
TO: Joseph J. Merenda, Director
Existing Chemical Assessment Division/OTS
NOTE
In an initial "For Your Information" (FYI) notice (FYI-OTS-0886-
0506 S Initial), the submitting company claimed its name and the
exact identity of the subject chemical to be TSCA Confidential
Business Information (TSCA CBI). In addition, the submitting
company claimed the production volume and use of the subject
chemical to be CBI. In the "sanitized" version of the company's
initial FYI notice, the company reported non-confidentially that
the subject chemical is a pyrazole carboxamide. In a follow-up
FYI notice (FYI-OTS-0487-0506 Followup Response), the Eli Lilly
Company withdrew its CBI claims for company identity, chemical
identity, and intended use of the subject chemical. According to
the "declassified" version of Eli Lilly's initial FYI notice and
the company's non-confidential followup response, the subject
chemical is 5-cyano-l-(l,1-dimethylethyl)-N-methyl-lH-pyrazole-4-
carboxamide, a research and development (R&D) substance intended
for use as a broadleaf herbicide.
SUBMISSION DESCRIPTION
In FYI-OTS-0886-0506 S Initial, Eli Lilly provided the following
summarized findings from an oral toxicity study of this pyrazole
carboxamide in dogs:
This status report is the result of a preliminary evaluation of
information that has been submitted to EPA. The statements made in this status
report should not be regarded as expressing final Agency policy or intent with
respect to the subject chemical (s). Any review of this status report should take
into account that the report may be based on incomplete information.
136
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Page 2 of 10
"In a preliminary toxicity study, a pyrazole carboxamide
was administered daily by capsule to two beagle dogs of
each sex for three days at 0.5 mg/kg body weight, for two
weeks at doses of 1.5 or 5.0 mg/kg, and for 11 days at
10 mg/kg. At a dose of 10 mg/kg, tonic/clonic convul-
sions, myoclonic jerking, ataxia and hypoactivity were
observed sporadically in all [of the] dogs from test day
4 through study termination, but there was no histopatho-
logic evidence of central or peripheral nervous system
abnormalities. With the exception of emesis in one dog
(given 1.5 mg/kg), all animals given 0.5, 1.5, or 5.0
mg/kg body weight appeared normal throughout the study
and no effects were detected at any dose levels in body
weights, organ weights, electrocardiograms, histopath-
ology, clinical chemistry, hematology or in neurological
examinations."
In submitting these summarized toxicologic findings to the Agency
on an FYI basis, Eli Lilly stated the company's belief that "the
exposure of certain chemicals is too low to be within the scope of
[TSCA Section] 8(e) if:
"the chemicals are handled only by company research and
development [(R&D)] personnel who are trained in working
with hazardous chemicals, and
"the personnel are supplied with all appropriate safety
equipment, such as laboratory exhaust hoods, dust masks,
rubber gloves, aprons, etc. and
"the personnel handle the chemicals only in company
laboratories, test plots, or pilot plants, and
"no other company is likely to be working with the
compound."
In its review of the initial FYI submission, EPA stated that the
neurotoxicological effects (i.e., tonic/clonic convulsions, myo-
clonic jerking, ataxia, hypoactivity) that reportedly occurred
sporadically from day 4 to termination in all dogs receiving the
10 mg/kg dose level are of concern especially considering the small
amount of pyrazole carboxamide administered. Although the submitter
stated that there was no histopathologic evidence of central or
peripheral nervous system abnormalities, EPA noted that it is not
necessary to have a histopathological correlate to convulsions.
In addition, EPA noted that the lower doses (i.e., 0.5, 1.5 or 5.0
mg/kg) administered may have altered the seizure thresholds in the
absence of frank seizures in the exposed animals.
Based on EPA's review of the information contained in the initial
FYI notice, EPA informed Eli Lilly in writing (EPA letter dated
March 3, 1987) that the Agency believed that the neurotoxicologic
findings'presented in the initial FYI notice provided reasonable
support for a conclusion that the subject chemical substance can
137
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Page 3 of 10
cause serious or prolonged incapacitation and as such should have
been submitted formally to the Agency pursuant to Section 8(e), the
"substantial risk" information reporting provision of TSCA.
In its March 3, 1987 letter, EPA requested Eli Lilly to submit a
full copy of the final report from the company's 2-week oral dog
study. In addition, Eli Lilly was requested to describe 1) the
nature and results of all other studies (especially neurotoxicity
studies) that the company had conducted on the subject chemical,
and 2) the actions the company had taken to notify its workers
about the reported toxicologic findings. Finally, Eli Lilly was
asked to submit further information explaining its decision not to
submit the neurotoxicologic findings under Section 8(e).
In response to EPA's March 3, 1987 letter, Eli Lilly provided (FYI-
OTS-0487-0506 Followup Response) all of the information requested
by EPA. In addition to a full copy of the final report from the
2-week oral study in dogs, Eli Lilly submitted the final reports
from a number of in vitro and in vivo toxicologic studies of the
subject chemical. Eli Lilly also provided an Experimental Compound
Safety Data Sheet that summarizes the toxicity of this pyrazole
carboxamide as follows:
"ACUTE EXPOSURE; The median lethal dose of 181977 [(the
subject pyrazole carboxamide) ] was greater than 500 mg/kg
of body weight when administered orally to mice and male
rats, and between 50 and 500 mg/kg in female rats. Signs
of toxicity were leg weakness, clear ocular discharge,
poor grooming, chromorhinorrhea, salivation, ataxia,
hypoactivity, lethargy, and coma.
"DERMAL EXPOSURE: Single doses of 2000 mg of 181977 per
kg of body weight, applied to the skin of rabbits for 24
hours, caused no systemic toxicity or dermal irritation.
"OCULAR EXPOSURE: single doses of 181977, when instilled
into rabbit eyes, caused corneal dullness to slight
corneal opacity, slight iritis, and slight to moderate
conjunctivitis within one hour after exposure. Corneal
and iridal irritation cleared within 24 hours, while
conjunctival irritation cleared between two and seven
days after exposure.
"SUBCHRONIC EXPOSURE: in a six week dietary study, rats
received average daily doses of 57, 149, 317, or 727 mg
of 181977 per kg of body weight. Treatment-related
effects included decreased body weight, weight gain and
food consumption; decreased weights of heart, kidneys,
adrenals and ovaries; and an increase in liver weight;
and a dose-related increase in hepatic microsomal enzyme
activity (except in females at 57 mg/kg) . Histopathology
revealed the presence of prominent hyaline droplets in
the kidneys of males at the three highest doses. In a
two-week study in dogs, all animals survived daily oral
138
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Page 4 of 10
doses of 0.5, 1.5, 5.0, or 10.0 mg/kg. [The] signs of
toxicity were only observed at 10.0 mg/kg and included
tonic/clonic seizures, tremors, soft stools and depressed
appetite. CNS effects were reversible and disappeared
within several hours of each treatment. There were no
treatment-related effects detected on body weights, organ
weights, electrocardiograms, histopathology, hematology,
clinical chemistry or neurological examinations. The no-
effect level was considered to be 5.0 mg/kg.
"REPRODUCTION: In a preliminary teratology study in rats
given oral doses of 25, 100, 175, or 250 mg/kg 181977,
there were no fetal abnormalities noted during gross
examination.
"MUTAGENICITY STUDIES; Compound 181977 was negative in
the [modified Ames Salmonella tvphimurium (bacteria)]
gradient plate assay and the DNA repair [/synthesis] assay
in primary rat hepatocytes."
Eli Lilly also submitted the following summarized final results
from a dose-ranging study of this pyrazole carboxamide in beagle
dogs:
"Two groups of dogs, each consisting of one male and one
female, were administered a single oral dose of 5 or 10
mg of . . . [pyrazole carboxamide] . . . per kg of body
weight. The test material was placed in gelatin capsules
for dose administration. Each dog was fed four hours
after dosing and observed for signs of toxicity several
times daily for six days.
"... The female dog that received a dose of 5 mg of
. . . [pyrazole carboxamide] per kg of body weight was
normal throughout the study. The male dog that received
this same dose had myoclonic jerking that began approxi-
mately 2.5 hours after dosing and lasted for 30 minutes.
This dog was normal three hours after dose administration
and remained normal for the rest of the study.
"Male and female dogs that received 10 mg of . . .
[pyrazole carboxamide] per kg of body weight had three
and two instances of convulsions, respectively, that
occurred from one to three hours after dosing. Each
convulsive episode lasted approximately one to two
minutes and was followed by myoclonic jerking which
persisted for three to four hours after dosing in each
dog. Excessive salivation was seen in each dog following
the seizures. In addition, emesis (three times) and
hypoactivity (once) were observed in the male dog. Both
animals were normal five hours after dose administration
and on the remaining test days. No treatment-related
changes in body weight were observed in any dog during
the study."
139
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Eli Lilly's Experimental Compound Safety Data Sheet also contains
the following "CONCLUSION" regarding the mammalian toxicity of the
subject pyrazole carboxamide:
"Compound 181977 is an ocular irritant. No mutagenic or
teratogenic effects have been associated with 181977.
Repeated exposure in dogs caused reversible central
nervous system effects (convulsions, ataxia, tremors,
mild seizures) at 10.0 mg/kg body weight."
In addition, Eli Lilly provided summary information with regard to
the conduct and results of acute aquatic and avian species toxicity
studies. Excerpts from those summaries are presented below:
o Rainbow Trout (Salmo aairdneril - ". . . the acute NOEC
was at least 16 mg/L and the 96-hour LC50 with 95% confi-
dence limits was 62.5 (52.5, 74.4) mg/L.M
o Bluegill (Lepomis macrochirusl - ". . . the acute NOEC
was at least 30mg/L and the 96-hour LC50 was greater than
100 mg/L."
o Water flea fDaphnia magna) - ". . . the acute NOEC was
at least 30mg/L and the 48-hour EC50 was greater than 100
mg/L."
o Bobwhite (Colinus virainianus) - M. . . the single oral
dose 14-day LD50 was estimated to be greater than 500 but
less than 2000 mg/kg."
Eli Lilly also provided 1) a list of studies in progress that
included a 2-week feeding study in mice and pharmacokinetics and
metabolism studies in rats, and 2) a list of proposed studies that
included chronic toxicity studies in mice and rats as well as a
metabolism/pharmacokinetics study in beagle dogs.
in its followup response, Eli Lilly reiterated the company's
rationale (i.e., the four criteria described previously in this
status report) for not submitting the neurotoxicologic findings
under Section 8(e). In addition, Eli Lilly asked that EPA provide
guidance about the weight that exposure potential should be given
in a company's Section 8(e) reporting decision-makirig process.
SUBMISSION EVALUATIOM
According to the submitted information, this pyrazole carboxamide
has acute oral LD50s of approximately 500 mg/kg in rats and mice;
a~te. doses near the LD50 caused possible temporary neurotoxic
effects in rodents. When tested in rabbits, the compound itself
caused slight, temporary eye irritation, no dermal irritation and
not dermal toxicity; however, when a dry, flowable formulation
containing the subject chemical was applied topically, slight to
moderate irritation and possible systemic toxicity was observed.
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The repeated administration of non-lethal doses of this pyrazole
carboxamide to rats (0.4% or 1.0% in the diet; average of 317 or
727 mg/kg/day, respectively) for 6 weeks resulted in neurotoxic
signs (generalized and limb weakness) and adverse renal and hepatic
effects as well as possible adverse blood effects. The renal and
hepatic effects were seen at 0.18% (average of 149 mg/kg/day) and
induction of hepatic enzymes was still evident in the male rats
receiving this pyrazole carboxamide at 0.07% in the diet (average
of 57 mg/kg/day).
The neurotoxic effects were evident at much lower doses in Beagle
dogs. An acute oral dose (via capsule) of 5 or 10 mg/kg was found
to cause neurotoxic signs (myoclonic jerking at 5 and 10 mg/kg;
convulsions at 10 mg/kg). Multiple doses up to 5 mg/kg/day in dogs
did not cause any observable effects in dogs. At 10 mg/kg/day,
however, apparent neurotoxic effects characterized by tonic/clonic
convulsions, myoclonus, hypoactivity and ataxia were observed; no
functional deficits were observed during neurological examinations
and no morphological changes were found in the nerve tissues during
the histopathological examinations.
The submitted information provides evidence that this pyrazole
carboxamide is neurotoxic. It would be desirable for the proposed
subchronic (90-day) studies in rats and mice to include specific
observations for neurotoxic effects and reliable histopathological
examinations of the nervous system tissues. The studies designed
to determine the blood levels of pyrazole carboxamide in rats (in
progress) and dogs (proposed) may shed some light on the difference
in sensitivity between dogs and rodents.
With regard to the pilot teratology study, EPA believes that the
lowest adverse effect level for maternal toxicity is the highest
dose level tested (i.e., 250 mg/kg/day). This is in contrast to
Eli Lilly's report claiming that the lowest adverse effect level
was 175 mg/kg/day. Regarding developmental toxicity, no adverse
effects of treatment were seen in the mean number of corpora lutea
or implantations per litter, preimplantation loss, percentage of
resorptions, dead fetuses, mean number of viable fetuses per litter
or fetal weight. Therefore, an effect level for developmental
toxicity was not achieved in this study.
Based on the summarized final results from genotoxicity studies,
the Agency concludes that this pyrazole carboxamide does not induce
unscheduled DNA synthesis in primary rat hepatocytes. Further, EPA
believes that the prokaryote gene mutation data are inconclusive.
It is not possible for the Agency to fully evaluate the summaries
of the ecotoxicity studies supplied by Eli Lilly; however, if the
acute values provided in the summaries are valid, they would be
considered of low concern unless either exposure were high or great
chronicity occurred. The symptoms observed in the bobwhite study
(i.e., loose feces at 50, 500 and 2000 mg/kg? lethary at 2000
mg/kg) persisted in some cases for 13 days post-dosing, provide one
indication of chronicity; the deaths (8/12 birds) observed in the
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2000 mg/kg dose group up to 7 days post-dosing provide another.
It should be noted that an avian dietary study, rather than an
acute oral LD50 study, would most likely provide a better measure
of the avian hazard posed by this pyrazole carboxamide.
CURRENT PRODUCTION AND USE
According to Eli Lilly's "declassified" initial FYI notice, all of
the subject chemical produced thus far "has been kept within the
control of the research component of the company." In addition,
Eli Lilly reported that all company personnel working with this
chemical "are fully trained and familiar with safety precautions
for handling toxic chemicals." Finally, Eli Lilly reported that
because "the compound is patented and no licenses have been
issued," Eli Lilly believes that "no other company is likely to be
working with the compound." According to one of the studies con-
tained in Eli Lilly's non-confidential followup response, this
pyrazole carboxamide is intended for use as a broadleaf herbicide.
Eli Lilly reported further in its followup response letter that "in
May 1987, this compound will fall outside of Lilly's four criteria,
if Lilly's current plans continue." Finally, Eli Lilly reported
in its followup response letter that "in February 1987, a Lilly
scientist presented a paper at a Weed Science Society of America
meeting that identified the compound, named Lilly as the developer
of the compound, and described the potential uses of the compound."
NOTE
According to staff of the Registration Division in the
Office of Pesticide Programs (OPP/OPTS/EPA), Eli Lilly
had not yet applied (as of mid-June 1989) for an EUP or
registration for the subject chemical under FIFRA. This
information was verified by the Chemical Screening Branch
during a June 22, 1989 phone conversation with Eli Lilly.
During that phone conversation, Eli Lilly reported non-
confidential ly that 1) the subject chemical will probably
not be used as an herbicide in the United States, and 2)
all ongoing field research on the chemical is now being
conducted in Europe.
COMMENTB/RECOMMENDATIQNfi
In addition to conducting additional studies to better define the
toxicity of this chemcical, Eli Lilly reported that 1) workers were
informed of the company's "high to severe toxicity" hazard ranking
for the chemical, 2) precautionary label statements and statements
of practical treatments accompanied all formulations that were
developed for field testing, and 3) requirements were issued for
workers to wear the appropriate safety equipment and protective
clothing.
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Following a review of the information contained in FYI-OTS-0886-
0506 Initial and FYI-OTS-0487-0506 Followup Response, EPA has
determined that the neurotoxicologic findings presented therein
should have been submitted to EPA formally under Section 8(e), the
"substantial risk" information reporting provision of TSCA. The
basis for the Agency's determination is as follows:
Under TSCA, EPA can regulate certain activities that
involve chemical substances and mixtures. A substance
that is manufactured, processed or distributed in com-
merce solely as a pesticide is excluded by Section 3 of
TSCA from TSCA regulation. In accordance with EPA's TSCA
Chemical Substance Inventory reporting regulations (43
FR 64585, December 23, 1977, Appendix A, Comments 37, 38
and 39), however, a chemical substance which is in the
process of research and development (R&D) as a pesticide
is subject to TSCA until the manufacturer or importer
demonstrates the intent to create a pesticide by sub-
mitting to EPA an application for an experimental use
permit (EUP) or registration under FIFRA. It should be
noted that EPA affirmed this interpretation in the recent
amendments to the Agency's TSCA Section 5 "Premanufacture
Notification Rule" (51 FR 15098; April 22, 1986). Prior
to the EUP or registration stages, therefore, the Agency
treats the substance as a "chemical substance" under the
jurisdiction of TSCA, including Section 8(e) of TSCA.
Section 8(e) of TSCA states "any person who manufactures,
[imports,] processes or distributes in commerce a chemi-
cal substance or mixture and who obtains information
which reasonably supports the conclusion that such
substance or mixture presents a substantial risk of
injury to health or the environment shall immediately
inform the [EPA] Administrator of such information unless
such person has actual knowledge that the Administrator
has been adequately informed of such information."
The preface to Part V of EPA's TSCA Section 8(e) policy
statement ("Statement of Interpretation and Enforcement
Policy? Notification of Substantial Risk" 43 FR 11110;
March 16, 1978) explains that a "substantial risk of
injury to health or the environment is a risk of
considerable concern because of (a) the seriousness of
the effect . . . and (b) the fact or probability of its
occurrence." With regard to the seriousness of the
effect, Part V explains that EPA considers the types of
health effects for which substantial risk information
must be reported to include "any pattern of effects or
evidence that the chemical substance or mixture can
produce . . . toxic effects resulting in . . . serious
or prolonged incapacitation." Information concerning
these types of serious effects can be obtained directly
or inferred from designed studies (e.g., studies in
animals) as described in Part VI of the Section 8(e)
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policy statement. Part VI explains also that a subject
"person is not to delay reporting under Section 8(e) of
TSCA until he obtains conclusive information that a
substantial risk exists, but is to immediately report
any evidence that reasonably supports that conclusion."
With regard to the "fact or probability of its [(i.e.,
the serous effect's)] occurrence" criterion, Part V of
the Section 8(e) policy statement explains that certain
types of adverse health effects (e.g., neurotoxicity)
are considered so serious that relatively little or no
weight should be attached to the chemical's exposure in
determining whether a risk is substantial. Further,
EPA's response to Comment 31 in Appendix B of the policy
statement (as it pertains to a question on research and
development (R&D) chemicals) states that the occurrence
of serious effects such as those alluded to in Part V(a)
(e.g., neurotoxicity) presuppose exposure to the chemical
and must be reported immediately under Section 8(e).
Therefore, if a subject company obtains (i.e., possesses
or knows of) substantial risk information with regard to
a chemical substance during R&D of that chemical as a
pesticide, reporting is required under TSCA Section 8(e)
if such information is obtained by the company prior to
the application for an EUP for or registration of that
chemical as a pesticide under FIFRA (even though such
information might be submitted to EPA at a later date).
Considering the preceding discussion and in view of the fact that
neurotoxicity is clearly a serious toxic effect that can result in
serious or prolonged incapacitation, EPA has determined that the
neurotoxicologic information on this pyrazole carboxamide should
have been submitted to the Agency pursuant to Section 8(e) of TSCA
in accordance with the reporting procedures outlined in Part IX of
the TSCA Section 8(e) policy statement. Further, EPA believes that
the Section 8(e) policy statement is sufficiently clear with regard
to the weight that should be given to exposure in determining TSCA
Section 8(e)-applicability/reportability.
a) The Existing Chemical Assessment Division (ECAD/OTS) will
notify Eli Lilly about the Agency's decision regarding
the Section 8(e)-reportability of the neurotoxicologic
findings for this pyrazole carboxamide. Eli Lilly will
be informed also that the Chemical Screening Branch
(CSB/ECAD/OTS) has delivered the company's initial and
followup response submissions to the OTS Document Control
Officer (DCO) for appropriate handling and filing under
Section 8(e) of TSCA.
b) In regard to the above referenced submissions, Eli Lilly
will be asked to submit full copies of the final reports
(including the actual experimental protocols, results of
gross and histopathologic examinations, results of any
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statistical analyses, etc.) from the ongoing/planned
studies cited in FYI-OTS-0487-0506 Followup Response
(i.e., those studies mentioned in the next to the last
paragraph of the Submission Description section of this
status report).
c) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of this pyrazole carboxamide.
d) The Chemical Screening Branch will transmit copies of
this status report to OSHA, NIOSH, CPSC, FDA, NTP,
OW/EPA, OSWER/EPA, OAR/EPA, ORD/EPA, OPP/OPTS/EPA and
OCM/OPTS/EPA. In addition, copies of this report will
be provided to the Environmental Assistance Division/OTS
(formerly the TSCA Assistance Office/OTS)) for further
distribution.
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\ UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
i *2 i
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Page 2 of 3
mg/kg. [Maternal] food consumption and body weight gain
were decreased at all dose levels. The major malforma-
tion seen was gastroschisis. Maternal and fetal toxicity
were observed at all dose levels "
SUBMISSION EVALUATION
The reported results indicate that this halophenylcycloalkenyl
substituted aryl ester caused maternal toxicity and developmental
toxicity in the performed study. Maternal toxicity (evidenced by
reduced weight gain and lethality) was observed at all dose levels
administered. The developmental toxicity was also observed at all
doses given. There was a significant increase in post-implantation
loss and reduction in the number of dams with viable litters at
doses of 150 mg/kg or more. In addition, mean fetal body weight
was reduced in all treated groups, but the differences were not
statistically significant. The incidence of malformations was also
increased in all treated groups. The most common malformation was
gastroschisis, observed in 1 fetus at 100 mg/kg, 22 fetuses from
6/6 litters at 150 mg/kg (statistically significant) and 4 fetuses
from 1/1 litter at 250 mg/kg. The other observed malformations
included tail anomalies (2 fetuses, 1 each from the 100 mg/kg and
150 mg/kg groups), filamentous tail (2 fetuses from 2/6 litters in
the 150 mg/kg group) , exencephaly (2 fetuses from 1/1 litter at 250
mg/kg), and adactaly (1 fetus from 1/1 litter in the 250 mg/kg dose
group).
An evaluation of the overall significance of the submitted findings
should be possible upon the Agency's receipt of a full copy of the
final report (including the actual experimental protocol, results
of gross/histopathological examinations, results of any statistical
analyses, etc.) from this rat teratology study.
CURRENT PRODUCTION AND USE
In view of Rhone-Poulenc's CBI claim, no information with regard
to the TSCA Chemical Substance Inventory status or use(s) of the
subject chemical will appear in this report. The submitter stated
non-confidentially that "a relatively small amount of this material
has been synthesized for testing only and none has been distributed
external to Rhone-Poulenc Inc."
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will ask Rhone-Poulenc to
ensure that EPA receives a full copy of the final report
(including the actual experimental protocol, results of
gross and histopathological examinations, results of any
statistical analyses, etc.) from the rat teratology study
that was the subject of the company's TSCA Section 8(e)
submission.
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Page 3 of 3
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity or exposure information, Rhone-Poulenc will be
requested to describe the actions that the company has
taken or plans to take 1) to notify workers and others
about the reported data, and 2) to reduce or eliminate
exposure to the subject chemical substance. In addition,
Rhone-Poulenc will be asked to describe the nature and
results, if available, of all studies (other than those
submitted already to EPA or those cited in the published
scientific literature) about which Rhone-Poulenc is aware
or that the company has conducted, is conducting or plans
to conduct that are designed to determine the toxicity
of or the exposure to the subject chemical.
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of this halophenylcycloalkenyl substituted
aryl ester.
The Chemical Screening Branch will send copies of this
Status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; copies of this
report will be sent also to the Environmental Assistance
Division/OTS (formerly the TSCA Assistance Office/OTS)
for further distribution.
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, OC 20460
PESTICIDES AND
/ml
TOXIC SUBSTANCES
DATE: SEP 2 6 I989 APPROVED:
SUBJECTS status Report1 8EHQ-0889-0817 INIT
8EHQ-0989-0817 SUPP
/ItfrK^nu1
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OFTS
TO: Frank. D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
In the initial TSCA Section 8(e) submission (8EHQ-0889-0817 INIT),
PPG Industries, Inc. provided preliminary findings from a 13-week
inhalation study of 1,3-dioxolane (CAS No. 646-06-0) in rats. PPG
stated that this inhalation toxicity study was "a project of the
Halogenated Solvents Industry Alliance (HSIA) with PPG Industries,
Dow Chemical Company, and Vulcan Chemicals as the study sponsors."
PPG submitted the following summary information with regard to the
conduct and preliminary results of this study:
"In the [inhalation] study, groups of male and female
rats were exposed to dose levels of 0, 300, 1000 and 3000
ppm 1,3-dioxolane. Unaudited draft hematology data from
the study at the end of thirteen weeks show an apparent
dose related decrease in white cell counts which were
statistically significant in comparison to controls at
3000 ppm for males and 1000 and 3000 ppm for females.
Determination of the myeloid (M) to erythroid (E) ratio
from bone marrow smears at the end of thirteen weeks
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
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8EHQ-0989-0817 SUPP
Page 2 of 4
showed an apparent decrease in the M/E ratio only for the
3000 ppm males and females. There were no significant
body weight effects observed in the study. Based on the
available data, 300 ppm is clearly a no observed effect
level (NOEL).
"Satellite groups of animals which had been exposed for
13 weeks at the same dose levels as animals in the main
study were continued in a recovery phase following the
end of the exposure period. Hematology data show the
white cell counts for these animals to have returned to
the normal range of values for the control animals by the
end of an eight week recovery period. The animals in
these satellite groups will undergo a complete necropsy
and potential target organs (based on the 13 week main
group) will be evaluated histologically."
PPG reported further that the 13-week inhalation study also had a
group of rats exposed to 2000 ppm of a commercial PPG formulation
of l,1,l-trichloroethane (CAS No. 71-55-6) that contains <4% 1,3-
dioxolane as a stabilizer. According to PPG, "no adverse effects
were observed in the animals in this group."
Finally, PPG reported that "based on consideration of the 300 ppm
NOEL observed in this [13-week inhalation] study, the permissible
exposure levels for use of 1,1,l-trichloroethane, and the absence
of adverse effects in this study following exposure to 2000 ppm of
formulated 1,1,l-trichloroethane containing 1,3-dioxolane, . . .
[PPG believes that] there is an adequate margin of safety in [the]
present use conditions. Therefore, PPG does not believe that this
new [hematological] finding represents a significant risk."
In the supplemental Section 8(e) submission (8EHQ-0989-0817 SUPP),
the Dow Chemical Company provided a copy of the final report from
a 2-week vapor inhalation of 1,3-dioxolane in Fischer 344 rats.
The SUMMARY section of the submitted report presents the following
information about the conduct and results of this 2-week study:
"Groups of male and female Fischer 344 rats were exposed
to concentrations of 1,3-dioxolane targeted to Ije 0, 500,
2000, and 5000 ppm. Exposures were for six hours per day
for nine days at mean analytical concentrations of 0,
516, 2319, and 5132 ppm.
"Parameters examined included body weight, organ weights,
hematology, clinical chemistry, and gross and microscopic
pathology. Exposure related and concentration-dependent
effects were slight incoordination (5000 ppm males and
females) during and following each exposure, decreased
mean body weight during week two of exposure (5000 ppm
males and females), and decreased mean white blood cell
(WBC) counts (2000 and 5000 ppm males and females). The
transitory incoordination did not cause microscopic
changes in [the] tissues examined from the central and
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8EHQ-0989-0817 SUPP
Page 3 of 4
peripheral nervous system. The decreased mean WBC counts
were not associated with morphologic alterations in the
bone marrow, spleen, thymus, or lymph nodes. In addition,
there were no exposure-related microscopic changes in any
other organ or tissue.
"Male and female rats were comparable to control rats
following nine exposures to 500 ppm 1,3-dioxolane."
SUBMISSION EVALUATION
Immediately upon receipt, the Chemical Screening Branch sent full
copies of the initial and supplemental Section 8(e) submissions to
the Test Rules Development Branch (TRDB/ECAD/OTS) for inclusion in
their review of available toxicologic and exposure information on
1,3-dioxolane and 1,1,1-trichloroethane. These chemicals were
recommended by the Interagency Testing Committee (ITC) for testing
under Section 4 of TSCA. It should be noted the Agency published
TSCA Section 8(a) and Section 8(d) information gathering rules on
1,3-dioxolane and 1,1,1-trichloroethane. Full copies of the initial
and supplemental submissions were immediately sent to staff of the
Risk Analysis Branch (RAB/ECAD/OTS) for inclusion in their ongoing
review of 1,1,1-trichloroethane.
CURRENT PRODUCTION AND USE
Information pertaining to the production and uses of, as well as
the potential for exposure to, 1,3-dioxolane can be found in the
following TSCA Section 4 testing-related Federal Register notices:
48 FR 51839 (November 14, 1983) and 49 FR 32133 (August 10, 1984).
COMMENTS/RECOMMENDATIONS
In the initial submission, PPG stated that PPG's 1,3-dioxolane
supplier, workers and 1,1,1-trichloroethane formulation customers
are being notified about the reported toxicological findings. PPG
also stated that the company will ensure that handling procedures
in PPG's plant are adequate.
The following discussion pertains to the relationship between TSCA
Section 8(e) reporting and reporting that takes place pursuant to
Section 4 and Section 8(d) of TSCA. The Section 8(e) reporting
requirement applies to any substantial risk information obtained
2 As defined in the Agency's March 16, 1978 TSCA Section 8(e) policy statement
("Statement of Interpretation and Enforcement Policy; Notification of Substantial Risk" 43 FR
11110), the term "substantial risk information" is any new information that offers reasonable
support for a conclusion that a subject chemical or mixture presents a substantial risk of injury
to health or the environment; new information is that information about which EPA is not
already adequately informed.
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Page 4 of 4
during a study 1) conducted under Section 4, or 2) "listed" under
Section 8(d) as being underway, unless such information, when
obtained, is otherwise required to be submitted to EPA under
Section 4 or Section 8(d). To date, the Agency has received a
number of Section 8(e) notices containing interim findings from
studies that are being conducted under Section 4 or "listed" under
Section 8(d). The Section 8(e) reporting that takes place in such
instances occurs typically before reporting of the information is
required under Section 4 or Section 8(d). If required reporting
under Section 4 or Section 8(d) occurs before or coincidental with
an obligation to report pursuant to Section 8(e), however, the
information does not need to be submitted also under Section 8(e) .
The purpose of this exemption is not to change substantially the
TSCA Section 8(e) reporting obligation, but is merely to avoid
duplicative reporting except in those cases where timeliness of
reporting is paramount.
a) The Chemical Screening Branch will ask PPG to ensure that
EPA receives a full copy of the final report (including
the actual experimental protocol, results of gross and
histopathological examinations, results of statistical
analyses, etc.) from the 13-week inhalation study cited
in the submission.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, Dow will be asked to describe
the actions that Dow has taken or plans to take 1) to
notify workers and others about the reported information,
and 2) to reduce or eliminate exposure to 1,3-dioxolane.
b) The Chemical Screening Branch will immediately transmit
complete copies of all incoming information to, TRDB and
RAB/ECAD/OTS.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA, and TRDB and
RAB/ECAD/OTS; in addition, copies of this status report
will be provided to staff of the Environmental Assistance
Division/OTS (formerly the TSCA Assistance Office/OTS)
for further distribution.
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
(ft>
WASHINGTON, DC 20460
DATE: SEP 2 6 1989 APPROVED:
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0889-0818 S
8EHQ-0989-0818 8 SUPP
38»«««
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
The submitting company has claimed its company name to be TSCA
Confidential Business Information (CBI). Staff of the Information
Management Division will review all incoming correspondence related
to the company's TSCA CBI claim.
SUBMISSION DESCRIPTION
In its initial and supplemental TSCA Section 8(e) notices, the
submitter reported that l-bromo-2-fluoroethane (BFE; CAS No. 762-
49-2) caused extreme acute toxicity (lethality) via the oral and
inhalation routes of exposure in rats and via dermal and ocular
exposure in rabbits. According to the initial submission, the oral
(rat) and dermal (rabbit) LD50s were found to be ~5 mg/kg and <50
but >20 mg/kg, respectively. Further, all rabbits reportedly died
within 3 hours in acute eye and dermal irritation studies. With
regard to the acute inhalation toxicity of BFE, the company stated
in its supplemental submission that all rats died after a 1 hour
exposure to an atmosphere of approximately 1000 ppra BFE.
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk* information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
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8EHQ-0989-0818 S SUPP
Page 2 of 3
The submitter stated that the reported acute toxicity studies had
been conducted because the company received a TSCA Section 8(c)
allegation concerning "tightness in the chest of a few workers."
The submitter also stated that an "initial examination [of workers]
did not confirm any obvious medical effects."
SUBMISSION EVALUATION
The submitted summary information indicates that BFE is extremely
toxic by virtually all routes of exposure. An evaluation of the
overall significance of the reported findings should be possible
upon EPA's receipt of complete copies of the final reports from all
of the acute toxicity studies cited in the company's submissions.
CORRENT PRODUCTION AND USE
In the "sanitized" version of the initial Section 8(e) notice, the
submitting company reported that BFE "is not listed on the non-
confidential TSCA Inventory." In addition, the submitter stated
that BFE "has been manufactured solely for export under 40 CFR
720.30(e) for use as a pharmaceutical intermediate."
As indicated by the submitter, l-bromo-2-fluoroethane was not found
on the non-confidential printed and computerized versions of EPA's
TSCA Chemical Substance Inventory. No other information regarding
the use(s) of BFE was located in the secondary literature sources
consulted by EPA.
According to the submitting company, workplace monitoring studies
have shown that individual worker exposure to BFE is 1.5 ppm or
less and workplace area exposure is 8 ppm or less.
COMMENTS/RECOMMENDATIONS
With regard to further actions, the submitting company stated that
additional medical examinations and more animal toxicity tests are
planned. Also, the company stated that the BFE Material Safety
Data Sheet (MSDS) and product label have been updated to reflect
the reported toxicologic findings. In addition, the submitting
company stated that foreign BFE customers had been notified about
the reported findings. Finally, the submitter stated that "based
on the results of the [reported acute rat/rabbit toxicity] range-
finding studies, manufacturing of BFE has been suspended until an
exposure limit of 0.05 ppm can be maintained."
Although the reported toxicologic findings are clearly of the type
required to be submitted to EPA under Section 8(e) of TSCA, it is
not totally clear at this time that the manufacture of a chemical
solely for export as a drug intermediate is a commercial activity
subject in and of itself to TSCA and therefore Section 8(e). This
matter has been referred to the Office of the General Counsel.
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a) The Chemical Screening Branch will ask the submitter to
ensure that EPA receives a full copy of the final report
(including the actual experimental protocol, results of
gross and histopathological examinations, results of any
statistical analyses, etc.) from each study cited in the
company's initial and supplemental Section 8(e) notices.
The submitter will be requested also to keep the Agency
apprised of any significant findings from the medical
examinations reportedly planned by the company.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, the submitter will be requested
to describe the nature and results, if available, of all
studies (other than those submitted already to the Agency
or those cited in the published scientific literature)
about which the company is aware or that the company has
conducted, is conducting or plans to conduct that are
designed to determine the toxicity of or the exposure to
l-bromo-2-fluoroethane.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of l-bromo-2-fluoroethane.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and OGC/EPA; in
addition, copies of this status report will be sent to
the Environmental Assistance Division/OTS (formerly the
TSCA Assistance Office/OTS) for further distribution.
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Page 1 of 3
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
OFFICE OF
PESTICIDES AND
DATE: SEP 2 9 1989 APPROVED!
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0889-0819 8
8EHQ-0989-0819 SUPP
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Eli Lilly and Company has claimed the exact identity of the subject
chemical to be TSCA Confidential Business Information (TSCA CBI).
Staff of the Information Management Division (IMD/OTS) will review
all of the incoming correspondence related to the company's TSCA
CBI claims. In the "sanitized" version of its initial Section 8(e)
submission, Eli Lilly reported non-confidentially that the subject
chemical is a "substituted quinazoline.11
SUBMISSION DESCRIPTION
In its initial TSCA Section 8(e) submission, Eli Lilly stated that
preliminary testing of this substituted quinazoline in an acute
oral toxicity study in mice resulted in a "median lethal dose less
than 50 mg/kg." Eli Lilly provided the following summary regarding
the conduct and results of this in vivo study:
"The acute toxicity of the compound administered1 orally
to female CD-I mice was evaluated. There were three
animals in each of the three dose groups, and the animals
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
KQTE
156
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8EHQ-0889-0819 S
8EHQ-0989-0819 SUPP
Page 2 of 3
received either 50, 500, or 2000 mg/kg of the compound.
There was one survivor following a single oral dose of
50 mg/kg of this compound. All [of the] other animals at
each dose level died by Test Day 2. Antemortem signs of
toxicity included ataxia, coma, hypoactivity, lethargy,
ptosis, and tremors. The surviving animal [from the 50
mg/kg group] was normal by Test Day 3."
In its supplemental Section 8(e) submission, Eli Lilly provided
summary information regarding the conduct and results of a recently
completed bacterial mutagenicity assay using Salmonella typhimurium
and Escherichia coli. According to Eli Lilly, this substituted
quinazoline did not exhibit any mutagenic activity in the presence
or absence of exogenous metabolic activation.
SUBMISSION EVALUATION
The submitted summary information indicates that this substituted
quinazoline is extremely toxic via oral administration but is not
mutagenic in bacteria. An evaluation of the overall significance
of the reported findings should be possible upon EPA's receipt of
complete copies of the final reports from the acute mouse oral
toxicity and bacterial mutagenicity studies that were cited in the
company's initial and supplemental TSCA Section 8(e) submissions.
It should be noted that EPA recently received two TSCA Section 8(e)
notices from Eli Lilly and Company in which the company reported
two other "substituted quinazolines" to be extremely toxic (LD50s
of less than 50 mg/kg) in acute oral toxicity studies in mice. The
reader's attention is directed to the "Status Reports" prepared by
the Agency in response to these previous Section 8(e) submissions
(8EHQ-0689-0806 S and 8EHQ-0789-0808 S) .
CURRENT PRODUCTION AND USE
In view of Eli Lilly's TSCA CBI claim, no information regarding
the TSCA Chemical Substance Inventory status or use of the subject
chemical will appear in this status report. In its initial TSCA
Section 8(e) submission, Eli Lilly stated non-confidentially that
the company "has manufactured only 1.9 grams" of this substituted
quinazoline.
COMMENTS/RECOMMENDATIONS
In its initial submission, Eli Lilly stated that company employees
have been notified about the acute toxicity findings for this
substituted quinazoline. In addition, Eli Lilly reported that the
subject chemical substance is labelled as "hazardous." Finally,
Eli Lilly stated that "no other toxicology data have been generated
on this compound."
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8EHQ-0989-0819 SUPP
Page 3 of 3
a) The Chemical Screening Branch will request Eli Lilly to
ensure that EPA receives complete copies of the final
reports (including the actual experimental protocols,
results of gross/histopathological examinations, results
of any statistical analyses, etc.) from the acute mouse
oral toxicity and bacterial mutagenicity studies cited
in the company's submissions.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of this substituted quinazoline.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this report will be sent to the Environmental
Assistance Division/OTS (formerly the TSCA Assistance
Office/OTS) for further distribution.
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 9
OFFICE OF
PESTICIDES AND
DATE: NOV -3 1989 APPROVED: ///?/^TOXICSUBSTANCES
Chemical Screening Branch/ECAD
TO: Charles M. Auer, Acting Director
Existing Chemical Assessment Division/OTS
SUBMISSION DESCRIPTION
On behalf of the "Ad-Hoc Committee of Phosphorus Manufacturers,"
the Monsanto Company submitted preliminary findings from a one-
generation rat reproduction study of elemental phosphorus (CAS No.
7723-14-0). (The Committee's member companies, who manufacture,
import or distribute elemental phosphorus in the U.S., are listed
on the last page (Page 9) of this status report.) In its TSCA
Section 8(e) submission (8EHQ-0889-0820 INIT), Monsanto provided
the following summary information about the conduct and preliminary
results of this one-generation reproduction study:
"In this study, elemental phosphorus was administered by
gavage in either corn oil or tricaprylin at a dose level
of 0.075 mg/kg/day to rats 100 days prior to mating,
through mating, and either through day 15 of gestation
or throughout gestation. The preliminary results show
the occurrence of deaths in treated dams during the last
two days of gestation and during parturition. A similar
effect was seen in rats dosed throughout gestation and
those withdrawn from treatment after gestation day 15."
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Tone Substances Control Act (TSCA), as well as on a "For Your Information" (FYI) basis.
The statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical Any review of this status report should
take into account that the report may be based on incomplete information.
SUBJECT: Status Report1 8EHQ-0889-0820 INIT
8EHQ-0889-0820 SUPP
1PVT-OT«-O7ftli-0423 INIT
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In a supplemental Section 8(e) notice (8EHQ-0889-0820 SUPP), the
FMC Corporation stated that FMC concurred in Monsanto's submission
of the subject information to EPA under Section 8(e) of TSCA.
It should be noted that the Agency previously received a "For Your
Information" (FYI) notice (FYI-OTS-0785-0423) in which the Monsanto
Company submitted the following summary information with regard to
the conduct and results of a one-generation reproduction study of
elemental phosphorus in rats:
"Methods
"Elemental yellow phosphorus (Elemental P) in corn oil
was administered by gavage to three groups of 15 male and
30 female 8 week-old Sprague-Dawley derived . . . rats
at dosage levels of 0.005, 0.015, [or] 0.075 mg/Kg/day.
All [of the] animals received a constant volume of corn
oil, 5.0 ml/Kg/day. Treatment began 80 days prior to
mating and continued throughout mating, gestation and
lactation periods. A control group of 15 males and 30
female rats received the vehicle, corn oil, and a
comparable regimen. While this study was originally
designed to be a one-litter, one-generation reproduction
study, because of low fertility in all groups in the
first litter, the study was extended to a two-litter,
one-generation study. [The] dosing was continued between
the two mating periods. All adult and weaning animals
were observed for mortality and clinical signs of
toxicity twice daily. Detailed physical examinations were
performed weekly. Male body weights were recorded
weekly. Female body weights were recorded weekly and on
days 0, 6, 13 and 20 of gestation, [and] on days 0, 4,
14, and 21 of lactation. Adult food consumption was
measured weekly except during mating for males and
females. Females were smeared for ten days prior to
mating to establish estrous cycle. Smearing was
continued until evidence of copulation [was] observed.
Pups were examined twice daily and counted on days 0, 4,
14 and 21 of lactation. [The] individual pup weights
were recorded on days 0, 4, 14 and 21 of lactaticm.
"All [of the] pups were sacrificed at weaning while the
parental animals were sacrificed after weaning of [the]
Fib litter. Complete post-mortem examinations were per-
formed on 10 Fo parental males per group, all Fo parental
females, all Fo females which did not deliver litters, 10
Fib pups per sex per group, 5 Fia pups per sex per group
and all animals that died on study or were killed in a
moribund condition. All other animals were examined
externally, sacrificed by carbon dioxide asphyxiation and
discarded
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"Results
"The incidence of mortality among control, low, mid and
high level male rats was 1, 2, 0 and 0, respectively.
These deaths were not considered to be related to [the]
administration of test compound. Mortality among female
rats was 4, 1, 1 and 16 for the control, low, mid- and
high dosage groups, respectively. While the exact cause
of deaths in the high dosage group is not known (except
for one female which died of rupture of uterine walls),
these deaths are considered to be related to difficulty
at parturition because seven females died on gestation
day 21 or 22 after Fia mating and six females died on the
last two days of gestation after Fxb matings. There was
no evidence of difficulty in giving birth in the 0.015
and 0.005 mg/Kg dosage groups. There were no apparent
clinical signs of toxicity among animals treated with
Elemental P except for hair loss on both forelimbs in
the 0.075 mg/Kg/day dosage group.
"Mean body weights for Fo males in the low and mid-dosage
group, while not statistically different, were slightly
lower than controls throughout the study. In the high
dosage group, mean body weights of male rats were com-
parable to controls for the first part of the study (15
weeks) but appeared to be lower than controls for the
latter part of the study. However, there was no dose-
related decrease and thus the significance of these
changes is unknown. Mean body weights in females treated
with Elemental P were considered to be comparable to
controls. F0 mean body weights of treated females were
comparable to controls during gestation and lactation for
both litters. (The] food consumption data for treated
rats were also comparable to controls throughout the
study.
"While there was no significant difference in male and
female fertility indices in the control and treated
groups, the fertility index for male and female [rats]
in all groups for the Fia mating was low. The lowest
values [observed] occurred in the control group; the male
and female fertility index in the control group 73.3 and
60.0, respectively. These values were just outside the
historical range at . . . [the testing laboratory]. Thus
a decision was made to mate the parental animals for one
more litter. Male and female fertility indices of treated
animals for the Fib matings were comparable to controls.
Estrous cycle determined prior to Fja and Fib matings
showed occasional irregularities (prolonged estrous and
post-estrous) at equal frequencies in control and treated
groups. The mean length of gestation in the treated
groups was comparable to controls.
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"Mean number of viable pups in the Fia litter at 0.075
mg/Kg/day were slightly lower than controls, but this
change was not statistically significant. There was a
concomitant slight increase in the mean number of dead
pups in the Fia litter. [A] similar trend was also
observed in the Fib litter. Mean numbers of viable and
dead pups in the low and mid-dosage level animals for
both the Fia and Fib litters were comparable to controls.
Pup survival through weaning for both Fia and Fib litters
for all treated groups was comparable to controls.
"Mean pup weights at birth and throughout lactation were
comparable to controls. The appearance and behavior of
pups at birth and throughout lactation was not adversely
affected by treatment with Elemental P.
"There were no compound-related gross changes at necropsy
of the Fo, Fia or Fib generations. There were no compound-
related microscopic changes [observed] in the Fo and Fib
generations.
"Conclusions
"[The] administration of Elemental P at a dosage level
of 0.075 mg/Kg/day adversely affected parturition for
both litters. Mean number of live pups was also slightly
reduced in the 0.075 mg/Kg/day dosage group. The no-
observable-adverse-effect-level [(i.e., NOAEL) ] in this
study was considered to be 0.015 mg/Kg/day."
In submitting the preceding information to EPA on an FYI basis,
Monsanto noted that "while certain toxic effects of exposure to
phosphorus are well known," the adverse parturition-related effect
described in the submitted report may not be well known. Monsanto
also acknowledged the fact that "difficulty at parturition is an
infrequently observed event in rat reproduction studies." Further,
Monsanto stated specifically that the "administration of 0.07 5
mg/Kg/day of elemental phosphorus in corn oil to rats for 80 days
prior to mating, during mating and gestation was considered to have
resulted in difficulty in delivery, so much so that 13 females in
this group died on gestation days 21 or 22 (seven females during
generation of a first litter and six females during generation of
a second litter)." Monsanto also presented the following hypo-
thesis with regard to the influence that the corn oil vehicle may
have exerted on phosphorus bioavailability during the study:
"The corn oil vehicle used to prevent reaction of the
phosphorus with gastric juices and intestinal fluids
probably influenced the tissue bioavailability of [the]
phosphorus. It may not only have protected phosphorus
from degradation to phosphate ion, but may have permitted
relatively small amounts of phosphorus to have direct
access to cells."
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In conclusion, Monsanto offered the following information regarding
the significance of the findings reported to EPA on an FYI basis,
rather than under Section 8(e), the "substantial risk" information
reporting provision of the Toxic Substances Control Act (TSCA):
"This information does not indicate that [elemental]
yellow phosphorus presents a substantial risk of injury
to health of the environment because it is extremely
unlikely that anyone would ingest phosphorus at levels
sufficiently high to result in adverse effects."
SUBMISSION EVALUATION
TSCA Section 8fe^ Submission
Based on a preliminary evaluation of Monsanto's TSCA Section 8(e)
submission, which consists of a brief written summary and some data
tables, the performed one-generation reproduction study provides
evidence of the maternal and developmental toxicity of elemental
phosphorus. In this study, elemental phosphorus was tested at a
single dosage level of 0.075 mg/kg/day in corn oil or tricaprylin
as follows:
Duration of
Group Vehicle
1 corn oil
corn oil
corn oil
tricaprylin
Phosphorus
0.075 mg/kg
0.075 mg/kg
tricaprylin 0,075 mg/kg
Treatment
throughout
gestation
throughout
gestation
until day 15
of gestation
throughout
gestation
throughout
gestation
Although the submitted summary provides no evidence that there was
a treatment-related effect on male fertility, female fertility was
found to be slightly reduced in all phosphorus-treated groups (the
pregnancy rate was -8-10% less than controls) . The most significant
finding was increased mortality of dams during the last few days
of pregnancy and during parturition. The increased mortality was
observed in those groups receiving phosphorus in either corn oil
or tricaprylin throughout gestation, as well as in the single group
in which treatment with phosphorus in corn oil was stopped on day
15 of gestation. In group 2, 6 dams died on gestation day 21, 1
on day 22, and 1 on day 23. In group 3, 5 dams died on day 21 and
3 on day 22. In group 5, 4 dams died on day 21 and 2 on day 22.
No parturition-related deaths occurred in either the corn oil or
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tricaprylin control groups. In this study, there was also some
evidence of developmental toxicity in that the mean litter sizes
of the phosphorus-treated groups were found to be slightly reduced
compared to their respective control groups. The mean litter sizes
for test groups 2 and 3 were 9.7 and 11.7, respectively, while the
litter size in the corn oil control group (group 1) was 12.8; the
mean litter size of group 5 was 11.8, while litter size in the
tricaprylin control group (group 4) was 12.9. At the time that
Monsanto submitted the preliminary report to the Agency, this one-
generation reproduction study was still in the lactation period of
the Fi pups and further information about the pup body weights and
pup survival was not yet available.
FYI Submission
In the FYI submission, Monsanto provided summary results of a one-
generation rat reproduction study of elemental phosphorus. This FYI
submission consisted only of a cover letter and a short summary
report of the study; none of the actual data were provided. In
this previous study, elemental phosphorus was administered to rats
by gavage at doses of 0, 0.005, 0.015, or 0.075 mg/kg/day in corn
oil. According to the summary, there were no effects on male or
female fertility, or on body weight, and there were apparently no
clinical signs of toxicity. However, in the high-dose group (0.075
mg/kg/day), there was an increase in mortality of dams prior to or
during parturition. This is the same result as that obtained in
the study cited in Monsanto's current Section 8(e) submission.
The FYI submission summary also states that the litter size was
slightly reduced in the high-dose group (again, a similar result
to that reported in the current Section 8(e) submission), but that
pup weight, survival, appearance and behavior of treated pups were
found to be comparable to controls.
Overall Evaluation
The individual Section 8(e) and FYI submissions provide evidence
that very low exposures to elemental phosphorus (0.075 mg/kg/day)
can have a deleterious effect on dam survival just prior to and
during parturition. The biological explanation for this serious
adverse effect is not at all clear. Parturition is a very complex
sequence of events, requiring accurate biological timing. From the
summary information presented in Monsanto's Section 8(e) and FYI
submissions, the observed parturition failure could be interpreted
as being maternal or fetal in origin, and/or could represent
maternal hormonal imbalance or other factors or fetal deficit,
including death.
In order for EPA to attempt to evaluate the overall significance
of the reported toxicologic findings, Monsanto should be asked to
submit complete copies of the final reports from the reproduction
studies cited in the company's Section 8(e) and FYI submissions.
In addition, it would be of interest to know why this particular
type of toxicologic study was conducted with elemental phosphorus.
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CURRENT PRODUCTION AND OSE
A review of the production range (includes importation volumes)
statistics for phosphorus (CAS No. 7723-14-0), which is listed in
the initial TSCA Inventory, showed that about 380 million to 1.76
billion pounds were reported as produced/imported in 1977. This
production range information does not include any data claimed to
be TSCA Confidential Business Information (CBI) by the person(s)
who reported for the TSCA Inventory, nor does it include any data
that would compromise TSCA CBI. All data reported for the initial
TSCA Inventory, including the production range data, are subject
to the limitations contained in the TSCA Inventory Reporting
Regulations (40 CFR 710).
Monsanto did not provide any information on the use(s) of elemental
phosphorus; secondary literature references revealed that elemental
phosphorus is used in rodenticides, smoke screens and analytical
chemistry (gas analysis).
COMMENTS/RECOMMENDATIONS
All members of the "Ad-Hoc Committee of Phosphorus Manufacturers"
reportedly received a copy of Monsanto's Section 8(e) submission.
Following a preliminary review of FYI-0TS-0785-0423, it is EPA's
initial position that the parturition-related maternal toxicity
findings presented therein should have been submitted to the Agency
under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substances Control Act (TSCA) . The basis for
EPA's position in this matter is as follows:
Section 8(e) states that "any person who manufactures,
[imports,] processes or distributes in commerce a chemi-
cal substance or mixture and who obtains information
which reasonably supports the conclusion that such sub-
stance or mixture presents a substantial risk of injury
to health or the environment shall immediately inform the
[EPA] Administrator of such information unless such
person has actual knowledge that the Administrator has
been adequately informed of such information."
The preface to Part V of EPA's TSCA Section 8(e) policy
statement explains that a "substantial risk of injury to
health ... is a risk of considerable concern because
of (a) the seriousness of the effect . . . and (b) the
fact or probability of its occurrence." With regard to
the seriousness of the effect, Part V states that EPA
considers the types of health effects for which substan-
tial risk information must be reported to include "any
pattern of effects or evidence that the [tested] chemical
substance or mixture can produce . . . birth defects or
toxic effects resulting in death, or serious or prolonged
incapacitation [Part V(a) (2) ]." The information regarding
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these effects can be obtained directly or inferred from
designed tests (e.g., studies in animals) as described
in Part VI of the TSCA Section 8(e) policy statement.
Part VI explains also that a "person is not to delay
reporting until he obtains conclusive information that
a substantial risk exists, but is to immediately report
any evidence that reasonably supports that conclusion."
With regard to the "fact or probability of its [(i.e.,
the serious effect's)] occurrence" criterion, Part V of
the Section 8(e) policy statement explains that certain
types of adverse health effects (e.g., those described
in Part V(a)(2) of the policy statement) are considered
by EPA to be so serious that relatively little or no
weight should be attached to the subject chemical's
exposure in determining whether a risk is substantial.
Further, EPA's response to Comment 31 in Appendix B of
the Section 8(e) policy statement, as it pertains to a
question on R&D chemicals, states that the occurrence of
serious effects such as those described in Part V(a)(1)
or (2) of the policy statement presuppose exposure to the
tested chemical and must be reported immediately to EPA
under Section 8(e).
Considering the preceding discussion, EPA believes that the serious
parturition-related toxicity data contained in FYI-OTS-0785-042 3
offer reasonable support for a conclusion of substantial risk and
as such should have been submitted under Section 8(e) of TSCA.
a) The Existing Chemical Assessment Division will provide
the Monsanto Company ample opportunity (20 working days)
to rebut EPA's initial position on the TSCA Section 8(e)-
applicability/reportability of the information contained
in the company's FYI submission.
The Chemical Screening Branch will also ask Monsanto to
ensure that EPA receives a full copy of the final report
(including the actual experimental protocol, results of
gross and histopathological examinations, results of any
statistical analyses, etc.) from the one-generation rat
reproduction studies cited in the company's TSCA Section
8(e) and FYI submissions. In addition, Monsanto will be
asked to provide the specific rationale for the conduct
of such studies on elemental phosphorus.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity and/or exposure data, Monsanto will be requested
to describe the actions that Monsanto and other members
of the "Ad-Hoc Committee of Phosphorus Manufacturers"
have taken or plan to take 1) to notify workers/others
about the reported toxicological findings, and 2) to
reduce or eliminate exposure to elemental phosphorus.
Monsanto will be asked also to describe the nature and
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results, if available, of all studies (other than those
submitted already to EPA or those published in the open
scientific literature) about which Monsanto and other
"Ad-Hoc Committee" companies are aware or that Monsanto
or those companies have conducted, are conducting, or
plan to conduct that are designed to determine the
toxicity of or the exposure to elemental phosphorus.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of elemental phosphorus.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this report will be sent to the Environmental
Assistance Division/OTS (formerly the TSCA Assistance
Office/OTS) for further distribution.
Members of the "Ad-Hoc Committee of Phosphorus Manufacturers
FMC Corporation
Monsanto Company
Hoechst AG Knapsack
Stauffer Chemical Company
Occidental Chemical Corporation
Albright & Wilson, Americas, Inc.
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sr*,
,11,, . v vf?
FROMs David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TOs Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
The submitting company claimed its company name and the identity
of one of the subject chemicals to be TSCA Confidential Business
Information (CBI). According to non-confidential information that
was provided in the submitting company's "sanitized" cover letter
and attached Material Safety Data Sheet (MSDS) , ethyl cyanoacrylate
(CAS No. 7085-85-0) is the major component (95%) of the subject
cyanoacrylate adhesive product. The submitting company will be
asked to provide a non-CBI generic name for the minor component.
Staff of the Information Management Division will be reviewing all
incoming correspondence related to the company's TSCA CBI claims.
SPBMI88ION DESCRIPTION
In the "sanitized" (i.e., non-confidential) version of its TSCA
Section 8(e) notice, the submitter stated that 1) "a customer which
uses [a] cyanoacrylate adhesive among other chemicals reported that
three pregnant women [had] experienced premature childbirths," and
2) "two [of the] premature babies died and one continues on life
support." The submitting company provided the following summary
information regarding this situation:
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA), The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
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8EHQ-0989-0821 S
Page 2 of 4
"The three women, according to their employer, were
packing large plastic auto parts following the gluing
process. The gluing operation and packing activities are'
apparently immediately adjacent to one another. . . .
[The submitting company understands] that there is no
local exhaust for the gluing operation but that large
pedestal fans are provided. Again, according to the
employer, the women were exposed for only about six
weeks' duration when the premature deliveries occurred."
The submitting company noted that despite the fact that "there is
no evidence to substantiate a causal relationship," the company's
decision to report this information to EPA under Section 8(e) was
based primarily on 1) the multiple occurrences of premature births,
2) the similarity between the affected womens1 exposure/working
relationships, and 3) the seriousness of the observed human health
effects.
The submitting company reported that neither component of this
cyanoacrylate adhesive product "has any history of causing ill
effects." The submitting company reported further that "a search
of the literature and commercial data bases reveals little or no
information relative to health studies conducted on these specific
component chemicals." The submitter noted, however, that when the
search was broadened to cyanoacrylates as a class, literature was
located on the mutagenic effects of 2-cyanoacrylate monomer when
tested in bacterial strains TA98, TA100, TA1535 and TA1538 in an
Ames assay. In addition, the submitter reported that while the
broadened literature search also confirmed the "known toxic and
respiratory effects" of over-exposure to cyanoacrylate vapors,
"information concerning the mutagenicity or teratogenicity effects
is lacking."
SUBMTgSTQN EVALUATION
In view of the serious nature of the observed adverse effects, the
submitting company should continue to investigate this matter and
should seek answers to a number of very important questions. For
example:
1. To what other chemicals were the affected women exposed
occupationally as well as non-occupationally?
2. How was the estimate of 6 weeks of exposure derived?
3. Were the affected women employed at the facility for the same
length of time and/or during the same time interval(s)?
4. Did all three of the women deliver at approximately the same
time?
5. How far along in pregnancy were the women when their premature
deliveries occurred?
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8EHQ-0989-0821 S
Page 3 of 4
6. What are the ages, previous employment and pregnancy outcome
histories of the affected women?
7. What was the health status of the women before the premature
deliveries occurred? What is the status presently?
8. Where and in what capacity are/were their husbands employed?
9. Was any workplace air monitoring conducted before, during
and/or after the incident(s)?
10. Has OSHA and/or NIOSH been informed about or conducted any
followup investigations with regard to the incident(s)?
CURRENT PRODUCTION AND USE
The submitter reported non-confidentially that both components of
the subject cyanoacrylate adhesive product are listed on EPA's TSCA
Chemical Substance Inventory.
In view of the submitting company's TSCA CBI claim, no use or TSCA
Inventory production/importation information related to the minor
component of the product will appear in this status report.
EPA's review of the production range (includes importation volumes)
statistics for the major component (CAS No. 7085-85-0), which is
listed in the Agency's initial TSCA Inventory, showed that 112,000
to 1,122,000 pounds of this chemical were reported as manufactured
and/or imported in 1977. This production range information does
not include any data that were claimed to be TSCA Confidential
Business Information (TSCA CBI) by the person(s) who reported for
the TSCA Inventory, nor does it include any information that would
compromise TSCA CBI. All of the data reported for the initial TSCA
Inventory, including the production range data, are subject to the
limitations contained in the TSCA Inventory Reporting Regulations
(40 CFR 710).
COMMENTS/RECOMMENDATIONS
The submitter reported that the company "will continue to research
this issue and will explore the merits of conducting teratogenicity
studies."
a) The Chemical Screening Branch will ask the submitting
company to ensure that EPA is apprised about any further
significant findings regarding the reported human health-
related incident (e.g., answers to important questions
such as those listed in the SUBMISSION EVALUATION section
of this status report). The submitting company will be
asked also to provide a non-confidential generic name for
the minor component of the subject cyanoacrylate adhesive
product.
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Page 4 of 4
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, the submitter will be requested
to describe the actions that the company has taken or
plans to take on an interim basis to 1) notify workers
and others about the reported information, and 2) reduce
or eliminate exposure to this cyanoacrylate adhesive
and/or its component chemicals. The submitter will be
informed that EPA should be kept apprised of any results
of studies that the company conducts or may learn about
that are designed to determine the potential develop-
mental toxicity of this cyanoacrylate adhesive product
and/or its component chemicals.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of the subject cyanoacrylate adhesive
product and/or its component chemicals.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this report will be sent to the Environmental
Assistance Division/OTS (formerly the TSCA Assistance
Office/OTS) for further distribution.
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jf ^2^ UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
\«/
DATE: SEP 2 7 1989 APPROVED:
SDL ^kl
SUBJECT: Status Report1 8EHQ-0989-0822
*« <*
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBMISSION DESCRIPTION
The CIBA-GEIGY Corporation submitted summary information regarding
a chronic study of FAT 65029/G (the disodium salt of 2,2'-([1,1'-
biphenyl ] -4,4 • -diyldi-2,1-ethenediyl) bis-benzenesulfonic acid; CAS
No. 27344-41-8) in rats. A "Preliminary Report" included in the
submission presents the following information about the conduct and
results of this study (performed by the parent company (CIBA-GEIGY
Limited in Basel, Switzerland):
"The test material, FAT 65029/G, was administered to
Sprague-Dawley derived rats of both sexes in their daily
food for two years at concentrations of 500 (group 2) ,
5,000 (group 3) and 50,000 (group 4) ppm (mg/kg diet).
Each group/sex consisted of 80 animals; a control group
(group 1) of the same size received unmedicated diet.
"The preliminary results of the [two year] study revealed
proliferative lesions in the exocrine pancreas of both
sexes at the following incidences.
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk1 information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
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Page 2 of 3
sex
males
females
dose group
group i
group 2
group 3
group 4
group l
group 2
group 3
group 4,
1
nodular hyper-
plas La
6/78
12/78
6/79
51/78
i/7a
1/79
1/80
10/79
adenoma
0/7&
0/78
2/79
18/18
1/76
0/79
0/80
2/19
carcinoma
0/78
0/78
0/79
2/78
1/78
0/79
0/80
0/79
adenoma and
carcinoma
combined
0/78
0/78
2/79
20/78
2/78
0/79
0/80
2/79
proliferative
leaioris
6/78
12/78
6/79
54/78
3/78
1/79
1/80
12/79
"It was concluded that an oncogenic response occurred in
the male rats at the high dose of 50,000 ppm. No such
finding was observed at the lower dose levels in the
males, nor at any dose in the females.
"The treatment with FAT 65029/G did not significantly
affect general health and longevity of the animals.1'
With regard to the reported results, CIBA-GEIGY stated that "the
significance of this organ specific finding, particularly in view
of the magnitude of the dose level (50,000 ppm), is questionable."
gPPMIggJQW EVALUATION
An evaluation of the overall significance of the reported findings
should be possible upon EPA's receipt of a full copy of the final
report of this chronic study. (CIBA-GEIGY stated the final report
should be available in late 1989 or early 1990.)
CURRENT PRODUCTION AMD USE
A review of the production range (includes importation volumes)
statistics for CAS No. 27344-41-8, which is listed in the initial
TSCA Chemical Substance Inventory, showed that no 1977 manufacture/
importation was reported or that all manufacture and/or importation
information reported was claimed to be TSCA Confidential Business
Information (TSCA CBI) by the person(s) reporting for the initial
TSCA Inventory and cannot be disclosed (Section 14(a) of TSCA;
U.s.C. 2613(a)). All data reported for the initial TSCA Inventory,
including the production range data, are subject to the limitations
contained in the TSCA Inventory Reporting Regulations (40 CFR 710).
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CIBA-GEIGY did not submit any information with regard to the use(s)
of FAT 65029/G nor was such information located in the secondary
literature sources consulted by EPA.
COMMENTS/RECOMMENDATIONS
CIBA-GEIGY reported that "notification of workers and customers
will be provided through revised Material Safety Data Sheets in
accordance with the OSHA Hazard Communication Standard (29 CFR
1910.1200) ."
a) The Chemical Screening Branch will ask CIBA-GEIGY to
ensure that EPA receives a complete copy of the final
report (including the actual experimental protocol,
results of gross and histopathological examinations,
results of statistical analyses, etc.) from the 2-year
bioassay cited in the company's submission.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure information, CIBA-GEIGY will be asked
to describe the nature and results, if available, of all
studies (other than those submitted already to the Agency
or those cited in the published scientific literature)
about which CIBA-GEIGY is aware or that the company has
conducted, is conducting or plans to conduct that are
designed to determine the toxicity of or the exposure to
the subject chemical.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of the subject chemical substance.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this report will be sent to the Environmental
Assistance Division/OTS (formerly the TSCA Assistance
Office/OTS) for further distribution.
174
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^eos%
m
\ PBOlt0<
Page 1 of 3
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF
PESTICIDES AND TOXIC SUftSTANCKS
date: OCT I 7 1989
APPROVED:
SUBJECT: Status Report1 8EHQ-0989-0823
if &
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
The Mobay Corporation provided a complete copy of the final report
(written in German) from an oral teratologic study of 0-(2,4-
dichlorophenyl)-O-ethy1-S-n-propylphosphorodithioate (Tokuthion;
Prothiophos; CAS No. 34643-46-4) in rats. Mobay's Section 8(e)
cover letter presents the following summary information about the
conduct and preliminary results of the study:
"The test material was administered [by gavage] to Wistar
rats at dosage levels of 0, 10, 30 and 100 mg/kg ([on]
days 6-15 of gestation). The overall no-effect dose was
10 mg/kg. Frank maternal toxicity was registered in the
30 and 100 mg/kg/day dosage groups, as evidenced by
decreased body weight gain (30 and 100 mg/kg/day) and
clinical signs of toxicity (100 mg/kg/day). While no
evidence of teratogenicity was observed, fetotoxicity was
evident at the high-dose level in the form of reduced pup
and placental weights and an increase in the incidence
of delayed/incomplete skeletal ossification. To the best
of . . . [Mobay's] knowledge, this is a new finding."
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information repotting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
175
Printfd on Rtcychd Ptfr
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8EHQ-0989-0823
Page 2 of 3
Mobay reported that when completed, an English translation of the
final report of this study (which was performed by Mobay's parent
company, Bayer AG in West Germany) will be sent to EPA.
SUBMISSION EVALUATION
According to the provided summary, maternal toxicity was observed
at doses of 30 and 100 mg/kg. Dams in both dose groups exhibited
reduced body weight gain; dams in the 100 mg/kg group also showed
unspecified clinical signs of toxicity. Developmental toxicity was
reportedly observed only among the fetuses from the 100 mg/kg dose
group and consisted of reduced fetal body weight and an increased
incidence of delayed/incomplete skeletal ossification. The overall
significance of the reported toxicologic results should be possible
upon EPA's receipt of a complete copy of the English translation
of the full final report from this teratologic study of Tokuthion
in rats.
CURRENT PRODUCTION AND QBE
The subject chemical is not listed in the non-confidential printed
or computerized versions of the TSCA Chemical Substance Inventory.
According to Mobay, "Tokuthion is manufactured in the United States
by Mobay for export to Japan." In addition, Mobay stated that "the
potential for exposure under production conditions is low." Mobay
reported non-confidentially by phone on October 12, 1989 that 1)
Tokuthion is manufactured in the United States solely for export
for use as a pesticide, and 2) Tokuthion is not registered for use
as a pesticide in the United states.
Immediately upon receipt of this TSCA Section 8(e) submission, the
Chemical Screening Branch transmitted a complete copy of the cover
letter to the Office of Pesticide Programs (OPP) in EPA's office
of Pesticides and Toxic Substances (OPTS).
COMMENTS/RECOMMENDATIONS
Mobay stated that the company is 1) advising its employees about
the reported toxicological findings, and 2) reviewing existing
"standards for handling Tokuthion in the workplace."
Considering that 1) Mobay is manufacturing Tokuthion in the U.S.
solely for export for use as a pesticide, 2) Tokuthion is not
registered for use in the U.S., 3) the export of an unregistered
pesticide is covered by Section 17 of the Federal Insecticide,
Fungicide and Rodenticide Act (FIFRA), and 4) the "Definitions"
section (Section 3) of TSCA contains exclusionary language related
to pesticides, it is not clear that Mobay was technically required
to submit the teratology study findings on Tokuthion to EPA under
Section 8(e) of TSCA. While this matter has been referred to the
staff of the Office of the General Counsel (OGC) for resolution,
it is important to note that EPA recognizes and appreciates the
fact that Mobay acted in a prudent manner in formally submitting
the company's teratology study findings on Tokuthion.
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8EHQ-0989-0823
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a) The Chemical Screening Branch will ask Mobay to ensure
that EPA receives a full copy of English translation of
the final report (including the actual experimental pro-
tocol, results of the gross/histopathologic examinations,
results of statistical analyses, etc.) from the subject
teratology study of Tokuthion.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, Mobay will be asked to describe
the nature and results, if available, of all studies
(other than those submitted already to EPA or those cited
in the published scientific literature) about which Mobay
is aware or that Mobay has conducted, is conducting or
plans to conduct that are designed to determine the
toxicity of or the exposure to Tokuthion.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of the subject chemical substance.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAS/EPA, OGC/EPA and OPP/OPTS/EPA; in
addition, copies of this status report will be provided
to the Environmental Assistance Division/OTS (formerly
the TSCA Assistance Office/OTS) for further distribution.
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<7 fif.
f S UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
DATE: OCT I 9 1989 APPROVED:
/A
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0989-0824 S
8EHQ-0989-0824 S SUPP
FROM: David R, Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
The submitting company has claimed its company name and the exact
identities of the subject chemicals as TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. In the "sanitized" version of its initial TSCA
Section 8(e) notice, the company reported non-confidentially that
the subject chemical is an "aryl substituted azole carboxamide."
In a supplemental submission, the company reported information
about a chemical substance identified non-confidentially as an
"azide impurity" of the aryl substituted azole carboxamide.
SUBMISSION DESCRIPTION
In its initial submission, the submitting company provided the
following summary information about the conduct and preliminary
results of a subchronic feeding and pilot reproduction study of
this aryl substituted azole carboxamide in rats:
"This study consisted of a standard 90-day rat .feeding
study (10 rats/sex/group) with an additional satellite
group of 10 females/group that were mated to the males
after 9 weeks of exposure and allowed to deliver their
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk?' information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
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8EHQ-0989-0824 S INIT/SUPP
Page 2 of 4
young. The mated females and their pups were sacrificed
on gestation [lactation ?] day 4 in order to obtain a
preliminary indication as to [the] potential reproductive
effects. Dietary concentrations of aryl substituted azole
carboxamide were 0, 10, 100, 1000, 5000 and 20,000 ppm.
"No mortality occurred during the study. [The] parental
toxicity was observed at 5000 and 20,000 ppm and included
significantly decreased body weight gain, slight anemia,
increases in several clinical chemistry parameters (al-
kaline phosphates, BUN, SGPT and albumin) and increases
in liver and possibly thyroid weights. No effect was
noted on mating or fertility indices. There was a large
decrease in pup survival (Days 0-4) and pup weight (Days
0 and 4) at 20,000 ppm but no effect on either of these
parameters was noted at 5000 ppm. Mean litter size was
slightly lower than controls at both 5000 and 20,000 ppm
but the significance of these decreases was
questionable."
In its supplemental submission, the company reported that an "azide
impurity" in this aryl substituted azole carboxamide was found to
be positive in 1) an in vitro cytogenetics assay, and 2) bacterial
mutagenicity assays in Salmonella tvphimurium and Escherichia coli.
According to the submitter, the "identification and testing of the
impurity were conducted by a foreign partner of [the submitting
company] which also produces the parent chemical." The submitting
company stated further that the parent compound, "which contained
approximately 6 ppm of the azide impurity, was not found to be
genotoxic in either bacterial point mutation assays or in a mouse
micronucleus assay." The submitter provided copies of the final
reports of the genotoxicity studies of the azide impurity itself
and the parent chemical with the azide impurity.
SUBMISSION EVALDATION
According to the summary information contained in the company's
initial submission, parental toxicity (evidenced by decreased body
weight gain, anemia, increased liver and thyroid weights, and
increases in several clinical chemistry parameters) was evident
after exposure to 5000 or 20,000 ppm of the parent chemical.
Developmental toxicity was also evident at these two dose levels?
exposure to 20,000 ppm resulted in decreased pup weight and pup
survival, while exposure to 5000 ppm and 20,000 ppm resulted in
reduced litter size. A more complete evaluation of the overall
significance of the findings should be possible upon the Agency's
receipt of a full copy of the final report from this subchronic
feeding and pilot reproduction study in rats.
Staff of the Toxic Effects Branch (TEB/HERD/OTS) has been asked to
evaluate the genotoxicity data from the company's supplemental
submission.
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8EHQ-0989-0824 S INIT/SUPP
Page 3 of 4
CURRENT PRODUCTION AND USE
In view of the submitter's TSCA CBI claims, no information about
the TSCA Chemical Substance Inventory status or use(s) of this aryl
substituted azole carboxamide will appear in this status report.
The submitting company stated non-confidentially that this chemical
substance is being imported and used exclusively for research and
development (R&D).
COMMENTS/RECOMMENDATIONS
In its supplemental submission, the company reported that in order
"to ensure that the potential adverse findings of the impurity do
not impact the parent compound, procedures will be put in place to
keep the azide levels in all future lots of the parent chemical
below 2 ppm."
In the supplemental submission, the submitting company stated its
belief that the azide impurity was not subject to TSCA because the
impurity "is not being manufactured or processed for commercial
purposes." The submitter's contention is not correct. Chemical
substances not under TSCA jurisdiction and therefore not covered
by Section 8(e) are discussed in Section 3 of TSCA and include:
(1) pesticides (as defined in the Federal Insecticide, Fungicide
and Rodenticide Act (FIFRA)) ;
(2) tobacco and tobacco products;
(3) source materials, special nuclear materials and byproducts
(as defined in the Atomic Energy Act (AEA) of 1954 and the
regulations issued under the AEA);
(4) foods, food additives, drugs, cosmetics and devices (as
defined in the Federal Food, Drug and Cosmetic Act (FFDCA)).
Therefore, except for chemicals specifically excluded by definition
from TSCA jurisdiction, TSCA (and therefore TSCA Section 8(e))
coverage includes, but is not limited to, the following types of
chemical substances:
(1) research and development (R&D) chemicals (including those
intended for use as pesticides prior to application for an
Experimental Use Permit (EUP) or a pesticide registration
under FIFRA);
(2) laboratory reagents?
(3) low volume chemicals;
(4) polymers;
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Page 4 of 4
(5) chemicals that are manufactured solely for export;
(6) intermediates (including non-isolated intermediates);
(7) catalysts;
(8) byproducts;
(9) impurities;
(10) biotechnology products.
Although some rules promulgated under other sections of TSCA may
exempt certain chemical substances or certain types of commercial
activities, such exemptions typically apply only to the rule that
is issued and do not apply to TSCA in general or to Section 8(e)
of TSCA specifically.
a) The Chemical Screening Branch will ask the submitter to
ensure that EPA receives a full copy of the final report
(including the actual experimental protocol, results of
gross and histopathological examinations, results of any
statistical analyses, etc.) from the 90-day feeding and
reproduction study cited in the initial submission.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, the submitter will be requested
to describe the actions that the company has taken or
plans to take to 1) notify workers and others about the
reported information, and 2) to reduce or eliminate the
exposure to this aryl substituted azole carboxamide. In
addition, the company will be requested to describe the
nature and results, if available, of all studies (other
than those submitted already to EPA or those cited in the
published scientific literature) about which the company
is aware or that the company has conducted, is conducting
or plans to conduct that are designed to determine the
toxicity of the aryl substituted azole carboxamide or its
azide impurity.
b) The Chemical Screening Branch will review the reported
information to determine the need for any further OTS
assessment of this aryl substituted azole carboxamide
and/or its azide impurity.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
ow/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EFA; in addition,
copies of this report will be sent to the Environmental
Assistance Division/OTS (formerly the TSCA Assistance
Office/OTS) for further distribution.
181
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 3
OFFICE OF
yM. It/nfo
PESTICIDES AND
TOXIC SUBSTANCES
DATE: OCT 12 1989 APPROVED
SUBJECT: status Report1 8EHQ-0989-0825 S
FROM: David R. Williams, section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Rhone-Poulenc Inc. has claimed the exact identities of the subject
chemicals to be TSCA Confidential Business Information (CBI). The
Information Management Division will review all of the incoming
correspondence related to the company's TSCA CBI claim. In the
"sanitized" version of its Section 8(e) submission, Rhone-Poulenc
stated non-confidentially that the subject chemical substances are
"substituted anilides."
SUBMISSION DESCRIPTION
Rhone-Poulenc provided the following summary information about the
conduct and preliminary results of teratological studies of three
(3) substituted anilides:
"Compound 1
"Doses used in the rat teratology screen on Compound 1
were 0, 12.5, 25, 50, and 75 mg/kg/day. [ (The Iroute of
exposure and the gestation days on which dosing occurred
was not given in the submission.) ] There were ten animals
per group. Four dams out of 10 died at 75 mg/kg. Body
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
NOTE
182
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8EHQ-0989-0825 S
Page 2 of 3
weight gains were markedly depressed at 50 and 75 rag/kg
and embryolethality was seen at these same dose levels.
The major malformations seen at 75 and 50 mg/kg included
gastroschisis, cephalocele, anophthalmia and exencephaly.
Soft tissue and skeletal evaluations are being performed
at 25 mg/kg.
"Compound 2
"Doses used in the rat teratology screen on Compound 2
were 0, 15, 40, 80, and 120 mg/kg/day. [(The route of
exposure and the gestation days on which dosing occurred
was not given in the submission.) ] There were ten animals
per group. Seven dams out of 10 died at 120 mg/kg and
2 out of 10 [died] at 80 mg/kg. Body weight gains were
markedly depressed at 40, 80 and 120 mg/kg, total embryo-
lethality was seen at 80 and 120 mg/kg and partial
embryolethality [was seen] at 40 mg/kg/day. The major
malformations seen at 40 mg/kg included domed head,
gastroschisis, cephalocele, anophthalmia, omphalocele,
and exencephaly. Soft tissue and skeletal evaluations
are being performed at 15 mg/kg.
"Compound 3
"Doses used in the rat teratology screen on Compound 3
were 0, 10, 20, 40, and 60 mg/kg/day. [(The route of
exposure and the gestation days on which dosing occurred
was not given in the submission.) ] There were ten animals
per group. Five dams out of 10 died at 60 mg/kg and 2 out
of 10 [died] at 40 mg/kg. Body weight gains were markedly
depressed at 20, 40 and 60 mg/kg and embryolethality was
seen at 40 and 60 mg/kg. No major malformations were seen
at any dose tested. Soft tissue and skeletal evaluations
are being performed at 20 mg/kg."
SUBMISSION EVALUATION
The submitted summary information provides evidence of potential
maternal and developmental toxicity for all three compounds. The
maternal toxicity (as evidenced by reduced weight gain and death)
was observed following exposure to Compound 1, Compound 2 or
Compound 3 at doses as low as 50 mg/kg, 40 mg/kg, or 20 mg/kg,
respectively. Developmental toxicity was apparent after exposure
to Compound 1 at doses as low as 50 mg/kg and consisted of embryo-
lethality and an increased incidence of malformations including
gastroschisis, cephalocele, anophthalmia and exencephaly. Exposure
to Compound 2 at doses as low as 40 mg/kg also resulted in embryo-
lethality and an increased incidence of malformations including
domed head, gastroschisis, cephalocele, anophthalmia, omphalocele
and exencephaly. Although no "major malformations" were observed,
embryolethality was observed after exposure to Compound 3 at doses
as low as 40 mg/kg.
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8EHQ-0989-0825 S
Page 3 of 3
At the time of Rhone-Poulenc's Section 8(e) submission, soft tissue
and skeletal evaluations of the fetuses from these studies had not
been completed; therefore, no information with regard to potential
developmental toxicity at the lower doses of the three compounds
was available for review.
CURRENT PRODUCTION AND USE
In view of Rhone-Poulenc's TSCA CBI claim, no information regarding
the TSCA Chemical Substance Inventory status or use(s) of these 3
chemicals will appear in this status report. Rhone-Poulenc stated
non-confidentially in its submission that "relatively small amounts
of these materials have been synthesized for testing only."
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will ask Rhone-Poulenc to
ensure that EPA receives full copies of the final reports
(including the actual experimental protocols, results of
gross and histopathological examinations, results of any
statistical analyses, etc.) from the teratology studies
cited in the company's submission.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, Rhone-Poulenc will be asked to
describe the actions that the company has taken or plans
to take 1) to notify workers/others about the reported
information, and 2) to reduce or eliminate exposure to
the subject chemical substances. Rhone-Poulenc will be
requested also to describe the nature and results, if
available, of all studies (other than those submitted
already to EPA or those cited in the published scientific
literature) about which Rhone-Poulenc is aware or that
the company has conducted, is conducting or plans to
conduct that are designed to determine the toxicity of
these substituted anilides.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of the subject chemicals.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA? in addition,
copies of this status report will be provided to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
1
of 4
DATE:
OCT I 9 i
APPROVED
SUBJECT: Status Report1 8EHQ-0989-0826 S
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
The submitting company has claimed its company name to be TSCA
Confidential Business Information (CBI). Staff of the Information
Management Division will review all incoming correspondence related
to the company's TSCA CBI claim.
SUBMISSION DESCRIPTION
The submitting company provided full copies of the final reports
from a wide variety of ^ vitro/in vivo toxicity and environmental
studies of N-amino-N-(carboxymethyl)glycine. According to the
submitter, this chemical was the subject of a TSCA Section 5 "Pre-
Manufacture Notification" (PMN No. P-88-1267) previously submitted
to EPA. The cover letter to the company's Section 8(e) submission
presents the following information about the conduct and results
of the performed studies:
Ma) Substance was classed as a material of slight
[acute] percutaneous toxicity by using CD
rats.
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
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8EHQ-0989-0826 S
Page 2 of 4
"b) Substance caused delayed contact hypersensi-
tization in guinea pigs.
"c) The daily, oral administration of the substance
at 10 mg/kg/day [for 4 weeks to CD rats] pro-
duced adverse reactions which included changes
suggestive of renal toxicity.
Administration at 1.0 or 0.1 mg/kg/day was
essentially without effect, and the higher of
these dosages was considered [to be] a 'no
toxic effect' level.
"d) It was concluded in the [mouse micronucleus]
study that the substance induced no significant
damage to chromosome structure. . .
"e) It was estimated that the 96-hour LC50 for
[rainbow trout exposed to] the substance was
341 or 301 mg/1 based respectively on [the]
nominal or mean, measured concentrations.
Hf) The 48-hour EC50 for immobilization of Daphnia
magna by the substance was calculated to be
44.0 or 28.2 mg/1, based respectively on [the]
nominal or mean, measured concentrations (95%
confidence limits 34.5-54.2 or 21.4-36.1).
"g) Estimates of [the] biotic degradation based on
dissolved organic carbon (DOC) removal ranged
from 4% on day 7 to 21% on day 28 which indi-
cated that the substance was not readily
degradable under the conditions of the test.
A separate investigation on biodegradability
was [also] performed. . . Overall, it was
concluded that the substance was not ulti-
mately degraded under the biotic or abiotic
test conditions employed, but it may readily
undergo partial degradation following one or
more abiotic pathways.
4.
"h) [In previous studies sent to the Agency with
P-88-1267,] the substance . . . was found to
be non-irritant to the skin [of rabbits], and
irritant (with slight to moderate initial pain
response) in the [rabbit] eye. No mutagenic
activity was detected in the Ames [bacteria]
test. [According to an acute rat oral study
also submitted with P-88-1267, the chemical
was found to have an approximate LD50 of 104
mg/kg (male/female rats combined).]"
The company's Section 8(e) cover letter also presents the following
"CONCLUSION" regarding the performed studies:
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8EHQ-0989-0826 S
Page 3 of 4
"Acute effects: possibly related mainly to the acidity
of the [test] material, these could be significant in
the immediate area of any major, accidental release.
Ingestion or skin contact should be avoided, as should
[the] discharge or run-off into waterways. However, an
absence of acute irritant or toxic effects will provide
an indicator of minimal exposure, and toxicity to fish
or freshwater invertebrates is unlikely to be high.
"Effect of prolonged exposure: skin contact should be
minimized to avoid possible sensitization, and the kidney
may be a target organ for subchronic exposure (at high
levels: based on limited, rodent data only). In view of
the possibility of only partial degradation by abiotic
pathways in water, discharge of chemically unmodified
[test material] should be minimized.
"Handling procedures of the type normally applied to
acidic materials (pH 2-3) are therefore likely to require
only minor adaption for adequately safe industrial use
of the substance."
SUBMISSION EVALUATION
Staff of the Chemical Screening Branch, in conjunction with staff
of the Health and Environmental Review Division (HERD/OTS) and
other appropriate OTS Divisions, will evaluate the data presented
in this TSCA Section 8(e) submission in context with previous "New
Chemicals Program" (NCP) reviews of toxicological and other data
submitted to the Agency with P-88-1267.
CURRENT PRODUCTION AND USE
According to the "sanitized" (i.e., non-confidential) version of
P-88-1267 obtained from* EPA's public document files, the subject
chemical (identified therein as a "hydrazine derivative") has an
"open, non-dispersive use." No further information regarding the
use of this chemical was contained in the sanitized versions of
either P-88-1267 or 8EHQ-0989-0826 S. According to IMD/OTS staff,
a TSCA Section 5 "Notice of Commencement" (NOC) for P-88-1267 has
been received by the Agency.
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will request the submitter
to provide the Chemical Abstract Service (CAS) Registry
Number, if known, for the subject chemical substance.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, the submitter will be requested
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8EHQ-0989-0826 S
Page 4 of 4
to describe the actions that the company has taken or
plans to take to notify workers/others about the reported
toxicologic findings. In addition, the submitting company
will be requested to describe the nature and results, if
available, of all studies (other than those submitted
already to EPA or those cited in the published scientific
literature) about which the company is aware or that the
company has conducted, is conducting or plans to conduct
that are designed to determine the toxicity of or the
exposure to the subject chemical substance.
b) The Chemical Screening Branch will continue to review the
reported information in order to determine the need for
further OTS assessment of the subject chemical substance.
c) The Chemical Screening Branch will send copies of this
Status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and CCD/OTS/OPTS;
in addition, copies of this status report will be sent
to the Environmental Assistance Division/OTS (formerly
the TSCA Assistance Office/OTS) for further distribution.
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Page 1 of 4
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
OFFICE OF
^r\t PESTICIDES AND
OCT 2 6 1S85 APPROVED! (JWL toxic substances
Status Report1 8EHQ-0989-0827 S
8EHQ-1089-0827 S SUPP
David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE (Also see NOTE on Page 4 of this status report)
The submitting company has claimed its company name and the exact
identity of the subject chemical to be TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. In the "sanitized" versions of its initial and
supplemental submissions, the company reported non-confidentially
that the subject chemical is an "N-aryl-cyclic imidate."
It should be noted further that shortly after EPA's receipt of this
initial TSCA Section 8(e) submission, the Agency received another
initial Section 8(e) notice on a chemical substance also identified
generically as an N-aryl-cyclic imidate. The reader's attention
is directed to the status report prepared in response to this other
submission (8EHQ-0989-0828 S).
W
DATE:
SUBJECT:
FROM:
TOS
SUBMISSION DESCRIPTION
In its initial Section 8(e) submission, the company provided the
following summary information regarding the conduct and preliminary
results of a teratological study of the subject chemical in rats:
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
189
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Page 2 of 4
"In this study, H-aryl-cyclic imidate was administered
by gavage to 4 groups of 25 mated female rats at dose
levels of o, 15, 150, and 500 mg/kg/day during gestation
days 6-18. Surviving dams were sacrificed on gestation
day 20. [The] fetuses were removed, weighed, sexed, and
examined for possible external, visceral, and skeletal
malformations or variations.
"Six dams from the 500 mg/kg/day group died during the
study. Other signs of maternal toxicity at this dose
level included substantial weight loss (-12 g) during
gestation days 6-9, decreased food consumption through-
out the dosing period, decreased excreta, mucoid feces
and red material around the mouth. Clinical signs and
weight gain in the other animals were normal although
there may have been a slight transient depression in
[the] food consumption at 150 mg/kg/day during gestation
days 6-9. Mean liver weights were increased 26% and 49%
in the 150 and 500 mg/kg/day groups, respectively.
"No effect was noted on the number of fetuses or on fetal
weights. [The] post-implantation loss at 500 mg/kg/day
was just outside of the historical control range (1.3
versus an upper limit of 1.2) but was not statistically
different from the [concurrent] control value (0.9) . The
only external malformations noted in this study consisted
of one fetus at 15 mg/kg/day with microphthalmia/anoph-
thalmia and one fetus at 500 mg/kg/day with cleft palate.
There was no indication that either of these defects were
related to treatment. There were no visceral or skeletal
malformations noted. However, there appeared to have been
a slight increase in several minor skeletal variations
at 500 mg/kg/day. Together with the possible effect on
post-implantation loss, these data suggest that the test
article may induce a very slight degree of developmental
toxicity in rats, but only at the severely maternally
toxic dose level of 500 mg/kg/day."
In its supplemental submission, the company provided the following
summary information regarding the conduct and preliminary results
of a 3-month pilot reproduction study of this N-aryl-cVclic imidate
in rats:
"In this study, 6 groups of 10 male and 20 female rats
were administered the subject chemical via the diet for
approximately 3 months. Dose levels were 0, 10, 100,
1000, 5000 and 15000 ppm. Half of the females in each
group were mated (1:1) with the males after approximately
10 weeks of exposure. The unmated females and all of the
males were sacrificed after 13 weeks of exposure. The
mated females were allowed to deliver and raise their
pups until lactation day 4, at which time the dams and
the pups were sacrificed.
190
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Page 3 of 4
"No mortality occurred during the study. By the end of
the study, mean body weights of the high dose (15000 ppm)
animals were about 6-7% lower than those of controls.
Slight anemia and several clinical chemistry changes
indicative primarily of liver damage were noted at 5000
and 15000 ppm. Liver weights and possible thyroid
weights were increased at > 100 ppm. Gross kidney and
liver lesions were noted at the same 2 dose levels but
histopathology results are not yet available. Thus,
based upon the increased liver weights, the NOEL for
systemic effects appears to be 10 ppm. Adverse repro-
ductive effects consisting of decreased litter size,
increased number of dead pups, decreased pup weights and
decreased pup survival were observed at 5000 ppm and
15000 ppm but no reproductive effects were observed at
< 1000 ppm."
SUBMISSION EVALUATION
The submitted summary information relating to the teratologic study
provides evidence of maternal toxicity following exposure to dose
levels as low as 150 mg/kg. The exposure to 500 mg/kg resulted in
death (6/2 5 dams), and decreased food consumption and body weight
gain; clinical signs of toxicity included decreased excreta, mucoid
feces and "red" material around the mouth. Exposure to 150 mg/kg
also resulted in decreased food consumption, and exposure to 150
mg/kg or more resulted in increased absolute liver weight. Evidence
of developmental toxicity was seen only following exposure to 500
mg/kg, and consisted of increased post-implantation loss and an
increased incidence of skeletal "variations."
The supplemental information on the 3-month rat reproduction study
provides evidence of maternal toxicity at dietary doses as low as
100 ppm. At 15000 ppm, the dams were found to have a mean body
weight 6-7% lower than the concurrent controls. At doses of 5000
and 15000 ppm, "slight" anemia was reportedly observed along with
unspecified clinical chemistry changes indicative primarily of
liver damage; unspecified gross liver and kidney lesions were also
seen at these two upper doses. Increased liver weights and possibly
thyroid weights were reportedly found at dose levels of 100 ppm and
above. Developmental toxicity was observed at both 5000 and 15000
ppm but apparently not at doses of 1000 ppm and below. The adverse
reproductive effects were reported to include decreased litter
size, increased numbers of dead pups, decreased pup body weights
and decreased pup survival.
An EPA evaluation of the overall significance of the toxicological
findings reported in the initial and supplemental TSCA Section 8(e)
submissions should be possible upon the Agency's receipt of full
copies of the final reports from these two studies.
191
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Page 4 of 4
CPBBBNT PBQPPCTIQW AMP PSB
In view of the submitter's TSCA CBI claims, no information about
the TSCA Chemical Substance Inventory status or use(s) of the
subject chemical will appear in this status report. The submitter
did report non-confidentially in its submissions, however, that
this N-aryl-cyclic imidate is currently being manufactured solely
for research and development (R&D) purposes.
CQMMENTff/RBCQMMENPftTIQITg
a) The Chemical Screening Branch will ask the submitter to
ensure that EPA receives a full copy of the final report
(including the actual experimental protocol, results of
gross and histopathological examinations, results of any
statistical analyses, etc.) from the oral rat teratology
study and the 3-month rat reproduction study cited in the
company's initial and supplemental Section 8(e) notices,
respectively.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, the submitter will be requested
to describe the actions that the company has taken or
plans to take 1) to notify workers and others about the
reported information, and 2) to reduce or eliminate
exposure to the subject chemical substance. In addition,
the submitter will be asked to describe the nature and
results, if available, of all studies (other than those
submitted already to EPA or those cited in the published
scientific literature) about which the company is aware
or that the company has conducted, is conducting or plans
to conduct that are designed to determine the toxicity
of the subject chemical.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of this N-aryl-cyclic imidate.
c) The Chemical Screening Branch will send copies of this
Status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this report will be sent to the Environmental
Assistance Division/OTS for further distribution.
NOTE The reader's attention is directed to the status report
prepared by EPA in response to 8EHQ-0190-0870 S.
192
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Page 1 of 3
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
OFFICE OF
DATES 2 6
PESTICIDES AND
APPROVED:
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0989-0828 8
PROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
The submitting company has claimed its company name and the exact
identity of the subject chemical to be TSCA Confidential Business
Information (CBI); the Information Management Division will review
all incoming correspondence on these CBI claims. In the "sanitized"
version of the notice, the company stated non-confidentially that
the subject chemical is an "N-aryl-cyclic imidate."
It should be noted also that EPA recently received an initial TSCA
Section 8(e) submission, as well as a supplemental submission, on
a chemical also identified non-confidentially as an N-aryl-cyclic
imidate. The reader's attention is directed to the "Status Report"
prepared by EPA in response to these prior submissions (8EHQ-0989-
0827 S Initial and 8EHQ-1089-0827 S Supplement).
SUBMISSION DESCRIPTION
The submitting company provided the following summary information
regarding the conduct and preliminary results of a teratological
study of the subject chemical in rats:
"In this study, N-aryl-cyclic imidate was administered
by gavage to 4 groups of 25 mated female rats at dose
levels of 0, 30, 300, and 1000 mg/Jcg/day during gestation
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
NOTE
193
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Page 2 of 3
days 6-18. Surviving dams were sacrificed on gestation
day 20. [The] fetuses were removed, weighed, sexed and
examined for possible external, visceral, skeletal mal-
formations or variations.
"One animal from the 1000 mg/kg/day group was sacrificed
moribund. All other animals survived until scheduled
termination. Clinical signs of toxicity (red material
around nose, decreased excreta, urogenital staining, soft
stool, etc.) were common [among dams] in the high-dose
(1000 mg/kg/day) group. A few instances of salivation
were noted at both 300 and 1000 mg/kg/day. Maternal
weight gain was affected only at 1000 mg/kg/day. Animals
at this level lost weight during gestation days 6-9 (mean
change of -4 grams versus +6 grams for controls) but
gained more weight than controls during gestation days
9-12 (27 grams versus 20 grams). [The] food consumption
during gestation days 6-9 was greatly decreased at 1000
mg/kg/day and slightly decreased at 300 mg/kg/day. A
slight increase in [maternal] food consumption appeared
to have occurred once dosing was terminated (gestation
days 16-20). Liver weights were increased in all treat-
ment groups in a dose-related manner (9-49%), although
the effect at the low dose [level] was not statistically
significant.
"No effect was noted on the number of fetuses or [on]
implantation losses. Mean fetal weights were slightly
decreased at 1000 mg/kg/day. Although the decrease was
statistically significant, the mean fetal weight for this
group (3.4 grams) was within the normal values (range of
3.3 - 3.9, mean of 3.5) seen historically. Single cases
of external or visceral malformations were noted in 1
control, 1 mid-dose and 2 high-dose animals. These con-
sisted of a filamentous tail (control), undescended
testes (mid-dose), omphalocele (high-dose) and multiple
anomalies (probably twinning, high-dose). There was no
indication that any of these defects were treatment
related. No skeletal malformations were noted, but the
high-dose fetuses exhibited an increased incidence of
numerous skeletal variations, primarily reduced ossifi-
cation of various bones. Together with the slight
decrease in fetal weights, the skeletal variations
suggest that this N-aryl-cyclic imidate induced a slight
degree of developmental toxicity at the high dose level."
SUBMISSION EVALUATION
The submitted summary provides evidence of maternal toxicity at all
doses administered (i.e., 30 - 1000 mg/kg) . Exposure to 1000 mg/kg
resulted in death (1/25 dams), and decreased food consumption and
body weight gain? clinical signs of toxicity included salivation,
decreased excreta, soft stools, urogenital staining and "red"
material around the mouth. The exposure to 300 mg/kg resulted in
194
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Page 3 of 3
decreased food consumption, and an increased incidence of saliva-
tion. Further, there was a dose-related increase in absolute liver
weight at all dose levels. Developmental toxicity was apparently
only evident following exposure to 1000 mg/kg, and consisted of
decreased fetal body weight and an increased incidence of skeletal
"variations." EPA's evaluation of the overall significance of the
reported findings should be possible upon the Agency's receipt of
a complete copy of the final report from this study.
CURRENT PRODUCTION AND USE
In view of the submitter's TSCA CBI claims, no information about
the TSCA Chemical Substance Inventory status or use(s) of the
subject chemical will appear in this status report. The submitter
did report non-confidentially, however, that this N-aryl-cyclic
imidate is currently being produced exclusively for research and
development (R&D).
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will ask the submitter to
ensure that EPA receives a complete copy of the final
report (including the actual experimental protocol,
results of gross and histopathological examinations,
results of statistical analyses, etc.) from the oral
teratology study cited in the company's submission.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, the submitter will be requested
to describe the actions that the company has taken or
plans to take 1) to notify workers and others about the
reported information, and 2) to reduce or eliminate
exposure to the subject chemical substance. In addition,
the submitter will be asked to describe the nature and
results, if available, of all studies (other than those
submitted already to EPA or those cited in the published
scientific literature) about which the company is aware
or that the company has conducted, is conducting or plans
to conduct that are designed to determine the toxicity
of the subject chemical.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of this N-aryl-cyclic imidate.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
ow/epa, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be provided to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
195
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j?*081** PaSe 1 of 4
CT
1 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
%mi
PBO^fc°
WASHINGTON, DC 20460
DATE:
OCT 2 3
APPROVED:
rM-
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report 8EHQ-1089-0829
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
The BASF Corporation and the GAF Chemicals Corporation submitted
summary information with regard to an oral (gavage) teratology
study of 2-pyrrolidinone (2-pyrrolidone? CAS No. 616-45-5) in rats.
A submitted "SUMMARY REPORT" presents the following information
about the conduct of this study, which was performed in Canada and
co-sponsored by GAF and BASF AG (the West German parent company of
the BASF Corporation):
"Groups of 25 mated female Sprague-Dawley (CD) rats were
treated by gavage, with 2-pyrrolidone, at dosage levels
of 0, 190, 600 or 1,900 mg/kg/day from days 6 to 15 of
gestation, inclusive.
"On day 20 of gestation, the females were killed and
given a gross necropsy examination. The uterine contents
were examined and the fetuses were weighed and examined
externally and internally."
The BASF/GAF Section 8(e) submission cover letter presents the
following information regarding the results of this oral teratology
study:
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
196
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8EHQ-1089-0829
Page 2 of 4
"... [The obtained] data show a low incidence of anal
atresia with absent or reduced tails at the high dose of
1,900 mg/kg/day. This dose also caused a deficit in
maternal body weight gain, an absolute body weight loss
in the interval of [gestational] days 6 through 9, and
lower mean fetal weights. No abnormalities were observed
during gross pathological examination, nor were the
number of live or dead fetuses, numbers of resportions,
pre- or post-implantation losses affected by exposure to
1,900 mg/kg/day.
"The mid-dose exposure to 600 mg/kg/day failed to produce
any significant effects to the litters although a deficit
in maternal body weight gains was demonstrated."
In a previous TSCA Section 8(e) submission (8EHQ-1087-0695), the
CIBA-GEIGY Corporation provided the final reports from mouse and
rat teratology studies of N-methylpyrrolidone (NMP; CAS No. 872-
50-4) conducted by BASF AG in 1970-1971. The final report from the
BASF AG mouse teratology study of NMP stated that a teratological
study of 2-pyrrolidone had been conducted by BASF AG in 1970. At
the Agency's request, the BASF Corporation obtained and provided
(8EHQ-1287-0695 Foliowup Response) an English translation of this
1970 teratology study in which 2-pyrrolidone was given orally or
intraperitoneally (ip) to mice; the BASF Corporation also submitted
an English translation of a 1971 BASF AG teratology study in which
2-pyrrolidone was administered orally to rats. EPA is currently
reviewing BASF AG's 1970-71 teratology studies in conjunction with
other available toxicity and exposure data on 2-pyrrolidone; EPA
is also reviewing available toxicity and exposure data on other
pyrrolidone derivatives. In addition to the previously cited TSCA
Section 8(e) submissions on NMP (8EHQ-1087-0695 et seq.), EPA has
received a "For Your Information" (FYI) submission on NMP (FYI-OTS-
0588-0611) and TSCA Section 8(e) submissions on N-vinylpyrrolidone
(8EHQ-0785-0561 S et seq.) and N-(2-hydroxyethyl)pyrrolidone (8EHQ-
0682-0448 S et seq.). Further, the Test Rules Development Branch
(TRDB/ECAD/OTS) is reviewing available toxicity and exposure data
on NMP, a chemical substance that was recommended for testing under
Section 4 of TSCA by the Consumer Product Safety Commission (CPSC).
For more information about this Section 4-related NMP activity, the
reader is referred to the September 1989 issue (Volume 10; No. 3,
Page 9) of the OTS Chemicals-in-Progess Bulletin; a copy of this
OTS publication can be obtained by contacting the Environmental
Assistance Division (EAD/OTS) by phone at (202) 554-1404, or by
writing:
Environmental Assistance Division
Office of Toxic Substances (TS-799)
U.S. Environmental Protection Agency
401 "M" Street, S.W.
Washington, D.C. 20460
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SUBMISSION EVALUATION
The Toxic Effects Branch (TEB/HERD/OTS) has been asked to review
the rat (oral) teratology study data provided by BASF and GAF in
the present Section 8(e) notice in conjunction with the BASF AG
1970-71 mouse (ip and oral) and rat (oral) teratology studies of
2-pyrrolidone received previously by the Agency in 8EHQ-1287-0695
Followup Response.
CURRENT PRODUCTION AND USE
A review of the production range (includes importation volumes)
statistics for 2-pyrrolidone (CAS No. 616-45-5), which is listed
in the initial TSCA Chemical Substance Inventory, has shown that
between 0 and 1000 pounds were reported as being manufactured
and/or imported in 1977. This production range information does
not include any data that were claimed to be TSCA Confidential
Business Information (TSCA CBI) by the person(s) who reported for
the TSCA Inventory, nor does it include any information that would
compromise TSCA CBI. All of the data reported for the initial
TSCA Inventory, including the production range data, are subject
to the limitations contained in EPA's TSCA inventory Reporting
Regulations (4 0 CFR 710).
According to the present Section 8(e) notice, 2-pyrrolidone "is
used almost exclusively as an intermediate and is, therefore, con-
sumed by the producer in the synthesis of down-stream products."
According to the 10th Edition of the Condensed Chemical Dictionary,
2-pyrrolidone is a "light yellow liquid" produced "from acetylene
and formaldehyde by high-pressure synthesis" and has the following
uses: "Plasticizer and coalescing agent for acrylic latexes in
floor polishes; solvent for polymers, insecticides, polyhydroxylic
alcohols, sugar, iodine, specialty inks, monomer for Nylon-4."
COMMENTS/RECOMMENDATIONS
BASF and GAF reported that both companies are currently revising
their 2-pyrrolidone Material Safety Data Sheets (MSDSs) and are
notifying customers about the reported toxicological findings.
a) The Chemical Screening Branch will ask BASF and GAF to
ensure that EPA receives a full copy of the final report
(including the actual experimental protocol, results of
gross and histopathological examinations, results of any
statistical analyses, etc.) from the teratology study
cited in the companies' Section 8(e) submission.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure information, both BASF and GAF will be
asked to describe .the actions they have taken or plan to
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take 1) to notify their own workers about the reported
information, and 2) to reduce or eliminate exposure to
2-pyrrolidone. In addition, BASF and GAF will be asked
to describe the nature and results, if available, of all
studies (other than those submitted already to the Agency
or those cited in the published scientific literature)
about which the companies are aware or that the companies
have conducted, are conducting or plan to conduct that
are designed to determine the toxicity of or the exposure
to 2-pyrrolidone.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of 2-pyrrolidone.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and TRDB/ECAD/OTS;
copies of this status report will be provided also to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
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*,£5^ 1 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
+ w£ WASHINGTON, DC 20460
'*<¦ PBOlfc°
DATE: NOV ~2
APPROVED:
rftok. ublm
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-1089-0830
-l' '***
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
The Hoechst Celanese Corporation provided the following summary
information with regard to the conduct and preliminary results of
an acute skin corrosivity study of allylamine (2-propene-l-amine;
CAS No. 107-11-9) in rabbits:
"... [Preliminary verbal and hard copy data received
from the performing laboratory] indicate that one of
three New Zealand albino rabbits died as the result of
a three minute skin exposure to 0.5 ml [of allylamine],
or approximately 176 mg/kg. The animal survived through
the one hour observation period but died in the interim
between the one and twenty-four hour observation points.
The two surviving animals exhibited signs of toxicity
including decreased activity and labored breathing
through observation day four but survived through the
seven day observation period. All three [of the] test
animals exhibited evidence of skin corrosion immediately
after the three minute exposure which persisted through-
out the [seven day] observation period."
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
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In submitting this information to EPA under Section 8(e) of TSCA,
Hoechst Celanese stated that "a literature report by Hine et al.
(Hine, C.H. et al., The Toxicity of Allylamines, Archives of
Environmental Health. 1: 65/343-74/352 (October I960)) indicates
a dermal LD50 of 35 mg/kg from an occluded exposure 1 for several
hours,* with reported times of death ranging from three to twenty-
four hours." Hoechst Celanese stated further that the company
believes "that the present test result indicates that allylamine
may be more readily absorbed through the skin than previously
demonstrated."
SUBMISSION EVALUATION
The submitted information does indicate that allylamine is more
toxic than previously described. An evaluation of the overall
significance of the reported findings should be possible upon EPA's
receipt of a complete copy of the final report from the company's
acute dermal toxicity study of allylamine in rabbits.
CURRENT PRODPOTION AND USE
A review of the production range (includes importation volumes)
statistics for allylamine (CAS No. 107-11-9), which is listed in
the initial TSCA Chemical Substance Inventory, has shown that
between 1 million and 10 million pounds were reported as being
manufactured and/or imported in 1977. These production range data
information do not include any data that were claimed to be TSCA
Confidential Business Information (TSCA CBI) by the person(s) who
reported for the initial TSCA Inventory, nor does it include any
information that would compromise TSCA CBI. All data reported for
the initial TSCA Inventory, including the production range data,
are subject to the limitations that are contained in EPA's TSCA
Inventory Reporting Regulations (40 CFR 710) .
According to the 10th Edition of the Condensed Chemical Dictionary,
allylamine has the following uses: "Pharmaceutical intermediate;
inorganic synthesis."
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will ask Hoechst Celanese
to ensure that EPA receives a complete copy of the final
report (including the actual experimental protocol, the
results of gross/histopathological examinations, etc.)
from the company's acute rabbit dermal toxicity study
that was cited in the submission.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, Hoechst Celanese will be asked
to describe the actions that the company has taken or
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Page 3 of 3
plans to take 1) to notify workers and others about the
reported findings, and 2) to reduce or eliminate exposure
to allylamine. In addition, Hoechst Celanese will be
asked to describe the nature and results, if available,
of all studies (other than those submitted already to EPA
or those cited in the published scientific literature)
about which Hoechst Celanese is aware or that the company
has conducted, is conducting or plans to conduct that are
designed to determine the toxicity of or the exposure to
allylamine.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of allylamine.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this report will be sent to the Environmental
Assistance Division/OTS (formerly the TSCA Assistance
Office/OTS) for further distribution. Finally, a copy
of this status report will be provided to the American
Conference of Governmental Industrial Hygienists (ACGIH) .
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? £% ro
I UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
ISSZ
%. _.r<
^ WASHINGTON, DC 20460
DATE:
NOV 14 1989 RPPR0VED! n/ajn
OFFICE: OF
PESTICIDES AND
TOXIC substances
SUBJECT: Status Report1 8EHQ-1089-0831
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
As an update to previous "For Your Information" (FYI) letters sent
to the Agency in 1977 and 19802, ICI Americas Inc. reported that,
to date, 35 ICI workers in the United Kingdom (UK) who worked in
the magnesium (Mg) and high temperature sodium (HTS) processes for
making 4,41-bipyridyl (CAS No. 553-26-4) have developed keratoses.
ICI reported further that "a continuous low temperature sodium
(LTS) process was substituted for the Mg and HTS processes in the
mid 1960's." In addition, ICI stated that "the LTS process is much
cleaner and as a result of work practices and personal protective
equipment requirements, potential exposures are minimized." ICI
also stated that "in the LTS process, no 'tarry' by-products, which
were believed to be the cause of [the] keratoses in people involved
with the Mg and HTS processes, are produced." ICI stated further,
however, that the company recently received information from ICI
PLC (the parent company in the UK) that 1) "keratoses have been
identified in three employees who work in the LTS plant at Widnes
(UK)" and 2) "these people are the only employees involved solely
with the LTS process to exhibit such skin lesions."
fc-
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
2 According to ICI Americas Inc., the Agency assigned these previous letters to the FYI
No. 0113 file; copies of the two FYI letters were enclosed with ICI's TSCA Section 8(e)
submission.
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In its TSCA Section 8(e) submission, ICI provided the following
information about the company's U.S. production of 4,4•-bipyridyl:
"ICI Americas Inc. operates a plant at Bayport, Texas
using the LTS process to make 4,4•-bipyridyl. Strict
industrial hygiene practices have been followed since the
[Bayport] plant began production of 4,4'-bipyridyl in
1977. Health professionals at the Bayport site have
actively surveyed employees via annual physicals and
special programs. There are no findings of keratoses,
Bowens disease or squamous cell carcinoma in potentially
exposed employees. Those employees have been briefed on
the current situation.
"It is believed that the problem evidenced in the UK is
associated with the raw materials, intermediates or by-
products [that are] associated with the manufacture of
4,4'-bipyridyl, as the pure compound has been subjected
to a lifetime skin painting study in mice and showed no
evidence of skin disease. Furthermore, quaternization
of 4,4 • -bipyridyl to paraquat is carried out in five
countries in plants owned or controlled by ICI PLC and
there is no evidence to suggest a causal relationship
between paraquat and keratomas."
In its TSCA Section 8(e) submission, ICI also included a full copy
of the following published scientific article: "Premalignant and
neoplastic skin lesions associated with occupational exposure to
•tarry1 byproducts during manufacture of 4,4'-bipyridyl11 British
Journal of Industrial Medicine 1982; 39: 76-81.
SUBMISSION EVALUATION
Staff of the Statistical Analysis and Epidemiology Section/Design
and Development Branch in the Exposure Evaluation Division/OTS has
been asked to review the new epidemiologic findings in context with
those 1) previously reported to the Agency on an FYI basis, and 2)
presented in the scientific paper published in 1982.
CURRENT PRODUCTION AND USE
A review of the production range (includes importation volumes)
statistics for 4,4•-bipyridyl (CAS No. 553-26-4), which is listed
in the initial TSCA Chemical Substance Inventory, has shown that
no 1977 manufacture/importation was reported or that 'all of the
manufacture and/or importation data reported were claimed as TSCA
Confidential Business Information (CBI) by the person(s) reporting
for the initial Inventory and cannot be disclosed (Section 14(a)
of TSCA; U.S.C. 2613(a)). All data reported for the TSCA Inventory,
including the production range data, are subject to the limitations
contained in the TSCA Inventory Reporting Regulations (40 CFR 710) .
According to ICI, 4,4' -bipyridyl is an intermediate used in the
manufacture of paraquat (an herbicide).
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COMMENTS/RECOMMENDATIONS
ICI stated that as a result of the reported information, "a major
review of toxicological data and operating practices is being
developed" and "will include a detailed comparative review of the
operating practices at all ICI plants that produce 4,4 • -bipyridyl."
a) The Chemical Screening Branch will request ICI Americas
to keep the Agency apprised of significant additional
findings from ongoing ICI studies involving the company's
4,4 ' -bipyridyl production workers. In addition, ICI will
be asked to submit a complete copy of the final report
(including the actual experimental protocol, results of
gross and histopathological examinations, results of any
statistical analyses, etc.) from the mouse skin painting
study of 4,4'-bipyridyl cited in ICI's TSCA Section 8(e)
submission.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity or exposure data, please describe the nature and
results, if available, of all studies (other than those
submitted already to the Agency or those cited in the
published scientific literature) about which ICI is aware
or that ICI has conducted, is conducting, or plans to
conduct that are designed to determine the toxicity of
4,4'-bipyridyl.
b) The Chemical Screening Branch will review the submitted
information further in order to determine the need for
additional OTS assessment of the reported findings.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA? in addition,
copies of this report will be sent to the Environmental
Assistance Division/OTS (formerly the TSCA Assistance
Office/OTS) for further distribution.
205
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I ^ | UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
PRO'11'0'"
DATE: OCT 2 6 i989
from:
APPROVED
: 71*- iof»fr
SUBJECT: status Report1 8EHQ-1089-0832
David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
Huls America Inc. provided the following summary information with
regard to triethoxysilane (CAS No. 998-30-1) and a recent workplace
incident involving this chemical substance:
"Triethoxysilane is a known skin and eye irritant. The
onset of symptoms with respect to the eyes can sometimes
be delayed by a few hours. In all cases known to Hills
America where the symptoms were reliably ascribed to
known exposure, the exposures were at a concentration
whereby the presence of triethoxysilane vapors were
readily detected by smell.
"As a result of an accident investigation report . . . ,
it appears that delayed symptoms of eye irritation may
result from prolonged exposure to triethoxysilane at
concentrations near or below the odor threshold.
"Specifically, . . . five employees at the Huls America
pilot plant site in Bristol, Pennsylvania were working
in an area where triethoxysilane was being processed. In
such situations, it is the practice to wear eye goggles
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
206
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if the odor of triethoxysilane is apparent. Since no
odor or, in retrospect, only a trace odor was apparent,
eye goggles were not worn during the period of exposure,
which lasted an entire eight hour shift. Several hours
after the exposure, two of the [five] employees reported
experiencing eye irritation and were subsequently treated
at a local hospital emergency room. As a precautionary
measure, the other three employees were sent for a medi-
cal examination for eye irritation. These three employees
also received medical attention. It should be noted,
however, that all five employees have returned to work
with no apparent permanent effects. A followup investi-
gation determined that triethoxysilane, which was present
in the work area, is most probably the causative agent."
SUBMISSION EVALUATION
Immediately upon receipt, the Chemical Screening Branch sent full
copies of this TSCA Section 8(e) notice to the Risk Analysis Branch
(RAB/ECAD/OTS) for inclusion in their ongoing review of available
toxicity and exposure information on organosilanes. It should be
noted that EPA has received a number of Section 8(e) and "For Your
Information" (FYI) submissions on organosilanes. In addition, the
Chemical Screening Branch did prepare (in 1986) a "Chemical Hazard
Information Profile" (CHIP) covering a number of organosilanes.
CURRENT PRODUCTION AND U8E
A review of the production range (includes importation volumes)
statistics for triethoxysilane (CAS No. 998-30-1), which is listed
in the initial TSCA Chemical Substance Inventory, has shown that
between 0 and 1000 pounds of this chemical substance were reported
as manufactured and/or imported in 1977. This production range
information does not include any data that were claimed to be TSCA
Confidential Business Information (TSCA CBI) by the person(s) who
reported for the TSCA Inventory, nor does it include any informa-
tion that would compromise TSCA CBI. All of the data reported for
the initial TSCA Inventory, including the production range data,
are subject to the limitations contained in the TSCA Inventory
Reporting Regulations (40 CFR 710).
Hlils America did not provide any information on the use(s) of
triethoxysilane, nor was such information located in the secondary
literature sources consulted by EPA.
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will ask Hiils America to
ensure that EPA is kept apprised of any further medical-
related developments arising^ from the reported workplace
incident. In addition, Hu-ls America will be requested
to report the triethoxysilane vapor concentrations, if
known, in the work area preceding, during and after the
cited incident.
207
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Page 3 of 3
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, Hiils America will be requested
to describe the actions that the company has taken or
plans to take 1) to notify workers and others about the
reported information, and 2) to reduce or eliminate
exposure to triethoxysilane. in addition, Hiils America
will be asked to describe the nature and results, if
available, of all studies (other than those submitted
already to EPA or those cited in the published scientific
literature) about which Hiils America is aware or that the
company has conducted, is conducting or plans to conduct
that are designed to determine the toxicity of or the
exposure to triethoxysilane.
b) As was the case for the initial submission, the Chemical
Screening Branch will immediately copy and send all of
the reported information to the Risk Analysis Branch for
review.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and RAB/ECAD/OTS;
a copy of this report will be sent also to the American
Conference of Governmental Industrial Hygienists (ACGIH) .
In addition, copies of this status report will be sent
to the Environmental Assistance Division/OTS (formerly
the TSCA Assistance Office/GTS) for further distribution.
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
DATE: QQJ- 2 9 i989 APPROVED! *1$*JFj
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-1089-0833 S
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
Eli Lilly and Company has claimed the exact identity of the subject
chemical to be TSCA Confidential Business Information (CBI). Staff
of the Information Management Division will review all incoming
correspondence related to this TSCA CBI claim. In the "sanitized"
version of the submission, Eli Lilly reported non-confidentially
that the subject chemical is a "substituted guinoline" that "has
not been characterized."
SUBMISSION DESCRIPTION
Eli Lilly reported that preliminary results from an acute oral
toxicity study in mice showed that this substituted quinoline has
"a median lethal dose less than 50 mg/kg." Eli Lilly provided the
following summary regarding the conduct and results of this study:
"The acute toxicity of the compound administered orally
to female CD-I mice was evaluated. There were three
animals in each of the three dose groups, and the animals
received either 50, 500, or 2000 mg/kg of the compound.
There were no survivors following a single oral dose of
50 mg/kg of this compound. All [of the] deaths occurred
by Test Day 1. Antemortem signs of toxicity included
ataxia, coma, hypoactivity, and lethargy."
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
209
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Page 2 of 2
SUBMISSION EVALUATION
The submitted summary information indicates that this substituted
quinoline is extremely toxic via oral administration to mice._ An
evaluation of the overall significance of the reported findings
should be possible upon EPA's receipt of a complete copy of the
final report from the acute mouse oral toxicity study cited in the
company's Section 8(e) submission.
CURRENT PRODUCTION AND USE
In view of Eli Lilly's TSCA CBI claim/ no information regarding
the TSCA Chemical Substance Inventory status or use(s) of this
substituted quinoline will appear in this report. Eli Lilly did
report non-confidentially, however, that only 1.6 grams of this
research chemical have been manufactured as of the date of the
company's submission.
COMMENTS/RECOMMENDATIONS
In its submission, Eli Lilly stated that company employees were
notified about the acute toxicity findings for this substituted
quinoline. In addition, Eli Lilly reported that the subject
chemical substance was already labelled as "hazardous." Finally,
Eli Lilly stated that "no other toxicology data have been generated
on this compound."
a) The Chemical Screening Branch will ask Eli Lilly to
ensure that EPA receives a complete copy of the final
report (including the actual experimental protocol,
results of gross and histopathological examinations,
results of statistical analyses, etc.) from the acute
oral toxicity study cited in the company's submission.
Eli Lilly will be asked also to submit, if and when
available, a full chemical characterization of the test
material.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of this substituted quinoline.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA; ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be provided to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
210
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
DATE:
OCT 2 9 198:
APPROVED:
SUBJECTS Status Report1 8EHQ-1089-0834 S
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
Eli Lilly and Company has claimed the exact identity of the subject
chemical to be TSCA Confidential Business Information (CBI). Staff
of the Information Management Division will review all incoming
correspondence related to this TSCA CBI claim. In the "sanitized"
version of the submission, Eli Lilly reported non-confidentially
that the subject chemical is an "organo tin compound" that "has not
been characterized."
SUBMISSION DESCRIPTION
Eli Lilly reported that preliminary results from an acute oral
toxicity study in mice showed that the chemical has "a median
lethal dose [of] less than 50 mg/kg." Eli Lilly provided the
following summary regarding the conduct and results of this study:
"The acute toxicity of the compound administered orally
to female CD-I mice was evaluated. There were three
animals in each of the three dose groups, and the animals
received either 50, 500, or 2000 mg/kg of the compound.
There were no survivors following a single oral dose of
this compound. All [of the] deaths occurred by Test Day
3. Antemortem signs of toxicity included ataxia, coma,
hypoactivity, piloerection, hunched posture and tremors."
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
211
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Page 2 of 2
SUBMISSION EVALUATION
The submitted summary information indicates that this organo tin
compound is extremely toxic via oral administration to mice. An
evaluation of the overall significance of the reported findings
should be possible upon EPA's receipt of a complete copy of the
final report from the acute mouse oral toxicity study cited in the
company's Section 8(e) submission.
CURRENT PRODUCTION AND USE
In view of Eli Lilly's TSCA CBI claim, no information regarding
the TSCA Chemical Substance Inventory status or use(s) of this
organo tin compound will appear in this report. Eli Lilly did
report non-confidentially, however, that this organo tin compound
is a "research" chemical.
COMMENTS/RECOMMENDATIONS
In its submission, Eli Lilly stated that company employees have
been notified about the acute toxicity findings for this organo tin
compound. In addition, Eli Lilly reported that the subject chemical
substance was already labelled as being potentially "hazardous."
Finally, Eli Lilly stated that a "mouse oral screen retest and a
gradient plate assay for genetic toxicology are scheduled for this
compound."
a) The Chemical Screening Branch will ask Eli Lilly to
ensure that EPA receives a complete copy of the final
report (including the actual experimental protocol,
results of gross and histopathological examinations,
results of statistical analyses, etc.) from the acute
oral toxicity study, the acute oral toxicity retest, and
the genotoxicity study cited in the company's submission.
Eli Lilly will be requested also to- submit, if and when
available, a full chemical characterization of the test
material.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of this organo tin compound.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be provided to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
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A*08**,
Page 1 of 9
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
DATE: 0£C 28 1989 APPROVED:
SUBJECT: Status Report1 8EHQ-1089-0835 S INIT
8EHQ-1188-0835 8UPP (**)
8EHQ-0989-0835 S SUPP (**)
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS
NOTE
The BASF Corporation has claimed the exact identity of the subject
chemical to be TSCA Confidential Business Information (CBI). Staff
of the Information Management Division will review all of BASF's
correspondence related to this TSCA CBI claim. In the "sanitized"
version of its Section 8(e) submission, the company reported non-
confidentially that the chemical is a "triazole derivative."
SUBMISSION DESCRIPTION
In its Section 8(e) submission, BASF provided summary information
regarding a two-generation rat reproduction study of this triazole
derivative. BASF's Section 8(e) cover letter presents the following
information about the conduct and preliminary results of this study
which was performed by BASF's parent company, BASF AG, located in
West Germany:
"... [The subject triazole derivative] was continuously
administered in the feed to Wistar rats (25 animals per
sex per group) at concentrations of 0, 30, 300 and 1,500
ppm. The preliminary results presented here were obtained
and evaluated after weaning of [the] Fia pups.
1 This status report is the result of a preliminary evaluation of information submitted to
EPA on a "For Your Information" (FYI) basis .and under Section 8(e), the "substantial risk"
information reporting provision of the Toxic Substances Control Act (TSCA). The statements
made in this status report should not be regarded as expressing final Agency policy or intent
with respect to the subject chemical. Any review of this status report should take into account
that the report may be based on incomplete information.
(**) Formerly FYI-OTS-1188-0653 INIT and FYI-OTS-0989-0653 S FLWP.
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"Clear signs of toxicity were seen for both males and
females at the 1,500 ppm treatment level in the form of
reduced feed consumption and reduced body weight/body
weight change. A reduction in feed consumption was also
observed during the lactation period in the 3 00 ppm dose
level
"At the highest treatment level [(1,500 ppm)], pregnancy
was confirmed for only 8 out of 25 females. Three females
died during delivery and 5 females delivered a total of
20 pups. Nine pups were stillborn and the remaining 11
died or were cannibalized within 4 days after birth.
Thus, no pups were available for the formation of a
second generation at this [high] dose level. For this
reason, the study is being terminated. At the 300 ppm
dose level, an increase in the number of stillborn pups
was observed. In addition, more pups died and more pups
were cannibalized than in the control group. There were
no substance-related teratogenic effects observed,
especially no cleft palates, a typical triazole-induced
malformation. . ."
In a previous "For Your Information" (FYI) notice (FYI-OTS-1188-
0653 INIT), BASF provided the following summary information about
the conduct and preliminary results of a rat oral teratology study
of this triazole derivative, identified non-confidentially by BASF
at that time simply as a "developmental fungicide."
"The test substance was administered to pregnant Wistar
rats (25/group) by gavage daily for a period of 10 days
(day 6-15 post coitum) in doses of 20, 60 and 180 mg/kg
body weight/day. For comparison, a control group of sham
treated animals was used. The dams were sacrificed on
day 20 p.c.; the fetuses were developed by cesarean
section and examined macroscopically.
"Clear signs of maternal toxicity were observed at 20
mg/kg b.w. and the dose levels above. Signs of embryo-
toxicity expressed by increased numbers of resorptions
and reduced numbers of live fetuses were seen at the 60
and 180 mg/kg b.w. levels. Malformations (exclusively
cleft palates) in the presence of marked maternal toxi-
city occurred only at the highest dose level of 180 mg/kg
b.w. About 50% of the fetuses in about 90% of the litters
of this dose group were involved."
In this FYI notice, BASF stated that this type of malformation
(i.e., cleft palate) "has been reported for chemicals of similar
structure." BASF also stated that because "the malformations only
occurred at a dose far beyond the threshold for maternal toxicity,
the possible risk - if at all - for developmental toxicity in man
can be assumed to be low."
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With regard to other studies on this developmental fungicide, BASF
reported in its initial FYI submission that further studies were
being performed "in the course of toxicological evaluation of the
compound in order to establish a NOEL [(i.e., no-observed-effeet-
level) ] for maternal toxicity in rats and to investigate prenatal
toxicity in a second species and reproductive toxicity in a multi-
generation study." (Note: The multigeneration study cited in BASF's
initial FYI appears to be the subject of the present Section 8(e)
submission.) In its initial FYI, BASF also provided the following
information about the labelling of this developmental fungicide:
"[The] BASF Corporation will ensure that all future
deliveries of experimental samples will be labelled to
reflect the teratogenic potential of this class of
chemicals. This is a provisional measure until it has
been confirmed in the multigeneration study and the
teratogenicity study in a second species that malforma-
tions due to this fungicide only occur in the presence
of marked maternal toxicity. Results of future studies
being conducted for pesticide registration will be
submitted to EPA when they become available."
In evaluating the summary information contained in BASF's initial
FYI submission and despite the fact that the submission consisted
of only a two-page letter with no tabulated data, EPA believed that
the reported information indicated clearly that the tested chemical
caused serious developmental toxicity and maternal toxicity of an
unknown magnitude. With regard to maternal toxicity, the submission
stated that "clear signs of maternal toxicity" were observed at all
of the dose levels tested; however, no information was presented
concerning the nature of these toxic signs or in how many of the
dams these signs were observed. With regard to the developmental
toxicity, reduced numbers of live fetuses and increased numbers of
resorptions were reportedly observed in both the 60 and 180 mg/kg/
day dose groups; again, no numbers were presented regarding these
observations. At 180 mg/kg/day dose, 50% of the fetuses from 90%
of the litters reportedly had cleft palate, a major malformation.
In its evaluation of the summary information contained in BASF's
initial FYI submission, EPA noted also that the company's attempt
to dismiss the serious adverse developmental effects on the basis
of concurrent maternal toxicity was not appropriate. EPA pointed
out that it has been the Agency's longstanding position that one
cannot automatically assume that developmental effects occurring
at maternally toxic dose levels result only from the maternal
toxicity. EPA noted further that this longstanding position was
reaffirmed in the Agency's 1986 Risk Assessment Guidelines and a
published summary2 of an EPA workshop on developmental/maternal
2 Kimmel, G.L., Kimmel, CA. and Francis, E.Z. "Implications of the [EPA] Consensus
Workshop on the Evaluation of Maternal and, Developmental Toxicity" Terat., Carcinogen,
and Mutagen. 7:329-338 (1987).
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toxicity. Finally, the Agency pointed out that 1) the mother and
embryo/fetus may be sensitive to the same dose of a chemical, and
2) the adverse effects that are experienced by the mother may be
reversible while those that affect the offspring may be permanent.
Following a review of the summary information presented in FYI-OTS-
1188-0653 INIT, EPA informed BASF in writing on August 16, 1989
that the Agency believed that the developmental toxicity findings
presented in that FYI notice should have been submitted formally
under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substances Control Act (TSCA). BASF was
afforded 20 working days to rebut the Agency's initial position
with regard to the TSCA section 8(e)-applicability/reportability
of the serious adverse developmental effects information contained
in BASF's initial FYI submission. In addition, BASF was requested
to provide the exact identity (including CAS Registry Number, if
known) for the developmental fungicide. Further, BASF was asked
to submit a full copy of the final report (including the actual
experimental protocol, results of gross and histopathological
examinations, results of any statistical analyses, etc.) from the
rat oral teratology study that was cited in the company's initial
FYI submission.
In response to EPA's written request for additional information,
BASF submitted (FYI-OTS-O989-0653 S FLWP) an explanation of why the
preliminary findings from the rat oral teratology study were not
sent to EPA under TSCA Section 8(e). In addition, BASF provided
the exact identity of the subject chemical (claimed as TSCA CBI)
as well as summary information about the conduct and preliminary
results from l) the rat oral teratology study that was cited in the
company's initial FYI submission, and 2) several ongoing rat and
rabbit teratology studies of the subject chemical:
Rat Teratology Studies
"Because the . „ . [rat oral teratology study cited in
BASF's initial FYI submission] did not establish a NOAEL
[(i.e., no-observed-adverse-effect-level)] for maternal
toxicity , the protocol for that study was amended to
specify that the study would be used as a range-finding
study. A second rat teratology study with . . . [this
triazole derivative] was then initiated by BASF AG in
which dose levels of 0, 5, 15 and 45 mg/kg body weight/
day were administered [by gavage]. The protocol for the
second study was the same as the first, except thai: the
skeletons and organs of the fetuses were to be examined
microscopically.
3 According to FYJ-OTS-0989-0653 S FLWP, "clear signs of maternal toxicity in the form
of impaired food comumption and impaired body weight gain were observed at all three dose
levels [(20, 60 and 180 mgjkg/day) in the rat oral teratology study cited in BASF's initial FYI
submission] "
216
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"In the second [rat oral teratology] study, 15 mg/kg was
established as a NOEL for maternal effects. At the 45
mg/kg level, again signs of maternal toxicity in the form
of impaired food consumption and impaired body weight
gain were observed. External examination of the fetuses
has shown no increased incidence of malformations or any
cleft palates. [Microscopic] examination of the fetal
organs is underway and the skeletons are being prepared
for examination."
Rabbit Teratology Studies
"In a range-finding teratology study with rabbits . . .
[the triazole derivative] was administered orally by
gavage during days 7 through 19 post-insemination at dose
levels of 0, 50, 150 and 300 mg/kg body weight/day (5
animals per dose group). Maternal toxicity was demon-
strated at the 150 and 300 mg/kg levels in the form of
impaired food consumption and impaired body weight gain.
Embryolethality was observed at the 150 and 3 00 mg/kg
dose levels. No increased incidence of malformations,
especially cleft palates, was observed in the 50 mg/kg
dose group after external and soft tissue examinations
of the fetuses.
"Based on the results from the range-finding study, a
rabbit teratology main study with . . . [this triazole
derivative] was initiated using [oral] dose levels of 0,
5, 20 and 80 mg/kg body weight/day (15 animals per dose
group). Maternal toxicity was demonstrated in the form
of impaired food consumption and impaired body weight
gain at the 80 mg/kg dose level. Fetotoxicity was
observed in the form of increased post-implantation
losses only at the 80 mg/kg level. Again, no increased
incidence of malformations, especially cleft palates, was
observed in this teratology main study with rabbits. The
skeletal examination [of the fetuses] has not been
completed."
In FYI-OTS-0989-0653 S FLWP, BASF also provided a number of data
tables from the cited rat and rabbit oral teratology studies. In
addition, BASF stated that final reports from all of the teratology
studies (2 in rats and 2 in rabbits) are expected to be finalized
and forwarded to EPA by mid-1990.
With regard to reporting rationale, BASF stated that the company
believed it was justified in submitting the developmental toxicity
findings for this triazole derivative on an FYI basis because 1)
the teratogenic effects were observed at maternally toxic dose
levels, 2) the adverse developmental effects information was not
"new" because such effects had been observed and reported for other
triazole derivatives, and 3) the potential for exposure to the
subject chemical was "minimal due to limited distribution to
qualified researchers."
217
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SUBMISSION EVALUATION
Taken alone or in combination, the reported study findings provide
evidence for maternal/parental, developmental and/or reproductive
toxicity after exposure to this triazole derivative.
Rat Teratology Studies (FYI submissions)
The rat studies demonstrated maternal toxicity (evidenced by a
significant reduction in food consumption and body weight gain)
after exposure to doses of 4 5 mg/kg/day or more. Developmental
toxicity was also evident after exposure to 4 5 mg/kg or more.
Further, exposure to 45 mg/kg resulted in a significant increase
in resorptions, while increasing the dose to 180 mg/kg resulted in
a significant increase in the incidence of cleft palate. At the
time of reporting, the fetal skeletal evaluations had not been
completed.
Rabbit Teratology Studies fFYI submissions)
The rabbit studies demonstrated maternal toxicity (evidenced by a
significant reduction in food consumption and body weight gain) as
well as developmental toxicity (evidenced by a significant increase
in resorptions) after exposure to doses of 80 mg/kg or more. Again,
the fetal skeletal evaluations had not been completed at the time
of reporting.
Rat Reproduction Study (Section 8(e) submission)
Although this study was not completed at the time of reporting (the
FjA pups had just been weaned), the submitted preliminary results
do provide evidence for reproductive and developmental toxicity.
Parental toxicity (evidenced by a significant reduction in food
consumption and body weight gain, and a significant reduction in
fertility) was observed following dietary exposure to 1500 ppm.
Developmental toxicity was observed after exposure to 30 ppm (the
lowest dose tested) or more. Exposure to 300 ppm or more resulted
in a significant increase in the length of gestation, a significant
increase in stillbirths and concomitant decrease in live pups, and
a significant decrease in postnatal survival? exposure to 30 ppm
resulted in a significant increase in stillbirths.
In order to evaluate the overall significance of the reported
toxicological findings, BASF should be asked to ensure that EPA
receives full copies of the final reports from all o£ the cited
studies.
CURRENT PRODUCTION AND USE
According to the BASF Corporation's TSCA Section 8(e) submission,
this triazole derivative is currently being evaluated by BASF AG
as a fungicide for which the BASF Corporation plans to apply for
a registration under the U.S. Federal Insecticide, Fungicide and
218
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Rodent icicle Act (FIFRA) . BASF also reported that, thus far, the
company has only imported small amounts of the subject chemical
from BASF AG for distribution to testing facilities.
COMMENTS/RECOMMENDATIONS
The following discussion addresses the Section 8(e)-applicability/
reportability of the adverse developmental effects information that
was presented in BASF's initial and followup FYI submissions (i.e.,
FYI-OTS-1288-0653 INIT and FYI-OTS-0989-0653 S FLWP):
Under TSCA, the Agency can regulate certain activities
involving chemical substances and mixtures. A substance
that is manufactured, processed or distributed in com-
merce solely as a pesticide is excluded by Section 3 of
TSCA from TSCA regulation. In accordance with EPA's TSCA
Chemical Substance Inventory reporting regulations (43
FR 64585, December 23, 1977, Appendix A, Comments 37, 38
and 39) , however, a chemical substance which is in the
process of research and development (R&D) as a pesticide
is subject to TSCA until the manufacturer or importer
demonstrates intent to create a pesticide by submitting
to EPA an application for an experimental use permit
(EUP) or registration under FIFRA. It should be noted
that the Agency affirmed this interpretation in the
recent amendments to the TSCA Section 5 "Premanufacture
Notification Rule" (51 FR 15098; April 22, 1986). Prior
to the EUP or registration stages, therefore, the Agency
treats such a substance as a "chemical substance" under
the jurisdiction of TSCA, including Section 8(e) of TSCA.
TSCA Section 8(e) states "any person who manufactures,
[imports,] processes or distributes in commerce a chemi-
cal substance or mixture and who obtains information
which reasonably supports the conclusion that such sub-
stance or mixture presents a substantial risk of injury
to health or the environment shall immediately inform the
[EPA] Administrator of such information unless such
person has actual knowledge that the Administrator has
been adequately informed of such information."
The preface to Part V of EPA's TSCA Section 8(e) policy
statement ("Statement of Interpretation and Enforcement
Policy; Notification of Substantial Risk" 43 FR 11110;
March 16, 1978) explains that a "substantial risk of
injury to health ... is a risk of considerable concern
because of (a) the seriousness of the effect . . . and
(b) the fact or probability of its occurrence."
With regard to the seriousness of the effect, Part V
explains that EPA considers the types of health effects
for which substantial risk information must be reported
to include "any pattern of effects or evidence that the
chemical substance or mixture can produce . . . birth
defects or toxic effects resulting in death, or serious
219
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Page 8 of 9
or prolonged incapacitation.11 The information regarding
these effects can be obtained directly or inferred from
designed studies (e.g., studies in animals) as described
in Part VI of the policy statement. Part VI explains
also that a "person is not to delay reporting until he
obtains conclusive information that a substantial risk
exists, but is to immediately report any evidence that
reasonably supports that conclusion."
With regard to the "fact or probability of its [(i.e.,
the serious effect's)] occurrence" criterion, Part V of
the Section 8(e) policy statement explains that certain
types of adverse health effects (e.g., birth defects)
are considered so serious that relatively little or no
weight should be attached to the chemical's exposure in
determining whether a risk is substantial. Further, EPA's
response to Comment 31 in Appendix B of the Section 8(e)
policy statement, as it pertains to a question on R&D
chemicals, states that the occurrence of serious effects
such as those described in Part V(a) of the Section 8(e)
policy statement (e.g., birth defects) presuppose the
exposure to the chemical substance and must be reported
immediately to EPA under Section 8(e). Therefore, if a
subject company obtains substantial risk information
about a chemical substance during R&D of that chemical
as a pesticide, reporting would be required under TSCA
Section 8(e) if such information is obtained prior to
the application for an EUP for, or registration of, that
chemical as a pesticide under FIFRA (even though such
information might be submitted to EPA at a later date).
The following discussion addresses the submitter's rationale for
not reporting the subject findings under Section 8(e) of TSCA:
Section 8(e) of TSCA requires timely submission of
evidence (including preliminary evidence) from animal
studies that implicates the tested chemical as causing
serious toxicologic effects (e.g., cancer, neurotoxicity,
birth defects or other serious developmental effects).
The decision to report the observance of such serious
toxicological effects should not hinge in any way on a
judgement of either the actual or potential exposure to
the chemical or a judgement about the degree of relevancy
of the findings to an overall assessment of human risk.
In other words, the decision to report under Section 8(e)
in many cases should be based simply on the observance
of serious toxicologic effects.
Specifically with regard to the issue of developmental
and maternal toxicity, the observance of a statistically
or biologically significant increase in a teratogenic
effect or other serious embryotoxic or fetotoxic effects
(e.g., significant embryo or fetal lethality, spontaneous
abortion) should be reported to EPA under Section 8(e)
220
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regardless of the level of maternal toxicity observed in
the study or the potential for exposure to the tested
chemical substance.
While EPA agrees with BASF that a body of knowledge does
exist for potential developmental and other toxic effects
posed by exposure to triazole and several of the triazole
derivatives, the observed developmental effects for the
subject triazole derivative under the parameters of the
performed studies were not known by EPA. Therefore, EPA
considers BASF's findings to be "new" information for the
purposes of Section 8(e) reporting.
Considering the preceding discussions, EPA has determined that the
toxicological information in FYI-OTS-1188-0653 INIT and FYI-OTS-
0989-0653 S FLWP is "new" information that reasonably supports the
conclusion that the subject triazole derivative can cause terato-
genic and other serious adverse developmental effects. As such,
BASF's findings should have been submitted to the Agency formally
under Section 8(e) of TSCA.
a) The Existing Chemical Assessment Division will inform
BASF about EPA's decision regarding the Section 8(e)-
applicability/reportability of the findings contained in
FYI-OTS-1188-0653 INIT and FYI-OTS-0989-0653 S FLWP. BASF
will be informed also that the Chemical Screening Branch
has delivered these two FYI notices to the OTS Document
Control Officer (DCO) for immediate processing and filing
as supplemental Section 8(e) submissions to the present
Section 8(e) submission (8EHQ-1089-0835 S INIT).
BASF will be asked to ensure that EPA recieves a complete
copy of the final report from each study that was cited
in BASF's Section 8(e) and/or FYI submissions immediately
upon BASF's receipt of the study report.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of the subject triazole derivative.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA, and OCM/OPTS/EPA;
in addition, copies of this status report will be sent
to the Environmental Assistance Division/OTS (formerly
the TSCA Assistance Office/OTS) for further distribution.
221
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Page 1 of 3
* UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WJ WASHINGTON, DC 20460
DATE: NOV I 4 1989 APPROVED:
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-1089-0836
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
In its TSCA Section 8(e) submission, the CIBA-GEIGY Corporation
reported that the subject chemical substance, Chimassorb 119 (CAS
No. 106990-43-6), had been the subject of a TSCA Section 5 "Pre-
Manufacture Notification" (PMN No. P-87-328) for which a "Notice
of Commencement" (NOC) was filed with EPA on December 10, 1987.
According to CIBA-GEIGY, Chimassorb 119 . is N,N«'1-[1,2-ethane-
diylbis[[[4,6-bis[butyl(1,2,2,6,6-pentamethyl-4-piperidinyl] ] -
bis[N' ,N1 '-dibutyl-N' ,N' '-bis(l,2,2,6,6-pentamethyl-4-piperidinyl-
1,3,5-triazine-2,4,6-triamine.
SUBMISSION DESCRIPTION
The CIBA-GEIGY Corporation provided a complete copy of the final
report from a 90-day feeding study of Chimassorb 119 (CAS No.
106990-43-6) in rats. CIBA-GEIGY's cover letter presents the
following information about the conduct and results of this study:
"In [the study], rats, were fed diets containing 0, 150,
800, 3000, and 12000 ppm CAS No. 106990-43-6. The primary
finding was an increased presence of phagocytic cells
(foamy macrophages) in a number of organs such as,lymph
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report shpuld
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
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8EHQ-1089-0836
Page 2 of 3
nodes, small and large intestine, liver, spleen, ovary,
adrenal gland, and kidney. These tissue reactions lead
to secondary histopathological findings such as inflam-
matory and necrotizing changes. In addition, signs of
anemia were present along with [a] disturbance in liver
and kidney function. The no-observable-effect-level
(NOEL) for the increase in foamy macrophages was below
150 ppm (approximately 9.8 mg/kg BW/day) 11
SUBMISSION EVALUATION
Immediately upon receipt, a complete copy of this Section 8(e)
submission was sent by the Chemical Screening Branch to staff of
the Chemical Control Division (CCD/OTS); CCD is responsible for
EPA's "New Chemicals Program" (NCP) under Section 5 of TSCA. It
should be noted also that EPA has received a number of Section 8(e)
submissions on piperidinyl-based UV light stabilizers; in 1988, the
Chemical Screening Branch prepared a "Chemical Hazard Information
Profile" (CHIP) on several of these chemicals. With regard to the
present Section 8(e) submission, the Chemical Screening Branch will
review the data on Chimassorb 119 in context with the information
contained in 1) the previously received Section 8(e) notices, and
2) the CHIP document on piperidinyl-based UV light stabilizers.
CURRENT PRODUCTION AND USE
In its TSCA Section 8(e) submission, CIBA-GEIGY reported that
Chimassorb 119 is "an imported material at a very early stage of
commercial development." In addition, CIBA-GEIGY reported that
Chimassorb 119 has "been sold to two customers in total quantities
of less than 1000 lbs., as a major component of a light stabilizer
formulation for polymers." CIBA-GEIGY stated further that because
"the material is identified on the label and Material Safety Data
Sheet as a sensitizer, the recommended handling precaution of 'wear
impervious gloves' should protect against dermal exposure." In
conclusion, CIBA-GEIGY stated that "because a granular form of the
material is sold, inhalation exposure [to Chimassorb 119] is not
expected to be significant."
COMMENTS/RECOMMENDATIONS
a) In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, the Chemical Screening Branch
will ask CIBA-GEIGY to describe the nature and results,
if available, of all studies (other than those submitted
already to EPA or those cited in the published scientific
literature) about which CIBA-GEIGY is aware or that the
company has conducted, is conducting or plans to conduct
that are designed to determine the toxicologic properties
of the subject chemical substance.
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8EHQ-1089-0836
Page 3 of 3
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of the subject chemical.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and CCD/OTS; in
addition, copies of this status report will be provided
to the Environmental Assistance Division/OTS (formerly
the TSCA Assistance Office/OTS) for further distribution.
224
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Page 1 of 4
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
OFFICE OF
PESTICIDES AND
DATE: NOV **7 1989 APPROVED?
/Ifo. "I"/*)
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-1089-0837 S
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE (See NOTE on Page 4 of this status report)
The submitting company has claimed its company name and the exact
identity of the subject chemical to be TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. In the "sanitized" version of its Section 8(e)
notice, the company reported non-confidentially that the subject
chemical is an "alkyl trialkoxysilane."
SUBMISSION DESCRIPTION
The submitting company provided summary information regarding the
conduct and preliminary results of several in vivo toxicity studies
and one in vitro genotoxicity study of this alkyl trialkoxysilane.
In an acute toxicity study involving the oral administration of the
subject chemical to rats at a single oral dose of from 1000 to 4000
mg/kg, the LD50 was reported to be approximately 2200 mg/kg (males
and females combined) with the times to death ranging from 3 to 12
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
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Page 2 of 4
days. The principle toxic signs reported among animals receiving
an oral dose of 2000 mg/kg and above were "diarrhea, kyphosis, red
or brown staining of the fur in the urogenital area, sluggishness,
prostration, and (at 6 to 13 days post-dosing) hind-limb paralysis
to variable extents (characterized by a dragging motion of the
limbs)." In addition, front limb paralysis was reportedly observed
in one animal at 9 days post-dosing. According to the submitted
summary, no clinical signs were apparent among those animals that
received a dose of 1000 mg/kg. Histopathological examinations of
tissues from the animals that died as well as those animals that
survived reportedly showed kidney and nervous system lesions that
were dose dependent in terms of severity.
In an acute toxicity study involving the oral administration of the
subject chemical to rabbits at a single oral dose of from 1000 to
4000 mg/kg, the LD50 was reported to be approximately 2600 mg/kg
(males and females combined). The clinical signs reportedly seen
at 4000 mg/kg included "unsteady gait, diarrhea, red perineal
stains, sluggishness, emaciation, and prostration." In addition,
"convulsions" were reported for one animal at 7 days post-dosing.
There were no signs of limb paralysis among the treated animals.
Although histopathologic examinations are not yet completed, gross
observations reportedly included discolored lung and kidneys in the
animals that died or survived treatment and altered renal cortex
in only those animals that died. The submitter noted that because
this particular study had been conducted with non-starved rabbits,
an additional oral toxicity study will be performed using starved
animals.
In an acute occluded dermal toxicity study in which the subject
chemical was applied at a dose of from 2.0 to 16.0 ml/kg to the
shaven skin of rabbits, the LD50 was reported to be approximately
3730 mg/kg (males and females combined); the times to death ranged
from 4 to 13 days. Among rabbits receiving a dose of greater than
2.0 ml/kg, the clinical signs reportedly included "sluggishness,
prostration, emaciation and (in two animals) hind limb paralysis
(at 7 and 12 days respectively); no clinical signs were observed
in animals at the 2.0 ml/kg dose level. Gross examination showed
discolored lungs and kidneys in the dead and sacrificed animals,
and enlarged kidneys and blood in the urine of the dead animals;
histopathological examinations are reported to be underway.
In primary eye and skin irritation studies in rabbits, the subject
chemical reportedly produced "only minor transient conjunctivitis"
following instillation of 0.1 ml into the conjunctival sac, but did
not produce any evidence of "local injury or inflammation" after
4-hour occluded dermal contact with a dose of 0.5 ml.
In an acute inhalation study in which rats were exposed for 6 hours
to a "substantially saturated vapor" of the subject chemical, no
deaths or clinical signs were reportedly seen during exposure or
during the 14-day post-exposure observation period. The submitted
summary reports that no gross pathological effects were observed
in this study.
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Page 3 of 4
In another inhalation study, 15 Fischer 3 44 male rats were exposed
(whole body) to an aerosol of the subject chemical for 6 hours/day,
5 days/week for 4 weeks. According to the provided summary, "the
average exposure concentration (gravimetrically determined) was 150
mg/m3, and the average mass median aerodynamic diameter was 3 urn."
The results of this 4-week inhalation study were reported to be as
follows:
"Six animals died between days 2 and 17 post-exposure,
and a further animal, in [a] moribund condition, was
sacrificed on day 18. Signs of toxicity included hind
limb paresis (days 15 to 24), emaciation, dehydration,
rapid shallow breathing, and periocular and perinasal
encrustation. Absolute body weights were decreased for
the second, third, and fourth weeks. Neurobehavioral
observations indicated a decreased rearing frequency,
abnormal hind limb gait, and decreased mobility. Necropsy
of [the] animals revealed mottled lungs and kidneys only.
Histological procedures are yet to be conducted on [the]
tissues removed at necropsy."
Finally, the submitted summary states that no evidence of mutagenic
activity was seen in the presence or absence of exogenous metabolic
activation in an Ames assay using Salmonella tvphimurium (bacteria)
strains TA98, TA100, TA1535, TA1537 and TA1538.
SUBMISSION EVALUATION
Most notable among the reported toxicological findings are the
observed neurotoxic and nephrotoxic effects. An EPA evaluation of
the overall significance of the reported toxicological findings
should be possible upon the Agency's receipt of complete copies of
all of the studies that were cited in the company's Section 8(e)
submission.
It should be noted that immediately upon receipt, the Chemical
Screening Branch transmitted a copy of the incoming Section 8(e)
submission to staff of the Risk Analysis Branch (RAB/ECAD/OTS) for
inclusion in their ongoing review of available toxicological and
exposure data on organosilanes. It should be noted also that the
Agency has received a number of TSCA Section 8(e) and "For Your
Information" (FYI) submissions on organosilanes. In addition, the
Chemical Screening Branch prepared (in 1986) a "Chemical Hazard
Information Profile" (CHIP) that covered a number of organosilane
chemicals.
CURRENT PRODUCTION AND USE (See UOTE on Page 4 of this status report)
In view of the submitting company's TSCA CBI claims, no information
regarding the TSCA Chemical Substance Inventory status or use(s)
of this alkyl trialkoxysilane will appear in this status report.
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Page 4 of 4
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will request the submitting
company to ensure that EPA receives a full copy of the
final report (including the actual experimental protocol,
results of gross/histopathological examinations, results
of statistical analyses, etc.) from each study cited in
the company's TSCA Section 8(e) submission.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, the submitting company will be
requested to describe the actions that the company has
taken or plans to take 1) to notify workers and others
about the reported data, and 2) to reduce or eliminate
exposure to this alkyl trialkoxysilane. In addition, the
submitting company will be asked to describe the nature
and results, if available, of all studies (other than
those submitted already to the Agency or those cited in
the open scientific literature) about which the company
is aware or that the company has conducted, is conducting
or plans to conduct that are designed to determine the
toxicity of or the exposure to the subject chemical.
b) As was the case for the initial submission, the Chemical
Screening Branch will forward full copies of all reported
information to the Risk Analysis Branch for review.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and RAB/ECAD/OTS;
in addition, copies of this report will be sent to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
NOTE In a letter dated February 7, 1991 (8EHQ-0291-0837 SUPP),
the Union Carbide Chemicals and Plastics Company withdrew
its claim of confidentiality for the company's name and
the exact identity of the subject chemical. According to
this February 7, 1991 letter, the subject chemical is
"1,10-bis-trimethoxysilyldecane" (CAS No. 122185-09-5).
It should be noted also that Union Carbide reported in
this supplemental letter that the company had "ceased R&D
work with this chemical."
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 2
DATE: NOV -7 1989 APPROVED:
»/«fa
OFFICE OF
PESTODE8 AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-1089-0838 S
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
The 3M Company claimed the exact identity of the subject chemical
substance to be TSCA Confidential Business Information (CBI); the
Information Management Division (IMD/OTS) will be reviewing all of
the incoming correspondence related to 3M's TSCA CBI claim. In the
"sanitized" version of its Section 8(e) notice, 3M reported non-
confidentially that the subject chemical is a "hydrazine compound."
SUBMISSION DESCRIPTION
The 3M Company provided the following summary information about the
conduct and preliminary results of an acute oral toxicity study of
this hydrazide compound in rats:
11 [According to a verbal report received from the contract
testing laboratory, the subject chemical caused] . . .
temporary ataxia, defined by the lab as 'incoordination
of muscular activity involving locomotion,• appearing at
the 24-hour observation period in 5/5 male rats and 2/5
female rats after an oral dose of 5 g/kg. None of the
animals died within the 14-day observation period of the
single dose limit test."
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
NOTE
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Page 2 of 2
SUBMISSION EVALUATION
An evaluation of the overall significance of the reported findings
should be possible upon EPA's receipt of a full copy of the final
report from the subject acute oral toxicity study.
CURRENT PRODUCTION AND USE
In view of 3M's TSCA CBI claim, no information regarding the TSCA
Chemical Substance Inventory status or use(s) of this hydrazide
compound will appear in this report. 3M reported non-confidentially
that the subject chemical is at the research and development (R&D)
stage.
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will ask 3M to ensure that
EPA receives a full copy of the final report (including
the actual experimental protocol, results of gross and
histopathological examinations, results of statistical
analyses, etc.) from the acute oral toxicity study cited
in the company's Section 8(e) submission.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, 3M will be requested to describe
the actions that the company has taken or plans to take
1) to notify workers/others about the reported findings,
and 2) to reduce or eliminate exposure to this hydrazide
compound. In addition, 3M will be asked to describe the
nature and results, if available, of all studies (other
than those submitted already to EPA or those cited in the
published scientific literature) about which 3M is aware
or that the company has conducted, is conducting or plans
to conduct that are designed to determine the toxicity
of or the exposure to the subject chemical substance.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of this hydrazide compound.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be provided to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
DATE: NOV 2 0 I08.; APPROVED!
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: status Report1 8EHQ-1189-0839
PROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
The Olin Corporation provided the final report of a guinea pig skin
sensitization study of a chemical identified only as "Poly-Tergent
CS-1 Analogue." Olin's cover letter presents the following summary
information about the conduct and results of this study:
"Ten male Hartley guinea pigs were dosed topically with
a 10% concentration of the subject chemical [substance].
Nine induction applications were administered over a
three week period. The test animals were challenged with
the same concentration and dose of the test chemical two
weeks later at two sites, the original and a virgin site.
Forty-eight hours after the first challenge, a second
challenge was conducted in a manner identical to the
first. Reactions to the skin were read at 6, 24 and 48
hours following each induction and challenge dose. The
negative control group also consisted of 10 male Hartley
guinea pigs. The animals in the control group were dosed
topically with distilled water only during the induction
phase. Following the induction phase, the control animals
were challenged with a non-irritating concentration of
the test chemical. The procedure for induction, challenge
and observations in the control group was identical to
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "Substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
231
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Page 2 of 3
that used for the treatment group. Five of ten animals
[in the treated group] exhibited a positive response at
the six-hour observation following the first challenge
. . . Nine of ten animals exhibited a positive response
at the six-hour observation [point] following the second
challenge. Based on the results from the exposure of the
treatment group compared to the negative control group,
the test chemical is judged [as] having the potential to
cause allergic skin sensitization in humans."
In its submission, Olin also reported that the company concluded
"that if used improperly, the subject chemical could present a
substantial risk to health or the environment."
SUBMISSION EVALUATION
An EPA evaluation of the overall significance of the reported
toxicologic findings should be possible upon the Agency's receipt
of information on the exact identity of, and the CAS No. (if known)
for, "Poly-Tergent CS-l Analogue." [See Note on Page 3]
CURRENT PRODUCTION AND USE
According to information provided in the submitted final report,
the subject chemical is an "experimental surfactant." Olin did not
provide any additional information regarding the specific use(s)
or production of this substance.
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will ask Olin to provide
the exact identity of and CAS No. (if known) for "Poly-
Tergent CS-l Analogue."
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, Olin will be asked to describe
the actions that the company has taken or plans to take
1) to notify workers/others about the reported findings,
and 2) to reduce or eliminate exposure to the subject
chemical. In addition, Olin will be asked to describe
the nature and results, if available, of all 'Studies
(other than those submitted already to EPA or those cited
in the open scientific literature) about which Olin is
aware or that Olin has conducted, is conducting or plans
to conduct that are designed to determine the toxicity
of or the exposure to the subject chemical.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of this experimental surfactant.
232
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Page 3 of 3
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be provided to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
Note In a letter dated January 12, 1990 (8EHQ-0190-0839 FLWP),
01in informed EPA that 1) Poly-Tergent CS-1 Analogue is
an "oxyalkylated linear alcohol-carboxylic acid adduct,"
and 2) no CAS No. has been assigned to the chemical.
233
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¦*«° 3r<*
I UNITED STATES ENVIRONMENTAL PROTECTION AGENCY page 1 of 3
wj$ WASHINGTON, DC 20460
DATE: 26 1989 approved:
office of
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-1189-0840 S
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
The submitting company has claimed its company name and the exact
identity of the subject chemical to be TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. In the "sanitized" version of its Section 8(e)
notice, the submitter reported non-confidentially that the subject
chemical is an "oxo-(substituted amino)acetic acid hydrazide." The
submitter also reported non-confidentially that the chemical is the
subject of a previous TSCA Section 5 Pre-Manufacture Notification
(PMN No. 88-468).
SUBMISSION DESCRIPTION
The submitting company provided summary information regarding the
conduct and preliminary results of a two-week study of the subject
chemical administered orally at doses of 0, 10, 30, 100, 300 and
1000 mg/kg to male and female Sprague-Dawley rats. The submitting
company reported that this two-week study was designed to determine
the appropriate dose levels for a 90-day study. According to the
submission, the company recently obtained the following results
from the two-week study:
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
234
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8EHQ-1189-0840 S
Page 2 of 3
"1. [The] in-life responses were confined to instances of
salivation at 1000 mg/kg (no clinical signs at 300
mg/kg). There were no effects on bodyweight increments
or food intake at 1000 mg/kg.
"2. Minor reductions (<10%) in erythrocytic characteristics
were noted at 1000 mg/kg. Erythrocyte morphology and
leucocyte numbers were unaffected.
"3. An approximately two-fold increase in thyroid size was
noted in females at 30, 100, 300 and 1000 mg/kg. Histo-
pathological examinations of tissues demonstrated that
the changes in thyroid weights were associated with loss
of colloid, hypertrophy and hyperplasia. The thyroids
of male animals were unaffected at all administered
dosage levels."
In providing the thyroid-related findings to EPA, the submitter
questioned the significance of those findings for the. following
reasons:
"1. There are many examples of naturally occurring materials,
pharmaceuticals, agrichemicals and industrial chemicals
that cause similar changes in the thyroid gland. As far
as . . . [the company is] aware, these chemicals affect
the thyroids in both sexes. Therefore, the response in
females only is unique and may indicate that confounding
variables are involved.
"2. There are no documented cases of hydrazine compounds
causing thyroid effects. This suggests the possibility
that the [obtained] results may be an artifact, and
should be examined more closely in the [ongoing] 90-day
subchronic toxicity study."
With regard to the ongoing 90-day study, the submitter reported
that the study will involve "measurement of thyroid function and
[an] assessment of reversibility [of effects]."
SUBMISSION EVALUATION
Immediately upon receipt, the Chemical Screening Branch sent a full
copy of this Section 8(e) notice to the Chemical Control Division
(CCD/OTS) which is responsible for the TSCA Section 5 New Chemicals
Program (NCP).
CURRENT PRODUCTION AND USE
The submitter of the Section 8(e) notice stated non-confidentially
that the subject chemical substance is a research and development
(R&D) compound that is "being handled only by technically qualified
individuals that are trained in handling substances that have not
235
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8EHQ-1189-0840 S
Page 3 of 3
been fully evaluated for health effects." The "sanitized" version
of PMN No. 88-4 68, which was obtained from EPA's public files,
states non-confidentially that the subject chemical substance is
1) an intermediate, and 2) a member of the "HALS" chemical family.
It should be noted that the term "HALS" is an acronym typically
used for "Hindered-Amine Light Stabilizer" compounds. It should
be noted also that the Chemical Screening Branch prepared (in 1988)
a "Chemical Hazard Information Profile" (CHIP) covering a number
of HALS.
COMMENT 8/RECOMMENDATIONS
The submitter of the Section 8(e) notice stated that the subject
chemical's Material Safety Data Sheet (MSDS) will be revised to
reflect the toxic effects observed in the two-week pilot study.
a) The Chemical Screening Branch will ask the submitter of
the Section 8(e) notice to ensure that EPA receives full
copies of the final reports (including the actual experi-
mental protocols, the results of gross/histopathological
examinations, the results of statistical analyses, etc.)
from the two-week pilot and 90-day subchronic toxicity
studies cited in the company's Section 8(e) submission.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity and/or exposure information, the Section 8(e)
submitter will be requested to describe the nature and
results, if available, of all studies (other than those
submitted already to EPA or those cited in the published
scientific literature) about which the company is aware
or that the company has conducted, is conducting or plans
to conduct that are designed to determine the toxicity
of the subject chemical.
b) As was the case for the initial Section 8(e) submission,
copies of all followup correspondence pertaining to the
submission will be provided to CCD/OTS.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, QSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and CCD/OTS/OPTS?
in addition, copies of this report will be sent to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
236
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» 4% V, Page 1 of 2
I JLjL J UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
DATE: NOV 20 1989 APPROVED:
rfbL
OFFICE OF
PE8DCI0ES AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-1189-0841
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
E. I. DuPont de Nemours & Company, Inc. provided the following
summary information regarding the conduct and preliminary results
of an acute dermal irritation study of tetra-n-butylphosphonium
phenylphosphinate (TBPP; CAS No. unknown) in rabbits:
"Approximately 200 mg/kg of body weight of TBPP was
applied to the clipped, intact skin of six New Zealand
white rabbits and held in place with gauze and rubber
sheeting to retard evaporation and to keep the test
material in contact with the skin. TBPP produced severe
skin irritation with necrosis and death. Other clinical
signs included lethargic behavior, incoordination of
[the] head and front limbs, and convulsions."
SUBMISSION EVALUATION
An evaluation of the overall significance of the reported findings
should be possible upon the Agency's receipt of a full copy of the
cited acute dermal irritation study.
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA wider Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
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Page 2 of 2
CURRENT PRODUCTION AND USE
According to DuPont's Section 8(e) submission, TBPP is a research
and development (R&D) chemical synthesized by the company. DuPont
did not provide any information on the use(s) of TBPP nor was such
information located in the secondary literature sources consulted
by EPA. DuPont did report, however, that the company has "elected
not to pursue TBPP on a commercial basis."
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will ask DuPont to ensure
that EPA receives a complete copy of the final report
(including the actual experimental protocol, results of
gross and histopathological examinations, results of
statistical analyses, etc.) from the acute rabbit skin
irritation study of TBPP cited in the submission. In
addition, DuPont will be asked to provide the CAS No. (if
known) for TBPP.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, DuPont will be asked to describe
the actions that DuPont has taken or plans to take to
notify workers and others about the reported information.
In addition, DuPont will be asked to describe the nature
and results, if available, of all studies (other than
those submitted already to the Agency or those cited in
the published scientific literature) about which DuPont
is aware or that DuPont has conducted, is conducting or
plans to conduct that are designed to determine the
toxicity of TBPP.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of the subject chemical substance.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be provided to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
238
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 3
OFFICE OF
PEST1CIOE8 AND
date: DEC -7 1989 approved:
7%. ajt^
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-1189-0842 S
***¦
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
The CIBA-GEIGY Corporation has claimed the exact identity of the
subject chemical to be TSCA Confidential Business Information (TSCA
CBI) . The Information Management Division will review all incoming
correspondence related to the company's TSCA CBI claim. In the
"sanitized" version of its TSCA Section 8(e) notice, CIBA-GEIGY
stated non-confidentially that the subject chemical substance is
a "substituted benzdioxolcarbonitrile."
SUBMISSION DESCRIPTION
CIBA-GEIGY provided the results of a preliminary embryotoxicity and
teratogenicity study of this substituted benzdioxolcarbonitrile
administered orally to presumed pregnant Sprague-Dawley rats at
dose levels of 0, 100, 300, 1000 or 2000 mg/kg/day on days 6-15 of
gestation. According to the submitted information, maternal
toxicity (indicated by reduced body weight gain) was seen at all
dose levels, and developmental toxicity (evidenced by incomplete
ossification of the 5th and 6th sternebrae, 4th metacarpus and/or
hyoid bone) was observed at 300 mg/kg/day and higher.
CIBA-GEIGY stated that the company plans to conduct a "definitive"
teratology study of this substituted benzdioxolcarbonitrile.
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
NOTE
239
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Page 2 of 3
In submitting these findings to EPA under Section 8(e) of TSCA,
CIBA-GEIGY stated that 1) "all of the delayed ossification effects
were observed at maternally toxic dose levels," and 2) "this type
of delayed bone ossification is not considered particularly serious
by some toxicologists and is even discounted by others as a true
teratogenic effect." CIBA-GEIGY stated also that "the doses chosen
were of a sufficient magnitude (there was one fatality [among the
dams] in the 2000 mg/kg group) that any significant embryotoxic/
teratogenic events would have been observed."
SUBMISSION EVALUATION
This submission provides evidence for maternal and developmental
toxicity following exposure to the subject chemical substance.
Maternal toxicity was observed in all treated groups and one dam
in the highest dose group (2000 mg/kg) died. At 2000 mg/kg, there
was a significant reduction in the mean maternal body weight on
gestational days 9 and 15. In addition, there was a significant
decrease in maternal body weight gain during the treatment period
at all dose levels. There were no apparent clinical signs and the
necropsy revealed no gross lesions.
With regard to developmental toxicity, there was a significant
increase in the incidence of delayed ossification of the hyoid bone
observed at 2000 mg/kg, while exposure to 1000 or 2000 mg/kg caused
a significant increase in the incidence of delayed ossification of
the 4th metacarpus. The exposure to 3 00 mg/kg or more resulted in
a significant increase in the incidence of delayed ossification of
the 5th and 6th sternebrae.
CHEMICAL USE/EXPOSURE INFORMATION
In view of the submitter's TSCA CBI claim, no information about the
TSCA Chemical Substance Inventory status of the subject chemical
will appear in this report. CIBA-GEIGY reported non-confidentially
that this compound is a research and development (R&D) chemical
that is being evaluated for use as a pesticide. According to the
SUMMARY AND CONCLUSIONS section of the submitted non-confidential
version of the teratology study report, the tested chemical "is
known to possess fungicide properties."
COMMENTS/RECOMMENDATIONS
It is important to point out that it is inappropriate to assume
that adverse developmental effects observed at maternally toxic
dose levels result only from maternal toxicity. Both the mother
and the fetus may be sensitive to the same dose; adverse effects
on the mother may be reversible, while those experienced by the
fetus can be permanent. It is equally important to note that while
EPA agrees with CIBA-GEIGY that delayed skeletal ossification is
not typically viewed as being as serious as some other adverse
developmental effects, delayed ossification is considered by EPA
to be a sensitive sign of developmental toxicity and should not be
discounted. For the purposes of determining TSCA Section 8(e)
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8EHQ-1189-0842 S
Page 3 of 3
applicability, therefore, the observation of a biologically or
statistically significant increase in delayed skeletal ossification
(or another more serious adverse developmental effect), even if
seen only in the presence of serious maternal toxicity, should be
considered immediately for reporting under Section 8(e) of TSCA.
EPA's longstanding position with regard to this matter is fully
consistent with the March 16, 1978 Section 8(e) policy statement
("Statement of Interpretation and Enforcement Policy? Notification
of Substantial Risk" 43 FR 11110). Part V of EPA's Section 8(e)
policy statement explains that the types of information considered
by the Agency to be reportable pursuant to Section 8(e) include
"any pattern of effects or evidence which reasonably supports the
conclusion that the [tested] chemical substance or mixture can
produce . . . birth defects or other toxic effects resulting in
death, or serious or prolonged incapacitation." Part V explains
also that the information concerning such serious effects can be
obtained directly by observation of their occurrence or inferred
from animal studies. Finally, it should be noted that EPA has
received numerous Section 8(e) submissions based on animal studies
in which serious developmental effects were observed at dose levels
that resulted in extreme toxicity (e.g., lethality) in the dams.
a) The Chemical Screening Branch will ask CIBA-GEIGY to
ensure that EPA receives a complete copy of the final
report (including the actual experimental protocol,
results of gross/histopathologic examinations, results
of statistical analyses, etc.) from the "definitive"
teratology study that the company plans to conduct.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, CIBA-GEIGY will be requested to
describe the actions that CIBA-GEIGY has taken or plans
to take 1) to notify workers/others about the reported
information, and 2) to reduce or eliminate exposure to
the subject chemical. In addition, CIBA-GEIGY will be
asked to describe the nature and results, if available,
of all studies (other than those submitted already to EPA
or those cited in the published scientific literature)
about which CIBA-GEIGY is aware or that CIBA-GEIGY has
conducted, is conducting or plans to conduct that are
designed to determine the toxicologic properties of this
substituted benzdioxolcarbonitrile.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of the subject chemical substance.
*
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ord/epa, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be provided to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
241
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f mrm
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Page 1 of 3
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
DATES NOV 30
APPROVED:
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report 8EHQ-1189-0843 S
FROM:
TO:
NOTE
)>A&tSfv* '
David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
The CIBA-GEIGY Corporation has claimed the exact identity of the
subject chemical to be TSCA Confidential Business Information
(CBI). Staff of the Information Management Division will review
all incoming correspondence related to the company's CBI claim.
In the "sanitized" version of its Section 8(e) submission, the
company reported non-confidentially that the subject chemical is
a "halogenated benzoyl urea."
SUBMISSION DESCRIPTION
CIBA-GEIGY provided the following summary information regarding the
conduct and preliminary results of a 3-month feeding study of the
subject chemical in rats:
Feeding level (rats)
(ppm) 0 25 150 1500 15000
No. of
Sex animals 20 10 10 10 20
Male 0/20 0/10 0/10 0/10 9/20
Female 0/20 0/10 0/10 1/10 8/20
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
Incidence of
tonic-clonic
seizure
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8EHQ-1189-0843 S
Page 2 of 3
CIBA-GEIGY reported further that "in the control and highest dose
group, ten (10) animals per sex were kept for a 4-week recovery
period before sacrifice." CIBA-GEIGY also reported that "tonic-
clonic seizures were observed in two males of the high dose group
(15000 ppm) during the last week of the recovery period."
In its Section 8(e) notice, CIBA-GEIGY also provided the following
summary information regarding the conduct and preliminary results
of a 3-month feeding study of the subject chemical in mice:
Feeding level (mice)
(ppm) 0 1000 3000 9000
No. of
Sex animals 10 10 10 10
Incidence of
tonic-clonic Male 0/10 1/10 7/10 6/10
seizure Female 0/10 1/10 6/10 3/10
CIBA-GEIGY reported that "it is not clear from the preliminary
information whether or not the tonic-clonic seizures noted in the
mouse study occur only at the time of death."
SUBMISSION EVALUATION
An Agency evaluation of the overall significance of the reported
neurotoxicologic findings should be possible upon receipt of full
copies of the final reports from the 3-month feeding studies of
this halogenated benzoyl urea in rats and mice.
CURRENT PRODUCTION AND USE
In view of the submitter's CBI claim, no information regarding the
TSCA Chemical Substance Inventory status of the subject chemical
will appear in this report. CIBA-GEIGY reported non-confidentially
that the subject chemical was a research a:nd development (R&D)
compound being evaluated by the company for use as a pesticide.
COMMENTS/RECOMMENDATIONS
CIBA-GEIGY reported that the Material Safety Data Sheet (MSDS) for
the subject chemical was being updated to reflect the fact that
tonic-clonic seizures had been observed in animal studies.
a) The Chemical Screening Branch will ask CIBA-GEIGY to
ensure that EPA receives complete copies of the final
reports (including the actual experimental protocols,
results of gross/histopathological examinations, results
of any statistical analyses, etc.) from the 3-month mouse
and rat feeding studies cited in the submission.
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8EHQ-1189-0843 S
Page 3 of 3
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, CIBA-GEIGY will be requested to
describe the nature and results, if available, of all
studies (other than those submitted already to the Agency
or those cited in the published scientific literature)
about which CIBA-GEIGY is aware or that CIBA-GEIGY has
conducted, is conducting or plans to conduct that are
designed to determine the toxicologic properties of the
subject chemical.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of the subject chemical.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in.addition,
copies of this status report will be provided to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
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(•$%
i
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 4
DATE: 0BC-7I989
APPROVED
: /M- -j-h
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECTS status Report1 8EHQ-1189-0844 S
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE (See NOTE on Page 4 of this status report)
The submitter has claimed its name and the exact identity of the
subject chemical to be TSCA Confidential Business Information
(CBI). Staff of the Information Management Division will review
all incoming correspondence related to these TSCA CBI claims. In
the "sanitized" version of this TSCA Section 8(e) notice, it was
reported non-confidentially that the subject chemical is an "alkyl
halide."
SUBMISSION DESCRIPTION
The submitter provided the following summary information regarding
the conduct and preliminary results of an inhalation teratology
study of this alkyl halide in rabbits:
"Pregnant rabbits were exposed to the test compound at
0, 20, 40 and 80 ppm via inhalation for 6 hours per day
during the period of organogenesis (days 7-19). Severe
clinical maternal toxicity was observed in the high dose
exposed animals. However, clinical signs reversed upon
cessation of exposure.
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
245
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8EHQ-1189-0844 S
Page 2 of 4
". . . [The contract laboratory performing this study
recently reported that] an increased incidence of missing
gall bladder was observed on necropsy examination of the
fetuses. The incidence in the high dose group was sig-
nificantly different from the control group. [The]
incidence in control vs. high dose groups was 1.1% vs.
8.2% of the fetuses, and 4.8% vs. 26.3% of the litters.
Other malformations and total malformations were not
significantly different from the control.
"Maternal endpoints of body weight and body weight gain
were decreased in the high dose group females compared
to control. Clinical signs of maternal toxicity were
noted in the high dose females. There were no treatment
related effects in pregnancy rates, pre-implantation
loss, resorptions, litter size, fetal weights, fetal sex
ratio, or gravid uterine weights.
"Skeletal malformations had not been tabulated at the
time of [receipt of the contract laboratory's] oral
report. Histopathology was completed on one fetus with
missing gall bladder to confirm that the defect was not
accompanied by other liver effects.1'
In providing these preliminary findings to EPA under Section 8(e)
of TSCA, the submitter stated that "there is published literature
linking missing gall bladder to heredity" and offered the following
comments regarding interpretation of the reported findings:
"There is considerable doubt whether the malformation is
compound related. This test was done using New Zealand
white rabbits. In addition, the occurrence of missing
gall bladder in this study is associated with a common
male used for insemination. . . . [The submitter has]
commissioned a mating test of the suspected male to
determine the genetic linkage of this malformation. [In
addition, the submitter has] commissioned a repeat of the
high dose study."
In conclusion, the submitter stated its belief that a "combination
of a positive mating test and the lack of an increased incidence
of gall bladder in the repeat of the high dose [teratology] study
will unequivocally demonstrate the malformation being reported in
this [TSCA Section 8(e)] notice is hereditary and not test compound
related."
SUBMISSION EVALUATION
This Section 8(e) submission provides evidence for both maternal
and developmental toxicity after inhalation exposure to the subject
chemical. Maternal toxicity (evidenced by a significant reduction
in body weight/body weight gain and clinical signs (e.g., lethargy,
right-sided head tilt, slight ataxia, and/or lateral recumbency))
246
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8EHQ-1189-0844 S
Page 3 of 4
was observed in the highest dose group (80 ppm). Developmental
toxicity seen at 80 ppm was evidenced by an increased incidence of
malformations (23/159 fetuses in 12/20 litters at 80 ppm versus
4/190 fetuses in 3/21 control litters). Much of the observed
increase was due to a significant increase in the number of fetuses
with no gall bladder.
An evaluation of the reported findings should be possible upon the
Agency's receipt of a full copy of the final report from the
subject inhalation teratology study as well as complete copies of
the final reports from the repeat high dose teratology and mating
studies cited in the submission. It is these latter two studies
that the submitter believes will "unequivocally demonstrate" that
the observed adverse developmental effects are hereditary and not
related to exposure to the tested alkyl halide.
CURRENT PRODUCTION AND USE (See NOTE on Page 4 of this status report)
In view of the submitter's TSCA CBI claims, no information about
the TSCA Chemical Substance Inventory status or use(s) of this
alkyl halide will appear in this status report.
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will ask the submitter to
ensure that the Agency receives a complete copy of the
final report (including the actual experimental protocol,
the results of gross and histopathological examinations,
the results of any statistical analyses, etc.) from the
rat inhalation teratology study, the repeat high dose rat
inhalation teratology study, and the rat mating study
cited in the submission.
In view of EPA's general interest in company actions
taken on a voluntary basis in response to chemical
toxicity or exposure information, the submitter will be
asked to describe the actions that have been taken or
are planned to 1) notify workers and others about the
reported data, and 2) reduce or eliminate exposure to
this alkyl halide. In addition, the submitter will be
asked to describe the nature and results, if available,
of all studies (other than those submitted already to EPA
or those cited in the published scientific literature)
about which the submitter is aware or that the submitter
has conducted, is conducting or plans to conduct that are
designed to determine the toxicity of or the exposure to
the subject chemical.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of this alkyl halide.
24?
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8EHQ-1189-0844 S
Page 4 of 4
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be provided to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
NOTE According to a "declassified" (no longer confidential)
version of the initial TSCA Section 8(e) submission, the
Methyl Bromide Industry Panel is the submitter and the
subject chemical is methyl bromide (CAS No. 74-83-9).
248
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 3
OFFICE OF
/Mt-
PESTICIDES AND
DATE: OGC • I 1989 APPROVED:
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-1189-0845
PROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
The Eastman Kodak Company provided the following summary informa-
tion about the conduct of and preliminary findings from a 4-week
rat oral toxicity study of (4-(1-methylbutoxy)-phenyl)hydrazine
monohydrochloride (CAS No. unknown):
"Groups of five male and five female rats were given
doses of 0, 15, 45, or 135 mg/kg of the test compound in
corn oil five days per week for four weeks. Treatment-
related clinical signs were only seen in the 135 mg/kg
animals. Significant alterations in hematology were
observed at all dose levels for both sexes. Abnormalities
included decreased red blood cell counts and altered red
blood cell indices (increased mean corpuscular volume,
increased mean corpuscular hemoglobin, and decreased mean
corpuscular hemoglobin concentration). Red blood cell
morphological abnormalities included alterations in size,
shape, and staining characteristics. There was a dose-
dependent increase in reticulocyte and Heinz body counts.
"There was a dose-dependent increase in spleen weight in
both sexes. Spleens were grossly darkened and enlarged.
Histologically, there was increased extramedullary
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). Vie statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
249
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8EHQ-1189-0845
Page 2 of 3
hematopoiesis and hemosiderin deposition in spleens,
kidneys, and livers. Other observations [(e.g., dose-
related increases in bilirubin levels)] made during this
study . . . [were described in a study summary included
by Eastman Kodak in its submission]."
In providing these findings to EPA, Eastman Kodak stated that "a
no-effect level for red blood cell toxicity was not obtained in
this study; however, the effects observed in the 15 mg/kg groups
were slighc, suggesting that few or no toxic effects would be
observed at doses less than 15 mg/kg." Eastman Kodak also noted
that the adverse effects seen in the 4-week study "are consistent
with known actions of substituted hydrazines."
Eastman Kodak also submitted the final results from a number of
acute toxicity studies of the subject chemical. According to the
provided summaries, the chemical was found to have oral LD50's of
544 mg/kg and 769 mg/kg in male and female rats, respectively, and
the dermal LD50 in rats was reported to be in excess of 2000 mg/kg.
Although in an acute guinea pig dermal irritation study, a single
occluded dose of .5 g was reported to be only slightly irritating,
an acute eye irritation study in rabbits showed the chemical to be
severely irritating. The subject chemical was reported further to
be negative in a guinea pig skin sensitization study.
Finally, Eastman Kodak submitted a copy of a Material Safety Data
Sheet (MSDS) that had been updated to reflect the results of the
company's 4-week rat oral toxicity study of the subject chemical
substance.
PBE AND EXPOSURE POTENTIAL
Eastman Kodak provided the following information about the use of
and potential for exposure to the subject chemical:
"This compound is a research and development chemical
being pursued as a site-limited intermediate in a multi-
step synthesis. None of the intermediate appears in the
final product. The intermediate was originally designated
as health hazards unknown - avoid all contact. Based on
the acute toxicity testing, employees will be required
to wear company-supplied clothing, gloves, face shield
and safety glasses. In addition, employees will be
required to wear respiratory protection when a potential
for inhalation exposure exists "
COMMENTS/RECOMMENDATIQN8
Eastman Kodak stated that the company will 1) continue to evaluate
employee exposure to the subject chemical, and 2) consider the need
for additional toxicological testing of the compound.
250
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8EHQ-1189-0845
Page 3 of 3
a) The Chemical Screening Branch will ask Eastman Kodak to
ensure that EPA receives a complete copy of the final
report (including the actual experimental protocol,
results of gross and histopathological examinations,
results of statistical analyses, etc.) from the 4-week
toxicity study cited in the submission. In addition,
Eastman Kodak will be asked to keep the Agency apprised
of the nature and results of other toxicity or exposure
studies the company conducts, or about which the company
becomes aware, that pertain to the subject chemical.
b) The Chemical Screening Branch will review the reported
information as part of the "FIRST REVIEW" phase in the
Existing Chemical Program (ECP) in order to determine the
need for further OTS assessment of the subject chemical
at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be provided to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
251
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 3
DATES DEC -7 1989 APPROVED:
/ML
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECTS status Report1 8EHQ-1189-0846
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
The Chemical Manufacturers Association (CMA) Cumene Panel submitted
preliminary results from an inhalation study in which cumene (CAS
No. 98-82-8) vapor was administered at doses of 0, 100, 500 or 1200
ppm for 6 hours/day, 5 days/week for 13 weeks to male and female
Fischer 344 rats. According to CMA, this study, which involved a
neurotoxicologic evaluation, was conducted as part of the testing
requirements under a TSCA Section 4 Test Rule (40 CFR 799.1285);
the study co-sponsors are listed on page 3 of this status report.
CMA stated that a final report of this study will be sent to EPA
by the December 9, 1989 test rule deadline. CMA's Section 8(e)
notice contained the following summary information about the study:
"Ophthalmic findings, prior to sacrifice, noted focal
nuclear cataracts in all groups of rats. [The] reported
observations include focal nuclear cataracts in five of
the twenty-one control group females and in one of the
twenty-one control group males. In the males, the number
of focal nuclear cataracts was increased at all exposure
concentrations, with eleven of twenty rats exhibiting
the cataracts at the uppermost concentration of [the]
test material. In the females, there was an increased
incidence of focal nuclear cataracts at the higher dose
levels.
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk? information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report shpuld
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
252
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8EHQ-1189-0846
Page 2 of 3
"Although focal nuclear cataracts in the Fischer 344 male
rats were observed at each exposure level in a [curaene]
treatment-related effect, the biological significance of
these observations remains unclear as these same lesions
were also noted in the untreated female and male control
groups."
CMA also provided the following information regarding additional
observations made during the study:
"Neurotoxicological evaluations in [the cumene-]treated
male rats have shown a statistically significant decrease
in motor activities compared to control animals. These
changes include a statistically significant decrease in
ambulatory activity 23 to 25 hours after previous [vapor]
exposures of 1200 and 500 ppm for weeks 4, 9 and 13, and
a statistically significant decrease in total activity
(including ambulatory, fine motor, and rearing activity)
at 23 to 25 hours after previous exposure of 1200 ppm for
Week 13. There were no motor activity changes observed
in female rats at any exposure tested.
"Although there were statistically significant changes in
motor activity, no correlation could be made histologi-
cally. After comparable exposure, functional observation
batteries were negative for both male and female animals,
and no other significant effects in these studies have
been observed. In addition to these findings, the follow-
ing observations were also noted at one hour after a
single six-hour exposure (but not at six and twenty-four
hours after exposure):
- gait abnormalities in males at 1200 ppm
- decreased rectal temperature in males
and females at 1200 ppm
- increased activity in both sexes at 1200
ppm and in females only at 500 ppm."
USE AND EXPOSURE POTENTIAL
Information regarding the uses of and the potential for exposure
to cumene is located in the proposed and final TSCA Section 4 Test
Rules (50 FR 46104, November 6, 1985; 53 FR 28195, July 27, 1988;
respectively).
COMMENTS/RECOMMENDATIONS
To date, EPA has received a number of TSCA Section 8(e) submissions
from trade associations on behalf of their member companies. In the
COMMENTS /RECOMMENDATIONS portion of the status report that was pre-
pared by EPA in response to TSCA Section 8(e) submission number
8EHQ-0186-0587, the Agency reiterated its position with regard to
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8EHQ-1189-0846
Page 3 of 3
the Section 8(e) reporting obligations of trade associations and
their member companies. It is important to note also that EPA has
received several TSCA Section 8(e) submissions containing interim
results of studies being conducted pursuant to Section 4 of TSCA.
EPA's position regarding the relationship between TSCA Section 4
and Section 8(e) was reiterated in the COMMENTS/RECOMMENDATIONS
portion of the status report that was prepared by the Agency in
response to Section 8(e) submission number 8EHQ-0589-0797.
a) In view of EPA's general interest in actions taken on a
voluntary basis in response to chemical toxicity/exposure
data, CMA will be requested to describe the actions that
it or its member companies have taken or plan to take 1)
to notify workers and others about the reported findings,
and 2) to reduce or eliminate exposure to cumene.
b) As was the case with the initial submission, the Chemical
Screening Branch will immediately transmit all reported
information to staff of the Test Rules Development Branch
(TRDB/ECAD/OTS) for inclusion in their ongoing review of
toxicologic and exposure data on cumene.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and TRDB/ECAD/OTS;
in addition, copies of this status report will be sent
to the Environmental Assistance Division/OTS (formerly
the TSCA Assistance Office/OTS) for further distribution.
Study Co-Sponsors
Allied Signal Corporation
Aristech Chemical Company
Ashland Oil Company
Amoco Corporation
Champlin Refining & Chemicals, Inc.
Chevron Chemical Company
Coastal Eagle Pt. Oil Co., Inc.
Dow Chemical Company
Georgia Gulf Corporation
Koch Refining Company
Shell Oil Company
Texaco Chemical Company
254
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON. D C 20460
Page 1 of 8
DATE: OCT 26 1990 APPROVED:
«hh°
SUBJECTS Status Report1 8EHQ-1189-0847 INIT (Chevron)
8EHQ—1289-0847 SUPP (CIBA-GEIGY)
8EHQ-0290-0847 SUPP (Chevron)
PROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS
TO: Frank D. Kover, Chief
Chemical Screening Branch/ECAD/OTS
SUBMISSION DESCRIPTION
In the initial TSCA Section 8(e) submission (8EHQ-1189-0847 INIT),
Chevron International Oil Company, Inc. provided information with
regard to an in vitro Chinese Hamster ovary (CHO) cell chromosomal
aberration study of 2-(3,4-epoxycyclohexyl-5,5-spiro-3,4-epoxy)-
cyclohexane-ra-dioxane. In a supplemental Section 8(e) submission
(8EHQ-0290-0847 SUPP), Chevron Environmental Health Center, Inc.
reported that the test material was "Union Carbide Cycloaliphatic
Epoxy Resin ERL-42342 . . . (CAS No. 3388-03-2)." Chevron's initial
Section 8(e) submission presents the following summary information
about the conduct and preliminary results of the company's study:
"Preliminary evaluation of . . . [the results from this
in vitro study] indicates that this compound produced a
statistically significant increase in aberration-bearing
cells without metabolic activation after 20 hours of
continuous treatment and with metabolic activation at 14
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk f information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect jo the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
2 Trademark of the Union Carbide Corporation (now the Union Carbide Chemicals and
Plastics Company, Inc.)
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and 20 hours after a 2-hour treatment. Treatment was at
75 to 300 ug/ml and 300 to 600 ug/ml without and with
metabolic activation, respectively. The observed response
was positive but not dose-responsive. A final report for
this study has not yet been issued."
According to Chevron's initial Section 8(e) submission, the tested
chemical substance is known by several names including: "Ba 421579.
AraWW* CY-1753, BaKeUW* ERfr-42344 (or simply £RL-4?34) ." After
being informed about Chevron's intention to file a Section 8(e)
notice, the CIBA-GEIGY Corporation reported (8EHQ-1289-0847 SUPP)
that Union Carbide's ERL-4234 "is similar in chemical composition
to one of . . . [CIBA-GEIGY's] former products known as Araldite
CY-175 (commercial name) which in turn was similar to Ba 42*579
(early R&D code designation)." [Note: According to the printed
version of the Agency's initial TSCA Chemical Substance Inventory,
the CAS No. for Araldite CY-175, Bakelite ERL-4234, and ERL-4234
is 26616-47-7 and refers to the homopolymeric form of the cyclo-
aliphatic epoxy resin assigned CAS No. 3388-03-2.]
In the initial Section 8(e) notice, Chevron also submitted a copy
of a September 19, 1969 final report entitled "Carcinogenicity of
Ba 42'579, Ba 42*580 and Ba 42'581 in Dermal Application to Mice."
The "INTRODUCTION" and "SUMMARY" sections of the submitted final
report provided the following information about the conduct and
results of preliminary dose range-finding and chronic mouse skin-
painting studies that were performed by CIBA Limited (located in
Basel, Switzerland) "to investigate the carcinogenicity of the
three synthetic resins Ba 42*579, Ba 42'580 and Ba 42'581":
"Preliminary studies [designed] to establish tolerance
and dosages were conducted . . . using Chester Beatty
stock mice. . . The findings indicated that the [3] test
compounds were essentially non-irritant, and that thrice-
weekly applications of 30% solutions in acetone would be
tolerated. . . . [The chief laboratory investigator]
recommended that each material should be applied at a
concentration of 15% for the initial three weeks with
subsequent increases in concentration to the maximum
[dose] tolerated.
2 "Araldite" is a CIBA-GEIGY Corporation trademark.
* "Bakelite" is a trademark of the Union Carbide Corporation (now the Union Carbide
Chemicals and Plasties Company, Inc.)
- It is reasonable to assume that the commercial product consists primarily of
unpofymerized monomeric material Any homopofymer present is probably responsible for
improving the properties of the commercial product (e.g., viscosity). Epoxy-function commercial
products of this type usually consist of low molecular weight species that are readily available
for further reaction with other products such as Bisphenol A-type resins.
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HIn . . . [the chronic study, three groups (52/sex/group)
of •hysterectomy-derived, specific pathogen-free mice']
were painted three tines per week on the shaved dorsal
skin with [resin] solutions in acetone, (0.3 ml/mouse/
treatment) for a total of 52 weeks, followed by a 28 week
observation period. [A fourth group of 52 males and 52
females served as untreated controls for the study.]
"Due to the severity of the local [dermal irritation]
response to Ba 42'581 at the initial dose of 15%, and the
resultant mortality, replacement mice, born within ±24
hours of the original stock, were obtained.
"A further two-fold reduction in the concentration of
Ba 42'581 to 3.75% resulted in [an] improved tolerance.
Ba 42"579 and Ba 42'580 were applied at 15% and were well
tolerated throughout the [52-week] treatment period.
"The following reactions to treatment were noted:
"1. All mice treated with Ba 42*581 showed complete
depilitation of the dorsal surface, which, in the
majority of cases, extended beyond the treated area.
Only the male members of this group showed signs of
mild erythema and some scaling; this may, however,
have been related in part to the pugnacity of those
mice. During the observation period, hair growth
gradually resumed in the females of this group,
although there were no such improvement in the male
survivors.
"2. Among mice treated with Ba 42'579 and Ba 42'580, no
mortalities occurred which could be directly attri-
butable to treatment. Mortalities among mice treated
with Ba 42*581 were relatively numerous, particu-
larly among [the] males; death was usually preceded
by a general loss of condition, apparently related
to treatment, superimposed by injury and infection
arising from the pugnacious habit of these mice.
"3. Slightly inferior body weights were recorded for
both sexes treated with Ba 42'579 and Ba 42*581.
"4. All three [synthetic resin] compounds produced a
significant number of both benign and malignant
tumors, whereas no epithelial tumors arose in the
untreated control mice. Ba 42'581, dosed at one
quarter the concentration of the other two com-
pounds, clearly showed, the greater tumorigenicity.
'*5. The distribution of abscopal tumors appeared un-
related to treatment. [Abscopal 'denotes tumors
arising at any site other than the area of painted
skin.•]
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"6. It may, therefore, be concluded that under the
present [testing] conditions, Ba 42'579, Ba 42'580
and Ba 42'581 are carcinogens for mouse skin, with
Ba 42'581 exhibiting greater activity than either
of the other two compounds. "
In its initial submission, Chevron also provided 1) a copy of a
CIBA-GEIGY Corporation letter (dated May 25, 1977) informing the
EPA Administrator that CIBA-GEIGY had "received information which
supports the conclusion that Araldite CY-175 ... is a suspect
animal carcinogen," and 2) several enclosures that accompanied the
May 25, 1977 letter to EPA, including:
o a copy of a form letter by which CIBA-GEIGY
was notifying its ARALDITE CY-175 customers
that the chemical was "a suspect animal
carcinogen." This draft notification letter
also states that Araldite CY-175 is a com-
ponent of XylokR Resin 235 NK-756, XylokR
Hardener 231 N-90 and AralditeR CY-185.
o a copy of a revised (May 23, 1977) CIBA-GEIGY
Material Safety Data Sheet (MSDS) for Xylok
Resin 235 NK-75, a formulated "Novolac-Type"
resin solution containing ~75% Araldite CY-
175, ~22% methyl ethyl ketone (CAS No. 78-93-
3), and ~3% methyl isobutyl ketone (CAS No.
108-10-1). (This MSDS states that Araldite
CY-175 is a "suspect animal carcinogen.")
In the initial TSCA Section 8(e) submission, Chevron also included
a copy of a revised (March 14, 1989) MSDS for HyjetR IV-A , which
contains ~3% cycloaliphatic epoxy resin (CAS No. 3388-03-2), ~79%
tributyl phosphate (CAS No. 123-73-8), -12% trialkylphenyl phos-
phate (CAS No. 68937-41-7) and <7% other additives. The "ADDITIONAL
HEALTH DATA" section of Chevron's Hyjet IV-A MSDS presents the
following information about the product:
". . . [Hyjet IV-A] contains a cycloaliphatic epoxide
additive [(CAS No. 3388-03-2)]. This ingredient caused
cancer in the skin of mice when applied as a 15% solution
in acetone. The epoxide was applied three times per week
for a year and never removed. Since the acetone would
quickly evaporate, this equates to continuous skin con-
tact with 100% cycloaliphatic epoxide. As a result of
this exposure, 15% of the treated mice developed skin
cancer
- "Xylok" is a CIBA-GEIGY Corporation trademark.
- "Hyjet" is a Chevron trademark.
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"Because of the international sale and use of Chevron
Hyjet fluids, the label uses a risk phrase mandated by
the European Economic Community (EEC). The label warning
'Possible Risk of Irreversible Effects' is intended to
convey . . . [Chevron's] concern that prolonged and
repeated skin contact with the [cycloaliphatic] epoxide
can be harmful. It is . . . [Chevron's] belief that
Chevron Hyjet IV-A can be worked with safely with no
further precautions than would be required for [the use
of] any aviation hydraulic fluid using similar base
stocks."
In its supplemental Section 8(e) submission, Chevron provided an
April 14, 1989 revised MSDS for Union Carbide Cycloaliphatic Epoxy
Resin ERL-4234. The "HEALTH HAZARD DATA" section of the MSDS states
that ERL-4234 "has been shown to be tumorigenic in mice by long-
term repeated application to the skin." In addition, the "SPECIAL
PRECAUTIONS" section of the ERL-4234 MSDS states that this chemical
substance "causes cancer in laboratory animals."
In its supplemental Section 8(e) submission, CIBA-GEIGY provided
copies of the following enclosures that reportedly accompanied the
company's May 25, 1977 letter to the EPA Administrator:
o the product labels for Xylok Resin 235 NK-75,
Xylok Hardener 231 N-90, and Araldite CY-185.
Each of these product labels states "Prolonged
or repeated contact of liquid or breathing of
vapors or mists may cause delayed or serious
injury." According to CIBA-GEIGY's May 25,
1977 letter, revised labels conforming to the
Society of the Plastics Industry (SPI) "Class
6 Hazard Category" guidelines were being "pre-
pared and affixed to all future shipments of
these products by July 15, 1977." According
to CIBA-GEIGY, the SPI Class 6 Hazard Category
warning is as follows: "Suspected carcinogen
in animals. The product can cause a carcino-
genic response when applied topically to Qr
inhaled by experimental animals."
o a revised (May 23, 1977) MSDS for CIBA-GEIGY's
Xylok Hardener 231 N-90, a product containing
-50% Araldite CY-175, ~7% methyl ethyl ketone,
and -3* 2-methoxy ethanol (CAS No. 109-86-4).
This MSDS states that Araldite CY-175 is a
"suspect animal carcinogen."
o a revised (May 23, 197,7) MSDS for CIBA-GEIGY's
Araldite CY-185, a "modified cycloaliphatic
epoxy resin" product containing -70% Araldite
CY-175. This MSDS also states that Araldite
CY-175 is a "suspect animal carcinogen."
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According to CIBA-GEIGY's supplemental TSCA Section 8(e) notice,
"Araldite CY-175, per se, was withdrawn as an imported product in
1976" and "all use of Araldite CY-175" was discontinued in the
company's other products in 1979. In addition, CIBA-GEIGY stated
that the company "learned in 1976 that Ba 42*579 was prepared by
a manufacturing process that changed significantly after 1968."
CIBA-GEIGY reported further that the company has "never imported,
manufactured, processed, or distributed . . . [the other two tested
synthetic resins (Ba 42*580 and Ba 42*581)] in the United States."
In the supplemental TSCA Section 8(e) notice, CIBA-GEIGY stated
that the 1969 chronic mouse skin-painting study final report had
been in the company's files prior to the passage of TSCA in 1977.
CIBA-GEIGY also stated that due to post-1968 manufacturing changes
for Ba 42'579, "the relevance of the study reported in 1969 was
questionable with respect to the product subsequently marketed as
Araldite CY-175." In addition, CIBA-GEIGY stated that although
the company has "not had occasion to reconsider this [1969] study
for many years," CIBA-GEIGY*s current evaluation of the study is
as follows:
". . . . This was a poorly conducted study of limited
value because only one dose was used and there was no
vehicle control group. In addition, the dosing solution
concentration was changed for about 1 month during the
study. The results were limited to application site
lesions that consisted of epithelial hyperplasia and
tumors. There was no evidence of absorption, as demon-
strated by the absence of systemic effects, including
treatment related tumors. It is . . . [the company's]
opinion that skin tumors limited to the application site
in animals are not relevant to human health."
SUBMISSION EVALUATION
In Vitro Chromosomal Aberration Study
The submitted summary indicates that ERL-4234 produced chromosonu
aberrations in cultured mammalian cells. An EPA evaluation of tl
overall significance of the findings should be possible when tl
Agency receives a full copy of the final report.
1969 Chronic Skin-Application Study
Although there are a number of limitations of the 1969 study, the
results clearly show that Ba 42*579 (as well as the other two test
materials) produced a significant incidence of benign and malignant
epithelial tumors when applied dermally 3 times per week for 1 year
to the shaved dorsal skin of male and female mice; no epithelial
tumors were observed in the untreated controls. While the Agency
recognizes the fact that an acetone (vehicle) control group was not
used in this study, it is important to point out that chronic
application of acetone to the skin of mice has not been shown to
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result in an oncogenic response. Therefore, it is highly unlikely
that the tumors seen in the study were due to the vehicle. Further,
it is important to note that only the Ba 42'581 dosage levels were
changed (reduced) during the study due to the fact that this test
material was not tolerated well by the mice; the dose levels of the
other two compounds (Ba 42'579 and Ba 42'580) remained constant
throughout the study.
COMMENTS/RECOMMENDATIONS
In contrast with CIBA-GEIGY's current opinion about the relevance
of application site tumors in animal studies, EPA believes that
statistically or biologically significant tumorigenic responses
seen in animal studies (including exposure site-specific tumors)
are relevant to assessing potential carcinogenic risks for humans.
Despite CIBA-GEIGY's assertion (in 8EHQ-1289-0847 SUPP) that the
post-1968 manufacturing changes for Ba 42*579 led the company to
question the relevance of the 1969 chronic dermal application study
findings with respect to Araldite CY-175, it is quite apparent
that, in May of 1977, CIBA-GEIGY believed those findings to be
sufficiently relevant to Araldite CY-175 that they felt compelled
to report the study outcome to the EPA Administrator and to notify
others in writing that the company had done so.
Further, the 1969 chronic dermal application study findings appear
to have been viewed by CIBA-GEIGY to some degree in the context of
the actual statutory language of Section 8(e) of TSCA; the copy of
CIBA-GEIGY's May 25, 1977 letter to the EPA Administrator states
specifically that the company had recently "received information
which supports the conclusion that Araldite CY-175 ... is a
suspect animal carcinogen." [EPA emphasis added] CIBA-GEIGY's
interpretation that the 1969 study findings were significant is
reflected in the content of their customer notification letters and
the worker protection-related revisions that were made to MSDSs and
product labels. Other companies (e.g., Union Carbide and Chevron)
apparently interpreted the 1969 study findings in a similar manner
because specific animal cancer-related revisions were also made to
their MSDSs and product labels.
Although EPA has not located any record showing that CIBA-GEIGY's
"May 25, 1977 letter was ever received by the Agency, there is no
reason to believe that the letter was not received. Further, it is
important to point out that, in May 1977, EPA had not yet developed
its Section 8(e) policy statement ("Statement of Interpretation and
Enforcement Policy; Notification of Substantial Risk" 43 FR 11110;
March 16, 1978), nor had EPA developed a formal document receipt,
tracking and filing system for Incoming Section 8(e) notices or a
mechanism for Agency followup to such notices.
Based on a review of the submitted information, and considering
Chevron's apparent belief that EPA was not adequately apprised of
the cancer findings from the 1969 chronic mouse dermal application
261
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study, EPA believes that Chevron acted appropriately under the
circumstances in formally submitting a complete c^opy of that final
report to the Agency under Section 8(e) of TSCA.
a) The Chemical Screening Branch will ask Chevron to ensure
that EPA receives a complete copy of the final report
(including the actual experimental protocol, data, the
results of statistical analyses, etc.) from the in vitro
chromosomal aberration study cited in the company's
initial TSCA Section 8(e) submission.
The Chemical Screening Branch will request CIBA-GEIGY to
provide exact chemical names and CAS Registry Numbers (if
known) for BA 42'580 and 42'581. (See KOTE below.)
b) As part of the initial phase of the OTS Existing Chemical
Program (ECP), staff of the Chemical Screening Branch
will screen the reported information to determine the
need for further OTS assessment of the subject chemical
substance(s) at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA. In addition,
copies of this status report will be transmitted to the
Environmental Assistance Division (EAD/OTS) for further
distribution. Finally, copies of this status report will
be sent also to Chevron, CIBA-GEIGY and Union Carbide.
MOTE In a followup response letter dated December 12, 1990
(8EHQ-1290-0847 FLWP), CIBA-GEIGY provided the following
information about the chemical identities of BA 42'580
and BA 42'581:
BA 42 1580 Spiro[l,3-dioxane-5,31 -[7]oxabicyclo[4.1.0]-
heptane], 2-[2-[2-(oxiranylmethoxy)ethoxy]-
ethyl]- (CAS No. 2155-38-6)
BA 42'581 7-Oxabicyclo[4.1.0]heptane, 3-[(oxiranyl-
methoxy)methyl]- (CAS No. 10578-42-4)
l/z/4t '
8 •
- TSCA Section 8(e) states that "Any person who manufactures, [imports,] processes or
distributes in commerce a chemical substance or mixture and who obtains information which
reasonably supports the conclusion that such substance or mixture presents a substantial risk of
injury to health or the environment shall immediately inform the [EPA] Administrator of such
information unless such person has actual knowledge that the Administrator has been
adequately informed of such information." (emphasis added)
262
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080
DATE:
SUBJECT:
FROM:
TO:
NOTE
The Eastman Kodak Company claimed the exact identity of the subject
chemical substance to be TSCA Confidential Business Information
(TSCA CBI). The Information Management Division will review all
incoming correspondence related to the company's CBI claim. In the
"sanitized" version of its Section 8(e) submission, Eastman Kodak
reported non-confidentially that the subject chemical substance is
a "substituted hydrazine."
SUBMISSION DESCRIPTION
Eastman Kodak provided a copy of the final report from an acute
rat oral toxicity study in which the subject chemical was found to
produce convulsions "at dose levels which did not result in other
signs of systemic toxicity." In its cover letter, Eastman Kodak
provided the following summary information regarding the conduct
and results this study:
"In an acute oral gavage toxicity study, oral LD50 values
of 78 mg/kg and 55 mg/kg were calculated for male and
female rats, respectively. All animals receiving doses
of 156 mg/kg or more and some of those receiving a dose
of 78 mg/kg died following administration of the test
material. The remainder of the 78 mg/kg group and all
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
DEC I 3 1989 approved
Status Report1 8EHQ-1189-0848 S
David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Page 1 of 3
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
263
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8EHQ-1189-0848 S
Page 2 of 3
animals administered doses of 39 mg/kg survived the 14-
day observation period and gained weight normally.
Abnormal clinical signs, in all [of the] dose groups,
were observed only on the day [the] animals were dosed.
"At the 312 mg/kg and 156 mg/kg dose levels, abnormal
clinical signs included slight to severe weakness,
convulsions, tremors, and brown ocular discharges. At
78 mg/kg, abnormal clinical signs consisted of slight
weakness and convulsions. At 39 mg/kg, all animals
appeared clinically normal throughout the study.
"The only significant necropsy lesion observed during
this study was minimal necrosis of the mucosa of the
glandular stomach in one female rat from the 156 mg/kg
dose group.
"The effects seen in this study are consistent with [the]
known actions of substituted hydrazines. The No-Observed-
Effect-Level (NOEL) for convulsions was 39 mg/kg."
Eastman Kodak also provided a Material Safety Data Sheet (MSDS)
that was updated to reflect the reported toxicologic findings.
USE AND EXPOSURE POTENTIAL
In view of the submitter's CBI claim, no information regarding the
TSCA Chemical Substance Inventory status of the subject chemical
will appear in this status report. In its submission, Eastman Kodak
provided the following information about the use of and potential
for exposure to the subject chemical:
"This compound is a research and development chemical
being evaluated as a site-limited intermediate in a
multistep synthesis. None of the intermediate appears
in the final product. . . . [Eastman Kodak is] not
aware of any adverse health problems associated with its
synthesis or use to make the final chemical. The original
health hazard evaluation of this intermediate resulted
in a 'Health Hazards Unknown' rating. This rating is
accompanied by a statement to employees to 'Avoid all
contact.' ... [Eastman Kodak personnel] will continue
to handle the material in the same manner based on the
new toxicology data. Employees will be required to wear
Tyvek suits, air hoods, gloves, and safety glasses when
working with this material.11
COMMENTS/RECOMMENDATIONS
In addition to updating the Material Safety Data Sheet to reflect
the reported findings, Eastman Kodak stated that the company is
currently evaluating the need for additional toxicological testing
of the subject chemical.
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8EHQ-1189-0848 S
Page 3 of 3
a) In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, Eastman Kodak will be asked to
describe the nature and results, if available, of all
studies (other than those submitted already to EPA or
those cited in the published scientific literature) about
which Eastman Kodak is -aware or that Eastman Kodak has
conducted, is conducting or plans to conduct that are
designed to determine the toxicological properties of the
subject chemical.
b) As part of the "FIRST REVIEW" phase in the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will "screen" the reported information in order
to determine the need for further OTS assessment of the
subject chemical at the present time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be provided to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 3
DATES DEC I 9 1989 APPROVED:
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT! Status Report1 8EHQ-1289-0849 8
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
The Procter & Gamble Company (P&G) claimed the exact identity of
the subject chemical to be TSCA Confidential Business Information
(CBI). Staff of the Information Management Division will review
all incoming correspondence related to P&G's TSCA CBI claim. In
the "sanitized" version of its TSCA Section 8(e) submission, P&G
reported non-confidentially that the subject chemical substance is
a "substituted organic ammonium chloride."
SUBMISSION DESCRIPTION
P&G submitted a report from a pilot, range-finding developmental
toxicity study of this substituted organic ammonium chloride irt
rats. The "SYNOPSIS" section of the submitted report presents the
following information about the conduct and results of the study:
"Mated female Charles River COBSR CDR rats, consecutively
assigned to one control and three treatment groups of
five animals each, were used in this range-finding study
to determine dosage levels of . . .[the subject chemical]
for a developmental toxicity study. Dosage levels of
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk11 information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemkal(s). Any review of this status report should take into account that the report may be
based on incomplete information.
NOTE
266
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8EHQ-1289-0849 S
Page 2 of 3
500, 1000, and 1500 mg/kg/day were administered orally
by gavage as a single daily dose on days 6 through 15 of
gestation. The control group received the vehicle only,
distilled deionized water, on a comparable regimen. The
500 and 1000 mg/kg/day groups were dosed at a volume of
10.0 ml/kg. The control group and the 1500 mg/kg/day
group were dosed at a volume of 15.0 ml/kg. Uterine
examinations were performed on all surviving females on
gestation day 20.
"Maternal toxicity was apparent as shown by three deaths
in the 1500 mg/kg/day group and body weight losses for
the 1000 and 1500 mg/kg/day groups during the treatment
period (gestation days 6-15) and inhibited body weight
gains [on] days 16-20. Inhibited body weight gains were
also evident for the 500 mg/kg/day group during the study
beginning with gestation day 6.
"Developmental toxicity was evident at the 1000 and 1500
mg/kg/day dosage levels as increased post-implantation
loss, including total litter resorptions at both levels
and [a] reduced number of viable fetuses at the 1000
mg/kg/day dosage level. Based on these considerations,
dosage levels of 200, 400 and 800 mg/kg/day have been
suggested for a ['definitive, large-scale1] developmental
toxicity study in rats with . . . [the subject chemical
substance]."
In its Section 8(e) submission, P&G reported that the No-Observed-
Effect-Level (NOEL) for developmental toxicity in the pilot study
was 500 mg/kg/day.
USE AND EXPOSURE POTENTIAL
P&G stated non-confidentially that the substituted organic ammonium
chloride is not listed on the public portion of EPA's TSCA Chemical
Substance Inventory. In addition, P&G reported that the subject
chemical is being evaluated solely for research and development
(R&D) in the U.S. and has not been manufactured or processed for
commercial distribution. P&G reported further that the "anticipated
exposures to the subject chemical in . . . [P&G's] R&D efforts and
in contemplated product applications are 5 to 6 orders of magnitude
less than the 500 mg/kg/day NOEL." Finally, P&G reported that "in
keeping with . . . [P&G's] standard procedure for handling all new
chemical substances," P&G has handled and will continue to handle
the subject chemical substance "with appropriate caution" in the
company's laboratory.
COMMENTS/RECOMMENDATIONS
In its Section 8(e) submission, P&G stated that all P&G employees
working with the subject chemical have been informed about the
reported toxicologic findings.
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Page 3 of 3
a) The Chemical Screening Branch will ask P&G to ensure that
EPA receives a full copy of the final report (including
the actual experimental protocol, results of gross/histo-
pathologic examinations, results of statistical analyses,
etc.) from the "large-scale developmental toxicity study"
cited in P&G's submission.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, P&G will be asked to describe the
nature and results, if available, of all studies (other
than those submitted already to EPA or those cited in the
open scientific literature) about which P&G is aware or
that P&G has conducted, is conducting or plans to conduct
that are designed to determine the toxicologic properties
of the subject chemical.
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP) , staff of the Chemical Screening
Branch will "screen" the reported information in order
to determine the need for further OTS assessment of the
subject chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be provided to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
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ti Page 1 of 2
| UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
„ WASHINGTON, DC 20460
DATES OEC I 8 1989 approved:
SUBJECT: Status Report1 8EHQ-1289-0850
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
OFFICE OF
PE8TICIDE8 AND
TOXIC SUBSTANCES
SUBMISSION DESCRIPTION
The Mobay Corporation provided a copy of a final report (written
in German) from an acute oral toxicity/antidote study of 0-ethyl-
O-methylethyl-O-[2-(1,1-dimethylethyl) -pyrimidin-5-yl]-thiono-
phosphorous acid ester (MAT 7484; CAS No. unknown) in female rats.
According to Mobay, this study, which was conducted in West Germany
by BAYER AG (Mobay's parent company), showed that MAT 7484 has an
acute oral LD50 value of 1.3 mg/kg when tested alone. LD50 values
ranging from 1.6 to 4.8 mg/kg were found when MAT 7484 was tested
in combination with atropine sulfate or Pralidoxim (Protopam ) or
Obidoxim (ToxogoninR) or atropine/Pralidoxim or atropine/Obidoxim.
USE AND EXPOSURE POTENTIAL
According to Mobay, MAT 7484 "is used in research and development
activities with fewer than ten individuals potentially exposed to
the technical material in preparation of the low active ingredient
formulations for research."
COMMENTS/RECOMMENDATIONS
Mobay reported that the company is 1) informing its employees about
*the submitted toxicologic findings, and 2) reviewing the internal
Mobay standards for handling MAT 7484 in the workplace.
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
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Page 2 of 2
a) In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure information, Mobay will be asked to
describe the nature and results, if available, of all
studies (other than those submitted already to the Agency
or those cited in the published scientific literature)
about which Mobay is aware or that Mobay has conducted,
is conducting or plans to conduct that are designed to
determine the toxicity of the subject chemical.
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will "screen" the reported information in order
to determine the need for further OTS assessment of the
subject chemical at this time.
c) The Chemical Screening Branch will send copies of this
Status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be provided to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
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f rtmK* \ UNITED STATES ENVIRONMENTAL PROTECTION AGENCY Page 1 of 3
WASHINGTON, DC 20460
DATE: DEC | 9 1989 APPROVED
SUBJECTS status Report1 8EHQ-1289-0851 S
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
OFFICE Of
PESTICIDES AND
TOXIC SUBSTANCES
NOTE
(See NOTE on Page 3 of this Status Report)
The submitting company has claimed its company name and the exact
identity of the subject chemical to be TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. In the "sanitized" version of its Section 8(e)
notice, the company reported non-confidentially that the subject
chemical is a "diaryl ether."
SUBMISSION DESCRIPTION
The submitting company provided the following summary information
regarding the conduct and preliminary results of a pilot teratology
study of this diaryl ether in rabbits:
"In this study, [the diaryl ether] was administered by
gavage to 6 groups of mated female rabbits at dose levels
of 0, 50, 100, 250, 500 and 750 mg/kg during gestation
days 7-19. Surviving dams were sacrificed on gestation
day 29. Fetuses were removed, weighed, sexed and examined
for possible malformations.
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA utider Section 8(e), the "Substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
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Page 2 of 3
"Six of seven females dosed at the 750 mg/kg/day level
died during the study. Five of eight at 500 mg/kg/day
also died. No mortality was observed at 250 mg/kg/day
level although one dam died at 100 mg/kg/day. Significant
body weight losses were noted at dosages of 250 mg/kg/day
and above. No maternal toxicity was evident at [the] 100
mg/kg/day [dose level].
"Post-implantation loss, dead fetuses and late resorption
were substantially increased at 250 mg/kg/day. [The]
fetal weights were not affected and no significant mal-
formations or variations were observed."
USE AND EXPOSURE POTENTIAL (See NOTE on Page 3 of this Status Report)
In view of the submitter's TSCA CBI claims, no information about
the TSCA Chemical Substance Inventory status or use of the subject
chemical will appear in this status report. The submitter did
report non-confidentially, however, that this diaryl ether is being
manufactured solely for research and development (R&D) purposes.
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will ask the submitter to
ensure that the Agency receives a complete copy of the
final report (including the actual experimental protocol,
results of gross/histopathological examinations, results
of statistical analyses, etc.) from the pilot teratology
study cited in the submission.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, the submitter will be requested
to describe the actions that the company has taken or
plans to take 1) to notify workers and others about the
reported data, and 2) to reduce or eliminate exposure to
this diaryl ether. In addition, the submitter will be
asked to describe the nature and results, if available,
of all studies (other than those submitted already to EPA
or those cited in the published scientific literature)
about which the company is aware or that the company has
conducted, is conducting or plans to conduct that are
designed to determine the toxicologic properties of the
subject chemical substance.
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will "screen" the reported information in order
to determine the need for further OTS assessment of the
subject chemical at this time.
27 2
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8EHQ-1289-0851 S
Page 3 of 3
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA? in addition,
copies of this status report will be provided to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
NOTE In an April 4, 1991 followup letter (8EHQ-0491-0883 S
Followup Response), the submitting company reported non-
confidential ly that the diaryl ether which was cited in
8EHQ-1289-0851 S Initial and the diaryl ether which was
cited in 8EHQ-0290-0883 S Initial are the same chemical
substance. The reader's attention is directed to the
status report that was prepared by EPA in response to
8EHQ-0290-0883 S Initial.
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 3
OFFICE OF
DATE: Q£C 20 1989 APPROVED
TOXIC SUBSTANCES
PESTOD68 AND
SUBJECT: status Report1 8EHQ-1289-0852 S
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
The Shell Oil Company submitted final reports from several acute
animal toxicity studies of EPIKUREr 1061 (CAS No. 2716-10-1) and
EPIKUREr 1062 (CAS No. 2716-12-3) . In the cover letter to its TSCA
Section 8(e) notice, Shell provided the following summary informa-
tion about the conduct and preliminary results of acute oral LD50
studies of the subject chemicals in male and female rats:
"After receiving 3150 or 5000 mg/kg of EPIKURE 1061
administered by gavage, microscopic examination revealed
hepatic inflammation and mild liver damage in both sexes
as well as testicular degeneration and atrophy in the
surviving males. In a companion study, rats received a
single oral dose of EPIKURE 1062 at a level of 5000
mg/kg. Examination at necropsy revealed reduced testes
size and enlargement of the liver and spleen. Microscopic
examination showed mild liver damage and severe tubular
degeneration of the testes. A repeat [acute rat oral]
study with EPIKURE 1062 at 5000 mg/kg also showed reduced
testes size. No other results were reported in the repeat
study •'
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk? information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
274
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8EHQ-1289-0852 S
Page 2 of 3
Shell also reported that "preliminary information from an ongoing
study involving daily oral doses of EPIKURE 1062 tend to substanti-
ate the findings of the . . . [acute oral toxicity studies being
reported to EPA under Section 8(e).]"
According to the submitted final reports, both EPIKURE 1061 and
EPIKURE 1062 were found to have rat oral LD50s of greater than 5000
mg/kg and rat dermal LD50s of greater than 2000 mg/kg. Although
neither compound was reported to be irritating to rabbit skin after
a 4-hour exposure, both materials were reported to cause slight to
moderate conjunctival redness up to 24 hours after administration
to rabbit eyes and a slight pain response immediately following eye
exposure. Finally, neither compound was reported to exhibit any
skin sensitizing potential in guinea pigs.
OSE AND EXPOSURE POTENTIAL
According to a commercial non-confidential computerized data base
(CAS ONLINE), the identities of the subject chemical substances are
as follows:
CAS No. 2716-10-1 Benzenamine, 4,4'-[l,4-phenylenebis(l-
(EPIKURE 1061) methylethylidene)]bis-
CAS No. 2716-12-3 Benzenamine, 4,4'-[l,4-phenylenebis(l-
(EPIKURE 1062) methylethylidene)]bis[2,6-dimethyl-
Shell stated non-confidentially that EPIKURE 1061 and EPIKURE 1062
are being "manufactured, processed, and distributed in commerce
under a TSCA Section 5(e) Consent Order which limits their use to
specific applications." Shell also stated that the major use of
these products to date "has been as intermediates in the production
of Consent Order resins." Shell noted that "the Consent Order also
specifies the types of protective equipment that must be used when
handling these products." Finally, Shell reported that the "Consent
Order requires informed consent letters to users, specific warning
statements, and training for employees and contractors."
COMMENTS/RECOMMENDATIONS
Shell stated that in addition to considering other forms of hazard
communication, the company is revising the current Material Safety
Data Sheets (MSDSs) for EPIKURE 1061 and EPIKURE 1062 to reflect
the reported toxicologic findings.
a) The Chemical Screening Branch will ask Shell to ensure
that the Agency receives a complete copy of the final
report (including the actual experimental protocol, the
results of gross and histopathologic examinations, the
results of statistical analyses, etc.) from the ongoing
repeated-dose study of EPIKURE 1062 that was cited in the
submission.
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8EHQ-1289-0852 S
Page 3 of 3
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, Shell will be asked to describe
the nature and results, if available, of all studies
(other than those submitted already to EPA or those cited
in the open scientific literature) about which Shell is
aware or that Shell has conducted, is conducting or plans
to conduct that are designed to determine the toxicity
of or the exposure to the subject chemical substances.
b) As was the case for the Shells initial TSCA Section 8(e)
notice, the Chemical Screening Branch will immediately
send complete copies of all reported information to staff
of the Chemical Control Division (CCD/OTS) for review and
appropriate followup attention.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and CCD/OTS/OPTS;
in addition, copies of this status report will be sent
to the Environmental Assistance Division/OTS (formerly
the TSCA Assistance Office/OTS) for further distribution.
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(s»)
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 3
DATE: DEC I 9 1989 APPROVED
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECTS Status Report 8EHQ-1289-0853 S
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
The submitting company has claimed its company name and the exact
identity of the subject chemical to be TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. In the "sanitized" version of its Section 8(e)
notice, the company reported non-confidentially that the subject
chemical substance is a "heterocyclic amide" and an "end-use active
ingredient."
SUBMISSION DESCRIPTION
The submitting company reported that this heterocyclic amide was
found to elicit a positive response in an Unscheduled DNA Synthesis
(UDS) Mutagenicity Assay using cultured rat primary hepatocytes.
According to the submitter, "an earlier conducted non-guideline,
but scientifically valid, UDS assay gave [a] negative indication
for mutagenic effects." Further, the submitter reported that "all
other mutagenicity assays for this end-use active ingredient have
given favorable negative results." Finally, the submitting company
reported that "all other studies to date have not demonstrated any
significant oncogenicity responses."
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk1 information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
277
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8EHQ-1289-0853 S
Page 2 of 3
U8E AND EXPOSURE POTENTIAL
In view of the submitter's TSCA CBI claims, no information about
the TSCA Chemical Substance Inventory status or specific use of
this heterocyclic amide will appear in this status report. The
submitter did report non-confidentially that the subject chemical
is in the "Development Phase" and is handled in small quantities
by laboratory and field personnel. The submitter also reported
that "as an added precaution, laboratory personnel with possible
exposure handle this material in a laboratory hood using good
laboratory technique" and "field personnel use personal protective
equipment during application trials."
COMMENTS/RECOMMENDATIONS
Although a positive in vitro genotoxicity test, when considered
alone, may not be sufficient to offer reasonable support for a
conclusion of substantial risk, (as that term is defined in EPA's
TSCA Section 8(e) policy statement ("Statement of Interpretation
and Enforcement Policy; Notification of Substantial Risk" 43 FR
11110; March 16, 1978)), EPA does believe that such information is
of value in assessing the possible risks posed by exposure to the
tested chemical or mixture. Further, EPA believes that a positive
genotoxicity test result, in combination with other information
(e.g., knowledge of actual/potential exposure to and/or high pro-
duction of the tested chemical or mixture), would suggest the need,
in many cases, to conduct further studies designed to determine
the toxicologic properties of or the exposure to that chemical
substance or mixture. EPA expects the results of such additional
studies to be considered also for submission under Section 8(e) of
TSCA.
a) The Chemical Screening Branch will ask the submitter to
ensure that EPA receives a complete copy of the final
report (including the actual experimental protocol, data,
results of statistical analyses, etc.) from the positive
UDS assay cited in the company's submission. In addition,
the company will be asked to submit full copies of the
final reports from all of the other genotoxicity studies
cited in the submission.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, the submitter will be requested
to describe the nature and results, if available, of all
studies (other than those submitted already to the Agency
or those cited in the published scientific literature)
about which the company is aware or that the company has
conducted, is conducting or plans to conduct that are
designed to determine the toxicity of this heterocyclic
amide.
278
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8EHQ-1289-0853 S
Page 3 of 3
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemical Program (ECP), staff of the Chemical Screening
Branch will "screen" the reported information in order
to determine the need for further OTS assessment of the
subject chemical at this time.
c) The chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be provided to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
279
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V, Page 1 of 2
S3 - * UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
9
$ cm '
t®.
^ WASHINGTON, DC 20460
DATE: DEC 2 I 1989 APPROVED J
^ n\v^
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-1289-0854 S
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
The submitting company claimed its company name, the exact identity
and the specific use of the subject chemical substance to be TSCA
Confidential Business Information (CBI). Staff of the Information
Management Division will review all incoming correspondence related
to the company's TSCA CBI claims. In the "sanitized" version of its
Section 8(e) notice, the company reported non-confidentially that
the subject chemical is a "heterocyclic amine."
SUBMISSION DESCRIPTION
The submitting company reported that this heterocyclic amine, when
tested in an Ames Salmonella tvphimurium (bacteria) mutagenicity
assay, caused an "increase in the number of histidine revertants
per plate" in strain TA1535 in the absence of exogenous metabolic
activation. According to the submitting company, "increases were
not induced in any of the other four [bacterial] tester strains."
USE AND EXPOSURE POTENTIAL
In view of the submitter's TSCA CBI claims, no information about
the TSCA Chemical Substance Inventory status or specific use of
this heterocyclic amine will appear in this status report. In its
Section 8(e) notice, the submitter reported non-conf identially that
; This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information repotting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
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Page 2 of 2
the subject chemical is "an isolatable process intermediate." In
addition, the submitter reported that the "potential for exposure
is low." Finally, the submitter reported that "personnel with
possible exposure handle this material in a laboratory hood."
COMMENTS/RECOMMENDATIONS
Although a positive in vitro genotoxicity test, when considered
alone, may not be sufficient to offer reasonable support for a
conclusion of substantial risk (as that term is defined in EPA's
TSCA Section 8(e) policy statement ("Statement of Interpretation
and Enforcement Policy; Notification of Substantial Risk" 43 FR
11110; March 16, 1978)), EPA does believe that such information is
of value in assessing the possible risk(s) posed by exposure to the
tested chemical or mixture. Further, EPA believes that a positive
genotoxicity test result, in combination with other information
(e.g., knowledge of actual/potential exposure to and/or high pro-
duction of the tested chemical or mixture), would suggest the need,
in many cases, to conduct further studies designed to determine
the toxicity of or the exposure to that chemical or mixture. EPA
expects the results of such additional studies to be considered
also for submission under Section 8(e) of TSCA.
a) The Chemical Screening Branch will ask the submitter to
ensure that EPA receives a full copy of the final report
(including the actual experimental protocol, data, etc.)
from the in vitro mutagenicity study that was cited in
the submission.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, the submitter will be requested
to describe the nature and results, if available, of all
studies (other than those submitted already to the Agency
or those cited in the published scientific literature)
about which the company is aware or that the company has
conducted, is conducting or plans to conduct that are
designed to determine the toxicity of this heterocyclic
amine.
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemical Program (ECP), staff of the Chemical Screening
Branch will "screen" the reported information in order
to determine the need for further OTS assessment of the
subject chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be provided to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
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Page 1 of 2
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
^ WASHINGTON, DC 20460
DATE:
DEC 28 1989 APPROVED:
SUBJECT: Status Report1 8EHQ-1289-0855
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBMISSION DESCRIPTION
The American Cyanamid Company reported that the company recently
received information about 2-hydroxy-4-methoxybenzophenone (CAS No.
131-57-7). Specifically, American Cyanamid stated that the company
received National Toxicology Program (NTP) preliminary reports from
90-day feeding and dermal toxicity studies in mice and rats and a
sperm morphology/vaginal cytology evaluation in rodents. According
to American Cyanamid, the obtained reports "have not been reviewed
by the NTP and may be considered extremely preliminary." Further,
American Cyanamid stated that the company found it "difficult to
interpret the [obtained] data." American Cyanamid did not provide
any information with regard to the nature of the findings from any
of the five (5) cited studies.
USE AND EXPOSURE POTENTIAL
American Cyanamid did not provide any information with regard to
the use of or the potential for exposure to 2-hydroxy-4-methoxy-
benzophenone. According to CHEMCYCLOPEDIA 88 (a publication of the
American Chemical Society (ACS)), the subject chemical substance
is 1) a "light absorber for plastics and coatings," and 2) a "UVB
sunscreen."
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk?' information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
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Page 2 of 2
COMMENTS/RECOMMENDATIONS
Assuming that 1) one or more of the obtained NTP reports contain
information of the type required to be submitted to EPA pursuant
to Section 8(e) of TSCA, and 2) the NTP did not formally release
those reports or information from those reports or the conducted
studies to the general public, American Cyanamid was correct in
reporting those NTP studies/reports to EPA under Section 8(e) of
TSCA. Further, American Cyanamid should be reminded that Part IX
("Reporting Requirements") of EPA's Section 8(e) policy statement
("Statement of Interpretation and Enforcement Policy; Notification
of Substantial Risk" March 16, 1978; 43 FR 11110) explains that a
Section 8(e) notice should include a summary of the adverse effects
being reported.
a) The Chemical Screening Branch will ask NTP for copies of
all available reports pertaining to the subject studies.
The Chemical Screening Branch will remind the American
Cyanamid Company that a Section 8(e) submission should
include a summary of the adverse effects being reported.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity and/or exposure data, American Cyanamid will be
asked to describe the actions that the company has taken
or plans to take 1) to notify workers/others about the
obtained findings, and 2) to reduce or eliminate exposure
to the subject chemical. In addition, American Cyanamid
will be requested to describe the nature and results, if
available, of all studies (other than those submitted
already to the Agency or those cited in the published
scientific literature) about which American Cyanamid is
aware or that the company has conducted, is conducting
or plans to conduct that are designed to determine the
toxicity of or the exposure to the subject chemical.
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemical Program (ECP), staff of the Chemical Screening
Branch will review the studies in order to determine the
need for further OTS assessment of the subject chemical
at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be provided to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
283
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? '•& Page 1 of 3
I | UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
DATES JAN ~5 1990 APPROVED: (jl6^
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-1289-0856
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
E. I. DuPont de Nemours & Company, Inc. provided the following
summary information about the conduct and preliminary results of
chronic inhalation studies of vinyl fluoride (CAS No. 75-02-5)
being performed pursuant to a TSCA Section 4 test rule:
"Groups of approximately 95 male and female Crl:CDR rats
and 95 male and female Crl :CD-1r(ICR) BR mice are being
exposed to vinyl fluoride at design concentrations of 0
ppm, 25 ppm, 250 ppm or 2500 ppm. These studies were
initiated in March, 1989? the study duration is 24 months
for rats and 18 months for mice. While no significant
observations have been noted in the rat study to date,
a significant increase in mortality has been noted in
male mice exposed to 2500 ppm of the test compound. When
evaluated as a percent of the animals at risk in that
group (i.e., the number of animals (60) designated for
the terminal sacrifice) , mortality was observed to be 35%
at approximately 9 months into the study. A high inci-
dence of gross liver and lung lesions has also been noted
in those animals dying unscheduled deaths (either found
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
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dead or sacrificed in extremis). In mice exposed to 2500
ppm vinyl fluoride, 10 of 24 had grossly observable liver
masses, compared to 0 of 5 controls. Many of these
masses were red and cystic and/or hemorrhagic. These
gross observations are consistent with the diagnosis of
hemangiosarcoma of the liver. The incidence of lung
nodules was also increased in the 2500 ppm male mice
group (10 of 24) versus controls (0 of 5) . Consequently,
it was decided that liver tissue collected from all mice
dying unscheduled deaths be evaluated microscopically.
[The] lung tissue from animals on test have not yet been
evaluated microscopically.
"Microscopic evaluation of the livers has confirmed that
the lesions are hemangiosarcomas. In the 2500 ppm male
mice, the incidence of hepatic hemangiosarcoma was 11 of
18 compared to 0 of 3 in controls. Background incidence
of this lesion, based on a previous study at [DuPont's]
Haskell Laboratory, is approximately 5% in mice. Further-
more, the background lesions observed in controls usually
occur later than approximately 500 days on test. The mean
days on test for observation of liver tumors in the mice
exposed to 2500 ppm vinyl fluoride is approximately 220
days. Hemangiosarcoma of the liver has also been observed
in the following groups: 1 of 3 male mice exposed to 25
ppm vinyl fluoride, 1 of 3 female mice exposed to 250 ppm
vinyl fluoride, and 2 of 8 female mice exposed to 2500
ppm vinyl fluoride. Thus, the high incidence of liver
hemangiosarcoma, especially at the 2500 ppm level, and
the early onset of the lesion at all levels, suggest the
effect to be compound-related."
USE AND EXPOSURE POTENTIAL
Information on the uses and the potential for exposure to vinyl
fluoride can be found in the documentation for the Section 4 test
rule on vinyl fluoride, a chemical in the "Fluoroalkenes" category
recommended for testing by the Interagency Testing Committee (ITC).
In the Section 8(e) submission, DuPont reported that the company
"is the sole domestic manufacturer of vinyl fluoride" and presented
•the following information regarding workplace exposure:
"DuPont previously established an Acceptable Exposure
Limit (AEL) for vinyl fluoride of 100 ppm (8 hour time-
weighted average [(TWA)]. Workplace exposure, however,
is routinely below 1 ppm. In light of [DuPont's] current
findings, DuPont has reduced the existing AEL to 1 ppm
(8 hour time-weighted average). DuPont has taken the
necessary action to notify the appropriate employees of
these [toxicological] results and ensure implementation
of the reduced AEL."
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Page 3 of 3
COMMENTS/RECOMMENDATI0N8
It is important to note that the Agency has received several TSCA
Section 8(e) submissions containing interim results of studies
being conducted pursuant to Section 4 of TSCA. EPA's position
regarding the relationship between TSCA Section 4 and Section 8(e)
reporting was reiterated in the COMMENTB/RECOMMENDATIONB portion
of the status report prepared by the Agency in response to TSCA
Section 8(e) submission number 8EHQ-0589-0797. It should be noted
also that EPA has issued TSCA Section 8(a) and 8(d) information
gathering rules for vinyl fluoride.
a) The Chemical Screening Branch will ask DuPont to ensure
that EPA is kept abreast of all further significant
findings from the company's ongoing chronic inhalation
studies of vinyl fluoride in mice and rats.
b) As was the case for DuPont's initial TSCA Section 8(e)
notice, the Chemical Screening Branch will immediately
send complete copies of all reported information to the
Test Rules Development Branch (TRDB/ECAD/OTS) for review.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and TRDB/ECAD/OTS;
in addition, copies of this status report will be sent
to the Environmental Assistance Division/OTS (formerly
the TSCA Assistance Office/OTS) for further distribution.
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 2
DATE:
JAN -51990
APPROVED:
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECTS Status Report1 8EHQ-1289-0857 S
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Branch Chief
chemical Screening Branch/ECAD/OTS/OPTS
Eli Lilly and Company has claimed the exact identity of the subject
chemical to be TSCA Confidential Business Information (CBI). The
Information Management Division (IMD/OTS) will review all incoming
correspondence related to this TSCA CBI claim. In the "sanitized"
version of the submission, Eli Lilly reported non-confidentially
that the subject chemical is an "indolocarbazole" that "has not
been characterized."
SUBMISSION DESCRIPTION
Eli Lilly reported that preliminary results from an acute oral
toxicity study in mice showed that the chemical has "a median
lethal dose [of] less than 50 mg/kg." Eli Lilly submitted the
following summary relating to the conduct and results of the study:
"The acute toxicity of the compound administered orally
to female CD-I mice was evaluated. There were three
animals in each of the three dose groups, and the animals
received either 50, 500, or 2000 mg/kg of the compound.
There were no survivors following a single oral dose of
50 mg/kg of this compound. All deaths occurred by Test
Day 2. Antemortem signs of toxicity included ataxia,
hypoactivity, lethargy, piloerection, ptosis, and
tremors."
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
NOTE
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Page 2 of 2
USE AND EXPOSURE POTENTIAL
In view of Eli Lilly's TSCA CBI claim, no information regarding
the use of this indolocarbazole will appear in this status report.
Eli Lilly did report non-confidentially, however, that 1) this
indolocarbazole is a "research compound," and 2) less than 10 grams
of the chemical have been manufactured thus far.
COMMENTS/RECOMMENDATIONS
In its submission, Eli Lilly stated that company employees have
been informed about the acute toxicity of this indolocarbazole.
In addition, Eli Lilly reported that the subject chemical substance
was already labelled as being hazardous. Finally, Eli Lilly stated
that a "gradient plate assay" for genotoxicity is being performed
for this chemical.
a) The Chemical Screening Branch will ask Eli Lilly to
ensure that EPA receives a complete copy of the final
report (including the actual experimental protocol,
results of gross and histopathological examinations,
results of statistical analyses, etc.) from the acute
oral toxicity study cited in the company's submission.
In addition, Eli Lilly will be asked to ensure that the
Agency receives a complete copy of the final report from
the "gradient plate" assay cited also in the submission.
Eli Lilly will be requested also to submit, if and when
available, a full chemical characterization of the test
material.
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemical Program (ECP), staff of the Chemical Screening
Branch will review the reported information in order to
determine the need for further OTS assessment of this
indolocarbazole at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be provided to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
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w
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 3
dates JAN -5 1990
APPROVED:
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECTS status Report1 8EHQ-1289-0858 S
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TOs Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
The submitting company has claimed its company name and the exact
identity of the subject chemical to be TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. In the "sanitized" version of its Section 8(e)
notice, the company reported non-confidentially that the subject
chemical is an "alkyl ketone."
SUBMISSION DESCRIPTION
The submitting company provided final results from three (3) oral
(gavage) teratology studies of this alkyl ketone, two (2) in rats
and one (1) in rabbits. The submitter's TSCA Section 8(e) cover
letter presents the following summary information about the conduct
and results of these studies:
"In the first [rat] teratogenicity study, [alkyl ketone]
dose levels were 0, 15, 45 and 135 mg/kg/day and in the
second study, [alkyl ketone] dose levels were 0, 5, 10,
and 13 5 mg/kg/day. In both studies, 24 pregnant female
rats per dose level were dosed on days 7-16 (inclusive)
of gestation. . . .
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
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Page 2 of 3
"The conclusion from these two [rat] studies is that
[this alkyl ketone] was teratogenic [(vertebral defects)]
and that a clear no-effect level for vertebral defects
was not determined. The no-effect level for fetotoxicity
was 5 mg/kg/day."
"[In the rabbit study,] twenty rabbits per dose level
were dosed on days 7-19 (inclusive) of gestation at dose
levels of 0, 15, 45, or 135 mg/kg/day. [The alkyl ketone]
was considered not to be teratogenic in this study. [The
chemical] was fetotoxic at 13 5 mg/kg/day, as assessed by
increases in the incidence of minor defects and skeletal
variants. [The alkyl ketone] was embryolethal at 45 and
13 5 mg/kg/day; the no-effect level for embryolethality
was 15 mg/kg/day."
The submitter also reported that the company had recently received
the following additional information regarding this alkyl ketone:
"Longterm studies in both rodent and non-rodent species
have successfully completed their in-life phases, with
the study data still under evaluation. [The] preliminary
results from the two year mouse oncogenicity study indi-
cate [that] there is a low incidence of liver cell
tumors. This finding seen at study termination is in the
highest dose group (1000 ppm) only. The study data have
not yet been fully validated; therefore, it would be
premature to give definitive tumor incidences at this
stage. Study reports are in preparation. There is no
evidence of oncogenicity from the other species tested
and no indication that [the alkyl ketone] has a potential
for genotoxicity from the battery of in vitro tests
completed to date."
Finally, the submitter stated that the company has "requested that
a review of all toxicological studies involving this chemical be
undertaken" and that EPA will be "advised as additional information
is obtained."
USE AND EXPOSURE POTENTIAL
In view of the submitter's TSCA CBI claims, no information about
the TSCA Chemical Substance Inventory status or use of the subject
chemical will appear in this report. According to the submitting
company, "trained employees use appropriate protective equipment"
when working with the chemical.
COMMENTS/RECOMMENDATIONS
The submitting company reported that an employee briefing on the
reported findings is in preparation.
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Page 3 of 3
a) The Chemical Screening Branch will ask the company to
submit complete copies of the final reports (including
the actual experimental protocols, results of gross and
histopathological examinations, results of statistical
analyses, etc.) from the longterm studies that were cited
in the company's Section 8(e) submission. In addition,
the company will be asked to submit full copies of the
final reports from the genotoxicity studies cited also
in the submission.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, the submitter will be requested
to describe the actions the company has taken or plans
to take to reduce or eliminate exposure to the subject
chemical. In addition, the submitter will be asked to
describe the nature and results, if available, of all
studies (other than those submitted already to the Agency
or those cited in the published scientific literature)
about which the company is aware or that the company has
conducted, is conducting or plans to conduct that are
designed to determine the toxicity of or the exposure to
the subject chemical.
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will review the reported information in order to
determine the need for further OTS assessment of this
alkyl ketone at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be provided to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
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s*,,
{W
Vj Page 1 of 2
* UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
DATE:
JAN - 5 19
APPROVED:
-------
8EHQ-1289-0859
Page 2 of 2
USE AND EXPOSURE POTENTIAL
Halocarbon did not provide any information with regard to the use
of or the potential for exposure to QC2 or its constituents.
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will request Halocarbon to
submit information regarding the exact chemical identity
(including CAS No., if known) for each constituent of the
tested QC2 mixture.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, Halocarbon will be requested to
describe the actions that the company has taken or plans
to take 1) to notify workers/others about the reported
information, and 2) to reduce or eliminate exposure to
QC2 or its constituents. In addition, Halocarbon will be
asked to describe the nature and results, if available,
of all studies (other than those submitted already to EPA
or those cited in the published scientific literature)
about which Halocarbon is aware or that the company has
conducted, is conducting or plans to conduct that are
designed to determine the toxicity of or the exposure to
QC2 or its constituents.
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will review the reported information in order to
determine the need for further OTS assessment of QC2 or
its constituents at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be provided to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
293
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 2
OFFICE OF
PESTICIDES AND
DATE: JAN "91990 APPROVED:
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0190-0860 S
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
The submitter has claimed the company name to be TSCA Confidential
Business Information (CBI). The Information Management Division
will review all incoming correspondence related to this CBI claim.
SUBMISSION DESCRIPTION
The submitter provided the final results of an acute inhalation
study "designed to assess the toxic effects and determine the
median lethal concentration of ['the products obtained from the
pyrolysis of polybromotrifluoroethylene•(CAS No. 55157-25-0)1 when
administered by inhalation as a vapor to Sprague-Dawley CD rats
(5/sex/group) for four hours [at doses of 0.50, 2.4, or 4.9 mg/1
air]." The submitter's cover letter contained the following summary
information regarding the results of this study:
"Within hours of [the] exposure, signs of toxicity such
as labored breathing or gasping followed by death were
noted at 4.9 and 2.4 mg/1. At 0.50 mg/1, [the] signs of
toxicity persisted for up to 21 days without complete
recovery. These animals also showed weight losses for
up to 14 days after [the] exposure before showing some
recovery. The calculated LC50 = 0.88 mg/1."
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
NOTE
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Page 2 of 2
USE AND EXPOSURE POTENTIAL
The submitter did not provide any information regarding the use(s)
of or the potential for exposure to the tested material, nor was
such information located in the secondary literature sources that
were consulted by EPA.
COMMENTS/RECOMMENDATIONS
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
that are taken on a voluntary basis in response to
chemical toxicity/exposure data, the submitter will be
asked to describe the actions the company has taken or
plans to take 1) to notify workers and others about the
reported information, and 2) to reduce or eliminate any
exposure to the tested material. The submitter will be
asked also to provide copies of Material Safety Data
Sheets and labels that have been revised to reflect the
reported findings. In addition, the submitter will be
asked to describe the nature and results, if available,
of all studies (other than those submitted already to EPA
or those cited in the published scientific literature)
about which the company is aware or that the company has
conducted, is conducting or plans to conduct that are
designed to determine the toxicity of or the exposure to
the tested material.
b) The reported information will be reviewed by the Chemical
Screening Branch as part of the "FIRST REVIEW" phase of
the OTS Existing Chemicals Program (ECP) in order to
determine the need for further assessment of the subject
chemicals at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
295
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 2
DATE: JAN -91990 APPROVED!
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0190-0861 8
»- ¦ ¦ >
PROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
The CIBA-GEIGY Corporation has claimed the exact identity of the
subject chemical to be TSCA Confidential Business Information
(CBI). Staff of the Information Management Division will review
all incoming correspondence related to this CBI claim. In the
"sanitized" version of its Section 8(e) notice, CIBA-GEIGY stated
non-confidentially that the subject chemical is a "substituted
polycyclic lactone" for which the company "has requested the
specific chemical name and CAS registry number . . . from the
Chemical Abstracts Services ..."
SUBMISSION DESCRIPTION
CIBA-GEIGY provided preliminary findings from a range-finding rat
teratology study of the subject chemical substance. According to
the company, "presumed pregnant rats were dosed with 0, 1, 10, 50
or 100 mg/kg of the test material." CIBA-GEIGY did not provide any
information regarding the route of exposure and the gestation days
on which dosing occurred. CIBA-GEIGY stated that "maternal toxicity
indicated by reduced weight gain was observed at [both] the 50 and
100 mg/kg dose levels." In addition, CIBA-GEIGY reported that the
chemical "produced [fetal] gastroschisis" at the maternally toxic
doses of 50 and 100 mg/kg.
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
NOTE
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Page 2 of 2
USE AND EXPOSURE POTENTIAL
CIBA-GEIGY stated that this substituted polycyclic lactone "is a
research and development compound being evaluated for pesticidal
purposes . . . under the supervision of technically qualified
personnel [who are] knowledgeable in handling potentially hazardous
chemicals."
COMMENTS/RECOMMENDATIONS
CIBA-GEIGY stated that all of its workers who currently handle this
substituted polycyclic lactone are being apprised of the reported
toxicologic findings. In addition, CIBA-GEIGY stated that these
workers are being reminded "that this is an experimental compound
and should be handled in such a manner as to minimize or prevent
any exposure." Finally, CIBA-GEIGY reported that the company plans
conduct a "definitive teratology study" for the subject chemical.
a) The Chemical Screening Branch will request CIBA-GEIGY to
ensure that EPA receives full copies of the final reports
(including the actual experimental protocols, results of
gross and histopathological examinations, results of any
statistical analyses, etc.) from the range-finding and
definitive teratology studies cited in the submission.
CIBA-GEIGY will be asked also to submit the exact name
and CAS No., when available, for the subject chemical.
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to chemical
toxicity/exposure data, CIBA-GEIGY will be requested to
provide copies of any Material Safety Data Sheets and
labels that have been revised to reflect the reported
toxicologic findings. In addition, CIBA-GEIGY will be
asked to describe the nature and results, if available,
of all studies (other than those submitted already to EPA
or those cited in the published scientific literature)
about which CIBA-GEIGY is aware or that the company has
conducted, is conducting or plans to conduct that are
designed to determine the toxicologic properties of the
subject chemical.
,,b) The reported information will be reviewed by staff of the
Chemical Screening Branch as part of the "FIRST REVIEW"
phase of the Existing Chemicals Program (ECP) in order
to determine the need for further OTS assessment of the
subject chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
297
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 3
JAN ~ 9 1990 approved:
OFFICE OF
PESTICIDES ANO
TOXIC SUBSTANCES
DATE:
SUBJECT: Status Report1 8EHQ-0190-0862 S
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS
The submitting company has claimed its company name and the exact
identity of the subject chemical to be TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. The company reported non-confidentially that the
subject chemical is an "alkoxy aryloxy nitrobenzene."
SUBMISSION DESCRIPTION
The submitting company reported that "preliminary results obtained
from a pilot rat teratology study suggest that [this alkoxy aryloxy
nitrobenzene] may produce substantial developmental toxicity in the
presence of only slight to moderate maternal toxicity." The company
provided the following summary information about the conduct and
preliminary results of the study:
"In this study, [the alkoxy aryloxy nitrobenzene] was
administered by gavage to 6 groups of 8 mated female rats
at dose levels of 0, 25, 100, 250, 500 and 1000 mg/kg/day
during gestation days 6-15. Surviving dams were sacri-
ficed on gestation day 20. Fetuses were removed, weighed,
sexed and examined for possible external malformations.
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
NOTE
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8EHQ-0190-0862 S
Page 2 of 3
"All [of the] animals survived until scheduled C-section.
Maternal body weight gain was reduced at >2 50 mg/kg/day
and possibly also at 100 mg/kg/day but riot in a clear
dose-related manner. Increases in post-implantation loss
and decreases in fetal weight were noted at >100 mg/kg/
day but again the changes at >250 mg/kg/day were not
dose-related and the effects at 100 mg/kg/day were mini-
mal. The increased post-implantation loss and decreased
fetal weights were probably largely responsible for the
decreased maternal weight gain, particularly during the
latter parts of gestation. External malformations were
noted in 1, 3 and 2 fetuses (1, 2 and 2 litters) from the
100, 250, and 500 mg/kg/day groups, respectively. No mal-
formations were noted in the controls or at 2 5 or 1000
mg/kg/day."
USE AND EXPOSURE POTENTIAL
The submitting company stated non-confidentially that the chemical
is being manufactured solely for research and development (R&D)
purposes.
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will ask the submitter to
ensure that EPA receives a full copy of the final report
(including the actual experimental protocol, results of
gross and histopathological examinations, results of any
statistical analyses, etc.) from the cited pilot study.
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as corporate actions
that are taken on a voluntary basis in response to
chemical toxicity/exposure data, the submitter will be
asked to describe the actions that the company has taken
or plans to take 1) to notify workers/others about the
reported information, and 2) to reduce or eliminate
exposure to the subject chemical. The submitter will be
asked also to provide copies of Material Safety Data
Sheets and labels that have been revised to reflect the
reported toxicologic findings. In addition, the submitter
will be requeisted to describe the nature and results, if
available, of all studies (other than those submitted
already to the Agency or those cited in the published
scientific literature) about which the company is aware
or that the company has conducted, is conducting or plans
to conduct that are designed to determine the toxicity
of or the exposure to the'subject chemical.
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP), the Chemical Screening Branch
will review the reported information to determine the
need for further assessment of the chemical at this time.
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Page 3 of 3
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA? in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
300
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w
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY Page 1 of 3
WASHINGTON, DC 20460
date: -IAM 3 0 1990
APPROVED:
t ' ^Wl <3 /'
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0190-0863
FROM: Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
The Upjohn Company provided a full copy of an epidemiology draft
report in which the preliminary assessment of three recently
identified bladder cancer cases in workers in their North Haven,
Connecticut plant indicates "that there may be an elevated risk of
bladder cancer in the plant population." Upjohn reported that this
study was undertaken to assess the significance of the these
recently identified bladder cancer cases and "to determine the
availability of information and feasibility of conducting a study
on employees at [the North Haven] plant where diamine products,
including 3,31-dichlorobenzidine (CAS No. 91-94-1), [benzidine, CAS
No. 92-87-5; ortho-dianisidine, CAS No. 119-90-4; and ortho-
tolidine, CAS No. 119-93-7] were produced between 1945 and 1989."
According to the submitted report, the "production of dianisidine
ceased in 1974 and the last batch of ortho-tolidine was made in
1977. Dichlorobenzidine operations were terminated at the plant in
1989." Both the production and sale of benzidine were reportedly
terminated in 1965.
Upjohn reported that "one cancer incidence study has already been
conducted on workers employed before 1965 when benzidine was pro-
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
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Page 2 of 3
duced. That study indicated a statistically significant association
between exposure to diamines and bladder cancer." The following
summary information is from this previously published report:
"Meigs et al. [1986] published a report on a historical
cohort study of essentially all NHFC (North Haven Fine
Chemical) plant workers (n = 984) who had been employed
for at least 1 day between plant start-up in 1945 and May
31, 1965 . . . For males only, there was a non-signifi-
cantly elevated standardized incidence ratio (SIR) of
1.34 for all malignant cancer sites (except non-melanoma
skin) and a significantly increased SIR of 3.43 for
malignant bladder [tumors] (observed/expected = 8/2.3,
CI (confidence internal): 1.48-6.76). The mean latent
period was 21 years for those individuals developing
bladder tumors."
In Appendix E of its submission, Upjohn discussed the preliminary
assessment of the three recently detected bladder cancer cases in
workers hired after 1965. Upjohn reports that "these cases are of
interest because the plant terminated benzidine production and
sales in 1965 and after that date, exposures [at the North Haven
plant] would have been limited to 3,3'-dichlorobenzidine, ortho-
dianisidine or ortho-tolidine.11 The standardized incidence ratio
for this preliminary study was reported to be 5.09 (observed/
expected = 3/0.589; 95% confidence interval = 1.02-14.88).
USE AND EXPOSURE POTENTIAL
Upjohn reported that 3 ,3 ' -dichorobenzidine was always the principal
diamine produced at the North Haven plant and that it no longer
produces any diamine products. The Condensed Chemical Dictionary
(10th Edition) states that the diamines cited in this submission
may be used as components of dyes and pigments and as chemical
intermediates for various applications.
COMMENTS/RECOMMENDATIONS
In its submission, Upjohn reported that when the final report is
completed, the company will design follow-up studies and activities
to determine what association exists between diamine exposure and
the observed incidence of bladder cancer.
a) The Chemical Screening Branch will ask Upjohn to ensure
that EPA receives a complete copy of the final report
(including the actual study protocol, results of any
statistical analyses, etc.) from the epidemiological
study cited in the submission.
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Upjohn will be asked to describe
the actions the company has taken or plans to take to
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Page 3 of 3
notify workers and others about the reported findings.
Upjohn will be asked also to provide copies of such
notification(s).
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will review the reported information in order to
determine the need for further assessment of the subject
chemical(s) at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
Reference
Meigs, J.W. et al. "Bladder Tumor Incidence Among Workers Exposed
to Benzidine: A Thirty-Year Follow-Up" JNCI, 1986; 76:1-8.
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g A x
{mj
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 4
DATE:
SUBJECT!
PROM:
TO:
APPROVED:
T. &Z j/tibo
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
FEB I 3
Status Report1 8EHQ-0190-0864
Jacqueline T. Favilla, Biologist *0 f¦
Chemical Risk Identification Section/CSB
James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
gPPMIgglPW PBPCRIPTI9W
The Goodyear Tire and Rubber Company submitted "a copy of an
interim report issued by the National Institute for Occupational
Safety and Health (NIOSH)." This report describes a NIOSH Health
Hazard Evaluation (HHE) of bladder cancer incidence among workers
at Goodyear*s plant in Niagara Falls, N.Y. Although Goodyear
states in its cover letter that it "has assisted NIOSH in the
collection of data used in this study ... this is an interim report
by NIOSH, rather than a final report, and Goodyear reserves the
right to draw its own conclusion from the data." The following
information is provided in the submission regarding the occurrence
of bladder cancer among workers:
"In February, 1988, a representative of the Oil,
Chemical, and Atomic Workers (OCAW) International Union
requested that NIOSH conduct a Health Hazard Evaluation
of ... [the Goodyear Niagara Falls chemical manufacturing
plant]. The union requested this evaluation because eight
cases of bladder cancer had been reported between 1973
and 1988 among current and former employees of the plant.
The union believed that these workers had been exposed
to ortho-toluidine [CAS No. 95-53-4], a suspect bladder
carcinogen.
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
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Page 2 of 4
"In response to this request, NIOSH investigators visited
the plant ... [and] identified bladder cancer cases from
records of the company, the union, and the New York State
Cancer Registry. The number of bladder cancer cases
observed among Goodyear workers was compared to the
number expected based on New York State incidence rates.
The study was restricted to the time period 1973 through
1988 because New York State Cancer Registry records were
thought to be relatively complete during that time
period.
"There were 14 cases of bladder cancer observed and 3.54
expected based on New York State incidence rates among
the 1749 individuals ever employed at the plant. The
ratio of observed to expected cases (also known as the
Standardized Risk Ratio or SIR) of 3.95 was found to be
highly statistically significant (p«*0.00002) indicating
that this risk was very unlikely to have occurred by
chance. There were 8 cases observed and 1.20 (SIR-6.64?
p~0,00004) expected among 795 workers ever employed in
an area of the plant where workers were definitely
exposed to o-toluidine and aniline [CAS No. 62-53-3].
There were 4 cases observed and 1.05 expected (SIR-3.81;
p-0.02) among workers considered to have possible
exposure to o-toluidine and aniline because they worked
in maintenance, janitorial/yard and shipping departments.
The SIR among 681 workers considered "probably unexposed"
was not significantly different from 1.00. Therefore,
the excess risk of bladder cancer is associated with
exposure to o-toluidine and aniline."
In the letter transmitting the HHE to Goodyear, NIOSH explained
-that the completed evaluation is "an interim, rather than a final
report" because NIOSH "would like to conduct a more extensive
evaluation of exposure to o-toluidine and aniline among current
workers before completing the Health Hazard Evaluation. In
addition to the Health Hazard Evaluation report, which will
complete the investigation of the bladder cancer excess at the
plant, [NIOSH] will analyze the mortality experience of the workers
and report this separately."
NIOSH also reported that this "interim report is being distributed
... to management and union officials and to public health agencies
... [as well as] investigators at the Mt. Sinai School of Medicine
who have assisted in the study."
V8» m BSFQ8VM MTOTIM.
In the submission, it was reported that both o-toluidine and
aniline are "premix chemicals" used in the production of Wingstay
100, an antioxidant that is utilised mainly at Goodyear plants.
Aniline is also a "premix chemical" utilized in the production of
Morfax, a rubber accelerator that is manufactured and commercially
marketed by Goodyear.
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Page 3 of 4
The Condensed chemical Dictionary (10th edition) lists the uses of
o-toluidine as "textile printing dyes, vulcanization accelerator,
organic synthesis" and the aniline uses include rubber accelerators
and antioxidants, pharmaceuticals, petroleum refining, herbicides,
and fungicides.
The 1989 National Toxicology Program Fifth Annual Report on
Carcinogens Summary provides the following production information
on o-toluidine:
"In 198 6, there were three producers of o-toluidine and
one producer of o-toluidine hydrochloride. No production
volumes are available for o-toluidine hydrochloride;
however, the Chem Sources USA directory identified 12
suppliers in 1986 (Chem Sources, 1986). In 1983, U.S.
production of o-toluidine was between 11 and 21 million
pounds; the Chem Sources USA identified 34 companies as
suppliers of o-toluidine in 1983 (EPA ETD, 1984)."
The June 19, 1989 issue of the "Chemical and Engineering News"
estimates the 1988 production volume of aniline to be in excess of
one billion pounds.
COMMENTS/RECOMMENDATIONS
It should be noted that in December of 1987, the above referenced
bladder cancers were the subject of a "For Your Information" (FYI-
AX-0188-0266 Sequence E) report submitted by the Oil, Chemical and
Atomic Workers International Union. Follow-up actions taken by the
Chemical Screening Branch (CSB) at that time determined that an
evaluation was being conducted by NIOSH. CSB requested that all
interested parties keep EPA apprised of further developments.
It should be noted also that the Interagency Testing Committee
(ITC) recommended aniline for testing under Section 4 of TSCA; a
Testing consent Order has been signed (53 FR 31804). Further, o-
toluidine was the subject of a Chemical Hazard Information Profile
(CHIP) prepared in 1984 by CSB. Finally, the Agency has published
TSCA Section 8(d) information gathering rules covering aniline and
o-toluidine.
In the summary of the Health Hazard Evaluation, NIOSH recommended
that the following actions be undertaken by Goodyear: 1) assess
current exposures to o-toluidine and aniline; 2) notify current
and former workers about the risk; 3) establish a bladder cancer
screening program for current and former workers; and 4) continue
to monitor bladder cancer incidence in the cohort.
a) The Chemical Screening Branch will ask Goodyear to ensure
that EPA receives a complete copy of the final Health
Hazard Evaluation prepared by NIOSH, as well as the full
report (including the actual study protocol, results of
statistical analyses, etc.) on the mortality experience
among workers at the Niagara Falls plant.
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Page 4 of 4
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Goodyear will be requested to
describe the actions that the company has taken or plans
to take 1) to notify workers/others about the reported
information, and 2) to reduce or eliminate exposure to
the subject chemicals. Goodyear will be asked to provide
copies of such notifications.
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will review the reported information in order to
determine the need for further assessment of the subject
chemicals at this time.
As was the case with the initial submission, staff of the
Chemical Screening Branch will send full copies of all
reported information to TRDB/ECAD/OTS for inclusion in
the ongoing TSCA Section 4 review of aniline.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and TRDB/ECAD/OTS?
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
307
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 3
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
DATES «"tB 14 1990
APPROVED:
8UBJECT: Status Report1 8EHQ-0190-0865 S
QucLuHL /V.
FROM: Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE (Also see NOTE on Page 3 of this status report.)
The submitting company has claimed its company name and the exact
identity of the subject chemical as TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. In the "sanitized" version of its Section 8(e)
notice, the company reported non-confidentially that the subject
chemical is a "heterocyclic substituted acetanilide."
SUBMISSION DESCRIPTION
The submitting company provided the following summary information
regarding the conduct and preliminary results of a pilot rabbit
oral teratology study of this heterocyclic substituted acetanilide:
"[In this study, the test compound] was mixed with corn
oil and administered daily by gavage at dose levels of
0, 15, 30, 60, 120 and 240 mg/kg/day to 6 groups of 7
artificially inseminated female New Zealand White rabbits
during gestation days 7 through 19. All surviving
animals were sacrificed on gestation day 29.
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
308
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8EHQ-0190-0865 S
Page 2 of 3
"One treatment-related death was seen in each of the 120
and 240 mg/kg/day treatment groups. Two additional
deaths occurred at 240 mg/kg/day but were due to
mechanical injury. Abortions occurred in 3/6, 4/6, and
2/3 of the gravid females at 60, 120 and 240 mg/kg,
respectively. Abortions were not observed in lower dose
groups. As a result, the number of gravid females
examined at necropsy were 3, 2 and 1 at dose levels of
60, 120 and 240 mg/kg, respectively. Clinical
observations observed only at the high dose included head
tilt, ataxia, prostrate and lethargic animals.
"Severe body weight losses were observed at dose levels
of 60 mg/kg and above throughout the treatment period.
No effects on body weight were observed at dose levels
of 15 and 30 mg/kg/day.
"Necropsy findings possibly related to treatment were
observed at dose levels of 60 mg/kg and above. Liver
weights were increased at dose levels of 60 mg/kg and
above.
"The single surviving gravid female in the 240 mg/kg/day
group had total litter resorption. No post-implantation
loss was observed in the two animals observed at 120
mg/kg/day or at dose levels of 60 mg/kg and below. Fetal
weights were decreased at 60 and 120 mg/kg/day. No
treatment-related effect was observed on post-
implantation loss or fetal weight at 15 and 30 mg/kg/day.
"One aborted fetus and one fetus at cesarean section in
the 60 mg/kg/day group and 3 aborted fetuses at 120
mg/kg/day had the malformation, dome shaped head. A
determination as to whether this is a developmental
effect is difficult because the morphology of the cranium
can be altered mechanically by the abortion process. No
malformations or variations were observed at dose levels
of 15 and 30 mg/kg day."
USE AND EXPOSURE POTENTIAL
T£e submitter reported non-confidentially that this heterocyclic
substituted acetanilide is being manufactured exclusively for
research and development (R&D) purposes.
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will ask the submitter to
ensure that EPA receives a complete copy of the final
report (including the actual experimental protocol,
results of gross and histopathological examinations,
results of statistical analyses, etc.) from the pilot
teratology study cited in the submission.
309
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8EHQ-0190-0865 S
Page 3 of 3
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, the submitter will be requested
to describe the actions that the company has taken or
plans to take 1) to notify workers/others about the
reported information, and 2) to reduce or eliminate
exposure to this heterocyclic substituted acetanilide.
The submitter will be asked also to provide copies of
Material Safety Data Sheets and labels that have been
revised to reflect the reported findings. In addition,
the submitter will be asked to describe the nature and
results, if available, of all studies (other than those
submitted already to EPA or those cited in the published
scientific literature) about which the company is aware
or that the company has conducted, is conducting or plans
to conduct that are designed to determine the toxicity
of this chemical.
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will review the reported information in order to
determine the need for further assessment of the subject
chemical at this time,
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
NOTE The reader's attention is directed to the status report
prepared by EPA in response to 8EHQ-0190-0869 S.
310
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY Page L of 3
WASHINGTON, DC 20460
OFFICE OF
DATE:
SUBJECT:
FROM: Martha G. Price, Ph.D., Chemist^(/^>-^* [J^)2 N4- V
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
The CIBA-GEIGY Corporation has claimed the product trade name as
TSCA Confidential Business Information (CBI). In the "sanitized"
version of its Section 8(e) notice, the company reported non-
confidentially that the subject product is a 40% aqueous solution
of 2-propenoic acid, sodium phosphinate polymer, produced from a
CBI % mixture by weight of acrylic acid and sodium hypophosphite
(CAS No. 71050-62-9) . Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims.
SUBMISSION DESCRIPTION
CIBA-GEIGY provided the following summary information regarding the
conduct and preliminary results of a 90-day oral gavage study of
the subject product in the rat:
"The test material was administered daily by gavage to
Sprague-Dawley rats for 8 weeks at dose levels of 100
(group 2), 500 (group 3), and 2500 rag/kg (group 4). Dose
groups consisted of 40 animals (20 M/20F). Control (group
1) and top dose (group 4) contained additional animals
(M/F) to be kept for a 4 week treatment free period.
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information repotting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
(A)
FEB I 4 1990 approved: fiwlrzfahc
Status Report1 8EHQ-0190-0866 S
PESTICIDES AND
TOXIC SUBSTANCES
311
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8EHQ-0190-0866 S
Page 2 of 3
"Treatment related signs of osteomalacia associated with
hyperphosphaturia and calciuria developed in animals of
both sexes by week 8 of the study. No significant
changes are apparent in blood calcium and phosphate
concentrations "
According to CIBA-GEIGY, this 90-day study is being conducted in
France for CIBA-GEIGY*s parent company (CIBA-GEIGY Limited of
Basel, Switzerland). CIBA-GEIGY also stated that the final report
for the study is expected in the second half of 1990.
ygB AND ESPQggPB PQTgNTIftfr
CIBA-GEIGY stated, "This product is used in water treatment
applications for calcium (scale) control in boilers." CIBA-GEIGY
also reported that although the product is manufactured in the
United States, all of the product is exported to the United
Kingdom. CIBA-GEIGY reported further that a similar product, which
is a 50% aqueous solution of the same active ingredient, is
manufactured and sold in the U. S. Additionally, CIBA-GEIGY stated
that the company submitted a TSCA Section 5 "Pre-Manufacture
Notification" (PMN No. P89-853) for "Bellasol S 45/S 49, the
sodium salt of the chemical substance in question." (Immediately
upon receipt of this CIBA-GEIGY Section 8(e) submission, the
Chemical Screening Branch sent a complete copy of the submission
to the Chemical Control Division (CCD/OTS), which is responsible
for implementing EPA's TSCA Section 5 New Chemicals Program (NCP) .)
COMMENTS/RECOMMENDATIONS
In its submission, CIBA-GEIGY Corporation reported that the company
will revise its label and Material Safety Data Sheet to reflect
these new findings and notify its workers and customers.
a) The Chemical Screening Branch will ask CIBA-GEIGY to
ensure that EPA receives a complete copy of the final
report (including the actual experimental protocol,
results of gross and histopathological examinations,
results of statistical analyses, etc.) from the 90-day
study cited in the submission.
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, CIBA-GEIGY will be requested to
describe the actions the company has taken or plans to
take to reduce or eliminate exposure to 2-propenoic acid,
sodium phosphinate polymer. In addition, CIBA-GEIGY will
be asked to provide copies of Material Safety Data Sheets
and labels that have been revised to reflect the reported
findings. Further, CIBA-GEIGY will be asked to describe
the nature and results, if available, of all studies
(other than those submitted already to EPA or those cited
in the open scientific literature) about which CIBA-GEIGY
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8EHQ-0190-0866 S
Page 3 of 3
is aware or that the company has conducted, is conducting
or plans to conduct that are designed to determine the
toxicity of or the exposure to the subject product and/or
2-propenoic acid, sodium phosphinate polymer.
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will review the reported information in order to
determine the need for further assessment of the subject
chemical/product at this time.
c) The Chemical Screening Branch will send copies of this
Status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA, and CCD/OTS? in
addition, copies of this status report will be sent to
the Environmental Assistance Division/OTS (formerly the
TSCA Assistance Office/OTS) for further distribution.
313
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY Page 1 of 3
WASHINGTON, DC 20460
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
DATE:
FEB I 4 1990
APPROVED:
SUBJECT: Status Report1 8EHQ-0190-0867
QuoUt*6 MCO
FROM: Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
TO: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
The Eastman Kodak Company provided the following information about
the conduct and results of an acute oral toxicity study of N-ethyl-
2-hydroxy-5-nitrobenzenemethanamine (CAS No. 71130-60-4) in rats:
"Groups of five male and five female rats were
administered single doses of 5000, 2500, 1250, 625, or
312 mg/kg of the test article. The clinical
symptomatology following the exposures was generally
indicative of absorption and excretion of the test
article (color changes in the excreta or body surface
staining) or non-specific in nature (reduced feces,
weakness, or convulsions prior to death).
"After a dose of 5000 mg/kg, abnormal clinical signs
consisted of weakness and urine discoloration by the test
article. All animals died within four hours of dosing.
Terminal or agonal convulsions were observed in two of
five male rats, but none of the female rats, two hours
after dose administration. Because the animals were in
distress, showing signs of moderate weakness just prior
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
314
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Page 2 of 3
to the convulsions, it was not possible to determine
whether the convulsions were due to the test article or
whether they were due to hypoxia. Nonetheless, the
convulsions occurred only at a dose level which was
approximately four times the estimated acutely lethal
median dose level. Deaths were also observed after doses
of 2500 mg/kg (10/10 animals), 1250 mg/kg (6/10 animals),
or 625 mg/kg (1/10 animals), but not at a dose level of
312 mg/kg. No convulsions were observed at doses below
5000 mg/kg."
The oral LD50 values for male and female rats in this acute oral
study were estimated by Eastman Kodak to be 1165 mg/kg and 1014
mg/kg, respectively.
Eastman Kodak also provided summary information from previously
conducted studies indicating that the test compound caused slight
skin irritation in an acute skin irritation study and moderate
irritation in an eye irritation study. The acute dermal LD50 was
reported to be greater than 1 g/kg. Finally, the company provided
a copy of the Material Safety Data Sheet (MSDS) for the subject
chemical.
PSE AND EXPOSURE POTENTIAL
The submitter reported that "this chemical is a low volume
intermediate used to manufacture a photographic chemical. None of
the intermediate appears in the final chemical." In addition, the
company reported that:
"Good general ventilation is used in all manufacturing
processes and supplementary local exhaust ventilation
and/or respiratory protection is used if needed. This
material is manufactured as an acetone-wet cake.
Employees wear a full face cartridge respirator if
needed, and aprons, gloves, and safety glasses with side
shields. Then the material is dried. Employees wear a
half or full face cartridge respirator with dust
prefilter and safety glasses with side shields when
discharging the dryer."
COMMENTS/RECOMMENDATIOMS
In its submission, Eastman Kodak reported that the company has
reviewed their "current handling precautions" and they "are deemed
to be adequate." In addition, Eastman Kodak has reported that they
are evaluating the need for further testing.
It should be noted that typically, neurotoxic effects observed in
dying animals are not, in and of themselves, considered by EPA to
be reportable under Section 8(e) of TSCA. This appears to be the
case for the present Eastman Kodak submission. It is important to
point out that in many cases, already reportable data regarding
extremely or highly toxic (lethal) substances will be accompanied
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Page 3 of 3
by information concerning observed neurotoxic effects. In short
or long term exposure studies in which serious neurotoxic signs and
symptoms (e.g., convulsions, sleep induction, paralysis and other
serious signs of motor dysfunction, narcosis, serious behavioral
dysfunction) are observed in non-moribund animals, however, EPA
believes that specific reporting of the neurotoxic effects should
take place.
a) In view of EPA's interest in company actions taken on a
voluntary basis in response to new chemical toxicity/
exposure data, Eastman Kodak will be asked to describe
the nature and results, if available, of all studies
(other than those submitted already to EPA or those cited
in the published scientific literature) about which the
company is aware or that the company has conducted, is
conducting or plans to conduct that are designed to
determine the toxicity of this chemical.
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will review the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
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^ 'Vi
I | UNITED STATES ENVIRONMENTAL PROTECTION AGENCY Page 1 of 3
^ WASHINGTON, DC 20460
% P*tS^
date: mar ~ 8 1990
FROM:
TO:
APPROVED
f. /CT jjs! 9o
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0190-0868 8
Martha G. Price, Ph.D., Chemis
Chemical Risk Identification Section/CSB
James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
The submitting company has claimed its company name and the exact
identity of the subject chemical as TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. In the "sanitized" version of its Section 8(e)
notice, the company reported non-confidentially that the subject
chemical is an "N-arylcyclic imidate".
SUBMISSION DESCRIPTION
The submitting company provided a cover letter and the final report
of a range-finding rat teratology study. The following summary
information is drawn from both the cover letter and the Summary
section of the final report. The cover letter states:
The test material "was administered daily by gavage to
6 groups of mated female rats at dose levels of 0, 50,
125, 250, 500, and 1000 mg/kg/day during gestation days
6-15."
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
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Page 2 of 3
"All dams survived until scheduled sacrifice. Decreased
maternal weight gain was evident only in the high dose
animals during the first 3 days of dosing. No
malformations were noted in fetuses from any dose level
but a slight increase in post-implantation loss and
decrease in fetal weights were noted at 1000 mg/kg/day."
The Summary of the final report states:
"Clinical signs of toxicity were slight at [lower dose
levels] and moderate at a dose level of 1000 mg/kg/day.
A reduced group mean body weight gain occurred in the
1000 mg/kg/day group during the first three days of
compound administration. Mean body weights in this group
were lower than the control throughout the study period.
Thyroid gland and liver weights were increased in the
250, 500, and 1000 mg/kg/day groups.
"Fetal effects noted in this study consisted of a
moderately reduced mean fetal body weight and an
increased postimplantation loss in the 1000 mg/kg/day
group. No external fetal malformations or variations
were noted in this study.
"In conclusion, findings...indicated that a dose level
of 1000 mg/kg/day would produce some degree of maternal
and developmental toxicity but would not be considered
excessive for a definitive developmental toxicity study."
It should be noted that EPA has received other TSCA Section 8(e)
notices on compounds identified generically as N-arylcyclic
imidates. The reader's attention is directed to the status reports
prepared by EPA in response to 8EHQ-0989-0827 S and 8EHQ-0989-
0828 S.
U8E AND EXPOSURE POTENTIAL
In view of the submitter's TSCA CBI claims, no information
regarding the TSCA Chemical Substance Inventory status or uses of
the subject chemical will appear in this status report.
The submitter stated nonconfidentially that this N-arylcyclic
imidate "is currently an R&D material." The submitter also stated,
"The selected route of administration was oral because this is a
possible route of exposure for the general human population."
COMMENTS 7 RECOMMENDATIONS
a) The Chemical Screening Branch will ask the submitter to
provide the exact chemical name for the subject chemical.
•
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
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8EHQ-0190-0868S
Page 3 of 3
toxicity/exposure data, the submitter will be requested
to describe the actions that the company has taken or
plans to take l) to notify workers/others about the
reported information, and 2) to reduce or eliminate
exposure to the subject chemical. The submitter will be
asked also to provide copies of Material Safety Data
Sheets and labels that have been revised to reflect the
reported findings. In addition, the submitter will be
asked to describe the nature and results, if available,
of all studies (other than those submitted already to EPA
or those cited in the published scientific literature)
about which the submitter is aware or that the company
has conducted, is conducting or plans to conduct that are
designed to determine the toxicity of or the exposure to
the subject chemical.
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch.will review the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
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* A \
I 282 5 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY Page 1 of 3
WASHINGTON, DC 20460
PRO^°
DATES ^AR - 3 i9S0 approved: ft zU/lo
8UBJECT: Status Report1 8EHQ-0190-0869 S
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
FROM: Martha G. Price, Ph.D., Chemist
Chemical Risk Identification Secition/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE (First see NOTE on Page 3 of this status report)
The submitting company has claimed its company name and the exact
identity of the subject chemical as TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. In the "sanitized" version of its Section 8(e)
notice, the company reported non-confidentially that the subject
chemical is a "heterocyclic substituted aryl diester".
SUBMISSION DESCRIPTION
The submitting company provided a cover letter and the final report
of a range-finding rat teratology study. The following summary
information regarding the conduct and results is drawn from both
the cover letter and the Summary and Results and Conclusions
sections of the final report. The cover letter states:
The test material "was administered daily by gavage at
dose levels of 0, 50, 100, 200, 400, and 800 mg/kg/day
to 6 groups of 8 mated female rats during gestation days
6 through 15."
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
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Page 2 of 3
"All treated groups had decreased body weight gain for
the full treatment period (days 6-16) ranging from 20%
at 50 mg/kg/day to 127% at 800 mg/kg/day..."
"There were no treatment-related effects on maternal
gross necropsy findings or organ weights. There were no
treatment-related effects on post implantation loss,
number of viable fetuses, numbers of implantation sites
and corpora lutea and sex ratios."
"There were no treatment related external fetal
malformations at any dose level."
The Summary of the final report states:
"Survival was 100% at all dose levels. Moderate clinical
signs of toxicity were observed at a dose level of 800
mg/kg/day and similar findings were occasionally observed
at a dose level of 400 mg/kg/day."
"In conclusion, maternal toxicity was expressed by
inhibited body weight gain at all dose levels and was
excessive at dose levels of 400 mg/kg/day and above.
....No NOAEL (no observable adverse effect level) was
observed for maternal toxicity."
The Results and Conclusion of the final report states:
"Mean fetal weights were severely decreased in the 100,
200, 400 and 800 mg/kg/day groups when compared to the
control group. Mean fetal body weight was slightly
decreased in the 50 mg/kg/day group, however, it was
within the range of the WIL historical control data."
USE AND EXPOSURE POTENTIAL
In view of the submitter's TSCA CBI claims, no information
regarding the TSCA Chemical Substance Inventory status or uses of
the subject chemical will appear in this status report.
The submitter stated nonconfidentially that the heterocyclic
substituted aryl diester "is an experimental material that is
currently being evaluated in R&D." The submitter also stated, "The
selected route of administration was oral because this is a
possible route of exposure for the general human population."
COMMENTS/RECOMMENDATIONS
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well ak company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, the submitter will be requested
to describe the actions that the company has taken or
plans to take 1) to notify workers/others about the
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Page 3 of 3
reported information, and 2) to reduce or eliminate
exposure to the subject chemical. The submitter will be
asked also to provide copies of Material Safety Data
Sheets and labels that have been revised to reflect the
reported findings. In addition, the submitter will be
asked to describe the nature and results, if available,
of all studies (other than those submitted already to
EPA or those cited in the published scientific
literature) about which the submitter is aware or that
the company has conducted, is conducting or plans to
conduct that are designed to determine the toxicity of
or the exposure to the subject chemical.
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will review the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
MOTE In a letter dated April 11, 1990, the submitting company
reported non-confidentially that the subject chemical is
actually a "heterocyclic substituted acetanilide" for
which a previous Section 8(e) notice (8EHQ-0190-0865 S)
was submitted. The reader's attention is directed to the
status report prepared by the Agency in response to this
previous submission.
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im)
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY Page 1 of 3
WASHINGTON, DC 20460
DATES MAR -8 1990 APPROVED I
SUBJECT: Status Report1 8EHQ-0190-0870 S
FROM: Martha G. Price, Ph.D., Chemist
Chemical Risk Identification Section/CSB ^
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
NOTE (First see NOTE on Page 3 of this status report.)
The submitting company has claimed its company name and the exact
identity of the subject chemical as TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. In the "sanitized" version of its Section 8(e)
notice, the company reported non-confidentially that the subject
chemical is a "heterocyclic enamine".
SUBMISSION DESCRIPTION
The submitting company provided the following summary information
regarding the conduct and preliminary results of a gavage pilot rat
teratology study:
The test material "was administered by gavaga to 6 groups
of 8 mated female rats at dose levels of 0, 50, 100, 250,
500, and 1000 mg/kg/day during gestation days 6-18."
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
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Page 2 of 3
"Mortality occurred in 2 out of 8 animals at 1000
mg/kg/day. Substantial weight losses were noted at 1000
mg/kg/day during gestation days 6-9. Slight weight
losses during this same interval were noted at 500
mg/kg/day. Abnormal clinical signs were noted at 1000,
500 and possibly 250 mg/kg/day. A dose-related increase
in liver weights (-43% to 2.7-fold) was noted at all dose
levels. Implantation loss was not affected at any dose
level but there appeared to be a slight decrease in fetal
weights at 1000 mg/kg/day. In addition, 5 fetuses from
3 litters at 1000 mg/kg/day exhibited external
malformations. There was a single fetus each with
umbilical hernia, omphalocele, exencephaly, cephalocele
and a tail defect. There was also one control fetus that
exhibited an umbilical hernia."
QBE AND EXPOSURE POTENTIAL
In view of the submitter's TSCA CBI claims, no information
regarding the TSCA Chemical Substance Inventory status or uses of
the subject chemical will appear in this status report. The
submitter stated nonconfidentially that, "The material is currently
being manufactured exclusively for R&D purposes."
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will ask the submitter to
ensure that EPA receives a complete copy of the final
report (including the actual experimental protocol,
results of gross and histopathological examinations,
results of statistical analyses, etc.) from the oral
pilot rat teratology study cited in the submission. In
addition, the submitter will be requested to provide the
exact chemical name for the subject chemical.
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, the submitter will be requested
to describe the actions that the company has taken or
plans to take 1) to notify workers/others about the
reported information, and 2) to reduce or eliminate
exposure to the subject chemical. The submitter will be
asked also to provide copies of Material Safety Data
Sheets and labels that have been revised to reflect the
reported findings. In addition, the submitter will be
asked to describe the nature and results, if available,
of all studies (other than those submitted already to EPA
or those cited in the published scientific literature)
about which the submitter is aware or that the company
has conducted, is conducting or plans to conduct that are
designed to determine the toxicity of or the exposure to
the subject chemical.
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8EHQ-0190-0870 S
Page 3 of 3
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will review the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
NOTE In a letter dated April 11, 1990, the submitting company
reported non-confidentially that the subject chemical is
actually an "N-aryl-cyclic imidate" for which a previous
Section 8(e) notice (8EHQ-0989-0827 S) was submitted.
The reader's attention is directed to the status report
prepared by EPA in response to this previous submission.
IT*
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^ UNITED STATES ENVIRONMENTAL PROTECTION AGENCY Page i Qf 2
^ WASHINGTON, DC 20460
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Page 2 of 2
observed only at the high dose level. This was manifested
by a decreased mean fetal body weight (approximately 14%)
and a slightly increased post-implantation loss. Microph-
thalmia and/or anophthalmia was detected in 2 fetuses
(from the same litter) in the high dose group. This mal-
formation is normally seen at a low incidence in control
animals. However, the significance of the finding in this
study is unclear because of the small numbers of litters
and fetuses examined."
USE AND EXPOSURE POTENTIAL
The submitter reported non-confidentially that this ethoxylated
alkyl amine "is an inert ingredient in a pesticide formulation."
COMMENTS/RECOMMENDATIONS
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, the submitter will be asked to
describe the actions that the company has taken or plans
to take 1) to notify workers/others about the reported
information, and 2) to reduce or eliminate exposure to
the subject chemical. The submitter will be asked also
to provide copies of Material Safety Data Sheets/labels
that have been revised to reflect the reported findings.
In addition, the submitter will be asked to describe the
nature and results, if available, of all studies (other
than those submitted already to EPA or those cited in the
published scientific literature) about which the company
is aware or that the company has conducted, is conducting
or plans to conduct that are designed to determine the
toxicity of or the exposure to this chemical.
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will review the reported information to determine
the need for further assessment of the subject chemical
at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this report will be sent to the Environmental
Assistance Division/OTS for further distribution.
NOTE In a non-CBI, March 27, 1990 followup letter (8EHQ-0490-
0871 FLWP), the Monsanto Company stated that its initial
submission was no longer TSCA CBI. According to the
"declassified" initial submission, the subject chemical
is "Ethoxylated tallow amines"
327
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i £B ^
lavj
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY Page 1 of 3
WASHINGTON, DC 20460
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
DATE:
MAR 5 1990
APPROVED
SUBJECT: Status Report1 8EHQ-0290-0872 S
H.
FROM: Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
The CIBA-GEIGY Corporation claimed the exact identity of the
subject chemical as TSCA Confidential Business Information (CBI).
Staff of the Information Management Division will review all
incoming correspondence related to the company's TSCA CBI claim.
In the "sanitized" version of its Section 8(e) notice, CIBA-GEIGY
reported non-confidentially that the subject chemical substance is
a "substituted polycyclic dione."
SUBMISSION DESCRIPTION
CIBA-GEIGY provided the following summary information regarding
the conduct and preliminary results of a range finding teratology
study in rats:
"Presumed pregnant rats were dosed with 0, 125, 2 50, 500,
750, or 1000 mg/kg of test material. Signs of maternal
toxicity included deaths (at 1000 mg/kg only) and
decreased maternal body weight and body weight gains
(>500 mg/kg). Four of eight females treated with 1000
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
NOTE
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Page 2 of 3
mg/kg died by day 12 of gestation. Of the four surviving
animals, three were pregnant. However, only one of these
surviving dams had viable implants (5 viable fetuses in
a total of 17 implantations) . Four out of the five
surviving fetuses from that single dam had phalanges
which were fused, reduced, or missing. This effect was
confined to the distal portion of the forepaws. Similar
findings were not observed in fetuses from the 750 mg/kg
group in which maternal toxicity was also severe, nor in
fetuses from any other treated group. The fetal effects
noted are considered to be secondary to the excessive
maternal toxicity observed in the 1000 mg/kg group."
USE AND EXPOSURE POTENTIAL
CIBA-GEIGY reported non-confidentially that this compound "is a
research and development compound being evaluated for pesticidal
purposes." Further, these evaluations "are being conducted under
the supervision of technically qualified personnel, knowledgeable
in handling potentially hazardous chemicals." CIBA-GEIGY stated
that the compound does not have a CAS registry number, to the best
of their knowledge.
COMMENTS/RECOMMENDATIONS
CIBA-GEIGY stated that all workers who currently handle this
compound are being notified of the reported toxicologic findings.
In addition, CIBA-GEIGY reported that these workers are being
reminded "that this is an experimental compound and should be
handled in such a manner as to minimize or prevent any exposure."
Finally, CIBA-GEIGY reported that the company plans to conduct a
definitive teratology study.
In this submission, CIBA-GEIGY asked for EPA guidance "on whether
developmental effects seen at maternally lethal doses (versus
maternally toxic doses) are [Section] 8(e) reportable." It is
EPA's position that statistically or biologically significant
increases in teratogenic or other serious embryotoxic or fetotoxic
effects (e.g., significant embryo or fetal lethality, spontaneous
abortion) should be reported under Section 8(e) regardless of the
Jevel of maternal toxicity (including lethality) seen in the study.
a) The Chemical Screening Branch will ask CIBA-GEIGY to
ensure that EPA receives a complete copy of the final
report (including the actual experimental protocol,
results of gross and histopathological examinations,
results of statistical analyses, etc.) from the range
finding teratology study cited in the submission.
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
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Page 3 of 3
toxicity data, CIBA-GEIGY will be asked to describe the
nature and results, if available, of all studies (other
than those submitted already to EPA or those cited in the
published scientific literature) about which the company
is aware or that the company has conducted, is conducting
or plans to conduct that are designed to determine the
toxicity of this chemical.
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will review the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY Page 1 of 2
WASHINGTON, DC 20460
OFFICE OF
PESTICIDES AND
date: MAR - 8 1990
APPROVED!
TOXIC SUBSTANCES
SUBJECT: status Report1 8EHQ-0290-0873 S
FROM: Martha G. Price, Ph.D., Chemist
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
The submitting company has claimed its company name and the exact
identity of the subject chemicals as TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. In the "sanitized" version of its Section 8(e)
notice, the company reported non-confidentially that the subject
chemical is an "aromatic amine".
SUBMISSION DESCRIPTION
The submitting company provided the following summary information
regarding the conduct and preliminary results of a chronic
toxicity/carcinogenicity study in rats:
"For two years test animals were fed ad libitum feed
dosed with 0.0, 0.02%, 0.16% and 0.32% of the test
article."
"Malignant and benign tumors were observed in both
control and high dose groups. The incidence and
distribution of tumors were similar to those known to
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
NOTE
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Page 2 of 2
occur spontaneously in male and female rats of this
strain and age. In the case of female mammary gland
tumors, there were increased benign tumors in the control
group and increased malignant tumors in the high dose
group. The increase in malignant tumors was
statistically significant at P<0.05, not at P<0.01. Both
types of tumors were present in both groups."
P8B AND EXPOSURE POTENTIAL
In view of the submitter's TSCA CBI claims, no information
regarding the TSCA Chemical Substance Inventory status or uses of
the subject chemical will appear in this status report.
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will ask the submitter to
ensure that EPA receives a complete copy of the final
report (including the actual experimental protocol,
results of gross and histopathological examinations,
results of statistical analyses, etc.) from the 2 year
study cited in the submission.
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, the submitter will be requested
to describe the actions that the company has taken or
plans to take 1) to notify workers/others about the
reported information, and 2) to reduce or eliminate
exposure to the subject chemical. The submitter will be
asked also to provide copies of Material Safety Data
Sheets and labels that have been revised to reflect the
reported findings, in addition, the submitter will be
asked to describe the nature and results, if available,
of all studies (other than those submitted already to EPA
or those cited in the published scientific literature)
about which the submitter is aware or that the company
has conducted, is conducting or plans to conduct that are
designed to determine the toxicity of or the exposure to
the subject chemical.
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will review the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c} The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPAf in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
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*
J
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 3
DATE:
SUBJECT:
FROM:
TO:
MAR I 1990
APPROVED
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
Status Report1 8EHQ-0290-0874 8
Oudt£(L H l0/L(Kh$c*O
Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
The submitting company has claimed its company name and the exact
identity of the subject chemical as TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. In the "sanitized" version of its Section 8(e)
notice, the company reported non-confidentially that the subject
chemical is a "substituted guanidinium aryl sulfonate."
SUBMISSION DESCRIPTION
The submitting company provided the following summary information
regarding the conduct and preliminary results of a pilot rat
reproduction study of this substituted guanidinium aryl sulfonate.
"[In this study, the test compound] was mixed in the diet
and fed to 4 groups of 10 male and 10 female Sprague
Dawley rats at dose levels of 0, 100, 300, and 750 ppm.
Treatment was for 4 weeks prior to mating and throughout
the mating, gestation and lactation periods. Following
4 weeks of treatment, animals were paired on a one male
to one female basis. All animals were observed daily for
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
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Page 2 of 3
viability and gross signs of toxicity. Pups were
examined and weighed on the day of delivery and on days
4, 7, 14, and 21 of lactation. All animals (F0 and Fi)
were sacrificed on lactation day 21. F0 animals received
a gross necropsy. Fi animals were examined externally.
"Body weight gain was severely decreased compared to
control in both Fo males and females at 750 ppm after 13
weeks of treatment. Body weight gain was also decreased
in males (-12%) and females (-26%) at 300 ppm.
"The number of matings leading to pregnancy was decreased
at 750 ppm. Due to the effect on mating performance,
only 5/10 females produced a litter at 750 ppm. One
female at 750 ppm subsequently lost her litter. Litter
size was reduced at birth at 750 ppm. An increase in pup
mortality both pre-birth and from birth to weaning was
observed at 750 ppm. Mean pup weights were lower than
controls throughout the pre-weaning period. No effects
on mating performance, pup survival, or pup weight were
observed at doses below 750 ppm."
QBE AND EXPOSURE POTENTIAL
The submitter reported non-confidentially that this substituted
guanidinium aryl sulfonate is being manufactured exclusively for
research and development (R&D) purposes.
COMMENT S/RECOMMEND ATION8
a) The Chemical Screening Branch will ask the submitter to
ensure that EPA receives a complete copy of the final
report (including the actual experimental protocol,
results of gross and histopathological examinations,
results of statistical analyses, etc.) from the study
cited in the submission.
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, the submitter will be requested
to describe the actions that the company has taken or
plans to take 1) to notify workers/others about the
reported information, and 2) to reduce or eliminate
exposure to the subject chemical. The submitter will be
asked also to provide copies of Material Safety Data
Sheets and labels that have been revised to reflect the
reported, findings. In addition, the submitter will be
asked to describe the nature and results, if available,
of all studies (other than those submitted already to EPA
or those cited in the published scientific literature)
about which the company is aware or that the company has
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Page 3 of 3
conducted, is conducting or plans to conduct that are
designed to determine the toxicity of the subject
chemical.
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will review the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
335
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USB i
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY Page 1 of 3
WASHINGTON, DC 20460
DATES MAR -8 1990
APPROVED:
$ /Jawi- l/p/fo
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECTS Status Report1 8EHQ-0290-0875 8
FROM: Martha G. Price, Ph.D., Chemist
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
The submitting company has claimed its company name and the exact
identity of the subject product constituents as TSCA Confidential
Business Information (CBI). Staff of the Information Management
Division will review all incoming correspondence related to the
company's TSCA CBI claims. In the "sanitized" version of its
Section 8(e) notice, the company reported nonconfidentially that
the subject product is "MILC phosphate ester-based hydraulic
fluid." The submitter also reported that this hydraulic fluid
has been given the military designation, MIL-H-19457C or MILC.
SUBMISSION DESCRIPTION
The submitting company provided the following summary information
regarding the conduct and preliminary results of an oral
reproductive study in rats:
"The assessment of the reproductive performance of
Fischer 344 rats given daily, oral doses of MILC was done
by a continuous breeding protocol."
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
336
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Page 2 of 3
Dose levels were 0.56, 1.12, and 1.68 g/kg/day.
•'Male and female rats were given a single, daily, oral
dose of the test material.. .beginning 7 days prior to
pairing, continuing for the following 63-day breeding
period (Phase I) , and through a 28-day postbreeding
interval."
"There was a decreased number of litters in groups
exposed to MILC after the 63-day breeding period.
Following the 28-day postbreeding interval a crossover
mating (Phase II) was performed to determine the affected
sex. There was no break in the dosing regimen between
Phases I and II. .. .The cohabitation period was for 8 days
during which males and females were dosed with either
vehicle or test material. After cohabitation, females
continued to receive either vehicle or test material for
the duration of a 28-day postcohabitation.11
"The preliminary results indicate that the oral
administration of high dose levels of MILC appeared to
cause infertility in female rats and possibly in male
rats."
The submission also reported summary information regarding an oral
reproductive study in male and female rats using the described
continuous breeding protocol. While the test material is not
disclosed nonconfidentially, the submitter reported, "the daily
oral administration of 0.40gm(0.3ml)/kg/day caused infertility in
male rats, but not females."
USE AND EXPOSURE POTENTIAL
The submitter did not provide any information regarding the
potential for exposure to MILC. Other than that the tested product
is an hydraulic fluid, the submitter did not provide any
information regarding the specific uses of MILC.
COMMENTS/RECOMMENDATIONS
It should be noted that immediately upon receipt of this Section
8(e) notice, the Chemical Screening Branch provided a full copy of
the submission to the Test Rules Development Branch (TRDB/ECAD) for
inclusion in their ongoing review of phosphate esters.
a) The Chemical Screening Branch will ask the submitter to
ensure that EPA receives a complete copy of the final
report (including the actual experimental protocol,
results of gross and histopathological examinations,
results of statistical analyses, etc.) from the two rat
oral reproductive studies cited in the submission.
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Page 3 of 3
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, the submitter will be requested
to describe the actions that the company has taken or
plans to take 1) to notify workers/others about the
reported information, and 2) to reduce or eliminate
exposure to the product or its constituent(s). The
submitter will be asked also to provide copies of
Material Safety Data Sheets and labels that have been
revised to reflect the reported findings. In addition,
the submitter will be asked to describe the nature and
results, if available, of all studies (other than those
submitted already to EPA or those cited in the published
scientific literature) about which the submitter is aware
or that the company has conducted, is conducting or plans
to conduct that are designed to determine the toxicity
of or the exposure to the product or its constituent(s) .
As in the case of the initial submission, the Chemical
Screening Branch will provide copies of any reported
information to TRDB/ECAD.
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and TRDB/ECAD/OTS;
in addition, copies of this status report will be
transmitted to the Environmental Assistance Division/OTS
(formerly the TSCA Assistance Office/OTS) for further
distribution.
338
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY Page x of 3
.4? WASHINGTON, DC 20460
HpnCfiV'
DATE:
MAR 51990
APPROVED:
f. ikL
OFFICE OF
PEST1CIOE8 AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0290-0876
FROM: Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
ICI Americas Inc. has submitted a copy of a manuscript entitled
"Animal Models for Predicting Hypersensitivity Reactions to Small
Molecules" that has reportedly been accepted for publication in
Immunotoxicology and Immunotoxicity of Metals. In the submission
cover letter, ICI Americas reported that this "manuscript describes
method development on an animal model for predicting respiratory
allergy." The ICI Americas submission also included a data table
outlining the serological, pulmonary and dermal responses of guinea
pigs injected intradermally with methylene diphenyldiisocyanate
(MDI; CAS No. 101-68-8). According to ICI Americas, the data
indicate "that MDI injected intradermally in quinea pigs can elicit
a sensitization reaction including a pulmonary response as measured
by respiratory rate." ICI Americas also stated that although it is
well known that inhalation of MDI can induce pulmonary sensitiza-
tion in exposed animals and humans, the "animal data on intradermal
injections indicate new information regarding route of exposure."
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial riskinformation reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
339
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Page 2 of 3
USE AND EXPOSURE POTENTIAL
The Condensed chemical Dictionary (10th Edition) states that MDI
is used to prepare polyurethane resins and spandex fibers and to
bond rubber to rayon and nylon.
COMMENTS/RECOMMENDATIONS
Immediately upon receipt, the Chemical Screening Branch provided
a full copy of this TSCA Section 8(e) notice to the Risk Analysis
Branch (RAB/ECAD/OTS) for inclusion in its ongoing review of MDI
and other diisocyanates. It should be noted that the Chemical
Screening Branch prepared a "Chemical Hazard Information Profile"
(CHIP) on MDI in 1984. Further, MDI is the subject of Section 8(d)
and 8(c) information gathering rules.
In its Section 8(e) notice, ICI Americas reported that the provided
information was also being submitted to EPA under Section 8(d) of
TSCA. The following discussion pertains to the relationship between
the TSCA Section 8(e) and Section 8(d) reporting obligations. The
Section 8(e) reporting requirement applies to any "substantial
risk" information obtained during the conduct of a study the final
report of which is required ultimately to be submitted to EPA under
Section 8(d) of TSCA. For example, EPA has received a number of
Section 8(e) submissions concerning interim results of studies
"listed" under Section 8(d) as being underway. The Section 8(e)
reporting that took place in such instances occurred because a
Section 8(e) obligation was incurred before submission of the final
report of the study was required under Section 8(d). In other
words, if the required reporting pursuant to Section 8(d) occurs
prior to or coincidental with the incurring of a Section 8(e)
requirement, the information does not need to be submitted also to
the Section 8(e) docket. The purpose of this particular exemption
is not to change substantially the Section 8(e) obligation, but is
designed merely to avoid requiring duplicative reporting except in
those cases where timeliness considerations are paramount.
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, ICI Americas will be requested
to describe the actions that the company has taken or
plans to take 1) to notify workers/others about the
reported information, and 2) to reduce or eliminate
exposure to the subject chemical. In addition, ICI
Americas will be asked also to provide copies of Material
Safety Data Sheets and labels that have been revised to
reflect the reported findings.
b) The Chemical Screening Branch will continue to forward
all reported information to the Risk Analysis Branch for
inclusion in their ongoing evaluation of MDI as well as
other diisocyanates.
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Page 3 of 3
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA, RAB/ECAD/OTS;
in addition, copies of this status report will be sent
to the Environmental Assistance Division/OTS (formerly
the TSCA Assistance Office/OTS) for further distribution.
341
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1
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY page 1 of 3
WASHINGTON, DC 20460
DATE: MAR - 8 1990
APPROVED S
(J*nr\ ?hko
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0290-0877
FROM: Martha G. Price, Ph.D., Chemist
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
7
SUBMISSIOM DESCRIPTION
Technical Assessment Systems, Inc. (TAS), on behalf of the Albright
& Wilson Company, Ltd., provided the following summary information
regarding the conduct and preliminary results of an oral gavage
teratology study in rabbits:
"Tetrakishydroxymethylphosphonium sulfate (THPS; Cas No.
55566-30-8) has been produced for approximately 2 0 years.
No reported incidents of adverse heath effects have been
encountered by Albright & Wilson, Ltd. during this
period."
"New information regarding developmental toxicity in
laboratory animals has become available....Specifically
...reduced weight and an increased incidence of eye and
limb defects were observed in the offspring of dams
treated at the highest dose (60 mg/kg/day, from day 7 to
day 19 of gestation). These effects on offspring
occurred in the presence of marked maternal toxicity,
characterised by weight loss and reduced food intake.
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
342
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Page 2 of 3
"At lower dose levels (i.e., 6 or 18 mg/kg/day) ,
variations were within the expected range and were not
attributed to treatment with the test article."
According to the submission, a range-finding study of THPS has also
been conducted in pregnant rabbits dosed by gavage at doses up to
and including 80 mg/kg/day. According to the submitter, "Although
evidence of maternal toxicity was found in that study, it was
reported that there were no apparent adverse effects on fetal
values and no external fetal abnormalities."
USE AND EXPOSURE POTENTIAL
According to information contained in previous TSCA Section 8(e)
submissions, THPS is used in the manufacture of flame retardants
for textiles and has recently been shown to have biocidal activity.
COMMENTS/RECOMMENDATIONS
In its submission, TAS reported that Albright & Wilson will notify
customers of this new information on THPS product labels and MSDS.
In addition, Albright & Wilson is planning to undertake a similar
rabbit teratology study with a chemically related product,
tetrakishydroxymethylphosphonium chloride (THPC; CAS No. 124-64-1).
It should be noted that the Agency has received other Section 8(e)
submissions on THPS and THPC. The reader's attention is directed
to the status reports prepared by EPA in response to 8EHQ-0780-0369
and 8EHQ-0689-0804.
a) The Chemical Screening Branch will ask Albright & Wilson
to ensure that EPA receives a complete copy of the final
report (including the actual experimental protocol,
results of gross and histopathological examinations,
results of statistical analyses, etc.) from the two
rabbit oral teratology studies of THPS cited in the
submission. In addition, the submitter will be asked to
provide, when available, the full copy of the final
report of the rabbit teratology study on THPC, now in the
planning stage.
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as compainy actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Albright & Wilson will be
requested to describe the actions that the company has
taken or plans to take to reduce or eliminate exposure
to THPS. Albright & Wilson will be asked also to provide
copies of Material Safety Data Sheets and labels that
have been revised to reflect the reported findings. In
addition, Albright & Wilson will be asked to describe the
nature and results, if available, of all studies (other
than those submitted already to EPA or those cited in the
published scientific literature) about which Albright &
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Page 3 of 3
Wilson is aware or that the company has conducted, is
conducting or plans to conduct that are designed to
determine the toxicity of or the exposure to THPS.
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will review the reported information in order to
determine the need for further assessment of THPS and
THPC at this time.
c) The Chemical Screening Branch will send copies of this
Status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
344
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A**05**.
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 6
DATE:
MAR - T I990
APPROVED:
SUBJECT: Status Report1 8EHQ-0290-0878
ft? &nr\. l/f/%0
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD
TO: James F. Darr, Section Head
Chemical Risk Identification Section/CSB/ECAD
SUBMISSION DESCRIPTION
In conjunction with a TSCA Section 8(e)-related "Consent Agreement"
(TSCA 89-H-21), the Monsanto Company submitted complete copies of
the final reports from pilot and definitive teratology studies of
the following four chemical substances in rats:
Diethylaniline (CAS No. 91-66-7)
N-Isopropylaniline (CAS No. 768-52-5)
Isopropylamine (CAS No. 75-31-0)
0,0-Dimethyl ester of phosphorochloridothioic acid
(Methyl PCT; CAS No. 2524-03-0)
Monsanto also provided summaries describing the conduct and results
of the definitive teratology studies; these summaries are found on
pages 1 and 2 of the attachment to this status report. It should
be noted that in providing these summaries to the Agency, Monsanto
pointed out that the summaries are not all-inclusive and may not
highlight all of the adverse effects observed in the studies.
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
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Page 2 of 6
DSE AND EXPOSURE POTENTIAL
Monsanto did not provide any information with regard to the uses
of, and the potential for exposure to, the subject chemicals.
According to the Condensed Chemical Dictionary (10th Edition), the
chemicals have the following uses:
Diethvlaniline
"Organic synthesis; dyestuff intermediate."
N-Isopropvlaniline
"Dyeing acrylic fibers; chemical intermediate."
Isopropvlamine
"Solvent; intermediate in synthesis of rubber accelerators,
pharmaceuticals, dyes, insecticides, bactericides, textile
specialities, and surface-active agents; de-hairing agent;
solubilizer for 2,4-D acid."
Methvl PCT
"Intermediate for insecticides, pesticides, fungicides; oil
and gasoline additives; plasticizers; corrosion inhibitors;
flame retardants; flotation agents."
COMMENTS/RECOMMENDATIONS
It should be noted that EPA has received another TSCA Section 8(e)
submission on diethylaniline. The reader's attention is directed
to the status report prepared by the Agency in response to TSCA
Section 8(e) submission number 8EHQ-0282-043 0.
It should be noted also that EPA has received other Section 8(e)
submissions on N-isopropylaniline. The reader's attention is
directed to the status report prepared by the Agency in response
to Section 8(e) submissions 8EHQ-1287-0702 and 8EHQ-1287-0703.
Finally, it should be noted that EPA has received TSCA Section 8(e)
and "For Your Information" (FYI) submissions on, and prepared (in
1982) a "Chemical Hazard Information Profile" (CHIP) for the 0,0-
dimethyl ester of phosphorochloridothioic acid (methyl PCT). The
reader's attention is directed to this CHIP as well as the status
report prepared by EPA in response to TSCA Section 8(e) submission
number 8EHQ-0381-0387; the reader's attention is directed also to
FYI submission number FYI-OTS-0683-0249 et seq.
a) In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, Monsanto will be requested to
describe the actions that the company has taken or plans
346
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Page 3 of 6
to take 1) to notify workers/others about the reported
information, and 2) to reduce or eliminate exposure to
the subject chemicals. Monsanto will be asked to submit
copies of Material Safety Data Sheets and labels that
have been revised to reflect the reported findings. In
addition, Monsanto will be asked to describe the nature
and results, if available, of all studies (other than
those submitted already to EPA or those cited in the
published scientific literature) about which Monsanto is
aware or that Monsanto has conducted, is conducting or
plans to conduct that are designed to determine the
toxicity of or the exposure to the subject chemicals.
b) The reported information will be reviewed by staff of the
Chemical Screening Branch as part of the "FIRST REVIEW"
phase of the Existing Chemicals Program (ECP) in order
to determine the need for further OTS assessment of the
subject chemicals at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA? in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
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ATTACHMENT
8EHQ-0290-0878
Page 4 of 6
-1-
TSCA 8(e) Audit
Summary Memo
Compound:
Diethylaniline
Study No:
BD-85-125
Study Type:
Rat Teratology
Results have been obtained from a rat teratology study with
diethylaniline. In this study, diethylaniline was administered by gavage
to 4 groups of mated female rats at dose levels of 0, 50, 250, and 500
mg/kg/day. Surviving dams were sacrificed on gestation day 20. Fetuses
were removed, weighed, sexed and examined for external, visceral and
skeletal malformations and variations.
At 500 mg/kg, 5/29 dams died and there was a statistically significant
reduction in maternal body weight gain. Body weight gain was reduced at 50
and 250 mg/kg but these differences were not statistically significant. A
statistically significant increase in late resorptions and a statistically
significant decrease in fetal weights were observed at 500 mg/kg.
[See NOTE number 1 on page 3 of this attachment.]
Results have been obtained from a rat teratology study with
N-Isopropylaniline. In this study, N-isopropylaniline was administered by
gavage to 4 groups of mated female rats at dose levels of 0, 30, 100 and
350 mg/kg/day. Surviving dams were sacrificed on gestation day 20.
Fetuses were removed, weighed, sexed and examined for external, visceral
and skeletal malformations and variations.
At 350 ng/kg, 2/25 daas died and maternal body weight gain was reduced.
Statistically significant increases in post implantation loss and dead
fetuses, and a statistically significant decreaae in fetal weight were
observed at 350 mg/kg. A statistically significant increase in fetal
malformations was observed at 350 mg/kg.
[See NOTE number 2 on page 3 of this attachment]
TSCA 8(e) Audit
Summary Memo
Compound:
Study No:
Study Type:
N-Isopropylani1ine
IR-83-295
Rat Teratology
348
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ATTACHMENT (Continued) PaSe 5 of 6
-2-
TSCA 8(e) Audit
Summary Memo
Compound: Isopropylamine
Study No: ML-86-400
Study Type: Rat Teratology
Results have been obtained from a rat teratology study with
isopropylamine. In this study, isopropylamine was administered via
inhalation to 4 groups of mated female rats at dose levels of 0, 50, 500
and 1000 mg/m3. Surviving dams were sacrificed on gestation day 20.
Fetuses were removed, weighed, sexed and examined for external, visceral
and skeletal malformations and variations.
Statistically significant reductions in maternal body weight gains were
observed at 500 and 1000 mg/m3. Resorptions were statistically increased
at 500 mg/m3 but not at 1000 mg/m3. The lack of dose response for this
parameter indicates that the effect was not treatment related. One
skeletal variation was increased at 1000 mg/m3 compared to control. This
skeletal variation was an example of reduced ossification which may not
adversely affect survival or health.
TSCA 8(e) Audit
Summary Memo
Compound: Methyl PCT
Study No: ML-84-378
Study Type: Rat Teratology
Results have been obtained from a rat teratology study with Methyl PCT. In
'this study, Methyl PCT was administered via inhalation to 4 groups of mated
female rats at concentrations of 0, 5, 20, and 80 mg/m3 during gestation
days 6-15. Surviving dans were sacrificed on gestation day 20. Fetuses
were removed, weighed, sexed and examined for possible external malformations.
A statistically significant reduction in maternal body weight gain and a
statistically significant reduction in fetal weight were observed at 80
mg/m3.
[See NOTE number 3 on page 3 of this attachment]
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Page 6 of 6
ATTACHMENT (Continued)
-3-
notes
1. Diethylaniline
The "ABSTRACT" section of the final report
states, "At the high-dose level, the incidence
of fetuses with unossified sternebral elements
(particularly the fifth and sixth sternebrae)
was increased suggestive of a retardation in
ossification."
2. N-Isopropylaniline
According to the "SYNOPSIS" section of the
final report, the malformations seen in the
study involved "primarily bent ribs, scapulae
and limb bones."
3. Methyl PCT
The "ABSTRACT" section of the final report
states that adverse implantation or very early
resorption effects were observed at 20 and 80
mg/m .
350
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY Page 1 of 3
WASHINGTON, DC 20460
OFFICE OF
PESTICIDES AND
DME: MAR - 8 1990
APPROVED:
z/tL
SUBJECT: Status Report1 8EHQ-0290-0879 S
S
FROM: Martha G. Price, Ph.D., Chemist
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
The submitting company has claimed its company name and the exact
identity of the subject chemical as TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. In the "sanitized" version of its Section 8(e)
notice, the company reported non-confidentially that the subject
chemical is a "halo alkyl substituted aryl diester."
SUBMISSION DESCRIPTION
The submitting company provided a cover letter and the final report
of a dose range-finding rat teratology study. The following
summary information regarding the conduct and results is drawn from
both the cover letter and the Summary and the Discussion and
Conclusions sections of the final report. The cover letter states:
The test material "was administered by gavage to 6 groups
of mated female rats at dose levels of 0, 50, 100, 200,
400 and 800 mg/kg/day during gestation days 6-15."
Tfye Summary of the final report states:
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial riskM information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
NOTE
351
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8EHQ-0290-0879S
Page 2 of 3
"Mortality was 100% at a dose level of 800 mg/kg/day.
Clinical signs of toxicity and a statistically
significant group mean body weight loss during the
initial three days of compound administration were
observed at this dose level."
"Postimplantation loss in the 400 mg/kg/day group was
slightly higher than in the control group, however, one
female in this treated group had a completely resorbed
litter. At a dose level of 400 mg/kg/day, an umbilical
herniation of the intestines was seen in two fetuses in
the litter....Mean thyroid gland weights were increased
in the 200 and 4 00 mg/kg/day groups and mean liver
weights were increased in a numerical trend in the 50,
100, 200 and 400 mg/kg/day groups. No other signs of
maternal or fetal toxicity were observed at any dose
level."
The Discussion and Conclusions of the final report states:
"Clinical signs of an adverse treatment-related effect
and a moderate group mean body weight loss during the
initial three days of compound administration were
observed in the 400 mg/kg/day group."
"Findings...indicated that a dose level of 400 mg/kg/day
caused moderate maternal toxicity."
USE AND EXPQ8URE POTENTIAL
In view of the submitter's TSCA CBI claims, no information
regarding the TSCA Chemical Substance Inventory status or uses of
the subject chemical will appear in this status report.
The submitter stated nonconfidentially that, "The material in
question is currently being manufactured exclusively for R&D
purposes.11
COMMENTS/RECOMMENDATIONS
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, the submitter will be requested
to describe the actions that the company has taken or
plans to take 1) to notify workers/others about the
reported information, and 2) to reduce or eliminate
exposure to the subject chemical. The submitter will be
asked also to provide copies of Material Safety Data
Sheets and labels that have been revised to reflect the
reported findings. In addition, the submitter will be
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Page 3 of 3
asked to describe the nature and results, if available,
of all studies (other than those submitted already to EPA
or those cited in the published scientific literature)
about which the submitter is aware or that the company
has conducted, is conducting or plans to conduct that are
designed to determine the toxicity of or the exposure to
the subject chemical.
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will review the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
353
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PRC^t0<
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 3
DATE:
SUBJECT:
MAR I 6 1990
APPROVED:
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
FROM:
TO:
Status Report1 8EHQ-0290-0880 8
Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE (See NOTE on Page 3 of this status report)
The submitting company has claimed its company name and the exact
identity of the subject chemicals as TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. In the "sanitized" version of its Section 8(e)
notice, the company stated non-confidentially that the subject
chemicals are a "substituted diisocyanate polymer" and a "carbo-
cyclic diisocyanate." The submitter also stated non-confidentially
that these particular generic names were accepted by EPA when the
original Pre-Manufacturing Notices (PMNs) were submitted to the
Agency under Section 5 of TSCA.
SUBMISSION DESCRIPTION
The submitting company provided the following summary information
with regard to the conduct and preliminary results of repeated dose
inhalation studies in rats and mice:
"Groups of rats and mice (5/sex/species/group) were
exposed by inhalation 6 hrs/day, 5 days/week for 4 weeks
to three aerosol concentrations of [the substituted
diisocyanate polymer] in butyl acetate. Target adduct
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk' information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
354
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8EHQ-0290-0880 S
Page 2 of 3
aerosol concentrations were 50, 150 and 500 mg/m3.
Corresponding measured butyl acetate concentrations were
110, 315 and 1122 mg/m3. Controls were exposed to butyl
acetate alone (1055 mg/m3). [The carbocyclic diisocyanate
monomer] concentrations were estimated to be 25, 75, and
250 ppb due to its presence at 0.5% in the adduct.
"The preliminary results show dose related increased lung
weights in both species. Microscopic examinations have
been conducted only on controls and high dose animals.
These show interstitial pneumonia and accumulation of
macrophages in the lung of the high dose animals which
was not seen in controls. No significant changes were
reported in the nasal passages or larger airways. There
were no other treatment-related effects for the various
end-points evaluated.
"[Toxicologic information] developed on the [carbocyclic
diisocyanate] monomer shows that it causes lesions in the
nasal passages but not in the lower respiratory tract.
The lesions in the present study are at a different site
than those in the monomer study. 3M and Union Carbide
have submitted information under 8(e) (8EHQ-0387-0659)
on butyl acetate aerosol "
The submitter reports that the observed effects "may be due to
butyl acetate/aerosol particulate exposure." The submitter also
reported that the company will determine whether further actions
are necessary after completion of the microscopic examination of
the respiratory tract tissues from the present study of rats and
mice.
USE AND EXPOSURE POTENTIAL
The submitter did not provide any information regarding the use(s)
of or the potential for exposure to the tested materials.
C0MMENT8/RECOMMENDATIONS
a) The Chemical Screening Branch will ask the submitter to
ensure that EPA receives complete copies of the final
reports (including the actual experimental protocols,
results of gross and histopathological examinations,
results of statistical analyses, etc.) from all of the
studies on the monomer and polymer compounds cited in
the submission.
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, the submitter will be requested
to describe the actions that the company has taken or
plans to take 1) to notify workers/others about the
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Page 3 of 3
reported information, and 2) to reduce or eliminate
exposure to the subject chemicals. The submitter will be
asked also to provide copies of Material Safety Data
Sheets and labels that have been revised to reflect the
reported findings. In addition, the company will be asked
to describe the nature and results, if available, of all
studies (other than those submitted already to the Agency
or those cited in the published scientific literature)
about which the company is aware or that the company has
conducted, is conducting or plans to conduct that are
designed to determine the toxicity of or the exposure to
the subject chemicals.
b) As was the case for the initial submission, the Chemical
Screening Branch will provide a full copy of all reported
information to the Chemical Control Division (CCD/OTS)?
CCD is responsible for administering the OTS Section 5
"New Chemicals Program" (NCP). As part of the "FIRST
REVIEW" phase of the OTS "Existing Chemicals Program"
(ECP), staff of the Chemical Screening Branch will review
the reported information in order to determine the need
for further assessment of the subject chemicals at this
time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and CCD/OTS/OPTS;
in addition, copies of this status report will be sent to
the Environmental Assistance Division/OTS (formerly the
TSCA Assistance Office/OTS) for further distribution.
MOTE According to the "declassified" (i.e., no longer confidential)
version of the initial submission, the submitting company is
the American Cyanamid Company and the subject chemicals are:
o l,3-bis[l-isocyanato-l-methylethyl]benzene (Monomer)
(CAS No. Unknown)
o 1,3-bis[l-isocyanato-l-methylethyl]benzene/tri-
methylolpropane adduct (Polymer)
(CAS No. 94857-19-9)
356
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^a"'%
las;
Page 1 of 5
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF
iiAn on innn . a /i pesticides and toxic substances
datei MAR 3 0 1990 approved:
3/30/90
SUBJECT: status Report1 8EHQ-0290-0881 8
FROM: Martha G. Price, Ph.D.,
Chemical Risk Identification Section/CSF
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
The submitting company has claimed its company name and the exact
identity of the subject chemical as TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. In the "sanitized" version of its Section 8(e)
notice, the company reported non-confidentially that the subject
chemical is a "cyclohexanedione."
SUBMISSION DESCRIPTION
The submitting company provided a cover letter, an overview report,
and six final reports listed below:
1. An Overview of Teratogenicity Studies in the Rat
2. Teratogenicity Study in the Rat
3. Teratogenicity Study in the Rat, Revised
4. Second Teratogenicity Study in the Rat
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the"substantial riskf information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
357
Printtdon Rtcydtd Paper
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8EHQ-0290-0881 S
Page 2 of 5
5. Second Teratogenicity Study in the Rat, Revised
6. Teratogenicity Study in the Rabbit
7. First Supplement to Teratogenicity Study in the
Rabbit.
The following information regarding the conduct and results of
these studies is drawn from summaries provided by the submitter:
"Rat Teratology Pregnant rats were orally dosed at 7-16
days of gestation with 0, 3, 30, 300 mg/kg/day. Severe
maternal toxicity was observed at 300 mg/kg/day as an
increase in maternal deaths and decreases in body weight,
food consumption, and general condition. Maternal
toxicity was not observed at 3 or 30 mg/kg/day.
Fetotoxicity at 300 mg/kg/day was observed as an increase
in intrauterine deaths and a decrease in live fetuses,
fetal weight and fetal ossification. A decrease in
ossification was also observed at 30 mg/kg/day.
Teratogenic effects were observed at 300 mg/kg/day as an
increase in the incidence of slight vertebral changes.
These changes may have been secondary to the severe
toxicity observed at this dose level; however, experience
with this structural alteration led to the conclusion
that it is a compound-related effect.
"In a second teratology study in rats, pregnant rats were
orally dosed at 7-16 days of gestation with 0, 0.5, 1,
3, or 200 mg/kg/day. At 200 mg/kg/day there was
significant maternal toxicity observed as an increase in
maternal deaths, a decrease in body weight gain and food
consumption, and an increase in the incidence of abnormal
clinical signs. Fetotoxic effects were also noted at 200
mg/kg/day as a decrease in fetal weight and ossification.
As in the previous study, there was an increase in
slightly misshapen vertebrae that was considered to be
a compound-related teratogenic effect. No maternal
toxicity, fetotoxic, or teratogenic effects were noted
at 0.5, 1, or 3 mg/kg/day.
"When these studies (Reports 2 and 4) were first read,
any fetuses with a direct connection between adjacent
vertebrae were recorded as having a defect while slightly
misshapen vertebrae were ignored. Following additional
experience with defects of this type, it was considered
that these misshapen vertebrae formed part of a continuum
of change and the skeletons were re-assessed for this
defect (Reports 3 and 5).
In "An Overview of Teratogenicity Studies in the Rat" it is also
stated:
358
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8EHQ-0290-0881 S
Page 3 of 5
"The overall conclusion from both experiments is that
treatment with the cyclohexanedione is associated with
reduced foetal weight and reduced foetal ossification at
doses which produce frank maternal toxicity. This is
considered indicative of a foetotoxic effect. The
dysmorphogenesis, seen only at a dose of 300mg/kg/day,
is probably secondary to the severe maternal toxicity
caused by an inappropriately high dose level, and may
represent an extreme foetotoxic response. The slight
foetotoxicity seen at 30mg/kg/day may also be maternally
mediated though no overt signs of toxicity were seen in
dams receiving this dose."
"A dose of 3mg/kg/day was established as a no-effect
level in these studies."
The summaries provided by the submitter continue:
"Rabbit Teratology Although the cyclohexanedione was not
teratogenic in this study, (Reports 6 and 7) , we are
submitting the information to aid you in assessing the
overall teratogenic potential of this compound.
"Pregnant rabbits were dosed at 7-19 days of gestation
with 0, 2.5, 20, or 100 mg/kg body weight/day. At 100
mg/kg/day, an increased incidence of abortion, late
intrauterine deaths, decrease in the number of live
fetuses, and increase in the incidence of preimplantation
losses were noted. These changes were accompanied by
decreases in maternal body weight gain and food
consumption. No embryo- or fetotoxic effects were noted
at 2.5 or 20 mg/kg/day. No teratogenic effects were seen
at any dose level.
"Subchronic Toxicity Two subchronic rat studies were
conducted. In a 28-day study, rats were fed diets
containing 0, 50, 250, 1250 or 5000 ppm. At 5000 ppm
there were decreases in body weight gain, food
consumption and slight increases in relative liver and
testicular weights. Hepatic changes were indicative of
an adaptive physiologic response to the presence of the
cyclohexanedione. There was an increase in epididymal
spermatids, and an increase in spermatid "debris" in the
testes.
"In a 90-day rat study, rats were fed diets containing
0, 50, 250, 2500 ppm cyclohexanedione. At 2500 ppm there
were decreases in body weight gain and food consumption,
small changes in biochemical and hematological
parameters, slight increases in liver weight, and slight
decreases in kidney weight. The no-effect level in this
study was judged to be 250 ppm.
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Page 4 of 5
"Two dog studies were conducted. In a 90-day dog study,
dogs were orally dosed with 0, 0.5, 5, or 50 mg/kg/day.
At 50 mg/kg/day, there were slight hepatic, adrenal, and
hematological changes. The no-effect level in this study
was judged to be 5 mg/kg/day.
"In a 1-year study, dogs were dosed orally with 0, 0.5,
5, or 50 mg/kg/day. At 50 mg/kg/day, changes were
observed in the liver and the adrenals. Liver weight
increases were accompanied by histological evidence of
fatty change. Adrenal weight was increased and
accompanied by marked vacuolation. Changes in clinical
parameters included an increase in plasma alanine
transaminase and reduced plasma protein indicative of
hepatic toxicity. Also observed at 50 mg/kg/day were
reductions in plasma cholesterol and triglycerides. At
5 mg/kg/day one dog had evidence of fatty change in the
liver accompanied by increases in alanine transaminase
activity. The no-effect level for this study was judged
to be 0.5 mg/kg/day.
"Chronic Toxicity In a lifetime feeding study, hamsters
were fed diets containing 0, 250, 2500, 7500 ppm. At 7500
ppm, kidney weights were decreased in females and liver
and testes weights were increased in males.
"Histologically, there was an increase in the incidence
of lipofuscin deposition in the kidneys. There were no
compound-related increases in the incidence of tumors in
this study. The no-effect level was judged to be 2500
ppm,
"A long-term mouse feeding study was not conducted with
this cyclohexanedione since the hamster was judged to be
a more appropriate species to test for long-term effects.
"Also, our parent company has informed us that there was
a compound-related increase in the incidence of Leydig
cell tumors in a long term rat study. We are trying to
obtain a copy of the study report.
"Mutagenicity The cyclohexanedione was not mutagenic in
two Ames assays, a micronucleus study, an L51784 mouse
lymphoma study, or a cytogenicity study."
USE AND EXPOSURE POTENTIAL
In view of the submitter's TSCA CBI claims, no information
regarding the TSCA Chemical Substance Inventory status of the
subject chemical will appear in this status report.
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Page 5 of 5
The submitter stated nonconfidentially that, "This chemical is an
experimental pesticide that has been field tested at several of our
test farms. Trained employees use appropriate protective equipment
when working with test materials at these sites."
COMMENTS/RECOMMENDATIONS
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, the submitter will be requested
to describe the actions that the company has taken or
plans to take 1) to notify workers/others about the
reported information, and 2) to reduce or eliminate
exposure to the subject chemical. The submitter will be
asked also to provide copies of Material Safety Data
Sheets and labels that have been revised to reflect the
reported findings. In addition, the submitter will be
asked to describe the nature and results, if available,
of all studies (other than those submitted already to EPA
or those cited in the published scientific literature)
about which the submitter is aware or that the company
has conducted, is conducting or plans to conduct that are
designed to determine the toxicity of or the exposure to
the subject chemical.
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will review the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
361
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 3
OFFICE OF
PESTICIDES AND
DATES MAR 3 0 1990 approved: T, lko)% T0XCSUBSTANCES
FROM: Martha G. Price, Ph.D., Che
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
Amoco Oil Company provided the following summary information with
regard to formation and detection of polychlorinated dibenzo-para-
dioxins and polychlorinated dibenzofurans (PCDD/PCDF) at and near
the company's Yorktown, Virginia, refinery:
"Last year, the oil industry became aware and informed
EPA that polychlorinated dibenzo-para-dioxins and
polychlorinated dibenzofurans were being generated during
the reactivation of the catalyst from the catalytic
reformer processing unit. In some refineries, water is
used to scrub the off-gases, and the dioxins and furans
have been detected in the scrubber water. This water is
treated in the refinery water treatment facilities prior
to discharge. In an effort to characterize our refinery
waste water streams and to determine if these compounds
were being discharged into the environment, Amoco
recently analyzed water samples from various points in
our Yorktown refinery and one sample of water from the
York River upstream from the refinery for dioxins and
furans.
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
SUBJECT: Status Report 8EHQ-0290-0882
362
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Page 2 of 3
"One grab sample was taken at each location. Published
EPA methods were used to analyze the samples for dioxins
and furans. As expected, polychlorinated dioxins and
furans were detected in the scrubber water (sample:
"Reformer Spray Tur"). This water is combined with other
process water and treated at the refinery's water
treatment plant prior to discharge to the York River. The
discharge to the York River, sample 001 effluent,
contained 0.351 parts per trillion (ppt) total furans
and 0.483 ppt total dioxins. None of the most toxic
species, 2,3,7,8 TCDD, was found in the discharge water.
The refinery draws its process watfer from the York River,
upstream from the refinery. A sample of this intake water
was also analyzed and found to contain 0.461 ppt of
dioxins. 2,3,7,8 TCDD was not found in this sample nor
were any furans detected."
Amoco*s submission also contained some analytical data on water
samples from process water and waste water streams from various
points in Amoco*s Yorktown refinery.
USE AND EXPOSURE POTENTIAL
Other than that the refinery waste water streams are discharged
after treatment into the York River, Amoco did not provide any
information on the potential for exposure to the subject chemicals.
CQWMBWTg/RBCPWMgyPATIQyg
In the submission Amoco stated that these data would also be
provided to EPA's Region 3 Office and to the State of Virginia.
The Agency has received a number of TSCA Section 8(e) and "For Your
Information" (FYI) submissions on halogenated dibenzodioxins and
dibenzofurans.
a) The Chemical Screening Branch will ask Amoco to ensure
that EPA is kept apprised of all further significant
findings from the company's additional studies into the
reported matter.
Additionally, Amoco will be asked to provide the date on
which and to whom at EPA (including title and office) the
cited notice of PCDD/PCDF detection was given "last year"
to the Agency.
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to chemical
toxicity/exposure information, Amoco will be requested
to describe the actions that the company has taken or
plans to take 1) to notify workers/others about the
reported information, and 2) to reduce or eliminate
exposure to PCDD/PCDF. In addition, Amoco will be asked
363
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Page 3 of 3
to describe the nature and results, if available, of all
studies (other than those submitted already to EPA or
those cited in the published scientific literature) about
which Amoco is aware or that the company has conducted,
is conducting or plans to conduct that are designed to
determine the exposure to PCDD/PCDF.
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will review the reported information in order to
determine the need for further assessment of the subject
chemicals at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and Region 3; in
addition, copies of this status report will be sent to
the Environmental Assistance Division/OTS (formerly the
TSCA Assistance Office/OTS) for further distribution.
364
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[m)
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 3
WASHINGTON, DC 20460
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
DATES MAR I 6 1990 APPROVED*
SUBJECTI Status Report1 8EHQ-0290-0883 8
8EHQ-0390-0883 8 SUPP
QiuictA W
FROM: Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
NQTB (See NOTE on Page 3 of this Status Report)
The submitting company has claimed its company name and the exact
identity of the subject chemical as TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. The "sanitized" versions of these Section 8(e)
notices identify the subject chemical substance non-confidentially
as a "diaryl ether."
SUBMISSION DESCRIPTION
In its initial section 8(e) notice, the submitting company provided
the following summary information about the conduct and preliminary
results of a rat teratology study conducted on this diaryl ether:
" In this study, [the test compound] was administered by
gavage to 4 groups of 25 mated female rats at dose levels
of 0, 50, 250, 1000 mg/kg/day during gestation days 6-
16. Dams were sacrificed on gestation day 20. Fetuses
were removed, weighed and sexed and examined for possible
external malformations.
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the"substantial risk' information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency polity or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
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8EHQ-0390-0883 S SUPP
Page 2 of 3
"Body weight gains were similar in all dose-groups.
High-dose dam liver weights were statistically increased.
Both fetus and litter incidence of renal papilla(e) not
developed and/or distended ureter(s) were increased in
a dose-related fashion; these fetal observations were not
statistically significant."
In the supplemental TSCA Section 8(e) submission, the company
stated that "verbal reports from the testing laboratory indicate
that these [fetal] effects were nearly all unilateral, slightly
distended ureters." In the supplemental submission, the company
also provided the following information about additional results
from this rat teratology study:
"The incidence of rudimentary 14th rib(s) was increased
in a dose-related manner and this finding was [found to
be] statistically significant for litters at the high-
dose. Occurrences of 14th full rib(s) were also seen in
mid- and high-dose fetuses, although those observations
were not statistically significant."
QBE AND EXPOSURE POTENTIAL (see NOTE on Page 3 of this Status Report)
The submitter reported non-confidentially that this diaryl ether
is manufactured exclusively for research and development (R&D)
purposes.
COMMENTS/RECOMMENDATIONS
It should be noted that EPA has received several TSCA Section 8(e)
notices on compounds identified as "diaryl ethers." The reader's
attention is directed to the "Status Reports" prepared by EPA in
response to these other Section 8(e) notices (8EHQ-0988-0751 S,
8EHQ-1289-0851 S, and 8EHQ-0290-0888 S) . (see NOTE on following page.)
a) The Chemical Screening Branch will ask the company to
ensure that EPA receives a complete copy of the final
report (including the actual experimental protocol,
results of gross and histopathological examinations,
results of statistical analyses, etc.) from the rat
teratology study cited in the submissions.
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity data, the submitter will be asked to describe
the actions that the company has taken or plans to take
1) to notify workers and/or others about the reported
information, and 2) to reduce or eliminate exposure to
the subject chemical. The submitter will be asked also
to provide copies of Material Safety Data Sheets and
labels that have been revised to reflect the reported
findings. In addition, the submitter will be asked to
describe the nature and results, if available, of all
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Pace 3 of 3 8EHQ-0290-0883 S
y J WJ- ° 8EHQ-0390-0883 S SUPP
studies (other than those submitted already to EPA or
those cited in the published scientific literature) about
which the company is aware or that the company has
conducted, is conducting or plans to conduct that are
designed to determine the toxicity of or the exposure to
the subject chemical.
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will review the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA? in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
NOTE In an April 4, 1991 followup letter (8EHQ-0491-0883 S
Followup Response), the submitting company stated non-
confidentially that the diaryl ether which was cited in
8EHQ-0290-0883 S Initial and the diaryl ether which was
cited in 8EHQ-1289-0851 S Initial are the same chemical
substance. The reader's attention is directed to the
status report that was prepared by EPA in response to
8EHQ-1289-0851 S Initial.
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
DATE:
SUBJECT!
6 !9<
APPROVED:
OFFICE OF
PESTCIDE8 AND
TOXIC SUBSTANCES
FROM:
TO:
Status Report1 8EHQ-0290-0884
8EHQ-0290-0884 8UPP
Jacqueline T. Favilla, Biologist
Chemical Risk Identification Section/CSB
James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
The ARCO Chemical Company provided summary information about the
conduct and preliminary results of a 9-day probe inhalation study
in rats and an oral developmental toxicity probe study in rabbits;
both studies involved exposure to isopropanol (CAS No. 67-63-0).
In a supplemental submission, Exxon Chemical Americas provided
summary information from the rabbit probe study cited in ARCO's
submission. Both of the submitters noted that they are members of
the Chemical Manufacturers Association (CMA) Isopropanol Panel, the
sponsor of the studies. The studies were initiated to establish
appropriate dose levels for other toxicity studies to be conducted
in accordance with a TSCA Section 4 final test rule on isopropanol
(54 FR 43252, October 23, 1989).
The initial submission provides the following summary information
regarding these probe studies:
Rat Study
"... Five CD rats per sex per group were exposed to
either 0, 1,000, 5,000, 10,000 or 15,000 ppm of
isopropanol vapor for 6 hours/day for a total of nine
exposures in 12 days. All surviving animals were sacri-
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s), Any review of this status report should take into account that the report may be
based on incomplete information.
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ficed on day 12. At that time, a gross necropsy was
performed and a histopathological examination was
conducted on livers and kidneys from the groups exposed
to the two lowest isopropanol concentrations and on the
control group.
". . . Results of that evaluation indicated that only
[the] males exposed to isopropanol vapors exhibited an
unexpected kidney effect: hyaline droplet nephropathy.
Four of five males exposed to 1000 ppm and five of five
males exposed to 5,000 ppm of isopropanol were noted
having this finding."
Rabbit Study
"... [Pregnant] rabbits were given isopropanol solution
by gavage on gestational days 6 through 18 [at doses of
0, 312.5, 625, or 1250 mg/kg/day at a dosing volume of
2.0 ml/kg] and all survivors were sacrificed on gesta-
tional day 30.
"... Preliminary results indicated that these pregnant
rabbits appeared, to be more sensitive to the lethal
effects of isopropanol than . . . expected.
"Based on the assumption that rabbits sacrificed when
moribund in this probe study would have died on test,
these animals plus animals which did die were used to
calculate a repeated dose oral LD50 value. This value
was estimated to be 585 mg/kg/day with a 95% confidence
interval of 443 to 772 mg/kg/day. This LD50 represents
an 8-fold lowering of this parameter as compared to the
acute oral LD50 (4830 mg/kg) reported in non-pregnant
rabbits."
USE AND EXPOSURE POTENTIAL
According to the Condensed Chemical Dictionary (10th edition),
isopropanol uses include manufacture of acetone and its
derivatives, manufacture of glycerol and isopropyl acetate,
solvent, deicing agent for liquid fuels, preservatives, and
lotions. For more detailed information regarding the uses of and
exposure potential to isopropanol, the reader's attention is
directed to the proposed TSCA Section 4 test rule (53 FR 8368,
March 16, 1988).
COMMENTS/RECOMMENDATIONS
In their respective submissions, both companies reported that they
will provide information to supplement these probe study summaries
when such information becomes available. It should be noted here
that EPA has published a TSCA Section 8(d) information gathering
rule covering isopropanol.
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The following discussion pertains to the relationship between TSCA
Section 8(e) reporting and the reporting of results from studies
required to be conducted under Section 4 of TSCA. The Section 8(e)
reporting requirement applies to any "substantial risk" information
obtained during a study being conducted under Section 4 unless the
information at the time it is obtained is required to be reported
under Section 4. To date, the Agency has received many Section 8(e)
notices concerning the interim results of studies conducted under
Section 4. The Section 8(e) reporting that takes place in these
cases typically occurs when a Section 8(e) obligation is incurred
before reporting of the study finding/report is required under
Section 4. In other words, if other required reporting occurs
before or coincidental with a Section 8(e) reporting obligation,
the information does not have to be submitted under Section 8(e).
The purpose of this exemption is not to change substantially the
Section 8(e) obligation, but is designed merely to avoid dupli-
cative reporting except in cases where timeliness considerations
are paramount.
a) The Chemical Screening Branch will ask the submitters to
ensure that EPA receives complete copies of the final
reports (including the actual experimental protocols,
results of gross and histopathological examinations,
results of statistical analyses, etc.) from the rat and
rabbit probe studies cited in the submission.
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, the submitters will be requested
to describe the actions that they have taken or plan to
take 1) to notify workers/others about the reported
information, and 2) to reduce or eliminate exposure to
the subject chemical. The submitters will be asked also
to provide copies of Material Safety Data Sheets and
labels that have been revised to reflect the reported
findings.
b) As was the case with the initial and supplemental
submissions, staff of the Chemical Screening Branch will
send full copies of all reported information to
TRDB/ECAD/OTS for review.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and TRDB/ECAD/OTS;
in addition, copies of this status report will be sent
to the Environmental Assistance Division/OTS (formerly
the TSCA Assistance Office/OTS) for further distribution.
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
m 15 MO awboved. iLft
Status Report1 8EHQ-0290-0885
Jacqueline Favilla, Biologist
Chemical Risk Identification Sectlon/CSB
James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
Crompton & Knowles Corporation, U.S.A., provided the following
summary information regarding an incident that occurred at its
Tertre, Belgium plant:
". . .A plant worker at the Belgium facility was
transporting a pallet of drums containing Reactive Black
5 [(CAS No. 17095-24-8)] on a tow motor when a drum of
the dye fell off the pallet resulting in the worker being
exposed to the dust of this dye. The worker experienced
an asthmatic attack, left the area and went outside the
plant for air. He was sent to the hospital and was
absent from work for one day. He returned to his
previous job but has been restricted from working with
the dye.
"At present, Crompton & Knowles, U.S.A., has no
additional information concerning the worker, the nature
and extent of his allergies or the medical determination
made at the time of the incident. We are reporting this
information to EPA because the incident ... appears to
confirm other data in the literature which implicates
Reactive Black 5 as a human respiratory sensitizer."
DATE:
SUBJECTS
FROM:
TOt
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial riskf information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
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8EHQ-0290-0885
Page 2 of 2
PSg AND ESPpspfig PQTgyTIAL
According to the Colour Index (3rd edition), Reactive Black 5 is
used for "dyeing cellulose." Reactive Black 5 is listed on the non-
confidential version of EPA's TSCA Chemical Substance Inventory.
COMMENTS/RECOMMENDATIONS
The summary information, as provided in this submission, is not
sufficient to permit EPA to make a determination at this time
regarding the TSCA Section 8(e)-applicability/reportability of the
described incident.
a) Crompton & Knowles will be asked to keep EPA apprised of
the health status of the exposed worker.
The Chemical Screening Branch will ask Crompton & Knowles
to ensure that the Agency receives copies of any medical
evaluations of the exposed worker or reports generated
by the company designed to determine the health status
of the exposed worker.
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Crompton & Knowles will be
requested to describe the actions that the company has
taken or plans to take 1) to notify workers/others about
the reported information, and 2) to reduce or eliminate
exposure to the Reactive Black 5. Crompton & Knowles will
be asked also to provide copies of Material Safety Data
Sheets and labels that have been revised to reflect the
reported findings. In addition, Crompton & Knowles will
be requested to describe the nature and results, if
available, of all studies (other than those submitted
already to EPA or those cited in the published scientific
literature) about which Crompton & Knowles is aware or
that the company has conducted, is conducting or plans
to conduct that are designed to determine the toxicity
of or the exposure to the subject chemical.
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will review the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
Status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA? in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
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8EH(^0.290-0886
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
DATES
MPR I 4 1990
APPROVED!
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: status Report1 8EHQ-0290-0886
FROM: Jacqueline Favilla, Biologist
Chemical Risk Identification Sectjfon/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
The Unocal Corporation provided the following information regarding
the conduct and preliminary results of a proportionate mortality
(PMR) study of hematopoietic cancer deaths and an investigation of
a possible cluster of multiple myeloma cases among petroleum and
pipeline workers:
"Existing company records were utilized for the PMR
study. All known company death certificates were
assembled to create the . . . mortality database . . .
[for] deaths occurring between 1976 and 1985 inclusive.
. . . Cause of death proportions for Oil and Gas (O&G)
division were compared with cause of death proportions
for the rest of the company. In certain analyses, deaths
for Pipeline (P/L) workers were included with O&G deaths.
Comparisons were made also to the cause of death
proportions among U.S. adult males for 1980 . . .
"There were 2458 deaths available for study, with 70 due
to hematopoietic cancers. . . Almost every comparison
in the hematopoietic cancers has a proportionate
mortality ratio (PMR) greater than 1.00, indicating a
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk' information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
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8EHQ -0290-0886
possible association between having worked O&G or P/L
assignments and dying of these cancers. The comparisons
with the U.S. males are statistically significant at p
.05 as indicated by confidence limits where both the
upper and lower limits are greater than 1.00 . . .
"The PMR for all hematopoietic cancers combined was 2.03
(confidence limits: 1.23-3.35) when O&G was compared with
the rest of Unocal and the proportionate cancer mortality
ratio (PCMR) was 2.09 (1.28-3.43) for the same comparison
••The second analysis consisted of an investigation of an
apparent cluster of five multiple myeloma cases among Oil
and Gas employees who had been ascribed to [the] Ardmore,
Oklahoma Oil and Gas field. One of these was included
in the current PMR analysis. Upon initial investigation,
it appears that the Ardmore office was a district office
and that the employees in question worked in different
locations and had different jobs . . .
"In summary, the weight of the evidence of all the
studies performed to date suggests limited evidence of
an association between death due to hematopoietic cancers
and working Oil and Gas and Pipeline assignments."
COMMENTS/RECOMMENDATIONS
Unocal reported that it is examining the feasibility of conducting
a scientifically valid case-control study of the relationship
between hematopoietic cancer deaths and petroleum and pipeline
workers. Also, Unocal is now conducting a further, more detailed
evaluation of the five multiple myeloma cases.
a) The Chemical Screening Branch will ask Unocal to ensure
that EPA receives a full copy of the final report of the
PMR study (including the actual study protocol, results
of statistical analyses, etc.) as well as the full final
report of the investigation of the cluster of multiple
myeloma cases that were cited in the submission.
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Unocal will be requested to
describe the actions that the company has taken or plans
to take 1) to notify workers/others about the reported
information, and 2) to reduce or eliminate exposure.
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will review the reported information in order to
determine the need for further assessment of the reported
findings at this time.
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8EHQ-0290-0886
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
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U3£
?
Page 1 of 2
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
dates MAR 3 0 1990
APPROVED:
^ /ja/v-y 3 jlohn
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECTS Status Report1 8EHQ-0290-0887 S
PROM: Martha G. Price, Ph.D., Chemi
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
The submitting company has claimed its company name and the exact
identity of the subject chemical as TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. In the "sanitized" version of its Section 8(e)
notice, the company reported non-confidentially that the subject
chemical is a "substituted acetic acid ester."
SUBMISSION DESCRIPTION
The submitting company provided the following summary information
regarding the conduct and preliminary results of a pilot rat
teratology study:
"Preliminary results... indicate that the compound may
produce some developmental toxicity. In this study,
substituted acetic acid ester was administered by gavage
to 6 groups of mated female rats at dose levels of 0, 10,
80, 100, 200 and 600 mg/kg/day during gestation days 6-
15. Surviving dams were sacrificed on gestation day 20.
Fetuses were removed, weighed, sexed and examined for
possible external malformations.
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
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8EHQ-0290-0887 S
Page 2 of 2
"At [a] dose level of 200 mg/kg/day, the number of viable
fetuses were decreased, the mean resorptions were
increased and the mean fetal body weights were decreased.
At the high dose (600 mg/kg/day), female mortality was
80%."
ysg MP gSPQgPRE POTENTIAL
In view of the submitter's TSCA CBI claims, no information
regarding the TSCA Chemical Substance Inventory status of the
subject chemical will appear in this status report. The submitter
stated nonconfidentially that, "The material in question is
currently being manufactured exclusively for R&D purposes."
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will ask the submitter to
ensure that EPA receives a complete copy of the final
report (including the actual experimental protocol,
results of gross and histopathological examinations,
results of statistical analyses, etc.) from the pilot
teratology study cited in the submission.
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, the submitter will be requested
to describe the actions that the company has taken or
plans to take 1) to notify workers/others about the
reported information, and 2) to reduce or eliminate
exposure to the subject chemical. The submitter will be
asked also to provide copies of Material Safety Data
Sheets and labels that have been revised to reflect the
reported findings. In addition, the submitter will be
asked to describe the nature and results, if available,
of all studies (other than those submitted already to EPA
or those cited in the published scientific literature)
about which the submitter is aware or that the company
has conducted, is conducting or plans to conduct that are
designed to determine the toxicity of or the exposure to
the subject chemical.
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will review the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
377
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 3
OFFICE OF
PESTICIDES AND
DATE! MAR I 61990 APPROVED:
IT. l/at/le
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0290-0888 8
jjit-til 'U:- W Lc>/ICA*' % £0
FROM: Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
The submitting company has claimed its company name and the exact
identity of the subject chemical as TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. In the "sanitized" version of its Section 8(e)
notice, the company reported non-confidentially that the subject
chemical is a "diaryl ether."
gUBMisgioy DEsgRiPTipy
The submitting company provided the final report of a pilot rat
teratology study conducted with this diaryl ether. The SUMMARY
section from this report presents the following summary information
regarding the conduct and results of this study:
"[The test compound] was admixed in MazolaR corn oil and
administered orally by gavage to five groups of eight
bred Sprague Dawley COBSR CDR rats once daily from
gestation days 6 through 15. Dosage levels of 25, 50,
100, 300 and 600 mg/kg/day were selected based on the
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
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8EHQ-0290-0888 S
Page 2 of 3
results of a preliminary range-finding toxicity study.
For comparative purposes, a concurrent control group,
also composed of eight bred females, was dosed with
MazolaR corn oil on a comparable regimen at 5 ml/kg/day.
"One animal in the 600 mg/kg/day group died on gestation
day 11. Survival was 100% in all of the other study
groups. Clinical observations which could be related to
the administration of [the test compound] were noted in
in the 300 and 600 mg/kg/day groups. Maternal body
weight gains were severely reduced in the 600 mg/kg/day
group during the treatment and post-treatment periods.
In the 300 mg/kg/day group, mean body weight gain was
moderately reduced the last portion of the treatment
period and was severely reduced thereafter. Mean spleen
and liver weights were statistically elevated in the 300
and 600 mg/kg/day groups when compared with the control
group? in addition, kidney weights were slightly elevated
in the 600 mg/kg/day group. The mean spleen weights were
slightly elevated but not statistically significant at
the 50 and 100 mg/kg/day levels. Severe embryolethality
and severely reduced mean fetal weights occurred at dose
levels of 300 and 600 mg/kg/day. No external malforma-
tions or developmental variations were seen in any of
the treated groups."
USE AND EXPOSURE POTENTIAL
The submitting company stated non-confidentially that this diaryl
ether has only been prepared for research and development (R&D)
purposes.
COMMENTS/RECOMMENDATIONS
It should be noted that EPA has received several TSCA Section 8(e)
notices on compounds identified as "diaryl ethers." The reader's
attention is directed to the "Status Reports" prepared by EPA in
response to these other Section 8(e) notices (8EHQ-09S8-0751 S,
8EHQ-1289-0851 S, and 8EHQ-0290-0883 S).
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity, the submitter will be requested to describe
the actions that the company has taken or plans to take
1) to notify workers and/or others about the reported
information, and 2) to reduce or eliminate exposure to
the subject chemical. The submitter will be asked also
to provide copies of Material Safety Data Sheets and
labels that have been revised to reflect the reported
findings. In addition, the submitter will be asked to
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8EHQ-0290-0888 S
Page 3 of 3
describe the nature and results, if available, of all
studies (other than those submitted already to EPA or
those cited in the published scientific literature) about
which the company is aware or that the company has
conducted, is conducting or plans to conduct that are
designed to determine the toxicity of or the exposure to
the subject chemical.
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will review the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
380
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
OFFICE OF
PE8HCIDE8 AND
date: APR - 3 1990
APPROVED:
TOXIC SUBSTANCES
SUBJECT: status Report1 8EHQ-0290-0889 8
PROM: Martha G. Price, Ph.D., ChemlstCwUV \i^
Chemical Risk Identification Section/CS
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
The submitting company has claimed its company name and the exact
identity of the subject chemical as TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. In the "sanitized" version of its Section 8(e)
notice, the company reported non-confidentially that the subject
chemical is a "substituted acetanilide."
SUBMISSION DESCRIPTION
The submitting company provided the following summary information
regarding the conduct and final results of both a range-finding
teratology study and the follow-up teratology study in rats:
"Pilot Rat Teratology Study. Results have been obtained
from a pilot rat teratology study with the substituted
acetanilide. In this study, the substituted acetanilide
was administered by gavage to 6 groups of mated female
rats at dose levels of 0, 150, 300, 600, 1000 and 1500
mg/kg/day. surviving dams were sacrificed on gestation
day 20. Fetuses were removed, weighed, sexed and examined
for external malformations and variations.
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the"substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
note
381
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8EHQ-0290-0889 S
Page 2 of 3
"All dams died or were sacrificed in extremis at dose
levels of 600 mg/kg/day and above. One dam died at 150
and at 300 mg/kg/day. No deaths occurred in the control
group. Total resorptions were slightly increased at 300
mg/kg/day."
f
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8EHQ-0290-0889 S
Page 3 of 3
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will review the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
383
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.B> Page 1 of 3
I | UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
DATE:
APPROVED:
m 30 1990
8UBJECT: Status Report1 8EHQ-0290-0890 8
OFFICE OF
PESTICIDE8 AND
zh*h* T0XICSUBSTANCES
p
PROM: Martha G. Price, Ph.D.,
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
WOTB
The submitting company has claimed its company name and the exact
identity of the subject chemical as TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. In the "sanitized" version of its Section 8(e)
notice, the company reported non-confidentially that the subject
chemical is an "acetophenone oxime."
gUgMIgglQP PESCRIPTIQE
The submitting company provided the following summary information
regarding the conduct and final results of both a range-finding
teratology study and the follow-up teratology study in rats:
"In a pilot rat teratology study acetophenone oxime was
administered by gavage to 7 groups of mated female rats
at dose levels of 0, 5, 10, 20, 40, 80 and 160 mg/kg/day
during gestation days 6-15. Surviving dams were
sacrificed on gestation day 20. Fetuses were removed,
weighted, sexed and examined for possible external
malformations.
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
334
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8EHQ-0290-0890 S
Page 2 of 3
"Maternal body weight gains were statistically reduced
at 160 mg/kg and slightly reduced at 80 mg/kg. An
increase in clinical observations was observed at dose
levels of 20 mg/kg and above. An increase in post
implantation loss (due to early resorptions), an increase
in fetal lethality and a decrease in fetal body weight
were observed at 160 mg/kg. Late resorptions were
increased at 80 mg/kg. An increase in fetal anasarca was
observed at 160 mg/kg and equivocally increased at 80
mg/kg.
"In a follow-up rat teratology study, acetophenone oxime
was administered by gavage to 4 groups of mated female
rats at dose levels of 0, 5, 30 and 60 mg/kg/day.
Surviving dams were sacrificed on gestation day 20.
Fetuses were removed, weighed, sexed and examined for
external, visceral and skeletal malformations and
variations.
"Maternal body weight gains were slightly reduced at 30
and 60 mg/kg. A statistically significant increase in
post implantation loss and a statistically significant
decrease in fetal body weights compared to control were
observed at 60 mg/kg. Skeletal variations were
statistically increased at 30 and 60 mg/kg. However, the
variation increased at 30 mg/kg was an example of reduced
ossification which may not adversely affect survival or
health. Fetal malformations were statistically increased
at 60 mg/kg."
USE AND EXPOSURE POTENTIAL
In view of the submitter's TSCA CBI claims, no information
regarding the TSCA Chemical Substance Inventory status of the
subject chemical will appear in this status report.
The submitter stated nonconfidentially that the acetophenone oxime
is "an obsolete R&D chemical."
OOMMENTS/RECOMMENDATIONS
It should be noted that EPA has received another TSCA Section 8(e)
notice on a compound identified generically as acetophenone oxime.
The reader's attention is directed to the status report prepared
by EPA in response to 8EHQ-1287-0708.
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, the submitter will be requested
to describe the actions that the company took to notify
workers/others about the reported information. The
submitter will be asked also to provide copies of
385
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8EHQ-0290-0890 S
Page 3 of 3
Material Safety Data Sheets and labels that were revised
to reflect the reported findings. In addition, the
submitter will be asked to describe the nature and
results, if available, of all studies (other than those
submitted already to EPA or those cited in the published
scientific literature) about which the submitter is aware
or that the company conducted to determine the toxicity
of the subject chemical.
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will review the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
386
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page l of 3
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
DATE:
•' 9 ' !
APPROVED!
SUBJECT: Status Report1 8EHQ-0290-0M1 8
QucLctA, M f^o
FROM: Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
The submitting company has claimed its company name and the exact
identity of the subject chemical as TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. In the "sanitized" version of its Section 8(e)
notice, the company reported non-confidentially that the subject
chemical is a "aryl alkyl ether."
gVBMIgglQH DESCRIPTION
The submitting company provided the final report of a pilot rat
teratology study of this aryl alkyl ether. The submitter provided
the following summary information regarding the conduct and results
of this study:
" [The test compound was] administered by gavage to 6
groups of mated female rats at dose levels of 0, 25, 50,
100, 175 and 300 mg/kg/day during gestations days 6-15.
Surviving dams were sacrificed on gestation day 20.
Fetuses were removed, weighed, sexed and examined for
possible external malformations.
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk? information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
NOTE
387
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8EHQ-0290-0891 S
Page 2 of 3
" A statistically significant reduction in maternal body
weight gain compared to control was observed at 3 00
mg/kg. An increase in clinical observations were
reported at dose levels of 100 mg/kg and higher. A non-
statistical increase in post implantation loss was
observed at 300 mg/kg/day. One fetus in one litter at
300 mg/kg had the external malformation, microphthalmia,
versus none in the control. However, this type of
malformation occurs spontaneously in this strain of rat
and the relation of this single incidence to treatment
could not be determined."
USE AND EXPOSURE POTENTIAL
The submitter reported non-confidentially that this aryl alkyl
ether is a research chemical.
COMMENTS/RECOMMENDATIONS
It should be noted that EPA has received a TSCA Section 8(e) notice
on a compound identified as an alkvl aryl ether. The reader's
attention is directed to the status report prepared by EPA in
response to this previous Section 8(e) notice (8EHQ-1188-0771 S).
a) In view of EPA's interest in effective and appropriate
hazard and risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity data, the submitter will be asked to describe
the actions that the company has taken or plans to take
1) to notify workers and others about the reported
information, and 2) to reduce or eliminate exposure to
the subject chemical. The submitter will be asked also
to provide copies of Material Safety Data Sheets and
labels that have been revised to reflect the reported
findings. In addition, the submitter will be asked to
describe the nature and results, if available, of all
studies (other than those submitted already to EPA or
those cited in the published scientific literature) about
which the company is aware or that the company has
conducted, is conducting or plans to conduct that are
designed to determine the toxicity of the subject
chemical.
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will review the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
388
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8EHQ-0290-0891 S
Page 3 of 3
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
389
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Page 1 of 7
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBMISSION DESCRIPTION
In conjunction with a TSCA Section 8(e)-related "Consent Agreement"
(TSCA 89-H-21), the Monsanto Company submitted complete copies of
the final reports from in vivo toxicity studies of the following
four chemical substances:
2,3-Dichloropropene (CAS No. 78-88-6)
1,1,2,2,3-Pentachloropropane (CAS No. 16714-68-4)
Carbonyl Sulfide (CAS No. 463-58-1)
0,0-Dimethyl ester of phosphorochloridothioic acid
(Methyl PCT; CAS No. 2524-03-0)
Monsanto also provided summaries describing the conduct and results
of the performed studies; the submitted summaries are located in
the four page attachment to this status report. It should be noted
that in providing these summaries to the Agency, Monsanto pointed
out that the summaries are not all-inclusive and may not highlight
all of the adverse effects observed in the studies.
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
^t0SX
k5S8
*Vk f-»
PR0^fc
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
DATE:
H - 7 1990
APPROVED:
7- Cbrvs. 3/f4i
SUBJECT: status Report1 8EHQ-0290-0892
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD
TO: James F. Darr, Section Head
Chemical Risk Identification Section/CSB/ECAD
390
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8EHQ-0290-0892
Page 2 of 7
USE AND EXPOSURE POTENTIAL
Monsanto did not provide any information about the uses of, or the
potential for exposure to, the subject chemical substances. The
Merck Index (10th Edition) presents the following information about
the use of 2,3-dichloropropene:
2.3-Dichloropropene
"Together with 1,2-dichloropropane, [1,3-dichloropropene] and
related chlorinated hydrocarbons in the so-called DD Mixture
[used] as a soil fumigant."
The Condensed Chemical Dictionary (10th Edition) has the following
information about the uses of carbonyl sulfide and Methyl PCT:
Carbonyl Sulfide
"Synthesis of thio organic compounds."
Metnyl PCT
"Intermediate for insecticides, pesticides, fungicides; oil
and gasoline additives; plasticizers; corrosion inhibitors;
flame retardants; flotation agents."
No information with regard to the use(s) of or the potential for
exposure to 1,1,2,2,3-pentachloropropane was found in the secondary
literature sources consulted by EPA.
COMMENTS/RECOMMENDATIONS
It should be noted that a number of "For Your Information" (FYI)
notices on 2,3-dichloropropene have been received by the Agency;
the reader's attention is directed to the following FYI files:
FYI-OTS-0784-0330, FYI-OTS-0485-0396, and FYI-OTS-0786-0499.
Considering that EPA published a TSCA Section 8(d) information
gathering rule on this chemical (52 FR 16022; May l, 1987), the
Chemical Screening Branch provided a complete copy of the present
Section 8(e) submission to the Office of Solid Waste (OSW/OSWER),
the EPA office for which the Section 8(d) rule was written.
It should be noted also that EPA has received TSCA Section 8(e) and
"For Your Information" (FYI) submissions and prepared (in 1982) a
"Chemical Hazard Information Profile" (CHIP) on the 0,0-dimethyl
ester of phosphorochloridothioic acid (methyl PCT). The reader's
attention is directed to this CHIP as well as the status reports
prepared by EPA in response to TSCA Section 8(e) submission numbers
8EHQ-0381-0387 and 8EHQ-0290-0878; the reader's attention is also
directed to FYI-OTS-0683-0249 et seq.
a) In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, Monsanto will be requested to
391
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8EHQ-0290-0892
Page 3 of 7
describe the actions that the company has taken or plans
to take 1) to notify workers/others about the reported
information, and 2) to reduce or eliminate exposure to
the subject chemicals. Monsanto will be asked to submit
copies of Material Safety Data Sheets and labels that
have been revised to reflect the reported findings. In
addition, Monsanto will be asked to describe the nature
and results, if available, of all studies (other than
those submitted already to EPA or those cited in the
published scientific literature) about which Monsanto is
aware or that Monsanto has conducted, is conducting or
plans to conduct that are designed to determine the
toxicity of or the exposure to the subject chemicals.
b) The reported information will be reviewed by staff of the
Chemical Screening Branch as part of the "FIRST REVIEW"
phase of the Existing Chemicals Program (ECP) in order
to determine the need for further OTS assessment of the
subject chemicals at this time. Any information received
on 2,3-dichloropropene will be sent also to OSW/OSWER/EPA
for review.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
392
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ATTACHMENT
-1-
8EHQ-0290-0892
Page 4 of 7
TSCA 8(e) Audit
Summary Memo
Compound: 2,3-Dichloropropene
Study no.: BD-78-125
Study type: one Generation Rat Reproduction Study
Results have been obtained from a one generation rat reproduction
study on 2,3-Dichloropropene. tn this study, 2,3-
dichloropropene was administered via inhalation to 3 groups of
rats at dose levels of 0, l and 5 ppm prior to mating, and
throughout gestation and lactation. The effects of treatment on
litter size, pup birth weight and postnatal weight gain and pup
survival were determined.
Male fertility was slightly decreased at both treatment
concentrations. Pup survival was decreased at 5 ppm for days l
4 postpartum.
393
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ATTACHMENT
-2-
8EHQ-0290-0892
Page 5 of 7
TSCA 8(e) Audit
Summary Memo
Compound: 1,1,2,2,3-Pentachloropropane
Study no.: BD-83-48
Study type: Pilot Rat Teratology
Results have been obtained from a pilot rat teratology study with
1,1,2,2,3-pentachloropropane. In this study, pentachloropropane
was administered by gavage to 6 groups of mated female rats at
dose levels of 0, 50, 100, 150, 250 and 350 mg/kg/day. Surviving
dams were sacrificed on gestation day 20. Fetuses were removed,
weighed, sexed and examined for external malformations and
variations.
All dams died or were sacrificed in extremis at 250 and 350
mg/kg/day and 3/5 dams died at 150 mg/kg/day. Maternal body
weight gains were moderately reduced at 150 mg/kg/day and
slightly reduced at 100 mg/kg/day. Fetal body weights were
slightly reduced compared to control at 150 mg/kg/day.
Study No.: BD-83-303
Study Type: Rat Teratology
Results have been obtained from a rat teratology study with
pentachloropropane. In this study, pentachloropropane was
administered by gavage to 4 groups of mated female rats at dose
levels of 0, 20, 50 and 125 mg/kg/day. Surviving dams were
sacrificed on gestation day 20. Fetuses were removed, weighed,
sexed and examined for external, visceral and skeletal
malformations and variations.
Maternal body weight gain was statistically reduced compared to
control at 125 mg/kg. A statistically significant reduction in
fetal body weight was observed at 125 mg/kg. visceral and
skeletal variations and visceral malformations were increased at
125 mg/kg.
394
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ATTACHMENT
-3-
TSCA 8(e) Audit
Summary Memo
Compound: Carbonyl Sulfide
Study no.: ML-83-316
Study type: One Generation Rat Reproduction Study
Results have been obtained from a one generation rat reproduction
study on carbonyl sulfide. In this study, carbonyl sulfide was
administered via inhalation to 4 groups of rats at dose levels of
0, 10, 60 and 182 ppm prior to mating, and throughout gestation
and lactation. The effects of treatment on litter size, pup
birth weight and postnatal weight gain and pup survival were
determined.
A statistically significant reduction in male fertility was
observed at the high dose of 182 ppm. Pup survival was slightly
decreased at 182 ppm on days 0-4 postpartum.
8EHQ-0290-0892
Page 6 of 7
395
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ATTACHMENT
-4-
8EHQ-0290-0892
Page 7 of 7
TSCA 8(e) Audit
Summary Memo
Compound: Methyl PCT
Study no.: MR-82-88
Study Type: Dominant Lethal Assay
Methyl PCT was administered via gavage once daily for 5 days to 3
groups of 10 male Sprague-Dawley rats at dose levels of 7.5, 2 5
and 75 mg/kg/day. A control group of 10 male rats received the
vehicle corn oil only. Each male was cohoused with two virgin
females for 5 day mating periods each week for 7 weeks following
treatment. The females were sacrificed 14 days from the mid-
week of cohousing and the number of corpora lutea and live and
dead implants were determined.
The mean number of implantations was significantly reduced at 75
mg/lcg/day on weeks 4 and 5 post treatment and at 7.5 mg/kg/day on
week 5. Preimplantation losses were significantly increased at
75 mg/kg/day on weeks 4 and 5 and at 7.5 mg/kg/day on week 5.
The number of dead implants was significantly increased at 75
mg/kg/day on weeks 3 and 6, at 25 mg/kg/day on weeks 1 and 5, and
at 7.5 mg/kg/day on weeks 3 and 6. The number of live implants
per female were significantly reduced at 7 5 mg/kg/day on week 5,
at 25 mg/kg/day on week 1 and at 7.5 mg/kg/day on week 5.
396
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Page 1 of 3
y,°'X
m
I
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
J? WASHINGTON, DC 20460
puc«t&
DATE: MM 28 00 APPROVED:
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: status Report1 8EHQ-0290-0893
FROM: Jacqueline T. Favilla, Biologist
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
In its cover letter, the Amoco Chemical Company provided the
following summary information regarding the conduct and results of
two acute toxicity studies on tertiary butyl ethylbenzene (CAS No.
37871-12-8) in rabbits:
"Tertiary butyl ethylbenzene was applied at a dose of 2
g/kg of body weight to the shaved backs of five male and
five female rabbits. The test article was left in
contact with the skin for 24 hours and then removed. The
rabbits were observed during this time and for 14 days
thereafter.
"In the first study, five animals displayed slight
tremors of the hindlimbs and/or forelimbs upon movement
during the post-exposure observation period. Tremors were
not observed when the animals were at rest. The initial
observation of hindlimb tremors was made in one female
rabbit, 30 hours after test article administration.
Subsequently, the same observation was noted in three
male and one female rabbit on the 8th day of the post-
exposure period. Also on the eighth day, tremors of the
This status report is the result of a preliminary evaluation
of information that has been submitted to EPA under Section 8(e),
the "substantial risk" information reporting provision of the Toxic
Substances Control Act (TSCA). The statements made in this status
report should not be regarded as expressing final Agency policy or
intent with respect to the subject chemical(s). Any review of this
status report should take into account that the report may be based
on incomplete information.
397
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8EHQ-0290-0893
Page 2 of 3
forelimbs were observed upon movement in the female
rabbit that persisted until the end of the study in all
but one animal whose tremors were observed on days 8
through 11. No histopathology was performed.
"In the second study, four animals (two male and two
female [rabbits]) displayed slight tremors of the
hindlimbs upon movement. As in the previous study, no
tremors were observed when the animals were at rest. One
male exhibited the tremors on day 5 only and the other
male displayed tremors on days 9 and 10 only. The two
females exhibited tremors upon movement from day 4 until
the end of the study.
"Since the original observation was confirmed in the
second study, we now conclude that tertiary butyl
ethylbenzene possesses neurotoxic activity."
The "Summary" section of the final report from the first study
provides the following additional information regarding the results
of the dermal toxicity of t-butyl ethylbenzene:
"No deaths occurred during the study. Therefore, the
acute median lethal dermal dose (LD50) was estimated to
be greater than 2 g/kg of body weight.
"... Dermal irritation (i.e., edema, erythema and/or
eschar formation) was observed within the application
site of all rabbits following unwrapping. Eschar
formation, hardening, cracking and/or bleeding of the
application site skin was also noted in most rabbits
during the study. New or repaired skin was evident in
some rabbits, but complete recovery from all signs of
dermal irritation was seen in only two rabbits by the end
of the study ..."
It should be noted that the final report of the first acute rabbit
dermal toxicity study, as well as the final report from an acute
inhalation toxicity study in rats, was the subject of a recent "For
Your Information" (FYI) submission (FYI-OTS-0290-0740). The cover
letter to this FYI notice provides the following summary regarding
the conduct and results of the acute inhalation study;
"Five male and five female rats were exposed by nose only
for four hours to 4.9 mg/1 of the test material. No
deaths or clinical signs were observed during the 14 day
observation period."
USE AMD EXPOSURE POTEMTf
The Amoco Chemical Company did not provide any information
regarding the use of or the potential for exposure to t-butyl
ethylbenzene, nor was such information located in the secondary
literature sources consulted by EPA.
398
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8EHQ-0290-0893
Page 3 of 3
COMMENTS/RECOMMENDATIONS
In its Section 8(e) submission, the Amoco Chemical Company reported
that it is incorporating the information obtained from the acute
rabbit dermal toxicity studies into the Material Safety Data Sheet
and label for t-butyl ethylbenzene.
a) The Chemical Screening Branch will ask Amoco to ensure
that EPA receives a complete copy of the final report
(including the actual experimental protocol, results of
gross and histopathological examinations, results of
statistical analyses, etc.) from the second acute rabbit
dermal toxicity study cited in the company's Section 8(e)
submission.
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Amoco will be requested to
describe the actions that the company has taken or plans
to take 1) to notify workers/others about the reported
information, and 2) to reduce or eliminate exposure to
the subject chemical. Amoco will be asked also to provide
copies of the Material Safety Data Sheet and label that
have been revised to reflect the reported findings. In
addition, Amoco will be asked to describe the nature and
results, if available, of all studies (other than those
submitted already to EPA or those cited in the published
scientific literature) about which Amoco is aware or that
it has conducted, is conducting or plans to conduct that
are designed to determine the toxicity of or the exposure
to t-butyl ethylbenzene.
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will review the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA? in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
399
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v \ Page l of 3
I | UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
date: MAR 2 9 1990
APPROVED:
idL l//? ho
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT!
FROM:
TO:
status Report1 8EHQ-0290-0894
M bO/trOu*^ cO
Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
EM Industries, Inc. provided the following summary information
regarding the preliminary results of guinea pig skin sensitization
assays performed on a liquid crystal material, 4-pentylphenyl 4-
methoxybenzoate (CAS No. 38444-13-2):
"Preliminary results of Magnusson-Kligmann Maximization
tests performed on this material indicated an 85% (17/20)
rate of sensitization in guinea pigs for the pure
substance and a rate of sensitization for liquid crystal
mixtures containing 4-pentylphenyl 4-methoxybenzoate
proportional to the concentration of 4-pentylphenyl
4-methoxybenzoate in the mixture."
EM Industries, Inc. expressed a concern that individuals exposed
to respirable mists of 4-pentylphenyl 4-methoxybenzoate may be at
risk of developing respiratory hypersensitivity. The submitter
further stated that:
"Hypersensitivity resulting from the action of a
sensitizer on the skin can range from mild to serious,
but for the most part is restricted to dermal phenomena:
1 77lis status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk* information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
400
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8EHQ-0290-0894
Page 2 of 3
itching, rashes, redness, swelling. Such allergies are
somewhat limited in extent and severity and usually
subside a relatively short while after removal of the
sensitizing agent ointments and medications can be
applied with relative ease.
"Respiratory allergies, on the other hand, are generally
regarded as serious conditions and can be life threat-
ening if of sufficient severity. They are generally
difficult to treat and even a short reaction of moderate
severity can result in serious consequences, either
direct (such as passing out from lack of oxygen) or
indirect (such as an accident precipitated by dizziness
or panic). Moreover, if the reaction is severe, the
resulting condition could be debilitating."
USE AND EXPOSURE POTENTIAL
EM Industries, Inc. provided the following information regarding
the uses and potential for exposure to 4-pentylphenyl 4-methoxy-
benzoate:
"Traditional use of this material by itself or in
mixtures for closed liquid crystal display units,
regardless of sensitization potential does not represent
substantial risk to human health, however, new
information regarding the use of this and other liquid
crystal materials in cosmetic and spray applications
indicates that exposures to materials such as these are
likely to be greater than existing EPA estimates and may
be of a nature previously unrecognized by the assessment
staff at the U.S. EPA. While cosmetic applications are
not subject to TSCA, the use of this material in thin
films for visualization may present heretofore unassessed
hazard.
"If this material by itself or in a mixture is spray
applied to an article (with an artists air brush) as has
been performed for purposes of research and development,
the mist formed could travel and present an inhalation
hazard. If the material is as potent a sensitizer in
humans as in guinea pigs, a proportion of individuals
exposed to sufficient amounts via inhalation of respir-
able mists and with sufficient frequency may run the risk
of developing respiratory hypersensitivity of some sort."
QQMWBMTg/RBCCHWBMPMIOMg
a) The Chemical Screening Branch will ask EM Industries,
Inc. to ensure that EPA receives a complete copy of the
final report (including the actual experimental protocol*,
results of gross and histopathological examinations,
results of statistical analyses, etc.) from the sensi-
tization assays cited in the submission.
401
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Page 3 of 3
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, EM Industries, Inc. will be
requested to describe the actions that the company has
taken or plans to take 1) to notify workers/others about
the reported information, and 2) to reduce or eliminate
exposure to the subject chemical. EM Industries, Inc.
will be asked also to provide copies of Material Safety
Data Sheets and labels that have been revised to reflect
the reported findings. In addition, EM Industries, Inc.
will be asked to describe the nature and results, if
available, of all studies (other than those submitted
already to EPA or those cited in the published scientific
literature) about which the company is aware or that the
company has conducted, is conducting or plans to conduct
that are designed to determine the toxicity of or the
exposure to the subject chemical.
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will review the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA? in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
402
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I >ab ^ UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
OFFICE OF
PESTfCfDES AND
TOXIC SUBSTANCES
DATE: MAR 2 9 (990 APPROVED:
SUBJECT: Status Report1 8EHQ-0390-0895 8
QucdUsU' fa k)/UUCftA~>
FROM: Judith N. Loranger, Biologist
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
The submitting company has claimed its company name and the exact
identity of the subject chemical as TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. In the "sanitized" version of its Section 8(e)
notice, the company reported non-confidentially that the subject
chemical is a "pyridine carboxylate."
SUBMISSION DEfiCRIPTIOM
The submitting company provided the final reports from pilot rat
and rabbit teratology studies, and a developmental toxicity/
teratology study in rabbits. The submitting company also provided
the following summary information regarding the conduct and results
of the these toxicity studies:
Pilot Rat Teratology Study
"In this study, [the test compound] was administered by
gavage to 6 groups of mated female rats at dose levels
of 0, 25, 50, 100, 200 and 400 mg/kg/day during gestation
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk* information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency polky or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
403
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8EHQ-0390-0895 S
Page 2 of 3
days 6-15. Surviving dams were sacrificed on gestation
day 20. Fetuses were removed, weighed, sexed and examined
for possible external malformations.
"At 400 mg/kg/day, 5/8 dams died, body weight gain was
significantly reduced compared to control and clinical
observations were increased. An increase in post implan-
tation loss which was not statistically significant and
a slight reduction in fetal body weight were observed at
400 mg/kg/day."
Pilot Rabbit Teratology Study
"[The test compound] was administered by gavage to 6
groups of artificially inseminated female rabbits at dose
levels of 0, 100, 250, 500, 750 and 1000 mg/kg/day.
Surviving dams were sacrificed on gestation day 29.
Fetuses were removed, weighed, sexed and examined for
external malformations.
"Maternal deaths were observed in 4/7, 3/7 and 5/7 dams
at 500, 750 and 1000 mg/kg respectively. Abortions,
reduced body weight gain and clinical observation related
to treatment occurred in dams at dose levels of 250 mg/kg
and higher. As a result of deaths and abortions in the
750 and 1000 mg/kg groups, there were no surviving
pregnant females at the scheduled necropsy. Fetal body
weights were severely reduced at 500 mg/kg and slightly
reduced at 500 mg/kg and slightly reduced at 250 mg/kg."
Rabbit Teratology Study
" In this study, [the test compound] was administered by
gavage to 4 groups of artificially inseminated female
rabbits at dose levels of 0, 10, 75 and 175 mg/kg/day.
Surviving dams were sacrificed on gestation day 29.
Fetuses were removed, weighed, sexed and examined for
external, visceral and skeletal malformations and
variations.
"Abortions occurred in 0/20, 2/20, 1/20 and 1/20 dams at
0, 10, 75 and 175 mg/kg/day respectively. Maternal body
weight gains were decreased compared to control at 175
mg/kg/day. Post implantation loss was increased at 75
mg/kg/day, but not at 175 mg/kg/day. Fetal body weights
were slightly reduced at 175 mg/kg/day, but were within
historical control range. A statistically significant
increase in one skeletal variation was observed at 75 and
175 mg/kg/day. The response for this skeletal variation
did not follow a dose-related pattern and the incidences
at both dose levels were within historical control range.
404
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8EHQ-0390-0895 S
Page 3 of 3
A non-statistically significant increase in one mal-
formation (carpal flexure) was observed at 175 mg/kg/day.
The incidence for this malformation at 175 mg/kg/day was
outside of historical control range."
V9B AffP ESPQ8PRB FOTBMTXMt
According to the OBJECTIVE section of the pilot rabbit teratology
study, " the selected route of administration [for this study] was
oral since this is the potential route of human exposure.** The
submitter did not provide any additional information regarding the
use(s) of or the potential for exposure to this chemical.
COMMEMTa/RECOMMBlTOATIOMB
It should be noted that EPA has received several TSCA Section
8(e) notices on compounds identified as "pyridine carboxylates."
The reader's attention is directed to the "Status Reports" prepared
by EPA in response to these other TSCA Section 8(e) notices
(8EHQ-1287-0707 S and 8EHQ-0288-0716 S) .
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, the submitter will be requested
to describe the actions that the company has taken or
plans to take 1) to notify workers/others about the
reported information, and 2) to reduce or eliminate
exposure to the subject chemical. The submitter will be
asked also to provide copies of Material Safety Data
Sheets and labels that have been revised to reflect the
reported findings. In addition, the submitter will be
asked to describe the nature and results, if available,
of all studies (other than those submitted already to
EPA or those cited in the published scientific
literature) about which the company is aware or that
the company has conducted, is conducting or plans to
conduct that are designed to determine the toxicity of
or the exposure to the subject chemical.
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will review the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
405
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^t0!X
Page 1 of 3
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
dates APR - 3 1990
APPROVED:
OFFICE OF
PESTICIDES AND
A U L L TOXIC SUBSTANCES
{(, Um^ HtiMo
SUBJECT: status Report1 8EHQ-0390-0696 B
i
PROM: Martha G. Price, Ph.D., ChemistdA^^Cf ^ A
Chemical Risk Identification Section/CSB ^
TO: Janes F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
The submitting company has claimed its company name and the exact
identity of the subject chemical as TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. In the "sanitized*' version of its Section 8(e)
notice, the company reported non-confidentially that the generic
name of the subject chemical is "Substituted Acetanilide I."
SUBMISSION DESCRXPTION
The submitting company provided the following summary information
regarding the conduct and final results of both a pilot teratology
study and the follow-up teratology study in ratss
"In the pilot rat teratology study the substituted
acetanilide was administered by gavage to 6 groups of
mated female rats at dose levels of 0, 10, 50, 250, 750
and 1000 mg/kg/day. Surviving dams were sacrificed on
gestation day 20. Fetuses were removed, weighed, sexed
and examined for external malformations and variations.
1 This status report is the result of a preliminary evaluation of information that has
been submitted to EPA under Section 8(e), the "substantial risk?' information reporting
provision of the Toxic Substances Control Act (TSCA). The statements made in this status
report should not be regarded as expressing final Agency policy or intent with respect to the
subject chemical(s). Any review of this status report should take into account that the
report may be based on incomplete information.
406
-------
8EHQ-0390-0896 S
Page 2 of 3
"All dams died or were sacrificed in extremis at 1000
mg/kg/day and 4/5 dams died at 750 mg/kg/day. Maternal
body weight gains were moderately decreased at 750
mg/kg/day and slightly decreased at 250 mg/kg/day. Early
resorptions were increased at 750 mg/kg/day. The data at
750 mg/kg/day was from one female which had a total
litter resorption.
"In the rat teratology study...the same material was
administered by gavage to 4 groups of mated female rats
at dose levels of 0, 30, 100 and 300 mg/kg/day. Surviving
dams were sacrificed on gestation day 20. Fetuses were
removed, weighed, sexed and examined for external,
visceral and skeletal malformations and variations.
"Maternal body weight gains were slightly reduced at 300
mg/kg. A statistically significant decrease in fetal body
weights compared to control was observed at 300 mg/kg."
USE AND EXPOSORB POTENTIAL
In view of the submitter's TSCA CBI claims, no information
regarding the TSCA Chemical Substance Inventory status or use of
the subject chemical will appear in this status report.
COMMENTfl/RECQMMENDATXONfl
It should be noted that EPA has received other TSCA Section 8(e)
notices on compounds identified generically as Substituted
Acetanilides. The reader's attention is directed to the status
reports prepared by EPA in response to 8EHQ-0290-0889 S and 8EHQ-
0390-0897 S.
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, the submitter will be requested
to describe the actions that the company has taken or
plans to take 1) to notify workers/others about the
reported information, and 2) to reduce or eliminate
exposure to the subject chemical. The submitter will be
asked also to provide copies of Material Safety Data
Sheets and labels that have been revised to reflect the
reported findings. In addition, the submitter will be
asked to describe the nature and results, if available,
of all studies (other than those submitted already to
EPA or those cited in the published scientific
literature) about which the submitter is aware or that
the company has conducted, is conducting or plans to
conduct that are designed to determine the toxicity of
or the exposure to the subject chemical.
407
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8EHQ-0390-0896 S
Page 3 of 3
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will review the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
408
-------
Page 1 of 3
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WW
\ ,
-------
8EHQ-0390-0897 S
Page 2 of 3
"All dams died at 1200 mg/kg and 2/5 died at 600 mg/kg.
A severe reduction in maternal body weight gain was
observed at 300 mg/kg and a slight reduction in body
weight gain was observed at 150 mg/kg. A
non-statistically significant increase in post
implantation loss was observed at 300 and 600 mg/kg/day.
"In a follow-up rat teratology study, the substituted
acetanilide was administered by gavage to 4 groups of
mated female rats at dose levels of 0, 50, 200 and 400
mg/kg/day. On gestation day 20 surviving dams were
sacrificed. Fetuses were removed, weighed, sexed and
examined for external, visceral and skeletal
malformations and variations.
"Maternal body weights were moderately decreased at 400
mg/kg/day. A non-statistically significant decrease in
fetal body weights was observed at 400 mg/kg/day.
Dwarfism was observed in 5 fetuses in one litter at 400
mg/kg/day vs. 0 in the control. The report stated that
single litters with multiple fetuses with dwarfism have
been seen in historical controls."
USE AND EXPOSURE POTENTIAL
In view of the submitter's TSCA CBI claims, no information
regarding the TSCA Chemical Substance Inventory status or use of
the subject chemical will appear in this status report.
COMMENTS/RECOMMENDATIONS
It should be noted that EPA has received other TSCA Section 8(e)
notices on compounds identified generically as Substituted
Acetanilides. The reader's attention is directed to the status
reports prepared by EPA in response to 8EHQ-0290-0889 s and 8EHQ-
0390-0896 S.
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, the submitter will be requested
to describe the actions that the company has taken or
plans to take 1) to notify workers/others about the
reported information, and 2) to reduce or eliminate
exposure to the subject chemical. The submitter will be
asked also to provide copies of Material Safety Data
Sheets and labels that have been revised to reflect the
reported findings. In addition, the submitter will be
asked to describe the nature and results, if available,
of all studies (other than those submitted already to EPA
or those cited in the published scientific literature)
about which the submitter is aware or that the company
410
-------
8EHQ-0390-0897 S
Page 3 of 3
has conducted, is conducting or plans to conduct that
are designed to determine the toxicity of or the exposure
to the subject chemical.
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will review the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
411
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 3
OFFICE OF
PEST1CIDE8 AND
date: MAR 3 0 1990 approved: ^ T, ikokd TOXIC8UBSTANCE3
FROM: Martha G. Price, Ph.D., Che
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
E. I. DuPont de Nemours & Company, Inc. provided the following
summary information regarding the conduct and preliminary results
of a single-dose rat gavage study on 4,4'-(l,3-phenylenebis-
(oxy)bisbenzenamine [RODA; CAS No. 2479-46-1]:
"This study was conducted to determine whether RODA is
potentially retinotoxic.
"In this study, male albino rats were exposed to RODA by
gavage at dosages of 130, 200, 310, 460, 690 and 1000
mg/kg using 1-4 rats per dose level. After 1 and 8 days
post exposure, rats from the 130, 200, 310 460 and 1000
mg/kg groups were examined for funduscopic changes by
indirect ophthalmoscopy. All rats surviving the 14-day
postexposure observation period were killed and the eyes
processed for histopathologic examination by light
microscopy.
"The results of this study showed that RODA is slightly
toxic (approximate lethal dosage ¦ 690 mg/kg) by gavage.
The ophthalmoscopic examinations revealed a pale fundus,
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
SUBJECT: Status Report1 8EHQ-0390-0898
412
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8EHQ-0390-0898
Page 2 of 3
seen initially 1 day after treatment at 1000 mg/kg and
in most rats at dosages of 130 mg/kg or greater 8 days
after exposure. Additional ophthalmoscopic changes were
found in the rats administered 460 and 1000 mg/kg RODA.
At 460 mg/kg, ophthalmologic changes included unilateral
subcapsular and posterior cortical cataract, posterior
synechiae, incomplete mydriasis, and small globe; these
changes may have been due to a preexisting lesion not
noted at the time of dosing. At 1000 mg/kg, bilateral
linear corneal opacities (possibly due to corneal drying)
were found ophthalmoscopically. Upon microscopic
examination, bilateral retinopathy, characterized by
retinal pigment epithelium hyperplasia, disruption of
retinal photoreceptor inner and outer segments and
retinal arcade/rosette formation were found at dosages
of 130 mg/kg or greater; no no observable effect level
was demonstrated. Although only a few animals were used
in this study, the severity of the retinal lesions did
not appear to be dose related. Based on these results,
we conclude that RODA is retinotoxic in rats."
USE AND EXPOSURE POTENTIAL
RODA is a research and development chemical within Du Pont. No
other information was provided regarding the use of or the
potential for exposure to RODA.
COMMENTS/RECOMMENDATIONS
EPA has received other Section 8(e) notices on compounds found to
cause retinopathic effects in animals. As an example, the reader's
attention is directed to the status report prepared by the Agency
in response to Section 8(e) submission number 8EHQ-1085-0571.
a) The Chemical Screening Branch will ask Du Pont to ensure
that EPA receives a complete copy of the final report
(including the actual experimental protocol, results of
gross and histopathological examinations, results of
statistical analyses, etc.) from the oral gavage study
cited in the submission.
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Du Pont will be requested to
describe the actions that the company has taken or plans
to take 1) to notify workers/others about the reported
information, and 2) to reduce or eliminate exposure to
the subject chemical. Du Pont will be asked also to
provide copies of Material Safety Data Sheets and labels
that have been revised to reflect the reported findings.
In addition, Du Pont will be asked to describe the nature
and results, if available, of all studies (other than
those submitted already to EPA or those cited in the
413
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8EHQ-0390-0898
Page 3 of 3
published scientific literature) about which Du Pont is
aware or that the company has conducted, is conducting
or plans to conduct that are designed to determine the
toxicity of or the exposure to the subject chemical.
b) As part of the "FIRST REVIEW" phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will review the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA? in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
414
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Page ! of 3
im
I
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
J' WASHINGTON, DC 20460
DATE! JUN -7 1990
FROM:
TO:
APPROVED:
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECTS Status Report1 8EHQ-0390-0899
Martha G. Price, Ph.D., Cheitfi's
Chemical Risk Identification Section/CSB
James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
The P Q Corporation provided the following summary information
regarding the conduct and final results of acute toxicity bioassays
for daphnid and for rainbow trout with tetramethylammonium
silicate, CAS No. 56982-91-3:
"A sample of The P Q Corporation tetramethylammonium
silicate was tested for potential lethality to . . .
(Rainbow Trout (Salmo crairdneri)). The 96-hour [Toxic
Level] TL50 was calculated to be greater than 100 mg/1.
"A sample of The P Q Corporation tetramethylammonium
silicate was tested for potential lethality to . . .
(Daohnia magna). The 48-hour TL50 was calculated to be
3.4 mg/1 (upper limit 4.1 mg/1 - lower limit 2.8 mg/1)."
[NOTE: According to further data provided by the company
in an addendum to the initial submission, the daphnid 48-
hour TL50 value was recalculated to be approximately 1.55
mg/1, and the rainbow trout 96-hour TL50 was recalculated
to be approximately 45.7 mg/1.]
1 This status report is the result of a preliminary evaluation of information that has
been submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substances Control Act (TSCA). The statements made in this status
report should not be regarded as expressing final Agency policy or intent with respect to the
subject chemical(s). Any review of this status report should take into account that the
report may be based on incomplete information.
415
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8EHQ-0390-0899
Page 2 of 3
USE AND EXPOSURE POTENTIAL
The P Q Corporation did not provide any information regarding the
use of or the potential for exposure to tetramethylammonium
silicate, nor was such information located in The Condensed
Chemical Dictionary (10th edition) consulted by EPA.
COMMENTS/RECOMMENDATIONS
The preface to Part V of EPS's March 16, 1978 TSCA Section 8(e)
policy statement ("Statement of Interpretation and Enforcement
Policy; Notification of Substantial Risk" 43 FR 11110) provides
general guidance regarding the Section 8(e)-reportability of
effects observed in aquatic toxicity studies. Part V(b)(3) of the
policy statement provides the following specific guidance regarding
the results of such studies:
"['The Agency considers effects for which substantial
risk information must be reported to include'] any non-
trivial adverse effect, heretofore unknown to the [EPA]
Administrator, associated with a chemical known to have
bioaccumulated to a pronounced degree or to be wide-
spread in environmental media." [emphasis added]
Based on professional judgement and in the absence of evidence to
the contrary, EPA does not believe that tetramethylammonium
silicate will bioaccumulate. Further, the P Q Corporation did not
provide, nor has EPA located, any information to suggest that this
chemical substance has been found to be widespread in any
environmental media. Therefore, it is EPA's opinion that in the
absence of such supplemental and supporting information, the data
showing that tetramethylammonium silicate is moderately toxic to
certain aquatic species does not appear to warrant formal reporting
to EPA under Section 8(e) of TSCA.
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, The P Q Corporation will be
requested to describe the actions that the company has
taken or plans to take to reduce or eliminate
environmental aquatic exposure to the subject chemical.
The P Q Corporation will be asked also to provide copies
of Material Safety Data Sheets and labels that have been
revised to reflect the reported findings. In addition,
The P Q Corporation will be asked to describe the nature
and results, if available, of all studies (other than
those submitted already to EPA or those cited in the
published scientific literature) about which is aware or
that the company has conducted, is conducting or plans
to conduct that are designed to determine the toxicity
of or the environmental exposure to the subject chemical.
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b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
417
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m | UNITED STATES ENVIRONMENTAL PROTECTION AGENCY page 1 of 3
<•, J? WASHINGTON, DC 20460
date: APR 31990
APPROVED:
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0390-0900
QujL&t/L tH
FROM: Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
gUBHisgtoy pggqgmiQN
The Methyl Tertiary Butyl Ether Health Effects Testing Task Force
submitted summary interim results from a chronic inhalation study
in which methyl tert-butyl ether (MTBE; CAS No. 1634-04-4) is being
administered to F-344 rats and CD-I mice for 18 months. According
to the MTBE Task Force, the study was initiated as a result of a
TSCA Section 4 Testing Consent Agreement for MTBE (40 CFR 799.5000;
53 FR 10391; March 31, 1988). The Section 8(e) notice contained
the following summary information about the study:
"Fifty animals per species per sex are [being] exposed
to concentrations of 8,000; 3,000; 400 and 0 ppm. . .
No mortality has been seen in the rats of either sex.
However, the mortality in the female and male mice is now
12 and 18 percent respectively in the 8,000 ppm exposure
group. Five male mice in the 8,000 ppm group and 1 male
mouse in the 400 ppm group have been found dead and were
noted to have obstructive uropathy. A further male mouse
at the 8,000 ppm level, currently living, has a distended
bladder which is indicative of the same condition. No
incidence has been observed in the unexposed (control)
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA), The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
418
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Page 2 of 3
animals nor in the female mice of any exposure group.
This obstructive uropathy is believed [to be] due to
physical matter blocking the urethral canal (known to be
narrower in the male mouse than in the female), rather
than due to an infection since histopathology from the
kidneys and other tissues appears to be normal. Addi-
tionally, the urine samples from one of the deceased
animals is within the normal range in terms of protein
content, specific gravity and lack of occult blood.
"Historically, this obstructive uropathy or dysuria has
been found particularly in unexposed male mice of this
CD-I strain (Maita et al., 1988). The incidence of
obstructive uropathy observed in this study appears to
occur earlier when compared to other studies and may be
due to a possible exacerbation of this condition by the
high exposure to MTBE."
A list of the companies sponsoring this chronic inhalation study
of MTBE can be found on page 3 of this status report.
USE AND EXPOSURE POTENTIAL
Information regarding the uses of and the potential for exposure
to MTBE is located in the final TSCA Section 4 Testing Consent
Order on methyl tert-butyl ether (53 FR 10391, March 31, 1988).
CQffliBWT6/R8MWBWPATt9MB
It should be noted that EPA has received a number of "For Your
Information" (FYI) submissions on MTBE. MTBE is also the subject
of TSCA Section 8(a) and 8(d) information gathering rules.
A discussion regarding the Section 8(e) reporting obligations of
trade associations and their member companies can be found in the
COMMENTB/REOOMMBNPATION8 section of the status report prepared by
EPA in response to Section 8(e) submission number 8EHQ-0186-0587.
Immediately upon receipt, the Chemical Screening Branch provided
a full copy of this TSCA Section 8(e) notice to the Test Rules
Development Branch (TRDB/ECAD/OTS) for inclusion in its ongoing
review of MTBE. It is important to point out that the Section 8(e)
reporting requirement applies to any substantial risk information
obtained during a study conducted under Section 4 of TSCA unless
such information, when obtained, is otherwise required to be sub-
mitted to EPA under Section 4 of TSCA. To date, EPA has received
a number of TSCA Section 8(e) notices containing interim results
of studies conducted under Section 4 of TSCA. The Section 8(e)
reporting that takes place in such instances occurs typically
before reporting of the information is required under Section 4.
If required reporting under Section 4 occurs before or coincidental
with an obligation to report under Section 8(e), the information
419
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Page 3 of 3
does not need to be submitted also under Section 8(e). The purpose
of this exemption is not to change substantially the Section 8(e)
reporting obligation, but is merely to avoid duplicative reporting
except in those cases in which the timeliness of such reporting is
paramount.
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, the MTBE Health Effects Testing
Task Force will be requested to ask the study sponsors
to describe for EPA the actions that the companies have
taken or plan to take 1) to notify workers/others about
the reported information, and 2) to reduce or eliminate
exposure to MTBE. The MTBE Health Effects Testing Task
Force will be requested also to ask the study sponsors
to provide to EPA copies of MTBE Material Safety Data
Sheets and labels that have been revised to reflect the
reported findings.
b) As was the case with the initial submission, staff of the
Chemical Screening Branch will send copies of all
reported information to TRDB/ECAD/OTS for review.
c) The Chemical Screening Branch will send copies of this
Status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and TRDB/ECAD/OTS;
in addition, copies of this status report will be sent
to the Environmental Assistance Division/OTS (formerly
the TSCA Assistance Office/OTS) for further distribution.
Reference
Maita, K., et al. (1988) Mortality, Major Cause of Morbundity, and
Spontaneous Tumors in CD-I Mice. Toxic. Path., 16:340-347.
Sponsoring CQropanieg
Amoco Corporation
ARCO Chemical Company
Exxon Chemical Company
Sun Refining and Marketing Company
Texaco Chemical Company
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
OFFICE OF
PESTICIDES AND
DATE! m -7 1990
APPROVED:
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EKQ-0390-0901 and 8EHQ-0390-0902
FROM: Martha G. Price, Ph.D., Chemis^ '/V i ^—
Chemical Risk Identification Section/C^^^y
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
In 8EHQ-0390-0902, Exxon Chemical Americas provided the following
summary information regarding the conduct and final results of
hematotoxicity and genotoxicity studies of 1,3-butadiene (CAS No
106-99-0) in mice and hamsters:
"1,3-Butadiene...has been previously reported as a
carcinogen in rodents and is classified by the
International Agency for Cancer Research as a Class 2B.
1,3-butadiene has been shown to cause bone marrow effects
in mice but not the rat. To further understand the range
of species susceptibility for this target organ, Exxon
conducted simultaneous exposures of mice and hamsters to
a concentration of 1,3-butadiene (1,000 ppm in air, for
six hours on each of two consecutive days) that was known
to produce hematotoxicity and micronuclei increase in
mice. 1,3-butadiene genotoxicity has not been previously
evaluated in the hamster.
"As expected, under these identical conditions, 1,3-buta-
diene produced substantial hematotoxicity and an 11.2-
fold increase in micronuclei formation (p <0.01) in the
B6C3F1 mouse. By comparison, no statistically significant
I This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
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8EHQ-0390-0902
Page 2 of 4
hematotoxicity (only a small downward trend) and a
marginal increase in micronuclei (p <0.05) were seen in
the Syrian hamster. The negative (air) control responded
in an appropriate manner. When compared to the negative
control (air), a 1.4 fold increase in the number of
micronuclei was observed for the hamster; in mice the
response was a 11.2 fold increase. Thus under the
conditions of this study 1,3-butadiene was clastogenic
in both species, however, it is substantially less toxic
to hamster bone marrow than to the mouse and it is only
marginally genotoxic to the hamster.
"This is a further indication of a species difference in
the response to 1,3-butadiene, as already evidenced by
existing metabolism data for different species. Based on
the above study and other studies in the literature, the
mouse is the most sensitive species to 1,3-butadiene. In
terms of bone marrow response and clastogenic activity,
the mouse is substantially greater than the hamster, with
no response for the rat or primate."
In 8EHQ-0390-0901, Exxon Chemical Americas provided the following
summary information regarding the conduct and final results of
hematotoxicity and genotoxicity studies of isoamylene (CAS No
26760-64-5) in mice. Isoamylene is a branched chain monoolefin
existing as two isomeric forms, 2-methyl-2-butene (CAS No 513-35-9)
and 2-methyl-l-butene (CAS No 563-46-2):
"As part of a study of structure-activity relationship,
Exxon conducted a micronucleus assay in the mouse by the
inhalation route. 1,3-butadiene was used as a positive
control. Isoamylene produced a dose-related statistically
significant increase in the micronucleus formation in
bone marrow (which is a measure of clastogenic activity)
and a dose-related significant decrease in the mean per
cent of polychromatic erythrocytes (which is a measure
of toxicity). Hence in this in vivo assay, isoamylene was
toxic and clastogenic in mouse bone marrow.
"A more detailed description of the study and the results
observed is as follows:
"B^CsFt mice were exposed to two six-hour exposures of
commercial isoamylene at target concentrations of 1,000,
3,260 and 10,000 ppm in air. Bone marrow samples were
collected and prepared for evaluation of the micronuclei
formation in polychromatic erythrocytes of the bone
marrow. 1,3-butadiene at a target concentration of 1,000
ppm in air was used as a positive control. 1,3-butadiene
produced a statistically significant increase (p <0.01)
in the number of micronuclei when compared to the
negative control (air). This response is comparable to
that previously reported in the literature.
422
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8EHQ-0390-0902
Page 3 of 4
"The isoamylene (90.1 per cent 2-methyl-2-butene and 8.9
percent 2-methyl-1-butene) produced a dose-related
statistically significant decrease in the mean per cent
of polychromatic erythrocytes and a dose-related
statistically significant increase in micronuclei; the
latter increase was significant from control at 3,260
ppm. Under the conditions of this assay, isoamylene
induced clastogenic abnormalities for B6C3F1 mice at 3,260
to 10,000 ppm when evaluated 24 hours after the last
treatment.
"2-Methyl-2-butene (of 85 per cent purity) has been
previously evaluated and reported inactive in four
genotoxicity assays: S. typhimurium, E. coli, S.
cerevisiae and rat liver chromosome assay. These used
metabolic activating system derived from the rat and not
the mouse. The activity observed in this micronucleus
study reported here may be a reflection of the mouse
metabolism."
USE AND EXPOSURE POTENTIAL
Exxon stated that isoamylene is manufactured by Exxon as a chemical
intermediate for the production of commercial polymers. Exxon also
stated that 1,3-butadiene has a variety of uses as a chemical raw
material. According to The Condensed Chemical Dictionary (10th
edition), 1,3-butadiene uses include "synthetic elastomers
(styrene-butadiene, polybutadiene, neoprene; nitriles) ABS resins;
chemical intermediate."
COMMENTS/RECOMMENDATIONS
The Agency has received a number of TSCA § 8(e) and "For Your
Information" (FYI) submissions on 1,3-butadiene. In addition, the
Chemical Screening Branch prepared a Chemical Hazard Information
Profile (CHIP) in 1981. In 1985, 1,3-Butadiene was referred to
OSHA through TSCA §9(a). The Risk Analysis Branch is evaluating
current information and coordinating a response to OSHA.
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Exxon will be requested to
describe the actions that the company has taken or plans
to take 1) to notify workers/others about the reported
information, and 2) to reduce or eliminate exposure to
the subject chemicals. Exxon will be asked also to
provide copies of Material Safety Data Sheets and labels
that have been revised to reflect the reported findings.
In addition, Exxon will be asked to describe the nature
and results, if available, of all studies (other than
those submitted already to EPA or those cited in the
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8EHQ-0390-0902
Page 4 of 4
published scientific literature) about which Exxon is
aware or that the company has conducted, is conducting
or plans to conduct that are designed to determine the
toxicity of or the exposure to the subject chemicals.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of isoamylene
at this time. All incoming information relating to 1,3-
butadiene will be sent to staff of the Risk Analysis
Branch (RAB/ECAD) for review.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and RAB/ECAD/OTS;
in addition, copies of this status report will be sent
to the Environmental Assistance Division/OTS (formerly
the TSCA Assistance Office/OTS) for further
distribution.
424
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^tos^
(A
I
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY Page 1 of 3
WASHINGTON, DC 20460
DATE:
SUBJECT:
FROM:
to:
APR 2 4 1990
APPROVEDJ
: ^L. IF'
8EHQ-0390-0903 8
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
Status Report1
i drfA H ^ a+4 * J
Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
The submitting company has claimed its company name and the exact
identity of the subject chemical as TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. In the "sanitized" version of its Section 8(e)
notice, the company reported non-confidentially that the subject
chemical is a "naphthalenol aromatic azo dye of alkyl compounds."
SUBMISSION DEBCRIPTIOM
The submitting company provided the final report of a definitive
in vivo mouse micronucleus assay and a draft report of an in vitro
mutagenicity study on the naphthalenol aromatic azo dye compound.
The following information regarding the conduct of the mouse micro-
nucleus assay is contained in the SUMMARY section of the submitted
final report:
"[This study was conducted to assess the ability of the
test compound to induce micronuclei (MN) in peripheral
erythrocytes following oral administration to male and
I This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk' information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
425
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8EHQ-0390-0903 S
Page 2 of 3
female Swiss-Webster mice. Based upon the results of
the range-finding study] the doses selected for the
definitive assay were 1200, 2500, and 5000 mg/kg BW
[body weight]. The positive control selected for the
definitive assay was benzene (500 mg/kg).
The submitter reported in the cover letter that "the micronucleus
results were considered inconclusive by the test laboratory since
a statistically significant elevation in micronucleated RNA
containing erythrocytes is observed in only one treatment group
and the dose-response trend is not significant."
According to the CONCLUSION section of the in vitro bacterial
mutagenicity study (Ames test), the test compound was found to
exhibit mutagenic activity by "inducing frameshift mutations
following metabolic activation (and weak activity without
metabolic activation)."
The submitter provided a copy of the Material Safety Data Sheet
(MSDS) that will be revised by the company to reflect the
reported findings for the subject chemical.
QBE AND EXPOSURE POTENTIAL
The submitter reported non-confidentially that "this substance is
used to color petroleum products." In addition, the submitter
provided the following information regarding the potential for
exposure to this chemical:
"This substance is handled in a closed system at our
production facility. The total number of people in the
facility potentially exposed to this material is no
greater than 39. Periodic industrial hygiene
monitoring for air contaminants in the production area
shows that those volatile materials associated with the
process and manufacture of this material are well
within the Permis-sible Exposure Limits established by
the Occupational Safety and Health Administration."
The submitter reported that contact with workers in the field is
unlikely because the system is mechanical and enclosed. In
addition, the submitter noted that workers will be reluctant to
get the dye on their clothing since it is extremely difficult to
remove the dye completely from clothing.
The submitter also reported that "the potential for exposure to
the individual consumer is extremely small."
COMMENTS/RECOMMENDATIONS
In its submission, the submitter reported that a third
mutagenicity study is underway and will be sent to the Agency as
soon as the results are available.
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Page 3 of 3
Although a positive in vitro genotoxicity test, when considered
alone, may not be sufficient to offer reasonable support for a
conclusion of substantial risk (as that term is defined in EPA's
TSCA Section 8(e) policy statement ("Statement of Interpretation
^nd Enforcement Policy; Notification of Substantial Risk" 43 FR
11110; March 16, 1978)), EPA does believe that such information is
of value in assessing the possible risk(s) posed by exposure to the
tested chemical or mixture. Further, EPA believes that a positive
genotoxicity test result, in combination with other information
(e.g., knowledge of actual/potential exposure to and/or high pro-
duction of the tested chemical or mixture), would suggest the need,
in many cases, to conduct further studies designed to determine
the toxicity of or the exposure to that chemical substance or
mixture. EPA expects the results of such additional studies to be
considered also for submission under Section 8(e) of TSCA.
a) The Chemical Screening Branch will ask the submitter to
ensure that EPA receives complete copies of the final
reports (including the actual experimental protocol,
results of gross and histopathological examinations,
results of statistical analyses, etc.) from the range-
finding micronucleus assay and the on-going mutagenicity
study cited in the submission.
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, the submitter will be asked also
to provide copies of Material Safety Data Sheets and
labels that have been revised to reflect the reported
findings, in addition, the submitter will be asked to
describe the nature and results, if available, of all
studies (other than those submitted already to EPA or
those cited in the published scientific literature) about
which the company is aware or that the company has
conducted, is conducting or plans to conduct that are
designed to determine the toxicity of or the exposure to
the subject chemical.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA? in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
427
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
APR 2 4 1990
OFFICE OF
PESTICI0E8 AND
TOXIC SUBSTANCES
DATE:
APPROVED:
SUBJECT: status Report1 8EHQ-0390-0904
FROM: Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
Akzo Chemicals Inc. provided the following summary information
regarding the conduct of a developmental range-finding toxicity
study in rabbits:
" ...gravid rabbits were exposed to 100, 300, 1000, or
3000 ppm CS2 (carbon disulfide? CAS No. 75-15-0) vapor
for 6 hrs/day during days 6-19 of gestation."
An addendum to this submission provided the following summary
information regarding the preliminary results of this developmental
toxicity study:
"Maternal Toxicity
"Four of six animals in the 3000 ppm group died during
the 6 hour dose period on the first day of exposure. The
remaining two animals in the 3000 ppm group were
sacrificed due to moribund condition following the first
day of exposure.
I This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
428
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"Clinical signs of maternal toxicity were observed in
the 1000 ppm group and included tremors in one animal on
Gestation Day 16 and ataxia in one animal on Gestation
Day 15. Two animals exhibited tremor on Day 16.
"Low food consumption was observed in one animal in the
100 ppm group, 3 animals in the 300 ppm group and 5
animals in the 1000 ppm group. Diet consumption was low
in these animals during the exposure period and returned
to normal by Gestation Day 23. Mean maternal body weights
were slightly lower in the 1000 ppm group, on Gestation
Day 18 compared to the 100 and 300 ppm groups, as well
as historical control values.
Reproduction Parameters
"Rabbits were euthanitized on Gestation-29 and received
a Cesarean section, six females from each exposure group
surviving the treatment regimen were examined and all 18
females were pregnant. Corpora lutea counts and
implantation totals were comparable among exposure groups
and the historical control.
"Postimplantation loss was significantly increased in
the 1000 ppm group when compared to the 100 and 300 ppm
groups. A slight increase relative to historical control
was also observed in the low exposure, but not the
mid-exposure group. Postimplantation loss consisted
predominantly of early resorptions.
Fetal Evaluations
"No dead fetuses were observed in any dose group. The
number of live pups was significantly lower in the 1000
ppm group when compared to the 100 and 300 ppm groups
and the historical control. This was due to the large
increase in postimplantation loss in the 1000 ppm group.
"The mean fetal body weights were significantly lower in
the 1000 ppm group when compared to both the 100 and 300
ppm.dose groups, as well as the historical control. Mean
crown rump lengths were comparable among the 100 and 300
concentration groups, but was diminished in the 1,000 ppm
concentration group.
"No malformations were observed in the 100 and 300 ppm
concentration groups. However, there was a significant
increase in the number of gross anatomic malformations
observed during the external exams of the 1000 ppm
exposure group;three of six litters in the 1000 ppm dose
group contained fetuses with external malformations. One
of the six litters consisted of all early resorptions.
The two remaining litters in the 1000 ppm dose group
contained both live, (externally) normal fetuses and
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Page 3 of 4
early resorptions. A total of 10 major external
malformations in 9 individual fetuses (in three litters)
were observed in the total of 30 fetuses in the 1000 ppm
group. Three of six fetuses in one litter were observed
with umbilical hernia. Four of ten fetuses in another
litter had various tail malformations from absent to
shortened and crooked tail. Two of two fetuses in another
litter were observed with major cranial malformations.
One fetus was observed with a meningocele, abnormally
shaped head and abnormally shaped left eye. A second
fetus was observed with hydrocephaly.11
In the cover letter accompanying the initial submission, Akzo
Chemicals Inc. reported that "the preliminary data suggest that
the no [observed] effect level (NOEL) for CS2-induced developmental
toxicity and reproduction indices is at least 3 00 ppm occurring in
does which display equivocal maternal toxicity (i.e., lowered food
consumption)." In addition, Akzo reported that "the developmental
toxicity observed at 1000 ppm CS2 in the range-finding study is
similar to that reported for rabbits receiving 25-125 mg/kg CS2 by
gavage (Jones-Price, 1984)."
PfiE AND EXPOSURE POTENTIAL
The Condensed Chemical Dictionary (10th Edition) states that carbon
disulfide may be used in the manufacture of viscose rayon,
cellophane, carbon tetrachloride and flotation agents. Carbon
disulfide may also be used as a solvent.
COMMENTS/RECOMMENDATIONS
Akzo Chemicals Inc. reported that they will sponsor a definitive
developmental toxicity study and this study will be forwarded to
the Agency.
a) The Chemical Screening Branch will ask Akzo Chemicals
Inc. to ensure that EPA receives complete copies of the
final reports (including the actual experimental
protocol, results of gross and histopathological
examinations, results of statistical analyses, etc.) from
the range-finding and definitive developmental studies
cited in the submission.
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Akzo Chemicals Inc. will be
requested to describe the actions that the company has
taken or plans to take 1) to notify workers/others about
the reported information, and 2) to reduce or eliminate
exposure to the subject chemical. Akzo Chemicals Inc.
will be asked also to provide copies of Material Safety
Data Sheets and labels that have been revised to reflect
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the reported findings. In addition, Akzo Chemicals Inc.
will be asked to describe the nature and results, if
available, of all studies (other than those submitted
already to EPA or those cited in the published scientific
literature) about which the company is aware or that the
company has conducted, is conducting or plans to conduct
that are designed to determine the toxicity of or the
exposure to the subject chemical.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA? in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
Reference
Jones-Price et al. "Teratologic evaluation of carbon disulfide
administered to New Zealand White Rabbits on gestational days 6
through 19", Final Study Report, NCTR Contract No. 222-80-2031 (C),
February, 1984.
431
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Ub.
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY Page 1 of 3
WASHINGTON, DC 20460
DATE:
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
APR 2 4 1990
APPROVED:
nhoht
SUBJECT: Status Report1 8EHQ-0390-0905 8
FROM: Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
The submitting company has claimed its company name and the exact
identity of the subject chemical as TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. The submitter did provide the following non-
confidential generic name for the subject chemical: "aromatic
amine."
SUBMISSION DESCRIPTION
The submitting company provided the following information regarding
a recent incident in Mexico:
"On 6 February 1990 we were informed by our customer that
a trailer carrying technical grade [of the subject
chemical] had overturned in a remote area of Mexico and
a quantity of [the compound] was spilled. We were later
I This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
432
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Page 2 of 3
told that clean up crews were sent to rectify the
situation and that all spilled [material] had been
recovered and placed securely in closed drums for proper
disposal.
"Several days later, 15 February 1990, we were told that
a number of workers from the clean up crew may have been
exposed to small quantities of [the aromatic amine] even
though they were given appropriate protective equipment.
We learned that one of the cleanup workers died following
payment for work performed. The best evidence is that the
death was attributed to excessive drinking. Subsequently,
as a precaution, we were told that a number of the clean
up workers were taken to a local hospital and examined.
They were given blood test for methemoglobin ... The test
was negative for all - no methemoglobin was found.
However, two workers were found to have elevated blood
levels of the liver enzyme transaminase. These levels
fell and all of the workers were subsequently released."
USB AND EXPOSURE POTENTIAL
The submitter did not provide any information regarding the use of
the subject chemical.
CQMMPNTg/RBgPMMBmTTQFg
Although the information provided by the submitter does not appear
to be of the type required for submission under Section 8(e), the
"substantial risk" information reporting provision of TSCA, the
subject information does appear to be of the type required to be
recorded/maintained by the submitter under section 8(c), a
mandatory recordkeeping provision of TSCA. On August 22, 1983,
the Agency published (48 FR 38178) a final rule that requires
chemical manufacturers and certain chemical processors to maintain
records of significant adverse reactions alleged to have been
caused by a TSCA-covered chemical substance or mixture. This TSCA
Section 8(c) rule also requires that allegations that involve
significant adverse reactions in workers be maintained for 30 years
and that other recordable allegations be kept for 5 years. It
should be noted also that the Agency is empowered to inspect and/or
require submission of corporate TSCA Section 8(c) records and has
done so on a number of occasions to date.
a) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
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8EHQ-0390-0905 S
Page 3 of 3
The Chemical Screening Branch will send copies of this
Status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
434
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
DATE:
MOT 301990
APPROVED
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT. Status Report1 8EHQ-0390-0906 S Initial
8EHQ-049G-0906 S Supp
FROM: Jacqueline T. Favilla, Biologist
Chemical Risk Identification Sectioi
'
»nfcSB
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
Baker Performance Chemicals, Inc. provided final reports of 96-hour, static, acute toxicity studies of the
fathead minnow (Pimeohales promelasl and a 48-hour, static, acute toxicity study of the daphnid fDaphnia
magnal with Baker 417 (Magnaclear W 241). In a supplemental submission, Baker Performance Chemicals
provided a final report of a 96-hour acute toxicity test in algae (Selenastrum capricornutumV In the cover
letters of both submissions, the company stated non-confidentially that this substance is the subject of a
TSCA Section 5 "Pre-Manufacture Notice" (PMN) with the reference number P-88-2100.
COMMENTS/RECOMMENDATIONS
The non-confidential version of P-88-2100 obtained from the OTS public files states that the generic name
of this substance is "cationic terpolymer of aciylamide" and that its use is "water clarification."
a) In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity/exposure data, the company will be requested to describe
the actions that it has taken or plans to take 1) to notify workers and others about the
reported data, and 2) to reduce or eliminate exposure to the subject chemical. The
company will be asked to provide copies of Material Safety Data Sheets and labels that have
been revised to reflect the reported findings. In addition, the company will be asked to
describe the nature and results, if available, of all studies (other than those submitted
already to EPA or those cited in the published scientific literature) about which the
company is aware or that it has conducted, is conducting or plans to conduct that are
designed to determine the toxicity of the subject chemical
b) As was the case with the initial Section 8(e) submission, the Chemical Screening Branch
will notify the Chemical Control Division (CCD/OTS) about all incoming information.
c) Copies of this status report will be sent to NIOSH, OSHA, CPSC, FDA, NTP,
OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and CCD/OTS; copies
will be sent also to the Environmental Assistance Division/OTS for further distribution.
1 This status report reflect* Information submitted to EPA under Section 8(e), the "substantial lisk" information reporting provision
of the Toode Substance* Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemkal(*). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Man (Room G-004), 401 "M" Street S.W., Washington, DC. 204«0. All requests tor TSCA
Section 8(e) notices should be addressed to EPA's Ftaedom of Information Office (A-101).
435
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Page 1 of 3
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
DATE: APR 20 1990 APPROVED
SUBJECT! Status Report1 8EHQ-0390-0908 8
:^aw?
OFFICE Of
PESTICIDES AND
TOXIC SUBSTANCES
FROM: Jacqueline T. Favilla, Biologist .
Chemical Risk Identification Sectix>n/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
Ricoh Electronics Inc. reported non-confidentially that the subject
chemical is 4,41-[oxybis(2,1-ethanediylthio)]bisphenol, commonly
known as DD-63. Ricoh also reported non-confidentially that this
chemical is the subject of a TSCA Section 5 Pre-Manufacture Notice
(PMN No. P89-651) and a Section 5 Consent Order. According to the
sanitized version of P89-651 obtained from EPA's public files, the
subject chemical substance has the following CAS Registry Number:
90884-29-0.
SUBMISSION DESCRIPTION
Ricoh Electronics Inc. provided final reports of a subacute 28-day
oral gavage study in the rat and a 96-hour acute toxicity study
(LC50) in carp with DD-63. The following summary information was
given in the cover letter of these reports:
"In a subacute 28-day oral toxicity study with DD-63 by
daily gavage in the rat, elevated serum inorganic
phosphate levels were observed in male rats at all dose
levels (50, 200, and 1000 mg/kg/day) and in female rats
at the highest dose level; however, these levels were
within the normal range. The toxicological significance
I This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency polity or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
437
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Page 2 of 3
of these changes is unclear. At the highest dose level,
other findings include diarrhea, decreased body weight
gain, and changes in blood chemistry in male and female
rats, and changes in hematologic parameters in females
only."
"In the [acute toxicity study in carp], 10 fish per
concentration were exposed for 96 hrs in semi-static
system to a concentration range of 1.0 to 10 mg/1 forming
a geometric progression with a factor 1.8 and a blank
control . . . After 24 hours of exposure all fish had
died at nominally 5.6 and 10 mg/1. At 3.2 mg/1, mortality
of fish was recorded from 48 hours of exposure resulting
in 90% mortality at the end of the test. No mortality
was observed at or below 1.8 mg/1 or the controls.
"The LC50 of DD-63 ranged from 1.0 to 1.6 mg/1, with no
mortality observed at 0.7 to 1.1 mg/1."
It should be noted that the sanitized version of P89-651 contains
the results of a wide variety of in vitro mutagenicity and in vivo
mammalian toxicity studies, as well as aquatic species toxicity
studies, of DD-63.
USE AND EXPOSURE POTENTIAL
In its TSCA Section 8(e) submission, Ricoh Electronics Inc. did not
provide any non-confidential information with regard to the use of
or the potential for exposure to DD-63. The sanitized version of
P89-651 states that DD-63 is used in the "manufacture of office
machine paper" and provides some information about the potential
for exposure to the chemical.
COMMENTS/RECOMMENDATIONS
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Ricoh Electronics Inc. will be
requested to describe the actions that the company has
taken or plans to take 1) to notify workers/others about
the reported information, and 2) to reduce or eliminate
exposure to the subject chemical. Ricoh Electronics Inc.
will be asked also to provide copies of Material Safety
Data Sheets and labels that have been revised to reflect
the reported findings. In addition, Ricoh will be asked
to describe the nature and results, if available, of all
studies (other than those submitted already to EPA or
those cited in the published scientific literature) about
which Ricoh is aware or that the company has conducted,
is conducting or plans to conduct that are designed to
determine the toxicity of or the exposure to the subject
chemical.
438
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8EHQ-039CM0908
Page 3 of 3
b) As was the case with the initial Section 8(e) submission,
the Chemical Screening Branch will send full copies of
all reported information to the Chemical Control Division
(CCD/OTS) for review; CCD is responsible for implementing
EPA's Section 5 "New Chemicals Program" (NCP).
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and CCD/OTS/OPTS;
in addition, copies of this report will be transmitted
to the Environmental Assistance Division/OTS (formerly
the TSCA Assistance Office/OTS) for further distribution.
439
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
DATE: m 21 MO APPROVED:
/Znr\ f/zzAi
TOXIC SUBSTANCES
PESTICIDES AND
OFFICE OF
SUBJECT: Status Report1 8EHQ-03900909
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
Mitsubishi Gas Chemical America, Inc. submitted final reports of a negative in vivo Mouse Micronucieus
Test and a Chinese Hamster Ovary (CHO) Cell Assay considered by the company to be "not clastogenic"
with m-xylenediamine (CAS No. 1477-55-0).
COMMENTS/RECOMMENDATIONS
It is EPA's position that the provided studies did not warrant reporting under Section 8(e) of TSCA;
however, it must be made clear that EPA may not be aware of other information that was used by the
company in its determination to submit these reports to EPA under Section 8(e). It is important to note
also that although a positive in vitro genotoxicity test, when considered alone, may not be sufficient to offer
reasonable support for a conclusion of substantial risk (as that term is defined in EPA's TSCA Section 8(e)
policy statement ("Statement of Interpretation and Enforcement Policy; Notification of Substantial Risk" 43
FR 11110; March 16, 1978)), EPA does believe that such information is of value in assessing the possible
risk(s) posed by exposure to the tested chemical or mixture. Further, EPA believes that a positive
genotoxicity test result, in combination with other information (e.g., knowledge of actual/potential exposure
to and/or high production of the tested chemical or mixture), would suggest the need, in many cases, to
conduct further studies designed to determine the toxicity of or the exposure to the chemical(s). EPA
expects the results of such additional studies to be considered also for submission under Section 8(e).
a) The company will be asked to describe the nature and results, if available, of all studies
(other than those submitted already to EPA or those cited in the published scientific
literature) about which the company is aware or that it has conducted, is conducting or
plans to conduct that are designed to determine the toxicity of the subject chemical.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
FDA, CPSC, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
440
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Page 1 of 4
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
DATES MAY - I 1990
APPROVED
TOXIC SUBSTANCES
PESTICIDES AND
SUBJECT: Status Report1 8EHQ-0390-0910 S
FROM: Martha G. Price, Ph.D., Chemist
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
The submitting company has claimed its company name as TSCA
Confidential Business Information (CBI). Staff of the Information
Management Division will review all incoming correspondence related
to the company's TSCA CBI claim. In the "sanitized" version of
its Section 8(e) notice, the company reported non-confidentially
that the subject chemical is 2-ethylhexanol, CAS No. 104-76-7.
SUBMISSION DESCRIPTION
The submitting company provided the following summary information
regarding the conduct and preliminary results of a prenatal
toxicity study in rats after gavage administration of 2-ethyl-
hexanol :
"All alcohols investigated were administered to pregnant
Wistar rats (10/group) by gavage for 10 consecutive days
(days 6-15 post coitum) in daily doses of 1, 5 or 10
mmol/kg body weight.
I This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
NOTE
441
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8EHQ-039 0—0910 S
Page 2 of 4
"For comparison, two control groups were used. Control
Group No. I was dosed with double distilled water, while
Control Group No. 2 was dosed with the emulsifier (double
distilled water with approximately 0.005% Cremophor EL) .
"Food consumption and body weights of the animals were
recorded regularly throughout the study period. The state
of health of the animals was checked daily.
"On day 20 p.c., all surviving females were sacrificed
and assessed by gross pathology. The fetuses were
dissected from the uterus, weighed and further
investigated for any external, soft tissue and/or
skeletal findings.
"At the highest dose level (1,300 mg/kg body weight/day
-10 mmol/kg body weight) distinct signs of maternal
toxicity were observed. 6 dams of this group died on days
9, 10 or 13 p.c. Food consumption was markedly reduced,
mean body weights/body weight gains and corrected body
weight gains were clearly impaired (body weight loss on
days 6-10 p.c.; reduced body weight gains during days
10-15 p.c.). Severe adverse clinical symptoms (e.g.,
abdominal or lateral position, unsteady gait and apathy)
were recorded. Light brown-gray discoloration of the
liver was noted in the animals with intercurrent death.
Moreover, distinctly reduced mean gravid uterus weights
were seen. Clear signs of embryo/fetotoxicity,
substantiated by a distinctly increased number of
resorptions, markedly increased postimplantation loss and
reduced mean fetal body weights occurred. In a total of
28 fetuses, one fetus with rare external malformations
(atresia ani and acaudia) was found. A higher frequency
of fetuses exhibited soft tissue variations (dilated
renal pelvis and/or hydroureter). Moreover, a higher
number of fetuses with skeletal malformations, variations
and retardations was recorded.
"At 650 mg/kg body weight/day (~5 mmol/kg body weight),
only marginal signs of maternal toxicity were present (2
dams with piloerection).
"Slight embryo/fetotoxicity was observed in this group
in form of marginally reduced mean fetal body weights
and an increased number of fetuses with skeletal
variations and retardations.
"At the lowest dose (130 mg/kg body weight/day ~1 mmol/kg
body weight), no adverse substance-related effects on
dams or fetuses were seen.
442
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8EHQ-0390-0910 S
Page 3 of 4
"Overall... in the present study, obvious signs of
developmental toxicity (including teratogenicity)
occurred only when severe maternal toxicity was evident."
USE AND EXPOSURE POTENTIAL
The submitter did not provide any information regarding the use of
or the potential for exposure to 2-ethylhexanol. According to The
Condensed Chemical Dictionary (10th edition), 2-ethylhexanol is
used as a "plasticizer for PVC resins, defoaming agent, wetting
agent, organic synthesis, solvent mixtures for nitrocellulose,
paints, lacquers, baking finishes, penetrant for mercerizing
cotton, textile finishing compounds, plasticizers, inks, rubber,
paper, lubricants, photography, dry cleaning."
It should be noted that 2-ethylhexanol was recommended for testing
under TSCA Section 4 by the Interagency Testing Committee. The
reader's attention is directed to 52 FR 28698 (August 3, 1987) for
further information about use and exposure to 2-ethylhexanol.
COMMENTS/RECOMMENDATIONS
The submitter reported that the company will notify all customers
of these results and submit additional information to the EPA as
it becomes available.
It should be noted that EPA has received other TSCA Section 8(e)
and "For Your Information" (FYI) submissions on 2-ethylhexanol.
This chemical is also the subject of TSCA Section 8(d) information
gathering rule. According to the submitter, this prenatal toxicity
screening study with 2-ethylhexanol was "listed" under TSCA 8(d)
under the following study title, "The behavior of 2-ethylhexanol
in a short-term teratogenicity screening model in rats."
a) The Chemical Screening Branch will ask the submitter to
ensure that EPA receives a complete copy of the final
report (including the actual experimental protocol,
results of gross and histopathological examinations,
results of statistical analyses, etc.) from the prenatal
toxicity study cited in the submission.
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, the submitter will be requested
to describe the actions that the company has taken or
plans to take 1) to notify workers about the reported
information, and 2) to reduce or eliminate exposure to
the subject chemical. The submitter will be asked also
to provide copies of Material Safety Data Sheets and
labels that have been revised to reflect the reported
findings.
443
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8EHQ-0390-0910 S
Page 4 of 4
b) As was the case with the initial submission, staff of
the Chemical Screening Branch will send full copies of
all reported information to TRDB/ECAD/OTS for review.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and TRDB/ECAD/OTS;
in addition, copies of this status report will be
transmitted to the Environmental Assistance Division/OTS
(formerly the TSCA Assistance Office/OTS) for further
distribution.
444
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Page 1 of 3
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
OFFICE OF
PESTICIDES AND
DATE: MAY -2 1990
APPROVED:
TOXIC SUBSTANCES
SUBJECTS Status Report1 8EHQ-0390-0911 8
FROM: Martha G. Price, Ph.D., Chemist
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
The submitting company has claimed its company name as TSCA
Confidential Business Information (CBI). Staff of the Information
Management Division will review all incoming correspondence related
to the company's TSCA CBI claim. In the "sanitized" version of
its Section 8(e) notice, the company reported non-confidentially
that the subject chemical is isodecanol, CAS No. 25339-17-7.
SUBMISSION DESCRIPTION
The submitting company provided the following summary information
regarding the conduct and preliminary results of a prenatal
toxicity study in rats after gavage administration of isodecanol:
"All alcohols investigated were administered to pregnant
Wistar rats (10/group) by gavage...for 10 consecutive
days (days 6-15 post coitum) in daily doses of 1, 5 or
10 nmol/kg body weight.
l_ This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
NOTE
445
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8EHQ-0390-0911
Page 2 of 3
"Food consumption and body weights of the animals were
recorded regularly throughout the study period. The state
of health of the animals was checked daily.
"On day 20 p.c., all surviving females were sacrificed
and assessed by gross pathology. The fetuses were
dissected from the uterus, weighed and further
investigated for any external, soft tissue-and/or
skeletal findings.
"At the highest dose level (1,580 mg/kg body weight/day
-10 nmol/kg body weight) distinct signs of maternal
toxicity were observed. 4 dams of this group died or had
to be sacrificed in a moribund state on days 9 or 10 p.c.
Food consumption was markedly reduced and mean body
weights were clearly impaired (body weight loss on days
6-10 p.c. ; reduced body weight gains during the treatment
and the post-treatment periods; clearly reduced corrected
body weight gain). Severe adverse clinical symptoms
(e.g., abdominal or lateral position, unsteady gait and
apathy) were recorded. Light brown-gray discoloration of
the liver was noted in the animals which died
intercurrently. Clear signs of embryo/fetotoxicity,
substantiated by an increased postimplantation loss, an
increased number of resorptions, clearly reduced mean
fetal body weight, and a higher frequency of fetuses with
skeletal retardations were found. In addition, two out
of 59 fetuses from two different litters showed a rare
external malformation; both fetuses had no external
genitals.
"At 790 mg/kg body weight/day (~5 nmol/kg body weight),
signs of maternal toxicity were still present,
substantiated by reduced food consumption, trend to
reduced body weight gain and adverse clinical signs
(e.g., unsteady gait).
"Substance related embryo/fetotoxicity was not observed
at this dose level.
"At the lowest dose (158 mg/kg body weight/day ~1 nmol/kg
body weight), no adverse substance-related effects on
dams or fetuses were seen.
"Overall...in the present study, obvious signs of
developmental toxicity (including teratogenicity)
occurred only when severe maternal toxicity was evident."
446
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8EHQ—03 90—0911 S
Page 3 of 3
USE AND EXPOSURE POTENTIAL
The submitter did not provide any information regarding the use of
or the potential for exposure to isodecanol. According to The
Condensed Chemical Dictionary (10th edition), isodecanol is used
as an "antifoaming agent in textile processing.11
COMMENTS/RECOMMENDATIONS
The submitter reported that the company will notify all customers
of these results and submit additional information as it becomes
available to the EPA.
a) The Chemical Screening Branch will ask the submitter to
ensure that EPA receives a complete copy of the final
report (including the actual experimental protocol,
results of gross and histopathological examinations,
results of statistical analyses, etc.) from the prenatal
toxicity study cited in the submission.
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, the submitter will be requested
to describe the actions that the company has taken or
plans to take 1) to notify workers about the reported
information, and 2) to reduce or eliminate exposure to
the subject chemical. The submitter will be asked also
to provide copies of Material Safety Data Sheets and
labels that have been revised to reflect the reported
findings. In addition, the submitter will be asked to
describe the nature and results, if available, of all
studies (other than those submitted already to EPA or
those cited in the submission or the published scientific
literature) about which the submitter is aware or that
the company has conducted, is conducting or plans to
conduct that are designed to determine the toxicity of
or the exposure to the subject chemical.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
447
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(A)
<1 mortfc
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 4
OFFICE OF
date: APR 30 1990
APPROVED:
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0390-0912 S
FROM: Martha G. Price, Ph.D., Chemist
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
The submitting company has claimed its company name as TSCA
Confidential Business Information (CBI). Staff of the Information
Management Division will review all incoming correspondence related
to the company's TSCA CBI claim. In the "sanitized" version of
its Section 8(e) notice, the company reported non-confidentially
that the subject chemicals are two isononyl alcohols (CAS No.
69515-81-1) with different distributions of linear and branched
isomers.
SUBMISSION DESCRIPTION
The submitting company provided the following summary information
regarding the conduct and preliminary results of a prenatal
toxicity study in rats after gavage administration of two isononyl
alcohols:
"All alcohols investigated were administered to pregnant
Wistar rats (10/group) by gavage...for 10 consecutive
days (days 6-15 post coitum) in daily doses of 1, 5 or
10 nmol/kg body weight.
I This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
NOTE
448
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8EHQ—039 0—0912
Page 2 of 4
"For comparison, two control groups were used. Control
Group No. 1 was dosed with double distilled water, while
Control Group No. 2 was dosed with the emulsifier (double
distilled water with approximately 0.005% Cremophor EL) .
"Food consumption and body weights of the animals were
recorded regularly throughout the study period. The state
of health of the animals was checked daily.
"On day 20 p.c., all surviving females were sacrificed
and assessed by gross pathology. The fetuses were
dissected from the uterus, weighed and further
investigated for any external, soft tissue and/or
skeletal findings."
The following is a summary of the preliminary results reported for
Isononyl Alcohol I:
"At the highest dose level (1,440 mg/kg body weight/day
10 nmol/kg body weight) severe signs of maternal toxicity
were observed. All 10 dams of this group died or had to
be sacrificed in a moribund state on days 9, 10 or 11
p.c. after showing reduced food consumption, reduced mean
body weights/body weight loss and severe clinical
symptoms (like lateral or abdominal position, apathy and
unsteady gait) the days before death. At necropsy, a
light brown-gray discoloration of the liver of all
animals was the most important finding.
"Due to the intercurrent death of all dams, no data on
corrected body weight gain, uterus weight, reproduction
parameters, placental and fetal body weights and on fetal
external, soft tissue or skeletal findings were available
for further assessment.
"At 720 mg/kg body weight/day (-5 nmol/kg body weight),
clear signs of maternal toxicity were still present,
substantiated by reduced food consumption, reduced body
weight gain and adverse clinical signs (e.g., unsteady
gait).
"Embryo/fetotoxicity was observed in this group in form
of slightly reduced mean fetal body weights and an
increased number of fetuses with soft tissue variations
(mainly hydroureter) and with skeletal variations and
retardations.
"At the lowest dose (144 mg/kg body weight/day ~1 nmol/kg
body weight), no maternal toxic effects, but marginal
embryo/fetotoxic effects (increased number of fetuses
with hydroureter) were recorded."
449
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8EHQ-0390-0912
Page 3 of 4
The following is a summary of the preliminary results reported for
Isononyl Alcohol 2:
"At the highest dose level (1,44 0 mg/kg body weight/day
-10 nmol/kg body weight) distinct signs of maternal
toxicity were observed. 3 dams of this group died or had
to be sacrificed in a moribund state on days 8, 9 or 10
p.c. Food consumption was markedly reduced and mean body
weights were clearly impaired (body weight loss on days
6-10 p.c.; reduced body weight gains during the whole
treatment period and reduced corrected body weight gain).
Severe adverse clinical symptoms (e.g., abdominal or
lateral position, unsteady gait and apathy) were
recorded. Light brown-gray discoloration of the liver was
noted in the animals which died intercurrently. Clear
signs of embryo/fetotoxicity were seen, substantiated by
a markedly reduced mean fetal body weight, a higher
frequency of fetuses with a specific soft tissue
variation (hydroureter) and a higher frequency of fetuses
with skeletal variations and retardations. In addition,
2 fetuses (out of 91 examined) from one litter showed
rare external malformations; one fetus had no external
genitals and for the other one a meningocele was noted.
"At 720 mg/kg body weight/day (~5 nmol/kg body weight),
clear signs of maternal toxicity were still present,
substantiated by a slightly reduced food consumption,
reduced body weight gain and adverse clinical signs
(e.g., unsteady gait).
"Embryo/fetotoxicity was observed in this group in form
of an increased number of fetuses with soft tissue
variations (hydroureter).
"At the lowest dose (144 mg/kg body weight/day ~l nmol/kg
body weight), no adverse substance-related effects on
dams or fetuses were seen.
"Overall, for the alcohols reported above (i.e., Isononyl
Alcohol I and Isononyl Alcohol 2),...in the present
studies, obvious signs of developmental toxicity
(including teratogenicity for Isononyl Alcohol 2)
occurred only when severe maternal toxicity was evident."
USE AND EXPOSURE POTENTIAL
The submitter did not provide any information regarding the use of
or the potential for exposure to isononyl alcohols. According to
The Condensed Chemical Dictionary (10th edition), isononyl alcohol
is used as "a basis of plasticizers such as diisononyl adipate."
450
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8EHQ-0390-0912
Page 4 of 4
COMMENTS/RECOMMENDATIONS
The submitter reported that the company will notify all customers
of these results and submit additional information to the EPA as
it becomes available.
a) The Chemical Screening Branch will ask the submitter to
ensure that EPA receives a complete copy of the final
report (including the actual experimental protocol,
results of gross and histopathological examinations,
results of statistical analyses, etc.) from the prenatal
toxicity study cited in the submission.
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, the submitter will be requested
to describe the actions that the company has taken or
plans to take l) to notify workers about the reported
information, and 2) to reduce or eliminate exposure to
the subject chemicals. The submitter will be asked also
to provide copies of Material Safety Data Sheets and
labels that have been revised to reflect the reported
findings. In addition, the submitter will be asked to
describe the nature and results, if available, of all
studies (other than those submitted already to EPA or
those cited in the submission or in the published
scientific literature) about which the submitter is aware
or that the company has conducted, is conducting or plans
to conduct that are designed to determine the toxicity
of or the exposure to the subject chemicals.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
chemicals at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
451
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0*.
s
«
p«oitC?
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY Page 1 of 3
WASHINGTON, DC 20460
DATE:
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
APR 2 5 1990
approved:
subject:
from:
TO:
Status Report1 8EHQ-0390-0913 S
H jLo/ttfU-q
Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
The submitting company has claimed its company name and the exact
identity of the subject chemical as TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. In the "sanitized" version of its Section 8(e)
notice, the company reported non-confidentially that the subject
chemical is an "aryl alkyl heterocyclic carboxylate."
SUBMISSION DESCRIPTION
The submitting company provided the final report of a 6-week pilot
dog study of this aryl alkyl heterocyclic carboxylate. The
submitter's cover letter presents the following summary information
regarding the conduct and results of this study:
"[The test compound was] administered daily via capsule
[at doses of 0, 300, 600 or 1000 mg/kg/day] to 5 groups
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
452
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8EHQ-0390-0913 S
Page 2 of 3
of 1 male and 1 female dog for up to 6 weeks. Because of
excessive toxicity (vomiting, tonic convulsions, ataxia,
drowsiness and/or inappetence), the dosing of these
animals was suspended after 3 days. Dosing was resumed
at 800 mg/kg/day after a 5-day recovery period but the
animals were sacrificed on day 11 because excessive
toxicity was still apparent. Excessive toxicity
(vomiting, poor food consumption, subdued behavior,
tremors, unsteady gait, weight loss and/or hematological
changes) were also noted in at least one animal at both
300 and 600 mg/kg/day, and one animal of each was
sacrificed prior to study termination. There may have
been some clinical chemistry and/or hematology changes
in the remaining animal at 3 00 mg/kg/day and in one of
the two animals at 100 mg/kg/day but the effects, if any,
were minimal. At the dose levels that produce excessive
toxicity, manifestations suggestive of CNS effects were
observed."
USE AND EXPOSURE POTENTIAL
The submitter reported non-confidentially "that this material is
exclusively being tested for research and development (R&D)
purposes only."
COMMENTS/RECOMMENDATIONS
a) in view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity, the submitter will be reguested to describe the
actions that the company has taken or plans to take 1)
to notify workers/others about the reported information,
and 2) to reduce or eliminate exposure to the subject
chemical. The submitter will be asked also to provide
copies of Material Safety Data Sheets and labels that
have been revised to reflect the reported findings. In
addition, the submitter will be asked to describe the
nature and results, if available, of all studies (other
than those submitted already to EPA or those cited in the
published scientific literature) about which the company
is aware or that the company has conducted, is conducting
or plans to conduct that are designed to determine the
toxicity of the subject chemical.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NI0SH, 0SHA, CPSC, FDA, NTP, 0SWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA? in addition,
453
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8EHQ-0390-0913 S
Page 3 of 3
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
454
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY Page 1 of 3
WASHINGTON, DC 20460
OFFICE OF
APR 2 7 1990
A—- T- ch/io
PESTICIDES AND
DATE:
APPROVED:
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0390-0914 S
Qt^eUzJb M o
FROM: Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE (See NOTE on Page 3 of this Status Report)
The submitting company has claimed its company name and the exact
identity of the subject chemical as TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. The submitter reported non-confidentially that
the subject compound is a "substituted di-phenyl ether."
SUBMISSION DESCRIPTION
The submitting company reported non-confidentially that preliminary
results from a 2-year chronic toxicity/oncogenicity study indicate
that the tested compound may have caused neurotoxic effects (i.e.,
convulsions) in B6C3F1 mice. (Submitted data tables indicate that
the test compound was administered to mice by an unspecified route
at dose levels of 0, 50, 300, 1000, or 2000 ppm.) The submitter
reports that "at the present time we have not established that this
is in fact a compound related effect since as can be seen from the
data there is also a substantial incidence of convulsions in [the]
control group animals as well as in all dose groups." A letter
accompanying the submitted data tables states that no convulsions
were noted for any group in an ongoing rat study (dose levels,
route of exposure and duration not specified). This letter states,
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
455
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8EHQ-0390-0914 S
Page 2 of 3
however, that an increased incidence of malocclusions observed in
rats in the 2 highest dose groups may be "related to behavioral
changes, such as increased or decreased chewing activity."
USE/EXPOSURE POTENTIAL (See NOTE on Page 3 of this Status Report)
The submitter stated non-confidentially that the subject chemical
substance is being evaluated as an herbicide for registration under
the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA).
COMMENTS/RECOMMENDATIONS
In its submission, the submitter reported that the company is
currently conducting neurotoxicity-related evaluations of the data
from the chronic mouse study. The company further stated that the
results of these additional assessments will be provided to EPA.
a) The Chemical Screening Branch will ask the submitter to
ensure that EPA receives complete copies of the final
reports (including the actual experimental protocols,
results of gross/histopathological examinations, results
of any statistical analyses, etc.) from the mouse and rat
studies cited in the company's submission.
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity information, the submitter will be requested to
describe the actions that the company has taken or plans
to take l) to notify workers/others about the reported
information, and 2) to reduce or eliminate exposure to
the subject chemical. The submitter will be asked also
to provide copies of Material Safety Data Sheets and
labels that have been revised to reflect the reported
findings. In addition, the submitter will be asked to
describe the nature and results, if available, of all
studies (other than those submitted already to EPA or
those cited in the published scientific literature) about
which the company is aware or that the company has
conducted, is conducting or plans to conduct that are
designed to determine the toxicity of this substituted
di-phenyl ether.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), the Chemical Screening Branch
will screen the reported information to determine the
need for further assessment of the subject chemical at
this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this report will be sent to the Environmental
Assistance Division/OTS for further distribution.
456
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8EHQ-0390-0914 S
Page 3 of 3
NOTE In a letter dated July 23, 1990 (8EHQ-0790-0914 FLWP) ,
Mitsui Petrochemicals (America), Ltd. reported non-
confidentially that the subject chemical is 1-methoxy-l-
methyl-3-[4-(3,4-dihydro-2-methoxy-2,4,4-trimethyl-7-
benzopyranyloxy)phenyl]urea (CAS No. unknown), which
comprises 25% (w/w) in PAL6000, a product for which a
FIFRA Experimental Use Permit (63098-EUP-l) was granted
by EPA on June 14, 1990.
457
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-------
h
m
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
DATE: Wfif I 0 BQO APPROVED;
SUBJECT: Status Report1 8EHQ-0390-0916 S
: 7T, b'/nfac
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
T-&M
FROM: Jacqueline T. Favilla, Biologist
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
A confidential company submitted a final report of a positive L5178Y TK+/- Mouse Lymphoma Forward
Mutation Assay with Independent Repeat conducted on a research and development (R & D) compound
identified generically as a "semicarbazone." The cover letter of the submission reports that an Ames Test
and an In Vivo Mouse Micronucleus Assay with this compound were negative.
COMMENTS/RECOMMENDATIONS
In its cover letter, the submitter stated that in addition to standard precautionary labeling, all R & D
chemicals bear an additional warning statement. It should be noted here that the Agency has received
another TSCA Section 8(e) submission on a compound identified generically as a semicarbazone. The
reader's attention is directed to 8EHQ-0390-0907 S.
Although a positive in vitro genotoxicity test, when considered alone, may not be sufficient to offer
reasonable support for a conclusion of substantial risk (as that term is defined in EPA's TSCA Section 8(e)
policy statement ("Statement of Interpretation and Enforcement Policy; Notification of Substantial Risk" 43
FR 11110; March 16, 1978)), EPA does believe that such information is of value in assessing the possible
risk(s) posed by exposure to the tested chemical or mixture. Further, EPA believes that a positive
genotoxicity test result, in combination with other information (e.g., knowledge of actual/potential exposure
to and/or high production of the tested chemical or mixture), would suggest the need, in many cases, to
conduct further studies designed to determine the toxicity of or the exposure to that chemical substance or
mixture. EPA expects the results of such additional studies to be considered also for submission under
Section 8(e) of TSCA
The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA, CPSC, FDA, NTP,
OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition, copies of this status
report will be transmitted to the Environmental Assistance Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "NT Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
459
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£ JQL "I UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
% Page 1 of 1
_ APPROVED: At^L-
MAY 91960
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
DATE:
SUBJECT: Status Report1 8EHQ-0490-0917
j
FROM: Jacqueline T. Favilla, Biologist '
Chemical Risk Identification Sect&n/CSB
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
The BFGoodrich Company submitted a letter that it received from the BASF Corporation regarding the
results of a re-analysis and update of a Rohm & Haas Company epidemiology study of ethyl acrylate
(CAS No. 140-88-5) and methyl methaciylate (CAS No. 80-62-6). This study was the subject of an earlier
"For Your Information" (FYI) submission from the Rohm and Haas Company; the reader's attention is
directed to FYI-OTS-0290-0300 Sequence B.
COMMENTS/RECOMMENDATIONS
It should be noted here that EPA has received numerous TSCA Section 8(e) and FYI submissions on
acrylates.
a) In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity/exposure data, the company will be requested to describe
the actions that it has taken or plans to take 1) to notify workers and others about the
reported data, and 2) to reduce or eliminate exposure to the subject chemicals. The
company will be asked to provide copies of Material Safety Data Sheets and labels that
have been revised to reflect the reported findings. In addition, the company will be asked
to describe the nature and results, if available, of all studies (other than those submitted
already to EPA or those cited in the published scientific literature) about which the
company is aware or that it has conducted, is conducting or plans to conduct that are
designed to determine the toxicity of the subject chemicals.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA, OPP/EPA, and
CREB/HERD/OTS/EPA; in addition, copies of this status report will be transmitted to
the Environmental Assistance Division/OTS for further distribution.
1 This stalus report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are
available for public inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460.
All requests for TSCA Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
460
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY Page 1 of 3
WASHINGTON, DC 20460
P*0t*°
date: MAY 21990
APPROVED
'
-------
8EHQ-0490-0918 S
Page 2 of 3
interrupted Definitive Teratology Study
"Based on the results of the dosage-range pilot study,
dosages of 0 (vehicle), 62.5, 125, 250 mg/kg/day of [the
test compound] were administered to 20 rabbits per group
on days 6 to 18 of presumed gestation. Because there were
13 deaths and seven abortions in the high dosage group,
this study was terminated prior to scheduled Caesarean-
sectioning on day 29 of gestation (only one pregnant high
dosage group doe survived to day 25 of gestation). The
125 and 250 mg/kg/day dosages of [the compound] inhibited
maternal body weight gain and feed consumption.11
Repeat Definitive Teratology Study
"80 artificially inseminated female rabbits were assigned
(20 to a group) to a vehicle control and three test
substance-administered dosage groups using computer-
generated random units (weight ordered). Dosages of 0,
37.5, 75, or 150 mg/kg/day of [the compound] were
administered by stomach tube to the presumed pregnant
rabbits at a dosage volume of 10 ml/kg on days 6 through
18 of presumed gestation. The vehicle was aqueous 0.5%
(w/v) carboxymethyl cellulose. The control 9rouP
received the vehicle containing an amount of HiSil
equivalent to that in the high dosage group. All dosages
were adjusted daily for changes in body weight.
"Maternal toxicity was evident as adverse clinical signs,
inhibited body weight, inhibited feed consumption (75 and
150 mg/kg/day dosage groups) and abortion/premature
delivery (150 mg/kg/day dosage group). The only adverse
effect on embryo/fetal development was the low incidence
of abortion/premature delivery that occurred in the high
dosage group. No adverse effect on embryo/fetal
viability, growth or morphology was revealed by [an]
evaluation of the term Caesarean-delivered fetuses.
"On the basis of these results, the maternal no-
observable effect level (NOEL) for [the subject chemical]
is 37.5 mg/kg/day, and the developmental NOEL is 75
mg/kg/day."
In its cover letter, the submitting company also reported that "an
additional teratology study has been conducted in rats without any
indication of significant adverse findings." In addition, the
submitter reported that the provided information related to a
compound for which mutagenicity data had been reported to EPA on
December 11, 1989. [NOTE: A TSCA Section 8(e) submission (8EHQ-
1289-0853 S) dated December 11, 1989 was received by the Agency on
December 12, 1989 and pertained to genotoxicity data on a chemical
identified as a "heterocyclic amide." The reader's attention is
directed to the status report prepared for 8EHQ-1289-0853 S.]
462
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8EHQ-0490-0918 S
Page 3 of 3
USE AND EXPOSURE POTENTIAL
The submitter reported non-confidentially that this heterocyclic
amide is a research and development (R&D) compound that was
produced outside of the United States. The submitter stated that
"the volumes produced are small and; therefore, exposure is
minimal. . . . All R&D compounds are handled with extreme
precaution until all safety assessments have been completed and
appropriate clearances have been obtained."
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will ask the submitter to
ensure that EPA receives complete copies of the final
reports (including the actual experimental protocols,
results of gross and histopathological examinations,
results of statistical analyses, etc.) from all of the
teratologic studies cited in the submission.
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity, the submitter will be reguested to describe the
actions that the company has taken or plans to take to
notify workers/others about the reported information.
The submitter will be asked also to provide copies of
Material Safety Data Sheets and labels that have been
revised to reflect the reported findings. In addition,
the company will be asked to describe the nature and
results, if available, of all studies (other than those
submitted already to EPA or those cited in the published
scientific literature) about which the company is aware
or that the company has conducted, is conducting or plans
to conduct that are designed to determine the toxicity
of the subject chemical.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this report will be sent to the Environmental
Assistance Division/OTS for further distribution.
463
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
DATE: 30 1990 PROVED: s/j*M
SUBJECT: Status Report1 8EHQ-0490-0919 S
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
FROM: Martha G. Price, Ph.D., Che
Chemical Risk Identification Section/CSB W ^
TO: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS
SUBMISSION DESCRIPTION
Eastman Kodak Company provided final reports of acute toxicity tests on an R&D chemical identified as
"substituted carbonothioic hydrazide" after central nervous system effects were noted in the oral toxicity study
in rats. Other reports provided were dermal toxicity in rats, eye and dermal irritation in rabbits, and a skin
sensitization study in guinea pigs.
COMMENTS/RECOMMENDATIONS
The submitter reported that the new toxicity information has been incorporated into the MSDS.
a) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarten, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
464
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
Page 1 of 2
DATE:
JAN - 3 1991
APPROVED:
If> (jastn
(J I fa hi
)A/m—
SUBJECT: Status Report1 8EHQ-0490-0920 S
OFFICE OF
PESTICIDES AND TOXIC SUBSTANCES
FROM: Martha G. Price, Ph.D., Chemist [/\/VCas~\/
Chemical Risk Identification Section/CSB U L)
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
A confidential submitting company provided a draft study report of a mouse micronucleus test on "alkenoyl
disubstituted cycloalkane" which, according to the company, has been assigned EPA ACCESSION #35406.
COMMENTS/RECOMMENDATIONS
Although a positive in vitro genotoxicity test, when considered alone, may not be sufficient to offer reasonable
support for a conclusion of substantial risk (as that term is defined in EPA's TSCA Section 8(E) policy
statement ("Statement of Interpretation and Enforcement Policy; Notification of Substantial Risk" FR 11110:
March 16, 1978), EPA does believe that such information is of value in assessing the possible risk(s) posed
by exposure to the tested chemical or mixture. Further, EPA believes that a positive genotoxicity test result,
in combination with other information (e.g., knowledge of actual/potential exposure to and/or high
production of the tested chemical or mixture), would suggest the need, in many cases, to conduct further
studies designed to determine the toxicity of or the exposure to that chemical substance or mixture. EPA
expects the results of such additional studies to be considered also for submission under Section 8(e) of TSCA.
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final report (including the actual experimental protocol, results of
gross/histopathologic examinations, results of any statistical analyses, etc.) from the study cited
in the submission.
In view of EPA's general interest in company actions that are taken on a voluntary basis in
response to chemical toxicity/exposure data, the company will be requested to describe the
actions that it has taken or plans to take 1) to notify workers and others about the reported
data, and 2) to reduce or eliminate exposure to the subject chemical. The company will be
asked to provide copies of Material Safety Data Sheets and labels that have been revised to
reflect the reported findings. In addition, the company will be asked to describe the nature
and results, if available, of all studies (other than those submitted already to EPA or those
cited in the published scientific literature) about which the company is aware or that it has
conducted, is conducting or plans to conduct that are designed to determine the toxicity of
the subject chemical.
This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final
Agency policy or intent with respect to the subject chemicals(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
465
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8EHQ-0490—0920 S
Page 2 of 2
b) As part of the initial phase of the OTS Existing Chemicals Program (ECP), staff of the
Chemical Screening Branch will screen the reported information in order to determine the
need for further assessment of the subject chemical at this time.
c) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
466
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Page 1 of 3
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
DATE! APR 2 0 1990
APPROVED:
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0490-0921 8
FROM: Jacqueline T. Favilla, Biologist {Jt
Chemical Risk Identification Section/
CjZefu^ai
Vh/pSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
Ricoh Electronics Inc. reported non-confidentially that the subject
chemical is 4,4'-[methylenebis(oxy-2,1-ethanediylthio)]bisphenol,
commonly known as DD-70. Ricoh also reported non-confidentially
that this chemical substance is the subject of a TSCA Section 5
Pre-Manufacture Notice (PMN No. P87-1760) and a Section 5 Consent
Order. According to CAS ONLINE, a publicly available computerized
database, this chemical has the following CAS Registry Number:
93589-69-6.
SUBMISSION DESCRIPTION
Ricoh Electronics Inc. provided an incident report on the
accidental discharge of DD-70 to a waterway from its Santa Ana,
California plant. The following scenario was described in Ricoh's
letter:
"Process water, clean up and rinse water from a paper
coating operation flows into a settling pit before
discharge to an industrial sewer. The industrial sewer
flows to a POTW, from which Ricoh has a permit to
discharge.
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
467
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8EHQ-0490-0921 S
Page 2 of 3
"Between 12 am and 7 am on March 13, 1990, the outflow
pump, which moves the water from the settling pit to the
sewer line, failed due to a piece of wood jamming the
pump impeller. This caused an unknown amount of process
water to overflow the settling pit and flow into a storm
water runoff drain on site. The storm drain is an
underground concrete pipe which then flows into a rock
lined, dirt storm water channel, approximately 1.5 miles
away. It is impossible to determine the quantity of
process water which entered into the storm water system.
The process water did contain less than one percent of
DD-70.
"Santa Ana Fire Department was requested by Orange County
Emergency Management Agency (OCEMA) to flush the concrete
storm drain with 1500 gallons of water to the dirt storm
channel for collection. Ricoh was ordered by OCEMA to
hire a clean up company to vacuum the dirt storm channel
and collect the liquid for disposal at the local POTW.
The total amount of liquid vacuumed out of the storm
channel was 30,000 gallons.
"The total spill was contained at the dirt storm channel.
The spill, to the best of our knowledge, has not
contaminated any further waterway."
In its letter, Ricoh also reported the following:
"The settling pit does have a high level alarm, which was
functional the night of the spill. The alarm has a bell
and red light to indicate a high level in the settling
pit. The Mixing Supervisor was aware of the alarm and
its function. There was no written procedure existing
for what actions needed to be done in the event of the
alarm being sounded."
It was also noted in the 8(e) submission that there were no known
injuries or environmental effects resulting from this discharge of
DD-70, and that there have been no previous accidental discharges
of DD-70. Following this accidental spill, Ricoh reported that it
had notified all appropriate Federal and state agencies, including
EPA Region 9 and EPA headquarters. Ricoh also reported that it had
implemented the following countermeasures:
"1. A screen was designed and installed around the pump
to prevent the impeller from jamming again.
"2. A written procedure was developed and implemented
for what actions need to be followed in the event
of the alarm being triggered again."
468
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8EHQ-0490-0921 S
Page 3 of 3
USE AMD EXPOSURE POTENTIAL
In its TSCA Section 8(e) submission, Ricoh Electronics Inc. did not
provide any non-confidential information with regard to the use of
DD-70. The sanitized version of P87-1760 states that DD-70 is used
in the "manufacture of office machine paper" and provides some
information about the potential for exposure to the chemical.
COMMENTS/RECOMMENDATIONS
It should be noted that the sanitized version of P87-1760 contains
the results of an in vitro mutagenicity test and in vivo mammalian
toxicity studies, as well as a Material Safety Data Sheet (MSDS)
for DD-70.
a) Ricoh Electronics Inc. will be requested to keep EPA
apprised of any further developments which may occur as
a result of this accidental discharge of DD-70.
b) As was the case with the initial Section 8(e) submission,
the Chemical Screening Branch will send full copies of
all reported information to the Chemical Control Division
(CCD/OTS) for review; CCD is responsible for implementing
EPA's Section 5 "New Chemicals Program" (NCP).
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA, CCD/OTS/OPTS and
EPA's Region IX Office. In addition, copies of this
status report will be transmitted to the Environmental
Assistance Division/OTS (formerly the TSCA Assistance
Office/OTS) for further distribution.
469
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Page 1 of 3
^t0SX
3
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Km WASHINGTON, DC 20460
WO,fc°
datej JUL 23)990 approved: (lu^ ihskn
FROM:
MOTE
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0490-0922 S
Martha G. Price, Ph.D., ChemistT^-^L
O?.
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
The submitting company has claimed its company name and the exact
identity of the subject chemical as TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. In the "sanitized" version of its Section 8(e)
notice, the company reported non-confidentially that the subject
chemical is a "chlorinated hydrocarbon."
SUBMISSION DESCRIPTION
The submitting company provided the following summary information
regarding the conduct and final results of a one-generation
reproduction fertility study of "chlorinated hydrocarbon" in rats.
"This study was conducted...to assess the reproductive
performance and fertility of male and female CD® rats (10
males and 20 females per group) at dose levels of 1 and
5 ppm. The study included both an untreated control and
an untreated chamber-exposed control. The test substance
was administered via inhalation for 6 hours per day, 5
days per week for a 10 week premating treatment period,
a mating period and the first 14 days of gestation.
I This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
470
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8EHQ-0490-0922 S
Page 2 of 3
"Females were allowed to deliver litters and offspring
were evaluated during a 21 day lactation period. At the
end of the 21 day lactation period all Fo and F1 animals
were sacrificed and gross necropsies performed. Gonads
from the Fo animals were examined histopathologically.
"There were no unusual in-life observations or mortality
in any of the Fo animals.
"The mean body weights of the untreated control Fo males
were greater than the chamber-exposed controls throughout
the premating treatment period.
"The mean body weights of the female untreated controls
and the low and high-dose females were slightly greater
than the chamber-exposed controls during gestation. Mean
maternal body weights of all groups were comparable
through the lactation period.
"Fo reproduction data (mating, pregnancy and fertility
indices) were comparable in all groups.
"The mean number of pups alive on Days 0, 4, 14 and 21
of lactation was slightly greater in the untreated
control and high-dose group than in the chamber-exposed
control or low-dose group. However, pup survival indices
evaluated on Days 0, 1, 4, 14 and 21 of lactation for the
treated groups were unremarkable.
"Mean pup body weights in the high-dose, on Days 4, 14
and 21 of lactation, and in the untreated control, on
Days 14 and 21 were slightly reduced compared to the
chamber-exposed controls.
"Sex distribution patterns in all groups were
unremarkable.
"There were no gross observations in any of the F1
animals at necropsy which were attributable to the
administration of the test material.
"The mean terminal body weights of the untreated control,
low- and high-dose Fo males and the high-dose Fo females
were slightly greater than the respective chamber-exposed
controls.
"The mean absolute and relative organ weights and the
mean organ/brain weight ratios for the Fo animals of all
groups were unremarkable.
"There were no gross observations in any of the Fo
animals at necropsy which were attributable to the
administration of the test material. Likewise,
471
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8EHQ-0490-0922 S
Page 3 of 3
microscopic examination of the gonads of the male and
female Fo parents revealed no indication of a compound
related effect."
IIBE AND EXPOSURE POTENTIAL
In view of the submitter's TSCA CBI claims, no information
regarding the TSCA Chemical Substance Inventory status or use of
the subject chemical will appear in this status report.
COMMENTS/RECOMMENDATIONS
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, the submitter will be requested
to describe the actions that the company has taken or
plans to take 1) to notify workers/others about the
reported information, and 2) to reduce or eliminate
exposure to the subject chemical. The submitter will be
asked also to provide copies of Material Safety Data
Sheets and labels that have been revised to reflect the
reported findings. In addition, the submitter will be
asked to describe the nature and results, if available,
of all studies (other than those submitted already to
EPA or those cited in the published scientific
literature) about which the submitter is aware or that
the company has conducted, is conducting or plans to
conduct that are designed to determine the toxicity of
or the exposure to the subject chemical.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
472
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
OFFICE OF
DATE:
m "2 1990 APPROVED:
'0
TOXIC SUBSTANCES
PESTICIDES AND
SUBJECT: Status Report1 8EHQ-0490-0923 S
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
A confidential submitting company provided a final report of a range-finding teratology study of "substituted
acetanilide III" administered by gavage to pregnant rabbits at doses of 0, 10, 25, 75, 150 or 300 mg/kg/day
on days 7-19 of gestation. To date, EPA has received several TSCA Section 8(e) notices on chemicals
identified generically as substituted acetanilides (Section 8(e) No. 889 S, 896 S, 897 S and 955 S).
COMMENTS/RECOMMENDATIONS
a) In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity/exposure data, the company will be requested to describe
the actions that it has taken or plans to take 1) to notify workers and others about the
reported data, and 2) to reduce or eliminate exposure to the subject chemical. The
company will be asked to provide copies of Material Safety Data Sheets and labels that have
been revised to reflect the reported findings. In addition, the company will be asked to
describe the nature and results, if available, of all studies (other than those submitted
already to EPA or those cited in the published scientific literature) about which the
company is aware or that it has conducted, is conducting or plans to conduct that are
designed to determine the toxicity of the subject chemical.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
473
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-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
OFFICE OF
DATE: JUN - 7 |990 APPROVED:
TOXIC SUBSTANCES
PESTICIDES AND
SUBJECT: Status Report1 8EHQ-0490-0925 S
S
FROM: Martha G. Price, Ph.D., Che
Chemical Risk Identification
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
A confidential submitting company provided two final reports on an R&D chemical identified as
"heterocyclic thioester": (1) A one-generation reproduction study administered in the feed to rats at dose
levels of 0, 100, 1000, 2500, and 5000 ppm prior to mating and throughout gestation and lactation. (2) A
pilot teratology study administered by gavage to female rabbits at dose levels of 0, 30, 100, 300, and 1000
mg/kg/day.
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mail (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
475
-------
/ G *
[m>
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
DATE:
MAY 41990
APPROVED:
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0490-0926 S
QudUA fa
FROM: Judith M. Loranger, Biologist
Chemical Screening Branch/ECAD/OTS
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
A confidential submitter provided final reports of rat and mouse 1-month dietary feeding range-finding
studies of an R&D chemical identified as "diaryl ether IV." The compound was administered to mice at
concentrations of 0, 200, 1000 or 5000 ppm and administered to rats at concentrations of 0, 500, 2500 or
10000 ppm. To date, EPA has received several TSCA Section 8(e) submissions on chemicals identified
generically as diaryl ethers (Section 8(e) No. 751 S, 851 S, 883 S, 888 S and 930 S).
COMMENTS/RECOMMENDATIONS
a) In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity data, the company will be requested to describe the actions
that it has taken or plans to take to notify workers and others about the reported data.
The company will be asked to provide copies of Material Safety Data Sheets and labels that
have been revised to reflect the reported findings. In addition, the company will be asked
to describe the nature and results, if available, of all studies (other than those submitted
already to EPA or those cited in the published scientific literature) about which the
company is aware or that it has conducted, is conducting or plans to conduct that are
designed to determine the toxicity of the subject chemical.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting prevision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
476
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
OFFICE OF
T
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 Of 1
DATE: JUM -T 1980 APPROVED:
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0490-0928 °
FROM: Martha G. Price, Ph.D., Chemist"
Chemical Risk Identification Sectioi
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
A confidential submitting company provided two final reports on an R&D chemical identified as
"heterocyclic carboxylic acid ester": (1) A one-generation reproduction study administered in the feed to rats
at dose levels of 0, 1000, 10,000, and 20,000 ppm prior to mating and throughout gestation and lactation.
(2) A teratology study administered by gavage to mated female rats at dose levels of 0, 200, 1000, and 2500
mg/kg/day.
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
478
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
^ WASHINGTON, DC 20460 page 1 of l
DATE: 7 |ggp APPROVED: sfa/ft
SUBJECT: Status Report1 8EHQ-0490-0929 S
>
FROM: Jacqueline T. Favilla, Biologist W_ rf
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBMISSION DESCRIPTION
A confidential company reported that a laboratoiy researcher received severe hand burns that he alleged
were caused by a "halogenated ether." The submitter noted that this effect has not been previously reported
for this chemical. The company believes that the effect was the result of a combination of chemicals, but
filed the Section 8(e) report for the halogenated ether because of the researcher's high level of exposure to
this particular chemical. The company provided numerous documents related to the researcher's injury.
COMMENTS/RECOMMENDATIONS
Although the information provided by the submitter does not appear to be of the type required for
submission under Section 8(e), the "substantial risk" information reporting provision of TSCA, the subject
information does appear to be of the type required to be recorded/maintained by the company under Section
8(c), a mandatory recordkeeping provision of TSCA On August 22, 1983, the Agency published (48 FR
38178) a final rule that requires chemical manufacturers and certain chemical processors to maintain records
of significant adverse reactions alleged to have been caused by a TSCA-covered chemical substance or
mixture. This TSCA Section 8(c) rule also requires that allegations that involve significant adverse reactions
in workers be maintained for 30 years and that other recordable allegations be kept for 5 years. It should
be noted also that the Agency is empowered to inspect and/or require submission of corporate TSCA Section
8(c) records and has done so on a number of occasions to date.
The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA, CPSC, FDA, NTP,
OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition, copies of this status
report will be transmitted to the Environmental Assistance Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
479
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-ito S>*,
cr * J>.
JSL 1 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
532/
WASHINGTON, DC 20460 ^
Page 1 of 2
OFFICE OF
MAY A1990 a K— / / pest,c,DESand
DATE: APPROVED: (k^ (J. /\ltnn_ fll/d* toxic substances
SUBJECT: Status Report1 8EHQ-0490-0930 S
FROM: Judith M. Loranger, Biologist
Chemical Screening Branch/ECAD/OTS
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
A confidential submitting company provided summarized findings from a number of in vitro and in vivo
toxicity studies of an R&D compound identified as "diaiyl ether V," which, according to the company
"apparently consists of 2 isomers." The toxicologic studies cited by the company are as follows:
1. A pilot rat teratology study,
2. 6 month subchronic pilot feeding studies in rats and mice,
3. A pilot rat reproduction study,
4. A tumor promotion assay (species not specified), and
5. In vitro cytogenetic assay (of a metabolite).
To date, EPA has received several TSCA Section 8(e) notices on chemicals identified generically as diaryl
ethers (Section 8(e) No. 751 S, 851 S, 883 S, 888 S, and 926 S).
COMMENTS/RECOMMENDATIONS
The company stated that all "personnel that might be exposed to the substance have been notified about
the [reported] results."
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives full copies of the final reports (including the actual experimental protocols, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from all of the
studies cited in the submission.
In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity, the company will be requested to describe the nature and
results, of available, of all studies (other than those submitted already to EPA or those cited
in the published scientific literature) about which the company is aware or that it has
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarter*, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
480
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8EHQ-0490-0930 S
Page 2 of 2
conducted or plans to conduct that are designed to determine the toxicity of the subject
chemical. The company will be asked to provide copies of Material Safety Data Sheets and
labels that have been revised to reflect the reported findings.
The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
481
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iSEZ
V^w r<
*
U)
0
:/
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
DATE:
APPROVED:
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
m 9
SUBJECT: Status Report1 8EHQ-0490-0931 S
FROM: Jacqueline T. Favilla, Biologist
Chemical Risk Identification Secticm/C^B
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
The Givaudan Corporation submitted final reports of oral subacute toxicity studies in rats, mice, monkeys
and guinea pigs, and subchronic oral toxicity studies in rats and dogs of 4-(l,l-dimethylethyl)-alpha-
methylbenzenepropanal (CAS No. 80-54-6), a perfumery raw material. The company also submitted a final
report of a subacute oral toxicity study in rats of 3-[4-(l,l-dimethylethyl)phenyl]-2-methyl-2-propenal (CAS
No. 13586-68-0). According to the cover letter, "male rats exhibited adverse effects on the testes" in the
subacute studies of both chemicals and in the subchronic study of 4-(l,l-dimethylethyl)-alpha-
methylbenzenepropanal.
COMMENTS/RECOMMENDATIONS
a) In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity/exposure data, the company will be requested to describe
the actions that it has taken or plans to take 1) to notify workers and others about the
reported data, and 2) to reduce or eliminate exposure to the subject chemicals. The
company will be asked to provide copies of Material Safety Data Sheets and labels that have
been revised to reflect the reported findings. In addition, the company will be asked to
describe the nature and results, if available, of all studies (other than those submitted
already to EPA or those cited in the published scientific literature) about which the
company is aware or that it has conducted, is conducting or plans to conduct that are
designed to determine the toxicity of or the exposure to the subject chemicals.
b) As part of the initial phase of the OTS Existing Chemicals Program (ECP), staff of the
Chemical Screening Branch will screen the reported information in order to determine the
need for further assessment of the subject chemical(s) at this time.
c) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information rcnortinp „m, • ¦
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressine final a
policy or intent with respect to the subject chemical(s). Full copies of nonconfidential Section 8(e) notices are available Lrl?
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All reauest* for ?^!'C
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
482
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(&)
H> el?
Pn&*-
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
DATE: m 41990 APPROVED:
SUBJECT: Status Report1 8EHQ-0490-0932
7T- ckJio
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
FROM: Jacqueline T. Favilla, Biologist '*-ht
-------
^*0 srA.
\J\
w
*1 P«0^fe
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
DATE: KW 7 MO APPROVED:
SUBJECT: Status Report1 8EHQ-0490-0933
FROM: Jacqueline T. Favilla, Biologist
Chemical Risk Identification Section/CSB'
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBMISSION DESCRIPTION
General Electric Company reported a fire that occurred at the General Electric Company Technical Center
located in Washington, West Virginia on April 4, 1990. Results from wipe samples taken on April 6, 1990
indicated that polychlorinated biphenyl (PCB) levels ranged from non-detectable to 400+ jtg/100 cm2. The
company noted that the source of the PCBs has not yet been identified and that no transformers were
involved in the fire.
COMMENTS/RECOMMENDATIONS
In its submission, General Electric informed EPA that workers were dismissed and the building was closed
indefinitely. General Electric also stated that the incident was reported to the National Response Center
EPA Region III, and the West Virginia Emergency Response Commission; experts on PCB decontamination
are being consulted.
The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA, CPSC, FDA, NTP
OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA, CRB/EED/OTS and EPA's Region III'
office; in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
¦ r pp a under Section 8("el. the "substantial risk" information reporting provision
i This status report reflects in Statements made in this status report should not be regarded as expressing final Agency
of the Toxic Substan^nol AjWS—™ « of ^ Section 8(e) notices are available for public
Fl^tl'?tEPr!toZar.ers NorthJast Mai. (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
SecS 8(e) notices should be addressed to EPA's Freedom of Information Off.ce (A-101).
484
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^osr<*.
m
\
I
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 2
DATE; MY 4 1990 APPROVED:
? I°ik
30
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0490-0934 S
QuutlZA H
FROM: Judith M. Loranger, Biologist
Chemical Screening Branch/ECAD/OTS
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION (See NOTE on Page 2 of this Status Report)
A confidential submitting company provided a copy of the protocol and tabular results of a 2-week range-
finding rat oral toxicity study of a chemical generically identified as a "phosphoroamidate." According to
the submission, the compound was administered daily by gavage at doses of 250, 500, 1000 or 2000 mg/kg.
The company reported that a TSCA Section 5 "Pre-Manufacture Notice" (PMN) was submitted for this
chemical and that "the PMN period is currently under voluntary suspension in order to .. . conduct a variety
of toxicity and environmental fate tests."
COMMENTS/RECOMMENDATIONS
a) The submitter will be asked to ensure that EPA receives a full copy of the final report
(including the results of gross/histopathologic examinations, results of statistical analyses,
etc.) from the 2-week gavage study cited in the submission.
In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity, the company will be requested to describe the actions that
it has taken or plans to take to notify workers and others about the reported data. The
company will be asked to provide copies of Material Safety Data Sheets and labels that have
been revised to reflect the reported findings. In addition, the company will be asked to
describe the nature and results, if available, of all studies (other than those submitted
already to EPA or those cited in the published scientific literature) about which the
company is aware or that it has conducted, is conducting or plans to conduct that are
designed to determine the toxicity of the subject chemical.
b) As was the case with the initial Section 8(e) submission, the Chemical Screening Branch
will notify the Chemical Control Division (CCD/OTS) of the receipt of in-coming
information; CCD is responsible for implementing EPA's TSCA Section 5 "New Chemicals
Program" (NCP).
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are
available for public inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460.
All requests for TSCA Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
485
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8EHQ-0490-0934 S
Page 2 of 2
c) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA OPP/OPTS/EPA, and
CCD/OTS/OPTS; in addition, copies of this status report will be transmitted to the
Environmental Assistance Division/OTS for further distribution.
NOTE In a followup letter dated June 21, 1990 (8EHQ-0690-0934 FLWP), Enimont America Inc.
reported non-confidentially that the subject chemical is N-(n-butyl)thiophosphoric triamide
(NBPT; CAS No. 94317-64-3). Enimont also reported non-confidentially that NBPT is the
subject of TSCA Section 5 PMN submission number P89-538.
486
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^tos^
(mj
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
DATE:
MAY 81990
APPROVED:
^ jjtAnf/tf/jo
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0490-0935
^UjoLLCL ft ^0
FROM: Judith M. Loranger, Biologist
Chemical Screening Branch/ECAD/OTS
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
A confidential submitter provided a copy of draft tabular results of a rabbit developmental toxicity study
of a chemical generically identified as "an imidazole derivative," an intermediate reported to be used in the
production of a pesticide. Test animals received the compound at doses of 0, 100, 500 or 1000 mg/kg/day
by an unspecified route, for an undisclosed amount of time.
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final report (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the
developmental toxicity study cited in the submission.
In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity/exposure data, the company will be requested to describe
the actions that it has taken or plans to take 1) to notify workers and others about the
reported data, and 2) to reduce or eliminate exposure to the subject chemical. The
company will be asked to provide copies of Material Safety Data Sheets and labels that
have been revised to reflect the reported findings. In addition, the company will be asked
to describe the nature and results, if available, of all studies (other than those submitted
already to EPA or those cited in the published scientific literature) about which the
company is aware or that it has conducted, is conducting or plans to conduct that are
designed to determine the toxicity of the subject chemical.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA NTP, OSWER/EPA, OW/EPA, ORD/EPA OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are
available for public inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460.
All requests for TSCA Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
487
-------
5^
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
FROM: Martha G. Price, Ph.D., Chemist
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
BASF Corporation provided preliminary results of a subchronic feeding study of L-2-chloropropionic acid,
isobutyl ester (CAS No. 83261-15-8) after signs of neurotoxicity were noted in rats.
COMMENTS/RECOMMENDATIONS
BASF reports that it does not currently produce or market L-2-chloropropionic acid, isobutyl ester. They
also report that in 1986 BASF supplied two customers with R&D samples of this material; both customers
will be notified of these results.
BASF stated that they will forward the final report to the Agency when it is received.
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final report (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) which BASF
plans to forward.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
488
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\
mi
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 3
+ ,
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8EHQ-0490-0937 Init. and SUPPs
Page 2 of 3
pregnant rats (in both studies) received the sodium salt of amino-
tri(methylene phosphoric acid) via gastric intubation at doses of
100, 500, or 1000 mg/kg/day on days 6-15 of gestation:
Pilot Rat Teratology Study
"Signs of maternal toxicity were noted in 500 and 1000
mg/kg treated dams. Signs of developmental toxicity
(increased resorptions) were also observed at 500 and
1000 mg/kg. Results from this study suggest that while
this material induces developmental effects in rats, it
does so only at dose levels that also produce significant
maternal toxicity.
Definitive Rat Teratology Study
"Signs of maternal toxicity were observed at 1000 mg/kg.
Signs of possible developmental toxicity (statistically
significant increase in resorptions) were observed at 100
and 1000 mg/kg. However, the response for this effect did
not follow a dose-related pattern and the incidences at
both dose levels were within historical control range
and thus are likely unrelated to treatment. Common
multiple external malformations were observed in six of
sixteen fetuses only in one litter at 1000 mg/kg and were
not statistically significant. Because of this occurrence
in only one litter and lack of skeletal and visceral
examination confirmation, it was decided that the
observed malformations are of questionable biological
relevance."
In another supplemental submission, Monsanto provided the final
report of a chronic toxicity/oncogenicity study of a related
compound, aminotri(methylene phosphonic acid) (DEQUEST 2000; CAS
No. 6419-19-8) in which the chemical was administered to rats via
the diet at dose levels of 50, 150, or 500 mg/kg/day for 24 months.
The following summary information accompanied the submission:
"An unusual tumor type (osteosarcoma-axilla) was observed
in one male animal at 500 mg/kg. The biological
relevance of a single rare tumor cannot be determined.
Because of the structural similarity to ethylenediamine-
tetra(methylenephosphonic acid), the observation of a
single osteosarcoma is being reported."
Monsanto reported that the Material Safety Data Sheet (MSDS) for
DEQUEST 2000 will be revised to reflect the new findings.
TTflK AMD EXPOSURE POTENTIAL
Monsanto stated that DEQUEST 2000 is used as a deflocculant and a
sequestrant. Monsanto did not provide any use information for the
sodium salt of aminotri(methylene phosphoric acid) nor was such
information located in the literature sources consulted by EPA.
490
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8EHQ-0490-0937 Init. and SUPPs
Page 3 of 3
COMMENTS/RECOMMENDATIONS
It should be noted that the Risk Analysis Branch (RAB/ECAD/OTS) is
currently conducting a review of ethylenediaminetetra(methylene-
phosphonic acid) (EDITEMPA).
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Monsanto will be requested to
describe the actions that the company has taken or plans
to take 1) to notify workers/others about the reported
information, and 2) to reduce or eliminate exposure to
the subject chemicals. Monsanto will be asked also to
provide copies of Material Safety Data Sheets and labels
that have been revised to reflect the reported findings.
In addition, Monsanto will be asked to describe the
nature and results, if available, of all studies (other
than those submitted already to EPA or those cited in the
published scientific literature) about which Monsanto is
aware or that the company has conducted, is conducting
or plans to conduct that are designed to determine the
toxicity of or the exposure to the subject chemicals.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
chemicals at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and RAB/ECAD/OTS;
in addition, copies of this status report will be sent
to the Environmental Assistance Division/OTS for further
distribution.
491
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Page 1 of 2
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
DATES JUL 231990 APPROVED:
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0490-0938
FROM: Martha G. Price, Ph.D., Chemist
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
In conjunction with a TSCA §8(e) Consent Agreement (TSCA 89-H-21),
Monsanto Company provided the following summary information
regarding the conduct and final results of a pilot rat teratology
study and the subsequent rat teratology study on o,p-
toluenesulfonamide, Santicizer 9 Plasticizer, (CAS No. 88-19-7 and
NO. 70-55-3):
In the pilot rat teratology study, dose levels of 0, 100, 500,
1000, 1500, and 2000 mg/kg/day were admimnistered orally by gavage
on days 6-15 of gestation.
"Signs of maternal toxicity were noted at 500 mg/kg and
all higher levels. Signs of developmental toxicity
(increased resorptions and postimplantation loss) were
noted at 1500 and 2000 mg/kg. Results from this study
suggest that while this material induces developmental
effects in rats, it does so only at dose levels that also
produce maternal toxicity."
In the rat teratology study, dose levels of 0, 50, 250, and 500
mg/kg/day were administered orally by gavage on days 6-15 of
gestation.
* This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
492
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8EHQ-0490-0938 S
Page 2 of 2
"Signs of maternal toxicity were observed at 250 and 500
mg/kg. Signs of developmental toxicity included
statistically significant decreased fetal body weight at
250 and 500 mg/kg and a statistically significant
increase in postimplantation loss at 500 mg/kg. An
increase in developmental variations (unossified
sternebrae) observed in pups of 500 mg/kg treated dams
was correlated with the fetal weight reduction seen in
this group. Results from this study suggest that while
this material induces developmental effects in rats, it
does so only at dose levels that also produce maternal
toxicity."
USE AND EXPOSURE POTENTIAL
Other than that it is a plasticizer, Monsanto provided no
information on the use of the subject product. According to The
Condensed Chemical Dictionary (10th edition), "Santicizer" is a
trademark for a series of plasticizers, including various
sulfonamides, phthalates, and glycollates.
Monsanto stated that "Monsanto Company no longer manufactures nor
markets this chemical and all of Monsanto's commercial activity on
this product ceased in 1985."
COMMENT 8/RECOMMENDATION8
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Monsanto Company will be
requested to describe the actions that the company has
taken or plans to take 1) to notify workers/others about
the reported information. In addition, Monsanto Company
will be asked to describe the nature and results, if
available, of all studies (other than those submitted
already to EPA or those cited in the published scientific
literature) about which Monsanto Company is aware or that
the company has conducted, is conducting or plans to
conduct that are designed to determine the toxicity of
or the exposure to the subject product chemicals.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
chemicals at this time.
c) The Chemical Screening Branch will send copies of this
Status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
493
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I
ss>
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
m
> V WASHINGTON, DC 20460 _ , ,
Page 1 of 1
DATE: | 7 990 APPROVED:
SUBJECT: Status Report1 8EHQ-04900939 INITIAL & SUPPLEMENT
FROM: Martha G. Price, Ph.D., Chemist^tAyi '
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBMISSION DESCRIPTION
In conjunction with a TSCA §8(e) Consent Agreement (TSCA 89-H-21), Monsanto Company provided in
the initial submission a final report of a pilot rat teratology study on trans-stilbene (CAS No. 103-30-0)
administered by gavage to mated female rats at dose levels of 0, 1, 3, 9, 27, and 80 mg/kg/day. In the
supplemental submission Monsanto provided a final report of a two-generation rat reproduction study and
rat fertility study on trans-stilbene administered by gavage to rats at dose levels of 0, 0.5, 2, and 8 mg/kg/day
prior to mating and throughout gestation and lactation for two generations.
COMMENTS/RECOMMENDATIONS
Monsanto reported that it no longer manufactures nor markets this chemical.
(a) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA NTP, OSWER/EPA OW/EPA ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
imfwvtinn at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
494
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\
im
I
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
*t#*cn*°
Page 1 of 1
ir,
OFFICE OF
PESTdDe8 AND
j i — i rcoiiMwcannw
DATE: 1'ImY 2 4 UJU APPROVED: UfU^i U / A/fri. fhlko toxic substances
SUBJECT: Status Report1 8EHQ-049CM)940
QosoLctiC V Aj)zvCLt-$c^)
FROM: Judith M. Loranger, Biologist
Chemical Screening Branch/ECAD/OTS
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
In conjunction with a TSCA Section 8(e)-related "Consent Agreement" (TSCA 89-H-21), the Monsanto
Company submitted a copy of a rat teratology study of ethylenediaminetetra(methylenephosphonic acid)
(EDITEMPA; CAS No. 1429-50-1). Mated female rats were dosed by gavage at levels of 0.5, 1 or 2 g/kg
of the test compound from gestation day 6 through gestation day 19.
COMMENTS/RECOMMENDATIONS
Monsanto reported that they no longer manufacture or market this chemical in the United States.
It should be noted that EPA has received a number of TSCA Section 8(e) and "For Your Information"
(FYI) submissions on this compound. A Chemical Hazard Information Profile was prepared (in 1984) on
EDITEMPA and its tetrapotassium and hexasodium salts. Immediately upon receipt of this Section 8(e)
submission, the Chemical Screening Branch notified the Risk Analysis Branch (RAB/ECAD/OTS); RAB is
expected to include the reported information in their ongoing review of phosphonic acid compounds,
including EDITEMPA Finally, it should be noted that EDITEMPA is the subject of a TSCA Section 8(a)
information gathering rule.
a) As was the case with the initial submission, staff of the Chemical Screening Branch will
notify the Risk Analysis Branch about the receipt of any additional incoming information
on EDITEMPA
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA NTP, OSWER/EPA, OW/EPA, ORD/EPA OAR/EPA OPP/OPTS/EPA and
RAB/ECAD/OTS; in addition, copies of this status report will be transmitted to the
Environmental Assistance Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are
available for public inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C 20460.
All requests for TSCA Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
495
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use
c°
"V rue**-
J
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page l of 3
DATE:
AUG 2 4 !99u
APPROVEDS
SUBJECT: Status Report1 8EHQ-0490-0941
FROM: Martha G. Price, Ph.D., Chemist
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBMISSION DESCRIPTION
In conjunction with a TSCA §8(e) Consent Agreement (TSCA 89-H-21),
Monsanto Company provided the following summary information
regarding the conduct and final results of both a pilot rat
teratology study and the subsequent rat teratology study on 1,3-
Dimethylbenzene, Benzylated (CAS No. 68908-87-2):
"A pilot study with pregnant Charles River CD rats
(IRD-77177A) was performed to determine dosage levels for
a teratology study. [Benzylated 1,3-dimethylbenzene] was
administered by gavage at 10, 30, 100, 300 and 1000
mg/kg/day to pregnant rats from gestation day 6 through
day 15. A control group received the vehicle, 0.5%
Methocel, at 10 ml/kg/day.
"During gestation the females were observed for clinical
signs of effect, mortality and body weight gains. The
rats were sacrificed on gestation day 20 and the uterine
contents examined for viable and nonviable fetuses, early
and late resorptions, and total implantations.
- This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
496
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8EHQ-0490-0941 S
Page 2 of 3
"There were no changes in appearance or behavior which
were attributed to [benzylated 1,3-dimethylbenzene] for
those females receiving 300 mg/kg/day or less. There were
no compound related differences for the number of viable
or nonviable fetuses, resorptions, implantations, corpora
lutea or maternal body weight gains, for females with
dosage levels of 100 mg/kg/day or less. There was a
slight decrease in body weight gains during gestation and
an increase in early resorptions and a slight decrease
in number of viable fetuses attributed to treatment for
those females receiving 300 mg/kg/day. All rats given
1000 mg/kg/day died by the fifth day of treatment."
The summary for the follow-up rat teratology study follows:
"Pregnant Charles River CD rats were used to evaluate the
teratogenic potential of [benzylated 1,3-dimethylbenzene]
in this study. The compound was administered by gastric
intubation at dosage levels of 30, 100 and 300 mg/kg/day
from days 6 through 15 of gestation. A control group
received the vehicle, 0.5% aqueous methylcellulose, at
10 ml/kg/day.
"During gestation the females were observed for clinical
signs of effect, mortality and body weight changes.
Cesarean sections were performed on gestation day 20. The
number of viable and nonviable fetuses, early and late
resorptions, corpora lutea and total implantations were
recorded. The fetuses were weighed, sexed, and examined
for external, soft tissue, and skeletal anomalies and
variations.
"There were no changes in appearance or behavior
attributable to treatment with [benzylated 1,3-
dimethylbenzene] at dosage levels of 30 and 100
mg/kg/day. One rat in the 100 mg/kg/day dosage group and
two rats in the 300 mg/kg/day dosage group died; the
cause of death was not determined at necropsy. There were
slightly reduced mean maternal body weight gains during
the first six days of treatment in the rats in the 100
mg/kg/day dosage group. Maternal toxicity was evidenced
at the 300 mg/kg/day dosage level. Slight maternal mean
body weight loss was observed during the first six days
of treatment and hair loss was observed for 14 of the 25
rats. Hair loss was first recorded two to six days after
the initiation of treatment and continued until sacrifice
or death. Hair loss was also noted for 2 rats in the
control group and 7 rats in the 100 mg/kg/day dosage
group.
"There were no statistically significant or biologically
meaningful differences in the mean number of viable
fetuses, implantations, post implantation losses, corpora
lutea, or in the male to female sex ratio between any of
497
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8EHQ—0490-0941 S
Page 3 of 3
the [benzylated 1,3-dimethylbenzene] treated groups and
the control group. Fetal toxicity in the 100 and 300
mg/kg/day dosage groups was evidenced by decreased mean
fetal body weights when compared to the control group.
There were no malformations in the control group or the
30 mg/kg/day dosage group. There was one malformed fetus
in each of two litters in the 100 mg/kg/day dosage group
and six malformed fetuses in 4 litters in the 300
mg/kg/day dosage group."
P8E AND EXPOSURE POTENTIAL
Monsanto did not provide any information regarding the use of or
the potential for exposure to benzylated 1,3-dimethylbenzene, nor
was such information located in the secondary literature sources
consulted by EPA.
COMMENTS/RECOMMENDATIONS
In its submission, Monsanto stated that "Monsanto Company no longer
manufactures nor markets this chemical and all of Monsanto's
commercial activity on this product ceased in 1987."
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Monsanto will be requested to
describe the actions that the company took to notify
workers/others about the reported information. In
addition, Monsanto will be asked to describe the nature
and results, if available, of all studies (other than
those submitted already to EPA or those cited in the
published scientific literature) about which Monsanto is
aware or that the company conducted that were designed
to determine the toxicity of or the exposure to the
subject chemical.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
498
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^eir%
1 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC20460 Page 1 of 3
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
DATE:
MAY 91990
APPROVED:
SUBJECTS Status Report1 8EHQ-0490-0942
FROM: Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
In conjunction with a TSCA Section 8(e)-related "Consent Agreement"
(TSCA 89-H-21), the Monsanto Company submitted a complete copy of
a rat teratology study of SteroxR DJ Surfactant (poly (oxy-1,2-
ethanediyl) alpha-dodecylphenyl-omega-hydroxy; CAS No. 9014-92-0).
The SYNOPSIS Section from this report presents the following
summary information regarding the conduct and results of this
study:
"Mated Charles River COBSR CDR rats consecutively
assigned to one control and three treatment groups of 25
animals each were used to determine the teratogenic
potential of SteroxR DJ Surfactant. Dosage levels of
50, loo, and 500 mg/kg/day were administered orally by
gavage as a single daily dose on days 6 through 15 of
gestation at a constant volume of 10 ml/kg. The control
group received the vehicle only, deionized water, on a
1 This status report is the result of a preliminary evaluation of information that has
been submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substances Control Act (TSCA). The statements made in this status
report should not be regarded as expressing final Agency policy or intent with respect to the
subject chemical(s). Any review of this status report should take into account that the
report may be based on incomplete information.
499
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8EHQ-0490-0942
Page 2 of 3
comparable regimen. Cesarean sections were performed on
all females on gestation day 20 and the fetuses were
removed for teratologic evaluation.
"Survival was 100% in the control and all treated groups.
"Antemortem findings attributed to treatment included
increased hair loss with increase in dosage level, and
excess salivation in the 100 and 500 mg/kg/day groups.
Wet, matted haircoat around the mouth and/or anogenital
area, rales and soft stool occurred in the 500 mg/kg/day
group only. Necropsy findings in all treated groups were
comparable to those of the control group.
"Group mean maternal body weight gain values for the 50
mg/kg/day dosage group were comparable to those of the
control group during the overall treatment and gestation
periods (days 6 to 15 and 0 to 20, respectively). There
was a slight decrease in this parameter for the 100
mg/kg/day group and a notable decrease for the 500
mg/kg/day group over these periods, and were considered
to be treatment-related.
"There were no biologically meaningful differences
between the control and treated groups in regard to
uterine examination parameter values.
"Fetal sex ratio values-for all treated groups and mean
fetal body weight values for the low- and mid-dose groups
were comparable to the control group values. Fetal body
weight values for the high-dose group were significantly
(p<0.01) less in comparison to the control group value,
and were also outside the historical control range and
considered treatment-related.
"An increase in the incidence of retarded bone
ossification occurred in the 500 mg/kg/day dosage group
when compared to the control group. This finding, in
conjunction with reduced fetal body weight for this
group, were considered indicative of fetotoxicity.
Fetotoxicity was not evident at the mid-dose and low-dose
levels.
"Although an increased incidence of microphthalmia was
observed at the 500 mg/kg/day dosage level this anomaly
is not an uncommon finding in test animals of this
species and strain."
ITflE AND EXPOSURE POTENTIAL
Monsanto did not provide any information regarding the use of this
specific surfactant nor was such information located in the
secondary literature sources consulted by EPA.
500
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8EHQ-0490-0942
Page 3 of 3
COMMENTS/RECOMMENDATIONS
In its submission, Monsanto reported that the results from this
study were incorporated into the current Material Safety Data Sheet
for this product.
It should be noted that EPA has received a number of TSCA Section
8(e) and "For Your Information" (FYI) submissions on a variety of
surfactants.
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Monsanto will be requested to
describe the actions that the company has taken or plans
to take 1) to notify workers/others about the reported
information, and 2) to reduce or eliminate exposure to
the subject chemical. Monsanto will be asked also to
provide copies of Material Safety Data Sheets and labels
that have been revised to reflect the reported findings.
In addition, Monsanto will be asked to describe the
nature and results, if available, of all studies (other
than those submitted already to EPA or those cited in the
published scientific literature) about which Monsanto
is aware or that the company has conducted, is conducting
or plans to conduct that are designed to determine the
toxicity of or the exposure to the subject chemical.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS for further
distribution.
501
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
Page 1 of 1
DATE: JUL | 7 1990 APPROVED
OFFICE OF
PESTICIDES AND TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0490-0943
FROM: Martha G. Price, Ph.D., Chem
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
In conjunction with a TSCA §8(e) Consent Agreement (TSCA 89-H-21), Monsanto Company provided a
final report of a rat teratology study on the 1-cyclohexylethyl ester of butanoic acid (CP 80624) (CAS No.
63449-88-7) administered by gavage to pregnant rats at dose levels of 0, 100, 300, 1000, and 3000 mg/kg/day.
COMMENTS/RECOMMENDATIONS
Monsanto reports that it no longer manufacturers nor markets this chemical.
a) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statement* made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
502
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^osM. Page 1 of 3
(
as
| UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
r<& WASHINGTON, DC 20460
DATES AUG 2 4 1990 APPROVED! A^Z-, ™c substances
SUBJECTS Status Report1 8EHQ-0490-0944
OFFICE OF
PESTICIDES AND
(/ y/iifyo
FROM: Martha G. Price, Ph.D., Chemis
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
In conjunction with a TSCA §8(e) Consent Agreement (TSCA 89-H-21),
Monsanto Company provided the following summary information
regarding the conduct and final results of a pilot rat teratology
study on PHOSGARD® 2XC20 (CAS No. 38051-10-4):
"Pregnant Charles River COBS* CD* rats were used to
determine dosage levels of Phosgard 2XC20 for a
teratology study. Dosage levels of 100, 200, 400, 800 and
1600 mg/kg/day were administered orally by gavage as a
single daily dose on days 6 through 19 of gestation at
volumes of 0.07, 0.14, 0.27, 0.54 and 1.09 ml/kg,
respectively. The control group received distilled water
on a comparable regimen at a volume equal to the high
dose group (1.09 ml/kg). Uterine examinations were
performed on all surviving rats on gestation day 20.
"One rat in the 800 mg/kg/day dosage group and all rats
in the 1600 mg/kg/day dosage group died between gestation
days 7 and 9. Causes of death could not be determined at
necropsy. A post-dose increase in activity was noted in
rats in the 200, 400 and 800 mg/kg/day dosage groups. An
increase in anogenital staining and dry red matter around
- This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
503
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8EHQ-0490-09 44
Page 2 of 3
the nose and forepaws occurred in rats in the 4 00 and 800
mg/kg/day dosage groups. There were no biologically
meaningful differences in mean uterine examination values
in any treated group, or in mean maternal body weight
gains in the 100, 200 or 400 mg/kg/day dosage groups when
compared to the control group. A severe reduction in mean
maternal body weight gain was noted over the entire
treatment period in the 800 mg/kg/day dosage group.
"There were no biologically meaningful differences in the
mean numbers of viable fetuses, postimplantation loss,
early or late resorptions, total implantations or corpora
lutea in the 100, 200, 400 or 800 mg/kg/day treatment
groups when compared to the control group means. While
there was a slight increase in mean postimplantation loss
(1.0 per dam) in the 800 mg/kg/day dosage group, it was
comparable to the mean historical control value (0.9 per
dam)."
USE AND EXPOSURE POTENTIAL
Monsanto did not provide any information regarding the use of or
the potential for exposure to PHOSGARD* 2XC20. According to The
Condensed Chemical Dictionary (10th edition), "PHOSGARD" C-22-R
is a trademark for a flame retardant organophosphorus compound.
It should be noted that EPA has also received a TSCA §8(e)
submission, 8EHQ-0490-0947, on PHOSGARD* C-22-R.
COMMENT8/RECOMMENDATIONS
Monsanto stated that "Monsanto Company no longer manufactures nor
markets this chemical [PHOSGARD* 2XC20] and all of Monsanto's
commercial activity on this product ceased in 1982."
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Monsanto will be requested to
describe the actions that the company took to notify
workers/others about the reported information. In
addition, Monsanto will be asked to describe the nature
and results, if available, of all studies (other than
those submitted already to EPA or those cited in the
published scientific literature) about which Monsanto is
aware or that the company conducted that were designed
to determine the toxicity of or the exposure to the
subject chemical.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
504
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8EHQ-0490-0944
Page 3 of 3
c) The Chemical Screening Branch will send copies of this
Status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
505
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
» - - x, WASHINGTON, DC 20460 ~ , , .
Page 1 of 1
OFFICE OF
/\ ^ A j , PESTICIDES AND
DATE: j 1 ,rpr APPROVED: V < (JaSirv. fill/jo toxic substances
SUBJECT: Status Report1 8EHQ-0490-0945 INITIAL & SUPPLEMENTS
FROM: Martha G. Price, Ph.D., Chemist (Xy[ ^—'j) kV/
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
In conjunction with a TSCA §8(e) Consent Agreement (TSCA 89-H-21), Monsanto Company provided a
number of reports on oxoacetic acid homopolymer, sodium salt, "Builder U" (CAS No. 70205-95-7). The
initial submission contains an MSDS for the chemical and a final report of a two-generation rat reproduction
study administered in drinking water at dose levels of 0, 600, 3000, and 15,000 ppm prior to mating and
throughout gestation and lactation for two generations. In the supplemental submissions, Monsanto
provided final reports of pilot (1) rat and (2) rabbit teratology studies administered by gavage at dose levels
of 0, 125, 250, 500, 1000, and 2000 mg/kg/day, (3) a final rabbit teratology study administered by gavage at
dose levels of 0, 50, 250, and 500 mg/kg/day, and (4) a final rat teratology study administered by gavage at
dose levels of 0, 250, 1000, and 2500 mg/kg/day.
COMMENTS/RECOMMENDATIONS
Monsanto reported that it no longer manufactures nor markets this chemical.
(a) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA, and
IMD/OTS/EPA; in addition, copies of this status report will be transmitted to the
Environmental Assistance Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
506
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^t0SK%
w
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY Page 1 of 3
WASHINGTON, DC 20460
DATES
FROM:
JUN 4 1990
APPROVED:
SUBJECT: Status Report1 8EHQ-0490-0946
4dL
T .bh/qo
PESTICIDES AND
TOXIC SUBSTANCES
Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
In conjunction with a TSCA Section 8(e)-related "Consent Agreement"
(TSCA 89-H-21), the Monsanto Company provided a copy of the final
report of a one generation reproduction study of iminodiacetic acid
(CAS No. 142-73-4) in rats. Monsanto also provided the following
summary information regarding the conduct and results of this
study:
"Male and female albino rats were administered
iminodiacetic acid (IDA) at targeted levels of 0, 200,
2000 or 6000 parts per million (ppm) in the diet. The
diet mixtures were shown to be homogeneous and stable
over the period of use, and mean analytical values
obtained during the entire study were within 5% of target
levels.
"There were no clinical observations nor gross or
microscopic findings considered to be related to the test
material. slight (not statistically significant) body
weight decreases were seen in adult males at the T-3
[6000 ppm] levels only and were probably a result of
minor reductions in food consumption.
I This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
507
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8EHQ—0490-0946
Page 2 of 3
"There were no adult mortalities, but analysis of pup
survival indicated a dose-related, non-statistically
significant, decrease in pup survival during the
lactation day 0 to day 4 period.
"There were no statistically significant differences in
litter size at birth, number of pups born dead or in pup
body weights. Although significant (p < 0.05) decreases
in litter size were apparent at the low and high test
levels on days 7 and 14 after birth, these were not
considered treatment-related.
"There was no conclusive evidence of toxicity to the
adults of offspring in this study. Therefore, the
highest level (6000 ppm) is considered a no effect level
(NOEL) for reproductive toxicity."
USE AND EXPOSURE POTENTIAL
Monsanto did not provide any information regarding the use(s) of
or the potential for exposure to this chemical, nor was such
information located in the secondary literature sources consulted
by EPA.
COMMENTS/RECOMMENDATIONS
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Monsanto will be requested to
describe the actions that the company has taken or plans
to take 1) to notify workers/others about the reported
information, and 2) to reduce or eliminate exposure to
the subject chemical. Monsanto will be asked also to
provide copies of Material Safety Data Sheets and labels
that have been revised to reflect the reported findings.
In addition, Monsanto will be asked to describe the
nature and results, if available, of all studies (other
than those submitted already to EPA or those cited in the
published scientific literature) about which their
company is aware or that the company has conducted, is
conducting or plans to conduct that are designed to
determine the toxicity of or the exposure to the subject
chemical.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
508
-------
8EHQ-0490-0946
Page 3 of 3
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS for further
distribution.
509
-------
^eos^
(9K
9
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
^ WA WASHINGTON, DC 20460 n . . .
% Page 1 of 1
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
DATE:
-------
s*,
(m.
r<
PH0lt
i
9
X
Page 1 of 4
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
DATE:
AUG J 4 1990
APPROVED: L/Umi*
ts
o/vy
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
ihko
SUBJECT: Status Report1 8EHQ-0490-0948
FROM: Martha G. Price, Ph.D., Chemist^^^Y^/L^^^'Ct^
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
In conjunction with a TSCA §8(e) Consent Agreement (TSCA 89-H-21),
Monsanto Company provided the following summary information
regarding the conduct and final results of both a pilot rat
teratology study and the subsequent rat teratology study on
TETRATHAL*, tetrachlorophthalic anhydride (CAS No. 117-08-8):
"This pilot study was conducted for Monsanto Company to
evaluate the toxicity of Tetrathal in the pregnant rat.
Test material was administered by qastric intubation to
mated female CD® rats (five females/group) during the Day
6-19 gestation interval. Dose levels were 250, 500, 1000,
1750 and 2500 mg/kg/day. Females were sacrificed on Day
20 of gestation and uterine implantation data evaluated.
Fetuses recovered at this time were evaluated externally
for malformations. Included in the study was a vehicle
(corn oil) control group (five mated females).
"One female in the 1000 mg/kg dose group and two females
in the 2500 mg/kg dose group died during the study. No
mortality was seen in the control group or at the 250,
500 or 1750 mg/kg dose levels. During the gross post-
mortem evaluations of the one female that died at the
- This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
511
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8EHQ-0490-094 8
Page 2 of 4
1000 mg/kg dose level and one of two females that died
at the 2500 mg/kg dose level, an oily fluid was seen in
the thoracic cavity. Death of these two animals may have
been accidental and possibly related to a mis-dosing
situation.
"No clear dose-related effect of treatment on mean body
weight change during the Day 6-20 gestation interval was
evident. Usinq corrected Day 2 0 body weight data, a mean
weight loss was seen during the Day 6-20 gestation
interval at the 500, 1000 and 2500 mg/kg dose levels. A
mean weight gain was seen in the control, 250 mg/kg and
1750 mg/kg dose groups during this same interval.
"During the in-life physical evaluations, several females
at the higher dose levels (1750 and 2500 mg/kg) had
yellowish staining of the fur in the ano-genital region.
Soft stool was also noted in several females at these
same dose levels.
"No treatment effect was evident at any of the dose
levels in regards to uterine implantation data or
maternal gross postmortem findings.
"Fetal evaluations indicated a slight but consistent
reduction in mean weights (both sexes) at the 2500 mg/kg
dose level. External evaluation of fetuses recovered at
all treated levels did not reveal an increase in
malformations."
In the follow-up rat teratology study, TETRATHAL® is identified as
CP 626. The summary for this study follows:
"This study was conducted for the Monsanto Company to
evaluate the embryotoxic and/or teratogenic potential of
CP 626 in the rat. Test material was administered by
gastric intubation at dose levels of 250, 1000 and 2000
mg/kg/day. Each dose group was comprised of 24 mated CD
female rats and each female was treated during the Day
6-19 gestation interval. Females were sacrificed on Day
20 of gestation and uterine implantation data recorded.
Fetuses recovered at this time were weighed, sexed and
examined for external, soft tissue and skeletal
malformations. Included in this study was a vehicle (corn
oil)-treated control group.
"One female died in each of the low- and mid-dose groups
(mortality rate = 4.2%) and two females died in the
high-dose group (mortality rate = 8.3%). In each case
mortality was attributed to dosing-related injury and not
treatment-related. None of the control females died
during the study.
512
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8EHQ—0490-0984
Page 3 of 4
"No treatment-related effect was evident in maternal body
weight data.
"During the physical in-life evaluations, several mid-
and high-dose females were noted as lethargic soon after
daily dosing. This observation was most prominent in the
high-dose group and was seen as early as Day 6 of gesta-
tion. Additionally, four high-dose females had a pale eye
color on Day 20 of gestation; this type of observation
was seen in one low-dose female on Day 20 of gestation
but not seen in the mid-dose females. Pale eye color was
not noted among the control females throughout the study.
"No adverse effects of treatment were evident in uterine
implantation data (mean number of resorptions/fetuses;
mean percentage of resorptions/fetuses to implants) or
maternal gross postmortem examinations.
"Mean fetal weights were comparable to control in the
low- and mid-dose groups and significantly lower than
control in the high-dose group. No treatment-related
effect on fetal sexing data was evident. The types and
incidences of ossification variations noted during the
fetal skeletal evaluations were comparable between the
control, low- and mid-dose groups. In the high-dose
group, a slight increase in the incidence of fetuses with
asymmetric/unossified sternebrae and incompletely
ossified thoracic vertebral centra was indicated.
"External, soft tissue and skeletal evaluations of
fetuses recovered from the low- and mid-dose females did
not reveal an increase in malformation rate. In the
high-dose group, a slight increase in the incidence of
fetuses with skeletal malformations was seen (incidence
of fetuses with skeletal malformations for the control
and high-dose groups was 1.9% and 4.6%, respectively).
The types of vertebral/rib defects seen in several
high-dose fetuses are not commonly seen in the rat fetus.
The presence of these types of malformations though seen
in low incidence both in fetuses affected and litters
involved is suggestive of a marginal teratogenic response
at the high-dose level.
"Thus, CP 626 administered by gastric intubation to
pregnant rats at dose levels of 250 and 1000 mg/kg during
the 6-19 gestation interval was not maternally toxic,
embryotoxic or teratogenic. At the 2000 mg/kg dose level,
CP 626 demonstrated some maternally toxic affects
(lethargic response post-dosing) and embryo-fetotoxicity
(reduced fetal weights). A marginal teratogenic response
was also suggested at this dose level."
513
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8EHQ-0490-0984
Page 4 of 4
USE AND EXPOSURE POTENTIAL
Monsanto did not provide any information regarding the use of or
the potential for exposure to tetrachlorophthalic anhydride.
According to The Condensed Chemical Dictionary (10th edition),
tetrachlorophthalic anhydride is used as an intermediate in dyes,
pharmaceuticals, plasticizers, and other organic materials, and as
a flame-retardant in epoxy resins.
COMMENTS/RECOMMENDATIONS
In its submission, Monsanto stated, "Developmental effects noted
for this chemical are discussed in the current Monsanto Material
Safety Data Sheet for TETRATHAL®." EPA has also received a "For
Your Information" (FYI) submission, FYI-OTS-0787-0559, on tetra-
chlorophthalic anhydride.
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Monsanto will be requested to
describe the actions that the company has taken or plans
to take 1) to notify workers/others about the reported
information, and 2) to reduce or eliminate exposure to
the subject chemical. Monsanto will be asked also to
provide copies of Material Safety Data Sheets and labels
that have been revised to reflect the reported findings.
In addition, Monsanto will be asked to describe the
nature and results, if available, of all studies (other
than those submitted already to EPA or those cited in the
published scientific literature) about which Monsanto is
aware or that the company has conducted, is conducting
or plans to conduct that are designed to determine the
toxicity of or the exposure to the subject chemical.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
Status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
514
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,10s*. Page 1 of 3
I KM|Ky UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
*1
DATE:
SUBJECT:
FROM:
TO:
APPROVED:
(J c>
Status Report1 8EHQ-0490-0949
r/c;.
J fyo
is tu J
Martha G. Price, Ph.D., Chemis
Chemical Risk Identification Section/CSB
James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBMISSION DESCRIPTION
In conjunction with a TSCA §8(e) Consent Agreement (TSCA 89-H-21),
Monsanto Company provided the following summary information
regarding the conduct and final results of a rat teratology study
on l,l»-(1,1,3-trimethy1-1,3-propanediyl)biscyclohexane (HLD) , (CAS
No. 38970-72-8):
"This study, conducted for the Monsanto Company, was
designed to evaluate the embryotoxic and/or teratogenic
potential of HLD (CP 85020) . The test substance was
administered via gastric intubation to female Charles
River CD® (Sprague-Dawley derived) rats (20/group) at
dose levels of 300, 1000 and 3000 mg/kg/day (due to an
error in formulation of dosing suspensions, actual doses
given were 290, 905 and 2277 mg/kg/day, respectively)
during the period of organogenesis (Days 6-15 of
gestation). Females were sacrificed on Day 21 of
gestation and fetuses were examined for external,
skeletal and soft tissue malformations.
"Two concurrent vehicle control groups were used for this
study...
- This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
515
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8EHQ-0490-0949
Page 2 of 3
"Parameters evaluated include: maternal mortality and
pregnancy, in-life physical observation, body weight
gain, necropsy observations and uterine implantation
data. Fetal parameters include: size and sex data,
ossification variation data, and fetal malformation data.
"High-dose females gained more weight during the dosing
period, and the low- and high-dose groups had higher
implantation efficiency values. Neither of these
differences were considered indicative of an adverse
effect of treatment.
"Low-dose females had a higher number of resorption sites
and the incidence of dams with two or more resorptions
was also increased. Similar effects on resorption data
were not observed at the mid- or high-dose groups. In the
absence of a dose relationship, resorption data were not
considered to be effected by treatment.
"Fetal body weights (both sexes) for each of the treated
groups were higher than control and fetal length data
(crown-rump distance) revealed no differences.
"Thus, HLD (CP 85020) administered by gastric intubation
at dose levels of 290, 905 and 2277 mg/kg/day from Days
6-15 of gestation was not considered to be either
embryotoxic or teratogenic in the rat."
USE AND EXPOSURE POTENTIAL
Monsanto did not provide any information regarding the use of or
the potential for exposure to HLD.
COMMENTS/RECOMMENDATIONS
In its submission, Monsanto stated, "Results from the referenced
study are discussed in the current Monsanto Material Safety Data
Sheet for this product."
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Monsanto will be requested to
describe the actions that the company has taken or plans
to take 1) to notify workers/others about the reported
information, and 2) to reduce or eliminate exposure to
the subject chemical. Monsanto will be asked also to
provide copies of Material Safety Data Sheets and labels
that have been revised to reflect the reported findings.
In addition, Monsanto will be asked to describe the
nature and results, if available, of all studies (other
than those submitted already to EPA or those cited in the
published scientific literature) about which Monsanto is
516
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8EHQ-0490-0949
Page 3 of 3
aware or that the company has conducted, is conducting
or plans to conduct that are designed to determine the
toxicity of or the exposure to the subject chemical.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
517
-------
f/n h»
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY page 1 of 2
WASHINGTON, DC 20460
o*°
OFFICE OF
r> 4 ¦ " A - PESTICIDES AND
DATE! APPROVED: 1/7 Varv-i^ toxic substances
SUBJECT: Status Report1 8EHQ-0490-0950
£PcccLttf- H J
FROM: Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
In conjunction with a TSCA Section 8(e)-related "Consent Agreement11
(TSCA 89-H-21), the Monsanto Company provided the final report of
a rat teratology study of the sodium salt of diethylenetriamine-
penta(methylene phosphonic acid) (DEQUEST 2061 Phosphonate; CAS No.
22042-96-2). In this study, mated female rats were dosed by gavage
at levels of 500, 1000 or 2000 mg/kg of the test compound from
gestation day 6 through 19. Monsanto provided the following
summary information regarding the results of this study:
"Signs of maternal toxicity were noted in 2000 mg/kg
treated dams. Increased skeletal variations and a low
incidence of vertebral anomalies occurred at the 1000 and
2 000 mg/kg dose levels. Though the incidence of verte-
bral anomalies was low, this type of anomaly has a rare
spontaneous occurrence and thus may be related to treat-
ment ."
Monsanto reported that the "results from the referenced study [of
DEQUEST 2061 Phosphonate] are discussed in the current Monsanto
Material Safety Data Sheets (MSDSs) for DEQUEST 2060 and 2066
deflocculant and sequestrant."
I This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
518
-------
8EHQ-0490-0950
Page 2 of 2
It should be noted that EPA recently received a TSCA Section 8(e)
submission on diethylenetriaminepenta(methylene phosphonic acid).
The reader's attention is directed to the status report prepared
by EPA in response to 8EHQ-0490-0951.
USE AND EXPOSURE POTENTIAL
Monsanto did not provide any specific information regarding the
use(s) of DEQUEST 2061 Phosphonate nor was such information found
by EPA in the secondary literature consulted.
COMMENTS/RECOMMENDATIONS
It should be noted that the Risk Analysis Branch (RAB/ECAD/OTS) is
currently conducting a review of ethylenediaminetetra(methylene-
phosphonic acid) (EDITEMPA).
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Monsanto will be requested to
describe the actions that the company has taken or plans
to take 1) to notify workers/others about the reported
information, and 2) to reduce or eliminate exposure to
the subject chemical. Monsanto will be asked also to
provide copies of Material Safety Data Sheets and labels
that have been revised to reflect the reported findings.
In addition, Monsanto will be asked to describe the
nature and results, if available, of all studies (other
than those submitted already to EPA or those cited in the
published scientific literature) about which Monsanto
is aware or that the company has conducted, is conducting
or plans to conduct that are designed to determine the
toxicity of or the exposure to the subject chemical.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and RAB/ECAD/OTS;
in addition, copies of this status report will be sent
to the Environmental Assistance Division/OTS for further
distribution.
519
-------
^t08%
im
G°
PKO^
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY Page 1 of 2
WASHINGTON, DC 20460
DATE:
MAY 2 4 1990
APPROVED:
ML
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT:
FROM:
TO:
zhiho
Status Report1 8EHQ-0490-0951
Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
In conjunction with a TSCA Section 8(e)-related "Consent Agreement"
(TSCA 89-H-21), the Monsanto Company provided the final report of
a one generation rat reproduction study of diethylenetriaminepenta-
(methylenephosphonic acid) (CAS No. 15827-60-8) . Monsanto provided
the following summary information regarding the conduct and results
of this study:
"Results have been obtained from a One Generation Rat
Reproduction study on diethylenetriaminepenta(methylene
phosphonic acid). In this study, this material was
administered via the diet to 3 groups of rats at dose
levels of 300, 1000 and 3000 ppm. Diethylenetriamine-
penta (methylenephosphonic acid) administration to the F0
generation females was initiated at the onset of gesta-
tion and continued throughout gestation and lactation.
Dietary administration continued to the F1 generation
animals through a growth period and mating, gestation and
lactation period for 2 successive litters.
"Signs of maternal toxicity were observed at 3 000 ppm.
Decreases in mean live offspring weights, attributed to
lower maternal body weights, were noted at 3 000 ppm.
I This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
520
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8EHQ—0490-0951
Page 2 of 2
Results from this study suggest that while this material
induces developmental effects in rats, it does so only
at a dose level that also produces maternal toxicity."
Monsanto has reported that "results from the referenced study are
discussed in the current Monsanto Material Safety Data Sheet (MSDS)
for DEQUEST 2060 deflocculant and sequestrant."
It should be noted that EPA recently received a TSCA Section 8(e)
submission on the sodium salt of diethylenetriaminepenta(methylene
phosphonic acid). The readers attention is directed to the status
report prepared in response to 8EHQ-0490-0950.
USE AMD EXPOSURE POTENTIAL
As stated previously, DEQUEST 2060 is used a deflocculant and
sequestrant.
COMMENTS/RECOMMENDATIONS
It should be noted that the Risk Analysis Branch (RAB/ECAD/OTS) is
currently conducting a review of ethylenediaminetetra(methylene-
phosphonic acid) (EDITEMPA).
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Monsanto will be requested to
describe the actions that the company has taken or plans
to take 1) to notify workers/others about the reported
information, and 2) to reduce or eliminate exposure to
the subject chemical. Monsanto will be asked also to
provide copies of Material Safety Data Sheets and labels
that have been revised to reflect the reported findings.
In addition, Monsanto will be asked to describe the
nature and results, if available, of all studies (other
than those submitted already to EPA or those cited in the
published scientific literature) about which Monsanto
is aware or that the company has conducted, is conducting
or plans to conduct that are designed to determine the
toxicity of or the exposure to the subject chemical.
b) As part of the initial phase of the 0TS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and RAB/ECAD/OTS;
copies of this report will be sent to the Environmental
Assistance Division/OTS for further distribution.
521
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Page 1 of 3
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
m zm
PESTICIDES AND
TOXIC SUBSTANCES
DATE:
APPROVED
SUBJECT: Status Report 8EHQ-0490-0952 8
FROM:
Jacqueline T. Favilla, Biologist 0
Chemical Risk Identification Section/efSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
yOTg (See NOTE on Page 3 of this status report)
The submitting company has claimed its company name and the exact
identity of the subject chemical as TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. In the "sanitized" version of its Section 8(e)
notice, the company reported non-confidentially that the subject
chemical is a "carbamic acid nitrile."
8PBMI88ION DESCRIPTION
The submitting company provided the following summary information
regarding the conduct and preliminary results of a study designed
to evaluate the carcinogenic potential of the subject chemical in
male and female Crl:CD-I(ICR)-BR mice:
"Sixty animals/sex/group received the compound in
drinking water at dose levels of 0, 70, 200 or 600 ppm.
Because survival was very good at 80 weeks, the study was
extended to 100 weeks in males and 104 weeks in females.
The preliminary report showed eight cases of benign
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
522
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8EHQ-0490-0952 S
Page 2 of 3
granulosa-theca tumors of the ovary in the high dose
group females. Two similar tumors were identified in the
concurrent control group, while diagnosis of a possible
third tumor was compromised due to tissue necrosis. The
pathology report also noted five instances of ovarian
hyperplastic lesions which were described as 'borderline
to tumors,' a term not commonly employed among
pathologists.
"Pairwise statistical comparison between the control and
the high dose groups was significant (p<0.05) if the
necrotic case in the control group was excluded from the
analysis, but not if it was included. . . A consulting
pathologist . . . reported that in his opinion the
problematic necrotic tissue was not tumorous, and
therefore the observed increase in tumors was
statistically significant by pairwise comparison."
". . .No effects on mortality and morbidity were
observed in the male mice."
U8g AND EXPOSURE POTENTIAL (see NOTE on Page 3 of this status report)
In view of the submitter's TSCA CBI claims, no information
regarding the TSCA Chemical Substance Inventory status or use(s)
of the subject chemical will appear in this status report.
COMMENTS/RECOMMENDATIONS
In its submission, the company reported that a final report of this
study will be submitted to EPA when it becomes available, and that
the company is considering what, if any, additional research may
be appropriate. Also, the company stated that it will review its
MSDSs and product labeling and make appropriate revisions.
a) The Chemical Screening Branch will ask the submitting
company to ensure that EPA receives a complete copy of
the final report (including the actual experimental
protocol, results of gross/histopathologic examinations,
results of statistical analyses, etc.) from the chronic
drinking water study cited in the submission.
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, the company will be requested to
describe the actions that the company has taken or plans
to take 1) to notify workers/others about the reported
information, and 2) to reduce or eliminate exposure to
the subject chemical. The company will be asked also to
provide copies of Material Safety Data Sheets and labels
that have been revised to reflect the reported findings.
523
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8EHQ-0490-0952 S
Page 3 of 3
in addition, the company will be asked to describe the
nature and results, if available, of all studies (other
than those submitted already to EPA or those cited in the
published scientific literature) about which the company
is aware or that the company has conducted, is conducting
or plans to conduct that are designed to determine the
toxicity of or the exposure to the subject chemical.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
NOTE According to non-confidential information contained in a
May 15, 1991 followup letter and enclosure (8EHQ-0591-
0952 FLWP), the actual identity of the subject chemical
is no longer considered confidential and is reported to
be "hydrogen cyanamide." According to the printed 1985
Edition of EPA's TSCA Chemical Substance Inventory, the
CAS No. assigned to this chemical is 420-04-2. The non-
confidential enclosure also states that this chemical is
a pesticide "for which an application for registration
has been filed with EPA's Office of Pesticide Programs"
under Section 3 of the Federal Insecticide, Fungicide,
and Rodenticide Act (FIFRA). In terms of TSCA-covered
use and the potential for exposure, the enclosure states
non-confidentially that because the "chemical industry
applications of hydrogen cyanamide involve its use as a
chemical intermediate, principally captive, the compound
does not involve potential exposure to the general
public."
524
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Page 1 of 1
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
Air Products and Chemicals, Inc., provided initial findings of a ground water monitoring program being
conducted at its former Arcair facility in Lancaster, Ohio under the direction of the Ohio EPA and the
Fairfield County Department of Health. The following Volatile Organic Compounds were detected: 1,1,1-
trichloroethane (CAS No. 71-55-6), 1,1-dichloroethane (CAS No. 75-34-3), and 1,1-dichloroethylene (CAS
No. 75-35-4).
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will ask Air Products to ensure that EPA is kept apprised
of all further significant findings from the company's additional studies into the reported
matter.
b) As was the case with the initial submission, staff of the Chemical Screening Branch will
notify RAB/ECAD/OTS, CTB/ECAD/OTS, and EPA Region 5 of all incoming reported
information.
c) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA,
RAB/ECAD/OTS, CTB/ECAD/OTS, and EPA Region 5; in addition, copies of this status
report will be transmitted to the Environmental Assistance Division/OTS for further
distribution.
* A \
I 1 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
DATE: JUN - 7 1990 APPROVED: Y. t/nfoo
SUBJECT: Status Report1 8EHQ-049CM)953
FROM: Martha G. Price, Ph.D., Chemist
Chemical Risk Identification Section/CSB
1 This status report reflects information submitted to EPA under Section 8(e), the Substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
525
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sr^.
322/
v ,-r
% pro^0
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
DATE: JUN 2 8 1990 APPROVED: JjfaA ^
SUBJECT: Status Report1 8EHQ-0490-09S4/5
FROM: Martha G. Price, Ph.D., Chemist
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
Page 1 of 1
OFFICE OF
PESTICIDES AND TOXIC
SUBSTANCES
SUBMISSION DESCRIPTION (Sec NOTE Below)
Allied-Signal Incorporated provided summary results on an R&D chemical identified as "vinyl ether terminated
ester" after signs of neurotoxicity were noted in a single dose (5 g/kg body weight) oral lethality study in rats.
COMMENTS/RECOMMENDATIONS
Allied-Signal reported they plan to conduct a multiple dose oral LD50 study on this material. Allied-Signal
also stated a TSCA §5 Pre-manufacture Notification (PMN) was submitted for this material. They further
reported the results of the study have been communicated to those studying the use of the material.
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final report (including the actual experimental protocol, results of
gross/histopathologic examinations, results of any statistical analyses, etc.) from the range-
finding probe study cited in the submission.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA, and
CCD/OTS/EPA; in addition, copies of this status report will be transmitted to the
Environmental Assistance Division/OTS for further distribution.
NOTE In a letter dated March 15,1991 (8EHQ-0391-0954 Supplement), Allied-Signal Inc. withdrew
confidentiality claims and identified the tested chemical substance non-confidentially as "bis-
(4-vinyloxybutyl)isophthalate." In this March 15,1991 supplemental letter, Allied-Signal also
reported non-confidentially that the PMN for this substance (PMN 90-300) was submitted to
the Agency on December 27,1989.
IdSftrAo. V faivi y/t/y
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Tonic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing
fiml Agency policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available
for public inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C 20460. All
requests for TSCA Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
526
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(®)
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
OFFICE OF
DATE: JIJN - T '090 APPROVED:
TOXIC SUBSTANCES
PESTICIDES AND
SUBJECT: Status Report1 8EHQ-0490-0955 S
FROM: Martha G. Price, Ph.D., Ch
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
A confidential submitting company provided a final report of a reproduction study of an R&D chemical
identified as "substituted acetanilide" administered in the feed to rats at dose levels of 0, 100, 1000, and 4000
ppm prior to mating and throughout gestation and lactation for two generations.
COMMENTS/RECOMMENDATIONS
The Agency has received a number of TSCA §8(e) submissions on "substituted acetanilide" including 8EHQ-
0290-0889 S, 8EHQ-0390-0896 S, and 8EHQ-0390-0897 S.
a) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
527
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
JUN 4 !W
APPROVED:
DATE:
SUBJECT: Status Report1 8EHQ-0490-0956 S
/JutU&U H
FROM: Judith M. Loranger, Biologist
Chemical Screening Branch/ECAD/OTS
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
A confidential submitting company provided summarized findings from a pilot rat teratology study of an
R&D compound identified as a "diaryl ketone." The compound was administered by gavage at dose levels
of 0, 25, 50, 100, 200, or 400 mg/kg/day during gestation days 6-18.
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final report (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the pilot
teratology study cited in the submission.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/ECAD;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are
available for public inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460.
All requests for TSCA Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
528
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON DC 20460
Page 1 of 1
SUBJECT:
DATE:
TOXIC substances
PESTICIDES AND
OFFICE OF
FROM: Martha G. Price, Ph.D., Chemist \ J
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
The Dow Chemical Company provided summarized results of acute toxicity screening tests on "substituted
pyrimidines" after neurotoxic effects were observed. The tests reported were dermal evaluations in rabbits
and oral toxicity in rats.
COMMENTS/RECOMMENDATIONS
Dow Chemical reported that they will communicate these results to their employees who work with these
chemicals.
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final report (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the
studies cited in the submissions.
In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity/exposure data, the company will be requested to describe
the actions that it has taken or plans to take 1) to reduce or eliminate exposure to the
subject chemicals. The company will be asked to provide copies of Material Safety Data
Sheets and labels that have been revised to reflect the reported findings. In addition, the
company will be asked to describe the nature and results, if available, of all studies (other
than those submitted already to EPA or those cited in the published scientific literature)
about which the company is aware or that it has conducted, is conducting or plans to
conduct that are designed to determine the toxicity of the subject chemicals.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemicalfs). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
529
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W
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
DATE: JUN ~ 4 1990 APPROVED:
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0490-0959 S
FROM: Martha G. Price, Ph.D., Chem
Chemical Risk Identification !i
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
A confidential submitting company provided summarized results of acute toxicity screening tests on an R&D
chemical identified as "amine metal complex" after neurotoxic effects were noted in an eye irritation study
in rabbits and an oral toxicity study in rats. The other test results provided were dermal absorption in
rabbits.
COMMENTS/RECOMMENDATIONS
The submitter reported that they will communicate these results to their employees who work with this
chemical.
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final report (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the studies
cited in the submission.
In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity/exposure data, the company will be requested to describe
the actions that it has taken or plans to take 1) to reduce or eliminate exposure to the
subject chemical. The company will be asked to provide copies of Material Safety Data
Sheets and labels that have been revised to reflect the reported findings. In addition, the
company will be asked to describe the nature and results, if available, of all studies (other
than those submitted already to EPA or those cited in the published scientific literature)
about which the company is aware or that it has conducted, is conducting or plans to
conduct that are designed to determine the toxicity of the subject chemical.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
530
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Page 1 of 2
OFFICE Of
PESTICIDES AND
TOXIC SUBSTANCES
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
Hoechst Celanese Corporation has submitted summarized findings of chronic toxicity/oncogenicity studies
in rats and mice of ethyl l-(2,4-dichlorophenyl)-5-trichloromethyl-(lH)-l,2,4-triazole-3-carboxylate (CAS No.
103112-35-2). The test compound was administered to rats at dose levels of 0, 200, 800 or 3200 ppm in the
diet for 30 months. Mice received 0, 100, 500 or 2500 ppm of the test compound in the diet for 24 months.
The company also reported that a battery of mutagenicity studies was performed on this compound and its
major metabolite.
COMMENTS/RECOMMENDATIONS
Hoechst Celanese reported that when the studies are available they will be submitted to the Agency.
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final reports (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from all studies
cited in the submission.
In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity/exposure data, the company will be requested to describe
the actions that it has taken or plans to take 1) to notify workers and others about the
reported data, and 2) to reduce or eliminate exposure to the subject chemical. The
company will be asked to provide copies of Material Safety Data Sheets and labels that
have been revised to reflect the reported findings. In addition, the company will be asked
to describe the nature and results, if available, of all studies (other than those submitted
already to EPA or those cited in the published scientific literature) about which the
company is aware or that it has conducted, is conducting or plans to conduct that are
designed to determine the toxicity of the subject chemical.
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
m)
\f ,
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8EHQ-0490-0960
Page 2 of 2
As part of the initial phase of the OTS Existing Chemicals Program (ECP), staff of the
Chemical Screening Branch will screen the reported information in order to determine the
need for further assessment of the subject chemical at this time.
The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
532
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
OFFICE Of
TOXIC SUBSTANCES
PESTICIDES AND
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
In the initial submission, a confidential company provided final reports of oral rat range-finding and
definitive teratology studies of a substance identified generically as "amino acid I." The doses in the range-
finding study were 0, 125, 250, 500, 1000 or 1500 mg/kg/day on gestation days 6-15; the doses in the
definitive study were 0, 25, 100 or 400 mg/kg/day on days 6-15 of gestation. The supplement contained the
final report of a rat subchronic inhalation/reproduction study of this chemical administered at doses of 0,
0.86, 9.6, or 102 mg/m3 prior to mating and throughout gestation and lactation.
COMMENTS/RECOMMENDATIONS
a) In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity/exposure data, the company will be requested to describe
the actions that it has taken or plans to take 1) to notify workers and others about the
reported data, and 2) to reduce or eliminate exposure to the subject chemical. The
company will be asked to provide copies of Material Safety Data Sheets and labels that have
been revised to reflect the reported findings. In addition, the company will be asked to
describe the nature and results, if available, of all studies (other than those submitted
already to EPA or those cited in the published scientific literature) about which the
company is aware or that it has conducted, is conducting or plans to conduct that are
designed to determine the toxicity of the subject chemical.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be sent to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toodc Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemkal(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
533
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Page 2 of 2
"Typical pigments with the generic structure [shown above] include C.I. Pigment Yellow 12,
13, 14, 17, 83, [16, 106, 114, 126, 127, 152, 174, 176,]; C.I. Pigment Orange 13 and 34; C.I.
Pigment Red 38." [Hoechst Celanese, in its submission, provided a list of its brand names
that correspond to these pigments.]
"Letters have been issued to Hoechst Celanese and Hoechst AG marketing departments and
customers, as well as through industry organizations (ETAD- Ecological and Toxicological
Association of the Dyestuffs Manufacturing Industry, and DCMA- Dry Color Manufacturers'
Association), describing the new findings and advising the industry against the use of the
affected pigments in polymer applications above 200°C." [Copies of some of these
communications were enclosed in the Hoechst Celanese submission.]
In the letter that was sent to its customers, Hoechst Celanese noted the following information:
"3,3'-Dichlorobenzidine is classified as a suspect carcinogen by the U.S. Department of
Health and Human Services National Toxicology Program (NTP) and the International
Agency for Research on Cancer (IARC). This classification reflects the fact that there is
evidence in experimental animals but no clear evidence in humans for carcinogenicity. 3,3'-
DCB is also regulated by OSHA as a suspect carcinogen. We are revising Material Safety
Data Sheets (MSDS) and technical literature accordingly."
In the supplemental TSCA Section 8(e) notice, the Dominion Colour Corporation also reported the results
of the Hoechst AG research on diarylide pigments and provided in its letter a list of its own brand names
for pigments that may be affected. Dominion Colour reported, "Letters are being provided to all distributors
and customers who we know or suspect may be using the concerned products under the above conditions."
COMMENTS/RECOMMENDATIONS
It should be noted here that the Agency recently received (8EHQ-0190-0863) a draft report of an
epidemiologic study indicating a possible elevated risk of bladder cancer among workers at a plant where
diamine products, including 3,3'-dichlorobenzidine, were manufactured.
a) The Chemical Screening Branch will request Hoechst Celanese to ensure that EPA receives
a full copy of the final report (including the actual experimental protocol) from the diarylide
pigment study cited in the submission.
In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity/exposure data, Hoechst Celanese and Dominion Colour will
be asked to provide examples of Material Safety Data Sheets and labels that have been
revised to reflect the reported findings. In addition, Hoechst Celanese will be asked to
describe the nature and results, if available, of all studies (other than those submitted
already to EPA or those cited in the published scientific literature) about which the
company is aware or that it has conducted, is conducting or plans to conduct that are
designed to determine the potential for exposure to 3,3'-dichlorobenzidine.
b) All reported information will be forwarded to appropriate OTS staff for review within the
OTS Existing Chemicals Program (ECP).
c) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be sent to the Environmental Assistance
Division/OTS for further distribution.
535
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,,kl 1,01 rt8*rded " "P"**1"* *8"™*
536
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i a \
\2EI]
V „
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY Page 1 of 2
WASHINGTON, DC 20460
DATE
JUN 5
APPROVED:
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECTS Status Report1 8EHQ-0590-0965
H *-0
FROM: Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
In conjunction with a TSCA Section 8(e)-related "Consent Agreement"
(TSCA 89-H-21), the Monsanto Company submitted final reports from
a pilot rat teratology study and a definitive rat teratology study
of benzene, C10-C16 alkyl derivatives (Alkylate 215; CAS No. 68648-
87-3). In the pilot teratology study, the compound was administered
via gastric intubation to mated female rats during days 6-15 of
gestation at dose levels of 125, 250, 500, 1000 or 2000 mg/kg/day.
Monsanto provided the following summary information regarding the
results of this study:
"In the pilot study, signs of maternal toxicity were
observed at 2000 mg/kg. An increase in early resorptions
observed at 2000 mg/kg when compared to the concurrent
control group was attributed to the absence of resorption
sites among the control females. The increase was not
considered treatment-related by the laboratory Study
Director since the mean number of resorption sites seen
in the treated group was similar to historical control
data. The validity of this initial conclusion was
strengthened by the failure of the definitive study (i)
conducted at the same laboratory (ii) using the same
dosing solution preparation procedures, to corroborate
this pilot study finding."
* This status report is the result of a preliminary evaluation of information that has
been submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substances Control Act (TSCA). The statements made in this status
report should not be regarded as expressing final Agency policy or intent with respect to the
subject chemical(s). Any review of this status report should take into account that the
report may be based on incomplete information.
538
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8EHQ-0590-0965
Page 2 of 2
In the definitive teratology study, Alkylate 215 was administered
to pregnant rats during days 6-15 of gestation at dose levels of
125, 500, or 2000 mg/kg/day. Monsanto provided the following
summary information regarding the results of this study:
"Signs of maternal toxicity were observed at 500 and 2 000
mg/kg. Signs of developmental toxicity included increased
ossification variations at 500 and 2000 mg/kg (statisti-
cally significant at 2000 mg/kg only) and an increase in
skeletal malformations (considered a developmental effect
consistent with other ossification variations by the
laboratory Study Director) at 2000 mg/kg only."
USE AND EXPOSURE POTENTIAL
Monsanto did not provide any information about the use(s) of or the
potential for exposure to Alkylate 215, nor was such information
located in the secondary literature sources consulted by EPA.
COMMENTS/RECOMMENDATIONS
It should be noted that EPA has received another TSCA Section 8(e)
submission on Alkylate 215 (8EHQ-0590-0970).
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Monsanto will be requested to
describe the actions that the company has taken or plans
to take 1) to notify workers/others about the reported
information, and 2) to reduce or eliminate exposure to
Alkylate 215. Monsanto will be asked also to provide
copies of Material Safety Data Sheets and labels that
have been revised to reflect the reported findings. In
addition, Monsanto will be asked to describe (by way of
short summaries) the nature and results, if available,
of all studies (other than those submitted already to EPA
or those cited in the published scientific literature)
about which Monsanto is aware or that the company has
conducted, is conducting or plans to conduct that are
designed to determine the toxicity of or the exposure to
Alkylate 215.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, 0RD/EPA, OAR/EPA and OPP/OPTS/EPA? copies of this
status report will be sent also to the Environmental
Assistance Division/OTS for further distribution.
539
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^ UNITED STATES ENVIRONMENTAL PROTECTION AGENCY Page i of 3
WASHINGTON, DC 20460
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
DATE:
SUBJECT:
FROM:
TO:
JUN 41990
APPROVED
Status Report1 8EHQ-0590-0966
tyjLcUxjL* // X4A.4U
Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
In conjunction with a TSCA Section 8(e)-related "Consent Agreement"
(TSCA 89-H-21), the Monsanto Company submitted summary information
on a pilot rabbit teratology study and a final report of a
definitive rat teratology study of N-(l,3-dimethylbutyl)-N-phenyl-
p-phenylenediamine (Santoflex 13, CAS No. 793-24-8). In the pilot
teratology study, pregnant rabbits were orally administered 0, 30,
100, or 3 00 mg/kg of the test compound from days 6 through 18 of
gestation. Monsanto provided the following summary information
regarding the results of this study:
"Significant maternal toxicity in terms of mortality
(80%) occurred at a dosage of 300 mg/kg while abortions
were increased at 100 mg/kg. Signs of developmental
toxicity included increased resorptions at 30, 100, and
300 mg/kg with pup survival for 24 hours in an incubator
after maternal C-section reduced at the low-dose of 30
mg/kg only."
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
540
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8EHQ-0590-0966
Page 2 of 3
In the definitive rat teratology study, rats received oral dosages
of 0, 10 or 30 mg/kg of the test compound from days 6 through 18
of gestation. Monsanto provided the following information
regarding the results of this study:
"Signs of maternal toxicity (abortions and body weight
changes) were noted in 30 mg/kg treated dams. Signs of
developmental toxicity (slight increases in resorptions
and fetal death) were observed at 10 and 30 mg/kg.
Because there were no statistically significant
differences between control and treated groups for these
responses and no trend was evident, these responses are
considered of questionable biological relevance."
It should be noted that EPA has received previously the results of
in vitro genotoxicity studies on Santoflex 13. The readers
attention is directed to 8EHQ-0187-0681 FLWP.
USE AND EXPOSURE POTENTIAL
Monsanto did not provide any information regarding the use of or
the potential for exposure to this chemical, nor was such
information located in the secondary literature sources consulted
by EPA.
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will ask Monsanto to ensure
that EPA receives a complete copy of the final report
(including the actual experimental protocol, results of
gross and histopathological examinations, results of
statistical analyses, etc.) from the pilot rabbit
teratology study cited in the submission.
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Monsanto will be requested to
describe the actions that the company has taken or plans
to take l) to notify workers/others about the reported
information, and 2) to reduce or eliminate exposure to
the subject chemical. Monsanto will be asked also to
provide copies of Material Safety Data Sheets and labels
that have been revised to reflect the reported findings.
In addition, Monsanto will be asked to describe the
nature and results, if available, of all studies (other
than those submitted already to EPA or those cited in the
published scientific literature) about which Monsanto
is aware or that the company has conducted, is conducting
or plans to conduct that are designed to determine the
toxicity of or the exposure to the subject chemical.
541
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8EHQ-0590-0966
Page 3 of 3
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA? in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS for further
distribution.
542
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m
9
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY Page 1 of 3
WASHINGTON, DC 20460
DATE:
SUBJECT:
PROM:
TO:
JUN 51990
APPROVED
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
status Report1 8EHQ-0590-0967
QuoUtfc M to u)
Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
In conjunction with a TSCA Section 8(e) "Consent Agreement" (TSCA
89-H-21), the Monsanto Company provided the final reports of a
pilot rat teratology study and a definitive rat teratology study
of a product identified as a "solution of aromatic polyimide
precursor (65701-07-7) in ethanol (CAS No. 64-17-5) and n-methyl
pyrrolidone (CAS No. 872-50-4)" (Skybond 700 Polyimide Resin). In
the pilot teratology study, treated animals received oral dosages
of o, 250, 500, 1000 or 2000 nig/kg/day of the test material during
days 6-15 of gestation. In the definitive study, rats received
oral dosages of 0, 100, 270, or 700 mg/kg/day of the test material
during days 6-15 of gestation. Monsanto provided the following
summary information regarding the results of these two studies:
Pilot rat teratology study
"Signs of maternal toxicity were noted in all treatment
groups. Due to significant mortality, data on develop-
mental effects was available from only one surviving 2000
mg/kg treated dam and an increase in fetal death was
noted for this dam. This finding of a single dam and its
representation of group data and its relationship to
treatment is judged to be unclear. Fetal body weight was
I This status report is the result of a preliminary evaluation of information that has
been submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substances Control Act (TSCA). The statements made in this status
report should not be regarded as expressing final Agency policy or intent with respect to the
subject chemical(s). Any review of this status report should take into account that the
report may be based on incomplete information.
543
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8EHQ-0590-0967
Page 2 of 3
decreased at the next to high dose level of 1000 mg/kg.
Results from this study suggest that while Skybond 700
polyimide resin induces developmental effects in rats,
it does so only at a dose level that also produces
maternal toxicity."
Definitive rat teratology study
"Signs of maternal toxicity were noted in all treatment
groups. Signs of developmental toxicity included an
increase in variations at 700 mg/kg and statistically
significant decreases in fetal body weights at 27 0 and
700 mg/kg. Results from this study suggest that while
Skybond 700 polyimide resin induces developmental effects
in rats, it does so only at dose levels that also produce
maternal toxicity."
A copy of the 1986 Skybond 7 00 Material Safety Data Sheet (MSDS)
was included with this submission.
USE AND EXPOSURE POTENTIAL
Other than the fact that Skybond 700 is a "polyimide resin,"
Monsanto did not provide any information about the use(s) of or the
potential for exposure to this product, nor was such information
located in the secondary literature sources consulted by EPA.
COMMENTS/RECOMMENDATIONS
In its submission, Monsanto reported that "the specific information
concerning the test results will be noted in the next revision of
the Material Safety Data Sheet." Monsanto also noted that "the
current Material Safety Data Sheet recommends that special care
should be taken to minimize exposure, particularly for women of
child-bearing potential. In addition, labels recommend that
precautions include use of a adequate ventilation; avoiding eye,
skin, or clothing contact; avoiding breathing vapors; and washing
thoroughly after handling." It should be noted that EPA has
received both TSCA Section 8(e) and "For Your Information" (FYI)
submissions on ethanol and n-methyl pyrrolidone in the past. In
addition, the Chemical Testing Branch (CTB/ECAD) is currently
reviewing available information on n-methyl pyrrolidone.
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Monsanto will be asked to
describe (by way of short summaries) , the nature and
results, if available, of all studies (other than those
submitted already to EPA or those cited in the published
scientific literature) about which Monsanto is aware or
that the company has conducted, is conducting or plans
to conduct that are designed to determine the toxicity
of or the exposure to Skybond 700 or its constituents.
544
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8EHQ-0590—0967
Page 3 of 3
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
chemicals at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, CTB/ECAD/OTS and OPP/OPTS/EPA?
in addition, copies of this status report will be sent
to the Environmental Assistance Division/OTS for further
distribution.
545
-------
\ UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
0
«
WASHINGTON, DC 20460 p j Qf x
DATE:
JUN 27 (goo APPROVED: ZL^z.-, ih/lL
OFFICE OF
SUBJECT: Status Report1 8EHQ-059(M)968 MtiaVSupplements pesticides and
, , TOXIC SUBSTANCES
FROM: Jacqueline T. Favilla, Biologist
Chemical Risk Identification Section/€SB
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
Under a TSCA Section 8(e) "Consent Agreement" (TSCA 89-H-21), the Monsanto Company provided a final
report of a 2-year rat dietary toxicity/carcinogenicity study of TCC® soap bacteriostat (N-(4-chIorophenyl)-
N'-(3,4-dichlorophenyl)urea; CAS No. 101-20-2) conducted at doses of 0, 25, 75 or 250 mg/kg/day. In the
supplemental submissions, final reports of a number of dermal and dietary reproduction and/or
developmental toxicity studies in rats and rabbits and a 1-year feeding study in male rats were submitted.
COMMENTS/RECOMMENDATIONS
In the initial submission cover letter, Monsanto stated that the current TCC* soap bacteriostat Material
Safety Data Sheet (MSDS) "reports testicular effects seen with repeated dietary feeding of this chemical" and
that the final report of the 2-year rat study "was submitted to the U.S. Food and Drug Administration in
1981 to supplement the administrative record regarding the FDA's tentative final order (monograph)
covering over-the-counter topical antimicrobial drug products." Monsanto also reported that all of these
studies were submitted to FDA from 1969 through 1983. A review of the non-confidential version of EPA's
TSCA Chemical Substance Inventory showed that TCO soap bacteriostat is listed.
a) In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity/exposure data, Monsanto will be asked to describe the
actions that it has taken or plans to take 1) to notify workers/others about the reported
data, and 2) to reduce or eliminate exposure to the subject chemical. The company will be
asked to provide copies of MSDSs and labels that have been revised to reflect the reported
findings. Monsanto will also be asked to describe the nature and results, if available, of all
studies (other than those submitted already to EPA or those cited in the published scientific
literature) about which the company is aware or that it has conducted, is conducting or
plans to conduct that are designed to determine the toxicity of the subject chemical.
b) The reported information will be screened in order to determine the need for further
assessment of the subject chemical at this time.
c) Copies of this status report will be sent to NIOSH, OSHA, CPSC, FDA, NTP,
OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; copies of this report
will be sent also to the Environmental Assistance Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
546
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 2
OFFICE OF
PESTICIDES AND
JUN 5 j
TOXIC SUBSTANCES
DATE:
APPROVED:
SUBJECT: Status Report1 8EHQ-0590-0969
FROM: Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
In conjunction with a TSCA Section 8(e) "Consent Agreement" (TSCA
89-H-21) , the Monsanto Company provided the final report of an oral
teratology study of benzene, Ci4.3o-alkyl derivatives (Therminol 55;
CAS No. 68855-24-3) administered to pregnant rats at doses of 0,
400, 800, or 1600 mg/kg/day on days 6-15 of gestation. The company
provided the following summary information regarding the results
of this study:
"Signs of maternal toxicity were noted at 800 and 1600
mg/kg. A non-statistically significant increase in
variations was noted at 1600 mg/kg. However, since the
majority of the findings came from a single litter, they
are judged [by the company] to likely be the result of
delayed maturation and not attributable to a treatment
related effect."
A copy of a 1986 Therminol 55 Material Safety Data Sheet (MSDS) was
provided at the end of the submitted final report of the oral rat
teratology study.
I This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
547
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8EHQ-0590-0969
Page 2 of 2
USE AND EXPOSURE POTENTIAL
According to the submitted MSDS, Therminol 55 is a "heat transfer
fluid." Monsanto did not provide any further information regarding
the use(s) of or the potential for exposure to Therminol 55, nor
was such information located in the secondary literature sources
consulted by EPA.
COMMENTS/RECOMMENDATIONS
In its submission, Monsanto reported that the company has updated
the current Therminol 55 MSDS to include results from the provided
oral teratology study in rats.
It should be noted that EPA has received a TSCA Section 8(e) notice
(8EHQ-0590-0983) on Therminol 66 and a "For Your Information" (FYI)
submission (FYI-OTS-0480-0066) on spent Therminol 66.
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Monsanto will be requested to
describe the actions that the company has taken or plans
to take 1) to notify workers/others about the reported
information, and 2) to reduce or eliminate exposure to
the subject chemical. Monsanto will be asked also to
provide copies of Material Safety Data Sheets and labels
that have been revised to reflect the reported findings.
In addition, Monsanto will be asked to describe the
nature and results, if available, of all studies (other
than those submitted already to EPA or those cited in the
published scientific literature) about which Monsanto is
aware or that the company has conducted, is conducting
or plans to conduct that are designed to determine the
toxicity of or the exposure to the subject chemical.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this report will be sent to the Environmental
Assistance Division/OTS for further distribution.
548
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
" i
53£i
> - • " y t*)
FROM: Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
In conjunction with a TSCA Section 8(e)-related "Consent Agreement"
(TSCA 89-H-21), the Monsanto Company provided complete copies of
the final reports from pilot and definitive rat teratology studies
of benzene, C10-16 alkyl derivatives (Alkylate 230; CAS No. 68648-
87-3). In the pilot rat teratology study, mated female rats were
administered the test compound by gavage at dose levels of 0, 12 5,
250, 500, 1000 or 2000 mg/kg/day on days 6-15 of gestation. In the
definitive study, mated female rats received the test compound by
gavage at doses of 0, 125, 500 or 2000 mg/kg/day on gestation days
6-15. The cover letter that accompanied the initial submission
provides the following summary information regarding these studies:
"In the pilot study, signs of maternal toxicity were
noted in 500, 1000 and 2000 mg/kg treated dams. Although
an increase in early resorptions was noted at 2000 mg/kg,
this response was not corroborated by the definitive
study. . . conducted at the same laboratory using the
same dosing solution preparation procedures and dose
levels.
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
549
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8EHQ-0590-0970
Page 2 of 2
"In the subsequent definitive teratology study, signifi-
cant maternal toxicity occurred at dosages of 500 and
2000 mg/kg. A statistically significant increase in
variations (ossification variations and distended renal
pelvis/tortuous ureter) was also seen at 500 and 2000
mg/kg. Results from this study suggest that while
Alkylate 23 0 induces developmental effects in rats, it
doses so only at dose levels that also produce
significant maternal toxicity."
USE AND EXPOSURE POTENTIAL
Monsanto did not provide any information about the use(s) of or the
potential for exposure to Alkylate 230, nor was such information
located in the secondary literature sources consulted by EPA.
COMMENTS/RECOMMENDATIONS
It should be noted that EPA recently received TSCA Section 8(e)
notices (8EHQ-0590-0965 et seq.) on Alkylate 215, a material with
the same CAS Registry Number (CAS No. 68648-87-3) as Alkylate 230.
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Monsanto will be requested to
describe the actions that the company has taken or plans
to take 1) to notify workers/others about the reported
information, and 2) to reduce or eliminate exposure to
Alkylate 230. Monsanto will be asked also to provide
copies of Material Safety Data Sheets and labels that
have been revised to reflect the reported findings. In
addition, Monsanto will be asked to describe (by way of
short summaries) the nature and results, if available,
of all studies (other than those submitted already to EPA
or those cited in the published scientific literature)
about which Monsanto is aware or that the company has
conducted, is conducting or plans to conduct that are
designed to determine the toxicity of or the exposure to
Alkylate 230.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information to determine
the need for further OTS assessment of Alkylate 230.
c) The Chemical Screening Branch will send copies of this
Status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, 0RD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this report will be sent to the Environmental
Assistance Division/OTS for further distribution.
550
-------
(ft)
% PR&V
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
DATE:
JUL I 7 1990
APPROVED:
SUBJECT: Status Report1 8EHQ-0590-0971
FROM:
: Martha G. Price, Ph.D., ChemisX^-^ Aa.
Chemical Risk Identification Section/CSB
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
In conjunction with a TSCA §8(e) Consent Agreement (TSCA 89-H-21), Monsanto Company provided a
final report of a rat fertility and general reproductive performance study on dibutyl phthalate (CAS No.
84-74-2) administered orally in the diet to rats at dose levels of 0, 5, 50, and 500 mg/kg/day.
COMMENTS/RECOMMENDATIONS
Dibutyl phthalate has been the subject of several TSCA §4 test rules as well as TSCA §8(a) and §8(d) rules.
a) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA OPP/OPTS/EPA
CTB/ECAD/OTS, and RAB/ECAD/OTS; in addition, copies of this status report will be
transmitted to the Environmental Assistance Division/OTS for further distribution.
1 This statu* report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
551
-------
^t0 •**,
Page 1 of 4
W
\ PKCfl*-
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
DATE:
APPROVED
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
AUG 2 4 !990
SUBJECT: Status Report1 8EHQ-0590-0972
FROM: Martha G. Price, Ph.D., Chemist 'M-
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
In conjunction with a TSCA §8(e) Consent Agreement (TSCA 89-H-21),
Monsanto Company provided the following summary information
regarding the conduct and final results of both a pilot rat
teratology study and the subsequent rat teratology study on
nitrated orthene or 1,2-dichloro-4-nitrobenzene (CAS No. 99-54-7).
The summary for the pilot study states:
"Mated female rats were dosed daily, by gavage, with
Nitrated Orthene from days 6-15 of gestation at dose
levels of 200, 300, 400, 500, and 600 mg/kg/day. All
animals died spontaneously in the four highest dose
levels, and two animals died spontaneously at the 200
mg/kg dose level. The 200 mg/kg dose level exhibited a
mean body weight loss during the first four days of
treatment and reduced gains for days 10-13, 13-16, and
16-21. These differences resulted in a 32% weight
difference from the control group for the period of days
6-21 of gestation. The more severe clinical findings were
varying degrees of respiratory problems, loss of muscle
coordination, seizures and/or convulsions, prostration,
pale extremities, hunched posture, and unthriftiness
(poor general health). These findings were noted in most
_ This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
552
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8EHQ-0590-0972
Page 2 of 4
animals which died spontaneously, but were observed in
only one of the four animals which survived to scheduled
sacrifice in the 200 mg/kg group. Gross postmortem
findings on animals dying spontaneously included
pronounced blood vessels in the intestines, pale and
mottled livers, and multiple hemorrhages of the pyloric
region of the stomach. A slight reduction in mean fetal
body weight was exhibited at the 200 mg/kg dose level.
No abnormalities were noted during-gross fetal
examinations."
The summary for the follow-up rat teratology study follows:
"Mated female Sprague-Dawley rats, in groups of 25, were
dosed with nitrated orthene by gavage at nominal dosage
rates of 10, 30 and 100 mg/kg/day from gestation days 6
through 15. A control group was dosed with an equivalent
volume of corn oil vehicle. Females were sacrificed on
gestation day 21 and nidations were measured. All fetuses
were examined externally and approximately equal numbers
of fetuses from each group were examined for visceral or
skeletal findings.
"Analytical data demonstrated that solutions of nitrated
orthene in corn oil were homogeneous and that no
significant decomposition of nitrated orthene solutions
occurred over a 28 day period. Analytical values of
nitrated orthene concentrations for solutions used in the
study were within 11% of the nominal values: 0.916 mg/ml
(nominal 1 mg/ml), 3.31 mg/ml (nominal 3 mg/ml) and 10.8
mg/ml (nominal 10 mg/ml).
"All mated females survived to scheduled sacrifice. Toxic
effects were observed in the high dose level females as
body weight loss for gestation days 6-10 and reduced mean
body weights on gestation days 10, 13 and 16. On
gestation day 16 the mean body weight of high dose level
females was about 5% lower than the control group value.
Although not considered to be a definitive indication of
toxicity, urogenital staining was observed in the high
dose level females. The only effect judged to be
indicative of possible toxicity in mid dose level females
was reduced body weight gain and food consumption for
gestation days 6-10; however, mean body weights for this
group were not statistically different from control
values. No treatment related body weight effects or
clinical signs were observed in low dose level females.
Reduced food consumption (g/animal/day) was observed on
gestation days 6-10 for all three dose level groups, but
this was not considered to be indicative of a toxic
effect for the low dose level females because it was not
accompanied by statistically significant effects on body
weight or body weight change. No treatment related
postmortem findings were observed.
553
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8EHQ-0590-0972
Page 3 of 4
"Reproductive data did not indicate any treatment related
effects on postimplantation loss or number of live
fetuses/dam and pregnancy rates were comparable for all
groups. Although mean early resorptions/dam in the high
dose level group were higher than the control group value
the difference was not statistically significant. Fetal
weights and sex distribution of fetuses from all dose
levels were comparable to control group values.
"No statistically significant differences were observed
for incidence of total malformations or individual
malformations between any of the treatment groups and the
control group. Two types of malformations, anophthalmia/
microphthalmia and folded retina, were observed in
control group fetuses and in treatment group fetuses.
Because the incidence of the these malformations was not
statistically different from the incidence in the control
group and because these malformations were not observed
in the mid level dose group these malformations are not
considered to be treatment related. A few malformations
were uniquely observed in the treatment groups. The
incidence of these malformations was primarily restricted
to occurrence in single fetuses. Malformations observed
in the low dose level group or mid dose level group were
observed only in single fetuses except for anophthalmia/
microphthalmia and bent ribs with each observed in two
fetuses. None of the mid dose level malformation findings
occurred in the high dose level group and none of the low
dose level findings were observed in both the mid and
high dose level groups. Because of the lack of dose
related pattern and low incidence, the few malformation
findings in the low and mid dose level groups are not
considered to be treatment related. Malformations
observed uniquely in the high dose group mostly occurred
in one litter and in one fetus of this litter. Six of the
nine fetuses with malformations in the high dose group
were from two litters and six of the twenty-two
malformation findings were from a single fetus with
multiple findings. Four malformations were observed in
each of two fetuses only in the high dose level group:
gastroschesis, small oral opening, skull misshapen and
nasal passages misshapen. However, these findings were
restricted to three litters and four fetuses. The low
incidence levels and the restricted distribution of
findings suggest that the malformations observed in the
high dose level group may represent spontaneous events
rather than treatment related effects.
"No treatment related effects on variations were observed
with the possible exception of dilated ureters. The
incidence of dilated ureters in the mid and high dose
level groups was elevated compared to control group
values. Although the increase was not statistically
554
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8EHQ-0590-097 2
Page 4 of 4
significant after application of the Bonferroni
inequality correction for comparison of multiple
treatments with control, a test for linear trend in
proportion was statistically significant. This suggests
the possibility that increases in the proportions of
fetuses with dilated ureters in the mid and high dose
levels may have been treatment related."
USE AND EXPOSURE POTENTIAL
Monsanto did not provide any information regarding the use of or
the potential for exposure to l,2-dichloro-4-nitrobenzene.
According to The Condensed Chemical Dictionary (10th edition),
1,2-dichloro-4-nitrobenzene is used as an intermediate.
COMMENTS/RECOMMENDATIONS
In its submission, Monsanto stated, "Monsanto Company no longer
manufactures nor markets this chemical and all of Monsanto's
commercial activity on this product ceased in 1985."
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Monsanto will be requested to
describe the actions that the company took to notify
workers/others about the reported information. In
addition, Monsanto will be asked to describe the nature
and results, if available, of all studies (other than
those submitted already to EPA or those cited in the
published scientific literature) about which Monsanto is
aware or that the company conducted that were designed
to determine the toxicity of or the exposure to the
subject chemical.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
555
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ytosr%
(&
T*> r<*
/we*0
I
Page 1 of 3
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
DATE:
SUBJECT:
FROM:
TO:
?&'
APPROVED
V (jton^
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
status Report1 8EHQ-0590-0973
Martha G. Price, Ph.D., Chemist
Chemical Risk Identification Section/CSB
James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
In conjunction with a TSCA §8(e) Consent Agreement (TSCA 89-H-21),
Monsanto Company provided the following summary information
regarding the conduct and final results of a rat teratology study
on ortho-nitrochlorobenzene (CAS No. 88-73-3), also known as 2-
chloronitrobenzene:
"Mated female Sprague-Dawley rats received orthonitro-
chlorobenzene (ONCB) in corn oil, orally by gavage, on
days 6-15 of gestation. In one study, mated females were
exposed to ONCB levels of o, 25, 75, or 150 mg/kg/day. Due
to severe maternal toxicity and mortality, all females at
the 150 mg/kg level were terminated prior to scheduled
sacrifice. In a second study, mated females were exposed
to ONCB levels of 0 or 100 mg/kg/day. Concurrent control
groups received the corn oil vehicle only.
"Dams undergoing scheduled sacrifice were sacrificed on
gestation day 21, implantations were described, and
fetuses were removed from the uterus. Fetuses were
subjected to a gross external examination and processed
for subsequent visceral or skeletal examination. Abnormal
fetal findings were classified as malformations or
variations.
i This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk' information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
556
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"No evidence of maternal toxicity was exhibited at the 25
mg/kg level. Urinary staining and alopecia were noted at
75 mg/kg. However, no meaningful clinical signs were noted
at 100 mg/kg. One death occurred at each of the 75 and 100
mg/kg levels on gestation days 9 and 20, respectively. The
cause of these deaths could not be determined. Clinical
signs and mortality are not considered to be definiitive
evidence of test material-related maternal toxicity at
the 75 and loo mg/kg levels. Severe maternal toxicity was
evident at the 150 mg/kg level as high mortality and overt
clinical signs.
"Maternal toxicity was evident for gestation days 6-10 as
a reduction in maternal body weight gain at the 75 mg/kg
level, and a body weight loss at 100 mg/kg, when compared
to their respective control groups. These differences were
accompanied by reductions in maternal food consumption for
days 6-10 at 75 mg/kg, and for days 6-16 at 100 mg/kg. The
reductions noted at 75 mg/kg were recovered later in
gestation.
"Maternal reproductive parameters and fetal body weight
in the treatment groups were comparable to the respective
control groups, except for the mean number of early
resorptions at the 75 mg/kg level. However, no meaningful
increase was evident at 100 mg/kg. Therefore, ONCB is not
considered to be embryotoxic or fetotoxic at levels of 100
mg/kg or less.
"No biologically-meaningful differences in the number of
litters exhibiting malformations were evident in the
treatment groups when compared to their respective control
groups. An increase in the number of litters exhibiting
the variation 'cervical # 7 rib' was evident at 25 and 75
mg/kg, and also '13 full pair of ribs with lumbar #1
rudimentary rib' at 75 mg/kg. However, no increase in the
incidence of these findings was evident at 100 mg/kg when
compared to its respective control group. Therefore, these
differences are not considered to be meaningful.
"In conclusion, treatment with orthonitrochlorobenzene did
not exhibit a teratogenic effect at levels of 100
mg/kg/day or less, though maternal toxicity was exhibited
at 75 and 100 mg/kg/day."
USE AND EXPOSURE POTENTIAL
Monsanto did not provide any information regarding the use of or
the potential for exposure to 2-chloronitrobenzene. According to
lilfi CQnflensefl Chemical Dictionary (10th edition) , 2-chloronitro-
benzene is used as an intermediate, especially for dyes.
557
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Page 3 of 3
rOMMENT8/RECQMMENDATI0N8
In its submission, Monsanto reported that results considered
treatment-related from this study are discussed in the current
Monsanto Material Safety Data Sheet.
The Chemical Screening Branch prepared a CHIP on 2-chloronitro-
benzene in 1983; in addition, the Risk Analysis Branch conducted
risk assessment activities.
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Monsanto will be requested to
describe the actions that the company has taken or plans
to take 1) to notify workers/others about the reported
information, and 2) to reduce or eliminate exposure to
the subject chemical. Monsanto will be asked also to
provide copies of Material Safety Data Sheets and labels
that have been revised to reflect the reported findings.
In addition, Monsanto will be asked to describe the nature
and results, if available, of all studies (other than
those submitted already to EPA or those cited in the
published scientific literature) about which Monsanto is
aware or that the company has conducted, is conducting or
plans to conduct that are designed to determine the
toxicity of or the exposure to the subject chemical.
b) As part of the initial phase of the OTS Existing Chemicals
Program (ECP), staff of the Chemical Screening Branch will
screen the reported information in order to determine the
need for further assessment of the subject chemical at
this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
558
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^tosx
* A \
% WW*0"'
Page 1 of 3
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
DATE:
?4
approved:
~IA
ifz ho
an^-'
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: status Report1 8EHQ-0590-0974
FROM: Martha G. Price, Ph.D., Chemist^-^-^
Chemical Risk Identification Section/CSB \J '
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
In conjunction with a TSCA §8(e) Consent Agreement (TSCA 89-H-21),
Monsanto Company provided the following summary information
regarding the conduct and final results of a rat teratology study
on N-formylpiperidine (CAS No. 2591-86-8):
"Mated female albino rats received l-formylpiperidine,
by gavage, once daily from days 6 through-20 of gestation
at doses of 110, 220 or 440 mg/kg.
"Maternal effects included significant reductions in
weight gains during the treatment period in the groups
receiving the intermediate and high doses, largely
influenced by dose related changes in all treated groups
during the first four days of treatment. These were
significant in the two higher dose groups and included
weight loss in the high dose group. After day 10 of
gestation, mean body weights paralleled those of the
control group. Parallel significant reductions in food
consumption were seen in all treated groups beginning
during days 6-10 of gestation and showed dose
relationships in severity and duration. Except for one
treatment-related death in the high dose group, maternal
- This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). Pie statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
559
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8EHQ—0590—097 4
Page 2 of 3
survival was not affected. Most treatment-related
clinical signs observed in high dose animals first
occurred on days 7, 8 or 9 and were of short duration.
The most substantial of these, seen in only 6 females,
included tremors, convulsive movements and apparent
weakness of the legs. No treatment related gross
postmortem findings were seen. In utero survival in the
high dose group was affected by treatment, as evidenced
by a significant increase in resorptions. No effects were
seen on other reproductive parameters.
"Fetal weights were significantly reduced in the group
treated with the high dose. Except for a dose related
incidence of anasarca there was no other evidence of
fetal toxicity. An increased incidence of litters with
abnormal fetuses in the high dose group did not show any
specific malformation or syndrome. In view of the overt
maternal toxicity at the two higher dose levels and the
relative lack of fetal toxicity, except at the high dose,
it is possible that the malformations seen resulted from
excessive dosage overwhelming the maternal homeostatic
responses. Since treatment did not produce malformations
in fetuses except at doses overtly toxic to these dams,
1-formylpiperidine would not be classified as a teratogen
in the albino rat under "the test conditions used."
USE AND EXPOSURE POTENTIAL
Monsanto did not provide any information regarding the use of or
the potential for exposure to N-formylpiperidine. According to
The Condensed Chemical Dictionary (10th edition), 1-formyl-
piperidine is used as a solvent for polar and nonpolar compounds
as well as many high polymers, for gas absorption, and for plastics
modifiers.
COMMENT8/RECOMMENPATIONS
In its submission, Monsanto stated, "Since Monsanto does not
manufacture N-formylpiperidine, no unique Material Safety Data
Sheet has been prepared. Monsanto does maintain a commercial
interest in this chemical as a process intermediate.11
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Monsanto will be requested to
describe the actions that the company has taken or plans
to take 1) to notify workers/others about the reported
information, and 2) to reduce or eliminate exposure to
the subject chemical. In addition, Monsanto will be
asked to describe the nature and results, if available,
of all studies (other than those submitted already to EPA
or those cited in the published scientific literature)
about which Monsanto is aware or that the company has
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8EHQ-0590-0974
Page 3 of 3
conducted, is conducting or plans to conduct that are
designed to determine the toxicity of or the exposure to
the subject chemical.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
601
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
DATE: JUN 7 HQ0 APPROVED:
TOXIC SUBSTANCES
OFFICE OF
PESTICIDES AND
SUBJECT: Status Report* 8EHQ-0590-0975 Initial
8E11Q-0590-0976 Initial
FROM: Jacqueline T. Favilla, Biologist
Chemical Risk Identification Sectic
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
Under a TSCA Section 8(e) "Consent Agreement" (TSCA 89-H-21), the Monsanto Company provided final
reports of rat oral pilot and definitive teratology studies of MCS 1441 (8EHQ-0590-0975) and NCP (8EHQ-
0590-0976) administered on gestation days 6-15. In the pilot study of MCS 1441, the doses were 0, 10, 50,
300, 1000 or 5000 mg/kg; MCS 1441 doses in the definitive study were 0, 20, 200 or 400 mg/kg. In the pilot
study of NCP, doses of 0, 10, 50, 500,1000 or 5000 mg/kg were used; NCP doses in the definitive study were
0, 50, 150 or 500 mg/kg. Monsanto stated that NCP and MCS 1441 contain phosphoric acid, triphenyl ester
(CAS No. 115-86-6); phosphoric acid, (l-methyl-l-phenylethyl)phenyl diphenyl ester (CAS No. 34364-42-
6); phosphoric acid, nonylphenyl diphenyl ester (CAS No. 38638-05-0).
COMMENTS/RECOMMENDATIONS
Monsanto reported that the company's commercial activity for MCS 1441 and NCP ceased in 1985.
a) The Chemical Screening Branch will ask Monsanto to report the proportions of the
components in NCP and MCS 1441. In view of EPA's general interest in company actions
that are taken on a voluntary basis in response to chemical toxicity/exposure data, the
company will be requested to describe the nature and results, if available, of all studies
(other than those submitted already to EPA or those died in the open scientific literature)
about which the company is aware or that it has conducted that were designed to determine
the toxicity of or the exposure to NCP, MCS 1441, or their constituents.
b) As was the case for the initial notices, all reported information will be brought to the
attention of the Chemical Testing Branch (CTB/ECAD/OTS) for inclusion in their ongoing
review of aryl phosphates under Section 4 of TSCA
c) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and
CTB/ECAD/OTS; copies of this report will be sent also to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 6(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
602
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0 sr.,,
.5322/
Page 1 of 3
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
DATE: <** I'lMO APPROVED
SUBJECT:
FROM:
TO:
: ^l+*h T fhnr^ C. Jit fat
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
Status Report1 6EHQ-0590-0977 Initial
8EHQ-0590-0977 Supplement
Jacqueline T. Favilla, Biologist
Chemical Risk Identification Secti/fen/^SB
James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
In conjunction with a TSCA Section 8(e) "Consent Agreement" (TSCA
89-H-21), the Monsanto Company provided summarized results of a
rabbit range-finding teratology study, and final reports of the
definitive rabbit teratology study and a three-generation repro-
duction rat study of N,N'-bis(l,4-dimethylpentyl)-p-phenylene-
diamine (Santoflex* 77, CAS No. 3081-14-9). The following summary
information regarding the conduct and final results of the pilot
rabbit study was provided:
"A pilot rabbit teratology study was conducted with
groups of pregnant rabbits orally administered 0, 10,
30, 100, or 300 mg/kg of Santoflex* 77. All maternal
animals given 100 or 300 mg/kg died. At 30 mg/kg,
abortions were seen along with increased fetal
resorption. At 10 mg/kg, normal numbers of implants,
resorptions, and fetuses were obtained but there was
maternal weight loss during the treatment period (seen
also in this control group)..."
\ This status report is the result of a preliminary evaluation of information that has
been submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substances Control Act (TSCA). The statements made in this status
report should not be regarded as expressing final Agency policy or intent with respect to the
subject chemical(s). Any review of this status report should take into account that the
report may be based on incomplete information.
603
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8EHQ-0590-0977
Page 2 of 3
Monsanto provided the following summarized information regarding
the definitive teratology study in which Santoflex® 77 was
administered orally to pregnant rabbits at dose levels of 0, 3.0
or 10.0 mg/kg/bw from gestation days 6 through 18:
"An increase in abortions occurred in dams exposed to a
dosage of 10 mg/kg."
In a supplemental submission, the following summarized information
was provided by Monsanto regarding a three-generation rat
reproduction feeding study conducted at doses of 0, 30, 100, or 300
ppm Santoflex* 77:
"Signs of significant maternal toxicity were noted at
100 and 300 ppm. Signs of developmental toxicity
(statistically significant reductions in pup survival
and postnatal weight gain) were also noted at 100 and
300 ppm. Results from this study suggest that while
[Santoflex* 77] induces developmental effects in rats,
it does so only at dose levels that also produce
significant maternal toxicity."
In the cover letter of this supplemental submission, the company
reported that the "current Monsanto Material Safety Data Sheet for
Santoflex* 77 antiozonant reports on developmental effects seen
with repeated dietary feeding of this chemical."
USE AND EXPOSURE POTBMTT1T.
The condensed Chemical Dictionary (10th edition) identifies
"Santoflex" as a Monsanto trademark "for a series of rubber
antioxidants and antiozonants."
A review of the non-confidential version of EPA's TSCA Chemical
Substance Inventory showed that Santoflex* 77 is listed.
COMMENTS/RECOMMENDATIONS
It should be noted here that the Agency has received summary in
vitro genotoxicity data on Santoflex* 77; the reader's attention
is directed to 8EHQ-0187-0681 FLWP.
a) EPA will request Monsanto to provide a complete copy of
the final report (including the actual experimental
protocol, results of gross and histopathological
examinations, results of statistical analyses, etc.) from
the rabbit range-finding teratology study cited in the
submission.
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Monsanto will be requested to
describe the actions that the company has taken or plans
604
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8EHQ-0590-0977
Page 3 of 3
to take 1) to notify workers/others about the reported
information, and 2) to reduce or eliminate exposure to
the subject chemical. Monsanto will be asked also to
provide copies of Material Safety Data Sheets and labels
that have been revised to reflect the reported findings.
In addition, Monsanto will be asked to describe the
nature and results, if available, of all studies (other
than those submitted already to EPA or those cited in the
published scientific literature) about which Monsanto is
aware or that the company has conducted, is conducting
or plans to conduct that are designed to determine the
toxicity of or the exposure to the subject chemical.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
605
-------
(SSB
pnO^
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
(9
Page 1 of l
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0590-0978
DATE: ju BOO APPROVE01
dy/
-------
Page 1 of 3
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
DATE:
AUG 2 4
APPROVED:
SUBJECT: Status Report1 8EHQ-0590-0979
ac
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
FROM: Martha G. Price, Ph.D., Chemis
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
In conjunction with a TSCA §8(e) Consent Agreement (TSCA 89-H-21),
Monsanto Company provided the following summary information
regarding the conduct and final results of a Two Generation Rat
Reproduction Study on hexamethylene diamine, 1,6-diaminohexane (CAS
No. 124-09-4):
"Hexamethylene diamine was administered orally in the diet
at dosage levels of 50, 150 or 500 mg/kg/day to treated
groups of 26 males and 26 females each in two consecutive
generations. The control group received the basal
laboratory diet, ground Purina Certified Rodent Chow*
#5002. The F0 and F1 parents were mated once to produce
F1 and F2 offspring, respectively.
"Two F0 rats failed to survive to scheduled sacrifice, one
low- and one mid-dose male. The deaths occurred between
study weeks 8 and 14. In the F1 generation, two female
parents died; a control group rat died during week 35 and
a low-dose female died during week 32.
I This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
607
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8EHQ-0590-0979
Page 2 of 3
"Parental body weight evaluation revealed cross-
generational trends that were considered treatment-
related. Male weekly body weights of the high-dose groups
in both generations (FO and Fl) were reduced when compared
to the respective control group values. Food consumption
for these animals was also decreased during both
generations. Reduced high-dose female body weights were
also observed in the Fl generation, however similar
findings were not noted in the FO animals. Food
consumption values for the high-dose females in both
generations were reduced in relation to those of the
control groups. Weight gain inhibition during the overall
gestation periods was seen in both generations of high-
dose females.
"Several litter parameters were also affected by treatment
at the high-dose level. Significant reductions in litter
size at birth, and decreased pup weights on lactation days
14 and 21 were observed in the high-dose groups of both
generations.
"There were no meaningful differences noted between the
control and treated animals of either generation in regard
to antemortem observations, lactation female body weights,
fertility indices, copulatory interval, gestation length,
nesting and nursing behavior, and Fl and F2 pup survival
and appearance at any dosage level.
"There were no test article-related differences in the
results of organ weight (testes), macroscopic or
microscopic evaluations of the treated groups in relation
to those of the control at any dosage level.
"In conclusion, the 150 mg/kg/day dosage level was
considered the dietary 'no effect1 level based on the
results of both generations.
"Signs of significant maternal toxicity were noted at 500
mg/kg in both the FO and Fl generations. A statistically
significant decrease in litter size at birth and reduced
postnatal weight gains occurred in offspring of 500 mg/kg
tesated animals of both generations. Results from this
study suggest that while hexamethylene diamine induces
developmental effects in rats, it does so only at a dose
level that also produces significant maternal toxicity."
TTflE AND EXPOSURE POTENTIAL
Monsanto did not provide any information regarding the use of or
the potential for exposure to hexamethylene diamine. According to
The condensed Chemical Dictionary (10th edition), hexamethylene-
diamine is used for formation of high polymers such as nylon 66.
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Page 3 of 3
COMMENTS/RECOMMENDATIONS
In its submission Monsanto stated, "Results from the reference study
are discussed in the current Monsanto Material Safety Data Sheet for
hexamethylene diamine."
The Chemical Screening Branch prepared a Chemical Hazard Information
Profile on hexamethylenediamine in 1978.
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Monsanto will be requested to
describe the actions that the company has taken or plans
to take l) to notify workers/others about the reported
information, and 2) to reduce or eliminate exposure to
the subject chemical. Monsanto will be asked also to
provide copies of Material Safety Data Sheets and labels
that have been revised to reflect the reported findings.
In addition, Monsanto will be asked to describe the nature
and results, if available, of all studies (other than
those submitted already to EPA or those cited in the
published scientific literature) about which Monsanto is
aware or that the company has conducted, is conducting or
plans to conduct that are designed to determine the
toxicity of or the exposure to the subject chemical.
b) As part of the initial phase of the OTS Existing Chemicals
Program (ECP), staff of the Chemical Screening Branch will
screen the reported information in order to determine the
need for further assessment of the subject chemical at
this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
609
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Page 1 of 6
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
DATE:
v jg 2 ^ 1990
APPROVED:
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: status Report1 8EHQ-0590-0980 INITIAL fc SUPPLEMENT
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
In conjunction with a TSCA §8(e) Consent Agreement (TSCA 89-H-21),
Monsanto Company provided initial and supplemental submissions on
para-nitrochlorobenzene, (CAS No. 100-00-5), also known as PNCB or
4-chloronitrobenzene. The initial submission contained the
following summary information regarding the conduct and final
results of a two-generation rat reproduction study:
"This study was conducted for Monsanto Company [at
Bio/dynamics] to evaluate the effects of /7-Nitrochloro-
benzene on the reproductive performance and fertility of
rats through two consecutive generations. Test material
was administered by gastric intubation daily at dose
levels of 0.1, 0.7 and 5.0 mg/kg/day to Fo and F1
generation animals (15 male and 30 female CD* rats/group)
during a premating growth period and through the ensuing
mating, gestation and lactation intervals (one litter/
generation). F1 animals continued on treatment during a
post-weaning period (approximately 30 days). Included in
this study was a vehicle (corn-oil)-treated control group
(15 males and 30 females/generation).
]_ This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
FROM: Martha G. Price, Ph.D.,
Chemical Risk Identifica
610
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Page 2 of 6
"Some mortality was encountered in the control and
treated groups during the Fo and F1 generations. Most of
this mortality was attributed to dosing related injury.
No treatment-related effect on mortality was indicated.
"No adverse effect of treatment was evident in body
weight data during the growth intervals for the Fo and
F1 males or Fl females. Slightly lower mean weights were
seen in the treated Fo females during the growth period.
Though some of these differences between the control and
a treated group were statistically significant, no clear
dose-relationship was indicated. Mean weight gain for the
females during the Fo growth period was also lower than
control in each of the treated groups; however, these
differences from control data were not statistically
significant and no clear dose-relationship was evident.
"Mean food consumption data during the growth periods
were comparable between the control and treated groups
for the Fo and Fl males and Fl females. In the Fo
females, mean food consumption data during the growth
period were comparable between the control, low- and
mid-dose groups. In the high-dose Fo female group, mean
food consumption was significantly higher than control
early in the growth period (Weeks 1-3 and 6) and
comparable to control at remaining weeks of the growth
period.
"Mean body weight and food consumption data for the Fl
adults during the post-weaning interval did not reveal
an adverse effect of treatment. Some statistically
significant differences existed between data for the
control and treated groups, however, no trend was
indicated to suggest a treatment-related effect for these
parameters.
"No effect of treatment was indicated in physical in-life
evaluation data or maternal body weight data
(gestation/lactation periods) for the Fo and Fl adult
generations.
"Mating indices for the Fo females were comparable
between the control and low-dose group and slightly lower
than control in the mid- and high-dose groups
(differences in female mating indices between the
control, mid- and high-dose groups were not statistically
significant) . Male mating indices for the Fo animals were
comparable between the control and treated groups. Male
fertility indices and female pregnancy rates for the Fo
animals were comparable between the control, low- and
mid-dose groups and lower than control in the high-dose
group (these latter differences in pregnancy/fertility
indices between the control and high-dose group were not
statistically significant).
611
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Page 3 of 6
"In the Fl generation, female mating indices were
slightly lower than control in each of the treated
groups; however, these differences were not statistically
significant and no clear dose-relationship was indicated.
Male mating indices, male fertility indices and female
pregnancy rates for the Fl adults were comparable between
the control and treated groups. No effect on fertility
was indicated during the Fl generation.
"No adverse effect of treatment was indicated for either
the Fo or Fl generations in regard to gestation length
or parturition data, litter size data during lactation,
litter survival indices, mean pup weight data or pup sex
distribution data.
"In the Fo generation, Fl pup survival indices during
lactation (Days 0-4, 4-21) were comparable between the
control, low- and mid-dose groups and significantly lower
than control in the high-dose group. During the Fl litter
interval, much of the pup mortality encountered in the
high-dose group was attributed to the loss of pups from
entire litters (two high-dose females experienced
complete pup mortality within their litters). This was
particularly significant in reducing the pup survival
index at the high-dose level during the Day 4-21
lactation interval. Excluding data for this one litter,
the pup survival index for the high-dose group during the
Day 4-21 interval was 99.2%, which was similar to control
data. In the Fl generation, survival indices for the F2
pups during lactation were comparable between the control
and all treated groups. No consistent effect on pup
survival was evident through both litter intervals of the
study to suggest an adverse effect due to treatment.
"No adverse effect of treatment was evident from gross
postmortem observations of the Fl and F2 pups, dead pup
observations (Fl and F2 litter intervals) or histo-
pathological evaluation of tissues from selected Fl and
F2 pups.
"Histopathological evaluation of testes/epididymides of
Fo control and high-dose males revealed bilateral
degeneration/atrophy of epithelium in two of 15 high-dose
animals and bilateral maturation arrest of the germinal
epithelium in one of 15 high-dose animals. Epididymal
observations (oligospermia) were also noted in these same
high-dose males. Similar observations were not noted in
the Fo control males. Other microscopic findings in the
testes and epididymides of high-dose males occurred
sporadically and were not considered to be related to the
administration of /?-Nitrochlorobenzene.
612
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8EHQ-0590-098 0
Page 4 of 6
"Histopathological evaluation of tissues from the F1
adult animals revealed extramedullary hematopoiesis and
reticuloendothelial cells containing brown pigment, both
of variable degrees, in the spleens of all animals in all
groups; however, these findings appeared to be somewhat
more pronounced in the high-dose males and females. Other
pathomorphology findings observed microscopically in
treated animals did not appear to be related to
administration of p-Nitrocholorobenzene."
The supplemental submission contained the following summary
information regarding the conduct and final results of a chronic
rat study:
"This study, conducted for the Monsanto Company [at
Bio/dynamics], was designed to assess the long-term
toxicity and oncogenicity of p-Nitrochlorobenzene
administered orally, via gavage, to Sprague-Dawley rats
(60 animals/sex/group) at dose levels of 0.1, 0.7 and 5.0
mg/kg/day for at least 24 months. Control animals
(60/sex) received the vehicle, corn oil, at the same dose
volume (5 ml/kg) as the test animals. Physical
observations and body weight and food consumption
measurement were performed pretest and at selected
intervals throughout the study. Hematology and clinical
chemistry parameters and urinalyses were evaluated at 6,
12, 18 and 24 months. All surviving animals were
sacrificed after 24 months of test substance
administration and gross postmortem examinations and
histopathological evaluation of selected tissues were
performed on all animals. Selected organs were weighed
and organ/body weight ratios calculated.
"PNCB administration produced dose-related methemo-
globinemia in mid- and high-dose males and females.
Methemoglobin levels in mid-dose animals were
approximately 3 to 4 times those of control animals,
while high-dose levels were approximately 10 to 15 times
control levels. A slight anemia was apparent in high-dose
animals as demonstrated by slightly decreased hemoglobin,
hematocrit and erythrocyte values with concommitant
slight increases in numbers of reticulocytes.
"Microscopic examination revealed increases in the
incidence and/or severity of accumulation of brown
pigment (hemosiderin) in the spleens of high-dose males
and females. These findings correlated with elevated
spleen weights for this group.
"The total neoplasm incidence and the incidence of benign
and malignant neoplasms in treated animals were lower
than or comparable to incidence in control animals.
613
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8EHQ-0590-098 0
Page 5 of 6
"Distribution of various types of neoplasms was generally
similar in control and treated groups. However,
interstitial cell tumors of the testes were seen at a
higher incidence in treated animals than in control
animals. Incidence in control animals was 1/60 (1.7%) and
incidence in high-dose animals was 6/60 (10%). In low-
and mid-dose animals, incidence was 4/59 (6.8%) and 5/60
(8.3%), respectively. These differences appear to
represent an unusually low incidence of these tumors in
control animals rather than an oncogenic effect of PNCB.
The control incidence of interstitial cell tumors of the
testes in this strain of rat for fourteen studies
conducted at Bio/dynamics is 116/1185 (10%) with a range
of 3.4% to 23.4%. The control incidence in this study is
below the historical range, while the incidence in
high-dose animals is comparable to that historically seen
in untreated animals. Mean testes weights and testes/body
weight ratios for treated animals were slightly higher
than those of control animals.
"Evaluation of mortality, physical observations, body
weights, food consumption, ophthalmoscopic examinations,
clinical chemistry studies and urinalyses revealed no
consistent differences between control and treated
animals which were attributed to PNCB administration."
USE AND EXPOSURE POTENTIAL
Monsanto did not provide any information regarding the use of or
the potential for exposure to 4-chloronitrobenzene. According to
The Condensed Chemical Dictionary (loth edition), 4-chloronitro-
benzene is used as an intermediate, especially for dyes; for
manufacture of p-nitrophenol, from which parathion is made; for
agricultural chemicals? and for rubber chemicals.
COMMENTS/RECOMMENDATIONS
In its submission, Monsanto reported that results considered
treatment-related from this study are discussed in the current
Monsanto Material Safety Data Sheet.
The Chemical Screening Branch prepared a CHIP on 4-chloronitro-
benzene in 1983; in addition, the Risk Analysis Branch conducted
risk assesment activities. EPA has received a "For Your
Information" (FYI) submission, FYI-OTS-1085-0455, on 4-chloronitro-
benzene and an 8(e) submission, 8EHQ-0590-0973, on 2-
chloronitrobenzene.
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Monsanto will be requested to
614
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8EHQ-0590-0980
Page 6 of 6
describe the actions that the company has taken or plans
to take l) to notify workers/others about the reported
information, and 2) to reduce or eliminate exposure to
the subject chemical. Monsanto will be asked also to
provide copies of Material Safety Data Sheets and labels
that have been revised to reflect the reported findings.
In addition, Monsanto will be asked to describe the
nature and results, if available, of all studies (other
than those submitted already to EPA or those cited in the
published scientific literature) about which Monsanto is
aware or that the company has conducted, is conducting
or plans to conduct that are designed to determine the
toxicity of or the exposure to the subject chemical.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
615
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e A \
u».
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
^ WASHINGTON, DC 20460 page j ()f- j
DATE: JUL I 0 I960 APPROVED: 7/^v/fo
OFFICE OF
PESTICIDES AND
SUBJECT: Status Report 1 8EHQ-0590-0981 INIT & SUPP TOXIC SUBSTANCES
FROM: Jacqueline T. Favilla, Biologist ^
Chemical Risk Identification Section/CeB
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
Under a TSCA Section 8(e) "Consent Agreement" (TSCA 89-H-21), the Monsanto Company provided the
following final reports: rat and rabbit dermal reproduction and/or teratology and mouse dominant lethal
studies of dimethylacetamide (DMAC, CAS No. 127-19-5), as well as rat dermal reproduction and/or
teratology and mouse dominant lethal studies of dimethylformamide (DMF, CAS No. 68-12-2). In a
supplement, Monsanto provided final reports of rat pilot and definitive teratology studies of DMAC.
COMMENTS/RECOMMENDATIONS
EPA has received a number of TSCA Section 8(e) and/or "For Your Information" (FYI) notices on DMAC
and DMF. DMF is also the subject of a 1981 Chemical Hazard Information Profile (CHIP) prepared by the
Chemical Screening Branch (CSB) and of TSCA Section 8(d) and 8(a) information gathering rules.
a) Monsanto will be requested to describe the actions that it has taken or plans to take 1) to
notify workers and others about the reported data, and 2) to reduce or eliminate exposure
to DMF and DMAC. Monsanto will be asked to provide copies of Material Safety Data
Sheets and labels that have been revised to reflect the reported findings. In addition,
Monsanto will be asked to describe the nature and results, if available, of all studies (other
than those submitted already to EPA or those cited in the published scientific literature)
about which the company is aware or that it has conducted, is conducting or plans to
conduct that are designed to determine the toxicity of DMF and DMAC.
b) As was the case for the initial notice, the Risk Assessment Branch (RAB/ECAD/OTS) will
be notified of further reported information for inclusion in its review of DMF. As part of
the initial phase of the OTS Existing Chemicals Program (ECP), CSB will screen the
information on DMAC in order to determine the need for further OTS assessment.
c) CSB will send copies of this status report to NIOSH, OSHA, CPSC, FDA, NTP,
OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA, and RAB/ECAD; in
addition, copies of this status report will be sent to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
616
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
OFFICE OF
PESTICIDES AND
DATE: 111! I I APPROVED: 1/ ' J//1 fas) toxic substances
| T 1990 APPROVED:^**?
SUBJECT: Status Report1 8EHQ-0590-0982
FROM: Martha G. Price, Ph.D., Chemist
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
In conjunction with a TSCA §8(e) Consent Agreement (TSCA 89-H-21), Monsanto Company provided a
final report of a rat teratology study on SANTICIZER® 97, di(C7_9-alkyl) adipate (CAS Nos. 68515-75-3,
151-32-6, and 14697-48-4) administered by gavage to pregnant rats at dose levels of 0, 1000, 4000, and 7000
mg/kg/day.
COMMENTS/RECOMMENDATIONS
The Chemical Screening Branch prepared a CHIP on Adipate Plasticizers in 1978.
a) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquartera, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
617
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page l of 3
JUN 5 layO
OFFICE Of
PESTICIDES AND
TOXIC SUBSTANCES
DATE
APPROVED:
SUBJECT: Status Report1 8EHQ-0590-0983
FROM: Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
In conjunction with a TSCA Section 8(e) "Consent Agreement" (TSCA
89-H-21), the Monsanto Company provided the final reports of an
oral rat range-finding study and a definitive teratology study of
Therminol 66 (a mixture of terphenyl (CAS No. 26140-60-3) and
hydrogenated terphenyl (CAS No. 61788-32-7)). According to the
provided final reports, Therminol 66 was administered to pregnant
rats at doses of 0, 125, 250, 500, 1000 or 2000 mg/kg/day on days
6-15 of gestation in the range-finding study, and at doses of o,
125, 500 or 1500 mg/kg/day on gestation days 6-15 in the definitive
teratology study. Monsanto submitted the following summary
information about the results of these studies:
Range-Finding Study
"Signs of maternal toxicity were noted in 1000 and 2 000
mg/kg treated dams. Signs of developmental toxicity
(increased resorptions and decreased fetal body weight)
were noted at 2000 mg/kg. Results from this study suggest
that while Therminol 66 . . . induces developmental
effects in rats, it does so only at a dose level that
also produces maternal toxicity."
1 This status report is the result of a preliminary evaluation of information that has
been submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substances Control Act (TSCA). The statements made in this status
report should not be regarded as expressing final Agency policy or intent with respect to the
subject chemical(s). Any review of this status report should take into account that the
report may be based on incomplete information.
618
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Definitive Study
8EHQ-0590-0983
Page 2 of 3
"Signs of significant maternal toxicity were noted in
[the] 1500 mg/kg treated dams. Statistically significant
decreases in fetal body weights, increases in resorptions
and variations and a statistical increase in malforma-
tions were also seen at 1500 mg/kg. Results from this
study suggest that while Therminol 66 . . . induces
developmental effects in rats, it does so only at a dose
level that also produces maternal toxicity."
A copy of a 1983 Therminol 66 Material Safety Data Sheet (MSDS)
was included at the end of the submitted final report of the range-
finding teratology study.
USE AND EXPOSURE POTENTIAL
According to the submitted MSDS, Therminol 66 is a "heat transfer
fluid." Monsanto did not provide any further information regarding
the use(s) of or the potential for exposure to Therminol 66, nor
was such information located in the secondary literature sources
consulted by EPA.
COMMENTS/RECOMMENDATIONS
In its submission, Monsanto reported that the company has updated
the current Therminol 66 MSDS to include results from the provided
oral teratology studies in rats.
It should be noted that EPA has received a "For Your Information"
(FYI) submission (FYI-OTS-0480-0066) on spent Therminol 66 and a
TSCA Section 8(e) submission (8EHQ-0590-0969) on Therminol 55.
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Monsanto will be requested to
describe the actions that the company has taken or plans
to take 1) to notify workers/others about the reported
information, and 2) to reduce or eliminate exposure to
the subject product and/or its constituents. Monsanto
will be asked also to provide copies of Material Safety
Data Sheets and labels that have been revised to reflect
the reported findings. In addition, Monsanto will be
asked to describe the nature and results, if available,
of all studies (other than those submitted already to EPA
or those cited in the published scientific literature)
about which Monsanto is aware or that the company has
conducted, is conducting or plans to conduct that are
designed to determine the toxicity of or the exposure to
the subject product and/or its constituents.
619
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8EHQ-0590-0983
Page 3 of 3
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
product and its constituents.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this report will be sent to the Environmental
Assistance Division/OTS for further distribution.
620
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53SJ
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY Page 1 of 2
WASHINGTON, DC 20460
FROM:
TOS
JUN 2 5 1990
DATE:
APPROVED:
OFFICE OF
PESTICIDES AND
k TOXIC SUBSTANCES
SUBJECT! Status Report1 8EHQ-0590-0984
^U-ctUtAs H t^O
Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION (See NOTE on Page 2 of this Status Report)
In conjunction with a TSCA Section 8(e)-related "Consent Agreement"
(TSCA 89-H-21), the Monsanto Company provided a final report of an
inhalation teratology study of "Flux Oil" (a mixture reported to
contain predominantly diphenyl ethane (CAS No. 38888-98-1), ethyl
diphenyl ethane mixed isomers (CAS No. 64800-83-5), and alkyl
tetrahydro-naphthalenes (CAS No. 68412-24-8)). In this study, mated
female rats were exposed to Flux Oil concentrations of 0, 20, 100
or 400 mg/m3 for six hours per day on days 6-15 of gestation. The
following information was presented in the summary section of the
submitted final report:
"In conclusion, maternal toxicity was observed at
exposure levels of 400 and 100 mg/m3 but not at 20 mg/m3.
No treatment related embryotoxicity or fetotoxicity was
observed at any of the exposure levels. An increase in
litters with malformations and litters with bent ribs was
observed at the 400 mg/m3 level. These observations are
considered to be possible indications of a treatment
related effect, although it is also possible that the
effects are not treatment related. Moreover, significant
maternal toxicity was evident in the high exposure level
females and the effects observed may have been secondary
]_ This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
621
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8EHQ-0590-0984
Page 2 of 2
to maternal toxicity. No treatment related effects on
malformations or variations were observed at the 100 or
2 0 mg/m3 exposure levels."
USE AND EXPOSURE POTENTIAL
Other than the fact that the tested product is a flux oil, Monsanto
did not provide any further information regarding the use(s) of or
the potential for exposure to this mixture.
COMMENTS/RECOMMENDATIONS
Monsanto reported that "birth defects noted in the referenced study
are discussed in the Monsanto Material Safety Data Sheets (MSDS)
for products containing flux oil components."
a) In view of EPA/s interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Monsanto will be requested to
describe the actions that the company has taken or plans
to take 1) to notify workers/others about the reported
information, and 2) to reduce or eliminate exposure to
the subject product or its components. Monsanto will be
asked also to provide copies of Material Safety Data
Sheets and labels that have been revised to reflect the
reported findings. In addition, Monsanto will be asked
to describe (by way of short summaries) the nature and
results, if available, of all studies (other than those
submitted already to EPA or those cited in the published
scientific literature) about which Monsanto is aware or
that the company has conducted, is conducting or plans
to conduct that are designed to determine the toxicity
of or the exposure to this product or its components.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
chemicals at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA? in addition,
copies of this report will be sent to the Environmental
Assistance Division/OTS for further distribution.
NOTE A Material Safety Data Sheet submitted by Monsanto in an
August 10, 1990 followup letter (8EHQ-0890-0984 FLWP)
reports that Flux Oil also contains CAS No. 68398-19-6
(Benzene, ethyl(phenylethyl)-, mono-Ar-ethyl deriv.).
622
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8EHQ-0590-0985
Page 2 of 2
NOTE According to AT&T's July 20, 1990 followup response letter (8EHQ-0790-0985 FLWP), the
tradename for B-65 opaque gel is "Type B Lightguide Cable Filling Compound." A Material
Safety Data Sheet (MSDS) enclosed with that letter reports that this product contains the
following major and minor components:
Paraffinic Hydrocarbon (CAS No. 66070-54-0) (87%)
Amorphous Silicon Dioxide (CAS No. 67762-90-7) (<6%)
624
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kNit°sr^ Page 1 of 3
^ \
I I UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
% WASHINGTON, DC 20460
PRO^°
DATE:
AUG <% 4 !990
APPROVED:
SUBJECT: status Report1 8EHQ-0590-0986 8
FROM: Martha G. Price, Ph.D., Chemist
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
NOTE
The submitting company has claimed its company name and the exact
identity of the subject chemical as TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. In the "sanitized" version of its Section 8(e)
notice, the company reported non-confidentially that the subject
chemical is an "aromatic sulfenamide #1."
SUBMISSION DESCRIPTION
The submitting company provided the following summary information
regarding the conduct and final results of a pilot teratology study
in rats on "aromatic sulfenamide #1":
"A pilot study with mated Charles River CD* female rats
was performed to determine dosage levels for a teratology
study. [Aromatic sulfenamide #1] was administered by
gavage at 10, 50, 300, and 1000 and 3000 mg/kg/day to
pregnant rats from gestation day 6 through day 15. Two
control groups received the vehicle, corn oil, at 10
ml/kg/day.
- This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
625
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8EHQ-0590-0986 S
Page 2 of 3
"During gestation the females were observed for clinical
signs of effect, mortality and body weight changes. The
uterine contents were examined for viable and nonviable
fetuses, early and late resorptions, total implantations
and the ovaries were examined for corpora lutea at
sacrifice.
"There were no changes in appearance or behavior
attributable to treatment between the control rats and
rats treated with 10, 50 or 300 mg/kg/day.
"There were no biologically meaningful differences in the
mean number of viable or nonviable fetuses, early or late
resorptions, implantations or corpora lutea in rats
receiving 10, 50 and 300 mg/kg/day. Slight loss in
maternal body weight was seen in the 300 mg/kg/day dosage
group in the first 3 days of treatment and slightly
reduced maternal body weight gains for the treatment
period were seen when compared to either control group.
There was an increase in the mean number of early
resorptions and a corresponding decrease in the mean
number of viable fetuses in the 1000-mg/kg/day dosage
group.
"Three of the four rats in the 1000-mg/kg/day dosage
group had staining of the anogenital region. Maternal
body weight losses were observed in this group during the
entire treatment period.
"Three of the four rats in the 3000-mg/kg/day dosage
group died by gestation day 12. Signs of maternal
toxicity were seen in these rats before death and in the
surviving rats in this group.
"A dose level of 1000 mg/kg/day is considered excessive
for a teratology study."
USE AND EXPOSURE POTENTIAL
In view of the submitter's TSCA CBI claim, no information regarding
the TSCA Chemical Substance Inventory status or use of the subject
chemical will appear in this status report.
COMMENTS/RECOMMENDATIONS
EPA has received two other TSCA §8 (e) submissions on "aromatic
sulfonamides", 8EHQ-0590-0987 S and 8EHQ-0590-0988 S.
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, the submitter will be requested
to describe the actions that the company has taken or
626
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8EHQ-0590-0986 S
Page 3 of 3
plans to take l) to notify workers/others about the
reported information, and 2) to reduce or eliminate
exposure to the subject chemical. The submitter will be
asked also to provide copies of Material Safety Data
Sheets and labels that have been revised to reflect the
reported findings. In addition, the submitter will be
asked to describe the nature and results, if available,
of all studies (other than those submitted already to EPA
or those cited in the published scientific literature)
about which the submitter is aware or that the company
has conducted, is conducting or plans to conduct that are
designed to determine the toxicity of or the exposure to
the subject chemical.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
627
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i a \
mj
fmcC*-°
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 3
APPROVED:
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
DATE:
SUBJECT: Status Report 8EHQ-0590-0987 8
FROM: Martha G. Price, Ph.D., Chemi
Chemical Risk Identification oeui.j.uii/wD
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
The submitting company has claimed its company name and the exact
identity of the subject chemical as TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
will review all incoming correspondence related to the company's
TSCA CBI claims. In the "sanitized" version of its Section 8(e)
notice, the company reported non-confidentially that the subject
chemical is an "aromatic sulfenamide #3."
SUBMISSION DESCRIPTION
The submitting company provided the following summary information
regarding the conduct and final results of a pilot teratology study
in rats on "aromatic sulfenamide #3":
"A pilot study with mated Charles River CD* female rats
was performed to determine dosage levels for a teratology
study. [Aromatic sulfenamide #3] was administered by
gavage at 10, 50, 300, 1000 and 3000 mg/kg/day to
pregnant rats from gestation day 6 through day 15. Two
control groups received the vehicle, corn oil, at 10
ml/kg/day.
- This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
628
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8EHQ-0590-0987 S
Page 2 of 3
"During gestation the females were observed for clinical
signs of effect, mortality and body weight changes. The
uterine contents were examined for viable and nonviable
fetuses, early and late resorptions, total implantations
and the ovaries were examined for corpora lutea at
sacrifice.
"There were no changes in appearance or behavior in rats
treated with 1000 mg/kg/day or less when compared to the
control rats. Body weight gains were similar to the
control rats receiving 10, 50, and 300 mg/kg/day. There
were no biologically meaningful differences in the mean
number of viable or nonviable fetuses, early or late
resorptions, implantations or corpora lutea in the rats
treated with 10 and 50 mg/kg/day when compared to the
control rats.
"There was an increase in post implantation losses in
the 300- and 1000-mg/kg/day dosage groups when compared
to the first control group. Body weight loss was seen in
the 1000-mg/kg/day dosage group for the first 3 days of
treatment while body weight gains for the remainder of
gestation were similar to the controls.
"One rat in the 3000-mg/kg/day dosage group died on
gestation day 15. Body weight losses, red nasal discharge
and staining of the anogenital area were seen in all rats
in this group. At the scheduled sacrifice, the two
surviving pregnant rats in the 3000-mg/kg/day dosage
group had only resorptions.
"A dosage level of 1000 mg/kg/day should produce some
maternal toxicity in a teratology study."
USE AND EXPOSURE POTENTIAL
In view of the submitter's TSCA CBI claim, no information regarding
the TSCA Chemical Substance Inventory status or use of the subject
chemical will appear in this status report.
COMMENTS/RECOMMENDATIONS
EPA has received two other TSCA §8(e) submissions on "aromatic
sulfenamides", 8EHQ-0590-0986 S and 8EHQ-0590-0988 S.
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, the submitter will be requested
to describe the actions that the company has taken or
plans to take 1) to notify workers/others about the
reported information, and 2) to reduce or eliminate
629
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8EHQ—0590—0987 S
Page 3 of 3
exposure to the subject chemical. The submitter will be
asked also to provide copies of Material Safety Data
Sheets and labels that have been revised to reflect the
reported findings. In addition, the submitter will be
asked to describe the nature and results, if available,
of all studies (other than those submitted already to
EPA or those cited in the published scientific
literature) about which the submitter is aware or that
the company has conducted, is conducting or plans to
conduct that are designed to determine the toxicity of
or the exposure to the subject chemical.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, fda, ntp, oswer/epa,
OW/EPA, ORD/EPA, OAR/EPA and 0PP/0PTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
630
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Page 1 °f 4
i UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
(m,
V
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8EHQ-0590-0988 S
Page 2 of 4
"During gestation the females were observed for
clinical signs of effect, mortality and body weight
changes. The uterine contents were examined for viable
and nonviable fetuses, early and late resorptions,
total implantations and the ovaries were examined for
corpora lutea at sacrifice.
"Maternal body weight gains for the 10- and
50-mg/kg/day dosage groups were similar to the control
groups. There was a slight body weight loss in the
first 3 days of treatment in the 300-mg/kg/day dosage
group, however, the mean weight gain for the entire
gestation period was comparable to the controls. Mean
maternal body weight losses were seen in the first 6
days of treatment and reduced mean maternal body weight
gains were seen for the remainder of gestation in the
1000-mg/kg/day dosage group.
"All rats in the 3 000-mg/kg/day dosage group died by
gestation day 11. Severe maternal body weight losses,
red nasal and ocular discharge and staining of the
anogenital region were observed in these rats prior to
death, one rat in the 1000-mg/kg/day dosage group died
on gestation day 13. The signs of toxicity noted in
this rat were similar to those noted in all rats in the
3000-mg/kg/day dosage group. Three of the four rats in
the 1000-mg/kg/day group had yellow staining of the
anogenital area.
"There were no biologically meaningful differences
between either control group and the 10-, 50-, 300- and
1000-mg/kg/day treatment groups in the mean number of
viable or nonviable fetuses, late resorptions,
implantations or corpora lutea. An increase in the mean
number of early resorptions was seen in the 300- and
1000-mg/kg/day dosage groups but the mean number of
early resorptions was similar for the 10- and 50—
mg/kg/day dosage groups when compared to the first
control group.
"Due to maternal toxicity a dosage level of 1000
mg/kg/day is considered excessive for a teratology
study."
The summary for the follow-up rat teratology study follows:
"Pregnant Charles River COBS® CD® rats were used to
determine the teratogenic potential of [aromatic
sulfenamide #2]. Dosage levels of 0, 100, 300, 500 and
900 mg/kg/day were administered orally by gavage as a
single daily dose on days 6 through 15 of gestation at
a constant volume of 10 ml/kg. The control group
received the vehicle only, Mazola® corn oil, on a
comparable regimen. Cesarean sections were performed
on all surviving dams on gestation day 20.
632
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8EHQ-0590-0988 S
Page 3 of 4
"Due to the early deaths of five rats and due to signs
of excessive maternal toxicity and weight loss in the
remaining animals, the rats in the 900 mg/kg/day dosage
group were sacrificed and discarded.
"A severe increase in matting and/or staining of the
ventral surface or anogenital region was noted in the
300 and 500 mg/kg/day dosage groups. A slight to
moderate decrease in mean maternal body weight gain was
noted in the 3 00 mg/kg/day dosage group during the
treament period. A severe decrease in mean maternal
body weight gain and adjusted body weight on gestation
day 20 occurred in the 500 mg/kg/day dosage group when
compared to the control group.
"Survival was 100% in all the groups except for one rat
that died on gestation day 9 in the 500 mg/kg/day
dosage group. A slight decrease in mean fetal body
weight was observed in the 100 and 300 mg/kg/day dosage
groups when compared to the control group mean with a
statistically significant decrease (p<0.01) in the 500
mg/kg/day dosage group.
"A very slight increase in the number of fetuses and
litters with malformations was noted in the 500
mg/kg/day dosage group when compared to the control
group, due primarily to three fetuses, each from a
different litter, with a thread-like tail and small
anus. This same malformation was also observed in one
fetus in the 100 mg/kg/day dosage group.
"Treatment with [aromatic sulfenamide #2] did not
produce a teratogenic response when administered to
pregnant Charles River COBS* CD® rats at a dosage level
of 500 mg/kg/day or less."
PSE AND EXPOSURE POTENTIAL
In view of the submitter's TSCA CBI claim, no information
regarding the TSCA Chemical Substance Inventory status or use of
the subject chemical will appear in this status report.
COMMENTS/RECOMMENDATIONS
EPA has received two other TSCA §8(e) submissions on "aromatic
sulfonamides", 8EHQ-0590-0986 S and 8EHQ-0590-0987 S.
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, the submitter will be requested
to describe the actions that the company has taken or
plans to take 1) to notify workers/others about the
633
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8EHQ-0590—0988 S
Page 4 of 4
reported information, and 2) to reduce or eliminate
exposure to the subject chemical. The submitter will
be asked also to provide copies of Material Safety Data
Sheets and labels that have been revised to reflect the
reported findings. In addition, the submitter will be
asked to describe the nature and results, if available,
of all studies (other than those submitted already to
EPA or those cited in the published scientific
literature) about which the submitter is aware or that
the company has conducted, is conducting or plans to
conduct that are designed to determine the toxicity of
or the exposure to the subject chemical.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical
Screening Branch will screen the reported information
in order to determine the need for further assessment
of the subject chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP,
OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be
transmitted to the Environmental Assistance
Division/OTS (formerly the TSCA Assistance Office/OTS)
for further distribution.
634
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON. D C. 20460
Page 1 of 2
SUBJECT: Status Report1 8EHQ-fl59(H)989 S
DATE:
JUL 31990
APPROVED:
FROM: Judith M. Loranger, Biologist
Chemical Screening Branch/ECAD/OTS
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION (gee NOTE on Page 2 of this Status Report)
A confidential submitting company provided the final report from a rat teratology study of a compound
generically identified as a "heterocyclic amine." The compound was administered by gavage at dose levels
of 0, 50 250, or 500 mg/kg/day during gestation days 6-15.
COMMENTS/RECOMMENDATIONS
It should be noted that EPA has previously received a TSCA Section 8(e) submission on a compound
that was generically identified as a heterocyclic amine. The reader's attention is directed to the "Status
Report" prepared by EPA in response to this Section 8(e) notice (8EHQ-1289-0854 S).
a) In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity, the company will be requested to describe the actions that
it has taken or plans to take 1) to notify workers and others about the reported data, and
2) to reduce or eliminate exposure to the subject chemical. The company will be asked to
provide copies of Material Safety Data Sheets and labels that have been revised to reflect
the reported findings. In addition, the company will be asked to describe (by way of short
summaries^ the nature and results, if available, of all studies (other than those submitted
already to EPA or those cited in the published scientific literature) about which the
company is aware or that it has conducted, is conducting or plans to conduct that are
designed to determine the toxicity of the subject chemical.
b) As part of the initial phase of the OTS Existing Chemicals Program (ECP), staff of the
Chemical Screening Branch will screen the reported information in order to determine the
need for further review of the subject chemical at this time.
c) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial j n.
provision of the Toxic Substances Control Act (TSCA). Statements made in this status report thouW not be re^rded « «Press,n«
final Agency policy or intent with respect to the subject chemical(s). Full copies of pop-confidents w«*hiMton D C 20460
available for public inspection at EPA Headquarter.! Northeast Mall (Room G-004), 401 "NT Street S^W., Washrngton, D.C. 20460.
All requests tor TSCA Section 8(e) notices should be addressed to EPA's Freedom of Information Office tA-iu y
635
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8EHQ-0590-0989 S
Page 2 of 2
NOTE In a followup letter dated February 15, 1991 (8EHQ-0291-0989 Followup Response), the
Monsanto Company withdrew the TSCA CBI claim covering its identity as the submitter of
this Section 8(e) notice. In this February 15,1991 letter, Monsanto also stated that all other
confidentiality claims associated with the submission would be withdrawn by the company
after August 15, 1991.
636
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 2
OFFICE OF
DATE: JUL !7«0 APPROVED:
UT 1 hi
TOXIC SUBSTANCES
PESTICIDES AND
SUBJECT: Status Report1 8EHQ-0590-0990 S
S
C^LCu/u^
FROM: Jacqueline T. Favilla, Biologist
Chemical Risk Identification Sectic
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION (See NOTE on Page 2 of this Status Report)
A confidential company provided final reports of rat oral range-finding and definitive studies of a "diaryl
amine" administered on gestation days 6-15. Doses in the range-finding study were 0, 10, 50, 100, 150 or
200 mg/kg/day; doses in the definitive study were 0, 5, 25, or 50 mg/kg/day.
COMMENTS/RECOMMENDATIONS
a) In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity/exposure data, the company will be requested to describe
the actions that it has taken or plans to take 1) to notify workers and others about the
reported data, and 2) to reduce or eliminate exposure to the diaryl amine. The company
will be asked to provide copies of Material Safety Data Sheets and labels that have been
revised to reflect the reported findings. In addition, the company will be asked to describe
the nature and results, if available, of all studies (other than those submitted already to EPA
or those cited in the published scientific literature) about which the company is aware or
that it has conducted, is conducting or plans to conduct that are designed to determine the
toxicity of this diaryl amine.
b) As part of the initial phase of the OTS Existing Chemicals Program (ECP), staff of the
Chemical Screening Branch will screen the reported information in order to determine the
need for further assessment of the subject chemical.
c) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflect* information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substance* Control Act (TSCA). Statement* made in this status report should not be regarded a* expressing final Agency
policy or intent with respect to the subject chemical(s). Pull copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mali (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
637
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8EHQ-0590-0990 S
Page 2 of 2
NOTE According to the declassified, fully non-confidential version of the initial TSCA Section 8(e)
notice, the Monsanto Company is the submitter and the tested material is DPG Accelerator
(1,3-diphenyl guanidine; CAS No. 102-06-7).
T GO* s k hi
638
-------
(m)
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY Page 1 of 2
WASHINGTON, DC 20460
DATE:
SUBJECT:
FROM:
TO:
JUL I 01990
APPROVED:
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
Status Report1 8EHQ-0590-0991 8
6 H ^o/az+j2f cO
Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
The submitter claimed the company name as TSCA Confidential
Business Information (CBI). The Information Management Division
will review all incoming correspondence related to this CBI claim.
SUBMISSION DESCRIPTION
The submitter provided information pertaining "to effects observed
in an employee handling various metal salts, including those of
iridium." The submitter reported that:
"The employee has developed contact dermatitis on the
face, numbness of both cheeks, and numbness and tingling
of the lip and perinasal area. The employee was tested
for dermal sensitization to several metal salts and
antigens from the North America Full Test. The only
positive response was to potassium hexachloroiridate
(III) . It is unclear at this time whether the other
reported effects are secondary to the dermatitis or have
another basis in origin. A review of medical records of
employees in this area and of our TSCA 8(c) files has
identified a potentially-related case. An employee
exhibited deficits in the trigeminal nerve. A subsequent
* This status report is the result of a preliminary evaluation of information that has
been submitted to EPA under Section 8(e), the "substantial risk1 information reporting
provision of the Toxic Substances Control Act (TSCA). The statements made in this status
report should not be regarded as expressing final Agency policy or intent with respect to the
subject chemical(s). Any review of this status report should take into account that the
report may be based on incomplete information.
63q
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8EHQ—0590-0991 S
Page 2 of 2
investigation concluded that it was unclear whether this
effect was directly related to an agent or process in the
workplace."
The submitter provided a copy of the Material Safety Data Sheet
{MSDS) for potassium hexachloroiridate (III). The submitter stated
that animal studies show that potassium hexachloroiridate is
slightly toxic by the oral route and moderately irritating by the
dermal route; no systemic effects were reportedly caused by skin
absorption following acute exposure.
USE AND EXPOSURE POTENTIAL
The submitter reported that "employees are required to wear
disposable suits or laboratory jackets with disposable sleeves over
the jackets, impermeable gloves, eye protection, and half-mask
respirators. Based on the new information, employees will be
required to wear a Powered Air Purifying Respirator (PAPR) with a
hood instead of the half-mask respirator."
The submitter did not provide any information regarding the use(s)
of or the potential for exposure to potassium hexachloroiridate or
any of the unspecified metal salts cited in this submission nor was
such information located in the secondary literature sources
consulted by EPA.
COMMENTS/RE CQMMENDATIQMS
The submitter reported that the new toxicity information has been
added to the enclosed MSDS. In addition, the submitter reported
that they are currently evaluating the need for further testing.
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, the submitter will be requested
to ensure that EPA is apprised of any further significant
information obtained by the company during its
investigation into the possible causes(s) of the observed
adverse human health effects.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
chemicals at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this report will be sent to the Environmental
Assistance Division/OTS for further distribution.
540
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.N1tOS^
I I UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
% ^ WASHINGTON. DC 20460 Page j. of X
OFFICE OF
PESTICIDES AND
DA lli: |i {| ; -t ii-\ APPROVED: ("(!"i ffio toxic substances
): * lf< 6*.nn] f/nki
SUBJECT: Status Report1 8EHQ-059W)992 S
FROM: Martha G. Price, Ph.D., Chemil^-^
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
BASF Corporation provided a final report of a rat teratology study of an imported R&D pesticide identified
as a "substituted pyridazine compound" administered by gavage at dose levels of 0, 2.5, 5.7, 13.0 or 30.0
mg/kg/day to pregnant rats.
COMMENTS/RECOMMENDATIONS
BASF stated that they will "notify everyone who worked with the material."
(a) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
641
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
Page 1 of 1
DATE: AUG 2 4 1990
OFFICE OF
PESTICIDES AND TOXIC
SUBSTANCES
SUBJECT; Status Report1 8EHQ-0590-0993 S
FROM: Martha G. Price, Ph.D., Chemis
Chemical Risk Identification Sec
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION (See NOTE Below)
A confidential submitting company provided a final report of a lifetime carcinogenicity study in mice on a
chemical identified as an "alkyl phosphoric acid" administered by gavage at dose levels of 0, 50, 150 or 500
mg/kg/day.
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA NTP, OSWER/EPA, OW/EPA ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS (formerly the TSCA Assistance Office/OTS) for further distribution.
NOTE According to a "declassified" (i.e., no longer confidential) version of this submission, the
Monsanto Company is the submitter and the subject chemical is identified as the sodium salt
of N-nitroso-N-(phosphonometh " ' '
1 jj,jj ttatus report reflect* information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarter, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
642
Printed on Recycled Paper
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page l of 3
dates JUL 2 4 660
APPROVED:
OFFICE OF
PESTICIDES AND
<0 TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0590-0994
juaCocA, ^/i£Lx$t>0
FROM: Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
Atochem North America, Inc. provided a partial Dow Chemical Company
acute aquatic toxicity study of tertiary dodecylmercaptan (CAS No.
25103-58-6) in Daphnia magna. According to the Dow report, this
acute aquatic toxicity study was conducted to "try to understand
the cause of observed toxicity in the latex effluent of the Dow
Chemical Company's Allyn's Point Plant in Gales Ferry, CT." The
Dow report presents the following 48-hour static acute LC50 values
for Daphnia magna:
PSE AND EXPOSURE POTENTIAL
Atochem did not provide any information regarding the use(s) of or
the potential for exposure to tertiary dodecylmercaptan, nor was
any specific use or exposure information for this chemical located
in the secondary literature sources consulted by EPA.
I This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
LC50 (95%Confidence Interval)
NOEL
24 h (mg/L)
48 h (mg/L)
0.831 (0.74-0.95)
0.598 (0.51-0.70)
0.26
0.0
643
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8EHQ-0590-0994
Page 2 of 3
SUBMISSION EVALOATION
EPA's preliminary review of the reported findings indicates that
only one tested dose (0.160 mg/L) was below the EPA-predicted
aqueous solubility limit of 0.200 mg/L and this tested dose killed
only 3% of the daphnids within 48 hours. EPA predicts that the
daphnid 48-hour LC50 value of 0.598 mg/L will probably never be
attained in the environment because the concentration of t-dodecyl-
mercaptan would only be less than or equal to about 0.200 mg/L in
the environment. It is important to note that acetone was used to
artificially enhance the maximum water solubility limit under the
test conditions. Although available data suggest that adverse
effects may not occur at saturation during acute toxicity testing
with fish and daphnids, it is possible that toxicity may occur
during algal toxicity testing and chronic toxicity testing with
fish and daphnids. Additional testing may be needed to further
evaluate the toxicity of this compound.
COMMENTS/RECOMMENDATIONS
The preface to Part V of EPA's March 16, 1978 TSCA Section 8(e)
policy statement (Statement of Interpretation and Enforcement
Policy; Notification of Substantial Risk" 43 FR 11110) provides
general guidance regarding the Section 8(e)-reportability of
effects observed in aquatic toxicity studies. Part V(b) of the
policy statement provides more specific guidance regarding the
results of such studies. For example, Part V(b)(3) of the policy
statement explains:
"[The Agency considers the effects for which substantial
risk information must be reported to include] any non-
trivial adverse effect, heretofore unknown to the [EPA]
Administrator, associated with a chemical known to have
bioaccumulated to a pronounced degree or to be widespread
in environmental media."
Although the submitted aquatic toxicity data on t-dodecylmercaptan,
in and of themselves, do not appear to have warranted reporting
under Section 8(e), more information should be requested from Dow
with regard to the "observed toxicity in the latex effluent" from
Dow's facility in Gales Ferry, CT.
The Agency has received another "For Your Information" (FYI) notice
on t-dodecylmercaptan (FYI-OTS-0183-0234 et seq.)
In its submission, Atochem reported that the company "initiated
its own screening and full evaluation of the effects reported by
Dow." In addition, Atochem reported that they will provide the
results to EPA as soon as they become available.
644
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8EHQ-0590-0994
Page 3 of 3
a) The Chemical Screening Branch will ask Atochem to ensure
that the Agency is apprised in full about the results of
the company's ongoing screening/evaluation exercise. EPA
will request Dow to submit all relevant information about
the "observed toxicity in the latex effluent" from the
company's Allyn's Point Plant in Gales Ferry, CT.
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Atochem and Dow will be asked to
describe the actions that they have taken or plan to take
to reduce or eliminate exposure to t-dodecylmercaptan
(and/or other components of latex effluent). Atochem
and Dow will be asked also to submit copies of Material
Safety Data Sheets and labels that have been revised to
reflect the reported findings. In addition, Atochem and
Dow will be asked to describe the nature and results, if
available, of all studies (other than those submitted
already to EPA or those cited in the open scientific
literature) about which they are aware or that they have
conducted, are conducting or plan to conduct that are
designed to determine the toxicity of or the exposure to
t-dodecylmercaptan (and/or other components in latex
effluent). Dow and Atochem will be informed that EPA is
interested in aquatic toxicity studies (especially algae,
daphnids and fish) and environmental monitoring studies.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the reported
findings.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this report will be sent to the Environmental
Assistance Division/OTS for further distribution.
645
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^ UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
I
X ^ WASHINGTON, DC 20460 page 1 Qf j
DATE: JUL I 7 (990 APPROVED: 6*^- f/ts/fo
SUBJECT: Status Report1 8EHQ-0590-0995 S
FROM: Martha G. Price, Ph.D., Chemist(Ax^4^^^^ *-<¦—
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
OFFICE OF
PESTICIDES ANO
TOXIC SUBSTANCES
A confidential submitting company provided preliminary results of a pilot rat teratology study on an R&D
chemical identified as "haloalkyl heteroaromatic amide" administered by gavage to mated female rats at dose
levels of 0, 5, 25, 50, 75, and 125 mg/kg/day.
COMMENTS/RECOMMENDATIONS
The submitter reported that all personnel that might be exposed to the substance are being notified about
the preliminary results.
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final report (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the pilot
rat teratology study cited in the submission.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantia! risk'1 information reporting provision
of the Tone Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
646
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
DATE: JUN 7 1990 APPROVED:
TOXIC SUBSTANCES
PESTICIDES AND
OFFICE OF
SUBJECT: Status Report1 8EHQ-059(M)996 Initial
FROM: Jacqueline T. Favilla, Biologist
Chemical Risk Identification Sec
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
General Electric Company provided a final report of an acute delayed neurotoxicity study with cyclic
neopentanetetraylbis(octadecylphosphite) [Weston 618; CAS No. 3806-34-6] administered by gavage twice
(on treatment days 1 and 22) to hens at doses of 0, 500, 2,000 or 5,000 mg/kg. General Electric reported
that the subject chemical "is a commercial product used mainly for food packaging plastics formulated to
comply with appropriate Food and Drug Administration regulations."
COMMENTS/RECOMMENDATIONS
It should be noted that the Agency previously received a TSCA Section 8(e) submission on another "Weston"
product (8EHQ-1287-0706).
a) In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity/exposure data, the company will be requested to describe
the actions that it has taken or plans to take 1) to notify workers and others about the
reported data, and 2) to reduce or eliminate exposure to the subject chemical. The
company will be asked to provide copies of Material Safety Data Sheets and labels that have
been revised to reflect the reported findings. In addition, the company will be asked to
describe the nature and results, if available, of all studies (other than those submitted
already to EPA or those cited in the published scientific literature) about which the
company is aware or that it has conducted, is conducting or plans to conduct that are
designed to determine the toxicity of or exposure to the subject chemical.
b) As part of the initial phase of the OTS Existing Chemicals Program (ECP), the Chemical
Screening Branch will screen the reported information to determine the need for further
assessment of the subject chemical at this time.
c) Copies of this status report will be sent to NIOSH, OSHA, CPSC, FDA NTP,
OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; copies of this report
will be sent also to the Environmental Assistance Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
647
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
OFFICE OF
DATE; JUL 2 7 1980 APPROVED:
TOXIC SUBSTANCES
PESTICIDES AND
SUBJECT: Status Report1 8EHQ-0590-0997 S
FROM: Jacqueline T. Favilla, Biologist
Chemical Risk Identification SectioryCSB
TO: James P. Darr, Section Head, Chemical Risk
Identification Section/CSByECAD/OTS
SUBMISSION DESCRIPTION
The Dow Chemical Company submitted summarized findings of a rat dermal teratology study conducted at
doses of 0, 7.5, 25, and 75 mg/kg/day with a research and development (R & D) pesticide identified
generically as a "substituted diphenyl ether." Dow also reported that results of a teratology probe study of
this substituted diphenyl ether were previously reported in FYI-OTS-1089-0715.
COMMENTS/RECOMMENDATIONS
The Agency has received other TSCA Section 8(e) as well as FYI submissions on substituted diphenyl ethers.
The reader's attention is directed to 8E #'s 623 and 731, and FYI #'s 483 and 580.
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final report (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the study
cited in the TSCA 8(e) and FYI submissions.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
' This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Todc Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemicals). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notice* should be addressed to EPA's Freedom of Information Office (A-101).
648
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f £* %
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
DATE: JUL 2 6 1990 APPROVED
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0590-O998 S
FROM: Jacqueline T. Favilla, Biologist ^
Chemical Risk Identification Sectioft/CSB
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
A confidential company provided summarized preliminary findings of an oral pilot rat teratology study
conducted at doses of 0, 10, 30, 100, 300, or 700 mg/kg/day during gestation days 6-15 with a research and
development (R & D) compound identified generically as "aryloxy substituted nitrobenzene."
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final report (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the study
cited in the submission.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA NTP, OSWER/EPA, OW/EPA ORD/EPA OAR/EPA and OPP/OPTS/EPA,
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
649
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| UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460 Page 1 Of 3
PRO^°
DATE: AUG 2 9 1990 APPROVED:
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0690-0999
FROM: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
TO: Frank D. Kover, Chief
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
The American Cyanamid Company submitted the following summary
information regarding the conduct and preliminary results of an
inhalation teratology study of methyl methacrylate (MMA; CAS No.
80-62-6) in rats:
"Groups of 25 presumed pregnant female Crl:CB BR rats
were exposed to average methyl methacrylate (MMA) vapor
concentrations of 0, 287, 664, 1185, and 1964 ppm. [The]
animals were exposed for six hours per day from gestation
day 6 through gestation day 15. Body weight and feed con-
sumption were measured on study days 0, 6, 8, 10, 13, 16
and 20. Clinical signs were recorded daily. On gestation
day 20, the dams received a visceral examination and
uterine weights were recorded; the number of corpora
lutea, implantation sites and resorptions were recorded.
Fetal endpoints included location, sex and condition of
each fetus, fetal weights, and external alterations. Half
of the animals received a soft tissue examination; [the]
fetuses were prepared for skeletal examinations.
- This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
650
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8EHQ-0690-0999
Page 2 of 3
"All animals exposed to MMA survived the exposure period.
Review of the data indicated a statistically significant
decrease in maternal body weight in all MMA exposure
groups on gestation day 8. By gestation day 10, there
was a trend towards decreased weight but this difference
was no longer significant. By study day 16, only dams
in the two highest MMA exposure groups had statistically
depressed body weights as compared to control. [The] feed
consumption data paralleled the decrement in body weight.
There were no treatment related clinical signs in the
dams. Upon examination of the pups on gestation day 20,
an unacceptable number of rats were found to be pregnant.
Based on this, this study is considered to be invalid and
will serve as the range-finding study for a repeat in-
halation teratology study to be conducted. Examination
of the pups from this [range-finding] study failed to
detect any indication of embryolethality, embryotoxicity
or soft tissue anomalies.
"The decrease in body weight seen here is comparable to
weight decrements seen in male and female rats exposed
to MMA vapor in a 10 day study sponsored by the National
Toxicology Program (NTP TR 314; NIH Publication No. 87-
2570) "
American Cyanamid stated that the subject teratology study had been
"conducted for the Methacrylate Producers Association, of which
CYRO Industries, a subsidiary of the American Cynamid Company, is
a member."
P8E AND EXPQ8PRE POTENTIAL
According to the Condensed Chemical Dictionary (10th Edition),
methyl methacrylate has the following uses: "Monomer for polymeth-
acrylic resins; impregnation of concrete."
COMMENTS/RECOMMENDATIONS
Based on a preliminary review of the summary findings presented in
this Section 8(e) notice, the reported information appears not to
have warranted submission to EPA under Section 8(e) of TSCA. In
taking this position regarding Section 8(e)-reportability, however,
it should be noted that EPA is not aware of any additional relevant
information that was available to and/or considered by the company
in deciding to report the subject findings under Section 8(e).
It should be noted that the Agency has received other Section 8(e)
and "For Your Information" (FYI) submissions pertaining to methyl
methacrylate. In addition, methyl methacrylate is the subject of
651
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8EHQ-0690-0999
Page 3 of 3
TSCA Section 8(a) and 8(d) information gathering rules. It should
also be noted that the Chemical Testing Branch (CTB/ECAD/OTS) is
currently reviewing available toxicologic and exposure information
on a number of chemicals in the aerylate category.
a) The Chemical Screening Branch will ask American Cyanamid
to submit a full copy of the report (including the actual
experimental protocol, results of gross/histopathological
examinations, results of statistical analyses, etc.), if
available, from the "range-finding" inhalation teratology
study cited in the submission.
b) As was the case with the initial submission, staff of the
Chemical Screening Branch will immediately inform the
Chemical Testing Branch about all reported information.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and CTB/ECAD/OTS;
in addition, copies of this status report will be sent
to the Environmental Assistance Division/OTS for further
distribution.
652
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^i08x
| UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
\ 1 r
-------
8EHQ-0690-1000 S
Page 2 of 3
"All animals were observed daily for overt signs of
toxicity. Body weights were measured on gestation days
0, 6, 9, 12, 15, 19, 24 and 29. The rabbits were sacri-
ficed on gestation day 29 and necropsied. Pregnancy
status was determined at that time.
"Mortality occurred in the 6, 15 and 25 mg/kg/day groups
between gestation days 8 and 18. Clinical signs of toxi-
city were observed in all [of the imide] treated groups
and included primarily rales, labored breathing or
gasping, mucoid stools and reduced or no defecation.
Additionally, salivation occurred shortly after dosing.
Substantial body weight losses were noted in all [imide-
treated] groups during treatment.
"A single abortion was noted in the control and 15
mg/kg/day groups. In addition, two rabbits aborted in
the 25 mg/kg/day group. Although abortions are not
unusual for rabbits, it appears that the abortions in the
15 and 25 mg/kg/day groups were treatment-induced as a
result of the substantial [maternal] body weight loss and
pathological changes. [The] pathological changes were
correlated with clinical signs noted in these animals
prior to death or abortion (rales, mucoid stools).
"In summary, maternal toxicity was evident at all dosage
levels tested in this study, ranging from substantial in
the 3 mg/kg/day group to excessive at dosage levels of
6 mg/kg/day and above. Consequently, dosage levels of
0.3, 1.5 and 3.0 mg/kg/day were selected for a subsequent
teratology study."
USE/EXPOSURE POTENTIAL (See NOTE on Page 3 of this Status Report)
In view of the submitter's CBI claim, no information regarding the
TSCA Chemical Substance Inventory status or use(s) of the tested
imide will appear in this status report.
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will ask the submitter to
ensure that EPA receives complete copies of the final
reports (including the actual experimental protocols,
results of gross/histopathological examinations, results
of statistical analyses, etc.) from the range-finding and
subsequent teratology studies cited in the submission.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure data, the submitter will be requested
to describe the actions that the company has taken or
654
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8EHQ-0690-1000 S
Page 3 of 3
plans to take 1) to notify workers and others about the
reported information, and 2) to reduce or eliminate
exposure to the subject chemical. In addition, the
submitter will be asked to describe the nature and
results, if available, of all studies (other than those
submitted already to EPA or those cited in the published
scientific literature) about which the company is aware
or that the company has conducted, is conducting or plans
to conduct that are designed to determine the toxicity
of or the exposure to the subject chemical.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further OTS assessment of the
subject chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA? in addition,
copies of this report will be sent to the Environmental
Assistance Division/OTS for further distribution.
NOTE In a letter dated September 28, 1990 (8EHQ-1190-1000 S
Supplement) , the submitting company withdrew its TSCA CBI
claim for the identity of the subject chemical substance
and reported non-confidentially that the chemical is N-
phenylmaleimide (CAS No. 941-69-5). It should be noted
that EPA has received other TSCA Section 8(e) and "For
Your Information" (FYI) submissions on this chemical.
whko
655
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I
yi0,%
m)
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
JUL I 8 1990
DATE:
APPROVED:
SUBJECT: Status Report1 8EHQ-0690-1001 S
QudUXJU H U/iP-tlxsJ
FROM: Judith M. Loranger, Biologist
Chemical Screening Branch/ECAD/OTS
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
NOR-AM Chemical Company provided summarized results from a 28-day rat repeat dose toxicity study of
an experimental insecticide generically identified as a "halogenated alkyl ester." The accompanying cover
letter stated that "neuronal degeneration was observed in rats at doses of 225 mg/kg (1/3 males) and 1000
mg/kg (2/3 males and 2/3 females).. . Clinical signs of neurological disorder were seen at 1000 mg/kg. No
effects were seen at 50 mg/kg." The route of administration was not specified in the submission.
Along with the summary information, NOR-AM provided a copy of the draft Material Safety Data Sheet
(MSDS) and label information for each experimental formulation.
COMMENTS/RECOMMENDATIONS
NOR-AM reports that "personnel who may have samples in their possession will be informed of the above
data and further instructed on safe handling and disposal procedures."
a) The Chemical Screening Branch will request NOR-AM to ensure that EPA receives a full
copy of the final report (including the actual experimental protocol, results of
gross/histopathologic examinations, results of statistical analyses, etc.) from the 28-day study
cited in the submission.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are
available for public inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460.
All requests for TSCA Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
656
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
DATE: ^ I 0 1990 ^pROVED; ijxrUc
SUBJECT: Status Report1 8EHQ-0690-1002
QccaLtstb M ^0 fLO^b-€f cO
FROM: Judith M. Loranger, Biologist
Chemical Screening Branch/ECAD/OTS
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
On behalf of certain members of the Glycol Ethers Panel (Olin Corporation, the Dow Chemical Company,
Oxy Petrochemicals, Inc. and Union Carbide Chemicals and Plastics Company, Inc.), the Chemical
Manufacturers Association (CMA) submitted preliminary results showing adverse male reproductive system
effects in a rat subchronic neurotoxicity study of triethylene glycol monomethyl ether (TGME; CAS No. 112-
35-6). The submission summarized the findings of a 90-day drinking water study in which rats received
TGME at dose levels of 0, 0.4,1.2, or 4 g/kg/day. CMA also reported that "a concurrently conducted dermal
study showed no adverse testicular effects at the same exposure level, 4 g/kg/day, the highest dose
investigated."
COMMENTS/RECOMMENDATIONS
CMA reported that "the final report on the study will be submitted to EPA in accordance with the
provisions of the (TSCA Section 4) Testing Consent Order " (54 FR 13470).
It should be noted that TGME is the subject of TSCA Section 8(a) and 8(d) information gathering rules.
a) As was the case for the initial submission, the Chemical Screening Branch will notify the
Chemical Testing Branch (CTB) about the receipt of any additional incoming information
on TGME.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and
CTB/ECAD/OTS; in addition, copies of this status report will be transmitted to the
Environmental Assistance Division/OTS for further distribution.
(m)
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are
available for public inspection at EPA Headquarters, Northeast Mall (Room G-O04), 401 "M" Street S.W., Washington, D.C. 20460.
All requests for TSCA Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
657
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j? 3 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460 pa„e i of j
'«< «,o^0 b
DA-m JUL 2 3 1990 approved: Aw, (/, q f7
SUBJECT: Status Report1 8EHQ-0690-1003
FROM: Martha G. Price, Ph.D., 1
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBMISSION DESCRIPTION
The Dow Chemical Company provided summarized results of acute and two-week inhalation toxicity studies
on isoamylene oxide (CAS No. 5076-19-7) in rats. Additionally, Dow reported summarized results, including
neurotoxic effects, of an acute dermal toxicity study in rats, conducted overseas by Dow's European
subsidiary.
COMMENTS/RECOMMENDATIONS
Dow Chemical reported they do not, "manufacture, process or distribute isoamylene oxide, except that Dow
obtained isoamylene from Europe for the purpose of conducting the...studies discussed above." Dow
Chemical further reported they have communicated the data from these studies to Dow Europe.
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final reports (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the
studies cited in the submission.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
658
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£ ** \
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
OFFICE OF
PESTICIDES AND
JUL I 01990 a _ TOXIC SUBSTANCES
DATE: APPROVED: jW, (J Qgfir\ l/w/fo
SUBJECT: Status Report1 8EHQ-0690-1004 S
QUjcLlzK H j
FROM: Judith M. Loranger, Biologist
Chemical Screening Branch/ECAD/OTS
TO: James F. Dart, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
Allied-Signal, Inc. submitted the summarized findings from an acute rat oral toxicity study of an R&D
compound identified as an "aliphatic ketoxime." Possible neurotoxic effects were observed in the treated
animals.
COMMENTS/RECOMMENDATIONS
It should be noted that EPA has received another TSCA Section 8(e) submission on a compound identified
as an aliphatic ketoxime (8EHQ-0690-1005 S).
Allied-Signal, Inc. reported that this compound is being evaluated in their laboratories and also by a few
other companies "considering the use of this material." Allied-Signal, Inc. also reported that these "results
have been communicated to those studying the use of the material."
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final report (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the oral
toxicity study cited in the submission.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are
available for public inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460.
All requests for TSCA Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
659
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w
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
OFFICE OF
PESTICIDES AND
DATE:
JUL I 0 1990
APPROVED:
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0690-1005 S
^3'j /LtxAj ho -c*J
FROM: Judith M. Loranger, Biologist
Chemical Screening Branch/ECAD/OTS
TO: James F. Darr, Section Head, Chemical Risk
SUBMISSION DESCRIPTION
Allied-Signal, Inc. submitted the summarized findings from acute oral and dermal toxicity studies of a
compound identified as an "aliphatic ketoxime." Possible neurotoxic effects were observed in the treated
animals (species not specified).
COMMENTS/RECOMMENDATIONS
It should be note that EPA has received another TSCA Section 8(e) submission on a compound identified
as an aliphatic ketoxime (8EHQ-0690-1004 S).
Allied-Signal, Inc. reported that this compound is being evaluated in their laboratories and also by a few
other companies "considering the use of this material." Allied-Signal, Inc. also reported that these "results
have been communicated to those studying the use of the material."
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives full copies of the final reports (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the
toxicity studies cited in the submission.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Full copies of non-confldential Section 8(e) notices are
available for public inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460.
All requests for TSCA Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
Identification Section/CSB/ECAD/OTS
660
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ijasz/
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460 n , , ,
\ Page 1 of 1
OFFICE Of
PESTICIDES AND
DATE: 17 1990 APPROVED: t/^/90 T0)
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
(saszi
£ WASHINGTON, DC 20460 page \ Qf 1
DATE: AUG 3 1990 APPROVED: TOXIC SUBSTANCES
OFFICE OF
PESTICIDES AND
SUBJECT: Status Report1 8EHQ-0690-1007
FROM: Jacqueline T. Favilla, Biologist
Chemical Risk Identification Sectien/CSB
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
FMC Corporation reported summarized findings of a 28-day oral mouse range-finding study with tributyl
phosphate (CAS No. 126-73-8) conducted at doses of 0, 100, 1,000, 5,000, or 20,000 ppm. At 20,000 ppm,
all animals died or were sacrificed in a moribund condition within 10 days after initiation; neurotoxic signs
(lethargy, tremors) were noted in these animals prior to death. FMC noted that this study was conducted
in accordance with the final test rule for tributyl phosphate under TSCA Section 4 (54 FR 33400-15).
COMMENTS/RECOMMENDATIONS
Tributyl phosphate is the subject of TSCA Section 8(a) and 8(d) information gathering rules as well as a
TSCA 8(c) request for records and reports regarding significant adverse reactions.
a) In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity/exposure data, FMC will be requested to describe the
actions that it has taken or plans to take 1) to notify workers and others about the reported
data, and 2) to reduce or eliminate exposure to the subject chemical. FMC will be asked
to provide copies of Material Safety Data Sheets and labels that have been revised to reflect
the reported findings.
b) The Chemical Screening Branch will notify the Chemical Testing Branch (CIB) of all
reported information for inclusion in the ongoing TSCA Section 4 review of tributyl
phosphate.
c) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA OPP/OPTS/EPA and
CTB/ECAD/OTS; in addition, copies of this status report will be transmitted to the
Environmental Assistance Division/OTS for further distribution.
1 This statu* report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 204<0. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
662
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£ r~i
I | UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON. DC 20460 page j Qf j
DATE:
JUL 2 6 199D
APPROVED:
T. /£L
SUBJECT: Status Report1 8EHQ-0690-1008
FROM: Jacqueline T. Favilla, Biologist J
Chemical Risk Identification Section/CSB
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
BASF Corporation reported summarized preliminary results of an oral prenatal toxicity study of
glutardialdehyde (CAS No. 111-30-8), administered at doses of 0, 5, 15, or 45 mg/kg/bw on days 7-19 post
insemination to pregnant Himalayan rabbits. BASF also reported that all customers and BASF employees
will be notified of the results of this study, and that additional information on glutardialdehyde will be
submitted to EPA as it becomes available.
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will request BASF to ensure that EPA receives a full copy
of the final report (including the actual experimental protocol, results of
gross/histopathologic examinations, results of any statistical analyses, etc.) from the study
cited in the submission. In view of EPA's general interest in company actions that are
taken on a voluntary basis in response to chemical toxicity/exposure data, BASF will be
requested to describe the actions that it has taken or plans to take to reduce or eliminate
exposure to the subject chemical. BASF will be asked to provide copies of Material Safety
Data Sheets and labels that have been revised to reflect the reported findings. In addition,
BASF will be asked to describe the nature and results, if available, of all studies (other than
those submitted already to EPA or those cited in the published scientific literature) about
which the company is aware or that it has conducted, is conducting or plans to conduct that
are designed to determine the toxicity of glutardialdehyde.
b) As part of the initial phase of the OTS Existing Chemicals Program (ECP), the Chemical
Screening Branch will screen the reported information to determine the need for further
assessment of the subject chemical at this time.
c) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA NTP, OSWER/EPA, OW/EPA, ORD/EPA OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
663
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? arm
uszz
\ <
\
*
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
JUL I 8 foon
DATE: l33U APPROVED:
If. /Or*, nft
-------
8EHQ-0690-1009
Page 2 of 2
The Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final reports (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the
studies cited in the submission.
In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity/exposure data, the company will be requested to describe
the actions that it has taken or plans to take 1) to notify workers and others about the
reported data, and 2) to reduce or eliminate exposure to the subject chemical. The
company will be asked to provide copies of Material Safety Data Sheets and labels that
have been revised to reflect the reported findings. In addition, the company will be asked
to describe (by way of short summaries') the nature and results, if available, of all studies
(other than those submitted already to EPA or those cited in the published scientific
literature) about which the company is aware or that it has conducted, is conducting or
plans to conduct that are designed to determine the toxicity of the subject chemical.
As was the case with the initial submission, staff of the Chemical Screening Branch will
notify the Risk Analysis Branch about the receipt of any additional incoming information
on MDMS.
The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and
RAB/ECAD/OTS; in addition, copies of this status report will be transmitted to the
Environmental Assistance DivisionyOTS for further distribution.
665
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
OFFICE OF
DATE:
.. JUL I 7 1990 APPROVED:
10
TOXIC SUBSTANCES
PESTICIDES AND
SUBJECT: Status Report1 8EHQ-0690-1010 S
FROM: Martha G. Price, Ph.D., Chemisl
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
A confidential submitting company provided preliminary results of a pilot rat teratology study on an R&D
chemical identified as "aryloxy-alkoxy-nitrobenzene II" administered by gavage to mated female rats at dose
levels of 0, 10, 30, 75, 150, and 300 mg/kg/day.
COMMENTSARECOMMENDATIONS
The Agency has received another TSCA §8(e) submission, 8EHQ-0190-0862 S, on an "alkoxy aryloxy
nitrobenzene."
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final report (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the pilot
rat teratology study cited in the submission.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
666
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i
\
mi
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
H> WASHINGTON, DC 20460 „ . , .
\ Page 1 of 1
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
dates JUL 2 7 1990 APPROVED:
SUBJECT: Status Report1 8EHQ-0690-I0U S
FROM: Jacqueline T. Favilla, Biologist t-
Chemical Risk Identification Seciion/JoSB
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
A confidential company submitted preliminary summarized results from a pilot rat teratology study conducted
at doses of 0,10, 30, 100,300 and 600 mg/kg/day during gestation day 6-15 with a research and development
(R & D) compound identified generically as "aryloxy-substituted alky] carboxylic acid ester."
COMMENTS/RECOMMENDATIONS
a) Hie Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final report (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the pilot
rat teratology study cited in the submission.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflect* information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Taric Substances Control Act (TSCA). Statements nude in this status report should not be regarded as expressing final Agency
policy or intent with respect to tbe subject chemical(i). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarter!, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C 20460. All request* for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
667
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
DATE: JtJL 2 6 1990 APPROVED:
TOXIC SUBSTANCES
PESTICIDES AND
OFFICE OF
SUBJECT: Status Report1 8EHQ-0690-1012 S
FROM: Jacqueline T. Favilla, Biologist
Chemical Risk Identification
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
A confidential company submitted a summary report of a pilot rat teratology study conducted at doses of
0, 10, 30, 100, 300, or 700 mg/kg/day during gestation days 6-15 with a research and development (R & D)
compound identified generically as "aryl-substituted amino amide."
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final report (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the pilot
rat teratology study cited in the submission.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
668
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(fit)
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
DATE: jy[_ 26 1990 APPROVED: JLsw ^7 (bsY\ hll^O
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHCMJ690-1013 S
FROM: Jacqueline T. Favilla, Biologist
Chemical Risk Identification Sectioft/CSB
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
A confidential company submitted preliminary results of an oral pilot teratology study in rats conducted at
doses of 0, 10, 30, 100, 300, or 700 mg/kg/day during gestation days 6-15 with a research and development
(R & D) compound identified generically as an "aryl methyl sulfone."
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final report (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the pilot
rat teratology study cited in the submission.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toodc Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
polity or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarter*, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
669
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Page 1 of 3
Ui
9
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
A WASHINGTON, DC 20460
DATE:
approved: h- [fry 1
{ 1ihoho
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0690-1014 8
PROM: Martha G. Price, Ph.D., ChemistOyA*)
Chemical Risk Identification Section/CSB
TO: James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
The submitting company has claimed its company name and the exact
identity of the subject chemical as TSCA Confidential Business
Information (CBI). Staff of the Information Management Division
"will review all incoming correspondence related to the company's
TSCA CBI claims. In the "sanitized" version of its Section 8(e)
notice, the company reported non-confidentially that the subject
chemical is a "halogenated substituted benzene."
SUBMISSION DESCRIPTION
The submitting company provided information regarding the conduct
and preliminary results of a developmental toxicty study in rats
on halogenated substituted benzene, identified as "the compound"
in the following summary:
"In the developmental toxicity study in rats, the
compound was administered by gavage to four groups of
mated female rats at dose levels of 0, 100, 400, 800 and
1600 mg/kg/day during gestation days 6-15. Preliminary
results indicate that maternal lethality/toxicity
- This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
670
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8EHQ-0690-1014 S
Page 2 of 3
occurred at the highest dose tested, with six of twenty-
five females (25%) sacrificed. Five died, and one was
sacrificed moribund by day 12 of gestation. All six were
pregnant, while of the 19 surviving animals at this dose
level, seventeen (89%) were pregnant. Decreased body
weight gain and food consumption occurred in the 19
surviving animals and the other dose levels. Low to
moderate maternal toxicity occurred in the 100, 400, and
800 mg/kg/day dose groups, decreased food consumption
occurred in the 100 mg/kg/day dose groups, and decreased
body weight gain and food consumption occurred in dose
groups above 100 mg/kg/day. Embryo/fetotoxicity was
manifested in this group as a decrease (11%) in the
number of viable fetuses and mean fetal body weight
(23%). Micropthalmia was detected in 35 (17%) fetuses
from 7 (41.2%) litters, umbilical herniation of the
intestine in 1 (0.5%) fetus and 1 (5.0%) litter, agnathia
and aglossia in 3 fetuses (1.4%) from 3 (17.6%) litters,
malpositioned pinnae in 1 fetus (0.5%) and 1 (5.9%)
litter and a common truncus arteriosus in 1 fetus (0.5%)
and 1 (5.9%) litter.
"Significantly similar findings were not observed in
fetuses from any other treated group but maternal
toxicity was exhibited in all groups. Although
developmental toxicity was observed at 1600 mg/kg, there
was excessive maternal mortality and toxicity at this
dose level. These findings indicate the compound is less
toxic to the embryo/ fetus than the maternal organisms."
USE AND EXPOSURE POTENTIAL
In view of the submitter's TSCA CBI claims, no information
regarding the TSCA Chemical Substance Inventory status of the
subject chemical will appear in this status report.
The submitter stated that the compound is used as a flame retardant
in plastics.
C0MMENTS/REC0MMENDATI0N8
The submitter reported that the company has recently initiated a
developmental toxicity study in rabbits and a two generation
reproduction study in rats on halogenated substituted benzene.
a) The Chemical Screening Branch will ask the submitter to
ensure that EPA receives a complete copy of the final
report (including the actual experimental protocol,
results of gross and histopathological examinations,
results of statistical analyses, etc.) from the
developmental toxicity study summarized in the submission
as well as the two other cited studies which have been
initiated on this compound.
671
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8EHQ-0690-1014 S
Page 3 of 3
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, the submitter will be requested
to describe the actions that the company has taken or
plans to take 1) to notify workers/others about the
reported information, and 2) to reduce or eliminate
exposure to the subject chemical. The submitter will be
asked also to provide copies of Material Safety Data
Sheets and labels that have been revised to reflect the
reported findings. In addition, the submitter will be
asked to describe the nature and results, if available,
of all studies (other than those submitted already to EPA
or those cited in the published scientific literature)
about which the submitter is aware or that the company
has conducted, is conducting or plans to conduct that are
designed to determine the toxicity of or the exposure to
the subject chemical.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
672
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<4
1222/
"tv.
DATE:
V
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
APPROVED:
3 m
SUBJECT: Status Report1 8EHQ-0690-1015
FROM: Jacqueline T. Favilla, Biologist
Chemical Risk Identification SectiortyCS/j
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
22-
Page 1 of 1
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBMISSION DESCRIPTION
Shell Oil Company provided final reports of five in vitro mutagenicity assays with Epon HPT Resin 1071
(EPIKOTE 1071, CAS No. 103490-06-8); weak positive responses were noted in two separate assays. In its
cover letter, Shell Oil reported that this substance is the subject of a TSCA Section 5 "Pre-Manufacture
Notice" (PMN No. P-86-500) and Consent Order and this information is being incorporated into the MSDS.
COMMENTS/RECOMMENDATIONS
Although a positive in vitro genotoxicity test, when considered alone, may not be sufficient to offer
reasonable support for a conclusion of substantial risk (as that term is defined in EPA's TSCA Section 8(e)
policy statement ("Statement of Interpretation and Enforcement Policy; Notification of Substantial Risk" 43
FR 11110; March 16, 1978)), EPA does believe that such information is of value in assessing the possible
risk(s) posed by exposure to the tested chemical or mixture. Further, EPA believes that a positive
genotoxicity test result, in combination with other information (e.g., knowledge of actual/potential exposure
to and/or high production of the tested chemical or mixture), would suggest the need, in many cases, to
conduct further studies designed to determine the toxicity of or the exposure to that chemical substance or
mixture. EPA expects the results of such additional studies to be considered also for submission under
Section 8(e) of TSCA.
a) In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity/exposure data, Shell will be requested to describe the actions
that it has taken or plans to take 1) to notify workers and others about the reported data,
and 2) to reduce or eliminate exposure to EPIKOTE 1071. Shell will be asked to provide
copies of Material Safety Data Sheets and labels that have been revised to reflect the
reported findings.
b) The Chemical Screening Branch will notify the Chemical Control Division (CCD/OTS)
about all incoming information; CCD is responsible for implementing EPA's Section 5 "New
Chemicals Program" (NCP).
c) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and
CCD/OTS; in addition, copies of this status report will be transmitted to the Environmental
Assistance Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
673
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f **
WASHINGTON, DC 20460 D„_ , , ,
% />«o^C Pa6e 1 of 1
^ UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
DATE: JUL 2 7 1900 APPROVED: ^
SUBJECT: Status Report1 8EIIQ-0690-1016 S
FROM: Jacqueline T. Favilla, Biologist
Chemical Risk Identiflcation Seaion^CSB
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
Eli Lilly and Company reported summarized preliminary findings of an in vitro mutagenicity assay and an
acute oral toxicity study in mice conducted with a research compound identified generically as "substituted
quinoline." Lilly also reported that the LC50 was found to be less than 50 mg/kg, the compound is labelled
as hazardous, and that personnel have been notified of these findings.
COMMENTS/RECOMMENDATIONS
It should be noted here that the Agency has received another TSCA Section 8(e) submission on a compound
identified generically as substituted quinoline. The reader's attention is directed to 8EHQ-1089-0833 S.
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives full copies of the final reports (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the studies
cited in the submission.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
674
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l52E)
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
'P. fob*'—~
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
DATE: JUu 2 7 1990 APPROVED:
SUBJECT: Status Report1 8EIIQ-0690-1017
FROM: Jacqueline T. Favilla, Biologist Ucd^- ^
Chemical Risk Identification Sectron/CSB
TO: David R. Williams, Section 8(e) Coordinator/
CSB/ECAD/OTS
SUBMISSION DESCRIPTION
Eastman Kodak Company provided preliminary summarized results of acute aquatic studies of fathead
minnow fPimephales promelas). daphnid (Daphnia magna), gammarid fGammarus fasciatus), and rainbow
trout and green algal CSelenastrum capricornutum') inhibition studies with crotonaldehyde (CAS #4170-30-
3). Kodak submitted a Material Safety Data Sheet (MSDS).
COMMENTS/RECOMMENDATIONS
In its submission, Eastman Kodak Company stated that this chemical is subject to a TSCA Section 4 Testing
Consent Order (40 CFR 799, November 9,1989). It should also be noted that crotonaldehyde is the subject
of TSCA Section 8(a) and Section 8(d) information gathering rules.
a) In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity/exposure data, Kodak will be requested to describe the
actions that it has taken or plans to take 1) to notify others about the reported data, and
2) to reduce or eliminate exposure to the subject chemical.
b) The Chemical Screening Branch will notify the Chemical Testing Branch (CTB) of all
reported information for inclusion in the ongoing TSCA Section 4 review of crotonaldehyde.
c) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and
CTB/ECAD/OTS; in addition, copies of this status report will be transmitted to the
Environmental Assistance Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
675
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^eos^
* \
I | UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
PnO^
DATE: JUL I 8 1990 APPROVED lUr/lo
SUBJECT: Status Report1 8EHQ-0690-1018
QucUAt
FROM: Judith M. Loranger, Biologist
Chemical Screening Branch/ECAD/OTS
TO: James F. Dan, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
Page 1 of 2
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBMISSION DESCRIPTION
Vista Chemical Company provided preliminary results of in vitro cytotoxicity and cell transformation assays
of silicon carbide fibers (CAS No. 409-21-2), asbestos (CAS No. 1332-21-4) and various alumina whisker
samples (CAS No. 1344-28-1) in cultured mammalian cells.
COMMENTS/RECOMMENDATIONS
Vista reported that they neither manufacture nor distribute silicon carbide fibers or asbestos. Vista stated
that "the V6 [alumina material] is solely a research material at this time." Vista further reports that they
have no current plans for "making V6 commercially available. . . [In addition], future recipients of the V6
material have been or will be appraised of these findings and advised of proper handling procedures with
an appropriate Material Safety Data Sheet [MSDS]." Vista submitted a copy of the current MSDS with this
submission. Vista reported that they are continuing their investigations of the biological activity of various
fibrous materials.
Although a positive in vitro genotoxicity test, when considered alone, may not be sufficient to offer
reasonable support for a conclusion of substantial risk (as that term is defined in EPA's TSCA Section
8(e) policy statement ("Statement of Interpretation and Enforcement Policy; Notification of Substantial
Risk" 43 FR 11110; March 16,1978)), EPA does believe that such information is of value in assessing the
possible risk(s) posed by exposure to the tested chemical or mixture. Further, EPA believes that a positive
genotoxicity test result, in combination with other information (e.g., knowledge of actual/potential exposure
to and/or high production of the tested chemical or mixture), would suggest the need, in many cases, to
conduct further studies designed to determine the toxicity of or the exposure to that chemical substance or
mixture. EPA expects the results of such additional studies to be considered also for submission under
Section 8(e) of TSCA
1 This status report reflect* information submitted to EPA under Section 8(e), the "substantial risk" information reporting ,
provision of the Toxic Substances Control Act (TSCA). Statements made in this tutus report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are
available for public inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460.
All requests for TSCA Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
676
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8EHQ-0690-1018
Page 2 of 2
a) The Chemical Screening Branch will request Vista to ensure that EPA receives full copies
of the final reports (including the actual experimental protocols, and results of any statistical
analyses, etc.) from the studies cited in the submission.
In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity/exposure data, the company will be requested to describe
(by way of short summaries') the nature and results, if available, of all studies (other than
those submitted already to EPA or those cited in the published scientific literature) about
which the company is aware or that it has conducted, is conducting or plans to conduct that
are designed to determine the toxicity of the fibrous materials.
b) It should be noted that EPA has received a number of TSCA Section 8(e) and "For Your
Information" (FYI) submissions on asbestos and other fibrous compounds. Immediately
upon receipt of this Section 8(e) submission, the Chemical Screening Branch notified the
Chemical Control Division (CCD/OTS); CCD is currently collecting and evaluating
information on asbestos and other fibrous materials.
c) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and
CCD/OTS; in addition, copies of this status report will be transmitted to the Environmental
Assistance Division/OTS for further distribution.
677
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^tosx
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
DATE: 0uL 26 1990 APPROVED:
SUBJECT: Status Report1 8EHQ-0690-1019
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
FROM: Jacqueline T. Favilla, Biologist
Chemical Risk Identification SmiojfyCSB
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
CIBA-GEIGY Corporation provided a final report of an oral 28-day subacute rat toxicity study conducted
at doses of 0, 10, 50, 250, or 1000 mg/kg/day with XB 4458, the reaction product of 1-methyl imidazol, CAS
No. 616-47-7 and zinc octoate, CAS No. 557-09-5. According to the cover letter of the submission, the
product "is an imported research and development (R & D) material used as a latent accelerator for
anhydride-cured epoxy resin systems for electrical power applications." CIBA-GEIGY reported that it has
or will revise the Material Safety Data Sheet (MSDS) and notify potential customers and CIBA-GEIGY
workers of the findings of this study.
COMMENTS/RECOMMENDATIONS
The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA, CPSC, FDA, NTP,
OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition, copies of this status
report will be transmitted to the Environmental Assistance Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to GPA's Freedom of Information Office (A-101).
678
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I*c*t°
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
DATE: AUG 31990 APPROVED:
SUBJECT: Status Report1 8EHQ-0690-1020
FROM: Jacqueline T. Favilla, Biologist
Chemical Risk Identification Sec
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
The Occidental Chemical Corporation (OxyChem) provided a final report of a 28-day rat inhalation study
conducted at doses of 0, 0.01, 0.03 or 0.10 mg/L with orthochlorobenzylchloride (OCBC), CAS No. 611-
19-8. According to the cover letter of the submission, the NOAEL for OCBC was determined to be 0.03
mg/L, the compound may effect the hemopoietic system (changes in myeloid/erythroid ratios) and may be
a pulmonary sensitizer (proliferative changes in the tracheobronchial lymph nodes and metaplastic changes
in the respiratory tract at the high dose). OxyChem also stated that it no longer manufactures or sells
this material.
COMMENTS/RECOMMENDATIONS
a) The company will be asked to describe the nature and results, if available, of all studies
(other than those submitted already to EPA or those cited in the published scientific
literature) about which the company is aware or that it has conducted, is conducting or
plans to conduct that are designed to determine the toxicity of the subject chemical.
b) As part of the initial phase of the OTS Existing Chemicals Program (ECP), staff of the
Chemical Screening Branch will screen the reported information in order to determine the
need for further assessment of the subject chemical at this time.
c) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
' This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information repotting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
679
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
OFFICE OF
SUBJECT: Status Report1 8EHQ-0790-1021
DATE! JUL 2 7 1990 APPROVED:
TOXIC SUBSTANCES
PESTICIDES AND
FROM: Jacqueline T. Favilla, Biologist
Chemical Risk Identification Se
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
Hoechst Celanese Corporation provided English summaries of rabbit skin and eye irritation studies of Diazo
Y (benzenediazonium, 3-methyl-4-(l-pyrrolidinyl)-, trichlorozincate(l-), CAS No. 52572-38-0). Full final
reports in German were also provided. Hoechst Celanese reported that it has notified its domestic supplier
and its manufacturing facility of the results of these studies.
COMMENTS/RECOMMENDATIONS
a) In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity/exposure data, the company will be requested to describe
the actions that it has taken or plans to take 1) to notify workers about the reported data,
and 2) to reduce or eliminate exposure to the subject chemical. The company will be asked
to provide copies of Material Safety Data Sheets and labels that have been revised to reflect
the reported findings. In addition, the company will be asked to describe the nature and
results, if available, of all studies (other than those submitted already to EPA or those cited
in the published scientific literature) about which the company is aware or that it has
conducted, is conducting or plans to conduct that are designed to determine the toxicity of
the subject chemical.
b) As part of the initial phase of the OTS Existing Chemicals Program (ECP), staff of the
Chemical Screening Branch will screen the reported information in order to determine the
need for further assessment of the subject chemical at this time.
c) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
In addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This statu* report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to tbe subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
680
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{mi
\ UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460 n , , ,
X P«o^° Page 1 of 1
DATE:
JUL
1990
APPROVED:
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EIIQ-0790-1022 S
FROM: Jacqueline T. Favilla, Biologist
Chemical Risk Identification Seqtfon/C^B
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
A confidential company provided a final report of a 28-day rat oral toxicity study conducted on a substance
identified generically as a "substituted hydrocarbyl sulfide," at doses of 0, 100, 300 or 1000 mg/kg/day.
COMMENTS/RECOMMENDATIONS
a) In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity/exposure data, the company will be requested to describe
the actions that it has taken or plans to take 1) to notify workers and others about the
reported data, and 2) to reduce or eliminate exposure to the subject chemical. The
company will be asked to provide copies of Material Safety Data Sheets and labels that have
been revised to reflect the reported findings. In addition, the company will be asked to
describe the nature and results, if available, of all studies (other than those submitted
already to EPA or those cited in the published scientific literature) about which the
company is aware or that it has conducted, is conducting or plans to conduct that are
designed to determine the toxicity of the subject chemical.
b) As part of the Initial phase of the OTS Existing Chemicals Program (ECP), staff of the
Chemical Screening Branch will screen the reported information in order to determine the
need for further assessment of the subject chemical at this time.
c) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(c), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chcmical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
6R1
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
- J' WASHINGTON, DC 20460 _ , , ,
Page 1 of 1
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
DATE; JUL 2 7 1990 APPROVED: C/lsm f //7/?{)
SUBJECT: Status Report1 8E1IQ-0790-1023 S
FROM: Jacqueline T. Favilla, Biologist ^
Chemical Risk Identification Sectfon/CSB
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
BASF Corporation provided a final report on the results of an acute rat inhalation toxicity study of 1,1'-
(4-methyl-l,3-phenylene)bis-lH-pyrrale-2,5-dione (CAS No. 6422-83-9). BASF reported that the LC50 was
estimated to be 0.09 mg/L.
COMMENTS/RECOMMENDATIONS
BASF reported in its submission that "all BASF handling operations and industrial hygiene procedures are
currently being reviewed to ensure that all exposure to the dust is minimized," and that employees will be
notified of the new information from this study.
a) The company will be asked to provide copies of Material Safety Data Sheets and labels that
have been revised to reflect the reported findings. In addition, the company will be asked
to describe the nature and results, if available, of all studies (oiher than those submitted
already to EPA or those cited in the published scientific literature) about which the
company is aware or that it has conducted, is conducting or plans to conduct that are
designed to determine the toxicity of the subject chemical.
b) As part of the initial phase of the OTS Existing Chemicals Program (ECP), staff of the
Chemical Screening Branch will screen the reported information in order to determine the
need for further assessment of the subject chemical at this time.
c) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
' This status report reflects information submitted to EPA under Section 8(e), ihe "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
682
-------
im>
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
~ A WASHINGTON, DC 20460
DATE: A(J6 3 1990 APPROVED:
SUBJECT: Status Report1 8EHQ-0790-1024
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
FROM
: Jacqueline T. Favilla, Biologist
Chemical Risk Identification SectJon/^SB
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
General Electric Company provided a draft report of a developmental rabbit toxicity study conducted at
doses of 0, 50, 200 or 400 mg/kg/day with N-n-butyl-4-nitro-phthalimide (4-NBPI), CAS No. 54395-37-8.
According to the cover letter of the submission, "this material is being evaluated for site-limited use as a
monomer in the production of thermoplastic resin."
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final report (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the
developmental rabbit toxicity study cited in the submission. In view of EPA's general
interest in company actions that are taken on a voluntary basis in response to chemical
toxicity/exposure data, the company will be requested to describe the actions that it has
taken or plans to take 1) to notify workers and others about the reported data, and 2) to
reduce or eliminate exposure to the subject chemical. The company will be asked to •
provide copies of Material Safety Data Sheets and labels that have been revised to reflect
the reported findings. In addition, the company will be asked to describe the nature and
results, if available, of all studies (other than those submitted already to EPA or those cited
in the published scientific literature) about which the company is aware or that it has
conducted, is conducting or plans to conduct that are designed to determine the toxicity of
the subject chemical.
b) As part of the initial phase of the OTS Existing Chemicals Program (ECP), staff of the
Chemical Screening Branch will screen the reported information in order to determine the
need for further assessment of the subject chemical at this time.
c) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast MaU (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
683
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(ft4
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
. .v WASHINGTON, DC 20460 Dam,nf1
Page 1 of 1
DATE: AUG 3 1990 APPROVED: ^
SUBJECT: Status Report1 8EHQ-Q790-1025 S
FROM: Jacqueline T. Favilla, Biologist
Chemical Risk Identification Secpon^SB
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBMISSION DESCRIPTION
A confidential company provided summarized preliminary findings of an oral pilot rat teratology study
conducted at doses of 0, 10, 25, 50, 100 or 200 mg/kg/day during gestation days 6-15 with a R & D
compound identified generically as "haloalkyl amine."
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final report (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the pilot
rat teratology study cited in the submission.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
' This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Todc Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemica!(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarter*, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20440. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
684
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' | UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460 page ± Qf l
OFFICE OF
PESTICIDES AND
DATE: AUG 3 1990 APPROVED: Ufa**, U. Dm*, P/mkr, ™»cb™c»
>: IP fixity
SUBJECT: Status Report1 8EHQ-0790-1026 S
FROM: Jacqueline T. Favilla, Biologist
Chemical Risk Identification Secttfn/C$B
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
A confidential company provided summarized preliminary findings of an oral pilot rat teratology study
conducted at doses of 0, 25, 50, 100, 200 or 300 mg/kg/day during gestation days 6-15 with a R & D
compound identified genetically as "aryloxy substituted benzenamine."
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final report (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the pilot
rat teratology study cited in the submission.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflect* information submitted to EPA under Section 8(e), the "•ubttanUai rW Information reporting provision
of the Toodc Substances Control Act (TSCA). Statements made tn this status report should not be retarded as eatpressing final Agency
policy or intent with respect to die subject chemical(s). Full copies of non-confkientiat Section 8(e) notices are avaflable for public
inspection at EPA Headquarter!, Northeast Mall (Room G-004), 401 "M" Sum S,W., Washington, D.C. 20460. All requests fear TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-1OT).
6.85
-------
^"L8r%
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
^ WASHINGTON, DC 20460
*(¦ pncfl*-
mlJt*
DATE:
AUG 3 1900 APPROVED: ^vv ?h/ho
SUBJECT: Status Report1 8EHQ-0790-1027
FROM: Jacqueline T. Favilla, Biologist
Chemical Risk Identification Section/QSB
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
Page 1 of 1
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBMISSION DESCRIPTION
General Electric Company provided a draft report of a 10-day repeated exposure rat inhalation toxicity study
conducted at doses of 0, 67, 200 or 670 mg/m3 with 2,6-dimethylphenol (2,6-xylenol), CAS No. 576-26-1.
According to the cover letter of the submission, "all male/female rats in 670 mg/m3 group exhibited moderate
squamous metaplasia of olfactory epithelium." The cover letter also states that the substance'is primarily
used as a monomer in the production of thermoplastic resins."
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final report (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the rat
inhalation toxicity study cited in the submission. In view of EPA's general interest in
company actions that are taken on a voluntary basis in response to chemical
toxicity/exposure data, the company will be requested to describe the actions that it has
taken or plans to take 1) to notify workers and others about the reported data, and 2) to
reduce or eliminate exposure to the subject chemical. The company will be asked to
provide copies of Material Safety Data Sheets and labels that have been revised to reflect
the reported findings. In addition, the company will be asked to describe the nature and
results, if available, of all studies (other than those submitted already to EPA or those cited
in the published scientific literature) about which the company is aware or that it has
conducted, is conducting or plans to conduct that are designed to determine the toxicity of
the subject chemical.
b) As part of the initial phase of the OTS Existing Chemicals Program (ECP), staff of the
Chemical Screening Branch will screen the reported information in order to determine the
need for further assessment of the subject chemical at this time.
c) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
* This statu* report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Man (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. AH requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
686
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^eD!X
" ^ ri
USE
a UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
*
WASHINGTON, D.C. 20460
^ proX&
Page 1 of 1
OFFICE OF
PESTICIDES AND TOXIC SUBSTANCES
DATE: SEP | 0 1990 APPRQVED:
SUBJECT: Status Report1 8EHQ-0790-1028 S
FROM: Jacqueline T. Favilla, Biologist
Chemical Risk Identification Secti
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 8
DATE:
SUBJECT:
FROM:
TOs
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SEP i 3 1990
APPROVED I
hu>, /Ann
Ii Hu
Status Report1 8EHQ-0790-1029
Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
James F. Darr, Section Head
Chemical Risk Identification Section
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
The Mobil Research and Development Corporation provided summary
information regarding the conduct and results of carcinogenicity
screening trials of three samples of rare-earth Y (REY) crystals,
one sample of aluminum oxide and thirteen samples of proprietary
particulates including six alumina oxide-based catalysts. The
screening trials, sponsored by the Mobil Oil Corporation, were
conducted at the Institute of Oncology in Bologna, Italy. In the
submission, the Mobil Research and Development Corporation provided
tables that describe the study design (TABLE 1) and significant
results of the screening trials (TABLE 2) ? also included in the
submission were tabularized results of comparative studies of a
variety of asbestos and asbestos-related materials, as well as
other fibrous and non-fibrous materials (TABLES 3 and 4). The
submitted tables are located in the four page attachment to this
status report.
In the cover letter to its Section 8(e) notice, the Mobil Research
and Development Corporation provided the following statements about
the relevance and significance of the reported findings:
i This status report is the result of a preliminary evaluation of information that has
been submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substances Control Act (TSCA). The statements made in this status
report should not be regarded as expressing final Agency policy or intent with respect to the
subject chemical(s). Any review of this status report should take into account that the
report may be based on incomplete information.
688
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8EHQ-0790-1029
Page 2 of 8
"Direct injection methods for insoluble particulates are
suitable as chronic hazard screening procedures which
maximize the potential for adverse response, regardless
of mechanism. Negative results tend to reassure, while
strongly positive results can be cause for concern.
Minimal responses may raise the possibility of a
hazardous property, but are not suggestive of serious
risk. The responses reported here are virtually the
least that can be detected with this assay.
"Three mesotheliomas of serous cavities were observed in
a test population of 120 rats injected with the sample
of alumina, a response rate of 2.5% (TABLE 2). This
minimally detectable rate may be judged against those
elicited by various forms of asbestos in similar assays,
33-98% (TABLE 3).
"Although alumina injection was followed by mesotheliomas
in serous cavities, the same material did not elicit a
significant increase of tumors after subcutaneous
injection in 60 rats.
"Six proprietary catalyst samples tested in this study
were manufactured using the alpha-roonohydrate form of
alumina reported herein. None of the six catalyst
samples elicited significant carcinogenic responses in
any of the sites tested, 180 rats per sample. [The cover
letter notes also that no data from the screening of the
seven other proprietary particulates "were interpreted
. . . as [being] indicative of carcinogenicity."]
"Non-fibrous alumina is widely considered to be an
innocuous substance, based upon animal tests and
extensive human experience. A recent EPA review of these
extensive data resulted in the removal of non-fibrous
aluminum oxide from the SARA Title III list of toxic
substances (55 FR 5220; February 14, 1990).
"In a population of 60 male and female rats injected
subcutaneously with one of the samples of REY crystals,
anaplastic sarcoma was observed in 4 male rats, a
response rate of 7% (TABLE 2). This rate may be evalu-
ated against the response rates elicited by particulate
and soluble carcinogens in similar assays, mostly in the
range of 43-88% (TABLE 4).
"Of the three samples of REY crystals tested, only one
[REY crystals TE 16462] is considered to have elicited
a carcinogenic response. That same material did not
elicit tumors after injection in serous cavities in l?o
rats."
689
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8EHQ-0790-1029
Page 3 of 8
The submitter also stated that "although no tumors comparable to
those in TABLE 2 were observed in 90 male and 90 female concurrent
control animals, historical data indicate that 1 tumor in 60 rats
in either the subcutaneous or intraperitoneal sites is not
unexpected." The company also stated that "any mesothelioma in the
intrapleural site is considered to be significant by the primary
investigator, because of its rarity."
PSE AND EXPOSURE POTENTIAL
Mobil Research and Development Corporation reported that the
"alumina tested in this study was Versal Al203, a crystalline
hydrated form of aluminum oxide also known as pseudoboehmite, or
alpha-monohydrate." According to the submitter, this material "is
used by Mobil Chemical Company as a binder or extender in the
manufacture of zeolite-containing catalysts for petroleum and
petrochemical process applications." This material may also be
used "as a refractory specialty additive and as a reactant in the
manufacture of low sodium grade aluminum nitrate." In addition
Mobil stated that "the REY material is the Y form of the synthetic
zeolite faujasite, a defined crystalline structure, that has been
ion-exchanged with mixed rare earth (RE) cations. This material
. . . is used primarily as the active component in petroleum
cracking catalysts."
COMMENTS/RECOMMENDATIONS
The Mobil Research and Development Corporation stated that they
have notified the manufacturer of the tested alumina sample, the
American Petroleum Institute (API) and the Chemical Manufacturers
Association (CMA) about the results of this study.
EPA has received a number of TSCA Section 8(e) and "For Your
Information" (FYI) notices on alumina, asbestos, and other fibrous
materials. Staff of the Chemical Control Division (CCD/OTS) are
currently collecting/evaluating information on asbestos and other
fibers. The Economics and Technology Division (ETD/OTS) is
responsible for listing/delisting activities for chemicals on the
Toxic Release Inventory (Section 313 of the Emergency Planning and
Community Right-to-Know Act).
a) The Chemical Screening Branch will ask Mobil Research
and Development Corporation to ensure that EPA receives
a complete copy of the final report (including the actual
experimental protocol, results of gross/histopathological
examinations, results of statistical analyses, etc.) from
the studies cited in the submission. Mobil will be asked
also to provide the address of the Institute of Oncology
in order for EPA to request full copies of the studies,
the results of which appear in TABLES 3 and 4.
690
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8EHQ-0790-1029
Page 4 of 8
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Mobil Research and Development
Corporation will be requested to describe the actions
that the company has taken or plans to take 1) to notify
workers about the reported information, and 2) to reduce
or eliminate exposure to alumina and REY TE-16462. Mobil
Research and Development Corporation will be asked also
to provide copies of Material Safety Data Sheets and
labels that have been revised to reflect the reported
findings. In addition, Mobil Research and Development
Corporation will be asked to describe the nature and
results, if available, of all studies (other than those
submitted already to EPA or those cited in the published
scientific literature) about which they are aware or that
their company has conducted, is conducting or plans to
conduct that are designed to determine the toxicity of
or the exposure to these chemicals.
b) As was the case for the initial submission, the Chemical
Screening Branch will immediately inform CCD and ETD
about the receipt of information on fibrous materials
(CCD) and aluminum oxide (ETD). As part of the initial
phase of the OTS Existing Chemicals Program (ECP), staff
of the Chemical Screening Branch will screen the reported
information in order to determine the need for further
assessment of the other tested chemicals at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, QSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA, CCD/OTS and
ETD/OTS; in addition, copies of this status report will
be sent to the Environmental Assistance Division/OTS for
further distribution.
691,
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8EHQ-0790-1029
Page 5 of 8
Sponsor:
Principal Investigator:
Test Materials
in this Report:
Species:
Strain:
Sex:
Housing:
Feed/Water:
Injection Sites:
Dosage:
Experimental Groups:
Controls:
Age at Injection:
Age at Termination:
Evaluations:
Other Test Materials:
Total Test Population Size:
Table 1
Study Design
Mobil Oil Corporation
Princeton, New Jersey
Cesare Maltoni, MD
Institute of Oncology
Bologna, Italy
Alumina
REY Crystals, TE-16460
REY Crystals, TE-16461
REY Crystals, TE-16462
Rat
Sprague-Dawley, Charles River (Italy)
Males and Females
5/Makrolon™ Cage, sexes separate
Pellets/Tap in Glass Bottles, ad lib.
Subcutaneous
Intraperitoneal
Intrapleural
One test article, one site per rat;
25 mg of fine particulate in saline, one time
30/Sex/Injection Site/Test Material
30/Sex/Injection Site, Saline Injected
~4 weeks
105 -110 weeks
3x Daily Cage Observation
lx Weekly Palpation/Observation
Monthly Body Weight
Complete Gross Necropsy (moribund or sac)
Histopathology (standard list, plus lesions)
13 Proprietary Particulates
1620 males, 1620 females
692
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8EHQ-0790-1029
Page 6 of 8
Table 2
Test Results
Anaplastic Sarcomas
in Subcutaneous Injection Sitesf
(Number of Affected Animals per Group)
Test Articles
Site of Alumina REY Crystals REY Crystals REY Crystals
Injection Sex TE-16460 TE-16461 TE-16462
Subcutaneous Ml 0 1 4*
F 0 1 0 0
Mesotheliomas
in Serosal Injection Sitest
(Number of Affected Animals per Group)
Test Articles.
Site of Alumina REY Crystals REY Crystals REY Crystals
Injection
Sex
TE-16460
TE-16461
TE-16462
Intraperitoneal
M
2*
0
0
0
F
0
0
0
0
Intrapleural
M
0
0
0
0
F
1*
0
0
0
* Significant Response, 30 rats per sex per Group
t No tumors of these classes were observed in saline-injected control rats
693
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8EHQ-0790-01029
Page 7 of 8
Table 3
Results of Other Studies
Incidence of Mesotheliomas
after Serosal Injection of Asbestos or Erionite
in Sprague-Dawley Rats*
(percent of animals with local mesotheliomas)
Intraperitoneal
Intrapleural
Material
Injection
Injection
Crocidolite
98
45
Chrysotile (Canada)
80
65
Chrysotile (Canada)
75
33
Chrysotile (Rhodesia)
82
n.t.
Chrysotile (California)
73
n.t.
Amosite
90
n.t.
Anthophyllite
83
n.t.
Asbestos Cement
53
35
Erionite
50
88
*25 mg/site, one time; 20M and 20F/route/material
n.t. - not tested
Source: C. Maltoni, Institute of Oncology, Bologna, Italy
694
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8EHQ-0790-1029
Page 8 of 8
Table 4
Results of Other Studies
Incidence of Anaplastic Sarcomas
after Subcutaneous Injection of Various Chemicals
in Sprague-Dawley Rats*
Dose
% with
Material
(mg)
Anaplastic
Sarcomas
Chromium Alum *
30
15
Basic Chromium Sulfate *
30
28
Lead Chromate *
30
63
Basic Lead Chromate *
30
68
Molybdenum Orange *
30
88
Basic Zinc Chromate *
30
13
Basic Zinc Chromate *
30
43
Silica-coated Lead Chromate *
30
65
Adriamycin **
2
65
Epirubicin ***
5
50
Epirubicin ***
3
68
Epirubicin ***
2
78
Idarubicin ***
1
43
Controls ****
0
0
* 20 rats/sex/group
** 40 M + 42 F
*** Interim result
**** H5M+ 145 F
Source: C. Maltoni, Institute of Oncology, Bologna, Italy
695
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
Page 1 of 1
OFFICE or
PESTICIDES AND TOXIC SUBSTANCES
DATE: SEP 7 1990 APPROVED:
>C
SUBJECT: Status Report1 8EHQ-0790-1Q30
FROM: Jacqueline T. Favilla, Biologist
Chemical Risk Identification Sectiwn/C?B
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
The U.S. Operating Committee of the Ecological and Toxicological Association of the Dyestuffs
Manufacturing Industry (ETAD) submitted a draft report of an oral rat range-finding developmental toxicity
test with C.I. Disperse Blue 79:1 Purified Presscake (CAS No. 3618-72-2) administered at dose levels of 0,
500, 1000 or 2000 mg/kg/day on gestation days 6-15. ETAD noted that this study, as well as a definitive full
developmental toxicity study, are being conducted as part of the TSCA Section 4 Testing Consent Order for
C.I. Disperse Blue 79 (40 CFR Part 799, 54 FR 48102).
COMMENTS/RECOMMENDATIONS
It should be noted here that C.I. Disperse Blue 79 is the subject of TSCA Section 8(a) and 8(d) information
gathering rules.
a) The Chemical Screening Branch has notified the Chemical Testing Branch (CTB) of all
reported information for inclusion in the ongoing TSCA Section 4 review of C.I. Disperse
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA, CTB/ECAD/OTS and
OPP/OPTS/EPA; in addition, copies of this status report will be transmitted to the
Environmental Assistance Division/OTS for further distribution.
1 This ttatus report reflects information submitted to EPA under Section 8(e), the Substantia] risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(i). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. Alt requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
Blue 79.
696
Prk>t»don Recydld PapK
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S> 7
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON. D C. 20460
Page 1 of 1
DATE:
AUG 30 1990
APPROVED:
SUBJECT: Status Report1 8EHQ-0790-1031 S
FROM: Jacqueline T. Favilla, Biologist
Chemical Risk Identification Section/CsB
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
Eli Lilly and Company submitted preliminary summarized results of an acute oral mouse toxicity study
conducted at doses of SO, 500 or 2000 mg/kg with a research compound generically identified as "substituted
pyridopyridimine." Lilly reported that, "there were no survivors following a single oral dose of 50 mg/kg of
this compound. All deaths occured by hour 2. Antemortem signs of toxicity included hypoactivity, ataxia,
low carriage, and coma."
COMMENTS/RECOMMENDATIONS
The company reported that this compound is labelled as hazardous, and that workers and others were
notified of the reported toxicological findings.
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final report (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the
study cited in the submission.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substance* Control Act (TSCA). Statements made in this statin report should not be regarded as expressing final Agency
policy or intent with respect to the subject chetnical(t). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 70460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
697
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. Z0460 page j of j
OFFICE OF
PESTICIDES AND TOXIC SUBSTANCES
DATE: SEP 6 1990 APPROVED: Q - QfcY\ 'l/fc fa
SUBJECT: Status Report1 8EHQ-0790-1Q32
,-0 /
FROM: Jacqueline T. Favilla, Biologist c ' auc^utf..
Chemical Risk Identification Section/CSB/
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
ARCO Chemical Company reported an explosion and fire that occurred at the ARCO Chemical facility in
Channelview, Texas on July, 5, 1990. The company also reported that, "Immediately after the incident, the
company recovered approximately 250 fish which apparently died from the high chemical oxygen demand
(COD) content of the water. No dead fish have been observed since July 10 and continued monitoring has
indicated a return of normal fish activity in the area."
COMMENTS/RECOMMENDATIONS
ARCO Chemical Company stated that the EPA and other governmental authorities were notified in a timely
manner of the incident.
The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA, CPSC, FDA, NTP,
OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA and EPA's Region VI office; in
addition, copies of this status report will be transmitted to the Environmental Assistance Division/OTS for
further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "NT Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
698
Printed on Rtcydtd PV*r
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2> 1
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON. DC. 20460
Page 1 of 1
DATE: ,, _
AUB 3 0 1990
APPROVED:
SUBJECT: Status Report1 8EHQ-0790-1033
FROM: Jacqueline T. Favilla, Biologist
Chemical Risk Identification Section/OSB /
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
CIBA-GEIGY Corporation submitted final reports of two oral rat toxicity studies (one 14-day, the other
28-day) conducted at dose levels of 0, 250, 500, 1000 and 2000 mg/kg/day (14-day) and 0, 5, 50, and 500
mg/kg/day (28-day) with a research and development (R & D) material identified as acetic acid, [[[3,5-
bis(l,l-dimethylethyl)-4-hydroxy-phenyl]methyl]thio]-, Cjo^-isoalkyl esters (DP-118, TK 13011, CAS No.
118832-72-7). CIBA-GEIGY reported that this compound is being considered for use as an "antioxidant,"
and that the company will revise the MSDS and label, and notify workers and customers of the reported
findings.
COMMENTS/RECOMMENDATIONS
a) The company will be asked to provide copies of Material Safety Data Sheets and labels that
have been revised to reflect the reported findings.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
699
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
Page 1 of 2
OFFICE OF
PESTICIDES AND TOXIC SUBSTANCES
DATE: SEP 2 0 1990 APPROVED:
-------
8EHQ-0790-1034
Page 2 of 2
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final report (including the actual experimental protocol, results
of any statistical analyses, etc.) from the epidemiologic study cited in this submission. In
addition, the company will be asked to provide copies of Material Safety Data Sheets that
have been revised to reflect the reported findings.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
701
-------
tfto sr^r
o" %
!> T-
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
Page 1 of 1
DATE: SEP 7 1990 APPROVED:
V-M-i I
OFFICE OF
PESTICIDES AND TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0790-1035
FROM: Jacqueline T. Favilla, Biologist
Chemical Risk Identification Sectii
icm/C^B
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
Olin Corporation submitted preliminary results of an acute inhalation LC50 study conducted at doses of
0.05, 0.14, 0.16, 0.82, 1.40, or 1.50 mg/L with bis(l-hydroxy-2(lH)-pyridinethionato-0,S)-T-4) zinc (zinc
pyrithione, CAS No. 13463-41-7).
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final report (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the
inhalation study cited in the submission. In view of EPA's general interest in company
actions that are taken on a voluntary basis in response to chemical toxicity/cxposure data,
Olin Corporation will be requested to describe the actions that it has taken or plans to take
to 1) to notify workers and other about the reported data, and 2) to reduce or eliminate
exposure to the subject chemical. The Olin Corporation will be asked to provide copies
of Material Safety Data Sheets and labels that have been revised to reflect the reported
findings. In addition, the Olin Corporation will be asked to describe the nature and results,
if available, of all studies (other than those submitted already to EPA or those cited in the
published scientific literature) about which the company is aware or that it has conducted,
is conducting or plans to conduct that are designed to determine the toxicity of zinc
pyrithione.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-O04), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
702
Printed on Racy dad
-------
«eo sr^
s ^ UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
I ° WASHINGTON D C 20460
proi^ Page 1 of 1
DATE: SEP 3 1990 APPROVED: ][.
SUBJECT: Status Report1 8EHQ-0790-1036 S
FROM: Jacqueline T. Favilla, Biologist CIfa&M&toC'
Chemical Risk Identification Section/C^B
TO: James F. Darr, Section Head, Chemical Risk
Identiflcation Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
Eli Lilly and Company submitted preliminary summarized results of an acute oral mouse toxicity study
conducted at doses of 50, 500 or 2000 mg/kg with a research compound generically identified as "substituted
quinazoline IV." Lilly reported that, "There were no survivors following a single oral dose of 50 mg/kg of
this compound. The majority of deaths occurred within 4 hours of dosing and all deaths occurred by Test
Day 3. Antemortem signs of toxicity included ataxia, low carriage, coma, lethargy, poor grooming, hunched
posture, ptosis, piloerection, cool to the touch, and eyes white in color." Summarized results of a Gradient
Plate Assay were also reported; it was determined that substituted quinazoline IV is not mutagenic in this
assay.
COMMENTS/RECOMMENDATIONS
The company reported that this compound is labelled as hazardous, and that workers and others were
notified of the reported toxicological findings.
The Agency has received other TSCA Section 8 (e) submissions on substituted quinazolines. The reader's
attention is directed to 8E #'s 806, 808, and 819.
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives full copies of the final reports (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the
studies cited in the submission.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
* This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
703
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sv
^ *4
kW/, 1 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
532?/
WASHINGTON, DC 20460 pagc j Qf l
DATE: SEP I 3 1900 APPROVED: W/j/fc
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0790-1Q37 S
FROM: Jacqueline T. Favilla, Biologist
Chemical Risk Identification Section/CSB
TO: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS
SUBMISSION DESCRIPTION
A confidential company provided a final report of an oral rat 28-day toxicity study conducted at doses of
0, 100, 330 or 1000 mg/kg bw/day with a research and development (R & D) compound identified generically
as "substituted cyclohexane." According to the submission, adverse male reproductive system effects were
observed in the study.
COMMENTS/RECOMMENDATIONS
The company reported that employees will be informed of the findings and that standards for developing
and handling products containing the test material will be reviewed.
The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA, CPSC, FDA, NTP,
OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition, copies of this status
report will be transmitted to the Environmental Assistance Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 6(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
704
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*
d*
\
g UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
STjfi WASHINGTON, D.C. 20460 p of ,
(jh^v
-------
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON. D C 20460
Page 1 of l
DATE: SEP 3 |990 APPROVED:
SUBJECT: Status Report1 8EHQ-0890-1G39 S
FROM: Jacqueline T. Favilla, Biologist
Chemical Risk Identification Section/CSB'
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
A confidential submitting company provided final reports of two positive skin sensitization studies in humans
conducted with two research compounds generically identified as "mixture of sulfurized compounds". The
company reported that these compounds are being considered for use as "lubricant components."
COMMENTS/RECQMMHNDATIONS
The company reported that employees and customers will be informed of the skin sensitization findings.
In addition, the company will add these findings to their Material Safety Data Sheets.
a) The Chemical Screening Branch will request the submitting company to provide copies of
Material Safety Data Sheets and labels that have been revised to reflect the reported
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 Tliis status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
findings.
706
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Page 1 of 17
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SUBMISSION DESCRIPTION
8EHO—0990—10 65
In 8EHQ-0990-1065, Atochem North America, Inc. submitted the
following information about a 197 6 "incident in which workers
reported adverse health effects that may have been the result of
exposure to t-butylazo-2-hydroxy-butane (CAS No. 57910-79-9)," an
azo foaming agent formerly manufactured by the Pennwalt Corporation
(an Atochem predecessor) and sold under the trade name Lucel-4®.
"In 1976, a company named Proform, Inc. [which is located
in Eagan, Minnesota] purchased Lucel-4 from Pennwalt for
use as an azo foaming agent in polyester foam spraying
operations. In approximately September or October 1976,
a Proform employee who operated a Lucel-4 spraying gun
reported that he was experiencing difficulty with his
balance, dizziness, headaches, nausea, and blurred
vision. Ultimately, the physicians who examined him
determined that he had a permanent partial impairment in
the lower extremities. Although a conclusive identifica-
tion of the cause was not indicated, the physicians who
examined the employee believed that it was likely that
these were neurotoxic effects resulting from exposure to
Lucel-4.
"In that same time period, a second Proform employee
involved in the spraying of Lucel-4 reported symptoms
such as lack of night vision, blurred day vision, and
numbness of the extremities, and reportedly was hospi-
talized for approximately 30 days. Pennwalt never
received any detailed or corroborating information
concerning this second employee's reported injuries or
their relationship to Lucel-4.
"Finally, approximately 4-6 other Proform employees
involved in the Lucel-4 operations reportedly consulted
a physician in that same time period. Based on the
limited information Pennwalt received, it appears that at
least some of these workers may have exhibited neurotoxic
symptoms, but none of them was injured on a prolonged or
permanent basis.
"The background facts indicate that Lucel-4 was used in
connection with this incident in a manner contrary to
Pennwalt's customer instructions and sound industrial
hygiene practice, including improper ventilation, inade-
quate safety equipment, and failure of the employees to
follow minimal safety precautions or to heed the repeated
instructions of their supervisors about the use of the
product. For example, the employee who suffered permanent
partial disability ignored the repeated safety instruc-
tions and was regularly seen with Lucel-4 (which was blue
in color) all over his face and hands. As a result, in
709
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Page 3 of 17
a subsequent product liability lawsuit brought by this
employee, the jury found that both Proform and the
employee were negligent and that Pennwalt was not liable
in any way for the employee's injuries."
EPA's FYI-OTS-1080-0095 file contains a number of letters/documents
that pertain to Lucel-4. For example, this FYI file contains a
December 22, 1976 letter from the Minnesota Department of Labor and
Industry to the U.S. National Institute for Occupational Safety and
Health (NIOSH) with the following attachments:
o A November 5, 1976 Minnesota Department of Health (MDOH)
memorandum containing a report of a September 29/30, 1976
MDOH industrial hygiene investigation of Proform, Inc.
According to a cover sheet to the MDOH industrial hygiene
report, the objective of the MDOH investigation was to
"evaluate an occupational disease report from an employee
hospitalized allegedly because of exposure to Lucel-4 Azo
Foaming Agent and styrene."
o An October 5, 1976 letter addressed from Pennwalt to MDOH
containing a Product Bulletin, MSDS, and safe handling
instructions for Lucel-4, as well as Lucel®-6 (another
Pennwalt azo foaming agent; 1-((1,1-dimethylethyl)azo)-
cyclohexanol? CAS No. 54043-65-1).
FYI-OTS-1080-0095 also contains a January 19, 1977 letter from
NIOSH to Pennwalt regarding Lucel-4? an excerpt from this NIOSH
letter follows:
"The Minnesota Occupational Safety and Health Agency
(MOSHA) has reported to the National Institute for
Occupational Safety and Health (NIOSH) that a number of
[Proform, Inc.] employees . . . using Lucel-4 have
developed neurotoxic symptoms. In order to assess
whether the reported medical problems are associated with
Lucel-4, [it] is necessary to learn as much about the use
patterns as possible "
FYI-OTS-1080-0095 also contains a March 31, 1977 letter from
Pennwalt to NIOSH in which the company provided a description of
the manufacturing process for Lucel-4. Further, FYI-OTS-1080-0095
contains a letter dated April 5, 1977 in which NIOSH staff again
asked Pennwalt to provide information relating to Lucel-4 use and
exposure patterns. In a letter dated April 28, 1977 (also found in
FYI-OTS-1080-0095), Pennwalt provided the requested information to
NIOSH. (EPA's copy of this particular Pennwalt letter had been
sanitized by NIOSH so as to not disclose the names of Pennwalt's
Lucel-4 customers.) In this April 28, 1977 letter, Pennwalt stated
that Lucel-4 "is an experimental compound for which . . . [Pennwalt
is] attempting to develop a market." Pennwalt stated further that
Proform had discontinued their use of Lucel-4 and returned their
remaining Lucel-4 inventory stock to Pennwalt for sales credit.
7 in
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Page 4 of 17
Pennwalt also reported to NIOSH that "other than the [Proform]
incident . . . [Pennwalt had] received no significant complaints
relating to health from any [Lucel-4] users in the field."
It is important to note that FYI-OTS-1080-0095 also contains a
December 17, 1980 letter from Pennwalt to NIOSH in which Pennwalt
stated that Lucel-4 had been "discontinued due to an instance of
customer misuse."
Also included in FYI-OTS-1080-0095 is a January 19, 1981 letter
from Pennwalt to NIOSH containing copies of the final reports from
the following toxicologic studies of Lucel-4 and Lucel-6:
Lucel-4
1) Acute Rabbit Dermal LD50 Study (LUCEL-4); International
Research and Development Corp.; Report # 164-029; 8/10/73;
2) Acute Rat Oral LD50 Study (LUCEL-4); International Research
and Development Corp.; Report # 164-032; 11/30/73;
3) Acute Rat Inhalation LC50 Study (LUCEL-4); International
Research and Development Corp.; Report # 164-032; 12/5/73;
4) Subchronic (6-Month) Mouse Dermal Tox. Study (LUCEL-4);
International Research and Development Corp.; Report # 164-
047; 3/10/76;
5) Acute Rabbit Dermal LD50 Study (LUCEL-4); International
Research and Development Corp.; Report # 164-061; 3/26/76;
6) Acute Rabbit Eye Irritancy Test (LUCEL-4); International
Research and Development Corp.; Report # 164-061; 3/26/76;
7) Acute Rabbit Dermal Tox./Absorption Study (LUCEL-4);
International Research and Development Corp.; Report # 164-
064; 9/2/76; and
8) In Vitro Bacterial Mutagenicity Evaluation (LUCEL-4); Litton
Bionetics, Inc.; No Report #; 8/77.
Lucel-6
1) Acute Rabbit Dermal LD50 Study (LUCEL-6); International
Research and Development Corp.; Report # 164-046; 4/21/75;
2) Acute Rat Oral LD50 Study (LUCEL-6); International Research
and Development Corp.; Report # 164-045; 4/21/75;
3) Acute Rat Inhalation LC50 Study (LUCEL-6); International
Research and Development Corp.; Report # 164-044; 5/16/75;
4) Acute Rabbit Dermal Tox. Study (LUCEL-6); International
Research and Development Corp.; Report # 164-050; 7/23/75;
711
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Also included in Pennwalt's January 19, 1981 letter to NIOSH is a
January 24, 1975 letter and summary final report from the Roswell
Park Memorial Institute (Orchard Park Laboratories) regarding a
chronic (52-week) Swiss mouse skin-painting carcinogenicity study
conducted for Pennwalt on two chemical substances identified only
as a "t-butylazo compound containing a nitrile function" and a "t-
butylazo compound containing an hydroxy function." According to
the "Summary" section of the final report, "No tumors were seen in
mice painted with either of these compounds over a period of 52
weeks, using 2 or 3 concentrations ranging up to 5% in acetone."
The "Results" section of the final report provides the following
information regarding other study findings:
"Some of the mice treated with 5% of . . . [the t-butyl-
azo compound containing an hydroxy function] developed
hydronephrosis and retention of urine in the bladder.
This result was first noted during the 39th week when the
mice were about 47 weeks old. Although hydronephrosis is
seen occasionally in old Swiss mice, hydronephrosis with
distended bladders of this degree and at this age is rare
in . . . [the conducting laboratory's] colony. . . .[The
investigator has] never seen so many cases in a small
group of animals. . . .[The investigator concluded] that
urinary obstruction was caused in these animals, in part
at least, by the treatment. . . .[The investigator was]
unable to find any gross physical abnormality in the
[affected] animals that might cause this condition.
Other animals in the same [treated] group similarly
showed no gross abnormalities near the urinary tract.
Microscopic examination disclosed hydronephrosis of the
kidney, often with chronic cystitis. In a few [treated]
animals, there was some indication of hyperplasia of the
bladder or urethra epithelia, but this was not so
pronounced as to indicate it was causally related to
urinary obstruction. . . . [The laboratory investigator]
cannot identify the mechanism by which the urinary
obstruction occurred in these animals."
8EHQ-0890-1041
In 8EHQ-0890-1041, Atochem provided copies of the final reports
from a 4-week rat inhalation toxicity study, a pilot rat dermal
neurotoxicity study, and a 28-day rat dermal neurotoxicity study of
2-t-butylazo-2-hydroxy-5-methylhexane (BHMH; CAS No. 64819-51-8),
an azo foaming agent formerly marketed by Pennwalt under the trade
name Lucel-7®. Atochem*s cover letter presents the following
summary information about the conduct and results of these studies:
4-Week Subacute Inhalation Toxicity Study (International
Research and Development Corp.; Report # 164-085; 3/26/81)
"... Three groups (containing ten male and ten female
rats each) were exposed to vapor concentrations of 0.01
mg/L, 0.1 mg/L, or 0.5 mg/L BHMH for six hours per day,
712
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Page 6 of 17
five days per week, for four weeks. The report stated
that the results indicated that levels as low as 0.1 ing/L
'produced toxic effects as indicated by a failure to gain
body weight normally and a possible hindlimb paralysis,1
that 'levels approximating 0.1 mg/L were lethal after
only a few exposures,1 and that 'BHMH probably produced
a biochemical lesion of the central or peripheral nervous
system.1"
Pilot and 28-Dav Rat Dermal Neurotoxicity Studies (Food &
Drug Research Laboratories, Inc.; Report # 7247; 2/27/83)
. In the pilot phase of the study, test rats were
subjected to dermal application of Lucel-7 at six dose
levels: 15, 50, 100, 175, 350, and 500 mg/kg body weight.
The results indicated that 'dermal administration of
Lucel-7 at levels of 100 mg/kg or greater, produced
ataxia, hindlimb paralysis, and urinary incontinence,'
and that 'the initial onset of these neurotoxic signs was
dose dependent.1 In the main phase of the study, test
rats received dermal application of 100 mg/kg of five
different test substances, as well as Lucel-7 as a posi-
tive control [. . . 'because of its known neurotoxic
effects'] for five days per week for four weeks. The
results indicated that neurotoxic effects, including
hindlimb paralysis, ataxia, and urinary incontinence,
were observed only in animals receiving Lucel-7 as a
positive control. No effects were seen from exposure to
the five test substances."
[NOTE: According to the final report, the five test
substances were:
1. di-t-butylhydrazinium sulfate (CAS No. unknown);
2. Luazo-135-40XL (identity and CAS No. unknown);
3. 2-t-butylazo-2-(hydroxyethoxy)-4-methylpentane
(CAS No. unknown);
4. t-butylhydrazine hydrochloride2 (CAS No. 7440-27-3);
5. Luazo 82 (2-((l,1-dimethylethyl)azo)-2-methyl-
butanenitrile (CAS No. 52235-20-8).]
In 8EHQ-0890-1041, Atochem also provided the following background
information regarding the neurotoxic effects of Lucel-7 in animals
and humans:
2
- t-Butylhydrazine hydrochloride is one of the subject chemicals in another recent Atochem
TSCA Section 8(e) submission (8EHQ-0890-1042). The reader's attention is directed to the
status report prepared for that submission.
713
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"[T]he neurotoxicity of Lucel-7 has been widely reported
in the scientific literature, including reports of animal
studies and a worker exposure incident, (e.g., Horan JM,
Kurt TL, Landrigan PH, et al.f Neurologic Dysfunction
from Exposure to 2-t-Butylazo-2-Hydroxy-5-Methylhexane
(BHMH): A New Occupational Neuropathy, American Journal
of Public Health 75: 513-517, 1985; Spencer PS,
Beaubernard CM, Bischoff-Fenton MC, Kurt TL, Clinical and
Experimental Neurotoxicity of 2-t-Butylazo-2-Hydroxy-5-
Methylhexane, Annals of Neurology 17: 28-32, 1985;
Spencer PS, Beaubernard CM, Bischoff MC, Kurt TL,
Experimental Neurotoxicity of Lucel-7 (2-t-Butylazo-2-
Hydroxy-5-Methylhexane), The Toxicologist 3:1, 1983,
presented to the Society of Toxicologists in Las Vegas,
NV (March 7-11, 1983) ; Kurt TL, Webb CR, Toxic
Occupational Neuropathy: Texas, Morbidity Mortality
Weekly Reports 29: 529-530, 1980.) In addition, the
four-week subacute inhalation study [of Lucel-7] was
previously submitted to the National Institute for
Occupational Safety and Health [ (NIOSH) ] and is discussed
in the above-mentioned article by Horan JM, Kurt TL,
Landrigan PJ, et al."
Of particular interest and importance in FYI-OTS-1080-0095 is an
October 29, 1980 letter from a consultant medical toxicologist in
Texas addressed to Pennwalt; an excerpt from this letter follows:
. .[S]everal cases of severe neurotoxicity related to
Lucel-7 exposure [have been encountered] in a fiberglass
tub foaming operation. These people have severe peri-
pheral neuropathies of a sensory as well as motor nature
that begin distally and proceed proximally. All of them,
it appears, will have some permanent impairment, since
severe objective findings are persisting many months
after removal from exposure. In addition, these people
have experienced early in their courses of toxicity the
problems of decreased color vision, tunnel vision (loss
of peripheral vision), and some have now developed
cataracts "
FYI-OTS-1080-0095 also contains a Morbidity and Mortality Weekly
Report published by the U.S. Centers for Disease Control (CDC) on
November 7, 1980; excerpts from the report follow:
"In October, 1980, a medical toxicologist in Dallas,
Texas reported to the National Institute for Occupational
Safety and Health (NIOSH) that he had examined 4 persons,
ages 25-33 years, who had dysfunction of central and
peripheral nervous systems. All 4 persons were employed
in the manufacture of reinforced plastic bathtubs at
Lasco Industries [located] in Lancaster, Texas. Symptoms
had been of subacute onset and included mixed motor-
sensory peripheral neuropathy, loss of memory, decreased
attention span, and loss of color and peripheral vision.
714
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Page 8 of 17
"The first patient had onset in October 1979, 1 month
after the introduction to the Lasco plant of a new
foaming agent, Lucel-7 . . . All the other patients had
onset by late December. As spray applicators, the 4
affected workers had direct contact with Lucel-7. The
interval from the first exposure to this chemical to
onset of symptoms ranged from approximately 2 to 4 weeks.
Gloves and paper face masks were made available to
workers at the plant by Lasco management from the begin-
ning of Lucel-7 use, but wearing them was not required.
Protective clothing was not generally available until
after January 1980, and air-supplied respirators (which
were recommended by the manufacturer [(Pennwalt)]) were
not provided. Use of Lucel-7 was discontinued at Lasco
in April 1980.
"A NIOSH physician interviewed and examined the affected
workers on October 24, 1980. He confirmed the presence
of residual neurologic findings recorded by the medical
toxicologist [in Texas]. Nerve conduction studies and
electromyography documented the presence of distal,
patchy peripheral neuropathy in all 4 [Lasco] workers."
Another significant document contained in FYI-OTS-1080-0095 is an
internal Lasco Industries memorandum concerning the "Safe Handling
of Lucel-7." This particular memorandum is dated November 1, 1979
(shortly after introduction of Lucel-7 into the facility) and was
addressed to "Distribution." Some excerpts from this memorandum
follow:
"It is apparent from the symptoms that have occurred in
two individuals that the Lucel-7 is and has been handled
with some neglect to personal safety.
"This material is very toxic, especially from a skin
absorption standpoint. Personal contact with this liquid
must be avoided at all costs. The failure of these indi-
viduals to do so has resulted in their present condition.
It
• • • •
FYI-OTS-1080-0095 also contains a letter dated November 4, 1980
from Pennwalt to NIOSH with the following attachments:
1) LUCEL-7 Product Bulletin;
2) LUCEL-7 Safe Handling Instructions to Customers;
3) LUCEL-7 Material Safety Data Sheet (MSDS);
4) Acute Rabbit Dermal LD50 and Acute Rat Inhalation Studies
of LUCEL-7; Report # 164-070; International Research and
Development Corp.; 5/27/77;
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5) Primary Rabbit Eye Irritation and Acute Rat Oral LD50
Studies of LUCEL-7; Report # 164-071; International
Research and Development Corp.; 10/14/77;
6) Acute (1-Hour) Rat Inhalation LC50 Study of LUCEL-7;
Report # 164-071; international Research and Development
Corp.; 11/10/77; and
7) In Vitro Bacterial Mutagenicity Evaluation of LUCEL-7;
Litton Bionetics, Inc.; No Report #; 8/77.
FYI—OTS—1080-0095 also contains a November 28, 1980 letter from
NIOSH to Pennwalt in which NIOSH asked Pennwalt to provide answers
to a number of Lucel-4, Lucel-6 and Lucel-7 production, exposure,
and human health-related questions. In Pennwalt's response letter
dated December 17, 1980 (also included in FYI-OTS-1080-0095 but in
NIOSH-sanitized form to protect the company's confidential business
information), Pennwalt reported non-confidentially that since
Lucel-7 had been in production, no Pennwalt workers had experienced
any medical problems involving numbness, dizziness, or impairment
of strength, balance, coordination or vision. Pennwalt also stated
that there were no unusual or unexplained medical problems seen
among workers involved in Lucel-4, Lucel-6 or Lucel-7 production.
In a supplemental TSCA Section 8(e) submission (8EHQ-0491-1041
Supplement), Atochem provided copies of the final reports of the
following additional acute toxicity studies of Lucel-7:
1) Acute Dermal and Inhalation Toxicity Studies of Lucel-7
in Rats and Rabbits; Report # 164-068; International
Research and Development Corp.; 4/1/77; and
2) Acute Inhalation Toxicity Study of Lucel-7 in Rats;
Report # 164-074; International Research and Development
Corporation; 10/2/78.
SUBMISSION EVALUATION
EPA's preliminary evaluation of a number of the previously cited
Lucel-4, Lucel-6, Lucel-7 and other toxicologic studies follows.
Lucel-4
(Acute Rat Inhalation LC50 study; Report # 164-032; 12/5/7 3)
Groups of 10 male rats were exposed by inhalation to concentrations
of approximately 1.56, 3.125, 6.25, 25 or 50 mg/L Lucel-4 for one
hour. All rats exposed to 6.25 mg/L or greater died within 4 days.
All of the rats exposed to 1.56 or 3.125 mg/L survived for the
entire 14 day observation period. Signs observed during exposure
to 1.56 mg/L included eye squint, increased respiratory rate,
dyspnea, lacrimation, erythema and ataxia. These signs were no
716
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Page 10 of 17
longer observed at 24 hours post-exposure, although 2 rats did
exhibit transient corneal opacity. In addition to the previously
mentioned signs, rats exposed to 3.125 mg/L also exhibited pros-
tration and intermittent tremors. Most of the signs were still
observed at 24 hours post-exposure. At 48 hours post-exposure,
ataxia, decreased respiratory rate, and decreased motor activity
were observed. Signs of neurotoxicity were still evident on post-
exposure days 3-8. Decreased motor activity and circling movements
were observed on days 3-7 with circling continuing on day 8.
Lucel-6
(Acute Rat Inhalation LC50 Study; Report # 164-044; 5/16/75)
Groups of 10 rats (5 per sex per group) were exposed via inhalation
to concentrations of approximately 6.25, 12.5, 25, 100 and 200 mg/L
Lucel-6 for one hour. None of the animals exposed to 6.25, 12.5 or
25 mg/L died during the exposure or the 14 day post-exposure
observation period. Signs observed at all three doses during the
exposure period included changes in motor activity, eye squint,
erythema, salivation, lacrimation, clear nasal discharge, soft
stool, tachypnea and dyspnea. Nasal porphyrin discharge at 12.5
mg/L, and tremors and hypersensitivity to touch at 12.5 and 2 5
mg/L, were also observed. Flaccidity was observed beginning on day
one in the 6.25 and 12.5 mg/L groups and day two in the 25 mg/L
group. Recovery did not occur during the 14 day observation
period. There is no evidence to suggest that this effect does not
represent a permanent neurological lesion. In the 12.5 mg/L group
ataxia was reported in two rats on day 12 and one rat on days 13
and 14.
Exposure to higher concentrations of this compound (50 and 100
mg/L) produced death in female rats. One male in the 100 mg/L group
also died. Signs of neurotoxicity observed at these dose levels in
surviving animals included decreased motor activity, eye squint,
salivation, lacrimation, flaccidity, ataxia, tremors, clonic con-
vulsions and hypersensitivity to touch. A brief increase in motor
activity prior to the decrease, circling movements, subconvulsive
body jerking and prostration were also reported in the 100 mg/L
group.
Nine of ten rats in the 200 mg/L exposure group died, making it
impossible to evaluate the significance of reported signs. Deaths
occurred within 72 hours of exposure with 3 within the first 24
hours and an additional 5 by 48 hours post-exposure. The one
survivor, a male, continued to exhibit flaccidity and ataxia
throughout the 14 day exposure period.
The investigator stated in the study synopsis that human inhalation
exposure to this chemical substance should not be allowed.
717
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Lucel-7
(Acute Rabbit Dermal and Acute Rat Inhalation Studies;
Report # 164-068; 4/1/77)
This study was conducted with Lucel-7 to determine the acute dermal
LD50 in rabbits and the acute inhalation LC50 in rats. The acute
rabbit dermal LD50 for the chemical was found to be 707 mg/kg with
confidence limits of 500-1000 mg/kg; no other effects were reported
in the acute rabbit dermal toxicity portion study. The acute rat
inhalation LC50 was found to be greater than 20 mg/L; additional
effects reported included hypoactivity (4 rats on Day 1 and 2 rats
on Day 2, and 1 rat on Days 3-6), ataxia (3 rats on Day 1, 1 rat on
Days 2-5) , and inability use hind legs (1 rat on Day 2 and 1 rat on
Days 3 and 4).
(Acute Rabbit Dermal LD50 and Acute Rat Inhalation Studies;
Report # 164-070; 5/27/77)
The rat inhalation portion of this study was conducted to determine
the acute LC50 of Lucel-7. Ten rats were exposed to 20 mg/L for
one hour. This concentration was determined to exceed the LC50 in
that 6 of 10 rats died during exposure or during the post-exposure
observation period. Signs seen in the 4 surviving rats included
ataxia and hypoactivity.
(Acute (1-Hour) Rat Inhalation LC50 Study;
Report # 164-071; 11/10/77)
A second acute rat inhalation study of Lucel-7 involved exposure to
concentrations of approximately 2.55, 4.51, 7.94, 10.64 and 17.74
mg/L for one hour. The lowest concentration, 2.55 mg/L, resulted
in no deaths. Signs of toxicity observed included eye squint,
slight dyspnea and ataxia.
Slight ataxia, eye squint, salivation and nasal discharge were
observed in the animals exposed to 4.51 mg/L. One death occurred
on day one postexposure. Respiratory distress persisted for 7 days.
Exposure to a concentration of 7.94 mg/L resulted in dyspnea and
ataxia, which persisted for 10 days. All female and 2 of 5 male
rats died before the end of the 14 day observation period.
Rats exposed to 10.64 mg/L exhibited an initial increase in
activity. This was followed by ataxia on the day of exposure and
lack of coordination of movement and control of urination beginning
on postexposure day 1. Two deaths occurred on the day of exposure,
four deaths occurred during the next three days and two deaths
occurred on day six postexposure; two rats survived for the entire
14 day observation period.
Exposure to 17.74 mg/L also led to an initial increase in activity
followed by ataxia. The exposed animals lacked coordination and
control of urination beginning postexposure day 1. None of the
718
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Page 12 of 17
exposed animals survived for the entire 14 day observation period.
Four of the five male rats died within three hours of exposure.
The remaining male and five females died on postexposure day 4.
(Acute Rat Inhalation Toxicity Study;
Report # 164-074; 10/2/78)
This acute inhalation toxicity study of Lucel-7 in rats evaluated
the effects of a single 6-hour exposure to 0.86 mg/L in 6 male and
6 female Charles River CD rats. The animals were observed for 14
days following the exposure. During the exposure, tremors were
observed in 1 female rat after 2 hours, ataxia and slight dyspnea
in all rats beginning at 3 hours and continuing through the end of
the exposure period, and prostration and marked dyspnea (gasping)
in all females after 5 hours. All female rats died before the end
of the 14 day observation period; 1 died during exposure (after 40
minutes), 3 died on post-exposure Day 1, and the remaining 2 died
on post-exposure Day 2. Although none of the exposed male rats
died during the study, all male rats exhibited ataxia and dyspnea
through post-exposure Days 3-4; 2 male rats continued to exhibit
ataxia and dyspnea for the entire 14-day observation period.
(4-Week Subacute Rat Inhalation Study;
Report # 164*085; 3/2 6/81)
Groups of 10 rats per sex per dose were exposed to Lucel-7 vapor
concentrations of 0.01, 0.1 or 0.5 mg/L six hours per day, five
days per week for 4 weeks. The study design was very poor; animals
were observed for "pharmacotoxic" signs only once per week and
perfusions were performed at the end of the study. However, signs
of neurotoxicity were clearly seen. The lowest dose, 0.01 mg/L,
produced restricted movement and incoordination of hindquarters in
20% of the animals. Animals exposed to 0.1 mg/L had no movement in
their hindquarters or front legs. The animals recovered over a
period of four weeks, with recovery progressing from limb paralysis
to restricted movement to uncoordinated and awkward movement to
normal. A single exposure to 0.5 mg/L also led to loss of all
movement in hindquarters and front legs. All ten females in this
group died as did 4 of the 10 males. The remaining six animals
appeared to recover within two weeks.
This four-week inhalation study demonstrated that exposure to
concentrations of Lucel-7 as low as 0.01 mg/L can produce neuro-
toxicity. The study investigator concluded that, Lucel-7 "probably
produces a biochemical lesion of the central or peripheral nervous
system." A workplace Lucel-7 exposure limit of 0.1 ug/L or less
was recommended.
(Pilot Rat Dermal Neurotoxicity study;
Report # 7247; 2/17/83)
This study was designed to evaluate the potential neurotoxicity of
Lucel-7 upon dermal exposure. Five rats per sex per group were
exposed to 15, 50, 100, 175, 350 or 500 mg/kg of the test compound.
719
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Page 13 of 17
The study was planned for 28 days. However the 175, 350 and 500
mg/kg exposures were terminated on days 12, 11 and 5, respectively,
due to severe toxicity. Lucel-7 doses of 100 mg/kg and higher
produced clear evidence of neurotoxicity. Signs observed included
ataxia, hindlimb paralysis and urinary incontinence. Firm evidence
of neuropathology was observed in sections from both the spinal
cord and the sciatic nerve.
(28-day Rat Dermal Neurotoxicity Study;
Report # 7247? 2/17/83)
Ten male and ten female rats were dermally exposed to 100 mg/kg
Lucel-7. Several signs of severe neurotoxicity were reported.
Ataxia was observed beginning on postexposure day 23. Seven female
and four male rats exhibited ataxia on at least one day between day
2 3 and the termination of the study. Hindlimb paralysis was seen
in five female and two males rats. Urinary incontinence was found
in four females and one male.
Histopathological evidence of neurotoxicity was also obtained.
Eight of the females and one male had significant Wallerian type
degeneration of the sciatic nerve. Evidence of morphological
changes in the spinal cord was obtained from one male and three
females.
Unidentified t-Butvlazo Hydroxy compound
(Chronic Swiss Mouse Dermal Application Study;
Roswell Memorial Park Report; January 24, 1975)
Urinary retention was observed in some mice treated with 5% of this
particular compound and was attributed to treatment. Considering
that no gross abnormalities or pathological lesions were associated
with this condition, there may be a neurological basis for the
observed effect. The final report states that no mechanism by which
the urinary obstruction occurred was identified. The study did not
include evaluation of neurological function.
Although the investigator did not clearly report the incidence of
urinary retention, some information is available. The exposure
group originally contained 50 mice. Nineteen were reported dead
within 20 weeks of treatment. Urinary retention was first noted
during week 39, when 31 mice remained on study. Nine mice are
listed in table 2 as having hydronephrosis and 14 with varying
degrees of distended bladders. Therefore, 23 of 31, or about 75%
of the mice surviving 39 weeks or more postexposure were affected.
general Statement on Lucel-4, Lucel-6 and Luoel-7
The available animal and human data indicate clearly that dermal
and inhalation exposure to Lucel-4, Lucel-6 and Lucel-7 can result
in serious neurotoxicological effects in animals and/or humans.
720
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Page 14 of 17
PRODUCTION INFORMATION
Lucel-4
In 8EHQ-0990-1065, Atochem stated that "Lucel-4 was a developmental
substance and was never fully introduced as a commercial product."
In addition, Atochem stated that "Pennwalt ceased production of
Lucel-4 in 1979, and has not manufactured, processed or distributed
the substance since that time." According to a December 17, 1980
letter from Pennwalt to NIOSH (located in FYI-OTS-1080-0095),
Lucel-4 was "never released from commercial development. . . "
According to the non-confidential computerized version of EPA's
initial TSCA Chemical Substance Inventory, Pennwalt reported that
in 1977 the company manufactured 0-1000 pounds of Lucel-4 at the
company's facility in Crosby, Texas. No TSCA Inventory Update Rule
(IUR) data has been received by EPA to date for this chemical.
Lucel-6
According to that same December 17, 1980 letter from Pennwalt to
NIOSH, Lucel-6 was never marketed by Pennwalt.
According to the non-confidential computerized version of EPA's
initial TSCA Chemical Substance Inventory, Pennwalt reported that
in 1977 the company manufactured 0-1000 pounds of Lucel-6 at the
company's facility in Buffalo, New York. No TSCA Inventory Update
Rule (IUR) data has been received by EPA to date for this chemical
substance.
Lucel-7
In 8EHQ-0990-1041, Atochem stated that the company "no longer
manufactures, processes, or distributes Lucel-7. . According
to a November 10, 1980 letter from Pennwalt to NIOSH (found in FYI-
OTS-1080-0095), Pennwalt discontinued all manufacture and sale of
Lucel-7 in 1980 and announced a product recall in that same year.
According to the non-confidential computerized version of EPA's
initial TSCA Chemical Substance Inventory, Pennwalt reported that
in 1977 the company manufactured 0-1000 pounds of Lucel-7 at the
company's facility in Buffalo, New York. No TSCA Inventory Update
Rule (IUR) data has been received by EPA to date for this chemical.
COMMENTS/RECOMMENDATIONS
It is EPA's position that the neurotoxicologic effects observed in
animals and humans following exposure to Lucel-4, Lucel-6, and
Lucel-7 should have been reported in a timely manner to the Agency
under Section 8(e), the "substantial risk" information reporting
provision of TSCA. The following discussion provides the basis for
EPA's position:
721
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Page 15 of 17
TSCA Section 8(e) states, "Any person who manufactures,
[imports,] processes or distributes in commerce a chemi-
cal substance or mixture and who obtains [(i.e., knows of
or possesses)] information which reasonably supports the
conclusion that such substance or mixture presents a
substantial risk of injury to health or the environment
shall immediately inform the [EPA] Administrator of such
information unless such person has actual knowledge that
the Administrator has been adequately informed of such
information."
The preface to Part V of EPA's TSCA Section 8(e) policy
statement ("Statement of Interpretation and Enforcement
Policy? Notification of Substantial Risk" 43 FR 11110;
March 16, 1978) explains that a "substantial risk of
injury to health ... is a risk of considerable concern
because of (a) the seriousness of the effect . . . and
(b) the fact or probability of the occurrence [of that
serious effect]."
With regard to the seriousness of the effect, Part V of
the policy statement explains that EPA considers the
types of health effects for which substantial risk
information must be reported to EPA include " (1) "Any
instance of . . . serious or prolonged incapacitation,
including the loss of or inability to use a normal bodily
function with a consequent relatively serious impairment
of normal activities, if one (or a few) chemical(s) is
strongly implicated" or "(2) Any pattern of effects or
evidence that the chemical substance can produce . . .
toxic effects resulting in . . . serious or prolonged
incapacitation." Information regarding these types of
serious effects can be obtained either directly by the
observation of their occurrence or inferred from designed
studies in humans and/or animals as described in Part VI
of the Section 8(e) policy statement. With regard to
reports/studies of an undesigned, uncontrolled nature
(e.g., reports concerning and evidence of effects in
workers), Part VI states that the Agency anticipates that
"reportable effects will generally occur in a pattern,
where a significant common feature is exposure to the
chemical. However, a single instance of . . . serious
incapacitation in a human would be reportable if one (or
a few) chemical(s) was strongly implicated." As an
example of reportable information, Part VI of the policy
statement presents the following scenario involving
undesigned circumstances:
"A group of exposed workers experiencing
dizziness together with preliminary experi-
mental results demonstrating neurological
dysfunctions."
722
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Page 16 of 17
Part VI of the Section 8(e) policy statement explains
further that a "person is not to delay reporting until he
obtains conclusive information that a substantial risk
exists, but is to immediately report any evidence that
reasonably supports that conclusion."
With regard to the "fact or probability of its [(i.e.,
the serious effect's)] occurrence" criterion, Part V of
the Section 8(e) policy statement explains that certain
types of adverse health effects (e.g., neurotoxicologic
effects) are considered by EPA to be so serious that
relatively little or no weight should be attached to the
implicated chemical's exposure in determining whether a
risk is substantial.
As set out in Part III of the TSCA Section 8(e) policy
statement, a company is regarded as having obtained
substantial risk information at the time any officer or
employee capable of appreciating the significance of that
information obtains (i.e., possesses or knows of) such
information.
Parts III, IV and VIII of EPA's TSCA Section 8(e) policy
statement explain that reportable information "obtained"
by a company includes:
a) information obtained before January 1, 1977
and reviewed after January 1, 1977, but prior
to March 16, 1978 (the publication date of
EPA's TSCA Section 8(e) policy statement);
b) information obtained for the first time after
January 1, 1977 but before March 16, 1978; or
c) information obtained by the company for the
first time after March 16, 1978.
With regard to a) and b) above specifically, Part VIII of
EPA's TSCA Section 8(e) policy statement explains further
that reportable information includes not only written
reports, memoranda and other such documents that were
examined after January 1, 1977, but also information
referred to in discussions and conferences in which a
subject company participated after January 1, 1977.
Based on the preceding TSCA Section 8(e) policy-related discussion
and considering EPA's evaluation of the information contained in
the aforementioned Section 8(e) and FYI files, EPA has made the
following TSCA Section 8(e)-reportability determination:
After January 1, 1977, Pennwalt "obtained" laboratory
animal neurotoxicity information on Lucel-4, Lucel-6 and
Lucel-7, and human neurotoxicity information on Lucel-4
and Lucel-7. The animal and human neurotoxicity findings
723
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Page 17 of 17
for Lucel-4, Lucel-6, and Lucel-7 reasonably support the
conclusion that dermal and inhalation exposure to these
structurally-related chemical substances can result in
serious or prolonged incapacitation, including the loss
of, or the inability to use, a normal bodily function
with a consequent relatively serious impairment of normal
activities.
Therefore, the animal and human neurotoxicity information that was
obtained by Pennwalt prior to March 16, 1978 should have been sub-
mitted under Section 8(e) within 60 days of March 16, 1978; the
animal and human neurotoxicity information obtained by Pennwalt
after March 16, 1978 should have been submitted under Section 8(e)
within 15 working days of the date on which the company obtained
such information.
FURTHER EPA ACTIONS
a) The Chemical Screening Branch will ask Atochem to submit
complete copies of the final reports (including actual
experimental protocols, results of gross/histopathologic
examinations, results of statistical analyses, etc.) from
all studies that were performed by/for Pennwalt or about
which Pennwalt was aware that were conducted to determine
the toxicity of or the exposure to Lucel-4, Lucel-6 and
Lucel-7 to the extent that such study reports are not in
full already in the possession of EPA or the results
published in full in the open scientific literature. The
company will be asked also to report the exact identities
and/or CAS Registry Numbers (if known) for 1) the two
compounds cited in the January 24, 1975 final report of
the 52-week Swiss mouse skin-painting study, and 2) test
compounds l., 2. and 3. in the 28-day rat dermal toxicity
study in which Lucel-7 served as the positive control.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), the Chemical Screening Branch
will continue its review of the reported information in
order to determine the need for further assessment of the
subject chemicals at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA, OCM/OPTS/EPA and
the TSCA Inventory Team/IMD/OTS/OPTS/EPA; copies of this
status report will be provided also to the Environmental
Assistance Division/OTS for further distribution.
724
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
Page 1 of 5
DATE:
OFFICE OF
PESTICIDES AND TOXIC SUBSTANCES
SUBJECT: Status Report 8EHQ-0890-1042
FROM: Frank D. Kover, Chief
Chemical Screening Br
TO: Charles M. Auer, Director
Existing Chemical Assessment Division/OTS
SUBMISSION DESCRIPTION
Atochem North America, Inc. submitted full copies of final reports
from dermal rat teratology and reproduction/fertility studies of
SN5-5698-125 (a mixture of t-butylhydrazine hydrochloride (32%; CAS
No. 7400-27-3) and ferric chloride (9%; CAS No. 7705-08-0); the
balance of the tested mixture was not identified but is assumed to
be water). In addition, Atochem submitted full copies of final
reports from acute animal toxicity studies in which the oral LD50
for t-butylhydrazine hydrochloride was found to be ~800 mg/kg in
rats and ~45 mg/kg in rabbits. Atochem provided the following
summary information with regard to the conduct and results of the
dermal rat teratology and reproduction/fertility studies:
Rat Teratology Study
"In the teratology study, twenty-five inseminated female
rats were dermally exposed to 80, 150 or 800 mg/kg body
weight of the tested substance on gestation days 6-15.
The results showed a statistically significant increased
incidence of incomplete skeletal ossification in the mid-
and high-dose litters, and decreases in fetal body weight
and fetal crown length in the high-dose litters. The study
also showed substantial maternal toxicity, however, with
- This status report is the result of a preliminary evaluation of information that has
been submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substances Control Act (TSCA). The statements made in this status
report should not be regarded as expressing final Agency policy or intent with respect to the
subject chemical(s). Any review of this status report should take into account that the
report may be based on incomplete information.
725
Printed on Recycled Paper
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Page 2 of 5
dermal irritation at all dose levels and a decreased body
weight gain among high-dose animals during exposure to the
substance."
The cover letter accompanying the provided final report noted that
"No definite evidence for any teratogenic effect was obtained at
any dose level studied. . . [In addition, the report stated that
the skeletal findings were considered to be] variations related to
maternal toxicity and stress, and that the decreases in fetal body
weight and length are also considered secondary to maternal
toxicity.M
Rat Reproduction Study
"In the reproductive effects study, twelve male and
twenty-four female rats were given daily dermal
applications of the test substance at dose levels of 50,
160, or 500 mg/kg body weight, beginning nine and two
weeks prior to mating, respectively. The results showed
a dose-dependent decrease in the fertility index of
treated females. It also showed significantly decreased
numbers of corpora lutea, implantations, total and live
fetuses on gestation day 14 and decreased litter size at
birth in high-dose females, and a significantly decreased
number of total and live fetuses present per implantation
site on gestation day 14 at the mid-dose level."
The final report stated that "Taken together, these findings suggest
that ovulation, fertilization or early pregnancy were adversely
affected by repeated dermal exposure to 160 and 500 mg/kg body
weight [of the test compound]. However, maternal stress related to
dermal irritation and body weight loss may have also contributed to
these findings." Atochem also noted that while "t-butylhydrazine
hydrochloride is a minimal to slight skin irritant," ferric chloride
"is very acidic and a severe skin irritant, and thus is a major
cause of the observed dermal responses."
Submission Evaluation
The rat teratology toxicity study provides evidence of maternal
toxicity after dermal exposure to 250 and 800 mg/kg as demonstrated
by a significant reduction in mean body weight; exposure to 800
mg/kg also resulted in clinical signs of toxicity (alopecia and
anorexia). There was also evidence of developmental toxicity after
exposure to doses as low as 250 mg/kg. The exposure to 800 mg/kg
resulted in a significant reduction in mean fetal body weight and
mean fetal crown-rump length. At doses of 250 and 800 mg/kg, there
was a dose-related increase in several skeletal variations (delayed
ossification of the supraoccipital, absent hyoid) ? these differences
were statistically significant in the high dose group. In addition
there was a significant increase in the incidence of a rudimentary
14th rib at 250 mg/kg and a significant incidence of wavy ribs at
800 mg/kg.
726
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Page 3 of 5
The modified one-generation rat reproduction toxicity study provided
evidence of parental systemic toxicity after dermal exposure to 160
and 500 mg/kg as demonstrated by significant reductions in mean body
weights. At the 500 mg/kg dose level, evidence of reproductive
toxicity was observed. Male and female rats at this dose showed a
reduction in the fertility index and the females were found to have
a significant reduction in the number of corpora lutea and implanta-
tions. Histopathologic examination did not reveal any gross male
reproductive system lesions, but it is not clear how complete the
examination actually was. Developmental toxicity was also observed
at 500 mg/kg as evidenced by increased pre- and post-implantation
loss, as well as reduced litter size.
USE AND EXPOSURE POTENTIAL
In its Section 8(e) notice, Atochem stated that t-butylhydrazine
hydrochloride (which is listed on the Agency's non-confidential
initial TSCA Chemical Substance Inventory) is a component of a foam
initiation product marketed by Atochem. Hand-written notations on
the title pages of the rat teratology and reproduction/fertility
studies identify the tested product as "Luperfoam 329." As stated
previously, the tested product is a mixture that reportedly contains
32% t-butylhydrazine hydrochloride and 9% ferric chloride.
COMMENTS/RECOMMENDATIONS
The following discussion pertains to the TSCA Section 8(e)-
applicability/reportability of the findings from the submitted rat
dermal teratology and reproduction/fertility studies:
TSCA Section 8(e) states "any person who manufactures,
[imports,] processes or distributes in commerce a chemi-
cal substance or mixture and who obtains information which
reasonably supports the conclusion that such substance or
mixture presents a substantial risk of injury to health
or the environment shall immediately inform the [EPA]
Administrator of such information unless such person has
actual knowledge that the [EPA] Administrator has been
adequately informed of such information."
The preface to Part V of EPA's TSCA Section 8(e) policy
statement ("Statement of Interpretation and Enforcement
Policy; Notification of Substantial Risk" 43 FR 11110;
March 16, 1978) explains that a "substantial risk of
injury to health . . . is a risk of considerable concern
because of (a) the seriousness of the effect . . . and (b)
the fact or probability of its occurrence." With regard
to the seriousness of the effect, Part V explains that the
Agency considers the types of health effects for which
substantial risk information must be reported to include
"any pattern of effects or evidence that the chemical sub-
stance or mixture can produce . . . birth defects . . .
727
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Page 4 of 5
or serious or prolonged incapacitation." The information
concerning these types of serious effects can be obtained
directly or inferred from designed studies (e.g., studies
in animals) as described in Part VI of the Section 8(e)
policy statement. Part VI explains also that a subject
"person is not to delay reporting until he obtains con-
clusive information that a substantial risk exists, but
is to immediately report any evidence that reasonably
supports that conclusion."
With regard to the "fact or probability of its [(i.e., the
serious effect's)] occurrence" criterion, Part V of the
Section 8(e) policy statement explains that certain types
of adverse health effects (e.g., birth defects) are con-
sidered so serious that relatively little or no weight
should be attached to the tested chemical's exposure in
determining whether a risk is substantial. Further, the
Agency's response to Comment 31 in Appendix B of the TSCA
Section 8(e) policy statement also explains that the
occurrence of serious effects such as those described in
Part V(a) of the policy statement (e.g., birth defects,
serious or prolonged incapacitation) presuppose exposure
to the chemical(s) and must be reported immediately.
Considering the preceding policy discussion and EPA's review of the
information contained in 8EHQ-0890-1042, it is the Agency's position
that the serious adverse reproductive/developmental effects observed
in the two rat dermal studies of Luperfoam 329, which were conducted
for Pennwalt in late 1984, do meet the reporting criteria outlined
in the March 16, 1978 TSCA Section 8(e) policy statement and as such
should have been submitted previously under Section 8(e) of TSCA.
a) in view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Atochem will be asked to describe
the actions the company has taken or plans to take 1) to
notify workers and others about the reported information,
and 2) to reduce or eliminate exposure to the subject
product or its components. Atochem will be asked also to
provide copies of Material Safety Data Sheets and labels
that have been revised to reflect the reported findings.
In addition, the company will be asked to describe the
nature and results, if available, of all studies (other
than those submitted already to EPA or those cited in the
published scientific literature) about which they are
aware or that they have conducted, are conducting or plan
to conduct that are designed to determine the toxicity of
or the exposure to the subject product or its components.
b) As part of the initial phase of the OTS Existing Chemicals
Program (ECP), the Chemical Screening Branch will screen
the reported information to determine the need for further
assessment of the subject product and/or its components.
728
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Page 5 of 5
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and OCM/OPTS/EPA?
in addition, copies of this report will be sent to the
Environmental Assistance Division (EAD/OTS) for further
distribution.
729
-------
Page 1 of 6
132/
% ,c*
PBO1^
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
r/W1/ OFFICE OF
r, Y~) „ 4 J PESTICIDES AND TOXIC
DATE: MAY C 0 !99l APPROVED: ^h &***—¦ SUBSTANCES
SUBJECT: status Report1 8EHQ-0890-1043
FROM: Frank D. Kover, _
Chemical Screening Branch/ECAD
TO: Charles M. Auer, Director
Existing Chemical Assessment Division/OTS
SUBMISSION DESCRIPTION
Atochem North America, Inc. submitted final reports of chronic rat
and dog feeding studies involving diethylaminoethanol (DEAE; CAS
No. 100-37-8). Atochem provided the following summary information
with regard to the conduct and results of these studies which were
performed in the mid-1960s for the Pennsalt Chemicals Corporation :
Rat Study
"In the 2-year rat study, three groups of rats (initially
consisting of 35 males and 35 females each) were fed DEAE
for 24 months at dietary levels of 200, 500, or 1,000 ppm
(periodically increased to 10,000 ppm). At six and twelve
months each, five animals of each sex from each group
were sacrificed and examined. Testicular atrophy was
observed in none of the 34 control groups rats, three of
18 rats at the 200 ppm level, two of 17 rats at the 500
ppm level, and four of 15 rats at the 1,000 ppm level.
The report concluded: 1[I]t appears that testicular
- This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
- The Pennsalt Chemicals Corporation is a forerunner of the Pennwalt Corporation which
is a predecessor of Atochem.
730
Printed on Recy&tj
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Page 2 of 6
atrophy detected within each of the test groups is a
result of the ingestion of the test preparation, associ-
ated with the ageing of the animals since this finding
was not encountered at the six (6) and twelve (12) month
sacrifices. Statistical treatment of this data by means
of a "t" test showed the findings to be significant at
each of the three test levels. The test preparation does
not appear to produce a dose-related effect at the levels
employed for this study.'
"Testicular atrophy in aged rats is a commonly
encountered finding; the absence of it in control animals
in this study is surprising. There is no indication of
the historical incidence of this finding . . . but in
other laboratories similar incidences in control animals
would be within the limits of normal expectation. In the
absence of a dosage-response relationship and given the
normal expectation of testicular atrophy in control
animals, the results do not appear to be of toxicological
significance.11
Dog Study
"In the 1-year dog study, two groups of dogs (consisting
of three males and three females each) were fed DEAE for
365 days at dietary levels of 500 ppm (Group I) and 1000
ppm (Group II), respectively; an additional group (Group
III) was fed DEAE at 5000 ppm in the first 39 days of the
study and at 2,000 ppm to survivors for the 134th day
through termination of the study; and a fourth group
(Group IV) was fed at 10,000 ppm DEAE until the death of
all six animals. The results indicated that dogs of
Groups ill and IV 'exhibited severe cases of weakness,
tremors, convulsions and ataxia,• with two Group III
animals and all Group IV animals succumbing, and that all
animals in Group II 'exhibited at various times tremors
and/or shaking of the head from side to side.'
"Severe toxicity, inappetence and weakness preceded the
death of Group III and IV animals administered 5000 and
10,000 ppm. These effects were so severe that the
survivors at 5000 ppm were returned to a control diet
after 39 days of treatment. The apparent CNS effects
reported cannot be distinguished from generalized
debilitation and malnutrition. The occasional tremors
and/or head shaking noted from the 31st to 40th day of
administration with subsequent recovery in 4 of 6 dogs at
1000 ppm does not appear to display the consistency
normally associated with true CNS effects. In the absence
of histopathological confirmation of a morphological
lesion the observations are considered unlikely to be of
toxicological significance. Moreover, the study indicated
a no-effect level of 500 ppm DEAE, a level far in excess
of any likely human exposure."
731
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SUBMISSION EVALUATION
2-Year Rat Study
The terminal (2-year) sacrifice data from this chronic rat feeding
study provide clear evidence of serious male reproductive system
toxicity following dietary exposure to DEAE at doses as low as 2 00
ppm as demonstrated by a statistically significant incidence of
testicular atrophy and reduced to absent spermatogenesis; similar
effects were not observed in those animals sacrificed following 6
or 12 months of DEAE exposure. Further, there was no conclusive
evidence of female rat reproductive system toxicity after exposure
to the highest DEAE dose tested, which ranged from 1000 to 10,000
ppm over the 2-year study period.
The submitter argues that the observed adverse male reproductive
system effects lack toxicological significance because such effects
are typically seen in historical control animals. EPA believes,
however, that the fact that the concurrent controls in this 2-year
study did not exhibit any adverse testicular effects is overiding
in terms of initial interpretation (and Section 8(e)-reportability)
of the statistically significant incidence of testicular atrophy
and reduced to absent spermatogenesis seen only in the DEAE-exposed
male rats; the historical control data, in this case, may be of
some value in later stages of EPA's assessment of the overall
significance of the observed toxic effects.
1-Year Dog Study
Although the provided information shows that dogs receiving DEAE at
a dietary dose of 500 ppm did not exhibit any gross signs of ill
effects, clear distinguishable clinical signs of neurotoxicity were
seen in the animals in the 1000 ppm and above dose groups. The
gross signs of neurotoxicity observed in the 1000 ppm dose group
dogs included tremors and shaking of the head from side to side;
the dogs in the 5000 and 10,000 ppm groups experienced weakness,
ataxia, tremors and convulsions. Based on the clear clinical signs
of neurotoxicity observed in this chronic feeding study of DEAE in
dogs, it would be of interest to know if the company conducted or
plans to conduct any additional studies designed to assess further
the neurotoxic effects of this chemical substance.
USE AND EXPOSURE POTENTIAL
Atochem reported that DEAE is "a substance marketed by Atochem (and
its predecessor, Pennwalt Corporation) as an indirect food additive
regulated by the [U.S.] Food & Drug Administration and also as an
intermediate in the production of other chemicals." The Condensed
Chemical Dictionary gives the following information on DEAE uses:
"Water-soluble salts; fatty acid derivatives; textile
softeners; pharmaceuticals; anti-rust compositions;
emulsifying agents in acid media; derivatives containing
tertiary amine groups; curing agent for resins."
732
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Page 4 of 6
COMMENTS/RECOMMENDATIONS
Atochem reported that these studies were already submitted "to the
TSCA Interagency Testing Committee [ (ITC)] in response to a Federal
Register Notice seeking information in connection with a possible
DEAE test rule under TSCA Section 4." Atochem stated further that
these studies were also submitted previously to FDA "in connection
with a food additive petition."
It should be noted that the Agency has also received a "For Your
Information" (FYI) submission on DEAE (FYI-OTS-0689-0699 Init.).
The following discussion pertains to the TSCA Section 8(e)-
applicability/reportability of certain serious toxicologic effects
observed in the chronic DEAE feeding studies in rats and dogs:
Section 8(e) states that "Any person who manufactures
processes or distributes in commerce a chemical substance
or mixture and who obtains information which reasonably
supports the conclusion that such substance or mixture
presents a substantial risk of injury to health or the
environment shall immediately inform the Administrator of
such information unless such person has actual knowledge
that the Administrator has been adequately informed of
such information."
The preface to Part V of EPA's TSCA Section 8(e) policy
statement ("Statement of Interpretation and Enforcement
Policy; Notification of Substantial Risk" 43 FR 11110;
March 16, 1978) explains that a "substantial risk of
injury to health ... is a risk of considerable concern
because of (a) the seriousness of the effect . . . and
(b) the fact or probability of its occurrence." With
regard to the seriousness of the effect, Part V explains
that the Agency considers the types of health effects for
which substantial risk information must be reported to
include "any pattern of effects or evidence that the
chemical substance or mixture can produce . . . serious
or prolonged incapacitation." The information concerning
these types of serious effects can be obtained directly
or inferred from designed studies (e.g., studies in
animals) as described in Part VI of the Section 8(e)
policy statement. Part VI explains also that a subject
"person is not to delay reporting until he obtains con-
clusive information that a substantial risk exists, but
is to immediately report any evidence that reasonably
supports that conclusion."
With regard to the "fact or probability of its [(i.e.,
the serious effect's)] occurrence" criterion, Part V of
EPA's TSCA Section 8(e) policy statement explains that
certain types of adverse health effects (e.g., serious or
prolonged incapacitation) are considered by the Agency to
be so serious that relatively little or no weight should
733
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Page 5 of 6
be given to the tested chemical's exposure in determining
whether a risk is substantial. Further, EPA's response
to Comment 31 in Appendix B of the TSCA Section 8(e)
policy statement also explains that the occurrence of
serious effects such as those described in Part V(a) of
the policy statement (e.g., serious or prolonged
incapacitation) presuppose exposure to the chemical
substance(s) and must be reported immediately to the
Agency under Section 8(e) of TSCA.
Parts III, IV and VIII of the TSCA Section 8(e) policy
statement provide the following information with regard
to the time frames for reporting under Section 8(e):
o reportable information that was possessed by a
subject company prior to January 1, 1977 and
reviewed by the company after January 1, 1977,
but before March 16, 1978, should have been
submitted to the Agency within 60 days after
March 16, 1978;
o reportable information possessed by or known
to a subject company for the first time after
January 1, 1977, but before March 16, 1978,
should have been submitted to the Agency
within 60 days after March 16, 1978; and
o reportable information possessed by or known
to a subject company for the first time after
March 16, 1978 should be submitted to EPA
within 15 working days of the date on which
such information was obtained.
Part VIII of the Section 8(e) policy statement explains
further that reportable information includes not only
written reports, memoranda and other such documents
examined by a subject company after January 1, 1977, but
also, for example, information referred to in discussions
and/or conferences in which the company participated
after January 1, 1977, as well as information relating to
a chemical or mixture about which the subject company was
assessing health and/or environmental effects.
With regard to reporting exemptions, Part VII of the TSCA
Section 8(e) policy statement explains, for example, that
information need not be submitted under Section 8(e) of
TSCA if the information has been submitted already to the
Agency under a mandatory reporting provision of TSCA or
some other authority that is administered by the Agency
(e.g., FIFRA, CERCLA). The Section 8(e) policy statement
makes it clear, however, that there is no Section 8(e)
reporting exemption for information that is submitted to
another Federal agency. EPA's response to Comment 21 in
Appendix B of the Section 8(e) policy statement explains
734
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Page 6 of 6
that until successful information exchange systems are in
place and the policy statement is amended to exempt
certain kinds of reports made to other Federal agencies,
"substantial risk information must be reported to EPA."
(emphasis added)
Considering the preceding policy discussion and EPA's evaluation of
8EHQ-0890—1043, it is EPA's position that the serious neurotoxico-
logic and male reproductive system effects observed in the chronic
feeding studies of DEAE in dogs and rats, respectively, do meet the
reporting criteria outlined in the March 16, 1978 TSCA Section 8(e)
policy statement. In view of the fact that these chronic feeding
studies of DEAE were conducted in the mid-1960s, the time frame for
reporting to EPA under Section 8(e) would depend directly on the
date(s) after January 1, 1977 that the company "reviewed" the
results of these particular studies.
a) in view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Atochem will be asked to describe
the actions that the company has taken or plans to take
1) to notify workers/others about the reported findings,
and 2) to reduce or eliminate exposure to DEAE. Atochem
will be asked also to provide copies of Material Safety
Data Sheets and labels that have been revised to reflect
the reported findings. In addition, Atochem will be asked
to describe the nature and results, if available, of all
studies (other than those submitted already to EPA or
those cited in the published scientific literature) about
which Atochem is aware or that the company has conducted,
is conducting or plans to conduct that are designed to
determine the toxicity of or the exposure to DEAE. The
company will be informed that the Agency is especially
interested in the findings from any additional studies
conducted by or for Pennwalt or any of its predecessors
that address or which were designed specifically to
evaluate the neurotoxicity or male reproductive system
toxicity of DEAE.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of DEAE.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and OCM/OPTS? in
addition, copies of this report will be transmitted to
the Environmental Assistance Division/OTS for further
distribution.
735
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
DATE: OCT A !.;cu approved: &/£/o/f/fo
SUBJECT: Status Report1 8EHQ-0890-1044 S
8EHQ-0890-1044 S SUPP.
ryj-cUt&> H LO/lP-*- Cj o
FROM: Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
TO: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS
SUBMISSION DESCRIPTION
The 3M Company submitted final reports of in vitro mutagenicity assays of a compound generically identified
as "tribromomethyl substituted heterocycle." In these studies the compound was "shown to be strongly
positive in the Ames microsomal assay, both with and without activation, and also strongly positive in the
S. cerevisiae recombinogenicity assay, both with and without activation." 3M noted that "this chemical has
been manufactured and used solely as a research chemical by 3M and a small number of customers who
have evaluated paper coated with small amounts of the chemical." 3M then referred EPA to TSCA Section
5 "Low Volume Exemption notices L90-220 and -353 for further information" regarding this chemical.
COMMENTS/RECOMMENDATIONS
3M noted that "as of this date all distribution outside 3M has been halted" and that "customers have been
asked to return any unused product." They also noted that "all persons handling the chemical will be
informed of the findings."
Although a positive in vitro genotoxicity test, when considered alone, may not be sufficient to offer
reasonable support for a conclusion of substantial risk (as that term is defined in EPA's TSCA Section 8(e)
policy statement ("Statement of Interpretation and Enforcement Policy; Notification of Substantial Risk" 43
FR 11110; March 16, 1978)), EPA does believe that such information is of value in assessing the possible
risk(s) posed by exposure to the tested chemical or mixture. Further, EPA believes that a positive
genotoxicity test result, in combination with other information (e.g., knowledge of actual/potential exposure
to and/or high production of the tested chemical or mixture), would suggest the need, in many cases, to
conduct further studies designed to determine the toxicity of or the exposure to that chemical substance or
mixture. EPA expects the results of such additional studies to be considered also for submission under
Section 8(e) of TSCA
Immediately upon receipt of this Section 8(e) submission, the Chemical Screening Branch notified the
Chemical Control Division (CCD/OTS); CCD is responsible for administering EPA's TSCA Section 5 "New
Chemicals Program" (NCP).
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
* This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
736
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8EHQ-0890-1044
Page 2 of 2
As in the case of the initial TSCA Section 8(e) notice, the Chemical Screening Branch will
immediately inform appropriate staff of CCD about the receipt of any further TSCA Section
8(e) data pertaining to the subject chemical.
The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA, CCD/OTS and
OPP/OPTS/EPA; in addition, copies of this status report will be transmitted to the
Environmental Assistance Division/OTS for further distribution.
737
-------
.^osr%
(&)
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 2
DATE:
t3
APPROVED
• If<¦ lJpAn<
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0890-1045
fa
FROM: Paul N. McMahon, Biologist
Chemical Screening Branch/ECAD/OTS
TO: James F. Dan, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
In the initial submission, R. T. Vanderbilt Company, Inc. submitted a draft report of an acute inhalation
toxicology study of VANCIDE MZ-96 {zinc dimethyldithiocarbamate; CAS No. 137-30-4) in rats. According
to the company, the obtained data show that the subject chemical "would be classified as very toxic."
COMMENTS/RECOMMENDATIONS
It was also mentioned in the submission that Vancide MZ-96 is a pesticidal product registered under the
Federal Insecticide, Fungicide and Rodenticide Act (FIFRA). It was further reported that for a commercial
product use subject to TSCA, VANCIDE MZ-96 "is treated with an antidusting oil to minimize the risk of
exposure to airborne dust."
The Agency has received a "For Your Information" (FYI-OTS-0783-0252 et seq.) submission on the test
chemical and a Chemical Hazard Information Profile (CHIP) on this chemical was prepared by the Chemical
Screening Branch (CSB) in 1983.
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final report (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the acute
inhalation toxicology study cited in the submission.
In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity/exposure data, the company will be requested to describe
the actions that it has taken or plans to take 1) to notify workers and others about the
reported data, and 2) to reduce or eliminate exposure to the subject chemical. The
company will be asked to provide copies of Material Safety Data Sheets and labels that
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Tonic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are
available for public inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460.
All requests for TSCA Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
738
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8EHQ-0890-1045
Page 2 of 2
have been revised to reflect the reported findings. In addition, the company will be asked
to describe (by way of short summaries') the nature and results, if available, of all studies
(other than those submitted already to EPA or those cited in the published scientific
literature) about which the company is aware or that it has conducted, is conducting or
plans to conduct that are designed to determine the toxicity of the subject chemical.
As part of the initial phase of OTS Existing Chemicals Program (ECP), staff of the
Chemicals Screening Branch will screen the reported information in order to determine the
need for further assessment of the subject chemical at this time.
The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
739
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
DATE: SEP 13 1980
APPROVED:
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT:
Static Report 1 8EHQ-0890-1046
FROM: Paul N. McMahon, Biologist
Chemical Screening Branch/ECAD/OTS
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
E. I. Du Pont de Nemours & Company submitted preliminary results of a 2-week rat inhalation study with
HCFC-132c (l,l-dichloro-l,2-difluoroethane; CAS No. 1842-05-3). Du Pont reported that "in this study,
male rats were exposed for 6 hours/day, 5 days/week for 2 weeks to HCFC-132c at design concentrations of
0, 400, 2,000 and 10,000 ppm, followed by 2-week recovery period." According to the submission, adverse
male reproductive system effects were observed in this study. In the submission, Du Pont reported that the
subject chemical "is produced only in research quantities and is not used or sold commercially by Du Pont."
COMMENTS/RECOMMENDATIONS
The Agency has received numerous TSCA §8(e) and "For Your Information" (FYI) submissions on
chlorofluorocarbons (CFCs). The Chemical Control Division (CCD/OTS) has been notified about this
TSCA §8(e) submission for inclusion in their ongoing review of chlorofluorocarbons.
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final report (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the
inhalation study cited in the submission.
b) As was the case for the initial submission, the Chemical Screening Branch will immediately
notify CCD/OTS about the receipt of all reported information.
c) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and
CCD/OTS. In addition, copies of this status report will transmitted to the Environmental
Assistance Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are
available for public inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C 20460.
All requests for TSCA Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
740
-------
SU.
I
% -VVI/X. / WASHINGTON, D.C. 20460
\ UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
\ J
PRO^
Page 1 of 2
DATE: SEp 2 /[ ,qqn APPROVED: ^s/ft
PESTICIDES AND TOXIC
3U ywt- SUBSTANCES
SUBJECT: Status Report1 8EHQ-0890-1047 INIT & SUPP
FROM: Paul N. McMahon, Biologist
Chemical Screening Branch/ECAD/OTS
TO: James F. Darr, Section Head, Chemical Risk
Identification Section/CSB/ECAD/OTS
SUBMISSION DESCRIPTION
In the initial submission, the Dow Corning Corporation submitted summarized findings of an acute vapor
phase inhalation limit test of Dow Corning X1-6145A Additive (Hexamethoxydisilylethane; CAS No. 18406-
41-2) in rats. The company's supplemental submission contained a full copy of the final report of this acute
inhalation study. According to Dow Corning, the "results suggest that the test material poses a significant
acute inhalation hazard (LC50 <0.92 mg/L in the Sprague-Dawley rat) under the conditions of this study."
COMMENTS/RECOMMENDATIONS
In its initial submission, Dow Corning stated that the company is notifying customers about the reported
toxicologic findings. In addition, Dow Corning stated that the company will be modifying the Material
Safety Data Sheet (MSDS) to reflect the reported findings. According to the "ABSTRACT" section of the
submitted final report, Dow Corning is planning to conduct a study to determine the acute inhalation LC50
value for the subject chemical in rats.
The Agency has received numerous TSCA §8(e) and "For Your Information" (FYI) submissions on
organosilanes. In 1986, the Chemical Screening Branch prepared a Chemical Hazard Information Profile
(CHIP) on several organosilanes.
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final report (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the
planned LC50 study cited in the submission.
In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity/exposure data, the company will be requested to describe
the actions that it has taken or plans to take to notify its own workers about the reported
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are
available for public inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460.
All requests for TSCA Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
741
Printed on Recycled Pep*'
-------
8EHQ-0890-1047 INIT & SUPP
Page 2 of 2
toxicologic findings, and 2) to reduce or eliminate exposure to the subject chemical. The
company will be asked to provide copies of Material Safety Data Sheets and labels that
have been revised to reflect the reported findings. In addition, the company will be asked
to describe (by way of short summaries) the nature and results, if available, of all studies
(other than those submitted already to EPA or those cited in the published scientific
literature) about which the company is aware or that it has conducted, is conducting or
plans to conduct that are designed to determine the toxicity of the subject chemical.
As part of the initial phase of the OTS Existing Chemicals Program (ECP), staff of the
Chemical Screening Branch will screen the reported information in order to determine the
need for further assessment of the subject chemical at this time.
The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
742
-------
*tD
2 £% \
I | UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
\ no*0 Page 1 of 1
OFFICE OF
SEP I 8 1390 PESTICIDES AND
DATE: APPROVED: toxic substances
SUBJECT: Status Report1 8EHQ-0890-1048 S
H to 1.(2. j- Cj L*D
FROM: Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
TO: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
E. I. Du Pont de Nemours & Company submitted summarized findings of a skin irritation test in rabbits
in which approximately 153-159 mg/kg/body weight of a research and development (R & D) chemical
intermediate identified generically as "alkenoic acid, substituted-, alkyl ester" was applied to the clipped,
intact skin of six New Zealand White rabbits. Du Pont reported that 2/6 rabbits died between 5 and 20
hours after treatment.
COMMENTS/RECOMMENDATIONS
Du Pont indicated that they have notified employees and the study contractor of these test results. In
addition, Du Pont has recommended the use of butyl rubber gloves for hand protection.
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final report (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the study
cited in the submission.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
* This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
polity or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
743
-------
^t0SK%
m
*<¦ PHO^
%
3
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
SEP I 8 iG90 , ,
DATE: APPROVED: Z2je04/^*^
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
OFFICE OF
SEP I 3 1990
APPROVED: 9/h/
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460 „ , , .
Page 1 of 1
WF1CEOF
PESTICIDES ANO
DATE: APPROVED: toxic substances
SUBJECT: Status Report1 8EHQ-0890-1051 S
ht U>'lo+$cJ
FROM: Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
TO: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
The Hoechst Celanese Corporation submitted final reports and/or summarized test results for a battery of
in vitro genetic toxicity tests conducted for the Xerox Corporation with 1,5-naphthalenedisulfonic acid, 2-
((4, 5-dihydro-3-methyl-5-oxo-l-(4-((2-(sulfooxy)ethyl)sulfonyl)phenyl)-lH-pyrazol-4-yl)azo)-, potassium sodium
salt (CAS No. 85940-63-2).
COMMENTS/RECOMMENDATIONS
Although a positive in vitro genotoxicity test, when considered alone, may not be sufficient to offer
reasonable support for a conclusion of substantial risk (as that term is defined in EPA's TSCA Section 8(e)
policy statement ('Statement of Interpretation and Enforcement Policy; Notification of Substantial Risk" 43
FR 11110; March 16, 1978)), EPA does believe thai such information is of value in assessing the possible
risk(s) posed by exposure to the tested chemical or mixture. Further, EPA believes that a positive
genotoxicity test result, in combination with other information (e.g., knowledge of actual/potential exposure
to and/or high production of the tested chemical or mixture), would suggest the need, in many cases, to
conduct further studies designed to determine the toxicity of or the exposure to that chemical substance or
mixture. EPA expects the results of such additional studies to be considered also for submission under
Section 8(e) of TSCA
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final reports (including the actual experimental protocol, data,
results of any statistical analyses, etc.) from the bacterial mutagenicity assay and the
chromosomal aberration assay (of the 50% product) cited in the submission.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
^fc0SX
*t phof ^
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices arc available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
746
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
OFFICE OF
SEP I 3 1990
APPROVED; 9/tsfrc
PESTICIDES AND
DATE:
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0890-1Q52 S
tyj&LtZfb M
FROM: Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
TO: David R, Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
The Rohm and Haas Company submitted summarized findings of a rat acute oral toxicity study conducted
at doses of 1, 2 or 5 g/kg with an exploratory research chemical generically identified as a "halophenyl
substituted monoheterocyclic compound." The following clinical signs indicating possible neurotoxic effects
were observed in treated animals: slow righting reflex, hyperexci lability, teeth grinding and convulsions.
COMMENTS/RECOMMENDATIONS
In the cover letter, Rohm and Haas stated that all personnel who come in contact with the test material
employ appropriate safety procedures designed to preclude any exposure.
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final report (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the study
cited in the submission.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(i). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
747
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v^0 sr„,
vT
PROlt°
Page 1 of 2
/
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
DATE: SEP 2 0 1900 APPROVED: ?A./?c
OFFICE OF
PESTICIDES AND TOXIC
SUBSTANCES
SUBJECT: Status Report1 8EHQ-0890-1053
FROM: Jacqueline T. Favilla, Biologist
Chemical Risk Identification Section/CS®
TO: David R.Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS
SUBMISSION DESCRIPTION
American Cyanamid Company submitted on a non-confidential basis an abstract of a preliminary draft report
of a NIOSH cohort mortality study of 18,254 workers who were exposed to ethylene oxide (CAS No. 75-
21-8) at plants producing sterilized medical supplies and spices. The company stated that preliminary NIOSH
data regarding a statistically significant excess of kidney and hematopoietic cancers were currently undergoing
review with initial statistical calculations being reevaluated.
COMMENTS/RECOMMENDATIONS
The Agency has received numerous TSCA Section 8(e) submissions on ethylene oxide. EPA has also
received a number of "For Your Information" (FYI) submissions on this chemical, including a summary of
the preliminary cohort mortality study from NIOSH (FYI-OTS-0890-0780). In addition, the Chemical
Screening Branch prepared a "Chemical Hazard Information Profile" (CHIP) on ethylene oxide in 1982.
Finally, the Risk Analysis Branch (RAB/ECAD/OTS) is currently evaluating available toxicologic and
exposure information on ethylene oxide, a Toxic Release Inventory (TRI) chemical.
a) The Chemical Screening Branch will request NIOSH to ensure that EPA receives a full copy
of the final report (including the actual experimental protocol, results of any statistical
analyses, etc.) from the NIOSH cohort mortality study cited in the submission.
In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity/exposure data, American Cyanamid will be asked to describe
the actions that it has taken or plans to take 1) to notify workers and others about the
reported findings, and 2) to reduce or eliminate exposure to ethylene oxide. The company
will be asked to provide copies of Material'Safety Data Sheets and labels that have been
revised to reflect the reported findings.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
748
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8EHQ-0890-1053
Page 2 of 2
A copy of the initial Section 8(e) submission, this status report, and all additional reported
information will be provided to the Risk Analysis Branch for inclusion in its ongoing
screening of ethylene oxide.
The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
749
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^t0 sr"v
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
" WASHINGTON, D.C. 20460
% J
pro^ Page 1 of 2
OFFICE OF
• . / /, PESTICIDES AND TOXIC
DATE: OCT 9 1990 APPROVED: Asubstances
SUBJECT: Status Report1 8EHQ-0890-1054 S
FROM: Paul N. McMahon, Biologist (%~Pfl/Mc AiaAv^
Chemical Screening Branch/ECAD/OTS
TO: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
A confidential company submitted summarized findings of an acute rabbit eye irritation study of a compound
generically identified as "Substituted Amine Polymer." The company noted that in past eye irritation studies
the substance "was found to be severely irritating", but it "caused no lethality." "In the present [eye irritation
study] lethality was observed in a few batches. Due to this inconsistency and the batch to batch variability
[the submitter concluded] that the toxicity was caused by a contaminant in the product."
COMMENTS/RECOMMENDATIONS
The company is in the process of characterizing the toxicity of the contaminant and "will submit the results
when they become available." The company has notified their employees and customers of the results of
the above mentioned study, but have "not initiated any changes in [their] standard industrial hygiene
procedures . . ." although they are emphasizing to their customers and employees the precautions
recommended in the MSDS.
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives full copies of the final reports (including the actual experimental protocols, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from all
studies cited in the submission including those involving the contaminant. The submitting
company will also be asked to provide the exact chemical identity, including CAS No. (if
known) of the contaminant.
In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity/exposure data, the company will be asked to provide copies
of Material Safety Data Sheets and labels. In addition, the company will be asked to
describe (by way of short summaries) the nature and results, if available, of all studies
1 Tha s atus report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting
proton of the Toxic Substances Control Act (TSCA). Statements made in this status report should no. be regarded T
final Agency policy or intent with respect to the subject chemical(s). Full copies of nonconfidential Section 8(e) notice? 8
available for public inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S W Washington nr%A^
Ail requests for TSCA Section 8(e) notices should be addressed to EPA's Freedom of Information Office' (A-101) ' ' '
750
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8EHQ-0890-1054
Page 2 of 2
(other than those submitted already to EPA or those cited in the published scientific
literature) about which the company is aware or that it has conducted, is conducting or
plans to conduct that are designed to determine the toxicity of the subject chemicals.
b) As part of the initial phase of the OTS Existing Chemicals Program (ECP), staff of the
Chemical Screening Branch will screen the reported information in order to determine the
need for further assessment of the subject chemicals at this time.
c) The Chemical Screening Branch will send copies of this status report to NIOSH, OS HA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
751
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or
*¦ UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
m.
a
w± WASHINGTON, D.C. 20460 _ ^
V (CS&-
TO: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS
SUBMISSION DESCRIPTION
The Dow Chemical Company submitted preliminary results of a dietary probe study in dogs conducted with
a research and development (R & D) compound identified generically as a "substituted diphenyl ether."
Dow reported that "animals receiving 350 mg/kg/day for one month exhibited decreased body weights,
reduced food consumption and a variety of organ systems effects including degenerative effects in the testes."
COMMENTS/RECOMMENDATIONS
The Dow Chemical Company reported that "this information will be communicated to research personnel
potentially exposed to this compound."
It should be noted here that the Agency has received other TSCA Section 8(e) as well as FYI submissions
on substituted diphenyl ethers.
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final report (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the
study cited in the submission.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
752
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^tos%
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
UK
J WASHINGTON, DC 20460 i> „ « <• 1
Paget of 1
DATE: SEP 2 0 1990 APPROVED: A9&0/4, ^
OFFiCE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0890-1056 S
"") , '/ 'f . y
FROM: Jacqueline T. Favilla, Biologist ' J <-
Chemical Risk Identification Section/CSB'
TO: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS
SUBMISSION DESCRIPTION
The Dow Chemical Company submitted summarized findings of a 1-year chronic dietary toxicity study in
dogs conducted with a research and development (R & D) compound identified genericaliy as a "substituted
diphenyl ether." Dow reports that "animals receiving 25 mg/kg/day were removed from the study for reasons
of morbidity or humane considerations due to dermatitis which apparently became infected by bacterial
organisms resulting in illness and debility."
COMMENTS/RECOMMENDATIONS
The Dow Chemical Company reported that "this information will be communicated to research personnel
potentially exposed to this compound."
It should be noted here that the Agency has received other TSCA Section 8(e) as well as FYI submissions
on substituted diphenyl ethers.
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final report (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the
study cited in the submission.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflect* information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded aa expressing final Agency
policy or intent with respect to the subject chemical(i). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarten, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C 20460. All requests for TSCA
Section 8(e) notice# should be addressed to EPA's Freedom of Information Office (A-101).
753
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i A 4
w
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 2
SEP 2 I 1990 . . 7 .
DATE: APPROVED: J
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHQ-0990-1057
QucUM. M
FROM: Judith M. Loranger, Biologist
Chemical Screening Branch/ECAD/OTS
TO: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
The FMC Corporation submitted preliminary results of an acute rat oral toxicity study of phenol,
isopropylated, phosphate (3:1) (CAS No. 68937-41-7; DuradR 110/KronitexR 50). According to FMC, "one
female exhibited signs of neurotoxicity (tremors and ataxia) between days 1 and 9."
COMMENTS/RECOMMENDATIONS
It should be noted that EPA has received another TSCA Section 8(e) submission on a compound with the
same Chemical Abstract Registry Number (8EHQ-1179-0317 et seq.) and numerous Section 8(e) and "For
Your Information" (FYI) submissions on a variety of aryl phosphate compounds. The Chemical Testing
Branch (CTB/ECAD/OTS) is currently collecting and evaluating information on aryl phosphate compounds.
In addition, it should be noted that numerous aryl phosphate compounds have been the subject of 8(a) and
8(d) information gathering rules.
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final report (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the acute
oral toxicity study cited in the submission.
In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity/exposure data, the company will be requested to describe
the actions that it has taken or plans to take 1) to notify workers and others about the
reported data, and 2) to reduce or eliminate exposure to the subject chemical. The
company will be asked to provide copies of Material Safety Data Sheets and labels that
have been revised to reflect the reported findings. In addition, the company will be asked
to describe (by way of short summaries') the nature and results, if available, of all studies
(other than those submitted already to EPA or those cited in the published scientific
literature) about which the company is aware or that it has conducted, is conducting or
plans to conduct that are designed to determine the toxicity of the subject chemical.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are
available for public inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460.
All requests for TSCA Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
754
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8EHQ-0990-1Q57
Page 2 of 2
As was the case for the initial submission, the Chemical Screening Branch will notify the
Chemical Testing Branch about the receipt of any additional incoming information on aryl
phosphate compounds.
The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and
CTB/ECAD/OTS; in addition, copies of this status report will be transmitted to the
Environmental Assistance Division/OTS for further distribution.
755
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
Page 1 of 1
OFFICE OF
PESTICIDES AND TOXIC
SUBSTANCES
DATE:
OCT I 2 1990 APPROVED: /*//f/fq
SUBJECT: Status Report1 8EHQ-0990-1058 S
FROM: Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
TO: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS
SUBMISSION DESCRIPTION (See NOTE Below)
A confidential company submitted summarized results of two oral rat range-finding studies on two different
formulations of an "unregistered pesticide" generically identified as Vcyano carbocycliccarboxylate." In both
range-finding studies, the test compound was administered to one male and one female rat at dose levels of
50, 500, 1000, 2500 or 5000 mg/kg. The submitter reported that the LD^q values for both studies were at or
below 50 mg/kg, "a level considered to be highly toxic."
COMMENTS/RECOMMENDATIONS
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives full copies of the final reports (including the actual experimental protocols, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the oral
rat range-finding studies cited in the submission.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
NOTE In a December 14,1990 followup letter (8EHQ-1290-1058 FLWP), the FMC Corporation
reported non-confidentially that it was the submitter of this TSCA Section 8(e) submission.
1 This statu* report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Pull copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
756
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 2
DATE
OCT I 7 1990
APPROVED: J
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
SUBJECT: Status Report1 8EHO-0990-1059 S
A/ O
FROM: Judith M. Loranger, Biologist
Chemical Screening Branch/ECAD/OTS
TO: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
A confidential company provided summarized results of two rabbit eye irritation studies with a compound
generically identified as an "alkaline oxidizer." In both studies, treatment-related signs of toxicity included:
"severe corneal opacity, severe conjunctival irritation ... and no reaction to light in the iris." The submitter
reported that "based on the test results from the two studies, [the test compound] was judged to be corrosive
since it produced damage which was considered to be irreversible."
COMMENTS/RECOMMENDATIONS
Although EPA is concerned in general about the acute toxicity of chemicals, it is not entirely clear to EPA
that the acute toxicologic findings, as presented in this Section 8(e) submission, warranted reporting under
Section 8(e) of TSCA. In making this initial statement about TSCA Section 8(e)-reportability, it must be
noted that EPA has not received copies of the final reports of the subject studies, nor is EPA aware of any
additional information that may have been available to or considered by the company in deciding to report
the subject findings formally under Section 8(e) of TSCA.
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives full copies of the final reports (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the eye
irritation studies cited in the submission. The submitter will also be asked to report the
pH of this alkaline oxidizer.
In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity/exposure data, the company will be requested to describe
the actions that it has taken or plans to take 1) to notify workers and others about the
reported data, and 2) to reduce or eliminate exposure to the subject chemical. The
company will be asked to provide copies of Material Safety Data Sheets and labels that
have been reivsed to reflect the reported findings. In addition, the company will be asked
* This status report reflect! information submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substance* Control Act (TSCA). Statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are
available for public inspection at EPA Headquarter*, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C 20460.
All requests for TSCA Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
757
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8EHQ-0990-1059 S
Page 2 of 2
to describe (by way of short summaries') the nature and results, if available, of all studies
(other than those submitted already to EPA or those cited in the published scientific
literature) about which the company is aware or that it has conducted, is conducting or
plans to conduct that are designed to determine the toxicity of or the exposure to the
subject chemical.
b) As part of the initial phase of the OTS Existing Chemicals Program (ECP), staff of the
Chemical Screening Branch will screen the reported information in order to determine the
need for further assessment of the subject chemical at this time.
c) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
758
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^l0sr%
^ ri
m
e UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
T
* —¦—WASHINGTON, D.C. 20460
% ^ PaSe 1 of 1
OFFICE OF
PESTICIDES AND TOXIC SUBSTANCES
SEP 2 0 KJ9Q • , /
DATE: APPROVED: /D@i6Ut<d
FROM: Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
TO: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS
SUBMISSION DESCRIPTION
A confidential company submitted summary results of acute toxicity and irritation studies on a R & D
compound generically identified as "haloalkyl amine II." The submitter reported that the oral and dermal
LD5Q values were <50 mg/kg and <200 mg/kg, respectively. The company indicated that "the compound
also proved to be toxic when placed in the conjunctival sac of the rabbit eye" but "is non-irritating to the
skin."
COMMENTS/RECOMMENDATIONS
It should be noted that the Agency has received another TSCA Section 8(e) submission on a compound
identified as a haloalkyl amine (8EHQ-0790-1025 S Init.).
The company reported that "appropriate personal protective measures, engineering controls and waste
disposal procedures are utilized by the researchers in order to effectively control and minimize human and
environmental exposure to this chemical." In addition, the submitter stated that "all potentially exposed
workers have been notified of the" results of the studies.
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives full copies of the final reports (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the
studies cited in the submission.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
^ This status report reflects information submitted to EPA under Section 8(e), the "substantia! risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
759
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sr4f
I 1 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
%, ,
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8EHQ-0990-1061
Page 2 of 3
labels that have been revised to reflect the reported findings. In addition, the company will
be asked to describe (by way of short summaries') the nature and results, if available, of all
studies (other than those submitted already to EPA or those cited in the published scientific
literature) about which the company is aware or that it has conducted, is conducting or
plans to conduct that are designed to determine the toxicity of the subject chemical.
b) As part of the initial phase of the OTS Existing Chemicals Program (ECP), staff of the
Chemical Screening Branch will screen the reported information in order to determine the
need for further assessment of the reported findings.
c) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
Attachment
761
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8EHQ-0990-1061
Page 3 of 3
ATTACHMENT I
Materi al:
Laboratory:
Test Species:
Routes:
],4-Hexadiene (99% cis)
Exxon Biomedical Sciences, Inc.
East Millstone, New Jersey
B603F1 mice and Crl CDBR rats (Tales only)
Inhalation (rats and mien)
Oral Gavage (mice only)
Dose Groups and Findings:
A. Inhalation Study - 6 hours/day for 2 days
Concentration
(vol. ppm in air)
10,000
3,260
1,000
Portalitv
Rats
0/4
0/4
0/4
Mice
4/4
4/4
0/4
B. Oral Gavage Study - Single dose in ethanol
1,4-Hexadiene
Dose
(ml/kg)
1.5
0.75
0.15
0.0
Ethanol
£amsr
(ml/kg)
p. 5
1.25
1.85
2.0
Mortalitv
Mice
4/4
1/4
2/4
0/4 "
762
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
Page 1 of 3
DATE:
SEP 2 6 1990
approved: ^
OFFICE OF
PESTICIDES AND TOXIC
SUBSTANCES
SUBJECT: Status Report1 8EHQ-0990-1062
f)tccLcLl // A.Q.-i
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8EHQ—0990-1062
Page 2 of 3
clinical chemistry, and necropsy examination. In
comparison to the control group, all male rats in the
DIPK-exposed groups exhibited an increase in the number
and severity of intracellular hyalin droplets accum-
ulating in the proximal convoluted tubules of the
kidneys. Mean absolute and relative liver weights were
significantly (p<0.05) heavier for the male and female
1221 ppm DIPK groups. In the 1221 ppm groups, hepatocyte
hypertrophy was observed in four male and all female
rats. Although mean absolute (female) and relative (male
and female) liver weights were significantly (p<0.05)
heavier for the 386 ppm DIPK groups in comparison to the
control groups, the differences were very slight, and no
microscopic evidence of hypertrophy was evident. The
no-observed-effect level for this study was considered
to be close to, but below 128 ppm DIPK based on accum-
ulation of renal hyalin droplets. The no-observed-adverse
-effect level was considered to be 386 ppm DIPK based on
increased liver weights."
In addition, Eastman Kodak provided summary information from an
acute oral toxicity study in rats, a dermal toxicity study in rats,
a dermal irritation study in guinea pigs, an eye irritation study
in rabbits and a skin sensitization study in guinea pigs. Eastman
Kodak reported that "the test article was slightly toxic by the
oral route with an estimated oral LD50 of 3536 mg/kg in rats. When
applied to the skin, the test article had an estimated acute lethal
dose of greater than 20 ml/kg for rats and did not produce abnormal
clinical signs. The test article was a slight skin irritant,
producing only slight erythema at the site of application. It was
not a skin sensitizer. When placed in the eye, the test article
produced only slight irritation."
Eastman Kodak reported that this new toxicity information has been
incorporated into the DIPK Material Safety Data Sheet (MSDS).
USE AND EXPOSURE POTENTIAL
Eastman Kodak stated that they produce crude and refined grades of
DIPK. The crude DIPK, "a co-product stream from another operation,
has been sold as a boiler fuel or as an octane improver' for blend-
ing into gasoline." Eastman Kodak reports that the production
volume ranged from 125,000-300,000 kg/yr. Eastman Kodak reports
that "refined DIPK-SG (the material used for toxicity testing)...
has been sold to a limited number of customers as a specialty
process solvent intended for use in closed systems, or as a
chemical intermediate.M
Eastman Kodak stated that DIPK production, drumming and tank truck
loading operations are located outdoors. In addition, sampling
764
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and truck loading operators reportedly "wear impervious gloves" and
"operators drumming DIPK-SG use cross-ventilation fans and wear
impervious gloves."
COMMENTS/RECOMMENDATIONS
In addition to providing copies of the revised DIPK MSDS and
modified product label statements, Eastman Kodak reported that
their customers will be notified of the reported findings.
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Eastman Kodak will be requested
to describe the actions that the company has taken or
plans to take to notify its own workers about the
reported information.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
compound at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
765
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$ £5
iSS/
%
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON DC 20460 Page 1 of 1
otr c I i;; " > - . /
DATE: APPROVED: 9M
SUBJECT: Status Report1 8EHQ-0990-1063
FROM: Judith M. Loranger, Biologist
Chemical Screening Branch/ECAD/OTS
TO: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
On behalf of a number of companies (*), the Industrial Health Foundation, Inc. submitted summarized
preliminary findings from an oral two-generation Sprague-Dawley rat reproductive toxicity study of
methylethylketoxime (MEKO; CAS No. 96-29-7) conducted as part of a TSCA §4 test rule. According
to the submitter, mortality occurred among the high dose (200 mg/kg/day) males and females by the end
of the eighth week prior to mating; the low and mid doses in this study are 50 and 100 mg/kg/day. The
submitter noted that a 1977 study of MEKO also conducted in Sprague-Dawley rats did not show any
mortality after 13 weeks at oral doses of 225 mg/kg/day. The submitter also noted that the "only
difference between the studies to this point is that the early study used methyl cellulose solution as the
vehicle whereas the current study uses water solutions." Finally, the submitter stated that while the data
from the present MEKO study are unexpected and currently unexplainable, the data do suggest "a
greater degree of sub-acute toxicity from MEKO than previously inferred."
COMMENTS/RECOMMENDATIONS
It should be noted that EPA has received a "For Your Information" submission (FYI #763) on MEKO.
In addition, EPA has issued TSCA §§ 8(a) and 8(d) rules on this chemical. Also, the Chemical Testing
Branch (CTB/ECAD/OTS) is evaluating available toxicological and exposure information on MEKO
under TSCA §4.
a) As was the case for the initial submission, the Chemical Screening Branch will provide a
copy of this status report to the Chemical Testing Branch.
b) The Chemical Screening Branch will also send copies of this status report to NIOSH,
OSHA, CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and
OPP/OPTS/EPA; in addition, copies of this status report will be transmitted to the
Environmental Assistance Division/OTS for further distribution.
(*) Allied-Signal, Inc.; Huls America, Inc.; AKZO Chemicals, Inc.; Aceto Corporation;
Mooney Chemical Inc.; Troy Chemical Company; and Dussek Campbell Ltd.
1 This status report reflects information submitted to EPA under Section 8{e), the "substantial risk" information reporting
provision of the Ta»c Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are
available for public inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460.
All requests for TSCA Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
766
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| UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
-VIV- T WASHINGTON, D.C. 20460
% ' ,/
^ PRC**-
Page 1 of 3
OFFICE OF
PESTICIDES AND TOXIC
SUBSTANCES
DATE: SEP 2 6 1990 APPROVED:
SUBJECT: status Report1 8EHQ-0990-1064
FROM: Paul N. McMahon, Biologist -
Chemical Risk Identification Section/CSB
TO: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
Union Carbide Chemicals and Plastics Company, Inc. submitted
preliminary results of a mouse oral developmental toxicity study
using triethylene glycol (CAS No. 112-27-6). The submitting
company provided the following summary information regarding the
conduct and preliminary results of this developmental study:
"Three groups each containing 30 plug-positive CD(TM)-
1 mice, were given undiluted triethylene glycol by gavage
on gestational days 6 through 15 at doses of 0.5, 5.0 and
10.0 ml/kg/day. An additional control group of 30
pregnant CD(TM)-1 mice were given deionized water at a
dosage of 10 ml/kg/day."
nl) Signs of maternal toxicity were present at 10.0 ml
kg' , in the form of hypoactivity and rapid audible
breathing.
"2) Maternal relative kidney weight (but not absolute
weight) was increased at 10 ml kg . . . Histology of the
kidneys was normal.
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
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" 3) Fetal body weights (male, female, and combined)
were statistically significantly reduced at 5.0 and
10.0 ml kg"1 . . . [The] gravid uterine weight showed a
dose-related, though not statistically significant,
decrease with increasing dosage.
"4) Statistically significant and dose related increases
were seen in the incidence of six skeletal variants at
10.0 ml kg"1 [poorly ossified cervical centra, reduced
number of caudal segments, proximal phalanges unossified,
proximal phalanges poorly ossified, poorly ossified
frontal bone, and poorly ossified supraoccipital bone]
and two skeletal variants at 5.0 ml kg'1 [poorly ossified
frontal bone and poorly ossified supraoccipital bone]."
The company summarized the above results by stating that, ". . .
mice receiving undiluted triethylene glycol . . . over the period
of organogenesis showed evidence of maternal toxicity at 10.0 ml
kg" , and developmental toxicity (fetotoxicity) in the form of
reduced fetal weights and skeletal variations at 5.0 and 10.0 ml
kg ." The no-effect dosage level was reported to be 0.5 ml kg"1.
USE AND EXPOSURE POTENTIAL
The Condensed Chemical Dictionary (10th Edition) states that
triethylene glycol is used as "[a] solvent and plasticizer in
vinyl, polyester and polystyrene resins; dehydration of natural
gas; humectant in printing inks; [and as an] extraction solvent."
COMMENTS/RECOMMENDATIONS
In its submission, Union Carbide stated that " [it] is in the
process of informing our customers and employees that [Union
Carbide is] reporting to the EPA under TSCA Section 8(e) the
information discussed herein."
It should be noted that the EPA has received a TSCA § 8(e)
submission (8EHQ-0290-0693 Supplement) and a "For Your Information"
(FYI) submission (FYI-OTS-0483-0240 Initial) on triethylene glycol.
a) The Chemical Screening Branch will ask Union Carbide to
ensure that EPA receives a complete copy of the final
report (including the actual experimental protocol,
results of gross and histopathological examinations,
results of statistical analyses, etc.) from the
developmental toxicity study cited in the submission.
768
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8EHQ-0990-1064
Page 3 of 3
In view of epa's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, Union Carbide will be requested
to describe the actions that the company has taken or
plans to take to reduce or eliminate exposure to the
subject chemical. Union Carbide will be asked also to
provide copies of Material Safety Data Sheets and labels
that have been revised to reflect the reported findings.
In addition, Union Carbide will be asked to describe the
nature and results, if available, of all studies (other
than those submitted already to EPA or those cited in the
published scientific literature) about which Union
Carbide is aware or that the company has conducted, is
conducting or plans to conduct that are designed to
determine the toxicity of or the exposure to the subject
chemical.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition,
copies of this status report will be transmitted to the
Environmental Assistance Division/OTS (formerly the TSCA
Assistance Office/OTS) for further distribution.
769
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S/4;v
ST
SSI
- - ,p
^ PRO1^
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF
PESTICIDES AND TOXIC
SUBSTANCES
8EHQ-0990-1065
NOTE: For the "status report" pertaining to 8EHQ-0990-1065,
the reader's attention is directed to the status report
prepared for 8EHQ-0890-1041.
770
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\ UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
—'/
PROlt
/ WASHINGTON, D.C. 20460
Page 1 of 1
DATR: OCT 9 !99f) APPROVFn- ^ /o/
-------
^tD s^.
JGL 5 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
VW7 ? WASHINGTON, D.C. 20460
OV* Page 1 0f 2
^ PRO1^
OCT 41990 - - / /,
DATE: APPROVED: /°/?/7o office of
PESTICIDES AND TOXIC
SUBSTANCES
SUBJECT: Status Report1 8EHQ-0990-1067
FROM: Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
TO: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS
SUBMISSION DESCRIPTION
The Dow Corning Corporation submitted a final report covering two bacterial reverse mutation assays
conducted with (3-chloropropyl)trimethoxysilane (DOW CORNING* Ql-2366 Silane) (CAS No. 2530-87-
2). In the cover letter, it was noted that a significant increase in revertant colonies was noted, indicating
that the test material "is considered mutagenic."
CQMMENTS/RECOMMENDATTONS
It should be noted that EPA has received other TSCA Section 8(e) submissions on this chemical (8EHQ-
1089-0780,8EHQ-1289-0780, 8EHQ-0190-0780, and 8EHQ-0690-0780) and numerous Section 8(e) and "For
Your Information" (FYI) submissions on a variety of silane compounds. A Chemical Hazard Information
Profile was prepared in 1986 on several organosilane compounds.
Although a positive in vitro genotoxicity test, when considered alone, may not be sufficient to offer
reasonable support for a conclusion of substantial risk (as that term is defined in EPA's TSCA Section 8(e)
policy statement ("Statement of Interpretation and Enforcement Policy; Notification of Substantial Risk" 43
FR 11110; March 16, 1978)), EPA does believe that such information is of value in assessing the possible
risk(s) posed by exposure to the tested chemical or mixture. Further, EPA believes that a positive
genotoxicity test result, in combination with other information (e.g., knowledge of actual/potential exposure
to and/or high production of the tested chemical or mixture), would suggest the need, in many cases, to
conduct further studies designed to determine the toxicity of or the exposure to that chemical substance or
mixture. EPA expects the results of such additional studies to be considered also for submission under
Section 8(e) of TSCA
1 This Status report reflects information submitted lo EPA under Section 8(e), the "substantial risk" information reporting provision
of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing final Agency
policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available for public
inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460. All requests for TSCA
Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
772
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In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity/exposure data, the company will be requested to describe
the actions that it has taken or plans to take 1) to notify workers and others about the
reported data, and 2) to reduce or eliminate exposure to the subject chemical. The
company will be asked to provide copies of Material Safety Data Sheets and labels that have
been revised to reflect the reported findings. In addition, the company will be asked to
describe the nature and results, if available, of all studies (other than those submitted
already to EPA or those cited in the published scientific literature) about which the
company is aware or that it has conducted, is conducting or plans to conduct that are
designed to determine the toxicity of the subject chemical.
As part of the initial phase of the OTS Existing Chemicals Program (ECP), staff of the
Chemical Screening Branch will screen the reported information in order to determine the
need for further assessment of the subject chemical at this time.
The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
773
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'b
u UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
* WASHINGTON, D.C. 20460 PaSe 1 of 1
*i pqo^
DATE OCT I 2 1990 APPROVED: /e/syVo
SUBJECT: Status Report1 8EHQ-0990-1068 office of
PESTICIDES AND TOXIC
SUBSTANCES
FROM: Judith M. Loranger, Biologist Qv-cLCtfu M xCk^ji
Chemical Screening Branch/ECAD/OTS ^
TO: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION (See NOTE Below)
Pfister Chemical, Inc. submitted the final report of a rabbit eye irritation study conducted on 4-(dimethyl
amino) benzenediazonium-5-sulfosalicyIate (Diazo 8 SS; no known CAS No.). According to Pfister, this rabbit
eye irritation study was conducted on Diazo 8 SS "as a part of a TSCA Section 5(a) premanufacture notice
(PMN) submission." Pfister reported that "the results of the study indicated that four of the six test rabbits
died within 24 hours after application of the test compound to the eyes. The remaining two rabbits were
moribund and were sacrificed... On necropsy of the two moribund test animals, one exhibited discolored
kidneys and hemorrhagic patches in the colon."
COMMENTS/RECOMMHNDATTONS
a) In view of EPA's general interest in company actions that are taken on a voluntary basis in
response to chemical toxicity/exposure data, the company will be requested to describe the
actions that it has taken or plans to take 1) to notify workers and others about the reported
data, and 2) to reduce or eliminate exposure to the subject chemical. The company will be
asked to provide copies of Material Safety Data Sheets and labels that have been revised to
reflect the reported findings.
b) As was the case for the initial submission, the Chemical Screening Branch will notify the
Chemical Control Division of the receipt of incoming information; CCD is responsible for
administering the OTS TSCA Section 5 "New Chemicals Program" (NCP).
c) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA ORD/EPA, OAR/EPA OPP/OPTS/EPA and
CCD/OTS; in addition, copies of this status report will be transmitted to the Environmental
Assistance Division/OTS for further distribution.
NOTE According to an MSDS provided by Pfister in a November 20,1990 letter (8EHQ-1190-1068
FLWP), the CAS No. for the subject chemical is 124737-31-1.
JL. a. T ulfki
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substances Control Act (TSCA). Statements made in this statu* report should not be regarded as expressing
final Agency polity or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are available
for public initpw'i™ at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C 20460. All
requests for TSCA Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
774
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**i0sr4>*
g UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
«. AAIAZ- J WASHINGTON, D.C. 20460
\ rf
¦*' PRO^
Page 1 of 2
DATE: n , | |0 APPROVED: /&//o/fo
SUBJECT: Status Report1 8EHQ-0990-1069
OFFICE OF
PESTICIDES AND TOXIC
SUBSTANCES
FROM: Paul N. McMahon, Biologist /V /^c
Chemical Screening Branch/ECAD/OTS
TO: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
Mitsubishi Yuka America, Inc. submitted a final report of a guinea pig dermal sensitization study with a
compound identified by the trade name MP-2000 or MP-200Qx. The company noted that the test compound
is a "condensate of aniline, o-toluidine and terephalaldehyde reaction product with maleic anhydride." Test
animals were exposed to the following concentrations of the test compound: 25% (w/v) by intradermal
induction, 50% (w/w) by topical induction, 50% (w/w) by topical challenge, and 25% and 50% (w/w) for
topical rechallenge. According to the submitter "The test compound produced a 80% (16/20) sensitisation
rate", which indicates that it is "a strong sensitiser to guniea pig skin." (see NOTE on page 2)
COMMENTS/RECOMMENDATIONS
The submitter also stated non-confidentiallly that the test compound was the subject of a Pre-Manufacturing
Notice CPMN P88-426~> under TSCA § 5. The submitter reported that this compound is only manufactured
in Japan at this time and has not been imported to the United States.
a) In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity/exposure data, the company will be requested to describe
the actions that it has taken or plans to take 1) to notify workers and others about the
reported data, and 2) to reduce or eliminate exposure to the subject chemical. The
company will be asked to provide copies of Material Safety Data Sheets and labels that
have been revised to reflect the reported findings. In addition, the company will be asked
to describe (by way of short summaries) the nature and results, if available, of all studies
(other than those submitted already to EPA or those cited in the published scientific
literature) about which the company is aware or that it has conducted, is conducting or
plans to conduct that are designed to determine the toxicity of the subject chemical.
* This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are
available for public inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460.
All requests for TSCA Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
775
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8EHQ-0990-1069
Page 2 of 2
b) As part of the initial phase of the OTS Existing Chemicals Program (ECP), staff of the
Chemical Screening Branch will screen the reported information in order to determine the
need for further assessment of the subject chemical at this time.
c) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and
CCD/OTS/OPTS; in addition, copies of this status report will be transmitted to the
Environmental Assistance Division/OTS for further distribution.
NOTE In a non-confidential supplemental letter dated November 6,1990 (8EHQ-1190-1069 SUPP),
Mitsubishi Yuka America, Inc. provided a copy of a Material Safety Data Sheet (MSDS)
for the tested chemical substance. According to the submitted MSDS, the subject chemical
has the following CAS Registry Number: 129217-90-9.
776
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Ui
O
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 1
WASHINGTON, D.C. 20460
% *,0^
OFFICE OF
PESTICIDES AND TOXIC SUBSTANCES
DATE: OCT 17 1990 APPROVED: ^c/,7/?o
SUBJECT: Status Report1 8EHQ-0990-1070 S
FROM: Paul N. McMahon, Biologist /V
Chemical Screening Branch/ECAD/OTS
TO: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
A confidential company submitted summarized results and a final report of a 28-day rat feeding study of an
R&D pesticide candidate generically identified as a "substituted nitrobenzene." The dose levels for the
study were 0, 10, 100, 1000 or 10,000 ppm. The submitter noted that "the principal toxicological effect in
[the] study was ... lesions of the cornea and iris [which] were evident at levels of 10 ppm or more." It was
also noted that "in males, the incidence of these lesions over the range 10-10,000 ppm was similar whereas
in females the incidence was dose-dependent."
COMMENTS/RECOMMENDATIONS
The Agency has received several TSCA § 8(e) submissions on compounds generically identified as
"substituted nitrobenzenes." The submitter also stated that they "are notifying all persons engaged in the
evaluation of this class of compounds of these results ..." and that "personal protection and work practices
will be evaluated and modified if necessary."
The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA, CPSC, FDA, NTP,
OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition, copies of this status
report will be transmitted to the Environmental Assistance Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemica!(s). Full copies of non-confidential Section 8(e) notices are
available for public inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460.
All requests for TSCA Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
777
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.\l£D sr-(/v
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
vWv * WASHINGTON, D.C. 20460
\ PROit° Page 1 of 1
DATE: OCT 22 1990 APPROVED: ZtfTSfrtfTl. V
SUBJECT: Status Report1 8EHQ-0990-1071
FROM: Paul N. McMahon, Biologist
Chemical Screening Branch/ECAD/OTS
TO: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
OFFICE OF
PESTICIDES AND TOXIC
SUBSTANCES
Motorola Inc. submitted a summarized account of employee complaints following exposure to Multicore
Solder X32B (comprised of 37% Lead; CAS No. 7439-92-1, 63% Tin; CAS No. 7440-31-5, and other
proprietary materials) and Multicore TTC-1 Tip Tinner (comprised of between 50 to 60% Lead and 30 to
40 % Tin). Both of the above mentioned products are manufactured by Multicore Solders, Inc. and not by
the submitter. Motorola noted that "effects . . . may have been caused by either one or both of the
materials . . Some of the employee complaints associated with the use of these products included:
headache, nausea, coughing, shortness of breath, bronchitis, irritated eyes, dizziness, stomach pain, fatigue,
and disorientation.
COMMENTS/RECOMMENDATIONS
Motorola submitted copies of the Material Safety Data Sheets (MSDS) for both products and they noted
thai "[Motorola] removed these materials from manufacturing use at this facility." The Chemical Control
Division (CCD/OTS) has been notified about this TSCA § 8(e) submission for inclusion in their ongoing
review of Lead-containing Solder.
a) In view of the EPA's interests in effective and appropriate hazard/risk communication, as
well as company actions taken on a voluntary basis in response to new chemical
toxicity/exposure data, Motorola will be requested to ensure that EPA is apprised of any
further significant information obtained by the company regarding the observed adverse
human health effects.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA OPP/OPTS/EPA and
CCD/OTS/OPTS; in addition, copies of this status report will be transmitted to the
Environmental Assistance Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded a* expressing
final Agency policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are
available for public inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460.
All requests for TSCA Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
778
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 2
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
DATE:
SUBJECT: Status Report1 8EHQ-0990-1072
FROM: Judith M. Loranger, Biologist
Chemical Screening Branch/ECAD/OTS
TO: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
The General Electric Company submitted the preliminary results of a medical examination program involving
company workers who reportedly "have variable exposure to a number of chemical additives used in a resin
compounding operation." An attached company communication reported the observation of "an excess of
an abnormal thyroid function tests (TSH) in the borderline hypothyroid range.. .[that] occurred in 9 of 42
individuals in the exposed group as compared to 1 of 15 individuals in the reference group." General Electric
Company reported that "if there is a workplace association, then it may be related to the use of brominated
flame retardants such as octabromodiphenyl ether, CAS No. 32536-52-0." Also in this submission, General
Electric Company provided a copy of a published article entitled "Hypothyroidism in Workers Exposed to
Polybrominated Biphenyl" (A.K. Bahn et al., New England Journal of Medicine, Vol. 302, No. 1, pages
31-33, Jan. 3, 1980).
COMMENTS/RECOMMENDATIONS
It should be noted that EPA has received a number of TSCA Section 8(e) submissions on brominated flame
retardants, including octabromodiphenyl ether. Octabromodiphenyl ether is also the subject of TSCA
Section 8(a) and 8(d) information gathering rules. In 1986, a Chemical Hazard Information Profile (CHIP)
was completed on a number of brominated diphenyl ethers, including octabromodiphenyl ether. Immediately
upon receipt of this Section 8(e) submission, the Chemical Screening Branch notified the Chemical Testing
Branch (CTB/ECAD/OTS); CTB is currently collecting and evaluating information on octabromodiphenyl
ether.
General Electric Company reported that "retests to confirm the observation and identify any intercurrent
disease will be conducted."
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives full copies of the "retests" cited in the submission.
* This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substance* Control Act (TSCA). Statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are
available for public inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460.
All requests for TSCA Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
779
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8EHQ-0990-1072
Page 2 of 2
In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity/exposure data, the company will be requested to describe
the actions that it has taken or plans to take 1) to notify workers and others about the
reported data, and 2) to reduce or eliminate exposure to the subject chemicals. The
company will be asked to provide copies of Material Safety Data Sheets and labels that
have been revised to reflect the reported findings.
As in the case of the initial TSCA Section 8(e) submission, the Chemical Screening Branch
will immediately inform appropriate staff of CTB about the receipt of any additional
incoming information.
The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and
CTB/OTS; in addition, copies of this status report will be transmitted to the Environmental
Assistance Division/OTS for further distribution.
780
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
OFFICE OF
PESTICIDES AND
OCT I 7 8S0
TOXIC SUBSTANCES
DATE:
APPROVED: AW/v/yc
SUBJECT: Status Report1 8EHQ-0990-1073 S
FROM: Judith M. Loranger, Biologist
Chemical Screening Branch/ECAD/OTS
TO: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
A confidential submitter provided summarized preliminary results of a rat teratology study of an R&D
compound genetically identified as an "aryloxy-substituted benzenamine II." In this study, the test compound
was administered by gavage to mated female rats at dose levels of 0, 100, 300 or 1000 mg/kg/day during
gestation days 6-15.
COMMENTS/RECOMMENDATIONS
It should be noted that EPA has received a TSCA Section 8(e) submission on a compound generically
identified as an "aryloxy substituted benzenamine" (8EHQ-0790-1026 S).
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final report (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the study
cited in the submission.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
* This statu* report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are
available for public inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460.
All requests for TSCA Section 8(e) notices should be addressed to GPA's Freedom of Information Office (A-101).
781
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o^08**.
I I UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 2
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
HOT 2 6
DATE:
APPROVED: sc/re/to
SUBJECT:
FROM:
status Report1 8EHQ-0990-1074
QvustctfI H L0/\o-~>
Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
TO: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
The General Electric Company submitted a full copy of the final
report of a rat intraperitoneal toxicity study conducted with
resorcinol diphosphate (CR733S), a chemical reported to be the
subject of a TSCA § 5 Pre-Manufacture Notice (PMN No. P89-234).
The "SUMMARY" section from this report presents the following
information regarding the conduct and results of this study:
"CR733S was administered to male rats by intraperitoneal
injection at a dose level of 500 mg/kg/day until the
anticipated effect of multinucleated giant cells in the
mesentery were confirmed by histopathology after 14
consecutive doses. After this, dosing terminated and the
recovery phase began. Animals were sacrificed periodi-
cally up to about 6 months post-treatment to monitor the
status of this lesion."
1 This status report is the result of a preliminary evaluation of information that has been
submitted to EPA under Section 8(e), the "substantial risk" information reporting provision of
the Toxic Substances Control Act (TSCA). The statements made in this status report should
not be regarded as expressing final Agency policy or intent with respect to the subject
chemical(s). Any review of this status report should take into account that the report may be
based on incomplete information.
782
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8EHQ-0990-1074
Page 2 of 2
"Treatment related effects were produced by the intra-
peritoneal administration of 500 mg CR733S/kg. These
effects included depressed plasma cholinesterase levels
and inhibition of monocytic nonspecific esterase in the
spleen, liver, bone marrow, and bronchoalveolar and peri-
toneal lavage. Histologically, a minimal granulomatous
inflammatory response and minimal to slight fat necrosis
were noted on the serosal and/or peritoneal surfaces of
some abdominal organs. The intensity of both of these
observations was decreased at 28 weeks compared to 15
days. Other incidental microscopic changes were not
considered to be related to administration of CR733S."
COMMENTS/RECOMMENDATIONS
a) In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, General Electric will be asked
to describe the actions that the company has taken or
plans to take 1) to notify workers/others about the
reported information, and 2) to reduce or eliminate
exposure to the subject chemical. General Electric will
be asked also to provide copies of Material Safety Data
Sheets and labels that have been revised to reflect the
reported findings. In addition, General Electric will be
asked to describe the nature and results, if available,
of all studies (other than those submitted already to EPA
or those cited in the published scientific literature)
about which General Electric is aware or that the company
has conducted, is conducting or plans to conduct that are
designed to determine the toxicity of or the exposure to
the subject chemical.
b) As part of the initial phase of the OTS Existing
Chemicals Program (ECP), staff of the Chemical Screening
Branch will screen the reported information in order to
determine the need for further assessment of the subject
chemical at this time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and CCD/OTS; in
addition, copies of this status report will be sent to
the Environmental Assistance Division/OTS for further
distribution.
783
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^ UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
1222,
V r
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Sr
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8EHQ-0990-1076 S
Page 2 of 2
In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity/exposure data, the company will be requested to describe
the actions that it has taken or plans to take to notify workers and others about the
reported data. The company will be asked to provide copies of Material Safety Data Sheets
and labels that have been revised to reflect the reported findings. In addition, the company
will be asked to describe (by way of short summaries'! the nature and results, if available,
of all studies (other than those submitted already to EPA or those cited in the published
scientific literature) about which the company is aware or that it has conducted, is
conducting or plans to conduct that are designed to determine the toxicity of the amides
from diethylenetriamine and hydrogenated tallow.
As part of the initial phase of the OTS Existing Chemicals Program (ECP), staff of the
Chemical Screening Branch will screen the reported information in order to determine the
need for further assessment of the subject chemicals at this time.
The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
786
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i A \
w
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 1
OFFfCE OF
PESTICIDES AND
OCT 2 2 1^90 TOXIC SUBSTANCES
DATE: APPROVED:
SUBJECT: Status Report1 8EHQ-099Q-1077
r)^.otu^L H
FROM: Judith M. Loranger, Biologist
Chemical Screening Branch/ECAD/OTS
TO: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
The Eastman Kodak Company reported the detection of benzene (CAS No. 71-43-2) "in soil from one of
five soil vapor sampling points on company property [exact site location not specified] at the limit of
detection of 0.01 ppm." Kodak further reported that "ambient air monitoring showed no benzene at the
limit of detection (0.01 ppm)." Eastman Kodak stated that these findings are not unexpected "in view of
the ongoing investigation of the presence of chemicals in groundwater on company property at this site."
Eastman Kodak concluded that "due to the hydrogeology of the area, groundwater in the affected region
would not be expected to adversely affect known drinking water sources."
COMMENTS/RECOMMENDATIONS
Eastman Kodak reported that "authorities from local and state agencies, and Region II of EPA have been
informed of our preliminary findings." In addition, Eastman Kodak reported that they "are in the process
of investigating the source of the benzene, assessing the extent and level of the soil contamination, and
determining any appropriate corrective action." Eastman Kodak is currently planning additional groundwater
monitoring.
a) In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity/exposure data, the company will be requested to ensure
that EPA is apprised of any further significant monitoring information obtained by the
company during its investigation into the reported environmental contamination.
b) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and
EPA Region II; in addition, copies of this status report will be transmitted to the
Environmental Assistance Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are
available for public inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C 20460.
All requests for TSCA Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
787
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vT ^
jOL \ UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
^l7Z » WASHINGTON, D.C. 20460
Page 1 of 2
DATE:
SUBJECT:
FROM:
TO: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
Allied-Signal Inc. submitted a summarized account of employee complaints following exposure to HOCUT
797-G, a semisynthetic cutting oil used as a coolant in machining operations. According to the submitter,
"several employees ... complained about experiencing sinus irritation, a gagging choking feeling, and bloody
noses while using [HOCUT 797-G]." These complaints were mainly noted by the submitter's employees
"during high speed machining, but not during lower speed machining operations." Two of the exposed
individuals were examined by the submitter's medical staff, one employee was seen by his physician, and
several others (who also complained of irritation) were not examined. Allied-Signal Inc. stated that their
supplier of HOCUT 797-G (E. R Houghton & Co.) had not received any reports of adverse effects to
workers. The exposure level of the subject product was reported "to be within the governmental acceptable
exposure level of 5 mg/m-* [for mineral oil, one of a number of components of HOCUT 797-G]."
COMMENTS/RECOMMENDATIONS
Allied-Signal stated that "These complaints were noted by our employees and entered into [the company's]
TSCA Section 8(c) allegation recordkeeping system," and that"[ the company has] taken steps to eliminate
the use of this material, and [has] implemented controls to preclude exposure where the use of this material
is still required." Allied-Signal stated that they have notified employees who use the subject product of
about the reported findings. Allied-Signal also provided a copy of the MSDS for HOCUT 797-G.
a) In view of EPA's interest in effective and appropriate hazard/risk communication, as well
as company actions taken on a voluntary basis in response to new chemical toxicity/exposure
data, Allied-Signal will be requested to ensure that EPA is apprised of any further
significant information obtained by the company regarding the observed adverse human
health effects.
OFF ice OF
PESTICIDES AND TOXIC
. i 1 PESTICIDES AND I
OCT I 2 1990 APPROVED: rfifiA/f///("<¦ ¦ /m/pt SUBSTANCES
Status Report 1 8EHQ-Q990-1078
Paul N. McMahon, Biologist
Chemical Screening Branch/ECAD/OTS
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substances Control Act (TSCA). Statements made ia this status report should not be regarded a* depressing
final Agency policy or intent with respect lo the subject chemical(a). Full copies of noa-confidential Section 8(e) notice* are
available for public inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C 20440.
All requests for TSCA Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
78B
Printed on Recycled
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8EHQ-0990-1078
Page 2 of 2
As part of the initial phase of the OTS Existing Chemicals Program (ECP), staff of the
Chemical Screening Branch will screen the reported information in order to determine the
need for further assessment of the subject product and/or its components at this time.
The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
789
-------
. ^ UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
US2?
OCT I 8 ' i' APPROVED: aD£6/J,//s^ > /°//f/?Q
V WASHINGTON, DC 20460 p 1 Qf 1
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
DATE:
SUBJECT: Status Report1 8EHQ-0990-1079 S
Jt cclttJu H i-O
FROM: Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
TO: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS
SUBMISSION DESCRIPTION
CIBA-GEIGY Corporation provided final reports of two in vitro mutagenicity studies conducted with an
R&D pesticide generically identified as a "substituted oxadiazole." According to the cover letter, "the
compound has been demonstrated to be clastogenic in a cytogenetic screening test in Chinese hamster
primary embryo cells and to have mutagenic activity in one strain of Salmonella tvphimurium (TA 100), after
metabolic activation."
COMMENTS/RECOMMENDATIONS
CIBA-GEIGY reported that "these evaluations are being conducted under the supervision of technically
qualified personnel, knowledgeable in handling potentially hazardous chemicals" and that "further
development work of this compound as a pesticide is on hold." In the cover letter, CIBA-GEIGY
Corporation reported that they will revise their Material Safety Data Sheet and label to reflect the new
findings. In addition, CIBA-GEIGY stated that they will "remind workers that this is an experimental
compound and should be handled in such manner as to minimize or prevent any exposure."
Although a positive in vitro genotoxicity test, when considered alone, may not be sufficient to offer
reasonable support for a conclusion of substantial risk (as that term is defined in EPA's TSCA Section
8(e) policy statement ("Statement of Interpretation and Enforcement Policy; Notification of Substantial
Risk" 43 FR 11110; March 16, 1978)), EPA does believe that such information is of value in assessing the
possible risk(s) posed by exposure to the tested chemical or mixture. Further, EPA believes that a positive
genotoxicity test result, in combination with other information (e.g., knowledge of actual/potential exposure
to and/or high production of the tested chemical or mixture), would suggest the need, in many cases, to
conduct further studies designed to determine the toxicity of or the exposure to that chemical substance or
mixture. EPA expects the results of such additional studies to be considered also for submission under
Section 8(e) of TSCA
a) The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA;
in addition, copies of this status report will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are
available for public inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460.
All requests for TSCA Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
790
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yt0!X
(ft)
<< PKOlt0
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
Page 1 of 3
DATE:
SUBJECT:
FROM:
TO:
OCT 2 2
APPROVED: " /c/zjJto
Status Report1 8EHQ-0990-1080 8
/"/ O fL4X-*~
Judith M. Loranger, Biologist
Chemical Risk Identification Section/CSB
David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
(See NOTE on Page 3 of this Status Report)
OFFICE OF
PESTICIDES AND
TOXIC SUBSTANCES
The submitting company has claimed its company name as TSCA
Confidential Business Information (CBI). Staff of the Information
Management Division will review all incoming correspondence related
to the company's TSCA CBI claim.
SUBMISSION DESCRIPTION
The submitter provided a copy of a consultant-generated report
evaluating the medical monitoring program and the results of urine
cytology monitoring at their facilities that produces organic dyes.
According to the submitter, the aromatic amines used in their
facilities to manufacture these dyes include;
Amine Identitv
CAS No.
Aniline
62-53-3
p-Butyl aniline
104-13-2
p-Cresidine
120-71-8
2,4-Dinitro aniline
97-02-9
p-Nitro aniline
100-01-6
o-tolidine
119-93-7
o-toluidine
95-53-4
p-toluidine
106-49-0
m-toluidine
108-44-1
2,5-xylidine
95-78-3
xylidines, mixed
1300-73-8
- This status report is the result of a preliminary evaluation of information that has
been submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substances Control Act (TSCA). The statements made in this status
report should not be regarded as expressing final Agency policy or intent with respect to the
subject chemical(s). Any review of this status report should take into account that the
report may be based on incomplete information.
791
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8EHQ-0990-1080 S
Page 2 of 3
The submitter reported that both o-toluidine and aniline are used
in substantial quantities at a confidential location. The submitter
reported that, as of June 1990, "approximately 40% of [the workers]
have a * Class 2' response to the urine cytology test at this
facility and this percentage is substantially higher than was
previously demonstrated." (The submitter defined a Class 2 response
as an observation of abnormal cells, usually a reaction to
inflammatory changes). The submitter further reported that "two
(and now believed to be three) individuals have a *Class 3'
response (indicating the presence of dysplasia) where ... no
reports of dysplasia were [previously] noted."
OSE AND EXPOSURE POTENTIAL
The submitter reported that o-toluidine and aniline "are handled in
essentially closed systems at this facility." In addition the
submitter reported that "the dye products manufactured from these
amines typically contain low residual amounts of these amines." The
submitter reported that "o-tolidine is no longer used at this
location."
COMMENTS/RECOMMENDATIONS
It should be noted that EPA has received numerous of TSCA Section
8(e) and "For Your Information" (FYI) submissions on amine
compounds. In addition, Chemical Hazard Information Profiles
(CHIPs) were prepared on several of these amine compounds. Our
records indicate that many of these chemicals were the subject of
Section 8(a) and 8{d) information gathering rules. The Chemical
Testing Branch (CTB/ECAD) is currently in the process of collecting
and evaluating information on aniline and related compounds and the
Risk Analysis Branch (RAB/ECAD) is reviewing information on o-
toluidine and aniline.
a) The submitter will be requested to ensure that EPA is
apprised of any further significant information obtained
by the company during its investigation into the possible
cause(s) of the observed adverse human health effects.
In view of EPA's interest in effective and appropriate
hazard/risk communication, as well as company actions
taken on a voluntary basis in response to new chemical
toxicity/exposure data, the submitter will be asked to
describe the actions that they have taken or plan to take
¦to 1) to notify workers/others about the reported
information, and 2) to reduce or eliminate exposure to
the subject chemicals. The submitter will be asked also
to provide copies of Material Safety Data Sheets and
labels that have been revised to reflect the reported
findings. In addition, the submitter will be asked to
describe the nature and results, if available, of all
792
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8EHQ-0990-1080 S
Page 3 of 3
studies (other than those submitted already to EPA or
those cited in the published scientific literature) about
which they are aware or that they have conducted, are
conducting or plan to conduct that are designed to
determine the toxicity of or the exposure to the subject
chemicals.
b) As was the case for the initial submission, the Chemical
Screening Branch will notify the Chemical Testing Branch
and Risk Analysis Branch of the receipt of additional
incoming information related to this submission.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA, RAB/ECAD/OTS and
CTB/ECAD/OTS? in addition, copies of this status report
will be transmitted to the Environmental Assistance
Division/OTS for further distribution.
NOTE in a November 7, 1990 letter, Morton International Inc.
stated that the company was withdrawing it CBI claims for
company name and the location of the company's facility
which is the subject of this Section 8(e) submission.
According to the sanitized (i.e., non-confidential)
version of a November 15, 1990 letter (8EHQ-1190-1080 S
Followup Response), the subject facility is located in
Paterson, New Jersey.
793
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sr
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8EHQ-0990-1081
Page 2 of 2
available, of all studies (other than those submitted already to EPA or those cited in the
published scientific literature) about which the company is aware or that it has conducted,
is conducting or plans to conduct that are designed to determine the toxicity/exposure of
the subject chemical.
As part of the initial phase of the OTS Existing Chemicals Program (ECP), staff of the
Chemical Screening Branch will screen the reported information in order to determine the
need for further assessment of the subject chemical at this time.
The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and
CCD/OTS/OPTS; in addition, copies of this status report will be transmitted to the
Environmental Assistance Division/OTS for further distribution.
795
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
Page 1 ofl
OFFICE OF
/ / PESTICIDES AND TOXIC
DATE: OCT 17 1990 APPROVED: ^ /o//7/9o SUBSTANCES
SUBJECT. Status Report1 8EHQ-0990-1082
FROM: Paul N. McMahon, Biologist
Chemical Screening Branch/ECAD/OTS
TO: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
Hoechst Celanese Corporation submitted preliminary results of a guinea pig skin sensitization study of
acetoxystyrene (CAS No. 2628-16-2). The submitter noted that "forty-eight hours after challenge exposure
. . . the maximum number of responding animals was 18 out of the 19 test animals," and that "a positive
response to the challenge dose was also observed in 12 of 19 animals with a 30% preparation of the test
material . . ." According to Hoechst Celanese, "the response in pre-treated animals clearly indicates that
acetoxystyrene is a potent skin sensitizer in guinea pigs . .."
COMMENTS/RECOMMENDATIONS
According to the 1990 Supplement to the 1985 Edition of the TSCA Inventory, the test compound was the
subject of a TSCA § 5 Premanufacture Notification (PMN) as indicated by the letter "P" which follows the
CAS No.
a) The Chemical Screening Branch will request the submitting company to ensure that EPA
receives a full copy of the final report (including the actual experimental protocol, results
of gross/histopathologic examinations, results of any statistical analyses, etc.) from the
guinea pig sensitization study cited in the submission.
In view of EPA's general interest in company actions that are taken on a voluntary basis
in response to chemical toxicity/exposure data, the company will be requested to describe
the actions that it has taken or plans to take 1) to notify workers and others about the
reported data, and 2) to reduce or eliminate exposure to the subject chemical. The
company will be asked to provide copies of Material Safety Data Sheets and labels that
have been revised to reflect the reported findings. In addition, the company will be asked
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(c) notices are
available for public inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460.
All requests for TSCA Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
SIS
% PBO^°
/
796
Printed on Recyded Papor
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8EHQ-0990-1082
Page 2 of 2
to describe (by way of short summaries') the nature and results, if available, of all studies
(other than those submitted already to EPA or those cited in the published scientific
literature) about which the company is aware or that it has conducted, is conducting or
plans to conduct that are designed to determine the toxicity of or the exposure to the
subject chemical.
As part of the initial phase of the OTS Existing Chemicals Program (ECP), staff of the
Chemical Screening Branch will screen the reported information in order to determine the
need for further assessment of the subject chemical at this time.
The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA and
CCD/OTS/OPTS; in addition, copies of this status report will be transmitted to the
Environmental Assistance Division/OTS for further distribution.
797
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rft0
i m)
\ rf
<1 PRO^
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
Page 1 of 1
OFFICE OF
PESTICIDES AND TOXIC SUBSTANCES
DATE: OCT 22 1990 APPROVED: /aAi/?o
SUBJECT: Status Report1 8EHQ-0990-1083 S
FROM: Paul N. McMahon, Biologist /V M1 —
Chemical Screening Branch/ECAD/OTS
TO: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
A confidential company submitted summarized preliminary findings of a 96 hour acute carp toxicity study
of 14 different R&D quinazolines and quinolines. According to the submitter "[the test] compounds are in
the early investigative stages as potential pesticides." According to the submitter 2 compounds (#5 & #
11) caused 100% mortality at 1 ppb; 11 compounds produced 100 % mortality at 5 ppb or 25 ppb; and the
1 remaining compound caused 100% mortality at 100 ppb.
COMMENTS/RECOMMENDATIONS
The Agency has received TSCA § 8(e) submissions on several quinazoline and quinoline compounds as well
as "For Your Information" (FYI) notices on several quinoline compounds. A Chemical Hazard Information
Profile (CHIP) was prepared on quinoline (CAS No. 91-22-5) by staff of the Chemical Screening Branch
in 1983. The submitter also noted that "information was previously submitted [by another company] to EPA
concerning compound numbered 11 [as is designated in the submission] under section 8(e) of TSCA."
The Chemical Screening Branch will send copies of this status report to NIOSH, OSHA, CPSC, FDA, NTP,
OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; in addition, copies of this status
report will be transmitted to the Environmental Assistance Division/OTS for further distribution.
1 This status report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are
available for public inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 M" Street S.W., Washington, D.C. 20460.
All requests for TSCA Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
798
Printed on Recycled Py,f
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I®.
o
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 1
WASHINGTON, D.C. 20460
DATE; OCT 22 |g)Q APPROVED: /ij/tx/e*
SUBJECT: Status Report1 8EHQ-099(M()84
FROM: Paul N. McMahon, Biologist f°^(NMrA^L&r\
Chemical Screening Branch/ECAD/OTS
TO: David R. Williams, Section 8(e) Coordinator
Chemical Screening Branch/ECAD/OTS/OPTS
SUBMISSION DESCRIPTION
OFFICE OF
PESTICIDES AND TOXIC SUBSTANCES
The Dow Corning Corporation provided a full copy of the final report of an acute oral LD50 study of
silacyclobutane (CAS No. 287-29-6) administered to rats at dose levels of 400, 790, 1590 and 2000 mg/kg.
According to the submitter, the LD50 for this research and development (R&D) chemical was found to be
~ 1539 mg/kg, indicating that the chemical was slightly toxic by oral administration. Dow Corning also noted
that all animals receiving 2000 mg/kg died within 24 hours following administration of the test material and
8/10 animals receiving 1,590 mg/kg of the test material died within the first 2 days post-administration; no
mortalities occurred in the 400 or 790 mg/kg groups. According to the "RESULTS" section of the provided
final report, lethargy and ataxia were among the clinical signs observed in the 790,1590 and 2000 mg/kg dose
groups; tonic convulsions were seen in the 1590 and 2000 mg/kg dose groups.
COMMENTS/RECOMMENDATIONS
EPA has received numerous TSCA §8(e) and "For Your Information" (FYI) submissions on organosilane
compounds. In 1986, the Chemical Screening Branch prepared a "Chemical Hazard Information Profile"
(CHIP) covering a number of organosilanes.
a) As part of the initial phase of the OTS Existing Chemicals Program, staff of the Chemical
Screening Branch will screen the reported information in order to determine the need for
further assessment of this chemical substance.
b) The Chemical Screening Branch will send copies of this report to NIOSH, OSHA, CPSC,
FDA, NTP, OSWER/EPA, OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA; copies
of this report will be sent also to the Environmental Assistance Division/OTS for further
distribution.
* Thi» statu* report reflects information submitted to EPA under Section 8(e), the "substantial risk" information reporting
provision of the Toxic Substances Control Act (TSCA). Statements made in this status report should not be regarded as expressing
final Agency policy or intent with respect to the subject chemical(s). Full copies of non-confidential Section 8(e) notices are
available for public inspection at EPA Headquarters, Northeast Mall (Room G-004), 401 "M" Street S.W., Washington, D.C. 20460.
All requests for TSCA Section 8(e) notices should be addressed to EPA's Freedom of Information Office (A-101).
799
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APPENDIX fi
THURSDAY, MARCH 16, 1978
PART V
ENVIRONMENTAL
PROTECTION
AGENCY
TOXIC SUBSTANCES
CONTROL ACT
Statement of Interpretation and
Enforcement Policy; Notification
of Substantial Risk
800
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11110
[6540-01]
ENVIRONMENTAL PROTECTION
AGENCY
(FRL 849-21
TOXIC SUtSTANCIS CONTIOL ACT
Notification of Subitontld iisk Undar
SmMwi !(•}
AGENCY: Environmental Protection
Agency.
ACTION: Statement of Interpretation
and enforcement policy.
SUMMARY; This action states EPA's
Interpretation of, and enforcement
policy concerning, section 8(e) of the
Toxic Substances Control Act (TSCA)
(90 Stat. 2029, 15 U.S.C. 2007). The
provisions of that section went into
effect on January 1, 1977.
Section 8(e) states that "any person
who manufactures, processes, or dis-
tributes In commerce a chemical sub-
stance or mixture and who obtains in-
formation which reasonably supports
the conclusion that such substance or
mixture presents, a substantial risk of
injury to health or the environment
shall immediately inform the Adminis-
trator of such information unless such
person has actual knowledge that the
Administrator has been adequately in-
formed of such information."
DATES: The policy expressed In this
document is in effect as of the date of
publication.
FOR FURTHER INFORMATION
CONTACT:
Frank D. Kover, Assessment Divi-
sion, Office of Toxic 8ubstances
(WH-657), Environmental Protec-
tion Agency, 401 M Street SW.,
Washington, D.C. 20400, 202-755-
2110.
SUPPLEMENTARY INFORMATION:
On September 9.1977, the Agency pro-
posed guidance (42 FR 45362) on its in-
terpretation of and policy concerning
the provisions of section 8(e). Al-
though the proposed "guidance" was
an Interpretive rule and statement of
policy exempt from the notice and
public comment provisions of the Ad-
ministrative Procedure Act (5 U.S.C.
553), the Agency solicited comments
on several Issues to make more in-
formed decisions. On October 11. the
comment period was extended from
October 15 to October 31, 1&77 (42 FR
S4857). On November 4, 1977, a supple-
mental notice to the proposed guid-
ance was published (42 FR 57744), de-
leting the November 15 date for re-
porting certain information obtained
before 1977 and stating that a new
date would be established in the final
guidance.
In developing this policy statement,
two meetings have been held (Febru-
NOTICES
ary 1, 1977, and October 28. 1977) with
selected representatives of industry
and environmental and other Inter-
ested groups. Comments submitted
pursuant to the February 1 meeting
were addressed In the preamble to the
September 9 proposal. Over 100 writ-
ten comments have been submitted
pursuant to the September 9 proposal
from trade associations, businesses, en-
vironmental groups, labor unions,
State and Federal agencies, and other
interested parties. Appendix B de-
scribes significant Issues raised in
these comments and the Agency's re-
sponse to them.
The major modifications to the Sep-
tember 9 proposal are summarized In
points 1 through 7 below.
(1) Pursuant to some question over
the definition and nature of "guid-
ance," this document is now described
more accurately as a "policy state-
ment." It Is exempt from the notice
and public comment provisions of the
Administrative Procedure Act, as well
as provisions concerning delayed effec-
tive dates.
(2) Many commenters expressed the
view that to apply these requirements
to officers and employees of a business
organization would result in ill-consid-
ered, premature reports and would un-
fairly subject employees to conflicting
responsibilities as individual respon-
dents and as corporate agents. Other
commenters expressed support for the
view that certain employees have a re-
sponsibility to report pertinent infor-
mation, and felt that the phrase "ca-
pable of appreciating pertinent infor-
mation" appropriately described those
employees.
The September 9 proposal would
have applied section 8(e) requirements
to commercial establishments as well
as to employees capable of appreciat-
ing pertinent information, but stipu-
lated enforcement priorities Intended
to encourage corporate processing and
centralised reporting of such informa-
tion (42 FR 45363). The Intent was to
ensure that pertinent Information ob-
tained by employees is promptly and
appropriately considered, while mini-
mising duplicative or Ill-considered
submissions.
The Agency now feels that these ob-
jectives would best be served by allow-
ing commercial establishments—under
certain conditions designed to ensure
full disclosure—to assume exclusive re-
sponsibility for reporting to EPA any
substantial-risk information obtained
by Individual officers or employees.
Accordingly, this polity statement
stipulates that Individual officers and
employees will have fully discharged
their section 8(e) obligations once they
have notified the designated responsi-
ble company supervisor or official of
pertinent information, provided, that
the employing company or firm has
established, internally publicizes, and
affirmatively Implements procedures
governing such notifications. These
procedures, at a minimum, must: <1)
Specify the information that must be
reported: (2) Indicate how the notifica-
tions are to be prepared and submit-
ted: (3) note the Federal penalties for
falling to report; and (4) provide a
mechanism for promptly notifying of-
ficers and employees who have submit-
ted reports of the company's disposi-
tion of those reports, including wheth-
er or not they were submitted to EPA
(and if not, informing employees of
their right to report to EPA, as pro-
tected by TSCA section 23). EPA be-
lieves these four criteria will ensure
prompt and appropriate processing of
pertinent information.
Establishment of such procedures
notwithstanding, all officials responsi-
ble and having authority for the orga-
nization's execution of its section 8(e)
obligations retain personal liability for
ensuring that substantia]-risk informa-
tion is reported to EPA.
(3) The September 9 proposal stated.
In Part III. that a person obtains in-
formation when he is aware that it
"may suggest" substantia] risk. Nu-
merous commenters questioned the
Administrator's authority to compel
the reporting of information which
"may suggest" substantial risk. The
Administrator agrees that section 8(e)
addresses information that "reason-
ably supports the conclusion" of sub-
stantial risk and has deleted the "may
suggest" provision, but emphasizes
that "reasonably supports the conclu-
sion" of substantial risk is not identi-
cal to a conclusive demonstration of
substantial risk. The former typically
occurs, and must be reported, at an
earlier stage. Part VI in this policy
statement provides Agency interpreta-
tion of the types of information that
"reasonably support" such a conclu-
sion.
(4) Numerous commenters requested
clarification of different aspects of
Part V of the September 9 proposal
("Information Which Reasonably Sup-
ports a Conclusion of Substantia]
Risk"), particularly concerning envi-
ronmental effects, and suggested dif-
ferent interpretations of what consti-
tutes a "substantial risk". The Agency
continues to locus in this policy state-
ment on the effects set forth in the
September 9 proposal, but clarifies
that the substantiality of a risk is a
function of both the seriousness of the
effect and the probability of its occur-
rence (see Part V).
(5) Numerous commenters main-
tained that section 8(e) only applies
prospectively to information obtained
after January 1. 1977. The Agency dis-
agrees, as explained in the preamble
to the September 9 proposal. This
policy statement continues to apply
section B(e) to Information obtained
before 1977 of which a person has
FfDCIAL ICOISTM, VOL 43, NO. S3—THUtSO
801
-------
been aware since January 1, 1977. In
response to requests for clarification,
the statement defines what constitutes
such awareness. In this manner, EPA
Intends to limit the need for searches
of historical records and files.
<6) This policy statement now pro-
vides that any information published
in scientific literature, in any lan-
ffuage, is exempt if It is referred to in
abstracts published by specified ab-
stracting services.
17) This policy statement describes
In a new Part X how to submit claims
of confidentiality.
Accordingly, the Administrator's in-
terpretation of and policy towards sec-
tion 8(e) is set forth below.
Dated: February 24, 1978.
Douglas Costle
Administrator.
I. Definitions
The definitions set forth In TSCA
section 3 apply to these requirements.
In addition, the following definitions
•re provided for purposes ot this
policy statement:
The term "manufacture or process
"for commercial purposes' " means to
manufacture or process; (I) For distri-
bution in commerce, including; for test
marketing purposes, (2) for use as a
catalyst or an intermediate, (3) for the
exclusive use by the manufacturer or
processor, or (4) for product research
and development.
The term "person" includes any nat-
ural person, corporation, firm, com-
pany. Joint-venture, partnership, sole
proprietorship, association, or any
other business entity, any State or po-
litical subdivision thereof, any munici-
pality. any Interstate body and any de-
partment. agency, or Instrumentality
of the Federal Government.
The term "substantial-risk informa-
tion" means Information which rea-
sonably supports the conclusion that a
chemical substance or mixture pre-
sents a substantial risk of injury to
health or the environment
II. Persons Subject to the
Requirement
Persons subject to section 8(e) re-
quirements include both natural per-
sons and business entities engaged fn
manufacturing, processing, or distrib-
uting in commerce a chemical sub-
stance or mixture. In the cue of busi-
ness entities, the president, chief ex-
ecutive officer, and any other officers
responsible and having authority for
the organization's execution of Its sec-
tion 8(e) obligations must ensure that
the organization reports substantial-
risk Information to EPA. The business
organization is considered to have ob-
tained any information which any of-
ficer or employee capable of appreciat-
ing the significance of that informa-
tion has obtained. It is therefore In-
NOTICES
cumbent upon business organizations
to establish procedures for expedi-
tiously processing pertinent informa-
tion In order to comply with the
schedule set forth In Part IV.
Those officers and employees of
business organizations who are capa-
ble of appreciating the significance of
pertinent information are also subject
to these reporting requirements. An
employing organization may relieve its
individual officers and employees of
any responsibility for reporting sub-
stantial-risk Information directly to
CPA by establishing, internally publi-
cizing, and affirmatively implementing
procedures for employee submission
and corporate processing of pertinent
Information. These procedures, at a
minimum, must:
-------
11112
spondent hu actual knowledge that
the Administrator is already Informed
of them.
(11) Information respecting these ef-
fects can be obtained either directly,
by observation of their occurrence, or
inferred from designed studies u dis-
cussed in Part VI.
The Agency considers effects for
which substantial-risk information
must be reported to include the fol-
lowing:
(a) Human health effect*—(1) Any
instance of cancer, birth defects, mu-
tagenicity, death, or serious or pro-
longed incapacitation, including the
loss of or inability to use a normal
bodily function with a consequent rel-
atively serious impairment of normal
activities, if one (or a few) chemlcal(s)
is strongly Implicated.
(2) Any pattern of effects or evi-
dence which reasonably supports the
conclusion that the chemical sub-
stance or mixture can produce cancer,
mutation, birth defects or toxic effects
resulting in death, or serious or pro-
longed Incapacitation.
(b) Environmental effecU—(1) Wide-
spread and previously unsuspected dis-
tribution in environmental media, as
indicated in studies (excluding materi-
als contained within appropriate dis-
posal facilities).
(2) Pronounced bioaccumulatlon.
Measurements and Indicators of pro-
nounced bioaccumulatlon heretofore
unknown to the Administrator (includ-
ing bloaccumillation in fish beyond
5,000 times water concentration in a
30-day exposure or having an n-oc-
tanol/water partition coefficient
greater than 25,000) should be report-
ed when coupled with potential for
widespread exposure and any non-triv-
lal adverse effect.
(3) Any n on-trivial adverse effect,
heretofore unknown to the Adminis-
trator, associated with * chemical
known to have bloaccumulated to a
pronounced degree or to be wide-
spread in environmental media.
(4) Ecologically significant changes
In species' Interrelationships; that is,
changes in population behavior,
growth, survival, etc. that la turn
affect other species' behavior, growth,
or survival.
Examples Include: (I) Excessive stim-
ulation of primary producers (algae,
macrophytes) in aquatic ecosystems,
e.g.. resulting In nutrient enrichment,
or eutrophlcatlon, of aquatic ecosys-
tems.
(ii) Interference with critical blogeo-
chemical cycles, such as the nitrogen
cycle.
(5) Facile transformation or degra-
dation to a chemical having aa unac-
ceptable risk as defined above.
(c) Emergency incidents of environ-
mental contamination—Any environ-
mental contamination by a chemical
substance or mixture to which any of
NOTICES
the above adverse effects has been as-
cribed and which because of the pat-
tern. extent, and amount of contami-
nation (1) seriously threatens humans
with cancer, birth defects, mutation,
death, or serious or prolonged inca-
pacitation, or (2) seriously threatens
non-human organisms with large-scale
or ecologically significant population
destruction.
VI. Nature and Sources or Informa-
tion Which "Reasonably Supports
THE Conclusion" Of SUBSTANTIAL
Risk
Information attributing any of the
effects described In Part V above to a
chemical substance or mixture is to be
reported if it is one of the types listed
below and if It is not exempt from the
reporting requirement by reason of
Part VII of this policy statement. A
person la not to delay reporting until
he obtains conclusive Information that
a substantial risk exists, but is to Im-
mediately report any evidence which
"reasonably supports" that conclusion.
Such evidence will generally not be
conclusive aa to the substantiality of
the risk; it should, however, reliably
ascribe the effect to the chemical.
Information from the following
sources concerning the effects de-
scribed in Part V will often "reason-
ably support" a conclusion of substan-
tial risk. Consideration of corrobora-
tive information before reporting can
only occur where it is Indicated below.
(1) Designed, controlled studies. In
assessing the quality of Information,
the respondent is to consider whether
It contains reliable evidence ascribing
the effect to the chemical. Not only
should final results from such studies
be reported, but also preliminary re-
sults from Incomplete studies where
appropriate. Designed, controlled stud-
ies Include:
(1) In vivo experiments and tests.
(11) In vitro experiments and tests.
Consideration may be given to the ex-
istence of corroborative information, if
necessary to reasonably support the
conclusion that a chemical presents a
substantial risk.
<1111 Epidemiological studies.
(Iv) Environmental monitoring stud-
ies.
(2) Reports concerning and studies
of undesigned, uncontrolled circum-
stance*. It Is anticipated here that re-
portable effects will generally occur In
a pattern, where a significant common
feature Is exposure to the chemical.
However, a single Instance of cancer,
birth defects, mutation, death, or seri-
ous Incapacitation in a human would
be reportable if one (or a few)
chemlcal(s) was strongly implicated.
In addition, it is possible that effects
less serious than those described In
Part V(a) may be preliminary manifes-
tations ol the more. serious eflecta
and, together with another triggering
piece of Information, constitute repor-
table information; an example would
be a group of exposed workers experi-
encing dizziness together with prelimi-
nary experimental results demonstrat-
ing neurological dysfunctions.
Reports and studies of undesigned
circumstances Include:
(i) Medical and health surveys.
(11) Clinical studies.
(Hi) Reports concerning and evi-
dence of effects In consumers, workers,
or the environment.
VII. Information Which Need Not Bb
Reported
Information need not be reported if
It:
(a) Has been published by EPA in re-
ports;
(b) Has been submitted in writing to
EPA pursuant to mandatory reporting
requirements under TSCA or any
other authority administered by EPA
(including the Federal Insecticide,
Fungicide and Rodenticide Act, the
Clean Air Act, the Federal Water Pol-
lution Control Act, the Marine Protec-
tion. Research, and Sanctuaries Act.
the Safe Drinking Water Act, and the
Resource Conservation and Recovery
Act), provided that the information:
(1) Encompasses that required by Part
IX (c) through (f); and (2) is from now
on submitted within the time con-
straints set forth in Part IV and iden-
tified as a section ft(e> notice in accor-
dance with Part IX(b>;
(c) Has been published in the scien-
tific literature and referenced by the
following abstract services: (1) Agric-
ola, (2) Biological Abstracts. (3)
Chemical Abstracts, (4) Dissertation
Abstracts, (5) Index Medlcus, (6) Na-
tional Technical Information Service.
(d) Is corroborative of well-estab-
lished advene effects already docu-
mented in the scientific literature and
referenced as described in (c) above,
unless such information concerns
emergency Incidents of environmental
contamination as described in Part
V(c), or
(e) Is contained In notification of
spills under section 311(bX5) of the
Federal Water Pollution Control Act
VIII. Information First Received st
a Person Prior to the Erracxivs
Date or TSCA
Any substantial risk Information
possessed by a person prior to January
1,1977, of which he is aware after that
date shall be reported within 00 days
of publication of this policy statement.
The Agency considers that a person Is
"aware" of:
(a) Any Information reviewed after
January 1, 1977, including not only
written reports, memoranda and other
documents examined after January 1,
1977, but also information referred to
in discussions and conferences In
which the person participated alter
January 1,1977;
KOtRAl atOtSTM, VOL 4), NO. 53—TMMSOAY, MARCH It, 1*71
803
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(b) Any Information the contents of
which a person has been alerted to by
date received after January 1. 1977, In-
cluding any Information concerning a
chemical for which the person is pres-
ently assessing health and environ-
mental effects;
(c) Any other information of which
the person has actual knowledge.
IX. Reporting Requirements
Notices shall be delivered to the
Document Control Officer, Chemical
Information Division, Office of Toxic
Substances (WH-557), Environmental
Protection Agency, 401 M Street SW.,
Washington, D.C. 20460. /-#***-.
A notice should: '
(a) Be sent by certified mail, or in
any other way permitting verification
of its receipt by the Agency,
(b) State that it 1* being submitted
In accordance with section 8(e),
(c) Contain the job title, name, ad-
dress, telephone number, and signa-
ture of the person reporting and the
name and address of the manufactur-
ing. processing, or distributing estab-
lishment with which he Is associated,
(d) Identify the chemical substance
or mixture (Including, If known, the
CAS Registry Number),
(e) Summarise the adverse effects
being reported, describing the nature
and the extent of the risk involved,
and
(f) Contain the specific source of the
information together with a summary
and the source of any available sup-
porting technical data.
For emergency incidents of environ-
mental contamination (see Part V(c».
a person shall report the Incident to
the Administrator by telephone as
soon as he has knowledge of the Inci-
dent (see below for appropriate tele-
phone contacts). The report should
contain as much of the information re-
quired by instructions (b) through (f)
above as possible. A written report, in
accordance wfth instructions (a)
through (f) above. Is to be submitted
within IS days. Twenty-four hour
emergency telephone numbers are:
Rerfon I (Maine, Rhode Island, Connecti-
cut. Vemont, Massachusetts, New Ramp-
shire), 811-223-7285.
Region II (New York, New Jersey, Puerto
Rico, Virgin Islands), 201-548-87JO.
Region III (Pennsylvania, West Virginia.
Virginia, Maryland, Delaware, District of
Columbia), 215-587-9898.
Region IV (Kentucky. Tennessee, North
Carolina, South Carolina, Georgia, Ala-
bama, Mississippi, Florida), 404-881-4082.
Region V (Wisconsin. Illinois, Indiana.
Michigan, Ohio. Minnesota), 313-353-
2318.
Region VI (New Mexico. Texas, Oklahoma.
Arfcinf" Louisiana). 314-749-3840.
Region VII (Nebraska, Iowa. Missouri.
Kansas). 018-374-3778.
Region VIII (Colorado. Utah. Wyoming.
Montana. North Dakota, South Dakota).
303-837-3880.
Region IX (California, Nevada. Arizona.
Hawaii. Ouam). 413-558-8254.
NOTICES
Region X (Washington, Oregon, Idaho,
Alaska). 206-442-1200.
X. Confidentiality Claims
(a) Any person submitting a notice
to EPA under section 8(e) of TSCA
may assert a business confidentiality
claim covering all or part of the infor-
mation contained In the notice. Any
Information covered by a claim will be
disclosed by EPA only to the extent,
and by means of the procedures, set
forth in 40 CFR Part 2 (41 FR 36902,
September 1,1976).
(b) If no claim accompanies the
notice at the time It is submitted to
EPA, the notice will be placed In an
open file to be available to the public
without further notice to the submit-
ter.
(c) To assert a claim of confidential-
ity for Information contained In a
notice, the submitter must submit two
copies of the notice.
(1) One copy must be complete. In
that copy the submitter must indicate
what information, If any. is claimed as
confidential by marking the specified
information on each page with a label
such as "confidential," "proprietary,"
or "trade secret."
(2) If some information in the notice
|g claimed as confidential, the submit-
ter must submit a second copy. The
second copy must be complete except
that all information claimed as confi-
dential in the first copy must be de-
leted.
(3) The first copy of the notice will
be disclosed by EPA only to the
extent, and by means of the proce-
dures, set forth In 40 CFR Part 2. The
second copy will be placed In an open
file to be available to the public.
(d) Any person submitting a notice
Containing Information for which they
are asserting a confidentiality claim
should send the notice in a double
envelope.
(1) The outside envelope should bear
the same address outlined in section
IX of this policy statement.
(2) The Inside envelope should be
clearly marked "To be opened only by
the OTS Document Control Officer."
XI. Failuu To Retoxt Information
Section 15(3) of TSCA makes It un-
lawful for any person to fall or refuse
to submit information required under
section 8
-------
11114
Response: The Agency considers that dif-
ferent sections of TSCA. having different
purposes, are appropriately directed to dif-
ferent respondents. In the case of section
8(e), officers and employees who are capable
of appreciating the significance of Informa-
tion have a legitimate responsibility to Ik
alert to and report substantial-risk Informa-
tion. The guidance has been modified so
that natural persons and business entitles
can fulfill their section 8 examination of
Information that by Itself Is not subject to
section 8 comtuamcb
Comment 9: Fifteen calendar days Is Insuf-
ficient to determine whether Information
which "may suggest" substantial risk should
be reported; it Is even insufficient to accom-
modate normal procedural time constraints
(corporate processing, mailing, holidays,
etc.).
Response: The Agency has changed the
compliance period to 15 business days. It is
Imperative that procedures be established to
expedite the reporting of substantial-risk In-
formation, not that reporting conform to
existing procedures.
Comment 10: Allow from 30 to 90 days for
the second phase of reporting; alternatively,
do not prescribe a time limit for additional
reporting.
Response: Having deleted the "may sug-
gest" criterion, the Agency sees no need to
provide a second phase to the reporting
period. Supplemental Information that Is
generated after a section 8(e) notification
should. If appropriate, be Immediately re-
ported.
Comment 11: Allow from 30 to 130 days to
report pre-19T! Information; this period
should commence; (a) upon final publica-
tion, (b) January 1, 1978, (c) following the
Inventory reporting period since many of
the same corporate personnel will be imple-
menting both requirements.
Response: The policy statement prescribes
a to day reporting period, commencing Im-
mediately upon publication. Section 8(e) has
been In effect since January 1. 1S17; post-
ponement in reporting substantial-risk In-
formation is not warranted.
p. arrecTS aim rwrojuunoK that must sk
axroRTts
Comment 12: The reporting of "any In-
stance" of cancer, birth defects, etc.. In
humans Is too broad and such Information
will be of little use: chemical workers, like
the general population, develop cancer* and
other ailments of uncertain etiology.
Response: This policy statement clarifies
that the reporting of single occurrences of
human cancer or other serious effects will
depend upon evidence strongly implicating
(me (or a few) chemlcal(s).
Comment 13: Dermal ailments and nausea
are poorly chosen examples of precursor
symptoms. Deleting these examples will
avoid unduly emphasizing them when other
symptoms may be more important, yet will
not eliminate the obligation to report them
If they are suspected precursors.
Jtespoiue The Agency agrees.
Comment 14: How are reportable data dis-
tinguished from routine tests including
range tests such as LDw's 1
Response: This policy statement direct*
the reporting of specified effects when un-
known to the Administrator. Many routine
tests are baaed on a knowledge of toxicity
associated with a chemical; unknown effects
occurring during such a range test may have
to be reported if they are those of concern
to the Agency and If the information meets
the criteria set forth in Parts V and VI.
Comment IS: The most widespread "in
vitro" test is the Ames test, which is subject
to considerable debate. Clarify the circum-
stance* under which positive results of in
vitro tests must be reported.
Response: Part VI clarifies that the re-
porting of in vitro testa will depend upon
the existence of corroborative information
U necessary to reasonably suppoj t the con-
clusion of substantial risk.
Comment it: The description of "extreme
persistence" as a substantial risk Is an exam-
ple of the need to redefine Part V(c) ("Envi-
ronmental Effects"). Persistence and bto-
accumulatlon should be considered risks
only when coupled with toxicity and signifi-
cant exposure.
KOttAL IKMSTft, VOL 4J, MO. «—TMUtSOAY, MAftCH It, 1V7>
805
-------
NOTICES
11115
Response: Part V now clarifies those et-
feet* for which reporting depends upon a
significant exposure potential. Persistence
by Itself Is no longer itemized as a report-
able effect but rather la considered to be a
component of exposure. potential; it mif
also underlie the measurements described in
Part V(b)(l). Laboratory Indicators of pro-
nounced bioaccumulation are to be reported
when coupled with potential for widespread
exposure and any non-trivial adverse effect.
Comment 17: The n-octanol/water parti-
tion coefficient addresses a physico-chemi-
cal property, not biological effects, and la
not alone an Indicator of substantial risk;
further, the values stated (or the coefficient
and the bioaccumulation factor In fish do
not correspond.
Response: The Agency acknowledges the
numerical error and has amended the values
to correspond. This policy statement now
directs the reporting of an experimental
measurement of bioaccumulation when
coupled with an adverse effect and potential
tor widespread exposure.
Comment it: The requirement that Infor-
mation which "links" an effect to a chemi-
cal be reported is too broad and contradicts
the statutory language of "reasonably
supports".
Response: The Agency has provided In a
new Part VI Its Interpretation of "reason-
ably supports".
Comment 19: A determination that infor-
mation "reasonably supports the conclu-
slon" of substantial risk cannot be made In-
dependently of considerations of use since
the method and manner of using a chemical
may influence the occurrence of an effect;
in particular, the criteria should reflect a
distinction between normal and abnormal
uses of chemicals.
Response; The Agency considers that the
appropriate components of a "substantial
risk" with respect to a chemical are (a) the
seriousness of the effect, and cb) total expo-
wire potential. The method and manner of
using a chemical is one of several factors de-
termining Its exposure potential. As de-
scribed In Part V, the importance of expo-
sure potential as a component of "substan-
tial risk" depends upon the kind of effect of
concern. Thus, the effects described In Part
V(a) are so serious that relatively little
weight to given to exposure: the effects de-
scribed in Parts V (b) and (c) involve a sig-
nificant exposure or exposure potential.
The Agency further considers that a defi-
nition of "normal" use for a particular
chemical will often depend upon a knowl-
edge of the risks associated with the
chemical.
a. information that xxsd hot as rcfortd
Comment 20: Information published In
scientific literature In languages other than
English should be exempted If published in
summary form by abstracting services. Can
the accuracy of English language abstracts
and commercial translations of foreign lit-
erature be assumed?
Response: This policy statement now pro-
vides that Information published in scien-
tific literature, whether in English or an-
other language. Is exempt from reporting If
published in summary form by certain
specified abstract services.
Comment 21: Information exchange sys-
tems with other Federal agencies should be
immediately established so that respondents
need not report to EPA Information already
reported to other Agencies, and vice versa.
Such duplicative reports are unduly burden-
some.
Response: EPA is coordinating this pro-
gram with other agencies now. When this
coordination is successfully completed, the
policy statement will be amended to exempt
from the reporting requirement information
that has been submitted to other specified
agencies. In the meantime, substantial-risk
information must be reported directly to
EPA; such a report does not discharge any
reporting obligation to other agencies.
F. INFORMATION FIRST RECETTCD PRIOR TO TKg
Rrrxcriv* dat* of tsca
Comment 22: The tense of the verb "ob-
tains" reveals that section 8(e) was Intended
to be applied prospectively to Information
newly acquired after January 1.1077. Utilize
section 8(d) or other rules to acquire Infor-
mation obtained before then.
Response: As discussed in the preamble to
the September 9 proposal, the Agency con-
siders section 8(e) to apply to risk informa-
tion possessed by or known to a person
before, on. or after January 1, 1077. Con-
cerning information first obtained before
1977, this policy statement continues to re-
quire reporting of Information received If a
person has been aware of It since January 1,
1977, for the reasons discussed in the Sep-
tember 9 preamble.
Comment 23: The term "aware" is too
vague to be of any help In responding to
these requirements. Since many corporate
employees are potentially subject to these
requirements, and given uncertainty over
the extent to which they ought to be aware
of pre-1977 Information, this provision tends
to compel the very file search It was Intend-
ed to avoid. The term "aware" should be
further defined, possibly In terms of actual
knowledge.
Response: The Agency In Part VIII of this
policy statement now defines the pre-1977
Information of which a person 1s considered
to be aware.
O. CONFIDENTIAL INFORMATION
Comment 24: EPA should delay guidance
until procedures are published governing
the treatment of confidential submissions.
Comment 25: EPA should treat all submis-
sions as confidential until the Information to
verified.
Comment 28.° EPA should automatically
publish section 8(e) notices.
Response to Comments 24 through 26;
EPA has Included a new Part X which de-
scribes how to submit a claim of confiden-
tiality and states that any or all of the In-
formation submitted may be claimed as con-
fidential. Such Information will be disclosed
by EPA only to the extent, and by means of
the procedures, set forth in 40 CFR Part 2.
H. MHCtLLMftOUS
Comment 27: What Is the statutory basis
or need tor guidance? What to Its exact
status under the Administrative Procedure
Act?
Response: This policy statement sets forth
EPA's interpretation of and policy concern-
ing TSCA section 8it). As an interpretive
rule and statement of policy it to not subject
to the comment period and delayed effec-
tive date provisions of the Administrative
Procedure Act (5 U.8.C. 553). Although
TSCA does not mandate a policy statement,
the Agency of necessity must develop the
criteria which will govern enforcement ac-
tivities. Trade associations and businesses
were among those who previously expressed
Interest In such a statement to guide their
compliance.
Comment 21: Clarify whether these re-
quirements apply to chemicals previously
but no longer manufactured, processed, or
distributed In commerce by a person.
Response: Information obtained before
1977 must be reported If the person has
been aware of it since January 1, 1977, as
prescribed by Part VIII. Concerning chemi-
cals which a person has discontinued manu-
facturing, processing, or distributing since
January 1, 1977, Information obtained
before the time of discontinuation Is subject
to these requirements. It is expected that
the acquisition of Information after that
time will be minimal; however, should addi-
tional Information be acquired. It may trig-
ger the reporting described in Part VIII.
Comment 2t: Clarify the meaning of "sub-
stantial risk" relative to other risks ad-
dressed by TSCA.
Response: A substantial risk to defined In
Part V(a) of this policy statement as a risk
of considerable concern because of (a) the
seriousness of the effect, and (b) the fact or
probability of Its occurrence. As opposed to
other risks addressed by TSCA, economic or
social benefits of use, or costs of restricting
use, are not to be considered In determining
whether a risk is "substantial".
Comment 30: To what extent are "users"
of chemicals subject to these requirements?
Response: The Agency considers that
many industrial uses of chemicals actually
fall within the scope of "processing" chemi-
cals. A manufacturer, processor, or distribu-
tor who obtains substantial-risk Information
concerning chemicals he handles should be
alert to the possibility he may have to
report It.
Comment 31: Are chemicals manufac-
tured, processed and distributed in com-
merce In small quantities solely for purpose*
of research and development subject to
these requirements?
Response: In general, the Agency consid-
ers that much manufacturing, processing,
and distribution in commerce of chemicals
In small quantities solely for purposes of re-
search and development Is conducted for
"commercial purposes". Such purposes
would include the sale and distribution of
such materials, as well as their use by the
manufacturer or processor in activities (for
example, product research and development
and studies assessing the feasibility and
safety of using chemicals) preceding his or a
client's commercial use of such materials or
others on a larger scale.
As described in Part V. the Agency consid-
ers that "substantial risks" depend In part
upon an exposure potential. Thus, the oc-
currence of the effects described in Part
V(a) presuppose exposure to the chemical
and must be reported; reporting of the
other effects will depend upon a potential
for significant levels of exposure.
Comment 31: Are raw materials, interme-
diates, and Inert Ingredients produced or
used In the manufacture of a pesticide sub-
ject to TSCA?
Response: The Administrator considers
that raw materials. Intermediates and Inert
Ingredients produced or used in the manu-
facture of a pesticide are substances or mix-
tures which can be regulated under T8CA.
In order to be considered a pesticide, a
substance must be Intended for use as a pes-
ticide. Raw materials. Intermediates, and
Inert ingredients produced or used in the
manufacture of a pesticide are not them-
selves regulated under FIFRA (unless they
happen to be pesticides themselves) and.
therefore, are subject to TSCA. The pestl-
FIOCRAl RiOiSTER, VOC 43, NO. 51-TMUMOAY, MARCH U,
806
-------
11116
NOTICES
ctde regulations at 40 CFR 162.4 are consis-
tent with this view.
Comment 33: Are Intermediates and cata-
lysts Intended solely for use In the produc-
tion of a food, food additive, druf, cosmetic,
or device subject to TSCA?
Response The Administrator consider*
that intermediates and catalysts Intended
solely for use In the production of a food,
food additive, drug, cosmetic,, or device are
excluded from regulation under TSCA. The
definitions of the FFDCA provide that
chemical substances which are intended for
use u a component of a food, food additive,
drug, cosmetic, or device are encompassed
within the meaning of such terms, respec-
tively. The FDA considers Intermediates
and catalysts to be such components. There-
fore, they are subject to regulation under
the FFDCA. Any such substance Is excluded
from regulation under TSCA Insofar as It is
actually manufactured, processed, or dis-
tributed in commerce solely for use in the
production of a food, food additive, drug,
cosmetic, or device.
Comment 34: Employees should have the
option to submit reports anonymously.
Rerponte: EPA considers that any person
may report information to EPA under
TSCA. Those who are required to do so
under section 8(e) are persons who manu-
facture. process, or distribute In commerce
chemical substances or mixtures, including
not only business entitles but also such em-
ployees as described In Part II. In order to
establish that such persons have discharged
their obligations, and In order to encourage
responsible review of the qusJIty of informa-
tion and the substantiality of risks, EPA be-
lieves that notlflers should Identify them-
selves. Section 23 will adequately protect
employees from discrimination pursuant to
notifications they have made under section
8(e).
CFR Doe. 78-7064 Filed 3-18-78; 8:49 am]
MOTE
According to technical amendments published
by EPA in the May 29, 1987 FEDERAL REGISTER
(52 FR 20083), TSCA Section 8(e) submissions
are to be addressed to the Agency as follows:
Document Processing Center (TS-790)
(Attn: Section 8(e) Coordinator)
Office of Toxic Substances
U.S. Environmental Protection Agency
401 "M" Street, S.W.
Washington, D.C. 20460
nociAi tionm, voi. a, no. s*—tmwsoay, march u. wt
807
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APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 5C-00-# CHEMICAL NAME: FORMALDEHYDE
SUBMISSION 1: 8EH9-06S9-D804 &EH4-049Q-0924
CAS NUMBER: 50-2?-$ CHEMICAL NAFIE: BENZENE, 1,1»-{2. 2,2-TRICHLOROETKYLIDENE)BI5l
-------
APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 71-43-2 CHEMICAL NAME: BENZENE
SUBMISSION •: 8EHQ-0990-1077
CAS NUMBER: 71-55-6 CHEMICAL NAME: ETHANE, 1,1,1-TRICHLORO-
SUBMISSION i: 8EHQ-0889-0817 8EHQ-0490-0953
CAS NUMBER: 72-54-8 CHEMICAL NAME: BENZENE, 1,1¦-<2,2-DICHL0R0ETHYLIDENE5BISI4-CHLORO-
SUBMISSION *: 8EH9-0790-1Q34
CAS NUMBER: 72-56-0 CHEMICAL NAME: BENZENE, l,l,-(2,2-DICHLOROETHYLIDENE)BIS[«-ETHYL-
SUBMISSION i: 8EH9-079Q-1034
CAS NUMBER: 74-83-9 CHEMICAL NAME: METHANE, BROMO-
OD
g SUBMISSION *: 8EHQ-U89-0844
CAS NUMBER: 74-83-9 CHEMICAL NAME: METHYL BROMIDE
SUBMISSION ».- 8EHQ-1189-0844
CAS NUMBER: 75-02-5 CHEMICAL NAME: ETHENE, FLU0R0-
SUBMISSION •: 8EHQ-1289-0856
CAS NUMBER: 75-02-5 CHEMICAL NAME: VINYL FLUORIDE
SUBMISSION >: 8EHQ-1289-Q856
CAS NUMBER: 75-15-0 CHEMICAL NAME: CARBON DISULFIDE
SUBM1SSIOH t: 8EH$-t>390-0904
CAS NUMBER: 75-21-8 CHEMICAL NAME: ETHYLENE OXIDE
SUBMISSION •: 8EHQ-0890-1053
-------
APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 75-21-8 CHEMICAL NAME: OXIRANE
SUBMISSION •: 8EHQ-0890-1053
CAS NUMBER: 75-31-0 CHEMICAL NAME: 2-PROPANAMINE
SUBMISSION •: 8EHQ-0290-0878
CAS NUMBER: 75-34-3 CHEMICAL NAME: ETHANE, 1,1-DICHLORO-
5UBMISSI0N t: 8EHQ-0490-0953
CAS NUMBER: 75-35-4 CHEMICAL NAME: ETHENE, 1,1-DICHLORO-
SUBMISSION •: 8EHQ-0490-0953
CAS NUMBER: 75-71-8 CHEMICAL NAME: METHANE, DICHLORODIFLUORO-
oo
O SUBMISSION »: 8EHQ-0589-0799
CAS NUMBER: 75-71-8 CHEMICAL NAME: REFRIGERANT 12
SUBMISSION »: 8EHQ-0589-0799
CAS NUMBER: 78-88-6 CHEMICAL NAME: 1-PROPENE, 2,3-DICHLGRO-
SUBMISSION >: 8EHQ-0290-0892
CAS NUMBER: 78-93-3 CHEMICAL NAME: 2-BUTANONE
SUBMISSION •: 8EHQ-U89-0847
CAS NUMBER: 80-54-6 CHEMICAL NAME: BENZENEPROPANAL, 1-(1,1-DIMETHYLETHYLALPHA.-METHYL-
SUBMISSION •: 8EHQ-0490-0931 S
CAS NUMBER: 80-62-6 CHEMICAL NAME: METHYL METHACRYLATE
SUBMISSION •: 8EHQ-0490-0917 8EHQ-0690-0999 *
-------
APPENDIX B: STATUS REPORTS 8Y CAS NUMBER
CAS NUMBER: 80-62-6 CHEMICAL NAME: 2-PROPENOIC ACID, 2-METHYL-, METHYL ESTER
SUBMISSION •: 8EHQ-0490-0917 8EHQ-0690-0999 *
CAS NUMBER: 84-74-2 CHEMICAL NAME: 1,2-BENZENEDICARBOXYLIC ACID, DIBUTYL ESTER
SUBMISSION •: 8EHQ-0590-0971
CAS NUMBER: 88-19-7 CHEMICAL NAME: BENZENESULFONAMIDE, 2-METHYL-
SUBMISSION »: 8EH$-0490-0938
CAS NUMBER: 88-19-7 CHEMICAL NAME: O-TOLUENESULFONAMIDE
SUBMISSION *: 8EHQ-0490-0938
CAS NUMBER: 88-73-3 CHEMICAL NAME: BENZENE, 1-CHLORO-2-MITRO-
SUBMISSION •: 8EHQ-0590-0973
CAS NUMBER: 88-75-5 CHEMICAL NAME: PHENOL, 2-NITRO-
SUBMISSION «: 8EHQ-0590-0978
CAS NUMBER: 91-66-7 CHEMICAL NAME: BENZENAMINE, N,N-DIETHYL-
SUBMISSION *: 8EHQ-0290-0878
CAS NUMBER: 91-94-1 CHEMICAL NAME: BENZIDINE, 3,3'-DICHLORO-
SUBMISSION •: 8EHQ-Q190-0863 8EHQ-0490-Q962
CAS NUMBER: 91-94-1 CHEMICAL NAME: tl.l'-BIPHENYL]^,*1-DIAMINE, 3,3'-DICHLORO-
SUBMISSION •: 8EHQ-019Q-0863 8EHQ-0490-0962
CAS NUMBER: 92-87-5 CHEMICAL NAME: BENZIDINE
SUBMISSION «: 8EHQ-0190-0863
-------
CAS NUMBER: 92-87-5
SUBMISSION #: 8EHQ-0190-0863
CAS NUMBER: 95-53-4
SUBMISSION t: 8EH9-0190-086*
CAS NUMBER: 95-53-
-------
APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 98-82-8 CHEMICAL NAME: CUMENE
SUBMISSION •: 8EHQ-1189-0846
CAS NUMBER: 99-54-7 CHEMICAL NAME: BENZENE, 1,2-DICHLORO-4-NITRO-
SUBMISSION #: 8EHQ-0590-0972
CAS NUMBER: 99-54-7 CHEMICAL NAME: ORTHENE, NITRATED
SUBMISSION t: 8EH9-0590-0972
CAS NUMBER: 100-00-5 CHEMICAL NAME: BENZENE, 1-CHL0R0-4-NITR0-
SUBMISSION t: 8EHQ-0590-0980
CAS NUMBER: 100-01-6 CHEMICAL NAME: ANILINE, P-NITRO-
00
£ SUBMISSION «: 8EHQ-0990-1080 S
CAS NUMBER: 100-01-6 CHEMICAL NAME: BENZENAMINE, 4-NITRO-
SUBMISSION *: 8EHQ-0990-1080 S
CAS NUMBER: 100-37-8 CHEMICAL NAME: ETHANOL, 2-(DIETHYLAMINO)-
SUBMISSION •: 8EHQ-0890-1043
CAS NUMBER: 101-20-2 CHEMICAL NAME: TCC SOAP BACTERIOSTAT
SUBMISSION »: 8EHQ-0590-0968
CAS NUMBER: 101-20-2 CHEMICAL NAME: UREA, N-<4-CHLOROPHENYL)-N•-(3,4-DICHLOROPHENYL)-
SUBMISSION t: 8EHQ-0590-0968
CAS NUMBER: 101-68-8 CHEMICAL NAME: BENZENE, 1,1'-METHYLENEBISt4-ISOCYANATO-
SUBMISSION •: 8EHQ-0289-0784 8EHQ-0290-0876
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APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 102-06-7 CHEMICAL NAME: DPG ACCELERATOR
SUBMISSION t: 8EHQ-0590-0990
CAS NUMBER: 102-06-7 CHEMICAL NAME: GUANIDINE, N,N'-DIPHENYL-
SUBMISSION I: 8EHQ-0590-0990
CAS NUMBER: 103-30-0 CHEMICAL NAME: BENZENE, 1,1•-<1,2-ETHENEDIYL)BIS-, (E)-
SUBMISSION #: 8EHQ-0490-0939
CAS NUMBER: 103-30-0 CHEMICAL NAME: STILBENE, TRANS-
SUBMISSION t: 8EH9"0490"0939
CAS NUMBER: 104-13-2 CHEMICAL NAME: ANILINE, P-BUTYL-
CO
£ SUBMISSION #: SEHQ-099O-1O8Q S
CAS NUMBER: 104-13-2 CHEMICAL NAME: BENZENAMINE, 4-BUTYL-
SUBMISSION t: 8EHQ-0990-1080 S
CAS NUMBER: 104-42-7 CHEMICAL NAME: ANILINE, P-DODECYL-
SUBMISSION «: 8EHQ-0990-1080 S
CAS NUMBER: 104-42-7 CHEMICAL NAME: BENZENAMINE, 4-DODECYL-
SUBMISSION »: 8EHQ-0990-1080 S
CAS NUMBER: 104-76-7 CHEMICAL NAME: 1-HEXANOL, 2-ETHYL-
SUBMISSION I: 8EHQ-0390-0910 S
CAS NUMBER: 106-49-0 CHEMICAL NAME: BENZENAMINE, 4-flETHYL-
SUBMISSION t: 8EH
-------
APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 106-49-0 CHEMICAL NAME: P-TOLUIDINE
SUBMISSION f: 8EH«-0990-1080 S
CAS NUMBER: 106-99-0 CHEMICAL NAME: 1,3-BUTADIENE
SUBMISSION #: 8EHQ-0390-0901 8EHQ-0390-0902
CAS NUMBER: 107-11-9 CHEMICAL NAME: 2-PR0PEN-1-AMINE
SUBMISSION •: 8EHQ-1089-0830
fcAS NUMBER: 107-15-3 CHEMICAL NAME: 1,2-ETHANEDIAMINE
SUBMISSION *: 8EHQ-0589-0801
CAS NUMBER: 107-30-2 CHEMICAL NAME: METHANE, CHLOROMETHOXY-
SUBMISSION #: 8EHQ-0589-0799
CAS NUMBER: 108-10-1 CHEMICAL NAME: 2-PENTANONE, 4-METHYL-
SUBMISSION t: 8EH0-1189-0847
CAS NUMBER: 108-44-1 CHEMICAL NAME: BENZENAMINE, 3-METHYL-
SUBMISSION *: 8EHQ-0990-1080 S
C.AS NUMBER: 108-44-1 CHEMICAL NAME: M-TOLUIDINE
SUBMISSION *: 8EHQ-0990-1080 S
CAS NUMBER: 111-30-8 CHEMICAL NAME: 6LUTARDIALDEHYDE
SUBMISSION •: BEHQ-0690-1008
CAS NUMBER: 111-30-8 CHEMICAL NAME: PENTANEDIAL
SUBMISSION «: 8EHQ-0690-1008
-------
APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 111-92-2 CHEMICAL NAME: 1-BUTANAMINE, N-BUTYL-
SUBMISSION »: 8EHQ-0990-1080 S
CAS NUMBER: 112-27-6 CHEMICAL NAME: ETHANOL, 2, 2 » - [ 1,2-ETHANEDIYLBIS(OXY) ] BIS-
SUBMISSION »: 8EHQ-0990-1064
CAS NUMBER: 112-35-6 CHEMICAL NAME: ETHANOL, 2-[2-(2-METH0XYETH0XY)ETHOXY]-
SUBMISSION t: 8EHQ-069Q-1002
CAS NUMBER: 112-96-9 CHEMICAL NAME: OCTADECANE, 1-ISOCYANATO-
SUBMISSION t: 8EHQ-0689-0802
CAS NUMBtft: 115-10-6 CHEMICAL NAME: METHANE, OXYBIS-
SUBMISSION #: 8EHQ-0589-0799
CAS NUMBER: 115-86-6 CHEMICAL NAME: PHOSPHORIC ACID, TRIPHENYL ESTER
SUBMISSION #: 8EHQ-0590-0975 8EHQ-0590-0976
CAS NUMBER: 117-08-8 CHEMICAL NAME: 1,3-IS0BENZ0FURANDI0NE, 4,5,6,7-TETRACHLORO-
SUBMISSION »: 8EHQ-0490-0948
CAS NUMBER: 117-08-8 CHEMICAL NAME: TETRATHAL
SUBMISSION »: 8EHQ-0490-0948
CAS NUMBER: 119-90-4 CHEMICAL NAME: [1,1' - BIPHENYL]-4,4'-DIAMINE, 3,3'-DIMETHOXY-
SUBMISSION #: 8EHQ-0190-0863
CAS NUMBER: 119-90-4 CHEMICAL NAME: O-DIANISIDINE
SUBMISSION #: 8EH9-0190-0863
-------
APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 119-93-7 CHEMICAL NAME: 11»1•-BIPHENYL]-4,4'-DIAMINE# 3,3'-DIMETHYL-
SUBMISSION »: 8EHQ-0190-0863 8EHQ-0990-1080 S
CAS NUMBER: 119-93-7 CHEMICAL NAME: O-TOLIDINE
SUBMISSION I: 8EHQ-0190-0863 8EHQ-0990-1080 S
CAS NUMBER: 120-71-8 CHEMICAL NAME: BENZENAMINE, 2-METH0XY-5-METHYL-
SUBMISSION #: 8EHQ-0990-1080 S
CAS NUMBER: 120-71-8 CHEMICAL NAME: P-CRESIDINE
SUBMISSION #: 8EHQ-0990-1080 S
CAS NUMBER: 123-86-4 CHEMICAL NAME: ACETIC ACID, BUTYL ESTER
SUBMISSION *: 8EHQ-0290-0880
CAS H'JMBER: 124-09-4 CHEMICAL NAME: 1,6-HEXANEDIAMINE
SUBMISSION t: 8EHQ-0590-0979
CAS NUMBER: 124-64-1 CHEMICAL NAME: PHOSPHONIUM, TETRAKIS(HYDROXYMETHYLCHLORIDE
SUBMISSION t: 8EHQ-0689-0804 8EHQ-0290-0877
CAS NUMBER: 126-73-8 CHEMICAL NAME: PHOSPHORIC ACID TRIBUTYL ESTER
SUBMISSION »: 8EHQ-1189-0847 SEHQ-0690-1007
CAS NUMBER: 127-19-5 CHEMICAL NAME: ACETAMIDE, N,N-DIMETHYL-
SUBMISSION •: 8EHQ-0590-0981
CAS NUMBER: 131-57-7 CHEMICAL NAME: METHANONE, (2-HYDROXY-4-METHOXYPHENYL)PHENYL-
SUBMISSION »: 8EHQ-1289-0855
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APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 131-72-6 CHEMICAL NAME: 2-BUTENOIC ACID, 2-(1-METHYLHEPTYL)-4,6-DINITROPHENYL ESTER,
(E)-
SUBMISSION •: 8EHQ-0790-1034
CAS NUMBER: 137-30-4 CHEMICAL NAME: VANCIDE MZ-96
SUBMISSION >: 8EHQ-0890-1045
CAS NUMBER: 137-30-4 CHEMICAL NAME: ZINC, BIS(DIMETHYLCARBAMODITHIOATO-S, S' (T-4)-
SUBMISSION I: 8EHQ-089Q-1045
CAS NUMBER: 140-88-5 CHEMICAL NAME: ACRYLIC ACID, ETHYL ESTER
SUBMISSION •: 8EHQ-0490-0917
CAS NUMBER: 140-88-5 CHEMICAL NAME: ETHYL ACRYLATE
SUBMISSION #: 8EHQ-0490-0917
CAS NUMBER: 140-88-5 CHEMICAL NAME: 2-PR0PEN0IC ACID, ETHYL ESTER
SUBMISSION »: 8EHQ-0490-0917
CAS NUMBER: 142-73-4 CHEMICAL NAME: GLYCINE, N-(CARBOXYMETHYL)-
SUBMISSION *: 8EHQ-0490-0946
CAS NUMBER: 149-30-4 CHEMICAL NAME: 2(3H)-BENZOTHIAZOLETHIONE
SUBMISSION #: 8EHQ-0889-0813
CAS NUMBER: 151-13-6 CHEMICAL NAME: HEXANEDIOIC ACID, DINONYL ESTER
SUBMISSION •: 8EHQ-0590-0982
CAS NUMBER: 287-29-6 CHEMICAL NAME: SILACYCLOBUTANE
SUBMISSION i: 8EHQ-0990-1084
-------
CAS NUMBER: 288-13-1
SUBMISSION »: BEHfl-0789-0807 S
CAS NUMBER: 288-88-0
SUBMISSION «: 8EH9-0459-0792
CAS NUMBER: <409-21-2
SUBMISSION *: 8EHQ-0690-1018
CAS NUMBER: <409-21-2
SUBMISSION «: 8EHQ-0690-1018
CAS NUMBER: <>20-04-2
SUBMISSION I: SEHQ-0490-0952 S
CAS NUMBER: 420-04-2
SUBMISSION i: SEHQ-0490-0 952 S
CAS NUMBER: 463-58-1
SUBMISSION • : SEHQ-0290-0892
CAS NUMBER: 513-35-9
SUBMISSION •: 8EHQ-0390-0901
CAS NUMBER: 541-85-5
SUBMISSION #•- 8EHQ-0489-07 93
CAS NUMBER: 541-85-5
SUBMISSION t: 8EHQ-0489-0793
! B: STATUS REPORTS BY CAS NUMBER
CHEMICAL NAME: 1H-PYRAZ0LE
CHEMICAL NAME: 1H-1 ,2 ,4-TRIAZOLE
CHEMICAL NAME: SILICON CARBIDE FIBERS
CHEMICAL NAME: SILICON CARBIDE, (SIC)
CHEMICAL NAME: CYANAMIDE
CHEMICAL NAME: CYANAMIDE, HYDROGEN
CHEMICAL NAME: CARBON OXIDE SULFIDE, (COS)
CHEMICAL NAME: 2-BUTENE, 2-METHYL-
CHEMICAL NAME: 3-HEPTANONE, 5-METHYL-
CHEMICAL NAME: KETONE, ETHYL-SEC-AMYL
-------
APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 542-88-1
SUBMISSION •: 8EHQ-0589-0799
CAS NUMBER: 542-88-1
SUBMISSION *: 8EHQ-0589-0799
CAS NUMBER: 553-26-4
SUBMISSION •: 8EHQ-1Q89-0831
CAS NUMBER: 556-52-5
SUBMISSION t: 8EHQ-0789-0809
CAS NUMBER: 556-52-5
SUBMISSION t: 8EHQ-0789-0809
CAS NUMBER: 557-09-5
SUBMISSION •: 8EHQ-0690-1019
CAS NUMBER: 563-46-2
SUBMISSION t: 8EHQ-0390-0901
CAS NUMBER: 565-80-0
SUBMISSION «: 8EHQ-0990-1062
CAS NUMBER: 576-26-1
SUBMISSION »: SEHQ-0790-1027
CAS NUMBER: 592-45-0
SUBMISSION •: 8EHQ-0990-1061
CHEMICAL NAME: BIS(CHLOROMETHYL)ETHER (BCME)
CHEMICAL NAME: METHANE, OXYBIStCHLORO-
CHEMICAL NAME: 4,4•-BIPYRIDINE
CHEMICAL NAME: GLYCIDOL
x
CHEMICAL NAME: 0X1RANEMETHAN0L
*
CHEMICAL NAME: OCTANOIC ACID. ZINC SALT
CHEMICAL NAME: 1-BUTENE, 2-METHYL-
CHEMICAL NAME: 3-PENTANONE, 2,4-DIMETHYL-
CHEMICAL NAME: PHENOL, 2,6-DIMETHYL-
CHEMICAL NAME: 1,4-HEXADIENE
-------
APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 598-73-2 CHEMICAL NAME: ETHENE, BROMOTRIFLUORO-
SUBMISSION •: 8EHQ-1289-0859
CAS NUMBER: 611-19-8 CHEMICAL NAME: BENZENE, 1-CHL0R0-2-
-------
APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 79i-2*-8 CHEMICAL NAME: SANTOFLEX 13
SUBMISSION •: 8EHQ-6590-0 966
CAS NUMBER: 919-30-2 CHEMICAL NAME: 1-PROPANAMINE, 3-(TRIETHOXYSILYL)-
SUBMISSION •: 8EHQ-0389-0780
CAS NUMBER: 919-30-2 CHEMICAL NAME: SILANE A-1100
SUBMISSION #: 8EHQ-0389-0780
CAS NUMBER: 941-69-5 CHEMICAL NAME: 1H-PYRR0LE-2.5-DI0NE, 1-PHENYL-
SUBMISSION •: 8EHQ-0690-1000 S
CAS NUMBER: 998-30-1 CHEMICAL NAME: SILANE, TRIETHOXY-
SUBMISSION •: 8EHQ-1089-0832
CAS NUMBER: 1300-73-8 CHEMICAL NAME: BENZENAMINE, AR,AR-DIMETHYL-
SUBMISSION •: 8EHQ-0990-1080 S
CAS NUMBER: 1300-73-8 CHEMICAL NAME: XYLIDINE (MIXED)
SUBMISSION «: 8EHQ-0990-1080 S
CAS NUMBER: 1309-64-4 CHEMICAL NAME: ANTIMONY OXIDE (SB203)
SUBMISSION •: 8EHQ-0589-0797
CAS NUMBER: 1318-23"** CHEMICAL NAME: ALUMINUM OXIDE, ALPHA-MONOHYDRATE
SUBMISSION *: 8EHQ-0790-1029
CAS NUMBER: 1318-23-6 CHEMICAL NAME: BOEHMITE, (AL(OH)O)
SUBMISSION i: 8EH9"0790"1029
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APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 1S32-21-4 CHEMICAL NAME: ASBESTOS
SUBMISSION •: 8EHQ-0690-1018 8EHQ-0790-1029
CAS NUMBER: 1336-36-3 CHEMICAL NAME: 1,1'-BIPHENYL, CHLORO DERIVS.
SUBMISSION «: 8EHQ-0490-0933
CAS NUMBER: 1336-36-3 CHEMICAL NAME: POLYCHLORINATED BIPHENYLS (PCB)
SUBMISSION i: 8EHQ-0490-0933
CAS NUMBER: 13*4-28-1 CHEMICAL NAME: ALUMINA WHISKERS
SUBMISSION *: 8EHQ-0690-1018
qq CAS NUMBER: 1344-28-1 CHEMICAL NAME: ALUMINUM OXIDE (AL203)
w SUBMISSION *: 8EHQ-0690-1018
CAS NUMBER: 1429-50-1 CHEMICAL NAME: DEQUEST 2041
SUBMISSION *: 8EHQ-0490-0940
CAS NUMBER: 1429-50-1 CHEMICAL NAME: PHOSPHONIC ACID, [1,2-ETHANEDIYLBISCNITRILOBIS(METHYLENE)]]T
ETRAKIS-
SUBMISSION •: 8EHQ-0490-0940
CAS fiUMBER: 1453-58-3 CHEMICAL NAME: 1-H-PYRAZOLE, 3-METHYL-
SUBMISSION «: 8EHQ-0389-0786 S
CAS NUMBER: 1477-55-0 CHEMICAL NAME: 1,3-BENZENEDIMETHANAMINE
SUBMISSION i: 8EHQ-0390-0909 *
CAS NUMBER: 1634-04-4 CHEMICAL NAME: PROPANE, 2-METHQXY-2-METHYL-
SUBMISSION •: 8EHQ-0390-0900
-------
APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 1842-05-3 CHEMICAL NAME: ETHANE, 1,1-DICHLORO-l,2-DIFLUORO-
SUBMISSION t: 8EHQ-0890-1046
CAS NUMBER: 1842-05-3 CHEMICAL NAME: HCFC-132C
SUBMISSION «: 8EHQ-0890-1046
CAS NUMBER: 2155-38-6 CHEMICAL NAME: BA 42'580
SUBMISSION •: 8EHQ-1189-0847
CAS NUMBER: 2155-38-6 CHEMICAL NAME: SPIROE1,3-DIOXANE-5,3»-[7]OXABICYCLO[4.1.0JHEPTANE] , 2-[2-
-(OXIRANYLMETHOXY)ETHOXY]ETHYL]-
SUBMISSION t: 8EHQ-1189-0847
CAS NUMBER: 2421-28-5 CHEMICAL NAME: 3,3»,4,4¦-BENZOPHENONETETRACARBOXYLIC ACID DIANHYDRIDE
SUBMISSION •: 8EHQ-0589-0796
CAS NUMBER: 2421-28-5 CHEMICAL NAME: 1,3-IS0BENZ0FURANDI0NE, 5,5'-CARBONYLBIS-
SOlBMISSION •: 8EHQ-0589-0796
CAS NUMBER: 2479-46-1 CHEMICAL NAME: BENZENAMINE, 4,4'-C1,3-PHENYLENEBIS(OXY)BIS-
SUBMISSION #: 8EHQ-0390-0898
CAS NUMBER: 2479-46-1 CHEMICAL NAME: RODA
SUBMISSION t: 8EHQ-0390-0898
CAS NUMBER: 2512-29-0 CHEMICAL NAME: BUTANAMIDE, 2-[(4-METHYL-2-NITROPHENYL)AZ0]-3-0X0-N-PHENYL
SUBMISSION •: 8EK9-0490-0962
CAS NUMBER: 2512-29-0 CHEMICAL NAME: PERMANENT YELLOW G TYPE
SUBMISSION #: 8EHQ-0490-0962
-------
APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 2512-29-0 CHEMICAL NAME: C. I. PIGMENT YELLOW 14
SUBMISSION •: 8EHQ-0490-0962
CAS NUMBER: 2524-03-0 CHEMICAL NAME: PHOSPHOROCHLORIDOTHIOIC ACID, 0,0-DIMETHYL ESTER
SUBMISSION •: 8EHQ-0290-0878 8EHQ-0290-0892
CAS NUMBER: 2530-87-2 CHEMICAL NAME: DOU CORNING 91-2366 SILANE
SUBMISSION •: 8EHQ-0990-1067
CAS NUMBER: 2530-87-2 CHEMICAL NAME: SILANE, (3-CHLOROPROPYL)TRIMETHOXY-
SUBMISSION t: 8EHQ-0990-1067
CAS NUMBER: 2536-05-2 CHEMICAL NAME: BENZENE, 1,1'-METHYLENEBISt2-IS0CYANAT0-
oo
K SUBMISSION •: 8EHQ-0289-0784
CAS NUMBER: 2540-99-0 CHEMICAL NAME: 1,3-ISOBENZOFURANDIONE, 5,5'-SULFONYLBIS-
SUBMISSION •: 8EHQ-0489-0795
CAS NUMBER: 2540-99-0 CHEMICAL NAME: 4,4•-SULFONYLBIS(PHTHALIC ANHYDRIDE)
SUBMISSION *: 8 EHQ-048 9-07 95
CAS NUMBER: 2591-86-8 CHEMICAL NAME: 1-PIPERIDINECARBOXALDEHYDE
SUBMISSION •: 8EHQ-0590-0974
CAS NUMBER: 2628-16-2 CHEMICAL NAME: PHENOL, 4-ETHENYL-, ACETATE
SUBMISSION *: 8EHQ-0990-1082
CAS NUMBER: 2628-16-2 CHEMICAL NAME: STYRENE, ACETOXY-
SUBMISSION »: 8EHQ-0990-1082
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APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 2716-16-1 CHEMICAL NAME: BENZENAMINE, 4,4'-[1>4-PHENYLENEBISC1-METHYLETHYLIDENE) IBIS-
SUBMISSION t: 8EM<}-i 28 9-3852 S
CAS NUMBER: 2716-10-1 CHEMICAL NAME: EPIKURE 1061
SUBMISSION •: 8EHQ-1289-0852 S
CAS NUMBER: 2716-12-3 CHEMICAL NAME: BENZENAMINE, 4,4'-C1,4-PHENYLENEBIS(1-METHYLETHYLIDENE)3BIS[
2,6-DIMETHYL-
SUBMISSION «: 8EHQ-1289-0852 S
CAS NUMBER: 2716-12-3 CHEMICAL NAME: EPIKURE 1062
SUBMISSION »: 8EHQ-1289-0852 S
00 CAS NUMBER: 3081-14-9 CHEMICAL NAME: 1,4-BENZENEDIAMINE, N,N•-BIS(1,4-DIMETHYLPENTYL)-
to
SUBMISSION »: 8EHQ-0590-0977
CAS NUMBER: 3081-14-9 CHEMICAL NAME: SANTOFLEX 77
SUBMISSION »: 8EHQ-0590-0977
CAS NUMBER: 3388-03-2 CHEMICAL NAME: ARALDITE CY-175
SUBMISSION •: 8EHQ-1189-0847
CAS NUMBER: 3388-03-2 CHEMICAL NAME: BAKELITE ERL-4234
SUBMISSION •: 8EHQ-1189-0847
CAS NUMBER: 3388-03-2 CHEMICAL NAME: BA 42'579
SUBMISSION •: 8EHQ-1189-0847
CAS NUMBER: 3388-03-2 CHEMICAL NAME: ERL-4234
SUBMISSION #: 8EHQ-1189-0847
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APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 3S88-03-2 CHEMICAL NAME: SPIROt1,3-DIOXANE-5,3'-C730XABICYCL0I4.1.01HEPTANE], 2-(7-0X
ABICYCL0C4.1.0]HEPT-3-YL)-
SUBMISSION «: 8EHQ-U89-0847
CAS NUMBER: 3520-72-7 CHEMICAL NAME: PERMANENT ORANGE G TYPE
SUBMISSION •: 8EHQ-0490-0962
CAS NUMBER: 3520-72-7 CHEMICAL NAME: C.I. PIGMENT ORANGE 13
SUBMISSION t: 8EHQ-0490-0962
CAS NUMBER: 3520-72-7 CHEMICAL NAME: 3H-PYRAZ0L-3-0NE, 4,4•-t(3,3•-DICHLOROt1,1•-BIPHENYL]-4,4•-D
IYL)BIS(AZ0)]BISC2,4-DIHYDR0-5-METHYL-2-PHENYL-
SUBMISSION *: 8EHQ-0490-0962
CAS NUMBER: 3618-72-2 CHEMICAL NAME: ACETAMIDE, N-[5-tBIS[2-(ACETYLOXY)ETHYLlAMINO]-2-[(2-BROMO-4
»6-DINITROPHENYL)AZOl-4-METHOXYPHENYL]-
SUBMISSION «: 8EHQ-0790-1030
CAS NUMBER: 3618-72-2 CHEMICAL NAME: C. I. DISPERSE BLUE 79:1 (PURIFIED PRESSCAKE)
SUBMISSION •: 8EH9-0790-1030
CAS NUMBER: 3806-34-6 CHEMICAL NAME: 2,4,8,10-TETRAOXA-3,9-DIPH0SPHASPIR0C5.5]UNDECANE, 3,9-BIS(0
CTADECYLOXY)-
SUBMISSION *: 8EHQ-0590-0996
CAS NUMBER: 3806-34-6 CHEMICAL NAME: UESTON 618
SUBMISSION •: 8EHQ-0590-0996
CAS NUMBER: 4109-96-0 CHEMICAL NAME: CHLOROSILANE A-199
SUBMISSION *: 8EHQ-0689-0803
CAS NUMBER: 4109-96-0 CHEMICAL NAME: SILANE, DICHLORO-
SUBMISSION •: 8EHQ-0689-0803
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APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 4170-3P"3 CHEMICAL NAME: 2-BUTENAL
SUBMISSION «: BEHQ-0690-1017
CAS NUMBER: 4170-30-3 CHEMICAL NAME: CROTONALDEHYDE
SUBMISSION •: SEHQ-0690-1017
CAS NUMBER: 4351-70-6 CHEMICAL NAME: PHOSGARD C-22-R
SUBMISSION •: BEHQ-0490-0947
CAS NUMBER: 4351-70-6 CHEMICAL NAME: PHOSPHONIC ACID. 11 — t Ct2-CHL0R0ETH0XY)12-Cti JROETHYL)PH0SPHI
NYL10XY]ETHYL J-, 1-CBIS(2-CHLOROETHOXYJPHOSPHINYL]ETHYL 2-CH
LOROETHYL ESTER
SUBMISSION •: »EH«-0490-0947
CAS NUMBER: 4531-49-1 CHEMICAL NAME: BUTANAMIDE, 2,2'-[(3,3'-DICHLOROt1,1'-BIPHENYL]-4,4¦-DIYL)BI
S(AZO)IBISIN-(2-METHOXYPHENYL)-3-0X0"
SUBMISSION I: BEHQ-0490-0962
£kS NUMBER: 4531-49-1 CHEMICAL NAME: PERMANENT YELLOW GG TYPE
SUBMISSION I: SEH4-0490-0962
CAS NUMBER: 4531-49-1 CHEMICAL NAME: C. I. PIGMENT YELLOW 17
SUBMISSION •: BEHQ-0490-0962
CAS NUMBER: 5076-19-7 CHEMICAL NAME: ISOAMYLENE OXIDE
SUBMISSION •: 8EHQ-0690-1003
CAS NUMBER: 5102-B3-0 CHEMICAL NAME: BUTANAMIDE, 2,2*-[(3,3'-DICHLORO[1,1•-BIPHENYL]-4,4'-DIYL)BI
S(AZO)1BIS[N~(2,4-DIMETHYLPHENYL)-3-0X0-
SUBMISSION I: BEH9-0490-0962
CAS NUMBER: 5102-B3-0 CHEMICAL NAME: PERMANENT YELLOW GR TYPE
SUBMISSION •: 8EHQ-0490-0962
-------
APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 5102-23-0 CHEMICAL NAME: C.I. PIGMENT YELLOkl 13
SUBMISSION t: 8EHQ-0490-0962
CAS NUMBER: 5567-15-7 CHEMICAL NAME: BUTANAMIDE, 2,2»-[(3,3'-DICHLOROt1,1'-BIPHENYL]-«,4•-DIYL)BI
S(AZ0)]BIStN-C<»-CHL0R0-2,5-DIMETH0XYPHENYL)-3-0XQ-
SUBMISSION *: 8EHQ-0490-0962
CAS NUMBER: 5567-15-7 CHEMICAL NAME: PERMANENT YELLOW HR TYPE
SUBMISSION #: 8EHQ-0490-0962
CAS NUMBER: 5567-15-7 CHEMICAL NAME: C. I. PIGMENT YELLOM 83
SUBMISSION «: 8EHQ-0490-0962
oo tA5 NUMBER: 5979-28-2 CHEMICAL NAME: BUTANAMIDE, N,N'-(3, 3'-DIMETHYLtl, 1'-BIPHENYL]-
-------
APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 6358-87-8 CHEMICAL NAME: C. I. PIGMENT RED 38
SUBMISSION t: 8EHQ-0490-0962
CAS NUMBER: 6358-87-8 CHEMICAL NAME:
SUBMISSION #: 8EHQ-0490-0962
1H-PYRAZ0LE-3-CARB0XYLIC ACID, 4,4 '-[C3,3'-DICHLOROC1, 11-BIP
HENYL]-4,4'-DIYL)BIS(AZ0)]BIS[4,5-DIHYDR0-5-0X0-l-PHENYL-, D
IETHYL ESTER
CAS NUMBER: 6358-87-8 CHEMICAL NAME: VULCAN FAST RED B
SUBMISSION #: 8EHQ-0490-0962
CAS NUMBER: 6419-19-8 CHEMICAL NAME: DEQUEST 2000
SUBMISSION •: 8EHQ-0490-0937
CO
o CAS NUMBER: 6419-19-8 CHEMICAL NAME: PHOSPHONIC ACID, [NITRILOTRIS(METHYLENE)]TRIS-
SUBMISSION *: 8EHQ-0490-0937
CAS NUMBER: 6422-83-9 CHEMICAL NAME: 1H-PYRR0LE-2,5-DIONE, 1,1'-(4-METHYL-1,3-PHENYLENE)BIS-
SUBMISSION #: 8EH9-0790-1023 S
CAS NUMBER: 7085-85-0 CHEMICAL NAME: 2-PR0PEN0IC ACID, 2-CYAN0-, ETHYL ESTER
SUBMISSION »: 8EHQ-0989-0821 S
CAS NUMBER: 7400-27-3 CHEMICAL NAME: HYDRAZINE, (1,1-DIMETHYLETHYL)-, MONOHYDROCHLORIDE
SUBMISSION •: 8EH9-0890-1042
CAS NUMBER: 7439-92-1 CHEMICAL NAME: LEAD
SUBMISSION »: 8EHQ-0990-1071
CAS NUMBER: 7440-31-5 CHEMICAL NAME: TIN
SUBMISSION #: 8EHQ-0990-1071
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APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 7705-08-0 CHEMICAL NAME: IRON CHLORIDE (FECL3)
SUBMISSION «: 8EH9-0890-1042
CAS NUMBER: 7723-14-0 CHEMICAL NAME: PHOSPHORUS
SUBMISSION •: 8EHQ-0889-0820
CAS NUMBER: 9014-92-0 CHEMICAL NAME: POLYCOXY-l,2-ETHANEDIYL), .ALPHA.-CDODECYLPHENYL)-.OMEGA.
DROXY-
SUBMISSION *: 8EHQ-0490-0942
CAS NUMBER: 9014-92-0 CHEMICAL NAME: STEROX DJ SURFACTANT
SUBMISSION t: 8EHQ-049Q-0942
HUMBER: 9016-87-9 CHEMICAL NAME: ISOCYANIC ACID, POIYMETHYLENEPOLYPHENYLENE ESTER
SUBMISSION ft: 8EHQ-0289-0784
CAS NUMBER: 10578-42-4 CHEMICAL NAME: BA 42*581
SUBMISSION ft: 8EHQ-1189-0847
CAS NUMBER: 10578-42-4 CHEMICAL NAME: 7-0XABICYCL0I4.1.0]HEPTANE. 3-1(OXIRANYLMETHOXY)METHYL]-
SUBMISSION ft: 8EHQ-1189-0847
CAS NUMBER: 11097-69-1 CHEMICAL NAME: AROCHLOR 1254
SUBMISSION ft: 8EHQ-0490-0933
CAS NUMBER: 13463-41-7 CHEMICAL NAME: ZINC, BISC1-HYDROXY-2(1H)-PYRIDINETHIONAT0-O,5)-, CT-4J-
SUBMISSION ft: 8EHQ-0790-1035
CAS NUMBER: 13463-41-7 CHEMICAL NAME: ZINC PYRITHIONE
SUBMISSION ft: 8EHQ-0790-1035
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APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 13565-96-3 CHEMICAL NAME: BISMUTH MOLYBDENUM OXIDE, CBI2M006)
SUBMISSION t: 8EHQ-0389-0789
CAS NUMBER: 13586-68-0 CHEMICAL NAME: 2-PROPENAL, 3-[4-(1,1-DIMETHYLETHYLJPHENYLI-2-METHYL-
SUBMISSION «: 8EHQ-0490-0931 S
CAS NUMBER: 14024-41-0 CHEMICAL NAME: IRIDATE(3~), HEXACHLORO-, TRIPOTASSIUM, (OC-6-11)-
SUBMISSION *: 8EH3-0590-0991 S
CAS NUMBER: 14059-33-7 CHEMICAL NAME: BISMUTH VANADIUM OXIDE,
-------
APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 16714-68-4
SUBMISSION *: 8EHQ-0290-0892
CAS NUMBER: 16881-77-9
SUBMISSION «: 8EH9-0690-1009
CAS NUMBER: 17095-24-8
SUBMISSION 8EHQ-B290-0885
CAS NUMBER: 17095-24-8
SUBMISSION •: 8EH«-0290~0885
CAS NUMBER: 18406-41-2
SUBMISSION «: 8EH9-0890-1047
CAS NUMBER: 18406-41-2
SUBMISSION «: 8EHQ-0890-1047
CAS NUMBER: 20592-85-2
SUBMISSION •: 8EHQ-0490-0937
CAS NUMBER: 22042-96-2
SUBMISSION «: 8EHQ-0490-0950
CAS NUMBER: 22042-96-2
SUBMISSION *: 8EHQ-O490-O95O
CAS NUMBER: 22042-96-2
SUBMISSION »: 8EHQ-0490-095D
CHEMICAL NAME: PROPANE, 1,1,2,2,3-PENTACHLORO-
CHEMICAL NAME: SILANE, DIMETHOXYMETHYL-
CHEMICAL NAME: 2,7-NAPHTHALENEDISULFONIC ACID, 4-AMIN0-5-HYDR0XY-3,6-BISC[4
-[[2-CSULF00XYJETHYL1SULFONYL3PHENYL1AZ03-, TETRASODIUM SALT
CHEMICAL NAME: C.I. REACTIVE BLACK 5
CHEMICAL NAME: 2,7-DIOXA-3,6-DISILAOCTANE, 3,3,6,6-TETRAMETHOXY-
CHEMICAL NAME: DOM CORNING X1-6145A ADDITIVE
CHEMICAL NAME: PHOSPHONIC ACID, INITRILOTRIS(METHYLENE)1TR1S-, SODIUM SALT
CHEMICAL NAME: DEQUEST 2061
CHEMICAL NAME: DEQUEST 2066
CHEMICAL NAME: PHOSPHONIC ACID, [[(PHOSPHONOMETHYL)IMINO]BIStC2,1-ETHANEDIY
LNITRILO)BIS(METHYLENE)33TETRAKIS-, SODIUM SALT
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APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 25103-58-6 CHEMICAL
SUBMISSION t: 8EHQ-0590-0994 *
CAS NUMBER: 25339-17-7 CHEMICAL
SUBMISSION »: 8EHQ-0390-0911 S
CAS NUMBER: 25550-98-5 CHEMICAL
SUBMISSION *: 8EHQ-0490-0963
CAS NUMBER: 26140-60-3 CHEMICAL
SUBMISSION «: 8EHQ-0590-0983
CAS NUMBER: 26616-47-7 CHEMICAL
ao
OJ
SUBMISSION •: 8EH«"1189"0847
CAS NUMBER: 26760-64-5 CHEMICAL
SUBMISSION «: 8EHQ-0390-0901
OAS NUMBER: 26760-64-5 CHEMICAL
SUBMISSION *: 8EHQ-0390-0901
CAS NUMBER: 27344-41-8 CHEMICAL
SUBMISSION *: 8EHQ-0989-0822
CAS NUMBER: 27344-41-8 CHEMICAL
SUBMISSION •: 8EHQ-0989-0822
CAS NUMBER: 32536-52-0 CHEMICAL
SUBMISSION •: 8EHQ-0990-1072
NAME: TERT-DODECANETHIOL
NAME: ISODECANOL
NAME: PHOSPHOROUS ACID, DIISODECYL PHENYL ESTER
NAME: TERPHENYL
NAME: SPIROCl,3-DIOXANE-5,3,-[7 3OXABICYCLO[4.1.0]HEPTANEl, 2-C7-0X
ABICYCLOU.l. 03HEPT-3-YL)-, HOMOPOLYMER
NAME: BUTENE, 2-METHYL-
NAME: ISOAMYLENE
NAME: BENZENESULFONIC ACID, 2,21-(11,1•-BIPHENYL1-4,4•-DIYLDI-2,1-
ETHENEDIYLJBIS-, DISODIUM SALT
NAME: FAT 65029/6
NAME: BENZENE, 1,1 ¦-OXYBIS-, OCTABROMO DERIV.
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APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 34364-42-6
SUBMISSION *: 8EHQ-0590-0975
CAS NUMBER: 34643-46-4
SUBMISSION •: 8EHQ-0989-0823
CAS NUMBER: 34643-46-4
SUBMISSION i: 8EHQ-0989-0823
CAS NUMBER: 34643-46-4
SUBMISSION •: 8EHQ-0989-0823
CAS NUMBER: 37871-12-8
SUBMISSION t: 8EHQ-0290-0893
CAS NUMBER: 38051-10-4
SUBMISSION «: 8EHQ-0490-0944
CAS NUMBER: 38051-10-4
SUBMISSION t: 8EHQ-0490-0944
CAS NUMBER: 38444-13-2
SUBMISSION «: 8EHQ-0290-0894
CAS NUMBER: 38638-05-0
SUBMISSION i: 8EHQ-C590-0975
CAS NUMBER: 38888-98-1
SUBMISSION i: 8EH4-0590-0984
CHEMICAL NAME: PHOSPHORIC ACID, C1-METHYL-l-PHENYLETHYLJPHENYL DIPHENYL EST
ER
8EHQ-0590-0976
CHEMICAL NAME: PHOSPHORODITHIOIC ACID, 0-(2»4-DICHL0R0PHENYL)-, O-ETHYL S-P
ROPYL ESTER
CHEMICAL NAME: PROTHIOFOS
CHEMICAL NAME: TOKUTHION
CHEMICAL NAME: BENZENE, (1,1-DIMETHYLETHYL)ETHYL-
CHEMICAL NAME: PHOSGARD 2XC20
CHEMICAL NAME: PHOSPHORIC ACID, 2,2-BIS(CHL0R0METHYL)-l,3-PR0PANEDIYL TETRA
KIS(2-CHL0R0ETHYL) ESTER
CHEMICAL NAME: BENZOIC ACID, 4-METHOXY-, 4-PENTYLPHENYL ESTER
CHEMICAL NAME: PHOSPHORIC ACID, NONYLPHENYL DIPHENYL ESTER
8EHQ-0590-0976
CHEMICAL NAME: BENZENE, (PHENYLETHYL)-
-------
APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 38970-72-8 CHEMICAL NAME: CYCIOHEXAME, 1,1•-(I,1,3-TRIMETHYL-l,3-PROPANEDIYL3BIS-
SUBMISSION •: 8EH9-0490-0949
CAS NUMBER: 38970-72-8 CHEMICAL NAME: HLD
SUBMISSION I: 8EHQ-0490-0949
CAS NUMBER: 47073-92-7 CHEMICAL NAME: CYANIC ACID, ETHYLIDENEBIS-4,1-PHENYLENE ESTER
SUBMISSION t: 8EHQ-0189-0781 S
CAS NUMBER: 52372-38-0 CHEMICAL NAME: BENZENEDIAZONIUM, 3~METHYL-4-<1-PYRR0LIDINYL) -, TRICHLOROZIN
CATE(l-)
SUBMISSION *: 8EH4-0790-1D21
CAS NUMBER: 52572-38-0 CHEMICAL NAME: DIAZO Y
SUBMISSION «: 8EHQ-0790-1021
CAS NUMBER: 54395-37-8 CHEMICAL NAME: 1H-ISOINDOLE-1.3-(2H)-DIONE, 2-BUTYL-5-NITR0-
SUBMI5SION •: 8EH9-0790-1924
CAS NUMBER: 55157-25-0 CHEMICAL NAME: ETHENE, BROMOTRIFLUORO-, HOMOPOLYMER
SUBMISSION «: 8EH9-0190-08&0 5
CAS NUMBER: 55566-30-8 CHEMICAL NAME: PHOSPHONIUM, TETRAKIStHYDROXYMETHYL)-» SULFATE C2:1J (SALT)
SUBMISSION •: 8EHQ-0689-0804 SEHQ-0290-0877
CAS NUMBER: 56982-91-3 CHEMICAL NAME: SILICATE, TETRAMETHYL AMMONIUM
SUBMISSION I: 8EHQ-D390-0S99 »
CAS NUMBER: 57910-79-9 CHEMICAL NAME: 2-BUTANOL, 2-1(1,1-DIMETHYLETHYL>AZO]-
SUBMI5SION •: 8EHQ-0990-1065
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APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 57910-79-9 CHEMICAL NAME: LUCEL-4
SUBMISSION *: 8EHQ-0990-1065
CAS NUMBER: 61788-32-7 CHEMICAL NAME: TERPHENYL, HYDROGENATED
SUBMISSION »: 8EHQ-0590-0983
CAS NUMBER: 61791-26-2 CHEMICAL NAME: AMINES, TALLOW ALKYL, ETHOXYLATED
SUBMISSION •: 8EHQ-0190-0871 S
CAS NUMBER: 63*02-26-6 CHEMICAL NAME: HYDRAZINECARBOXALDEHYDE, 2-C4-AMIN0PHENYL)-
SUBMISSION •: 8EHQ-0189-0779
CAS NUMBER: 63*49-88-7 CHEMICAL NAME: BUTANOIC ACID, 1-CYCLOHEXYLETHYL ESTER
00
^ SUBMISSION *: 8EH4-0490-0943
CAS NUMBER: 63470-53-1 CHEMICAL NAME: GOLD, DIMETHYL-1,1,1-TRIFLU0R0-2,4-PENTANEDIONATO
SUBMISSION «: 8EHQ-0589-0800
CAS NUMBER: 64800-83-5 CHEMICAL NAME: BENZENE, ETHYL(PHENYLETHYL)-
SUBMISSION •: 8EHQ-0590-0984
CAS NUMBER: 64819-51-8 CHEMICAL NAME: 2-HEXANOL, 2-[(1,1-DIMETHYLETHYL)AZO]-5-METHYL-
SUBMISSION t: 8EHQ-0890-1041
CAS NUMBER: 64819-51-8 CHEMICAL NAME: LUCEL-7 AZO FOAMING AGENT
SUBMISSION I: 8EHQ-0890-1041
CAS NUMBER: 65701-07-7
SUBMISSION «: 8EHQ-0590-0967
CHEMICAL NAME: 1,2-BENZENEDICARBOXYLIC ACID, 4,4'-CARB0NYLBIS-, AR.AR'-DIET
HYL ESTER, COMPD. WITH 1,3-BENZENEDIAMINE
-------
APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 65701-07-7 CHEMICAL NAME: SKYBOND 700 POLYIMIDE RESIN
SUBMISSION *: 8EHQ-0590-0967
CAS NUMBER: 66070-54-0 CHEMICAL NAME: I-DECENE, POLYMER WITH l-QCTEHE> HYDROGENATED
SUBMISSION t: 8EHQ-0590-0985 *
CAS NUMBER: 67762-90-7 CHEMICAL NAME: SILOXANES AND SILICONES, DI-ME, REACTION PRODUCTS WITH SILIC
A
SUBMISSION #¦' 8EHQ-0590-09U *
CAS NUMBER: 68398-19-6 CHEMICAL NAME: BENZENE, ETHYL(PHENYLETHYL)-, MONO-AR-ETHYL DERIV.
SUBMISSION t: BEHQ-0590-0984
CD CAS NUMBER: 68412-24-8 CHEMICAL NAME: NAPHTHALENE, 1,2,3.4-TETRAHYDRO-, C1-4-ALKYL DERIVS.
u>
® SUBMISSION t: 8EHQ-0590-09B4
CAS NUMBER: 68515-75-3 CHEMICAL NAME: HEXANEDIOIC ACID, DI-C7-9-BRAHCHED AND LINEAR ALKYL ESTERS
SUBMISSION B¦ 8EHQ-0590-0982
CAS NUMBER: 68515-81-1 CHEMICAL NAME: ISONONYL ALCOHOL
SUBMISSION «: SEHfl-0390-0912 S
CAS NUMBER: 68648-87-3 CHEMICAL NAME: ALKYLATE 215
SUBMISSION 9: 8EHQ-0590-0965
CAS NUMBER: 68648-87-3 CHEMICAL NAME: ALKYLATE 230
SUBMISSION #: 8EHQ-0590-0970
CAS NUMBER: 6864B-S7-3 CHEMICAL NAME: BENZENE, C10-16-ALKYL DERIVS.
SUBMISSION t: 8EHS-0590-0965 8EHQ-0590-0970
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APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 68855-24-3 CHEMICAL NAME: BENZENE, C14-30-ALKYL DERIVS.
SUBMISSION »: 8EH9-0590-0969
CAS NUMBER: 68855-24-3 CHEMICAL NAME: THERMINOL 55
SUBMISSION t: 8EHQ-0590-0969
CAS NUMBER: 68908-87-2 CHEMICAL NAME: BENZENE, 1,3-DIMETHYL-, BENZYLATED
SUBMISSION I: 8EHQ-0490-0941
CAS NUMBER: 68920-82-1 CHEMICAL NAME: AMIDES, FROM DIETHYLENETRIAMINE AND HYDROGENATED TALLOM
SUBMISSION • : 8EHQ-0990-1076 S
CAS NUMBER: 68937-41-7 CHEMICAL NAME: DURAD 110
SUBMISSION «: 8EHQ-0990-1057
CAS NUMBER: 68937-41-7 CHEMICAL NAME: KRONITEX 50
SUBMISSION «: 8EHQ-0990-1057
CAS NUMBER: 68937-41-7 CHEMICAL NAME: PHENOL, ISOPROPYLATED, PHOSPHATE (3:1)
SUBMISSION t: 8EHQ-1189-0847 8EHQ-0990-1057
CAS NUMBER: 70205-95-7 CHEMICAL NAME: BUILDER U
SUBMISSION *: 8EKQ-0490-0945
CAS NUMBER: 70205-95-7 CHEMICAL NAME: OXOACETIC ACID HOMOPOLYMER, SODIUM SALT
SUBMISSION *: 8EHQ-0490-0945
CAS NUMBER: 71050-62-9 CHEMICAL NAME: 2-PR0PEN0IC ACID, POLYMER WITH SODIUM PHOSPHINATE
SUBMISSION ft: 8EHQ-0190-0866 S
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APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 71130-60-4 CHEMICAL NAME: PHENOL, 2-[ (ETHYLAMINO)METHYL]-4-NITRO-
SUBMISSION •: 8EHQ-0190-0867 *
CAS NUMBER: 73160-32-4 CHEMICAL NAME: 2-BUTANONE, 0,0'-(ETHENYLMETHYLSYLYLENE)DIOXIME,
-------
APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 103U2-35-2
SUBMISSION «: 8EHQ-0490-0960
CAS NUMBER: 103490-06-8
SUBMISSION »: 8EHS-0690-1015
CAS NUMBER: 1Q3490-06-8
SUBMISSION *: 8EHQ-0690-1015
CAS NUMBER: 106990-43-6
SUBMISSION •: 8EHQ-1089-0836
CAS NUMBER: 106990-43-6
SUBMISSION *: 8EH9-1089-0836
CAS NUMBER: 118832-72-7
SUBMISSION *: 8EHQ-0790-1033
CAS NUMBER: 118832-72-7
SUBMISSION *: 8EHQ-0790-1033
CAS NUMBER: 122185-09-5
SUBMISSION t: 8EHQ-1089-0837 S
CHEMICAL NAME: 1(H)-1,2,4-TRIAZ0LE-3-CARB0XYLATE, ETHYL l-(2,4-DICHLOROPHEN
YD-5-TRICHL0R0METHYL-
CHEMICAL NAME: EPIKOTE 1071
CHEMICAL NAME: EPON HPT RESIN 1071
CHEMICAL NAME: CHIMASSORB 119
CHEMICAL NAME*. l,3,5-TRIAZINE-2.4,6-TRIAMINE, N,N» • »-Il,2-ETHANEDIYLBIS£[I4
,6-BIS[BUTYL (1,2,2,6,6-PENTAMETHYL-4-PIPERIDINYL)AMINOD-1» 3,
5-TRIAZ1N-2-YL3IMINOJ-3,1-PROPANEDIYL33-BISCN',N••-DIBUTYL-N
• ,N*,-BIS(l,2,2,6,6-PENTAMETHYL-4-PIPERIDINYL)-
CHEMICAL NAME: ACETIC ACID, 1113,5-BIS(1,1-DIMETHYLETHYL)-4-HYDROXYPHENYL3M
ETHYL JTHIO]-, C10-14-ISOALKYL ESTERS
CHEMICAL NAME: DP-118
CHEMICAL NAME: DECANE, 1,10-BIS-TRIMETHOXYSILYL-
CAS NUMBER: 124737-31-1 CHEMICAL NAME: BENZENEDIAZONIUM, 4-(DIMETHYLAMINO)-, 5-SULF0SALICYIATE
SUBMISSION •: SEHQ-0990-1068
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APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 124737-31-1 CHEMICAL NAME: DIA20 B SS
SUBMISSION *: 8EHQ-0990-1068
CAS NUMBER: 129217-90-9 CHEMICAL NAME: CONDENSATE OF ANILINE, O-TOLUIDINE AND TEREPHTHALALDEHYDE,
EACTION PRODUCT WITH MALEIC ANHYDRIDE
SUBMISSION #: BEHQ-Q 990-1069
CAS NUMBER: 129217-90-9 COMICAL NAME: MP-2000
SUBMISSION «: 8EHQ-0990-1069
-------
CAS NUMBER: 127-19-5
SUBMISSION •: 8EHQ-0590-0981
CAS NUMBER: 3618-72-2
SUBMISSION •: 8EHQ-0790-1030
CAS NUMBER: CONFIDENT
SUBMISSION *: 8EHQ-0190-0865 S
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EHQ-0290-0889 S
CAS NUMBER: CONFIDENT
SUBMISSION ff: 8EHQ-0390-0896 S
CAS NUMBER: CONFIDENT
SUBMISSION »: 8EHQ-0390-0897 S
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EHQ-0490-0923 S
CAS NUMBER: 123-86-4
SUBMISSION »: 8EHQ-0290-0880
CAS NUMBER: CONFIDENT
SUBMISSION t: 8EH9-0290-08S7 S
CAS NUMBER: 118832-72-7
SUBMISSION »: 8EHQ-0790-1033
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: ACETAMIDE, N,N-DIMETHYL-
CHEMICAL NAME: ACETAMIDE, N-[5-CBISC2-(ACETYLOXY)ETHYL]AMINO]-2-[(2-BR0M0-4
,6-DINITR0PHENYL)AZ0]-«-METH0XYPHENYLl-
CHEMICAL NAME: ACETANILIDE, HETEROCYCLIC SUBSTITUTED
8EHQ-0190-0869 S
CHEMICAL NAME: ACETANILIDE, SUBSTITUTED
8EHQ-0490-0955 S
CHEMICAL NAME: ACETANILIDE, SUBSTITUTED, (I)
CHEMICAL NAME: ACETANILIDE, SUBSTITUTED, (II)
CHEMICAL NAME: ACETANILIDE, SUBSTITUTED, (III)
CHEMICAL NAME: ACETIC ACID, BUTYL ESTER
CHEMICAL NAME: ACETIC ACID ESTER, SUBSTITUTED
CHEMICAL NAME: ACETIC ACID, [[[3,5~BIS(1,1-DIMETHYLETHYL)-$-HYDROXYPHENYL]M
ETHYL3THI01-, C10-14-IS0ALKYL ESTERS
-------
CAS NUMBER: CONFIDENT
SUBMISSION «: 8EHQ-0290-0890
CAS NUMBER: 88485-37-4
SUBMISSION *: 8EHQ-Q990-1081
CAS NUMBERt 140-88-5
SUBMISSION •> 8EHQ-0490-0917
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EHQ-0989-0821
CAS NUMBER: CONFIDENT
SUBMISSION *: 8EHQ-0990-1059
CAS NUMBER: CONFIDENT
SUBMISSION i: 8EHQ-0890-1048
CAS NUMBER: CONFIDENT
SUBMISSION i: 8EHQ-0490-0920
CAS NUMBER: 68448-87-3
SUBMISSION •: 8EH9-0590-0965
CAS NUMBER: 48648-87-3
SUBMISSION «: 8EHQ-0590-0970
CAS NUMBER: CONFIDENT
SUBMISSION #: 8EHQ-0389-0787
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: ACETOPHENONE OXIME
CHEMICAL NAME: ACETOPHENONE OXIME, 0-( 1, 3-DIOXOLAN-2-YL-METHYL)-2,2, 2-TRIFL
U0R0-4' -CHLORO-
CHEMICAL NAME: ACRYLIC ACID, ETHYL ESTER
CHEMICAL NAME: ACRYLIC POLYMER
CHEMICAL NAME: ALKALINE OXIDIZER
K
CHEMICAL NAME: ALKENOIC ACID, SUBSTITUTED-, ALKYL ESTER
CHEMICAL NAME: ALKENOYL DISUBSTITUTED CYCLOALKANE
CHEMICAL NAME: ALKYLATE 215
CHEMICAL NAME: ALKYLATE 230
CHEMICAL NAME: ALKYL HETEROCYCLE
-------
CAS NUMBER: CONFIDENT
SUBMISSION »: 8EHQ-0990-1066 S
CAS NUNBER: CONFIDENT
SUBMISSION •: 8EHQ-0990-1066 S
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EHQ-0990-10S8 S
CAS NUMBER: 1344-28-1
SUBMISSION *: 8EHQ-0690-1018
CAS NUMBER: 1318-23-6
2 SUBMISSION #: 8EHQ-0790-1029
cn
CAS NUMBER: 1344-28-1
SUBMISSION *: 8EHQ-0690-1018
CAS NUMBER: NONE
SUBMISSION *: 8EHQ-0390-0915
CAS NUMBER: CONFIDENT
SUBMISSION *: 8EHQ-0690-1012 S
CAS NUMBER: CONFIDENT
SUBMISSION t: 8EHQ-0590-0995 S
CAS NUMBER: CONFIDENT
SUBMISSION *: 8EHQ-1289-0853 S
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: ALLYLOXY KETAL
CHEMICAL NAME: ALLYLOXY PRECURSOR, UNKETALIZED
CHEMICAL NAME: ALPHA-CYANOCARBOCYCLIC CARBOXYLATE
CHEMICAL NAME: ALUMINA WHISKERS
CHEMICAL NAME: ALUMINUM OXIDE, ALPHA-MONOHYDRATE
CHEMICAL NAME: ALUMINUM OXIDE (AL2C?)
CHEMICAL NAME: ALUMINUM PRODUCTION PROCESS
CHEMICAL NAME: AMIDE, ARYL-SUBSTITUTED AMINO
CHEMICAL NAME: AMIDE, HALOALKYL HETEROAROMATIC
CHEMICAL NAME: AMIDE, HETEROCYCLIC
8EHQ-0490-0918 S
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APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CAS NUMBER: 68920-82-1 CHEMICAL NAME: AMIDES, FROM DIETHYL ENETRIAMINE AND HYDROGENATED TALLOW
SUBMISSION »: 8EHQ-0990-1076 S
CAS NUMBER: CONFIDENT CHEMICAL NAME: AMIDE. SUBSTITUTED ORGANIC
SUBMISSION «: 8EH9-0690-1006 S
CAS NUMBER: CONFIDENT CHEMICAL NAME: AMINE, AROMATIC
SUBMISSION »: 8EH9-0290-0873 S 8EHQ-0390-0905 S *
CAS NUMBER: CONFIDENT CHEMICAL NAME: AMINE, ARYL
SUBMISSION t: 8EHQ-0 S 8EHQ-0590-0989 S
CAS NUMBER: CONFIDENT CHEMICAL NAME: AMINE METAL COMPLEX
SUBMISSION •: 8EHQ-0490-0959 S
CAS NUMBER: CONFIDENT CHEMICAL NAME: AMINE POLYMER, SUBSTITUTED
SUBMISSION •: 8EHQ-0890-1054 S
CAS NUMBER: 61791-26-2 CHEMICAL NAME: AMINES, TALLOW ALKYL, ETHOXYLATED
SUBMISSION »: 8EH9-0190-0871 S
-------
CAS NUMBER: CONFIDENT
SUBMISSION I: 8EHQ-0490-0961 S
CAS NUMBER: UNKNOWN
SUBMISSION »: 8EHQ-0790-1029
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EHQ-0989-0825 S
CAS NUMBER: CONFIDENT
SUBMISSION «: 8EHQ-0989-0823 S
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EHQ-0989-0825 S
CAS NUMBER: 62-53-3
SUBMISSION t: 8EHQ-0190-0864
CAS NUMBER: 104-13-2
SUBMISSION t: 8EHQ-0990-1080 S
CAS NUMBER: 104-42-7
SUBMISSION «: 8EHQ-0990-1080 S
CAS NUMBER: 100-01-6
SUBMISSION •: 8EHQ-0990-1080 S
CAS NUMBER: 97-02-9
SUBMISSION •: 8EHQ-0990-1080 S
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: AMINO ACID (I)
CHEMICAL NAME: AMOSITE
CHEMICAL NAME: AN1LIDE (III), SUBSTITUTED
CHEMICAL NAME: AN1LIDE (II), SUBSTITUTED
CHEMICAL NAME: ANILIDE (I), SUBSTITUTED
CHEMICAL NAME: ANILINE
8EHQ-0990-1080 S
CHEMICAL NAME: ANILINE, P-BUTYL-
CHEMICAL NAME: ANILINE, P-DODECYL-
CHEMICAL NAME: ANILINE, P-NITRO-
CHEMICAL NAME: ANILINE, 2,4-DINITRO-
-------
CAS NUMBER: UNKNOWN
SUBMISSION t: 8EHQ-0790-1029
CAS NUMBER: 1309-64-4
SUBMISSION I: 8EHQ-0389-0797
CAS NUMBER: 3388-03-2
SUBMISSION •: 8EHQ-1189-0847
CAS NUMBER: NONE
SUBMISSION •: 8EHQ-1189-0847
CAS NUMBER: 11097-69-1
SUBMISSION «: 8EHQ-0490-0933
CAS NUMBER: CONFIDENT
SUBMISSION «: 8EHQ-0289-0782
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EHQ-0390-0913
CAS NUMBER: CONFIDENT
SUBMISSION t: 8EHQ-0290-0879
CAS NUMBER: 1332-21-4
SUBMISSION •: 8EH4-0690-1018
CAS NUMBER: UNKNOWN
SUBMISSION •: 8EHQ-0790-1029
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: ANTHOPHYLLITE
CHEMICAL NAME: ANTIMONY OXIDE (SB203)
CHEMICAL NAME: ARALDITE CY-175
CHEMICAL NAME: ARALDITE CY-185
CHEMICAL NAME: AROCHLOR 1254
CHEMICAL NAME: AROMATIC SULFONAMIDE, SUBSTITUTED
CHEMICAL NAME: ARYL ALKYL HETEROCYCLIC CARBOXYLATE
CHEMICAL NAME: ARYL DIESTER, HALO ALKYL SUBSTITUTED
CHEMICAL NAME: ASBESTOS
8EH9-0790-1029
CHEMICAL NAME: ASBESTOS CEMENT
-------
CAS NUMBER: CONFIDENT
SUBMISSION •: BEHQ-0989-C824 S
CAS NUMBER: 3388-03-2
SUBMISSION *: 8EHQ-1189-Q847
CAS NUMBER: 3388-03-2
SUBMISSION •: 8EHQ-1189-0847
CAS NUMBER: 2155-38-6
SUBMISSION •: 8EHQ-1189-0847
CAS NUMBER: 10578-42-4
SUBMISSION *: 8EHQ-1189-0847
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EHQ-1189-0842 S
CAS NUMBER: 62-53-3
SUBMISSION »: 8EHQ-019O-O864
CAS NUMBER: 1300-73-S
SUBMISSION *: 8EHQ-0990-10B0 S
CAS NUMBER: CONFIDENT
SUBMISSION «: 8EHQ-0790-1026 S
CAS NUMBER: CONFIDENT
SUBMISSION «: 8EHQ-0990-1073 S
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: AZOLE CARBOXAMIDE, ARYL SUBSTITUTED
CHEMICAL NAME: BAKELITE ERL-4234
CHEMICAL NAME: BA 42'579
CHEMICAL NAME: BA 42'580
CHEMICAL NAME: BA 42*581
CHEMICAL NAME: BENZDIOXOLCARBONITRILE. SUBSTITUTED
CHEMICAL NAME: BENZENAMINE
8EH«-0990-1080 S
CHEMICAL NAME: BENZENAMINE, AR,AR-DIMETHYL-
CHEMICAL NAME: BENZENAMINE, ARYLOXY SUBSTITUTED
CHEMICAL NAME: BENZENAMINE (II), ARYLOXY SUBSTITUTED
-------
CAS NUMBER: 91-66-7
SUBMISSION
CAS NUMBER: 768-52-5
SUBMISSION
CAS NUMBER: 120-71-8
SUBMISSION
CAS NUMBER: 95-53-*
SUBMISSION
CAS NUMBER: 97-02-9
CO
g SUBMISSION
CAS NUMBER: 95-78-3
SUBMISSION
CAS NUMBER: 108-44-1
SUBMISSION
CAS NUMBER: 104-13-2
SUBMISSION
CAS NUMBER: 104-42-7
SUBMISSION
CAS NUMBER: 106-49-0
SUBMISSION
•: 8EHQ-0290-0878
»: 8EHQ-0290-0878
*: 8EHQ-0990-1080 S
•: 8EHQ-0190-0864
•: 8EHQ-0990-1080 S
•: 8EHQ-0990-1080 S
#: 8EHQ-0990-1080 S
•: 8EHQ-0990-1080 S
#: 8EHQ-0990-1080 S
•: 8EHQ-0990-1080 S
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: BENZENAMINE, N,N-DIETHYL-
CHEMICAL NAME: BENZENAMINE, N-U-METHYL ETHYL) -
CHEMICAL NAME: BENZENAMINE, 2-METH0XY-5-METHYL-
CHEMICAL NAME: BENZENAMINE, 2-METHYL-
8EHQ-0990-1080 S
CHEMICAL NAME: BENZENAMINE, 2,4-DINITRO-
CHEMICAL NAME: BENZENAMINE, 2,5-DIMETHYL"
CHEMICAL NAME: BENZENAMINE, 3-METHYL-
CHEMICAL NAME: BENZENAMINE, 4-BUTYL-
CHEMICAL NAME: BENZENAMINE, 4-DODECYL-
CHEMICAL NAME: BENZENAMINE, 4-METHYL-
-------
CAS NUMBER: 100-01-6
SUBMISSION «: 8EHQ-0990-1080
CAS NUMBER: 2*79-46-1
SUBMISSION •: 8EHQ-0390-0898
CAS NUMBER: 2716-10-1
SUBMISSION • : &EHQ-12B9-0852
CAS NUMBER: 2716-12-3
SUBMISSION «: 8EHQ-1289-0852
CAS NUMBER: 71-43-2
SUBMISSION ft: 8EHQ-0990-1077
CAS NUMBER: 68648-87-3
SUBMISSION t: 8EHQ-0590-0965
CAS NUMBER: 68855-24-3
SUBMISSION •: SEH9-0590-0969
CAS NUMBER: 3081-14-9
SUBMISSION #: $EHQ-0590-0977
CAS NUMBER: 793-24-8
SUBMISSION •: 8EH4-0590-Q966
CAS NUMBER: 32572-38-0
SUBMISSION i: 8EHQ-0790-1021
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: BENZENAMINE, 4-NITRO-
CKEMICAL NAME: BENZENAMINE, 4,4¦-{1,3-PHENYLENEBIS(OXY)BIS-
CHEMICAL NAME: BENZENAMINE, 4,4'-[1,4-PHENYLENEBIS(1-METHYLETHYLIDENE)]BIS-
CHEMICAL NAME: BENZENAMINE, 4,4*-[1,4-PHENYLENEBISC1-METHYLETHYLIDENE)]BIS[
2,6-DIMETHYL-
CHEMICAL NAME: BENZENE
CHEMICAL NAME: BENZENE, C10-16-ALKYL DERIVS.
8EHQ-0590-0970
CHEMICAL NAME: BENZENE, C14-30-ALICYL DERIVS.
CHEMICAL NAME: 1,4-BENZENEDIAMINE, N,N'-BISC1,4-DIMETHYLPENTYL)-
CHEMICAL NAME: 1,4-BENZENEDlAMINE, N-(1,3-DIMETHYLBUTYL)-N1-PHENYL-
CHEM1CAL NAME: BENZENEDIAZONIUM, 3-METHYL-4-C1-PYRROLIDINYLTRICHLOROZIN
CATE(l-)
-------
CAS NUMBER: 124737-31-1
SUBMISSION •: 8EHQ-0990-1068
CAS NUMBER: 84-74-2
SUBMISSION i: 8EHQ-0590-0971
CAS NUMBER: 65701-07-7
SUBMISSION *: SEH9-0590-0967
CAS NUMBER: 1477-55-0
SUBMISSION *: 8EH9~0390~0909
CAS NUMBER: (4800-83-5
SUBMISSION «: 8EHQ-Q590-0984
CAS NUMBER: 68398-19-6
SUBMISSION •: 8EHQ-0590-0984
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EHQ-0690-1014 S
CAS NUMBER: 38888-98-1
SUBMISSION •: 8EHQ-0590-0984
CAS NUMBER: 80-54-6
SUBMISSION *: 8EH4-0490-093I S
CAS NUMBER: 88-19-7
SUBMISSION «: 8EHQ-0490-0938
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: BENZENEDIAZOHIUM, 4-
-------
CAS NUMBER: 70-55-3
SUBMISSION *: 8EHQ-0490-0938
CAS NUMBER: 27344-41-8
SUBMISSION #: 8EHQ-0989-0822
CAS NUMBER: 611-19-8
SUBMISSION *: 8EHQ-0690-1020
CAS NUMBER: 88-73-3
SUBMISSION »: 8EHQ-0590-0973
CAS NUMBER: 100-00-5
SUBMISSION i: 8EHQ-0590-0980
CAS NUMBER: 98-82-8
SUBMISSION •: 8EHQ-U89-0846
CAS NUMBER: 37871-12-8
SUBMISSION *: 8EHQ-0290-0893
CAS NUMBER: 2336-05-2
SUBMISSION •: 8EHQ-0289-0784
CAS NUMBER: 101-68-8
SUBMISSION i: 8EHQ-0289-0784
CAS NUMBER: NONE
SUBMISSION • : 8EHQ-0990-1072
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: BENZENESULFONAMIDE, 4-METHYL-
CHEMICAL NAME: BENZENESULFONIC ACID, 2,2'-([1,1•-BIPHENYL]-4,4'-DIYLDI-2,1-
ETHENEDIYL)BIS-, DISODIUM SALT
CHEMICAL NAME: BENZENE, 1-CHL0R0-2-(CHLOROMETHYL)-
CHEMICAL NAME: BENZENE, 1-CHL0R0-2-NITR0-
CHEMICAL NAME: BENZENE, 1-CHLQR0-4-NITR0-
CHEMICAL NAME: BENZENE, (1-METHYLETHYL)-
CHEMICAL NAME: BENZENE, (1,1-DIMETHYLETHYL)ETHYL-
CHEMICAL NAME: BENZENE, 1,1'-METHYLENEBISE2-IS0CYANAT0-
CHEMICAL NAME: BENZENE, 1,1'-METHYLENEBISt4-IS0CYANAT0-
8EHQ-0290-0876
CHEMICAL NAME: BENZENE, 1,1¦-OXYBIS-, BROMINATED DERIV.
-------
CAS NUMBER: 32536-52-0
SUBMISSION •: 8EHQ-0990-1072
CAS NUMBER: 103-30-0
SUBMISSION t: 8EH4-049Q-0939
CAS NUMBER: 72-54-8
SUBMISSION ft: 8EHQ-0790-1034
CAS NUMBER: 72-56-0
SUBMISSION t: 8EHQ-0790-1034
CAS NUMBER: 50-29-3
SUBMISSION ft: 8EHQ-0790-1034
CAS NUMBER: 99-54-7
SUBMISSION •: 8EHQ-0590-0972
CAS NUMBER: 68908-87-2
SUBMISSION ft: 8EHQ-0490-0941
CAS NUMBER: 92-87-5
SUBMISSION •: 8EHQ-0190-0863
CAS NUMBER: 91-94-1
SUBMISSION ft: 8EHQ-0190-0863
CAS NUMBER: 612-83-9
SUBMISSION ft.- 8EHQ-0190-0863
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: BENZENE. 1,1'-OXYBIS-, OCTABROMO DERIV.
CHEMICAL NAME: BENZENE, 1,1•-(1,2-ETHENEDIYL)BIS", (E)-
CHEMICAL NAME: BENZENE, 1,1•-(2,2-DICHLOROETHYLIDENE)BISI4-CHLORO-
CHEMICAL NAME: BENZENE, 1,1•-(2,2-DICHL0R0ETHYLIDENEJBISI4-ETHYL-
CHEMICAL NAME: BENZENE, 1,1'-(2,2,2-TRICHL0R0ETHYLIDENE)BISl4-CHLORO-
CHEMICAL NAME: BENZENE, 1,2-DICHLORO-4-NITRO-
CHEMICAL NAME: BENZENE, I,3-DIMETHYL", BENZYLATED
CHEMICAL NAME: BENZIDINE
CHEMICAL NAME: BENZIDINE, 3,3'-DICHL0R0-
8EHQ-0490-0962
CHEMICAL NAME: BENZIDINE, 3,3'-DICHLORO-, DIHYDROCHLORIDE
-------
CAS NUMBER: 38444-13-2
SUBMISSION •: 8EHQ-029D-0894
CAS NUMBER: 2421-28-5
SUBMISSION »: SEHQ-0589-0796
CAS NUMBER: 149-30-4
SUBMISSION •: 8EH3-0889-0813
CAS NUMBER: UNKNOUN
SUBMISSION I: 8EH$-0990-1072
CAS NUMBER: 1336-36-3
SUBMISSION •: 8EH^-0490-0933
CAS NUMBER: 92-87-5
SUBMISSION •: 8EH4-0190-0863
CAS NUMBER: 91-94-1
SUBMISSION «: 8EHQ-0190-0863
CAS NUMBER: 612-83-9
SUBMISSION #.* BEHQ-tl 90-0863
CAS NUMBER: 119-90-4
SUBMISSION •: 8EH4-0190-0863
CAS NUMBER: 119-93-7
SUBMISSION t: 8EH4-0190-SS63
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: BENZOIC ACID, 4-METHOXY-, 4-PENTYLPHENYL ESTER
CHEMICAL NAME: 3,3»,4,4•-BENZOPHENONETETRACARBDXYLIC ACID DIANHYDRIDE
CHEMICAL NAME: 2C3H)-BENZ0THIAZ0LETHI0NE
CHEMICAL NAME: 1,1'-BIPHENYL, BROMO DERIVS.
CHEMICAL NAME: 1.1'-BIPHENYL, CHLORO DERIVS.
CHEMICAL NAME: t1,1'-BIPHENYL]-4,4•-DIAMINE
CHEMICAL NAME: [1,1'-BIPHENYL3-4,41"DIAMINE, 3,3'-DICHLORO-
8EHQ-0490-0962
CHEMICAL NAME: [1,1'-BIPHENYL]-4,4•-DIAMINE, 3,3'-DICHL0R0-, DIHYDROCHLORID
E
CHEMICAL NAME: 11,1 *-BIPHENYL]-4,4•-DIAMINE, 3,3'-DIMETHOXY-
CHEMICAL NAME: t1,1•-BIPHENYL]-4,41"DIAMINE, 3,3»-DIMETHYL-
8EH4-0990-1080 S
-------
CAS NUMBER: 553-26-4
SUBMISSION #: 8EHQ-1089-0831
CAS NUMBER: 542-88-1
SUBMISSION #: 8EHQ-0589-0799
CAS NUMBER: 13565-96-3
SUBMISSION •: 8EK9-0389-D789
CAS NUMBER: 14059-33-7
SUBMISSION •: 8EHQ-0389-0789
CAS NUMBER: CONFIDENT
CO
SUBMISSION #: 8EHS-0790-1028 S
CAS NUMBER: UNKNOWN
SUBMISSION •: 8EHQ-0290-0880
CAS NUMBER: 1318-23-6
SUBMISSION #: 8EHQ-0790-1029
CAS NUMBER: 70205-95-7
SUBMISSION t: 8EHQ-0490-0945
CAS NUMBER: 106-99-0
SUBMISSION i: 8EHQ-0390-0901
CAS NUMBER: 5979-28-2
SUBMISSION i: 8EHQ-0490-0962
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: 4,4'-BIPYRIDINE
CHEMICAL NAME: BIStCHLOROMETHYL)ETHER (BCME)
CHEMICAL NAME: BISMUTH MOLYBDENUM OXIDE, CBI2M006)
CHEMICAL NAME: BISMUTH VANADIUM OXIDE, (BIV04)
CHEMICAL NAME: BISCSUBSTITUTED PHENYL) SUBSTITUTED AMINO HETEROMONOCYCLE
CHEMICAL NAME: 1,3-BISCl-CYANATO-l-METHYLETHYL]BENZENE
CHEMICAL NAME: BOEHMITE, (AL(OH)O)
CHEMICAL NAME: BUILDER U
CHEMICAL NAME: 1,3-BUTADIENE
8EHQ-0390-0902
CHEMICAL NAME: BUTANAMIDE, N,N'-(3,3•-DIMETHYL[1,1•-BIPHENYL]-4,4•-DIYL)BIS
[2-1(2,4-DICHLOROPHENYL)AZO 3-3-OXO-
-------
CAS NUMBER: *531-49-1
SUBMISSION t: 8EHQ-0490-0962
CAS NUMBER: 5102-83-0
SUBMISSION t: 8EHQ-0490-0962
CAS NUMBERS 5567-15-7
SUBMISSION •: 8EHQ-O490-O962
CAS NUMBER: 6358-85-6
SUBMISSION »: 8EHQ-049D-0962
CAS NUMBER: 2512-29-0
SUBMISSION •: 8EHQ-049D-G962
CAS NUMBER: 111-92-2
SUBMISSION ¦: 8EHQ-0990-10&0 S
CAS NUMBER: 43449-8S-7
SUBMISSION t: 8EH9-0490-0943
CAS NUMBER: 57910-79-9
SUBMISSION •: 8EH9-0990-1065
CAS NUMBER: 78-93-3
SUBMISSION •: 8EHQ-1189-0847
CAS NUMBER: 73160-32-4
SUBMISSION t: 8EHQ-0889-0810 S
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: BUTANAMIDE, 2,2»-[(3,3*-DICHLOROC1,1'-BIPHENYL]-4,4'-DIYL)BI
S(AZO)]BIStN-(2-METHOXYPHENYL)-3-OXO-
CHEMICAL NAME: BUTANAMIDE, 2,2'-£C3,3•-DICHLOROt1,1'-BIPHENYL]-4,4•-DIYL)BI
S(AZO)]BIStN-(2,4-DIMETHYLPHENYL)-3-OXO-
CHEMICAL NAME: BUTANAMIDE, 2,2*-t(3*5'-DICHLOROt1,1'-BIPHENYL]-4,4¦-DIYL)BI
S(AZO)]BIS[N-(4-CHL0RO-2,5-DIMETHOXYPHENYL)-3-0X0-
CHEMICAL NAME: BUTANAMIDE, 2,2'-t(3,3'-DICHLOROt1.1'-BIPHENYL]-4,4'-DIYL)BI
StAZ0)]BISl3-0X0-N-PHENYL-
CHEMICAL NAMEi BUTANAMIDE, 2-C(4-HETHYL-2-NITR0PHENYL)AZO]-3-OXO-N-PHENYL-
CHEMICAL NAME: 1-BUTANAMINE, H-BUTYL-
CHEMICAl NAME: BUTAHOIC ACID, 1-CYCLOHEXYLETHYL ESTER
CHEMICAL NAME: 2-BUTANOL, 2-tC1,1-DIMETHYLETHYL)AZ03-
CHEMICAL NAME: 2-BUTAN0NE
CHEMICAL NAME: 2-BUTAN0NE, 0,0"-(ETHENYLMETHYLSYLYIENE)DIOXIME, (E,Z)-
-------
CAS NUMBER: 96-29-7
SUBMISSION i: 8EHQ-0990-1063
CAS NUMBER: 4170-30-3
SUBMISSION *: 8EHQ-0690-1017
CAS NUMBER: 513-35-9
SUBMISSION *: 8EH9-039Q-0901
CAS NUMBER: 563-46-2
SUBMISSION •: 8EHQ-8390-0901
CAS NUMBER: 26760-64-5
SUBMISSION *: 8EHQ-0390-0901
CAS NUMBER: 131-72-6
SUBMISSION >: 8EHQ-I790-1034
CAS NUMBER: 94317-64-3
SUBMISSION *: 8EH9-0490-0934 S
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EHQ-1289-0857 S
CAS NUMBER: 75-15-0
SUBMISSION t: 8EHQ-0390-0904
CAS NUMBER: 463-58-1
SUBMISSION •: 8EH9-0290-0892
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: 2-BUTANONE, OXIME
CHEMICAL NAME: 2-BUTENAL
CHEMICAL NAME: 2-BUTENE, 2-METHYL-
CHEMICAL NAME: 1-BUTENE, 2-METHYL-
CHEMICAL NAME: BUTENE, 2-METHYL-
CHEMICAL NAME: 2-BUTENOIC ACID, 2-t1-METHYLHEPTYL)-4,6-DINITROPHENYL ESTER,
(E)-
CHEMICAL NAME: N-CN-BUTYL>THIOPHOSPHORIC TRIAMIDE
CHEMICAL NAME: CARBAZOLE, INDOLO-
CHEMICAL NAME: CARBON DISULFIDE
CHEMICAL NAME: CARBON OXIDE SULFIDE, (COS)
-------
CAS NUMBER: CONFIDENT
SUBMISSION *: 8EH4-0690-1011 S
CAS NUMBER; CONFIDENT
SUBMISSION *: 8EHQ-0490-0928 S
CAS NUMBER: 104990-43-6
SUBMISSION t: 8EHQ-1089-CB36
CAS NUMBER: 83261-15-8
SUBMISSION •: 8EHQ-0490-0936
CAS NUMBER: 4109-96-0
SUBMISSION «• 8ENQ-0689-0803
CAS NUMBER: 129217-90-9
SUBMISSION •: 8EHQ-0990-1069
CAS NUMBER: 120-7l-S
SUBMISSION •: 8EH9-099O-1O8O S
CAS NUMBER: UNKNOUN
SUBMISSION »: 8EH*-0790-1029
CAS NUMBER: 4170-30-3
SUBMISSION «: 8EHQ-0690-1017
CAS NUMBER: 98-82-8
SUBMISSION ff: 8EH9-U89-0846
APPENDIX C: STATUS REPORTS Br CHEMICAL NAME
CHEMICAL NAME: CARBOXYLIC ACID ESTER, ARYLOXY-SUBSTITUTED ALKYL
CHEMICAL NAME: CARBOXYLIC ACID ESTER, HETEROCYCLIC
CHEMICAL NAME: CHIMASSORB 119
CHEMICAL NAME: L-2-CHLOROPROPRIONIC ACID, ISOBUTYL ESTER
CHEMICAL NAME: CHLOROSILANE A-199
CHEMICAL NAME: CONDENSATE OF ANILINE, Q-TOLUIDINE AND TEREPHTHALALDEHYDE,
EACTION PRODUCT UITH MALEIC ANHYDRIDE
CHEMICAL NAME: P-CRESIDINE
CHEMICAL NAME: CROCIDOLITE
CHEMICAL NAME: CROTONALDEHYDE
CHEMICAL NAME: CUMENE
-------
CAS NUMBER: NONE
SUBMISSION *: 8EHQ-0990-1078
CAS NUMBER: 420-04-2
SUBMISSION «: 8EHQ-0490-0952 S
CAS NUMBER: 420-04-2
SUBMISSION t: 8EH9-0490-0952 S
CAS NUMBER: 47073-92-7
SUBMISSION t: 8EHQ-0189-0781 S
CAS NUMBER: 101657-77-6
a-
g SUBMISSION t: 8EHQ-0189-0781 S
CAS NUMBER: NONE
SUBMISSION *: 8EHQ-0989-0821 S
CAS NUMBER: UNKNOWN
SUBMISSION •: 8EHQ-0590-0964
CAS NUMBER: CONFIDENT
SUBMISSION #: 8EHQ-0790-1037 S
CAS NUMBER: 38970-72-8
SUBMISSION •: 8EHQ-0490-0949
CAS NUMBER: 50-29-3
SUBMISSION •: 8EHQ-0790-1034
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: CUTTING FLUID
CHEMICAL NAME: CYANAMIDE
CHEMICAL NAME: CYANAMIDE, HYDROGEN
CHEMICAL NAME: CYANIC ACID, ETHYLIDENEBI5-4,1-PHENYLENE ESTER
CHEMICAL NAME: CYANIC ACID, METHYLENEBISC2,6-DIMETHYL-4,1-PHENYLENE) ESTER
CHEMICAL NAME: CYANOACRYLATE ADHESIVE
CHEMICAL NAME: CYCLIC 1,4-PERFLUOROBUTANE DISULFONIMIDE, LITHIUM SALT
CHEMICAL NAME: CYCLOHEXANE, SUBSTITUTED
CHEMICAL NAME: CYCLOHEXANE, 1,1•-(1,1,3-TRIMETHYL-l,3-PROPANEDIYL)BIS-
CHEMICAL NAME: DDT
-------
CAS NUMBER: CONFIDENT
SUBMISSION *: 8EHQ-0390-0908 S
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EHQ-0490-0921 S
CAS NUMBER: 122185-09-5
SUBMISSION *: 8EHQ-1089-0837 S
CAS NUMBER: 66070-34-0
SUBMISSION *: 8EHQ-0590-0983
CAS NUMBER: 6419-19-8
00
£ SUBMISSION *1 8EHQ-0490-0937
CAS NUMBER: 1429-50-1
SUBMISSION •: 8EHQ-0490-0940
CAS NUMBER: 13827-60-8
SUBMISSION *: 8EHQ-0490-0950
CAS NUMBER: 22042-96-2
SUBMISSION #: 8EHQ-0490-0950
CAS NUMBER: 22042-96-2
SUBMISSION «: 8EHQ-0490-0950
CAS NUMBER: 119-90-4
SUBMISSION •: 8EHQ-0190-0863
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: DD-63
CHEMICAL NAME: DD-70
CHEMICAL NAME: DECANE, 1,10-BIS-TRIMETHOXYSILYL-
CHEMICAL NAME: 1-DECENE, POLYMER WITH 1-OCTENE, HYDR06ENATED
*
CHEMICAL NAME: DEQUEST 2000
CHEMICAL NAME: DEQUEST 2041
CHEMICAL NAME: DEQUEST 2060
8EHQ-0490-0951
CHEMICAL NAME: DEQUEST 2061
CHEMICAL NAME: DEQUEST 2066
CHEMICAL NAME: O-DIANISIDINE
-------
CAS NUMBER: NONE
SUBMISSION »: 8EHQ-0490-0962
CAS NUMBER: 52572-38-0
SUBMISSION •: 8EHG-0790-1021
CAS NUMBER: 124737-31-1
SUBMISSION •: 8EHQ-0990-1068
CAS NUMBER: NONE
SUBMISSION t: 8EH4-0290-0882
CAS NUMBER: 18406-41-2
SUBMISSION •: 8EHQ-0890-1047
CAS NUMBER: NONE
SUBMISSION •: 8EHQ-Q290-0882
CAS NUMBER: 646-06-0
SUBMISSION •: 8EHQ-O889-0817
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EHQ-0590-0997
CAS NUMBER: 3618-72-2
SUBMISSION t: 8EHQ-0790-1030
CAS NUMBER: 2530-87-2
SUBMISSION #: 8EHQ-0990-1067
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: DIARYLIDE PIGMENTS
CHEMICAL NAME: DIAZO Y
CHEMICAL NAME: DIAZO 8 SS
CHEMICAL NAME: DIBENZOFURANS. CHLORINATED
8EHQ-0890-1038
CHEMICAL NAME: 2,7-DIOXA-3,6-DISILAOCTANE, 3,3,6,6-TETRAMETHOXY-
CHEMICAL NAME: DIOXINS, CHLORINATED
8EHQ-0890-1038
CHEMICAL NAME: 1,3-DIOXOLANE
CHEMICAL NAME: DIPHENYL ETHER, SUBSTITUTED
8EH9-089D-1055 S 8EHQ-089&-1056 S
CHEMICAL NAME: C. I. DISPERSE BLUE 79:1 (PURIFIED PRESSCAKE)
CHEMICAL NAME: DOUI CORNING Ql-2366 SILANE
-------
CAS NUMBER: 18406-41-2
SUBMISSION *: 8EHQ-0890-1047
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EHQ-0990-1066 S
CAS NUMBER: 102-06-7
SUBMISSION •: 8EH9-0390-0990
CAS NUMBER: 118832-72-7
SUBMISSION *: 8EHQ-0790-1033
CAS NUMBER: 68937-41-7
SUBMISSION •: 8EHQ-0990-1057
CAS NUMBER: CONFIDENT
SUBMISSION *: 8EH4-0490-0920 S
CAS NUMBER: 103490-06-8
SUBMISSION •: 8EHQ-0690-1015
CAS NUMBER: 2716-10-1
SUBMISSION t: 8EHQ-1289-0852 S
CAS NUMBER: 2716-12-3
SUBMISSION »: 8EHQ-1289-0852 S
CAS NUMBER: 103490-06-8
SUBMISSION •: 8EHQ-0690-1015
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: DOU CORNING X1-6145A ADDITIVE
CHEMICAL NAME: DOM CORNING Xl-6169
CHEMICAL NAME: DPG ACCELERATOR
CHEMICAL NAME: DP-118
CHEMICAL NAME: DURAD 110
CHEMICAL NAME: EPA ACCESSION t 35406
CHEMICAL NAME: EPIKOTE 1071
CHEMICAL NAME: EPIKURE 1061
CHEMICAL NAME: EPIKURE 1062
CHEMICAL NAME: EPON HPT RESIN 1071
-------
CAS NUMBER: NONE
SUBMISSION *: 8EHQ-0889-0814
CAS NUMBER: UNKNOWN
SUBMISSION *: 8EHQ-0790-1029
CAS NUMBER: 3388-03-2
SUBMISSION »: 8EHQ-1189-0847
CAS NUMBER: 107-13-3
SUBMISSION »: 8EHQ-0589-0801
CAS NUMBER: NONE
™ SUBMISSION t: 8EHQ-0589-0801
CAS NUMBER: 762-49-2
SUBMISSION #: 8EHQ-0889-0818 S
CAS NUMBER: 75-34-3
SUBMISSION •: 8EHQ-0490-0953
CAS NUMBER: 1842-05-3
SUBMISSION •: 8EHQ-0890-1046
CAS NUMBER: 71-55-6
SUBMISSION *: 8EHQ-0889-0817
CAS NUMBER: 100-37-8
SUBMISSION •: 8EH9-0890-1043
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: EPOXY RESINS
8EHQ-1189-0847
CHEMICAL NAME: ERIONITE
CHEMICAL NAME: ERL-4234
CHEMICAL NAME: 1,2-ETHANEDIAMINE
CHEMICAL NAME: 1,2-ETHANEDIAMINE/CARBAMATE COMPLEX (PARTICULATE)
CHEMICAL NAME: ETHANE, 1-BR0M0-2-FLU0R0-
CHEMICAL NAME: ETHANE, 1,l-DICHLORO-
CHEMICAL NAME: ETHANE, 1,1-DICHLORO-l,2-DIFLU0R0-
CHEMICAL NAME: ETHANE, 1,1,1-TRICHLORO-
8EHQ-0490-0953
CHEMICAL NAME: ETHANOL, 2-CDIETHYLAMINO)-
-------
CAS NUMBER: 112-27-6
SUBMISSION #: 8EHQ-0990-1064
CAS NUMBER: 112-35-6
SUBMISSION •: 8EH4-0690-1002
CAS NUMBER: 88485-37-4
SUBMISSION t: 8EHQ-0990-1081
CAS NUMBER: 598-73-2
SUBMISSION »: 8EHQ-1289-0859
CAS NUMBER: 55157-25-0
SUBMISSION •: 8EHQ-0190-0860
CAS NUMBER: NONE
SUBMISSION t: 8EHQ-0190-0860
CAS NUMBER: 75-02-5
SUBMISSION #: 8EHQ-1289-0856
CAS NUMBER: 75-35-4
SUBMISSION »: 8EHQ-0490-0953
CAS NUMBER: CONFIDENT
SUBMISSION «: 8EHQ-0290-0891
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EHQ-0889-0811
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: ETHANOL, 2,2'-[1,2-ETHANEDIYLBI5(OXY)]BIS-
CHEMICAL NAME: ETHANOL, 2-t2-(2-METHOXYETHOXY)ETHOXY]-
CHEMICAL NAME: ETHANONE, l-(4-CHLOROPHENYL)-2,2,2-TRIFLUORO-, 0-(1,3-DI0X0L
AN-2-YLMETHYL JOXIME
CHEMICAL NAME: ETHENE, BROMOTRIFLUORO-
CHEMICAL NAME: ETHENE, BROMOTRIFLUORO-, HOMOPOLYMER
CHEMICAL NAME: ETHENE, BROMOTRIFLUORO-, HOMOPOLYMER, PYROLYSIS PRODUCTS OF
CHEMICAL NAME: ETHENE, FLUORO-
CHEMICAL NAME: ETHENE, 1,1-DICHLORO-
CHEIilCAL NAME: ETHER, ARYL ALKYL
CHEMICAL NAME: ETHER, ARYL PROPYL
-------
CAS NUMBER: CONFIDENT
SUBMISSION *: 8EHQ-1289-0851 S
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EHQ-0490-0926 S
CAS NUMBER: CONFIDENT
SUBMISSION ft: 8EHQ-0490-I930 S
CAS NUMBER: CONFIDENT
SUBMISSION ft: 8EH9-B490-0929 S
oo
0>
a>
CAS NUMBER: UNKNOWN
SUBMISSION ft: 8EH9-1289-0850
CAS NUMBER: 273**-*l-8
SUBMISSION ft: 8EHQ-0989-0822
CAS NUMBER: 50-00-8
SUBMISSION ft: 8EH4-0689-0804
CAS NUMBER: 68-12-2
SUBMISSION ft: 8EHQ-0590-9981
CAS NUMBER: 140-88-5
SUBMISSION »: 8EH9-0490-0917
CAS NUMBER: 75-21-8
SUBMISSION ft: 8EHQ-089Q-1053
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: ETHER, DIARYL
8EHQ-0290-0883 S 8EHQ-0290-0888 S
CHEMICAL NAME: ETHER, DIARYL, CIV)
CHEMICAL NAME: ETHER, DIARYL,
CHEMICAL NAME: ETHER, HALOGENATED
M
CHEMICAL NAME: ETHYL ACRYLATE
CHEMICAL NAME: ETHYLENE OXIDE
CHEMICAL NAME: 0-ETHYL-0-METHYLETHYL-0-I2-{1,1-DIMETHYLETHYL)-PYRIMIDIN-5-Y
Ll-THIONOPHOSPHOROUS ACID ESTER
CHEMICAL NAME: FAT 65029/G
CHEMICAL NAME: FORMALDEHYDE
8EHQ-0490-0924
CHEMICAL NAME: FORMAMIDE, N.N-DIMETHYL-
-------
CAS NUMBER: 111-30-8
SUBMISSION •: 8EHQ-0690-1008
CAS NUMBER: 556-52-5
SUBMISSION «: 8EHQ-0789-0809
CAS NUMBER: UNKNOWN
SUBMISSION *: 8EHQ-0989-0826 S
CAS NUMBER: 142-73-*
SUBMISSION «: 8EHQ-0490-0946
g, CAS NUMBER: UNKNOWN
2 SUBMISSION •: 8EHQ-0590-0993
CAS NUMBER: 63470-53-1
SUBMISSION *: 8EHQ-0589-0800
CAS NUMBER: 102-06-7
SUBMISSION •: 8EHQ-0590-0990
CAS NUMBER: CONFIDENT
SUBMISSION *: 8EHQ-0290-0874 S
CAS NUMBER: CONFIDENT
SUBMISSION *: 8EHQ-0389-0788 S
CAS NUMBER: CONFIDENT
SUBMISSION t: 8EHQ-0590-1001 S
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: GLUTARDIALDEHYDE
CHEMICAL NAME: GLYCIDOL
M
CHEMICAL NAME: GLYCINE, N-AMINO-N-(CARBOXYMETHYL)-
CHEMICAL NAME: GLYCINE, N-(CARBOXYMETHYL)-
CHEMICAL NAME: GLYCINE, N-NITROSO-, N-(PHOSPHONOMETHYLSODIUM SALT
CHEMICAL NAME: GOLD, DIMETHYL-1,1,1-TRIFLUORO-2.4-PENTANEDIONATO
CHEMICAL NAME: GUANIDINE, N.N'-DIPHENYL-
CHEMICAL NAME: GUANIDINIUM ARYL SULFONATE, SUBSTITUTED
CHEMICAL NAME: HALO ALKYL HYDROXY HETEROCYCLE
CHEMICAL NAME: HALOGENATED ALKYL ESTER
-------
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EHQ-1189-0843 S
CAS NUMBER: CONFIDENT
SUBMISSION «: 8EHQ-0S89-0816 S
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EHQ-0890-1052 S
CAS NUMBER: 1842-05-3
SUBMISSION •: 8EHQ-0890-1046
CAS NUMBER: 541-85-5
00
g SUBMISSION t: 8EH9-0489-0793
CAS NUMBER: 592-45-0
SUBMISSION •: 8EHQ-0990-1061
CAS NUMBER: 124-09-4
SUBMISSION »: 8EHQ-0590-0979
CAS NUMBER: 68515-75-3
SUBMISSION •: 8EHQ-0590-0982
CAS NUMBER: 14697-48-4
SUBMISSION •: 8EHQ-0590-0982
CAS NUMBER: 151-32-6
SUBMISSION t: 8EH9"0590-0982
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: HALOGENATED BENZOYL UREA
CHEMICAL NAME: HALOPHENYLCYCLOALKENYL SUBSTITUTED ARYL ESTER
CHEMICAL NAME: HALOPHENYL SUBSTITUTED MONOHETEROCYCLE
CHEMICAL NAME: HCFC-132C
CHEMICAL NAME: 3-HEPTANONE, 5-METHYL-
CHEMICAL NAME: 1,4-HEXADIENE
CHEMICAL NAME: 1,6-HEXANEDIAMINE
CHEMICAL NAME: HEXANEDIOIC ACID, DI-C7-9-BRANCHED AND LINEAR ALKYL ESTERS
CHEMICAL NAME: HEXANEDIOIC ACID, DIHEPTYL ESTER
CHEMICAL NAME: HEXANEDIOIC ACID, DINONYL ESTER
-------
CAS NUMBER: CONFIDENT
SUBMISSION «: 8EHQ-0290-0861 S
CAS NUMBER: 104-76-7
SUBMISSION •: 8EHQ-0390-0910 S
CAS NUMBER: 64619-51-8
SUBMISSION «: 8EHQ-0890-1Q41
CAS NUMB£R: 36970-72-8
SUBMISSION •: 8EHQ-0490-Q949
CAS NUMBER: HONE
SUBMISSION «•. 6EHQ-0990-1076
CAS NUMBER: NONE
SUBMISSION •: 8EHQ-0290-0879 S
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EHQ-1089-0838 S
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EH9-J189-0840 S
CAS NUMBER: CONFIDENT
SUBMISSION i: 8EH*-0499-0919 S
CAS NUMBER: 63402-26-6
SUBMISSION t: 8EH«-«189-Q779
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: HEXANEDIONE, CYCLO-
CHEMICAL NAME: l-HEXANOL, 2-ETHYL-
CHEMICAL NAME: 2-HEXANOL, 2-[(1,1-DIMETHYLETHYLJAZfl]-5-METHYL-
CHEMICAL NAME: HLD
CHEMICAL NAME: HOCUT 797-G
CHEMICAL NAME: HYDRAULIC FLUID, MILC PHOSPHATE ESTER-BASED
CHEMICAL NAME: HYDRAZIDE COMPOUND
CHEMICAL NAME: HYDRAZIDE, OXO-CSUBSTITUTED AMINO)ACETIC ACID
CHEMICAL NAME: HYDRAZIDE, SUBSTITUTED CARBONOTHIOIC
CHEMICAL NAME: HYDRAZINECARBOXALDEHYDE, 2"(WMINOPHENYL)-
-------
CAS NUMBER: CONFIDENT
SUBMISSION ¦: 8EHQ-11S9-0848 S
CAS NUMBER: 740Q-g7-3
SUBMISSION *: 8EHQ-089Q-1042
CAS NUMBER: UNKNOWN
SUBMISSION t: 8EHQ-1189-0845
CAS NUMBER: CONFIDENT
SUBMISSION *: 8EHQ-0490-0922 S
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EHQ-Q790-1022 S
CAS NUMBER: NONE
SUBMISSION •: 8EH4-1IS9-0847
CAS NUMBER: CONFIDENT
SUBMISSION *: 8EH4-Q989-0828 S
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EHQ-0989-0827 S
CAS NUMBER: CONFIDENT
SUBMISSION «: 8EH9-0190-0868 S
CAS NUMBER: CONFIDENT
SUBMISSION *: 8EH«~0490-0935 S
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: HYDRAZINE, SUBSTITUTED
CHEMICAL NAME: HYDRAZINE, C1,1-DIMETHYLETHYLJ-, MONOHYDROCHLORIDE
CHEMICAL NAME: HYDRAZINE, (4-(METHYLBUTOXY)-PHENYL>-, MONOHYDROCHLORIDE
CHEMICAL NAME: HYDROCARBON, CHLORINATED
CHEMICAL NAME: HYDROCARBYl SULFIDE, SUBSTITUTED
CHEMICAL NAME: HYJET IW-A
CHEMICAL NAME: IMIDATE {ID, N-ARYL-CYCLIC
CHEMICAL NAME: IMIDATE (I), N-ARYL-CYCLIC
8EHQ-0190-0870 S
CHEMICAL NAME: IMIDATE, N-ARYLCYCLIC
CHEMICAL NAME: IMIDAZOLE DERIVATIVE
-------
CAS NUMBER: 616-47-7
SUBMISSION »: 8EHQ-0690-1019
CAS NUMBER: 14024-41-0
SUBMISSION •: 8EHQ-0590-0991 S
CAS NUMBER: 7705-08-0
SUBMISSION •: 8EHQ-0890-1042
CAS NUMBER: 26760-64-5
SUBMISSION •: 8EHQ-0390-0901
CAS NUMBER: 5076-19-7
SUBMISSION •: 8EHQ-0690-1003
CAS NUMBER: 117-08-8
SUBMISSION •: 8EHQ-0490-0948
CAS NUMBER: 2421-28-5
SUBMISSION •: 8EHQ-0589-0796
CAS NUMBER: 2540-99-0
SUBMISSION •: 8EHQ-0489-0795
CAS NUMBER: 9016-87-9
SUBMISSION *: 8EH9-0289-0784
CAS NUMBER: 25339-17-7
SUBMISSION #: 8EHQ-0390-0911 S
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: 1H-IMIDAZOLE, 1-METHYL-
CHEMICAL NAME: IRIDATE(3-), HEXACHLORO-, TRIP0TAS5IUM, (OC-6-11)-
CHEMICAL NAME: IRON CHLORIDE
-------
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CAS NUMBER: 54395-37-8 CHEMICAL NAME: 1H-ISOINDDLE-1,3-(ZH)-DIONE, 2-BUTYL-5-NITR0-
SUBMISSION •: 8EH-
2 SUBMISSION •: 8EHQ-0490-095"} S
NJ
CAS NUMBER: 67-63-0 CHEMICAL NAME: ISOPROPANOL
SUBMISSION #: 8EHQ-0290-0884
CAS NUMBER: CONFIDENT CHEMICAL NAME: KETONE. ALKYL
SUBMISSION •: 8EHQ-1289-0858 S
CAS NUMBER: CONFIDENT CHEMICAL NAME: KETONE, CHLORINATED ALIPHATIC
SUBMISSION I: 8EHQ-0589-0798 S
CAS NUMBER: CONFIDENT CHEMICAL NAME: KETONE, DIARYL
SUBMISSION #: 8EHQ-0490-0956 S
CAS NUMBER: CONFIDENT CHEMICAL NAME: KETONE, DIHETEROCYCLIC
SUBMISSION t: 8EHQ-0389-0790 S
-------
CAS NUMBER: 5*1-85-5
SUBMISSION t: 8EH9-0489-0793
CAS NUMBER: CONFIDENT
SUBMISSION •: SEHQ-0690"1004 S
CAS NUMBER: CONFIDENT
SUBMISSION •: BEHQ-0690-1005 S
CAS NUMBER: 68937-41-7
SUBMISSION t: 8EHQ-0990-1057
CAS NUMBER: CONFIDENT
SUBMISSION »: 8EHQ-0190-0861 S
CAS NUMBER: NONE
SUBMISSION f: 8EHQ-0590-0994
CAS NUMBER: 7439-92-1
SUBMISSION »: 8EHS-0990-1071
CAS NUMBER: 57910-79-9
SUBMISSION •: 8EHQ-0990-1065
CAS NUMBER: 64819-51-8
SUBMISSION t: 8EHQ-0890-1041
CAS NUMBER: NONE
SUBMISSION •: 8EH3-C890-1042
00
-J
u>
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: KETONE, ETHYL-SEC-AMYL
CHEMICAL NAME: KETOXIME (I ), ALIPHATIC
CHEMICAL NAME: KETOXIME (II), ALIPHATIC
CHEMICAL NAME: KRONITEX 50
CHEMICAL NAME: LACTONE, SUBSTITUTED POLYCYCLIC
CHEMICAL NAME: LATEX EFFLUENT
CHEMICAL NAME: LEAD
CHEMICAL NAME: LUCEL-4
CHEMICAL NAME: LUCEL-7 A20 FOAMING AGENT
CHEMICAL NAME: LUPERFOAM 329
-------
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EHQ-0390-0906 S
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EHQ-0690-1004 S
CAS NUMBER: UNKNOWN
SUBMISSION •: 8ENQ-1289-0850
CAS NUMBER: NONE
SUBMISSION •: 8EHQ-0590-0975
CAS NUMBER: 74-83-9
SUBMISSION #: 8EHQ-1189-0844
CAS NUMBER: 107-30-2
SUBMISSION •: 8EHQ-0589-0799
CAS NUMBER: 75-71-8
SUBMISSION *: 8EHQ-0589-0799
CAS NUMBER: 115-10-6
SUBMISSION »: 8EH4-0589-0799
CAS NUMBER: 542-88-1
SUBMISSION •: 8EHQ-0589-0799
CAS NUMBER: 131-57-7
SUBMISSION •: 8EHQ-1289-0855
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: MAGNACLEAR W 241
CHEMICAL NAME: MAKO
CHEMICAL NAME: MAT 7484
CHEMICAL NAME: MCS 1441
CHEMICAL NAME: METHANE, BROMO-
CHEMICAL NAME: METHANE, CHLGROMETHOXY-
CHEMICAL NAME: METHANE, DICHLORODIFLUORO-
CHEMICAL NAME: METHANE, OXYBIS-
CHEMICAL NAME: METHANE, OXYBIS[CHLORO-
CHEMICAL NAME: METHANONE, C2-HYDR0XY-4-METH0XYPHENYL)PHENYL-
-------
CAS NUMBER: 74-83-9
SUBMISSION «: 8EHQ-U89-0844
CAS NUMBER: 80-62-6
SUBMISSION «: 8EHQ-0490-0917
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EHQ-0690-1005 S
CAS NUMBER: NONE
SUBMISSION
CAS NUMBER: NONE
SUBMISSION
CAS NUMBER: NONE
SUBMISSION
CAS NUMBER: NONE
SUBMISSION
CAS NUMBER: NONE
SUBMISSION
CAS NUMBER: NONE
SUBMISSION
*: 8EHQ-Q290-0875 S
•: 8EHQ-0190-0863
•: 8EH9-0490-Q962
»: 8EHQ-0790-1032
t: 8EHQ-0890-1041
•: 8EHQ-0190-0864
CAS NUMBER: 129217-90-9
SUBMISSION •: 8EHQ-0990-1069
CAS NUMBER: 129217-90-9
SUBMISSION *: 8EHQ-0990-1069
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: METHYL BROMIDE
CHEMICAL NAME: METHYL METHACRYLATE
8EHQ-0690-0999 *
CHEMICAL NAME: MIBKO
CHEMICAL NAME: MIL-H-19457C (HILC)
CHEMICAL NAME: MISC. CHEMICALS
8EH4-0190-0864 8EHQ-6390-0915
CHEMICAL NAME: MISC. CHEMICALS
8EHQ-0590-0991 S 8EHQ-0790-1029
CHEMICAL NAME: MISC. CHEMICALS
8EHQ-0790-1034 8EHQ-0890-1038
CHEMICAL NAME: MISC. CHEMICALS
8EHQ-0990-1078 8EHQ-0990-1080 S
CHEMICAL NAME: MORFAX PRODUCTION PROCESS
CHEMICAL NAME: MP-2000
CHEMICAL NAME: MP-2000X
-------
APPENDIX Cs STATUS REPORTS BY CHEMICAL NAME
CAS NUMBER: NONE CHEMICAL NAME: MULTICORE SOLDER X32B
SUBMISSION t: 8EHQ-0990-1071
CAS NUMBER: NONE CHEMICAL NAME: MULTICORE TTC-1 TIP TANNER
SUBMISSION #: 8EHQ-0990-1071
CAS NUMBER: 85940-63-2 CHEMICAL NAME: 1,5-NAPHTHALENEDISULFONIC ACID, 2~[ 14 ,5~DIHYDRO-3-METHYL-5-0
X0-l~[4-[[2~(SULF00XY)ETHYL]SULFONYL]PHENYL]-lH-PYRAZ0L-4-YL
]AZ03-, POTASSIUM SODIUM SALT
SUBMISSION •: 8EHQ-0890-1051 S
CAS NUMBER: 17095-24-8 CHEMICAL NAME: 2,7-NAPHTHALENEDISULFONIC ACID, 4-AMINO-5-HYDROXY-3,6-BIS[ [4
-t 12-
-------
CAS NUMBER: CONFIDENT
SUBMISSION #: 8EHQ-0990-1070 S
CAS NUMBER: 112-96-9
SUBMISSION *: 8EHQ-0689-0802
CAS NUMBER: 557-09-5
SUBMISSION *: 8EHQ-0690-1019
CAS NUMBER: NONE
SUBMISSION *: 8EHQ-0590-098*
CAS NUMBER: NONE
SUBMISSION •: 8EHQ-0290-0886
CAS NUMBER: NONE
SUBMISSION • : 8EHQ-0590-0985
CAS NUMBER: CONFIDENT
SUBMISSION I: 8EHQ-0998-107S S
CAS NUMBER: CONFIDENT
SUBMISSION 8: 8EHQ-0990-1D76 S
CAS NUMBER: CONFIDENT
SUBMISSION I: 8EHQ-10S9-0834 S
CAS NUMBER: 99-54-7
SUBMISSION i: 8EHQ-0590-0972
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: NITROBENZENE, SUBSTITUTED
CHEMICAL NAME: OCTADECANE, 1-ISOCYANATO-
CHEMICAL NAME: OCTANOIC ACID, ZINC SALT
CHEMICAL NAME: OIL, FLUX
CHEMICAL NAME: OIL (PETROLEUM), REFINING PROCESS
CHEMICAL NAME: B65 OPAQUE GEL
K
CHEMICAL NAME: ORGANIC ALCOHOL, SUBSTITUTED
CHEMICAL NAME: ORGANIC ESTER, SUBSTITUTED
CHEMICAL NAME: ORGANOTIN COMPOUND
CHEMICAL NAME: ORTHENE, NITRATED
-------
CAS NUMBER: 10578-42-4
SUBMISSION #: 8EHQ-1189-0847
CAS NUMBER: CONFIDENT
SUBMISSION »: 8EHQ-0990-1079 S
CAS NUMBER: 75-21-8
SUBMISSION «: 8EHQ-0890-1053
CAS NUMBER: 556-52-5
SUBMISSION •: 8EH9-0789-0809
CAS NUMBER: 70205-95-7
SUBMISSION •: 8EHQ-0490-0945
CAS NUMBER: UNKNOWN
SUBMISSION •: 8EHQ-1189-0839
CAS NUMBER: NONE
SUBMISSION •: 8EHQ-0390-0914 S
CAS NUMBER: 111-30-8
SUBMISSION »: 8EHQ-0690-1008
CAS NUMBER: 565-80-0
SUBMISSION #: 8EHQ-0990-1062
CAS NUMBER: 108-10-1
SUBMISSION «: 8EH9-1189-0847
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: 7-OXABICYCLOt4.1.0]HEPTANE, 3-t <0X1RANYLMETHOXY)METHYL]-
CHEMICAL NAME: OXADIAZOLE, SUBSTITUTED
CHEMICAL NAME: OXIRANE
CHEMICAL NAME: OXIRANEMETHANOL
M
CHEMICAL NAME: OXOACETIC ACID HOMOPOLYMER, SODIUM SALT
CHEMICAL NAME: OXYALKYLATED LINEAR ALCOHOL-CARBOXYLIC ACID ADDUCT
CHEMICAL NAME: PAL 6000
CHEMICAL NAME: PENTANEDIAL
CHEMICAL NAME: 3-PENTANONE, 2,4-DIMETHYL-
CHEMICAL NAME: 2-PENTANONE, 4-METHYL-
-------
CAS NUMBER: 3520-72-7
SUBMISSION *: 8EHQ-B490-0962
CAS NUMBER: 15793-73-4
SUBMISSION •: 8EHQ-«*9«-0962
CAS NUMBER: 6358-85-6
SUBMISSION B: 8EH4-Q490-0962
CAS NUMBER: UNKNOWN
SUBMISSION I: 8EHQ-0490-0962
CAS NUMBER: UNKNOWN
SUBMISSION •: 8EHQ-0490-0962
CAS NUMBER: 4531-49-1
SUBMISSION I: 8EH«-ft49l~0962
CAS NUMBER: UNKNOWN
SUBMISSION •: 8EHQ-Q490-0962
CAS NUMBER: 5102-83-0
SUBMISSION ¦: 8EHQ-0490-0962
CAS NUMBER: UNKNOWN
SUBMISSION *: 8EHQ-Q490-0962
CAS NUMBER: UNKNOWN
SUBMISSION •: 8EHQ-0490-0962
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: PERMANENT ORANGE G TYPE
CHEMICAL NAME: PERMANENT ORANGE RL TYPE
CHEMICAL NAME: PERMANENT YELLOW DBG TYPE
CHEMICAL NAME: PERMANENT YELLOW D6R TYPE
CHEMICAL NAME: PERMANENT YELLOW GGR TYPE
CHEMICAL NAME: PERMANENT YELLOW GG TYPE
CHEMICAL NAME: PERMANENT YELLOW GRL TYPE
CHEMICAL NAME: PERMANENT YELLOW GR TYPE
CHEMICAL NAME: PERMANENT YELLOW GRX TYPE
CHEMICAL NAME: PERMANENT YELLOW GRY TYPE
-------
CAS NUMBER: 2512-29-0
SUBMISSION #: 8EHQ-0490-0962
CAS NUMBER: UNKNOWN
SUBMISSION •: 8EHQ-0490-0962
CAS NUMBER: 5567-15-7
SUBMISSION «: 8EHQ-0490-0962
CAS NUMBER: 597 9-28-2
SUBMISSION •: 8EHQ-0490-0962
CAS NUMBER: UNKNOUN
SUBMISSION »: 8EHQ-0490-0962
CAS NUMBER: NONE
SUBMISSION •: 8EHQ-0290-0882
CAS NUMBER: 68937-41-7
SUBMISSION •: 8EHQ-1189-0847
CAS NUMkuK: 71130-60-4
SUBMISSION •: 8EHQ-0190-0867
CAS NUMBER: 88-75-5
SUBMISSION •: 8EHQ-0590-0978
CAS NUMBER: 576-26-1
SUBMISSION #: 8EHQ-07 90-1027
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: PERMANENT YELLOW G TYPE
CHEMICAL NAME: PERMANENT YELLOW G3R TYPE
CHEMICAL NAME: PERMANENT YELLOW HR TYPE
CHEMICAL NAME: PERMANENT YELLOW NCG TYPE
CHEMICAL NAME: PERMANENT YELLOW YR TYPE
CHEMICAL NAME: PETROLEUM REFINING PROCESS
CHEMICAL NAME: PHENOL, ISOPROPYLAT ED, PHOSPHATE (3:1)
8EHQ-0990-1057
CHEMICAL NAME: PHENOL, 2-[
-------
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CAS NUMBER: 2628-16-2 CHEMICAL NAME: PHENOL, t-ETHENYL-, ACETATE
SUBMISSION •: SEHQ-0990-10-62
CAS NUMBER: CONFIDENT CHEMICAL NAME: PHENOL, <»,
-------
CAS NUMBER: 22042-96-2
SUBMISSION t: 8EHQ-0490-0950
CAS NUMBER: 4351-70-6
SUBMISSION •: SEHQ-0490-0947
CAS NUMBER: 1429-50-1
SUBMISSION •: 8EHQ-Q490-0940
CAS NUMBER: 124-64-1
SUBMISSION •: 8EHQ-0689-0804
CAS NUMBER: 55566-30-8
SUBMISSION •: 8EHQ-0689-0804
CAS NUMBER: 38638-05-0
SUBMISSION •: 8EHQ-0590-0975
CAS NUMBER: 126-73-8
SUBMISSION •: 8EHQ-1189-0847
CAS NUMBER: 115-86-6
SUBMISSION «: 8EHQ-0590-0975
CAS NUMBER: 34364-42-6
SUBMISSION •: 8EHQ-0590-0975
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: PHOSPHONIC ACID, [[(PHOSPHONOMETHYL)IMINO]BISC(2,1-ETHANEDIY
LNITRILO)BIS(METHYLENE)]JTETRAKIS-, SODIUM SALT
CHEMICAL NAME: PHOSPHONIC ACID, [1—[C(2-CHL0R0ETH0XY)(2-CHL0R0ETHYL)PH0SPHI
NYL]OXY]ETHYL]-, l-[BIS(2-CHLOROETHOXY)PHOSPHINYL]ETHYL 2-CH
LOROETHYL ESTER
CHEMICAL NAME: PHOSPHONIC ACID, t1,2-ETHANEDIYLBIStNITRILOBIS(METHYLENE)1IT
ETRAKIS-
CHEMICAL NAME: PHOSPHONIUM, TETRAKIS(HYDROXYMETHYL)-, CHLORIDE
8EHQ-0290-0877
CHEMICAL NAME: PHOSPHONIUM, TETRAKIS(HYDROXYMETHYL)-, SULFATE (2:1) (SALT)
8EHQ-0290-0877
CHEMICAL NAME: PHOSPHORIC ACID, NONYLPHENYL DIPHENYL ESTER
8EHQ-0590-0976
CHEMICAL NAME: PHOSPHORIC ACID TRIBUTYL ESTER
8EHQ-0690-1007
CHEMICAL NAME: PHOSPHORIC ACID, TRIPHENYL ESTER
SEHQ-D590-097<
CHEMICAL NAME: PHOSPHORIC ACID, (1-METHYL-1-PHENYLETHYL)PHENYL DIPHENYL EST
ER
8EHQ-0590-0976
-------
CAS NUMBER: 38051-10-4
SUBMISSION «: 8EHQ-0490-0944
CAS NUMBER: 2524-03-0
SUBMISSION «: 8EHQ-0290-0878
CAS NUMBER: 34643-46-4
SUBMISSION •: 8EHQ-0989-0823
CAS NUMBER: 25550-98-5
SUBMISSION «: 8EHQ-0490-0963
CAS NUMBER: 7723-14-0
SUBMISSION •: 8EHQ-0889-0820
CAS NUMBER: 3520-72-7
SUBMISSION •: 8EHQ-0490-0962
CAS NUMBER: 15793-73-4
SUBMISSION •: 8EHQ-0490-0962
CAS NUMBER: 6358-87-8
SUBMISSION *: 8EHQ-0490-0962
CAS NUMBER: UNKNOWN
SUBMISSION #: 8EHQ-0490-0962
CAS NUMBER: UNKNOWN
SUBMISSION *: 8EHQ-0490-0962
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: PHOSPHORIC ACID, 2,2-BIS
-------
CAS NUMBER: 6358-85-6
SUBMISSION *: 8EHQ-0490-0962
CAS NUMBER: UNKNOWN
SUBMISSION •: 8EHQ-0490-0962
CAS NUMBER: UNKNOWN
SUBMISSION t: 8EH4-0490-0962
CAS NUMBER: 5102-83-0
SUBMISSION «: 8EH4-0490-0962
CAS. NUMBER: 2512-29-0
SUBMISSION •: 8EHQ-0490-0962
CAS NUMBER: UNKNOWN
SUBMISSION •: 8EHQ-0490-0962
CAS NUMBER: 5979-28-2
SUBMISSION i: 8EHQ-0490-0962
CAS NUMBER: 4531-49-1
SUBMISSION ft: 8EHQ-0490-0962
CAS NUMBER: UNKNOWN
SUBMISSION •: 8EHQ-0490-0962
CAS NUMBER: UNKNOWN
SUBMISSION •: 8EHQ-0490-0962
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: C. I. PIGMENT YELLOW 12
CHEMICAL NAME: C. I. PIGMENT YELL0VC126
CHEMICAL NAME: C. I. PIGMENT YELLOW 127
CHEMICAL NAME: C.I. PIGMENT YELLOW 13
CHEMICAL NAME: C. I. PIGMENT YELLOW 14
CHEMICAL NAME: C. I. PIGMENT YELLOW 152
CHEMICAL NAME: C. I. PIGMENT YELLOW 16
CHEMICAL NAME: C. I. PIGMENT YELLOW 17
CHEMICAL NAME: C. I. PIGMENT YELLOW 174
CHEMICAL NAME: C. I. PIGMENT YELLOW 176
-------
CAS NUMBER: NONE
SUBMISSION *: 8EHQ-0389-0789
CAS NUMBER: 5567-15-7
SUBMISSION *: 8EHQ-0490-0962
CAS NUMBER: 2591-86-8
SUBMISSION »: 8EHQ-0590-0974
CAS NUMBER: UNKNOWN
SUBMISSION *: 8EHQ-0990-1072
CAS NUMBER: 1336-36-3
SUBMISSION •: 8EHQ-0490-0933
CAS NUMBER: CONFIDENT
SUBMISSION *: 8EHQ-0290-0872 S
CAS NUMBER: 9014-92-0
SUBMISSION •: 8EHQ-0490-0942
CAS NUMBER: UNKNOWN
SUBMISSION •: 8EHQ-1189-0839
CAS NUMBER: 75-31-0
SUBMISSION «: 8EHQ-0290-0878
CAS NUMBER: 919-30-2
SUBMISSION •: 8EHQ-0389-0780
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: C. I. PIGMENT YELLOW 18*
CHEMICAL NAME: C. I. PIGMENT YELLOW 83
CHEMICAL NAME: 1-PIPERIDINECARBOXALDEHYDE
CHEMICAL NAME: POLYBROMINATED BIPHENYLS (PBB)
CHEMICAL NAME: POLYCHLORINATED BIPHENYLS (PCB)
CHEMICAL NAME: POLYCYCLIC DIONE, SUBSTITUTED
CHEMICAL NAME: P0LY(0XY-1,2-ETHANEDIYL), .ALPHA.-(DODECYLPHENYL.OMEGA.-HY
DROXY-
CHEMICAL NAME: POLY-TERGENT CS-1 ANALOGUE
CHEMICAL NAME: 2-PROPANAMINE
CHEMICAL NAME: 1-PROPANAMINE. 3-CTRIETHOXYSILYL)-
-------
CAS NUMBER: 94857-19-9
SUBMISSION #: 8EH$-0290-0880
CAS NUMBER: 16714-68-4
SUBMISSION t: 8EH4-0290-0892
CAS NUMBER: 1634-04-4
SUBMISSION *: 8EHQ-0390-0900
CAS NUMBER: CONFIDENT
SUBMISSION t: 8EH4-0990-1075 S
g> CAS NUMBER: 67-63-0
SUBMISSION «: 8EHQ-029O-O884
CAS NUMBER: 96-23-1
SUBMISSION *: 8EHQ-08S9-0812
CAS NUMBER: 13586-68-0
SUBMISSION *: 8EHQ-0490-0931 S
CAS NUMBER: 78-88-6
SUBMISSION i: 8EHQ-029Q-Q892
CAS NUMBER: 140-88-5
SUBMISSION •: 8EHQ-0490-0917
CAS NUMBER: 71050-62-9
SUBMISSION •: 8EH9~0190-0866 S
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: 1,3-PROPANEDIOL, 2-ETHYL-2-
-------
CAS NUMBER: UNKNOWN
SUBMISSION •: 8EHQ-0190-0866 S
CAS NUMBER: 7085-85-0
SUBMISSION •: 8EHQ-0989-0821 S
CAS NUMBER: 80-62-6
SUBMISSION *: 8EHQ-0490-0917
CAS NUMBER: 107-11-9
SUBMISSION t: 8EH9-1089-0830
® CAS NUMBER: 34643-46-4
^ SUBMISSION •: 8EHQ-0989-0823
CAS NUMBER: 288-13-1
SUBMISSION •: 8EHQ-0789-0807 S
CAS NUMBER: 6358-87-8
SUBMISSION •: 8EHQ-0490-0962
CAS NUMBER: 1453-58-3
SUBMISSION •: 8EHQ-0389-0786 S
CAS NUMBER: UNKNOWN
SUBMISSION •: 8EHQ-0886-0815
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EHS-0289-0783 S
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: 2-PROPENOIC ACID, POLYMER WITH SODIUM PHOSPHINATE, SODIUM SA
LT
CHEMICAL NAME: 2-PROPENOIC ACID, 2-CYANO-, ETHYL ESTER
CHEMICAL NAME: 2-PROPENOIC ACID, 2-METHYL-, METHYL ESTER
8EHQ-0690-0999 *
CHEMICAL NAME: 2-PR0PEN-1-AMINE
CHEMICAL NAME: PROTHIOFOS
CHEMICAL NAME: lH-PYfcAZOLE
CHEMICAL NAME: 1H-PYRAZ0LE-3-CARB0XYLIC ACID, 4,4"-[(3,3'-DICHLOROI1,1 *-BIP
HENYL 3-4,4 *-DIYL)BIS(AZO)]BIS[4,5-DIHYDRO-5-OXO-1-PHENYL-, D
IETHYL ESTER
CHEMICAL NAME: 1-H-PYRAZOLE, 3-METHYL-
CHEMICAL NAME: 1H-PYRAZOLE-4-CARBOXAMIDE, 5-CYAHO-1-C1,1-DIMETHYLETHYL)-N-M
ETHYL-
CHEMICAL NAME: PYRAZOLYL AMIDE, HETEROCYCLIC
-------
CAS NUMBER: 3520-72-7
SUBMISSION *: 8EHQ-0490-0962
CAS NUMBER: 15793-73-4
SUBMISSION •: 8EHQ-0490-0962
CAS NUMBER: CONFIDENT
SUBMISSION #: SEHQ-0590-0992 S
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EHQ-0390-0895 S
CAS NUMBER: CONFIDENT
SUBMISSION »: 8EHQ-0790-1031 S
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EHQ-0289-0785 S
CAS NUMBER: CONFIDENT
SUBMISSION i: 8EHQ-0490-0957 S
CAS NUMBER: 941-69-5
SUBMISSION t: 8EHQ-0690-1000 S
CAS NUMBER: 6422-83-9
SUBMISSION »: 8EHQ-0790-1023 S
CAS NUMBER: 616-45-5
SUBMISSION t: 8EHQ-1089-0829
CO
CD
CD
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: 3H-PYRAZ0L-3-0NE, 4,4*-[(3,3'-DICHLOROt1,1•-BIPHENYL]-4,41-D
IYL)BIS(AZO)]BISC 2,4-DIHYDRO-5-METHYL-2-PHENYL-
CHEMICAL NAME: 3H-PYRAZOL-3-ONE, 4,4'-[(3,3'-DICHLOROt1,1»-BIPHENYL]-4,4•-D
IYL)BIS(AZO)]BIS12,4-DIHYDRO-5-METHYL-2-(4-METHYLPHENYL)-
CHEMICAL NAME: PYRIDAZINE, SUBSTITUTED
CHEMICAL NAME: PYRIDINECARBOXYLATE
CHEMICAL NAME: PYRIDOPYRIDIMINE, SUBSTITUTED
CHEMICAL NAME: PYRIMIDINE, ACYLAMINO
CHEMICAL NAME: PYRIMIDINE, SUBSTITUTED
8EHQ-0490-0958 S
CHEMICAL NAME: 1H-PYRR0LE-2,5-DIONE, 1-PHENYL-
CHEMICAL NAME: 1H-PYRROLE-2,5-DIONE, 1,1 •-(4-METHYL-l,3-PHENYLENE)BIS-
CHEMICAL NAME: 2-PYRR0LIDIN0NE
-------
CAS NUMBER: NONE
SUBMISSION ir 8EHQ-1289-0859
CAS NUMBER.- CONFIDENT
SUBMISSION •: 8EHQ-0889-0819 S
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EHQ-0789-0808 S
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EHQ-0789-0806 S
CAS NUMBER: CONFIDENT
SUBMISSION «: 8EHQ-0790-1036 S
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EHQ-0990~1083 S
CAS NUMBER: CONFIDENT
SUBMISSION I: 8EHQ-099Q-1083 S
CAS NUMBER: CONFIDENT
SUBMISSION i: 8EHQ-1089-0833 S
CAS NUMBER: UNKNOWN
SUBMISSION #: 8EHQ-0790-1029
CAS NUMBER: 17095-24-8
SUBMISSION *: 8EHQ-0290-0885
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: QC2 (MIXTURE)
CHEMICAL NAME: QUINAZOLINE (III), SUBSTITUTED
CHEMICAL NAME: QUINAZOLINE (II), SUBSTITUTED
CHEMICAL NAME: QUINAZOLINE (I), SUBSTITUTED
CHEMICAL NAME: QUINAZOLINE (IV3, SUBSTITUTED
CHEMICAL NAME: QUINAZOLINES
CHEMICAL NAME: QUINOLINES
CHEMICAL NAME: QUINOLINE, SUBSTITUTED
8EHQ-0690-1016 S
CHEMICAL NAME: RARE EARTH Y (REY) CRYSTALS
CHEMICAL NAME: C.I. REACTIVE BLACK 5
-------
CAS NUMBER: NONE
SUBMISSION •: 8EHQ-0290-0882
CAS NUMBER: NONE
SUBMISSION »: 8EHQ-0390-0915
CAS NUMBER: 75-71-8
SUBMISSION *: 8EHQ-0589-0799
CAS NUMBER: UNKNOWN
SUBMISSION •: 8EHQ-0990-1074
CAS NUMBER: 2479-46-1
SUBMISSION *: 8EHQ-0390-0898
CAS NUMBER: NONE
SUBMISSION •: 8EH9-0490-0938
CAS NUMBER: NONE
SUBMISSION •: 8EHQ-0590-0982
CAS NUMBER: 793-24-8
SUBMISSION *: 8EHQ-0590-0966
CAS NUMBER: 3081-14-9
SUBMISSION •: 8EHQ-059D-0977
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EHQ-0390-0907 S
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: REFORMER SPRAY TUR
CHEMICAL NAME: REFRACTORY CERAMIC FIBER
CHEMICAL NAME: REFRIGERANT 12
CHEMICAL NAME: RESORCINOL DIPHOSPHATE
CHEIIiCAL NAME: RODA
CHEMICAL NAME: SANTICIZER 9 PLASTICIZER
CHEMICAL NAME: SANTICIZER 97
CHEMICAL NAME: SANTOFLEX 13
CHEMICAL NAME: SANTOFLEX 77
CHEMICAL NAME: SEMICARBAZONE
8EHQ-0390-0916 S *
-------
CAS NUMBER: 287-29-6
SUBMISSION t: 8EHQ-0990-1084
CAS NUMBER: 919-30-2
SUBMISSION t: 8EHQ-0389-0789
CAS NUMBER: 4109-96-4
SUBMISSION •: 8EH9-0689-0803
CAS NUMBER: 16881-77-9
SUBMISSION *: 8EHQ-0690-1009
CAS NUMBER: 998-30-1
a>
M SUBMISSION *: 8EHQ-1089-0832
CAS NUMBER: 2530-87-2
SUBMISSION t: 8EHQ-0990-1067
CAS NUMBER: 56982-91-5
SUBMISSION t: 8EHQ-0390-0899
CAS NUMBER: 409-21-2
SUBMISSION •: 8EH4-0690-1018
CAS NUMBER: 409-21-2
SUBMISSION t: 8EHQ-0690-1018
CAS NUMBER: 67762-90-7
SUBMISSION t: 8EHQ-0590-0985
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: SILACYCLOBUTANE
CHEMICAL NAME: SILANE A-1100
CHEMICAL NAME: SILANE, DICHLGRO-
CHEMICAL NAME: SILANE, DIMETHOXYMETHYL-
CHEMICAL NAME: SILANE, TRIETHOXY-
CKEMICAL NAME: SILANE, C3-CHLOROPROPYDTRIMETHOXY-
CHEMICAL NAME: SILICATE, TETRAMETHYL AMMONIUM
K
CHEMICAL NAME: SILICON CARBIDE FIBERS
CHEMICAL NAME: SILICON CARBIDE, (SIC)
CHEMICAL NAME: SILOXAHES AND SILICONES, DI-NE, REACTION PRODUCTS WITH SILIC
A
x
-------
CAS NUMBER; 69701-07-7
SUBMISSION *: 8EHQ-0590-0967
CAS NUMBER: HONE
SUBMISSION t: 8EH«-0490~0932
CAS NUMBER: NONE
SUBMISSION »: 8ENQ-0490-0932
CAS NUMBER: 2155-38-6
SUBMISSION •: 8EHQ-1189-0B47
oo CAS NUMBER: 3388-03-2
V0
to
SUBMISSION *: 8EHQ-1189-0847
CAS NUMBER: 26616-47-7
SUBMISSION t: 8EHQ-1189-0847
CAS NUMBER: 9014-92-0
SUBMISSION •: 8EH9-0490-0942
CAS NUMBER: 103-30-0
SUBMISSION 8: 8EHQ-0490-0939
CAS NUMBER: 2628-16-2
SUBMISSION t: 8EHQ-0990-1082
CAS NUMBER: CONFIDENT
SUBMISSION »: 8EHQ-1289-0849 S
appJtJix ? • s.iius - - ortt t c>rr*;:sAt ';ame
CHEMICAL NAME: SKYBOND 700 POLYIMIDE RESIN
CHEMICAL NAME: SLUDGE, API SEPARATOR BOTTOM
CHEMICAL NAME: SLUDGE, DISSOLVED AIR FLOTATION (DAF) FLOAT
CHEMICAL NAME: SPIROt1,3-DIOXAHE-5,3'~t7]0XABICYCL0t4.1.01HEPTANE1, 2-I2-C2
-(OXIRANYLMETHOXY)ETHOXY3 ETHYLJ-
CHEMICAL NAME: SPIROT1,3-DI0XANE-5,3'-[730XABICYCL0E4.1.0]HEPTANEJ, 2-(7-OX
ABICYCL0I4.1.0]HEPT-3-YL)-
CHEHICAL NAME: SPIROt1,3-DI0XANE-5,3'-[7JOXABICYCLOC4.1.01HEPTANE], 2-(7-OX
ABICYCLOC4.1.0JHEPT-3-YLHOMOPOLYMER
CHEMICAL NAME: STEROX DJ SURFACTANT
CHEMICAL NAME: STILBENE, TRANS-
CHEMICAL NAME: STYRENE, ACETOXY-
CHEMICAL NAME: SUBSTITUTED ORGANIC AMMONIUM CHLORIDE
-------
CAS NUMBER: CONFIDENT
SUBMISSION «: 8EHQ-0S90-1050 S
CAS NUMBER: CONFIDENT
SUBMISSION t: 8EHQ-099B-0986 S
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EH4-0390-0988 S
CAS NUMBER: CONFIDENT
SUBMISSION «: 8EH9-0390-0987 S
CAS NUMBER: CONFIDENT
00
SUBMISSION t: 8EHQ-0690-1013 S
01
CAS NUMBER: CONFIDENT
SUBMISSION *: 8EHQ-0789-0805 S
CAS NUMBER: CONFIDENT
SUBMISSION «: 8EHQ-0389-0791 S
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EHQ-Q489-0794 S
CAS NUMBER: 2540-99-0
SUBMISSION «: 8EHQ-0489-0795
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EHQ-0890-1039 S
APPENDIX C: STATUS REPORTS Br CHEMICAL NAME
CHEMICAL NAME: SUBSTITUTED PHENOXYETHER DERIVATIVE OF A POLYHETEROCYCLE
CHEMICAL NAME: SULFENAMIDE (#1), AROMATIC
CHEMICAL NAME: SULFENAMIDE («2), AROMATIC
CHEMICAL NAME: SULFENAMIDE (#3), AROMATIC
CHEMICAL NAME: SULFONE, ARYL METHYL
CHEMICAL NAME: SULFONE (ID, UNSATURATED
CHEMICAL NAME: SULFONE, UNSATURATED
CHEMICAL NAME: SULFONIC ACID, SUBSTITUTED ARYL-, ALKALI METAL SALT
CHEMICAL NAME: 4,4'-SULFONYLBIStPHTHALIC ANHYDRIDE)
CHEMICAL NAME: SULFURIZED COMPOUNDS, MIXTURE OF
-------
CAS NUMBER: 101-20-2
SUBMISSION t: 8EHQ-0590-0968
CAS NUMBER: 261*0-60-3
SUBMISSION *: 8EHQ-0590-0983
CAS NUMBER: 61788-32-7
SUBMISSION *: 8EHQ-0590-0983
CAS NUMBER: 25103-58-6
SUBMISSION *: 8EHQ-0590-0994
CAS NUMBER: UNKNOWN
SUBMISSION *: 8EHQ-0889-0814
CAS NUMBER: 3806-34-6
SUBMISSION *: 8EHQ-0590-0996
CAS NUMBER: 117-08-8
SUBMISSION «: 8EHQ-0490-0948
CAS NUMBER: 68855-24-3
SUBMISSION i: 8EHQ-0590-0969
CAS NUMBER: NONE
SUBMISSION t: 8EH9-0590-0983
CAS NUMBER: UNKNOWN
SUBMISSION •: 8EHQ-0890-1040
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: TCC SOAP BACTERIOSTAT
CHEMICAL NAME: TERPHENYL
CHEMICAL NAME: TERPHENYL, HYDROGENATED
CHEMICAL NAME: TERT-DODECANETHIOL
x
CHEMICAL NAME: TETRAGLYCIDYL ETHER, BIS-TRIMETHYLOLPROPANE
CHEMICAL NAME: 2, <• ,8,10-TETRAOXA-3,9-DIPH0SPHASPIR0[5.51UNDECANE, 3,9-BISCO
CTADECYLOXY)-
CHEMICAL NAME: TETRATHAL
CHEMICAL NAME: THERMINOL 55
CHEMICAL NAME: THERMINOL 66
CHEMICAL NAME: 1,2,4-THIADIAZOLE, POLY(3,5-DITHIO-
-------
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CAS NUMBER: CONFIDENT CHEMICAL NAME: THIOESTER, HETEROCYCLIC
SUBMISSION i: 8EHQ-0490-0925 S
CAS NUMBER: 7440-31-5 CHEMICAL NAME: TIN
SUBMISSION *: 8EHQ-0990-1071
CAS NUMBER: 34643-46-4 CHEMICAL NAME: TOKUTHION
SUBMISSION *: 8EH9-0989-0823
CAS NUMBER: 119-93-7 CHEMICAL NAME: O-TOLIDINE
SUBMISSION t: 8EHQ-0190-0863 8EHQ-0990-1080 S
CAS NUMBER: 70-55-3 CHEMICAL NAME: P-TOLUENESULFONAMIDE
SUBMISSION *: 8EHQ-0490-0938
CAS NUMBER: 88-19-7 CHEMICAL NAME: O-TGLUENESULFONAMIDE
SUBMISSION •: SEH4-0490-0938
CAS NUMBER: 95-53-4 CHEMICAL NAME: O-TOLUIDINE
SUBMISSION »: 8EHQ-0190-0864 8EHQ-0990-1080 S
CAS NUMBER: 106-49-0 CHEMICAL NAME: P-TOLUIDINE
SUBMISSION •: 8EH4-0990-1980 S
CAS NUMBER: 108-44-1 CHEMICAL NAME: K-TOLUIDINE
SUBMISSION i: 8EHQ-0990-1080 S
CAS NUMBER: 106990-43-6 CHEMICAL NAME: l,3,5-TRIAZINE-2,4,6-TRIAMINE, N,N"'-[1,2-ETHANEDIYLBISt[[4
,6-BIS[BUTYLCl,2,2,6,6-PENTAMETHYL-4-PIPERIDINYL)AMINO]-1,3
5-TRIAZIN-2-YLlIMlN0]-3,l-PROPANEDIYL]3-BISCN*,N*"-DIBUTYL-
' ,N"-BIS(1,2,2,6,6-PENTAMETHYL-4-PIPERIDINYL)-
SUBMISSION •: 8EHQ-1089-0836
-------
CAS NUMBER: 288-88-0
SUBMISSION #: 8EHQ-0489-0792
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EHQ-1089-0835 S
CAS NUMBER: 103112-35-2
SUBMISSION «: 8EH9-0490-0960
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EHQ-0890-1044 S
CAS NUMBER: NONE
SUBMISSION •: 8EHQ-0590-0985
CAS NUMBER: 101-20-2
SUBMISSION •: 8EHQ-0590-0968
CAS NUMBER: UNKNOUN
SUBMISSION «: 8EHQ-0390-0914 S
CAS NUMBER: CONFIDENT
SUBMISSION •: 8EHQ-0890-1049 S
CAS NUMBER: 137-30-4
SUBMISSION #: 8EHQ-0890-1045
CAS NUMBER: 75-02-5
SUBMISSION t: 8EHQ-1289-0856
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: 1H-1,2,4-TRIAZOLE
CHEMICAL NAME: TRIAZOLE DERIVATIVE
CHEMICAL NAME: 1(H)-1,2,4-TRIAZOLE-3-CARB0XYLATE, ETHYL 1 -(2,4-DICHLOROPHEN
YU-5-TRICHL0R0METHYL-
CHEMICAL NAME: TRIBROMOMETHYL SUBSTITUTED HETEROCYCLE
CHEMICAL NAME: TYPE B LIGHTGUIDE CABLE FILLING COMPOUND
*
CHEMICAL NAME: UREA, N-(4-CHLOROPHENYL)-N'-(3,4-DICHLOROPHENYL)-
CHEMICAL NAME: UREA, 1-METHOXY-1-METHYL-3-[4-(3,4-DIHYDRO-2-METHOXY-2,4,4-T
RIMETHYL-7-BENZOPYRANYLOXY)PHENYL]-
CHEMICAL NAME: VANADIUM COMPOUND. INORGANIC
CHEMICAL NAME: VANCIDE MZ-96
CHEMICAL NAME: VINYL FLUORIDE
-------
CAS NUMBER: 6358-87-8
SUBMISSION •: 8EHQ-0490-0962
CAS NUMBER: 3806-34-6
SUBMISSION •: 8EHQ-0590-0996
CAS NUMBER: NONE
SUBMISSION *: 8EHQ-0190-0864
CAS NUMBER: UNKNOWN
SUBMISSION i: 8EH9-0690-1019
CAS NUMBER: 95-78-3
SUBMISSION •: 8EHQ-0990-1080
CAS NUMBER: 1300-73-8
SUBMISSION •: 8EH9-0990-1080
CAS NUMBER: NONE
SUBMISSION 8: 8EHQ-1189-0847
CAS NUMBER: NONE
SUBMISSION 8: 8EHQ-1189-0847
CAS NUMBER: 137-30-4
SUBMISSION •: 8EHQ-0890-1045
CAS NUMBER: 13463-41-7
SUBMISSION #: 8EH«-0790-1035
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: VULCAN FAST RED B
CHEMICAL NAME: UESTON 618
CHEMICAL NAME: UINGSTAY 100 PRODUCTION PROCESS
CHEMICAL NAME: XB-4458
CHEMICAL NAME: 2,5-XYLIDINE
CHEMICAL NAME: XYLIDINE (MIXED)
CHEMICAL NAME: XYLOK HARDENER 231 N-90
CHEMICAL NAME: XYLOK 235 NK-75
CHEMICAL NAME: ZINC, BISCDIMETHYLCARBAMODITHIOATO-S,S¦)-, CT-4>-
CHEMICAL NAME: ZINC, BIS(l-HYDR0XY-2(lHJ-PYRIDINETHIONATO-O,S)-, CT-4)-
-------
ACUTE TOXICITY (ANIMAL)
SUBMISSION •: 8EHQ-0189-0779
8EHQ-0389-0788 :»
8EHQ-0789-0806 S
8EHQ-0889-0810 S
8EHQ-0989-0826 S
8EHQ-1089-Q834 S
8EHQ-1189-0841
8EHQ-1289-0850
8EHQ-1289-0859
8EHQ-0290-0893
8EHQ-0490-0920 S
8EHQ-0490-0958 S
8EHQ-0590-0985 *
8EHQ-0690-1004 S
8EHQ-0690-1016 S
8EHQ-0790-1031 S
8EHQ-0890-1040
8EHQ-0890-1048 S
8EHQ-0990-1057
8EHQ-0990-1060 S
8EHQ-0990-1068
ACUTE TOXICITY (HUMAN)
SUBMISSION •: 8EHQ-0889-0818 S
8EHQ-0390-0905 S *
APPENDIX (D): STATUS REPORTS BY INFORMATION TYPE
8EHQ-0389-0780
8EHQ-0589-0800
8EHQ-0789-0808 S
8EHQ-0889-0818 S
8EHQ-1089-0830
8EHQ-1089-0837 S
8EHQ-1189-0845
8EHQ-1289-0852 S
8EHQ-0190-0860 S
8EHQ-0390-0898
8EHQ-0490-0954 S
8EHQ-0490-0959 S
8EHQ-0590-0991 S
8EHQ-0690-1005 S
8EHQ-0790-1021
8EHQ-07 90-1035
8EHQ-0890-1045
8EHQ-0890-1052 S
8EHQ-0990-1058 S
8EHQ-0990-1061
8EHQ-0990-1076 S
8EKQ-1089-0832
8EHQ-0490-0929 S *
8EHQ-0389-0787 S
8EHQ-0689-0803
8EHQ-0789-0809 x
8EHQ-0889-0819 S
8EHQ-1089-0833 S
8EHQ-1089-0838 S
8EHQ-1189-0848 S
8EHQ-1289-0857 S
8EHQ-0190-0867 *
8EHQ-0490-0919 S
8EHQ-0490-0957 S
8EHQ-0590-0964
8EHQ-0690-1003
8EHQ-0690-1009
8EHQ-0790-1023 S
8EKQ-0790-1036 S
8EHQ-0890-1047
8EHQ-0890-1054 S
8EHQ-0990-1059 S *
8EHQ-0990-1062
8EHQ-0990-1084
8EHQ-0290-0885
8EHQ-0590-0991 S
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ACUTE TOXICITY (HUMAN)
SUBMISSION #- 8EHQ-0890-1042
ALLERGENICITY (ANIMAL)
SUBMISSION I: 8EHQ-0489-0795
8EHQ-0989-0826 S
8EHQ-1289-0852 S
8EHQ-0490-0919 S
8EHQ-0990-1069
ALLERGENICITY (HUMAN)
SUBMISSION •: 8EHQ-O290-O885
CELL TRANSFORMATION (IN VITRO)
SUBMISSION •: 8EHQ-0889-Q814
CHEMICAL/PHYSICAL PROPERTIES
SUBMISSION •: 8EHQ-0189-0779
8EHQ-0389-0789
8EHQ-0889-0814
8EHQ-1089-0832
8EHQ-0390-0899
8EHQ-0590-0991 S
8EHQ-Q790-1027
8EHQ-0990-1061
APPENDIX (D): STATUS REPORTS BY INFORMATION TYPE
8EH9-0990-1071
8EHQ-0589-0796
8EHQ-1189-0839
8EHQ-0290-0876
8EHQ-0790-1033
8EHQ-0990-1082
8EHQ-0590-0991 S
8EHQ-0690-1018
8EHQ-0990-1078
8EHQ-0689-0802
8 EH<)-1189-084 5
8EHQ-0290-0894
8EHQ-0990-1062
8EHQ-0890-1039 S
8EHQ-0189-0781 S
8EHQ-0589-0799
8EHQ-0989-0821 S
8EHQ-1189-0847
8EHQ-0390-0903 S
8EHQ-0690-1018
8EHQ-0790-1033
8EHQ-0289-0784
8EH9-0589-0801
8EHQ-0989-0826 S
8EHQ-0190-0867
8EHQ-0490-0962
8EHQ-0690-1019
8EHQ-0990-1058 S
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CHRONIC TOXICITY (ANIMAL)
SUBMISSION *: 8EHQ-0589-0797
8EHQ-1189-0847
8EHQ-0290-0873 S
8EHQ-0390-0914 S
8EHQ-0490-0960
8EHQ-0790-1029
8EHQ-0890-1053
CHRONIC TOXICITY (HUMAN)
SUBMISSION •: 8EHQ-1089-0831
vo
g 8EHQ-0290-0886
8EHQ-0490-0924
8EHQ-0990-1080 S
CLASTOGENICITY
SUBMISSION »:
(ANIMAL)
8EHQ-0389-0780
8EHQ-0390-0902
8EHQ-0490-0920 S
CLASTOGENICITY
SUBMISSION •:
(IN VITRO)
8EHQ-0389-0780
8EHQ-0889-0814
8EHQ-0990-1079 S
ONA DAMAGE/REPAIR
SUBMISSION •: 8EHQ-0889-0814
APPENDIX (D): STATUS REPORTS BY INFORMATION TYPE
8EHQ-0889-0812
8EHQ-1289-0856
8EHQ-0290-0881 S
8EHQ-0490-0930 S
8EHQ-0590-0968
8EHQ-0890-1043
8EHQ-0890-1056 S
8EHQ-0989-0822
8EHQ-1289-0858 S
8EHQ-0390-0900
8EHQ-0490-0952 S
8EHQ-0590-0993
8EHQ-0890-1050 S
8EHQ-0190-0863
8EHQ-0390-0915
8EHQ-0790-1034
8EHQ-0190-0864
8EHQ-0490-0917
8EHQ-0990-1072
8EHQ-0989-0826 S
8EHQ-0390-0903 S
8EHQ-0690-1015
8EHQ-0389~0791 S
8EHQ-1189-0847
8EHQ-0390-0901
8EHQ-0390-0909
8EHQ-0990-1061
8EHQ-0789-0805 S
8EHQ-0890-1051 S
8EHQ-1289-0853 S
8EHQ-0890-1051 S
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APPENDIX (D): STATUS REPORTS BY INFORMATION TYPE
ECOTOXICITY/AQUATIC TOXICITY
SUBMISSION «: 8EHQ-0989-0826 S
8EHQ-0390-0908 S
8EHQ-0790-1032
8EHQ-0390-0899 *
8EHQ-0590-0994 *
8EHQ-0990-1083 S
8EHQ-0390-0906
8EHQ-0690-1017
EMERGENCY INCIDENT OF ENV. CONTAMINATION
SUBMISSION «: 8EHQ-0490-0921 S
8EHQ-0490-0933
8EH9-0790-1032
ENV. OCCURRENCE/RELEASE/FATE
SUBMISSION *: 8EHQ-0589-0799
8EHQ-0390-0905 S
8EHQ-0490-0953
8EHQ-0990-1077
8EHQ-0989-0826 S
8EHQ-0490-0921 S
8EHQ-0790-1032
8EHQ-0290-0882
8EHQ-0490-0933
8EHQ-0890-1038
EPIDEMIOLOGY/CLINICAL
SUBMISSION #: 8EH9-0889-0818 S
8EHQ-1089-0832
8EHQ-0290-0886
8EHQ-0490-0917
8EHQ-0590-0991 S
8EHQ-0990-1065
8EHQ-0990-1078
8EHQ-0989-0821 S
8EHQ-0190-0863
8EHQ-0390-0905 S
8EHQ-0490-0924
6EHQ-0790-1034
8EHQ-0990-1071
8EHQ-0990-1080 S
8 EH<}-1089-0831
8EHQ-0190-0864
8EHQ-0390-0915
8EHQ-0490-0929
8EHQ-0890-1053
8EH9-0990-1072
GROUNDWATER CONTAMINATION
SUBMISSION *: 8EHQ-0490-0953
8EHQ-0990-1077
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APPENDIX (D): STATUS REPORTS BY INFORMATION TYPE
HUMAN EXPOSURE (ACCIDENTAL)
SUBMISSION •: 8EHQ-1089-0832
8EHQ-0490-0929 S
8EHQ-0990-1065
8EHQ-0290-0885
8EHQ-0490-0933
8EHQ-0390-0905 S
8EHQ-0490-0962
HUMAN EXPOSURE (MONITORING)
SUBMISSION t: 8EHQ-0289-0784
8EHQ-0589-0801
8EHQ-0190-0863
8EHQ-0490-0933
8EHQ-0690-1018
8EHQ-0990-1077
8EHQ-0389-0789
8EHQ-0889-0818 S
8EHQ-0290-0882
8EHQ-0$90-0953
8EHQ-0890-1038
8EHQ-0990-1078
8EHQ-0489-0793
8EHQ-1289-0856
8EHQ-0490-0924
8EHQ-0«90-0962
8EHQ-0890-1053
HUMAN EXPOSURE (PRODUCT CONTAMINATION)
SUBMISSION •: 8EHQ-0589-0799
8EHQ-0689-0804
8EHQ-0*90-0962
IMMUNOTOXICITY (ANIMAL)
SUBMISSION «: 8EHQ-0889-0817
IMMUNOTOXICITY (HUMAN)
SUBMISSION t: 8EHQ-0290-0876
MATERIAL SAFETY DATA SHEETS/LABELS
SUBMISSION •: 8EHQ-0190-0867 *
8EHQ-0490-0945
8EHQ-0590-0983
8EHQ-0390-0903 S
8EHQ-0590-0967
8EHQ-0590-0991 5
8EHQ-0*90-0919 S
8EHQ-0590-0969
8EHQ-0590-1001 S
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MATERIAL SAFETY DATA SHEETS/LABELS
SUBMISSION •: 8EHQ-0690-1017
8EHQ-0990-1071
METABOLISM/PHARMACOKINETICS (ANIMAL)
SUBMISSION •: 8EHQ-0490-0952 S
MUTAGENICITY CIN VITRO)
SUBMISSION »: 8EHQ-0389-0780
8EHQ-0789-0805 S
8EHQ-1089-0837 S
8EHQ-0390-0903 S
8EHQ-0490-0932
8EHQ-0690-1015
SEHQ-0890-1051 S
8EHQ-0990-1079 S
MUTAGENICITY CIN VIVO)
SUBMISSION *: 8EHQ-0290-0892
NEUROTOXICITY (ANIMAL)
SUBMISSION i: 8EHQ-0489-0793
8EHQ-0886-0815
8EHQ-1189-0841
8EHQ-1189-0858 5
8EHQ-0390-0898
APPENDIX (D): STATUS REPORTS BY INFORMATION TYPE
8EHQ-0690-1018 8EHQ-0990-1062
8EHQ-0990-1078
8 EHQ-038 9-07 91 S
8EHQ-0889-081*
8EHQ-1289-0854 S
8EHQ-0390-0916 S *
8EHQ-0490-0960
8EHQ-0690-1016 S
8EHQ-0990-1066 S
8EHQ-0589-07 98 S
8EHQ-0 989-0826 S
8EHQ-1289-0858 S
8EHQ-0490-0930 S
8EHQ-0690-1009
8EHQ-0890-1044 S
8EHQ-0990-1067
8EHQ-0390-0916 S * 8EHQ-0590-0981
8EHQ-0489-0794 S
8EHQ-1089-0837 S
8EHQ-1189-0843 S
8EHQ-0190-0867 K
8EHQ-0390-0913 S
8EHQ-0889-0811 S
8EHQ-1089-0838 S
8EHQ-1189-0846
8EHQ-0290-0893
8EHQ-0390-0914 S
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NEUROTOXICITY (ANIMAL)
SUBMISSION •: 8EHQ-0490-0919 S
8EHQ-0490-0936
8EHQ-0490-0958 S
8EHQ-0590-0964
8EHQ-0690-1002
8EHQ-0690-1005 S
8EHQ-0890-1041
8EHQ-0990-1057
NEUROTOXICITY (HUMAN)
SUBMISSION •: 8EHQ-0590-0991 S
ONCOGENICITY (ANIMAL)
SUBMISSION •: 8EHQ-0789-0809 *
8EHQ-1189-0847
8EHQ-0290-0873 S
8EHQ-0490-0960
8EHQ-0890-1050 S
ONCOGENICITY (HUMAN)
SUBMISSION *: 8EHQ-0190-0863
8EHQ-0390-0915
8EKQ-0790-1034
PRODUCT COMPOSITION/CHEMICAL IDENTITY
SUBMISSION »: 8EHQ-0389-0780
APPENDIX (D): STATUS REPORTS BY INFORMATION TYPE
8EHQ-0490-0931 S
8EHQ-Q490-0954 S
8EHQ-0490-0959 S
8EHQ-0590-0996
8EHQ-0690-1003
8EHQ-0690-1007
8EHQ-0890-1043
8EHQ-0990-1063
8EHQ-0490-0934 S
8EHQ-0490-Q957 S
8EHQ-049D-0963
8EHQ-0590-1001 S
8EHQ-0690-1004 S
8EHQ-0790-1028 S
8EHQ-0890-1052 S
8EHQ-0990-1076 S
8EHQ-0990-1065
8EHQ-0889-0812
8EHQ-1289-0856
8EHQ-0290-0881 S
8EHQ-0590-0993
8EHQ-0989-0822
8EHQ-1289-0858 S
8EHQ-0490-0952 S
8EHQ-0790-1029
8EHQ-0190-0864
8EHQ-0490-0917
8EHQ-0890-1053
8EHQ-0290-0886
8EHQ-0490-0924
8EHQ-0990-1080 S
8EHQ-0289-0782 S
8EHQ-0289-0783 S
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PRODUCT COMPOSITION/CHEMICAL IDENTITY
SUBMISSION •: 8EHQ-0289-0784
8EHQ-0389-0788 S
8EHQ-0389-0791 S
8EHQ-05S9-0799
8EHQ-0789-0806 S
8EHQ-0889-0816 S
8EHQ-0989-0821 S
8EHQ-0989-0827 S
8EHQ-1089-0834 S
8EHQ-1089-0838 S
8EHQ-1189-0843 S
8EHQ-1189-0848 S
8EHQ-1289-0853 S
8EHQ-1289-0858 S
8EHQ-0190-0862 S
8EHQ-0190-0868 S
8EHQ-0190-0871 S
8EHQ-0290-0874 S
8EHQ-0290-0880
8EHQ-0290-0887 S
8EHQ-0290-0890 S
8EHQ-0 390-0896 S
8EHQ-0390-0905 S *
8EHQ-0390-0908 S
8EHQ-0390-0916 S *
APPENDIX (D): STATUS REPORTS BY INFORMATION TYPE
8EHQ-0289-0785 5
8EHQ-0389-0789
8EHQ-0489-0794 S
8EHQ-0689-0804
8EHQ-0789-0808 S
8EHQ-0889-0817
8EHQ-0989-0824 S
8EHQ-0989-0828 S
8EHQ-1089-0835 S
8EHQ-1189-0840 S
8EHQ-1189-0844
8EHQ-1289-0849 S
8EHQ-1289-0854 S
8EHQ-1289-0859
8EHQ-0190-0865 S
8EHQ-0190-0869 S
8EHQ-0290-0872 S
8EHQ-0290-0875 S
8EHQ-0290-0881 S
8EHQ-029 0888 S
8EHQ-0290-0891 S
8EHQ-0390-0897 S
8EHQ-0390-0906 S
8EHQ-0390-0913 S
8EHQ-0490-0918 S
8EHQ-0389-0787 S
8EHQ-0389-0790 S
8EHQ-0589-0798 S
8EHQ-0789-0805 S
8EHQ-0889-0811 S
8EHQ-0889-0819 S
8EHQ-0989-0825 S
BEHQ-1089-0833 S
BEHQ-1089-0837 S
BEHQ-1189-0842 S
8EHQ-1189-0847
BEHQ-1289-0851 S
8EHQ-1289-0857 S
8EHQ-0190-0861 S
8EHQ-0190-0866 S
8EHQ-0190-0870 S
86HQ-0290-0873 S
8EHQ-0290-087 9 S
8EHQ-0290-0883 S
8EHQ-0290-0889 S
8EHQ-0390-0895 S
8EHQ-0390-0903 S
8EHQ-0390-0907 S
8EHQ-0390-0914 S
8EHQ-0490-0919 S
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PRODUCT COMPOSITION/CHEMICAL IDENTITY
SUBMISSION •: 8EHQ-0490-0920 S
8EH(»-Q*9t>-0923 S
8EHQ-0490-0927 S
8EHQ-0490-0930 S
8EHQ-0490-0934 S
8EHQ-0*90-0952 5
8EHQ-0490-0937 S
«EHQ-0<»90-096I S
8EH9-0590-0986 S
8EH9-0590-0989 5
8EHQ-0590-0993
8EHQ-G590-0998 5
8EHQ-0690-1005 S
8EHQ-0690-10U 5
8EH9-0690-I014 5
8EHft-0790-1023 S
8EHQ-0790-1028 S
8EHQ-0790-10J6 S
8EH9-989O-10W
8EHQ-0890-1049 S
8EHQ-0890-1054 S
8EHQ-0990-1059 S *
8EHQ-0990-1063
8EHQ-B 990-1071
8EH9-0990-1076 S
APPENDIX (D): STATUS REPORTS BY INFORMATION TYPE
8EM-0490-0921 S
8EHQ-0490-0925 S
8EHQ-0^90-0928 S
8EH9-0*90-0931 S
8EHQ-0490-0935 S
8EH9-0^90-0955 S
8EHQ-0490-0958 S
SEH9-0*90-0962
8EHQ-0590-0987 S
8EHQ-0590-0990
8EHQ-0590-0995 S
8EHQ-0590-1001 S
SEHQ-0690-1006 S
8EHQ-0690-1012 S
8EH«-ff«90-101< S
8EHQ-0790-1025 S
8EHQ-0790-1Q29
8EH9-0790-1037 5
8EHQ-D890-10« S
8EHQ-0890-1050 S
8EHQ-0890-1056 S
8EHQ-0990-1060 S
8EHQ-0990-1066 S
8EHQ-0990-1073 S
8EHQ-0990-1078
8EH«-0*9Q-0922 5
8EHQ-0*90-092& S
8EH9-0490-0929 S *
8EH
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PRODUCT COMPOSITION/CHEMICAL IDENTITY
SUBMISSION •: 8EHQ-0990-1083 S
PRODUCTION/USE/PROCESS
SUBMISSION t: 8EHQ-0189-0779
8EHQ-0289-0783 S
8EHQ-0389-0787 S
8EHQ-0389-0790 S
8EHQ-0489-0793
8EHQ-0589-0799
8EHQ-0689-0804
8EHQ-0789-0807 S
8EHQ-0889-0811 S
8EHQ-0886-0815
8EHQ-0889-0818 S
8EHQ-0989-0821 S
8EHQ-0989-0825 S
8EHQ-0989-0828 S
8EHQ-1089-0832
8EHQ-1089-0835 S
8EHQ-1189-0839
8EHQ-1189-0842 S
8EHQ-1189-0847
8EHQ-1289-0850
8EHQ-1289"0853 S
8EHQ-1289-0857 S
APPENDIX (D): STATUS REPORTS BY INFORMATION TYPE
8EHQ-0189-0781 S
8EHQ-0289-0784
8EHQ-0389-0788 S
8EHQ-0389-0791 S
8EHQ-0489-0794 S
8EHQ-0589-0800
8EHQ-0789-0805 S
8EHQ-0789-0808 S
8EHQ-0889-0813
8EHQ-0889-0816 S
8EHQ-0889-0819 S
8EHQ-0989-0823
8EHQ-0989-0826 S
8EHQ-1089-0829
8EHQ-1089-0833 S
8EHQ-1089-0836
8EHQ-1189-0840 S
8EHQ-1189-0843 S
8EHQ-1189-0848 S
8EHQ-1289-0851 S
8EHQ-1289-0854 S
8EHQ-1289-0858 S
8EHQ-0289-0782 S
8EHQ-0289-0785 S
8EHQ-0389-0789
8EHQ-0489-0792
8EHQ-0589-0798 S
8EHQ-0689-0802
8EHQ-0789-0806 S
8EHQ-0889-0810 S
8EHQ-0889-0814
8EHQ-0889-0817
8EHQ-0889-0820
8EHQ-0989-0824 S
8EHQ-0989-0827 S
8EHQ-1089-0831
8EHQ-1489-0834 S
8EHQ-1089-0838 S
8EHQ-1189-0841
8EHQ-1189-0845
8EHQ-1289-0849 S
8EHQ-1289-0852 S
8 EHQ-128-9-08 5 6
8EHQ-0190-0861 S
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APPENDIX (D>: STATUS REPORTS BY INFORMATION TYPE
PRODUCTION/USE/PRQCESS
SUBMISSION »: 8EHQ-0190-0862
S
8EHQ-0190-0863
8EHQ-0190-0864
8EHQ-0190-0865
S
8EHQ-0190-0866
s
8EHQ-0190-0867
8EH«-0190-0868
S
8EHQ-0190-0869
s
8EHQ-0190-0870
S
8EHQ-0190-0S71
s
8EHQ-0290-0872
s
8EHQ-0290-0874
s
8EHQ-0290-0875
s
8EHQ-0290-0877
8EHQ-0290-0879
s
8EHG-0290-0881
s
8EHQ-0290-0882
8EHQ-0290-0883
S
8EHQ-0290-0885
8EHQ-0290-0886
8EHQ-0290-0887
S
8EHQ-0290-0888
S
8EHQ-0290-0889
s
8EHQ-0290-0890
S
8EHQ-0290-0891
s
8EHQ-0290-0894
8EHQ-0390-0898
8EHQ-0390-0899
*
8EHQ-0390-0900
8EH9-0390-0901
8EHQ-0390-0902
8EHQ-0390-0903
s
8EHQ-0390-0907
s
8EHQ-0390-0913
s
8EHQ-0390-0914
s
8EHQ-0390-0915
8EHQ-0390-0916
s
If
8EHQ-0490-0917
8EH9-0490-0918
S
8EH«-0490-0919
s
8EHQ-0490-0924
8EHQ-0490-0925
s
8EH®-0490-0926
s
8EHQ-0490-0928
s
8EHQ-0490-0930
S
8EHQ-0490-0931
s
8EHQ-0490-0932
8EHQ-0490-0933
8EHQ-0490-0934
s
8EHQ-0490-0935
s
8EHQ-0490-0936
8EHQ-0490-0937
8EHQ-0490-0938
8EHQ-0490-0939
8EHQ-0490-0949
8EHQ-0490-0941
8EHQ-0490-0943
8EHQ-0490-0944
8EHQ-0490-0 945
8EHQ-0490-0950
8EHQ-0490-095I
8EH
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APPENDIX (D>! STATUS REPORTS »Y INFORMATION TYPE
PRODUCTION/USE/PROCESS
SUBMISSION «: 8EH9-0590-0976
8EHQ-0590-0981
8EH9-0590-0983
8EH4-0590-09S3
K
8EHQ-0590-0992
S
8EHQ-0590-0994
8EHQ-0590-0995
s
8EHQ-0590-0996
8EHQ-0590-0997
S
8EHQ-0590-0998
s
8EHQ-0690-0999
*
8EHQ-0590-1001
s
8EHQ-0690-1002
8EHQ-0690-1003
8EHQ-0690-1004
s
8EHQ-0690-1005
s
8EHQ-0690-1006
s
8EHQ-0690-1010
s
8EHQ-0690-1Oil
S
8EHQ-0690-1012
s
8EHQ-0690-1013
s
8EHQ-0690-1014
s
8EHQ-0690-1015
8EHQ-0690-1016
s
8EHQ-0690-1018
8EHQ-0690-1019
8EHQ-0790-1021
8EHQ-0790-1023
s
8EHQ-0790-1024
8EHQ-0790-1025
s
8EHQ-0790-1026
s
8EHQ-0790-1027
8EHQ-0790-1028
s
8EHQ-0790-1029
8EHQ-0790-1031
s
8EHQ-0790-1033
8EHQ-079O-1O34
8EHQ-0790-1036
s
8EHQ-0790-1037
s
8EHQ-0890-1039
s
8EHQ-0890-1040
8EHQ-0890-1041
8EHQ-0890-1042
8EHQ-0890-1043
8EHQ-0890-1044
s
8EHQ-0890-1045
8EHQ-0890-1046
8EHQ-0890-1047
8EHQ-0890-1048
s
8EHQ-0890-1049
s
8EHQ-0890-1050
s
8EHQ-0890-1052
s
8EHQ-0890-1053
8EHQ-0890-1054
s
8EHQ-0890-1055
s
8EHQ-0890-1056
s
8EHQ-0990-1058
s
8EHQ-0990-1060
s
8EHQ-0990-1061
8EHQ-0990-1062
8EHQ-0990-1063
8EHQ-0990-1065
8EHQ-0990-1066
s
8EHQ-0990-1069
8EHQ-0990-1070
s
8EHQ-0990-1071
8EHQ-0990-1072
8EHQ-0990-1073
s
8EHQ-0990-1074
8EHQ-0990-1075
s
8EHQ-0990-1076
s
8EHQ-0 990-1078
8EHQ-0990-1079
s
8EHQ-0990-1080
s
8EHQ-0990-1081
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PRODUCTION/USE/PROCESS
SUBMISSION t: BEHQ-0990-1083 S
REPORTING RATIONALE
SUBMISSION »: 8EHQ-0«89"0813
REPRODUCTIVE TOXICITY/TERATO. (ANIMAL)
SUBMISSION »: 8EHQ-0289-0783 S
8EHQ-0389-0790 S
8EHQ-0789-0807 S
10 8EHQ-0889-0813
° SEHQ-0989-0823
8EHQ-0989-0827 5
8EHQ-1089-0835 S
8EHQ-1289-0849 S
8EHQ-1289-0855
8EHQ-Q190-086Z S
8EHQ-0190-0869 S
8EHQ-0290-0872 S
8EHQ-0290-0877
8EHQ-0290-0881 S
8EHQ-0290-0887 S
8EHQ-0290-0890 S
8EHQ-0390-0895 S
8EHQ-0390-0904
8EHQ-0390-0911 S
APPENDIX (D): STATUS REPORTS BY INFORMATION TYPE
8EHQ-0886-0815
8EHQ-0289-0785 5
8EHQ-0489-0792
8EHQ-0889-0810 S
8EHQ-0889-0816 S
8EHQ-0989-0S24 S
8EHQ-09S9-0828 S
8EHQ-1189-0842 S
8EHQ-1289-0851 S
8EHQ-1289-0858 S
8EHQ-0190-0865 S
8EHQ-0190-0870 S
8EHQ-0290-0874 S
8EHQ-0290-0878
8EHQ-0290-0883 S
8EHQ-0290-0888 S
8EHQ-0290-0891 S
8EHQ-0390-0896 S
8EHQ-0390-0907 S
8EH9-0390-0912 S
8EHQ-0490-0933
8EHQ-0389-0786 S
8EHQ-0489-0794 S
8EHQ-0889-0811 S
8EHQ-0889-0820
8EHQ-0989-0825 S
8EHQ-1089-0829
8EHQ-1189-0844
8EHQ-1289-0852 S
8EHQ-0190-0861 S
8EHQ-0190-0868 S
8EHQ-0190-0871 S
8EHQ-0290-0875 S
8EHQ-0290-0879 S
8EHQ-0290-0884
8EHQ-0290-0889 S
8EHQ-0290-0892
8EHQ-0390-0897 S
8EHQ-0390-0910 S
8EHQ-0490-Q918 S
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REPRODUCTIVE TOXICITY/TERATO. (ANIMAL)
SUBMISSION «: 8EHQ-0490-0922 S
8EHQ-0490-0927 S
8EHQ-0490-0931 S
8EHQ-0490-0937
8EHQ-e490-0940
8EHQ-0490-0943
8EHQ-0490-0946
8EHQ-0490-0949
8EHQ-0490-0955 S
8EHQ-0590-0965
8EHQ-0590-0968
8EHQ-0590-0971
8EHQ-0590-0974
8EHQ—0590-0977
8EHQ-0590-0980
8EHQ-0390-0983
8EH9-0590-0987 5
8EHQ-0590-0990
8EHQ-0590-0997 S
8EHQ-0690-1000 S
8EHQ-0690-1006 S
8EHQ-0690-1011 S
8EHQ—0690-1014 S
8EHQ-0790-1026 S
8EHQ-0890-1042
APPENDIX ID): STATUS REPORTS
BY INFORMATION TYPE
8EHQ-0490-0923 S
8EHQ-0490-0928 S
8EHQ-0490-0932
8EHQ-0490-0938
8EHQ-0490-0941
8EHQ-0490-0944
8EHQ-0490-0947
8EHQ-0490-0950
8EHQ-8490-0956 S
8EHQ-8590-0966
8EHQ-0590-0969
8EHQ-0590-0972
8EHQ-I590-0975
8EHQ-I590-0978
8EHQ-0590-0981
8EHQ-8590-0984
8EHQ-0590-0988 S
8EHQ-0590-0992 S
8EHQ-0590-0998 S
8EHQ-0690-1002
8EHQ-0690-1008
8EHQ-0690-1012 S
8EHQ-0790-1024
8EHQ-0790-1030
8EHQ-0890-1043
8EHQ-0490-0925 S
8EHQ-0490-0930 S
8EHQ-0490-0935 S
8EHQ-0490-0939
8EHQ-0490-0942
8EHQ-0490-0945
8EHQ-0490-0948
8EHQ-0490-0951
8EHQ-0490-0961 S
8EHQ-0590-0967
8EHQ-0590-0970
8EHQ-0590-0973
8EHQ-0590-0976
8EHQ-0590-0979
8EHQ-0590-0982
8EHQ-0590-0986 S
8EHQ-0590-0989 S
8EHQ-0590-0995 S
8EHQ-0690-0999 *
8EHQ-0690-1003
8EHQ-0690-1010 S
8EHQ-0690-1013 S
8EHQ-0790-1025 S
8EH9-0790-1037 S
8EHQ-0890-1046
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APPENDIX (D): STATUS REPORTS BY
REPRODUCTIVE TOXICITY/TERATO. (ANIMAL)
SUBMISSION t: 8EHQ-0890-1055 S 8EHQ-0990-1063
8EHQ-0990-1Q73 S 8EHQ-0990-1075 S
REPRODUCTIVE TOXICITY/TERATO. (HUMAN)
SUBMISSION #: 8EH4-0989-0821 S
to
SUBACUTE TOXICITY (ANIMAL)
SUBMISSION •: 8EKQ-0389-0780
8EHQ-0389-0789
8EHQ-1089-0837 S
8EHQ-0290-0884
8EHQ-0490-0931 5
8EHQ-0690-1003
8EHQ-0690-1020
8EHQ-0790-1028 S
8EH9-0890-1041
8EHQ-0890-1056 S
8EHq-0990-1070 S
8EH«
8EH4
8EHQ
8EHQ-
8EHQ
8EHQ
8EH«
8EHQ
8EHQ
8EHQ
8EH4
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0689-
1189-
0390-
¦0490-
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0890-
0990-
-0990-
0781 S
0803
0845
0908 S
0934 S
1007
1022 S
1033
1046
1061
1081
SUBCHRONIC TOXICITY (ANIMAL)
SUBMISSION •: 8EH4-0489-0793
8EHQ-1189-0840 S
8EHC-1289-0855
8EHQ-0490-0930 S
8EHQ-0490-0936
8EHQ-0889-0817
8EHQ-1189-0843 S
8EHQ-0190-0866 S
8EHQ-0490-0931 S
8EHQ-0690-1002
INFORMATION TYPE
8EHQ-0990-1064
8EHC-0289-0782 S
8EH9-0989-0826 S
8EHQ-0290-0880
8EHA-0490-0926 S
8EH3-0690-0999 *
8EH4-0690-1019
8EHQ-07 90-1027
8EHQ-0790-1037 S
8EHQ-0890-1055 S
8EHQ-0990-1062
8EHQ-l089-0836
8EHQ-1189-0846
8EHQ-0290-0881 S
8EHQ-0490-0932
8EHQ-0890-1049 S
-------
SUBCHRONJC TOXICITY (ANIMAL)
SUBMISSION t: 8EHQ-0990-1063
TSCA 8(C) ALLEGATION
SUBMISSION «: 8EHQ-0889-0818
8EHQ-0490-0929
8EHQ-0990-1078
APPENDIX CD): STATUS REPORTS BY INFORMATION TYPE
8EHQ-099Q-1074
8EHQ-0989-082I S
8EHQ-D590-0991 S
8EHQ-0390-0905
8EHQ-0990-1071
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
o>
H*
8EHQ-0189-0779
CAS NUMBER
8EHQ-0389-0780
CAS NUMBER
CAS NUMBER
8EHQ-0189-0781 S
CAS NUMBER
CAS NUMBER
8EHQ-0289-0782 S
CAS NUMBER
8EHQ-02B9-0783 S
CAS NUMBER
8EHQ-0289-0784
CAS NUMBER
CAS NUMBER
CAS NUMBER
8EHQ-0289-0785 S
CAS NUMBER
8EHQ-0389-0786 S
CAS NUMBER
SUBMITTER:
43402-26-6
SUBMITTER:
919-30-2
919-30-2
SUBMITTER:
47073-92-7
101657-77-6
SUBMITTER:
CONFIDENT
SUBMITTER:
CONFIDENT
SUBMITTER:
101-68-8
2536-05-2
9016-87-9
SUBMITTER:
CONFIDENT
SUBMITTER:
1453-58-3
EASTMAN KODAK COMPANY
CHEMICAL NAME: HYDRAZINECARBOXALDEHYDE* Z-(4-AMINOPHENYL)-
UNION CARBIDE CORPORATION
CHEMICAL NAME: 1-PROPANAMINE, 3--
CHEMICAL NAME: SILANE A-1100
HI-TEK POLYMERS, INC.
CHEMICAL NAME: CYAHIC ACID, ETHYLIDENEBIS-4,1-PHENYLENE ESTER
CHEMICAL NAME: CYANIC ACID, METHYLENEBISt 2,6-DIMETHYL-4,1-PHENYLENE) ESTER
DOU CHEMICAL COMPANY
CHEMICAL NAME: AROMATIC SULFONAMIDE, SUBSTITUTED
CONFIDENTIAL
CHEMICAL NAME: PYRAZOLYL AMIDE, HETEROCYCLIC
DOU CHEMICAL COMPANY
CHEMICAL NAME: BENZENE, 1,1'-METHYLENEBI5I4-1SOCYANATO-
CHEMICAl NAME: BENZENE, 1,1'-METHYLENEBIS[2-ISOCYANATO-
CHEMICAL NAME: ISOCYANIC ACID, POLYMETHYLENEPOLYPHENYLENE ESTER
CONFIDENTIAL
CHEMICAL NAME: PYRIMIDINE, ACYLAMINO
CONFIDENTIAL
CHEMICAL NAME: 1-H-PYRAZOLE, 3-METHYL-
8ENQ-0389-0787 S SUBMITTER: CONFIDENTIAL
CAS NUMBER : CONFIDENT CHEMICAL NAME: ALKYL HETEROCYCLE
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-0389-0788 S
CAS NUMBER
8EHQ-0389-0789
CAS NUMBER
CAS NUMBER
CAS NUMBER
8EHQ-Q389-0790 S
CAS NUMBER
8EH9-03B9-0791 S
CAS NUMBER
8EHQt0489~0792
CAS NUMBER
8EHQ-0489-0793
CAS NUMBER
CAS NUMBER
8EHQ-0489-0794 S
CAS NUMBER
8EHQ-0489-0793
CAS NUMBER
CAS NUMBER
8EHQ-0589-0796
CAS NUMBER
CAS NUMBER
SUBMITTER: CONFIDENTIAL
CONFIDENT CHEMICAL NAME: HALO ALKYL HYDROXY HETEROCYCLE
SUBMITTER: BASF CORPORATION
NONE CHEMICAL NAME: C. I. PIGMENT YELLOU 184
13565-96-3 CHEMICAL NAME: BISMUTH MOLYBDENUM OXIDE. (BI2M006)
14059-33-7 CHEMICAL NAME: BISMUTH VANADIUM OXIDE, (BIV04)
SUBMITTER: CONFIDENTIAL
CONFIDENT CHEMICAL NAME: KETONE, DIHETEROCYCLIC
SUBMITTER: ELI LILLY AND COMPANY
CONFIDENT CHEMICAL NAME: SULFONE, UNSATURATED
SUBMITTER: MOBAY CORPORATION
288-88-0 CHEMICAL NAME: 1H-1,2,4-TRIAZOLE
SUBMITTER: IBM CORPORATION
541-85-5 CHEMICAL NAME: 3-HEPTANOHE, 5-METHYL-
541-85-5 CHEMICAL NAME: KETONE* ETHYL-SEC-AMYL
SUBMITTER: CONFIDENTIAL
CONFIDENT CHEMICAL NAME: SULFONIC ACID, SUBSTITUTED ARYL-, ALKALI METAL SALT
SUBMITTER: AMOCO CHEMICAL COMPANY
2540-99-0 CHEMICAL NAME: 1,3-ISOBENZOFURANDIONE, 5,5'-SULFONYLBIS-
2540-99-0 CHEMICAL NAME: 4,4'-SULFONYLBIS(PHTHALIC ANHYDRIDE)
SUBMITTER: AMOCO CHEMICAL COMPANY
2421-28-5 CHEMICAL NAME: 3.3",4,4'-BENZOPHENONETETRACARBOXYLIC ACID DIANHYDRIDE
2421-28-5 CHEMICAL NAME: 1,3-ISOBENZOFURANDIONE, 5,5•-CARBONYLBIS-
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APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
BEHQ-0589^0796 SUBMITTER: AMOCO CHEMICAL COMPANY
8EH9-0589-0797 SUBMITTER: ANTIMONY OXIDE INDUSTRY ASSOCIATION
CAS NUMBER 1309-64-4 CHEMICAL NAME: ANTIMONY OXIDE, (SB203)
8EHQ-0589-0798 S SUBMITTER: CONFIDENTIAL
CAS NUMBER : CONFIDENT CHEMICAL NAME: KETONE, CHLORINATED ALIPHATIC
BEHQ-0589-Q799 SUBMITTER: ALLIED-SIGNAL INC.
CAS NUMBER 75-71-8 CHEMICAL NAME: METHANE, DICHLORODIFLUORO-
CAS NUMBER : 75-71-8 CHEMICAL NAME: REFRIGERANT 12
CAS NUMBER : 107-30-2 CHEMICAL NAME: METHANE, CHLOROMETHOXY-
CAS NUMBER : 115-10-6 CHEMICAL NAME: METHANE, OXYBIS-
CAS NUMBER : 542-88-1 CHEMICAL NAME: BISCCHLOROMETHYL>ETHER (BCME)
CAS NUMBER : 5*2-88-1 CHEMICAL NAME: METHANE, OXYBIStCHLORO-
8EH4-0589-0800 SUBMITTER: AMERICAN CYANAMID COMPANY
CAS NUMBER : *3470-53-1 CHEMICAL NAME: GOLD, DIMETHYL-l,l,l-TRIFLUORO-2,4-PENTANEDIOHATO
8EHQ-0589-0801 SUBMITTER: UNION CARBIDE CORPORATION
CAS NUMBER : NONE CHEMICAL NAME: 1,2-ETHANEDIAMINE/CARBAMATE COMPLEX (PARTICULATE)
CAS NUMBER : 107-15-3 CHEMICAL NAME: 1,2-ETHANEDIAMINE
8EKQ-S689-0802 SUBMITTER: OLIN CORPORATION
CAS NUMBER : 112-96-9 CHEMICAL NAME: OCTADECANE, 1-IS0CYAHAT0-
8EH9-0689-0803 SUBMITTER: UNION CARBIDE CORPORATION
CAS NUMBER : 4109-96-0 CHEMICAL NAME: CHLQR05ILANE A-199
CAS NUMBER : 4109-96-0 CHEMICAL NAME: 5ILANE. D1CHLORO-
8EN«-0689-fl804 SUBMITTER: ALBRIGHT < WILSON COMPANY, LTD.
CAS NIHWfcK : fD-Bf-t CHtnit'AL NAHt r FOftMAtOEHrDE
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APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
vD
M
-J
8EHQ-0789-
CAS NUMBER
CAS NUMBER
-0805 S
CAS NUMBER
8EHQ-0789-0806 S
CAS NUMBER
8EHQ-0789-0807 S
CAS NUMBER
8EHQ-0789-
8EHQ-0789
0808 S
CAS NUMBER :
0809 *
CAS NUMBER :
CAS NUMBER :
8EHQ-0889-0810 S
CAS NUMBER :
8EHQ-0889-0811 S
CAS NUMBER :
8EHQ-0889-0812
CAS NUMBER :
8EH9-0889-0813
CAS NUMBER :
8EHQ-0889-0814
CA5 NUFIBfcK :
12«-6«-l
55566-30-8
SUBMITTER:
CONFIDENT
SUBMITTER:
CONFIDENT
SUBMITTER:
288-13-1
SUBMITTER:
CONFIDENT
SUBMITTER:
556-52-5
556-52-5
SUBMITTER:
73160-32-4
SUBMITTER:
CONFIDENT
CHEMICAL NAME: PHOSPHONIUM, TETRAKIS(HYDROXYMETHYL)-, CHLORIDE
CHEMICAL NAME: PHOSPHONIUM, TETRAKIS(HYDROXYMETHYL)-. SULFATE (2:1) (SALT)
ELI LILLY AND COMPANY
CHEMICAL NAME: SULFONE (II), UNSATURATED
ELI LILLY AND COMPANY
CHEMICAL NAME: QUINAZOLINE (I), SUBSTITUTED
CONFIDENTIAL
CHEMICAL NAME: 1H-PYRAZOLE
LILLY RESEARCH LABORATORIES
CHEMICAL NAME: QUINAZOLINE (II), SUBSTITUTED
DIXIE CHEMICAL COMPANY, INC.
CHEMICAL NAME: GLYCIDOL
CHEMICAL NAME: OXIRANEMETHANOL
CONFIDENTIAL
CHEMICAL NAME: 2-BUTANONE, 0,0'-(ETHENYLMETHYLSYLYLENE)DIOXIME, (E,Z)-
CONFIDENTIAL
CHEMICAL NAME: ETHER, ARYL PROPYL
SUBMITTER: HERCULES INCORPORATED
96-23-1 CHEMICAL NAME: 2-PROPANOL, 1,3-DICHLORO-
SUBMITTER:
l«9-30-«
SUBMITTER:
NOME
CHEMICAL MANUFACTURERS ASSOCIATION
CHEMICAL NAME: 2(3H)-BENZ0THIAZ0LETHI0NE
CIBA-GEIGY CORPORATION
CHtniUAL NAnt: EPOxV RESInS
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-0889-Q814
CAS NUMBER
8£H«-O886-0815
CAS NUMBER
SUBMITTER: C1BA-GEIGY CORPORATION
UNKNOWN CHEMICAL NAME: TETRAGLYCIDYL ETHER. BIS-TRIMETHYLOLPROPANE
SUBMITTER-- ELI LILLY COMPANY
UNKNOWN CHEMICAL NAME-- 1K-PYRAZ0LE-4-CARB0XAMIDE, 5-CYANO-l-{ 1 • 1-DIMETHYLETHYl )-H-M
ETHYL-
8EHQ-0889-
0816 S
CAS NUMBER
8EHQ-0889-0817
CAS NUMBER
CAS NUMBER
8EHQ-0889-
0818 S
CAS NUMBER
SUBMITTER:
CONFIDENT
SUBMITTER:
71-55-6
646-06-0
SUBMITTER:
762-49-2
RHOHE-POULENC INC.
CHEMICAL NAME: HALOPHENYLCYCLOALKENYL SUBSTITUTED ARYL ESTER
PPG INDUSTRIES. INC.
CHEMICAL NAME: ETHANE, 1,1.1-TRICHLDRO-
CHEMICAL NAME: 1.3-DIOXOLANE
CONFIDENTIAL
CHEMICAL NAME: ETHANE, 1-BR0M0-2-FLU0R0-
8EHQ-0889-0819 S
CAS NUMBER
SUBMITTER:
CONFIDENT
ELI LILLY AND COMPANY
CHEMICAL NAME: 9UINAZ0LINE (III), SUBSTITUTED
8EHQ-0889-
0820
CAS NUMBER
SUBMITTER:
7723-14-0
MONSANTO COMPANY
CHEMICAL NAME: PHOSPHORUS
8EHQ-D989-0821 S
CAS NUMBER
CAS NUMBER
CAS NUMBER
BEH^-0989-0822
CAS NUMBER
SUBMITTER:
CONFIDENT
NONE
7085-85-0
SUBMITTER:
27344-41-8
CONFIDENTIAL
CHEMICAL NAME: ACRYLIC POLYMER
CHEMICAL NAME: CYANOACRYLATE ADHESIVE
CHEMICAL NAME: 2-PR0PEN0IC ACID. 2-CYANO-, ETHYL ESTER
CIBA-GEIGY CORPORATION
CHEMICAL NAME: BENZENESULFONIC ACID, 2,2•-(tI.1'-BIPHENYL1-4,4'-DIYLDI-2,1-
ETHENEDIYL>BIS-» DISODIUM SALT
CAS NUMBER
27344-41-8
CHEMICAL NAME: FAT &5029/0
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EH«-0989-0822
SUBMITTER: CIBA-GEIGY CORPORATION
10
M
ID
8EHQ-0989-0823
CAS NUMBER :
CAS NUMBER :
CAS NUMBER :
8EH4-B989-0824 S
CAS NUMBER :
8EHQ-0989-0823 S
CAS NUMBER :
CAS NUMBER :
CAS NUMBER :
8EH3-0989-0826 S
CAS NUMBER :
8EHQ-0989-0827 S
CAS NUMBER :
8EH9-0989-0828 S
CAS NUMBER :
8EHQ-1089-0829
CAS NUMBER :
8EHQ-1089-0830
CAS NUMBER :
SUBMITTER: MOBAY CORPORATION
34643-46-4
34643-46-4
34643-46-4
CHEMICAL NAME: PHOSPHORODITHIOIC ACID, 0-(2,4-DICHLOROPHENYL)-, 0-ETHYL S-P
ROPYL ESTER
CHEMICAL NAME: PROTHIOFOS
CHEMICAL NAME: TOKUTHION
SUBMITTER: CONFIDENTIAL
CONFIDENT CHEMICAL NAME: AZOLE CARBOXAMIDE, ARYL SUBSTITUTED
SUBMITTER: RHONE-POULENC INC.
CONFIDENT CHEMICAL NAME: ANILIDE (III). SUBSTITUTED
CONFIDENT CHEMICAL NAME: ANILIDE (II). SUBSTITUTED
CONFIDENT CHEMICAL NAME: ANILIDE (I). SUBSTITUTED
SUBMITTER: CONFIDENTIAL
UNKNOUN CHEMICAL NAME: GLYCINE, N-AMINO-N-(CARBOXYMETHYL)-
SUBMITTER: CONFIDENTIAL
CONFIDENT CHEMICAL NAME: IMIDATE (I), N-ARYL-CYCLIC
SUBMITTER: CONFIDENTIAL
CONFIDENT CHEMICAL NAME: IMIDATE (II). N-ARYL-CYCLIC
SUBMITTER: BASF CORPORATION / GAF CHEMICALS CORPORATION
616-45-5 CHEMICAL NAME: 2-PYRROLIDINONE
SUBMITTER: HOECHST CELANESE CORPORATION
107-11-9 CHEMICAL NAME: 2-PROPEN-l-AMINE
8EHQ-1089-0831 SUBMITTER: ICI AMERICAS INC.
CAS NUnBtK : 553-ti-4 CHtniCAL MAPlt: 4.4•-BIPttTDlNE
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EKQ-1089-0832
CAS NUMBER
8EHQ-1089-0B33 S
CAS NUMBER
8EHQ-1089-0834 S
CAS NUMBER
8EHQ-1089-0835 S
CAS NUMBER
8EHQ-1089-0836
CAS NUMBER
CAS NUMBER
SUBMITTER: HULS AMERICA INC.
998-30-1 CHEMICAL NAME: SILANE, TRIETHOXY-
SUBMITTER: ELI LILLY AND COMPANY
CONFIDENT CHEMICAL NAME: 9UIN0LINE. SUBSTITUTED
SUBMITTER: ELI LILLY AND COMPANY
CONFIDENT CHEMICAL NAME: ORGANOTIN COMPOUND
SUBMITTER: BASF CORPORATION
CONFIDENT CHEMICAL NAME: TRIAZOLE DERIVATIVE
SUBMITTER: CIBA-GEIGY CORPORATION
106990-43-6 CHEMICAL NAME: CHIMASSORB 119
106990-43-6
CHEMICAL NAME: 1,3,5-TRIAZINE-2,4,6-TRIAMINE, N,N" '-11,2-ETHANEDIYLBISt [ [4
,6-BISIBUTYL(l,2.2,6,6-PENTAMETHYL-1-PIPERIDINYL)AMINO]-l,3,
5-TRIAZIN-2-YL JIMIN03-3,1-PROPANEDIYL J1 —BISEN *,N"'-DIBUTYL-N
• ,N* '-BISC1,2,2,6,6-PENTAMETHYL-
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-1189-0842 S
CAS NUMBER
8EHQ-1189-0843 S
CAS NUMBER
8EHQ-1189-0844
CAS NUMBER
CAS NUMBER
8EH9-1189-0845
CAS NUMBER
SUBMITTER: CIBA-GEIGY CORPORATION
CONFIDENT CHEMICAL NAME: BENZDIOXOLCARBONITRILE, SUBSTITUTED
SUBMITTER: CIBA-GEIGY CORPORATION
CONFIDENT CHEMICAL NAME: HALOGENATED BENZOYL UREA
SUBMITTER: METHYL BROMIDE INDUSTRY PANEL
74-83-9 CHEMICAL NAME: METHANE, BROMO-
74-83-9 CHEMICAL NAME: METHYL BROMIDE
SUBMITTER: EASTMAN KODAK COMPANY
UNKNOWN CHEMICAL NAME: HYDRAZINE, (4-(METHYLBUT0XY)-PHENYL)-
MONOHYDROCHLORIDE
8EHQ-1189-0846 SUBMITTER: CHEMICAL MANUFACTURERS ASSOCIATION
CAS NUMBER : 98-82-8 CHEMICAL NAME: BENZENE, C1-METHYLETHYL)-
CAS NUMBER : 98-82-8 CHEMICAL NAME: CUMENE
8EHQ-1189-0847
SUBMITTER: CHEVRON INTERNATIONAL OIL COMPANY, INC.
CAS
NUMBER :
NONE
CHEMICAL
NAME:
ARALDITE CY-185
CAS
NUMBER :
NONE
CHEMICAL
NAME:
EPOXY RESINS
CAS
NUMBER :
NONE
CHEMICAL
NAME:
HYJET IW-A
CAS
NUMBER :
NONE
CHEMICAL
NAME:
XYLOK HARDENER 231 N-90
CAS
NUMBER •-
NONE
CHEMICAL
NAME:
XYLOK 235 NK-75
CAS
NUMBER :
78-93-3
CHEMICAL
NAME:
2-BUTANONE
CAS
NUMBER :
108-10-1
CHEMICAL
NAME:
2-PENTAHONE, 4-METHYL-
CAS
NUMBER :
126-73-8
CHEMICAL
NAME:
PHOSPHORIC ACID TRIBUTYL ESTER
CAS
NUMBER :
2155-38-6
CHEMICAL
NAME:
BA 42'580
CAS
NUMBER :
2155-38-6
CHEMICAL
NAME:
SPIROI1,3-DIOXANE-5,3«-1710XABICYCL0E 4
CAS NUMBER
3388-03-2
-C OXIRANYLMETHOXY)ETHOXY]ETHYL 1-
CHEMICAL NAME: ARALDITE CY-175
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-1189-0847
CAS NUMBER
CAS NUMBER
CAS NUMBER
CAS NUMBER
CAS NUMBER
CAS NUMBER
CAS NUMBER
CAS NUMBER
8EHQ-1189-0848 S
CAS NUMBER
SUBMITTER: CHEVRON INTERNATIONAL OIL COMPANY, INC.
3388-03-2
3388-03-2
3388-03-2
3388-03-2
10578-42-4
10578-42-4
26616-47-7
68937-41-7
CHEMICAL NAME:
CHEMICAL NAME:
CHEMICAL NAME:
BAKELITE ERL-4234
BA 42*579
ERL-4234
CHEMICAL NAME: SPIROC1,3DIOXANE-5,3*-17lOXABICYCLOU.1.0]HEPTANEI. 2-C7-OX
AB1CYCL014.1-01HEPT-3-YL)-
CHEMICAL NAME: BA 42*581
CHEMICAL NAME: 7-0XABICYCL0C4.1.01HEPTANE], 3-[(OXIRANYLMETHOXY)METHYLl-
CHEMICAL NAME: SPIROt1,3-DIOXANE-5,3'-t710XABICYCL0U.1.0JHEPTANE1, 2-<7-OX
ABICYCLOE4.1.0JHEPT-3-YL)-, HOMOPOLYMER
CHEMICAL NAME: PHENOL, ISOPROPUA TED, PHOSPHATE C3:l)
SUBMITTER: EASTMAN KODAK COMPANY
CONFIDENT CHEMICAL NAME: HYDRAZINE, SUBSTITUTED
8EH4-1289-0849 S
CAS NUMBER
8EHQ-1289-0850
CAS NUMBER
CAS NUMBER
SUBMITTER: PROCTER I GAMBLE COMPANY
CONFIDENT CHEMICAL NAME: SUBSTITUTED ORGANIC AMMONIUM CHLORIDE
SUBMITTER: MOBAY CORPORATION
UNKNOWN
UNKNOWN
CHEMICAL NAME: 0-ETHYL-0-METHYLETHYL-0-[2-t1,1-DIMETHYLETHYL)-PYRIMIDIN-5-Y
Ll-THIONOPHOSPHOROUS ACID ESTER
CHEMICAL NAME: MAT 7484
8EHQ-1289-0851 S
CAS NUMBER
SUBMITTER: CONFIDENTIAL
CONFIDENT CHEMICAL NAME: ETHER, DIARYL
8EHQ-1289-0852 S
CAS HUMBER
CAS NUMBER
CAS NUMBER
SUBMITTER: SHELL OIL COMPANY
2716-10-1 CHEMICAL NAME: BEN2ENAMINE, 4,4'-11,4-PHENYLENEBIS(1-METHYLETHYLIDENE) 1BIS-
2716-10-1 CHEMICAL NAME: EP1KURE 1061
2716-12-3 CHEMICAL NAME: BENZENAMINE, 4,4'-[1,4-PHENYLENEBIS<1-METHYLETHYL IDENE)]BIS[
2,6-DIMETHYL-
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
to
to
Ul
8EHQ-1289-0852 S
CAS NUMBER
8EHQ-1289-0853 S
CAS NUMBER
8EHQ-1289-085* S
CAS NUMBER
8EH4-1289-
0855
CAS NUMBER
SUBMITTER:
2716-12-3
SUBMITTER:
CONFIDENT
SUBMITTER:
CONFIDENT
SUBMITTER:
131-57-7
SHELL OIL COMPANY
CHEMICAL NAME: EPIKURE 1062
CONFIDENTIAL
CHEMICAL NAME: AMIDE. HETEROCYCLIC
CONFIDENTIAL
CHEMICAL NAME: AMINE. HETEROCYCLIC
AMERICAN CYANAMID COMPANY
CHEMICAL NAME: METHANONE, (2-HYDR0XY-*-METH0XYPHENYL)PHENYL-
8EHQ-1289-0856
CAS NUMBER
CAS NUMBER
8EHQ-1289-0857 S
CAS NUMBER
8EH4-1289-0858 S
CAS NUMBER
8EHQ-1289-0859
CAS NUMBER
CAS NUMBER
8EHQ-0190-0860 S
CAS NUMBER
CAS NUMBER
SUBMITTER: E. I. DUPONT DE NEMOURS i COMPANY, INC.
75-02-5 CHEMICAL NAME: ETHENE, FLUORO-
75-02-5 CHEMICAL NAME: VINYL FLUORIDE
8EHS-019O-
0861 S
CAS NUflBtK
SUBMITTER:
CONFIDENT
SUBMITTER:
CONFIDENT
SUBMITTER:
NONE
598-73-2
5UBMITTER:
NONE
55157-25-0
SUBMITTER:
CUNt-iUkfll
ELI LILLY AND COMPANY
CHEMICAL NAME: CARBAZOLE. INDOLO-
CONFIDENTIAL
CHEMICAL NAME: KETONE, ALKYL
HALOCARBON PRODUCTS CORPORATION
CHEMICAL NAME: QC2 (MIXTURE)
CHEMICAL NAME: ETHENE, BROMOTRIFLUORO-
CONFIDENTIAL
CHEMICAL NAME: ETHENE, BROMOTRIFLUORO-, HOMOPOLYMER, PYROLYSIS PRODUCTS OF
CHEMICAL NAME: ETHENE, BROMOTRIFLUORO-, HOMOPOLYMER
CIBA-GEI6Y CORPORATION
CHtniCAL NAnc: LACTONE, SUBSTITUTED POLYCYCIIC
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-0190-0861 S
SUBMITTER: CIBA-GEIGY CORPORATION
\0
NJ
8EHQ-0190-0862 S
CAS NUMBER
8EHQ-0190-0863
CAS NUMBER
CAS NUMBER
CAS NUMBER
CAS NUMBER
CAS NUMBER
CAS NUMBER
CAS NUMBER
CAS NUMBER
CAS NUMBER
CAS NUMBER
CAS NUMBER
8EHQ-0190-0864
CAS NUMBER
CAS NUMBER
CAS NUMBER
CAS NUMBER
CAS NUMBER
CAS NUMBER
CAS NUMBER
SUBMITTER: CONFIDENTIAL
CONFIDENT CHEMICAL NAME: NITROBENZENE, ALKOXY ARYLOXY
SUBMITTER: UPJOHN COMPANY
NONE CHEMICAL NAME: MISC. CHEMICALS
91-94-1 CHEMICAL NAME: BENZIDINE, 3,3'-DICHLORO-
91-94-1 CHEMICAL NAME: 11,1' -BIPHENYL 1-4,4'-DIAMINE, 3,3"-DICHLORO-
92-87-3 CHEMICAL NAME: BENZIDINE
92-87-5 CHEMICAL NAME: t1,I•-BIPHENYL1-4,4•-DIAMINE
119-90-4 CHEMICAL NAME: t1,1•-BIPHENYL1-4,4•-DIAMINE, 3,3*-DIMETHOXY-
119-90-4 CHEMICAL NAME: O-DIANISIDINE
119-93-7 CHEMICAL NAME: 11,1¦-BIPHENYL1-4,4'-DIAMINE, 3,3'-DIMETHYL-
119-93-7 CHEMICAL NAME: O-TOLIDINE
612-83-9 CHEMICAL NAME: BENZIDINE, 3,3•-DICHLORO-, DIHYDROCHLORIDE
612-83-9
CHEMICAL NAME: [1,1'-BIPHENYL1-4,4'-DIAMINE, 3,3*-DICHLORO-, DIHYDROCHLORID
E
SUBMITTER: GOODYEAR TIRE t RUBBER COMPANY
NONE CHEMICAL NAME: MISC. CHEMICALS
NONE CHEMICAL NAME: MORFAX PRODUCTION PROCESS
HONE CHEMICAL NAME: WINGSTAY 100 PRODUCTION PROCESS
62-53-3 CHEMICAL NAME: ANILINE
62-53-3 CHEMICAL NAME: BENZENAMINE
95-53-4 CHEMICAL NAME: BENZENAMINE, 2-METHYL-
95-53-4 CHEMICAL NAME: O-TOLUIDINE
8EHQ-0190-0865 S
CAS MUrtBfcK
SUBMITTER:
CUNt-X IffcN I
CONFIDENTIAL
CHtrtlCAL NAPIfc :
aCETANILXOE, HETEROCYCLIC SUBSTITUTED
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-0190-e865 S SUBMITTER: CONFIDENTIAL
8EHQ-0190-0866 S SUBMITTER: CIBA-GEIGY CORPORATION
CAS NUMBER : UNKNOWN CHEMICAL NAME: 2-PR0PEN0IC ACID, POLYMER WITH SODIUM PHOSPHINATE, SODIUM SA
LT
CAS NUMBER : 71050-62-9 CHEMICAL NAME: 2-PR0PEN0IC ACID, POLYMER WITH SODIUM PHOSPHINATE
8EHQ-0190-0867 * SUBMITTER: EASTMAN KODAK COMPANY
CAS NUMBER : 71130-6D-* CHEMICAL NAME: PHENOL, 2-1CETHYLAMINQJMETHYLJ-4-NITRO-
8EHQ-0190-0868 S SUBMITTER: CONFIDENTIAL
CAS NUMBER : CONFIDENT CHEMICAL NAME: IMIDATE, N-ARYLCYCLIC
8EHQ-0190-0869 S SUBMITTER: CONFIDENTIAL
£ CAS NUMBER : CONFIDENT CHEMICAL NAME: ACETANILIDE, HETEROCYCLIC SUBSTITUTED
to
in
8EHQ-0190-0870 S SUBMITTER: CONFIDENTIAL
CAS NUMBER : CONFIDENT CHEMICAL NAME: IMIDATE (I), N-ARYL-CYCLIC
8EH9-0190-0871 S SUBMITTER: MONSANTO COMPANY
CAS NUMBER : 61791-26-2 CHEMICAL NAME: AMINES, ^LLOW ALKYL, ETHOXYLATED
8EH4-0290-0872 5 SUBMITTER: CIBA-GEIGY CORPORATION
CAS NUMBER : CONFIDENT CHEMICAL NAME: POLYCYCLIC DIONE, SUBSTITUTED
8EHQ-B290-087X S SUBMITTER: CONFIDENTIAL
CAS NUMBER : CONFIDENT CHEMICAL NAME: AMINE, AROMATIC
8EHQ-0290-0874 S SUBMITTER: CONFIDENTIAL
CAS NUMBER : CONFIDENT CHEMICAL NAME: GUAHIDIN1UM ARYL SULFONATE, SUBSTITUTED
8EHQ-0290-0875 S SUBMITTER: CONFIDENTIAL
LAS NUHStK : (.UNMUtNl CHtniUAL 11 Ant: PHOSfttAtE ESTER
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-0290-0875 S
CAS NUMBER
CAS NUMBER
8EHQ-0290-0876
CAS NUMBER
8EHQ-0290-0877
CAS NUMBER
CAS NUMBER
8EHQ-0290-0878
CAS NUMBER
CAS NUMBER
CAS NUMBER
CAS NUMBER
SUBMITTER: CONFIDENTIAL
NONF CHEMICAL NAME: HYDRAULIC FLUID, MILC PHOSPHATE ESTER-BASED
NONE CHEMICAL NAME: MIL-H-19457C (MILC)
SUBMITTER:
101-68-8
SUBMITTER:
124-64-1
35566-30-8
SUBMITTER:
75-31-0
91-66-7
768-52-5
2524-03-0
ICI AMERICAS INC.
CHEMICAL NAME: BENZENE, 1,1'-METHYLENEBISC4-ISOCYANATO-
ALBRIGHT t WILSON COMPANY, INC.
CHEMICAL NAME: PHOSPHONIUM, TETRAKIS(HYDROXYMETHYL)-, CHLORIDE
CHEMICAL NAME: PHOSPHONIUM, TETRAKIStHYDROXYMETHYL)-, SULFATE (2:1) (SALT)
MONSANTO COMPANY
CHEMICAL NAME: 2-PROPANAMINE
CHEMICAL NAME: BENZENAMINE, N,N-DIETHYL-
CHEMICAL NAME: BENZENAMINE, N-(1-METHYLETHYL)-
CHEMICAL NAME: PHOSPHOROCHLORIDOTHIOIC ACID, 0,0-DIMETHYL ESTER
8EHQ-0290-0879 5
CAS NUMBER
8EHQ-0290-0880
CAS NUMBER
CAS NUMBER
CAS NUMBER
SUBMITTER:
CONFIDENT
SUBMITTER:
UNKNOWN
123-86-4
94857-19-9
CONFIDENTIAL
CHEMICAL NAME: ARYL DIESTER, HALO AlKYL SUBSTITUTED
AMERICAN CYANAMID COMPANY
CHEMICAL NAME: 1,J-BIS[1-CYANATO-1-METHYLETHYL JBENZENE
CHEMICAL NAME: ACETIC ACID, BUTYL ESTER
CHEMICAL NAME: 1,J-PROPANEDIOL , 2-ETHYL-2-(HYDROXYMETHYL)-, POLYMER WITH 1,
3-BIS(1-ISOCYANATO-1-METHYLETHYL)BENZENE
8EHS-0290-08S1 S
CAS NUMBER
SUBMITTER:
CONFIDENT
CONFIDENTIAL
CHEMICAL NAME: HEXANEDIONE, CYCLO-
8EHQ-0290-0882 SUBMITTER: AMOCO OIL COMPANY
CAS NUMBER : NONE CHEMICAL NAME: DIBENZOFURANS, CHLORINATED
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-0290-0882
CAS NUMBER
CAS NUMBER
CAS NUMBER
8EHQ-0290-0883 S
CAS NUMBER
ftEHQ-0290-0884
CAS NUMBER
CAS NUMBER
SUBMITTER:
NONE
NONE
NONE
SUBMITTER:
CONFIDENT
SUBMITTER:
67-63-0
67-63-0
AMOCO OIL COMPANY
CHEMICAL NAME: DIOXINS, CHLORINATED
CHEMICAL NAME: PETROLEUM REFINING PROCESS
CHEMICAL NAME: REFORMER SPRAY TUR
CONFIDENTIAL
CHEMICAL NAME: ETHER* DIARYL
ARCO CHEMICAL COMPANY
CHEMICAL NAME: ISOPROPANOL
CHEMICAL NAME: 2-PR0PAN0L
8EHQ-0290-0885
CAS NUMBER
CAS NUMBER
8EHQ-0290-0886
CAS NUMBER
ftEHQ-0290-0887 S
CAS NUMBER
8EHQ-0290-0888 S
CAS NUMBER
8EHQ-0290-0889 S
CAS NUMBER
SUBMITTER:
17095-2^-8
17095-24-8
SUBMITTER:
NONE
SUBMITTER:
CONFIDENT
SUBMITTER:
CONFIDENT
SUBMITTER:
CONFIDENT
CROMPTON t KNOULES CORPORATION, U.S.A.
CHEMICAL NAME: 2,7-NAPHTHALENEDISULFONIC ACID. *-AMINO-5-HYDROXY-3»6-BISt[4
-[t2~(SULFOOXY)ETHYL]5ULF0NYLJPHENYL]AZ0]-, TETRASODIUM SALT
CHEMICAL NAME: C. I. REACTIVE BLACK 5
UNOCAL CORPORATION
CHEMICAL NAME: OIL (PETROLEUM), REFINING PROCESS
CONFIDENTIAL
CHEMICAL NAME: ACETIC ACID ESTER, SUBSTITUTED
CONFIDENTIAL
CHEMICAL NAME: ETHER, DIARYL
CONFIDENTIAL
CHEMICAL NAME: ACETANILIDE, SUBSTITUTED
8EHQ-0290-0890 S SUBMITTER: CONFIDENTIAL
CAS NUMBER : CONFIDENT CHEMICAL NAME: ACETOPHENONE OXIME
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHETHYL-
EM INDUSTRIES, INC.
CHEMICAL NAME: BENZOIC ACID, 4-METHOXY-, 4-PENTYLPHENYL ESTER
CONFIDENTIAL
CHEMICAL NAME: PYRIDINECARBOXYLATE
CONFIDENTIAL
CHEMICAL NAME: ACETANIL1DE, SUBSTITUTED, (I)
CONFIDENTIAL
CHEMICAL NAME: ACETANILIDE, SUBSTITUTED, til)
E. I. DUPONT DE NEMOURS I COMPANY, INC.
CHEMICAL NAME: BENZENAMINE, 4,4'-(1,3-PHENYLENEBIS
-------
8EHQ-0390-0899 * SUBMITTER
8EHQ-0390-0900 SUBMITTER
CAS NUMBER : 1634-04-4
8EHQ-0390-0901 SUBMITTER
CAS NUMBER : 106-99-0
CAS NUMBER : 313-35-9
CAS NUMBER : 563-46-2
CAS NUMBER ! 26760-64-5
CAS NUMBER : 26760-64-3
8EHQ-0390-0902 SUBMITTER
S CAS NUMBER : 106-99-0
vD
8EHQ-0390-0903 S SUBMITTER
CAS NUMBER : CONFIDENT
8EHQ-0390-0904 SUBMITTER
CAS NUMBER : 75-15-0
8EHQ-0390-0905 S * SUBMITTER
CAS NUMBER : CONFIDENT
8EHQ-0390-0906 S SUBMITTER
CAS NUMBER : CONFIDENT
8EHQ-0390-0907 S SUBMITTER
CAS NUMBER : CONFIDENT
8EH$-0390-0908 S SUBMITTER
CAb NUntlbK : CUNMUbNI
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
PQ CORPORATION
METHYL TERTIARY BUTYL ETHER TASK FORCE
CHEMICAL NAME: PROPANE, 2-METH0XY-2-METHYL-
EXXON CHEMICAL AMERICAS
CHEMICAL NAME: 1,3-BUTADIENE
CHEMICAL NAME: 2-BUTENE, 2-METHYL-
CHEMICAL NAME: 1-BUTENE, 2-METHYL-
CHEM1CAL NAME: BUTENE, 2-METHYL-
CHEMICAL NAME: ISOAMYLENE
EXXON CHEMICAL AMERICAS
CHEMICAL NAME: 1,3-BUTADIENE
CONFIDENTIAL
CHEMICAL NAME: NAPHTHALENOL AROMATIC AZO DYE OF AROMATIC COMPOUNDS
AKZO CHEMICALS INC.
CHEMICAL NAME: CARBON DISULFIDE
CONFIDENTIAL
CHEMICAL NAME: AMINE, AROMATIC
BAKER PERFORMANCE CHEMICALS, INC.
CHEMICAL NAME: MA6NACLEAR M 241
CONFIDENTIAL
CHEMICAL NAME: SEMICARBAZONE
RICOH ELECTRONICS INC.
CKtrUUAL NAI"lt: 00-61
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-0390-0908 S
CAS NUMBER
lO
W
o
8EHQ-0390-
0909 «
CAS NUMBER j
8EHQ-0390~0910 S
CAS NUMBER
8EHQ-0390-0911 S
CAS NUMBER
8EHQ-0390-0912 5
CAS NUMBER
CAS NUMBER
CAS NUMBER
8EHQ-0390-0913 S
CAS NUMBER
8EH4-0390-
091* S
CAS NUMBER
CAS NUMBER
8EH4-0390-0915
CAS NUMBER
CAS NUMBER
CAS NUMBER
SUBMITTER: RICOH ELECTRONICS INC.
CONFIDENT CHEMICAL NAME: PHENOL, 4,4*-10XYBIS(Z,1-ETHANEDIYLTHIO)IBIS-
SUBMITTER: MITSUBISHI GAS CHEMICAL AMERICA, INC.
1477-55-0 CHEMICAL NAME: 1,3-BENZENEDIMETHANAMINE
SUBMITTER: CONFIDENTIAL
104-76-7 CHEMICAL NAME: 1-HEXANOL, 2-ETHYL-
SUBMITTER: CONFIDENTIAL
25339-17-7 CHEMICAL NAME: ISODECANOL
SUBMITTER: CONFIDENTIAL
UNKNOWN CHEMICAL NAME: ISONONYL ALCOHOL 1
UNKNOWN CHEMICAL NAME: ISONONYL ALCOHOL 2
68515-81-1 CHEMICAL NAME: ISONONYL ALCOHOL
SUBMITTER: CONFIDENTIAL
CONFIDENT CHEMICAL NAME: ARYL ALKYL HETEROCYCLIC CARBOXYLATE
SUBMITTER: MITSUI PETROCHEMICALS (AMERICA), LTD.
NONE CHEMICAL NAME: PAL 6000
UNKNOWN CHEMICAL NAME: UREA, l-METHOXY-l-METHYL-3-I4-(3,4-DIHYDR0-2-METH0XY-2,4,4-T
RIMETHYL-7-BENZOPYRANYLOXY)PHENYL J-
SUBMITTER: ALUMINUM COMPANY OF AMERICA (ALCOA)
NONE CHEMICAL NAME: ALUMINUM PRODUCTION PROCESS
NONE CHEMICAL NAME: MISC. CHEMICALS
NONE CHEMICAL NAME: REFRACTORY CERAMIC FIBER
8EHQ-0390-0916 S * SUBMITTER: CONFIDENTIAL
CAS NUDBtK : tUNHUtNl CMtHlCAL NAflt: SEMCAMAZOhE
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EH4-0390-0916 S
SUBMITTER: CONFIDENTIAL
8EHQ-0490-0917
CAS NUMBER
CAS NUMBER
CAS NUMBER
CAS NUMBER
CAS NUMBER
8EHQ-0490-0918 S
CAS NUMBER
8EHQ-0490-0919 S
CAS NUMBER
8EHQ-0490-0920 S
CAS NUMBER
CAS NUMBER
8EHQ-0490-I921 S
CAS NUMBER
CAS NUMBER
8EHQ-Q49Q-0922 S
CAS NUMBER
8EHQ-0490-0923 S
CAS NUMBER
SUBMITTER: BF GOODRICH COMPANY
80-62-6 CHEMICAL NAME: METHYL METHACRYLATE
88-62-6 CHEMICAL NAME: 2-PROPENOIC ACID. 2-METHYL-, METHYL ESTER
140-88-5 CHEMICAL NAME: ACRYLIC ACID, ETHYL ESTER
140-88-5 CHEMICAL NAME: ETHYL ACRYLATE
140-88-5 CHEMICAL NAME: 2-PROPENOIC ACID, ETHYL ESTER
SUBMITTER: CONFIDENTIAL
CONFIDENT CHEMICAL NAME: AMIDE, HETEROCYCLIC
SUBMITTER: EASTMAN KODAK COMPANY
CONFIDENT CHEMICAL NAME: HYDRAZIDE, SUBSTITUTED CARBONCTHIOIC
SUBMITTER: CONFIDENTIAL
CONFIDENT CHEMICAL NAME: ALKENOYL DISUBSTITUTED CYCLOALKANE
CONFIDENT CHEMICAL NAME: EPA ACCESSION • 35406
SUBMITTER: RICOH ELECTRONICS INC.
CONFIDENT CHEMICAL NAME: DD-70
CONFIDENT CHEMICAL NAME: PHENOL, 4,4*-IMETHYLENEBISCOXY-2,1-ETHANEDI.YLTHIO)]BIS-
SUBMITTER: CONFIDENTIAL
CONFIDENT CHEMICAL NAME: HYDROCARBON, CHLORINATED
SUBMITTER: CONFIDENTIAL
CONFIDENT CHEMICAL NAME: ACETANILIDE, SUBSTITUTED, (III)
8EHQ-0490-0924 SUBMITTER: AMERICAN CYANAMID COMPANY
CAS NUMBER : 50-00-0 CHEMICAL NAME: FORMALDEHYDE
-------
8EHQ-0490-092*
SUBMITTER
8EHQ-0490-0925 S
CAS NUMBER
8EHQ-0490-0926 S
CAS NUMBER
8EHQ-0«90-0927 5
CAS NUMBER
8EHQ-0*90-0928 S
CAS NUMBER
8EHQ-0490-
0929 S N
CAS NUMBER :
8EH9-0490-0930 S
CAS NUMBER
8EHQ-0190-0931 S
CAS NUMBER
CAS NUMBER
8EHQ-0490-0932
CAS NUMBER
CAS NUMBER
8EHQ-0490-0933
CAS NUMBER
CAS NUMBER
SUBMITTER
CONFIDENT
SUBMITTER
CONFIDENT
SUBMITTER
CONFIDENT
SUBMITTER
CONFIDENT
SUBMITTER
CONFIDENT
SUBMITTER
CONFIDENT
SUBMITTER
80-5A-6
13586-68-0
SUBMITTER
NONE
NONE
SUBMITTER
1336-36-3
1336-36-3
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
AMERICAN CYANAMID COMPANY
CONFIDENTIAL
CHEMICAL NAME: THIOESTER, HETEROCYCLIC
CONFIDENTIAL
CHEMICAL NAME: ETHER, DIARYL, (IV)
CONFIDENTIAL
CHEMICAL NAME: AMINE, ARYL
CONFIDENTIAL
CHEMICAL NAME: CARBOXYLIC ACID ESTER, HETEROCYCLIC
CONFIDENTIAL
CHEMICAL NAME: ETHER. HALOGENATED
CONFIDENTIAL
CHEMICAL NAME: ETHER, DIARYL, (V)
GIVAUDAN CORPORATION
CHEMICAL NAME: BENZENEPROPANAl, *-t1,1-DIMETHYLETHYL)-.ALPHA.-METHYL-
CHEMICAL NAME: 2-PROPENAL, 3-[4-(l,1-DIMETHYLETHYL)PHENYL]-2-METHYL-
MOBIL RESEARCH AND DEVELOPMENT CORPORATION
CHEMICAL NAME: SLUDGE, API SEPARATOR BOTTOM
CHEMICAL NAME: SLUDGE, DISSOLVED AIR FLOTATION (DAF) FLOAT
GENERAL ELECTRIC COMPANY
CHEMICAL NAME: 1,1'-BIPHENYL, CHLORO DERIVS.
CHEMICAL NAME: POLYCHLORINATED BIPHENYLS (PCB)
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
•£>
U>
ut
8EHQ-0490-0933
CAS NUMBER
SUBMITTER: GENERAL ELECTRIC COMPANY
11097-69-1 CHEMICAL NAME: AROCHIOR 1254
BEHQ-0490-0934 S SUBMITTER: ENIMONT AMERICA INC.
CAS NUMBER : 94317-64-3 CHEMICAL NAME: N-
-------
APPENDIX E: SiATUS REPORTS BY SUBMISSION NUMBER
8EHQ-0490-0940 SUBMITTER: MONSANTO COMPANY
CAS NUMBER : 1*29-50-1 CHEMICAL NAME: PHOSPHONIC ACID, [1,2-ETHANEDIYLBIStNITRILOBIS(METHYLENE)]1T
ETRAKIS-
8EHQ-0490-0941 SUBMITTER: MONSANTO COMPANY
CAS NUMBER : 68908-87-2 CHEMICAL NAME: BENZENE, 1,3-DIMETHYL-, BENZYLATEO
8EHQ-0490-0942 SUBMITTER: MONSANTO COMPAHY
CAS NUMBER : 9014-92-0 CHEMICAL HAME: POLY(OXY-l,2-ETHANEDIYL ), .ALPHA.-CDODECYLPHENYL)-.OMEGA.-HY
DROXY-
CAS NUMBER : 9014-92-0 CHEMICAL NAME: STEROX DJ SURFACTANT
8EHQ-0490-0943 SUBMITTER: MONSANTO COMPANY
CAS NUMBER : 63449-88-7 CHEMICAL NAME: BUTANOIC ACID, 1-CYCLOHEXYLETHYL ESTER
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-0490-0948
CA5 NUMBER
CAS NUMBER
SUBMITTER: MONSANTO COMPANY
117-08-8 CHEMICAL NAME: 1,S-ISOBENZOFURANDIONE, 4, 5, 6 ,7-TETRACHLORO-
117-08-8 CHEMICAL NAME: TETRATHAL
8EHQ-0490-0949
CAS NUMBER
CAS NUMBER
8EHQ-0490-0950
CAS NUMBER
CAS NUMBER
CAS NUMBER
CAS NUMBER
CAS NUMBER
8EHQ-0490-0951
CAS NUMBER
CAS NUMBER
8EH9-0490-0952 S
CAS NUMBER
CAS NUMBER
8EHQ-0490-0953
CAS NUMBER
CAS NUMBER
CAS NUMBER
SUBMITTER: MONSANTO COMPANY
38970-72-8 CHEMICAL NAME: CYCLOHEXANE, 1,1'-(1,1,3-TRIMETHYL-l,5-PROPANEDIYL)BIS-
38970-72-8 CHEMICAL NAME: HLD
SUBMITTER:
15827-60-8
15827-60-8
22042-96-2
22042-96-2
22042-96-2
MONSANTO COMPANY
CHEMICAL NAME: DEQUEST 2060
CHEMICAL NAME: PHOSPHONIC ACID, [[(PHOSPHONOMETHYL)IMIN0]BIS[2,1-ETHANEDIYL
NITR1LOBIS(METHYLENE)]1TETRAKIS-
CHEMICAL NAME: DEQUEST 2061
CHEMICAL NAME: DEQUEST 2066
CHEMICAL NAME:
PHOSPHONIC ACID. [ [ (PHOSPHONOMETHYLJIMINOJBISt(2,1-ETHANEDIY
LNITRILO)BIS(METHYLENE)]JTETRAKIS-, SODIUM SALT
SUBMITTER: MONSANTO COMPANY
15827-60-8 CHEMICAL NAME: DEQUEST 2060
15827-60-8
CHEMICAL NAME: PHOSPHONIC ACID, [t(PHOSPHONOMETHYL)IMIN01BISI2.1-ETHANEDIYL
NITRILOBIS(METHYLENE)]]TETRAKIS-
SUBMITTER: CONFIDENTIAL
420-04-2 CHEMICAL NAME: CYANAMIDE
420-04-2 CHEMICAL NAME: CYANAMIDE, HYDROGEN
SUBMITTER: AIR PRODUCTS AND CHEMICALS, INC.
71-55-6 CHEMICAL NAME: ETHANE, 1,1,1-TRICHLORO-
75-34-3 CHEMICAL NAME: ETHANE, 1,1-DICHLORO-
75-35-4 CHEMICAL NAME: ETHENE, 1,1-DICHLORO-
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
w
cr>
&EHQ-Q490-Q9S4 S
CAS NUMBER
SEKQ-Q490-O955 S
CAS NUMBER
8EHQ-0490-0956 S
CAS NUMBER
8EHQ-0«90-0957 S
CAS NUMBER
8EH«-O*9O-0958 S
CAS NUMBER
8EHQ-0490-0959 S
CAS NUMBER
8EHfl-0*9Q-09«»
CAS NUMBER
SUBMITTER: ALLIED-SIGNAL INC.
UNKNOWN CHEMICAL NAME: I50PHTHALATE. BIS-(4-VINYL0XYBUTYL)-
SUBMITTER:
CONFIDENT
SUBMITTER:
CONFIDENT
SUBMITTER:
CONFIDENT
SUBMITTER:
CONFIDENT
SUBMITTER:
CONFIDENT
SUBMITTER:
103112-35-2
CONFIDENTIAL
CHEMICAL NAME: ACETANILIDE, SUBSTITUTED
CONFIDENTIAL
CHEMICAL NAME: KETONE. DIARYL
DOM CHEMICAL COMPANY
CHEMICAL NAME: PYRIMDINE, SUBSTITUTED
DOU CHEMICAL COMPANY
CHEMICAL NAME: PYRIMIDINE, SUBSTITUTED
CONFIDENTIAL
CHEMICAL NAME: AMINE METAL COMPLEX
HOECHST CELANESE CORPORATION
CHEMICAL NAME: 1CH)-1,2,«-TRIAZ0LE-3-CARB0XYLATE, ETHYL l-(Z,«-DICHLOROPHEN
YD-5-TRICHL0R0HETHYL-
8EHQ-0490-0961 S
CAS NUMBER
8EHQ-0^90-0962
CAS NUMBER
CAS NUMBER
CAS NUMBER
CAS NUMBER
CAS NUMBER
SUBMITTER:
CONFIDENT
CONFIDENTIAL
CHEMICAL NAME: AMINO ACID (I)
SUBMITTER: HOECHST CELANESE CORPORATION
NONE CHEMICAL NAME: DIARYlIDE PIGMENTS
NONE CHEMICAL NAME: MISC. CHEMICALS
UNKNOWN CHEMICAL NAME: PERMANENT YELLOW DOR TYPE
UNKNOWN CHEMICAL NAME: PERMANENT YELLOW GGR TYPE
UNKNOWN CHEMICAL NAME: PERMANENT YELLOW GRL TYPE
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
BEH4-0490-0962 SUBMITTER: H0ECH5T CELANESE CORPORATION
CAS
NUMBER
:
UNKNOWN
CHEMICAL
NAME:
PERMANENT YELLOW GRX TYPE
CAS
NUMBER
!
UNKNOWN
CHEMICAL
NAME:
PERMANENT YELLOW GRY *YPE
CAS
NUMBER
£
UNKNOWN
CHEMICAL
NAME:
PERMANENT YELLOW G3R TYPE
CAS
NUMBER
t
UNKNOWN
CHEMICAL
NAME:
PERMANENT YELLOW YR TYPE
CAS
NUMBER
s
UNKNOUH
CHEMICAL
NAME:
C. I. PIGMENT YELLOW 106
CAS
NUMBER
r
UNKNOWN
CHEMICAL
NAME:
C. I. FIGMENT YELLOW 114
CAS
NUMBER
:
UNKNOWN
CHEMICAL
NAME:
C. I. PIGMENT YELLOW 126
CAS
NUMBER
:
UNKNOWN
CHEMICAL
NAME:
C. I. PIGMENT YELLOW 127
CAS
NUMBER
!
UNKNOWN
CHEMICAL
NAME:
C. I. PIGMENT YELLOW 152
CAS
NUMBER
:
UNKNOWN
CHEMICAL
NAME:
C. I. PIGMENT YELLOW 174
CAS
NUMBER
:
UNKNOWN
CHEMICAL
NAME:
C. I. PIGMENT YELLOW 176
CAS
NUMBER
j
91-94-1
CHEMICAL
NAME:
BENZIDINE. 3,3"-DICHLORO-
CAS
NUMBER
t
91-94-J
CHEMICAL
NAME:
n,l'-BIPHENYL]-4,4'-DIAMINE, 3,3•-DICHLORO-
CAS
NUMBER
:
2512-29-0
CHEMICAL
NAME:
BUTAHAMIOE, 2"I(4-METHYL-2-NITR0PHENYL)AZ03-3-0X0-N-PHENYL-
CAS
NUMBER
:
2312-29-0
CHEMICAL
NAME:
PERMANENT YELLOW G TYPE
CAS
NUMBER
:
2512-29-Q
CHEMICAL
NAME:
C. I. PIGMENT YELLOW 14
CAS
NUMBER
s
3520-72-7
CHEMICAL
NAME:
PERMANENT ORANGE G TYPE
CAS
NUMBER
:
5520-72-7
CHEMICAL
NAME:
C. I. PIGMENT ORANGE 13
CAS
NUMBER
s
3520-72-7
CHEMICAL
NAME:
3H-PYRAZ0L-3-0NE. 4,4¦-1C3,3'-DICHLOROI1,1•-BIPHENYL]-4,4•-D
IYL>BIS]BISC2,4-DIHYDRO-5-METHYL-2-PHENYL-
CAS
NUMBER
:
4531-49-1
CHEMICAL
NAME:
BUTANAMIDE, 2.2'-t(3,3'-DICHlORO[1,1'-BIPHENYL]-4.4'-DIYLJBI
SCAZO)3BISCN-t2-METHOXYPHENYl)-3-OXD-
CA5
NUMBER
:
4531-19-1
CHEMICAL
NAME:
PERMANENT YELLOW GG TYPE
CAS
HUMBER
i
4511-49-1
CHEMICAL
NAME:
C. I. PIGMENT YELLOW 17
CAS
NUMBER
:
5102-83-0
CHEMICAL
NAME:
BUTANAM1DE, 2,2'-[C3,3,-DICHL0R0t1.1'-BIPHENYLJ-4.4*-DIYL>BI
S(AZO)1BISCN-C2.4-DIMETHYLPHENYL)-3-0X0-
CAS
NUMBER
:
5102-83-0
CHEMICAL
NAME:
PERMANENT YELLOW GR TYPE
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
SEHQ-0490-0962 SUBMITTER; MOECHST CELANESE CORPORATION
CAS
NUMBER
5102-83-0
CHEMICAL
NAME:
C. I. PIGMENT YELLOW 13
CAS
NUMBER
5567-15-7
CHEMICAL
NAME:
BUTANAMIDE, 2,Z'-t(3,3'-DICHLOROCl,1'-BIPHENYL1-4'"DIYL)BI
S( AZO)IBIStN-C^-CHLORO-2,5-DIMETHOXYPHENYL 1-3-OXO-
CAS
NUMBER
5567-15-7
CHEMICAL
NAME:
PERMANENT YELLOW HR TYPE
CAS
NUMBER
5567-15-7
CHEMICAL
NAME:
C. I. PIGMENT YELLOW 83
CAS
NUMBER
5979-28-2
CHEMICAL
NAME:
BUTANAMIDE, N,N*-(3,3'-DIMEi ..n[1,11"BIPHENYL]-4,4'-DIYL)BIS
C2-[(2,4-DICHLOROPHENYL >AZOJ-3-OXO-
CAS
NUMBER
5979-28-2
CHEMICAL
NAME:
PERMANENT YELLOW NCG TYPE
CAS
NUMBER
5979-28-2
CHEMICAL
NAME:
C. I. PIGMENT YELLOW 16
CAS
NUMBER
6358-85-6
CHEMICAL
NAME:
BUTANAMIDE, 2,2*-I(3,3'-DICHLOROI1,1 *-BIPHENYL1-4,4•-DIYL>BI
S(AZO)3BI5[3-OXO-N-PHENYL-
CAS
NUMBER
6358-85-6
CHEMICAL
NAME:
PERMANENT YELLOW DBG TYPE
CAS
NUMBER
6358-85-6
CHEMICAL
NAME:
C. I. PIGMENT YELLOW 12
CAS
NUMBER
6358-87-8
CHEMICAL
NAME:
C. I. PIGMENT RED 38
CAS
NUMBER
6358-87-8
CHEMICAL
NAME:
1H-PYRAZOLE-3-CARBOXYLIC ACID, 4,4'-C(3,3'-DICHLOROt1,1'-BIP
HENYL1-4 >4'-DIYL)BIS(AZQ)]BISt4,5-DIHYDR0~5-0X0-l-PHENYL-> D
IETHYL ESTER
CAS
NUMBER
6358-87-8
CHEMT CAL
NAME:
VULCAN FAST RED B
CAS
NUMBER
15793-73-4
CHEMICAL
NAME:
PERMANENT ORANGE RL TYPE
CAS
NUMBER
15793-73-4
CHEMICAL
NAME:
C. I. PIGMENT ORANGE 34
CAS
NUMBER
157 93-73-4
CHEMICAL
NAME:
3H-PYRAZ0L-3-0NE, 4,4•-[(3,3'-DICHLOROt1,I'-BIPHENYL1-4,4•-D
IYL)BIS( AZO)J BIS[2,4-DIHYDRO-5-METHYL-2-(4-METHYLPHENYL)-
8EHQ-04 90-0 963 SUBMITTER: GENERAL ELECTRIC COMPANY
CAS NUMBER : 25550-98-5 CHEMICAL NAME: PHOSPHOROUS ACID, DII50DECYL PHENYL ESTER
8EHQ-0590-0964 SUBMITTER: v COMPANY
CAS NUMBER : UNKNOWN CHEMICAL NAME". CYCLIC 1,4-PERFLUOROBUTANE DISULFOHIMIDE, LITHIUM SALT
8EH$-0590-0965 SUBMITTER: MONSANTO COMPANY
CAS NUnntK : b80*»«-0/-J LhtnitAL NAflfc: ALKTLAtE 2l5
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-0590-0965
CAS NUMBER
vD
u>
v£>
8EHQ-0590-
0966
CAS NUMBER
CAS NUMBER
8EH4-0590-0967
CAS NUMBER
CAS NUMBER
8EHQ-0590-0968
CAS NUMBER
CAS NUMBER
8EH9"0590-0969
CAS NUMBER
CAS NUMBER
8EHQ-0590-0970
CAS NUMBER
CAS NUMBER
8EHQ-0590-0971
CAS NUMBER
SUBMITTER:
68648-87-3
SUBMITTER:
793-24-8
793-24-8
SUBMITTER:
65701-07-7
65701-07-7
SUBMITTER:
101-20-2
101-20-2
SUBMITTER:
68855-24-3
68855-24-3
SUBMITTER:
68648-87-3
68648-87-3
MONSANTO COMPANY
CHEMICAL NAME: BENZENE, C10-16-ALKYL DERIVS.
MONSANTO COMPANY
CHEMICAL NAME: 1,4-BENZENEDIAMINE. N-(1,3-DIMETHYLBUTYL)-N'-PHENYL-
CHEMICAL NAME: SANTOFLEX 13
MONSANTO COMPANY
CHEMICAL NAME: 1,2-BENZENEDICARBOXYLIC ACID, 4,4•-CARBONYLBIS-, AR,AR'-DIET
HYL ESTER, COMPD. WITH 1,3-BENZENEDIAMINE
CHEMICAL NAME: SKYBOND 700 POLYIMIDE RESIN
MONSANTO COMPANY
CHEMICAL NAME: TCC SOAP BACTERIOSTAT
CHEMICAL NAME: UREA, N-(4-CHL0R0PHENYL)-N'-<3,4-DICHL0R0PHENYL)-
MONSANTO COMPANY
CHEMICAL NAME: BENZENE, C14-30-ALKYL DERIVS.
CHEMICAL NAME: THERMINOL 55
MONSANTO COMPANY
CHEMICAL NAME: ALKYLATE 230
CHEMICAL NAME: BENZENE, C10-16-ALKYL DERIVS.
8EHQ-0590-
0972
CAS NUMBER
CAS NUMBER
SUBMITTER: MONSANTO COMPANY
84-74-2 CHEMICAL NAME: 1,2-BENZENEDICARBOXYLIC ACID, DIBUTYL ESTER
SUBMITTER: MONSANTO COMPANY
99-54-7 CHEMICAL NAME: BENZENE, 1,2-DICHLORO-4-NITRO-
99-54-7 CHEMICAL NAME: ORTHENE, NITRATED
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
SEHQ-0590-0973 SUBMITTER: MONSANTO COMPANY
CAS NUMBER : 88-73-3 CHEMICAL NAME: BENZENE, 1-CHL0R0-2-NITR0-
8EHQ-0590-0974 SUBMITTER: MONSANTO COMPANY
CAS NUMBER : 2591-86-8 CHEMICAL NAME: 1-PIPERIDINECARBOXALDEHYDE
8EH3-0590-0975 SUBMITTER: MONSANTO COMPANY
CAS NUMBER : NONE CHEMICAL NAME: MCS 1441
CAS NUMBER : 115-86-6 CHEMICAL NAME: PHOSPHORIC ACID, TRIPHENYL ESTER
CAS NUMBER : 34364-42-6 CHEMICAL NAME: PHOSPHORIC ACID, tMtlUCAl NADt: BEMZEME, 1-ChLORO-l-NnRO-
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-0590-0980
SUBMITTER: MONSANTO COMPANY
8EHQ-0590-0981
CAS NUMBER
CAS NUMBER
SUBMITTER: MONSANTO COMPANY
68-12-2 CHEMICAL NAME: FORMAMIDE, N.N-DIMETHYL-
127-19-5 CHEMICAL NAME: ACETAMIDE, N.N-DIMETHYL-
8EHQ-0590-0982 SUBMITTER: MONSANTO COMPANY
CAS NUMBER : NONE CHEMICAL NAME: SANTICIZER 97
CAS NUMBER : 151-32-6 CHEMICAL NAME: HEXANEDIOIC ACID, DINONYL ESTER
CAS NUMBER : 14697-48-4 CHEMICAL NAME: HEXANEDIOIC ACID, DIHEPTYL ESTER
CAS NUMBER : 68515-75-3 CHEMICAL NAME: HEXANEDIOIC ACID, DI-C7-9-BRANCHED AND LINEAR ALKYL ESTERS
8EH4-0590-0983 SUBMITTER: MONSANTO COMPANY
CAS NUMBER : NONE CHEMICAL NAME: THERMINOL 66
CAS NUMBER : 26140-60-3 CHEMICAL NAME: TERPHENYL
CAS NUMBER : 61788-32-7 CHEMICAL NAME: TERPHENYL, HYDROGENATED
8EH4-0590-0984
CAS NUMBER
CAS NUMBER
CAS NUMBER
SUBMITTER: MONSANTO COMPANY
NONE CHEMICAL NAME: OIL, FLUX
38888-98-1 CHEMICAL NAME: BENZENE, tPHENYLETHYL)-
64800-83-5 CHEMICAL NAME: BENZENE, ETHYL(PHENYLETHYL)-
CAS NUMBER : 68398-19-6
CAS NUMBER : 68412-24-8
CHEMICAL NAME: BENZENE, ETHYL(PHENYLETHYLHONQ-AR-ETHYL DERIV.
CHEMICAL NAME: NAPHTHALENE, 1,2,3,4-TETRAHYDRO-, C1-4-ALKYL DERIVS.
8EHQ-0590-0985 *
CAS NUMBER : NONE
CAS NUMBER : NONE
SUBMITTER: AMERICAN TELEPHONE AND TELEGRAPH COMPANY
CHEMICAL NAME: B65 OPAQUE GEL
CHEMICAL NAME: TYPE B LIGHTGUIDE CABLE FILLING COMPOUND
CAS NUMBER : 66070-54-0
CAS NUMBER : 67762-90-7
CHEMICAL NAME: 1-DECENE, POLYMER WITH 1-OCTENE, HYDROGENATED
CHEMICAL NAME: SILOXANES AND SILICONES, DI-ME, REACTION PRODUCTS WITH SILIC
A
-------
II
1
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-0590-0985
8EHQ-0590
SUBMITTER: AMERICAN TELEPHONE AND TELEGRAPH COMPANY
8EHQ-0590-
0986 S
CAS NUMBER
0987 S
CAS NUMBER
SEHQ-0590-09S8 S
CAS NUMBER
8EHQ-0590-0989 S
CAS NUMBER
£ 8EHQ-0590-
tsj
0990
CAS NUMBER
CAS NUMBER
8EHQ-0590-0991 S
CAS NUMBER
CAS NUMBER
8EHQ-0590-0992 S
CAS NUMBER
SEHQ-0590-0993
CAS NUMBER
SUBMITTER:
CONFIDENT
SUBMITTER:
CONFIDENT
SUBMITTER:
CONFIDENT
SUBMITTER:
CONFIDENT
SUBMITTER:
102-06-7
102-06-7
SUBMITTER:
NONE
l«02
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
SEHQ-Q590-0994 * SUBMITTER: ATOCHEM NORTH AMERICA, INC.
8EHQ-Q590-0995 S SUBMITTER: CONFIDENTIAL
CAS NUMBER : CONFIDENT CHEMICAL NAME: AMIDE, HALOALKYL HETEROAROMATIC
SEHQ-0590-0996 SUBMITTER: GENERAL ELECTRIC COMPANY
CAS NUMBER : 3806-34-6 CHEMICAL NAME: 2,*,8,10-TETRA0XA-3,9-DIPHOSPHASPIROC5.51UNDECANE, 3,9-BIS<0
CTADECYLOXYJ-
CAS NUMBER : 3806-34-6 CHEMICAL NAME: MESTON 618
8EHQ-0590-0997 S SUBMITTER: DOW CHEMICAL COMPANY
CAS NUMBER : CONFIDENT CHEMICAL NAME: DIPHENYL ETHER. SUBSTITUTED
BEHQ-0590-0998 S SUBMITTER: CONFIDENTIAL
g CAS NUMBER : CONFIDENT CHEMICAL NAME: NITROBENZENE. ARYLOXY SUBSTITUTED
OJ
8EHQ-0690-0999 * SUBMITTER: AMERICAN CYANAMID COMPANY
CAS NUMBER : 80-62-6 CHEMICAL NAME: METHYL METHACRYLATE
CAS NUMBER : 80-62-6 CHEMICAL NAME: 2-PROPENOIC ACID, 2-METHYL-, METHYL ESTER
BEH4-0690-1000 S SUBMITTER: CONFIDENTIAL
CAS NUMBER : 9*1-69-5 CHEMICAL NAME: IH-PYRROLE-2,5-DIONE, 1-PHENYL-
8EH9-0590-1001 S SUBMITTER: NOR-AM CHEMICAL COMPANY
CAS NUMBER : CONFIDENT CHEMICAL NAME: HALOGENATED ALKYL ESTER
8EHQ-0690-1002 SUBMITTER: CHEMICAL MANUFACTURERS ASSOCIATION
CAS NUMBER : 112-35-6 CHEMICAL NAME: ETHANOL, 2-l2-(2-METH0XYETH0XY)ETH0XY]-
8EH4-0690-1003 SUBMITTER: DOW CHEMICAL COMPANY
CAS NUMBER : 5076-19-7 CHEMICAL NAME: ISOAMYLENE OXIDE
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-0690-M04 S
CAS NUMBER :
CAS NUMBER :
SEHQ-0690-1005 S
CAS NUMBER :
CAS NUMBER :
BEHQ-069D-1006 S
CAS NUMBER :
8EHQ-0690-1007
CAS NUMBER :
8EHQ-0690-1008
CAS NUMBER :
CAS NUMBER :
8EHQ-0690-1009
CAS NUMBER :
8EHQ-0690-1010 S
CAS NUMBER :
8EHQ-0690-1011 S
CAS NUMBER :
8EHQ-0690-1012 S
CAS NUMBER :
8EHQ-0690-1013 S
CAS NunstK t
SUBMITTER:
CONFIDENT
CONFIDENT
SUBMITTER:
CONFIDENT
CONFIDENT
SUBMITTER:
CONFIDENT
SUBMITTER:
126-73-8
SUBMITTER:
111-30-8
111-30-8
SUBMITTER:
16881-77-9
SUBMITTER:
CONFIDENT
SUBMITTER:
CONFIDENT
SUBMITTER:
CONFIDENT
SUBMITTER:
CUNMUtNl
ALLIED-SIGNAL INC.
CHEMICAL NAME: KETOXIME <13, ALIPHATIC
CHEMICAL NAME: MAKO
ALLIED-SIGNAL INC.
CHEMICAL NAME: KETOXIME (II), ALIPHATIC
CHEMICAL NAME: MIBKO
PROCTER < GAMBLE COMPANY
CHEMICAL NAME: AMIDE, SUBSTITUTED ORGANIC
FMC CORPORATION
CHEMICAL NAME: PHOSPHORIC ACID TRIBUTYL ESTER
BASF CORPORATION
CHEMICAL NAME: GLUTARDIALDEHYDE
CHEMICAL HAME: PENTANEDIAL
UNION CARBIDE CHEMICALS AND PLASTICS COMPANY. INC.
CHEMICAL NAME: SILANE, DIMETHOXYMETHYL-
CONFIDENTIAL
CHEMICAL NAME: NITROBENZENE (II), ALKOXY ARYLOXY
CONFIDENTIAL
CHEMICAL NAME: CARBOXYLIC ACID ESTER, ARYLOXY-SUBSTITUTED ALKYL
CONFIDENTIAL
CHEMICAL NAME: AMIDE, ARYL-SUBSTITUTED AMINO
CONFIDENTIAL
CHtrilCAL MAHt: SuLFONE, ARTL nETMTL
-------
8EHQ-0690-1013 5
8EH9-0690-1014 S
CAS NUMBER
ftEHQ-0690-1015
CAS NUMBER
CAS NUMBER
8EHQ-0690-1016 S
CAS NUMBER
AEHQ-0690-1017
CAS NUMBER
CAS NUHBER
8EHQ-061D-1018
CAS NUMBER
CAS NUMBER
CAS NUMBER
CAS NUMBER
CAS NUMBER
SEHfl-0690-1019
CAS NUMBER
CAS NUMBER
CAS NUMBER
8EHQ-0690-1020
CAS NUMBER
SUBMITTER
SUBMITTER
: CONFIDENT
SUBMITTER
: 103*90-06-8
: 103490-06-8
SUBMITTER
: CONFIDENT
SUBMITTER
: 4170-30-J
: 4170-30-3
SUBMITTER
: 409-21-2
: 409-21-2
: 1332-21-4
: 1344-28-1
: 1344-28-1
SUBMITTER
: UNKNOWN
: 557-09-5
: 616-47-7
SUBMITTER
: 611-19-8
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
CONFIDENTIAL
CONFIDENTIAL
CHEMICAL NAME: BENZENE, HALOGENATED SUBSTITUTED
SHELL OIL COMPANY
CHEMICAL NAME: EPIKOTE 1071
CHEMICAL NAME: EPON HPT RESIN 1071
ELI LILLY AND COMPANY
CHEMICAL NAME: QUINOlINE. SUBSTITUTED
EASTMAN KODAK COMPANY
CHEMICAL NAME: 2-IUTENAL
CHEMICAL NAME: CROTONALDEHYDE
VISTA CHEMICAL COMPANY
CHEMICAL NAME: SILICON CARBIDE FIBERS
CHEMICAL NAME: SILICON CARBIDE, (SIC)
CHEMICAL NAME: ASBESTOS
CHEMICAL NAME: ALUMINA WHISKERS
CHEMICAL NAME: ALUMINUM OXIDE. CAL203)
CIBA-GE1GY CORPORATION
CHEMICAL NAME: XB-4458
CHEMICAL NAME: OCTANOIC ACID, ZINC SALT
CHEMICAL NAME: 1H-IMIDAZOLE, 1-METHYL-
OCCIDENTAL CHEMICAL CORPORATION
CHEMICAL NAME: BENZENE. l-CHLORO-2-(CHLOROMETHYL)-
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-0690-1020 SUBMITTER: OCCIDENTAL CHEMICAL CORPORATION
8EHQ-0790-1021 SUBMITTER: HOECHST CELANESE CORPORATION
CAS NUMBER : 52572-38-0 CHEMICAL NAME: BENZENEDIAZONIUM, 3-METHYL-4-(1-PYRROLIDINYL) -» TRICHLOROZIN
CATE(1- )
CAS NUMBER : 52572-38-0 CHEMICAL NAME: DIA20 Y
8EHQ-0790-I022 S SUBMITTER: CONFIDENTIAL
CAS NUMBER : CONFIDENT CHEMICAL NAME: HYDROCARBYL SULFIDE, SUBSTITUTED
8EHQ-0790-1023 S SUBMITTER: BASF CORPORATION
CAS NUMBER : 6422-83-9 CHEMICAL NAME: 1H-PYRROLE-2.5-DIONE, 1,1'-<4-METHYL-l,3-PHENYLENEJBIS-
8EH4-0790-1024 SUBMITTER: GENERAL ELECTRIC COMPANY
S CAS NUMBER : 54395-37-8 CHEMICAL NAME: 1H-ISOINDOLE-1.3-(2H)-DI0NE, 2-BUTYL-5-NITR0-
c\
8EH9-0790-1025 S SUBMITTER: CONFIDENTIAL
CAS NUMBER : CONFIDENT CHEMICAL NAME: AMINE, HALOALKYL
8EHQ-0790-1026 S SUBMITTER: CONFIDENTIAL
CAS NUMBER : CONFIDENT CHEMICAL NAME: BENZENAMINE, ARYLOXY SUBSTITUTED
8EHQ-0790-1027 SUBMITTER: GENERAL ELECTRIC COMPANY
CAS NUMBER : 574-24-1 CHEMICAL NAME: PHENOL, 2,6-DIMETHYL-
8EHS-0790-1028 S SUBMITTER: ROHM AND HAAS COMPANY
CAS NUMBER : CONFIDENT CHEMICAL NAME: BISCSUBSTITUTED PHENYL) SUBSTITUTED AMINO HETEROMONOCYCLE
8EH4-0790-1029 SUBMITTER: MOBIL RESEARCH AND DEVELOPMENT CORPORATION
CAS NUMBER : NONE CHEMICAL NAME: MISC. CHEMICALS
CAS NUMBER : UNKNOWN CHEMICAL NAME: AMOSITE
CAS NUMBER : UNKNOWN CHEMICAL NAME: ANTHOPHYLLITE
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-079Q-1029
CAS NUMBER
CAS NUMBER
CAS NUMBER
CAS NUMBER
CAS NUMBER
CAS NUMBER
CAS NUMBER
SUBMITTER: MOBIL RESEARCH AND DEVELOPMENT CORPORATION
UNKNOWN CHEMICAL NAME: ASBESTOS CEMENT
UNKNOWN CHEMICAL NAME: CROCIDOLITE
UNKNOWN CHEMICAL NAME: ERIONITE
UNKNOWN CHEMICAL NAME: RARE EARTH Y
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
10
00
8EHQ-0790-1034
CAS NUMBER
CAS NUMBER
8EH9-0790-1035
CAS NUMBER
CAS NUMBER
8EHQ-0790-1036 S
CAS NUMBER
8EH«-0790-1037 S
CAS NUMBER
8EHQ-0890-1038
CAS NUMBER
CAS NUMBER
CAS NUMBER
8EHQ-0890-1039 S
CAS NUMBER
8EHQ-0890-1040
CAS NUMBER
8EHQ-0B90-1041
CAS NUMBER
CAS NUMBER
CAS NUMBER
SUBMITTER:
72-56-0
131-72-6
SUBMITTER:
13*63-41-7
13463-41-7
SUBMITTER:
CONFIDENT
SUBMITTER:
CONFIDENT
ROHM AND HAAS COMPANY
CHEMICAL NAME: BENZENE, 1,1 *-(2,2-DICHLOROETHYLIDENE)BISI4-ETHYL-
CHEMICAL NAME: 2-BUTENOIC ACID, 2-(1-METHYLHEPTYL)-4,6-DINITROPHENYL ESTER.
IE>-
OLIN CORPORATION
CHEMICAL NAME: ZINC, BISC1-HVOR0XY-2
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-0890-1042 SUBMITTER: ATOCHEM NORTH AMERICA, INC.
CAS NUMBER : NONE CHEMICAL NAME: LUPERFOAM 329
CAS NUMBER : 7*00-27-3 CHEMICAL NAME: HYDRAZINE, (1,1-DIMETHYLETHYL, MONOHYDROCHLORIDE
CAS NUMBER : 7705-08-0 CHEMICAL NAME: IRON CHLORIDE. (FECL3)
8EHQ-0890-1043 SUBMITTER: ATOCHEM NORTH AMERICA, INC.
CAS NUMBER : 100-37-8 CHEMICAL NAME: ETHANOL, 2-(DIETHYLAMINO)-
8EHQ-0890-1044 S SUBMITTER: 3M COMPANY
CAS NUMBER : CONFIDENT CHEMICAL NAME: TRIBROMOMETHYL SUBSTITUTED HETEROCYCLE
8EHQ-0890-1045 SUBMITTER: R. T. VANDERBILT COMPANY, INC.
CAS NUMBER : 137-30-4 CHEMICAL NAME: VANCIDE MZ-96
<£> CAS NUMBER : 137-30-4 CHEMICAL NAME: ZINC, BIS(DIMETHYLCARBAMODITHIOATO-S,S')-, (T-4)-
to
8EH4-0890-1046 SUBMITTER: E. I. OUNlNt t)E MEMObRfc I COMPANY, INC.
CAS NUMBER : 1842-05-3 CHEMICAL NAME: ETHANE, 1,1-DICHL0R0-1,2-DIFLU0R0-
CAS NUMBER : 1842-05-3 CHEMICAL NAME: HCFC-132C
8EHQ-0890-1047 SUBMITTER: DOU CORNING CORPORATION
CAS NUMBER : 18406-41-2 CHEMICAL NAME: 2.7-DIOXA-3,6-DISILAOCTANE, 3,3,6,6-TETRAMETHOXY-
CAS NUMBER : 18406-41-2 CHEMICAL NAME: DOW CORNING X1-6145A ADDITIVE
8EHQ-0890-1048 S SUBMITTER: E. I. DUPONT DE NEMOURS t COMPANY, INC.
CAS NUMBER : CONFIDENT CHEMICAL NAME: ALKENOIC ACID, SUBSTITUTED-, ALKYL ESTER
8EHQ-0890-1049 S SUBMITTER: CONFIDENTIAL
CAS NUMBER : CONFIDENT CHEMICAL NAME: VANADIUM COMPOUND, INORGANIC
8EHQ-0890-1050 S
CAS NUMBER
SUBMITTER:
CONFIDENT
ROHM AND HAAS COMPANY
CHEMICAL NAME: SUBSTITUTED PHENOXYETHER DERIVATIVE OF A POLYHETEROCYCLE
-------
APPENDIX E= STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-0890-1050 5
SUBMITTER: ROHM AND HAAS COMPANY
8EHQ-0890-1051 S
CAS NUMBER
8EHQ-0890-
1032 S
CAS NUMBER
8EHQ-0890-1053
CAS NUMBER
CAS NUMBER
8EHQ-0890-1054 S
CAS NUMBER
8EH9-0890-1055 S
CAS NUMBER
8EHQ-0890-1056 S
CAS NUMBER
8EHQ-0990-1057
CAS NUMBER
CAS NUMBER
CAS NUMBER
8EH4-0990-1058 S
CAS NUMBER
SUBMITTER:
85940-63-2
SUBMITTER:
CONFIDENT
HOECHST CELANESE CORPORATION
CHEMICAL NAME: 1,5-NAPHTHALEHEDISULFOHIC ACID, 2-T14,5-DIHYDR0-3-METHYL-5-0
XO-l-[4-[[2-CSULFOOXY)ETHYL]SULFONYLJPHENYLJ-lH-PYRAZOL-4-YL
]AZOl~, POTASSIUM SODIUM SALT
ROHM AND HAAS COMPANY
CHEMICAL NAME: HALOPHENYL SUBSTITUTED MONOHETEROCYCLE
SUBMITTER: AMERICAN CYANAMID COMPANY
75-21-8 CHEMICAL NAME: ETHYLENE OXIDE
75-21-8 CHEMICAL NAME: DXIRANE
SUBMITTER:
CONFIDENT
SUBMITTER:
CONFIDENT
SUBMITTER:
CONFIDENT
SUBMITTER:
68937-41-7
68937-41-7
68937-41-7
SUBMITTER:
CONFIDENT
CONFIDENTIAL
CHEMICAL NAME: AMINE POLYMER, SUBSTITUTED
BOH CHEMICAL COMPANY
CHEMICAL NAME: DIPHENYL ETHER. SUBSTITUTED
DOU CHEMICAL COMPANY
CHEMICAL NAME: DIPHENYL ETHER, SUBSTITUTED
FMC CORPORATION
CHEMICAL NAME: DURAD 110
CHEMICAL NAME: KRONITEX 50
CHEMICAL NAME: PHENOL, ISOPROPYLATED, PHOSPHATE (3:1)
FMC CORPORATION
CHEMICAL NAME: ALPKA-CYANOCARBOCYCLIC CARBOXYLATE
8EHQ-0990-1059 S * SUBMITTER: CONFIDENTIAL
CAS HUnUtK : CUNMDfcNI CHbfllCAL NADh: ALKALINE OXIDIZER
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-0990-1059 S * SUBMITTER: CONFIDENTIAL
8EH9-0990-1060 S SUBMITTER: CONFIDENTIAL
CAS NUMBER : CONFIDENT CHEMICAL NAME: AMINE, HALOALKYL. (II)
8EHQ-0990-1061 SUBMITTER: EXXON CHEMICAL AMERICAS
CAS NUMBER : 592-*5-0 CHEMICAL NAME: 1,4-HEXADIENE
8EHQ-0990-1062 SUBMITTER: EASTMAN KODAK COMPANY
CAS NUMBER : 565-80-0 CHEMICAL NAME: 3-PENTANONE, 2,«-DIMETHYL-
8EHQ-0990-1063 SUBMITTER: INDUSTRIAL HEALTH FOUNDATION, INC.
CAS NUMBER : 96-29-7 CHEMICAL NAME: 2-BUTANONE, OXIME
8EHQ-0990-1064 SUBMITTER: UNIOH CARBIDE CHEMICALS AND PLASTICS COMPANY, INC.
CAS NUMBER : 112-27-6 CHEMICAL NAME: ETHANOL, 2,2*-11,2-ETHANEDIYLBIS(OXY)1BIS-
8EH9"0990-1065 SUBMITTER: ATOCHEM NORTH AMERICA, INC.
CAS NUMBER : 57910-79-9 CHEMICAL NAME: 2-BUTANOL, 2-[(1,1-DIMETHYLETHYL)AZO]-
CAS NUMBER : 57910-79-9 CHEMICAL NAME: LUCEL-4
8EHQ-0990-1066 S SUBMITTER: DOW CORNING CORPORATION
CAS NUMBER : CONFIDENT CHEMICAL NAME: ALLYLOXY KETAL
CAS NUMBER : CONFIDENT CHEMICAL NAME: ALLYLOXY PRECURSOR, UNKETALIZED
CAS NUMBER : CONFIDENT CHEMICAL NAME: DOU CORNING Xl-6169
8EH9-0990-1067 SUBMITTER: DOU CORNING CORPORATION
CAS NUMBER : 2530-87-2 CHEMICAL NAME: DOU CORNING Ql-2366 SILANE
CAS NUMBER : 2530-87-2 CHEMICAL NAME: SILANE, (3-CHL0R0PR0PYLJTRIMETHOXY-
8EHQ-0990-1068 SUBMITTER: PFISTER CHEMICAL, INC.
CAS NOnUtK : lZ*/3/-Al-l ChtPllCAL NAflfc: BENZENES! AZONiUPI, I 01PIETH YL AF11N0J - , 5-SuLPOSALICYLATE
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-0990-1068 SUBMITTER: PFISTER CHEMICAL, INC.
CAS NUMBER .- 124737-31-1 CHEMICAL NAME: DIAZ0 8 SS
8EHQ-0990-1069
CAS NUMBER
8EH9-0990-1070 5
8EHQ-0990-1071
CAS NUMBER
CAS NUMBER
CAS NUMBER
8EHQ-0990-1072
CAS NUMBER
CAS NUMBER
CAS NUMBER
CAS NUMBER
SUBMITTER-. MITSUBISHI YUKA AMERICA. IHC.
129217-90-9
CAS NUMBER ; 129217-90-9
CAS NUMBER : 129217-90-9
CHEMICAL NAME: CONDENSATE OF ANILINE, O-TOLUIDINE AND TEREPHTHALALDEHYDE,
EACTION PRODUCT WITH MALEIC ANHYDRIDE
CHEMICAL NAME: MP-2000
CHEMICAL NAME: MP-2000X
SUBMITTER: CONFIDENTIAL
CAS NUMBER CONFIDENT
CHEMICAL NAME: NITROBENZENE, SUBSTITUTED
SUBMITTER: MOTOROLA INC.
NONE CHEMICAL NAME: MULT1CORE SOLDER X32B
NONE CHEMICAL NAME: MULTICORE TTC-1 TIP TANNER
7*39-92-1 CHEMICAL NAME: LEAD
CAS NUMBER : 7**0-31-5
CHEMICAL NAME: TIN
SUBMITTER: GENERAL ELECTRIC COMPANY
NONE CHEMICAL NAME: BENZENE, 1,1•-OXYBIS-, BROMINATED DERIV.
UHKNOUN CHEMICAL NAME: 1,1•-BIPHENYL, BROMO DERIVS.
UNKNOWN CHEMICAL NAME: POLYBROMINATED BIPHENYLS (PBB)
32536-52-0 CHEMICAL NAME: BENZENE, 1,1 *-OXYBIS-, OCTABRONO DERIV.
8EH9-0990-1073 S SUBMITTER: CONFIDENTIAL
CAS NUMBER : CONFIDENT CHEMICAL NAME: BENZENAMINE CII), ARYLOXY SUBSTITUTED
8EHQ-0990-1074 SUBMITTER: GENERAL ELECTRIC COMPANY
CAS NUMBER : UNKNOWN CHEMICAL NAME: RESORCIHOL DIPHOSPHATE
8EHQ-0990-1075 S SUBMITTER: CONFIDENTIAL
CAS NUPIHtK : CUNMUtNl CHfcPUCAL NAflfc: PROPANOIC ACltJ ESTER, aRtL
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-0990-1076 S
CAS NUMBER
CAS NUMBER
CAS NUMBER
8EH9-0990-1077
CAS NUMBER
SUBMITTER: PROCTER « GAMBLE COMPANY
CONFIDENT CHEMICAL NAME: ORGANIC ALCOHOL, SUBSTITUTED
CONFIDENT CHEMICAL NAME: ORGANIC ESTER, SUBSTITUTED
68920-82-1 CHEMICAL NAME: AMIDES, FROM DIETHYLENETRIAMINE AND HYDROGENATED TALLOW
SUBMITTER: EASTMAN KODAK COMPANY
71-43-2 CHEMICAL NAME: BENZENE
8EH4-0990-1078
SUBMITTER: ALLIED-SIGNAL INC.
CAS
NUMBER :
NONE
CHEMICAL
NAME: CUTTING FLUID
CAS
NUMBER :
NONE
CHEMICAL
NAME: HOCUT 797-G
CAS
NUMBER :
NONE
CHEMICAL
NAME: MISC. CHEMICALS
1079
' S
SUBMITTER:
CIBA-GEIGY CORPORATION
CAS
NUMBER :
CONFIDENT
CHEMICAL
NAME: OXADIAZOLE, SUBSTITUTED
1080
i S
SUBMITTER:
MORTON INTERNATIONAL, INC.
CAS
NUMBER :
NONE
CHEMICAL
NAME: MISC. CHEMICALS
CAS
NUMBER :
62-53-5
CHEMICAL
NAME: ANILINE
CAS
NUMBER :
62-53-3
CHEMICAL
NAME: BENZENAMINE
CAS
NUMBER :
95-53-4
CHEMICAL
NAME: BENZENAMINE, 2-METHYL-
CAS
NUMBER :
95-53-4
CHEMICAL
NAME: O-TOLUIDINE
CAS
NUMBER :
95-78-3
CHEMICAL
NAME: BENZENAMINE, 2,5-DIMETHYL-
CAS
NUMBER :
95-78-3
CHEMICAL
NAME: 2,5-XYLIDINE
CAS
NUMBER :
97-02-9
CHEMICAL
NAME: ANILINE, 2,4-DINITRO-
CAS
NUMBER :
97-02-9
CHEMICAL
NAME: BENZENAMINE, 2,4-DINITRO-
CAS
NUMBER :
100-01-6
CHEMICAL
NAME: ANILINE, P-NITRO-
CAS
NUMBER :
100-01-6
CHEMICAL
NAME: BENZENAMINE, 4-NITRO-
CAS
NUMBER :
104-13-2
CHEMICAL
NAME: ANILINE. P-BUTYL"
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-0990-1Q80 S
SUBMITTER: MORTON INTERNATIONAL. INC.
to
VI
CAS
NUMBER
104-13-2
CHEMICAL
HAME:
BENZENAMINE, 4-BUTYL-
CAS
NUMBER
104-42-7
CHEMICAL
NAME:
ANILINE, P-DODECYL-
CAS
NUMBER
104-42-7
CHEMICAL
NAME:
BENZENAMINE, 4-DODECYL-
CAS
HUMBER
106-49-0
CHEMICAL
NAME:
BENZENAMINE, 4-METHYL-
CAS
NUMBER
106-49-0
CHEMICAL
NAME:
P-TOLUIDINE
CAS
HUMBER
108-44-1
CHEMICAL
NAME:
BEHZENAMINE. 3-METHYL-
CAS
HUMBER
108-44-1
CHEMICAL
NAME:
M-TOLUIDINE
CAS
NUMBER
111-92-2
CHEMICAL
NAME:
1-BUTANAMINE, N-BUTYL-
CAS
NUMBER
119-93-7
CHEMICAL
NAME:
[1,1'-BIPHENYL1-4,4'-DIAMINE, 3,3•-DIMETHYL-
CAS
NUMBER
119-93-7
CHEMICAL
NAME:
O-TOLIDINE
CAS
NUMBER
120-71-8
CHEMICAL
NAME:
BEHZENAMINE, 2-METHOXY-5-METHYL-
CAS
NUMBER
120-71-8
CHEMICAL
NAME:
P-CRESIDINE
CAS
NUMBER
1300-73-8
CHEMICAL
NAME:
BENZEHAMIHE, AR,AR-DIMETHYL-
CAS
NUMBER
1300-73-8
CHEMICAL
NAME:
XYLIDIHE (MIXED)
8EHQ-0990-108I
SUBMITTER: CIBA-GEIGY CORPORATION
CAS NUMBER : 88485-37-4
CAS NUMBER : 88485-37-4
CHEMICAL NAME: ACETOPHENONE OXIME, 0-(l,3-DI0X0LAN-2-YL-METHYL)-2,2.2-TRIFL
U0R0-4'-CHLORO-
CHEMICAL NAME: ETHANOHE, l-(4-CHL0R0PHENYL)-2,2,2-TRIFLUORO-, 0-(1,3-DIOXOL
AN-2-YLMETHYL JOXIME
8EHQ-0990-1082
CAS NUMBER
CAS NUMBER
8EHQ-0990-1083 S
CAS NUMBER
CAS NUMBER
SUBMITTER: HOECHST CELANESE CORPORATION
2628-16-2 CHEMICAL NAME: PHENOL, 4-ETHENYL-
2628-16-2 CHEMICAL NAME: STYRENE, ACETOXY-
ACETATE
SUBMITTER:
CONFIDENT
CONFIDENT
CONFIDENTIAL
CHEMICAL NAME: QUINAZ0L1HES
CHEMICAL NAME: QUINOLINES
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
#EH9-0»90-1084 SUBMITTER: DOM CORNING CORPORATION
CAS NUMBER : 287-29-6 CHEMICAL NAME: SILACYCLOBUTANE
<4>
U1
Ul
*U.S.GOVERNMENTPMNTINC OFFICE: 1991. 517. ooji.70 20
-------
REPORT DOCUMENTATION
PAGE
1. REPORT NO.
4. TNI* *rxl auMttl*
EPA 560/2-91-001
"Preliminary Evaluations of Initial TSCA
Section 8(e) Substantial Risk Notices"
January 1989 - September 1990
7. Authwuk Office of Toxic Substances/OPTS
U.S. Environmental Protection Agency (EPA)
L IMPlMl't *ixwilan Na.
k. RapMt Oat*
July 1991
L P»f«ormlo# Ofiamtiattan Rapt. No.
>. Motmlnf Organization Kama Addraw
Office of Pesticides and Toxic Substances (TS-788)
U.S. Environmental Protection Agency
401 "M" Street, S.W.
Washington, D.C. 20460
10. Unit Mo.
11. CMitrscKO or SranKO)
(O
«a>
IZ. SponifUig 0«ianlzatlan Mama and AMmi
Office of Pesticides and Toxic Substances (TS-788j
U.S. Environmental Protection Agency
401 "M" Street, S.W.
Washington. D.C. 20460
U. Tjrpa af Raport fc Partod Cowarad
01/01/89 to 09/30/90
14.
Ik. SupplamanUry Not**
1*. «Mnd (Limit 200 won*)
This volume contains, in ascending submission number order, "status reports"
(i.e., preliminary evaluations) prepared by the staff of the Office of Toxic
Substances in EPA's Office of Pesticides and Toxic Substances for initial
submissions received by EPA from chemical manufacturers, importers, processors
and distributors from January 1, 1989 to September 30, 1990 under Section 8(e)
the "substantial risk" information reporting provision of the Toxic Substances
Control Act (TSCA). The status reports contained in this compendium reflect
only the initial phase of the Agency's evaluation process for the submitted
information.
This TSCA Section 8(e) status report volume has been published by EPA for two
reasons. First, a volume of Section 8(e) status reports with appropriate
indices will make the submitted information more accessible. Second, this
volume may, by providing specific examples of submitted information and EPA's
preliminary evaluation of that information, help those persons who are subject
to Section 8(e) understand better the types of information that should be
submitted to EPA under this mandatory reporting provision of TSCA.
17. Document AaiNi %. Daaeriptart
Toxic Substances Control Act
TSCA
Section 8(e)
Substantial Risk
t. ldammar»/Opa» Cndad Tarmt
* CMATI flaM/Oraup
**• AvaltaMMy *ataman:
Unlimited Distribution
IS. SaoufRy
(TMf Rapart)
SB. Sacurtty CtoM OMt *«•)
21. Na. •<
969
XL Mca
0MANSt4m.it)
OPTIONAL POMI TTt (4-77)
(fimarly NDS-JI)
957
------- |