xvEPA
United States
Environmental Protection
Agency
Office of Pesticides
and Toxic Substances
Washington DC 20460
March 1987
EPA 560/2-87-001
Preliminary Evaluations
of Initial TSCA
Section 8(e)
Substantial Risk Notices
January 1, 1985 - December 31, 1986
A
-------
NOTICE TO ADMINISTRATOR OF SUBSTANTIAL RISKS. 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 [EPA] Administrator of such information
unless such person has actual knowledge that the Administrator
has been adequately informed of such information.
-- Section 8(e)r Toxic Substances Control Act (1976)
~
-------
EPA 560/2-87-001
MARCH 1987
PRELIMINARY EVALUATIONS OF INITIAL
TSCA SECTION 8(e) SUBSTANTIAL RISK NOTICES
JANUARY 1, 1985 TO DECEMBER 31, 1986
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
-------
Disclaimer
This volume has been reviewed by the Office of Pesticides and
Toxic Substances (OPTS), U.S. Environmental Protection Agency,
and approved for publication. The status reports contained in
this volume present the Agency's preliminary evaluations of the
submitted information and do not represent final Agency policy
or intent with respect to the submissions or subject chemicals.
Mention of company names, trade names, or commercial products
does not constitute an Agency endorsement or recommendation for
or against use.
ii
-------
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, processors, and
distributors between January 1, 1985, and December 31, 1986,
pursuant to Section 8(e), the "substaritial risk" information
reporting provision of the Toxic Substances Control Act (TSCAj
90 Stat. 2029, 15 U.S.C. 2607(e)). Status reports are prepared
by OTS for all initial TSCA Section 8(e) submissions and reflect
only part of the initial phase of the OTS evaluation process for
such information.
This volume is being distributed through the TSCA Assistance
Office (TAO) in OTS/OPTS. Persons wishing to obtain a copy of
this volume of Section 8(e) status reports should write to:
TSCA Assistance Office (TS-799)
u.S. Environmental Protection Agency
401 "M" Street, S.W.
Washington, D.C. 20460
The Agency 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 three previously published Section 8(e) status
report volumes (PB# 80-221609, PB# 81-145732, PB# 83-187815 and
PB# 87-129409) 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.
Such information will be considered at subsequent steps in the
OTS chemical assessment process. The submission of additional
information for, or comments on, these evaluations should be
directed to:
Mr. Frank D. Kover, 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
(TS-778)
iii
-------
Non-confidential versions of Section 8(e) submissions and EPA
status reports can be viewed in the OPTS public files which are
located at EPA Headquarters, Room G-004, Northeast Mall, 401 "M"
Street S.W., Washington, D.C. Copies of Section 8(e) submissions
and status reports can be obtained by writing to EPA's Freedom of
Information Office at the following address:
Freedom of Information Office
u.S. Environmental Protection
401 "M" Street, S.W.
Washington, D.C. 20460
(A-I01)
Agency
This and previous volumes of status reports have been published
by EPA for two reasons. First, volumes of status reports will
make reported information more accessible. Second, such volumes
may, by providing specific examples of submitted information and
EPA's evaluation of that information, help those persons subject
to Section 8(e) understand better the types of information that
should be submitted.
It is important to note that EPA's overall implementation of TSCA
Section 8(e) has resulted in heightened chemical industry aware-
ness of the potential risks posed by chemical substances. This
heightened awareness has led in many cases to voluntary corporate
actions designed to protect human health or the environment. For
example, many companies have reported that in direct response to
submitted Section 8(e) data, the following types of voluntary
health and environmental protection measures were initiated:
o formal notification of others (e.g., workers, customers)
about the reported data by way of letters and modifications
to product labels and Material Safety Data Sheets;
o changes made in manufacturing, processing and handling
procedures to reduce or eliminate chemical exposure;
U use or production of chemicals halted temporarily or
discontinued altogether; and
o 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 EPA's receipt thus far of over 525 voluntary
"For Your Information" (FYI) sub~issions that contain valuable
toxicologic, exposure and voluntary risk reduction information.
7}"1
, "
, I 1/ /..-'~
-/ I l-<----~~
Jo -h J. Merenda, Director
x'sting Chemical Assessment
DivisionjOTS
./
, .
iv
-------
Acknowledgment
In preparing the status reports contained in this compendium,
EPA's Office of Toxic Substances (OTS) has frequently found it
necessary to request additional information about, or clarifi-
cation of, the submitted data. OTS appreciates the efforts and
cooperation of the following companies, agencies and organiza-
tions that have submitted information reflected in this volume:
ALCOLAC
ALLIED-SIGNAL INC.
AMERICAN CYANM1ID COMPANY
AMERICAN HOECHST CORPORATION
AMOCO CORPORATION
ATLANTIC RICHFIELD COMPANY
AZS CORPORATION
BASF WYANDOTTE CORPORATION
CELANESE CORPORATION
CHEMICAL MANUFACTURERS ASSOCIATION
CHEVRON CHEMICAL COMPANY
CIBA-GEIGY CORPORATION
DOW CORNING CORPORATION
EASTMAN KODAK COMPANY
E. I. DU PONT DE NEMOURS & COMPANY, INC.
ELI LILLY AND COMPANY
ETHYL CORPORATION
FRAGRANCE MATERIALS ASSOCIATION (U.S.)
HERCULES INCORPORATED
Im1 CORPORATION
INTERNATIONAL LEAD ZINC RESEARCH ORGANIZATION INC.
INTERNATIONAL MINERALS & CHEMICAL CORPORATION
LEVER BROTHERS COMPANY (INCORPORATED)
MOBIL RESEARCH AND DEVELOPMENT CORPORATION
MONSANTO COMPANY
NALCO CHEMICAL COMPANY
NATIONAL STARCH AND CHEMICAL CORPORATION
NUODEX INC.
OLIN CORPORATION
PPG INDUSTRIES, INC.
PROCTER & GAMBLE COMPANY
ROHM AND HAAS COMPANY
R. T. VANDERBILT COMPANY, INC.
SMELTER ENVIRONMENTAL RESEARCH ASSOCIATION
SOCIETY OF THE PLASTICS INDUSTRY, INC.
SOHIO ENGINEERED MATERIALS COMPANY
SYNTEX (U.S.A.) INC.
TEXACO INC.
TOTAL PETROLEUM, INC.
UNION CARBIDE CORPORATION
U. S. DEPRARTMENT OF ENERGY
VELSICOL CHEMICAL CORPORATION
v
-------
Foreword
Contents
. . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 111
Acknowledgment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Introduction
v
.............................................. ..
1
Status Reports 8EHQ-0185-0542 S through 8EHQ-1286-0648 .....
Appendix A.
Appendix B.
Appendix C.
Appendix D.
Appendix E.
5
"Statement of Interpretation and Enforcement
Policy; Notification of Substantial Risk"
(43 FR 11110. March 16, 1978) .................. 389
Status Reports Listed by CAS Number ............ 397
Status Reports Listed by Chemical Name ......... 414
Status Reports Listed by Information Type ...... 439
Status Reports Listed by Submission Number ..... 448
vii
-------
Introduction
Section 8(e) of the Toxic Substances Control Act (TSCA; the Act)
states that "any person who manufactures, processes, or distri-
butes 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,
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 sub-
mitted and the procedures for doing so, EPA (following receipt
and review of public comments) published its March 16, 1978 TSCA
Section 8(e) policy statement ("Statement of Interpretation and
Enforcement Policy; Notification of Substantial Risk" 43 FR
11110). For easy referral when using this volume, EPA's TSCA
Section 8(e) policy statement has been reproduced as Appendix A
in the back of this volume.
The March 16, 1978 TSCA Section 8(e) policy statement expresses
the Agency's policy that the information subject to Section 8(e)
reporting is any "new" information that "reasonably supports" a
conclusion that a chemical substance or mixture presents a sub-
stantial risk of injury to health or the environment but need not
necessarily indicate conclusively that such a risk exists. A
determination of "substantial risk" does not include an evalu-
ation of economic or social benefits of the use of the chemical
and, therefore, is not synonymous with the term "unreasonable
risk" which is found in other sections of the Act. Although
EPA's receipt of information under Section 8(e) of TSCA does not
necessarily trigger immediate regulatory action, the information
which is submitted under TSCA Section 8(e) does receive priority
review and evaluation by EPA in order to determine an appropriate
course of Agency action.
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, approximately 650
initial TSCA Section 8(e) notices 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 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
1
-------
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 produc-
tion 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 TSCA Assistance Office (TAO/OTS/OPTS/EPA) 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 the OTS immediately
reviews, evaluates, and initiates appropriate follow-up actions
or activities for all information contained in "follow-up" and
"supplemental" TSCA Section 8(e) notices. By definition, follow-
up notices are those that contain information submitted directly
in response to an EPA request, whereas supplemental notices are
those that contain information not specifically requested by EPA.
A Document Control Number is used by EPA to identify TSCA Section
8(e) submissions and takes the following form: 8EHQ-0000-0000.
Starting at the left, the first four symbols identify the infor-
mation as a Section 8(e) submission received by EPA headquarters;
the next four digits identify the month and year (e.g., -0579-)
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 end of the Document Control Number to convey other
information. These additional characters and their meaning are
as follows:
S: indicates that the TSCA Section 8(e) submission was
sanitized to delete information that was claimed by the
submitting company to be TSCA Confidential Business
Information (TSCA CBI);
P: indicates that the Section 8(e) submission contained names
or other identification (e.g., Social Security Numbers) of
individuals, the release of which may violate the privacy Act
(such documents are sanitized to remove an individual's name
or other identifiers); and
*: indicates that, based on a preliminary evaluation, the
submission was considered by EPA to be unwarranted for
reporting under Section 8(e) of TSCA.
2
-------
When reviewing the status reports contained in this volume, the
reader should realize that the purpose of the OTS preliminary
evaluation is to determine the significance of the 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 evalua-
tion 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 mix-
ture for which a TSCA Section 8(e) notice has been filed.
3
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
D"T£:
FEB 2 I 1985
8EHQ-0185-0542 S
Page 1 of 4
(JJt-- 2-/'/1~
SUIJ£CT. Status Report* 8EHQ-0185-0542 S
n- Dav id R. Willi am s,~ ction B ( e) Coord ina tor
Chem1cal Risk Identification Sectio~/CSB
App=oved
Revision
Needed
TO Frank D. Kover, Branch Chief
I Chemical Screening Branch/ECAD/OTS/O?TS
Note
The submitting company has claimed its company name as TSCA
Confidential Business Information (TSCA CBI). The Information
Management Division (IMD/OTS) has requested the submitting
company to substantiate this confidentiality claim.
Submission Description
The submitting company provided the following information with
regard to nitrite-containing metalworking fluids:
"N-nitrosodiethanolamine (NDELA) can form in nitrite-containing
metalworking fluids. R. Preussmann, et al have reported on the
carcinogenic effects of NDELA (Cancer Research, 42, 5167, 1982).
The degree of exposure to NDELA by users of these-fluids has
been believed to be minimal because NDELA is also known to de-
compose rapidly under use conditions (D.P. Rounbehler and J.M.
Fajen, N-NITROSO COMPOUNDS IN THE FACTORY ENVIRONMENT (1983)).
"...[The submitting company has] recently discovered that for
those metalworking fluids that contain nitrite and high levels
of diethanolamine (DEA), the rate of NDELA formation may be
significantly greater than the rate of decomposition, resulting
in accumulation of NDELA. Specifically, ...[the submitting
company has] found that a product which contains 10% DEA in the
original concentrate can have as much as 600 ppmAof NDELA in a
used mix, while simple dilution of year-old sampies of the same
product concentrate tested at a level of 150 ppm. In contrast,
Rounbehler and Fajen reported typical levels of 1-5 ppm in con-
ventional nitrite-containing metalworking fluids."
Submission Evaluation
Information available to the Agency does not support the impres-
sion given by the submitter's statement that "...exposure to
NDELA in metalworking fluids was believed to be minimal because
NDELA is known to decompose rapidly under use conditions...."
-NOTE: T~is status reDort is the result of a orelimina=v
staff evaluation of i~fo~ation submitted to EPA. Sta~e;'ents
mace herein are no~ to be re~arded as ex~ressina final
Agency policy or intent with~res?ec~ to t~is ?articu~ar
chemical. .~y review of the status report should take into
consideration" the tact that it may be based on incomplete
information. 5
-------
8EHQ-0185-0542 S
Page 2 of 4
In fact, the Agency's analysis of available data indicates that
~he concentration of NDELA does not, on average, significant~y
lncrease or decrease with time in dilute (working) metalworklng
baths. This does not mean, however, that in individual metal-
working fluid baths, significant NDELA formation or degradation
cannot occur, as evidenced by the formation of significant levels
reported in this Section 8(e) submission.
The submitter, in commenting on the company's measurement of 600
ppm NDELA in a metalworking fluid sample, stated that a study
"...reported typical levels of 1-5 ppm NDELA in convention~l
nit7ite-co~taining metalworking fluids. II Here again, the 1nf<:>r-
matlon aval1able to EPA does not indicate that 1-5 ppm NDELA ln
nitrite-containing metalworking fluids is "typical." over 100
metalworking fluid samples have been analyzed for the presence of
nitrosamines by a number of investigators. The levels of NDELA
reported range from non-detected to 29,900 ppm in cutting fluid
concentrate. In samples of dilute metalworking fluids (working
baths) known to have been nitrite-containing formulations, the
nitrosamine (NDELA) levels ranged from below the detection limit
to as high as 315 ppm, with an average observed NDELA concentra-
tion of approximately 88 ppm.
Immediately upon receipt of this Section 8(e) submission, the
Chemical Screening Branch (CSB/ECAD/OTS) provided copies of the
notice to the Risk Management Branch (RMB/ECAD/OTS), Existing
Chemical Control Branch (ECCB/CCD/OTS), and Regulatory Impacts
Branch (RIB/ETD/OTS) for inclusion in the ongoing OTS evaluation
of the potential risks posed by exposure to nitrite-containing
metalworking fluids. It should be noted that in September 1984,
EPA published two "Chemical Advisories" that outline EPA's con-
cerns about nitrosamines in metalworking fluids. Copies of these
advisories may be obtained by calling toll free at 800-424-9065
or in the Washington D.C. area at 202-554-1404, or by writing to:
Ed Klein, Director
TSCA Assistance Office (TS-799)
Office of Toxic Substances
U.S. Environmental Protection Agency
401 "M" Street, S.W.
Washington, D.C. 20460
Current production and Use
Metalworking fluids (also known as cutting/grinding fluids) ~re
applied to cutting tools to aid in machine operation by se~vlng
as lubricants and/or coolants and by washing away ~et~l ChlpS.
An estimated 5 million gallons (approximately 40 mlillon pounds)
of nitrite-containing metalworking fluid concentrate were con-
sumed in the U.S. during 1983.
6
-------
8EHQ-0185-0542 S
Page 3 of 4
Comments/Recommendations
On the basis of the obtained results, the submitter reported that
the company is taking steps to 1) "withdraw this type of product
from the market" and 2) inform customers about the reported
findings.
EPA's Office of Toxic Substances (OTS) has received and evaluated
a number of TSCA Section 8(e) and liFoI' Your Information" (FYI)
submissions containing toxicity/exposure information on cutting
fluids and/or various nitrosamines. In addition, the Chemical
Screening Branch/ECAD has prepared Chemical Hazard Information
Profiles (CHIPS) on cutting fluids and certain N-nitroso com-
pounds, including nitrosodiethanolamine (NDELA).
a) The Chemical Screening Branch will request the submitting
company to provide the following information with regard to
the reported findings:
o
the length of time the metalworking fluid bath (from
which the sample reported to contain 600 ppm NDELA) had
been in use;
o
the NDELA concentration at the time this used metal-
working bath fluid was initially analyzed; and
o
if the used metalworking bath fluid sample was analyzed
for NDELA over time, indicate the interval of time
between each successive analysis and the NDELA concen-
tration measured at each successive analysis.
The Chemical Screening
company to provide the
the metalworking fluid
company to contain 10%
Branch will also ask the submitting
following information with regard to
concentrate that was reported by the
diethanolamine (DEA)
o
the product name(s) of the concentrate;
o
the actual chemical name, CAS Registry Number (if
known), and amount of each constituent (including
contaminants and impurities if detected) in the
concentrate;
o
the product name(s) of all products (if any) formulated
via dilution of the concentrate; and
o
the actual chemical name, CAS Registry Number (if
known) and amount of each constituent (including
contaminants and impurities if detected) in all
products (if any) formulated via dilution of the
concentrate.
7
-------
8EH~0185-0542 S
Page 4 of 4
In a~dition, the Chemical Screening Branch will request ~he
submltter to describe the nature and results of all studles,
assays, analyses, etc. conducted by or for the submitting
company in which a nitrosamine was detected at any level in
any metalworking fluid concentrate or dilution thereof.
Finally, the submitting company will be requested to ~rovide
a complete copy of the written cornrnunication(s) by WhlCh the
submitter's customers have been or are being notified about
the reported findings and/or the withdrawal of metalworking
fluids from commerce.
b) The Chemical Screening Branch will provide copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, RMB/ECAD/OTS, ECCB/CCD/OTS and
RIB/ETD/OTS. Copies of this status report will also be
provided to the TSCA Assistance Office (TAO/OTS/OPTS) for
further distribution.
8
-------
DATE:
~-6-
UNITED STATES EHVIROHMENTAL PROTECTION AGENCY
8EHQ-0185-0543
Pa ge 1 0 f 4
SUIJICT. Status Report*
8EHQ-0185-0543
Approved
~ 14sf
nOM. David R.
Chemical
Williams~ection 8(e) Coordinator
Risk Identification Section/CSB
Revision
Needed
TO Frank D. Kover, Branch Chief
'Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
On behalf of member companies of its vinyl Acetate Task Force,
the Society of the plastics Industry~ Inc. (SPI) submitted sum-
marized preliminary findings from a two-generation reproduction
study of rats dosed orally at 0, 200, 1000, and 5000 ppm vinyl
acetate (CAS NO. 108-05-4) in water. In addition, SPI reported
that a two-year in utero oral study and a two-year inhalation
study of vinyl acetate are also underway. According to SPI,
"The preliminary data indicate that when rats were first
treated with vinyl acetate via the oral route and bred to
produce off-spring for the in utero study and to start the
two generation reproduction study, a decrease in overall
fertility was noted in the high dose group (5000 ppm). The
observed effect was a reduction in the number of litters
produced, not a reduction in the number of pups per litter
or in the quality of the litters. The decrease was slight
and within the normal range for many labs. No such effects
were seen at the 200 ppm or the 1000 ppm dose level."
"In the breeding of the second gene~ation there was again a
marginal decrease in fertility in the high dose group. To
further evaluate whether this result was real, an additional
cross-mating study was done in which high dose treated males
were mated to control females and control males were mated
to treated high dose females. The object of this st~dy was
to obtain additional information on the fertility index an~
to assess whether there was an effect in the male or the
female. The results of this study again showed a marginal
decrease in the fertility index in treated males bred to
control females. When control males were bred to treated
females no such effect was observed. These effects were
seen in the presence of decreas~d body weight gain ...and
decreased water consumption."
-NOTE: T~is status recort is the resul~ of a preliminary
staff evaluation of i~formation subrnitt~c to EPA. Sta~e;'e~ts
mace herein are no~ to be re~arded as ex~ressir.c final
Agency policy or inten~ wi~h~res?ec~ to t~is particular
chemical. .~y review of the status repor~ should take into
consideration the tact tha~ it may be based on incorn?lete
information.
9
-------
8EHQ-0185-0543
Page 2 of 4
'The pattern seen in the earlier phases, plus the informa-
tion generated in this cross-mating, led ...[SPI] to con-
clude that there is a marginal but treatment-related effect
of vinyl acetate on male fertility in rats exposed via the
oral route at 5000 ppm in the drinking water. Further eval-
uation of the significance of these results is now under
review."
Submission Evaluation
Although the submitted information does indicate that vinyl
acetate can produce an adverse effect on the fertility of male
rats, complete copies of the final reports of the cited studies
are needed in order for EPA to evaluate more completely the
overall significance of the reported findings.
Immediately upon receipt of this Section 8(e) submission, the
Chemical Screening Branch (CSB/ECAD/OTS) sent a copy to the Risk
Management Branch (RMB/ECAD/OTS) for inclusion in the ongoing
evaluation of available toxicologic/exposure information on vinyl
acetate.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for vinyl acetate (CAS No. 108-05-4), which is listed
in the initial TSCA Inventory, has shown that 521 million to 2.6
billion pounds were reported as produced/imported in 1977. This
production range data does not include any production/importation
data claimed as TSCA Confidential Business Information (TSCA CBI)
by those person(s) reporting for the TSCA Inventory, nor does it
include any information that would compromise TSCA CBI. The data
submitted for the TSCA Inventory, including production range in-
formation, are subject to the limitations contained in the TSCA
Inventory Reporting Regulations (40 CFR 710).
According to the May 7, 1984 issue of Chemical & Engineering
News, an estimated 2 billion pounds of vinyl acetate were pro-
duced domestically in 1983. According to secondary literature
sources, the major use of vinyl acetate is in the manufacture of
polymers, such as poly(vinyl acetate), poly(vinyl alcohol), vinyl
chloride co-polymer, and ethylene-vinyl acetate co-polymers.
Comments/Recommendations
In view of the fact that a number of Section 8(e) notices have
been received thus far on behalf of chemical companies, the pur-
pose of the following discussion is to reiterate EPA'S policy
with regard to the TSCA Section 8(e) reporting obligation of
organizations/associations such as SPI, the American petroleum
Institute (API), the Chemical Manufacturers Association (CMA),
the Chemical Industry Institute of Toxicology (CIIT), etc~ a~d
companies that may be members of such organizations/assocIatIons.
10
-------
8EHQ-0185-0543
Page 3 of 4
Section 8(e) of the Toxic Substances Control Act states that
"any person who manufactures, [imports,] processes, or dis-
tributes 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 informa tion."
The Agency's TSCA Section 8(e) policy statement ("Statement
of Interpretation and Enforcement policy; Notification of
Substantial Risk" 43 FR 11110; March 16, 1978) states that
the term "person" includes "any natural person, corporation,
firm, company, joint-venture, sole proprietorship, associa-
tion, or any other business entity...." Therefore, the
obligation to immediately report substantial risk information
would apply to an organization/association such as SPI, CMA,
API, CIIT, etc. only if such organization/association engages
in the manufacture, import, processing, or distribution of
the chemical substance or mixture about which substantial
risk information has been obtained. However, it is more
likely that a Section 8(e) reporting obligation would be
incurred by a member (or non-member) company that obtains
the results (including preliminary results) from studies
conducted or sponsored by an organization/association, if
the obtained results meet the reporting criteria outlined
in the TSCA Section 8(e) policy statement and pertain to a
chemical substance or mixture that the company manufactures,
imports, processes, or distributes in commerce.
Part III of the TSCA Section 8(e) policy statement explains
that su~tantial risk information is obtained at that time
when any offi~er or employee of a subject company, who is
capable of appreciating the significance of the information,
possesses, or knows of, such information. With the exception
of information about "Emergency Incidents of Environmental
Contamination," the obligation to immediately report sub-
stantial risk information is considered discharged if EPA
receives the information 1) in accordance with the reporting
requirements specified in Part IX of the Section 8(e) policy
statement, and 2) not later than the 15th working day after
the date the information was obtained. Information need not
be reported, however, if the subject person has actual know-
ledge that the Agency has already been adequately informed
about the information. Part VII of the Section 8(e) policy
statement provides further guidance with regard to the types
of information that need not be reported to EPA under Section
8(e) of TSCA. In addition, Section 3 of TSCA itself lists
those materials (e.g., drugs, pesticides) that are not
regulated by TSCA.
Finally, it should be noted that a company that obtains
substantial risk information and relies on another party to
11
-------
8EHQ-0185-0543
Page 4 of 4
submit the information to EPA under Section 8(ej on the
7ompany's behalf, must ensure that the Agency receives the
information in a timely manner and in accordance with the
reporting requirements specified in Part IX of the Section
8(e) policy statement.
The cover letter of SPIts TSCA Section 8(e) submission indicated
that copies of the reported findings had also been sent to OSHA,
CPSC and FDA.
EPA's Office of Toxic Substances (OTS) has received and evaluated
a number of TSCA Section 8(e) and "For Your Information" (FYI)
submissions containing toxicologic and/or exposure data on vinyl
acetate. In addition, the Chemical Screening Branch has prepared
a Chemical Hazard Information Profile (CHIP) on vinyl acetate.
a)
b)
The Chemical Screening Branch will ask the members of
SPIts Vinyl Acetate Task Force to ensure that EPA is
apprised in a timely manner about future significant
findings from all studies cited in the submission and
to ensure that the Agency receives in a timely manner
complete copies of the final reports (including actual
experimental protocols and data) from those studies.
SPI will be asked to distribute copies of this status
report to the members of its vinyl Acetate Task Force.
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OW/EPA,
OSWER/EPA, OAR/EPA, ORD/EPA, and the Risk Management
Branch (RMB/ECAD/OTS). In addition, copies of this
status report will be provided to the TSCA Assistance
Office (TAO/OTS/OPTS/EPA) for further distribution.
12
-------
DA 1£:
t-M-1116
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
3EHQ-0285-0544
Page 1 of 3
APp=ovedc:J;t- 'p,/,f
SUIJttT, Status Report* 8EHQ-0 28 5-0 544
'10M, David R. Williams~ection 8(e) Coordinator
Chemical Risk Identification Section/CSB
Revision
Needed
TO, Fran~ D. Kover, Branch Chief
Chemlcal Screening Branch/ECAD/OTS/OPTS
Submission Description
The CIBA-GEIGY Corporation provided summarized final results from
an oral (rat) range-finding study and summarized preliminary
results from an ongoing oral (rat) teratology study of commercial
grade [[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methyl]thio]-
acetic acid, 2-ethylhexyl ester (CAS No. 80387-97-9). CIBA-GEIGY
provided the following information with regard to the design and
results of the ~ubject studies conducted at the toxicology labor-
atory at CIBA-GEIGY, Ltd. in Basel, Switzerland:
"In a preliminary range-finding study, the test material was
administered in peanut oil, by gavage, to 8 pregnant rats at
dose levels of 200 or 400 mg/kg/day from day 6 through 15 of
gestation. A control group of 8 dams was treated similarly
with the peanut oil vehicle only. No overt effects were
observed in the dams or the offspring of the 200 mg/kg/day
group. However, at the 400 mg/kg/day level, the resorption
rate was markedly increased (86%) and only 1 of 8 females
had live fetuses at sacrifice on day 21 post coitum.
"Based on these results, the dose levels for the standard
FDA Segment II [teratology] study were selected at 50, 150,
and 300 mg/kg/day. preliminary findings from this study
indicated a high resorption rate (61%) in the 300 mg/kg/day
group. Thirteen [13] of 23 dams in this group had no live
offspring (i.e., showed only resorption sites) and gross ex-
ternal examination of the fetuses from the remaining 10 dams
revealed a high incidence of malformations and/or anomalies
in 6 of the litters (from 1 to 12 fetuses affected per lit-
ter). The predominant type of malformation involved the
distal parts of the extremities (ectrodactyly and adactyly)."
In its submission, CIBA-GEIGY stated that "an analysis and report
will be prepared by the Basel toxicology laboratory, probably to
be completed by June or July of ...[1985]."
*NOTE: T~is status reDo=t is the result of a Drelimina=v
staff evaluation of i~for.mation submitted to EPA. State;e~ts
mace herein are no~ to be regarded as expressing final
Ase~cy policy or intent with res?ec~ to t~is particular
chemical. .~y review of the status report should take into
consideration the fact that it may be based on incomplete
informa tion.
13
-------
8EHQ-0285-0544
Page 2 of 3
Submission Evaluation
Although the submitted information does indicate that the subject
chemical and/or its metabolite(s) can cause adverse developmental
effects in rats, a more in-depth evaluation of the overall sig-
nificance of the reported findings should be possible upon EPA'S
receipt of complete copies of the final reports (including the
actual experimental protocols and data) from the range-finding
and Segment II teratology studies.
It should be noted that the tested chemical can hydrolyze to a
"hindered" phenol methylthioacetic acid and 2-ethylhexanol. The
2-ethylhexanol can undergo further metabolism to 2-ethylhexanoic
acid, a chemical structurally similar to the known developmental
toxicant, valproic acid (i.e., 2-propylpentanoic acid). The Test
Rules Development Branch (TRDB/ECAD/OTS) is currently evaluating
available toxicity/exposure information on 2-ethylhexanoic acid,
a chemical recommended by the Interagency Testing Committee (ITC)
for testing consideration under TSCA Section 4. The "hindered"
phenol methylthioacetic acid portion of the tested chemical con-
tains a butylated hydroxy toluene (BHT) moiety. Staff of the Risk
Management Branch (RMB/ECAD/OTS) is in the process of evaluating
the available toxicity/exposure data on BHT, a substance for
which the Chemical Screening Branch (CSB/ECAD/OTS) has prepared a
Chemical Hazard Information Profile (CHIP).
Current Production and Use
The tested chemical (CAS No. 80387-97-9) is listed in the non-
confidential version of the TSCA Inventory and was the subject of
a Premanufacture Notice (PMN) submitted to EPA under Section 5 of
TSCA.
CIBA-GEIGY stated that the tested chemical, which "is a very low
vapor pressure, semi-viscous, liquid, (approximately 4.5 x 10-7
mm Hg at 20°C), had [a] commercial use, or potential commercial
use, as an antioxidant for elastomers, adhesives and lubricating
oils." CIBA-GEIGY stated that "to date, about 2000 lbs. of this
substance has been commercially distributed to one customer."
Comments/Recommendations
In its submission, the CIBA-Geigy Corporation stated that a copy
of the final study report would be sent to EPA upon the company's
receipt and assessment of that report. In addition, CIBA-GEIGY
stated that the company is planning "to confirm the preliminary
results, analyze the complete result and determine the no effect
level." Finally, CIBA-GEIGY stated that in response to the sub-
mi t ted find ings, the company will I) "inform... [CIBA-GEIGY]
employees and all companies to whom this chemical substance was
distributed, whether for commercial or research and development
purposes, of these preliminary findings" and 2) "withdraw the
product from the market and recall, for proper disposal by CIBA-
GEIGY, any samples distributed."
14
-------
( a. )
(b)
( c )
8EHQ-0285-0544
Page 3 of 3
The Chemical Screening Branch will request the CIBA-
GEIGY Corporation to submit complete copies of final
reports (including the actual experimental protocols and
data) from the range-finding study and the segment II
teratology study cited in the submission.
The Chemical Screening Branch will review the reported
findings in order to determine the need for further OTS
assessment of the the subject chemical.
The Chemical Screening Branch will send copies of this
status report to OSHA, NIOSH, CPSC, FDA, NTP, OW/EPA,
OSWER/EPA, OAR/EPA, ORD/EPA, CCD/OTS, TRDB/ECAD/OTS, and
RMB/ECAD/OTS. Copies of this status report will also be
sent to the TSCA Assistance Office (TAO/OTS/OPTS/EPA)
for further distribution.
15
-------
UNITED STATES E~IVIRONMENTAL PROTECTION AGENCY
DATE:
tIR ,.8
3EH~-0285-0545 S
Page" of 4
App=oved r:Jt-
4141'5
.
SUIJEC:T. Status Report* 8EHQ-0 28 5-054 5 S
nOM, Davi? R. Williams~ection 8 (e) Coordinator
Chem1cal Risk Identification Section/CSB
Revision
Needed
Frank D. Kover, Branch Chief
TOI h . 1
C em1ca Screening Branch/ECAD/OTS/OPTS
Note
The CIBA-GEIGY Corporation has claimed the actual identity and
use of the subject substance to be TSCA Confidential Business
Information (TSCA CBI). The Information Management Division
(IMD/OTS/OPTS/EPA) has asked CIBA-GEIGY to substantiate these
claims. CIBA-GEIGY did report non-confidentially, however, that
the subject chemical is a "halophenoxy halophenyl substituted
heteromonocyclic heteromonocycle" which has the internal product
code: CGA-149071.
Submission Description
CIBA-GEIGY provided the following summarized preliminary findings
from a 52-week dietary feeding study of CGA-149071 in dogs:
"Ophthalmoscopic examinations (using focal illumination and
indirect opthalmoscopy) on dogs on test day 86 (week 13
examinations), revealed bilateral (unilateral in one dog),
equatorial, anterior cortical and posterior cortical
lenticular aberrations affecting all dogs in the high dose
group (6000 ppm) (10/10 male, 10/10 female). Opthalmo-
scopically, the lenticular changes were characterized as
va~uole~, water clefts, spoke-like opacities, and splitting
and separation of the lens suture lines with resultant "Y"
shaped fissures. All other ocular structures appeared
clinically unaffected at this time. No changes from normal
were seen in the eyes of other dogs on this experiment and
there appeared to be no visual deficit at this time."
CIBA-GEIGY also provided further information by phone concerning
this study. According to the company, beagles are being exposed
to the test chemical at doses of 0, 30, 1000, or 6000 ppm in the
feed. The company also stated that although the dogs in the 6000
ppm dose groups showed a slight (15%) weight loss and were slight-
ly anemic, no serious adverse effects (other than the serious ad-
verse eye effects found only the 6000 ppm groups) have been
observed thus far in any of the exposed animals.
-NOTE: T~is status reco=t is the resul~ of a prelirnina=y
staff evaluation of i~fo=mation submitt~ci to EPA. Sta~eme~ts
mace herein are no~ to be regarded as expressing final
Ase~cy policy or intent with respect ~o t~is ?articu~ar.
chemical. .~v review of the status report should taKe 1nto
consideration-the iact.that it may be based on incomplete
informa tion.
16
-------
3EHQ-0285-0545 S
Page 2 of 4
In its submission, CIBA-GEIGY reported that in response to the
preliminary findings, the company will:
" I.
Photograph the eyes of all dogs at this time.
2.
Perform monthly examinations of the eyes of the dogs.
3.
Remove the eyes during the scheduled 13-week necropsy
and during subsequent necropsies.
4 .
During histological processing of the eyes, remove
the lens of the left eye and process it separately
while processing the second eye routinely.
5.
Allow some dogs to undergo a period of compound
withdrawal, in which reversibility of the lenticular
changes might be seen in whole or in part."
Submission Evaluation
Although the submitted information indicates that CG-149071 can
cause lenticular aberrations, a more thorough evaluation of the
significance of the reported findings should be possible upon
EPA's receipt of a complete copy of the final repOrt (including
the actual experimental protocol and data) from the 52-week
dietary feeding study in dogs. It should be noted that although
systemic intoxication leading to lenticular aberrations is not
common, such adverse effects have been reported in the published
scientific literature to occur in laboratory animals and humans
following exposure to a number of substances.
CIBA-GEIGY stated in the submission that the observed lenticular
aberrations in the high dose groups did not appear to cause any
visual impairment. CIBA-GIEGY did not report, however, how the
dogs' visual integrity was tested/measured or if the sensitivity
of such measurements/tests was sufficient to detect subtle but
serious visual impairment over time. The proposed experimental
protocol changes and followup procedures appear to be appropriate
to determine whether the observed adverse effects are reversible.
Finally, it should be noted that CIBA-GEIGY's proposed hazard
communications pertain mainly to the avoidance of dermal and
ocular exposure and do not address the potential for inhalation
and/or oral exposure to the tested chemical. It may be, however,
that the physical/chemical properties of the substance preclude
such types of exposure.
Current Production and Use
The CIBA-GEIGY Corporation stated in its submission that the
tested chemical "is a research and development material which is
being evaluated for pesticidal purposes" and that the pesticidal
evaluations "have been conducted only under the supervision of
technicallY qualified personnel."
I
17
-------
8EHQ-0285-0545 S
Page 3 of 4
Comments/Recommendations
In its submission, the CIBA-GEIGY Corporation reported that the
company plans to provide the following notice to all personnel
who work with CGA-149071:
"Ocular changes in the dog have been noted after 13 weeks of
dietary exposure to high levels of CGA-149071. These changes
are areas of swelling in the lens. Gloves, goggles and
protective equipment should be used to prevent exposure to
CGA-l49071 until further information is available about this
effect."
In addition, CIBA-GEIGY reported that the CGA-l49071 container
labels will bear the following information:
"Eye changes in the dog have been noted in animal testing
with this compound. Wear gloves and goggles when handling
this compound."
----------------------------------------------------------------
The following discussion describes the relationship of the Toxic
Substances Control Act (TSCA) and the Federal Insecticide, Fungi-
cide and Rodenticide Act (FIFRA) to chemicals, pesticides, and
research and development (R&D) chemicals including those intended
as pesticides. Specifically. this discussion is intended to be
of assistance in determining whether to submit appropriate infor-
mation under TSCA ~8(e) or FIFRA ~6(a)(2).
EPA set forth its policy on the jurisdictional relationship
of TSCA to FIFRA in the TSCA Inventory reporting regulations
(43 FR 64585, December 23, 1977, Appendix A, Comments 37, 38
and 39). That jurisdictional policy is still in effect and
the responses to comments discussed in 43 FR 64585 are also
generally applicable to this dicussion.
Under TSCA, EPA can regulate certain activities involving
"chemical substances" and "mixtures." If a substance is
manufactured, processed, or distributed in commerce solely
for use as a pesticide, however, ~3 of TSCA excludes such
substance from TSCA regulation. If a substance has multiple
uses, only some of which are pesticidal, the remaining uses
fall within the jurisdiction of TSCA, with certain exceptions
(e.g., drugs).
In keeping with the policy expressed in the TSCA Inventory
regulations, EPA generally considers a substance to be a
pesticide within the meaning of FIFRA when that substance is
the subject of (1) a submission made to EPA as part of the
experimental use permit (EUP) process under FIFRA or (2) an
application for registration submitted to EPA under FIFRA.
Prior to this stage, however, the Agency treats the substance
18
-------
8EHQ-0285-0545 S
Page 4 of 4
as a "chemical substance" under the jurisdiction of TSCA.
Therefore, any "substantial risk" information on an R&D
substance that may arise prior to the EUP or registration
stage (even though such information might be submitted later
under FIFRA in an application for registration or experimen-
tal use permit) must be reported under TSCA ~8(e). EPA's
response to Comment 31 in Appendix B of the Agency's TSCA
~8(e) policy statement ("Statement of Interpretation and
Enforcement policy; Notification of Substantial Risk" 43 FR
11110; March 16, 1978)) provides additional guidance with
regard to the TSCA ~8(e) applicability and reportability of
information on R&D chemicals.
FIFRA ~6(a)(2) requires registrants to submit information
regarding unreasonable adverse effects of their pesticides on
the environment. In view of the fact that the FIFRA ~6(a) (2)
requirement exists for as long as a pesticide is registered
under FIFRA, any such information must be reported under
FIFRA ~6(a)(2) when the information becomes available to the
registrant. Registrants are not required to report this same
information under TSCA ~8(e). (See Part VII of EPA's TSCA
~8(e) policy statement.) If the substance is no longer a
registered pesticide but has uses that fall under the juris-
diction of TSCA, then reporting would be required under ~8(e)
for "substantial risk" information obtained on the chemical.
-----------------------------------------------------------------
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will request
the CIBA-GEIGY Corporation to ensure that EPA is apprised
in a timely manner about the nature of additional signi-
ficant results obtained from the ongoing dietary feeding
study of CGA-149071. CIBA-GEIGY will also be requested
to ensure that EPA receives a complete copy of the final
report (including actual experimental protocol and data)
from the subject study. In addition, CIBA-GEIGY will be
asked to describe the nature and available results of all
other studies that have been or are being conducted by or
for the company to determine the toxicity of or the expo-
sure to CGA-149071.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of CGA-149071.
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OW/EPA,
OSWER/EPA, OAR/EPA, ORD/EPA and OPP/OPTS/EPA. Copies of
this report will also be provided to the TSCA Assistance
Office (TAO/OTS/OPTS/EPA) for further distribution.
19
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DA TE:
APR I I 915
8EHQ-0285-0546
Page 1 of 6
\;Jlt~ 1/~/t)
SUBJECT: Status Report* 8EHQ-0285-0546 Approved:
FROM: David R. Williams~ection 8(e) Coordinator
Chemical Risk Identification Section/CSB
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Descriptio~
On behalf of its member companies, the International Lead Zinc
Research Organization (ILZRO), Inc. submitted a copy of a pre-
publication draft report entitled "Mortality in Employees of Lead
Battery Plants and Lead Production Plants, 1947-1980." According
to ILZRO, the subject study is an update of the results of previ-
ously pUblis£e~ ~Dalyses of mortality data for the same worker
population. " I ILZRO provided the following information con-
cerning the results of this new analysis:
"The report looks at two study groups occupationally exposed to
lead: 4,519 lead battery plant workers and 2,300 lead smelter
workers during the period 1947-1980. The limited lead exposure
data available for the two groups show that the study popula-
tion was exposed to lead in amounts far above current levels.
The study results are, in general, consistent with previously
published reports. However, certain statistical results may
represent new information. In particular, there was a stati-
stically significant excess of deaths from stomach cancer in
battery workers. The excess in number of deaths from stomach
cancers in lead smelter workers was not significantly greater
than for the general population. The report notes that 85% of
the stomach cancer deaths in battery workers and 89.9% of the
total deaths of battery workers occurred in men residing in
Pennsylvania which suggests that factors related to geogra-
phical residence or ethnicity may be important. The report
also notes that 'it is extremely doubtful [that] lead is a
carcinogen per se, the possibility remains that high local
concentrations could have a co-carcinogenic effect, particu-
larly operative in those whose dietary or alcohol intake pat-
terns are predisposed to higher-than-average gastric cancer
rates.' The report does not provide any basis for assessing
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this report should not be regarded
as expressing final EPA policy or intent with respect to th~ subject
chemical(s). Any review of this status report shoul~ take l~to account
the fact that the report may be based on incomplete lnformatlon.
20
-------
8EHQ-0285-0546
Page 2 of 6
the extent of risk, if any, associated with lead exposure
because there is no feasible way to establish the actual
exposure of the study population during their working life-
time. Such information is needed to relate epidemiologic
findings to risk estimates for chronic lead exposure...."
Submission Evaluation
The submitted report presents mortality analyses of 2,339 deaths
for men who had worked one year or more between 1946 and 1970 in
lead battery plants or in lead production facilities (smelters).
Previous biological monitoring of a number of these workers indi-
cated high level exposures to lead. For both groups (battery and
lead production workers), there was increased mortality from all
causes, from all neoplasms (specifically, cancers of the stomach,
liver and lung), from chronic nephritis, and from other hyperten-
sive disease (i.e., hypertensive conditions due to kidney damage
and not heart disease). More importantly, however, this study
showed a statistically significant trend between all-cause mor-
tality and cumulative lead exposure. This trend is qualitative
support for a possible dose response relationship.
The performed study was of historical prospective design and was
composed of 6,819 males from 10 battery plants (4,519 workers)
and 6 lead production plants (2,300 workers). In view of the
fact that the racial composition of these workers was not known,
the investigator used the mortality rates of u.s. white males to
derive the expected number of deaths. The investigator noted
that blood and urine monitoring from 1947-1972 indicated that
some of the workers had been heavily exposed to lead. For those
workers who had had their blood lead levels measured 3 or more
times, 22% of the battery workers (278 of 1387) and 27% of the
lead production workers (89 of 330) had blood lead means over 70
micrograms/deciliter. The current OSHA standard for blood lead
is 60 micrograms/deciliter. In addition, the investigator noted
that the cohort was fairly stable with the majority of workers
staying in the same job category.
The investigator studied these workers previously and published
several papers concerning those studies. In a follow-up study
through 1970 (1,356 deaths), a significant excess of deaths from
chronic renal disease and a nonsignificant excess of malignant
neop~astic deaths were observed for both battery workers and lead
production workers. In another follow-up study through 1975
(1~947 deaths), the investigator observed an excess of neoplastic
deaths only for smelter workers; this excess was explained mainly
by an excess of respiratory cancer deaths. The investigator also
noted that the excess mortality from chronic renal disease found
in the earlier follow-up analysis was not observed in the second
follow-up analysis.
The present analysis (i.e., the subject of this 8(e) submission)
extends the follow-up period through 1980, by which time 2,339
deaths had occurred. The investigator examined mortality in both
21
-------
8EHQ-0285-0546
Page 3 of 6
groups for (a) the entire 1947-1980 period, (b) the number of
years employed, (c) moving calendar periods, and (d) year of hire
(before or after January 1, 1946). In addition, a proportionate
mortality analysis of the deaths was performed to examine the in-
fluence of race. The analysis for all deaths between 1947-1980
showed significant excesses in mortality for both groups from all
causes (p
-------
8EHQ-0285-0546
Page 4 of 6
In conclusion, occupational lead exposure has a direct impact on
overall mortality, and the longer one is exposed, the greater the
impact. The submitted study supports previous evidence that lead
is a nephrotoxin and the observed excesses in hypertensive heart
disease mortality has been reported in other studies. More im-
portant are the significant excesses in neoplastic mortality, an
observation not easily found in the literature on lead-exposed
populations. Certainly ethnicity, diet, and personal habits
(e.g., smoking) are factors in cancer etiology, but the role of
lead cannot be diminished in light of the fact that excesses for
site-specific neoplasms (i.e., gastric cancers) were observed in
both groups of workers.
Immediately upon receipt of this Section 8(e) submission, the
Chemical Screening Branch provided copies to OW/EPA, OSWER/EPA,
OAR/EPA and ORD/EPA for use in any ongoing assessments of lead
toxicity and/or exposure.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for lead (CAS No. 7439-92-1), which is listed in the
initial TSCA Inventory, has shown that between 1.7 billion and
6.4 billion pounds were reported as produced and/or imported in
1977. This production range information does not include any
production/importation data claimed as TSCA Confidential Business
Information (TSCA CBI) by the person(s) reporting for the TSCA
Inventory, nor does it include any information that would compro-
mise TSCA CBI. The information submitted for the TSCA Inventory,
including the production range information, is subject to the
limitations contained in the TSCA Inventory Reporting Regulations
(40 CFR 710).
Lead is a heavy, blue-gray, soft metal that can be easily melted,
formed, rolled, cast, etc. The wide variety of lead uses include
the manufacture of pipes, coatings, and tanks; lead storage bat-
teries; metal alloys; pigments; organic/inorganic lead compounds
(e.g., tetraethyl lead which is used as a motor fuel additive);
and radiation shield materials. It should be noted that new EPA
standards will reduce the amount of lead in gasoline by 90% as of
January 1, 1986. According to EPA estimates, these new standards
will (by 1992) reduce by approximately I million the number of
persons with elevated blood lead levels.
Comments/Recommendations
In view of the fact that a number of Section 8(e) notices have
been received thus far on behalf of chemical companies, the pur-
pose of the following discussion is to reiterate EPA's policy
with regard to the TSCA Section 8(e) reporting obligation of
organizations/associations such as ILZRO, the American Petroleum
Institute (API), the Chemical Manufacturers Association (CMA),
the Chemical Industry Institute of Toxicology (CIIT), etc. and
companies that may be members of such organizations/associations.
23
-------
8EHQ-0285-0546
Page 5 of 6
Section 8(e) of the Toxic Substances Control Act states that
"any person who manufactures, [imports,] processes, or distri-
butes 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."
The Agency's TSCA Section 8(e) policy statement ("Statement of
Interpretation and Enforcement Policy; Notification of Substan-
tial Risk" 43 FR 11110; March 16, 1978) states that the term
"personh includes "any natural person, corporation, firm, com-
pany, joint-venture, sole proprietorship, association, or any
other business entity...." Therefore, the obligation to im-
mediately report substantial risk information would apply to an
organization/association only if that organization/association
engages in the manufacture, import, processing, or distribution
of the chemical substance or mixture about which substantial
risk information has been obtained. However, it is more likely
that an 8(e) reporting obligation would be incurred by a member
or non-member company that obtains the results (including pre-
liminary results) from studies conducted or sponsored by an
organization/association, if the obtained results meet the re-
porting criteria outlined in the Section 8(e) policy statement
and pertain to a chemical substance or mixture that the company
manufactures, imports, processes, or distributes in commerce.
Part III of the TSCA Section 8(e) policy statement explains
that substantial risk information is obtained at that time when
any officer or employee of a subject company, who is capable of
appreciating the significance of the information, possesses, or
knows of, such information. With the exception of information
on "Emergency Incidents of Environmental Contamination," the
obligation to immediately report substantial risk information
is considered discharged if EPA receives the information 1) in
accordance with the reporting requirements specified in Part IX
of the Section 8(e) policy statement, and 2) not later than the
15th working day after the date the information was obtained.
Information need not be reported, however, if the subject per-
'son has actual knowledge that EPA has already been adequately
informed about the information. Part VII of the Section 8(e)
policy statement provides further guidance with regard to the
types of information that need not be reported to the Agency
under TSCA Section 8(e). In addition, Section 3 of TSCA itself
lists those substances (e.g., drugs, pesticides) that are not
regulated by TSCA.
Finally, it should be noted that a company that relies on some
other party to submit information under Section 8(e) on the
company's behalf, must ensure that EPA receives the information
in a timely manner and in accordanye with the requirements in
Part IX of EPA's TSCA Section 8(e) policy statement.
24
-------
8EHQ-0285-0546
Pa ge 6 of 6
a)
The Chemical Screening Branch will request ILZRO, Inc. to
submit, when available, a complete copy of the final report
for the epidemiologic study "Mortality in Employees of Lead
Battery Plants and Lead Production Plants, 1947-1980."
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further OTS
assessment of lead.
c)
The Chemical Screening Branch will provide copies of this
status report to OSHA, NIOSH, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, OAR/EPA, and OPP/OPTS/EPA. Copies of the status
report will be sent also to the TSCA Assistance Office
(TAO/OTS/OPTS) for further distribution.
REFERENCES
.!/
y
1/
Cooper, W. et al. "Mortality of Lead Workers"~ J. Occ.
Med.~ 17~ 100-107 (1985)
Cooper, W. et al. "Mortality Study of Lead Workers"~
Archiv Za Higijenu Rad i Toksikologiju (Zagred)~ 26~ 209-
229~ (1976)
Cooper, W. et al. "Mortality in Workers in Lead Production
Facilities and Lead Battery Plants During the Period 1971-
1975." (This report was submitted to the International
Lead Zinc Research Organization on January 31, 1978).
25
-------
DAn;
APR I 0 1985
UNITED STATES Et-IVIROHMENTAL PROTECTION AGENCY
8EHQ-0385-0547
Page 1 of 3
SUIJ£CT, Status Report* 8EHQ-0385-0547
'IOM,David R. William~ection 8 (e) Coordinator
Chemical Risk Identification Section/CSB
1\pp=oved t:P--
4/11/rr
,
Revision
Needed
TO,Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Descriptio~
The Monsanto Company provided summarized preliminary results from
an ongoing toxicity/reproduction study of rats exposed via inhala-
tion to O,O-dimethylphosphorodithioaxe (CAS NO. 756-80-9) at doses
of 4.6, 26, or 161 mg/M3 for 6 hours/day, 5 days/week for 11 weeks
prior to mating. According to Monsanto, the preliminary data sug-
gest that at the two highest dose levels, O,O-dimethylphosphorodi-
thioate had a "deleterious effect" on the reproductive capacity of
male rats. In an addendum to the company's initial Section 8(e)
submission, Monsanto provided the following additional information
concerning the ongoing study:
"There were two sequential matings of treated males with un-
treated females, and of treated females with untreated males.
The endpoints were the number of impregnations and conceptions.
The measured mean exposure levels for this study were 0, 4.6,
26 and 172 mg/M3. There appeared to be no adverse effect on the
fertility of male rats exposed at the low dosage level. At the
mid dosage level no effect was noted at the first mating, while
a slight reduction in fertility was noted at the second mating.
Male rat fertility was markedly reduced at the high dosage le-
vel in both matings. There were fewer offspring in the high
exposure level females, but this effect is judged to be secon-
dary to maternal toxicity, as evidenced by various clinical
signs and body weight reductions of up to 28%. Since the males
are still on test, only gross observations have been made on
them. A previously known effect, corneal lesions, was noted at
all exposure levels. This is consistent with the known corro-
siveness of the material."
Submission Evaluation
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 (including the actual experimental protocol(s) and
data) from the ongoing inhalation toxicity/reproduction study.
-NOTE: This status reDo=t is the resul: of a prelirnina=y
staff evaluation of i~fo~a~ion submittec to ~PA. ~.Sta~eme~ts
mace herein are no~ 'to be regarded as ex?~~ss~r.q :~nal
Agency policy or i~tent with res?ec~ to ~~1S ?artlcul~r.
chemical. .~v reV1eW of the status repo-- shou~d tak= 1nto
consideration-the tact that it may be based on lncomplete
information. 26
-------
8EHQ-0385-0547
Page 2 of 3
Current production and Use
A review of the production range (includes importation volumes)
statistics for O,O-dimethylphosphorodithioate (CAS No. 756-80-9),
which is listed in the TSCA Inventory, has shown that between 11.1
million and 61 million pounds were reported as produced and/or im-
ported in 1977. This production range information does not include
any chemical production/importation data that were claimed as TSCA
Confidential Business Information (CBl) by those persons who re-
ported for the TSCA Inventory, nor does it include any information
that would compromise TSCA CBI. The data submitted for the TSCA
Inventory, including the production range information, are subject
to the limitations contained in the Inventory Reporting Regulations
(40 CFR 710).
Honsanto reported that it uses O,O-dimethylphosphorodithioate as an
intermediate in the manufacture of methyl parathion. According to
secondary literature sources, O,O-dimethylphosphorodithioate is
used to make O,O-dimethylphosphorochloridothioate, an intermediate
in the production of methyl parathion as well as a number of other
pesticides. Monsanto reported that the company's use of O,O-di-
methylphosphorodithioate "does not result in any exposures outside
the workplace." In addition, Monsanto reported that because the
company's "workplace exposures are maintained well below those used
in the rat study, workplace exposure to ...[O,O-dimethylphosphoro-
dithioate] does not present a hazard to ... [Monsanto] employees."
In the addendum, Monsanto stated that its internal workplace ex-
posure limit for O,O-dimethylphosphorodithioate is 0.4 mg/M3.
Comments/Recommendations
As stated previously, O,O-dimethylphosphorodithioate is used to
manufacture O,O-dimethylphosphorochloridothioate, a chemical that
has been reported (8EHQ-0381-0387 et seq.) to cause dominant lethal
effects when administered orally to male rats before mating. The
Chemical Screening Branch (CSB/ECAO/OTS/OPTS) has prepared Chemical
Hazard Information Profiles (CHIPs) on O,O-dimethylphosphorochlori-
dothioate and o,O-diethylphosphorochloridothioate; available toxi-
cologic and exposure data on these esters are being assessed by the
Risk Analysis Branch (RAB/ECAD/OTS/OPTS). In addition, it should
be noted that O,O-dimethylphosphorodithioate bears some degree of
structural analogy to the dialkylphosphorodithioate moieties of the
zinc dialkyldithiophosphates (ZOOPs). EPA has received a number of
TSCA Section 8(e) and "For Your Information" (FYI) submissions, and
TSCA Section 5 Premanufacture Notifications (PMNS) on ZOOPs.
a)
The Chemical Screening Branch (CSB/ECAO/OTS/OPTS) will request
the Monsanto Company to ensure that EPA receives a complete
copy of the final report (including the actual experimental
protocol(s) and data) from the ongoing toxicity/reproduction
study of O,O-dimethylphosphorodithioate.
27
-------
8EHQ-0385-0547
Page 3 of 3
In view of EPA's general interest in corporate actions that are
taken on a voluntary basis in response to toxicologic/exposure
information, the Chemical Screening Branch will ask Monsanto to
describe the actions the company has taken to notify its own
workers about the results of the ongoing toxicity/reproduction
study. In addition, Monsanto will be asked to describe the
nature and available results of all other studies that Monsanto
has conducted, is conducting, or plans to conduct to determine
the toxicity of O,O-dimethylphosphorodithioate.
b)
The Chemical Screening Branch will review the reported findings
in order to determine the need for further OTS assessment of
O,O-dimethylphosphorodithioate.
c)
The Chemical Screening Branch will send copies of this status
report to OSHA, NIOSH, CPSC, FDA, NTP, OSWER/EPA, OW/EPA,
OAR/EPA, ORD/EPA, OPP/OPTS/EPA, CCD/OTS, and RAB/ECAD/OTS.
Copies of this status report will be sent also to the TSCA
Assistance Office (TAO/OTS/OPTS/EPA) for further distribution.
28
-------
DATE:
MAY I 3 1985
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0485-0548
Page 1 of 3
SUBJECT:
status Report* 8EHQ-0485-0548
Approved:
\~ ,/Jr/5'f
FROM: James F. Darr, Section Head ~?r V(VYI..----
Chemical Risk Identificatiogse~tion/CSB
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Note (See NOI'E on page 3 of this status report)
The submitting company claimed its name and the exact chemical
identity and proilosed use of the subject chemical to be TSCA
Confidential Business Information (TSCA CBI). The Information
Management Division (IMD/OTS/OPTS) will request the company to
substantiate these confidentiality claims. The submitter des-
cribed the subject chemical non-confidentially as a "triazole"
currently at the research and development (R&D) stage.
Submission Description
The submitting company provided summarized preliminary results of
a teratology study of the subject chemical administered orally at
doses of 0, 62.5, 125, 250, or 500 mg/kg to pregnant rats. Ac-
cording to the submitter, the study results obtained thus far
"indicate dose and treatment-related increases in external mal-
formations among the fetuses from dams treated at 250 or 500
mg/kg, but not at 62.5 or 125 mg/kg." The submitter reported
that internal soft tissue and skeletal findings are not yet
available. The submitter also reported that "a completed rabbit
teratology study conducted at lower dose levels was negative."
The submitting company also provided a sanitized version of a
revised Material Safety Data Sheet (MSDS) which reflects the
preliminary results of the rat teratology study as well as the
final results of the rabbit teratology study. According to the
MSDS, the rabbit teratology study involved oral administration of
the chemical at doses of 0, 3, 10, or 30 mg/kg. In addition, the
MSDS states that the oral LD50's for the chemical were found to
be 639 mg/kg and 474 mg/kg in male and female rats, respectively.
The MSDS states also that the subject chemical was found to be
only slightly irritating to rabbit eyes and non-irritating to
rabbit skin. Finally, the MSDS notes that inhalation toxicity
studies have not as yet been conducted with the subject chemical.
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
29
-------
8EHQ-0485-0548
Page 2 of 3
Submission Evaluation
The submitted information does indicate that the tested chemical
can cause dose-related adverse developmental effects in rats. A
more complete evaluation of the overall significance of these
findings should be possible upon EPA's receipt of full copies of
the final reports (including the actual experimental protocol(s)
and data) from the rat and rabbit teratology studies cited in the
submission.
Current Production and Use
(See NarE on page 3 of this status report)
As previously stated, the subject chemical is in the research and
development (R&D) stage; the planned use of the chemical has been
claimed as TSCA CBI.
Comments/Recommendations
a)
The Chemical Screening Branch (CSB/ECAD/OTS/OPTS) will ask
the submitter to ensure that immediately upon completion,
EPA receives a full copy of the final report (including the
actual experimental protocol(s) and data) from the rat ter-
atology study, the preliminary results of which were cited
in the submission. In addition, the submitter will be re-
quested to submit a complete copy of the final report (in-
cluding the actual experimental protocol(s) and data) from
the rabbit teratology study cited in the submission.
In view of the Agency'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
request the submitting company to describe the nature and
available results of all studies (other than those cited in
the provided MSDS) that the company has conducted, is con-
ducting, or plans to conduct to determine the toxicity of
and/or the exposure to the subject chemical substance. The
submitting company will be requested also to describe the
actions that the company has taken (in addition to revising
and distributing the MSDS) to 1) notify workers and others
about the reported rat teratology findings, and 2) reduce
and/or eliminate exposure to the subject chemical.
b)
The Chemical Screening Branch will review the reported in-
formation 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 OSHA, NIOSH, CPSC, FDA, NTP, OW/EPA,
OSWER/EPA, ORD/EPA, OAR/EPA, and OPP/OPTS. In addition,
copies of this status report will be transmitted to the
TSCA Assistance Office (TAO/OTS/OPTS/EPA) for further
distribution.
30
-------
8EHQ-0485-0548
Page 3 of 3
NOTE
In a letter dated July 3, 1985 (8EHQ-0785-0548 Followup), the
Chevron Chemical Company withdrew all confidentiality claims for
the initial 8(e) submission. According to Chevron, the subject
chemical is (E)-1-(2,4-dichlorophenyl)-4,4-dimethyl-2-(1,2,4-
triazol-l-yl)-penten-3-o1 (CAS No. 76714-88-0), an R&D fungicide
for which Chevron plans to apply for an experimental use permit
(EUP) and registration under the Federal Insecticide, Fungicide
and Rodenticide Act (FIFRA).
Copies of this updated status report will be transmitted to all
Offices/Agencies listed in (c) of the Comments/Recommendations
section found on page 2 of the status report.
~ b~ ~ :11<65
31
-------
DATE:
MAY I 4 198~
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0485-0549 S
Page 1 of 4
SUBJECT: status Report*
8EHQ-0485-0549 S
Approved: ~ 5jltfJ '8'5'
FROM: James F. Darr, section Head ~ 'f. ~
Chemical Risk Identification Section/CSB
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The National Starch dnd Chemical Corporation provided the final
reports from acute (4-hour) and sub-acute (14-day) rat inhalation
studies of a high molecular weight (>6,000,000) sodium carbonate
stabilized sulfonated polystyrene, sodium salt (CAS No. 9080-79-
9). The submitting company reported that the results of these
studies suggest a possible risk of lung function impairment fol-
lowing inhalation of respirable dry polymer particles.
According to the provided acute study final report, Sprague-
Dawley rats (25/sex) were exposed via inhalation to a polymer
dust aerosol containing actual average concentrations of 1.2,
2.2, 3.0, or 4.6 mg/l for 4 hours followed by a 14-day observd-
tion period. The LC50s were found to be 2.6 mg/l and 3.5 mg/l
for male and female rats, respectively. The combined-sex LC50
was calculated to be 3.0 mg/l.
The following information concerning the conduct and results of
the 14-day sub-acute inhalation study was presented in the ab-
stract of the submitted final report:
"Five male and five female Sprague-Dawley rats were exposed to
a dust aerosol containing either 0.14, 0.34 or 1.07 mg/l (mean
average actual concentration by gravimetric determination) of
. . . [the polymer] for six hours daily, five days per week
(Monday-Friday), for two consecutive weeks. An additional
group of five animals per sex was designated to serve as the
control group.
"The animals were observed periodically during each exposure as
well as daily for external signs of toxicity and mortality.
Body weight was recorded periodically and food consumption was
determined weekly for all surviving animals. After the last
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e). the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this report should not be regarded
as expressing final EPA policy or intent with respect to th~ subject
chemical(s). Any review of this status report shoul~ take l~to account
the fact that the report may be based on incomplete lnformatlon.
32
-------
8EEQ-0485-0549 S
Page 2 of 4
exposure (tenth), the surviving animals of each test group were
randomizeJ to determine which animals would be assiyned to the
14-day post-ex~osure recovery period (satellite groups). The
animals which were selected (satellite groups) were observed
for signs of recovery and mortctlity. Selected hematological,
clinical chemistry and urine analysis determinations were made
after ten exposures on the animals not assigned to the satel-
lite groups. The same hematological and clinical chemistry
paranleters were also detenoined on all animals surviving the
14-day post-ex~osure recovery period. The animals designated
for clinical laboratory studies after ten exposures were sac-
rificed on study day 15. The animctls of the satellite groups
were sacrificed on study day 26. All animals were subjected to
a complete gross necropsy. The absolute and relative weights
of adrenal glands, brain, kidneys, liver, lungs (including
trachea) and gonads were determined for each animal. Detailed
llistopathological evaluations were performed on all animals in
the control and high exposure groups and on any animal that
expired on test.
"Under the condi tions of this study, the test article. . via
inhalation by "nose-only" exposure demonstrated compound-related
lesions consisting of an accumulation of septal cells in the al-
veoli, perivascular edema and vascular congestion of the lungs
in both sexes."
Submission Evaluation
The submitted acute inhalation study established a median lethal
concentration (LC50) for rats of both sexes at 3 mg/liter for a
four-hour exposure. Particle sizing indicated that a substantial
portion (perhaps 20%) could reach the alveoli. The findinys were
generally unremarkable, except that the study demonstrated that
an acute exposure to a high (e.g., median-lethal) concentration
of this polymer was associated with bronchiolar obstruction in
rats. If similar effects occurred in humans, it would raise
concern for chronic obstructive pulmonary disease (COPD).
'rile second stucJy was a 14-day dust aerosol inhalation study in
male and female rats exposed (nose-only) to 0.14, 0.34, or 1.2
r.I'9/1. Approx irna te ly 30 % of the particles were of a si ze that
would be expected to reach the alveoli. ~here appeared to be a
real, exposure-related, dose-related toxic effect. Several
animal deaths were attributed to pulmonary edema. Microscopic
examination of the lungs showed vascular congestion, perivascular
edema, and cellular debris (i.e., "septal cells. [that] most
likely are a mixture of alveolar Inacrophages and type-II pneumo-
cytes") in the alveolar spaces in the lungs of the exposed rats.
The alveolar cellular accumulation was not reversible in the 14-
day recovery period. This apparent killing of pulmonary alveolar
macrophages is reminiscent of findings as presented in several
previous submissions received by the Agency under Sections 5 and
8(e) of TSCA.
33
-------
8EHQ-0485-0549 S
Page 3 of 4
Killing of alveolar macrophages could impair local or general
host defense mechanisms and lung clearance, which could in turn
have adverse health consequences in situations involving chronic
exposure. Killing type-II pneumocytes could il:lpair the produc-
tion of pulmonary surfactant, which could in turn lead to lung
collapse in the affected area. The findings of "fluffy" lungs
upon acute exposure (with bronchiolar obstruction) does not pre-
clude the development of foci of collapsed alveoli in areas where
there was inadequate surfactant, and either effect (obstruction
or alveolar collapse) would impair yaseous exchange ill the lung.
The 14-day inhalation study is instructive on two points. First
it shows the iInlJortance of actually l~leasuring the concentration
and/or particle sizes of the test material within the eXlJosure
chamber; the nominal (estimated) concentrations in the 14-aay
study were far off the joark.. Second, the results of the study
show that a substance with a molecular weight of several ~illion
can elicit toxic effects.
Current Production
National Starch and Chemical clai~ed its production volume for
the polymer to be TSCA Confidential Business Information (TSCA
CBI). The Information f.1anagement Division (HlD/OTS/OP'l'S/EPA)
will request the submitting company to substantiate this claim.
A review of the production range (includes importation volumes)
statistics for CAS No. 9080-79-9, which is listed in the TSCA
Inventory, has shown that between 20 thousand and 201 thousand
pounds of this chemical were reported as produced/imported in
1977. This production ranye information does not include any
production/importation data claimed as confidential by the per-
son(s) reporting for the TSCA Inventory, nor does it include any
information which would compromise TSCA CBI. The data submitted
for the TSCA Inventory, including production range information,
are subject to the limitations contained in the TSCA Inventory
Reporting Regulations (40 CFR 710).
According to the submitter, the subject polymer is used as a
"fluid loss control additive [in liquid form) in oil field
applications." The submitter also reported that because the
company believes that "the greatest potential for human exposure
lies in the manufacture of the subject polymer," com~any em-
ployees are required "to wear protective clothing and utilize
toxic dust respirators during the manufacture and packaging
operations."
Comments/Recommendations
The National Starch and Chemical Corporation submitted the
following information with regard to the company's additional
risk-reduction activities for the subject polywer:
34
-------
8EHQ-0485-0549 S
Page 4 of 4
"'rhe submitting company has an active program to eliminate or
minimize the dust hazard due to this polymer. Changes in the
manufacturing process are being studied which will result in
less dust produced during the manufacturing and packaging pro-
cess. Additional changes to the manufacturing process are be-
ing considered to increase the particle size dijnension thereby
reducing respirable particles. Consideration is also being
given to changing the physical form of the end product from a
powder to a liguid. The submitting company has taken measures
to amend the product technical bulletin and MSDS [Material
Safety Data Sheet] to reflect a potential health hazard due
to inhalation of respirable ~articles. Customers will receive
the amended product information accompanied by an explanatory
covering letter, recommending appropriate dust protection
measures."
a) In view of EPl-, , s general interest in cO!:1pany actions that are
taken on a voluntar} basis in response to chemical toxicity or
exposure data, the Chemical Screening Branch (CSBjECADjOTS)
will request the National Starch and Chemical Corporation to
describe the nature and available results of all other studies
that the company has conducted, is conducting, or plans to
conduct to define the toxicity of andjor the exposure to the
subject polymer. National Starch and Chemical will be asked
also to provide complete copies of the updated product bul-
letinand MSDS for the tested ~olymer as well as a copy of
the customer notification letter.
b) The Chemical Screening Branch will review the reported infor-
mation to determine the need for further OTS assessment of the
subject polymer.
c) The Chemical Screening Branch will tranffiait copies of this
status report to NIOSH, OSHA, CPSC, NTP, OWjEPA, OSWERjBPA,
OARjEPA, and ORDjLPA. Copies of this status report will be
sent also to the TSCA Assistance Office (TAOjOTSjOPTS) for
further distribution.
35
-------
DATE:
MAY I 6 1985
UNITED STATES ENV"IRONMENTAl PROTECTION AGENCY
8EHQ-0485-0550
Page 1 of 5
APproved:~
8EHQ-0485-0550
S-f?/Y5
SUBJECT: Status Report*
FROM: James F. Darr, Section Head fk-,~ i: ~
Chemical Risk Identificatiorl7~~~~ion/CSB
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
E. I. Dupont de Nemours & Company, Inc. submitted summarized
preliminary results from a two-year study of rats exposed via
inhalation to respirable fibrils of poly p-phenylene terepthal-
amide (PPD-T) aramid fibers. According to DuPont,
"Exposure of test animals to respirable PPD-T aramid fibrils in
a two year inhalation study resulted in a low incidence of lung
tumors but only at the two highest levels of exposure - 100 ana
400 fibrils/cc of air. The lower [PPD-T aramid fibril] level
is greater than 500 to 1000 times that which typically occurs
in the workplace and both levels are attainable only under ar-
tificially generated conditions in the laboratory. The tumors
observed are of a type not found in humans. Exposures of ani-
mals at lower levels, but still many times greater than those
which typically occur under actual use conditions with PPD-T
aramid, are free of toxicologically significant effects."
DuPont also provided the following information with regard to the
conduct and results of the performed study:
"Exposure atmospheres for this study had to be artificially
generated since airborne concentrations of respirable PPD-T
fibrils at the levels selected for testing cannot normally be
obtained even by suspending commercially available PPD-T pulp
in air. [Pulp is a finely ground form of PPD-T fiber vlhich
because of its physical nature contains more fibrils than other
forms of the fiber.] Initial attempts with conventional dust-
generating techniques failed to produce sufficient concentra-
tions of respirable particles to conduct the test because
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this report should not be regarded
as expressing final EPA policy or intent with respect to th~ subject
chemical(s). Any review of this status report shoul~ take l~to account
the fact that the report may be based on incomplete lnformatlon.
36
-------
8EHQ-0485-0550
Page 2 of 5
respirable PPD-T fibrils are readily agglomerated by physical
entanglement and electrostatic attraction. To overcome this
natural bonding of fibrils in pulp, a high-pressure, air im-
pinging device was developed for the specific purpose of
separating the ultrafine fibrils from the pulp matrix and
keeping them suspended in air.
"In this study, 100 male and 100 female Sprague-Dawley rats
were exvosed to respirable PPD-T fibriLs at atmospheric concen-
trations of 0, 2.5, 25, 100 or 400 fibrils/cc, six hours a day,
five days a week. Lxposures at 0, 2.5, 25, and 100 fibrils/cc
were for 104 weeks. However, because of early mortality due to
obliterative bronchiolitis (i.e., the lower airways of the test
animals were blocked by the reaction to the massive dose of fi-
brils which reagglomerated in the lungs), rats were exposed to
400 fiorils/cc for only 52 weeks and were held for an addition-
al 52 weeks ~rior to sacrifice.
"All rats were sacrificed at the end of the 104-week exposure
period. Histopathological exawination of the lungs of these
rats showed no increased incidence of lung tumors at exposure
concentrations below 100 fibrils/cc. Those rats exposed to 100
fibrils/cc and 400 fibrils/cc revealed an incidence of tumors
identified as cystic keratinizing squamous cell carcinomas (6
of 56 females and 1 of 36 males at 400 fibrils/cc; 4 of 69 fe-
males and 0 of 68 males at 100 fibrils/cc). host tumors were
noninvasive, none metastasized to regional lymph nodes or other
vital organs and they were not life shortening. Slight fibro-
sis was also observed in the lungs of rats exposed to 100 or
400 fibrils/cc. This slight fibrogenic response was equivocal
at 25 fibrils/cc, and was not observed at 2.5 fibrils/cc.
"Among [those] rats sacrificed at interim times of three, six
and twelve months, no tumors were observed at any of the expo-
sure concentrations. A lung tumor (also a cystic keratinizing
sy:uamous cell carcinoma) \Vas observed in a female rat exposed
to 400 fibrils/cc and sacrificed at 18 months.
"In those rats found to have lung tumors, all other major
organs and tissues have been examined, and have been found to
be free of tumors or other compound related abnormalities.
"Ba~ed on .. [DuPont's] review of these test results and
other data, [DuPont believes] that current industrial
p~actices are sufficient to preclude exposures to humans that
would result in any adverse health effects. This is especially
true because of 1) the extreme difficulty in creating condi-
tions in which high levels of fibrils are suspended in air, and
2) the fact that. [Dupont knows] of no case from any cause
in which tumors of the type observed in the test rats have oc-
curred in man (the tumors observed in this study are identical
to some observed in rats exposed to high levels of several
other particulates)."
37
-------
8EHQ-0485-0550
Page 3 of 5
In addition to reporting the preliminary results of the 2-year
inhalation study, DuPont provided the following information with
regard to the results of other toxicologic studies of PPD-T:
"PPD-T polymer has very low acute oral toxicity (approximate
lethal dose is greater than 7500 mg/kg). Both human and animal
dermal tests have indicated no potential for skin sensitization
and minimal skin irritation. Previous published pulmonary toxi-
city studies [Lee et al., Pulmonary Response to Inhaled Kevlar@
Aramid Synthetic Fibers Toxicology and Applied Pharmacology;
71: 242-253; 1983] have shown that a two week exposure of rats
to extremely high concentrations (approximately 1000 fibrils/
cc) of respirable size particles can produce pulmonary fibrosis
that is detectable one month after cessation of exposure."
Submission Evaluation
Evidence that has been accumulating since about 1970 incredsirlg1y
lends credence to the view that the carcinogenicity of asbestos
fibers is due mainly to their submicroscopic, needle-li~e shape,
rather than to their chemical composition, physical/chemical pro-
perties, or impurities. It appears that asbestos fibers exhibit
maximal carcinogenic activity when they have diameters less than
1.5 urn and lengths greater than 8 urn. In addition, it appears
that tumorigenicity is enhanced by decreases in fiber diameter
and increases in fiber length.
Accordingly, mesotheliomas have been induced experimentally with
non-asbestos substances that occur naturally as fibers or that
are processed to critical fiber dimensions. Such substances in-
clude: the fibrous magnesium hydroxide minerals (i.e., brucite
and nemalith), various types of fibrous glass, and different
types of fibrous aluminum oxide. Non-fibrous samples of these
same materials have not been shown to date to exhibit oncogenic
activity in laboratory animals. Most of the experiments that
involve asbestos and asbestiform fibers have been conducted with
rodents exposed by intraperitoneal injection, a route of exposure
that appears to be much more sensitive than other exposure routes
(including inhalation) to detect the maximal carcinogenicity of
fibrous materials. Also, there is an increasing realization that
the carcinogenic potential of asbestos in humans is not limited
to induction of lung carcinomas and pleural mesothelioma, the
typical asbestos cancer. It has been shown that exposure to
asbestos can lead also to mesothelioma of the peritoneum and to
carcinoma of the larynx, esophagus, and stomach.
The potential risk(s) posed by human exposure to PPD-T aramid
fibers (the subject of the present submission) should be con-
sidered against the above background information. In DuPont's
two-year rat inhalation study, PPD-T ararnid fibers were found to
produce tumors only at the 100 and 400 fibrils/cc dose levels.
It is not known if these fibers have ever been tested via intra-
peritoneal injection in rodents.
38
-------
8EEQ-0485-0550
Page 4 of 5
Current Production and Use
Aramid fibers and a number of other substances (e.g., poly tetra-
fluoroethylene (Teflon@), polyethylene, f-'olYi)ropylene, polyester,
ductile iron pipe) may be used as partial, total or potential
substitutes for asbestos. In support of the Agency's asbestos
risk assessment activities, the Chemical Screening Branch
(CSB/ECAD/OTS/OPTS) has prepared an asbestos substitute "health
hazard profile" report on aramid fibers as well as the other
substances H1entioned above. 'l'he following use information for
aramid fibers is presented in the summary of that report (lAG 00.
DW-89930405-10-u, ~~ork AssignHlent 3, TasK 1; Sl\IC/JRB project No.
2-813-07-419-00; November 2, 1984):
"Aramid fibers, characterized by high tensile strength, medium
to low elongation, moderately high to ultra high modules, dnd
chemical and flame resistance, lend themselves to a variety of
applications as asbestos substitutes, including gaskets, brake
linings, friction materials, pump packing, and electrical paper
and tape."
In its TSCA Section 8(e) notice, DuPont provided the following
information concerning exposure to PPD-T aramid fibers:
"The exposure concentrations (400 fibrils/cc and 100 fibrils/cc
of respi rable dus t) that produced tunlOrs [in the 2-year inhala-
tion study] are well above those that can be generated in the
workplace. This opinion is supported by monitoring data using
procedures prescribed by NIOSH . .. [DuPont] has measured
airborne levels of respirable fibrils in . [DuPont's]
manufacturing operations and in some customers' plants. As
examples, in . [DuPont's] f iberrnanufacturi n9 opera tioris,
the fibril concentration is below the 0.1 fibril/cc detection
limit. 1n a customer operation in which PPD-~ arumid fieer
pulp was used in comuination with mineral fibers, the moni-
toring data indicate a typical PPD-T fibril concentration at or
below the detection limit of 0.1 fibril/cc. [DuPont has]
also monitored the grin6ing operations in which PPD-T pulp is
made and. [founu that] typical fibril levels were 0.2
fibrils/cc. DuPont has adopted a workplace exposure limit of
5 f ibrils/cc (b hr. time we igh tea averase [Tv/A]) for its ofJer-
ations and is suggesting this limit to its consumers."
Comments/Hecommenda tions
In addition to adoptin'0 and recorLlmendin'j a 5 fibril/cc 8-hour
T~.iA, DuPont reported that the company is transmi tting the pre-
liminary results of the 2-year study and DuPont's assessment of
the meaning of the results to Dupont employees, customers, com-
petitors, NIOSH, OSHA, and NCI. DuPont also stated that, upon
completion, d copy of the final report of the 2-year inhalation
study of PPD-T aramid fibers in rats would be subQitted to EPA.
39
-------
8EHQ-0485-0550
Page 5 of 5
It should be noted that EPA recently received a TSCA Section 8(e)
suGmission (8EHQ-0485-0553) reporting that ". . . intraperitoneal
injection of 25 mg (total dose) of 1.8 urn (mean di~aeter) refrac-
tory ce ra,nic fibers in Osborne-Hendel rats has resulted thus far
in an 86% incidence (19 of 22 rats) of abdominal tumors of peri-
toneal or omental origin." According to this submission, 18 of
the tumors were malignant mesotheliomas and 1 was a "relatively
well differentiated fibrosarcoma."
a)
The Chemical Screening Branch will request DuPont to submit
immediately to EPA a full copy of the actual experimental
protocol from DUPonts's chronic (2-year) PPD-T aramid fiber
inhalation study in rats. In addition, DuPont will be re-
quested to ensure that 1) EPA is apprised immediately about
all further significant findings from DuPont's 2-year PPD-T
aramid fiber inhalation study, and 2) the Agency receives
in a tin~ly manner complete copies of all future interim
reports as well as any draft final reports concerning the
study. DuPont will be asked also to ensure that the Agency
receives immediately upon completion a full copy of the
final report (including all data and experimental protocol
amendments) from DuPont's 2-year inhalation study of PPD-T
aramid fibers.
Finally, and in view of EPA's general interest in corporate
actions that are taken on a voluntary basis in response to
chemical toxicity or exposure information, DuPont will be
asked to describe the nature and available results of all
studies (other than those studies that have been published
or already submitted to EPA) about which DuPont is aware or
that DuPont has conducted, is conducting, or plans to con-
duct to detennine 1) the toxicity of ararnid fibers/aramid
fiber residues, or 2) the nature (e.g., physical character-
istics) and amount of aramid fiber/aramid fiber residues
generated during manufacture, processing, or use of aramid
fibers (e.g., in friction materials, durable panels).
b)
The Chemical Screening Branch will transmit a copy of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OH/EPA, ORD/EPA, OAR/EPA, CCD/OTS, HERD/OTS, RAB/ECAD/OTS,
and to the Asbestos Action Program/OPTS. A copy of this
status report will be provided also to the TSCA Assistance
Office (TAO/OTS) for further distribution.
40
-------
DATE:
MAY 1 4 1985
UNITED STA.TES ENVIRONMENTA.L PROTECTION A.GENCY
8EHQ-0485-0551
Page 1 of 5
SUBJECT:
Status Report* 8EHQ-0485-0551
APproved:;rbt- 1'18")
FROM: James F. Darr, Section Head ~ r ~
Chemical Risk Identificatiorllsection/CSB
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The International Minerals & Chemical Corvoration submitted a
pre-publication copy of a National Institute for Occupational
Safety and Health (NIOSH) "Health Hazard Evaluation" (HHE l~eport
No. HETA 82-257). This NIOSH report provides the details and
conclusions of a NIOSH investigation of occupational exposure to
zeranol (CAS No. 26538-44-3), an ingredient in one of a number of
human and veterinary drugs formulated, compressed, or packaged at
a tvlanufacturing Chemists, Inc. plant in Indianavol is, Indiana.
The following sUJnmary was presented in the submi tted report:
"In May 1982, the National Institute for Occupational Safety
and Health (NIOSH) was requested to evaluate occupational
exposure to an animal growth-promoter, zeranol. One female
worker had developed breast symptohls and weight gain, and her
male child had been found to have gynecoltlastia [Le., "exces-
sive development of the male mammary glands"]. Information
from other workers from the same plant revealed three children
of current workers and one child of another ex-worker with
gynecowastia. In one case, this was thought by the personal
physician to be due to a possible exogenous cause.
"Environmental sampling on May 15-17, 1984 found that personal
(breathing zone) exposures to zeranol (the active ingredient in
RalgroG» ranged from between 4.1 ug/rn3 to 1554 ug/m3. The
highest exposures were found in the production area (median of
6 ~ersonal air samples, 547 ug/m3. Median concentrations of
airborne zeranol in the packaging area and laboratory were 46
ug/m3 and 6.6 ug/m3, respectively. Me6ian concentrations of
zeranol in dermal (gauze-patcll) samples from the workers' palms
were 90 mg/sample in the ~roduction deparbnent, 1.3 mg/sample
in the packaging area, and 0.3 mg/sample in the laboratory.
==;:================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
41
-------
8EHQ-0485-055l
Page 2 of 5
Surface wipe samples for zeranol showed contamination levels
ran9ing fron nondetectable (ND) to 14 mg. Measurements made in
the lunch room showed levels of contamination ranginy from ND
to 4 mg. A wipe sample taken in the interior of a ceiling
supply-air duct in the production area revealed 5.1 mg of
zeranol. A sample of work clothing routinely laundered at home
was contaminated with 16 mg of zeranol. At present there are
no criteria or standards for occupational exposure to zeranol.
However, investigators have proposed occu~ational exposure
levels for estrogens. . . and waking comparable assumptions
one could propose a zeranol exposure limit ranging from 0.05-
0.3 mg/m3.
"Questionnaire interviews of the current workers and a compari-
son group of non-exposed volunteers showed more reporting of
breast symptoms in the exposed group, though the difference was
not statistically significant. There was no indication of a
difference in weight change between the two groups over dif-
ferent periods of time. Clinical examination of male partici-
pants in both groups showed no evidence of distinct subareolar
masses. One exposed worker had a serum estradiol level outside
the laboratory normal range. Levels of serum prolactin [(SP)],
[follicle-stimulating hormone] (FSH), and [luteinizing hormone]
(LH) were normal in all exposed workers. Laboratory analysis of
the blood by high performance liquid chromatography (HPLC) for
zeranol, its precursor, and its main metabolites detected none
of these compounds. (The limit of detection was 12.2 ng/ml for
zeranol, 27.1 ng/ml for zearalenone [the precursor], 18.8 ng/ml
for zearalanone [a metabolite] and 11.5 ng/ml for taleranol [a
metabolite].) Serum HDL-C [high density lipoprotein cholester-
ol] levels, covariance adjusteu for age and sex, were higher in
exposed workers than in the crnaparison group (p=0.0539, t test).
"On the basis of the data obtained during this investigation,
NIOSH has established that workers at this [Manufacturing
Chemists, Inc.] plant have considerable exposure to zeranol via
both airborne and skin contact routes, and this exposure poses
a potential health hazard to the workers. Additionally, there
is a risk of contamination of the home environment and result-
ing serious medical problems in exposed children. Due to the
potency of zeranol, the potential health effects, and the lack
of detailed information regarding human exposures, employee
exposure to zeranol should be reduced to the lowest feasible
level at this facility. Recommendations are included in . . .
this report to reduce potential hazards and to provide a better
work environment for the employees covered by this determina-
tion. Specifically, these recommendations are intended to help
reduce direct skin contact with zeranol powder, to reduce ex-
posure to zeranol dust, and to minimize the possibility of the
agent being brought home on the workclothes or shoes to contam-
inate the home environment."
42
-------
8EHQ-0485-0551
Page 3 of 5
The following conclusions were presented in the body of the
submitted NIOSH "Health Hazard Evaluation" report:
"This studY documented substantial exposures (both airborne and
dermatologic) to zeranol, and contamination of the luncll room,
verltilation ducts, and an item of worker's clothing. Exposed
workers reported more breast symptoms than a non-exposed com-
parison group. Anecdotal and other information indicated a
number of male children of different ages witll transient breast
symptoms. No definite cases of gynecomastia were observed
among the current male workers, and no zeranol was detected in
blood samples obtained. These negative physical and laboratory
findings, however, do not negate tile potential health hazard
documented by the envirornnental findings, the symptoms among
workers, and the reports of breast symptoms in workers'
children."
In the cover letter to its submission, the International Minerals
& Chemical Corporation stated that "certain NIOSH conclusions
. are not supported by the data in the report." Although no
information was provided to substantiate this contention, the
submitting company did report that its "data show that is im-
~robable that zeranol is reponsible for any of the inferred
effects on humans." The company did not describe the nature of
these data.
Submission Evaluation
An initial evaluation of only the information presented in the
submitted NIOSH report suggests that exposure to zeranol (as
opposed to the other substances reportedly handled at the plant)
would be most likely responsible for the observed adverse health
effects. The NIOSH findings also suggest that children may be
more sensitive than adults to exposure to zeranol.
Immediately upon receipt of this TSCA Section 8(e) submission,
the Chemical Screening Brancll (CSB/ECAD/OTS/OPTS) sent a copy to
the Office of Science Coordination/Food and Drug Administration.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for zeranol (CAS No. 26538-44-3), which is listed in
the TSCA Inventory, has shown that no 1977 production/importation
was reported or that all of the production range data reported
were claimed as TSCA Confidential Business Information (TSCA CBI)
by the manufacturer(s) and/or ilnporter(s) and cannot be disclosed
(Section 14(a) of the TSCA, D.S.C. 2613(a)). All of the data
submitted for the TSCA Inventory, including the production range
information, are subject to the limitations contained in the TSCA
Inventory Reporting Regulations (40 CFR 710).
43
-------
8EHQ-0485-0551
Page 4 of 5
According to the NIOSH report, zeranol (a non-steroidal anabolic
a-:Jent with SOJOE degree of estrogenic activity) is obtained by
catalytic dehydrogenation of zearalenone, an estrogenic mycotoxin
produced by a number of species of Fusarium, especially Fusarium
3raminearum, a fungus found on corn and barley in storage and in
the field. The NIOSH report states that in 1969, the U.S. Food
and Drug Administration (FDA) a~proved the use of Ralgro@ (which
contains zeranol as the active ingredient) for growth promotion
and feed efficiency in sheep and cattle; use is prohibited in
dairy or breeding animals. The NIOSH report also states that
because of zeranol's estrogenic activity, the chemical is sold in
some European countries as the pharmaceutical Frideron@ used to
treat human menopausal symptoms; zeranol has not been approved by
FDA for hwoan use in the United States.
Comments/Recommendations
It is EPA's initial position that the provided information did
not warrant reporting to EPA under Section 8(e), the substantial
risk information reporting provision of the Toxic Substances
Control Act (PL 94-469). The following discussion presents the
basis for EPA's position:
Section 8(e) of the Toxic Substances Control Act [TSCA] states
that.. any person who Joanufactures, [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] Adlninistrator of such information unless such person
has actual knowledge that the Administrator has been adequately
informed of such information."
It should be noted, however, that TSCA Section 3 excludes from
TSCA jurisdiction "any food, food additive, drug, cosmetic, or
device (as such terms are defined in Section 201 of the Federal
Food, DruS, and Cosmetic Act) when manufactured, processed, or
distributed in commerce for use as a food, food additive, drug
cosMetic, or device." According to the information currently
available to EPA, zeranol is and has been produced and distri-
buted solely for use(s) under the jurisdiction of the Federal
Food, Drug, and Cosmetic Act.
Therefore, the information contained in OEHQ-0485-055l did not
need to be reported to EPA under Section 8(e) of TSCA unless the
submitting company is or has engaged in the manufacture, importa-
tion, processing, or distribution of zeranol for use(s) covered
by TSCA.
44
-------
a)
b)
8EHQ-0485-0551
Page 5 of 5
The Chemical Screening Branch will ask the International
Minerals & Chemical Corporation to provide the com~any's
rational as to why zeranol and the information concerning
zeranol would fall under the jurisdiction of TSCA. The
International Minerals & Chemical Corporation will be asked
also if the company is or has ever engaged in zeranol manu-
facture, importation, processing, or distribution for any
use(s) other than use(s) covered by the Federal Food, Drug,
and Cosmetic Act.
The Chemical Screening Branch will review the reported
information in order to determine the need for further OTS
assessment of zeranol.
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OW/EPA,
ORD/EPA, OAR/EPA, OSWER/EPA, and to the Department of
Agriculture (DOA). Copies of the status report will be
sent also to the TSCA Assistance Office (TAO/OTS/OPTS) for
further distribution.
45
-------
DATE:
MAY 3 1 1985
UNITED STATES ENV"IRONMENTAL PROTECTION AGENCY
8EHQ-0485-0552 and
8EHQ-0585-0552 Supplement
Page 1 of 3
ZJI%-- (p/~j'6~
SUBJECT: Status Report* 8EHQ-0 485-0 55 2 and Approved:
8EHQ-0585-0552 Supplement
FROM: James F. Darr, Section Head ~ 7' ~
Chemical Risk IdentificatioWsection/CSB
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Olin Corporation reported that it was notified recently by
the Sandoz Chemicals Corporation (formerly Sodyeco, Inc.) that
"several [. . . Sandoz] employees experienced high blood pres-
sure, rapid pulse, headaches and flushing during and after the
manufacture of a 1,900 pound batch of DNPE [2,4-dinitrophenoxy-
ethanol; CAS No. 2831-60-9]." Olin reported that it had been
informed by Sandoz "that these symptoms, although not permanent
in nature, did not clear-up immediately but lasted several [(3-
5)] days." In addition, Olin reported that Sandoz informed Olin
that Sandoz workers have also "handled dinitrochlorobenzene, an
ingredient in the manufacture of DNPE, for several years without
any serious problems, although skin rashes have been reported."
In a supplemental submission (8EHQ-0585-0552 Supplement), the
Sandoz Chemicals Corporation reported that the affected workers
worked in the DNPE drying operation and had been wearing protec-
tive overalls and particulate filter-equipped air-stream helmets
during the DNPE drying operation.
Olin stated that Sandoz manufactures and supplies DNPE to Olin
for use "in the manufacture of Olin products for the united
States Government." According to Olin, both DNPE and dinitro-
chlorobenzene are manufactured at Sandoz plants in Charlotte,
North Carolina. In addition, Olin stated that Sandoz "purchases
caustic soda and ethylene glycol, the [other] major ingredients
for DNPE."
Olin stated that its previous DNPE supplier (the Hummel Chemical
Company) had advised Olin that Hummel "had not encountered any
health problems (other than skin rashes) during the approximately
15 years. . . [Hummel] manufactured DNPE" for Olin. Olin also
stated that Olin is not aware of any health problems associated
with Olin's use of DNPE.
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
46
-------
8EHQ-0485-0552 and
8EHQ-0585-0552 Supplement
Page 2 of 3
Finally, Olin stated that "numerous raw materials, intermediates
and products are involved in the manufacture of DNPE and, on the
basis of current toxicology known by Olin, it is difficult to
determine which chemical or compound may be the causative agent
of the above-described symptoms."
Submission Evaluation
It should be noted that there is an apparent discrepancy with
regard to the number and job functions of the affected workers.
In the supplemental 8(e) submission, Sandoz reported that 3 of
its workers involved in the DNPE drying operation were affected.
In the initial submission, however, Olin reported that 4 Sandoz
employees were affected (3 workers in the DNPE drying operation
and 1 worker in production of DNPE wet cake). Despite this dis-
crepancy, the adverse health effects that were observed in the
Sandoz workers appear to be chemical exposure related in that the
effects occurred during the DNPE drying operation (and possibly
during DNPE wet cake production) and subsided within one week
after removal of the affected workers from the DNPE operation(s).
With the exception of the sustained high systemic blood pressure,
the reported adverse effects are consistent with effects observed
following human exposure to simple nitroaromatic compounds (e.g.,
dinitrophenol, dinitrocresol). It is possible that DNPE, a pro-
cess contaminant, a residual starting material, and/or a metabo-
lite(s) of one or more of these chemical substances was/were
responsible for the observed adverse effects. In addition, it
should be noted that 1) the adverse effects may have been exacer-
bated by the high ambient temperatures expected to be found in
drying operations, and 2) the adverse health effects occurred
even though the workers wore protective equipment/clothing.
Current production and Use
A review of the production range (includes importation volumes)
statistics for 2,4-dinitrophenoxyethanol (CAS No. 2831-60-9),
which is listed in the TSCA Inventory, has shown that between 10
thousand and 100 thousand pounds of this chemical were reported
as produced/imported in 1977. This production range information
does not include any production/importation data claimed as TSCA
Confidential Business Information (TSCA CaI) by the person(s)
reporting for the Inventory, nor does it include any data that
would compromise TSCA CBI. All of the data submitted for the
TSCA Inventory, including the production range data, are subject
to the limitations contained in the TSCA Inventory Reporting
Regulations (40 CFR 710).
As stated previously, Olin reported that it uses DNPE in the
manufacture of products for the U.s. Government. Olin did not
disclose the nature of these products. No information regarding
the use(s) of DNPE was found in the secondary literature sources
consulted.
47
-------
8EHQ--0485-0552 and
8EHQ-0585-0552 SuppleI!'eIlt
Page 3 of 3
Comments/Recommendations
Olin reported that communications are continuing with Sandoz on
this incident. Olin stated also that its "investigation will
continue and possibly include, as further findings warrant, re-
view of existing data and information and development of addi-
tional industrial hygiene data, medical evaluation of current
employees, design and implementation of appropriate toxicologic
studies and inquiry regarding other similar work populations."
Sandoz reported that DNPE manufacture has been halted until
Sandoz is "confident that no further exposure of the chemical
will produce the [reported] symptomology . . . ." In addition,
Sandoz reported that its preclinical Safety Assessment Laboratory
has been reviewing the incident and is now conducting additional
studies. Finally, Sandoz reported that when DNPE production is
resumed, the chemical will be shipped in "wet cake" fonn to Olin
for drying and use.
a)
The Chemical Screening Branch (CSB/ECAD/OTS/OPTS) will
request the Olin Corporation and the Sandoz Chemicals
Corporation to describe the nature and available results
of any investigation(s)/test(s) that the companies have
conducted, are conducting, or plan to conduct to deter-
mine the cause(s) of the observed adverse human health
effects. In addition, both companies will be requested
to ensure that EPA is informed in a timely manner about
all future significant findings from such efforts.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment.
c)
The Chemical Screening Branch will send a copy of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OW/EPA,
OSWER/EPA, ORD/EPA, and OAR/EPA. Copies of this report
will be sent also the TSCA Assistance (TAO/OTS/OPTS)
for further distribution.
48
-------
DATE:
MAY 2 I 1985
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
8EHcr0485-0553
Page 1 of 5
SUBJECT:
Status Report* 3EHQ-0485-0553
Approved: ~ ,./t. "-/'1>
FROM:
James F. Darr, Section Head Lv., r~
CheQical Risk Identificatiorll-s;~tion/CSB
TO:
Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Sohio Engineered Ilaterials COHlpany (formerly known as the
Carborundum Company) ~rovided summarized prelililinary results from
ongoing intraperitoneal injection, intratracheal instillation,
and inhalation studies of r.lan-made refractory ceramic fibers in
rats and hamsters. According to the submitting company, these
studies are being conducted under the auspices of the Thermal
Insulation t'lanufacturers Association (TlIViA), a trade association
whose membership includes manufacturers and users of man-made
refractory fibers. The submi tter fJrovided the following inforHla-
tion concerning the conduct and results of these ongoing studies:
"[The ]Sohio Engineered f1aterials Company has learned from the
investigator that experiments involving intraperitoneal injec-
tion of 25 mg (total dose) of 1.8 uM (mean diameter) refractory
ceramic fibers in Osborne-Mendel rats has resulted thus far in
an 86% incidence (19 of 22 rats) of abdominal tumors of peri-
toneal or omental origin. The investigator has reported that
eighteen (18) of the tumors are mesotheliomas and one (1) a
relatively vvell differentiated fibrosarcoma. The investigator
further reported that the mesotheliomas appeared to be general-
ly anaplastic and very malignant histologically and that four
(4) of them involve the thoracic cavity through either direct
invasion of the diaphragm or vascular metastasis. In conversa-
tions with the investigator, he has indicated that the tumors
are pleomorphic, larger than expected and, in some cases, myxo-
matous. In all cases, the tumors resulted in the animals' death
(18(J-808 days post expos ure ) . Silllilar ly, UlCC Croc idol i te ex-
posed (25 mg intraperitoneally) concurrent positive control
Osborne-Mendel rats have shown an 80% (20 of 25) incidence of
abdominal mesothel ioma. In add i t ion, the tiled ian 1 i fespan of
the refractory fiber treated rats (495 days) was reduced as
compared to the positive controls (600 days)."
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
49
-------
8EHQ-0485-0553
Page 2 of 5
-,' ': "'-"-Y"'- " ,,',' -" ' "
'J.!/-\CI \~},~\~ ,:~tTt)e, Carborundum Company] previously reported [on a "For
ydi.rt"Information" (FYI) basis (FYI-OTS-0184-0288)] the occur-
rence of a single malignant mesothelioma in a Syrian hamster
which died in the ninth month of a 2-year refractory fiber (1.8
uf,1 mean diame ter) inhalation study. Histopa tholog ic examina-
tion has been completed on an additional 50 hamsters surviving
the 2-year exposure period. NO additional primary lung tumors
have been found in the group. Similar inhalation studies in
Osborne-hendel rats have also oeen conducted. While histo-
pathologic examination is not yet complete, no primary lung
tumors l1dve occurred in the 35 rats examined to date. In both
stuaies, the ani;rtals w~re exposed (nose only) to chamber con-
centrations of 14 ffig/t13 (200 fibers/cc) ot the refractory fiber
material uesinning at 100 days of age, 6 hours a day, 5 days
per week for 24 Donths.
"An aJcii tional part of the overall THlA research program on
these fibers includes intraperitoneal hamster (25 mg single
dose), as well as the intratracheal rat and intratracheal ham-
ster instillation (5 x 2 1119) studies. These investigations are
ongoing dnd no Jneanin':Jful resul ts are yet available. ."
In d sup~leillental FYI SUblnission (FYI-OTS-0434-0268 Supplement),
the Carborundum Com~any provided the following summarized infor-
wation concernin(j the conduct, IJrelilninary results, and initial
interpretations of the intraperitoneal inJection studies of re-
fractory ceraftlic fibers in hamsters dnd rats.
" [I]ntraperitoneal injection of 25 mg (total dose) of 1.8
uN (mean diameter) refractory [ceramic] fibers into Syrian ham-
sters has resulted in acute hemorrhagic peritonitis. Death, as
a result of splenic and peritoneal heHlorrhage, occurred typi-
cally within 12 days of administration and gave rise to approx-
imately 50% mortality. [The] antemortem observations included
lethargy, anorexia, "hunched" posture and, in some animals,
diarrhea. In addition, hunediately preceding death, animals
were observed to have pale mucous membranes and an apparent
accumulation of fluid in the abdominal cavity, identified as
blood upon necropsy.
" [The] rats (Osborne-Mendel) injected vIi th refractory
,ceramic fibers did not exhibit the acute hemorrhagic response
and neither rats nor hamsters similarly injected with either
crocidolite or glass fibers exhibited hemorrhagic peritoni-
tis. Currently, the causation of acute hemorrhagic peritonitis
in Syrian hdmsters following intraperitoneal injection of re-
fractory ceramic fibers is without explanation. Moreover, the
significance of this finding to humans cannot currently be
appreciated."
In its initial TSCA section 8(e) notice, the Sohio Engineered
Materials Company also submitted the following background in-
formation concerning the oncogenicity of a number of fibrous
clnd non-fibrous materials:
50
-------
8EHQ-0485-0553
Page 3 of 5
". [A]bdominal mesotheliomas have been observed in rats
after intraperitoneal injection of a wide variety of organic
and inorganic fibrous and non-fibrous substances such as fi-
brous glass, rock wool, refractory ceramic fibers, mineral
wool, attapulgite, asbestos, brucite and erionite. Further-
more, this abnormally sensitive inJection technique is a non-
physiological method of exposure, bypassing both normal pul-
monary ~rotective and clearance mechanisms. Moreover, the
current research program is incomplete. Therefore, it is not
possible to fully appreciate the significance of the current
findings. II
Finally, the Sohio Engineered Materials Company reported that
"a recent review of . [employee] x-rays and other medical
records indicates no occupationally-related health effects."
Submission Evaluation
The evidence that has been accumulating since about 1970 lends
increasing credence to the view that the carcinogenicity of as-
bestos fibers is due mainly to their submicroscopic, needle-like
shape, rather than to their chemical composition, physical/chemi-
cal properties, or impurities. It appears that asbestos fibers
exhibit maximal carcinogenic activity when they have diameters
less than 1.5 urn and lengths greater than 8 um. In addition, it
appears that oncogenicity is enhanced by decreases in fiber dia-
meter and increases in fiber length.
Accordingly, mesotheliomas have been induced experimentally with
non-asbestos substances that occur naturally as fibers or that
are processed to critical fiber dimensions. Such substances
include: the fibrous magnesium hydroxide minerals (i.e., brucite
and nemalith), various types of fibrous glass, and different
types of fibrous alumimum oxide. Non-fibrous samples of these
same materials have not been shown to date to exhibit oncogenic
activity in laboratory animals. Most of the experiments that
involve absestos and asbestiform fibers have been conducted with
rodents exposed by intraperitoneal injection, a route of exposure
that appears to be much more sensitive than other exposure routes
(including inhalation) to detect maximal carcinogenic activity of
fibrous materials. Also, there is an increasing realization that
the carcinogenic potential of asbestos in humans is not limited
to induction of lung carcinomas and pleural mesothelioma, the
tYfical asbestos cancer. It has been shown that exposure to as-
bestos can lead also to mesothelioma of the peritoneum and to
carcinoma of the larynx, esophagus, and stomach.
The potential risks posed by human exposure to refractory ceramic
fibers (the subject of the present submission) should be con-
sidered against the above background information. Although the
tested refractory ceramic fiber diameter of 1.8 um is slightly
above the apparently critical (in terms of maximal carcinogenic
response) asbestos fiber diameter of 1.5 urn, the intraperitoneal
51
-------
8EH(r0485-0553
Page 4 of 5
inJection of 25 mg ceramic fibers to rats caused an 86% incidence
of mal iyant tumors of }?er i toneal or oIdental or i9 in. Of the 19
;;-talignant tUJnors, 18 were found to be mesotheliomas and 1 was
found to be a well differentiated fibrosarcoma. These rei--'orted
findings ot the intraperitoneal injection study in rats lend cre-
dence to the poss ibil i ty that the single I!lesothel ioma observed
during the refractory ceramic fiber inhalation study in hamsters
was actually treatment-related and not a spontaneous occurrence.
Current Production and Use
In an addendum to its initial Section 8(e) notice, the Sohio
Engineered Uaterials Company rej?orted that the "refractory
ceramic fiber used in the animal studies has a chemical com-
position of alumina and silica - - nominally a 50/50 mix."
According to the submitter, these fibers are used typically in
high temperature operations in which the temperatures can range
from 1500° to 3000° Fahrenheit.
Comments/Recommendations
Sohio Lngineered ~jaterials Company stated that it is notifying
its customers and employees about the reported findings. The
submitting company also reported that it "maintains workplace ex-
posures to less than 2 fibers/cc and, as a precautionary measure,
conducts annual medical examinations, including chest x-rays, of
~otentially exposed employees." Finally, the submitter stated
that BPA would receive copies of the final reports of the ongoing
aniraal studies cited in the submission.
It should be noted that in a recent TSCA Section 8(e) notice
(8EhQ-0485-0550), E. 1. DuPont de Ner,10urs & Company, Inc. pro-
vided summarized preliminary results from a study of rats that
were exposed via inhalation to respirable fibrils ot poly p-
phenylene terephthalamide (PPD-T) aramid fibers at atmospheric
concentrations of 0, 2.5, 25, 100, or 400 fibrils/cc air for 6
hours/day, 5 days/week for 2 years. According to the submitted
information, rats exposed to the highest two doses only \vere
found to have developed lung tumors characterized histopatho-
logically as cystic keratinizing squamous cell carcinoHlas.
It should be noted also that in support of the Agency's asbestos
asse SSJ.1en t/re
-------
b)
c)
8EHQ-0485-0553
Page 5 of 5
a)
The Chemical Screening Branch will request the Sohio
Engineered Materials Company to provide immediately (if
available) full copies of the actual experimental proto-
cols from all of the Thermal Insulation Manufacturers
Association (TIMA)-sponsored studies that were cited in
the company's Section 8(e) submission. In addition, the
Sohio Engineered Materials Company will be requested to
ensure that 1) the Agency is apprised immediately about
all further significant results obtained from the cited
studies, 2) the Agency receives, in a timely manner,
complete copies of all future interim reports and the
draft final reports concerning the cited studies, and 3)
the Agency receives, immediately upon completion, full
copies of the final reports (including all data and any
protocol amendments) concerning the cited studies.
In view of the Agency's general interest in corporate
actions that are taken on a voluntary basis in response
to chemical toxicity/exposure information, the Chemical
Screening Branch will ask the Sohio Engineered Materials
Company to describe the nature and available results of
all studies (other than those already published in the
open scientific literature or already submitted to or
brought to the attention of the Agency) about which the
company is aware or that the company has conducted, is
conducting, or plans to conduct to determine 1) the tox-
icity of refractory ceramic fibers, and 2) the nature
(e.g., physical characteristics) and amount of refrac-
tory ceramic fibers generated during manufacturing,
processing, and use.
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of refractory ceramic fibers.
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OW/EPA,
OSWER/EPA, ORD/EPA, OAR/EPA, HERD/OTS, CCD/OTS, RAB/OTS,
and the Asbestos Action Program/OPTS. Copies of this
report will be sent also to the TSCA Assistance Office
(TAO/OTS/OPTS) for further distribution.
53
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0585-0554 S
DATE: MAY 28 1985 Page 1 of 3
'UIJECT, Status Report' 8EHQ-0585-0554 S Approved: ~ ~f{/'1>
FROM: James F. Darr, Section Head ~ ~ ~
Chemical Risk IdentificatioJ]sectionjCSB
TO: Frank D. Kover, Branch Chief
Chemical Screening BranchjECADjOTSjOPTS
NOTE
The submitting company claimed its identity and the identity of
an end-product to be TSCA Confidential Business Information (TSCA
CBI). The Information Management Division (IMDjOTS) has asked
the submitter to substantiate these confidentiality claims.
Submission Description
The submitter reported that diethyl sulfate (DES; CAS No. 64-67-
5) was detected by gas chromatography in p-ethoxyethylbenzoate
(CAS No. 23676-09-7), a chemical that the submitting company pur-
chases and uses in the manufacture of an end-product (identity
claimed to be TSCA CBI). The submitting company provided the
following information with regard to this new-found exposure to
diethyl sulfate:
"The levels of DES in . . . [p-ethoxyethylbenzoate] were
checked in lots and samples in . . . [the submitting com-
pany's] inventory. Fourteen lots were analyzed, twelve
from. . . [the] regular supplier and one each from poten-
tial alternate suppliers. The results ranged from 80 ppm
wt. to 1600 ppm wt.
"The process chemical [(p-ethoxyethylbenzoate)] is received
at . . . [the submitter's] plant in drums from which vessels
are filled as needed. Once charged to the vessel, there is
little opportunity for the DES to escape. The operator enters
the building containing the vessel about 3 times per shift.
The level of DES in that building is unknown; monitoring data
have not yet been obtained. It is apparent, however, from the
====================================================================================
* NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
54
-------
8EEQ-0585-0554 S
Page 2 of 3
saturated vapor pressure (0.19 mm Hg at 20°C) that the [DES]
concentration cannot exceed 0.25 to 0.3 ppm wt. and is prob-
ably less than this by at least an order of magnitude. [The]
handling instructions require the use of rubber gloves and
rubber boots. Supplied-air respirators are available in the
handling areas in case leaks or spills occur."
"The final product of this [manufacturing] process has been
analyzed (2 samples thus far) and no DES has been detectable.
The detectable limit of the method used was 50 ppb."
Submission Evaluation
Diethyl sulfate is moderately toxic via ingestion, is highly
irritating to the eyes (and other mucous membranes), and is
moderately irritating to the skin. The chemical has been found
to be mutagenic in a variety of in vitro and in vivo tests. The
results of studies in laboratory-animals indicate that diethyl
sulfate can cause cancer by injection (rats) and via repeated
skin application (mice). The findings of an epidemiologic study
of workers involved in the manufacture of ethyl alcohol (diethyl
sulfate was shown to be formed during the reaction sequence in a
process used formerly to make ethyl alcohol) are suggestive of a
risk of cancer from exposure to diethyl sulfate.
Immediately upon receipt of this TSCA Section 8(e) notice, the
Chemical Screening Branch (CSB/ECAD/OTS) provided a copy to the
Risk Analysis Branch (RAB/ECAD/OTS). The Risk Analysis Branch
has been evaluating available toxicologic and exposure data on
diethyl and dimethyl sulfate in order to determine the need for,
and scope of, formal or other EPA response to reduce potential
risks posed by exposure to these chemicals.
Current production and Use
A review of the non-confidential version of the TSCA Chemical
Substances Inventory shows that p-ethoxyethylbenzoate (CAS No.
23676-09-7) is not listed. As stated previously, the submitting
company purchases and uses p-ethoxyethylbenzoate in the manufac-
ture of an end-product, the identity of which was claimed by the
submitter to be TSCA CBI. No information concerning the use(s)
of p-ethoxyethylbenzoate was located in the secondary literature
sources consulted.
Comments/Recommendations
In an effort to reduce worker exposure to DES, the submitter
reported that industrial hygiene practices (other than those
mentioned previously) are being evaluated. In addition, the
submitter reported that "monitoring techniques and procedures
are being developed to determine the air concentrations of DES
Ss
-------
8EHQ-0585-0554 S
Page 3 of 3
in . . . [the submitter's] manufacturing unit." Finally, the
submitting company stated that its "current supplier has been
requested to reduce the level of DES in the process chemical
p-ethoxyethylbenzoate; . . . [the supplier] believes that he
can provide the product at less than 50 ppm wt. immediately."
EPA's Office of Toxic Substances has received other Section 8(e)
and "For Your Information" (FYI) submissions containing toxico-
logic and/or exposure data on diethyl and dimethyl sulfate. It
should be noted also that OTS has received a number of Section
8(e) submissions that have reported new-found exposure to toxic
chemical substances.
a)
The Chemical Screening Branch will request the submitting
company to describe the nature and available results of
all studies/tests that the company has conducted, is con-
ducting, and plans to conduct to determine the levels of
DES in the workplace, in process chemicals, and/or in end-
products.
b)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWERjEPA,
OW/EPA, OAR/EPA, ORD/EPA, and the Risk Analysis Branch
(RAB/ECADjOTS). Copies of this report will be sent also
to the TSCA Assistance Office (TAO/OTS/OPTS) for further
distribution.
56
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 4
DATE:
JUN 2 0 198~
SUBJECT: Status Report*
8EHQ-0585-0555
Approved: - (JIJt- (pI ;..t.f /rG'
FROM: James F. Darr, Section Head ~ p: j)1V7rL-
Chemical Risk Identificatio~sec~ion/CSB
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Ethyl Corporation provided an abbreviated final report from
an oral rat teratology study of SAYTEX@lll (brominated diphenyl-
oxide with bromination ranging mainly from 6 to 9 bromines per
molecule). Although SAYTEX@lll is technically a mixture, the
submitting company stated that this product is commonly known as
"octabromodiphenyl oxide." The submitter reported that diphenyl-
oxide molecules with 6, 7, 8. or 9 bromines per molecule have the
following CAS Numbers:
CAS Number
Bromines/Diphenyloxide Molecule
36483-60-0
6 Bromines
68928-80-3
7 Bromines
32536-52-0
8 Bromines
63936-56-1
9 Bromines
The following information concerning the conduct and results of
the subject teratology study of SAYTEX@lll in rats was presented
in the "Summary and Conclusion" section of the submitted report:
"pregnant Crl:COBS@CD@(SD)BR female rats were given corn oil
suspensions of SAYTEX@lll via gavage at dosages of O(Vehicle),
2.5, 10.0 or 25.0 mg/kg/day (days 6-15 of gestation). The dams
were sacrificed on day 20 of gestation, and the fetuses were
examined using "state-of-the-art" developmental toxicity meth-
odology. The study was performed in compliance with the EPA
guidelines and regulations. . . ."
------------------------------------------------------------------------------------
------------------------------------------------------------------------------------
* NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
57
-------
8EHQ-0585-0555
Page 2 of 4
"On the basis of data generated in this study, SAYTEX@lll is
more toxic to the conceptus than to the dam. The embryo/fetal
no-effect level is 2.5 mg/kg/day. The maternal no-effect level
is greater than 25.0 mg/kg/day (the 25.0 mg/kg/day dosage of the
test substance resulted in significant (P
-------
8EHQ-0585-0555
Page 3 of 4
than 0.3 mg/kg/day following dermal exposure). It should be
noted also that decabromodiphenyl oxide was shown to be develop-
mentally toxic in a teratology study conducted by Dow Chemical,
U.S.A. (Norris et al., 1975). In this DOW study, decabromodi-
phenyl oxide was administered orally to rats on days 6-15 of
gestation at dose levels of 10, 100 or 1000 mg/kg/day. There was
no evidence of maternal toxicity at any level of exposure. At
1000 mg/kg there was an increased incidence in the number of lit-
ters with fetuses exhibiting edema and delayed ossification of
the skull. The authors determined that the NOEL for decabromo-
diphenyl oxide was 100 mg/kg/day and stated that the significant
increase of resorptions observed at 10 and 100 but not at 1000
mg/kg were due to chance.
Current Production and Use
A review of the production range (including importation volumes)
statistics for the subject CAS Numbers, which are listed in the
initial TSCA Inventory, has shown that no 1977 manufacture or im-
portation was reported or that all of the production range data
reported were claimed as TSCA Confidential Business Information
(TSCA CBI) by the manufacturer(s) and/or importer(s) and cannot
be disclosed (Section 14(a) of TSCAi U.S.C. 2613(a)). The data
submitted for the TSCA Inventory, including the production range
information, are subject to the limitations contained in the TSCA
Inventory Reporting Regulations (40 CFR 710).
According to an Ethyl Corporation advertisement found in the 1985
OPD Chemical Buyers Directory, SAYTEX@lll is a flame retardant
used principally in "ABS [acrylonitrile/butadiene/styrene], nylon
and other thermoplastics." In its 8(e) notice, Ethyl stated that
exposure of the general public to SAYTEX@lll is prevented by the
plastic matrix. With regard to worker exposure, Ethyl provided
the following information:
". . . [Ethyl controls the] exposure to [SAYTEX@lll] in the
workplace to <0.05 mg/M3 by engineering controls, use of res-
pirators and industrial hygiene practice. ... [Ethyl's]
calculations show that exposure to 0.05 mg/M3 gives more than
a lOO-fold safety factor over the no-effect level in rats."
Comments/Recommendations
In its submission, the Ethyl Corporation stated that the company
has notified its customers and other suppliers about the reported
teratologic findings.
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will request
the Ethyl Corporation to submit a full copy of the final
report (including the actual data and any statistical
analyses of the data) from the oral teratology study of
SAYTEX@lll in rats. In addition, Ethyl will be requested
59
-------
8EHQ-0585-0555
Page 4 of 4
to provide a complete copy of the pilot teratology study
that was cited in the submitted abbreviated report as
"Appendix B" but was not appended to the submitted
report. Ethyl will be asked also to report (if known)
the exact chemical identity and actual amount of each
constituent (including impurities) in SAYTEX@lll.
In light of the Agency's general interest in company
actions that are taken on a voluntary basis in response
to chemical toxicity or exposure information, the Ethyl
Corporation will be asked if the company has notified or
plans to notify its own workers about the submitted tera-
tologic findings and, if so, to describe the nature of
such notification(s). In addition, the Ethyl Corporation
will be requested to describe the nature and available
results of all other studies (other than those published
in the scientific literature or already submitted for-
mally to EPA) about which Ethyl is aware or that Ethyl
has conducted, is conducting, or plans to conduct, that
are designed to determine l} the toxicity of SAYTEX@lll
or its constituents, or 2} the exposure to SAYTEX@lll or
its constituents during manufacture, processing, and use.
b}
The Chemical Screening Branch will ask DOw to provide a
complete copy of the final report (includin9 the actual
experimental protocol, data, statistical analyses, etc.)
fr~n the DOW rat teratology study of decabromodiphenyl
oxide that was cited in the 1975 Norris et ale paper.
c)
The Chemical Screening Branch will review the submitted
information in order to determine the need for further
OTS assessment of brominated diphenyloxide.
d)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWERjEPA,
OWjEPA, ORDjEPA and OARjEPA. In addition, copies of this
status report will be sent to the TSCA Assistance Office
(TAOjOTSjOPTS) for further distribution.
Reference
Norris, JM; Kociba, RJ; Schwetz, BA; Rose, JQ; Humiston, CG;
Jewett, GL; Gehring, PJ; and Mailhes, JB; "Toxicology of
Octabromobiphenyl and Decabromodiphenyl Oxide" Environmental
Health Perspectives Vol. 11: 153-161; 1975.
60
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 4
DATE:
JUN 2 8 1985
SUBJECT: Status Report* 8EHQ-0585-0556 S
Approved: Ja-- 7 h /r.s
FROM'James F. Darr, Section Head ~ r UAnr7...----
Chemical Risk IdentificatioJ/s~ction/CSB
TO'Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Note
The Rohm and Haas Company claimed the exact chemical identities
of the components of the subject products to be TSCA Confidential
Business Information (CBI). The Information Management Division
will ask the company to substantiate this claim. Rohm and Haas
did report non-confidentially, however, that the subject products
were "primarily mixtures of complex methacrylate monomers."
Submission Description
The Rohm and Haas Company submitted the followin9 information
concerning the conduct and results of a 2-week repeated skin
application study of two products (Monomer QM-867 (or Monomer
PCM-200) and Monomer QM-928 (or Monomer PCM-400» in rabbits:
"In a repeated skin application study, either of two lots of
the test substances QM-867 (Lots WJR-2272-l and WJR-2272-2) or
QM-928 (Lots WJR-2272-3 and WJR-2272-4) was applied to the un-
occluded, shaved backs of four groups of ten (5 male, 5 female)
New Zealand white rabbits. Materials were delivered at a con-
stant volume of 1 ml test substance/kg body weight. Water was
applied to ten (5 male, 5 female) sham-exposed (control) rab-
bits at a similar volume. The test substances (or water) were
administered once daily for ten total exposures over a two-week
period; dosing occurred on weekdays only, with recovery over
the weekend; skin irritation, clinical signs, and feed consump-
tion were assessed daily, body weight was measured twice week-
ly, and hematology and clinical chemistry parameters were
lneasured at the beginning and end of the study. All rabbits
were necropsied and organs examined grossly. Selected organs
were weighed. Tissue samples of the liver, kidneys, brain,
sciatic nerve, two sections of the spinal cord (cervical and
thoracolumbar) and selected lesions were processed for micro-
scopic examination.
------------------------------------------------------------------------------------
------------------------------------------------------------------------------------
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
61
-------
8EHQ-0585-0556 S
Page 2 of 4
"Based on mean skin irritation scores, severe skin irritation
was observed in both sexes of all treatment groups following
five days of dosing. In all treatment groups, one or more ani-
mals exhibited at least three of the following clinical signs:
ataxia, uncoordinated movement of the hind limbs, hyperrefle-
xia, extensor rigidity, prostration, and reduced body weight
gain. Histopathology findings correlated with clinical signs.
In every instance, rabbits exhibiting clinical neurotoxicity
showed axonal swelling (i.e., axonal degeneration) within the
thoracolumbar section of the spinal cord. In addition, one
rabbit which did not exhibit in-life signs, did show axonal
swelling in the spinal cord.
"Two rabbits (1 male and 1 female) treated with QM-867 and 2
males treated with QM-928 were killed prior to the scheduled
termination of the study. These animals had extensor muscle
rigidity of the limbs and were unable to access feed or water.
"There were no toxicologically significant changes in any of
the hematologic or clinical chemistry parameters examined, nor
in any other tissues examined histopathologically. Except for
a sliyht decrease in the absolute (but not relative) weight of
ovaries in females of Group 4, there were no statistically sig-
nificant differences in terminal organ weights of the liver,
kidney, adrenals, brain, gonads, or thyroid/parathyroids."
In its submission, Rohm and Haas also provided copies of Monomer
QM-867 and Monomer QM-928 Material Safety Data Sheets revised by
the company to reflect the reported neurotoxicologic findings in
rabbits. with regard to other toxic effects, the product safety
sheets state that Monomer QM-867 is moderately irritating to eyes
and slightly irritating to skin, and Monomer QM-928 is moderately
irritating to both skin and eyes. In addition, the safety sheets
report that the rabbit dermal and rat oral LD50s for both pro-
ducts exceed 5 grams/kg. Finally, the product safety sheet for
Monomer QM-928 indicates that this product caused "allergic
contact dermatitis in guinea pigs (13 out of 19 guinea pigs
responded positively)."
Submission Evaluation
Afthough the final reports of the performed studies are not yet
available for review by EPA, the investigators did reportedly
observe adverse neurological effects in rabbits exposed dermally
to either of 2 mixtures of complex methacrylate monomers. The
submitted information indicates that 15% (3 of 20) of the rabbits
exposed once per day for up to 10 days to approximately 1 g/kg of
the mixtures showed some signs of motor dysfunction, primarily
ataxia and extensor rigidity. Although the time to onset of the
neurotoxic signs was not reported, a total of 4 rabbits (2 ex-
posed to Monomer QM-867 and 2 exposed to Monomer QM-928) were
killed in a moribund state because of severe extensor rigidity
and consequent inability to eat. It should be noted that the
dermal application of both mixtures caused severe dermal
62
-------
8EHQ-0585-0556 S
Page 3 of 4
irritation after 5 days, thereby assuring absorption of the
tested products. In all rabbits that displayed clinical signs
(and I rabbit that did not display such signs), histopathologic
changes involving axonal swelling were observed in sections of
the thoracolumbar area of the spinal cord. No other significant
toxic effects were reportedly observed in hematology, clinical
chemistry, or histopathology (except for a decrease in absolute
ovary weights in one of the test groups).
In summary, 1 to 10 dermally applied doses of approximately I
g/kg of either of the two complex methacrylate monomer mixtures
appear to have caused potentially permanent motor system dysfunc-
tion and associated pathology in rabbits. It should be noted
that dermal exposure to methyl methacrylate has been associated
with varying degrees of loss of distal sensory function in
humans. In addition, motor system dysfunction and associated
pathology have been observed in animals exposed to methacrylamide
and hydroxyethyl acrylate.
Finally, it should be noted that the both the New and Existing
Chemicals Programs in EPA's Office of Toxic Substances (OTS) have
been evaluating toxicologic and exposure information on a number
of mono- and multi-functional acrylates.
Current Production and Use
In view of the fact that the Rohm and Haas Company has claimed
the exact chemical identities of the components of the two pro-
ducts to be TSCA CBI, no TSCA Inventory production information
for these chemicals will appear in this report. According to the
submission, "the major use of Monomer QM-867 and Monomer QM-928
is in polymer concrete products for concrete and spall repair or
re-surfacing." The submitter did not provide any information
concerning the other use(s) of the tested products.
Comments/Recommendations
In addition to revising the Material Safety Data Sheets for
Monomer QM-867 and Monomer QM-928, the Rohm and Haas Company
stated that it has informed its employees about the reported
neurotoxicologic findings in rabbits. In its submission, the
Rohm and Haas Company submitted a copy of a draft notification
letter to its licensees, licensee candidates, and consultants.
In this notification letter, Rohm and Haas stated that 1) the
company has scheduled additional toxicologic studies of Monomer
QM-867, Monomer QM-928, and another product (Monomer PCM-IIOO),
in an attempt to determine the cause(s) of the observed neuro-
toxicologic effects, 2) the company believes that its products
can be modified "to eliminate possible central nervous system
(CNS) effects without sacrificing technical efficacy," and 3)
the company is recalling existing inventories of Monomer QM-867,
Monomer QM-928 and Monomer PCM-IIOO except in certain critical
use situations determined by Rohm and Haas to be under tight
industrial hygiene control measures to avoid skin contact.
63
-------
8EHQ-0585-0556 S
Page 4 of 4
a) The Chemical Screening Branch (CSB/ECAD/OTS) will request
the Rohm and Haas Company to ensure that EPA receives a full
copy of the final report (including the actual experimental
protocol and data) from the 2-week rabbit dermal application
study of Monomer QM-867 and Monomer QM-928 that was cited in
the submission. In addition, the Rohm and Haas Company will
be asked to ensure that the Agency is apprised in a timely
Joanner about the results of all studies that the company is
conducting or plans to conduct to determine the cause(s) of
the neurotoxicologic effects observed in rabbits following
repeated dermal application of Monomer QM-867 and Monomer
QM-928. Finally, Rohm and Haas will be asked to provide a
complete copy of the final report (including the actual
experimental protocol and data) from each study for which
results were presented in summarized form in the "Toxicity
Information" sections of the submitted Monomer QM-867 and
Monomer QM-928 Material Safety Data Sheets.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further OTS
assessment of the subject products and/or their components.
c) The Chemical Screening Branch will transmit copies of this
status report NIOSH, OSHA, CPSC, FDA, NTP, OW/EPA, OAR/EPA,
OSWER/EPA, and ORD/EPA. In addition, copies of this report
will be sent to the TSCA Assistance Office (TAO/OTS/OPTS)
for further distribution.
64
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 5
DATE:
JUL
3 1985
SUBJECT: Status Report* 8EHQ-0 58 5-0 55 7
Approved: ~r
7hh-
FROM: James F. Darr, Section Head L'Ar~
Chemical Risk Identificatio~~~~tionjCSB
TO: Frank D. Kover, Branch Chief
Chemical Screening BranchjECADjOTSjOPTS
Submission Description
On behalf of one of its wholly-owned subsidiaries (the Amoco Oil
Company), the Amoco Corporation (formerly the Standard Oil Company
(Indiana» submitted a pre-publication report concerning the con-
duct and "results of a retrospective cohort mortality study of
over 10,000 oil refinery workers employed at ten oil refineries
owned and operated by [the] Amoco Oil Company." In its submis-
sion, Amoco stated the study "revealed statistically significant
elevations in mortality in three disease categories; namely, skin
cancers, benign neoplasms, and digestive system cancers." Amoco
noted that although "evaluations of these disease categories have
been reported previously for refinery populations," this investi-
9ation has brought to light additional information that Amoco
believes to be new. with regard to this new information, Amoco
stated that "the data indicate an association between workplace
exposure and skin cancer, specifically in jobs where employee ex-
posure to petroleum materials has been evaluated as routine rather
than occasional or none." The following information concerning
the results of the retrospective cohort mortality study of Amoco
oil refinery workers was presented in the report abstract:
"This retrospective cohort mortality study of 10,763 [Amoco]
oil refinery workers employed between 1970 and 1980 showed
that overall mortality for the cohort compared favorably with
that of the u.s. population. The Standardized Mortality Ratio
(SMR) for all causes of death was 73 for white males and 68
for black males. For most of the white male subgroups ana-
lyzed, SMRs for all cancers combined were higher than those
for all causes of death but were lower than would be expected
in the U.S. population."
"The study showed statistically significant elevations for
three disease categories: skin cancers, benign neoplasms, and
digestive system cancers. Significantly elevated skin cancer
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made i~ this 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
the fact that the report may be based on incomplete information.
65
-------
8EHQ-0585-0557
Page 2 of 5
SMRs were found for all white males hired in 1945 or later and
those with less than 15 years latency. When the white male
population was stratified by job type (Administrative, Mainte-
nance, Operations, and Unknown), a statistically significantly
elevated SMR of 378 was seen for Maintenance employees. When
white males were stratified by categories for exposure to re-
finery processes, exposure to light aromatic hydrocarbons, and
exposure to heavy oils using the groups none, occasional, rou-
tine, and unknown, [the] skin cancer SMRs were statistically
significantly elevated for the highest (routine) exposure
categories. For all three exposure categorizations, a dose-
response effect was demonstrated, where increasing exposure
was associated with increased mortality. Dose-response rela-
tionships observed among SMRs were confirmed by comparison of
directly standardized mortality rates for the exposure groups.
A total of 11 skin cancer deaths were observed; 10 of these
were melanomas. SMRs for benign neoplasms were statistically
significantly elevated for white males employed in Maintenance
positions (with an SMR of 374) and for those with routine ex-
posure to heavy oils (with an SMR of 357).
"Statistically significantly elevated SMRs for digestive sys-
tem cancers were seen in several white male subgroups. An
elevated SMR of 137 for all digestive cancers combined was
seen in employees of the Whiting [Indiana] refinery; the sto-
mach cancer SMR [at the Whiting, Indiana refinery] was also
statistically significantly elevated at 207. For the 10-
refinery population, an SMR of 139 for all digestive system
cancers was observed for those with routine exposure to light
aromatic hydrocarbons. The SMRs for all digestive system
cancers and stomach cancer were significantly elevated in
white males hired before 1940."
"The elevated SMRs for benign neoplasms and digestive system
cancers did not seem to be related to job type or refinery
exposure. On the other hand, the observed elevations in skin
cancer SMRs, along with the dose-response relationship, sup-
port the possibility that contact with petroleum or one of its
constituents is associated with skin cancer and melanoma in
particular."
In order to prevent a possible misinterpretation of the results of
the submitted retrospective mortality study and to give a clear
understanding of how the exposure categories were determined, the
ffinoco Corporation also submitted a highlighted report describing
the selection process for determining the exposure categories.
With regard to this exposure category selection process, Amoco
reported that the process "was based upon generalized qualitative
evaluations of job categories and not upon the [quantitive] ex-
posure history of individual employees." In other words, ffinoco
"did not measure the frequency and level of exposure received by
each individual employee in the study in order to assign them to
the exposure categories."
66
-------
8EHQ-0585-0557
Page 3 of 5
Submission Evaluation
The submitted cohort study examined the mortality experience of
all full-time regular employees who worked at 10 Amoco Oil Company
refineries for six months or more, at least one day of which was
b~tween January 1, 1970, and December 31. 1980. The year 1970 de-
flned the earliest availability of nearly complete computerized
records, and the cutoff date for followup was December 31, 1982.
The submitted information indicates that further study is antici-
pated, extending the eligibility definition as the computerized
data base is enlarged to include all those employed between 1940
and 1980.
Although the bulk of the cohort (10,763) was white male (9,187),
standardized mortality ratios (SMRs) were also computed for black
males (884) and white females (583). The Texas City (Texas) and
Whiting (Indiana) refineries contributed better than half of the
study population, leaving many causes of death unrepresented in
the remaining eight refineries. Furthermore, this reduces the
ability to detect patterns in elevations across individual re-
fineries. The cohort generally showed deficits (i.e., SMRs less
than 100), some statistically significant, in a variety of mor-
tality causes, both compared to the u.s. general population and
state-specific mortality rates; such deficits are more likely to
be indicative of the "healthy worker" phenoJnenon. Nevertheless,
significantly elevated SMRs were seen overall for skin cancer,
digestive system cancers, and benign neoplasms. These elevations
were largely attributable to the Whiting refinery. Other high
risk characterizations include 1) those white males who were ever
hourly workers, 2) white male maintenance workers, 3) white males
with less than 15 years exposure prior to diagnosis (3 skin cancer
deaths observed as compared to 0.6 expected (SMR=524); the total
white male group had 11 skin cancer deaths), and 4) routine ex-
posure in any of the three materials categorizations (refinery
products, light aromatic hydrocarbons, and heavy oils). The
investigators noted that individuals exposed routinely in one
of the three exposure categories tended to have been exposed
routinely in the others.
The investigators have very nicely compared their findings with
most other completed studies in the petroleum and refinery field.
With regard to a concern for kidney cancer, while the total number
of white male kidney cancer deaths is adequate to detect eleva-
tions, the subgroups had small numbers. Interestingly, half of
the white male kidney cancer deaths occurred in salaried workers.
Brain and CNS cancers do appear to be elevated at a few smaller
refineries and in salaried workers but, again, these small, un-
stable numbers together show an overall relative risk not signif-
icantly different from one. This observation is indicative of the
difficulties that can be encountered even with such a large study.
Although one table (i.e., Table 64) shows a quite reasonable abil-
ity to detect 2-3 fold relative risks in a variety of causes of
death, these are sex- and race-specific relative risks adjusted
only for age and not for other possible confounding factors. It
67
-------
8EHQ-0585-0557
Page 4 of 5
should be noted that the investigators did comment on the limited
availability of smoking information. It should be noted also that
dietary and skin complexion information could have been extremely
useful. In addition, a combining of the three exposure categories
(i.e., none/none/none, occasional/occasional/occasional, routine/
routine/routine) might have shown an interpretable dose-response
gradient. Finally, and most importantly, however, the power cal-
culations are based on the assumption that a specific number of
predetermined analyses will be carried out. When hundreds of SMRs
are computed, as they have been in the submitted study, the actual
level (~) overall is no longer that nominal level for which the
calculations have been carried out. Therefore, interpretation of
the study's detection capabilities becomes extremely difficult.
Comments/Recommendations
In the cover letter to its submission, Amoco reported that "in
light of the study results, particularly those regarding skin
cancer, Amoco will review past operational changes which have
reduced skin contact with petroleum materials and determine what
further steps are feasible [to reduce exposure], including in-
creased emphasis on employee personal and industrial hygiene."
It should be noted that EPA's Office of Toxic Substances (OTS) has
received and evaluated a number of TSCA Section 8(e) and "For Your
Information" (FYI) submissions containing toxicologic and/or expo-
sure information on a wide variety of petroleum refinery streams.
In addition, the Chemical Screening Branch (CSB/ECAD/OTS) has pre-
pared a Chemical Hazard Information Profile (CHIP) on 2 naphtha
petroleum solvents. Both the Risk Analysis Branch (RAB/ECAD/OTS)
and Test Rules Development Branch (TRDB/ECAD/OTS) are evaluating
available toxicologic and exposure data on a number of petroleum
refinery process streams and/or components of such streams.
(a)
The Chemical Screening Branch will request the Amoco
Corporation to ensure that the Agency is apprised about
significant findings from all further refinery worker
epidemiology studies/statistical analyses performed by
the company.
In view of the Agency's general interest in corporate
actions that are taken on a voluntary basis in response
to chemical toxicity/exposure data, the Amoco Corporation
will be asked if it has notified Amoco workers or other
petroleum refiners about the reported findings, and, if
so, to describe the nature of such notifications.
(b)
The Chemical Screening Branch will review the reported
information in order to determine the need for separate
OTS assessment of the reported findings and/or referral
of the findings to an ongoing assessment.
68
-------
8EHQ-0585-0557
Page 5 of 5
(c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, NTP, FDA, OW/EPA,
OSWER/EPA, ORD/EPA, OAR/EPA, and RAB and TRDB/ECAD/OTS.
In addition, copies of this status report will be sent
to the TSCA Assistance Office (TAO/OTS/OPTS) for further
distribution.
69
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 3
DATE:
~ 19~
SUBJECT:
Status Report*
8EHQ-0685-0558 S
Approved:
cJhv ~tp1 J~r
FROM: James F. Darr, Section Head ~;J' ~
Chemical Risk Identificatioffsection/CSB
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Note
The submittin<} company has claimed its company name and the exact
identity of the subject chemical to be TSCA Confidential Business
Information (TSCA CBI). The Information Management Division
(IMD/OTS) has requested the submitting company to substantiate
these confidentiality claims.
Submission Description
The submitting company provided the following information with
regard to the conduct and final results of a battery of in vitro
genotoxicity studies of a chemical identified by the submitter
generically as a "substituted oximidoalkane":
"The tests conducted were Ames Salmonella Mutagenesis,
Mouse Lymphoma Forward Mutation, in vitro Sister Chromatid
Exchange and the Balb-c 3T3 Cell Transformation assays. No
activity was detected in the Ames Salmonella assay. Dose
dependent increases in mutant frequency were induced with
and without activation in the Mouse Lymphoma Forward Muta-
tion assay. No increase in activity was observed in the in
vitro Sister Chromatid Exchange assay in the presence of--
activation, although activity was observed without activa-
tion. A significant increase in the frequency of trans-
formed foci was observed at the highest concentration in
the Balb-c 3T3 Cell Transformation assay. The results sug-
gest a potential for genetic activity but no judgment as
to potency can be made."
In its submission, the company provided copies of the final
re~orts of the Ames, Mouse Lymphoma, and Cell Transformation
assays. The submitting company stated that the results of the
Sister Chromatid Exchange assay were obtained verbally from the
testing laboratory and when the company receives the final report
=====~~=;~=~~=~~=~~~=~==~~~¥==~~=~~~=;~J;~;~=~=~~!~==~~=~~=~~=~~==~E~~=============
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
70
-------
8EHQ-0685-0558 S
Page 2 of 3
Submission Evaluation
The substituted oximidoalkane was tested for genotoxic activity
in a battery of short-term tests which included the Salmonella
typhimurium (bacteria)/mammalian microsomal assay (Ames assay),
the specific locus gene mutation assay in cultured mouse lymphoma
~5178~ cells, the in vitro Sister Chromatid Exchange (SCE) assay
In ChInese hamster ovary (CHO) cells, and the in vitro Balb-c 3T3
mouse cell transformation assay.
Although the substituted oximidoalkane was found to be negative
in the funes assay, the chemical did induce mutation at the TK
locus in cultured mouse lymphoma L5178Y cells when tested both
with and without exogenous metabolic activation. Based on these
results, the tested chemical is considered to be a mammalian cell
gene mutagen. The negative results from the Ames assay do not
affect this conclusion nor lessen concern for the genotoxicity of
this chemical substance.
The subject chemical was tested also for its ability to induce
cell transformation in cultured Balb-c 3T3 mouse cells. In this
assay, the chemical induced a dose-related increase in the number
of morphologically transformed foci in treated versus control
cultures. Although this increase was found to be statistically
significant only at the highest dose level, the biological sig-
nificance of this finding is enhanced by the dose-related nature
of the observed response. Based on these results, the substi-
tuted oximidoalkane is considered to be a weak transforming agent
in Balb-c 3T3 mouse cells in culture.
Finally, it was reported also that the substituted oximidoalkane
induced SCE formation in cultured CHO cells. Although no data
were presented to verify this statement, there is no apparent
reason to doubt its validity and, in the absence of evidence to
the contrary, the subject chemical should be considered positive
in this assay-
In view of 1) the known correlation between genotoxicity and
oncogenicity, and 2) the correlation between cell transforming
activity and oncogenicity, the substituted oximidoalkane should
be considered to be a potential oncogen in vivo.
Current Production and Use
Although the submitting company reported that this substituted
oximidoalkane is still in research and development (R&D), the
company did not provide any information with regard to the actual
or potential use(s) of the chemical. The company did report,
however, that "the number of people potentially exposed [to the
chemical] is very small" and that "exposure is being controlled
through prudent laboratory practices."
71
-------
8EHQ-0685-0558 S
Page 3 of 3
Comments and Recommendations
Although a positive in vitro genotoxicty test result, when
considered alone, maY-not be sufficient to offer reasonable
support for a conclusion of substantial risk, EPA believes that
such results are of value in assessing the possible risks posed
by chemicals to health and/or the environment. In addition, the
Agency believes that a positive genotoxicity test result in
combination with additional information (e.g., knowledge of po-
tential exposure to or high production of the chemical substance
or mixture) would suggest, in many cases, the need to conduct
other studies designed to better define the toxicity of and/or
the exposure to the chemical substance or mixture. The results
of such additional studies should be considered also for possible
submission to EPA under Section 8(e) of TSCA.
(a)
The Chemical Screening Branch (CSB/ECAD/OTS) will ask the
submitting company to ensure that EPA receives a complete
copy of the final report (including the actual experimen-
tal protocol and data) from the Sister Chromatid Exchange
assay cited in the submission.
In light of the Agency's general interest in corporate
actions that are taken on a voluntary basis in response
to chemical toxicity/exposure information, the Chemical
Screening Branch will ask the submitting company to de-
scribe the actions it has taken or plans to take to 1)
warn workers and others, and 2) reduce or eliminate ex-
posure to the substituted oximidoalkane. In addition,
the submitting company will be asked to describe the
nature and available results of all other studies that
the company has conducted, is conducting, or plans to
conduct to define the toxicity of and/or the exposure
to the substituted oximidoalkane.
(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, FDA, CPSC, NTP, OW/EPA,
OSWER/EPA, OAR/EPA, and ORD/EPA. Copies of this status
report will be sent also to the TSCA Assistance Office
(TAO/OTS/OPTS) for further distribution.
72
-------
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
Page 1 of 5
DATE:
JUl I 0 1985
SUBJECT: Status Report* 8EHQ-0685-0559 S
Approved:
/1;t- 7fG/'D5
FROM:James P. Darr, Section Head L"AIl5A1Vt...--
Chemical Risk Identificatiod!Se-;tion/CSB
TO'Prank 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 (TSCA CBI). The Information
Management Division (IMD/OTS/OPTS) will request the submitting
company to substantiate this claim.
Submission Description
The submitting company provided the following summary information
with regard to the results of both new and previously conducted
acute inhalation toxicity studies of tris(dimethylamino)silane
(CAS No. 15112-89-7) in rats:
". . .[The submitting company] originally conducted preliminary
investi3ations on the acute toxicity and primary irritancy of
tris(dimethylamino)silane, which included a study on the ef-
fects of a single exposure of rats to an atmosphere substan-
tially saturated with vapor frmn tris(dimethylamino)silane.
This was achieved by introducing samples of the test material
into the exposure chambers and allowing the atmosphere to equi-
librate overnight. Rats, in groups of 6, were then introduced
into the highly concentrated vapor. Of one group exposed for
17 minutes, all died. However, following an 8.5 minute expo-
sure, there were no mortalities among another group of rats
during a 14-day post-exposure observation period. These data
allowed the calculation of an Lt50 value of 12 minutes for ex-
posure to an atmosphere saturated with vapor from tris(dimeth-
ylamino)silane. Signs of toxicity included those of severe
irritancy.
"In view of the above initial finding, . . . [the company]
considered it appropriate to define the potential hazard from
the vapor by conducting a further acute inhalation study to de-
fine the LC50. This was achieved by exposing rats, in groups
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
73
-------
8EHQ-0685-0559 S
Page 2 of 5
of 6, for 4 hours to the following nominal concentrations of
tris(dimethylamino)silane: 2010, 1010 and 534 ppm. The atmos-
pheres were generated by a metering procedure, ~hich i~volved
feeding the liquid at a constant rate down the lnner slde of a
spirally corrugated surface of a minimally heated pyrex tube,
through which air was passed in a countercurrent fashion and
thence into the exposure chamber. The rate of feed of the li-
quid determined the atmospheric concentration of vapor. For
this [acute] study, the atmosphe~ic concentrations of tris(di-
methylamino)silane were not analytically measured. A 4-hour
exposure to 2010 or 1010 ppm resulted in the deaths of all
animals, with preceding signs of severe irritancy to ~he eyes
and respiratory tract. At 534 ppm, there were only mlld trans-
ient signs of eye irritation, but no mortalities occurred
during a 14-day post-exposure observation period. These data
allowed the calculation of a 4-hour LC50 of 734 ppm (95% con-
fidence limits of 603-893 ppm) for tris(dimethylamino)silane
under the conditions of the investigation.
"The above studies were interpreted as indicating that vapor
from tris(dimethylamino)silane is of moderate toxicity by acute
exposure to high concentrations in the atmosphere. It was con-
sidered that the irritant and toxic effects of tris(dimethyl-
amino)silane were due to dimethylamine which would be produced
in the moist chamber atmospheres. Indeed, applying a stoichio-
Jl1etric relationship of 3 parts of dimethylamine arising from
one part of tris(dimethylamino)silane and 2 parts of water,
then an equivalent LC50 in terms of hydrolysis products would
be 2202 ppm, which is close to published values on the acute
LC50 for dimethylamine vapor. On the basis of the above find-
ings, a warning of potential inhalation hazards was communi-
cated to . . . [the submitting company's] employees working
with tris(dimethylamino)silane, and steps were taken to assure
good mechanical ventilation of workspaces where the chemical is
handled. Respiratory protective equipment was made available
in circumstances where it could be anticipated that high con-
centrations of vapor may be encountered.
"Recently, . . . [the company] decided to investigate further
the toxicology of tris(dimethylamino)silane. In order to con-
firm the previous findings on the acute inhalation toxicity
[of the] vapor from the material, a further study was conducted
which involved the analytical measurement of tris(dimethyl-
amino)silane and dimethylamine in the chamber atmosphere. In
preliminary studies, again using a countercurrent stream of
air, it was found that highly variable concentrations of tris-
(dimethylamino)silane were detected in the atmosphere. In view
of this, and because of precipitation problems [encountered] in
the glass evaporators, it was decided to develop a method to
allow the maximum possibility for evaporation of tris(dimethyl-
amino)silane as the disperse vapor molecule. This was achieved
by metering the material into the vaporization tube against a
countercurrent stream of nitrogen, with the resultant tris(di-
methylamino)silane vapor being carried by dry nitrogen into the
74
-------
8EHQ-0685-0559 S
Page 3 of 5
chamber air intake duct. This resulted in significantly more
stable analytical data. Using this nitrogen stream generation
technique, groups of 10 male and 10 female rats were exposed to
the following analytically verified concentrations of tris(di-
methylamino)silane vapor: 395, 127, 62 and 23 ppm. The analyti-
cally measured dimethylamine concentrations were, respectively,
112, 31, 10 and 26 ppm. All rats died at concentrations of
tris{dimethylamino)silane vapor of 62 ppm and above. No ani-
mals died during or in a l4-day post-exposure observation
period following exposure to 23 ppm. Deaths occurred during
the first 24 hours after exposure to 395 and 127 ppm, but were
delayed between 2 and 14 days after 62 ppm. The concentration-
mortality data allowed calculation of a 4-hour LC50, for male
and female rats, to be established at 38 ppm (95% confidence
limits of 34-43 ppm) . . . .
"This 4-hour LC50 of 38 ppm for tris(dimethylamino)silane
vapor, based on analysis of chamber atmospheres, is very sig-
nificantly lower than that previously estimated at 734 ppm by a
nominal metering procedure. The comparatively low concentra-
tions of analytically measured dimethylamine vapor, with re-
spect to its known toxicity, suggest that the mortalities were
primarily the result of exposure to tris(dimethylamino)silane
vapor in the atmosphere. The findings indicate that tris(di-
methylamino)silane vapor is significantly more acutely toxic
than its major hydrolysis product, dimethylamine. In view of
the nitrogen generation technique employed in the investiga-
tions, the quantitative relevance of these findings to the
occupational environment is uncertain, since any tris(dimethyl-
amino)silane vapor released into the workplace is likely to be
hydrolyzed by water in the atmosphere to dimethylamine. How-
ever, the relative rate of this conversion will depend on both
the rate of emission of tris(dimethylamino)silane and the rela-
tive humidity of the workplace atmosphere."
Submission Evaluation
It is important to note that tris(dimethylamino)silane contains
two distinct functional groups (i.e., dimethylamine and silane).
Inhalation exposure to either dimethylamine or silane can result
in serious adverse respiratory system effects. Dimethylamine,
which can be compared to ammonia, has been shown to be a severe
respiratory tract irritant; exposure to silanes via inhalation
has been associated with respiratory hemorrhaging. In order to
evaluate the significance of the reported findings, the submitter
should be asked to provide a complete copy of the final report
(including the actual experimental protocol and histopathologic
data) from each acute toxicity study cited in the submission.
Current production and Use
A review of the production range (includes importation volumes)
statistics for tris(dimethylamino)silane (CAS No. 15112-89-7),
which is listed in the initial TSCA Inventory, has shown that
75
-------
8EHQ-0685-0559 S
Page 4 of 5
between 0 and 1000 pounds of this chemical were repoeted as pro-
duced/imported in 1977. This peoduction range information does
not include any production/importation data that were claimed as
TSCA Confidential Business Information (TSCA CBI) by those per-
son(s) reporting for the TSCA Inventory, nor does it include any
infor~ation that would compromise TSCA CBI. The data submitted
foe the TSCA Inventory, including production range infoemation,
are subject to the limitations contained in the TSCA Inventory
Reporting Regulations (40 CFR 710).
The submitting company reported that its only involvement with
tris(dimethylamino)silane is in the company's research and
development (R&D) laboratories where potential exposure to the
chemical is "extremely limited." No infoemation conceening the
actual or potential use(s) of tris(dimethylamino)silane was
provided by the submitting company or located in the secondary
literature sources consulted.
Comments/ReC~TImendations
The submitting company stated that as soon as the final report of
the recent acute inhalation toxicity study is completed a copy
would be sent to EPA. The submitting company also stated that
its employees, a company thought by the submitter to be involveci
in the manufacture, processing, or distribution of tris(dimethyl-
amino)silane, and an academic research laboratory known to be
working with the chemical were being notified about the reported
acute toxicity findings.
It should be noted that EPA's Office of Toxic Substances has
received a number of TSCA Section 8(e) and "For Your Information"
(FYI) submissions containing toxicologic/exposure information on
oeganosilanes. The Chemical Screening Branch (CSB/ECAD/OTS) has
prepared a Chemical Hazaed Information Profile (CHIP) on 3,4-
epoxycyclohexylethylteimethoxysilane and is now considering the
preparation of CHIPs on other organosilanes. The Risk Analysis
Branch (RAB/ECAD/OTS) is currently evaluating toxicologic and
exposure data on 3,4-epoxycyclohexylethyltrimethoxysilane. The
New Chemicals Progrilln in OTS has also been evaluating available
toxicologic and exposure data on organosilanes.
a) The Chemical Screening Branch will request the submitter to
ensure that EPA receives a complete copy of the final repoet
(including the actual experimental protocol and available
histopathologic data) from the company's recently conducted
acute rat inhalation toxicity study of tris(dimethylamino)-
silane. In addition, the submitter will be asked to provide
complete copies of the final eeports (including the actual
experimental protocols and histopathologic data) from all
other acute inhalation studies cited in the submission.
In view of the Agency's general interest in company actions
that are taken on a voluntaey basis in response to chemical
toxicity or exposure information, the submitter will be
76
-------
8EHQ-0685-0559 S
Page 5 of 5
asked to describe the nature and available results of all
other studies that the company has conducted, is conducting,
or plans to conduct to determine the toxicity of and/or the
exposure to tris(dimethylamino)silane.
b) The Chemical Screening Branch will review the reported in-
formation in order to determine the need for further OTS
assessment of tris(dimethylamino)silane.
c) The Chemical Screening Branch will transmit copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, OAR/EPA, and ORD/EPA. In addition, copies of this
status report will be sent to the TSCA Assistance Office
(TAO/OTS/OPTS) for further distribution.
77
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 3
DATE:
JLl 2 3 1985
SUBJECT: Sta tus Report*
8EHQ-0785-0560
Approved:
~ 1f~t-
FROM:James F. Darr, Section Head f1.._ob/\ P:?J~
Chemical Risk Identificatio~~~:~ion/CSB
TO:Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Nalco Chemical Company provided preliminary results from an
ongoing combined 2-generation Reproduction/Dominant Lethal study
of acrylamide monomer (CAS No. 79-06-1) in rats. According to
the submission, this ongoing study is being co-sponsored by Dow
Chemical U.S.A., the Standard Oil Company (Ohio), and the Nalco
Chemical Company who are all members of the Acrylamide Producers
Association, "a special projects group of [the] Synthetic Organic
Chemical Manufacturers Association (SOCMA)." In the cover letter
to its submission, Nalco provided the following summary informa-
tion concerning the conduct and available preliminary results of
the subject study:
". . . Acrylamide monomer is being administered in the
drinking water at 0, 0.5, 2.0 and 5.0 mg/kg/day to Fischer
344 rats. Male and female rats were treated for 10 weeks
prior to breeding. Females continued to receive chemical
during gestation and lactation of their Fl litters. Males
upon completion of their assigned FO parental responsibili-
ties were re-mated with naive (non-exposed) females for the
Dominant Lethal Assay. These preliminary draft results
through weaning of Fl animals and the Dominant Lethal portion
of the study indicate that 5.0 mg/kg/day but not 2.0 or 0.5
mg/kg/day acrylamide monomer produced in Fischer 344 rats the
following reproductive effects:
1. Dominant Lethal Portion
A. Although the number of eggs ovulated per dam was
equal among all dose groups, there was a significant
reduction in total implants per litter. Therefore
pre-implantation loss was significantly increased.
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
79
-------
8EHQ-0785-0560
Page 2 of 3
B. There was also an increase in non-viable implants per
litter, i.e., resorptions. Therefore, post-implanta-
tion loss was also increased.
2.
Reproduction portion (1st Generation)
Although males given acrylamide [monomer] appeared to be
able to successfully mate with females (no effect on
mating index), the litter size and the number of litters
was reduced compared to controls.
Additionally, parental animals in the 5.0 mg/kg/day group
and to a lesser extent those in the 2.0 mg/kg/day group,
as expected, displayed evidence of acrylamide intoxica-
tion. Animals in these groups had decreased body weights
(lower body weight gains) compared to controls. previous
investigations with acrylamide [monomer] have shown that
doses below 5 mg/kg/day produce peripheral neuropathy-"
Submission Evaluation
Immediately upon receipt of this TSCA Section 8(e) notice, the
Chemical Screening Branch (CSB/ECAD/OTS) forwarded copies to the
Risk Analysis Branch (RAB/ECAD/OTS) and Test Rules Development
Branch (TRDB/ECAD/OTS) for inclusion in their ongoing evaluations
of available toxicologic and exposure data on acrylamide.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for acrylamide (CAS No. 79-06-1), which is listed in
the initial TSCA Inventory, has shown that between 10 million and
51 million pounds were reported as produced and/or imported in
1977. This production range information does not include any
production or importation data that were claimed confidential by
the person(s) reporting for the TSCA Inventory, nor does it in-
clude any information which would compromise TSCA Confidential
Business Information. The data submitted for the TSCA Inventory,
including production range data, are subject to the limitations
contained in the Inventory Reporting Regulations (40 CFR 710).
The major applications of acrylamide include the chemical's use
as a cross-linking agent, in certain adhesive formulations, in
paper and textile sizes, as a soil conditioning agent, as a
flocculant, and in sewage and waste treatment.
Comments/Recommendations
In addition to sending copies of its TSCA Section 8(e) notice
to DOW Chemical U.S.A., the Standard Oil Company (Ohio), and
SOCMA, Nalco stated that any additional significant findings
from the ongoing study would be forwarded to EPA.
80
-------
8EHQ-0785-0560
Page 3 of 3
In April 1978, acrylamide was designated by the Interagency
Testing Committee (ITC) for health and environmental effects
testing under Section 4 of TSCA. In addition, final TSCA
Section 8(a) and 8(d) chemical information reporting rules
for acrylamide have been issued by the Agency. EPA has also
received several TSCA Section 8(e) and "For Your Information"
(FYI) submissions containing toxicologic and/or exposure data
on acrylamide.
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will ask the
Nalco Chemical Company to ensure that EPA receives a complete
copy of the final report (including the actual experimental
protocol, data, statistical analyses (if performed), etc.)
fron the ongoing 2-generation Reproduction/Dominant Lethal
study of acrylamide monomer cited in the submission.
b)
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, and TRDB and RAB/ECAD/OTS. In
addition, copies of this report will be sent to the TSCA
Assistance Office (TAO/OTS/OPTS) for further distribution.
81
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
'"' I 6 i985
Page 1 of 5
Approved: ~ Y'/I'{ Jr,-
SUBJECT: Status Report* 8EHQ-0785-056l S
FROM: James F. Darr, Section Head ~ 1} ~/
Chemical Risk Identification Section/CSB
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Note
The BASF Wyandotte Corporation claimed its sales and importation
volumes of the subject chemical to be TSCA Confidential Business
Information (TSCA CBI). The Information Management Division will
ask BASF Wyandotte to substantiate these confidentiality claims.
Submission Description
BASF Wyandotte submitted the results of several in vitro and in
vivo toxicity studies of l-ethenyl-2-pyrrolidinone (CAS No. 88-
12-0). These studies were conducted by the parent company, BASF
Aktiengesellschaft (BASF AG) in Ludwigshafen, West Germany. The
following summary with regard to the conduct and results of the
studies was provided by BASF in the submission's cover letter:
"In 1980, BASF AG initiated a toxicology program on l-ethenyl-
2-pyrrolidinone. At first a three-month inhalation study was
conducted in [Sprague-Dawley] rats at 0, 5, 15, 45, and 120 ppm
with 10 animals/sex/group. [Exposure to ethenyl-2-pyrrolidin-
one was carried out for 6 hrs. each working day for the dura-
tion of the three month study]. 120 ppm was lethal for the
rats [16/20 animals died]. The liver and the olfactory mucosa
of the nasal cavity were the target organs. The severity of
these changes was concentration-dependent with minimal changes
at 15 p~n in the liver and 5 ppm in the nasal mucosa. A sub-
sequent study established a no-effect level of 1 ppm.
"Because of the observation of liver toxicity in the first
study, in March 1983 BASF AG initiated a preliminary study to
investigate the rat liver's recovery from this toxicity. In
this study, female [Sprague-Dawley] rats were exposed to 45 ppm
for three months and sacrificed at 7 weeks (during treatment),
3 months (end of treatment), 12 and 24 months. The draft in-
terim reports show that there was evidence of hepatic toxicity
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
82
-------
8EHQ-0785-0561 S
Page 2 of 5
at 7 weeks which was more marked at three months. At the in-
terim kill at 12 months, there was marked recovery of liver
architecture and recovery from toxicity. Of the 15 animals,
each designated for kill at 24 months, 6 of the treated group
and 4 from the controls survived this period. There appeared
to be no difference in mortality between control and treated.
Of the animals killed at the termination, 2 possible carcinomas
were observed, and 2 other animals in the treated group had
nodular lesions originally reported as "neoplastic nodules".
In the control group one animal showed a nodular lesion similar
to the neoplastic nodules in the treated group. None of the
animals in the treated group dying or killed prior to termina-
tion showed evidence of carcinoma or neoplastic nodules.
"Additional toxicity testing conducted by BASF AG includes a
three-month inhalation test in [Syrian] hamsters as well as
3-week and 3-month drinking water studies in [Wistar] rats
and a 3-month gavage study in rats. These studies confirmed
the hepatotoxicity of l-ethenyl-2-pyrrolidinone to the rat;
however, the compound is not toxic to the hamster at the con-
centration tested."
BASF Wyandotte also reported that l-ethenyl-2-pyrrolidinone was
found to be negative in the following in vitro test systems: an
Ames Salmonella typhimurium (bacteria)Jmutagenicity assay (with
and without exogenous metabolic activation), a mouse lymphoma
cell forward mutation assay (with and without exogenous metabolic
activation), a Balb/3T3 mouse cell transformation assay, and an
unscheduled DNA synthesis (UDS) assay in rat hepatocytes.
Submission Evaluation
The performed subchronic inhalation toxicity study of l-ethenyl-
2-pyrrolidinone in Sprague-Dawley rats (conducted at 1, 5, 15, 45
and 120 ppm and terminated at 3 months) showed in the 15 and 45
ppm groups an increase in ITVer weights and in the 120 ppm group
clear signs of toxicity (e.g., severe liver damage, necrosis of
the nasal mucosa, and hemorrhagic diathesis). The subchronic
toxicity study in Wistar rats exposed to the chemical at 5, 12,
30 and 75 ppm in the drinking water and terminated at 13 weeks
showed in the 30 and 75 ppm groups kidney hypertrophy Tn males
only. Surprisingly, this particular finding did not appear to
have a light microscopically-detectable morphological basis. In
females there was no evidence of kidney hypertrophy although oc-
casional foci of calcification were observed. In the experiment
in which male and female Wistar rats were exposed to l-ethenyl-2-
pyrrolidinone via the drinking water for 3 or 4 weeks followed by
gavage for 13 weeks, dose-dependent liver hypertrophy was found.
This coexisted with focal parenchymal changes as well as "foci of
cellular alterations."
83
-------
8EHQ-0785-056l S
Page 3 of 5
Three to four months seems to represent the threshold beyond
which chronic toxic effects begin to appear in rats. Thus,
female Sprague-Dawley rats exposed to l-ethenyl-2-pyrrolidinone
via inhalation at 45 ppm for 3 months, followed by a 9 to 21
month observation period, showed degenerative liver parenchymal
changes and focal metaplasia resembling cirrhosis, proliferation
and cloudy vacuolar swelling of hepatocytes, and glycogen accumu-
lation in the proliferating cells. In addition, there were clear
hepatocellular carcinomas in 2 animals and "neoplastic nodules"
in the livers of 2 additional animals. Moreover, there were
occasional "foci of cellular alterations. II These foci had cells
with enlarged nuclei, some of which were "vesicular. II Cells in
the foci also showed glycogen accumulation.
There appears to be a marked difference in the susceptibility of
rats and hamsters to the toxic effects of l-ethenyl-2-pyrrolidin-
one. Male and female hamsters that underwent essentially the
same dosing schedule (a 3 month period of inhalation at 45 ppm
followed by a 15 month observation period) showed no pathological
changes. It is somewhat surprising that hamsters were chosen as
the second species as opposed to mice. Hamsters are well-known
to be relatively resistant to the carcinogenic action of a number
of chemical agents, as compared to rats and mice. Therefore, the
absence of pathological changes in hamsters exposed to l-ethenyl-
2-pyrrolidinone is not entirely surprising nor unexpected.
l-Ethenyl-2-pyrrolidinone was reported to be non-genotoxic in 4
short-term in vitro tests (an Ames test using 4 bacterial test
strains, a mouse cell transformation assay, a mouse lymphoma cell
forward mutation assay and an unscheduled DNA synthesis assay in
rat hepatocytes). It should be noted that the GAF Corporation
submitted (8EHQ-0682-0448 S et seq.) the results of several in
vitro genotoxicity studies of a structurally-related chemical.
In its Section 8(e) filing, GAF reported that 1-(2-hydroxyethyl)-
2-pyrrolidinone produced a positive mutagenic response in the
Ames test, a suggestive mutagenic response in a Chinese Hamster
Ovary (CHO)/HGPRT gene mutation assay, and negative responses in
CHO/Sister Chromatid Exchange (SCE), CHO/chromosomal aberration,
and Balb/3T3 mouse cell transformation assays.
On the basis of the data contained in the present submission, 1-
ethenyl-2-pyrrolidinone is hepatotoxic and appears to be a weak
hepatic carcinogen in rats. It should be noted also that in order
to clearly establish that l-ethenyl-2-pyrrolidinone is not geno-
toxic, it would be quite useful to test the chemical's ability to
covalently bind to DNA in vivo. In addition, it would be very
important to determine whether l-ethenyl-2-pyrrolidinone has the
ability to produce teratogenic or other adverse developmental
effects.
84
-------
8EHQ-0785-056l S
Page 4 of 5
Current Production and Use
A review of the production range (includes importation volumes)
statistics for l-ethenyl-2-pyrrolidinone (CAS No. 88-12-0), which
is listed in the initial TSCA Inventory, has shown that between 0
and 1 thousand pounds of this chemical were reported as produced/
imported in 1977. This production range information does not in-
clude any production/importation data that were claimed as TSCA
Confidential Business Information (TSCA CaI) by the person(s) re-
porting for the initial TSCA Inventory, nor does it include any
information that would compromise TSCA CBI. All information that
was submitted for the initial TSCA Inventory, including the pro-
duction range data, is subject to the limitations contained in
the TSCA Inventory Reporting Regulations (40 CFR 710).
In its submission, BASF Wyandotte reported that l-ethenyl-2-
pyrrolidinone is manufactured by BASF AG in West Germany and is
imported to the U.s. by BASF Wyandotte. BASF Wyandotte reported
also that the subject chemical "is used as a raw material for the
manufacture of a variety of chemical products." According to in-
formation contained in secondary literature sources, l-ethenyl-2-
pyrrolidinone is used as a reactive diluent in ultraviolet and
electron beam curable polymer systems; as an intermediate in the
production of modified phenolic resins used as plasticizers, dye-
stuff intermediates, and textile assistants; and as the starting
monomer for polyvinylpyrrolidone which has numerous applications
(e.g., pharmaceuticals, cosmetics, detergents, adhesives, beer
and wine clarification).
Comment/Recommendations
BASF Wyandotte stated that additional studies (e.g., in vivo DNA
binding, metabolism, teratogenicity, and chronic exposurer-are
being considered in order to define better the potential toxicity
of l-ethenyl-2-pyrrolidinone. In addition, BASF Wyandotte stated
that the company is notifying its customers about the reported
findings. Finally, BASF Wyandotte stated that all final reports
would be sent to EPA.
a)
The Chemical Screening Branch (CSB/ECAD/OTS/OPTS) will ask
the submitting company to ensure that EPA receives a complete
copy of the final report (including the actual experimental
protocol, data, statistical analyses (if performed), etc.)
from each study (including the in vitro 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
and/or exposure information, BASF Wyandotte will be asked to
describe the actions the company has taken to notify its own
workers about the reported findings. BASF Wyandotte will be
85
-------
8EHQ-0785-056l S
Page 5 of 5
asked also to describe the nature and available results of
all studies (other than those already published in the open
scientific literature or already reported to EPA) that have
been conducted by or known to the company that determine the
exposure to l-ethenyl-2-pyrrolidinone during its manufacture,
processing, and/or end-use.
b)
The Chemical Screening Branch will review the provided
information in order to determine the need for further
OTS assessment of l-ethenyl-2-pyrrolidinone.
c)
The Chemical Screening Branch will send copies of this
status report to OSHA, NIOSH, CPSC, FDA, NTP, OAR/EPA,
OH/EPA, OSWER/EPA, and ORD/EPA. In addition, copies of
this status report will be sent to the TSCA Assistance
Office (TAO/OTS/OPTS) for further distribution.
86
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
JU3 2 3 915
Page 1 of 6
Approved: ~
1Z1/1~
" ,
UBJECT: Status Report* 8EHQ-07 85-0 56 2 S
-pM;I!})~J-In/
FROM: Jam~'3 F. Darr, Section Head
Chemical Risk Identification Section/CSB
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Note
The submitting company has claimed its company name and the
actual identity and tradename of the subject chemical to be TSCA
Confidential Business Information (TSCA CBI). The Information
Management Division (IMD/OTS) will request the submitting company
to substantiate these confidentiality claims. The submitter did
provide the following non-confidential generic name for the sub-
ject chemical: "dichlorophenyl-alkoxyalkyl-oxoheteromonocycle."
Submission Description
The submi tting company provided preliminary and, in somes cases,
final results from a number of in vivo toxicologic studies on
dichlorophenyl-alkoxyalkyl-oxoheteromonocycle. According to the
submitted information, the chronic toxicity and possible carcino-
genic properties of the chemical were/are being examined in male
and female rats in the following 3-part study that was started
in September, 1983:
1) a 12-month study of 5 groups of 10 male and 10 female
rats exposed to the chemical at levels of 0, 500, 750,
2250 or 4500 ppm in the food;
2) an l8-month study of 5 groups of 10 male and 10 female
rats exposed to the chemical at levels of 0, 500, 750,
2250 or 4500 ppm in the food; and
3) a life-span study of 4 groups of 50 male and 50 female
rats exposed to the chemical at levels of 0, 500, 750
'or 2250 ppm in the food.
A submitted pathology report contained the following information
concerning results of the l2-month segment of the chronic feeding
study which ended in September, 1984:
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
87
-------
8EHQ-0785-0562 S
Page 2 of 6
"Microscopic examination revealed treatment-related changes
in the testis, the kidneys and the pituitary. The testis
lesions were characterized by (1) a dose-related increase in
incidence and severity of diffuse interstitial cell prolifera-
tion in all treatment groups, including the low-dose group
(the differences with the controls were statistically sig-
nificant in the 750, 2250 and 4500 ppm group (p < 0.01 for
each group» and (2) the presence of nodular interstitial
cell proliferation in all treatment groups (statistically
significant (p < 0.05) in the top-dose group only), while
this finding was completely absent in the controls.
"The testicular lesions observed in the low-dose group are
also considered to be treatment-related because the inci-
dence of diffuse interstitial cell proliferation showed a
dose-related increase in all treatment groups, including
the low-dose group, and since, moreover, nodular intersti-
tial cell proliferation (which is an unusual finding for
12 months old rats of the strain used), occurred also in
all treatment groups including the low-dose group.
"Tumours observed were a metastasizing adenocarcinoma of
the mammary gland and a fibromatous polyp of the uterus.
Since both tumours occurred in control females their occur-
rence is not related to treatment. The other abnormalities
observed are common findings in the strain of rats used.
They were about equally distributed among control and test
groups, or occurred only in one or two animals. Therefore
they were not ascribed to the feeding of the test substance.
"The kidney changes consisted of an increase in incidence
and severity of dilatation of the pars recta of the proximal
renal tubules. This increase occurred in the 2250 and 4500
ppm groups in both sexes, and in the the 750 ppm groups only
in females. Moreover, in females the normally occurring renal
mineralisation was absent in most of the test animals, in-
cluding those of the low-dose group. Since distinct signs of
degeneration or necrosis were absent the toxicological sig-
nificance of these renal changes is not clear.
"In the pituitary there was a dose-related increase in the
severity of cellular hypertrophy of pars distalis cells in
males only. Focal or diffusely distributed hypertrophic
cells were present in male rats of all groups, including
the controls. In controls and low-dose animals this phe-
nomenon occurred in about similar incidences and only to
a very slight degree, while in the higher dose groups (from
750 ppm and on) the cellular hypertrophy became increasingly
accentuated. Distinct evidence of degeneration was absent."
The following information was presented in the submission with
regard to the histopathologic findings from the 18-month segment
of the chronic oral feeding study in rats:
88
-------
8EHQ-0785-0562 S
Page 3 of 6
". . . [There is] a dose-related trend in the incidence
and severity of diffuse interstitial cell proliferation
and nodular interstitial cell proliferation in the testes.
In addition, there is now a dose-related trend in the inci-
dence of Leydig-cell tumors in the testes."
The submitting company also provided the following information
concerning the conduct and interim (week 0 to 13) results of a
I-year oral feeding study in dogs:
"In the present study four groups of beagle dogs, each
consisting of four males and four females, are treated
with the test substance at the dietary concentrations
of 0 (control), 400, 800, or 2400 ppm. The study was
started on September 20, 1984.
"One male dog in the top-dose group showed a bad health
condition from week 9 and onwards. The animal showed
severe anorexia and became very emaciated. Sometimes a
green discharge from the anus was observed. In week 9
also signs of pain were noticed. This dog was killed
in week 9. One male dog in the mid-dose group also
showed signs of emaciation from week 8 onwards. Other-
wise, no treatment-related changes were observed with
respect to behaviour and condition.
"The male dog of the high-dose group which had to be
killed in week 9 because of a very bad health condition
showed the following gross findings: enlarged and green
lymph nodes, markedly involuted thymus, cholelithiasis
[(gall stones)], haemorrhagic nodule (diam. 1 cm) on the
left hind leg, [and] several petechiae [(small bruises)]
on this leg.
"Upon microscopic examination several histopathological
lesions were observed. Perivasculitis was found of ves-
sels, mainly arteries, in the mediastrum, pelvic and scro-
tal region, and of some coronary vessels. Several thrombi
of amorpheus, eosinophilic material with polymorphonuclear
inflammatory cells were found intravascularly. The liver
showed slight congestion and slight accumulation of brown
pigment. All lymph nodes examined were inflamed. . .
One testis showed coagulation necrosis. Aspermatogenesis
was found in the contralateral testis. The thymus was
atrophic and marked cell depletion was found in the T-cell
dependent areas of the peripheral lymphoid tissues."
The submitter also provided a report that contained the following
information from a rabbit embryotoxicity/teratogenicity study:
"Suspensions of [the subject chemical] in 1% aqueous gum
tragacanth were administered [from days 6-19] to pregnant
New Zealand White rabbits by intra-oesophagic intubation at
dose levels of 0, 5, 10, 30 and 100 mg/kg body weight/day."
89
-------
8EHQ-0785-0562 S
Page 4 of 6
"The administration of [the test substance] did not induce
any abnormalities in behaviour. Haematury was observed in
a considerable number of rabbits of the 10, 30 and 100 mg/kg
dose groups. In the 5 mg/kg dose group, only one rabbit re-
vealed occult blood in the urine on day 27 of pregnancy only.
"[The] maternal performance was comparable in all groups;
the fertility indices ranged from 80.9 in the 30 mg/kg dose
group to 100 in the 100 mg/kg dose group. During the study
one or two rabbits in each group had an abortion; total lit-
ter resorption occurred in one or two rabbits of each group
except the highest dose group. Gestation indices ranged from
81.3 to 95.0 and were all within the normal range.
"[Maternal] body weight and food intake were not affected
by [the test substance]. Autopsy findings, organ weights
and litter data did not reveal any embryotoxic or foetotoxic
effect of [the test chemical].
"Upon foetal examination, no compound related visceral mal-
formations, anomalies or variants were observed. Micro-
scopic examination of foetal skeletons revealed skull bone,
rib and vertebral malformations in foetuses of the high-dose
group that were not observed in any of the other groups.
Further, the number of foetuses with supernumerary ribs was
significantly increased in the high-dose group as compared
to the controls.
"It was concluded that under the conditions of the present
embryotoxicity/teratogenicity study: a. the no-toxic-effect
level of [the test substance] for pregnant rabbits is less
than 5 mg/kg body weight/day; b. 100 mg/kg body weight/day
[of the test substance] is embryotoxic/teratogenic; c. the
no-embryotoxic/teratogenic-effect level of [the test sub-
stance] is 30 mg/kg body weight/day."
The submitting company also provided results of a two-generation
reproduction study conducted in male and female rats. In its
submission, the company reported that:
"Groups of male and female rats were administered 0, 500,
750, or 2250 ppm [of the test substance] in their diets.
The study is a two generation study with two litters per
generation and the in-life portion has ended. [The test
chemical] appears to have affected the mating and fertil-
ity indices in the second generation. . .. The histo-
pathology findings from. . . [this] reproductive study
corroborate and extend the findings from the chronic oral
toxicity and carcinogenicity study [in rats]."
Finally, the submitter provided the following information with
regard to the conduct and results of a 21-day sub-acute dermal
toxicity study in rabbits:
90
-------
8EHQ-0785-0562 S
Page 5 of 6
"Three groups of male and female rabbits were treated
dermally [with the test substance) for three weeks,
five days a week. . . [with] daily doses of [0,] 10,
30 or 100 mg/kg bodyweight.
"Significant treatment-related effects were observed
in males only. They consisted of decreased growth,
food intake and food efficiency, [reduced spermato-
genesis,] and histopathological changes in the testes
with 30 and 100 mg/kg/day and of decreased testes
weights with 100 mg/kg/day.
"It was concluded that 10 mg/kg/day is a no-adverse-
effect dose of [the test substance] for male albino
rabbits. . . . The highest test dose of 100 mg/kg/day
did not cause any significant adverse effects in fe-
male albino rabbits. Therefore, it was concluded that
under the conditions of the study [the test chemical]
is considerably more toxic for male than for female
albino rabbits."
Submission Evaluation
The submitted information relating to the chronic oral (feeding)
study in rats indicates that exposure to the subject chemical has
resulted thus far in a dose-dependent increase in the number of
rats with Leydig-cell tumors (0 in the controls, 1 at 500 ppm, 3
at 750 ppm, 4 at 2250 ppm, and 12 at 4500 ppm). Concurrently,
there was a marked dose-related increase in nodular interstitial
cell proliferation in the testes and an increased severity of
diffuse interstitial cell proliferation in the testes. Based on
a review of the submitted interim data, the submitting company's
stated concern that the subject chemical may pose an oncogenic
risk is clearly correct.
In addition, it is clear from the submitted data that exposure
to the subject chemical can result in serious adverse effects in
the male reproductive system (e.g., a dose-related incidence of
rats with Leydig-cell tumors, a dose-related increase in inter-
stitial cell proliferation in testes, reduced spermatogenesis,
interference with reproductive performance such as mating and
fertility). In addition, exposure to the test substance appears
also to result in developmental toxicity at doses below those
that cause the forms of maternal toxicity usually observed in
teratologic studies (e.g., decreased maternal body weight and
food consumption; increased liver weight). It should be noted,
however, that the hematuria reportedly observed in the dams in
the teratology study needs to be examined in further detail in
order to determine the impact of this effect, if any, on the
developing fetuses.
In order for EPA to determine the overall significance of the
reported toxic effects of this chemical, a complete copy of the
final report from each of the cited studies is needed.
91
-------
8EJIQ-0785-0562 S
Page 6 of 6
Current production and Use
In view of the fact that the submitting company has claimed the
exact chemical identity of the test substance to be TSCA CBI, no
information concerning the chemical's TSCA Inventory status or
production/importation volumes will appear in this status report.
In its submission, the company stated non-confidentially that the
dichlorophenyl-alkoxyalkyl-oxoheteromonocycle is a pesticide with
worldwide distribution that was undergoing field testing in the
united States.
Comments and Recommendations
In its submission, the submitting company reported that all u.s.
field testing with the subject chemical has been halted. The
submitter also reported that "all Cooperators have been notified
by letter that further field testing [with the chemical] is being
curtailed." Finally, the submitting company reported that it
plans no further development of the compound.
The Chemical Screening Branch (CSB/ECAD/OTS/OPTS) has notified
the Office of Pesticide Programs (OPP/OPTS) about the reported
information. OPP is now reviewing the information to determine
the applicability of, and the need for action under, the Federal
Insecticide, Fungicide and Rodenticide Act (FIFRA).
a) The Chemical Screening Branch (CSB/ECAD/OTS) will request
the submitting company to provide to EPA a complete copy
of the final report (including the actual experimental pro-
tocols, data, statistical analyses (if performed), etc.)
from each toxicologic study cited in the company's TSCA
Section 8(e) filing on the subject chemical.
In view of the Agency's general interest in corporate
actions that are taken on a voluntary basis in response
to chemical toxicity and/or exposure information, the
submitting company will be requested to describe those
actions the company has taken to notify its workers and
others about the reported toxicologic findings.
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 OSHA, NIOSH, CPSC, FDA, NTP, OW/EPA,
OSWER/EPA, OAR/EPA, ORD/EPA and the Office of Pesticide
Programs (OPP/OPTS/EPA). Copies of this report will be
sent also to the TSCA Assistance Office (TAO/OTS/OPTS)
for further distribution.
92
-------
UNITED STATES ENVIRONMENT'AL PROTECTION AGENCY
Page 1 of 4
DATE:
SEP
5 1985
SUBJECT: Status Report *
8EHQ-0785-0563
APproved::z;Jtu q/014/ ft{
FROM: James F. Darr, Section Head !hA~nA 'f'~
Chemical Risk Identificationa~~~ion/CSB
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Dow Corning Corporation submitted the following information
concerning the conduct and results (received verbally by the com-
pany from the performing laboratory) of a 5-day rat inhalation
study of tetramethoxysilane (CAS No. 681-84-5):
"Treatment: 10 male & 10 female Sprague Dawley rats
per dose level were exposed for 5 days, 6 hours per day
to silicic acid tetramethyl ester [tetramethoxysilane]
at chamber vapor concentrations of 5, 12, and 20 ppm.
[The] chamber temperature and relative humidity were
maintained within acceptable limits during treatment.
"Clinical Observations: No mortality was observed in
any of the treated groups. No adverse effects of the
eye were observed.
"Gross pathology: Seventeen of the 20 rats in the high
dose (20 ppm) group exhibited moderate lung hemorrhage
with no other adverse effects found. Fifteen of 20 rats
in the 12 ppm dose group exhibited mild lung hemorrhage
with no other adverse effects found. No effects were
found in 20 of 20 rats in the low (5 ppm) dose group."
[The submitter reported that this 5-day rat inhalation
study was conducted in order "to establish dose levels
for a 28-day inhalation study."]
The Dow Corning Corporation submitted the following background
information concerning the known toxicity of the tested chemical
and the company's rationale for submitting the 5-day inhalation
study resul ts to E.!'A u!:d~r ~~_c_t:.!
-------
8EHQ-0785-0563
Page 2 of 4
". . . [Tetramethoxysilane] has been. . . in commerce
for many years and has been regarded as hazardous and
a severe eye irritant that should be handled with ap-
propriate care. Information available to . . . [DOW
Corning] indicates [that the] known health effects are
due to vapor exposure and have identified the eye as
the most sensitive target site. Human health effects
considered in the current TLV [*] standards estimated
air concentrations of 200 to 300 ppm were required for
15 minutes to produce corneal damage and that exposure
to 1,000 ppm were required to produce injury requiring
hospitalization. It has been reported that lung func-
tion tests were always normal if corneal damage was
absent. This observation was based on a designed acute
vapor study in guinea pigs."
[*] In its Section 8(e) submission, Dow Corning reported that
the "current industrial hygiene standards, as established by the
American Conference of Governmental Industrial Hygienists, for
. . . [tetramethoxysilane] are represented by the following:"
Threshold Limit Value (TLV) for an 8-hour Time Weighted Average
(8-hour TWA) = 1 ppm (approximately 6 mg/cubic meter of air)
Threshold Limit value (TLV) for a Short Term Exposure Limit
(STEL) = 5 ppm (approximately 30 mg/cubic meter of air)
According to Dow Corning, the company's use of tetramethoxysilane
"is carried out with strict environmental controls appropriate to
the TLV limit of 1 ppm by persons having a high degree of techni-
cal training." In addition, it was reported that "there have
been no adverse health effects experienced at Dow Corning."
Submission Evaluation
Although the observed lung hemorrhages are consistent with the
adverse effects seen in the lungs of animals exposed via inhala-
tion to vapors of tetraethoxysilane or trimethoxysilane, it is
quite noteworthy that the observed lung hemorrhages did not occur
in conjunction with adverse eye effects. Based on the submitted
findings, it appears that the lack of the ocular effects does not
preclude the possiblity that toxic effects could occur elsewhere
in the body.
In order for EPA to evaluate better the overall significance of
these findings, DOW Corning should be asked to submit a complete
copy of the final report (including the actual experimental pro-
tocol, data, statistical analyses (if performed), etc.) from the
company's 5-day and 28-day tetrarnethoxysilane inhalation studies
in rats.
94
-------
8EJIQ-0785-0563
Page 3 of 4
Current Production and Use
A review of the production range (includes importation volumes)
statistics for tetramethoxysilane (CAS No. 681-84-5), which is
listed in the initial TSCA Inventory, has shown that from 0 to
1000 pounds were reported as produced/imported in 1977. This
pro?uction range information does not include any information
cla1med as TSCA Confidential Business Information (TSCA CBI) by
the person(s) reporting for the TSCA Inventory, nor does it in-
clude any information that would compromise TSCA CBI. The data
submitted for the TSCA Inventory, including the production range
data, are subject to the limitations contained in the Inventory
Reporting Regulations (40 CFR 710).
In its submission, Dow Corning reported that tetramethoxysilane
"is an industrial chemical that is used as an intermediate or in
chemical processing." According to secondary literature sources,
tetramethoxysilane applications include the chemical's use in
glass-frosting and in manufacture of specialty glass for fiber
optics and solar materials.
Comments/Recommendations
In its submission, Dew Corning stated that the company is in the
process of notifying other organosilicon chemical manufacturers
about the reported toxicologic findings. DOW Corning stated also
that, when available, a copy of the final report from the 5-day
rat inhalation study would be sent to EPA.
It should be noted that EPA's Office of Toxic Substances (OTS)
has received a number of Section 8(e) and "For Your Information"
(FYI) submissions containing toxicity and/or exposure information
on organosilanes. In particular, it should be noted that EPA has
received a Section 8(e) submission (8EHQ-0680-0347 et seq.) on
trimethoxysilane, a structural analog to tetramethoxysilane. The
Chemical Screening Branch (CSB/ECAD/OTS) has prepared a Chemical
Hazard Information profile (CHIP) on 3,4-epoxycyclohexylethyltri-
rnethoxysilane and is now considering the preparation of CHIPs on
other organosilanes. The Risk Analysis Branch (RAB/ECAD/OTS) is
currently evaluating available toxicity and exposure data on 3,4-
epoxycyclohexylethyltrimethoxysilane. The New Chemicals program
in OTS has also been evaluating available toxicity and exposure
data on organosilanes.
a) The Chemical Screening Branch (CSB/ECAD/OTS) will request the
Dow Corning Corporation to ensure that EPA receives a complete
copy of the final report (including the actual experimental
protocol(s), data, statistical analyses (if performed), etc.)
from the 5-day inhalation study and the 28-day inhalation
study (when completed).
95
-------
8EHQ-0785-0563
Page 4 of 4
In view of the Agency's general interest in corporate actions
that are taken on a voluntary basis in response to chemical
toxicity or exposure information, the DOW Corning Corporation
will be asked to describe the actions the company has taken to
notify its own workers about the reported toxicologic findings
for tetramethoxysilane.
b) The Chemical Screening Branch will review the submitted data
in order to determine the need for further OTS assessment of
tetramethoxysilane.
c) The Chemical Screening Branch will transmit copies of this
status report to OSHA, NIOSH, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, and OAR/EPA. Copies of this report will
be sent also to the TSCA Assistance Office (TAO/OTS) for
further distribution.
96
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 3
DATE:
SEP
6 1985
SUBJECT: status Report* 8EHQ-0885-0564 S
APproved:~ q/qfgr
/ I
FROM: James F. Darr, Section Head ~ 1: ~
Chemical Risk Identification Section/CSB
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Note
The submitting company has claimed its company name, a product
trade name, and the names of two other companies to be TSCA
Confidential Business Information (TSCA CBI). The Information
Management Division (IMD/OTS) will request the submitter to
substantiate all of these confidentiality claims.
Submission Description
The submitting company provided the following information
concerning the company's detection of three nitrosamines (N-
nitrosodiethanolamine, N-nitrosodimethylamine, and N-nitroso-
morpholine) in coolants from automobiles manufactured by two
companies whose identities were claimed to be TSCA CBI:
". . . [The submitting company] has obtained analytical data
which indicate that nitrosamines are formed in automobile cool-
ants containing triethanolamine even without nitrite added to
the coolant. These samples were obtained from automobiles at
dealerships in the U.S. The automobiles that were sampled did
not contain. . .[the submitter's coolant] product.
"Although the presence of nitrosamines in automotive coolants
has been reported in the literature, it has been reported that
coolants containing triethanolamine can contain nitrosamines
when nitrites are not added to the coolant. .. .[T]he levels
found in these samples were low, less than 5 ppm. . .. The
level of nitrosamines in the samples would be expected to be
much higher if the automobiles had been "topped Up" with a
nitrite containing coolant. A great deal of coolant sold in
the aftermarket contains nitrite and nitrite is widely used in
supplemental inhibitors. II
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
97
-------
8EHQ-0885-0564 S
Page 2 of 3
"The formation of nitrosamines when primary, secondary, or
tertiary amines react with nitrogen oxides and/or nitrites is
well known. The International Agency for Research on Cancer
(IARC) has concluded that there is sufficient evidence of ani-
mal carcinogenicity for serveral N-nitroso compounds including
N-nitrosodiethanolamine, N-nitrosodimethylamine, and N-nitroso-
morpholine. N-Nitrosodiethanolamine, for example, has been
reported to be carcinogenic to animals following oral admini-
stration and subcutaneous injection and N-nitrosodimethylamine
has been shown to be carcinogenic in several animal species.
"Use of nitrites and/or amines, primarily triethanolamine, in
automobile coolants has been reported in Sweden. There an at-
tempt was made to standardize automotive coolants because it
was recognized that nitrosamines could be formed when auto-
mobiles containing a triethanolamine-based fluid were "topped
up" with a nitrite-type of fluid. . .. Triethanolamine was
voluntarily removed from coolants in Sweden.
"This matter was also acknowledged in France; but no industry
standard has been established. The presence of nitrosamines in
several leading French brands of antifreeze was reported in the
literature. . .. [With regard to a provided copy of a French
article, the submitting company noted that] the authors recom-
mended that the use of sodium nitrite be abandoned as an anti-
corrosion additive.
". . . [The submitting company's] analytical data indicate
that the conclusion of the French authors does not completely
address the issue. The data indicate that nitrosamines are
formed in triethanolamine based automobile coolants even when
no nitrite was added to the coolant. Analysis of 17 samples
of automotive coolant obtained from. . . [two manufacturers']
vehicles at dealerships in the U.S. indicated low levels of
nitrosamines, primarily N-nitrosodiethanolamine. . .
". . .[The submitter's] analysis indicates that. . .[the two
car manufacturers'] use triethanolamine type coolants in many
of their vehicles. It is speculated that exhaust gasses leak-
ing into the coolant past the head gasket are the source of the
nitrosating agent. It is well known that combustion gasses in
automobile engines contain nitrogen oxides.
"Although. . .[the submitting company] does not believe that
the presence of these low levels of nitrosamines in the auto-
mobile coolants constitutes a substantial risk to health or the
environment, [the submitting company is providing] this infor-
mation to advise EPA of a potential problem. There could be
some [nitrosamine] exposure to mechanics at radiator repair
shops, import car dealerships, and to the "do it yourselfer"
coming into contact with nitrosamines formed in these coolants
when "topped up"."
98
-------
8EHQ-0885-0564 S
Page 3 of 3
Submission Evaluation
EPA's concern about human exposure to nitrosamines is well known
and is based mainly on a large number of animal studies in which
nitrosamine exposure by a variety of routes resulted in cancer.
It should be noted that EPA's Office of Toxic Substances has
received a number of TSCA Section 8(e) and "For your Information"
(FYI) submissions containing toxicologi~ and/or exposure data on
nitrosamines. In addition, the Chemical Screening Branch has
prepared Chemical Hazard Information Profiles (CHIPS) on several
nitrosamines.
Immediately upon receipt of this Section 8(e) submission, the
Chemical Screening Branch (CSB/ECAD/OTS) provided copies of the
notice to the Risk Analysis Branch (RAB/EACD/OTS) and Existing
Chemical Control Branch (ECCB/CCD/OTS) for inclusion in the on-
going OTS evaluation of available toxicologic and exposure data
on nitrosamines. It should be noted that in September 1984, EPA
published two "Chemical Advisories" that outline EPA's concerns
about nitrosamines in metalworking fluids. Copies of these ad-
visories may be obtained by calling toll free at 800-424-9065 or
in the Washington, D.C. area at (202)-554-1404, or by writing to:
Ed Klein, Director
TSCA Assistance Office (TS-799)
Office of Toxic Substances (OTS)
Environmental Protection Agency
401 "M" Street, S.W.
Washington, D.C. 20460
Comments/Recommendations
In its Section 8(e) notice, the submitting company stated that
it was notifying the two automobile manufacturers whose cars had
been found to contain nitrosamines in their coolants.
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, RAB/ECAD/OTS and ECCB/CCD/OTS.
Copies of this status report will be provided also to the
TSCA Assistance Office (TAO/OTS) for further distribution.
99
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
SEP 2 0 1985
Page 1 of 3
SUBJECT: Status Report* 8EHQ-0885-0565 S
APproved:~ q/t5lf~
I '
. H d ~P-or~
FROM: James F. Darr, Sectlon ea (J: --~~
Chemical Risk Identification section/CSB
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 several chemical substances and products to be TSCA
Confidential Business Information (TSCA CBI). The staff of the
Information Management Division (IMD/OTS) will ask the submitting
company to substantiate these confidentiality claims.
Submission Description
The submi tting company provided the following information wi th
regard to the results of acute animal studies designed to deter-
mine the level of "immers ion-type derma ti tis" associated wi th
chemical substances or mixtures:
"The reaction product of 1 mole of succinic anhydride
[(CAS No. 108-30-5)] and 1 mole of Jeffamine D-2000 [an
amine terminated polypropylene glycol; CAS No. 9046-10-
0)] in combination wi th other undetermined chemicals,
has been found to cause eye damage in guinea pigs fol-
lowing immersion to aqueous solutions. This is, to the
best of . [the submitting company's] knowledge, a
new chemical which is not listed on the TSCA Inventory.
"The eye damage was observed during preliminary testing
to create a new product. This laboratory testing in-
volved a de minimus amount of product. As a part of
the evaluation process, the mixture was tested on
guinea pigs for skin irritation potential. At the con-
clusion of the test, all the test animals were found to
be blind."
"Subsequent tests established that the presence of the
subject chemical is necessary to create the observed
response; however, it alone, in the absence of the
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
100
-------
8EHQ-0885-0565 S
Page 2 of 3
other mixture components [(i.e., alkanolamines, a bio-
cide package, an alkoxyamine, and mixed carboxylic
acids)] did not cause eye damage. In none of these
cases was skin irritation observed, suggesting that
some other mechanism than corrosivity was involved.
"Again, these results seem to indicate that the com-
bination of the subject chemical wi th at least one
other component is the cause of the observed effects.
There has not been time to determine which of the other
chemicals present might be responsible for the observed
effect. ...."
The submitter also provided a copy of a standard protocol used in
the dermal exposure studies using guinea pigs. The following is
an excerpt from the submitted protocol:
"All animals are ear-tagged with consecut ive numbers.
Each animal is placed in a stainless steel retainer and
then put in a 600 ml graduated heavy-walled beaker con-
taining the test material (approximately 275 ml). The
beakers are placed in the immersion tank which is a
constant temperature (40°C) water bath.
"The animals are placed in these retainers for four and
one-half hours on three consecutive days. The test so-
lutions are changed after 2.25 hours on each test day.
At the end of the four and one-half hours, the animals
are removed, washed, dried with a towel, and returned
to their cages.
"Three days after the last day of the test, the
[guinea] pigs' abdomens are shaved with the animal
clippers and given ratings, depending on the condition
of the skin of the abdomen. The ratings are from one
to ten, and the higher the rating, the better the con-
dition of the abdominal skin."
Submission Evaluation
Although the submitted information indicates that dermal exposure
to the "new" chemical in combination with one or more other sub-
stances can cause blindness, a complete copy of the final report
(including the actual experimental protocol(s), data, results of
histopathologic examinations, statistical analyses, etc.) from
each of the performed studies is needed in order for the Agency
to determine the overall significance of the reported toxicologic
findings.
Current Production and Use
A review of the non-confidential version of the ini tial TSCA
Inventory shows that the reaction product of 1 mole of succinic
anhydride and 1 mole of Jeffamine D-2000 is not listed.
101
-------
8EHQ-0885-0565 S
Page 3 of 3
The submi t ting company claimed the proposed use of the product
containing the new chemical to be TSCA CBI. The Information
Management Division (IMD/OTS) will also ask the submitter to
substantiate this confidentiality claim.
Comments/Recommendations
In its TSCA Section 8 (e) notice, the submi tting company stated
that based on the observed toxicologic effects, the company has
"eliminated plans to pursue the use of the new chemcal."
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will ask the
submi tting company to provide to EPA complete copies of the
final reports (including the actual exper imental protocols,
data, the results of gross and histopathologic examinations,
statistical analyses, etc.) from all company studies designed
to determine the toxicologic properties of the "new chemical"
alone or in combination with other chemicals/products.
In view of EPA's general interest in company actions taken on
a voluntary basis in response to chemical toxicity/exposure
information, the submitter will be requested to describe the
actions that the company has taken to notify its employees
about the reported findings.
b)
The Chemical Screening Branch will review the submitted data
in order to determine the need for further OTS assessment of
the subject chemical(s).
c)
The Chemical Screening Branch will transmi t copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, and OAR/EPA. Copies of this report will be
sent also to the TSCA Assistance Office (TAO/OTS) for further
distribution.
102
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
SEP
9 1985
Page 1 of 3
IU8JECT: Status Report*
8EHQ-0985-0566
Approved: [Jrr 1)tf[r5
FROM: James F. Darr, Section Head ~ 1: ~
Chemical Risk Identification Section/CSB
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Union Carbide Corporation submitted a written followup report
concerning an "emergency incident of environmental contamination"
(EIEC) that occurred at the Union Carbide South Charleston (West
virginia) plant on August 13, 1985. According to Union Carbide,
the incident involved the accidental release of UCON Lubricant
LB-250 (a polyalkylene glycol; CAS No. 9003-13-8), sulfuric acid
(CAS No. 7664-93-9), isopropyl alcohol (CAS No. 67-63-0), and
various reaction products of these substances. In its letter,
Union Carbide presented the following information with regard to
the events surrounding this incident:
"On August 13, product refining was being conducted at
the South Charleston plant where the polyalkylene glycol
is manufactured. The polyalkylene glycol is "purified"
by an ion exchange process. Sulfuric acid accidentally
entered the vessel containing the ion exchange resin and
the polyalkylene glycol in isopropyl alcohol. At about
8:00 P.M. on August 13, [the] conditions had reached a
point where [the] release of material from the reaction
of the sulfuric acid with the polyalkylene glycol and
isopropyl alcohol occurred. At approximately 8:30 P.M.,
operators activated the water deluge system to help knock
down the vapors. The reaction continued until about 9:00
P.M. when the safety valve on the ion exchange bed system
reseated.
"During the release, approximately 3500 Ibs. of chemicals
were released to the atmosphere. In addition, about 400
Ibs. of liquid chemicals were released which went into
the Kanawha River. Approximately 1220 Ibs. of additional
liquid chemicals entered the process sewer. The liquid
====================================================================================
* NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
103
-------
8EHQ-0985-0566
Page 2 of 3
chemicals were diluted with thousands of gallons of water
from the deluge system. To the extent that [a] chemical
analysis (gas chromatography) of residual material in the
reactor system is indicative of what was released, the
materials which entered the atmosphere were principally:
propylene [( CAS No. 115-07-1)] from dehydration of iso-
propyl alcohol, possibly other olef ins, propionaldehyde
[(CAS No. 123-38-6)] from acid-catalyzed degradation of
the polyalkylene glycol, and a trace amount. . . of sul-
furic acid. The liquid chemicals [that were] released to
the Kanawha River and the process sewer were primarily
the polyalkylene glycol and. . . [isopropyl alcohol].
[The Union Carbide Corporation reported in its submission
that the "analytical information of residual material may
be only partially relevant to a full understanding of the
chemicals released."]
"Nine employees at the plant during the incident later
reported to the plant dispensary. Of these [nine], seven
complained of irritation to the eyes, nose, throat and/or
skin. The other two employees had no complaints but re-
ported exposure to the release. A tenth employee who was
at home in an adjoining town reported to the dispensary
the next day with a complaint of irritation to the eyes,
nose, throat and skin. The irritation was iudged to be
non-serious, and the complaining employees were treated
and released. Another six residents of the area went to
area hospitals or urgent care centers shortly after the
incident with similar complaints of irritation, and were
also treated and released. The nature of the material
released is such that no chronic effects in persons ex-
posed and no long-tern1 environmental damage are expected
as a result of the incident. . [Union Carbide has]
had no reports of ecological damage in the Kanawha River
or adjacent areas."
Comments/Recommendations
In its submission, Union Carbide stated that it is preparing a
full internal report on the incident and that the report will be
submi tted to the Occupational Safety and Health Administration
(OSHA). In addition, Union Carbide stated that this incident was
not reported immediately by phone to the National Response Center
under the Comprehensive Environmental Response, Compensation and
Liability Act (CERCLA) "because the information available at the
time of the incident, and that available. . .[at the time of the
Union Carbide's written TSCA Section 8(e) submission], does not
indicate the release of a reportable amount [(i.e., a reportable
quantity or RQ)] of a chemical substance subject to the reporting
requirements of CERCLA." It should be noted, hmlever, tha t Union
Carbide did notify the EPA Region III Office by phone within 24
hours of the incident in accordance with the "emergency incident
of environmental contamination" (EIEC) reporting procedures that
104
-------
8EHQ-0985-0566
Page 3 of 3
are outlined in Parts IV and IX 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).
Finally, Union Carbide reported that the company will keep EPA
apprised of additional findings concerning the incident.
a) The Chemical Screening Branch (CSB/ECAD/OTS) will request the
Union Carbide Corporation to provide to EPA a full copy of the
company's internal report concerning this incident.
b) The Chemical Screening Branch will transmi t copies of this
status report to OSHA, NIOSH, ORD/EPA, OAR/EPA, OSvmR/EPA,
OW/EPA, and to EPA's Region III Office. In addition, copies
of this report will be provided to the TSCA Assistance Office
(TAO/OTS/OPTS) for further distribution.
105
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 4
DATE:
SEP 2 6 1985
SUBJECT: Status Report* 8EHQ-0985-0567
Approved: ~ it1/1S
FROM: James F. Darr, Section Head ~ r~
Chemical Risk Identificatio~Section/C~8
TO, Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/O~S/OPTS
Submission Description
E. 1. Dupont de Nemours & Company, Inc. provided the following
sumli1ari2ed information concerning the conduct and results of a
recently performed chronic inhalation study of 1,4-dichloro-2-
butene (1,4-DC8) in rats:
II . [Hale] rats were exposed to 1, 4-DCB vafJor for
approximately six hours per day, five days per week at
concentrations of 0 ppm, 0.1 ppm, 0.3 ppm or 1.U ppm.
Rats were exposed for 19 months and surviving rats were
held without exposure for an additional five months.
Compound-related nasal tumors were observed in all
groups exposed to 1,4-DCB. statistically siynificant
increases in the incidence of nasal tumors were observed
in all exposure groufJs for benign tumors and in the 1.0
ppm group for malignant tumors. ~"hen the incidences of
benign and mallynant tumors were combined, statistically
significant increases were observed in the 0.3 ppm and
1.0 ppm groups. NO other compound-related tumors were
observed. . . . ."
In its submission, Dupont also provided the following background
informa tion concerning the company I s recently conducted chronic
1,4-DCB vapor inhalation study:
"'llhis study was conducted as a result of the findings
from a prev ious [chronic inhala tionJ study on 1, 4-DCB
conducted by DuPont which indicated tnat there
were statistically significant increases in the inci-
dences of nasal tumors in [male and female rats exposed
to 0.5 ppm or 5.0/2.5 ppm. [" Rats in the hi\jh concen-
tration groups were exposed to 5.0 pplU for 30 weeKs
followed by 2.5 pprn for 23 weeks at which time exposures
were terminated and the anlmals held for an additional
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
106
-------
8EE~0985-0567
Page 2 of 4
52 weeks.lI] Follow~ng the preliminary f~ndings of the
initial inhalation stuuy which were reporteu to the
[OccuJ:.>ational Safety and Health Administration (OSHA),
the National Institute for Occupational Safety and
Health (NIOSH), the National Cancer Institute (NCI), and
the EPA] Administrator by letter dated October 7, 1977,
communications were made to. . [DuPont] employees and
to other producers of 1,4-lJCb. . [Du.t'ontJ also
undertook a pro,::!ram to assure that workplace exposure
l to 1, 4-LJCb] would not exceed 0.05 t?pm eiCjh t-hour and
twelve-llour time-weighted average.1I
Finally, DuPont reJ:.>orted that it hau conducted an epidemiologic
study IIthat followed ap~roximately 600 workers from 1956 through
1983 for cancer inc idence, and 1957 through 198 (J for mortality,
and did not indicate that employees are at an increased risk ot
developin,::! cancer. II
Submiss~on Evaluation
'llhe swumarized information provided by DuPont concerning the two
chronic rat inhalation studies indicates that 1,4-dichloro-2-
butene caused 1) a dose-dependent increase ~n the incidence at
rats with nasal tumors (oenign J:.>lus T,lalignant); 2) a statl.sti-
cally significant incidence of benl.gn naSd.L tWLlors at all dose
levels tested wi th the except~on ot the 5.0/2.5 PfJ1ll dose level;
and 3) statistl.cally si'::1niticant increases (increasing with dose)
in the incidence of malignant nasal tumors at the 0.3, 0.5, 1.0
and 5.0/2.5 pfJm dose levels. In addi tion, it should be noted
that in the earlier 1, 4-DCB inhalation study, a statistically
s~gnificant incidence of malignant nasal tumors had already been
olJserved by the 11th month in rats at the 5.0/2.5 J:.>pm 1,4-DCB
dose level.
In studies conducted by van Duuren et al. (Cancer- Research; 35,
2553-2557; 1975), in which 1, 4-DCB was~sted in mice via skin
application, subcutaneous inJection or intraperitoneal inJection,
low incidences of local sarcomas were Observed in the inJection
studies only. In reviewinej tile resul ts of these mouse studies,
the International Agency for Research on Cancer (IAkC LVlonograJ:.ih
No. 15; August 1977) concluded that van Duuren's data (the only
oncogenici ty-related data available to IARC at that t~me) were
insuff~c~ent to allow an evaluat~on of the carcinogenic activity
ot 1,4-LJCB. In l~ght of DuPont's rat data, however, the resul~s
of Van Duuren's mouse studies cannot be d~scounted and, in fact,
COUld be qui te mean~n':Jful for assessing the potent~al oncogenic
r~SK to humans posed by exposure to 1,4-DCB.Finally, it should
be noted that 1, 4-DCb has been founa to be mu tagenic ~n a numlJer
ot in vi tro and in v~vo short-term tests, the resul ts ot whicI}
are-reported in the open scientific l~terature.
107
-------
Current production and Use
8EHQ-0985-0567
Page 3 of 4
According to secondary literature source information, commercial
1,4-dichloro-2-butene (CAS NO. 764-41-0) contains from 95-98%
trans- (Le., E-) isomer (CAS No. 110-57-6) and from 2-5% cis-
(Le., Z-) isomer (CAS No. 1476-11-5). DuPont did not provide
any information concerning the purity of the tested 1,4-dichloro-
2-butene or the company's current production volume(s) or use(s)
of the chemical(s).
The following table presents aggregated 1977 non-confidential
TSCA Inventory production/importation range information for the
subject chemicals: (Note: This production/importation range in-
formation does not include any data claimed as TSCA Confidential
Business Infonnation (TSCA CBI) by those person(s) reporting for
the TSCA Inventory, nor does it include any information that
would compromise TSCA CBl. All of the data submi tted for the
TSCA Inventory, including the production/1mportation range data,
are sUbJect to the limi tat ions contained in the TSCA Inventory
~evorting Regulations (40 CFR 710)).
Chemical Name CAS Number prod./lmport. Range (pounds)
l,4-DCB 764-41-0 10,010,000 to 50,101,000
1,4-DCB (cis-) 1476-11-5 100,000,000 to 500,001,000
1,4-DCB (trans-) 110-57-6 100,000,000 to 500,000,000
According to secondary literature sources, the major use of 1,4-
dichloro-2-butene is as an intermediate in the manufacture of
chloroprene and hexamethylenediarnine.
Comments/Recommendations
In its Section 8(e) submiss10n, Dupont stated that in addition to
advising DuPont workers, other l,4-DCB manufacturers, NIOSH, OSHA
and NCI about the reported toxicologic findings, DUPont's current
workplace exposure limit for 1,4-DCB is being reconsidered. In
addition, DuPont stated that a final report of the recent chronic
1,4-DCB inhalation study is now in preparation and when completed
would be provided to EPA.
1,4-Dichloro-2-butene was included in a chlorinated alkenes
"Hazard Information Review" document (IR-2l3; October 31, 1980)
prepared under contract for the Interagency Testing Commi ttee
(ITC). It should be noted that this 1980 review fails to mention
the preliminary oncogenicity findings from DUPont's first chronic
1,4-DCB rat inhalation study which were submitted to EPA, NIOSH,
NCI, and OStiA by Dupont in October 1977 and published by Dupont
later in 1977 (Clary, JJ; Environmental Health perspectives; 21;
269-274; December 1977). The published preliminary oncogen1city
findin~s from first DuPont chronic 1,4-DCB inhalation study have
been cited, however, in a recent (1983) "Health and Environmental
108
-------
8EHQ-0985-0567
Page 4 of 4
Effects Profile" (HEEP, Number 176) prepared by EPA's Office of
Research and Development (ORD) for BPA's Office of Solid Waste
and Emergency Response (OSWER). Finally, volume II of the EPA
Chemical Acti vi ties Status Report (EPACASR; BPA ~ 60/'1'1 IS-84-001b;
February 1984) shows that trans-l, 4-DCB is currently regulated
under the Resource Conservation and Recovery Act (RCRA) and the
Comprehensive Environmental Response, Compensation and Liability
Act (CBRCLA; "Superfund").
a)
The Chemical Screenin':J Branch (CSB/ECAD/Orl'S) will request
DuPont to ensure that EPA receives a complete copy of the
final report (including tne actual eXl:Jerimental protocol,
test sample puri ty information, results of gross and histo-
pathologic examinations, statistical analyses, etc.) from the
company's recently completed chronic inhalation study of 1,4-
DCB in rats. In addition, DuPont will be requested to submit
full copies of the final reports from the epidemiologic study
and previous chronic 1, 4-DCB rat inhalation study cited in
the company's submission.
b)
The Chemical Screening Branch will review the reported data
in order to determine the need for further OTS assessment of
1,4-dichloro-2-butene.
c)
The Chemical Screening Branch will transmi t copies of this
status report to NIOSH, OSHA, CPSC, NTP, FDA, lTC, OS~vER/EPA,
OW/EPA, ORD/EPA and OAR/EPA. Copies of this report will be
provided also to the TSCA Assistance Office (TAO/OTS/OPTS)
for further distribution.
109
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 4
DATE:
OCT 2 4 1985
SUBJECT: Status Report*
8EHQ-0985-0568 S
Approved: (Jft- /O(~~J65'
FROM: James F. Darr, Section Head ~ 7} ~
Chemical Risk Identification Section/CSB
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 (TSCA CBI). The Information
Management Division (IMD/OTS) will request the submitting company
to substantiate this confidentiality claim.
Submission Description
The submitting company provided the final report from an acute
(4-hour) vapor inhalation study of an "experimental mixture" in
rats. According to the submitter, the test mixture contained 50%
1,1-diethoxy-2-trimethylsilyl-l-sila-2-azacyclopentane (DETMCP;
CAS NO. 21297-72-3), 15% 1,1-diethoxy-2-trimethylsilyl-l-sila-2-
azacyclopentane d imer (DETMCP d imer), 13% trimethylethoxys ilane
(TMES; CAS No. 1825-62-3; hydrolysis product of DETMCP) and 22%
unidentified chemical(s). The Summary section of the submitted
report contained the following information concerning the conduct
and results of the performed study:
"Five groups of 10 male and 10 female rats were exposed
by nose-only inhalation for a single period of 4 hours
to room air (Group 1) or to [1.78, 3.26, 8.05, or 12.98
mg/L of total] vapors of . . . [the test mixture] (Groups
2 to 5). vapor concentrations of the major (relatively
nonvolatile) component of the liquid, DETMCP, ranged
from 72 ppm (0.73 mg/L) to 214 ppm (2.16 mg/L) for the
various test groups. Vapor concentrations of a smaller
proportion (relatively volatile) component, TMES, ranged
from 218 ppm (1.05 mg/L) to 2244 ppm (10.82 mg/L). ."
[". .[Both vapor components (DETMCP and TMES)] were
monitored by gas chromatography during exposure. Most
probably because of differential rates of vaporization,
the ratio of these two components varied greatly wi th
increasing concentration of the total vapor. At the low
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e). the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
no
-------
8EHQ-098S-0S68 S
Pa<;e 2 of 4
dosage (1.78 mg/L), the ratio of DETMCP to TMES vapor
was 1 to 3; at the high dosage (12.98 mg/L), the ratio
was 1 to 10."] Animals were observed for 14 days after
treatment and then necropsied. Lungs, liver and kidney
were examined histopathologically.
"The median lethal concentration (LCSO) of . [the
test mixture] expressed in terms of total vapors was 3.7
mg/L and 4.8 mg/L for males and females, respectively,
and 4.6 mg/L for combined sexes.
"Mortali ty in the various test groups increased with
dose level except for high-dose females (214 ppm DETMCP)
where mortality was 10% lower than in the group treated
with 171 ppm DETMCP. This is not unusual, given the
normal intersubject variability in response. Treatment-
related clinical signs included respiratory rales, nasal
or oral discharge, labored respiration and ataxia. The
incidence, severity, and duration of these findings
generally increased with dose level.
"Marked body weight loss was observed in the treated
animals, and the magnitude and duration of weight loss
increased with dose.
"Treatment-related gross and histopathological findings
were observed in the respiratory tract of animals dying
during the study and animals sacrificed after 14 days.
These included tissue discoloration, fluid accumulation,
intra-alveolar hemorrhage and edema in early decedents,
and the incidence of these findings increased with dose
level. Interstitial pneumonia accompanied by epithelial
proliferation was frequently observed in late decedents
and animals which survived. Lung weight was statisti-
cally increased at dose levels of 114 ppm and higher.
Death was due to intra-alveolar hemorrhage associated
with perivascular edema."
It should be noted that the summarized results of several acute
animal toxicity studies of DETMCP were provided to the Agency on
a "For Your Information" (FYI) basis (FYI-OTS-1184-0365 S). In
.that FYI submission, the submitting company (company name claimed
as TSCA CBI) reported that additional studies would be conducted
to determine 1) the LCSO of DETMCP, and 2) if any volatilization
occurred during curing processes.
Submission Evaluation:
The adverse lung effects that were observed in the subject acute
inhalation toxicity study are very similar to those seen in acute
inhalation toxicity studies of trimethoxysilane vapors (Section
8(e) submission number 8EHQ-0680-0347 et seq.) in which the lungs
of rats failed to collapse. In the present study, mottled, un-
collapsed, and firm lungs were observed in all animals of both
III
-------
8ruiQ-0985-0568 S
Page 3 of 4
sexes at all doses except the low dose and control groups. In
addition, respiratory rales were observed in most of the animals
(15/20) at the lowest dose and in all other animals at all other
doses. It should be noted also that those rats surviving the 214
ppm exposure exhibited severe ataxia which disappeared on the day
following exposure but eventually reappeared as moderate ataxia
lasting for the duration of the study. Finally, the lungs of all
treated animals were found to be hemorrhag ic. This finding is
consistent with those from other studies of organosilanes.
Current production and Use
A review of the production range (includes importation volumes)
statistics for trimethylethoxysilane (CAS No. 1825-62-3), which
is listed on the non-confidential computerized version of the
TSCA Chemical Substance Inventory, indicates that from 0 to 1000
pounds of this chemical were reported as produced and/or imported
in 1977. (This information does not include any production or
importation data that were claimed as TSCA Confidential Business
Information (TSCA CBI) by the person(s) reporting for the initial
TSCA Inventory, nor does it include any information that would
compromise TSCA CBI. All of the data submitted for the initial
TSCA Inventory, including the production/importation range data,
are subject to the limitations contained in the TSCA Inventory
Reporting Regulations (40 CFR 710».
According to the Information
DETMCP has been added to the
Substance Inventory.
Management Division (IMD/OTS),
non-confidential TSCA Chemical
In FYI-OTS-1184-0365 S, the submitting company reported that a
mixture containing low levels of DETMCP was created for develop-
mental purposes only. In the Section 8(e) notice, the submitter
stated that the company is no longer producing the tested mixture
or DETMCP.
Comments/Recommendations
EPA's Office of Toxic Substances (OTS) has received a number of
TSCA Section 8(e) and "For Your Information" (FYI) submissions
containing toxicologic and/or exposure information on several
organosilanes. The Chemical Screening Branch (CSB/ECAD/OTS) has
prepared a Chemical Hazard Information Profile (CHIP) on 3,4-
epoxycyclohexylethyltrimethoxysilane and is now in the process of
preparing a CHIP on organosilanes as a class. The Risk Analysis
Branch (RAB/ECAD/O'I'S) has been evaluating available toxicologic
and exposure data on 3,4-epoxycyclohexylethyltrimethoxysilane.
The OTS New Chemicals Program has also been evaluating available
toxicologic and exposure data on a number of organosilanes.
a)
The Chemical Screening Branch will request the submi tting
company to provide complete copies of the final reports
(including the actual experimental protocols, results of
gross/histopathologic examinations, statistical analyses,
112
-------
8EHQ-0985-0568 S
Page 4 of 4
etc.) from all studies (including the volatilization study)
cited in FYI-OTS-1184-0365 S. In view of EPA's general
interest in company actions taken on a voluntary basis in
response to chemical toxici ty /exposure data, the submi tter
will be aksed to describe the actions the company has taken
to inform workers/others about the toxicologic findings.
b)
The Chemical Screening Branch will ensure that the data in
this Section 8(e) submission and FYI-OTS-lI84-0365 S are
considered for inclusion in the CHIP on organosilanes.
c) The Chemical Screening Branch
status report to NIOSH, OSHA,
OW/EPA, OAR/EPA, and ORD/EPA.
the TSCA Assistance Office
distribution.
will send copies of this
CPSC, FDA, NTP, OSWER/EPA,
Copies will be sent also to
(TAO/OTS/OPTS) for further
113
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
0-8.
Page 1 of 3
SUBJECT: Status Report* 8EHQ-I085-0569 APproved:~. :J~ft;
FROM: James F. Darr, Section Head ~.ihVl-J r ~
Chemical Risk Identification(7~ction/CSB
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Celanese Corporation provided standard operating procedures
(SOPs) and summarized results of acute in vivo oral, dermal, and
eye toxicity tests of n-octylamine (CAS No. 111-86-4). According
to the submitted information, all rats (6 rats per group) died
within 6 days, 1 day, and 1 day after a single oral administra-
tion of 100% n-octylamine at doses of 50, 500, or 5000 mg/kg
bodyweight, respectively. The performing laboratory's report
stated that no gross signs of toxicity (in terms of extreme ab-
normalities) were observed during the oral study. In the dermal
toxicity study, 4 rabbits per group received 100% n-octylamine at
doses of 200, 2000, or 3000 mg/kg bodyweight applied as a single
dose to the shaved unabraded skin of the back. All rabbits in
the 2000 and 3000 mg/kg dose groups died wi thin 3 and 2 days,
respectively, following exposure; hypoactivity and/or prostration
were reported to have preceded death. Although no animals in the
200 mg/kg dose group died during a 7-day post-exposure observa-
tion period, necrosis was reportedly observed at the site of skin
application. With regard to the eye irritation study, 0.1 ml of
100% n-octylamine placed directly into the lower conjunctival sac
of one eye of each of 4 rabbi ts was found to be corrosive and
produced severe corneal and conjunctival damage by the second day
of the study.
Submission Evaluation
Many alkylamines are known to be irritating to eyes and skin, and
n-octylamine demonstrated such activity in the performed studies.
With regard to lethality, the provided information indicates that
the dermal LD50 for n-octylamine in rabbits is between 200 and
2000 mg/kg and the oral LD50 for n-octylamine in rats is lower
than 50 mg/kg. It should be noted that a chemical wi th an oral
ra t LD50 value between 5 and 50 mg/kg is regarded generally as
being extremely toxic. It is important to note also that the
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
114
-------
8EHQ-I085-05E9
Page 2 of 3
NIOSH 1981-1982 Registry of Toxic Effects of Chemical Substances
(RTECS) reports that the intraperitoneal LD50 for n-octylamine in
mice is 100 mg/kg. In order for EPA to evaluate better the sig-
nificance of the reported toxicologic findings, Celanese should
be requested to submit complete copies of the actual experimental
protocols and all data from the performed studies.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for n-octylamine (CAS No. 111-86-4), which is listed
in the initial TSCA Inventory, has shown that between 0 to 2000
pounds of this chemical were reported as produced and/or imported
in 1977. This production range information does not include any
production/importation information claimed as TSCA Confidential
Business Informa tion (TSCA CBI) by the person( s) reporting for
the initial TSCA Inventory, nor does it include any information
that would compromise TSCA CBI. All information submi tted for
the TSCA Inventory, including the production range information,
is subject to the limi tat ions contained in the TSCA Inventory
Reporting Regulations (40 CFR 710).
In the cover letter to its TSCA Section 8(e) submission, Celanese
reported that n-octylamine is used primarily "as an intermediate
in the manufacture of pesticides and pharmaceuticals." No infor-
mation concerning the current production/importation volumes or
other uses of n-octylamine was found in the secondary literature
sources consulted.
Comments/Recommendations
According to the submitted SOPs, data derived from the performed
studies "may serve as a basis for classification and labelling of
the test material or for use in completing Material Safety Data
Sheets (MSDS)."
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will request the
Celanese Corporation to submit a complete copy of the actual
experimental protocol, data, results of gross/histopathologic
examinations, etc. from each acute in vivo 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
and/or exposure informa tion, the Chemical Screening Branch
will ask Celanese to describe the actions that the company
has taken to notify Celanese workers and others about the
reported toxicolog ic findings on n-octylamine. In addi tion,
Celanese will be asked to describe the nature and available
results of all other studies that Celanese has conducted, is
conducting, or plans to conduct to determine the toxicity of
and/or the exposure to n-octylamine.
115
-------
8£HQ-I085-0569
Page 3 of 3
b)
The Chemical Screening Branch will review the submitted data
in order to determine the need for further OTS assessment of
n-octylamine.
c)
The Chemical Screening Branch will send copies of this report
to OSHA, NIOSH, CPSC, FDA, CPSC, ORD/EPA, OSWER/EPA, OW/EPA,
OAR/EPA, and OPP/OPTS. Copies of this report will be
sent also to the TSCA Assistance Office (TAO/OTS) for further
distribution.
116
-------
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
Page 1 of 3
t'ATE:
NOV I 5 1985
SUBJECT: status Report*
8EHQ-I085-0570
Approved:
~
'1Iflrs-
FROM:James F. Darr, Section Head)~'~1 ~ /};'VV
Chemical Risk Identificatio Section/CSB
ro:Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Velsicol Chemical Corporation submitted draft "unaudited"
results of an oral teratology study of chlordene (CAS No. 3734-
48-3) in rats. The company provided the following information
with regard to the conduct and results of this study:
"In a teratology study where rats were exposed [orally
via gavage] to chlordene at 0, 30, 300 or 600 mg/kg/day,
a greater total number of malformations was observed in
fetuses from the 600 mg/kg/day feeding level. This num-
ber of malformations was not statistically significant
if the statistical unit for comparison is the Ii tter,
not the fetus. However, there was statistically sig-
nificant maternal toxicity at this feeding level. This
maternal toxicity was observed as weight loss and death.
Neither maternal toxicity nor compound related effects
were observed at the next highest [chlordene] exposure
level (300 mg/kg/day)."
In addition, velsicol provided the following summary information
with regard to the conduct and results of a pilot range-finding
teratology study of chlordene:
"In a preliminary oral range-finding teratology study in
rats with chlordene, overt maternal toxicity defined the
limi ts of exposure to chlordene by female rats during
the major period of organogenesis to dosages of less
than 1000 mg/kg/day. A decreased maternal weight gain
was observed over the entire treatment period (gestation
days 6 - 16) at 500 mg/kg/day or more. Based on the
results of this [preliminary range-finding teratology]
study, dosage levels of 0, 30, 300 and 600 mg/kg/day
were selected for the definitive teratology study."
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
117
-------
8EH
-------
8EHQ-1085-0570
Page 3 of 3
a)
The Chemical Screening Branch will ask the Velsicol Chemical
Corporation to ensure that the Agency receives full copies of
the final reports (including the actual experimental proto-
cols, data, results of gross/histopathologic examinations,
statistical analyses, etc.) from the company's preliminary
range-f inding and "defini tive" teratology studies ci ted 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
or exposure information, the Chemical Screening Branch will
ask Velsicol to describe the nature and available results of
all other studies (except those published in the open litera-
ture or those already submitted formally to the Agency) that
Velsicol has conducted, is conducting, or plans to conduct to
determine the toxicity of and/or the exposure to chlordene.
b)
The Chemical Screening Branch will review the reported data
in order to determine the need for further OTS assessment of
chlordene.
c)
The Chemical Screening Branch will send copies of this status
report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA, OAR/EPA,
OW/EPA, ORD/EPA and OPP/OPTS/EPA. Copies of this report will
be sent also to the TSCA Assistance Office (TAO/OTS/OPTS) for
further distribution.
119
-------
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
Page 1 of 4
DATE:
DEC I 0 1985
SUBJECT: Status Report*
8EHQ-1085-057l S
Approved:
~ Iz/4'~
FROM: James F. Darr, Section Head ~r~
Chemical Risk Identification Section/CSB
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Note
E. I. Dupont de Nemours & Company, Inc. has claimed the identity
of the tested chemical substance to be TSCA Confidential Business
Information (TSCA CBI). The company did state non-confidentially
that the chemical was an "aromatic diamine" and that the chemical
was the subject of a premanufacture Notice (PMN 85-335) submitted
to EPA under Section 5 of TSCA.
Submission Description
E. I. Dupont de Nemours & Company, Inc. (Dupont) provided the
following summary information concerning the conduct and results
of a recently performed sub-acute inhalation toxici ty study as
well as previously conducted toxici ty studies of the aromatic
diamine:
"Prior to animal testing, the substance was mechanically
pulverized to produce respirable particles. During the
study, rats were exposed to the aromatic diamine for six
hours per day, five days per week for two weeks to mean
atmospheric concentrations of 0, 5.1, 23 or 98 mg/m3.
The dusts generated for the animal exposures were highly
respirable (mass median aerodynamic diameters ranged
from 2.2-2.9 um).
"Clinical signs after exposure and after a fourteen-day
post exposure recovery period were unremarkable at all
levels of exposure. However, [the] histopathological
examination has shown compound-related effects on the
eyes , liver, spleen and ad renal glands. In the eyes,
bilateral chronic choroiditis and retinal disorganiza-
tion (retinopathy) were observed at all levels of
exposure.
------------------------------------------------------------------------------------
------------------------------------------------------------------------------------
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provisipn of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
120
-------
8EHQ-l085-0571 S
Page 2 of 4
"In earlier testing as reported wi th the PMN [( PMN 85-
335)], it was determined that the aromatic diamine was
mutagenic to Salmonella bacterial strains TA-98 and TA-
100. Additional testing [conducted] with a purified
sample, however, has shown that the aromatic diamine is
not mutagenic in the same bacterial strains. Irritation
tests showed that the chemical is not a skin irritant
but is a moderate eye irritant."
It should be noted that copies of the final reports of the above
referenced "earlier" toxicologic studies were submitted to EPA in
conjunction with PMN 85-335.
Submission Evaluation
The submitted summarized information indicates that the tested
aromatic diamine is neurotoxic, producing inflammation of the
choroid layer of the eye and pathologic changes in the retina.
Although these adverse effects were seen in all animals at all
doses administered, the effects were delayed at the lowest dose
(5/5 animals had developed choroiditis and retinopathy by the end
of the two week recovery period). It is important to note also
that neither a "no-observable-effect-level" (NOEL) nor a mini-
mally toxic dose level for the aromatic diamine was found in the
performed study.
The adverse eye effects reportedly observed in DuPont's study are
consistent with the adverse eye effects found in animals exposed
to certain aromatic diamines. In fact, a number of aromatic di-
amines have been used to produce the laboratory animal model for
retini tis pigmentosa, a pr inc iple cause of human bl indness. It
should be noted that while cats and monkeys have been found to be
typically susceptible to the retinopathic effects caused by these
chemicals, rats are gener~lly refractory to such effects. Also,
exposure to certain aromatic diamines has been reported to result
in visual disturbances in humans.
Current production and Use
In its Section 8(e) notice, Dupont reported that a "specially
ground material was required to obtain a sample with sufficient
particles of a respirable range to enable the [sub-acute inhala-
tion toxici ty] test to be conducted in a meaningful manner."
DuPont stated also that "it is highly unlikely that a substantial
level of respirable [aromatic diamine] dust would be encountered
in the manufacture and use of this material. II According to the
non-CBI version of PMN 85-335, the aromatic diamine is a "light
cream color powder" and is "used entirely for the manufacture of
monomer precur~or at a DuPont site." The non-CBI version of PMN
85-335 also presented the following information wi th regard to
the aromatic diamine manufacturing process:
121
-------
8EHQ-l085-0571 S
Page 3 of 4
"The. [aromatic diamine is produced at] semi-works
facilities that are used for a number of similar chemi-
cals. Exhaust ducts and shields are provided [in order]
to minimize potential operator exposure. Personal pro-
tective clothing, hard hats, and safety glasses are re-
quired at all times in the operating areas. Full face
shields, aprons, and gloves are also required while
handling liquid chemicals or the [aromatic diamine] pro-
duct. other special handling precautions are used in
full accordance with each raw material safety data
sheet. The reaction is carried out in a glass lined
vessel under a hydrogen atmosphere. Rupture discs and
exhaust vents protect the operator and equipment from
accidental over-pressure. All water soluble wastes from
the operation are diluted to low concentration and sent
to the site waste treatment area. Solids and catalysts
are recovered or incinerated. The product is dried to
remove excess fluid and packaged in plastic bags inside
fiber drums. Rubber gloves, apron, air mask, and face
shield are required to minimize operator exposure."
According to the Information Management Division (IMD/OTS), EPA
has not as yet received a "Notice of Commencement of Manufacture"
(NOC) for the aromatic diamine.
Comments/Recommendations
In its Section 8(e) submission, DuPont reported that the company
plans to notify DuPont "employees, suppliers, and those customers
or users, as appropriate, that are doing research or development
using materials containing the aromatic diamine." In addi tion,
Dupont reported that the company plans to conduct an industrial
hygiene monitoring study.
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will ask Dupont
to provide to the Agency a complete copy of the final report
(including the actual experimental protocol, data, results of
statistical analyses, results of gross and histopathological
examinations, etc.) from the two-week inhalation study of the
aromatic diamine in rats. In addition, DuPont will be asked
to submit, when available, a complete copy of the results of
the planned industrial hygiene monitoring 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
or exposure information, the Chemical Screening Branch will
ask DuPont to describe the nature and available results of
all studies (other than those already submitted to EPA) about
which the company is aware or that the company has conducted,
is conducting, or plans to conduct to determine the toxicity
(e.g., neurotoxicity, teratogenicity, carcinogenicity) of or
the exposure to the aromatic diamine.
122
-------
8ElQ-l085-0571 S
Page 4 of 4
b)
As was the case with DUPont's intial Section 8(e) submission
on the aromatic diamine, the Chemical Screening Branch will
immediately forward all of the reported information to the
Existing Chemical Control Branch (ECCB/CCD/OTS).
c)
The Chemical Screening Branch will transmit copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP. OSWER/EPA,
OAR/EPA, ORD/EPA, OW/EPA and CCD/OTS/OPTS. Copies of this
report will be provided also to the TSCA Assistance Office
(TAO/OTS/OPTS) for further distribution.
123
-------
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
Page 1 of 8
DATE:
ref 3 0 1985
ApprovedI" }J1/i~/A~ If/I)
'--;,'" /
SUBJECT: Status Report * 8EHQ-0585-0572 and
8EHQ-0985-0572 Fo11owup
FROM: Frank D. Kover, Chief d~ D. ~--
Chemical Screening Branch/ECAD/OTS
v
TO: Joseph J. Merenda, Director
Existing Chemical Assessment Division/OTS
Submission Description
In a "For Your Information" (FYI) submission (FYI-OTS-0585-0408),
the Union Carbide Corporation reported that it had been notified
informally about the findings from another company's inhalation
teratology study of 2-methoxy-l-propyl acetate in pregnant rab-
bits. In its initial FYI submission, Union Carbide provided the
following information concerning the results of this, as well as
other, teratologic studies of 2-methoxy-l-propyl acetate:
" [A] strong teratogenic effect was observed when
pregnant rabbits were exposed [by inhalation] to 545 ppm
of 2-methoxy-l-propyl acetate and. . . no effects were
observed at exposures of 145 ppm and 36 ppm. There was
no evidence of maternal toxic effects at any of these
exposure levels. A dermal teratology study was also
conducted on the acetate on rabbits at dosage levels of
1000 and 2000 mg/kg body weight with no indications of
adverse effects on the mothers or on the developing off-
spring. In addition, a rat inhalation teratology study
was conducted with evidence of maternal toxicity and em-
bryofetal toxicity at an air concentration of 2710 ppm,
but no evidence of adverse effects was noted at two
lower concentrations, 545 and 110 ppm."
In its FYI submission, Union Carbide stated that the company had
"received confirmation of . [the reported] information via
telephone conversations with the firm which conducted the [rabbit
inhalation teratology] study, BASF [(BASF Aktiengesellschaft)],
Ludwigshafen, West Germany." Union Carbide stated also that a
copy of the study report was requested but may not be received
"until the results have been publisbed in the open literature."
Union Carbide also provided the following additional information
with regard to 2-methoxy-l-propyl acetate:
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this report should not be regarded
as expressing final EPA policy or intent with respect to th~ subject
chemical(s). Any review of this status report should take lnto account
the fact that the report may be based on incomplete information.
124
-------
Page 2 of 8
II. 2- [M] ethoxy-I-propyl acetate is the minor com-
ponent of the two isomers present in [the] propylene
glycol monomethyl ether acetate currently marketed in
the United states by Union Carbide and others, and
commonly referred to as PM Acetate (CAS No. 108-65-6).
Commercial PM Acetate in . . . [the U.S.] contains
approximately 3 to 5 percent of the 2-methoxy-I-propyl
[acetate] isomer, the principal isomer being l-methoxy-
2-propyl acetate. Al though PM Acetate has not, to the
best of [Union Carbide's] knowledge, been sub-
jected to inhalation teratology studies, the parent
glycol ether has been tested and found to be free of
teratogenic effect.1I (See reference on the last page of
this status report.)
IIA considerable amount of data exist to indicate that
the acetate is readily hydrolyzed in the body to produce
the parent glycol ether and that consequently the toxi-
cological effects of the two - - [the] glycol ether and
its ester - - are considered comparable. Thus, [the]
available data support the view that PM Acetate is like-
wise free of teratogenic effect. II
Finally, Union Carbide provided the following information with
regard to the company's views concerning the TSCA Section 8 (e)-
applicability of findings contained in this FYI submission:
liTo determine whether the new data from the BASF study
might provide a reasonable basis to infer a substantial
risk of injury of health, in contradiction to the best
information hitherto available, all details of the study
and the findings will have to be analyzed. If the con-
clusion presented in the preliminary communication is
supported by the basic data which are not yet available
to us, we believe the information is reportable under
Sec. 8(e) of the Toxic Substances Control Act. Union
Carbide does not consider it appropriate to make a con-
clusion of substantial risk at this time. II
Following a review of the summary information presented in Union
Carbide's ini tial FYI submiss ion, EPA informed Union Carbide in
writing (EPA letter dated August 12, 1985) that EPA believed that
the BASF inhalation teratology study findings (about which Union
Carbide had been notified informally and which were subsequently
confirmed by Union Carbide via phone with BASF in West Germany)
constituted IIsubstantial risk" information and, as such, should
have been reported formally by Union Carbide to EPA under Section
8(e) of the Toxic Substances Control Act (TSCA). In that August
12, 1985 letter, the Union Carbide Corporation was requested to
provide additional information concerning the company's rationale
as to why the subject teratology findings were not submitted to
EPA under TSCA Section 8(e).
125
-------
Page 3 of 8
In a letter dated September 13, 1985 (FYI-OTS-0985-0408 Followup
Response), Union Carbide responded to EPA's questions/statements
concerning the TSCA Section 8 (e) -appl icabil i ty of the findings
from BASF's inhalation teratology study of 2-methoxy-l-propyl
acetate in rabbi ts. In this followup response, Union Carbide
reiterated its original position with regard to the TSCA Section
8(e)-applicability of the subject teratologic findings. In addi-
tion, Union Carbide reported that the company first learned about
the BASF rabbit inhalation teratology study findings via a telex
message from BP Chemicals (London, England). In order to obtain
addi tional information about the BASF findings, Union Carbide
stated that the company then placed a phone call to BASF in West
Germany. In its followup reponse, Union Carbide provided a 4-
page summary prepared from "rough notes" taken during Union
Carbide phone conversations with BASF and other foreign and U.S.
chemical companies. The following excerpt is from that submitted
summary and relates specifically to a phone conversation between
the Union Carbide Corporation's Assistant Director of Corporate
Applied Toxicology and a BASF toxicologist in West Germany:
". . . [BASF's toxicologist] said that BASF had conducted
both a dermal and an inhalation teratology study in rab-
bi ts of. . [2-methoxy-l-propyl acetate]. The dermal
study was conducted at dosage levels of 1000 and 2000
mg/kg body weight/day. No effects were seen in dams or
fetuses. The inhalation study was conducted at exposure
concentrations of 36, 145 and 545 ppm. At the highest
exposure level all fetuses had malformations in the ab-
sence of maternal toxicity. Both visceral and skeletal
malformations were seen including cardiovascular defects
and malformations of the extremi ties. No teratogenic
effects were seen at the lower two exposure concentra-
tions. . [BASF's toxicologist said] that BASF had
conducted a rat inhalation teratology study of . . .[2-
methoxy-l-propyl acetate] at exposure concentrations of
110, 545 and 2710 ppm. Split vertebra were seen at the
highest exposure level, but not at the lower exposure
levels. Maternal toxici ty evidenced as irritation was
observed at the 545 ppm air concentration. .. .[BASF's
toxicologist said also] that BASF had conducted a 28-day
subacute inhalation study in rats with. . .[2-methoxy-
I-propyl acetate] at the same exposure concentrations
(110, 545 and 2710 ppm) and signs of irritation were
aga in observed; however there were no effects on bone
marrow or blood. II
Submission Evaluation
Although no definitive teratogenic effects have been observed in
1) teratology studies of 2-methoxy-l-propyl acetate in rats (via
inhalation) and rabbits (via dermal application), or 2) inhala-
tion teratology studies of propylene glycol monomethyl ether
(containing approximately 98.7% 1~methoxy-2-propanol and 1.3% 2-
methoxy-l-propanol) in rats and rabbits, the overall significance
126
-------
Page 4 of 8
of the results of a study reportedly demonstrating for the first
time that 2-methoxy-l-propyl acetate is a strong teratogen via
inhalation in rabbits cannot be minimized even in the absence of
the details of and actual data from that study. It is important
to note also that the observed malformations/defects 1) appear to
be consistent with those seen in teratology studies of ethylene
glycol ethers and their derivatives, and 2) occurred in the ab-
sence of toxic effects in the exposed dams.
In activities under Sections 4, 5, 6, and 8 of TSCA, EPA's Office
of Toxic Substances (OTS) has received and has been evaluating
toxicologic and exposure data on a number of glycol ethers and
glycol ether derivatives. It has been well publicized that EPA
has been developing regulations designed to control exposure to
and/or require the testing of ethylene glycol ethers and their
deriva tives. For example, EPA has published an Advanced Notice
of proposed Rulemaking (ANPR 49 FR 2921; January 24, 1984) in
which EPA announced its intention to develop regulations under
TSCA to reduce the exposure to 2-methoxyethanol (ethylene glycol
monomethyl ether), 2-ethoxyethanol (ethylene glycol monoethyl
ether), and their acetates. In addition, several glycol ethers
have been recommended by the Interagency Testing Committee (ITC)
for testing under Section 4 of TSCA.
Current Production and Use
Neither 2-methoxy-l-propyl acetate nor l-methoxy-2-propyl acetate
are listed in the current non-confidential computerized version
of the 1977 TSCA Chemical Substance Inventory. According to the
1984 edition of the Alllerican Chemical Society's CHEMCYCLOPEDIA,
propylene glycol monomethyl ether acetate has a high degree of
solvency and slow rate of evaporation and is used in water-based
paints (as a coalescing agent), lacquers, and resin coating ap-
plications (e.g., cellulose ni trate, ethyl cellulose, acrylics,
polystyrene). In general~ the propylene glycol ethers and their
derivatives have been or are being developed by a number of com-
panies to replace ethylene glycol ethers and ethylene glycol
ether derivatives in certain applications.
In its followup submission, Union Carbide stated that the company
believes that the airborne concentrations of 2-methoxy-l-propyl
acetate are "well below 5 parts per million" at the Union Carbide
facility where PM Acetate is manufactured.
Comments/Recommendations
In its FYI submissions, Union Carbide stated that the company was
notifying customers, employees, and other U.S. companies known by
Union Carbide to manufacture, import, or market propylene glycol
monomethyl ether acetate. In addition, Union Carbide stated that
the Agency would be appr ised of any addi tional information as
soon as such information becomes available to the company.
127
-------
Page 5 of 8
Based on a review of the information presented by Union Carbide
in the initial and followup FYI submissions, it is EPA's position
that the findings from BASF's rabbit inhalation teratology study
of 2-methoxy-l-propyl acetate, about which Union Carbide was no-
tified initially on an informal basis and which were subsequently
confirmed by Union Carbide via telephone conversations with BASF
in West Germany, should have been reported to EPA under Section
8(e), the "substantial riskh information reporting provision of
TSCA. The basis for EPA's position is as follows:
Section 8 (e) states that "any person who manufactures,
processes, or distributes in commerce a chemical sub-
stance 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 per-
son has actual knowledge that the Administrator has been
adequately informed of such information."
The preface to Part V of EPA's March 16,1978 Section
8(e) policy statement ("Statement of Interpretation and
Enforcement policy; Notification of Substantial Risk" 43
FR 11110) states that "a substantial risk of injury to
health. is a risk of considerable concern because
of (a) the seriousness of the effect. (b) the fact
or probabili ty of its occurrence. ~Ji th regard to the
seriousness of the effect, Part V explains further that
that the Agency considers the health effects for which
substantial risk information must be reported to include
"any pattern of effects or evidence which reasonably
supports the conclusion that the chemical substance or
mixture can produce cancer, mutagenicity, birth defects
." The information concerning these effects can
be obtained directly or inferred from designed studies
(e.g., in vivo studies as described in Part VI of the
8 (e) policy statement). In addi tion, Part VI explains
that "a person is not to delay reporting until he ob-
tains conclusive information that a substantial risk
exists, but is to immediately report any evidence which
reasonably supports that conclusion." Part VI explains
further that "not only should final results from such
studies be reported, but also preliminary resul ts from
incomplete studies where appropriate."
With regard to the "fact or probability of its [i.e.,
the serious effects'] occurrence" criterion, Part V of
the policy document states that certain types of health
ef fects (e. g., birth defects, cancer) are so ser ious
that relatively little weight should be given to a
chemical's exposure in determining whether a risk is
substantial; the mere fact that an implicated chemical
is in commerce would consti tute sufficient evidence of
exposure.
128
-------
Page 6 of 8
with regard to the requirement that EPA's Administrator
be informed immediately about substantial risk informa-
tion, Part IV of the TSCA Section 8(e) policy statement
explains that the EPA Administrator is considered to be
informed immediately about substantial risk information
"if [the] information is received by EPA [in accordance
with the reporting procedures outlined in Part IX of the
TSCA Section 8(e) policy statementJ not later than the
15th working day after the date. . [a subject] person
obtained such information." Part III of the 8(e) policy
statement explains that EPA considers that a company has
"obtained" substantial risk information at the time that
any corporate officer or employee who is capable of ap-
preciating the significance of the information obtains
(i.e., possesses or knows of) such information.
Part VII of the Section 8(e) policy statement explains
that EPA considers the information about which the EPA
Administrator has been adequately informed (i.e., that
information that need not be reported to EPA under TSCA
Section 8(e» to be that information that has been, for
example, published in the open scientific literature and
abstracted by certain abstract services or submitted to
EPA in accordance with some other mandatory information
reporting requirement under TSCA or some other authority
administered by EPA.
In view of the preceding discussion and EP~'S evaluation of the
information presented in FYI-OTS-0585-0408 and FYI-OTS-0985-0408
Followup Response, EPA believes that Union Carbide obtained (by
way of a confirming phone conversation) information that inhaled
2-methoxy-l-propyl acetate caused birth defects in a rabbit tera-
tology study that was conducted by BASF Aktiengesellschaft in
West Germany- In addition, EPA believes that this information,
when combined with the knowledge that 2-methoxy-l-propyl acetate
comprises 3-5% of a product in U.S. commerce, provides reasonable
support for a conclusion that 2-methoxy-l-propyl acetate presents
a substantial risk of injury to human health as defined in EPA's
March 16, 1978 TSCA Section 8(e) policy statement. It is EPA's
position, therefore, that the subject birth defects information
should have been submitted to the Agency in accordance with the
reporting procedures outlined in Part IX of the March 16, 1978
TSCA Section 8(e) policy statement.
EPA believes that its position in this matter is consistent fully
with the guidance contained in 1) the March 16, 1978 Section 8(e)
policy statement and 2) "status reports" prepared and made public
by EPA's Office of Toxic Substances in response to initial TSCA
Section 8 (e) submissions (e. g., status report 8EHQ-1283-0503).
In addition, it should be noted that since the enactment of TSCA
on January 1, 1977, many members of the chemical industry have
formally submitted "substantial risk" information obtained under
circumstances similar to those encountered by Union Carbide.
129
-------
Page 7 of 8
Further, the Union Carbide Corporation filed a TSCA Section 8(e)
submission (8EHQ-0378-0105) in which the company stated that its
notice was "based largely on oral communications from several
sources. . . ."
wi th regard to the timeliness of reporting, Union Carbide did
notify EPA in writing within 15 working days of Union Carbide's
confirmatory phone conversation with BASF in West Germany. In
terms of completeness, however, it was only upon EPA's receipt of
Union Carbide's September 13, 1985 followup response letter that
the Agency learned that the "strong teratogenic effect" reported
by Union Carbide in the initial FYI submission involved defects
of the cardiovascular system and malformations of the extremi-
ties. The 4-page telephone summary contained in Union Carbide's
September 13, 1985 followup letter shows that the company had
obtained this more explicit information with regard to the actual
nature of observed teratogenic effects prior to the initial FYI
submission which was dated May 16, 1985.
a)
The Existing Chemical Assessment Division (ECAD/OTS/OPTS)
will inform the Union Carbide Corporation about the Agency's
determination with regard to the Section 8(e)-reportability
of the subject information. In light of this determination,
the Chemical Screening Branch (CSB/ECAD/OTS) has delivered
FYI-OTS-0585-0408 and FYI-OTS-0985-0408 Followup Response to
the OTS Document Control Officer for handling/public filing
under Section 8(e) of TSCA. .
In light of the fact that BASF Aktiengesellschaft reportedly
refused to provide to Union Carbide any further information
concerning the BASF teratology studies until such time that
the results are published in the open scientific literature,
the Chemical Screening Branch is attempting to obtain from
BASF Aktiengesellschaft full copies of the final reports from
their teratology studies of 2-methoxy-l-propyl acetate in
rats and rabbits. It should be noted that any person who
manufactures, imports, processes, or distributes 2-methoxy-l-
propyl acetate alone or as a component in any mixture in com-
merce in the U.S. and who obtains these reports (or any other
pertinent information from these studies) should be aware of
his/her obligation to submit such information to EPA immedi-
ately unless that person has actual knowledge that EPA has
already been adequately informed about the information. As
explained in Part IV of the Section 8 (e) policy statement,
supplemental information generated/obtained after an initial
8(e) notice is filed must be transmitted to EPA immediately.
b)
The Chemical Screening Branch will continue to review the
submitted information to determine the need for separate OTS
assessment and/or formal referral of the information to the
ongoing OTS assessments of glycol ethers and glycol ether
derivatives.
130
-------
Page 8 of 8
c)
The Chemical Screening Branch will send copies of this status
report to OSHA, NIOSH, CPSC, FDA, NTP, OAR/EPA, OSWER/EPA,
OW/EPA, RAB/ECAD/OTS, TRDB/ECAD/OTS, CCD/OTS and OCM/OPTS.
Copies of this status report will be sent also to the TSCA
Assistance Office (TAO/OTS) for further distribution.
Reference
Hanley, T.R.; Calhoun, L.L.; Yano, B.L.; and Rao, K.S. (1984)
"Teratologic Evaluation of Inhaled Propylene Glycol Monomethy1
Ether in Rats and Rabbits" Fundamental and Applied Toxicology;
Vol. 4: 784-794.
131
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 3
DATE:
nFr.
3 198~'
11-/()IfJf6r
SUBJECT: Status Report* 8EHQ-ll85-0573 APproved:~
FROM: James F. Darr, Section Head ~ T ~
Chemical Risk Identification Section/CSB
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
Nuodex Inc. reported that it was notified in writing by a foreign
supplier (Chemische Fabriek Servo B.V., Delden, Holland) that a
recently conducted acute skin application study of butyraldoxime
(CAS No. 110-69-0) in rabbits showed an LD50 value of between 100
and 200 mg/kg. In its Section 8(e) notice, Nuodex stated that it
was attempting to obtain a full copy of the final report of this
study from the foreign supplier.
Submission Evaluation
According to the NIOSH Registry of the Toxic Effects of Chemical
Substances (RTECS), butyraldoxime-has-been shown to have an LD50
of 200 mg/kg when injected intraperi toneally (ip) in mice. In
some acute toxicity classification systems, this ip LD50 value
indicates that the chemical is "very" toxic. Based on the newly
reported rabbit dermal LD50 value of between 100-200 mg/kg, how-
ever, butyraldoxime could now be classified as "extremely" toxic.
vh th regard to the adverse human health effects caused by over-
exposure to butyraldoxime, the following information was located
in a Material Safety Data Sheet (MSDS) contained in a publicly
available Material Safety Data Sheet collection (Material Safety
Data Sheets Service published by Information Handling Services of
Englewood, Colorado):
"If the [human] contact [with butyraldoxime] is of short
duration, the product will cause slight skin and eye ir-
ritation only. If the contact is of longer duration
(e.g., 24 hours), a moderate irritation will occur.
. [Butyraldoxime] may interfere wi th oxidation of
alcohol in the body resulting in the formation of in-
creased amounts of acetaldehyde, blotchy red marks, red
eyes, tiredness, [and] visible veins.u
,
------------------------------------------------------------------------------------
------------------------------------------------------------------------------------
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provisiDn of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
132
-------
8EHQ-1185-0573
Page 2 of 3
Current Production and Use
A review of the production range (includes importation volumes)
statistics for butyraldoxime (CAS No. 110-69-0), which is listed
in the initial TSCA Chemical Substance Inventory, has shown that
between 210 thousand and 2.1 million pounds were reported as pro-
duced and/or imported in 1977. This production range information
does not contain any production/importation data claimed as TSCA
Confidential Business Information (TSCA CBI) by the person(s) re-
porting for the initial TSCA Inventory, nor does it include any
information that would compromise TSCA CBL All data submitted
for the initial TSCA Inventory, including production range data,
are subject to the limi tat ions contained in the TSCA Inventory
Reporting Regulations (40 CFR 710).
In its TSCA Section 8(e) submission, Nuodex Inc. reported that it
imports butyraldoxime (as EXKIN@ 1) from Chemische Fabriek Servo
B. V. and then sells the chemical (as EXKIN@ No.1 Anti-Skinning
Agent) to the paint/coatings industry for use in solvent-based
coatings. According to secondary literature sources, anti-
skinning agents are mixed into paints and other coatings (e. g. ,
varnishes) to prevent oxidized film formation on exposed surfaces
in containers. Nuodex reported (by phone) that butyraldoxime
usually comprises less than 0.5% of final paint/coating formula-
tions. No information on current production/importation volumes
or other use (s) of bu tyraldoxime was located in the secondary
literature sources consulted.
Comments/Recommendations
According to the submission, Nuodex Inc. and Chemische Fabriek
Servo B.V. have updated their butyraldoxime Material Safety Data
Sheets to include the reported toxicologic information.
a)
The Chemical Screenin~ Branch (CSB/ECAD/OTS) will ask Nuodex
Inc. to ensure that EPA receives a complete copy of the final
report from the subject acute dermal toxici ty study as soon
as that report is obtained by the company. Nuodex will be
asked also to provide a full copy of the company's updated
EXKIN@ No.1 Anti-Skinning Agent MSDS as well as the foreign
supplier's updated EXKIN@ 1 MSDS.
In view of EPA's general interest in company actions that are
taken on a voluntary basis in response to chemical toxici ty
or exposure information, Nuodex will be asked to describe the
nature and available results of all studies that Nuodex has
conducted, is conducting, or plans to conduct to determine
the toxici ty of or the exposure to butyraldoxime. Nuodex
will be asked also to describe the nature of any further
actions the company has taken to notify workers and others
about the reported toxicologic findings on butyraldoxime.
133
-------
8EHQ-1185-0573
Page 3 of 3
b)
The Chemical Screening Branch will review the submitted data
in order to determine the need for further OTS assessment of
butyraldoxime.
c)
The Chemical Screening Branch will send copies of this status
report to OSHA, NIOSH, CPSC, FDA, NTP, ORD/EPA, OSWER/EPA,
OW/EPA, and OAR/EPA. Copies of this report will be sent also
to the TSCA Assistance Office (TAO) for further distribution.
134
-------
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
DATE:
DEC I 3 1985
Page 1 of 4
SUBJECT: Status Report*
8EHQ-1185-0574
d1/ ~ IbJlb/65
Approved: . . Jlv
L
FROM: James F. Darr, Section Head ~ r: ~
Chemical Risk Identificatiorllsection/CSB
roo Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Atlantic Richfield Company provided a full copy of an interim
(13 week) report from a subchronic (39 week) inhalation study of
silicon carbide (CAS No. 409-21-2) fibers in rats. According to
Atlantic Richfield, the objectives of the study are "to determine
(1) whether silicon carbide fibers when inhaled can cause lung
fibrosis; (2) the fibrogenic potency of silicon carbide fibers
relative to asbestos; and (3) what airborne concentrations of
silicon carbide fibers would not cause observable lung fibrosis."
Atlantic Richfield stated that the company hoped that the data
obtained from this study would help to provide "a scientific
basis for establishing an internal workplace exposure level [for
silicon carbide fibers]." The submitter's cover letter contained
the following information with regard to the conduct and interim
findings from the performed study:
"The study design included five groups, each consisting
of 50 male and 50 female rats. The negative control
group was given filtered air; the positive control
group, crocido1ite asbestos (1.5 urn in length x 0.2 urn
in diameter) at a concentration of 0.94 mg/m3 (equiva-
lent to 1298 fibers/cm3). The three groups exposed to
s il icon carbide fibers (4.5 urn in length x 0.5 urn in
diameter) received throughout the exposure period mean
mass concentrations of 3.93, 10.7, and 60.5 mg/m3 re-
spectively. These concentrations correspond to 630,
1746, and 7276 fibers/cm3. Exposures were for six hours
per day, 5 days per week for 13 weeks. Half the number
of animals were sacr i f iced at the end of the 13 weeks;
the remainder were scheduled for sacrifice after a six-
month (26 week) recovery period.
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
135
-------
8EIQ-1185-0574
Page 2 of 4
"Histopathologic examination of the rats' lungs from the
interim sacrifice showed mild chronic focal inflamma-
tion, as expected, with only minimal pulmonary fibrosis
in the silicon carbide [fiber]-exposed rats. However,
unexpected pleural changes also were detected. These
included focal and generally minimal to mild visceral
pleural fibrosis usually associated with subpleural in-
flammatory lesions. The incidence of these changes was
4, 2, and 12% in the low, mid and high [silicon carbide
fiber] dose groups respectively.
"Additionally, visceral and parietal pleural hyperplasia
was found in 6, 0, and 10% of the respective groups ex-
posed to the silicon carbide fibers. Most significant-
ly, this pleural hyperplastic effect was found in the
parietal pleura of two male rats in the low dose group.
While the hyperplasia observed can be regarded as mini-
mal, a silicon carbide fiber was present in both foci in
the parietal pleura, indicating that the fibers had pe-
netrated from the lungs into the chest cavity.
"Approximately 10% of the total number of animals ex-
posed to [the] s il icon carbide fibers had some pleural
changes. However, only a few an imals exh ibi ted both
pleural fibrosis and hyperplasia which may be a reflec-
tion of the sampling technique [used in the study]. No
changes of significance were observed in the lungs or
pleura of the negative control animals."
In reporting these interim findings to EPA, Atlantic Richfield
stated that "no special attempt was made to characterize the de-
gree of pleural involvement, thereby limiting the ability to
assess the true extent of this effect." Atlantic Richfield also
stated that the "interpretation of the results is further limited
by the lack of significant fibrotic and inflammatory activity in
the asbestos control group, a resul t possibly due to the small
fiber length of the material used in the study." Finally, the
Atlantic Richfield Company stated that it plans to "review the
results of the final sacrifice in an attempt to determine whether
the unexpected pleural fibrosis continues to be seen or if there
will be a significant regression of the preliminary findings."
Submission Evaluation
Immediately upon receipt of Atlantic Richfield's Section 8(e)
submission, copies were provided to the Risk Analysis Branch
(RAB/ECAD/OTS/OPTS), the Regulatory program Development Branch
(RPDB/CCD/OTS/OPTS) and the Asbestos Action Program/OPTS for
inclusion in the ongoing assessment of the potential risks posed
by exposure to natural and man-made fibrous materials.
136
-------
8EHQ-1185-0574
Page 3 of 4
Current Production and Use
A review of the production range (includes importation volumes)
statistics for silicon carbide (all forms, CAS No. 409-21-2),
which is listed in the initial TSCA Chemical Substance Inventory,
has shown that between 82.6 and 276.2 million pounds of this
chemical substance were reported as produced and/or imported in
1977. This production range information does not include any
data claimed as TSCA Confidential Business Information (TSCA CBI)
by the person( s) reporting for the intial TSCA Inventory, nor
does it include any information that would compromise TSCA CBI.
All data reported for the ini tial TSCA Inventory, including the
production range data, are subject to the limitations contained
in the TSCA Chemical Substance Inventory Reporting Regulations
(40 CFR 710) .
According to secondary Ii terature sources, silicon carbide is
used as an abras i ve in grinding, cutting, and polishing opera-
tions for metals, glass, and stone (e.g., granite). Other uses
reportedly include the manufacture of porcelain, shoe soles and
heat refractory materials (e.g., furnace bricks and linings). In
its fibrous form, silicon carbide is reportedly used as a heat-
resistant high-strength agent in certain composite materials.
Atlantic Richfield provided the following information concerning
the potential for worker exposure to silicon carbide fibers:
"At the present time, the potential for worker exposure
at Atlantic Richfield facilities is minimal
[because s il icon carbide fibers are] used in a closed
system. Further, the current [Material Safety
Data Sheet (MSDS)] instructions for handling [silicon
carbide fibers] indicate that the substance should be
regarded in the same hazard class as asbestos and that
personal protective equipment should be provided where
necessary. "
Comments/Recommendations
The Atlantic Richfield Company stated that copies of the final
interim report and the final study report would be sent to the
Agency as soon as those reports are received by the company.
a)
As was the case with the Atlantic Richfield Company's
initial Section 8(e) submission, the Chemical Screening
Branch (CSB/ECAD/OTS) will forward all of the reported
information to the Risk Analysis Branch (RAB/ECAD/OTS),
the Regulatory Program Development Branch (RPDB/CCD/OTS)
and the Asbestos Action program (AAP/OPTS) for inclusion
in the ongoing assessment of the potential risks posed
by exposure to natural and man-made fibrous materials.
137
-------
8EHQ-1185-0574
Page 4 of 4
In view of the Agency's general interest in corporate
actions that are taken on a voluntary basis in response
to chemical toxicity or exposure information, Atlantic
Richfield will be requested to describe the nature and
ava ilable results of all stud ies (other than those al-
ready reported formally to EPA or those published in the
open scientific literature) about which the company is
aware or that the company has conducted, is conducting,
or plans to conduct to determine the toxicity of and/or
the exposure to silicon carbide in any form.
b)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, OAR/EPA, ORD/EPA, RAB/ECAD/OTS, RPDB/CCD/OTS,
and the Asbestos Action program/OPTS. Copies of this
report will be sent also to the TSCA Assistance Office
(TAO/OTS/OPTS) for further distribution.
138
-------
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
Page 1 of 3
DATE:
DEC 2 0 /985
SUBJECT: Status Report*
8EHQ-1185-0575
Approved:
(;fI:#- I o/~ /tj 5"
FROM: James F. Darr, Section Head ~ ~ ~
Chemical Risk Identification~~ct-ion/CSB
ro: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Eastman Kodak Company provided the following summarized
information with regard to the conduct and results of an acute
oral LD50 study of 2-((4-amino-3-methylphenyl)ethylamino)ethanol
sulfate (CAS No. 25646-77-9):
"Groups of 5 male and 5 female rats per dose level were
given 25, 50, 100, 200 or 400 mg/kg of the test compound
in a single gavage dose as part of an oral LD50 test.
The acute oral LD50 was [deterIllined to be] 35 mg/kg in
females and 81 mg/kg in males. A number of animals were
subjected to gross and histopathological examination.
The most consistently and severely affected organ was
the kidney. Lesions in several organs were cons ide red
either directly or indirectly related to exposure to the
test compound. Such organs included the kidneys, lungs,
thymus, liver, heart, spleen, stomach, duodenum, and
testes. The [toxic] effects observed were related both
to dose and to the length of the survival period follow-
ing dosing. All animals examined showed lesions indica-
tive of renal toxici ty - Changes in the lung, thymus,
heart and spleen were thought to be secondary to renal
failure."
Eastman Kodak stated that the subject chemical is known to be a
skin/eye irritant as well as a skin sensitizer. Eastman Kodak
stated also that with the exception of irritation/sensitization,
the company is "not aware of any adverse health problems associ-
ated wi th the manufacture or use of this chemical or solutions
containing this chemical." Finally, Eastman Kodak stated that it
does not believe that the current handling procedures need to be
changed because those procedures "are designed to prevent skin
and eye irri tat ion and skin sensi tization and are sufficient to
protect against the reported toxicity."
====================================================================================
* NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e) ~ the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
139
-------
8EHQ-1185-0575
Page 2 of 3
Submission Evaluation
Although the submitted summarized information indicates that the
the tested chemical 1) borders on being classified as "extremely
toxic" on the basis of the reported rat oral LD50 values; and 2)
is toxic to the kidney as well as other organs, a full copy of
the final report from the performed study is needed in order for
the Agency to determine the overall significance of the reported
findings.
Current Production and Use
A review of the production. range (includes importation range)
statistics for 2-«4-amino-3-methyphenyl)ethylamino)ethanol sul-
fate (CAS No. 25646-77-9), which is listed in the initial TSCA
Chemical Substance Inventory, has shown that between 100 thousand
and 1 million pounus of this chemical were reported as produced
and/or imported in 1977. This production range information does
not include any information claimed as TSCA Confidential Busin.ess
Information (TSCA CBI) by the person(s) reporting for the initial
TSCA Inventory, nor does it include any information that would
compromise TSCA CBL All of the data reported for the ini tial
TSCA Inventory, including the production/importation data, are
subject to the limitations contained in the initial TSCA Chemical
Substance Inventory Reporting Regulations (40 CFR 710).
Eastman Kodak stated that the subject chemical "has been used in
the photographic industry for many years." No information on the
use(s) or current production/importation volumes of the chemical
was located in the secondary literature sources consulted by EPA.
Finally, Eastman Kodak provided the following information wi th
regard to the potential for exposure to the subject chemical:
"Potential employee exposure is mini:nized during [the]
manufacture and isolation of the damp and dry product by
the use of local exhaus t, gloves, safety glasses, and
coveralls. In addi t ion, employees wear air pur ifying
respi ra tors or use local exhaust when working wi th the
dry product. Currently, . [Eastman Kodak recommends
that its] customers use protective g loves and safety
g lasses and use good general room ventilation or local
exhaust when handling this chemical."
Comments/Recommendations
In its Section 8(e) submission, the East~an Kodak Company noted
that a copy of the rat oral LD50 study final report and copies of
the current product label and Material Safety Data Sheet (MSDS)
would be provided to EPA.
140
-------
8EIQ-1185-0575
Page 3 of 3
a)
The Chemical Screening Branch (CSB/ECAD/OTS/OPTS) will
request the Eastman Kodak Company to ensure that EPA
receives a complete copy of the final report (including
the actual experimental protocol, results of gross and
histopathologic examinations, etc.) from the rat oral
LD50 study cited in the submission.
In view of EPA' s general interest in corporate actions
taken on a voluntary basis in response to chemical tox-
icity or exposure information, the Chemical Screening
Branch will ask Eastman Kodak to describe the actions
the company has taken or plans to take to notify workers
and others about the reported toxicologic findings. In
addition, Eastman Kodak will be asked to describe the
nature and available results of all studies (other than
those published in the open scientific literature) about
which Eastman Kodak is aware or that Eastman Kodak has
conducted, is conducting, or plans to conduct to deter-
mine the toxicity of and/or the exposure to the subject
chemical.
b)
The Chemical Screening Branch will review the reported
data to determine the need for further OTS assessment of
2-«4-amino-3-methylphenyl)ethylamino)ethanol sulfate.
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, OAR/EPA, and ORD/EPA. In addi tion, copies of
this status report will be sent to the TSCA Assistance
Office (TAO/OTS/OPTS) for further distribution.
141
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
SUBJECT: Status Report*
8EHQ-1185-0576
Approved:
Page 1 of 3
~ J2/''lr7
DATE:
DEC 3 0 1985
FROM: James F. Darr i Section Head tk~ r ~
Chemical Risk IdentificationO~~ction/CSB
TO:Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Mobil Research and Development Corporation reported that "as
part of its ongoing program of evaluating petroleum products,
streams and components, . [the company] has investigated t"he
nature and basis of the dermal toxicity of a sample of fluid
catalytically cracked clarified oil" (CAS No. 64741-62-4; also
designated as clarified slurry oil (CSO». Mobil noted that CSO
is known to be "a potent dermal carcinogen and to cause systemic
toxici ty and early mortality when absorbed through the skin of
laboratory animals." Specifically, Mobil provided the following
information concerning the company's ongoing research activity:
". . .[Mobil's] research demonstrated lethal effects and
generalized systemic toxicity in rats after repeated
dermal application of CSO [at dose levels of 0, 8, 30,
125, 500 or 2000 mg/kg/day] in a 90-day subchronic
study. Dose rates of 8 mg/kg/day or greater produced a
variety of pathologic changes. The degree of liver
damage and of other organ/ system effects was dependent
upon dose and exposure time. Chemical analysis revealed
that the tested sample of CSO contained up to 22% carba-
zoles, a class of chemicals known to include carcino-
genic and hepatotoxic congeners. Using in vivo and in
vitro [skin absorption] techniques . ~ -Tthe Mobil
Research and Development Corporation has] found the car-
bazole derivatives to be the major dermal penetrants in
CSo.
"In particular, . . .[Mobil reported] the convergence of
several lines of evidence: (1) the [scienti fic] li tera-
ture shows that CSO is a dermal carcinogen and contains
substantial quanti ties of polynuclear aromatic hydro-
carbons; (2) [Mobil has] shown that, at low doses in a
subchronic study, a sample of CSO is markedly toxic to
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
142
-------
8EHQ-1185-0576
Page 2 of 3
the internal systems of rats by the dermal route; (3)
[Mobil has] found that the sample of CSO contained up to
22% carbazoles; (4) [Mobil has] demonstrated that carba-
zoles are readily bioavailable in animals by the dermal
route; and (5) the literature reports that some members
of the carbazole class are strong hepato-carcinogens and
are hepatotoxic in rodents. This evidence suggests tnat
the lethal and toxic effects observed with CSO may be
due, in whole or in part, to absorption of carbazoles."
In its sUbmission, the Mobil Research and Development Corporation
also provided 1) a short literature revie'N and bibliography of
studies conducted with catalytically cracked clarified oil; and
2) a table containing the range of chemical/physical properties
for 15 samples of catalytically cracked clarified oil from U.S.
oil refineries.
Submission Evaluation
Immediately upon receipt of this TSCA Section 8 (e) submission,
the Chemical Screening Branch (CSB/ECAD/OTS) provided a copy of
the submission to the Risk Analysis Branch (RAB/ECAD/OTS) for
inclusion in their ongoing assessment of available toxicologic
and exposure data on catalytically cracked clarified oil.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for catalytically cracked clarified oil (CSO; CAS No.
64741-62-4), which is listed in EPA 's 'rSCA Chemical Substance
Inventory, has shown that over 1 billion pounds of this material
were reported as produced and/or imported in 1977. This produc-
tion range information does not include any data claimed as TSCA
Confidential Business Information (TSCA CBI) by the person(s) re-
porting for the TSCA Inventory, nor does it include any data that
would compromise TSCA CBl. All of the data submitted for the
initial TSCA Inventory, including the production and importation
range data, are subject to the limitations contained in the TSCA
Inventory Reporting Regulations (40 CFR 710).
Appendix A of Volume I of the
Inventory contains the following
cracked clarified oil:
printed non-confidential TSCA
definition for catalytically
"A complex combination of hydrocarbons produced as the
residual fraction from distillation of the products from
a catalytic cracking process. It consists of hydrocar-
bons having carbon numbers predominantly greater than
C20 and boiling above approximately 350°C (662°F). This
stream is likely to contain 5 wt. % or more of 4- to 6-
membered condensed ring aromatic hydrocarbons."
143
-------
8EHQ-1185-0576
Page 3 of 3
:r:n its Section 8 (e) notice, the Mobil Research and Development
Corporation provided the following information with regard to the
uses of and the potential for exposure to catalytically cracked
clarified oil:
" . [Catalytically cracked clarified oil (CSO) ] is
used as feed stock for the production of carbon blacks,
petroleum coke and petroleum pitch; and sometimes it is
included as a component of heavy fuels, including Bunker
C and No.6 Fuel oil. Most of these materials are manu-
factured in sealed units, shipped in bulk and handled in
closed systems, usually at temperatures of 130 to 200°F.
Because of these conditions, the potential for human
contact with CSO and products containing it is minimal;
impervious protective equipment is recommended where
that potential exists."
Comments/Recommendations
The Mobil Research and Development Corporation stated that its
existing Material Safety Data Bulletin and product label (which
already have a warning to avoid all personal contact with cata-
lytically cracked clarified oil) have been revised to "emphasize
the need to avoid all personal contact by using impervious pro-
tective equipment." The submitter stated also that Mobil's em-
ployees and customers as well as other interested parties have
been notified about the reported findings.
It should be noted that EPA I s Office of Toxic Substances (OTS)
has received and reviewed a number of TSCA Section 8(e) and "For
Your Information" (FYI) submissions containing toxicologic and/or
exposure information on catalytically cracked clarified oil.
a)
The Chemical Screening Branch will ask the Mobil Reseach
and Development Corporation to submit complete copies of
the final reports from the 90-day rat dermal application
study, the in vitro and in vivo skin absorption studies,
and the Mobil refinery worker epidemiologic studies that
were cited in the submission.
b)
As was the case with Mobil's initial 8 (e) sUbmission,
the Chemical Screening Branch will immediately forward
all reported information to the Risk Analysis Branch for
inclusion in their ongoing assessment of catalytically
cracked clarified oil-
oJ
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, OAR/EPA, ORD/EPA and RAB/ECAD/OTS. In addition,
copies will be provided to the TSCA Assistance Office
(TAO/OTS) for further distribution.
144
-------
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
DATE: JAN 2 3 1986
"O"CT, Status Report' 8EHQ-1285-0577 APproved:~
FROM: James F. Darr, Section Head L:J 1 a;;;;'L--
Chemical Risk IdentificatioN7~e~tion/CSB
Page 1 of 7
ro: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The U.S. Department of Energy (DOE) submitted full copies of the
final reports from several in vivo studies designed to assess the
possible mutagenic and reproductive/developmental toxici ties of
the following chemicals or lnixtures of those chemicals:
EMP-I
ERR@-4205: bis(2,2-epoxycyclopentyl)ether
No. 2386-90-5)
(BECPE;
CAS
EMP-II
1,3-diaminobenzene (MPDA; CAS No. 108-45-2)
EMP-III
Arald i te@ 6010 (the dig lyc idyl
DGEBAi CAS No. 25068-38-6)
ether of
bisphenol
A.
,
EMP-IV
ZZL@-0820: a curing mixture containing 56.7 wt.% EMP-II,
30.3 wt% EMP-VI and 13.0 wt.% EMP-III
EMP-V
ERL@-2258: a resin mixture containing 50.0 wt.%
and 50 wt.% EMP-III
EMP-I
EMP VI
4,4'-methylenedianiline (4,4'-MDA; CAS No. 101-77-9)
According to the submitted reports, EMP-II, EMP-IV and EMP-V were
not considered to be teratogenic following oral administration to
pregnant rats at dose levels sufficient to produce maternal toxi-
city. However, EMP-V was considered to be embryotoxic in the rat
at doses sufficient to cause mild maternal toxicity. Further,
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
145
-------
8EgQ-1285-0577
Page 2 of 7
EMP-IV and EMP-V were both reported to be potentially teratogenic
following oral administration to pregnant rabbits at dose levels
sufficient to produce maternal toxicity. with regard to adverse
effects on the male rat reproductive system, orally administered
EMP-V (but not EMP-IV) was reported to produce a dose-dependent
reduction in sperm production as well as a strony, dose-dependent
dominant lethal effect. In a dominant lethal study in which male
rats were exposed to EMP-I via inhalation, a slight but statisti-
cally significant dominant lethal effect was found but was con-
sidered to be too weak to account for the strong dose-related
mutagenic effect observed in the rat oral dominant lethal study
of EHP-V (a 50:50 mixture of EMP-I and EMP-III). The following
discussion provides greater detail with regard to the conduct and
results of the performed studies.
In a preliminary teratology study, EMP-II, EMP-IV and EMP-V were
administered orally in 2% carbox~nethyl cellulose to groups of 9
pregnant Sprague-Dawley rats at the following doses: 45 mg/kg
(EMP-II); 50 or 100 mg/kg (EHP-IV); 600 or 1200 mg/kg (EMP-V).
Although no significant teratogenic effects were reportedly ob-
served, all tested materials at all treatment levels were found
to have caused varying degrees of maternal toxicity as evidenced
by lua ternal body we ight loss. In add i tion, both dose leve ls of
EMP-V were found to have caused embryotoxic effects manifested by
a significant reduction in fetal body we ight in both sexes of
offspring. In a more "defini tive" oral teratologic study usin']
more pregnant rats per dose group (i.e., 30 rats/group), EMP-II
(35 mg/kg), EMP-IV (40 and 80 mg/kg), and EMP-V (500 and 1000
mg/kg) were again found not to be teratogenic but were found to
produce maternal toxicity. As in the "preliminary" study, EMP-V
was shown to produce embryotoxic effects as manifested by sig-
nificantly delayed ossification of the sternabrae at 500 mg/kg
and reduced fetal body weight in both sexes of offspring at 1000
mg/kg. The submi tted final report presented the following con-
clusions with regard to these oral teratology studies in rats:
". . EMP-IV and EMP-V and EMP II were not teratogenic
in Sprague-Dawley rats at [oral] dose levels sufficient
to cause maternal toxicity- EMP-V was determined to be
embryotoxic in the rat, identified by a significantly
delayed ossification of the sternebrae at the 500 mg/kg
level and a reduced fetal body wei'Jht in both sexes at
dose levels of 600 mg/kg and above. These dose levels
of EMP-V were also r:lildly maternally toxic."
In teratology studies in New Zealand white rabbits, EMP-IV and
EMP-V were administered orally in 2% carboxymethyl cellulose to
groups of approximately 25 pregnant rabbits at dose levels of 25
and 50 mg/kg (EMP- IV) and 101, 165, and 270 mg/kg (EMP-V). The
following information concerning the results of these teratology
studies was contained in the Summary section of the submitted
final report:
146
-------
8EHQ-1285-0577
Page 3 of 7
"Maternal toxicity was demonstrated in at least the
high-dose level for. [both EMP-IV and EMP-V]. One
and four of the 25 and 26 rabbits at the low- and high-
dose levels of EMP-IV, respectively, died. No deaths
occurred at the low-dose level of EMP-V. One and five
of the 25 rabbits at the mid- and high-dose levels of
EMP-V, respectively, died. Common observations at ne-
cropsy in rabbits in both groups included diarrhea, loss
of appeti te, and hemorrhag ic lungs; rabbi ts rece iving
EMP-IV also had nasal exudate and blobdy urine. A de-
creased weight gain during treatment was also observed
for rabbits at the high-dose level of EMP-V.
"Four rabbits treated with the high-dose level of EMP-IV
had resorbed litters, and one other pregnancy resulted
in a spontaneous abortion, causing a significantly re-
duced average live litter size when those pregnancies
were included. Since resorbed and aborted Ii tters are
often a result of maternal toxicity, rather than a tera-
togenic or direct embryotoxic effect, the average live
Ii tter size was also evaluated excluding these pregnan-
cies. The average live litter size excludiny resorbed
and aborted litters was not significantly affected by
treatment with EMP-IV or EMP-V. The average percentage
of dead or resorbed embryos per implant (excluding to-
tally resorbed and aborted litters) and the average live
fetus weights were not significantly affected by treat-
ment wi th . [EMP- IV or EMP-V]. These resul ts ind i-
cate that EMP-IV and EMP-V are not embryotoxic in the
rabbit at dose levels [capable of] producing slight
maternal toxicity.
"The incidence of anyone individual malformation was
not significantly increased with either of the test
agents; however, the total percentage of fetuses wi th
any rnalfor:nation (including rib, limb, spinal, and skull
anomalies) was significantly increased at the low-dose
level of EMP- IV and the mid-dose level of EMP-V. Only
five viable litters were produced at the high-dose level
of EMP-IV (35 fetuses). One of these fetuses had a ma-
jor congenital anomaly; however, the incidence of mal-
formed fetuses was not significant at the high-dose
level of EMP-V.
"The results of these studies indicate that EMP-IV and
EMP-V are potentially teratogenic to Ne\'l Zealand Whi te
rabbits at dose levels sufficient to cause maternal
toxicity. The spontaneous malformation rate in the
concurrent vehicle control group was very low (1 of 161
fetuses were mal formed) and the increased inc idence of
malformed fetuses in the treated groups was not far
above a normal spontaneous rate for this strain of
rabbi t. Therefore, these compounds are not pos i tively
being identified as teratogens in this species."
147
-------
8EHQ-1285-0577
Page 4 of 7
Further with regard to the teratologic studies in rabbits,
Conclusion section of the submi tted final report contains
following information:
the
the
". .[Although EMP-IV and EMP-V] are not positively
being identified as teratogens in New Zealand vfuite rab-
bits, . [these materials] must be considered to be
potentially teratogenic at dose levels sufficient to
cause maternal toxicity in this species. previous work
wi th . [EMP-IV and EMP-V] determined that EMP-V was
embryotoxic in the rat at mildy maternally toxic dose
levels, but neither. [mixture] was found to be ter-
atogenic in this species. In regards to human health,
. [both EMP-IV and EMP-V] must be considered to be a
potential risk to the developing embryo at maternal ex-
posure levels approaching that which would also cause
maternal toxicity. Although these studies did not pro-
vide data at low dose levels, since the teratogenic re-
sponse of . [EMP-IV and EMP-V] was equivocal at the
very high dose levels tested, it is unlikely that a de-
velopmental hazard exists at a very low level of expo-
sure to EMP-IV or EMP-V. At exposure levels producing a
comparable degree of maternal toxicity, since EMP-V was
also found to be embryotoxic in the rat, it would be
considered to be more of a developmental hazard than
EMP-IV. II
In a study designed to assess possible in vivo mutagenic (i.e.,
dominant lethal) effects and possible adverse effects on sperma-
togenesis caused by either EMP-IV or EMP-V, these mixtures were
administered orally in 1% carboxymethyl cellulose to groups of
approximately 25 male Sprague-Dawley rats at dose levels of 20,
40 or 80 rng/kg/day (EMP-IV) and 250, 500, or 1000 mg/kg/day (EMP-
V) for 13 consecutive weeks. In the dominant lethal portion of
the study, male rats were bred to two female rats each after an
ini tial 10-week treatment period and continued to receive daily
doses during the 2-week mating period and for one week following
the mating period. The investigators noted that the daily treat-
ment beyond 10-weeks was to allow the separate evaluation of the
possible adverse effects on sperm production following a total
exposure of 13 weeks. The following information concerning the
dominant lethality portion of this subchronic study was presented
in the Summary section of the submitted final report:
"Evaluation of the females during mid-gestation revealed
that treatment of the males with EMP-IV did not result
in dominant lethal effects or [in] effects on fertility.
However, treatment with EMP-V resulted in a strong domi-
nant lethal effect with a clear dose response. In addi-
tion to the positive mutagenicity of EMP-V, a reduction
in the fertility of male rats was evident. Although
EMP-V was positive for mutagenicity in male germ cells,
it would be extremely unusual for a mutagen to affect
148
-------
8EHQ-1285-0577
Page 5 of 7
testicular tissue exclusively.
likely to be a general mutagen,
sues of either sex could be at
of this mixture."
Therefore, EMP-V is
in which case many tis-
risk following exposure
with regard to the results of the spermatogenesis portion of the
performed sub-chronic study, the following information was pre-
sented in the Summary section of the final report:
"EMP-IV hau no effect on sperm production except for a
small reduction in the percentage of motile cells re-
covered from the cauda epididymis in rats treated wi th
40 and 80 mg/kg/day. Treatment of rats with EMP-V re-
sulted in significantly decreased sperm production, epi-
didymal spernl numbers, and percentage of motile cells in
rats exposed to 1000 mg/kg/day. These resul ts clearly
indicate that EMP-V is deleterious to spermatogenesis in
Sprague-Dawley rats under the cond i tions used in this
stud Y . "
In another dominant lethal i ty study, EMP-I was administered via
inhalation to groups of approximately 25 male Sprague-Dawley rats
at dose levels rang ing from 0.05 to 0.3 mg/l for 6 hours/day, 5
days/week for 10 weeks. Following the last exposure, 20 males
from each group ~vere selected for lnating at a 2 female/l male
rat io. The Res ul ts and Di scuss ion section of the final report
contained the following infor!fiation concerning the findings from
this study as well as th8 relationship of these findings to those
of the oral dominant lethal study of EMP-IV and EMP-V described
previously:
". . .[A]lthough EMP-I exhibited some mutagenic activity
in this study, the activity observed was much less than
would be expected if it had been the primary cause of
the mutagenes is res ul ting from trea tment wi th the EMP-V
mixture. From the eEfects of this study, . . . [the in-
vestigators] conclude that EMP-I may have weak mutagenic
effects on the germ cells of male Sprague-Dawley rats.
It is difficult to compare the equivalency of [the] dose
levels received from inhalation and oral routes of expo-
sure. However, if the two routes of exposure can be
considered to del iver similar doses to the testes, the
data from this study would indicate that EMP-I was not
the sole or major contributor to the mutagenesis seen
following oral exposure to the EMP-V mixture."
Submission Evaluation
Immediately upon receipt of this Section 8(e) submission, the
Chemical Screening Branch (CSB/ECAD/OTS) provided copies of the
submitted reports to the Risk Analysis Branch (RAB/ECAD/OTS) and
the Test Rules Development Branch (TRDB/ECAD/OTS) for inclusion
in their ongoing evaluations of the available toxicologic or
149
-------
8EHQ-1285-0577
Page 6 of 7
exposure information on epoxides and 4,4'-methylenedianiline
(RAB/ECAD/OTS), phenylene diamines (TRDB/ECAD/OTS), and glycidol
and its derivatives (RAB/ECAD/OTS and TRDB/ECAD/OTS).
Current Production and Use
A review of the production range (includes importation volumes)
statistics for the subject chemicals, which are listed in the
ini tial TSCA Chemical Substance Inventory, has shown that the
following volumes were reported as manufactured and/or imported
in 1977. (Note: The following information does not include any
data claimed as TSCA Confidential Business Information (TSCA CBI)
by the person( s) reporting for the ini tial 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).)
Chemical CAS Number Production/Importation Range
BECPE 2386-90-5 0*
HPDA 108-45-2 110,000 to 1,100,000 Ibs.
DGEBA 25068-38-6 126,983,000 to 669,836,000 Ibs.
4,4'-MDA 101-77-9 10,030,000 to 50,301,000 Ibs.
* This "0" indicates that no production/importation was
reported for 1977 or that all of the production range
data that were reported were claimed as TSCA CBI by the
manufacturer( s) or importer( s) and cannot be disclosed
(Section 14(a) of TSCA, U.S.C. 2613(a)).
Although DOE's submission did not contain any information with
regard to DOE's use(s) of the subject chemicals or mixtures, it
is clear from the provided reports that the subject materials are
used in an epoxy resin hardening/curing process of some type.
Comments/Recommendations
According to DOE, additional studies on the subject chemicals and
mixtures are planned and/or underway. DOE has stated that copies
of the final reports from these additional studies would be sent
to EPA upon completion of those reports. In addition, DOE has
stated that workers involved with the subject chemicals/mixtures
have been notified about the reported toxicologic findings.
EPA's Office of Toxic Substances (OTS) has received and reviewed
a number of TSCA Section 8(e) and/or "For Your Information" (FYI)
submissions containing toxicologic or exposure data on several of
the chemical substances mentioned in DOE's Section 8(e) notice.
150
-------
8EHQ-1285-0577
Page 7 of 7
Al though anyone may submi t information to EPA under Section 8 (e) ,
the IIsubstantial risk" information reporting provision of TSCA,
only certain persons are required to do so. According to Section
8(e), lIany person who manufactures, [imports,] processes, or dis-
tributes in [US] 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 inforra the [EPA]
Administrator of such informa tion unless such person has actual
knowledge that the Administrator has been adequately informed of
such information. II The Agency's Section 8(e) policy statement
(" Statement of Interpretation and Enforcement policy; Notifi-
cation of Substantial Risk" 43 FR 11110; March 16, 1978) defines
the term "person" to include lIany natural person, corporation,
firm, company, joint-venture, sole proprietorship, association,
or any other business entity, any State or political subdivision
thereof, any municipali ty, any interstate body, and any depart-
ment, agency, or instrumental i ty of the Federal Government. II
[emphasis added] While it is clear that DOE is a "person" within
the TSCA Section 8(e) policy statement definition, the mandatory
obligation to report substantial risk information to EPA under
Section 8 (e) would not be incurred by DOE unless DOE is or has
engaged commercially in the manufacture, import, processing, or
distribution of the chemical substance(s) or mixture(s) about
which the substantial risk information was obtained.
a)
The Chemical Screening Branch will request DOE to ensure
that EPA rece ives complete copies of the final reports
(including the actual experimental protocols, results of
gross/histopathologic examinations, etc.) from all of
the studies reportedly underway or planned to determine
the reproductive/devel00nental toxicities of the subject
chemicals or mixtures.
b)
As was the case with DOE's initial Section 8(e) notice,
the Chemical Screening Branch will provide full copies
of all further DOE reports on the subject chemicals or
mixtures to RAB/ECAD and/or TRDB/ECAD staff.
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OAR/EPA, ORD/EPA, OW/EPA, OPP/OPTS/EPA, OCM/OPTS/EPA,
RAB/ECAD/OTS, and TRDB/ECAD/OTS. Copies of this status
report will be sent also to the TSCA Assistance Office
(TAO/OTS) for further distribution.
151
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 3
DATE:
JAN
9 1986
SUBJECT: Status Report *
8EHQ-1285-0578
Approved:
Z#- '/I~/fr,
FROM:James F. Darr, Section Head Jt.'~"Ar ~
Chemical Risk IdentificationV;::~ion/CSB
TO:Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
Syntex (U.S.A.) Inc. submitted the following summary information
wi tl1 regard to the conduct and results of several acute in vivo
toxicity studies of acetyl ferrocene (CAS No. 1271-55-2):--
"Oral toxicity studies were initially conducted on
groups of two male and two female rats at doses of 50,
150, and 500 mg/kg. All of the animals died within thir-
teen days after dosing, with most deaths occurring on
the second and third days. Toxic signs included inacti-
vity, kyphosis, rough coat, unthriftines~3, salivation
and ptosis. Female animals appeared to be more sensitive
than "males. These preliminary data suggested that the
oral LD50 for acetyl £errocene in rats was less than 50
mg/kg.
"To further confirm and define the oral toxicity of ace-
tyl ferrocene, the oral toxicity testing was repeated on
two groups of five male and five female rats. One group
was administered one dose at 50 rng/kg, and the second
group was given 5 mg/kg. All females in both groups died
within four days. All of the male rats given low doses
survived, but only one male rat survived at t'oe high
dose. A sexual difference in sensitivity was again ob-
served. The oral LD50 of acetyl ferrocene for female
rats appears to be less than 5 mg/kg, while the compar-
able LD50 for males seems to be between 5 mg/kg and 50
mg/kg.
"Eye irri"tation tests were then performed on three fe-
male rabbits. Doses of 30 mg/kg (100 mg/rabbi t) were
administered to each rabbit in the conjunctival sac of
the eye. All of the rabbits died on the second or third
days following dosing.
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
152
-------
8EHI]-1285-0578
Page 2 of 3
"Acute dermal toxicity tests were then conducted on
groups comprising two male and two female rats, at doses
of 50, 500 and 2000 mg/kg. Three animals from the high
dose group, and one animal from the medium dose group
died on the second and third days, respectively, follow-
ing dosing. The dermal LD50 in rats appears to be be-
tween 50 and 500 mg/kg."
In addition, Syntex stated that no adverse human health effects
have been reported to the company during the 15 years that acetyl
ferrocene has been used at one Syntex facility. Finally, Syntex
stated that in view of the absence of reported adverse effects in
Syntex workers, t"he submitted data suggest "that there may be
important differences in sensitivity between humans and animals."
Submission Evaluation
Based on the submitted summarized information, acetyl ferrocene
would be classified as "extremely" toxic. In order for EPA to
evaluate the overall significance of the reported findings, how-
ever, Syntex shoulti be asked to submit complete copies of the
final reports from all of the cited studies. It should be noted
that the NIOSH Registry of Toxic Effects of Chemical Substances
(RTECS) cites the results of a study demonstrating that acetyl
ferrocene has an LD50 value of 75 mg/kg in mice following intra-
venous injection. It should be noted also that the submitter's
argument concerning the species specificity of the toxic action
of acetyl ferrocene is weakened by observations of acute lethal-
ity at low doses in several species (rats, rabbits, and mice) and
via several routes of exposure (oral, dermal, and ocular admini-
stration as well as intravenous injection). The lack of reported
adverse health effects in Syntex workers could be explained just
as well by the possibility that the company's industrial hygiene
program has been sufficient to date in minimizing or eliminating
exposure to the subject chemical. In the absence of data to lend
support -to Syntex I s argument concerning species specificity, the
submitted information suggests that human exposure to even small
amounts of acetyl ferrocene could prove to be toxic if not fatal.
Current Production and Use
A review of the product ion range (includes importation volumes)
statistics for acetyl ferrocene (CAS No. 1271-55-2), which is
listed in the initial TSCA Chemical Substance Inventory, shows
that between 1,000 and 11,000 pounds were reported as produced
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) reporting for the initial
TSCA Inventory, nor does it include any information that would
compromise TSCA CBI. All of the information that was reported
for the initial TSCA Inventory, including the production range
information, is subject to the linli tations contained in the TSCA
Inventory Reporting Regulations (40 CFR 710).
153
-------
8EHQ-1285-0578
Page 3 of 3
In its Section 8(e) notice, Syntex stated that acetyl ferrocene
is an intermediate used in the manufacture of one of the com-
pany's ultimate products. (Syntex did not disclose the identity
of this product.) Syntex stated also that there is no current or
contemplated contact between acetyl ferrocene and the general
public. No information concerning the use(s) or current produc-
tion/ importation volumes of acetyl ferrocene was found in the
secondary literature sources consulted.
Comments/Recommendations
Syntex stated that based on the submitted toxicologic findings,
the company has 1) reviewed and modified current personal protec-
tive equipment requirements for acetyl ferrocene; and 2) updated
and distributed a revised acetyl ferrocene Material Safety Data
Sheet (MSDS) to "pertinent" Syntex employees. Syntex stated also
that the company is considering "performing additional testing to
further interpret the toxic potential of this chemical."
a)
The Chemical Screening Branch (CSB/ECAD/OTS) wi 11 ask
Syntex to provide to EPA a full copy of the final report
(including the actual experimental protocol, results of
gross and histopathologic examinations, results of any
statistical analyses, etc.) from each toxicologic study
cited in the company's submission.
In view of EPA's general interest in corporate actions
that are taken on a voluntary basis in response to chem-
ical toxicity or exposure data, Syntex will be asked to
describe the nature and available results of all other
studies that the company has conducted, is conducting,
or plans to conduct to determine the toxicity of and/or
the exposure to acetyl ferrocene.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of acetyl ferrocene.
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. In addition,
copies of this status report will be sent to the TSCA
Assistance Office (TAO/OTS) for further distribution.
154
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
JAN I 5 1986
Page 1 of 3
SUBJECT: Status Report*
8EHQ-l285-0579 S
Approved: ~
( /15 /1~
, ,
FROM: James F. Darr, Section Head 44-,..'''' J t t'f;:lr/.---
Chemical Risk Identification(tection/CSB
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 (TSCA CBI). The Information
Management Division (IMD/OTS) will request the submitting company
to substantiate this confidentiality claim.
Submission Description
The submitting company provided final results from an in vitro
mutagenicity study and several acute in vivo toxicologic-Studies
of p-vinyl phenol (CAS No. 2628-17-3)~ According to the submit-
ted information, p-vinyl phenol at doses of 200, 2000, or 4800
mg/kg caused the death (within 1 to 2 days) of all rabbits (4
rabbits per dose group) to which the chemical was administered
dermally as a solid moistened with saline solution. In addition,
the submitting company stated that edema and dermal corrosion
were observed during this acute rabbit dermal study. The sub-
mitter stated also that p-vinyl phenol was found to be highly
corrosive to the eyes of rabbits following instillation of 100 mg
of the chemical and that 1 of 4 rabbits exposed to the chemical
died (cause of death unknown) on the seventh day of the study.
Wi t'h regard to oral toxicity, the company reported that p-vinyl
phenol was found to have an oral LD50 greater than 500 mg/kg in
rats. Finally, the submitter reported that p-vinyl phenol was
non-mutagenic when tested with or without exogenous metabolic
ac,tivation in an Ames Salmonella typhimurium (bacteria) assay-
Submission Evaluation
Although p-vinyl phenol appears to be only slightly or moderately
toxic upon oral administration, based on the data from the acute
rabbit skin application study, the chemical can be categorized as
"extremely" toxic. Further, the results of the rabbit dermal ap-
plication and eye instillation studies demonstrate that p-vinyl
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
155
-------
8EHQ-1285-0579 S
Page 2 of 3
phenol is both highly irritating and corrosive. In addition, it
should be noted that the results of the eye instillation study
suggest that p-vinyl phenol may have produced systemic toxicity
resulting in the one death observed on the seventh day of that
study.
In order for the Agency to evaluate the overall significance of
the reported findings, the submitter should be requested to pro-
vide complete copies of the final reports (including the actual
experimental protocols, data, results of gross/histopathologic
examinations, results of statistical analyses, etc.) from all of
the studies (including the reportedly negative in vitro mutagen-
icity study) that were cited in the company's submission.
Current Production and Use
p-Vinyl phenol is not listed in the non-confidential computerized
version of the initial (1977) TSCA Chemical Substance Inventory.
Al though t11e submitting company did not provide any information
concerning the actual/planned use(s) of p-vinyl phenol, the sub-
mi tting company did state that "p-vinyl phenol is currently an
experimental material. .[that] has been made and handled sole-
ly for purposes of R&D in small quantities." The submitting com-
pany stated also that potential human or environmental exposure
to p-vinyl phenol "is limited by the fact that the material is a
solid. " No information concerning the use (s) of p-vinyl phenol
was located in the secondary literature sources consulted.
Comments/Recommendations
In its Section 8(e) notice, the submitting company stated that
"all employees who may come in contact with. . [p-vinyl phenol]
have been informed of the hazardous nature of this material and
have been instructed on the protective measures to be taken while
working with this material."
a)
The Chemical Screening Branch (CSB/ECAD/OTS/OPTS) will
request the submitter to provide to EPA complete copies
of the final reports (including the actual experimental
protocol, data, results of gross and histopathological
examinations, results of any statistical analyses, etc.)
from all of the studies (including the reportedly nega-
tive in vitro mutagenicity assay) that were cited in the
company's Section 8(e) submission.
In view of the Agency's general interest in corporate
actions that are taken on a voluntary basis in response
to chemical toxicity or exposure information, the sub-
mitting company will be requested to describe the nature
and available results of all other studies that the com-
pany has conducted, is conducting, or plans to conduct
to determine the toxicity of or the exposure to p-vinyl
pheno 1.
156
-------
8EHQ-1285-0579 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 p-vinyl phenol.
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, OAR/EPA, ORD/EPA and OPP/OPTS/EPA. Copies of
this status report will be provided also to the TSCA
Assistance Office (TAO/OTS) for further distribution.
157
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 3
DATE:
DEC 3 0 1985
SUBJECT: Status Report* 8EHQ-1285-0580 Approved:
FROM: James F. Darr, Section Head It - - ,,~
Chemical Risk Identification~ion/CSB
~
,t,I?Jdf~
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The In ternational Business Machines Corporation (IBM) provided
summarized final results from a battery of in vitro genotoxicity
assays of l-methylamino-4-(p-tolylamino)anthraquinone (Sudan Blue
GA; Color Index (C.I.) Solvent Blue 11; C.I. No. 61525; CAS No.
128-85-8). According to IBM, the tested chemical had been found
to be weakly mutagenic with and without metabolic activation both
in the Ames Salmonella typhimurium (bacteria) Assay and the Mouse
Lymphoma Cell Forward Mutation Assay. In addition, IBM reported
that the chemical had been found to cause chromosomal aberrations
only in the presence of metabolic activation in cultured Chinese
Hamster Ovary (CHO) cells. With regard to in vivo toxicity, IBM
reported that although an oral LD50 study had not been conducted,
the subject chemical was mildly irritating to the skin of guinea
pigs but was not a skin sensitizer.
Submission Evaluation
Although the submitted summarized information does indicate that
the subject chemical possesses some degree of genotoxic activity,
a full copy of the final report from each study (including the in
vivo guinea pig studies) cited in the 8(e) submission are needed
in order for the Agency to evaluate the overall significance of
the reported findings.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for Sudan Blue GA (CAS No. 128-85-8), which is listed
in the initial TSCA Chemical Substance Inventory, has shown that
from 0 and 1,000 pounds were reported as produced and/or imported
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e). the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
158
-------
8EHQ-l285-0580
Page 2 of 3
in 1977. This production range information does not include any
data claimed as TSCA Confidential Business Information (TSCA CBI)
by the person(s) reporting for the initial TSCA Inventory, nor
does it include any information that would compromise TSCA CBI.
All of the information reported for the initial TSCA Inventory,
including the production/importation range information, is sub-
ject to the limitations contained in the TSCA Inventory Reporting
Regulations (40 CFR 710).
In its TSCA Section 8(e) sUbmission, IBM provided the following
information concerning the company's use of and the potential for
exposure to Sudan Blue GA:
"IBM uses Sudan Blue GA exclusively in the manufacturing
of metallo-ceramic chips. ["Exposure is controlled in a
vented hood during the weighing of the dye stuff for in-
corporation into the paste coating in which [the dye] is
used."] After application and processing, the chips are
heated to 825 degrees Celsius [(825°C)] and the dye
stuff and paste are destroyed."
No information concerning other uses or the current production
volume of Sudan Blue GA was located in the secondary literature
sources consulted.
Comments/Recommendations
Although a positive in vitro genotoxicity test result, when con-
sidered alone, may not be sufficient to offer reasonable support
for a conclusion of substantial risk, EPA does believe that such
results are of value in assessing the possible risks posed by
chemicals to health or the environment. The Agency believes also
that positive genotoxicity test results in combination with other
information (e.g., knowledge of potential exposure to and/or high
production of the tested chemical or mixture) would suggest, in
many cases, the need to conduct further studies designed to de-
fine better the toxicologic properties of and/or the exposure to
the subject chemical or mixture. The results of such additional
studies should be considered also for possible submission to EPA
under Section 8(e) of TSCA.
a)
The Chemica 1 Screening Branch (CSB/ECAD/OTS/OPTS) will
request IBM to submit a full copy of the final report
(including the actual experimental protocol, data, the
results of gross/histopathological examinations, the
results of statistical analyses, etc.) from each study
cited in the company's submission.
In view of EPA's general interest in corporate actions
taken on a voluntary basis in response to chemical toxi-
city and/or exposure information, IBM will be asked to
describe the actions the company has taken to notify its
workers and others about the submitted findings. IBM
159
-------
8EHQ-1285-0580
Page 3 of 3
will be asked also to describe the nature and available
results of all other studies that IBM has conducted, is
conducting, or plans to conduct to define the toxicity
of and/or the exposure to Sudan Blue GA.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of Sudan Blue GA.
c)
The Chemical Screening Branch will send copies of this
status report to OSHA, NIOSH, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA and OAR/EPA. Copies of this report will
be sent also to the TSCA Assistance Office (TAO/OTS) for
further distribution.
160
-------
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
Page 1 of 2
DATE:
JAN 2 3 1986
SUBJECT: status Report*
8EHQ-1285-0581
Approved:
tY~ r)lhfrir
FROM:James F. Darr, Section Head ihA~~;JP:1)i:;:,,-
Chemical Risk IdentificationU~:~~ion/CSB
ro:Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The American Cyanamid Company provided the summarized results of
an acute rat oral study of Calcozine@ Red BG Liquid, a 45% solu-
tion of Color Index (C.L) Basic Red 12 (CAS No. 6320-14-5) in
acetic acid. Accordin
-------
8EHQ-1285-0581
Page 2 of 2
TSCA Conf idential Business Information (TSCA CBI) by the manu-
facturer( s) and/or importer( s) 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 contained in the TSCA
Inventory Reporting Regulations (40 CFR 710).
According to the submitter, "Basic Red 12 is a coal tar dye of
the methine class." According to secondary 1 i terature sources,
Basic Red 12, has a "bluish-pink" fluorescent hue and may be used
for both natural and synthetic fibers (e.g., silk, cotton, and
nylon), leather, paper, carbon paper, and pigments.
Comments/Recommendations
In its Section 8(e) submission, American Cyanamid stated that the
company has notified its customers about the reported toxicologic
findings and updated the Calcozine@ Red BG Liquid Material Safety
Data Sheet (MSDS).
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will ask
the &~erican Cyanamid Company to submit a complete copy
of the final report (including the actual experimental
protocol, results of gross/histopathologic examinations,
statistical analyses, etc.) from the company's acute rat
oral toxicity study of Calcozine@ Red BG Liquid.
In view of EPA' s general interest in corporate actions
that are taken on a voluntary basis in response to chem-
ical toxicity or exposure information, American Cyanamid
will be asked to describe both the nature and available
results obtained from all other studies that the company
has conducted, is conducting, or is planning to conduct
to determine the toxici ty of and/or exposure to Basic
Red 12 alone or in combination with other chemicals.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of C.I. Basic Red 12.
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, OAR/EPA, ORD/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.
162
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
JAN 3 0 1986
Page 1 of 3
FROM: James F.
Chemical
Approved: ~
/0 c;::
Darr, Section Head /Jo:.'mI" ~". ~.rv1--
Risk Identification Section/CSB
8EHQ-0186-0582 S
,/~/r(,
I
SUBJECT: Status Report*
~:Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Note
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 (IMD/OTS) has
requested the company to substantiate this confidentiality claim.
In an addendum da ted January 23, 1986, CIBA-GEIGY provided the
following generic names for the subject chemical: "chlorophenoxy
chlorophenyl alkyl substi tuted heteromonocycl ic heteromonocycle"
or "haloaryl biheteromonocycle."
Submission Description
The CIBA-GEIGY Corporation provided the following information
with regard to the conduct and preliminary results of a 13-week
dietary feeding study of the subject chemical in dogs:
"ophthalmoscopic examinations (using focal illumination
and indirect opthalmoscopy) on dogs on test day 71 (week
10 examinations), revealed bilateral equatorial, anter-
ior cortical and posterior cortical lenticular aberra-
tions affecting all dogs in the high level group (6000
ppm, (3/3 male, 3/3 female)) and 1 female from the 3000
ppm level. Ophthalmoscopically, the lenticular changes
were characterized as vacuoles, water clefts, spoke-like
opacities, and splitting and separation of the lens su-
ture lines with resultant "y" shaped fissures. All [of
the] other ocular structures appeared clinically unaf-
fected at this time. No changes from normal were seen
in the eyes of other dogs administered 3000 ppm or in
[those] dogs treated wi th 1000 or 100 ppm of the test
material and there appeared to be no visual deficit at
this time."
------------------------------------------------------------------------------------
------------------------------------------------------------------------------------
* NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report.may be based on incomplete information.
163
-------
8EHQ-0186-0582 S
Page 2 of 3
In its submission, CIBA-GEIGY stated that in
reported preliminary findings, the company will:
response
to
the
" 1.
Photograph the eyes of all dogs at this time.
2.
Perform bi-monthly examinations of the eyes of
the dogs.
3.
Remove the eyes at the scheduled 13-week
necropsy.
4 .
During histological processing of the eyes,
remove the lens of the left eye and process
it separately while processing the second eye
routinely."
Submission Evaluation
Although the submitted information does indicate that the tested
chemical can cause dose-related lenticular aberrations, a more
thorough evaluation of the significance of the reported findings
should be possible upon EPA's receipt of a full copy of the final
report (including the actual experimental protocol(s), results of
gross/histopathological examinations, results of any statistical
analyses, etc.) from the company's dietary feeding study in dogs.
In its submission, CIBA-GEIGY stated also that "there appeared to
be no visual deficit [in the exposed dogs]." CIBA-GEIGY
did not report, however, how the exposed dogs' visual integrity
was tested or if the sensi tivi ty of such tests was sensi tive
enough to detect subtle but serious visual disturbances.
It should be noted that although systemic intoxication leading to
lenticular aberrations is not common, such adverse effects have
been reported in the published scientific literature to occur in
labora tory an imals and humans following expos ure to a number of
substances. Finally, it should be noted that the preliminary
findings reported in the present submission are very similar to
those submitted on a previous occasion by CIBA-GEIGY pursuant to
Section 8(e) of TSCA. In BEHQ-0285-0545 S, CIBA-GEIGY submitted
the preliminary results of a dietary (dog) feeding study of CGA-
149071, an R&D chemical being evaluated for pesticidal purposes
and identified generically by CIBA-GEIGY as a "halophenoxy halo-
phenyl substi tu ted heteromonocyc 1 ic he te-romonocycle ."
Current Production and Use
In the present TSCA Section 8 (e) submission, CIBA-GEIGY stated
that the subject haloaryl biheteromonocycle "is a research and
development material which is being evaluated for pesticidal
purposes" and that the pesticidal evaluations "have been con-
ducted only under the supervision of technically qualified
personnel."
164
-------
8EHQ-Ol86-0582 S
Page 3 of 3
Comments/Recommendations
The CIBA-GEIGY Corporation reported that in addition to providing
a full copy of the final report from the cited study to EPA, the
company plans to provide the following notice to all personnel
who work with the subject chemical:
"Ocular changes in the dog have been noted after 10
weeks of dietary exposure to high levels of [the subject
chemical] . These changes are areas of swelling in the
lens. Gloves, gogg les and protect ive equipment should
be used to prevent exposure to [the chemical] until
further information is available about this effect."
In addition, CIBA-GEIGY reported that the labels on containers of
the subject chemical will bear the following information:
"Eye changes in the dog have been noted in animal
testing wi th this compound. Wear gloves and goggles
when handling this compound."
It should be noted that these proposed CIBA-GEIGY communications
pertain mainly to the avoidance of dermal and ocular exposure and
do not address the potential for inhalation or oral exposure to
the tested chemical.
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will ask
CIBA-GEIGY to ensure that EPA receives a complete copy
of the final report (including actual experimental pro-
tocol(s), results of gross/histopathologic examinations,
results of statistical analyses, etc.) from the dietary
feeding study which is the subject of the company's pre-
sent submission.
In view of EPA's general interest in corporate actions
that are taken on a voluntary basis in response to
chemical toxici ty or exposure information, CIBA-GEIGY
will be requested to describe the nature and available
results of all other studies that the company has con-
ducted, is conducting, or plans to conduct to determine
the toxicity of or the exposure to the subject chemical.
b)
The Chemical Screening Branch wi 11 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, OW/EPA,
OSWER/EPA, OAR/EPA, ORD/EPA and OPP/OPTS/EPA. Copies of
this report will also be provided to the TSCA Assistance
Office (TAO/OTS/OPTS/EPA) for further distribution.
165
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
JAN - 11986
Page 1 of 7
SUBJECT: Status Report* 8EHQ-0685-0583 S
8EHQ-I085-0583 S FLWP
FROM: Frank D. Kover, Branch Chief ~p.
Chemical Screening BranchjEC~'d
~~
TO: Joseph J. Merenda, Division Director
Existing Chemical Assessment DivisionjOTS
NOTE
Although the CIBA-GEIGY Corporation claimed the exact chemical
identity of the subject chemical as TSCA Confidential Business
Information (TSCA CBI), the company did provide the following
non-confidential code number for the chemical: CGA-143686. The
CIBA-GEIGY Corporation has been requested to substantiate this
confidentiality claim.
Submission Description
On a "For Your Information" (FYI) basis (FYI-OTS-0685-0420 S),
the CIBA-GEIGY Corporation provided the following information
concerning the conduct and interim results of a two-year dietary
oncogenicity and chronic toxicity study of CGA-143686 in mice:
"The dose levels [of CGA-143686J for the two-year dietary
oncogenicity and chronic toxicity study are [O,J 10, 100,
1000 and 2000 ppm. The results of microscopic examination
of the liver masses and nodules of animals dying on study
or sacrificed in extremis up to mon~1 22 indicate a sta-
tistically significant increase in liver tumors [(hepato-
cellular adenomas and carcinomas) J in male mice at tbe
2000 ppm dose level."
". . [TheJ historical incidence data for
tumors of this type in the male for the
facility is purported to be about 8%."
mouse liver
.[testingJ
In its initial FYI notice, CIBA~GEIGY also provided the following
information with regard to the conduct and available results of a
chronic feeding study of CGA-143686 in rats:
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
166
-------
Page 2 of 7
"In addition to. . [the 2-year oncogenicity and chronic
toxicity] mouse study, CGA-143686 is being fed to rats in
a two-year combined chronic toxicity / oncogenici ty study.
This study is also in the in-life phase. No oncogenic
response has been noted in this study."
Finally, CIBA-GEIGY stated that it believed that the results of
the chronic mouse feeding study did not warrant filing a Section
8(e) submission because the results were interim in nature.
Following a review of the summarized information presented in
CIBA-GEIGY's initial FYI submission, EPA informed CIBA-GEIGY in
writing (EPA letter dated September 19, 1985) that EPA believed
that the company's interim CGA-143686 oncogenicity results con-
stituted "substantial risk" information and, as such, should have
been submitted formally to the Agency pursuant to Section 8 (e) ,
the substantial risk information reporting provision of the Toxic
Substances Cotrol Act (TSCA). The basis for the Agency's initial
position with regard to the TSCA Section 8(e)-applicability of
the subject findings was as follows:
"The CIBA-GEIGY Corporation's stated position that Section
8(e) of TSCA does not pertain to interim results of toxi-
city studies is incorrect. Part VI of EPA's March 16, 1978
TSCA Section 8(e) policy document ("Statement of Interpre-
tation and Enforcement Policy; Notification of Substantial
Risk" 43 FR 11110) states that "a person is not to delay
reporting until he obtains [(i.e, possesses or knows of)]
conclusive information that a substantial risk exists, but
is to immediately report any evidence which reasonably
supports that cone Ius ion . " Part VI of the 8 (e) policy
document states further that "not only should [the] final
results from. . studies be reported, but also prelimi-
nary results from incomplete studies where appropriate."
In EPA's September 19, 1985 letter, CIBA-GEIGY was requested to
provide additional information concerning the company's rationale
as to why the subject findings were not submitted to the Agency
under Section 8(e) of TSCA.
In a letter dated October 22, 1985 (FYI-OTS-I085-0420 S Followup
Response), CIBA-GEIGY responded to EPA's questions and statements
with regard to the TSCA Section 8(e)-applicability of the interim
findings from the company's two-year dietary feeding and chronic
toxicity study of CGA-143686 in mice. In its followup response,
CIBA-GEIGY stated that although the company agreed with EPA that
interim results 0f such studies could be subject to TSCA Section
8(e) reporting, one of the major reasons the company did not re-
port the observed mouse liver tumors to EPA under Section 8 (e)
was that CIBA-GIEGY considered the findings to be only "limited"
evidence of carcinogenicity when viewed in the context of EPA's
November 23, 1984, proposed "Guidelines for Carcinogenic Risk
Assessment."
167
-------
Page 3 of 7
In addition, CIBA-GIEGY pointed out that the tested substance was
a research and development (R&D) c'hemical for which pesticide
field testing had been halted due to lack of efficacy and all
ongoing toxicologic studies of the chemical had been terminated.
According to CIBA.-GEIGY, the reports from the two-year dietary
toxicity/oncogenicity studies of CGA-143686 in mice and rats are
expected to be completed in the first and third quarters of 1986,
respectively. (In additional correspondence, CIBA-GEIGY stated
that a copy of the final report from an Ames test conducted with
an analog of CGA-143686 would be sent to EPA when t'hat report is
received from CIBA-GEIGY Limited in Basle, Switzerland.)
Finally, CIBA-GEIGY provided the following summarized information
concerning the purpose and results of other toxicologic studies
that the company had conducted with CGA-143686:
"28/90 Day Mouse Study- No observable effect level = <100
ppm. ilaximum tolerated dose = f'V 1000 ppm. This study was
toe range-finding study used to establish dose levels in
the two-year dietary oncogenicity and chronic toxicity
study in mice.
28/90 Day Rat Study. No observable effect level = 100
ppm. Maximum tolerated dose =N 1000 ppm. This study was
the range-finding study used to establish dose levels in
the two-year dietary oncogenicity and chronic toxicity
study in rats.
28 Day Dog Range-Finding Study. No observable effect
level = <1000 ppm. Maximum tolerated dose = <5000 ppm.
T'his study was to establish dose levels for a one-year dog
study. However, the one-year dog study was cancelled when
toe product was 'dropped from further development."
Submission Evaluation
The preliminary data from CIBA-GEIGY's two-year dietary study of
CGA-143686 in mice show t'hat the heptocellular carcinoma and the
hepatocellular adenoma plus hepatocellular carcinoma incidences
were statistically significant in male mice at the 2000 ppm dose
level when compared to concurrent controls. There is no reason-
able scientific justification or merit in invoking historical
control data in this case in view of the fact that the most re-
liable control data are those obtained under rigorously identical
laboratory conditions as those for exposed animals. (In the pre-
sent study, toe concurrent control mice showed much less than the
8% incidence of liver tumors reportedly observed in historical
control mice.) Al though statistical significance was not esta-
blished at 2000 ppm for hepatocellular adenomas in male or female
mice or for hepatocellular carcinomas or hepatocellular carcino-
mas plus adenomas in female mice, the latter two tumor incidences
were elevated sufficiently when compared to concurrent controls
to indicate that the tumorigenic response in the female mice was
168
-------
Page 4 of 7
treatment related. Finally, it is most important to note that
"limi ted" evidence of carcinogenicity (as that term is used in
the Agency I s proposed carcinogenicity "weight of the evidence"
classification system) should not be interpreted to mean that the
evidence can be dismissed or that the evidence is not reasonable
in terms of its ability to support a conclusion that the chemical
can cause cancer.
Current Production and Use
In view of the fact that CIBA-GEIGY asserted a con fidentiali ty
claim for the exact chemical identity of CGA-l43686, no informa-
tion concerning the chemical's TSCA Inventory status will appear
in this report. In its initial FYI submission, CIBA-GEIGY stated
that CGA-143686 was "a research and development (R&D) chemical
currently being evaluated solely for pesticidal purposes" and
that the pesticidal evaluations had been "conducted under tl1e
supervision of technically qualified personnel, knowledgeable in
handling potentially hazardous chemicals." In its followup re-
sponse letter, CIBA-GEIGY reported that CGA-143686 was, but is no
longer, being evaluated by the company as an herbicide.
Comments and Recommendations
In the initial FYI notice, CIBA-GEIGY stated that all personnel
involved with CGA-143686 would receive the following information:
"Preliminary results [obtained fromJ a two-year
oncogenicity and chronic toxicity study in mice indicate
there may be an increased incidence of liver tumors in
male mice at the highest feeding level. Confirmation of
this effect cannot be made until the study is complete
and all animals examined. Until [CIBA-GEIGY' sJ
evaluation is complete, CGA-l43686 should be handled in
such a manner as to prevent ingestion, inhalation, or
skin absorption."
===============================================~====~~========~:=
Following a review of FYI-OTS-0685-0420 Sand FYI-OTS-1085-0420 S
Followup Response, EPA's position is unchanged with regard to the
TSCA Section 8(e)-applicability/reportability of the interim on-
cogenici ty findings from CIBA-GEIGY' s two-year dietary study of
CGA-143686 in mice. The basis for EPA's decision is as follows:
Under TSCA, the Agency can regulate certain activities
involving "chemical substances" and "mixtures." If a
substance is manufactured, processed, or distributed in
commerce solely for use as a pesticide, however, Section
3 of TSCA excludes such substance from TSCA regulation.
(See Section 3 of TSCA for other exempt substances.)
169
-------
Page 5 of 7
In keeping with the policy expressed by EPA in the TSCA
Chemical Substance Inventory reporting regulations (43
FR 64585, December 23, 1977, Appendix A, Comment 37, 38
and 39), EPA considers a substance to be a "pesticide"
within the meaning of the Federal Insecticide, Fungicide
an Rodenticide Act (FIFRA) once that substance is the
subject of (1) a submission made to EPA as part of the
eXperi1l1enta1 use permit (EDP) process under !:"IFRA or (2)
an application for registration submitted to EPA under
FIFRA. Prior to the EDP or registration stage, however,
EPA treats the substance as a "chemical substance" under
the jurisdiction of TSCA.
TSCA Section 8(e) states that "any person who manufac-
tures, [imports, ] processes, or distributes in commerce
a chemical substance or mixture and who obtains informa-
tion which reasonably supports the conclusion that such
substance or mixture presents a substantial risk of in-
jury to heal~l or the environment shall immediately in-
form the Administrator of such information unless such
person has actual knowledge that the Administrator has
been adequately informed of such information."
The preface in Part V of EPA's March 16, 1978 Section
8(e) policy statement ("Statement of Interpretation and
Enforcement Policy~ Notification of Substantial Risk"
43 FR 11110) s-tates that "a substantial risk of injury
to health is a risk of considerable concern be-
cause 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 healtll effects for which sub-
stantial risk information must be reported to include
"any pattern of effects or evidence which reasonably
supports the conclusion that the chemical substance or
mixture can produce cancer, mutation, birth defects.
" The information concerning these effects can be
obtained directly or inferred from designed studies
(e.g., in vivo animal studies) as described in Part VI.
Part Vlexplains also that a subject "person is not to
delay reporting until he obtains conclusive information
that a substantial risk exists, but is to immediately
report any evidence which reasonably supports that con-
clusion. " In addition, Part VI explains that "not only
should final results from such studies be reported, but
also preliminary results from incomplete studies where
appropriate."
With regard to the "fact or probability of its [i.e.,
the serious effect's] occurrence" criterion, Part V of
the 8(e) policy document states that certain types of
nealth effects (e.g., cancer) ace considered to be so
serious that relatively little weight should be attached
to the chemical's exposure in determining whether a risk
170
-------
Page 6 of 7
is substantial. Further, EPA' s response to a question
concerning R&D chemicals (EPA response to Comment 31 in
Appendix B of the TSCA Section 8 (e) policy statement)
explains that the occurrence of serious effects such as
those described in Part V (a) of the policy statement
(e.g., cancer, birth defects) presuppose exposure to the
tested chemical and must be reported under Section 8(e).
Therefore, if a subject person obtains "substantial
risk" information concerning an R&D chemical prior to
the application for an experimental use permit (EUP) as
a pesticide or registration as a pesticide under FIFRA
(even though such information might be submitted at a
later date to EPA under FIFRA), the "substantial risk"
information must be reported under Section 8(e).
Finally, it is important to note that previously unknown
evidence (preliminary or otherwise) of chemical-induced
carcinogenicity observed in an animal study, regardless
of how that evidence could be classified ultimately un-
der various cancer risk assessment systems/guidelines,
should be considered for immediate submission to EPA
under Section 8 (e) of TSCA. It should be noted also
that the mere fact that cancer-related findings from an
animal study could be classified as "limited" evidence
of carcinogenicity (as that category is defined in EPA's
proposed cancer risk assessment guidelines) does not
preclude those findings in any way from reasonably sup-
porting a conclusion that the tested chemical can cause
cancer.
In view of the preceding discussion and EPA' s review of the
information contained in CIBA-GEIGY' s initial and followup FYI
submissions, EPA believes that the interim oncogenicity findings
from the 2-year dietary study of CGA-l43686 in mice do reasonably
support a conclusion that this TSCA-covered substance can cause
cancer. It is EPA's decision, therefore, that the subject cancer
findings should have been reported formally to the Agency under
Section 8(e) of TSCA.
a
The Existing Chemical Assessment Division (ECAD/OTS)
will notify CIBA-GEIGY about EPA's decision with regard
to the TSCA Section 8(e)-applicability/reportability of
~he company's interim oncogenicity findings in mice.
The Chemical Screening Branch (CSB/ECAD/OTS) will for-
ward FYI-OTS-0685-0420 S/FYI-OTS-I085-0420 S Followup
Response to the OTS Document Control Office (DCO) for
appropriate handling and public filing under Section
8(e) of TSCA.
b
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of CGA-143686.
171
-------
Page 7 of 7
c
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, NTP, FDA, OSWER/EPA,
OAR/EPA, OW/EPA, ORD/EPA, OCM/OPTS/EPA, and the Office
of Pesticide Programs (OPP /OPTS) . In addition, copies
of this report will be provided to the TSCA Assistance
Office (TAO/OTS/OPTS) for further distribution.
172
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
FEB 20 1986
Page 1 of 3
SUBJECT: status Report* 8EHQ-0 186-0584 Approved: ~
FROM: James F. Darr, Section Head iltn.£1 r ~7;;1---
Chemical Risk IdentificatioJl~ection/CSB
Z-/1-fj!ft,
.. ,
ro:Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Chevron Chemical Company provided the following summarized
infor:llation with regard to the conduct and results of an acute
oral LD50 study of RE-45550 (5-[(2-ethylthio)propyl]-2-(1-oxo-
propyl)-1,3-cyclohexanedionei CAS No. 99422-01-2) in rats:
"This study was conducted to determine the acute oral
toxici ty of RE-45550. A previous prel iminary acute
oral toxici ty study of RE-45550 found clinical
wotor activity effects but no concomitant histopatho-
logical lesions in the nervous system through four days
after dosin<). In this recent [acute oral] study, the
animals were held for 21 days after dosing to determine
whether any neuropathological changes would develop
over an extended study period. Five rats of each sex
were dosed in tragastr ically wi th [0, 50, 100,
150, 220, or] 330 mg/kg of RE-45550.
"In animals that received 220 or 330 mg/kg, RE-45550
induced motor effects wh ich included sl ight to severe
hindlimb and/or forelimb ataxia, splayed hindlimbs,
loss of pain reflex in paws, inability to grasp and/or
loss of ri'Jhting reflex. Other signs of toxicity in
these two groups included lacrimation, nasal and ocular
discharges, and pupillary miosis or mydriasis. With
the exception of one male in the 220 mg/kg dose group,
all animals in these two groups died or were sacrificed
in moribund condition. In [the] females dosed with 150
mg/kg, signs of toxici ty included slow pupil response
and mydriasis. No motor or nervous system effects were
observed in animals receiving 50,100 or 150 (males)
mg/kg of RE-4 5550. There was no mortal i ty in these
dose groups. The estimated LD50 value for both males
and females is approximately 170 mg/kg.
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
173
-------
8EHQ-0186...0584
pC3,<.:fe 2 of 3
"Histopathologically, degeneration of the spinal nerves
with hemorrhage of the spinal nerves, brain, and/or
spinal cord occurred in a dose-related manner in fe-
Illales at 150 mg/kg and higher and in males at 220 or
330 mg/kg. . . . These lesions are considered irrever-
sible and apparently take several days to develop after
treatment. The no-effect level was 150 mg/kg for males
and 100 mg/kg for female s, wh ich agreed wi th the in-
life observations. Compound-related congestion,
he1l10rrhage acute cysti tis or necrosis was present in
the urinary bladder of most animals of both sexes in
the 220 mg/kg group and in several animals at the 330
109/kg group.
"In summary, RE-45550 produced cl inical signs of
toxicity which correlated with microscopic pathological
lesions."
According to the submi tted informa tion, RE-45550 has not as yet
been tested for acute dermal, eye or inhalation toxicity but has
been found to be non-mutagenic when tested either in the presence
or absence of exogenous metabolic activation in two strains of
Salmonella typhimuriulIl (bacteria) in an in vitro Ames assay.
In its TSCA Section 8 (e) notice, Chevron reported that RE-45550
is structurally similar to RE-36015 (5-[(2-ethylthio)propyl]-3-
hydroxy-2'- (2-oxobutyl) -2-cyclohexene-l-one; CAS No. 79419-43-5).
It should be noted that in a previous TSCA Section 8(e) notice
(8EHQ-1283-0501 et seq.), Chevron reported that RE-36015 caused
severe and persistent paralysis in rats following acute oral
exvosure to non-lethal doses of the chemical.
Submission Evaluation
Based on the submitted summarized information, RE-45550 would be
classified as being "very toxic" by the oral route of exposure.
In addition to the observed lethality at 220 and 330 mg/kg, the
provided information reveals a number of clinical effects on the
motor system and widespread degeneration in the nervous system.
The upper doses were accompanied by such signs as 1 imb ataxia;
loss of the grasping, pain, and rightin] reflexes; and pupillary
dilatation and/or slowed pupillary response. Although the onset
and duration of the observed neurotoxicologic signs was not re-
ported, these signs were found to correlate wi th the hemorrhage
and degeneration of both peripheral and central neurons in the
spinal cord and brain stem observed in male and female rats at
220 and 330 mg/kg and in a few females at 150 mg/kg. Finally,
the sub!!1.itted summarized information indicates that exposure to
RE-45550 could resul t in renal dysfunction and possibly failure
as a consequence of the adverse effects observed histologically
in the urinary tract.
174
-------
8EHQ-0186-0584
Page 3 of 3
current/Production and Use
In the cover letter to its Section 8(e) notice, Chevron reported
that RE-45550 "is the fifth intermediate in a series of seven in
the production of a chemical, wh ich if developed successfully,
would be registered and sold as a pesticide.1I The company did
not report whether RE-45550 would be an isolated or non-isolated
intermediate in the final pesticide production process. A review
of the computerized version of the non-confidential TSCA Chemical
Substance Inventory shows that CAS No. 99422-01-2 is not listed.
Comments/Recommendations
In its Section 8(e) notice, Chevron submitted an interim version
of the company's RE-45550 Material Safety Data Sheet (MSDS). It
should be noted that the interim MSDS (which states that RE-45550
has an oral rat LD50 value of 222 mg/kg, whereas the Section 8(e)
submission states that the oral rat LD50 is 170 mg/kg), does not
appear to address the full extent or overall severity of some of
the reported toxicologic findings.
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will ask
the Chevron Chemical Company to provide complete copies
of the final reports (including the actual experimental
protocols, results of gross/histopathological examina-
tions, results of any statistical analyses, etc.) from
the two acute in vivo oral toxicity studies and the in
vitro mutagenicity study cited in the submission.
In view of EPA's general interest in corporate actions
taken on a voluntary basis in response to chemical tox-
icity or exposure i~formation, Chevron will be asked to
describe the nature and available results of all other
studies that the company has conducted, is conducting,
or plans to conduct to determine the toxicity of and/or
the exposure to RE-45550.
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, OW/EPA,
OSvVER/EPA, OAR/EPA, ORD/EPA and OPP/OPTS/EPA. Copies
of this status report will be provided also to the TSCA
Assistance Office (TAO/OTS) for further distribution.
175
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
FEB 25 1986
Page 1 of 7
SUBJECT: Status Report* 8EHQ-O 186-0585 S
Approved: frl)/~:1 ;tzr'{ J. /~ ~-k~
t .
. ~. . /J utt.v7.--
FROM: James F. Darr, Sect lon Head :.rh1£1 .~' :--
Chemical Risk Identification.Section/CSB
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The CIBA-GEIGY Corporation submitted final results from a 28-day
oral gavage study of Tinuvin@ 144 (CAS No. 63843-89-0)** in rats.
In the cover letter to its submission, CIBA-GEIGY presented the
following information wi th regard to the conduct and resul ts of
the performed study, which, according to the company, shows a
potential immunosuppressive activity for Tinuvin@ 144:
"Rats received daily gavage doses of 0, 60, 100, 300,
600 and 1000 mg/kg for 28 days. The corresponding
mortal i ty rates for these respective groups were as
follows: 0, 0, 30, 70, 80 and 100%. Where observa-
tions could be made, all [of the] dose levels produced
alterations in whi te blood cell parameters and thymus
weight as well as lesions in the spleen, abdominal
lymph node s, and 1 i ver. The les ions were de scr ibed as
abscesses ~vh ich occurred in 5 of 10 animals at 100
mg/kg and in 2 of 10 an imals at 60 mg/kg. In add i tion
to these lesions, there was a significant dose-related
decrease in thymus weight and thymic tissue atrophy.
The decrease in the weight of the thymus for males was
42%, 56% and 94% in the 60, 100 and 300 mg/kg groups,
respectively. Females showed decreases of 10%, 46%,
and 91% in the corresponding dose 9roups. Si9ni f icant
changes in the white blood cell parameters included
marked elevations in the number of leukocytes and seg-
mented neutrophiles, as well as dramatic reductions in
the number of lymphocytes."
(** Accordin9 to CIBA-GEIGY, the actual chemical identity of
Tinuvin@ 144 is: propanedioic acid, «3,5-bis(1,1-dimethylethyl)-
4-hydroxyphenyl)methyl)butyl-, bis(1,2,2,6,6-pentamethyl-4-piper-
idinyl) ester.)
------------------------------------------------------------------------------------
------------------------------------------------------------------------------------
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
176
-------
8EHQ-0186-0585 S
Page 2 of 7
Accordin'] to the submitted study report, asp erma to genesis was
observed in male rats exposed to Tinuvin@ 144 at doses of 300,
600, and 1000 mg/kg. In addition, the study report states that
increased blood clotting time was found in 1 male and 2 females
in the 300 @g/kg dose group.
According to a submitted Material Safety Data Sheet (MSDS),
Tinuvin@ 144 was found to have an oral LD50 of 1500 mg/kg (rats),
a dermal LD50 of >3100 mg/kg (rats), and a 4-hour LC50 of >0.46
mg/L (ratsi exposure to an aerosol containing approximately 60%
particles with sizes <7 microns). In addition, the provided MSDS
indicates that studies in rabbits have shown that the product is
non-irritating to the skin and only slightly irritating to the
eyes. The MSDS states also that sensitization studies in guinea
pigs showed the product to be negative following epidermal chal-
lenge but positive following intradermal challenge. Further, the
MSDS states that a study involving 80 human subjects exposed to
Tinuvin@ 144 showed an apparent dose-related increased incidence
of erythema but did not show sensitization. The Tinuvin@ 144
MSDS states also that the product was found to be negative in a
mouse phototoxicity study and in a guinea pig photosensitization
study. Finally, the submitted MSDS states that the product was
negative in an in vitro bacterial mutagenicity assay (Ames test).
Submission Evaluation
Immunosuppression is a very important and serious manifestation
of systemic toxicity and can leave the affected individual open
to 1) infection and/or 2) development of cancer; either can be
life-threatening or 1 ife-shortening. Al though CIBA-GEIGY's 28-
day study of Tinuvin@ 144 in rats is of too short a duration to
evaluate whether tumor development was favored, it does show that
the treated animals had an apparent susceptibil i ty to infection
(abscesses; poor general health) and that the chemical had an un-
mistakable dose-related impact on survival. Rats in the control
group and the 60 mg/kg/day group lived through the 28-day study.
At 100 mg/kg/day, 30% of the rats died in 11-27 days. At 300
mg/kg/day, 70% died in 5-10 days, while at 600 mg/kg/day, 80%
died in 4-7 days. At 1000 mg/kg/day, all rats died in 3-6 days.
The observed survival rates were approximately equal among males
. and females.
Female rats treated wi th 60 mg/kg/day gained weight at a rate
similar to controls while males treated with 60 mg/kg/day gained
weight at a similar rate for 21 days, and then leveled off. Rats
of either sex treated with 100 mg/kg/day gained weight but at a
much slower rate than the controls. Rats of ei ther sex treated
with the higher doses (i.e., 300, 600 or 1000 mg/kg/day) actually
lost weight in a dose-related manner. The observed decreases in
body we ight correlated well wi th the observed decreases in food
intake. Considering that this 28-day study involved exposure to
the subject chemical by gavage, unpalatability of the food does
not appear to be an issue.
177
-------
8ffiiQ-0186-0585 S
Page 3 of 7
The observed toxic signs reportedly included ataxia, muscular
hypotonia, ptosis of the eyelids, hunched posture ("kyphotic
carriage"), diarrhea, and gas in the intestines ("meteorism").
Neurohistochemical examinations of the sympathetic portion of the
autonomic nervous system (presumably conducted because of the
observed ptosis of the eyelids) did not reveal any difference
between control animals and two rats each from both the 60 and
100 mg/kg/day dose groups. It is unclear why 60 mg/kg/day was
chosen for examination in the neurohistochemical portion of the
study rather than a higher dose, because ptosis was not reported
in the 60 mg/kg/day group, but was reported in the higher-dose
groups. This curiosity may not be vital, however, because the
ataxia, hypotonia, and kyphotic carriage could be attributed
alternatively to pain or malaise resulting either directly from
treatment or secondarily from distention of the intestines wi th
gas ("meteorism").
Histological examination and hematology showed a large-scale
involvement of the reticuloendothelial immune system (thymus,
lymph nodes, spleen, liver, and circulating white blood cells).
The apparent increase in the total number of white blood cells
may be ei ther an artifact (e.g., as the resul t of serum-volume
losses following diarrhea-induced dehydration) or due to a real
increase in neutrophilic granulocytes (e.g., responding to acute
infection, as indicated by the observed abscesses). Further, the
observed depletion of circulating lymphocytes is consistent with
immunosuppression. The observed atrophy of the thymus is also
consistent wi th immunosuppression. The thymus is the source of
T-Iymphocytes that perform a variety bf immune functions. The
thymus is, however, a relatively insensitive indicator of immuno-
suppression. It is quite likely, therefore, that many other more
sensitive but unmeasured immune-system changes occurred prior to
the development of thymic atrophy.
A serious adverse effect observed in the 28-day gavage study but
not mentioned in the submitted Tinuvin@ 144 MSDS is the impaired
spermatogenesis in male rats in the 300, 600, or 1000 mg/kg/day
dose groups. Although this effect could be explained as being
due to stress, ill health, or impaired nutrition if it were found
in a 90-day study in rabbits for example, the rat testis is con-
sidered generally to be more hardy than the rabbit testis and a
28-day study covers only about half of the spermatogenic cycle.
It is possible, therefore, that Tinuvin@ 144 may have a direct
adverse effect on the testis and testicular function. Further
testing would be needed to sort out the cause(s) of the observed
impairment of spermatogenesis.
Another serious adverse effect that deserves attention, although
the submitted data are inadequate to permit its full appreciation
at this time, is the prolongation of clotting time. This effect,
which may have resulted from impaired liver function, could have
contributed significantly to the hemorrhage that was observed in
the lungs.
178
-------
8EHQ-0186-0585 S
page 4 of 7
In general, the reported adverse immune-system effects appear to
be of the type that one might expect to see in the first tier of
the National Toxicology Program's tier-testing scheme for immuno-
toxic effects: screening tests based on hematology, body weight,
organ weights (e.g., thymus, spleen, lymph nodes), and histology
(e.g., cellularity of spleen and thymus). A wide variety of more
specific and refined tests is available at the present time with
which to pursue more in-depth immunolog ic questions (e.g., cell-
mediated versus hwnoral immunity, effects on specific lymphocyte
populations, or host resistance to bacterial, viral, or parasitic
infection) .
Finally, it should be noted that Tinuvin@ 144 bears a striking
structural rese,TIblance to a chemical that was the subject of a
TSCA Section 5 "Pre-Manufacture Notice" (PMN No. 81-495) submit-
ted previously by CIBA-GEIGY. It would be of interest to know if
CIBA-GEIGY has conducted, is conducting, or plans to conduct any
studies to determine if tha t PMN chemical can cause adverse e f-
fects similar to those found in the 28-day study of Tinuvin@ 144.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for CAS No. 63843-89-0, which is listed in the initial
TSCA Chemical Substance Inventory, has shown that 1,000 to 10,000
pounds of this chemical were reported as produced and/or imported
in 1977. This production range information does not include any
production/importation data claimed as TSCA Confidential Business
Informa tion (TSCA CaI) by the person( s) reporting for the TSCA
Inventory, nor does it include any information that would compro-
mise TSCA CBI. All of the information submi tted to EPA for the
initial TSCA Inventory, including the production range informa-
tion, is subject to the limitations that are contained in the
TSCA Inventory Reporting Regulations (40 CFR 710).
In its submission, CIBA-GEIGY reported that the subject chemical
has a molecular '",eight of 685 and "is an off-white crystalline
powder hav:ing a melti~1 point of 146-150°C and a vapor pressure
of approxImately lxlO 0 mm Hg at 20°C." CIBA-GEIGY reported
also that Tinuvin@ 144 "is an ultraviolet light stabilizer used
in automobile coatings and polypropylene fibers." In add i tion,
CIBA-GEIGY provided the following information with regard to the
potential for exposure to Tinuvin@ 144:
"[The] workplace exposure to Tinuvin@ 144 is generally
1 imi ted to ini tial manual transfer operations. Subse-
quent mixing and master batch production operations are
carried out mechanically in larye scale mixiny
equipment.
"The product is flowable and particles adhere to one
another. Manual transfer operations thus produce mini-
mal dusting.
179
-------
8EHQ-0186-0585 S
Page 5 of 7
"The [product's] moderately high molecular weight and
limited water solubility should significantly reduce
skin penetration.
". [CIBA-GEIGY's] five major customers using this
product are health and safety conscious and already
employ protective equipment to reduce exposure to sol-
vents and other hazardous chemicals used in the same
operations. One customer requires "space sui ts" to be
worn when handling the product (because of [the] other
chemicals used).
"Once formulated into polypropylene masterba tches, ex-
posure to Tinuvin@ 144 is precluded as the polyolefin
pellets are generally 1/16 - 1/8" in diameter. User
exposure further downstream is also largely precluded
since the product is encapsulated within the plastic
substrate.
"In automotive coatings, Tinuvin@ 144 is completely
enclosed in the dried vehicle of the coating system."
Comments/Recommendations
In order to "further reduce any risk to CIBA-GEIGY workers and
downstream users," CIBA-GEIGY reported that the company has
revised the Tinuvin@ 144 Material Safety Data Sheet (MSDS) to
reflect the reported toxicologic findings and has revised the
Tinuvin@ 144 product label to read in part:
"NorrICE : Liver, lymphoid, and blood system effects were
seen in a feeding study conducted in laboratory animals.
The relevance of these findings to humans is unknown."
CIBA-GEIGY stated also that in accordance wi th the Occupational
Safety and Health Administration's (OSHA) Hazard Communication
Standard (29 CFR 1910.1200), CIBA-GEIGY's "customers will be no-
tified of these [toxicologic] findings via the revised MSDS and
label wi thin 90 days" and CIBA-GIEGY's "workers will be informed
via the revised MSDS and the company's OSHA Hazard Communications
program. "
In its submission, the CIBA-GEIGY Corporation requested EPA to
address the TSCA Section 8(e)-applicability of immunotoxicologic
findings. The purpose of the following discussion is to provide
the basis for EPA's position with regard to the reportability of
such findings under Section 8(e) of TSCA:
Section 8 (e) states that "any person who manufactures,
[imports,] processes, or distributes in commerce a chem-
ical substance or mixture and who obtains information
which reasonably supports the conclusion that such sub-
stance or mixture presents a substantial risk of injury
180
-------
8~-0186-0585 S
Page 6 of 7
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 in 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) states that "a substantial risk of in-
jury 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."
Hith regard to the seriousness of the effect, Part V
explains that the Agency considers the types of health
ef fects for wh ich substantial risk i nforma tion must be
reported to include "any pattern of effects or evidence
which reasonably supports the conclusion that the chemi-
cal substance or mixture can produce cancer, muti3.tion,
birth defects, or serious or prolonged incapacitation."
(Emphasis added~ Information concerning these effects
can be obtained directly or inferred fr~n designed stu-
dies (e.g., in vivo animar-8tudies) as described in Part
VI of the TSCA Section 8(e) policy statement. Part VI
explains also that a subject "person is not to delay re-
porting until he obtains conclusive inforJaation that a
substantial risk exists, but is to immediately report
any evidence which reasonably supports that conclusion."
In addi tion, Part VI explains that "not only should
final results from such studies be reported, but also
preliminary results from incomplete studies where ap-
propriate."
With regard to the "fact or probability of its [i.e.,
the serious effect'sL occurrence" criterion, Part V of
Section 8(e) policy statement explains also that certain
kinds of health effects are considered to be so serious
that relatively little weight should be attached to ex-
posure in determining whether a risk is substantial.
Based on the preceding discussion, it should be clear that if a
company obtains (i.e., possesses or knows of) "new" information
that offers reasonable support for a conclusion that exposure to
a TSCA-covered chemical substance/mixture which that company
manufactures, imports, processes or distributes in commerce can
cause or ultimately result in serious immunomodulation (i .e.,
immunosuppression or immunostimulation), that company should
report such information to EPA under Section 8(e) of TSCA within
15 working days in full accordance with the reporting procedures
outlined in Part IX of EPA's March 16,1978 Section 8(e) policy
statement.
181
-------
8EHQ-0186-0585 S
Page 7 of 7
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will ask
the CIBA-GEIGY Corporation to submit full copies of the
final reports (including the actual experimental proto-
cols, results of gross and histopathologic examinations,
results of statistical analyses, etc.) from all studies
cited in Part VI ("Health Hazard Data") of the company's
Tinuvin@ 144 Material Safety Data Sheet.
In view of the Agency' s general interest in corporate
actions taken on a voluntary basis in response to chem-
ical toxicity and/or exposure information, the Chemical
Screening Branch will request CIBA-GEIGY to describe the
nature and available results of all studies (other than
the subject 28-day gavage study and those ci ted in the
company's Tinuvin@ 144 MSDS) about lj;7hich CIBA-GEIGY is
aware includin~ those that the company has conducted, is
conducting or plans to conduct to determine the toxicity
of or the exposure to the subject chemical. CIBA-GEIGY
will be asked also to describe the nature and available
results of all studies (other than those submitted pre-
viously to EPA) about which CIBA-GEIGY is aware or that
the company has conducted, is conducting, or plans to
conduct to determine the toxicologic properties of the
chemical which was the subject of PMN No. 81-495.
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, OW/EPA,
OSWER/EPA, OAR/EPA, ORD/EPA, and OPP/OPTS/EPA. Copies
of this status report will be sent also to the TSCA
Assistance Office (TAO/OTS) for further distribution.
182
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: FEB I I 1986 Page 1 of 4
SUBJECT: status Report* 8EHQ-0186-0586 S APproved:~ i/t.-/ff,
FROM: James F. Darr, Section Head Jk,~ r!);;;;,,?-
Chemical Risk IdentificatioJlsectionjCSB
ro:Frank D. Kover, Branch Chief
Chemical Screening BranchjECADjOTSjOPTS
Note
The submitting company has claimed its company name and the exact
identity and actual use of the subject chemical substance to be
TSCA Confidential Business Information (TSCA CBI). Staff of the
Information Management Division (H1DjOTS) will request the sub-
mitting company to substantiate these confidentiality claims. In
its TSCA Section 8(e) notice, the company provided the following
non-confidential generic name for the subject chemical substance:
"2-chloro-N-methyl-N-S ubsti tuted-acetamide." In add i tion, the
submitter stated that 1) this chemical was the subject of a TSCA
Section 5 "Premanufacture Notice" (PMN No. P-84-393), and 2) the
performed toxicologic study was conducted under the terms of a
TSCA Section 5(e) "Consent Order."
Submission Description
In its TSCA Section 8(e) notice, the submitting company provided
the follm>ling summary information with regard to the conduct and
results of a 90-day dietary feeding study of 2-chloro-N-methyl-N-
substituted-acetamide in rats:
"Male and female Sprague-Dawley rats were fed diets
containing [the subject chemical substance] at levels
which provided daily dosages of 0, 500, 1100 and 2500
ppm for 13 consecutive weeks. The dosing regimen was
selected after evaluation of [the] results obtained in
a preliminary study (28-Day Dose-Range Toxici ty Study
in Rats.), which indicated body weight and food
consumption effects were likely in a 90-day toxicity
study at levels of 2500 ppm and greater.
------------------------------------------------------------------------------------
------------------------------------------------------------------------------------
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
183
-------
8EHQ-0186-0586 S
Page 2 of 4
"Under the conditions of this study, [the chemical] did
not cause mortali ty in ei ther sex at any dose level
studied. No treatment-related abnormalities, clinical
signs of toxicity or behavioral changes were noted.
Administration of [the chemical] did cause several
statistically s ignif icant differences in one or both
sexes when comparing body weight, body weight gain,
food consumption, food conversion and/or relative organ
weight data between [the] control and test groups. No
compound-related hematology or clinical chemistry ef-
fects were demonstrated after 13 weeks among groups.
"Relative kidney weights of mid and high-dose males
were significantly increased after 13 weeks when com-
pared to the control group. Microscopic examination of
urine sediment identified a significant increase in
cast formation in [the] males at all trea tment levels
studied. No gross pathological lesions indicative of a
treatment-related effect were noted among groups after
the 13 weeks. Microscopic find ings (intra tubular pro-
tein casts, hyaline droplets and tubular regeneration)
in the kidneys of males at one or all treatment levels,
which were characteristic of protein nephropathy, were
significantly increased when compared to the control
groups.
"The onset of significant decreases in body weight and
food consumption incurred by males at both the mid and
high-dose levels with no meaningful differences in
weekly food conversion (body weight gain per gram of
food consumed) suggested, at least in part, the cause
was due to decreased palatability of the test diets.
However, since no significant or dose-related decreases
in food consumption were noted for females during the
entire study and no recovery in body weight gain during
the second-half of the study period (weeks 7-13) was
demonstrated in males, tox ic i ty and not pala tab il i ty
was determined respons ible for the decreases noted in
the males. Toxicity is further supported by signifi-
cant increases in relative kidney weights at both the
mid and high-dose levels as well as by the significant
increase of cast formation in the urine and the treat-
ment-related pathological changes in the kidneys of
[the] male animals at all dose levels.
"Thus, administration of [the subject chemical] at the
dietary levels studied for 13 consecutive weeks pro-
duced toxicological and patholog ical effects in male
rats. No toxicological effects were evident in female
rats."
184
-------
8EHQ-0186-0586 S
Page 3 of 4
Submission Evaluation
Based on the submitted summary information, it does appear that
the subject chemical has a deleterious effect on the kidney of
male rats. Further evaluation of the reported findings should be
possible upon the Agency's receipt of full copies of the final
reports from the 28-day dose range-finding and 90-day dietary
studies cited in the submission.
It should be noted that immediately upon
Section 8(e) notice, the Chemical Screening
provided complete copies of the submission
Notice Management Branch (PNMB/CCD/OTS) and
Control Branch (ECCB/CCD/OTS) for review.
receipt of this TSCA
Branch (CSB/ECAD/OTS)
to the Premanufacture
the Existing Chemical
Current Production and Use
According to the non-confidential version of PMN No. P-84-393,
the proposed generic use of the subject chemical is as a starch
modif ier. In the Section 8 (e) notice, the submitting company
stated that 1) the substance "is currently being manufactured as
an intermediate" and 2) to the best of the submitting company's
knowledge, the s ubmi t ting company is sole U. S. manufacturer of
the chemical.
Wi th regard to potential exposure to the subject chemical, the
submitting company reported in its Section 8(e) submission that
\'iorkers exposed to the chemical" are required to wear NIOSH,
category 19c air-supplied, positive pressure respirators, imper-
vious gloves and clothing which covers exposed areas of the arms,
legs, and torso. II In addition, the submitter reported that all
workers who handle the chemical have attended II training programs"
on the hazards of the chemical. Finally, the submitter stated
that the product label reflects the reported toxicologic findings
and presents safe handling recommendations.
Comments/Recommendations
a)
The Chemical Screening Branch will ask the submitting
company to ensure that EPA receives complete copies of
the final reports (including the actual experimental
protocols, results of gross/histopathologic examina-
tions, the results of statistical analyses, etc.) from
the 28-day and 90-day studies ci ted in the company's
TSCA Section 8(e) submission.
In view of the Agency's general interest in corporate
actions that are taken on a voluntary basis in response
to chemical toxicity or exposure information, the sub-
mi tting company will be asked to describe the nature
and available results of all studies (other than those
reported already to the Agency) that the company has
185
-------
8EHQ-0186-0586 S
Page 4 of 4
conducted, is conducting, or is planning to conduct to
determine the toxici ty of and/or the exposure to the
subject chemical substance.
b)
As in the case of the initial TSCA Section 8(e) notice,
the Chemical Screening Branch will immediately forward
all additional information received on this chemical to
the Premanufacture Notice Management Branch/CCD/OTS and
the Existing Chemical Control Branch/CCD/OTS for review
and appropriate followup action.
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OW/EPA,
OSWER/EPA, OAR/EPA, ORD/EPA, OPP/OPTS/EPA, PNMB/CCD/OTS
and ECCB/CCD/OTS. Copies of this status report will be
sent also to the TSCA Assistance Office (TAO/OTS/OPTS)
for further distribution.
186
-------
UNITED STATES ENVIRONMENT.AL PROTECTION AGENCY
Page 1 of 5
DATE,
FEB I 3 1986
Approved :a 1/1 / ~(p
SUBJECT, 8EHQ-0 18 6-0587
FROM: James F. Darr, Section Head &"'_#-;7 7/.XvL.-
Chemical Risk Identificatio~~~tion/CSB
TO:Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Fragrance Materials Association (FMA) of the United States
submitted the following information concerning the conduct and
preliminary findings of oral and dermal teratologic studies of
phenylethyl alcohol (PEA; CAS No. 60-12-8) in rats. ( Accord ing
to the submitted information, the dermal study was sponsored by
the Research Institute for Fragrance Materials (RIFM) and the
oral study was sponsored by the Flavor and Extract Manufacturers'
Association (FEMA).)
"In the oral study, rats were given microencapsulated
PEA in the diet at levels of 0 (control), 1000, 3000,
or 10,000 ppm during days 6 to 15 of pregnancy. In the
dermal study (designed to maximize exposure by using
undiluted material under 24 hour/day occlusion at the
max imurn poss ible dosage), doses of 0 (control), 0.14,
0.43 and 1.40 ml/kg of neat material were applied topi-
cally during days 6 to 15 inclusive of pregnancy. An
occlusive bandage was used to minimize oral ingestion
of the test material and to minimize evaporation. This
bandage was put on immediately after dosing and not re-
moved until the following day. In both. . . [the oral
and dermal studies,] the animals were killed on day 20
of pregnancy and in utero development was assessed by
determination of Ii tter values and examination of the
fetuses for soft tissue and skeletal changes.
"At the high oral dose there was initial suppression of
maternal appetite and a slight overall vleight loss in
dams during the first two days of treatment. A slight-
ly higher incidence of fetuses with incomplete ossifi-
cation of some skeletal elements was concluded to be a
negligible detrimental effect. There were no effects
at the lower doses.
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
187
-------
8EHQ-0186-0587
Page 2 of 5
"Dermal treatment at the 1.4 ml/kg level resulted in
maternal toxicity as manifested by death of 3/35 ani-
mals, progressively marked clinical signs of reaction,
suppression of [the] mean food intake and growth rate.
This dose also resul ted in total loss (resorption) of
5/23 litters and 50% or more embryofetal wastage in a
further 4/18 litters. However, 7/18 animals carrying
to term had less than 10% early resorptions so that
there was obviously a marked difference between rats in
their response to treatment. The general reduction in
mean Ii tter size resul ting from these losses was also
accompanied by depress ion of fetal we igh t assessed at
day 20 of gestation. Additionally, morphological ab-
normalities were observed in virtually all fetuses.
Both soft tissue and skeletal changes were observed;
ossification was incomplete.
"At the 0.43 ml/kg dosage there was no clear ev idence
of any adverse effect on the parent animal and litter
parameters were comparable wi th those of the control
group. While the number of fetuses showing structural
changes in soft tissue were slightly higher than [the]
controls, no pattern was obvious. Skeletal examination
revealed the number of fetuses with cervical rib(s) and
those showing moderate degrees of reduced ossification
were significantly less than in the high dose but were
significantly higher than [in the] controls. These
cervical ribs were extremely small, usually just a dot
which was weakly stained. Studies are being planned
that will investigate the likelihood that these effects
would not persist into post-natal life or if they did,
whether they would have any functional significance.
"The lowest. [dermal dose] did not produce any
evidence of overt lOa ternal toxic i ty or adverse effect
on litter parameters. Neither the incidence nor dis-
tribution of structural changes recorded could be
cons idered to prov ide conc Ius i ve ev idence of associa-
tion wi th treatment; incidences of such changes were
slightly higher than control."
FMA's TSCA Section 8(e) submission also presented the following
information concerning ". . . comparative dermal absorption, dis-
tribution, metabolism and excretion studies in humans and rats"
recently initiated or planned by RIFM "to aid in determination of
r i s k to h urn a n s . "
"Studies are underway which are designed to obtain data
allowing exact extrapolation of absorbed dose from the
rat to the human. The initial results of these studies
indicate that about 60% of the [PEA] dose applied neat
and under occlusion to the rat is absorbed. Studies in
humans should begin in the near future. (General know-
ledge of relative permeabilities of rat skin and human
188
-------
8EHQ-0186-0587
Page 3 of 5
skin combined wi th consideration of the extreme condi-
tions of exposure used in the rat study would lead to
the conclusion that the assumption of 10% absorption by
humans under condi tions of normal exposure is grea tly
exaggerated.) "
Submission Evaluation
Immediately upon receipt of this TSCA Section 8 (e) notice, the
Chemical Screening Branch (CSB/ECAD/OTS) provided a copy to the
Risk Analysis Branch (RAB/ECAD/OTS) for inclusion in the ongoing
RAB/ECAD review of available toxicologic and exposure information
on phenylethyl alcohol. It should be noted that in 1985, the
Chemical Screening Branch prepared a Chemical Hazard Information
profile (CHIP) on phenylethyl alcohol (CAS No. 60-12-8) and its
acetate (CAS No. 103-45-7). In preparing that CHIP, CSB received
several" For Your Information" (FYI) submissions on phenylethyl
alcohol and its acetate.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for phenylethyl alcohol (CAS No. 60-12-8), which is
listed in the initial TSCA Inventory, has shown that between 1.34
million and 13.4 million pounds were reported as produced and/or
imported in 1977. This production range information does not
include any production or importation data that were claimed as
TSCA Confidential Business Information (TSCA CBI) by the per-
son(s) reporting for the TSCA Inventory, nor does it include any
information that would compromise TSCA CBI. All data submi tted
for the TSCA Inventory, including production range information,
are subject to the limitations contained in the TSCA Inventory
Reporting Regulations (40 CFR 710).
According to secondary literature sources, phenylethyl alcohol is
used as a fragrance in cosmetics, soaps, detergents, creams, lo-
tions, air fresheners, perfwnes (particularly rose perfumes), and
possibly paper products; other uses reportedly include: synthetic
flavoring agent, antimicrobial agent, preservative, mosqui to and
housefly repellant and chemical intermediate.
.
FMA's Section 8(e) submission contained the following information
wi th regard to the potential for human exposure to phenylethyl
alcohol:
"The best estimates of exposure are an average daily
exposure of about 12 mg/day and a 90%ile use level
exposure of about 32 mg/day. Assuming a weight of 50
kg and absorption of 10% of the dose, the 90%ile ab-
sOl.-bed dose would be 0.064 mg/kg/day. This gives a
safety factor of about 25,000 compared to the high dose
and about 2,500 compared to the low dose."
189
-------
8EHQ-Ol86-0587
Page 4 of 5
Comments/Recommendations
Although EPA considers that anyone may submit information to the
Agency under Section 8(e), the "substantial risk" information
reporting provision of the Toxic Substances Control Act (TSCA),
only certain persons are required to do so. In view of the fact
that a number of TSCA Section 8(e) submissions have been received
thus far by EPA from chemical trade/research associations, the
purpose of the following discussion is to reiterate EPA's policy
with regard to the TSCA Section 8(e) reporting obligation of such
organizations and chemical companies that may be members of such
organizations.
Section 8(e) states that "any person who manufactures,
[imports,] processes, or distributes in commerce a
chemical substance or mixture and who obtains informa-
tion which reasonably supports the conclusion that such
substance or mixture presents a substantial risk of in-
jury to heal th or the environ!nent shall immediately in-
form the [EPA] Administrator of such information unless
such person has actual knowledge that the Administrator
has been adequately informed of such information."
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 the Agency considers the term "person" to include
"any natural person, corporation, firm, company, joint-
venture, sole proprietorship, association, or any other
business entity. ." Therefore, the obligation to
immediately report substantial risk information to EPA
would apply to a chemical trade or research association
only if that organization itself is engaged in the manu-
facture, importation, processing, or distribution of the
chemical substance or mixture about which substantial
risk information has been obtained. It is more likely,
however, that a mandatory Section 8(e) reporting obliga-
tion would be incurred by a member or non-member company
that obtains the results (including preliminary results)
from studies conducted or sponsored by a chemical trade
or research association, if the obtained results meet
the reporting criteria outlined in the Agency's TSCA
Section 8(e) policy statement and pertain to a chemical
substance or mixture that the company manufactures, im-
ports, processes, or distributes in commerce.
Part III of the EPA's TSCA Section 8(e) policy statement
explains that substantial risk information is obtained
at that time when any company officer or employee who is
capable of appreciating the significance of the informa-
tion, either possesses, or knows of, that information.
Except in si tuations involving" Emergency Incidents of
Environmental Contamination" (EIECs), the obligation to
immediately report substantial risk information to EPA
190
-------
8EHQ-0186-0587
Page 5 of 5
is considered discharged if EPA receives the information
1) in accordance with the reporting requirements out-
lined in Part IX of the Section 8(e) policy statement,
and 2) not later than the 15th working day after the
date the information was obtained. The information need
not be reported to EPA, however, if the subject person
has actual knowledge that the Agency has already been
adequately informed about thr.lt information. part VII of
the TSCA Section 8(e) policy statement provides further
guidance with regard to the types of information that
need not be reported under Section 8(e). In addition,
Section 3 of TSCA itself lists those substances (e.g.,
drugs, pesticides) that are not covered by TSCA.
Finally, it should be noted that a company that relies
on some other party to submit information under Section
8(e) on the company's behalf, must ensure that EPA re-
ceives the information in a timely manner and in full
accordance with the requirements outlined in Part IX of
EPA's TSCA Section 8(e) policy statement.
--------------------------------------------------------
-----------.---------------.----.------------------.----------
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will ask
FMA to ensure that the Agency rece ives complete copies
of the final reports (including the actual experimental
protocols, results of gross and histopathologic examina-
t ions, resul ts of statist ical analyses, etc.) from all
studies cited in FMA's submission.
b)
The Chemical Screening Branch will immediately forward
all reported information on phenylethyl alcohol to the
Risk Analysis Branch/ECAD/OTS for inclusion in their
ongoing assessment of this chemical substance.
c)
The Chemical Screening Branch will transmit copies of
this status report to: NIOSH, OSHA, CPSC, FDA, NTP,
OW/EPA, OSWER/EPA, OAR/EPA, ORD/EPA, OPP/OPTS/EPA, and
RAB/ECAD/OTS. In addi tion, copies of th is report will
be sent to the TSCA Assistance Office (TAO/OTS/OPTS) for
further distribution.
191
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
SUBJECT: Status Report*
8EHQ-0286-0588
8EHQ-0286-0588
Page 1 ~
Approved: ~ ~ lq
-------
8EHQ-0286-0588
Page 2 of 2
a}
The Chemical Screening Branch will review the submitted
article to determine the need for further OTS assessment
of the reported findings.
b)
The Chemical Screening Branch will send copies of this
status report to OSHA, NIOSH, FDA, CPSC, NTP, OSWER/EPA,
OW/EPA, OAR/EPA, ORD/EPA and OPP/OPTS/EPA. In addition,
copies of this status report will be sent to the TSCA
Assistance Office for further distribution.
193
-------
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
Page 1 of 4
DATE:
MAR 2 8 1986
SUBJECT: status Report*
8EHQ-0386-0589 S
Approved: -t:P- 3/3f Is(p
FROM: James F. Darr, Section Head fb'J'I1..e'J T lJi:Vl--
Chemical Risk IdentificatioJ/-section/CSB
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Note
The CIBA-GEIGY Corporation has claimed the actual identity of the
subject substance to be TSCA Confidential Business Information
(TSCA CBI). The Information Hanagement Division (IMD/OTS) will
request CIBA-GEIGY to substantiate this confidentiali ty claim.
In its submission, CIBA-GEIGY did report non-confidentially that
the subject chemical was an azo dye haviny the following Color
Index (C.I.) name: C.I. Reactive Orange 12.
Submission Description
The CIBA-GEIGY Corporation reported that CIBA-GEIGY Ltd. (Basel,
Swi tzerland) had been notif ied by Imperial Chemical Industries
(ICI) PLC (Manchester, England) that C.I. Reactive Orange 12 was
a human respiratory sensitizer. In its Section 8(e) submission,
the CIBA-GEIGY Corporation reported that ICI had documented 10
cases of allerg ic symptoms (7 ICI employees and 3 employees in
customer facilities). According to CIBA-GEIGY, ICI stated that
the ICI Medical Officer's re-examination of ICI employee occupa-
tional records confirmed the ICI Medical Officer's opinion that
all affected ICI em~loyees suffered from acute allergic symptoms
between 1968 and 1985 as the result of exposure to C.I. Reactive
Orange 12. According to CIBA-GEIGY, ICI reported that in one
case the finding was confirmed by an inhalation challenge test
and confirmed in another case by the detection of elevated IgE
antibody levels to C.I. Reactive Orange 12.
In its Section 8 (e) s ubmiss ion, CIBA-GEIGY reported a Iso that a
CIBA-GEIGY product (Cibacron Golden Yellow 2R-A powder which
contains C. I. Reactive Orange 12) had been tested by CIBA-GEIGY
and found to be non-irritating to thi skin or eyes and to have an
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
194
-------
8EHQ-0386-0589 S
Page 2 of 4
oral (rat) LD50 of greater than 5 g/kg. In addition, CIBA-GEIGY
reported that Cibacron Golden Yellow 2R-A powder was found to be
a skin sensitizer in guinea pigs but not in humans.
with regard to the relative risk of pulmonary sensitization posed
by exposure to C.I. Reactive Orange 12 or to products containing
this azo dye, CIBA-GEIGY reported that the company believes that
the risk would be the highest in those circumstances involving
"uncontrolled exposure to a finely divided powdered form," less
serious under conditions involving exposure to granular material,
and almost negligible in those cases involving exposure to liquid
formulations. Finally, CIBA-GEIGY reported that the company "has
imported [C.I. Reactive Orange 12] dyes for over 8 years and has
never received any human health complaints from [CIBA-GEIGY]
employees or from the user industry's employees."
Submission Evaluation
Immunologic sensitization is a systemic condition that can be
initiated by either acute or chronic exposure to a chemical sub-
stance. Once sensitized, an affected individual may react mildly
or severely to further acute or chronic exposure to the causative
ayent. The si te of reaction is not necessarily pred ictable in
that the reaction can occur at the site of exposure and/or at a
si te or si tes in the body distant from the point of contact with
the causative agent. The duration of reaction and consequences
of reaction are not necessarily predictable either and may range
from quite short to long-term. ~Vhen a sensitization reaction
takes place in the pulmonary system, for example, that reaction
could have been provoked by inhalation or other (e.g., dermal)
exposure to the causative agent and may manifest itself by a mild
to severe asthmatic-like condition of unpredictable duration. In
some cases, sensitization reactions can be extremely serious, de-
bili tating and even life-threatening. It should be noted also
that a sensitization reaction can occur as the result of exposure
to a chemical structurally similar to the initial causative agent
(cross-sensitization). Cross sensitization reactions involving
C.I. Reactive Orange 12 may be of concern in that sensitization
reactions involving other azo dyes have been well documented.
Current Production and Use
In view of the fact that CIBA-GEIGY claiwed the exact identity of
the subject azo dye to be TSCA CBI, no pl.oduction/iJT' )ortation in-
formation derived from the non-confidential compui.:, '- i..zed version
of initial TSCA Chemical Substance Inventory will appear in this
status report. It should be noted that C.!. Reactive Orange 12
is listed in several publicly available computerized scientific
data bases (e.g., TOXLINE, CHEMLINE) as having been assigned the
follmiing Che!l1ical Abstract Service (CAS) Registry Numbe~: ~ 12225-
84-2. It should be noted also that CAS No. 12225-84-L.:eplaced
CAS No. 82600-93-9 for C.I. Reactive Orange 12. Neither of these
CAS Registry Numbers was found, however, in the non-confidential
computerized version of the TSCA Chemical Substance Inventory.
195
-------
8EHQ-0386-0589 S
Page 3 of 4
In its submission, CIBA-GEIGY reported non-confidentially that
the company imports C.l. Reactive Orange 12 lias a component of 5
dyestuff mixtures consisting of two different physical forms: in
granular or powder form as Cibacron Golden Yellow 2R-A, Cibacron
Golden yellow 2R and Cibacron Black GR-D; and in liquid form as
Cibacron Golden Yellow 2R LQ 25 and Cibacron Black GR LQ 40."
(Note: CIBA-GEIGY has asserted TSCA CBI claims for the amount of
C~Reactive Orange 12 in these dyestuff products and the total
volume of active ingredient C. I. Reactive Orange 12 imported by
the company in 1985. The Information Management Division will
request CIBA-GEIGY to substantiate these confidentiality claims
as well.)
Wi th regard to the use of C. I. React ive Orange 12, CIBA-GEIGY
stated that the dye is "used for piece dyeing of cellulosic knit
fabrics by an atmospheric exhaust process in becks." According
to secondary literature sources, C.l. Reactive Orange 12 can be
used also to dye and/or print wool, silk or nylon.
Comments/Recommendations
In its submission, CIBA-GEIGY stated that the company plans to
modify the Material Safety Data Sheet (MSDS) and label for all
granular and powdered products containing C.I. Reactive Orange 12
to reflect the potential for human respiratory sensitization. In
addition, CIBA-GEIGY stated that its employees as well as those
customers who purchased powdered or granular products containing
C.I. Reactive Orange 12 will be notified about this adverse human
health effect and the need for appropriate engineering controls
and/or personal protective equi~1ent. Finally, CIBA-GEIGY stated
that the company is planning to recommend to its customers that
when" sui table controls are not feasible or practical, potential
inhalation exposure, and therefore [the] risk of respiratory
sensitization, can be reduced to negligible levels by switching
to a liquid form of the dye. II
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will ask
CIBA-GEIGY to 1) provide to EPA a complete copy of the
ICI notification letter to CIBA-GEIGY concerning the 10
cases of pulmonary sensitization observed in workers ex-
posed to C.I. Reactive Orange 12, and 2) keep the Agency
abreast of any further developments with regard to hrnaan
pulmonary sensitization resulting from exposure to C.l.
Reactive Orange 12 or products containing this dye. In
addition, CIBA-GEIGY will be asked to provide to EPA a
complete copy of the final report (including the actual
experimental protocol, results of gross and histopatho-
logic examinations, results of any statistical analyses,
etc.) from each study (includ ing the human patch test)
of Cibacron Golden Yellow 2R-A cited in the company's
TSCA Section 8(e) submission.
196
-------
8EHQ-0386-0589 S
Page 4 of 4
In addition, the Chemical Screening Branch will request
ICI Americas Inc. to submit to EPA all information in
the company's possession or control which relates to the
risk of human pulmonary sensitization posed by exposure
to C.I. Reactive Orange 12.
Considering EPA's general interest in corporate actions
taken on a voluntary basis in response to chemical toxi-
city or exposure data, CIBA-GEIGY and ICI Americas Inc.
will be requested to describe the nature and available
results of all studies (other than those already sub-
mitted to EPA or those published in the open scientific
literature) about which the companies are aware or that
the companies have conducted, are conducting, or plan to
conduct to determine the toxicity of or exposure to C.I.
Reactive Orange 12 or products containin] this azo dye.
In addition, ICI kuericas Inc. will be asked to describe
the actions that the company has taken or plans to take
to 1) warn workers and others about the risk of respira-
tory sensitization posed by exposure to C. I. Reactive
Orange 12, and 2) reduce and/or eliminate exposure to
C.I. Reactive Orange 12 or products containing this dye.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of C.I. Reactive Orange 12.
c)
The Chemical Screening Branch will send copies of this
status report to OSHA, NIOSH, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, OAR/EPA, ORD/EPA, and OPP/OPTS/EPA. Copies of
this status report will be provided also to the TSCA
Assistance Office (TAO/OTS) for further distribution.
197
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
MAR 2 6 1986
Page 1 of 3
SUBJECT: status Report* 8EHQ-0386-0590 S APproved:~
FROM: James F. Darr, Section Head &-~'1 r 0;;:1.17..-
Chemical Risk Identification<7;~~tion/CSB
~/2-1llfp
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
Informa tion (TSCA CBI). The Information Management Div ision/OTS
will request the submitter to substantiate these confidentiality
claims. In its Section 8(e) submission, the company provided the
following non-confidential generic name for the subject chemical:
alkyl aryl phosphine. The submitting company reported that this
chemical had been the subject of a TSCA Section 5 Premanufacture
Notice (PMN No. 83-1023) and a TSCA Section 5(e) Consent Order.
Submission Description
The submitting company reported that a 28-day neurotoxicity study
of the alkyl aryl phosphine in male and female rats was conducted
pursuant to the conditions of a TSCA Section 5(e) Consent Order
and provided the following summarized information concerning the
conduct and preliminary histopathologic findings from that study:
"The brain, spinal cord, and peripheral nerves from 10
control and 10 [alkyl aryl phosphine-]treated rats were
evaluated microscopically. The treated rats rece ived
[alkyl aryl phosphine] at the rate of 25 mg/kg/day [for
28 days]. [The] microscopic evaluation of the tissues
revealed slight axonal swelling and pyknotic debris in
the reticular formation of the medulla and more promi-
nent axonal damage in the spinal cord and peripheral
nerves. In addition, there were foci of gliosis in the
central grey column of the spinal cord. These central
and peripheral lesions were present in 10/10 treated
rats and in 0/10 control animals."
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
198
-------
8EHQ-0386-0590 S
Page 2 of 3
In its submission, the company stated that the 25 mg/kg/day dose
"probably exceeded the max imum tolerated dose" for the chemical.
The submitting company stated also that "no clear clinical neuro-
logical effects" were observed by the testing laboratory in the
treated animals during the conduct of the 28-day study. Finally,
the submi tting company reported that the testing laboratory has
been directed "to prepare and evaluate tissue slides for ten test
animals in the mid dose group and ten test animals in the low
dose group." (Note: The mid and low dose levels were not speci-
fied in the Section 8(e) submission.)
Submission Evaluation
Although no overt clinical neurotoxic signs were observed in the
alkyl aryl phosphine treated-rats, it is clear from the submitted
preliminary pathology report that the alkyl aryl phosphine caused
neuropathologic effects when administered to rats at 25 mg/kg/day
for 28 days. Immediately upon receipt of this TSCA Section 8(e)
notice, the Chemical Screening Branch (CSB/ECAD/OTS) transmitted
copies of the information to the Premanufacture Notice Management
Branch (PNMB/CCD/OTS) and to the Existing Chemical Control Branch
(ECCB/CCD/OTS) for review and appropriate followup attention.
Current Production and Use
According to the information contained in the non-confidential
version of PMN No. 83-1023, the intended use of this new alkyl
aryl phosphine is as an industrial catalyst. According to the
non-conf idential publ ic docket for PMN No.8 3-1023, the Agency
has received a "Notice of Commencement" (NOC) of manufacture for
this chemical substance.
Comments/Recommendations
In its TSCA Section 8(e) submission, the company stated that upon
receipt of the preliminary report from this 28-day neurotoxicity
study, the company notified its "customers and manufacturing per-
sonnel to share this information and to request that all handling
of the PMN substance be done with the utmost care."
a)
The Chemical Screening Branch (CSB/ECAD/OTS) wi 11 ask
the submitting company to ensure that EPA receives in a
timely manner all future interim pathology reports and a
complete copy of the final report (including the actual
experimental protocol, results of gross/histopathologic
examinations, results of statistical analyses etc.) from
the company's 28-day neurotoxicity study of this alkyl
aryl phosphine in rats.
199
-------
8EHQ-0386-0590 S
Page 3 of 3
b)
upon receipt of the requested information, the Chemical
Screening Branch will send copies of that information
immediately to the PNMB/CCD/OTS and ECC13/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, OS~~ER/EPA,
OW/EPA, OAR/EPA, ORD/EPA, OPP/OPTS/EPA, PNMB/CCD/OTS and
ECCB/CCD/OTS. In adaition, copies of this status report
will be provided to the TSCA Assistance Office (TAO/OTS)
for further distribution.
200
-------
UNITED STATES ENV"IRONMENTAL PROTECTION AGENCY
Page 1 of 3
DATE:
APR
8 /986
SUBJECT: Status Report*
8EHQ-0386-0591
APproved:~ ~qf~~
FROM: James F. Darr, Section Head ~] r: C;;;1/1---
Chemical Risk Identificatio~ Section/CSB
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Procter & Gamble Company prov ided the following information
concerning the conduct and results of a repeated skin application
study of dioctyl dimethyl ammoni um chloride (CAS No.5 538-94-3)
in rabbits:
". . [This study in rabbits] involves examination of
progress i ve electrocard iogram [ (ECG) ] changes after
repeated dermal (occluded patch) exposure to dioctyl
dimethyl ammonium chloride. This study is still in
progress. However, a prel iminary examination of the
data, indicates that after 7-14 days, rabbits receiving
5-10 mg dioctyl dimethyl ammonium chloride/kg/day are
displaying ECG changes. These changes include premature
ventricular contractions and ventricular tachycardia.
This treatment regimen has also resulted in the death of
two animals after 7 and 11 days of [dermal] exposure to
10 mg/kg/day. A no-effect level for the cardiotoxic ef-
fects following [repeated] dermal exposure has not been
established.
"The results of. . [previously conducted] preliminary
in vitro skin penetration studies indicate that the rab-
TIt may be uniquely sensitive to dermally administered
dioctyl dLnethyl ammonium chloride, in part because of a
high rate of dermal absorption. It is widely recognized
that this species exhibi ts greater dermal penetration
than other species for a variety of chemical compounds.
In addition, . [previously conducted] interspecies
comparative studies have shown that the rabbit also may
be especially sensitive to dioctyl dimethyl ammonium
chloride-induced ECG alterations.
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
201
-------
8EHQ-0386-0591
Page 2 of 3
". . . [Wi th regard to the absorption and distribution
of dioctyl dimethyl ammonium chloride, Procter & 3amble
found] that following a single intravenous injection or
dermal application, dioctyl dimethyl ammoniwn chloride
(or metabolites) concentrates in the heart of rats and
rabbits to a greater extent than other tissues. Results
of tissue clearance studies show that after a single
intravenous bolus injection, the half life of dioctyl
dimethyl ammonium chloride and/or its metabolites from
rat cardiac tissue is approximately 4-8 days."
Submission Evaluation
Based on the preliminary data on the cardiotoxic effects observed
in rabbits following dermal exposure to dioctyl dimethyl ammonium
chloride, several mechanisms of action can be postulated. For
example, the chemical may act directly on the heart muscle (the
heart appears to have the highest concentration of the chemical
or a metabol i te ( s) thereof). Also, the chernical has a charged
nitrogen and alkyl substitutions on that nitrogen which make the
chemical structurally similar to drugs affecting the cholinergic
nervous system. It is not clear from the submi tted information
if there were any adverse dermal effects due to treatment. If
there was severe dermal irri tation, the adverse heart effects
could have been due to hyperemia and shock. In order for EPA to
evalua te more thoroughly the reported cardiotoxic effects, the
Procter & Gamble Company should be asked to provide a full copy
of the final report (including the actual experimental protocol,
results of gross and histopathologic examinations, blood pressure
measurements, identification of any metabolites, results of all
statistical analyses, etc.) from the company's repeated dermal
application study of dioctyl dimethyl ammonium chloride in rab-
bits. The company should be asked also to provide full copies of
the final reports from all other studies cited in the submission.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for dioctyl dimethyl ammonium chloride (CAS No. 5538-
94-3), which is listed in the ini tial TSCA Chemical Substance
Inventory, shows that no 1977 production/importation was reported
or that all of the production/importation information reported
was claimed as TSCA Confidential Business Information (TSCA CBI)
by the manufacturer(s) and/or importer(s) and cannot be disclosed
(Section l4(a) of TSCA; U.S.C. 2613(a)). All of the information
submitted for the TSCA Inventory, including the production range
information, is subject to the limitations contained in the TSCA
Inventory Reporting Regulations (40 CFR 710).
In its Section 8(e) notice, Procter & Gamble stated that dioctyl
dimethyl ammonium chloride is "used in a number of microbiocidal
products such as disinfectants, algicides and sanitizers, but the
extent of such usage is not known to . [procter & Gamble]."
Wi th regard to its use of d ioctyl dimethyl ammoni wn chlor ide,
202
-------
8EHQ-0386-059l
Page 3 of 3
Procter & Gamble stated that the company "has been evaluating the
safety of this material in research associated with the upstream
development of an experimental product." No other information
concern ing the use ( s) of d ioctyl dimethyl ammoni urn chlor ide was
located in the secondary literature sources consulted.
Comments/Recommendations
In its Section 8(e) submission, Procter & Gamble stated that its
research program wi th d ioctyl d iil1ethyl ammoni um chloride is not
as yet completed and that the chemical has been handled and will
continue to be handled with appropriate caution in the company's
ongoing laboratory work.
a)
The Chemical Screening Branch (CSB/ECAD/OTS/OPTS) will
ask Procter & Gamble to submit to EPA a full copy of the
final report (including the actual experimental proto-
col, results of gross and histopathologic examinations,
results of statistical analyses, etc.) frow each study
of dioctyl dimethyl ammonium chloride that was cited in
the company's TSCA Section 8(e) submission.
In view of EPA's general interest in corporate actions
taken on a voluntary basis in response to chemical toxi-
city or exposure data, the Procter & Gamble Company will
be requested also to describe the nature and available
res ul ts of all stud ies (other than those publ ished in
the open scientific literature or submitted previously
to EPA) about which Procter & Gamble is aware or tha t
the company has conducted, is conducting, or plans to
conduct to determine the toxicity of or the exposure to
d ioctyl dimethyl ammoni um chlor ide. Procter & Gamble
will be asked also to describe in greater detail the
actions the company has taken or plans to take to I)
notify its workers and others about the reported toxico-
logic findings, and 2) reduce ot:" eliminate exposure to
d ioctyl d i111ethyl ammoni lLm chloride.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of dioctyl dimethyl ammonium chloride.
In addition, copies of the reported information will be
sent to the Office of Pesticide programs (OPp/oP'rS) for
review and appropriate followup action under the Federal
Insecticide, Fungicide and Rodenticide Act (FIFRA).
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSHER/EPA,
OW/EPA, OAR/EPA, ORD/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.
203
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 4
DATE:
APR
1 1986
SUBJECT: status Report*
8EHQ-0386-0592
Approved: ~ 47/~1p
FROM: James F. Darr, Section Head tbL,~ P,' r'1r\--
Chemical Risk Identification9;ection/CSB
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Celanese Corporation submi tted a report concerning studies
conducted by the Departments of Neuropathology, Pathology and
Environmental Medicine at the New York University (NYU) Medical
Center (New York, New York). According to the" Introduction" of
the submitted report, these independently conducted studies were
designed "to investigate 1) the effects of chronic dermal appli-
cation of AA [(acrylic acid; CAS No. 79-10-7)], 2) its potential
as a tumor promoter in two stage carcinogenesis, [and] 3) the
abili ty of AA to bind to DNA in vi tro." The submi tted report
contained the following information wi th regard to the conduct
and results of a chronic in vivo study:
"Thirty [4 week old] female ICR/Ha Swiss mice per group
were randomly ass igned to test and control groups [and
then acclimatized for approximately 2 weeks].
"Experiments began when animals were 6 weeks of age.
Acrylic acid (4 mg) was applied to shaved dorsal skin by
micropipette in 0.1 ml acetone, 3 times per week for 1.5
years. This dose of AA was determined to be near the
maximum tolerated dose [(MTD)] in previous six week dose
response testing. Mice in another group were first ini-
tiated It'lith 20 ug DMBA [(dimethylbenzanthracene)]. . .,
then began receiving AA two weeks later (3 times per
week for 1.5 years). Control animals received acetone
alone or DMBA followed by acetone alone as described
above. Animals were observed daily and weighed every
other month. At the time of sacrifice (1.5 years), ani-
mals were necropsied. Tissue from skin, kidney, liver,
spleen, brain, bladder, and colon as well as any grossly
abnormal tissue were examined histologically.
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e). the substantial
risk information reporting provisiQn of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
204
-------
8EHQ-0386-0592
Page 2 of 4
"Acryl ic ac id produced skin tumors in both the Dr1BA/ AA
group and the AA alone group. Four tumors were observed
in the DMBA/AA group. (p<.05; Fisher exact test).
One of these tumors proved to be a squamous cell carci-
noma. In the AA alone group, two twnors were oberved,
both of which were squamous cell carcinomas. . . . This
is marginally significant when compared to historical
controls (p<.07; Fisher exact test). No skin tumors
were observed in [the DMBA/acetone or acetone alone con-
current] control groups. There was no statistical dif-
ference in the numbers of tumors or latency of twaor
appearance between the DMBA ini tia ted group and the AA.
alone group. This suggests that AA may act as a com-
plete carcinogen and not as a promoter. If these two
acrylic acid groups are combined, irrespective of DMBA,
the incidence of carcinoma is 5%.
"AA also produced an increase in leukemia which normally
occurs in 20 to 40% of historical controls and occurred
in 30% of the control groups in this study. Leukemia in
AA treated animals was 86%. The twnor incidence for the
sum total of all other tumor types was also significant-
ly different from control (pe05; Fisher exact test).
However, other than those discussed above, no single
tumor type alone was significant."
The submi t ted study report pcesented the following information
concerning the conduct and results of the in vi tro DNA bindiny
assay:
"Acrylic acid was reacted with calf thymus DNA at 37°C
and pH 7.0. DNA was hydrolyzed using acid and enzyme
hydrolysis. . . . Adduct formation was detected by ana-
lytical paper chromatography and high performance liquid
chromatography (HPLC). Adducts were isolated by prepar-
ative paper chromatog~aphy and purity [was] verified by
HPLC and/or paper chromatography. Structures were elu-
cidated by gas chromatography-mass spectrometry (GCMS)
. . .
"The adducts found by the in vitro reaction of AA with
calf thymus DNA were 1- ( 2-carboxyethyl) adenine, 3- (2-
carboxyethyl)cytosine, 7-(2-carboxyethyl)guanine, and 3-
(2-carboxyethyl) thymine. The reaction time of AA is
slow wi th a t J;2 in the order of days."
Submission Evaluation
The reported findings show that chronic application of acrylic
acid to the skin of mice resulted in 1) a substantial increase in
the incidence of leukemia over that seen il1 either concurrent or
historical control mice, and 2) a low and marginally significant
205
-------
8EHQ-0386-0592
Page 3 of 4
incidence of skin tumors when compared to either concurrent or
historical control mice. The reported in vitro acrylic acid-DNA
adduct formation resul ts provide furthersupport for an oncogenic
concern for acrylic acid.
Current production and Use
A review of the production range (includes importation volumes)
statistics for acrylic acid (CAS No. 79-10-7), which is listed in
the initial TSCA Chemical Substance Inventory, shows that between
221 million and 1.11 billion pounds 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) nor does it include any information that
would compromise TSCA CBI. All data reported for the in i tial
TSCA Inventory, including the production range data, are subject
to the 1 il;1i tations contained in the TSCA Inventory Reporting
Regulations (40 CFR 710).
According to secondary literature sources, acrylic acid is a
colorless fuming liquid used primarily as a captive intermediate
in the manufacture of acrylate esters. No information concerning
the current production/importation volumes of acrylic acid \vas
located in the secondary literature sources consulted.
Comlnen t s/Recommenda t ions
The Chemical Screening Branch has received a number of TSCA
Section 8(e) and "For Your Information" (FYI) notices on several
acrylic acid derivatives. In addition, the Chemical Screening
Branch has prepared Chemical Hazard Information Profiles (CHIPs)
on acrylic acid, ethyl acrylate, ethylhexyl acrylate and neo-
pentyl glycol diacrylate. The Office of Research and Development
(ORD/EPA) has prepared Health and Envirorunental Effects Profiles
(HEEPs) on acrylic acid and a number of acrylic acid derivatives.
Also, the Risk Analysis Branch (RAB/ECAD/OTS) has been evaluating
available toxicologic and exposure data (including TSCA Section
8 (a) exposure da ta) on several acryla tes. Fi nally, it should be
noted that the Office of Toxic Substances (OTS/OPTS/EPA) has re-
ce ived and evaluated a number of TSCA Sect ion 5 "Premanufacture
Notices" (PMNS) 011 acrylates and is now assessiWJ the potential
risks posed by acrylates as a class.
a)
The Chemical Screening Branch will consider revising the
existing CHIP on acrylic acid to include the submitted
findings and other toxicologic and exposure information
that has become available since the preparation of that
CHIP in 1981.
206
-------
8EHQ-0386-0592
Page 4 of 4
b)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, OAR/EPA, ORD/EPA, OPP/OPTS, CCD/OTS, HERD/OTS,
RAB/ECAD/OTS/OPTS, and to the TSCA Assistance Office
(TAO/OTS) for further distribution.
207
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
MAR 3 I 1986
Page 1 of 2
SUBJECT: Status Report*
8EHQ-0386-0593
Approved:
(JIJ-- :7/"/'6'<.
FROM: James F. Darr, Section Head th,v~;: t~-
Chemical Risk IdentificatioJl~ection/CSB
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Union Carbide Corporation submitted a written followup report
concerning an "~nergency Incident of Environmental Contamination"
that occurred on February 28, 1986. In its report, Union Carbide
provided the following information with regard to this incident:
"A rail car containing 20,000 gallons of ethoxyethyl
acetate (CAS No. 111-15-9) was reported to be derailed
and overturned on a trestle crossing the Ouachita River
near Grayson, Louisiana on the morning of February 18,
1986. Some material leaked from the dome of the tank
car, estimated by someone to be approximately 5 gallons
per minute, into the river. After the car was righted,
it continued to leak, at a substantially reduced rate,
apparently from a damaged bottom valve. Emergency re-
sponse personnel from Union Carbide facilities at Taft,
Louisiana and Seadrift, Texas were dispatched to the
scene and succeeded in transferring the material in the
tank C3.r to an undamaged one. According to railroad
personnel, Louisiana State Police were at the scene and
authorities of the town of Grayson were notified.
"Since the time of the inc iden t, Union Carbide has re-
ceived no reports of adverse ecological or envirorunental
effects as a result of the incident. Based on the amount
of material transferred to the undamaged tank car, an
estimated 1000 gallons were lost during the event. The
decision to . [immediately phone the EPA Region VI
Office in Dallas, Texas] was made at the time the tank
car was reported to be still leaking, and it was not
possible to know if adverse ecological or environmental
effects would occur."
------------------------------------------------------------------------------------
------------------------------------------------------------------------------------
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
208
-------
8EHQ-0386-0593
Page 2 of 2
Comments/Recommendations
Animal stud ies of 2-ethoxyethanol and/or its acetate ShOVI that
these chemical substances can cause develoiJmental, testicular,
hematolol)ic, and/or neurologic effects. The Chemica.l Screening
Branch (CSB/ECAD/OTS) has rece i ved a number of TSCA Section 8 ( e)
and "For Your Information" (FYI) notices on glycol ethers and
their derivatives, including 2-ethoxyethanol and its acetate.
Also, the Chemical Screening Branch has prepared Chemical Hazard
Information Profiles (CHIPS) on 2-ethoxyethanol, 2-methoxyethanol
and their acetates. The Risk Analysis Branch (RAB/ECAD/OTS) has
been evaluating available toxicplogic and exposure data on glycol
ethers and their derivatives. Finally, it should be noted that
the Chemical Control Division (CCO/OTS) is considering various
regulatory options wi th regard to reducin'j the risks posed by
exposure to 2-ethoxyethanol, 2-methoxyethanol and their acetates.
Immediately upon receipt of Union Carbide's followup report, the
Chemical Screening Branch sent copies of the report to the Office
of Solid Waste and Emergency Response (OSWER/EPA), the Of fice of
v~ater (OW/EPA), the Chemical Control Division (CCD/OTS), the Risk
Analysis Branch (RAB/ECAD/OTS) and to EPA's Region VI Office in
Dallas, Texas for review and any warranted followup action.
a)
The Chemical Screening Branch will transmi t copies of
this status report to NIOSH, OSHA, OSHER/EPA, OW/EPA,
OAR/EPA, ORD/EPA, CCD/OTS, RAB/ECAD/OTS and to EPA' s
Region VI Office (Dallas, TX). A copy of this status
report will be sent also to the TSCA Assistance Office
(TAO/OTS) for further distribution
209
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 4
DATE:
APR 1 6 1986
SUBJECT:
status Report*
8EHQ-0386-0594 S
Approved: ~ 1/"1 I'"G.
FROM: James F. Darr, Section Head ~ ~ U~
Chemical Risk IdentificationO~~~tion/CSB
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Note
(See Note on Page 4 of this status report)
The submi tting company has claimed its name and the identi ty of
the tested product to be TSCA Confidential Business Information
(TSCA CaI). The submitter reported on a non-confidential basis,
however, that 1) the product was a liquid mixture of octyltin
esters, and 2) the product contained the following chemical sub-
stance as the predominant component: dioctyltin bis(thioglycolic
acid), 2-ethylhexyl ester (CAS No. 15571-58-1). The Information
Management Division (IMD/OTS) will request the submitting company
to substantiate its TSCA CBI claims.
Submission Description
The company submitted a copy of the final report of a subchronic
feeding study of the subject octyltin esters mixture in male and
female rats. According to the provided study report, the subject
product was administered to groups of 40 rats (20 males and 20
females) at dietary levels of 0, 25, 50 or 100 ppm for 90 days.
These levels were reported to be equivalent to approx imately 0,
1.6, 3.3, and 6.6 mg/kg/day, respectively. The study report
states also that 10 male and 10 female rats from each group were
held for a 15-30 day post-exposure recovery period. In the cover
letter to its TSCA Section 8(e) submission, the company provided
the following information with regard to the results of this 90-
day feeding study:
"The test material did not produce any detrimental
effects in the following parameters: body wei'~ht gain,
food consumption, clinical chemistry/hematology values,
urine analysis and necropsy findings. Heights of the
thymus gland (absolute and relative) showed a statisti-
cally significant dose-related reduction in the 3.3 and
6.6 mg/kg groups. In addition, 2/10 females in the 6.6
------------------------------------------------------------------------------------
------------------------------------------------------------------------------------
* NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provis~on of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
210
-------
8EHQ-0386-0594 S
Page 2 of 4
mg/kg group showed very mild changes consisting of a
reduction in the cortical lymphocytes and a less clear
distinction between the cortex and medulla in the thymus
gland. In a post-dose recovery period lasting 15-30
days, the [adverse thymic] effects appeared reversible
as no alterations were seen in the 6.6 mg/kg group with
10 males and 10 females."
In its TSCA Section 8(e) submission, the company noted that the
"immuno-suppressive effects of dioctyltin compounds are generally
well known and can be controlled by appropriate engineering con-
trols and work practices." The submitter noted also that the
current u.s. Occupational Safety and Health Administration (OSHA)
Threshold Limit Value (TLV) is 0.1 mg/m3 for organotin compounds.
Submission Evaluation
In view of the observed statistically significant dose-related
thymic weight reduction in rats at the 3.3 and 6.6 mg/kg dose
levels (the no-observed-effect level (NOEL) was 1.6 mg/kg), the
submi tter' s concern that the tested chemical mixture may cause
immunotoxic effects appears to be well-founded even though the
adverse thymic effects were reported to be reversible in the high
dose animals following a 15-30 day post-exposure recovery period.
Considering that the thymus is a principle source of circulating
long-lived, immunologically competent l~nphocytes, the thymic
influence upon lymphocytes and immune competence is most critical
in the later stages of fetal development and in young animals and
is present but less cri tical in lnature animals. It is important
to note also that the thymus gland typically becomes atrophic and
involuted with age. Based on the weight range (120-142 grams) of
the rats at the beginning of the 90-day study, it is reasonable
to predict that the immunologic system of these adult animals
would continue to function normally even upon removal or atrophy
of the thymus. Removal or destruction of the thymus in neonates
or young animals, however, can lead to a failure of the body to
become seeded with immunologically competent lymphocytes.
It would be of interest to know if the submitting company has
conducted or is conducting studies designed to determine if ad-
verse immunologic effects occur in the off-spring as the resul t
of maternal exposure to the subject mixture or its components or
if adverse immunologic effects occur in young animals exposed to
the mixture or its components.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for the 2-ethylhexyl ester of dioctyltin bis(thiogly-
colic acid), which is listed in the ini tial TSCA Inventory, has
shown that 0 to 2000 pounds were reported as manufactured and/or
imported in 1977. This production range information does not
contain any data claimed as TSCA CBI by the person( s) reporting
211
-------
8EHQ-0386-0594 S
Page 3 of 4
for the initial 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).
In its Section 8(e) notice, the submitting company reported that
it imported the tested product in 1981 and since that time has
sent only one sample to one customer for development purposes.
In addition, the submitting company reported that all remaining
inventory of the product has been warehoused by the company since
1981 and will be "disposed of as waste, probably by incineration"
in the near future.
The company did not provide any information concerning the actual
or planned use(s) of the tested product nor was such information
located in the secondary literature sources consulted.
Comme n t s/ Re cornine nd a t ions
The submitting company stated that it is planning to notify its
warehouse workers about the reported toxicologic findings by way
of a revised Material Safety Data Sheet (MSDS) and product label.
The submitting company stated also that it is discontinuing all
furthec development work with the product.
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will ask
the submitting company to provide to EPA full copies of
the MSDS and product label that the company has revised
to reflect the reported toxicologic findings.
In view of EPA' s general interest in corporate actions
taken on a voluntacy basis in response to chemical toxi-
city or exposure data, the submitting company will be
asked to describe the nature and available resul ts of
all studies (other than those in the open scientific
literature) about which the company is aware or that the
company has conducted or is conducting to determine the
toxici ty of or exposure to the subject product or its
components.
b)
The Chemical Screening Branch will review the reported
infor:!llation in order to determine the need for further
OTS assessment of the tested product or its components.
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. Copies of
this status report will be provided also to the TSCA
Assistance Office (TAO/OTS) for further distribution.
212
-------
8EHQ-0386-0594 S
Page 4 of 4
Note
In a letter dated July 23, 1986 (8EHQ-0786-0594 FLWP Seq. D), the
CIBA-GEIGY Corporation s ta ted that the company no longer wished
to maintain as TSCA CBI the company's name or the identity of the
minor consti tuent of the subj ect product. Accord ing to the de-
classified version of CIBA-GEIGY's initial Section 8(e) notice,
the minor component of the product is the 2-ethylhexyl ester of
octyltin tris(thioglycolic acid) (CAS No. "27107-89-7).
A review of the production range (includes importation volumes)
statistics for the 2-ethylhexyl ester of octyltin tris(thiogly-
colic acid), which is listed in EPA's initial TSCA Chemical
Substance Inventory, has shown that between 0 and 1000 pounds of
this chemical were reported as manufactured and/or imported in
1977. This production range information does not contain any
data claimed to be TSCA CBI by. the person(s) reporting for the
TSCA Inventory nor does it include any data that would compromise
TSCA CRI. All data reported for the initial TSCA Inventory, in-
cluding the production range data, are subject to the limitations
contained in EPA' s ini tial TSCA Inventory Reporting Regulations
(40 CFR 710).
t!!f::j ..~
213
-------
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
Page 1 of 5
DATE:
APR 2 9 1986
Approved: t»- 114/
-------
8EHQ-0386-0595
Page 2 of 5
(0.12 mg/ml) and 7% (0.14 mg/ml). For the various con-
trols, the incidence of chromosome aberrations was 4%
for the negative (medium), 3% for the solvent (water)
and 26% for the positive control (cyclophosphamide).
These studies indicate a high clastogenic activity of
2,4-pentanedione by in vitro testing in the absence of
an activating system ~
On a "For Your Information" (FYI) basis, union Carbide submitted
previously the results of 4 in vitro genotoxicity studies of 2,4-
pentanedione (FYI-OTS-0186-0434 Sequence Band FYI-OTS-0286-0434
Sequence C). The compound was reported to be negative in Ames
Salmonella typhimurium (bacteria) and CHO/HGPRT gene mutation
assays both with and without metabolic activation. In a cyto-
genetics test in cultured CHO cells, 2,4-pentanedione reportedly
prod uced small increases in the number of chromosomal aberra-
tions. According to the provided final report, only one dose was
statistically different from concurrent controls both under acti-
va tion and non-act iva tion cond i tions. These test resul ts were
considered equivocal by the performing laboratory and by Union
Carbide, leading to a repeat of this study under different test
conditions. (The repeated study is the subject of the present
TSCA 8(e) submission.) In a Sister Chromatid Exchange (SCE)
assay using cultured CHO cells, a "steep" 2,4-pentanedione dose-
response was found with a statistically significant increase in
SCE's above concurrent control values reported for each 2,4-
pentanedione concentration tested ei ther wi th or wi thout meta-
bolic activation.
In its ini tial FYI submission (FYI-OTS-0885-0434 Sequence A) on
2,4-pentanedione, Union Carbide provided the final report from a
14-week study of rats exposed via inhalation to 2,4-pentanedione
vapor at concentrations of 0, 100, 300, or 650 ppm. According to
the submitted final report, there was a high incidence of mor-
tality accompanied by clinical abnormalities and tissue lesions
(including acute degeneration in the thymus and brain) in the
high dose animals.
In response to a wri tten Agency request for information on the
company's plans for additional toxicity testing, Union Carbide
stated that it was conducting neurotoxici ty stud ies involving
acute exposure of rats to 2,4-pentanedione vapor at or near the
lethal concentration (FYI-OTS-0386-0434 Sequence D). In its
Section 8(e) submission, the company reported that in "a study
currently nearing completion to determine the teratogenic poten-
tial from 2,4-pentanedione vapor to rats, there appears to be no
evidence at concentration[s] up to 400 ppm of any teratogenic or
embryotoxic effects."
In its TSCA Section 8(e) submission, Union Carbide offered the
following comments concerning the overall significance of the
positive in vitro cytogenetics test results reported to EPA under
Section 8Te):
215
-------
8EHQ-0386-0595
Page 3 of 5
"In the absence. of in vivo genotoxicity studies,
the possible adverse health effects of the recent [ly
reported] studies should be viewed in the light of other
recently conducted studies involving repeated exposure
to 2, 4-pentaned ione vapor. In part icular, the res ul ts
from a subchronic inhalation study and a teratology
study are relevant. In the subchronic inhalation study,
the results of which have already been submitted to the
Agency (FYI-OTS-0885-0434 [Sequence A]), there was no
ind ica tion of te st icular or bone marrow inj ury, wh ich
might be expected of a clastogen active in vivo. In a
study currently nearing completion [designed] to deter-
!nine the teratogenic potential from 2,4-pentanedione
vapor [exposure] to rats, there appears to be no evi-
dence at concentration[s] up to 400 ppm of any terato-
jenic or embryotoxic effects. These indications of a
lack of in vivo clastogenic potential accord wi th the
finding of ~in vi tro clastogenic potential in the
presence of a metabolic activating system."
SUb!llission Evaluation
According to the summarized resul ts of the cultured CHO cell
cytogenetics assay provided by Union Carbide in this Section 8(e)
submission, 2,4-pentanedione was tested at doses higher than
those tested in the original study (FYI-OTS-0186-0434 Sequence B
and FYI-OTS-0286-0434 Sequence C) both with and without exogenous
metabolic activation. In addition, the harvest times both with
and without activation were longer than those of the original
study (14 and 22 hours after initiation of treatment in the re-
cent study as compared to 10 and 6 hours after initiation of
treatment in the original study). The extended harvest times
were used to compensate for the long mitotic delay induced by
2 ,4-pentanedione - Although no substantial increases in chromo-
somal aberrations were observed with exogenous metabolic activa-
tion in the recent study, no statistical analyses were provided
in the 8(e) submission. Without exogenous metabolic activation,
on the other hand, the incidences of 2,4-pentanedione-treated
cells wi th chromosomal aberrations were increased substantially
(99%, 100%, and 95% for the three dose levels tested versus 20%
for the solvent control and 72% for the positive control (tri-
ethylene-melamine)).
The results from the other in vitro genotoxicity assays submitted
in FYI-OTS-0885-0434 et seq~indicate that while 2,4-pentanedione
is not mutagenic with or without exogenous metabolic activation
in the Ames Salmonella typhimurium (bacteria) or CHO/HGPRT assay,
the chemical did induce SCEs in cultured CHO cells when tested in
the presence or absence of metabolic activation.
In discussing the significance of the submitted test results,
Union Carbide stated that in view of the lack of data from in
vivo genotoxicity studies with 2,4-pentanedione, the results from
--
216
-------
8EHQ-0386-0595
Page 4 of 5
the company's subchronic inhalation and inhalation teratology
studies of 2,4-pentanedione are indicative of a lack of in vivo
clastogenic activi ty for this chemical. It should be noted,
however, that results from these particular types of studies are
not necessarily indicative of the clastogenic potential of a
chemical. A true evaluation of in vivo clastogenic potential
would require that an in vivo study designed to measure such an
end-point be conducted~ Until results of a such a study become
available, the in vi tro cytogenici ty test resul ts submi tted by
Union Carbide thus far provide the best indication of the clasto-
genic potential of 2,4-pentanedione.
In order for EPA to evaluate better the overall significance of
the reported findings, Union Carbide should be asked 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 in vitro cytogenetics study cited in
this Section 8(e) submission. In addition, Union Carbide should
be asked to ensure that EPA receives complete copies of the final
reports (including the actual experimental protocols, results of
gross and histopathologic examinations, results of statistical
analyses, etc.) from the company's ongoing inhalation teratology
and neurotoxicity studies of 2,4-pentanedione.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for 2,4-pentanedione (CAS No. 123-54-6), which is
listed in the initial TSCA Chemical Substance Inventory, has
shown that between 1.1 and 11.1 million pounds of this chemical
were reported as produced/imported in 1977. This production
range information does not include any production/importation
data claimed as TSCA Confidential Business Information (TSCA CBI)
by the person( s) reporting for the TSCA Inventory, nor does it
include any informa tion which would compromise TSCA CBI. All of
the information submitted for the TSCA Inventory, including the
production range information, is subject to the limitations con-
tained in the TSCA Inventory Reporting Regulations (40 CFR 710).
According to secondary literature sources, 2,4-pentanedione forms
organometallic complexes which are used as gasoline and lubricant
additives; driers for varnishes and printing inks; fungicides;
insecticides; dyes; and can be used as a solvent for cellulose
acetate and as an intermediate.
In FYI-OTS-0386-0434 Sequence D, Union Carbide reported that
"2,4-pentanedione is a specialty chemical of which Union Carbide
is the only domestic manufacturer; there are other producers in
West Germany, the United Kingdom, and Japan." In addition, Union
Carbide reported that "sales for a variety of applications, many
of which are based on the chemical's metal-chelating properties,
by Union Carbide were less than 5 million pounds in 1984 and
1985, including export sales." According to Union Carbide, 2,4-
217
-------
8EHQ-0386-0595
Page 5 of 5
pentanedione uses associated wi th the company's sales
chemical "are all industrial, and consist of 62% as [a]
intermediate, 35% in industrial chelating uses (mostly
chelates), and 3% unknown; there are no solvent uses to
company's] knowledge."
of this
chemical
as metal
. . . [ the
With regard to worker exposure to 2,4-pentanedione, union Carbide
stated in FYI-OTS-0386-0434 Sequence D that the company does not
have any data from its own operations or from users concerning
the actual workplace concentrations of 2,4-pentanedione during
routine processing or under exceptional circumstances.
Comments/Recommendations
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will ask
Union Carbide to ensure that EPA receives in a timely
manner a complete copy of the final report (including
the actual experimental protocol, results of statistical
analyses, etc.) from the in vitro CHO cell cytogenetics
study that was cited in the company's TSCA Section 8(e)
submission on 2,4-pentanedione. Union Carbide will be
requested also to ensure that the Agency rece ives in a
timely manner complete copies of the final reports (in-
cluding the actual experimental protocols, results of
gross and histopathologic examinations, etc.) from the
company's ongoin9 neurotoxici ty and teratology studies
of 2,4-pentanedione.
In view of EPA's general interest in corporate actions
that are taken on a voluntary basis in response to chem-
ical toxicity or exposure information, Union Carbide
will be asked also to describe the nature and available
resul ts of all stud ies (other than those reported pre-
viously to EPA or those published in the open scientific
literature) about which Union Carbide is aware or that
Union Carbide has conducted, is conducting, or plans to
conduct to determine the toxicity of or the eXfJosure to
2,4-pentanedione.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of 2,4-pentanedione.
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, NTP, FDA, OSWER/EPA,
OW/EPA, OAR/EPA, ORD/EPA and OPP/OPTS. In addition,
copies for this status report will be sent to the TSCA
Assistance Office (TAO/OTS) for further distribution.
218
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
SUBJECT: Status Report*
8EHQ-0486-0596 S
Page 1 of 3
Approved: t)1t- fill( /K(P
DATE:
APR I 4 1986
FROM: James F. Darr, Section Head ~ r~
Chemical Risk IdentificatioJ/section/CSB
TO: Frank D. Kover, Branch Ch ie f
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 (TSCA CBI). However, the submitting company reported
non-confidentially that the chemical was a halogenated aliphatic
carboxanilide. The Information Management Divison (IMD/OTS) will
request the company to substantiate all of the confidentiali ty
claims made in its Section 8(e) submission.
Submission Description
The submitting company provided the following information wi th
regard to the conduct and results of an acute eye irritation
study of this halogenated aliphatic carboxanilide in rabbits:
". . . [A] 10% granular formulation of the compound, when
placed in one eye of each of three New Zealand white
rabbits at a dose of 66 mg (equivalent in volume to 0.1
cc), caused moderate corneal opacity, slight to moderate
iritis, moderate conjunctivitis, and lens opacity with
prominent lateral suture lines. Hi th in 24 hours post-
treatment, lens opacity wi th prominent lateral suture
lines disappeared. An examination of treated eyes 48
hours post-exposure indicated faint lens opacity in one
animal, accompanied by corneal edema and cloudiness,
moderate corneal opacity and marked iritis, and normal
lenses in the remaining two animals. Seven days after
exposure, the treated eye of one rabbit was normal and
the remaining two rabb i ts had mild to severe corneal
opacity, mild to severe iritis, moderate conjunctivitis,
and one animal had peripheral corneal vascularization."
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
219
-------
8EHQ-0486-0596 S
Page 2 of 3
Submission Evaluation
In order for the Agency to evaluate the overall significance of
the reported eye toxicity, the company should be asked to submit
a complete copy of the final report (including the actual experi-
mental protocol, resul ts of gross/histopathologic examinations,
etc.) fr~n this acute eye irritation study in rabbits.
Current Production and Use
In view of the fact that the submi tting company has claimed the
exact identity of the subject chemical substance to be TSCA CBI,
no information with regard to the TSCA Inventory status of the
chemical will appear in this report. According to the submitting
company, less than 50 kilograms of this chemical substance have
been manufactured thus far. In addition, the submitting company
reported that approxima tely 25 employees work wi th the chemical,
and the exposure time averages 16 hours per year for each worker.
Al though the submi tting company claimed its use of the chemical
to be TSCA CBI, the company did state non-confidentially that 1)
the chemical substance has not been patented as yet, and 2) the
company is planning to apply for an Experimental Use Permit (EUP)
for the chemical. It should be noted that EPA issues EUPs under
the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA).
Comments/Recommendations
The submitter reported that the subject chemical is "labelled as
hazardous and all personnel who work with it are notified of the
chemical's properties and that eye protection is necessary."
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will ask
the submitting company to provide to EPA at this time a
complete copy of the final report (including the actual
experimental protocol, results of both gross and histo-
pa tholog ic examinations, e tc . ) from the eye i rr i ta tion
study cited in the company's TSCA Section 8(e) notice.
In view of EPA' s general interest in corporate actions
taken on a voluntary basis in response to chemical toxi-
ci ty or expos ure data, the s ubmi tting company will be
asked to describe the nature and results, if available,
of all other studies that the company has conducted, is
conducting, or is planning to conduct to determine the
toxicity of or the exposure to the subject chemical.
b)
The Chemical Screening Branch will review the reported
data to detergine the need for further OTS assessment of
the chemical at this time. In addition, the Chemical
Screening Branch will send copies of the reported data
to the Office of Pesticide Programs (OPP/OPTS/EPA).
220
-------
8EHQ-0486-0596 S
Page 3 of 3
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSHER/EPA,
OW/EPA, OAR/EPA, ORD/EPA, and OPP/OPTS/EPA. Copies of
this status report will be transmi tted also to the TSCA
Assistance Office (TAO/OTS) for further distribution.
221
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
SUBJECT:
Status Report*
8EHQ-0486-0597 S
Approved:
Page 1 of 4
~ 1ztJrr,
DATE:
APR 2 2 1986
FROM: James F. Darr, Section Head ~ r {J;'1/"/./
Chemical Risk Identification~;ection/CSB
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 (TSCA CBI). In its submission, the company reported
non-confidentially that the tested chemical was a "benzotriazole-
2-yl substituted hydroxyphenylpropionate ester" or more simply a
"substituted benzotriazole." The Information Management Division
(IMD/OTS) will ask the submi tting company to substantiate these
confidentiality claims.
Submission Description
The submitting company provided a final report from a 28-day oral
study of the substituted benzotriazole in male and female rats.
In the cover letter to its submission, the company provided the
following information with regard to the conduct and resul ts of
this sub-acute study:
"The test [ed] chemical was administered daily by gavage
for 28 days at doses of 0, 50, 200 and 1000 mg/kg body
weight to groups of 5 male and 5 female rats. There was
a consistent hepatotoxicity at the 1000 mg/kg level
where there were significant increases in liver weight
parameters, serum values (SGOT, SGPT, bilirubin, and
urea) and 1/5 males had extensive liver necrosis (+++
severi ty) . At the 50 mg/kg level, there were minimal
elevations in serum values; however, there was a 60-75%
increase in 1 iver we ight and two male rats had recent
liver necrosis (+ to ++ severity)."
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in'this 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
the fact that the report may be based on incomplete information.
222
-------
8EHQ-0486-0597 S
Page 2 of 4
According to a submitted Material Safety Data Sheet (MSDS), the
chemical has an oral rat LD50 of greater than 5 grams/kg and a
dermal rat LD50 of greater than 2 grams/kg. In addition, the
MSDS reports that the chemical is non-irritating to the skin of
rabbits following a 4-hour exposure and produces only slight and
reversible (after 48 hours) eye irritation in rabbits. The MSDS
reports further that the chemical was not found to produce skin
sensitization in guinea pigs. With regard to genotoxic effects,
the MSDS indicates that the chemical was negative in tests for
mutagenicity and clastogenicity. Finally, the MSDS reports that
the subject chemical 1) is not readily biodegradable (modified
Sturm Test), 2) has a 96-hour LC50 of >100 parts per million for
Zebra fish, and 3) has a 24-hour EC50 of >66 parts per million
for Daphnia magna.
Submission Evaluation
The most significant toxicologic findings acknowledged by the
submitter were in the high dose group and included increases in
liver weight parameters and serum values (SGOT, SGPT, bil irubin
and urea) and extensive liver necrosis in 1/5 male rats. At the
50 mg/kg dose level, the submitter noted that there were minimal
elevations in serum values and a 60-75% increase in liver weight
and liver necrosis in 2/5 male rats. The hepatomegaly reported
in the submitting company's study appears to be consistent with
that observed in a study in which administration of a substituted
benzotriazole at oral doses of 300 mg/kg/day for 14 or 28 days
caused an increase in liver weight in male rats. In this other
study, however, the observed change in liver weight was found to
be reversible.
In the summary presented by the submi tting company in its cover
letter, no mention was m~de about the significant increase found
in both absolute and relative kidney weights of female rats in
the mid and high dose groups (the kidney we igh ts of the treated
males did not show any marked alteration). In addition, the sub-
mitted pathology report states that in the high dose group there
was a decrease in the size of the thymus glands in 3/5 male rats
and small seminal vesicles in 2/5 male rats.
Current Production and Use
In view of the fact that the submitting company has claimed the
exact identity of the tested chemical substance to be TSCA CBI,
no information with regard to the TSCA Inventory status of the
chemical will appear in this report.
According to the submi tting company, the tested chemical is a
si te-limi ted intermediate imported for research and development
(R&D) purposes at one of the company's research laboratories.
223
-------
8EHQ-0486-0597 S
Page 3 of 4
The amount of this R&D intermediate that the company imported
during 1984-1985 has been claiffied as TSCA CB1.** The submitting
company reported that the R&D intermediate is present as an im-
purity (estimated by the company to be less than 1%) in a product
imported by the company for the past 3 years, first for R&D pur-
poses and then for commercial purpose s. The s ubmi t ting company
claimed the identi ty of this commercial product and the amount
imported during the last 3 years to be TSCA CB1.**
** The Infomation Management Division will request the
submitter to substantiate these TSCA CBI claims as well.
Comments/Recommendations
In its submission, the company stated that the MSDS and label for
the subject R&D chemical had been updated to reflect the reported
liver toxicity and that the company's workers are bein9 informed
about this toxicity. It is not clear, however, why the MSDS and
label were not revised to reflect also the other organ toxicities
observed in the company's 28-day study.
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will ask
the submitting company to provide to EPA a complete copy
of the final report (including the actual experimental
protocol, results of gross and histopathologic examina-
tions, results of statistical analyses, etc.) from each
toxicologic study cited in the submitted MSDS.
In view of EPA's general interest in corporate actions
that are taken on a voluntary basis in response to chem-
ical toxicity or exposure information, the submitting
company will be requested to describe the nature and
available results of all studies (other than those cited
in the submi tted MSDS) that the company has conducted,
is conducting, or is planning to conduct to determine
the toxicity of or exposure to the site-limited R&D in-
termediate. In addition, the submitting company will be
asked if it plans additional revisions to the MSDS and
label for this chemical to reflect the other toxicologic
findings from the company's 28-day oral study of the R&D
substance.
Finally, the submitting company will be requested to
describe the nature and available results of all studies
(other than those submitted already to EPA or those pub-
lished in the open scientific literature) about which
the company is aware or that the company has conducted,
is conducting, or is planning to conduct to determine
the toxicity of or the exposure to the product reported
to contain the subject R&D intermediate as a contaminant
at a level estimatea by the company to be less than 1%.
224
-------
8EHQ-0486-0597 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 the subject R&D intermediate or the
product reported to contain that substance.
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSHER/EPA,
OW/EPA, OAR/EPA, ORD/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.
225
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 4
DATE:
MAY
6 1986
SUBJECT: Status Report*
8EHQ-0486-0598
Approved:
!!JIP- 5"/b/Cp
. ~v'
-------
8EHQ-0486-0598
Page 2 of 4
excess in total cancers for the period 1956 through 1984
based on Du Pont rates (47 observed with 40 expected).
Within this group, . [Du Pont has] observed 9 cases
of cancer of the buccal cavi ty and pha rynx wi th 1.6
cases expected. Of these, 8 were observed in the \vage
roll group with 1.0 expected and 1 was observed in the
salary roll group with 0.6 expected. .. .[DU Pont has]
not observed an increased incidence of buccal cavity and
pharynx cancer in the [study] cohort exposed to both
acryloni tr ile and dimethyl fonnamide (2 observed and 1.6
expected) .
"In reviewing the mortality of the cohort exposed to di-
methylformamide but not acryloni trile, compared to Du
Pont rates, . [Du Pont has] observed 2 deaths from
cancer of the buccal cavi ty and pharynx wi th 0.8 ex-
pected. . [DU pont] did observe statistically sig-
nif icant excesses of deaths (p
-------
8EHQ-0486-0598
Page 3 of 4
all, 9 cases of such cancers were observed with only 1.6 expected
(SMR=563; p=O.00005). Eight (8) of these cancer cases were among
the wage roll workers as compared to 1.0 expected cases (SMR=800;
p=O.OOOOl). These 9 cancer cases contributed to the observed ex-
cess (not statistically significant) of total neoplastic deaths
(47 observed, 40 expected; SMR=118; p=O .15) . In the mortal i ty
analyses, Du pont found 2 deaths due to buccal cavity/pharyngeal
cancer giving a SMR of 250 (O.S expected; p=O.18). Significant
excesses in mortality in this study cohort were reported from all
causes (SMR=140; 225 observed), ischemic heart disease (SMR=134;
77 observed); external causes (SMR=161; 46 observed).
All S of the wage roll cases and the 1 salary roll cases were
reported to be smokers but comparisons do not reflect adjust-
ments; this may be a 1 imi tation of the analyses. Considering
that Du Pont uses company rates to calculate expected numbers,
this is a serious limitation only in the two separate job clas-
sification analyses if the workers' smoking patterns differ from
those of the average Du Pont wage roll or salary roll employee.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for dimethylformamide (CAS No. 68-12-2), which is
1 isted in the ini tial TSCA Chemical Substance Inventory, shows
that 50 million to 100 million pounds were reported as manu-
factured/imported in 1977. This production range information
does not contain any information claimed as TSCA Confidential
Business Information (TSCA CBI) by the persons reporting 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 1 imi tat ions contained in the TSCA Inventory Reporting
Regulations (40 CFR 710).
According to secondary Ii tera ture sources, dimethyl formamide is
used as a solvent in a wide variety of industrial applications
and in production of a wide variety of chemical substances (e.g.,
acrylic and mod-acrylic fibers, vinyl-based polymers used as
coatings). Some other applications of dimethylformamide include
its use as a solvent component of certain pesticide products, and
as a crystallization solvent (e.g., for pharmaceuticals).
Comments/Recommendations
EPA's Office of Toxic Substances (OTS) has received a number of
TSCA Section 8(e) and/or "For Your Information" (FYI) submissions
concerning acrylonitrile and dimethylformamide. In late 1981,
the Chemica 1 Screening Branch (CSB/ECAD/OTS) prepared a Chemical
Hazard Information Profile (CHIP) on dimethylformamide. Finally,
it should be noted that several other EPA program Off ices have
assessed or are assessing available toxicologic and exposure in-
formation on acrylonitrile and/or dimethylformamide.
228
-------
8EHQ-0486-0598
Page 4 of 4
a)
The Chemical Screening Branch will ask Du Pont to ensure
that the Agency receives as soon as possible a complete
copy of the final report (including the actual protocol,
the results of all statistical analyses, etc.) from this
expanded epidemiologic study.
b)
Upon receipt and review of a complete copy of the final
report from Du Pont's expanded epidemiologic study, the
Chemical Screening Branch will consider updating the
1981 CHIP on dimethylformamide to include t~e reported
information and other relevant toxicologic and exposure
information that has become available since 1981.
c)
The Chemical Screening Branch will send copies of this
status report to OSHA, NIOSH, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, OAR/EPA, ORD/EPA, and OPP/OPTS. In add i tion,
copies of this status report will be sent to the TSCA
Assistance Office (TAO/OTS) for further distribution.
229
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
SUBJECT: Status Report*
8EHQ-0486-0599
Page 1 of 3
Approved: zJ%'-1J-f /r",
DATE:
APR 2 9 1986
FROM: James F. Darr, Section Head dt h..J, r r;;:;'l--
Chemical Risk Identificatio«"section/CSB
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Eastman Kodak Company provided the following information with
regard to the conduct and preliminary results of several ongoing
acute oral and inhalation toxicity studies of the methyl ester of
3-methoxy propanoic acid (MMP) in rats:
"Single dose oral LD50 and single exposure inhalation
LC50 studies [of MMP] are being conducted on male and
female rats. These [acute toxicity] studies are still
in progress. . [and all findings reported herein are
preliminary]. In the oral LD50 study, all males at 1250
mg/kg appear normal. At 2500 mg/kg, 3 of 5 males appear
normal, I of 5 died wi thin a day, and 1 of 5 has shown
severe hindl imb weakness. At 5000 mg/kg, 4 of 5 males
died within one day, the single survivor showed hindlimb
weakness. All females at 5000 mg/kg died wi thin a day
of dosing. All males and females that (Hed during the
first day of the study were narcotized and not evaluated
for hindlimb weakness. After the first observation of
hindlimb weakness, 5 males were doseJ orally with 3500
mg/kg and 5 females at 1700 mg/kg. In males, 3 of 5
died within a day and 2 of 5 survived without apparent
ill effects. One of the males exhibited hindlimb weak-
ness before death. In females, 2 of 5 died wi thin tt;lO
days and 3 of 5 survived without apparent ill effects.
The one male and one female exposed to MMP in the oral
LD50 study and showing signs of hindlimb weakness have
been partially examined histologically. Noteworthy ef-
fects include necrosis of the thoracolumbar spinal cord
and brain stem. The necrotic lesions appear to be re-
lated to ischemia although no obstruction to blood flow
has been observed. Lesser affected areas of the spinal
cord and brain stem show perivascular hemorrhage. Peri-
pheral nerves and dorsal root ganglia appear unaffected.
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
230
-------
8EHQ-0486-0599
Page 2 of 3
"The inhalation study involved a single 6-hour exposure
[of male and female rats] to [MMP] vapor concentrations
of 965, 1968, or 3656 ppm. At the high dose, all males
and all but one of the females died during the exposure
period. The sole survivor was ataxic on removal from
the cage and is exhibitin'3 signs of hindlimb weakness.
Rats exposed to the lower [MMP] concentrations have not
exhibited hindl~nb weakness."
Eastman Kodak also provided the following information concerning
the conduct and prel iminary results of acute single dose oral
LD50 and single dose inhalation LC50 studies of the ethyl ester
of 3-methoxy propanoic acid (EMP) in rats:
"In the [acute] oral stud ies at 3500 mg/kg, 1 of 5 male
rats and 1 of 5 female rats showed hindlimb weakness
prior to death. At 5000 mg/kg, 1 of 5 males also showed
the hindlimb weakness and was perfused with formalin.
This animal has not yet been examined histologically.
In the [acute] inhalation studies, groups of 5 male and
5 female rats were exposed to [EMP] vapor concentrations
of 769 or 1571 ppm for a single 6-hour time period. No
hindlimb weakness or other neurological signs have been
observed."
Submission Evaluation
It is not clear from the submitted summarized information if EMP
and MMP are primary neurotoxic agents or if the observed neuro-
toxic effects occurred secondarily (e.g., possibly as the result
of hypoxia). In order for EPA to evaluate better the overall
significance of the reported findings, the Eastman Kodak Company
should be asked to ensure that EPA receives a full copy of the
final report (including the actual experimental protocol, results
of gross and histopathologic examinations, results of statistical
analyses, etc.) from each toxicity study cited in the submission.
Current Production and Use
A review of the non-confidential computerized version of the
ini tial TSCA Chemical Substance Inventory showed that the ethyl
ester of 3-methoxypropanoic acid (CAS No. 10606-42-5) is not
listed. A review of the production range (includes importation
volumes) statistics for the methyl ester of 3-methoxypropanoic
acid (CAS No. 3852-09-3), which is listed in the initial TSCA
Inventory, showed that no 1977 production or importation was re-
ported or that all of the production range information reported
has been claimed as TSCA Confidential Business Information (TSCA
CBI) by the person( s) reporting for the initial TSCA Inventory
and cannot be disclosed (Section l4(a) of TSCAj U.S.C. 2613(a».
All of the information, including the production range informa-
tion reported for the ini tial TSCA Chemical Substance Inventory
is subject to the 1 imi tations contained in the TSCA Inventory
Reporting Regulations (40 CFR 710).
231
-------
8EHQ-0486-0599
Page 3 of 3
Eastman Kodak reported in its Section 8(e) submission that the
company uses both MMP and EMP for research and development (R&D)
purposes. Eastman Kodak did not disclose, however, any informa-
tion concerning the specific use( s) of the chemical substances.
According to secondary literature sources, MMP may be used as an
intermediate in the manufacture of acrylic esters via a process
that avoids the use of propiolactone. No information concerning
the use(s) of EMP was located in the secondary literature sources
consulted by EPA.
Comments/Recommendations
In its submission, Eastman Kodak reported that the company has
taken steps to warn its workers about the potential toxici ty of
the subject chemicals and has established appropriate handling
precautions for the chemicals. In addition, Eastman Kodak stated
that copies of the final reports from the reported stud ies will
be sent to EPA upon completion of those reports.
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will ask
the Eastman Kodak Company to ensure that EPA receives
full copies of the final reports (including the actual
experimental protocols, results of gross and histopatho-
logic examinations, results of any statistical analyses,
etc.) from all toxicity studies cited in the company's
Section 8(e) submission.
In view of the Agency's general interest in corporate
actions that are taken on a voluntary basis in response
to chemical toxici ty or exposure informa tion, Eastman
Kodak will be asked to describe the nature and available
results of all other studies that the company has con-
ducted, is conducting, or plans to conduct to determine
either the toxicity of or the exposure to the ethyl or
methyl ester of 3-methoxypropanoic acid.
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 OSHA, NIOSH, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, OAR/EPA, ORD/EPA, and OPP/OPTS. In addition,
copies of this status report will be sent to the TSCA
Assistance Office (TAO/OTS) for further distribution.
232
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 3
DATE:
MAY 2 1 1986
SUBJECT: status Report*
8EHQ-0486-0600
APproved:~ ~27/f6
!"s1nj' 'r:r;-z.,
FROM: James F. Darr, Section Head' / . Lt~'Z1--
Chemical Risk Identificatio' Section/CSB
M:Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Union Carbide Corporation submitted a copy of a scientific
journal art icle enti tIed" Tumor igenic Ef fects in the Mucosa of
the Forestomach of Rats in Feeding Experiments wi th Propionic
Acid [(propanoic acid; CAS No. 79-09-4)]" which appeared in the
Bundesgesundhbl. in November, 1985. The following information
concerning the conduct and pre 1 iminary resul ts of the study was
presented in the English summary portion of the submitted paper:
"In a feeding experiment which is still underway, 3 groups
of male Wistar rats (90 in total) have been exposed to
propionic acid. After 20 weeks, 10 animals from each
group were sacrificed [and] the remaining ones will be
observed until death. In the sacrificed rats of group I
(4% propionic acid), pronounced hyperplasia, hyperplastic
ulcers and papillomas were found in the mucosa of the
forestomach. Histologically, proliferation of [the] basal
cells and carcinomatous changes of the squamous epithelium
could be demons tra ted in the mucosa of the fores tomach.
There were eros ive changes in the glandular epi theli urn of
these animals. In the sacrificed rats of group II (0.4%
propionic ac id), hyperplastic changes were found in the
region of the limiting ridge. The controls (group III)
sacrificed did not exhibit any pathological changes of the
mucosa of the stomach. It will be necessary to conduct
further studies wi th short-chain fatty ac ids under mod i-
fied experimental conditions to permit a re-assessment of
the risk posed by propionic acid as a food additive."
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
233
-------
8EHQ-0486-0600
Page 2 of 3
Union Carbide submitted also a full copy of an anonymous English
translation of a paper enti tIed II Communication from the [German]
Federal Board of Health Concerning a Meeting of Experts on the
Preservative Propionic Acidll which appeared in the January 1986
issue of the Bundesgesundhbl. The stated purpose of the meeting
was to IIclarify the question of whether the new findings place in
question the harmlessness of the use of propionic acid for the
preservation of foodstuffs.1I
Submission Evaluation
The submitted preliminary findings indicate that propionic acid,
administered to rats at 4% in the feed, induced carcinomatous
changes in the squamous epithelium of the forestomach after only
20 weeks of exposure. These results appear to be consistent with
the weak oncogenic activity of pentanoic acid and marginal onco-
genic activity of heptanoic acid toward the skin of mice observed
following chronic dermal application (see 8EHQ-OS84-0S14 et seq).
Overall, the resul ts of these long-term studies of short-chain
fatty acids suggest a need to systematically review this class of
chemicals for potential proliferative, genotoxic, and oncogenic
activities.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for propionic acid (CAS No. 79-09-4), which is listed
in the initial TSCA Chemical Substance Inventory, has shown that
from 61.2 million to 162 million pounds of this chemical were re-
ported as manufactured and/or imported in 1977. This production
range information does not include any information claimed as
TSCA Confidential Business Information (TSCA CBI) nor does it
include any information that would compromise TSCA CBI. All of
the data reported for the ini tial TSCA Inventory, includ ing the
production range data, are subject to the 1 imi tat ions contained
in the Inventory Reporting Regulations (40 CFR 710).
According to secondary literature sources, propionic acid is used
to produce propionate esters of which some are used as bread mold
inhibitors and antifungal agents. In addition, propionic acid is
reportedly used as an emulsifying agent and as a grain and wood
ch ip lJreservat ive. Other reported uses incl ude the manufacture
of herbicides, perfumes, artificial food flavorings, drugs, and
cellulose propionate thermoplastic.
Comments/Recommendations
According to Part VII(c) of EPA's March 16, 1978, Section 8(e)
policy statement (II Statement of Lnterpretation and Enforcement
policy; Notification of Substantial Riskll 43 FR 11110), informa-
tion need not be reported to EPA under TSCA Section 8(e) if, for
234
-------
8EHQ-0486-0600
Page 3 of 3
,~xample, the information has been 1) published by EPA in reports;
2) submitted already to EPA under a mandatory reporting provision
of another authority administered by EPA; or 3) published in the
open scientific literature and abstracted/referenced by Agricola,
Biological Abstracts, Chemical Abstracts, Dissertation Abstracts,
Index Medicus, or the National Technical Information Service. In
its TSCA Section 8(e) submission, Union Carbide stated that the
company had been unable to locate an abstract of ei ther of the
submitted articles in any of the abstracting services listed in
Part VII(c) of the Section 8(e) policy statement or in any other
abstracting services. EPA was equally unsuccessful in finding
abstracts of the submitted articles in the listed or any other
abstracting services. Therefore, Union Carbide' s report to EPA
under TSCA Section 8(e) was appropriate.
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will review
the reported findings in more detail to determine the
need for further OTS assessment of the potential risks
posed by exposure to propionic acid as well as other
short-chain fatty acids.
b)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSVJER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, and OPP/OPTS. In addition,
copies of th is report will be transmitted to the TSCA
Assistance Office (TAO/OTS) for further distribution.
235
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 3
DATE:
JUN
5 1986
SUBJECT:
Status Report*
APproved:~
~ '() r-
. c ""'1.1". fl. Lbn/
Darr, Sectlon Head: 1--
Risk Identification SectionjCSB
8EHQ-0586-0601
l1{~fv
FROM: James F.
Chern ical
TO: Frank D. Kover, Branch Chief
Chemical Screening BranchjECADjOTSjOPTS
Submission Description
On behalf of its six member companies, the Smelter Environmental
Research Association (SERA) provided a complete copy of the final
report from a SERA-funded epidemiologic study that was conducted
by the University of pittsburgh Graduate School of Public Health.
The "Executive Summary" section of the submitted report (entitled
"Mortality Among Copper and Zinc Smelter Workers in the United
Sta tes") presented the following inforraa tion \
-------
8EHQ-0586-060l
Page 2 of 3
"Aside from these two findings, this extensive examina-
tion of the mortali ty experience of siTIel ter workers in
the United States is essentially negative. This conclu-
sion is based on a very extensive analysis relating not
only to [the] patterns of mortality but also to specific
[the] responses to a wide variety of agents known to be
present in copper [and zinc] smelters. ."
In the cover letter to its Section 8(e) notice, SERA stated that
the study investigators found "a statistically significant trend
for emphysema mortali ty wi th increasing duration of exposure to
sulfur dioxide at peak values exceeding 24.00 PPM (parts per mil-
lion) in air." SERl>.. stated also that "the finding is based on a
small number of deaths and any confounding effects of cigarette
smoking could not be examined under the original study design."
SERA did not submit any comments on the arsenic-related findings.
Submission Evaluation
The subject epidemiologic study was organized into four phases
which included 1) standardized mortality ratio (SMR) analyses by
occupational job categories (e.g., mill workers, smelter only
workers), 2) SMR analyses by occupational category for trends
with duration of exposure and for time since first employed, 3)
SMR analyses by specific chemical exposures, and 4) a nested
case-control study of lung cancer. The SMR analyses of the
various occupational job categories did not reveal any associa-
tions with specific causes of death, with duration of exposure,
or 'vIi th time since first employed. Howeve r , the th i rd phase 0 f
the study showed 1) increased risks of emphysema for workers
exposed to sulfur dioxide, 2) increased risks of lung cancer for
workers exposed to arsenic, and 3) increased risks of lung cancer
for workers exposed to sulfur dioxide. Further analyses of the
lung cancer cases util izing a nested case-control approach sug-
gest that smoking and arsenic exposure may have been confounding
factors that could explain the sulfur dioxide/lung cancer associ-
ation. Further, logistic regression analyses, which examined the
lung cancer and arsenic relationship and did control for smoking,
suggest that lower level arsenic exposure might be a more potent
lung carcinogen than has been suspected from previous studies.
A brief review of the various methodologies and the statistical
analyses revealed that there are several factors that influence
interpretation of the study results. These factors incl ude 1)
the choice of the control population (mill workers) potentially
subject to some of the same adverse mortali ty effects as the
study cohort, and 2) the potential misclassification of exposure
levels due to use of a job description model rather than environ-
mental monitoring data. However, given that misclassification in
the submitted study would be random, the significant relationship
between sulfur dioxide exposure and emphysema is noteworthy even
though smoking histories were not obtained for emphysema deaths
and smoking could confound that relationship. As noted in the
case-control study, smoking did confound the sulfur dioxide/lung
237
-------
8EHQ-0586-0601
Page 3 of 3
cancer relationship. Also noteworthy is a concaved upward shaped
dose-response curve for lung cancer and arsenic exposure while
dose-response modelling from previous studies of this type have
suggested a linear relationship. The submitted report, however,
does not contain sufficient information wi th which to evaluate
this finding adequately.
Comments/Recommendations
SERA stated in the cover to its Section 8(e) submission that full
copies of the final report from the epidemiologic study had been
sent to all SERA member companies (ASARCO Inc.; Cominco, Ltd.;
Inspiration Consolidated Copper Company; Kennecott Ne~nont Mining
Corporation; Phelps Dodge Corporation; and the st. Joe Minerals
Corporation) .
EPA's Office of Toxic Substances (OTS) has received a number of
TSCA Section 8(e) and "For Your Information" (FYI) submissions
concerning the results of epidemiologic studies involving worker
exposure to a wide variety of heavy metals and/or other chemical
substances.
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will review
the provided report in more detail to determine the need
for further OTS assessment of the study findings.
b)
The Chemical Screening Branch will send copies of this
status report to OSHA, NIOSH, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, OAR/EPA, ORD/EPA and OPP/OPTS. Copies of this
status report will be sent also to the TSCA Assistance
Office (TAO/OTS) for further distribution.
238
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
JUN 2 4 1986
Page 1 of 3
SUBJECT:
status Report*
8EHQ-0586-0602 S
APproved:~ ~!~~/~y
I ' -
FROM: James F. Darr, Section Head ~1 r [;;;:-vz..,..
Chemical Risk IdentificatioU-se~tion/CSB
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 tested materials as TSCA Confidential Business
Information (TSCA CBI). Information Management Division (IMD/OTS)
staff will request the submitting company to substantiate all of
the company's TSCA CBI claims. In reporting under Section 8(e),
the submitting company stated non-confidentially that the company
was aware of the Agency's concerns about chemicals containing an
acrylate moiety and that the submitted data were expected to aid
the Agency in its ongoing efforts in evaluating possible adverse
health effects of acrylates.
Submission Description
The submitting company provided 9/15 final reports from a battery
of 5 genotoxicity studies conducted on each of 3 test materials.
Specifically, the 3 materials (II, III, and IV) were studied in
1) an Ames/Salmonella typhimurium (bacteria) Assay, 2) an in vivo
Mouse Micronucleus Chromosomal Aberration Assay, 3) an invitro
Rat Hepatocyte pr imary CuI ture DNA Repair Assay, 4) an in vi tro
Mammalian Cell Forward Gene Mutation Assay;, and 5) an Tn vitro
Hamster Ovary Cell Chromosomal Aberration Assay. According to
the submi t ter, all of the performed genotox icolog ic stud ies were
negative with the exception of statistically significant positive
results observed in the in vitro chromosomal aberration assays.
Submission Evaluation
An initial review of the submitted final reports shows that all 3
materials 'were negative in the Ames assay when tested with and
without exogenous metabolic activation in bacterial strains TA98,
'l'AIOO, TA1535, TA1537 and TA1538. Al though test materials III
and IV had orig inally showed some suggestive activi ty in strain
TA1538, no activity was evident in repeated tests.
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
239
-------
8EHQ-OS86-0602 S
Page 2 of 3
The only final report submi tted thus far from the in vivo mouse
micronucleus tests was the one for material IV. No increased
micronuclei were observed at sacrifice times of 30, 48 or 72
hours after a single intraperi toneal injection of 1000 mg/kg.
Further, no alteration from study controls was observed with
regard to the polychromatic erythrocyte (PCE)/normochromatic
erythrocyte (NCE) ratio. At the administered dose of 1000 mg/kg,
there were some signs of toxicity, however, and one of the test
animals rHed.
The company provided the final reports for the DNA repair assays
conducted on materials II and III. Both materials were negative
at test concentrations of up to 167 ug/ml and toxicity was seen
at higher doses.
Finally, the company submi tted the final study reports from the
cultured Chinese Hamster Ovary (CRO) cell chromosomal aberration
assays on materials II, III and IV. All 3 of the test materials
produced dose dependent increases in chromosomal aberrations both
with and without exogenous metabolic activation. The top 1 or 2
test material concentrations generally produced responses that
were statistically significant. only with test material II under
activated condi tions was the increase in aberrations found to be
lust at the level of statistical significance. The rest of the
observed responses were clearly positive.
Further evaluation of the overall significance of the reported
genotoxici ty findings should be poss ible upon EPA' s receipt of
the remaining 6 final reports from the performed studies.
Current Production and Use
In view of the submitter's TSCA CBI claims, no information with
regard to the initial TSCA Chemical Substance Inventory status of
the tested materials will appear in this status report.
Commen ts/Recommenda t ions
The submitting company stated that the 6 remaining final reports
will be sent to EPA as soon as the company receives the reports.
The Chemical Screening Bran.9h has received numerous TSCA Section
8(e) and For Your InformatIon (FYI) notices on acrylic acid and
its derivatives. Further, the Chemical Screening Branch has pre-
pared Chemical Hazard Information Profiles (CHIPS) on acrylic
acid, ethyl acrylate, ethylhexyl acrylate and neopentyl glycol
diacrylate. Also, the Risk Analysis Branch (RAB/ECAD/OTS) has
been evaluating available toxicologic/exposure data on several
acryla tes. Finally, EPA' s Chemical Control Divis ion/Off ice of
Toxic Substances (CCD/OTS) has received a number of TSCA Section
5 "Premanufacture Notices" (PMNs) on acrylates and is assessing
the potential risks posed by exposure to acrylates as a class.
240
-------
8EHQ-0586-0602 S
Page 3 of 3
a)
The Chemical Screening Branch (CSB/ECAD) will ask the
submi tting company to report to EPA the exact chemical
identity (including the CAS Registry Number, if known)
and amount (if known) of each constituent in each of the
tested materials cited in the company's initial Section
8(e) notice.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for separate
assessment of the tested materials and/or inclusion of
the reported findings into ongoing OTS assessments of
acrylates.
c)
The Chemical Screening Branch will send copies of this
status report to OSHA, NIOSH, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, OPP/OPTS/EPA, CCD/OTS, and
RAB/ECAD/OTS. In addition, copies of this status report
will be sent to the TSCA Assistance Office for further
distribution.
241
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 3
DATE:
JUN I 7 1986
SUBJECT: Status Report*
8EHQ-0686-0603
Approved: tJ1;t- "i'~/'iv
FROM: James F. Darr, Section Head,~rnR' T a;:;;1....--
Chemical Risk Identificatid~ section/CSB
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Union Carbide Corporation provided the following summarized
information with regard to the conduct and preliminary results of
a short-term repeated inhalation exposure study of I-propoxy-2-
propanol vapor (Propasol@ Solvent P; CAS No. 1569-01-3) in male
and female rats:
"Fischer 344 rats, in groups containing 10 males and 10
females, were exposed [via inhalation] to target concen-
trations of I-propoxy-2-propanol vapor of 0 (air control
group), 500, 1000 and 2000 ppm. Only [those] animals
free of ophthalmic abnormali ties on visual inspection
were included in the study. Exposures were 6 hours a
day, for 9 days over 2 weeks. During this period, the
analytically measured concentrations of vapor, expressed
as mean f: SD, were 0 (air control), 503 :t 21, 983 :t 65,
and 2000 :t 101 ppm. During routine daily inspection of
the animals for signs of [overt] toxicity, opacification
of the cornea was observed at 2000 ppm; this was seen in
13 of 20 rats after 4 days of exposure and in 17 of 20
rats after 9 days of exposure. Signs of sensory irrita-
tion of the eye, such as periocular wetness, were seen
only in 3 of the 20 animals exposed to 2000 ppm of the
vapor, and in these [3] animals only after the first
exposure day. On standard daily clinical inspection of
the animals exposed to 503 or 983 ppm of vapor, there
were no signs of corneal injury or sensory irritation of
the eye. A more detailed examination of the eyes was
conducted on the morning of the ninth day of exposure by
use of a magnifying lens. No corneal abnormalities were
seen in the control, 503, or 983 ppm groups. At 2000
ppm, one of the 20 exposed animals had normal eyes, 17
had corneal opaci ties, one had cloudy corneas, and one
had central corneal ulcers. Histological examination of
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
242
-------
8EHQ-0686-0603
Page 2 of 3
the eyes showed lesions in the corneas at all exposure
concentrations, but none in the air-alone controls. The
lesion was limited principally to the anterior portion
of the cornea, and [was] characterized by separation of
the epithelium from the underlying substantia propria,
patchy loss of the epithelium producing ulceration, in-
flammatory cell infiltration and vascularization of the
other substantia propria. There was also mineralization
of the outer stroma. ...."
In its TSCA Section 8(e)
during the "more than 20
I-propoxy-2-propanol,
of chronic eye injury
submission, Union Carbide reported that
years of manufacturing and marketing of
.[the company has] received no reports
ascribed to the chemical."
Submission Evaluation
Although the submitted summarized information does indicate that
inhalation exposure to I-propoxy-2-propanol can result in adverse
ocular effects, a more complete assessment of the overall signi-
f icance of the reported find ings should be poss ible upon EPA' s
receipt of a full copy of the final report from the cited study.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for I-propoxy-2-propanol (CAS No. 1569-01-3), which is
listed in the ini tial TSCA Chemical Substance Inventory, shows
that no 1977 manufacture/importation was reported or that all of
the manufacture and/or importation data reported were claimed as
TSCA Conf idential Business Information (TSCA CBI) by the manu-
facturer( s) and/or importer( s) and cannot be disclosed (Section
14(a) of TSCA, U.S.C. 2613(a)). All of the information provided
for the ini tial TSCA Inventory, includ ing the production range
information, is subject to the limitations that are contained in
the TSCA Inventory Reporting Regulations (40 CFR 710).
Union Carbide did not submit any information with regard to the
current production/importation volume or the specific use(s) of
I-propoxy-2-propanol; no information relating to current produc-
tion or importation volumes or specific use(s) of this chemical
was located in the secondary literature sources consulted.
Comments/Recornmenda tions
Union Carbide stated that the company plans to submi t to EPA a
full copy of the final report from the cited inhalation study as
soon as that report is received and reviewed by the company. In
addition, Union Carbide stated that the company is 1) notifying
employees and customers about the reported toxicologic findings,
and 2) revising the label and Material Safety Data Sheet for 1-
propoxy-2-propanol to reflect the reported toxicologic findings.
243
-------
8EHQ-0686-0603
Page 3 of 3
EPA's Office of Toxic Substances (OTS) has received a number of
TSCA Section 8(e) and "For Your Information" (FYI) submissions on
glycol ethers and their derivatives. In addition, the Chemical
Screening Branch prepared Chemical Hazard Information Profiles
(CHIPs) on 2-ethoxyethanol, 2-methoxyethanol and their acetates.
Further, the Test Rules Development Branch has been evaluating
available toxicologic and exposure information on 3 triethylene
glycol ether derivatives designated by the Interagency Testing
Commi ttee (ITC) for health effects testing under Section 4 of
TSCA. Finally, it should be noted that following cons ideration
of the various regulatory options for reducing the risks posed by
exposure to 2-ethoxyethanol, 2-methoxyethanol and their acetates,
the Agency recently referred these chemicals to the Occupational
Safety and Health Administration (OSHA) under Section 9 or TSCA
(see 51 FR 18488; May 20, 1986).
a)
The Chemical Screeni ng Branch (CSB/ECAD/OTS) will ask
Union Carbide to ensure that EPA receives a full copy of
the final report (including the actual experimental pro-
tocol, results of gross/histopathologic examinations,
etc.) from the inhalation study cited in the company's
TSCA Section 8(e) notice. In addition, Union Carbide
will be asked to provide to EPA copies of the I-propoxy-
2-propanol label and Material Safety Data Sheet revised
to reflect the reported toxicologic findings.
In view of EPA's general interest in corporate actions
taken on a voluntary basis in response to chemical toxi-
city and/or exposure data, the Chemical Screening Branch
will request the Union Carbide Corporation to describe
the resul ts of all stud ies (other than those publ ished
in the open scientific literature or those reported al-
ready to EPA) about which the company is aware or that
the company has conducted, is conducting, or plans to
conduct to determine the toxicity of or the exposure to
I-propoxy-2-propanol.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of I-propoxY-2-propanol.
c)
The Chemical Screening Branch will send copies of this
status report to OSHA, NIOSH, CPSC, FDA, NTP, OW/EPA,
OSWER/EPA, OAR/EPA, ORD/EPA, OPP/OPTS, CCD/OTS/OPTS,
RAB/ECAD/OTS and TRDB/ECAD/OTS. Copies of this report
will be provided also to the TSCA Assistance Office for
further distribution.
244
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
JUN I 3 1986
Page 1 of 3
SUBJECT: Sta tus Report*
8EHQ-0686-0604
APproved:~ ~II?/Kr
FROM: James F. Darr, Section Head jA nj.( ) !J: 0;:;,1...-
Chemical Risk Identification Section/CSB
TO'Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
On behalf of huoco Chemicals Company (a wholly owned subsidiary),
the Amoco Corporation provided the following summarized informa-
tion with regard to the conduct and preliminary findings from a
lifetime mouse skin painting study of a "heavy aromatic bottoms
stream from a paraxylene uni t" (**):
"[Fifty (50)] microliters of undiluted test material
were appl ied to the dorsal skin of 50 male mice, twice
per week, for the intended lifetime of the animals. The
results reported here are those found after 93 weeks of
dosing. Thirteen mice developed tissue mass (es) at the
application site, with a median latency period of 85.0
weeks. Of those, eight mice have been observed with a
single mass each, and five mice have multiple masses per
animal. Histopathological examinations of those masses
will be done at the end of the study. A concurrent con-
trol group of 120 mice is free of dermal masses through
93 weeks."
** According to the submitter, the identity of the test material
was submitted to EPA in 1978 for inclusion to the initial TSCA
Chemical Substance Inventory as a heavy aromatic solvent naphtha
(CAS No. 64742-94-5). The submitter stated, however, that the
"current Inventory description for this material may not be the
most accurate one" and that the company" is in the process of
evaluating the composition of this stream and will supply the
Agency with a more accurate description, if one is warranted,
under separate correspondence."
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
245
-------
8EHQ-0686-0604
Page 2 of 3
Submission Evaluation
Although the submitted summarized information indicates that the
tested material may possess some degree of oncogenic activity
toward the skin of male mice, an evaluation of the overall sig-
nificance of the reported findings should be possible upon EPA's
receipt of a full copy of the final report from the ongoing mouse
skin application study.
Current Production and Use
Appendix A in Volume 1 of the new (1985) printed version of the
initial TSCA Chemical Substance Inventory contains the following
definition for CAS No. 64742-94-5 (heavy aromatic solvent naphtha
(petroleum) ) :
"A complex combination of hydrocarbons obtained from
distillation of aromatic [petroleum] streams. It con-
sists predominantly of aromatic hydrocarbons having
carbon numbers predominantly in the range of C9 through
C16 and boiling in the range of approximately 165°C to
290°C (3300P to 554°P)."
A review of the production range (includes importation volumes)
statistics for CAS No. 64742-94-5, which is listed in the initial
TSCA Chemical Substance Inventory, has shown that over 1 billion
pounds were reported as manufactured and/or imported in 1977.
This cited production range information does not include any in-
formation claimed as TSCA Confidential Business Information (TSCA
CBI) by the person(s) reporting for the initial TSCA Inventory,
nor does it include any information that would compromise TSCA
CBI. All informa tion reported for the ini tial TSCA Inventory,
including the production range information, is subject to the
limitations contained in the TSCA Inventory Reporting Regulations
(40 CPR 710).
Comments/Recommendations
In its Section 8(e) notice, the Amoco Corporation stated that the
company will submit a copy of the final report from the ongoing
lifetime mouse skin application study once the final report from
the study is completed in mid-1987. Amoco stated further that,
in the interim, the company 1) is informing its employees about
the reported findings, and 2) "will revise the material safety
data sheets as necessary for t~is substance, and for products
containing this material, to reflect the potential hazard."
246
-------
8EHQ-0686-0604
Page 3 of 3
It should be noted that the Office of Toxic Substances (OTS) has
received numerous TSCA Section 8(e) and "For Your Information"
(FYI) submissions containing toxicologic and/or exposure data on
a number of petroleum, coal, and shale oil process streams.
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will ask
the Amoco Corporation to ensure that EPA receives a full
copy of the cited chronic mouse dermal application study
final report (including the actual experimental proto-
col, results of gross and histopathologic examinations,
results of any statistical analyses, etc.) immediately
upon the company's rece ipt of that final report. In
add i tion, Amoco will be asked to keep EPA appr ised of
significant results obtained from all future sacrifices
in this study.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of the tested material.
c)
The Chemical Screening Branch will send copies of this
status report to OSHA, NIOSH, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, and OPP/OPTS/EPA. Copies of
this report will be provided also to the TSCA Assistance
Office (TAO/OTS) for further distribution.
247
-------
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
Page 1 of 3
DATE:
JUL
7 1986
FROM: James F.
Chemical
Approved: !JII-'
. d ch --. ~-; r cr;::'1./'
Darr, Sectlon Hea ~:..~,
Risk Identification Section/CSB
8EHQ-0686-0605 S
'lft/'iC7
SUBJECT: Status Report*
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Note
The submi tting company claimed its company name as well as the
exact identities of the tested chemicals to be TSCA Confidential
Business Information (CBI). The Information Management Division
(IMD/OTS) staff will ask the submitting company to substantiate
these TSCA CBI claims. In its Section 8(e) notice, the company
stated non-confidentially that the test material was a mixture of
two complex organosilane oligomers which were the subject of
"premanufacture Notices" (PMNs) submitted to EPA previously under
Section 5 of TSCA. The company stated also that it had received
the submitted Section 8(e) information verbally.
Submission Description
The company submitted the following summarized information with
regard to the conduct and preliminary results of a sub-acute in-
halation toxicity study of the subject mixture in rats:
"This [organosilane oligomer] mixture was the subject of
a repeated 28-day inhalation study in which male and
female Fisher 344 rats were exposed to 0, 10, 40 or 150
mg/m3. The duration of the test was [for] six hours a
day, five days a week for four weeks. At the conclusion
of the study, [the] animals were necropsied and sub-
ject[ed] to an extensive histopathological evaluation.
The relevant findings from this investigation revealed
that the larynges of animals exposed at 150 mg/m3 [had]
suffered necrosis and ulceration. At the two lower con-
centrations (10 or 40 mg/m3), lesser effects were noted.
However, there was a clear concentration response rela-
tionship in these two [lower] exposure groups which was
characterized as squamous metaplasia and coincided with
the site of ulceration and necrosis seen in the animals
exposed to 150 mg/m3. ...."
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
248
-------
8EHQ-0686-0605 S
Page 2 of 3
Submission Evaluation
Although the reported findings do provide additional support for
EPA's concerns about the potential health risks posed by exposure
to organosilanes, an evaluation of the overall significance of
the submitted toxicologic findings should be possible upon EPA's
receipt of a full copy of the final report from the submi tting
company's 28-day repeated inhalation exposure study in rats.
Current Production and Use
Considering the submitter's TSCA CBI claims, no information with
regard to the production or use of the tested mixture or its con-
stituents will appear in this status report.
Comrnents/Recommenda tions
The Office of Toxic Substances has received a number of TSCA
Section 8(e) and/or "For Your Information" (FYI) submissions on
organosilanes. In add i tion, the Chemical Screening Branch has
prepared a Chemical Hazard Information Prof ile (CHIP) on 3,4-
epoxycyclohexylethyl trimethoxy silane and is in the process of
preparing a CHIP on other selected organosilanes. Further, the
Risk Analysis Branch (RAB/ECAD/OTS) has been reviewing available
toxicologic/exposure data on 3,4-epoxycyclohexylethyltrimethoxy
silane. Finally, the Office of Toxic Substances has received a
number of TSCA Section 5 PMNs on organosilanes.
a)
The Chemical Screening Branch will request the submitter
to ensure that the Agency receives a complete copy of
the final report (including the actual experimental pro-
tocol, the results of both gross and histopathological
examina tions, etc.) from the 28-day inhalation tox ic i ty
study cited in the company's Section 8(e) submission.
In view of the Agency's general interest in corporate
actions that are taken on a voluntary basis in response
to chemical toxici ty or exposure data, the submi tting
company will be asked also to describe the nature and
available results of all studies (other than those
submitted already to EPA) about which the company is
aware or that the company has conducted, is conducting,
or plans to conduct to determine the toxici ty or the
exposure to the tested mixture or its individual com-
ponents. In addi tion, the submi tting company will be
asked to describe the actions the company has taken or
is planning to take to 1) notify its workers and others
about the reported toxicologic findings, and 2) reduce
or eliminate exposure to the tested mixture or its com-
ponents.
b)
The Chemical Screening Branch will review the submitted
information and consider inclusion of that information
in the organosilane CHIP now in preparation.
249
-------
8EHQ-0686-0605 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. Copies of
this status report will be transmitted also to the TSCA
Assistance Office (TAO/OTS) for further distribution.
250
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 2
DATE:
JUL I 1 1986
.UBJECT: status Report* 8EHQ-0786-0606 S APproved:zi1'-
FROM: James F. Darr, Section Head ~/) r ~
Chemical Risk Identificatio~~ection/CSB
7/"/~~
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Note
The CIBA-GEIGY Corporation claimed the exact chemical identity of
the tested substance to be TSCA Confidential Business Information
(TSCA CBI). The Information Management Division (IMD/OTS) will
be requesting the company to substantiate this TSCA CBI claim.
CIBA-GEIGY provided the following non-confidential generic name
for the tested chemical: "heteromonocyclic carbomonocyclic urea."
Submission Description
CIBA-GEIGY submi tted the following summarized informa tion wi th
regard to the conduct and prel iminary resul ts from a two-year
dietary oncogenicity/chronic toxicity study of this heteromono-
cyclic carbomonocyclic urea in male and female mice:
"The dose levels for the two-year dietary. . study
were 10, 100, 750 and 1,500 ppm. Microscopic findings
in the second year of study showed an increase in inci-
dence of hepatocellular adenomas in males at the 100,
750 and 1,500 ppm dosage levels and in females at the
1,500 pprn dosage level. Because the [tested] compound
had been dropped [in late 1984] from further development
[by CIBA-GEIGY as a research and development chemical
intended solely for use as a pesticide product], micro-
scopic pathology was conducted only on liver masses and
nodules noted during the macroscopic examination. No
significant increase in the incidence of hepatocellular
carcinoma was evident in the test article treated mice."
In its submission, CIBA-GEIGY stated that no oncogenic response
has been noted for the subject chemical substance in a two-year
dietary feeding study in rats. In addition, CIBA-GEIGY reported
that the chemical was negative in an Ames Salmonella typhimurium
(bacteria) mutagenicity assay.
====================================================================================
* NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
251
-------
8EHQ-0786-0606 S
Page 2 of 2
Submission Evaluation
Al though the provided summarized prel iminary find ings ind ica te
that the tested chemical caused an increase in the incidence of
hepa tocellular adenomas in male mice at the upper doses and in
female mice at the highest dose, a more complete evaluation of
the reported resul ts should be possible upon EPA' s receipt of a
complete copy of the final report from the performed study.
Current Production and Use
The CIBA-GEIGY Corporation stated that the tested substance was a
research and development (R&D) chemical that was under evaluation
by the company solely for use as a pesticide product. According
to CIBA-GEIGY, the subject chemical substance had been tested by
"technically qual i f ied personnel, knowledgeable in handl ing po-
tentially hazardous chemicals." Finally, CIBA-GEIGY stated that
the tested chemical "was dropped in November 1984 as a possible
pesticide due to lack of sufficient pesticidal activity."
Comments/Recommendations
In its submission, CIBA-GEIGY stated that upon the company's
receipt and review of the final report of the two-year dietary
feed ing study in mice, the company would submi t a copy of that
report and the company's assessment of the results. CIBA-GEIGY
stated also that "notifications to persons working with [the
heteromonocycl ic carbomonocycl ic urea] will not be necessary as
supplies of the material no longer exist."
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will ask
CIBA-GEIGY to ensure that EPA receives a full copy of
the final report (including the actual experimental pro-
tocol, results of gross/histopathologic examinations,
etc.) from the two-year mouse dietary oncogenici ty and
chronic toxici ty study ci ted in the company' s ini tial
TSCA Section 8(e) submission.
b)
The Chemical Screening Branch will review the reported
findings 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 OSHA, NIOSH, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA. Copies of
this report will be provided also to the TSCA Assistance
Office (TAO/OTS/OPTS/EPA) for 'further distribution.
252
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
JUL I 5 1986
Page 1 of 3
SUBJECT: status Report* 8EHQ-0786-0607 S APproved:~
FROM: James F. Darr, Section Head j)~1 t: ;:;;:vz..-
Chemical Risk IdentificatioW'~~ctionjCSB
1/1~ /Sfp
. j
ro:Frank D. Kover, Branch Chief
Chemical Screening BranchjECADjOTSjOPTS
Note
The submitting company has claimed its name and the specific use
of the subject chemical as TSCA Confidential Business Information
(TSCA CBI). The Information Management Division (IMDjOTS) will
request the submi tting company to substantiate all of the TSCA
CBI claims made in the submission.
Submission Description
The submitting company reported the following summary information
with regard to the conduct and results of a series of short-term
in vivo toxicity studies of 2,2,6,6-tetramethylpiperidine-I-oxyl
(CAS No. 2564-83-2):
"Inhalation LC50-Limit Test
Five female and five male Sprague-Dawley rats were ex-
posed to the vapors of the test chemical, obtained by
slowly heating the test material to lOO°C. All ten of
the exposed rats died within 2 hours of the initiation
of the intended 4-hour exposure. A nominal concentra-
tion of 4.5 - 6.6 mgjliter was delivered, but, because
the material condensed on the surfaces of the delivery
apparatus and inhalation chamber during delivery, it is
estimated that the rats were actually exposed to vapor
concentrations at least lO-fold less than the nominal
concentration.
====================================================================================
* NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
253
-------
8EHQ-0786-0607 S
Page 2 of 3
Dermal LD50-Limit Test
The test chemical was applied, undiluted, to the backs
of two male and two female rabbits at a dose of 2.0
gm/kg body weight, and the application site was wrapped.
Two females and one male died within 24 hours after ap-
lication. The remaining male rabbit showed overt signs
of toxicity (i.e., lethargy, hypoactivity) at first, but
subsequently recovered.
Dermal Irritancy/Corrosivity Study
A 0.5 gm quantity of the chemical was applied to the
shaved back of each of 6 rabbi ts for a 4-hour period,
and the skin reaction was scored at 24 and 72 hours
after removal of the test material. A primary skin
irritation score of 6.5/8.0 was obtained.
Eye Irritation Study (Draize)
A 0.1 gm quantity of the [subject] chemical
in the everted eyel id of each of 6 rabbits.
hours, the maximum primary eye irritation
60.2/110.0."
was placed
After 24
score was
In reporting this information under Section 8(e), the submitter
stated that "taken together, these results indicate a toxicity
profile for 2,2,6,6-tetramethylpiperidine-l-oxyl that warrants
concern because of its potential to cause harm in humans."
Submission Evaluation
Based on an ini tial review of the provided summarized resul ts,
the subject chemical appears to be very toxic (at minimum) via
inhalation, can penetrate unabraded skin in sufficient amounts to
cause death, is extremely irritating upon dermal application, and
is severely irritating to the eyes. An evaluation of the overall
significance of the reported findings should be possible upon re-
ceipt of the final reports from the cited acute toxicity studies.
Current Production and Use
The subject
computerized
Inventory.
claimed the
chemical to
chemical was not located in the non-confidential
version of initial (1977) TSCA Chemical Substance
As stated previously, the submitting company has
information pertaining to the company's use of this
be TSCA CBI.
254
-------
8EHQ-0786-o607 S
Page 3 of 3
comments/Recommendations
In its TSCA Section 8(e) notice, the submitting company stated
that "persons who handle this substance have been informed of its
to~icity, and procedures have been reviewed to ensure safe work-
place practices." The company stated also that the final reports
from the cited acute toxicity studies will be sent to EPA as soon
as those reports are available.
a)
The Chemical Screening Branch (CSB/ECAD) will ask the
submi tting company to ensure that EPA receives a full
copy of the final report (including the actual experi-
mental protocol, results of gross and histopatholog ic
examinations, etc.) from each study that was cited in
the company's initial Section 8(e) notice.
In view of EPA's general interest in corporate actions
that are taken on a voluntary basis in response to chem-
ical toxicity or exposure data, the submitting company
will be requested to describe the nature and available
resul ts of all stud ies (other than those cited in the
open scientific literature or those submitted already to
the Agency) about which the company is aware or that the
company has conducted, is conducting, or is planning to
conduct to determine the toxicity of or the exposure to
2,2,6,6-tetramethylpiperidine-l-oxyl.
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 OSHA, NIOSH, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA and OPP/OPTS/EPA. Copies of
this report will be provided also to the TSCA Assistance
Office (TAO/OTS/OPTS) for further distribution.
255
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page
1 of 3
DATE:
JUL 2 I 1986
SUBJECT:
Status Report*
8EHQ-0786-0608 S
APproved:~~
7(21 {r(p
,
FROM: James F. Darr, Section Head ~'} T fl;"rz_-
Chemical Risk Identification SectionjCSB
TO: Frank D. Kover, Branch Chief
Chemical Screening BranchjECADjOTSjOPTS
Note
The submitting company claimed its name and the exact identity,
use, and production volume of the subject chemical substance to
be TSCA Conf idential Business Information (TSCA CBI). Staff of
the Information Management Division (IMDjOTS) will request the
submitting company to substantiate all of the TSCA CBI claims
made in the company's TSCA Section 8(e) submission. In its sub-
mission, the company stated non-confidentially that the subject
chemical was a "metal salt of a phosphoric acid ester."
Submission Description
The submi tting company provided the final resul ts from an Ames
Salmonella typhimurium (bacteria) mutagenicity assay, an in vitro
Chinese Hamster Ovary (CHO) cell sister chromatid exchange (SCE)
assay and a 28-day repeated skin application study of the subject
chemical in rats. According to the submitting company, the Ames
assay (with or without exogenous metabolic activation) as well as
the 28-day dermal appl ication study were nega tive. wi th regard
to the results of the SCE assay, the submitting company stated
that a "positive dose-related response" was observed. (The sub-
mitted final report from the SCE assay states that a significant
concentration-dependent increase in SCEs was observed in the pre-
sence but not in the absence of exogenous metabolic activation.)
Submission Evaluation
Although the submitting company stated that the 28-day dermal
study in rats was negative, the company provided only the proto-
col and narrative results sections of the final report. without
the actual data tables, the Agency cannot evaluate the reportedly
"negativei' findings from this in vivo study.
------------------------------------------------------------------------------------
------------------------------------------------------------------------------------
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
256
-------
8EHQ-0786-0608 S
Page 2 of 3
vJi th regard to the performed genotoxici ty assays, the Ames assay
was negative in the presence and absence of exogenous metabolic
activation in Salmonella typhimuriurn (bacteria) strains TA98,
TAIOO, TA1535, TA1537 and TA1538 up to toxic doses of the subject
chemical (dose range was from 0.3 - 1.0 mg/plate). The SCE assay
was negative under non-activation conditions up to a dose of 3.0
ug/ml (5.0 ug/ml was found to be toxic). under activated condi-
tions, there was a small but significant concentration dependent
increase in SCEs at test chemical concentrations up to 5.0 ug/ml
(10.0 ug/ml was found to be tox ic) . Al though this increase is
statistically significant, it may be of marginal biological sig-
nif icance especially when one cons iders that the s ubmi t ted final
report for the SCE assay states that a "repeat" SCE assay did not
duplicate the positive findings of the first SCE assay.
Current Production and Use
In light of the submitter's TSCA CBI claims, no information with
regard to production volume, use, or TSCA Inventory status of the
subject chemical will appear in this status report. According to
the submitter, the tested material "is currently being used for a
limited nUTJ.ber of products. "The submitter stated also that
to the extent the subject chemical is contained in such products,
exposure to the subject chemical can and should be controlled or
minimi zed as the res ul t of already reported concerns about the
potential oncogenic risks posed by exposure to the products them-
selves.
Comments/Recommendations
Although a positive in vitro genotoxicity test finding, when
considered by itself, may not be sufficient to offer reasonable
support for a conclusion of substantial risk (as defined in EPA's
TSCA Section 8(e) policy statewent ("Statement of Interpretation
and Enforcement Pol icy; Not i fica tion of Subs tan tial Ri sk" 4 3 FR
11110; March 16, 1978)), EPA does believe that such a finding is
of value in assessing the possible risks posed by exposure to the
tested chemical or mixture. Also, EPA believes that a positive
genotoxicity test result in combination with additional relevant
information (e.g., knowledge of potential exposure to and/or high
production of the subject chemical or mixture) would suggest, in
many cases, the need to conduct other studies designed to define
better the toxicity of or exposure to that chemical or mixture.
The results of such additional studies should be considered also
for possible submission to EPA pursuant to Section 8(e) of TSCA.
a)
The Chemical Screening Branch (CSB/ECAD) will ask the
submitting company to provide to EPA a complete copy of
the final report from the "repeat" SCE assay cited in
the SCE assay final report contained in the company's
initial TSCA Section 8(e) submission. In addition, the
257
-------
8EHQ-0786-0608 S
Page 3 of 3
submitting company will be asked to provide a full copy
of all data tables from the "negative" 28-day dermal
application study cited in the initial TSCA Section 8(e)
notice.
In view of EPA's general interest in corporate actions
taken on a voluntary basis in response to chemical toxi-
city or exposure data, the submitting company will be
asked to describe the nature and resul ts, if available,
from all studies (other than those submitted already to
EPA) that the company has conducted, is conducting, or
plans to conduct to determine the toxici ty 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 "metal salt of a phosphoric acid
ester."
c)
The Chemical Screening Branch will send copies of this
status report to OSHA, NIOSH, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, OAR/EPA, ORD/EPA, CCD/OTS/OPTS and OPP/OPTS. In
addition, copies of this status report will be provided
to the TSCA Assistance Office (TAO/OTS/OPTS) for further
distribution.
258
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
JUL 2 1 1986
Page 1 of 2
SUBJECT: status Report*
8EHQ-0786-0609 S
Approved:
~. 7/U/r~
/
FROM: James F. Darr r Section Head ~1 T 0;:117--
Chemical Risk Identification Section/CSB
~: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Note
R. T. Vanderbilt Company, Inc. has claimed the exact identity of
the subject chemical to be TSCA Confidential Business Information
(TSCA CBI). The company has reported non-confidentially by phone
that the chemical is a "heterocyclic derivative." Staff of the
Information Management Division (IMD/OTS) will be requesting the
company to substantiate this confidentiality claim.
Submission Description
R. T. Vanderbilt Company, Inc. provided the following information
with regard to the conduct and preliminary findings of an acute
(4-hour) inhalation study of the heterocyclic derivative in rats:
"Five male and five female Sprague-Dawley rats were
exposed to a liquid droplet aerosol of [the heterocyclic
derivative] at an average actual concentration of 5.2
mg/L for four consecutive hours. The animals were ob-
served periodically during and post-exposure for phar-
macotoxic signs and mortality. Under the conditions of
this study, the. . . [heterocyclic derivative] produced
100% mortality."
Submission Evaluation
An EPA evaluation of the overall significance of the reported
toxicity should be possible upon EPA's receipt of a full copy of
the final report from this study. The submitting company stated
in its submission that the final report would be sent to EPA as
soon as the company receives that report.
====================================================================================
* NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
259
-------
8EHQ-0786-0609 S
Page 2 of 2
Current production and Use
In view of the submi tting company's confidentiality claims, no
information concerning the TSCA Inventory status of the subject
chemical will be presented in this status report. According to
the submitting company, the subject chemical substance is an
"experimental compound" that "is being synthesized in small
quanti ties at [the company's] Research and Development
facilities and is handled by technical personnel." In addition,
the company reported that "the risk of exposure to airborne dust
is minimal."
Comments/Recommenda tions
a)
The Chemical Screening Branch (CSB/ECAD) will request
R. T. Vanderbilt Company, Inc. to ensure that the Agency
receives a full copy of the final report (including the
actual experimental protocol, the resul ts of gross and
histopathologic examinations, etc.) from the acute in-
halation study cited in the company's TSCA Section 8(e)
submission.
In view of EPA' s general interest in corporate actions
taken on a voluntary basis in response to chemical toxi-
city or exposure data, R. T. Vanderbilt Company, Inc.
will be asked to describe the actions that the company
has taken or plans to take to notify its workers about
the reported tox icolog ic find ings. In add i tion, the
company will be requested to describe the nature and
resul ts, if available, from all other studies that the
company has conducted, is conducting or plans to conduct
to determine the toxicity of or the exposure to the sub-
ject chemical substance.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of this heterocyclic derivative.
c)
The Chemical Screening Branch will send a copy of this
status report to OSHA, NIOSH, 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.
260
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
AUG I 2 1986
Page 1 of 3
iUBJECT:
Status Report*
APproved:~
~ t~
'- )
Darr, Section Head ~"1 . t~
Risk Identification Section/CSB
8EHQ-0786-0610
41'4~(p
FROM: James F.
Chemical
TO: Frank D. Kover, Branch Chie f
Chemical Screening Branch/ECAD/OTS/OPTS
Su~nission Description
Total Petroleum, Inc. provided full copies of the final reports
from an Ames Salmonella typhimuriwn (bacteria) mutagenicity assay
and an in vitro BALB/c-3T3 cell transformation assay of a mineral
seal oil. According to the submitter, both assays were positive.
In addition, the company reported that an in vitro chromosomal
aberration study had been conducted and foun~to be negative (the
company did not include a copy of the final report from this par-
ticular study in its submission). Total petroleum, Inc. reported
by phone that the tested mineral seal oil is a hydrodesulfurized
middle (petroleum) distillate (CAS No. 64742-80-9). In addition,
it should be noted that Total pe troleum, Inc. obtained the sub-
mitted study reports from the Pennzoil Products Company for whom
the studies had been conducted by a contract laboratory.
Submission Evaluation
The subject mineral seal oil (as an emulsion) was assayed only in
Salmonella typhimurium (bacteria) strain TA98 in the presence of
exogenous metabolic activation. A 2-3 fold increase in revertant
frequencies over background was found at almost all doses tested
regardless of the type of emulsifier used (10% F68 pluronic or
10% Tween 80). The provided data show that this mineral seal oil
was mutagenic under the conditions of the performed Ames assay.
With regard to the in vitro BALB/c-3T3 mouse cell transformation
assay, the mineral seal oil was tested as an emulsion in culture
medium containing 1% F68 pluronic. Based on the provided data,
the mineral seal oil was weakly active in this assay. Further,
it is unlikely that the observed activity was due to either the
F68 pluronic emulsifier or the relatively high concentrations of
mineral seal oil tested (indicated by the lack of cytotoxicity).
::===================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
261
-------
8EHQ-0786-06l0
Page 2 of 3
Current production and Use
According to the printed version of the initial TSCA Chemical
Substance Inventory, CAS No. 64742-80-9 is a complex combination
of hydrocarbons obtained from a petroleum stock by treating with
hydrogen to convert organic sulfur to hydrogen sulfide which is
removed; it consists of hydrocarbons having numbers predominantly
in the range of Cll to C25 and boiling in the range of approxi-
mately 205°C to 400°C (401°F to 752°F).
A review of the production range (includes importation volumes)
statistics for CAS No. 64742-80-9, which is listed in the initial
TSCA Chemical Substance Inventory, shows that over one bill ion
pounds were reported as manufactured and/or imported in 1977.
This production range information does not contain any },)roduc-
tion/importation range data claimed as TSCA Confidential Business
Information (TSCA CBI) by those persons reporting for the initial
TSCA Inventory, nor does it include any information that would
compromise TSCA CBI. All of the data submitted 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).
Total petroleum, Inc. did not provide any information on the
specific use(s} of this mineral seal oil nor was such information
located in the secondary literature sources consulted by EPA.
Comments/Recommendations
Although a positive in vitro genotoxicity test finding, when
considered by itself, may not be sufficient to offer reasonable
support for a conclusion of substantial risk (as 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 a finding is
of value in assessing the possible risks posed by exposure to the
tested chemical substance or mixture. Also, EPA believes that a
positive genotoxicity test result, in combination with additional
relevant information (e. g., the knowledge of potential exposure
to and/or high production of the subject chemical or mixture),
would suggest, in many cases, the need to conduct other studies
designed to define better the toxicity of or the exposure to that
chemical or mixture. The results of such additional tests should
be considered also for submission to EPA pursuant to Section 8(e}
of TSCA.
It should be noted that EPA's Office of Toxic Substances (OTS)
previously received and evaluated a TSCA Section 8(e) submission
on another mineral seal oil. In 8EHQ-0683-0480 et seq., Exxon
Company, U.S.A. reported that benign and malignant skin tumors
were found in a chronic mouse skin painting study of a chemically
neutralized middle (petroleum) distillate (CAS No. 64742-30-9).
262
-------
8EHQ-0786-06l0
Page 3 of 3
It should be noted also that OTS has received and evaluated many
TSCA Section 8 (e) and" For your Information" (FYI) notices con-
cerning petroleum, shale, and coal oils and process streams.
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will ask
Total Petroleum, Inc. to provide to EPA a complete copy
of the final report (including the actual experimental
protocol, data, etc.) from the chromosomal aberration
assay cited in the company's Section 8(e) submission.
In view of EPA' s general interest in corporate actions
taken on a voluntary basis in response to chemical toxi-
city or exposure data, Total petroleum, Inc. will be
requested to describe the actions the company has taken
or is planning to take to l) notify workers and others
about the reported toxicologic findings, and 2) reduce
or eliminate exposure to Total's mineral seal oil. In
addition, Total petroleum, Inc. will be requested to
describe the nature and results, if available, from all
studies (other than those submitted already to EPA or
those published in the open scientific literature) about
which the company is aware or that the company has con-
ducted, is conducting, or plans to conduct to determine
ei ther the toxici ty of or the exposure to this mineral
seal oil.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of the subject mineral seal oil.
c)
The Chemical Screening Branch will send copies of this
status report to OSHA, NIOSH, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, OAR/EPA, ORD/EPA, and OPP/OPTS/EPA. Copies of
this report will be sent also to the TSCA Assistance
Office (TAO/OTS/OPTS/EPA) for further distribution.
263
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 3
DATE:
/1LG I 3 1986
~ytf(,
SUBJECT: Status Report* 8EHQ-0786-06ll S APproved~
FROM:James F. Darr, Section Head ktrJ;:rvz.-
Chemical Risk Identificatio9 Section/CSB
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Hote
(See Note on Page 3 of this status report)
The submi tting company has claimed its company name to be TSCA
Confidential Business Information (TSCA CBI). The Information
Management Division (IMD/OTS) will request the submitting company
to substantiate this TSCA CBI claim.
Submission Description
The submitting company reported that it learned recently (via a
private communication) about the as yet unpublished results of a
clinical study involving 8 ethylene oxide-exposed workers and 8
matched control workers. According to the submitter, the study
had been conducted independently by scientists at the University
of Cal ifornia I s San Francisco General Hospi tal. The submitter
stated further that the performed study included central and per-
ipheral nervous system function tests designed to detect possible
neurotoxicity. The submitter stated also that the investigators
conducted a computerized psychometric test battery, nerve conduc-
tion studies, P-300 event potentials, EEG spectral analyses, and
neurolog ical and phys ical examinations. Finally, the submi tter
prov ided the following informa tion wi th regard to the primary
investigator's statements about the study findings which are
expected to appear soon in the published scientific literature:
"The findings of [the performed] study suggest
that in addition to the well documented peripheral
neuropatholog ical manifestations [associated] wi th
chronic [exposure to] ethylene oxide, there are subtle
central nervous dysfunctions which may result from
chronic low level exposure [to the chemical]. These
effects may occur at exposure levels believed to be
historically common to hospital sterilizing operations."
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
264
-------
8EHQ-0786-0611 S
Page 2 of 3
Submission Evaluation
Although the conducted tests are of the type that would allow for
detection of CNS dysfunction (including subtle changes), further
information concerning the conduct and resul ts of the performed
tests is necessary in order for EPA to evaluate properly the
overall significance of the reported findings. (In its Section
8(e) notice, the submitting company provided the name and address
of the primary investigator in order for the Agency to contact
the investigator directly for additional information pertaining
to the conduct and results of the performed tests.)
Immed iately upon EPA' s rece ipt of this submiss ion, the Chemical
Screening Branch (CSB/ECAD/OTS/OPTS/EPA) provided copies of the
notification to the Occupational Safety and Health Administration
(OSHA), National Institute for Occupational Safety and Health
(NIOSH), Food and Drug Administration (FDA) and EPA' s Office of
pesticide Programs (OPP/OPTS/EPA). It should be noted that on
June 22, 1984, OSHA promulgated (49 FR 25734) a final standard
for occupational exposure to ethylene oxide (permissible Exposure
Level (PEL) = 1 part per mill ion (ppm) as an 8 hour Time i-Je i9h ted
Average (TWA).
Current Production and Use
According to Chemical & Engineering News (July 9, 1986 issue),
approximately 5.7 billion and 5.8 billion pounds of ethylene
oxide were produced in the U.S. in 1984 and 1985, respectively.
Ethylene ox ide is used mainly as a chemical intermed ia te (e. g. ,
in the production of ethylene glycol) and as a chemosterilant/
fumigant (e.g., medical and surgical equipment/devices, packaging
materials, dried foods). According to staff of EPA's Office of
Pesticide Programs (OPP/OPTS/EPA), ethylene oxide is present as
the active ingredient in 38 pesticide products registered under
the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA).
Comments/Recommendations
It should be noted that EPA's Office of Toxic Substances (OTS)
has received a number of Section 8(e) and "For Your Information"
(FYI) notices on ethylene oxide. Further, the Chemical Screening
Branch prepared a Chemical Hazard Information profile on ethylene
oxide in 1982. In addition, OTS has promulgated Section 8(a) and
8(d) information reporting rules on ethylene oxide.
a)
The Chemical Screening Branch vlill attempt to obtain
further information concerning the conduct and resul ts
of the reported studies directly from the investigator.
265
-------
8EHQ-0786-0611 S
Page 3 of 3
b)
The Chemical Screening Branch will review the reported
findings in order to determine the need for further OTS
assessment of ethylene oxide or possible inclusion of
the reported findings into any ongoing EPA and/or other
Federal agency assessments of the potential risks posed
by exposure to ethylene oxide.
c)
The Chemical Screening Branch will send copies of this
status report to OSHA, NIOSH, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, OAR/EPA, ORD/EPA and OPP/OPTS/EPA. Copies of
this status report will be provided also to the TSCA
Assistance Office (TAO/OTS) for further distribution.
Note
In a letter dated August 14, 1986 (8EHQ-0886-0611 FLWP Seq. B),
the Union Carbide Corporation stated that the company no longer
wished to maintain its company name as TSCA CBI.
~
/V~1// f~
266
-------
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
Page 1 of 3
DATE:
AUG 2 0 1986
status Report* 8EHQ-0786-06l2 Approved :~
James F. Darr, Section Head ~,., i: o;:~
Chemical Risk Identification Section/CSB
rip /rt.
UBJECT:
FROM:
TO:
Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OT8/0PTS
Submission Description
ALCOLAC has reported that the company recently received a letter
from an English physician who provided the following information
regarding diallyl maleate (CAS Number: 999-21-3):
" [The physician has] just seen a patient with
dermatitis and the clinical picture suggests that he may
have become sensitized to the above chemical. From the
literature and. . . [ALCOLAC's diallyl maleate Material]
Safety Data Sheet, it is clear that the chemical is a
primary irritant both in the experimental animal and
man. 'I'here is no information with regard to its skin
sensitization properties. . . ."
Submission Evaluation
In order for EPA to evaluate the significance of the reported
finding, additional information would be needed (e.g., duration
of exposure(s), route(s) of exposure(s), time to onset of the
symptoms, results of clinical chemistry tests that may have been
perforraed, employment history includ ing previous or concomi tant
exposure(s) to other chemical substanCes).
:===================================================================================
*
NOTE: This status report ;s the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
267
-------
8EHQ-0786-0612
Page 2 of 3
Current Production and Use
A review of the production range (includes importation volumes)
statistics for diallyl maleate (CAS Number: 999-21-3), which is
1 isted in the ini tial TSCA Chemical Substance Inventory, shows
that 110 thousand to 1.1 million pounds were reported as manufac-
tured and/or imported in 1977. This production range information
does not include any information claimed as TSCA Confidential
Bus iness Informa tion (TSCA CBI) by the person ( s) reporting for
the ini tial TSCA Inventory nor does it include any information
that would compromise TSCA CBI. All information reported for the
initial TSCA Inventory, including the production range data, is
subject to the limitations that are contained in the initial TSCA
Inventory Reporting Regulations (40 CFR 710).
ALCOLAC did not provide any information concerning the spec i f ic
use (s) of d iallyl maleate. According to secondary 1 i tera ture
sources, diallyl maleate is a monomer used in the production of
certain polymers/copolymers and certain insecticides.
Comments/Recommendations
In its submission, ALCOLAC reported that the company has asked
the English physician for additional details on the reported case
of sensitization and to keep the company apprised of all further
developments with regard to this case.
Based on EPA's initial review of the summarized information as
presented in ALCOLAC's submission, it is not entirely clear that
the information provided by the company is of the type required
for submission to EPA under Section 8 (e), the substantial risk
informa tion reporting provision of TSCA. It is quite probable,
on the other hand, that the subject information is of the type
required to be maintained by ALCOLAC under the Section 8 (c) man-
datory recordkeeping provision of TSCA. On August 22, 1983, the
Agency published (48 FR 38178) a final rule that required full
compliance with TSCA Section 8(c) as of November 21, 1983. In
general, the final TSCA Section 8(c) rule requires chemical manu-
factures, importers, and certain processors to maintain records
of significant adverse reactions alleged to have been caused by
TSCA-covered chemical substances or mixtures. The final TSCA
Section 8(c) rule also requires that allegations involving sig-
nificant adverse reactions in employees be kept for 30 years and
that all other allegations be kept for 5 years. It should be
noted that EPA is empowered to both inspect and require the sub-
mission of Section 8 (c) records. On several occasions to date,
EPA has required certain chemical companies to submit their TSCA
Section 8(c) records on specific chemical substances of concern
to the Agency.
268
-------
8EHQ-0786-0612
Page 3 of 3
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will ask
ALCOLAC to ensure that the Agency is apprised in a time-
ly manner about all further information received by the
company concerning this case.
In view of EPA's general interest in corporate actions
taken on a voluntary basis in response to chemical toxi-
city or exposure data, ALCOLAC will be asked to describe
the actions the company has taken or plans to take to 1)
notify workers and others about the reported findings,
and 2) reduce or eliminate exposure to diallyl maleate.
In addi tion, ALCOLAC will be requested to describe the
nature and results, if available, of all studies (other
than those reported already to EPA or those published in
the open scientific literature) about which ALCOLAC is
aware or that ALCOLAC has conducted, is conducting, or
plans to conduct to determine the toxici ty of or the
exposure to diallyl maleate.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of diallyl maleate.
c)
The Chemical Screening Branch will send copies of this
status ret-'ort to NIOSH, OSHA, CPSC, FDA, NTP, OS\~ER/EPA,
OH/EPA, OAR/EPA, ORD/EPA, and to OPP/OPTS/EPA. Copies
of this status report will be provided also to the TSCA
Assistance Office (TAO/OTS) for further distribution.
269
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 4
DATE:
AUG I 9 1986
SUBJECT, Status Report' 8EHQ-0786-0613 S ADPrDved:~ 'lJJ.I/'t1<>
FROM: James F. Darr, Section Head Ck""""L') t ~
Chemical Risk Identificatiort7~~~tion/CSB
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Note
(See Note on Page 4 of this status report)
The CIBA-GEIGY Corporation has claimed the exact identity of the
tested chemical as TSCA Confidential Business Information (TSCA
CBI). The Information Management Division (IMD/OTS) will request
the company to substantiate this confidentiality claim. In its
submission, CIBA-GEIGY provided the following non-confidential
generic name for the chemical: "heterocyclic thiophosphate."
Submission Description
The CIBA-GEIGY Corporation submitted copies of the final reports
from a wide variety of in vitro and in vivo genotoxicity assays
of a heterocyclic thiophosphate. In summary, the tests included
1) several Ames Salmonella typhimurium (bacteria) mutagenicity
assays conducted with exogenous or host-mediated metabolic acti-
vation, 2) an in vitro L5178Y/TK% mouse cell mutagenicity assay,
3) DNA repair assays in cul tured hw-nan fibroblasts or cul tured
rat hepatocytes, 4) a Saccharomyces cerevisiae (yeast) cell/mam-
malian microsome mutagenicity assay, 5) a cell transformation
assay in cultured BALB/c-3T3 mouse cells, 6) a Sister Chromatid
Exchange (SCE) assay in Chinese hamster bone marrow cells, 7) a
nucleus anomaly assay in Chinese hamster bone marrow cells, and
8) a dominant lethal study in mice. CIBA-GEIGY reported that in
summary the provided results "indicate that the compound is posi-
tive in several short-term in vitro assays for mutagenic activity
but is negative when testedfor mutagenic activity in vivo."
In addi tion to submi tting the genotoxicity findings, CIBA-GEIGY
reported that to help clarify the significance of the observed
pos i tive in vi tro mutagenici ty resul ts, this heterocyclic thio-
phosphatels now being studied "in a number of other toxicity
tests, including lifetime dietary and oncogenicity studies in the
mouse and rat."
------------------------------------------------------------------------------------
------------------------------------------------------------------------------------
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
270
-------
8EHQ-0786-0613 S
Page 2 of 4
Submission Evaluation
Three separate Ames tests were performed each usin~ strains TA~8,
TAIOO, TA1535 and TA1537 with and without exogenous metabolic
activation. The top concentration used in any of the assays \vas
6250 ug/plate. The obtained data show that the subject chemical
induced the mutant frequency in strain TAIOO to over 2 times the
background at the higher concentrations used. This response was
seen both wi th and wi thout exogenous metabolic activation. (The
third assay was performed several years prior to the other two
and did not have high enough test ma terial concentrations which
may explain the observed negative finding.) The subject chemical
was negative in the other strains with and without activation in
all assays. Overall, the test chemical induced activity in TAIOO
to over 2 times background both with and without exogenous meta-
bolic activation.
Two separate host-mediated assays were conducted in male albino
mice with Salmonella typhimurium strains TA98, TAIOO, TA1535 and
TA1537 as indicator organisms. In the first trial of the first
assay, a slight but significant increase in mutant frequency with
TA98 at the top dose was observed (400 mg/kg; gavage; one admini-
stration) . However, this was not repeatable in the second trial
or in the second assay performed at higher doses. The several
animals that died during the experiments indicate that adequate
toxici ty was probably attained. It should be noted, however,
that no details concerning these deaths were provided. Overall,
the subject chemical appears to be negative in these assays.
In the cultured L5178Y/TKI mouse lymphoma cell assay, the subject
chemical was tested at concentrations up to 700 ug/ml without ex-
ogenous metabolic activation and up to 100 ug/ml with activation.
These dose ranges produced adequate toxicities (10-20% survival).
There was an induced mutant frequency at one concentration (175
ug/ml; 4.7% survival) under non-activated conditions, but this
response was at a very high toxicity and was not subsequently
repeatable. Overall, the test substance appears to be negative
in this assay under the experimental conditions employed.
Two Unscheduled DNA Synthesis (UDS) assays were submi tted, one
conducted in cultured rat hepatocytes and the other in cul tured
human fibroblasts. The subject chemical induced concentration
dependent increases in UDS to 2.91 times background (net gain of
8.52 nuclear grains over vehicle control) in rat hepatocytes and
to 8.49 times background (net gain of 5.94 nuclear grains over
vehicle control) in human fibroblasts. These results indicate a
positive response in both assays.
In the Saccharomyces cerevisiae (yeast) strain D7 assay, mitotic
crossing over, mitotic gene conversion and mutation induction was
examined both wi th and wi thout exogenous metabolic activation.
The subject chemical induced a concentration dependent increase
in convertants without activation (up to the 400 ug/ml top con-
centration). Some inconsistent increases in revertants were seen
271
-------
8EHQ-0786-0613 S
Page 3 of 4
also in the three separate trials reported. Overall, the tested
chemical was active for gene conversion with metabolic activation
and it appears that added metabolic activation reduces this gene
conversion activity.
'l'wo separate trials were performed wi th the subject chemical in
the cult ureo BAL13/ c-3T3 mouse cell trans forma t ion assay. In the
first trial, increased transformation frequencies were observed
at all doses (up to 8.4 ug/ml). These increases were not sta-
tistically significant, however, due probably to abnormally high
solvent control values. In the second trial, a statistically
significant increased transformation frequency (with an apparent
dose-dependent trend) was observed at the top four concentrations
tested. Overall, the subject chemical appears to be positive in
the BALE/c-3T3 mouse cell transformation assay.
In the Sister Chromatid Exchange (SCE) assay, Chinese hamsters
were dosed orally to up to 134 m~/kg of the test chemical for a
24 hour exposure. Higher doses (268 mg/kg and greater) killed
the majority of the animals. In view of the fact that 147 mg/kg
was lethal to the animals in the nucleus anomaly test (described
in the follovving paragraIJh), an appropriate high dose may have
been used. There was no evidence of increase SCEs at any of the
doses used. However, no data were presented to indicate any pos-
sible adverse effect related to cell cycle.
In the nucleus anomaly test, Chinese hamsters were exposed orally
to up to 135 mg/kg of the test substance once daily for two days.
Several animals died at the top dose indicating adequate dosing
(147 mg/kg was a lethal dose). The surviving animals were sacri-
ficed 24 hours after the second dose. There was no evidence of
increased nucleus anomalies (e.g., Jolly bodies, micronuclei) in
any of the survivors. In light of the fact that only one time
point following the last dosing was examined, however, an effect
that may be either time dependent or cell cycle dependent cannot
be ruled out at this time. Evidence pertaining to the cell cycle
effects by the subject chemical may alleviate this inadequacy.
In the dominant lethal study, male albino mice were dosed orally
with either 120 mg/kg or 360 mg/kg of the test substance and then
mated to females (3 females/week) over a 6 week period. There
were no apparent effects on pre-implantation 105s or on embryonic
deaths. It should be noted, however, that there were no signs of
toxicity reported in the dosed males, which indicates that higher
doses could have been used in this assay to determine possible
dominant lethal effects.
In conclusion, the results for any individual genotoxicity assay
are either negative or moderately positive. Due to the positive
responses observed in several of the performed assays, however,
this heterocyclic thiophosphate appears to possess an intrinsic
genotoxic activity, albeit not an overwhelming activity.
272
-------
8EHQ-0786-0613 S
Page 4 of 4
Current Production and Use
According to CIBA-GEIGY, the subject chemical "is a research and
development compound be ing inves t iga ted solely for pest ic id al
purposes." CIBA-GEIGY reported further that.. these evaluations
are being conducted under the supervision of technically quali-
fied personnel, knowledgeable in handling potentially hazardous
chemicals."
CommentsjRecommendations
In its Section 8(e) notice, CIBA-GEIGY reported that the company
plans to 1) submi t to EPA copies of the final reports from the
ongoing stud ies, 2) not ify all persons working with the subj ec t
chern ical about the submi t ted tox icolog ic find ings, and 3) label
the chemical to reflect the reported findings.
a)
The Chemical Screening Branch (CSBjECADjOTS) will ask
CIBA-GEIGY to ensure that EPA is apprised about any
significant interim findings from the ongoing studies
ci ted in the submission. In addi tion, CIBA-GEIGY will
be asked to ensure that EPA receives full copies of the
final reports (including the actual experimental proto-
cols, results of gross and histopathologic examinations,
etc.) from the ongoing studies cited in the submission.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of this heterocyclic thiophosphate.
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, NTP, FDA, OSWERjEPA,
OWjEPA, ORDjEPA, OARjEPA, and OPPjOPTSjEPA. Copies of
this report will be provided also to the TSCA Assistance
Office (TAOjOTSjOPTS) for further distribution.
Note
In a letter dated October 7, 1986, (8EHQ-I086-0613 FLWP Seq. B),
CIBA-GEIGY reported that the company no longer wished to maintain
the specific identity of the subject chemical to be TSCA CBI.
According to the declassified version of the company's initial
Section 8(e) notice, the tested chemical is "O,O-dimethyl-S-(6-
chlor-oxazolo(4,5-b)pyridin-2(3H)-on-3-yl-methyl)-thiophosphate."
~
Iz/ ~V/ Y'(,p
273
-------
UNITED STATES ENV'IRONMENTAL PROTECTION AGE~CY
Page 1 of 3
DATE:
SEP I 5 1986
Status Report' 8EHQ-0786-0614 S Approved: &roj J;...// r A;;..'t.--
/ 9/15/86
James F. Darr, Section Head ~/J r a;-~
Chemical Risk Identification Section/CSB
SUBJECT:
FROM:
TO:
Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Note
The submi tting company has claimed its name and the name of the
company that performed the provided study to be TSCA Confidential
Business Information (CBI). In addition, the submitter claimed
the amounts of the individual components in the tested mixture as
TSCA CBI. The Information Management Division (IMD/OTS/OPTS/EPA)
will request the submitter to substantiate these TSCA CBI claims.
Submission Description
The submi tting company provided the final resul ts from a 2-year
oncogenicity study of a mixture of octyltin trichloride (CAS No.
3091-25-6) and dioctyltin dichloride (CAS No. 3542-36-7) in rats.
According to the submitted report, this mixture was administered
to groups of 120 Tif:RAlf(SPF) rats (60 males and 60 females per
group) at doses of 0, 5.0, 15, 50 and 150 parts per million (ppm)
in the feed. In addition, the submitted report states that the
"calculated mean daily intake based on the actual concentration
of [the test mixture] was approximately 0.24, 0.69, 2.2, and 5.5
mg/kg b.w. in males and 0.26, 0.74, 2.3, and 6.0 mg/kg b.w. in
females." The following information concerning the resul ts of
the study was presented in the" Conclusion" section of the sub-
mitted report:
"Under the conditions of this test, no relevant differences
were found between treated and control animals for mortality
distribution, clinical observations and examinations, body
and organ weights, food and water consumption, as well as in
hematology, except an increased number of white blood cells
in female groups treated with 50 and 150 ppm [of the test
mixture,] respectively.
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete jnformation.
274
-------
8EHQ-0786-0614 S
Page 2 of 3
"A significantly increased frequency of primary tumors of
the thymus, especially thymic lyrnpholhas, was noted in fe-
males treated wi th 150 ppm [of the test Iilixture]. Furthec,
an increased inc idence of general i zed mal ignant lymphorr,as in
[the] males of the upper dose levels and in [the] females of
the top dose group was observed. In [those] aniffials treated
at the low dose levels (5.0 and 15 ppm), no increase was ob-
served, either in the inc idence of lJr imary thymic tumors or
generalized malignant lymphomas."
Submission Evaluation
The provided information indicates that the tested mixture (or
one of its components) is oncogenic when administered chronically
in the feed of male and female rats. In order for the Agency to
evaluate the overall significance of the reported findings, how-
ever, the submi tting company should be requested to provide a
complete copy of the final report (including information such as
the survival data, "time to tumor" data, individual animal tumor
data, individual animal weight data, food consumption data, etc.)
from this 2-year feeding study in rats.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for octyltin trichloride (CAS NO. 3091-25-6) and di-
octyltin dichloride (CAS No. 3542-36-7), which are listed in the
initial TSCA Chemical Substance Inventory, has shown that no 1977
manufacture/ importation of these chemicals was reported or that
all manufacture and/or importation data reported were claimed as
TSCA CBI by the person(s) reporting for TSCA Inventory and cannot
be disclosed (Section 14(a) of TSCA, U.S.C. 2613(a)). All of the
data submitted for the initial TSCA Inventory, including the pro-
duction range data, are subject to the limitations contained in
the TSCA Inventory Reporting Regulations (40 CFR 710).
According to the submitting company, both octyltin trichloride
and dioctyltin dichloride "are present in tetraoctyltin as minor
ingredients in the intermediate stage of the manufacture of di-
octyltin stabilizers currently used for indirect food additives."
The submitting company stated also that octyltin trichloride is
present in "trace quantities" and that dioctyltin dichloride "is
present to a max imurn of 1.5%." The s ubIl1i t ting company reported
further that the company does export the chemicals for a "limited
number of non-food applications."
Comments/Recommendations
According to the submitter, the company that performed the 2-year
study has already notified the U. S. Food and Drug Administration
(FDA) about the results of the study.
275
-------
8EHQ-0786-06l4 S
Page 3 of 3
It should be noted that EPA's Office of Toxic Substances (OTS)
has rece ived a number of Section 8 (e) and" For Your Information"
(FYI) submissions on various organotin compounds. In addition,
staff of the Test Rules Development Branch (TRDB/ECAD/OTS) has
evaluated available toxicity and exposure information on several
alkyl tin compounds recommended to EPA by the Interagency 'resting
Commi t tee (ITC) for testing under Section 4 of TSCA. Further,
EPA has published TSCA Section 8(a) and (d) information reporting
rules on those alkyl tins considered for testing under Section 4
of TSCA.
a
The Chemical Screening Branch will request the submitter
to provide to EPA a complete copy of the final report,
including all experimental data (such as those listed in
the Submission Evaluation section of this report), from
this 2-year feeding study in rats.
In view of EPA' s general interest in company actions
that are taken on a voluntary basis in response to chem-
ical toxicity or exposure information, the submitting
company will be requested to describe the actions the
company has taken or plans to take to notify its workers
about the reported toxicologic findings. In addition,
the submitting company will be asked to describe the
nature and results, if available, of all studies (other
than those published in the open scientific literature
or those submi tted already to the Agency) about which
the company is aware or that the company has conducted,
is conducting, or plans to conduct to determine the tox-
icity of and/or the exposure to dioctyltin dichloride or
octyltin trichloride or to mixtures that contain these
chemical substances.
b
The Chemical Screening Branch (CSB/ECAD/OTS) will review
the submitted information in order to determine the need
for further OTS assessment of the subject organotin com-
pounds.
c
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, NTP, FDA, OSWER/EPA,
OW/EPA, OAR/EPA, ORD/EPA, OPP/OPTS/EPA and TRDB/ECAD/
OTS/OPTS/EPA. In addi tion, copies of this report will
be sent to the TSCA Assistance Office (TAO/OTS/OPTS/EPA)
for further distribution.
276
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page I of 2
DATE:
AJJJ I 9 1986
iUBJECT:
Status Report*
8EHQ-0786-0615
Approved:
(JJt- rfl1~
FROM: James F. Darr, Section Head ~3 I: /);;~
Chemical Risk Identificatiot1 Section/CSB
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
Texaco Inc. provided a copy of a report entitled "Mortality illaong
vJorkers at a 1,3-Butadiene Production Facility." According to
Texaco, the submi tted report is "based on a cohort T:lOrtal i ty
study of 2586 male employees at the [Port Neches, TX] facilities
of [the] Neches Butane Products Company, a subsidiary of [the]
Texaco Butadiene Company." Texaco reported further that the sub-
ject epidemiologic study" is important because this plant is the
monomer-prod uc ing fac il i ty in a complex of plants incl ud ing two
styrene/butadiene rubber (SBR) production units" at which the
National Institute for Occupational Safety and Health (NIOSH) had
previously conducted a cohort mortali ty study. Texaco provided
the following information concerning the submitted report:
"The authors [of the study] noted increased standardized
mortality ratios (SMR's) for lymphosarcoma and reticulum
cell sarcoma which were statistically significant when
compared with the U.s. population but not [statistical-
ly] significant when compared to a local seven-county
population. In addition, there were elevated SMR's for
other lymphatic cancers which did not correlate with ex-
posure to butadiene. For these reasons, the authors of
the study stated that nothing conclusive can be stated
concerning an association between butadiene exposure and
any of these diseases."
Submission Evaluation
Immediately upon EPA's receipt of the submitted information, the
Chemical Screening Branch (CSB/ECAD/OTS/OPTS) sent copies to the
Occupational Safety and Heal th Administration (OSHA), National
Institute for Occupational Safety and Health (NIOSH), Office of
Air and Radiation (OAR/EPA), Exposure Evaluation Division/OTS,
Chemical Control Division/OTS and Risk Analysis Branch/ECAD/OTS
for inclusion in any ongoing 1,3-butadiene assessments.
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
277
-------
8EHQ-0786-0615
Page 2 of 2
Current production and Use
A review of the production range (includes importation volumes)
statistics for 1,3-butadiene (CAS No. 106-99-0), which is listed
in the initial TSCA Chemical Substance Inventory, has shown that
between 2.1 billion and 7.3 billion pounds were reported as manu-
factured/ imported in 1977. This production range information
does not include any data claimed as TSCA Confidential Business
Information (TSCA CBI) by the person(s) reporting for the initial
TSCA Inventory, nor does it include any information that would
comfJromise TSCA CBl. All of the data reported for the ini tial
TSCA Inventory, including the production range data, are subject
to the limi tat ions contained in the TSCA Inventory Reporting
Regulations (40 CFR 710).
According to secondary Ii terature sources, the primary use of
1,3-butadiene is as a raw material in the manufacture of syn-
thetic rubber and fibers. According to the June 9, 1986, issue
of Chemical & Engineering News, 2.45 and 2.53 billion pounds of
rubber grade 1,3-butadiene were produced in the U.S. in 1984 and
1985, respectively.
Comments/Recommendations
EPA's Office of Toxic Substances (OTS/OPTS/EPA) has received and
evaluated several TSCA Section 8 (e) and" For Your Information"
( FYI) notices on 1, 3-bu tad iene. Also, the Chemical Screening
Branch (CSB/ECAD/OTS) did prepare (in 1981) a Chemical Hazard
Information Profil.e (CHIP) on this chemical. EPA's Office of
Pesticides and Toxic Substances (OPTS/BPA), via Section 9 of TSCA
on October 10,1985 (50 FR 41393), referred 1,3-butadiene to OSHA
for regulation of workplace ex~osure. Further, the Office of Air
and Radiation (OAR/EPA) has published an .. intent to list" 1,3-
butadiene as a hazardous air pollutant under the Clean Air Act.
a)
'I'he Chemical Screening Branch will transmi t copies of
this status report to OSHA, NIOSH, CPSC, FDA, NTP,
OSvmR/EPA, OW/EPA, OAR/EPA, ORD/EPA, OPP/OPTS/EPA, EED
and CCD/OT3/0PTS/EPA, and RAB/ECAD/OTS/OPTS/EPA. Copies
of this report will be sent also to the TSCA Assistance
Office (TAO/OTS) for further distribution.
278
-------
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
Page 1 of 3
DATE:
AUG 2 6 1986
,UBJECT:
status Report* 8EHQ-0786-0616 Approved: ~
James F. Darr, Section Head ~-:) r a;-"1J"1.,,--
Chemical Risk Identification Section/CSB
~/~
FROM:
TO:
Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
R. T. Vanderbilt Company, Inc. provided the following summarized
information concerning the conduct and preliminary results of an
acute inhalation toxicity study of copper dimethyldithiocarbamate
(CAS No. 137-29-1) in rats:
"Groups of five male and five female Sprague-Dawley rats
(approximately 230-280 grams) were exposed to atmospheres
of copper dimethyldithiocarbamate dust for four hours. Six
exposure levels were used (0.052 - 2.98 mg/L) and in all
cases approximately 90 percent of the particles were less
than 5.5 microns.
"Signs noted during exposure at all levels comprised slow
irregular respiratory patterns, hunched appearance, and
closed eyes. The incidence and severity of these signs was
broadly exposure-level related. A no-effect-level was not
determined.
"All rats exposed to levels of 0.21 mg/L and above died
within 2 - 24 hours. No deaths occurred at 0.052 mg/L and
nine rats are expected to survive at 0.068 mg/L.
"Survivors at the two lower levels lost weight through day
3 but subsequently showed normal bodyweight increments.
Survivors were essentially asymptomatic from day 2 onwards
and there was no evidence of any delayed or residual path-
ology at sacrifice on day 14 (0.052 mg/L).
"The LC50 is estimated to be in the range of 0.08 - 0.12
mg/L and will be calculated more precisely when the study
is complete."
:::==== == = == == == == == = = = = = == ===:; = = = = = = = = = = = = = = = ===== = ==== ===== ==== == ====== = = ==== == == ===
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e). the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
279
-------
8EHQ-0786-06l6
Page 2 of 3
In its submission, R. T. Vanderbilt reported that this study had
been conducted in England and co-sponsored by R. T. Vanderbilt,
the pennwalt Corporation, and several un-named foreign companies.
Submission Evaluation
In order for the Agency to evaluate the overall significance of
the reported toxicologic findings, a complete copy of the final
report (including the actual experimental protocol, resul ts of
gross and histopathologic examinations, etc.) from the cited
acute inhalation study should be requested from the submitter.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for copper dimethyldithiocarbamate (CAS 137-29-1),
which is listed in the initial TSCA Chemical Substance Inventory,
has shown that no 1977 manufacture or importation was reported or
that all of the production range information reported was claimed
to be TSCA Confidential Business Information (TSCA CBI) and can-
not be disclosed (see Section 14(a) of TSCA; D.S.C. 2613(a)).
All of the information reported for the initial TSCA Chemical
Substance Inventory, including the production range information,
is subject to the limitations that are contained in the TSCA
Inventory Reporting Regulations (40 CFR 710).
In its Section 8(e) submission, R. T. Vanderbilt provided the
following informa tion wi th regard to worker exposure to copper
dimethyldithiocarbamate:
"At R. T. vanderbilt, worker exposure to airborne [copper
dimethyldithiocarbamate] powder is not expected. The com-
ound is manufactured in an automatic system, wherein the
powder is compounded with binders and converted to rod-
form. A small percentage of the powder is treated wi th
an ti-dusting oil before drying and grinding. pr ior to
conversion to the automatic system, the material was manu-
factured by a batch type method since 1950. NO complaints
as a result of exposure to the material have been received
during more than three decades of manufacture. Because of
the special treatment of the material, the risk of expo-
sure to airborne [copper dimethyldithiocarbamate] dust
should be minimal wi thin the manufacturing facili ty as
well as in the processing plant."
R. T. Vanderbilt did not submit any information regarding the use
of copper dimethyldithiocarbamate. According to secondary liter-
ature sources, this chemical is used primarily as an accelerator
for styrene/butadiene rubber (SBR).
280
-------
8EHQ-0786-0616
Page 3 of 3
Comments/Recommendations
It should be noted that EPA' s Of f ice of 'l'oxic Substances (OTS)
has received several "For Your Information" (FYI) submissions on
zinc dimethyldithiocarbamate, a rubber accelerator and fungicide
for fruits and vegetables. In addition, the Chemical Screening
Branch (CSB/ECAD/OTS) did prepare (in 1983) a Chemical Hazard
Information Profile (CHIP) on zinc dimethyldithiocarbamate. zinc
dimethyldithiocarbamate was selected for CHIP preparation on the
basis of a National Toxicology Program (NTP) study that shmled
carcinogenic effects on the male rat thyroid following chronic
oral administration of the chemical. The Risk Analysis Branch
(RAB/ECAD/OTS) has been evaluating available toxicologic and
exposure infonnation on zinc dimethyldithiocarbamate.
a) The Chemical Screening Branch (CSB/ECAD/OTS) will request
R. T. Vanderbilt to submit to EPA a com~lete copy of the
final report (including the actual experimental protocol,
resul ts of gross and histopatholog ic examinations, etc.)
from the co-sponsored acute rat inhalation toxicity study
cited in the company's subwission.
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, R. T. Vanderbilt will be asked
to describe the actions the company has taken or plans to
take to notify workers about the reported toxicologic
findings. In addition, R. T. Vanderbilt will be asked to
describe the nature and resul ts, if available, from all
studies (other than those submitted to the Agency already
or those cited in the open scientific literature) about
which R. T. Vanderbilt is aware or that the company has
conducted, is conducting, or plans to conduct to determine
the toxicity of or the exposure to copper dimethyldithio-
carbamate.
b) The Chemical Screening Branch will review the reported
information in order to detennine the need for further OTS
assessment of copper dimethyldithiocarbmoate.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OvijEPA, OAR/EPA, ORD/EPA, and OPP/OPTS/EPA. In addition,
copies of this status report will be provided to the TSCA
Assistance Office (TAO/OTS/OPTS) for further distribution.
281
-------
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
Page 1 of 2
DATE:
N.SISI9E
SUBJECT:
status Report*
8EHQ-0786-0617
Approved:
;1fr- 8k~/Yb
,
FROM:
James F. Darr, Section Head ~ r ~V1.-
Chemical Risk Identification Section/CSB
TO:
Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Union Carbide Corporation submitted information concerning an
"emergency incident of environmental contamination" (ECIC) that
occurred at 10:00 A.M. on July 9, 1986 at Conrail's railroad yard
located in Port Reading, New Jersey. According to Union Carbide,
the incident occurred when two tank cars, one containing ethanol
(CAS No. 64-17-5) and the other containing butyraldehyde (CAS No.
123-72-8), were punctured by the shelf couplers as the cars were
being humped. Union Carbide reported further that personnel from
the company's "HELP" team "went to the scene of the incident to
give necessary aid in containment, clean-up, and removal." Union
Carbide also provided the following details of the incident:
"The chemicals were contained wi thin the railroad yard,
vapors were held down, no evacuation took place, nor
were any exposures reported. [The] estimated loss of
butyraldehyde was 25,000 gallons, and [the] estimated
loss of ethanol was 18,000 gallons; both liquid releases
were to the ground. The spill was contained by use of
soda ash and, at the time of submission of this [written
Sect ion 8 (e) ] report, final clean-up of the spill was
taking place. Since the time of the inc iden t, Union
Carbide has received no reports of adverse ecological or
environmental effects, or of health effects resul ting
from the chemicals. .... The decision to notify the
. . [the Agency's Region II Office by phone on the day
of the incident] was made at the time the leakage was
occurring, at which time it was not possible to know if
adverse effects would or would not result."
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provis1on of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
282
-------
8EHQ-0786-0617
Page 2 of 2
comments/Recommendations
Immediately upon receipt of this TSCA Section 8(e) submission,
staff of the Chemical Screening Branch (ECAD/OTS/OPTS/EPA) sent
copies of the submission to EPA's Region II Office and to EPA's
Off ice of Sol id Waste and Emergency Response (OSHER/EPA).
a)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, OSWER/EPA, OW/EPA, OAR/EPA
and to EPA's Region II Office. In addition, copies of
this report will be sent to the TSCA Assistance Office
(TAO/OTS/OPTS) for further distribution
283
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 2
DATE:
~251986
SUBJECT:
Status Report* 8EHQ-0886-06l8 S Approved :(;/t-
James F. Darr, Section Head (a.~;) f lJ;:-'1I1..--
Chemical Risk Identificatio~~ection/CSB
1u /t~
FROM:
TO:
Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Note
The submi tting company has claimed its company name to be TSCA
Confidential Business Information (TSCA CBI). The Information
Management Division (IMD/OTS) will request the submitting company
to substantiate this TSCA CBI claim.
Submission Description
The submi tting company provided the following inforrna tion wi th
regard to the inhalation toxicity of certain cadmium compounds:
"It has come to. . [the submi tting company's] attention
from a phone conversation with the Fraunhofer Institute of
Aerosol Research and Toxicology in Hannover, West Germany,
that add i tional pre 1 imina ry study res ul ts have recently
become available concerning the inhalation toxicity of
cadmium compounds. These results, which are currently be-
ing presented at a toxicology meeting in Japan, indicate
that lung tumors have been observed in rats following ex-
posure to cadmium compounds other than cadmium chloride.
It is bel ieved these compounds are cadmi urn oxide, cadwi urn
sulfate, and cadmium sulfide. The inhalation regimen in-
volved exposures of about 20 hours/day, 7 days/week for 18
months. Previous results indicate that lung tumors have
not been seen in mice or hamsters."
Submission Evaluation
Complete copies of the actual experimental protocol (s), resul ts
of gross and histopathologic examinations, etc. are needed in
order for the Agency to evaluate the overall significance of the
reported oncogenicity findings.
------------------------------------------------------------------------------------
------------------------------------------------------------------------------------
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
284
-------
8EHQ-0886-06l8 S
Page 2 of 2
current proauction and Use
A rev iew of the produc tion range (incl udes importation volumes)
statistics for the sUbJect cadmium compounds, which are listed in
the initial TSCA Chemical Substance Inventory, shows that the
following amounts (pounds) were reported as manufactured and/or
imported in 1977:
CHEHICAL NAME CAS NO. PRODUCTION RANGE
Cadmium Oxide 1306-19-0 2.72 million to 27.2 million
Cadmi um Sulfide 1306-23-6 464 thousand to 4.65 million
Cadmi urn Sulfate 10124-36-4 232 thousand to 2.32 million
(Note: The above production range informa tion does not include
any data claimed as TSCA Confidential Business Information (TSCA
CBI) by the person( s) reporting for the ini tial TSCA Inventory,
nor does it include any data that would compromise TSCA CBI. All
data reported for the initial TSCA Inventory, including the pro-
duction range data, are subject to the 1 imi ta tions contained in
the initial TSCA Inventory Reporting Regulations (40 CFR 710).)
According to secondary literature sources, the cadmium compounds
cited above are used in a wide variety of industrial, pesticidal,
medicinal and/or veterinary applications.
Comments/Recommendations
EPA's Office of Toxic Substances (OTS) has received several TSCA
Section 8 (e) and" For Your Information" (FYI) notices on cadmi urn
compounds. In addi tion, a number of EPA Program Offices as well
as other Federal agencies have assessed or are in the process of
assessing the potential risks posed by exposure to cadmium and
cadmium compounds. Also, the International Agency for Research
on Cancer (IARC) has published two "Honographs" (1972 and 1976)
on cadmium and cadmium compounds.
a) The Chemical Screening Branch (CSB/ECAD/OTS) will ask the
submitting company to provide additional information that
would allow EPA to obtain further information about and/or
evaluate the significance of the reported findings.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further OTS
assessment or referral of the information to another EPA
Off ice or other Federal agency for cons idera tion in any
ongoing assessment of cadmium and cadmium compounds.
c) The Chernical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, OAR/EPA, ORD/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.
285
-------
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
Page 1 of 9
DATE:
U 19116
APproved/:/Pn f/l3/rt
r /
SUBJECT:
status Report* 8EHQ-0386-06l9
8EHQ-0586- 0619 FLWP
Frank D. Kover, Chief ~~ 0 ~
Chemical Screening Branc~;~AD
/' /'
;' /
! /
'-./
FROM:
TO:
Joseph J. Merenda, Director
Existing Chemical Assessment DivisionjOTS
Submission Description
On a IIFor Your Informationll basis (FYI-OTS-0386-0486 Initial),
the Monsanto Company provided the following information with
regard to the conduct and preliminary findings from a recently
completed intrapleural implantation study of calcium sodium
metaphosphate (CAS No. 23209-59-8) fibers in rats:
IIIn this test,. . . [calcium sodium metaphosphate] fibers
in gelatin pledgets were surgically implanted in the
pleural space of experimental rats. Each of 3 groups
consisted of approximately 75 males and 75 females at
the outset; sub-groups of 5 males and 5 females from
each group were sacrificed at 6, 12, and 18 month inter-
vals. No [calcium sodium metaphosphate] fiber-induced
fibrosarcomas were detected at these interim periods.
After the final sacrifice at 24 months, 3 of [the] 120
[calcium sodium metaphosphate fiber-exposed] animals had
fibrosarcomas. Also, at the final sacrifice in the posi-
tive control group, in which chrysotile asbestos had
been implanted, 5 of 121 animals had fibrosarcomas. In
the negative control group, no fibrosarcomas were ob-
served.1I [Note:, Monsanto reported by phone that gelatin
pledgets were surgically implanted in the pleural space
of the negative control rats.]
In the ini tial FYI submiss ion, Monsanto provided the following
comments with regard to evaluating the reported results:
liThe finding of pleural
(grea ter than 8 microns),
fibers were present in the
vitroll testing results has
hypothesize that phosphate
through enzymatic activity.
sarcomas means that long
thin (less than 1 micron)
pleural space. pr ior II in
led [Monsanto] to
fiber would biodegrade
------------------------------------------------------------------------------------
------------------------------------------------------------------------------------
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
286
-------
Page 2 of 9
"It is . . . [Monsanto's] opinion that the gelatin matrix
decreased the rate of dissolution and biodegradation of
the phosphate fiber due to chemical interaction with the
matrix.
"The incidence of pleural sarcomas seen in the phosphate
fiber study group approximated historical background
levels and was low compared to [the] res ul ts reported
for other fibrous materials. These results could
well reflect the biodegradability of the phosphate fiber
despite any reaction with the gelatin matrix.
"The tissue responses seen in the present study wi th
phosphate fiber were significantly different from those
observed wi th asbestos. [The] phosphate fiber produced
a very cellular, granulomatous reaction indicative of an
inflammatory response, while asbestos produced an
acellular lesion with a high collagen content."
In its initial FYI submission, Monsanto stated also that there is
a study now underway in which rats (80 rats/sex/exposure group)
are being exposed by inhalation to phosphate fiber at dose levels
of 0, 1, 5, or 25 mg/rn3 for 6 hours/day, 5 days/week for 2 years.
Monsanto noted that this study "was undertaken to evaluate the
carcinogenic potential of inhaled phosphate fiber, representing
the most likely route of human exposure." Honsanto noted also
that the high dose level (25 mg/m3) is 5 times greater than that
which would be considered "nuisance dust." Finally, r1onsanto
stated that while prel iminary resul ts from the ongoing 2-year
inhalation study were not expected until late 1987, the company
was "encouraged" by the fact that rats sacrificed after 3 months
of exposure show "no treatment-related pathological changes nor
any indication of fibrosis."
Following a review of the summarized information presented in
Monsanto's initial FYI notice, EPA informed Monsanto in wri tin9
(EPA letter dated April 14, 1986) that the Agency believed that
the company's oncogenicity findings for calcium sodiwn metaphos-
phate fibers consti tuted "substantial risk" information and, as
such, should have been submitted formally to the Agency pursuant
to Section 8(e), the substantial risk information reporting pro-
vision of the Toxic Substances Control Act (TSCA). In EPA's
April 14, 1986 letter, Monsanto was requested to provide the com-
pany's rationale as to why the subject cancer findings had not
been submitted under Section 8(e) of TSCA.
In a followup response letter dated May 15, 1986 (FYI-OTS-0586-
0486 Followup Response), Monsanto responded to EPA' s questions
concerning the Section 8(e)-applicability of the cancer findings
from the company's 2-year intrapleural implantation study of
calcium sodium metaphosphate fibers in rats. In this followup
response letter, Monsanto stated that the company "remains con-
vinced" that the reported findings "do not support the conclusion
that phosphate Fiber presents a substantial risk of injury to
287
-------
Page 3 of 9
health. ." and offered a number of comments and citations to
support the company's position. In addition, Monsanto provided a
complete copy of the final report from the 2-year intrapleural
implantation study and full copies of final reports from studies
designed to measure chemical dissolution, in vitro biodegradation
and in vivo animal lung clearance of phosphate fibers.
The following information concerning the conduct and resul ts of
the 2-year intrapleural implantation study was contained in the
SUMMARY section of the submitted final report from that study:
"A 24-month pulmonary oncogenicity study was conducted
wi th Osborne-Mendel strain [male and female] rats to
determine the effects of the test compound, calciwn
sodium metaphosphate [fibers], when implanted into the
pleural cavi ty. ." Responses induced by the test com-
pound were compared to those induced by implantation of
the positive control compound, chrysotile asbestos. The
study also consisted of a negative control group (gela-
tin plegdets). Gelatin pledgets containing 40 mg of the
test compound or asbestos (positive control) were im-
planted [surgically] into the pleural cavity of rats;
the negative control group animals were implanted wi th
sterilized gelatin pledgets [alone]. Each experimental
group consisted of 75 male and 75 female rats except the
negative and positive control female groups which con-
tained 74 and 76 animals, respectively- The surgical
implantation procedure [used] required two weeks. After
implantation, all animals were observed twice daily for
signs of mortality or morbidity or signs of toxicity. A
more detailed examination, including palpation for mas-
ses, was conducted at the time of determination of body
we igh ts. Body we igh ts were de terrnined on each animal
prior to dosing and biweekly (once every t\vO weeks)
during the first 14 weeks and every 4 weeks thereafter
throughout the remainder of the study. Animals found
dead or sacrificed moribund were subject [ed] to a com-
plete necropsy and gross examination; [the] tissues were
retained in 10% neutral buffered formalin for subsequent
histological examination. Interim sacrifices, 5 males
and 5 females in each group, were conducted after 26, 52
and 78 weeks; surviving animals were necropsied after
the [end of the] 24-month experimental period. Tissues
of all animals at necropsy were retained for subsequent
histological examination.
"Mortality of males and females receiving the test fiber
was essentially similar to that of the respective nega-
tive controls (gelatin pledget only) and to the positive
control animals (chrysotile asbestos). However, [the]
mortal i ty of males was higher than females. Likewise,
mean body weights of males and females treated with the
test fiber were essentially similar to that of the nega-
tive and positive control animals throughout the study.
288
-------
Page 4 of 9
"Gross examination of tissues at necrospy revealed no
lesions considered unique to the test fiber or asbestos.
Microscopic examination revealed the tissue response to
the test fiber to be cellular, while the tissue response
to the asbestos fiber was acellular, mostly collagenous.
In addition, microscopic examination revealed pleural
fibrosarcomas in near equal incidence in the test fiber
and asbestos males and females. Morpholog ically, the
fibrosarcomas induced by the test fiber were also more
cellular compared to asbestos in that the acellular col-
lagenous response characteristic of asbestos-induced
fibrosarcomas was not seen in the test fiber group. The
fibrosarcomas induced by the test fiber were probably
related to the continued presence of long thin fibers.
Other microscopic lesions observed were considered to be
normal findings expected in rats in chronic studies. II
[NOTE: In the followup response cover letter, Monsanto
stated that the incidence of pleural fibrosarcomas in
the asbestos exposed rats was 4 and not 5 as reported
initially by the company. In addition, Honsanto stated
that a consulting pathologist who reviewed the slides
from the study stated that "matted H1asses of fibers were
seen two years after their introduction" and "processes
of clearance by solution and metabolism cannot and did
not take place after this massive intrapleural dosage. "]
The following information with regard to the conduct and results
of a study designed to determine the in vitro biodegradability of
rad iolabelled calc i um sod i um metaphospha te fibers was presented
as an ABSTRACT in the submitted final report from that study:
liThe biodegradability of calcium sodium metaphosphate
fibers (phosphate fibers) was stud ied in cuI tured lung
cells. 3 2p [phosphorus] -rad iolabelled phosphate fibers
were incubated for Q-7 days in cuI ture medium in the
presence and absence of cultured rat lung epi thel ial
cells (LEC) and rat alveolar macrophages (RAM). The
degree of fiber solubilization was estim.ated daily by
filtering the extracellular medium and NaOH solubilized
cells through a 0.45 urn filter and monitoring radio-
activity in the filtrate. The [phosphate] fibers were
found to have limited solubility in culture media at 37
degrees C, with approximately 3% dissolved in seven days
(from approximately l% on day 0). Both LEC and RAM in-
creased the solubility of the fibers, reaching 7% and
20 %, respect ively, for the two cell types in 7 days.
[Monsanto's] results therefore suggest that phosphate
fibers are degradable by lung cells."
The following information concerning the conduct and results of a
study designed to determine the ability of phosphate fibers to be
cleared from the rat lung in vivo was contained in the ABSTRACT
section of the submitted final report from that study:
289
-------
Page 5 of 9
"Groups of 8 rats were exposed to calcium sodiu.m meta-
phosphate (CSM) fibers by an inhalation technique that
allowed [the study investigators] to bypass the nasal
turbinates or by intratracheal instillation. Control
rats were instilled with saline or sham-exposed via in-
halation. Comparable lung burdens were detected at 1
day post-exposure in rats exposed by inhalation or [by]
instillation. No statistically significant differences
were detected in lung fiber-burdens measured at 1, 7, 21
or 57 days post-exposure. However, after 176 days the
pulmonary concentration of inhaled CSM fibers was less
than the pulmonary concentration of [the] instilled CSM
fibers. Histopathologic examination of the lungs of the
same rats did not reveal any acute inflammatory response
or any evidence of a fibroproliferative response. Semi-
quantitative evaluation of the regional distribution
indicated a decreasing percentage of fibers in the con-
ducting airways and an increasing percentage of fibers
sequestered in the interstitium and alveolar ductal sep-
ta with time. Biochemical assessment of hydroxyproline,
elastin, DNA and protein did not reveal the presence of
a fibrotic response to the fibers. The CSM fibers were
cleared from the conducting airways and alveoli such
that at 6 months, most of the remaining fibers (7-16% of
[the] fiber burden on day 1) were sequestered within the
intersti tium wi th a minimal histiocytic response. The
[CSM] fibers did not demonstrate any inherently toxic
properties when deposited in the lungs of rats under the
exposure regimen used in these [in vivo] studies."
According to a submitted memorandwn concerning the results of a
fiber leaching/dissolution study, the total half-life (weight
basis) of phosphate fiber, in a non-stagnant situation, may be
"in the range of 2 to 16 months. . .from chemical and mechanical
forces in the absence of any biolog ical mechani sms. " In add i-
tion, the memorandum states that the leaching procedure "produced
a measurable increase in average fiber diameter and a decrease in
surface area." These findings are reportedly "consistent with
the [observed] weight loss being due to preferential dissolution
of the smaller particles which have a laryer surface to volume
ratio." 'l'he submitted memorandum states also that the findings
from this leaching study indicate that "some of the large fibers
among the standard broad particle size distribution could be ex-
pected to remain undissolved for several half-lives (Le., many
months or a few years)."
In its followup response letter, Monsanto provided the following
discussion summarizing Monsanto's position on the Section 8(e)-
reIJortabi 1 i ty of the cancer find ings from the company's 2-year
intrapleural implantation study of calcium sodium metaphosphate
in rats:
290
-------
Page 6 of 9
"In summary, Monsanto's position is that the results of
the intrapleural implant study cannot be extrapolated to
cancer risks in man. ... [The company has] provided
evidence that this position is universally accepted by
investigators who have conducted this test and also by
many governmental agencies. Moreover, . [Monsanto
feels that the company has] other data to show that
Phosphate Fiber will be cleared from the body under nor-
mal routes of exposure and thus will not approach the
high concentrations placed in the ple'ural cavi ty in this
[implanta tion] study. . [Monsanto' s] in vi tro data
has also shown that Phosphate Fiber is an order of mag-
nitude less toxic than asbestos."
Submission Evaluation
In reviewing the summarized information contained in Monsanto's
initial FYI notice, it was apparent to the Agency that surgically
implanted gelatin-enclosed calcium sodium metaphosphate fibers
and chrysotile asbestos fibers induced low but essentially equal
incidences of fibrosarcomas in rats. Al though Monsanto specu-
lated that the gelatin had decreased the expected dissolution and
enzymatic degradation (per the results of other studies) of the
phosphate fiber, EPA's position was then and is now that it is
equally plausible that the gelatin decreased substantially the
carcinogenic activi ty of both types of fibers by I) effect ively
reduc ing the pleural exposure to the fibers, and/or 2) altering
the biological activity of the fibers.
Monsanto's followup response provides additional information that
may be relevant to interpreting the extent to which the findings
reported initially should be relied upon in assessing human risk
posed by exposure to calcium sodium metaphosphate fibers. How-
ever, Monsanto has not provided any new information that refutes
the low but essentially equal incidences of malignant pleural
twnors observed in the calcium sodium metaphosphate and asbestos
exposed rats but not in the concurrent control rats. In fact,
several documents provided by Monsanto state that the malignant
pleural tW110rs found in the calcium sodium metaphosphate fiber-
treated rats were considered to be treatment-related.
In considering all of the information provided by Monsanto in its
initial and followup response FYI notices, the Agency's position
concerning the nature of the findings from the company's two-year
pleural implantation study is not changed. EPA believes that the
results of the performed study show clearly that calcium sodium
metaphosphate fiber, when implanted surgically into the pleura of
rats, produced a low incidence of fibrosarcomas.
Immediately upon receipt of Monsanto's initial and followup FYI
notices, the Chemical Screening Branch (CSB/ECAD/OTS) provided
copies to the Risk Analysis Branch (RAB/ECAD/OTS), Regulatory
Program Development Branch (RPDB/CCD/OTS), and Asbestos Action
program/OPTS for inclusion in the ongoing reviews of available
toxicologic/exposure information on fibrous materials.
291
-------
Page 7 of 9
Current production and Use
According to a pamphlet entitled "phosphate Fibers" provided to
the Agency previously by Monsanto, calcium sodium metaphosphate
fibers are cylindrical and are more like the chrysotile form of
asbestos rather than the ribbon-like amphibole form of asbestos.
The provided pamphlet states further that due to the tendency of
crystalline calcium sodium rnetaphosphate to "spl it lengthwise
into long fragments of smaller diameter," the fibers will open
further and their surface area will increase upon application of
mechanical stress. The pamphlet states also that this particular
property is important "in applications which require high surface
areas, such as paper products."
In its followup response letter, Monsanto provided the following
information with regard to the potential for worker exposure to
phosphate fibers:
". . [The Monsanto Company] is reassured by the low
exposure in the workplace to Phosphate Fiber. The use
of Phosphate Fiber does not produce airborne dust since
the finer fibers have a natural tendency to adhere to
larger fibers due to coulombic forces.
"Industrial hyg iene moni toring conducted in the pilot
plant supports this hypothesis in that exposures are at
or below 0.04 fibers/cc. . [The Monsanto Company
has] adopted an internal guideline of 2 f ibers/cc and
this 1 imi t has been communicated to . [Monsanto's]
customers via. . . [the] t1aterial Safety Data Sheet."
Comnents/Recommendations
In its ini tial FYI submission, Monsanto reported that copies of
that submission were being transmitted to all customers who were
participating in Monsanto's sampling program. In its followup
response letter, Monsanto stated the company had taken "prudent
action" by 1) notifying EPA in a timely manner about the pre-
liminary results of the 24-month intrapleural implantation study,
2) establishing a conservative interim phosphate fiber exposure
guideline, and 3) increasing industrial moni toring efforts to
assure that minimal phosphate fiber exposure levels have been
attained. Finally, Monsanto reported that the company is con-
tinuing its safety evaluation of phosphate fibers and plans to
utilize the results of the ongoing phosphate fiber inhalation
study in rats in that regard.
Following a review of the information presented in FYI-OTS-0386-
0486 and FYI-OTS-0586-0486 Followup Response, EPA's position is
unchanged with regard to the TSCA Section 8(e)-applicability/-
reportability of the observations from the Monsanto Company's
intrapleural implantation study of calcium sodium metaphosphate
fibers in rats. The basis for EPA's position is as follows:
292
-------
Page 8 of 9
Section 8(e) of the Toxic Substances Control Act states:
"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. "
The preface to Part V of EPA' s March 16, 1978 Section
8 (e) policy document (" Statement of Interpretation and
Enforcement policy; Notification of Substantial Risk" 43
FR 11110) 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 [i.e., the serious effect's] oc-
currence."
with regard to the seriousness of the effect, Part V of
the 8 (e) pol icy statement 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 mix-
ture can produce cancer. . ." [emphasis added] Infor-
Hlation regarding this effect can be obtained directly or
inferred from designed studies (e.g., in vivo studies)
as described in Part VI of the 8(e) policy statement.
Part VI states also that a subject "person is not to
delay reporting until he obtains conclusive infonnation
that a substantial risk exists, but is to immediately
report any evidence which reasonably supports that con-
clus ion. " In add i tion, Part VI of the 8 (e) pol icy
statement explains that "not only should final resul ts
from such studies be reported, but also preliminary
results from incomplete studies where appropriate."
with regard to the "fact or probability of its [Le.,
the serious effect's] occurrence" criterion, part V of
the 8(e) policy statement explains that certain types of
adverse health effects (e.g., cancer) are so serious
that relatively little weight should be given to the
chemical's exposure in determining whether a risk is
substantial.
Finally, Honsanto offers some apparently sound arguments
concerning the adequacy of the company's cancer findings
for risk assessment and extrapolation of those findings
to humans. Although these particular types of arguments
are important and are typically considered by EPA during
the overall cancer risk assessment process, they do not
alter the fact that a treatment-related carcinogenic
293
-------
Page 9 of 9
activi ty was observed in the performed study. In light
of the fact that Section 8(e) is a statutory reporting
requirement by which the Agency is to be notified im-
mediately about any new health risk-related information
that simply offers reasonable support for a conclusion
of substantial risk, arguments of the type contained in
Monsanto's FYI notices are not relevant to any great ex-
tent in determining Section 8(e)-reportability of cancer
find ings. The Monsanto Company's cancer findings, in
and of themselves, provide a sufficient basis for sub-
mitting the findings to EPA under Section 8(e) of TSCA.
In view of the preceding policy discussion and EPA's review of
the information contained in Monsanto's initial and followup FYI
notices, EPA believes that the evidence obtained from Monsanto's
two-year intrapleural implantation study in rats offers reason-
able support for the conclusion that calcium sodiwTI metaphosphate
fibers can cause cancer. It is EPA's decision, therefore, that
the subject cancer findings should have been submitted to the
Agency under Section 8(e) of TSCA.
a)
The Existing Chemical Assessment Division (ECAD/OTS)
will notify Monsanto in writing about EPA's decision
concerning the TSCA Section 8 (e) -reportabili ty of the
cancer findings presented in FYI-OTS-0386-0486 and FYI-
OTS-0586-0486 Followup Response. In view of this EPA
decision, the Chemical Screening Branch (CSB/ECAD/OTS)
has delivered all information contained in FYI-OTS-0386-
0486 and FYI-OTS-0586-0486 Followup Response to the OTS
Document Control Officer for appropriate handling/public
filing under Section 8(e) of TSCA.
The Monsanto Company will be asked to ensure that EPA
receives in a timely manner a full copy of the final
report (including the actual experimental protocol,
results of gross and histopathologic examinations,
results of any statistical analyses, etc.) from the
ongoing phosphate fiber inhalation study in rats.
b)
Upon receipt of the final report from the inhalation
study of calcill.1l1 sodium metaphosphate fibers in rats,
the Chemical Screening Branch (CSB/ECAD/OTS) will send
full copies of that report immediately to RAB/ECAD/OTS,
RPDB/CCD/OTS, and to the Asbestos Action Program/OPTS.
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, OAR/EPA, ORD/EPA, RAB/ECAD/OTS, RPDB/CCD/OTS,
OCM/OPTS, and the Asbestos Action program/OPTS. Copies
of this status report will be provided also to the TSCA
Assistance Office (TAO/OTS) for further distribution.
294
-------
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
DATE:
AUG 2 5 1986
Page 1 of 2
SUBJECT:
Status Report*
APproved:~ if2-5"J(fp
Darr, Section Head ~, 6""-vz.....
Risk Identificatio«-section/CSB
8EHQ-0886-0620
FROM: James F.
Chemical
TO: Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
On behalf of the individual industry members of the Phthalate
Esters Panel, the Chemical Manufacturers Association (CMA) pro-
vided the following summary information regarding the preliminary
results of several recently conducted genotoxicity studies:
liAs part of its negotiated [Section 4] testing program for
phthalate esters, CMA agreed to perform [in vitro L5178Y]
Mouse Lymphoma [cell forward mutagenici ty] and in vi tro
[mouse cell] transformation assays on certain commercially
significant [phthalate] esters. It was originally contem-
plated that CMA would also sponsor Ames. [bacterial
mutagenici ty] assays on the substances, but such testing
had been previously performed by the National Toxicology
program (NTP).
II [The cell] transformation and Ames assays for all [of]
the test substances have been completed and were negative.
On July 22, 1986, CMA was informed by the laboratory that
[di-n-butyl phthalate (DBP; CAS NO. 84-74-3)] gave weak,
dose-rela ted increases in the mutant frequency of L5178Y
cells when tested in the standard Mouse Lymphoma forward
mutation assay- . .. Responses were observed only in the
presence of an Aroclor-induced rat liver S-9 fraction, in-
dicating some participation of this system in the observed
activity. .... Results of a previous trial assay with
DBP gave weakly positive increases; however, these results
did not represent a clear dose-related response.
[Cl-1A was recently informed]. . . that [dimethyl phthalate
(DMP; CAS No. 131-11-3)] gave weak dose related increases
in mutant frequency in this assay in the presence of [the]
Aroclor-induced rat 1 iver S-9. II
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
295
-------
8EHQ-0886-0620
Page 2 of 2
Submission Evaluation
Immediately upon receipt of this notice, the Chemical Screening
Branch (CSB/ECAD/OTS) sent copies to the Test Rules Development
Branch (TRDB/ECAD/OTS) and Risk Analysis Branch (RAB/ECAD/OTS)
for inclusion in ongoing OTS assessments of phthalate esters.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for these phthalate esters, which are listed in the
initial TSCA Chemical Substance Inventory, has shown that the
following amounts (}?ounds) were reported as manufactured and/or
imported in 1977:
CHEMICAL NAHE
CAS NO.
PRODUCTION RALJGE
Di-n-Butyl Phthalate
84-74-2
15 million to 100.4 million
Dimethyl Phthalate
131-11-3
2.2 million to 22 million
(Note: 'rhe above production range information does not include
any data claimed as TSCA Confidential Business Information (TSCA
CBI) by the person(s) reporting for the TSCA Inventory, nor does
it include any da ta that would compromise TSCA CBl. All of the
data re}?orted for the initial TSCA Inventory, including the pro-
duction range data, are subject to the limitations contained in
the initial TSCA Inventory Reporting Regulations (40 CFR 710).)
In its TSCA Section 8(e) notice, CMA stated that the "producers
of DBP viho are members of the [Phthalate Esters] Panel are BASF
Corporation, Eastman Kodak Company and [the] US Diversified Group
(formerly USS Chemicals, a division of US Steel Corporation, now
USX) ." CMA stated also that the Eastman Kodak is the Phthalate
Esters Panel member who produces DMP. According to secondary
literature, DMP and DBP are used primarily as plasticizers.
Commen ts/ Recommenda t ions
CMA stated that complete copies of the final genotoxicity study
reports will be sent to EPA when those rel?orts become available.
EPA' s Office of Toxic Substances has received a number of TSCA
Section 8(e) and "For Your Information" (FYI) notices concerning
alkyl phthalates. In addi tion, the Chemical Screening Branch
recently prepared Chemical Hazard Information Profiles (CHIPs) on
diallyl phthalate and dimethoxyethyl phthalate. Further, EPA has
published TSCA Section 8(a) and (d) rules on alkyl phthalates.
The Chemical Screening Branch will send copies of this status
report to NIOSH, OSHA, CPSC, FDA, NTP, OW/EPA, OAR/EPA, ORD/EPA,
OSWER/ EPA, OPP/OPTS/ EPA, and to TRDB and RAB/ ECAD/OTS/OPTS/ EPA.
Copies of this report will be sent also to the TSCA Assistance
Office (TAO/OTS) for further distribution.
296
-------
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
Page 1 of 2
DATE:
SEP
4 1986
SUBJECT:
Status Report* 8EHQ-0886-062l S APproved:~
James F. Darr, Section Head ~11;;;:-~
Chemical Risk Identificatiort7~e~tion/CSB
Q/1fIP
FROM:
TO:
Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Note
The submitting company has claimed its name and exact identity of
the subject chemical to be TSCA Confidential Business Information
(TSCA CBI). The Information ~1anagement Division (IMD/OTS) will
ask the submitter to substantiate the company's confidentiality
claims. In the "sanitized" version of the notice, the submitter
reported non-confidentially that the subject chemical substance
is an alkylated aniline.
Submission Description
The submitting company provided summarized preliminary results of
a battery of in vitro genotoxicity studies and several acute in
vivo toxicity---studies conducted with this alkylated aniline.
According to the submitted information, the subject chemical was
found to be active in an Ames Salmonella typhimurium (bacteria)
mutagenicity assay, ,a DNA repair assay using cultured rat hepato-
cytes, and a cytogenetics assay in cultured Chinese Hamster ovary
(CHO) cells; the chemical was reported to be inactive in an in
vitro BALB/c-3T3 mouse cell transformation assay and an in vitro
CHO cell point mutation assay. vVith regard to in vivo toxicity,
the submi tter reported that this chemical was non-irri tating to
eyes or skin (the test species was not specified). The submitter
reported further that the alkylated aniline was found to have an
oral LD50 (rats; combined sexes) of 742.8 mg/kg and a dermal LD50
(rabbits) of 2000 mg/kg.
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
297
-------
8EHQ-0886-0621 S
Page 2 of 2
Submission Evaluation
Although the submitted information indicates that this alkylated
aniline is not irri tating to skin or eyes and is not extremely
toxic in terms of lethality, the reported in vitro test results
indicate that the chemical does possess some-degree of genotoxic
activity. In order for EPA to assess the overall significance of
the reported findings, however, the submitting company should be
asked to ensure that the Agency receives complete copies of the
final reports from all studies that were ci ted in the company's
Section 8(e) submission.
Current Production and Use
In view of the submitter's TSCA CBI claims, no information with
regard to the TSCA Chemical Substance Inventory status of this
alkylated aniline will appear in this report. According to the
submission, the submitting company is not a commercial producer
of the chemical nor does the company have any current plans to
commercialize the substance.
Comments/Recommendations
a) The Chemical Screening Branch (CSB/ECAD/OTS) will ask the
submitting company to ensure that EPA receives full copies
of the final reports (including the actual experimental
protocols, data, results of gross/histopathologic examina-
tions, results of statistical analyses, etc.) from all
studies cited in the company's Section 8(e) notice.
In view of EPA's general interest in company actions taken
on a voluntary basis in response to chemical toxicity or
exposure information, the submitting company will be asked
to describe the actions the company has taken or plans to
to take to notify workers and/or others about the reported
findings.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further OTS
assessment of this alkylated aniline.
c) The Chemical Screening Branch will provide copies of this
status report to OSHA, NIOSH, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, OAR/EPA, ORD/EPA, and OPP/OPTS/EPA. In add i tion,
copies of this status report will be provided to the TSCA
Assistance Office (TAO/OTS) for further distribution.
298
-------
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
DATE:
SEP
4 1986
Page 1 of 3
SUBJECT:
status Report* 8EHQ-0886-0622 S APproved:t]Jt-
James F. Darr, Section Head r1MMLJ T tr::"t.--
Chemical Risk IdentificationV;~~tion/CSB
qjt5j1tg
I
FROM:
TO:
Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Note
The submitting company has claimed
Confidential Business Information
Management Division (IMD/OTS) will
stantiate this TSCA CBI claim.
the company's name to be TSCA
(TSCA CBI). The Information
request the submitter to sub-
Submission Description
The submi tter reported that information recently brought to the
company's attention indicates that two (2) "employees exhibited a
reaction to workplace exposure, resulting in temporary headaches,
disorientation, chest tightness and a continuing inability to
consume alcoholic beverages wi thout a return of the headaches."
The submitter also provided the following information concerning
this situation:
"The employee reactions are possibly due to sensitization
or some other undetermined mechanism. These reactions
appear to resul t from exposure to chemical mixtures used
in electron beam cured coatings on paper or polymer film
substrates or [to] an unknown chemical(s) generated in the
process. [The company] has yet to determine what specific
chemical or chemicals may be responsible for the symptoms
being reported. The source of this information sterns from
employee verbal complaints of reported symptoms."
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
299
-------
8EHQ-0886-0622 S
Page 2 of 3
Submission Evaluation
Al though EPA has received a number of Section 8 (e) submissions
re':jard ing cases of possible sensi ti zation among cherl1ical workers,
this is the second Section 8(e) submission concerning workers who
exper ienced apparent alcohol/workplace chemical-reI a ted adverse
effects. In Section 8(e) submission number 8EHQ-0880-0355, the
Allied Chemical Corporation stated that several Allied employees
who worked with methylthioacetaldehyde oxime (CAS NO. 10533-67-2)
developed red splotches on the face and upper trunk, headaches,
and tachycarcHa following alcohol consumption. In this previous
Section 8(e) notice, Allied stated also that the observed effects
resembled those found following alcohol ingestion by persons re-
ceiving Antabuse@ (tetraethylthiuram disulfide), a drug used in
the treatment of alcoholism. In the preliminary evaluation of
Allied's TSCA Section 8(e) submission, EPA noted that there are a
number of chemicals/drugs capable of inhibi ting the enzyme that
converts acetaldehyde to acetic acid. (The first step in alcohol
metabolism involves the conversion of the alcohol to acetaldehyde
in the body.) EPA noted also that 1) introduction of alcohol in
the presence of such enZ~1e inhibitors can result in an excess of
acetaldehyde in the body, and 2) this acetaldehyde excess can
bring about adverse symptoms and signs related to circulatory,
respiratory, liver, and nervous system functions.
Comments/Recommendations
The submitting company stated that it is currently investigating
the situation and "until a determination is made as to the exact
cause of these s~1ptoms, precautions are being taken to isolate
the two employees that appear to be sensitized and to provide
respiratory and skin protection for other employees in the work-
place." The company stated also that EPA would be apprised of
any new information obtained during the company's investigation.
Based on EPA's initial evaluation of the information presented in
this notice, it is not entirely clear that the information pro-
vided by the company is of the type required for submission to
the Agency under Section 8 (e), the substantial risk information
reporting provision of TSCA. It is qui te probable, on the other
hand, that the subject information is of the type required to be
maintained by the submitting company under Section 8(c), the man-
datory recordkeeping provision of TSCA. On August 22, 1983, EPA
published (48 FR 38178) a final rule that requires chemical manu-
facturers, importers and certain processors to maintain records
of any significant adverse reaction alleged to have been caused
by TSCA-covered chemicals. The final TSCA Section 8(c) rule also
requires that allegations involving significant adverse reactions
in workers be kept for 30 years and that other recordable allega-
tions be kept for 5 years. It should be noted that the Agency is
empowered to both inspect and require submission of Section 8(c)
records and has done so on a number of occasions to date.
300
-------
8EHQ-0886-0622 S
Page 3 of 3
a) The Chemical Screening Branch (CSB/ECAD/OTS) will request
the submitter to ensure that EPA is informed immediately
about all significant findings from the company's investi-
gation into the causative agent(s) of the adverse effects
seen in two of the company's employees.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further OTS
assessment of this situation.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, OAR/EPA, ORD/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.
301
-------
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
Page 1 of 5
DATE:
SEP 3 0 1986
Status Report' 8EHQ-0986-0623 S ADPrDved~ I:ff:-r 'j;,..;, iT!;;...,
~' r-' 1hl' fl.. t
James F. Darr, Section Head 1{;1J,'1/1.,,-
Chemical Risk Identificatio Section/CSB
SUBJECT:
FROM:
TO:
Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Note
The submi t ting company claimed the company I s name and the exact
identity of the tested chemical to be TSCA Confidential Business
Information (TSCA CBI). Staff of the Information Management
Division (IMD/OTS/OPTS) will request the submi tting company to
substantiate these TSCA CBI claims. In the sanitized version of
the TSCA Section 8(e) notice, the submitting company reported
non-confidentially that the tested chemical was a substi tuted
diphenyl ether.
Submission Description
The submitting company provided the following summary information
with regard to the conduct and preliminary findings from an oral
teratology study in rats:
"Groups of 30 bred Fischer 344 rats were administered
the [substi tuted diphenyl ether] in aqueous solution by
oral gavage on days 6 through 15 of gestation at dose
levels of 0, 0.3, 1.0, or 7.5 mg/kg body weight/day.
Each fetus was examined externally and approximately 50%
of the fetuses from each Ii tter were examined for vis-
ceral al teration by the Staples technique.
[Skeletal examination] of fetuses is in progress.
"Indications of maternal toxicity were evidenced by an
increase in absolute and relative liver weights in high
dose (7.5 mg/kg/day) females. Accompanying the maternal
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
302
-------
8EHQ-0986-0623 S
Page 2 of 5
toxicity at the high dose was a significant decrease in
fetal body weight. In addition, visceral examination
revealed an increased incidence (not statistically iden-
tified) of a great vessel malformation in the high dose
group. This malformation involved a displacement of the
ascending aortic arch which occurred in one fetus in the
control group, two fetuses in the 1.0 mg/kg/day group
and 4 fetuses in the 7.5 mg/kg/day group. Although the
increased incidences of great vessel malformation were
not statistically identified, the clustering of 4 fe-
tuses from 4 different litters at the top dose level
suggests a possible teratogenic response."
The submi tting company also provided the following summarized
information with regard to the conduct and preliminary results of
a two-generation reproduction study of the subject chemical sub-
stance in rats:
". . . [G]roups of 30 rats/sex/dose level were given the
compound in the diet at dose levels of 0, 0.1, 0.3, 1.5
(males) or 3.0 (females) mg/kg/day for a period of 10
weeks. These animals were then bred (1 male: 1 female)
within dose groups for 3 weeks or until a sperm positive
vaginal smear was obtained. Females were allowed to de-
liver their litters and the offspring were evaluated for
growth and survival during lactation through weaning at
28 days of age. ....
"[Through 21 days of age,] there were no adverse effects
noted among the fO adults in either body weights or feed
consumption during the pre-mating, gestation, or lacta-
tion periods. Mating indices were also unaffected in
all of the dose groups.
"Among [those] Ii tters in the 3.0 mg/kg/day dose level,
a significant increase in the mortality of pups through
day 4 of lactation was observed. In addition, pup body
weights in the 3.0 mg/kg/day dose group were signifi-
cantly lower than the control group from birth through
day 21 of lactation. These effects were considered to
be a result of administration of the test compound.
Statistically identified differences in pup body weights
in the 0.1 and 0.3 mg/kg/day dose groups were also ob-
served; however r these [observed] differences may have
been secondary to the larger litter sizes seen in these
groups when compared to the control group. Further con-
clusions regarding these data await completion of the
lactation phase of the study."
It should be noted that on a "For Your Information" (FYI) basis
(FYI-OTS-0286-0483), the submi tting company provided previously
the following summarized inforrna tion wi th regard to the conduct
and results of a "probe" teratology study in rats:
303
-------
8EHQ-0986-0623 S
Page 3 of 5
"Groups of ten [(10)] bred female Fischer 344 rats were
administered [the test compound] by oral gavage on days
6 through 15 of gestation. Dose levels were 0, 3, 10
and 30 mg/kg body weight/day. On day 16, all animals
were sacrificed and examined for gross pathological
changes. The ovary and uterus of all animals were also
examined at this time.
"Evidence of maternal toxicity was observed in the 3, 10
and 30 mg/kg[/day] dose groups. The degree of maternal
toxicity was dose-related. pregnant rats in the 30 mg/
kg [/day] dose group exhibited a decrease in body weight
on gestation day 16, a decrease in body weight gain
during gestation days 6 through 8, 10 through 16, and 6
through 16, and an increase in kidney and liver weights.
pregnant rats in the 10 mg/kg[/day] dose group exhibited
a decrease in body weight gain during gestation days 6
through 8 and an increase in kidney and 1 i ver we igh ts.
Pregnant rats in the 3 mg/kg [jday] group exhibi ted an
increase in kidney and liver weights.
"Embryotoxic effects were observed in the high dose fe-
males. Pregnant rats in the 30 mg/kg [jday] dose group
exhibi ted an increase in the percent of implantations
undergoing resorption and the percent of 1 it ters wi th
resorptions. At the two lower dose levels, the resorp-
tion rates were comparable with the controls."
It should be noted that on September 8, 1986, the submitting
company provided to EPA a complete copy of the protocol fr~n the
oral teratology study cited in the company's 'I'SCA Section 8(e)
submission and a complete copy of the final report of the above
referenced "probe" teratology study (FYI-OTS-0986-0483 S Followup
Response). The Introduction and Purpose section of the final
report from the "probe" teratology study presented the following
information regarding the results of other studies conducted with
the subject chemical substance:
"A range-finding acute oral toxici ty study in male and
female rats indicated the LD50 [of the substituted di-
phenyl ether] to be appro x imately 500 mg/kg in both
sexes. Administration of 0, 10, 50, or 100 mg/kg
body weight/day to male Fischer 344 rats for 4 days via
gavage resulted in statistically increased liver and
kidney weights [observed] at all dose levels relative to
controls. . . .
"[The] preliminary results of a 2-week dietary probe in
which male Fischer 344 rats were given targeted doses of
0, 0.1, 1.0 or 10 mg/kg body weight/day and female rats
were given 0, 1.0, 10 or 100 mg/kg body weight/day iden-
tified the liver and the kidneys as potential target
tiss ues. Increases in absolute and rela t i ve 1 i ver and
kidney we igh ts were observed in male rats adI,1inistered
304
-------
8EHQ-0986-0623 S
Page 4 of 5
10 mg/kg body weight/day. Absolute and relative liver
weights were increased in females given 10 or 100 ffi9/kg
body weight/ day. Microscopic examination of the liver
revealed diffuse hepatocellular hypertrophy and altered
cytoplasmic tinctorial properties in male and female
rats receiving the highest dose level. Similar changes
were also observed in female rats given 10.0 mg/kg body
wei9ht/day and males given 1.0 mg/kg body weight/day. A
12% depression in body weights relative to controls was
also observed in top dose group female rats. Prelimi-
nary data reported for this [2-week] study suggest that
the no-observed-effect-level (NOEL) was between 1. 0 to
10 mg/kg body weight/day for female rats and 0.1 to 1.0
mg/kg body weight/day for male rats."
Finally, it should be noted that the final report from the
"probe" teratology study states that the oral route of exposure
had been selected for the "defini tive" teratology study because
the oral route is "a potential route of hUHlan exposure."
Submission Evaluation
According to the submi tted findings from the recently conducted
teratology study, soft tissue and external examination of the
fetuses showed a great vessel defect, the incidence of which,
while not statistically significant, was dose dependent (1 in
controls, 0 at 0.3, 2 at 1.0 and 4 at 7.5 mg/kg). At the highest
dose, there was also an observed increase in relative and abso-
lute maternal liver weights and a decrease in fetal body weights.
Further evaluation of the overall significance of the apparent
teratologic effect should be possible upon EPA' s receipt of a
full copy of the final report fran this study.
With regard to the two-generation reproduction study in rats, the
submitter reported that no effects were seen in the parents at
oral dose leve Is up to 3.0 g /kg/day. It should be noted, how-
ever, that the Fl generation from the 0.3 and 3.0 mg/kg exposure
groups showed a decreased body weight prior to weaning and an
increased rnortali ty prior to day 4 (a t 3.0 mg/kg only). As in
the case of the oral teratology study, further evaluation of the
overall significance of the results of this reproduction study
should be possible upon EPA's receipt of the final report.
Current Production and Use
In view of the subrni tting company's TSCA CBI claims, this status
report will not contain any information with regard to the TSCA
Chemical Substance Inventory status of the subject chemical sub-
stance. In its Section 8 (e) notice, the company reported non-
confidentially that the tested chemical "is at the research stage
and is being evaluated for use as a pesticide." According to the
Introduction and purpose section of the final report of the oral
"probe" teratology study (FYI-OTS-0986-0483 S Followup Response),
the chemical is undergoing evaluation as a potential herbicide.
305
-------
8EHQ-0986-0623 S
Page 5 of 5
Commen ts/Recommenda tions
'The submi tting company stated that in accordance wi th its long-
standing corporate policy, the company plans to infonn "relevant
employees" about the results of the reported studies.
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will ask
the submi tter to ensure that EPA receives a complete
copy of the final report (including the actual experi-
mental protocol, resul ts of gross and histopatholog ic
examinations, results of statistical analyses, etc.)
from the "definitive" oral teratology study that was
ci ted in the company's Section 8 (e) and FYI submissions
on this substituted diphenyl ether.
In view of EPA's general interest in corporate actions
taken on a voluntary basis in response to chemical toxi-
city or exposure data, the submitting company will be
requested also to describe the nature and resul ts, if
available, from all other studies that the company has
conducted, is conducting, or is planning to conduct to
determine either the toxicity of or the exposure to this
substituted diphenyl ether.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
O'TS assessment of this substituted diphenyl ether.
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OS\vER/EPA,
Ov)/EPA, OAR/EPA, ORD/EPA, and OPP/OPTS/EPA. Copies of
this status report will be transmitted also to the TSCA
Assistance Office (TAO/OTS) for further distribution.
306
-------
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
Page 1 of 4
DATE:
SEP 2 4 1986
Status Report* 8EHQ-0986-0624/5 S Approved: ~ ~a;:::;:4 -;;.J[)Juv!1-
rr Cj"<7'1 iI:, 0
James F. Darr, Section Head {l,./tMP", r C;;-'Vt."..--
Chemical Risk Identificatio~~~tion/CSB
IJECT:
FROM:
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 tested chemicals as TSCA Confidential Business
Information (TSCA CBI). Information Management Divsion (IMD/OTS)
staff will request the submi tter to substantiate these TSCA eBI
claims. The submi tter provided the following non-confidential
generic names for the subject chemical substances: a substituted
ni trobenzene (8EHQ-0986-0624 S) and a substituted chlorobenzene
(8EHQ-0986-0625 S).
Submission Description
The submitting company provided the following summarized interim
findings from a dietary feeding study of the subject chemicals in
male and female Sprague-Dawley rats:
"A significant increase in corneal opacity (milky or
cloudy eye condi tion) has been observed in some of the
treated animals at all [of] the dose levels employed in
the study. Microscopic examination of opaque cornea re-
vealed ulceration of the epithelium (outer layer of the
cornea) in some of the treated animals. Vascularization
including both capillaries and larger vessels was seen
in some affected areas. A dose response relationship is
not apparent at present for this lesion. Spontaneous
repair and reversal of the lesion is occurring in some
animals even though they continue to receive the test
diets. It is too early to determine whether the lesion
will completely reverse."
===================================================================================
* NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
307
-------
8EHQ-0986-0624j5 S
Page 2 of 4
In its TSCA Section 8(e) submissions, the company noted that
"while corneal toxicity is unusual, it is not unique to
[the tested chemical subs tances] bu t has been reported to occur
fran the administration of several dru~s, including indomethacin,
chloroquine, amiodarone and others." In its Section 8(e) submis-
s ions, the company also pro v ided the res ul ts of ophthalmoscopic
and biomicroscopic examinations associated with the performed
studies. fJi th regard to ei ther the substi tuted ni trobenzene or
the substituted chI oro benzene , the provided ophthalmoscopicjbio-
microscopic examination reports presented the following summary
information:
"In many of the rats, an inflamma tory corneal syndrome
was seen. Observations seem to indicate the following
stages in the syndrome. In its least severe stage, the
corneal syndrome was characterized by the presence of
fine granular deposits scattered throughout the corneal
epi thel ial cells or the basement membrane area s ubepi-
thelially. In this stage, the perilimbal area of the
cornea was spared. In its moderate stage, a central
corneal area, approximately half the surface, acquired a
somewhat roughened surface, apparently associated wi th
inter- or intraepithelial edema, and associated ~vith [a]
dess ica tion of the af fected [corneal] surface. There
was a tendency for corneal ulceration to occur wi thin
the edematous zone. In the severe stage [0£ the syn-
drome], the superficial lesion seemed to induce corneal
vascularization, which eventually encroached from every
quadrant of the cornea to invest the edematous and des-
sicated zone. The vascularization often becall1e severe
enough to impede intraocular examination. The vascular-
ization in many cases seemed to meet resistance when it
reached the area of the dessicated zone. In a few [of
the] cases, there seemed to be a partial recovery, with
partial clearing of the cornea and shutdown of the en-
gorged corneal vessels, leaving only ghost vessels. The
syndrome occurred both un i- and bilaterally, and was of-
ten asymmetr ic when bilateral. Biomicroscopic
examination of clinically unaffected eyes revealed that
many had coarse granular surface deposits in the medial
quadrant, generally forming an elliptical pattern. This
occurred in both treated and untreated animals, and is a
common finding in laboratory rats [that are] examined by
this method."
The ophthalmoscopicjbiomicroscopic
substituted nitrobenzene presented
unique to that chemical:
examination report for the
the following information
"The [observed corneal] syndrome was compound related,
though apparen tly not dose related. [The] males were
more frequently and more severely affected [than were
the females]. Four of 10 females (previously observed
to have the syndrome), but no males, were observed to be
308
-------
8EHQ-0986-0624/5 S
Page 3 of 4
in the healing stages of the disease, even though they
are still rece iving the test compound. In a group of
treated rats not previously observed to have the corneal
syndrome, [the] biomicroscopic examination revealed its
presence to a mild degree, affecting [the] males more
frequently than [the] females. Cataracts were
present in 2 treated males previously observed to have
[the] corneal disease. The cataracts are probably not
treatment related. The corneal 'disease syndrome may be
the result of toxic interference to the lacrimal glands
and tear film, but is more likely to be the resul t of
accumulation of toxic material in the corneal epithelial
layer. The site of accumulation may be determinable by
electron microscopic examination."
The ophthalmoscopic/biomicroscopic examination report for the
substituted chlorobenzene presented the following information
unique to that chemical:
"The [observed corneal] syndrome was compound related,
though apparen tly not dose related. [The] males are
frequently and more severely involved than [are the]
females. In a group of high dose rats not previously
observed to have the corneal syndrome, many have the
early stages of the disease, visible only biomicroscopi-
cally. Males were more frequently affected in this group
also. Some of the affected rats also had an unusual
fonn of retinal degeneration, involving the upper quad-
rants of the retina. This may be treatment related.
This type of retinal degeneration generally occurs in
much older rats. Three rats had cataracts, incl uding
two previously reported to be affected wi th the corneal
degeneration syndrome. The cataracts do not appear to
be treatment related. .... The corneal syndrome may
be related to disease processes involving the lacrimal
g lands and tear film, bu t more probably depos i tion of
toxic material in the corneal epithelial tissue. The
site of abnormal inclusions may be visible [by
electron microscopy]."
Submission Evaluation
In order for EPA to evaluate the overall significance of the
reported toxicologic findings, the submitting company should be
asked to ensure that EPA receives a full copy of the final report
(including the actual exper imental protocol, data, results of
gross and histopathological examinations, results of statistical
analyses, etc.) from the ongoing dietary study cited in the com-
pany's TSCA Section 8(e) submissions.
309
-------
8EHQ-0986-0624j5 S
Page 4 of 4
Current production and use
In view of the fact
exact identi ties of
CBI, no information
those chemicals will
that the submitting company has claimed the
the subject chemical substances to be TSCA
pertaining to the TSCA Inventory status of
appear in this report.
In its Section 8(e) notices, the submitting company stated that
the subject chemical substances were experimental pesticide can-
d ida tes that have been "manufactured in small quanti ties with
limited, controlled distribution." In addition, the company
reported that the chemicals are "handled only by technically
qualified persons including consulting scientists and company
scientific personnel using prudent laboratory practices."
Comments/Recommendations
The submi tting company stated that I) all persons working vii th
the subject chemicals will be notified immediately about the re-
ported toxicologic findings, and 2) the existing practices for
handling of these chemicals "will be evaluated and modified if
necessary."
a)
The Chemical Screening Branch (CSB/ECADjOTS) will ask
the s ubmi t ter to ens ure tha t I) the Agency is informed
in a timely manner about any further significant interim
findings from the ongoing dietary study cited in each of
the company's Section 8(e) submissions and 2) the Agency
receives a full copy of the final report (including the
actual experimental protocol, data, results of gross and
histopathologic examinations, results of any statistical
analyses, etc.) from the study.
b)
In view of EPA' s general interest in corporate actions
that are taken on a voluntary basis in response to chem-
ical toxici ty or exposure information, the submi tting
company will be asked also to describe the nature and
results, if available, from all studies (other than
those submi tted already to the Agency) about which the
company is aware or that the company has conducted, is
conducting, or is planning to conduct to determine the
toxicity of or the exposure to the subject chemicals.
The Chemical Screening Branch will review the submitted
information in order to determine the need for further
OTS assessment of the subject chemical substances.
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, NTP, FDA, OSVvER/EPA,
OW/EPA, OAR/EPA, ORD/EPA, and OPP/OPTS/EPA. Copies of
this status report will be provided also to the TSCA
Assistance Office (TAO/OTS) for further distribution.
310
-------
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
Page 1 of 6
DA TE: ocr - 8 I9EE;Z'74
SUBJECT: Status Report* 8EHQ-0986-0626 S, APproved:,:/Y/~ ~/ftf:
FROM: Frank D. Kover, Chief vr;.J.L({ /), /(fi~.......
Chemical Screening Branch/ECAD/OTS
(/
TO: Joseph J. Merenda, Director
Existing Chemical Assessment Division/OTS
NOTE:
The submitting company has claimed its company name and the exact
identity of the tested chemical to be TSCA Confidential Business
Information (TSCA CBI). The Information Management Division
(IMD/OTS) will ask the submitting company to substantiate these
conf idential i ty claims. The submi tting company has stated non-
confidentially that the chemical is a halogenated pyridine.
Submission Description
The submitting company provided the following summarized results
of an oral teratology study of the halogenated pyridine in rats:
"[G]roups of 29 bred Fischer 344 rats were administered
the test material on days 6 through 15 of gestation at
dose levels of 0 or 75 mg/kg/day. The fetuses were re-
moved and all [of the] live fetuses were examined for
external al tera tions. In addi tion, the tissues wi thin
the thoracic cavi ty were examined in order to
detect any vascular anomal ies. . ."
"At 75 mg/kg/day, decreased maternal weight gain during
dos ing, decreased feed consumption and increased water
consumption were observed. statistically signifi-
cant differences in [the] maternal weight gain during
the dosing period. Fetal body weights were also
decreased. visceral examination of tissues in the
thoracic cavity revealed a statistically significant in-
creased incidence of persistent right fourth aortic arch
in the treated group. No evidence of this malformation
was observed in the control group. .. ...."
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
311
-------
8EHQ-0986-0626 S
Page 2 of 6
In its TSCA section 8(e) submission, the company also provided
the follmving information wi th regard to the observed vascular
anomaly:
"During normal embryologic development, the left aortic
arch persists to become the true aortic arch, and the
right aortic arch combines with the right paired dorsal
aorta to become the right subclavian. The persistence
of the righ t aortic arch resul ted in a vascular ring
surrounding the esophagus and trachea."
In its TSCA Section 8(e) notice, the submitting company stated
that the reported findings confirmed those provided previously to
EPA on a "For Your Information" (FYI) basis (FYI-OTS-l085-0407 S
Supplement). In FYI-OTS-I085-0407 S Supplement, the submi tting
company provided the following summarized information about the
results of an oral teratology study of the halogenated pyridine
in rats:
"Groups of 24-28 bred Fischer 344 rats were administered
the test material on days 6 through 15 of gestation and
the fetuses removed by Cesarean section on day 21 of
gestation. Dose levels were 0, 5, 25 and 75 mg/kg/day.
Each fetus was examined externally, and approximately
half of the fetuses in each dose group were examined for
visceral alterations by the Staples technique. At the
top dose level (75 mg/kg/day), decreased food consump-
t ion throughou t ge s ta t ion and increased wa ter cons ump-
tion during the first 3 days of dosing were the only
indications of maternal effects. Fetal body weights
were significantly lower than controls in the top dose
group. visceral examination revealed a cardiovascular
malformation among fetuses in the top two dose groups
which had not previously been observed in this strain
within this laboratory. This malformation involved a
displacement or absence of the ascending aortic arch
which occurred in two fetuses in the 25 mg/kg/day dose
group, and 5 fetuses in the 75 mg/kg/day dose group.
Though the incidence of this [vascular] anomaly was not
statistically eleva ted when compared to controls, the
clustering of 5 fetuses at the top dose level with this
unusual malformation suggests a teratogenic response at
a dose level which does not produce maternal toxicity."
In the above referenced FYI supplement, the submitting company
stated also that it had previously reported to EPA the results of
a "probe" teratology study of thIs halogenated pyridine in rats
(FYI-0585-0407 S Initial). In FYI-OTS-0585-0407 S Initial, the
submitting company provided the following summarized information
concerning the results of this "probe" study in Fischer 344 rats:
"Ten bred females per dose level were dosed on days 6
through 15 of gestation by oral gavage. Dose levels
were 0, 50, 100 and 150 mg/kg/day. Necropsy occurred on
312
-------
8EHQ-0986-0626 S
Page 3 of 6
day 16 of gestation. Parameters measured included: body
weights and gains, food and water consumption, organ
weights (liver and kidneys), corpora lutea, implanta-
tions, resorptions and litter size. At the top dose,
there was a statistically significant increase in re-
sorptions and a statistically significant decrease in
litter size. The maternal animals showed a statistical-
ly significant decrease in body weight gain during days
6 through 16 and a statistically significant increase in
relative liver weight at the top dose. The maternal
animals also showed a statistically significant decrease
in body weight gain over days 6 through 16 at the next
to top dose. II [Note: According to the submitted data,
there was a dose-response trend in increased resorptions
and decreased Ii tter size, al though these differences
were statistically significant over controls only in the
high dose group.]
Submission Evaluation
According to the probe teratology study, which was the subject of
FYI-OTS-0585-0407 S Initial, oral administration of 100 mg/kg/day
produced minimal rna ternal ef fects and no adverse ef fects in the
fetus. In view of these findings, it may have been more prudent
to use 100 mg/kg/day as the highest dose level (instead of 75
mg/kg/day) for the oral teratology study that was the subject of
FYI-OTS-I085-0407 S Supplement; selection of 75 mg/kg/day as the
highest dose level could have resulted in an under-estimation of
the potential developmental toxicity of the test material.
The cardiovascular malformations reportedly observed in the oral
teratology study (which was the subject of FYI-OTS-l085-0407 S
Supplement), although not statistically different from controls,
are considered toxicologically significant because they are rare
malformations and were not observed in concurrent control rats or
historical control rats in the performing laboratory. It should
be noted also that the observed cardiovascular defects were dose-
related, occurring in 0, 2 and 5 fetuses in the low, middle and
high doses, respectively. In addition, these effects were found
in more than one litter (0, 2 and 4 litters, respectively), and
thus were not due to random occurrence in a single dam. On the
basis of these data alone, therefore, it is apparent that the
tested halogenated pyridine produced serious adverse effects on
the fetus at doses below those causing overt maternal toxicity.
In FYI-OTS-I085-0407 S Supplement, the submitter stated that
further work was planned to investigate the reproducibility of
the findings reported in that supplemental FYI notice. The
present TSCA Section 8(e) submission presents the results of this
further work.
The summarized data submitted under TSCA Section 8(e) show that
at the 75 mg/kg/day dose level, the tested chemical produced si-
gnif icant increases in persistent righ t 4th aortic arch, total
313
-------
8EHQ-0986-0626 S
Page 4 of 6
cardiovascular malformations (which included retroesophageal
right subclavian artery and hypoplastic atrium) and incomplete
diaphragm when compared to concurrent control rats. Overall, the
resul ts of the studies ci ted in the FYI supplement and the TSCA
Section 8(e) notice both indicate that the subject chemical sub-
stance when administered orally to pregnant Fischer 344 rats at
75 mg/kg/day on days 6 through 15 of gestation produced uncommon
cardiovascular malformations in the offspring. Although there
was some toxicity seen in the dams, the rarity and apparent dose
and litter response nature of the observed malformations suggests
that the malformations were primary tOKic effects due to exposure
to the chemical and not due secondarily to maternal malaise.
Current production and Use
In view of the submitter's TSCA CBI claims, no information with
regard to the TSCA Chemical Substance Inventory status of the
subject chemical will appear in this report.
Comments/Recommendations
In its initial FYI submission, the submitter stated that all
persons engaged in research on the subject chemical were being
notified by the company about the reported findings.
-----------------------------------------------_._----------------
---------------------------------------------------------.--------
At the time of EPA's receipt of this Section 8(e) notice, EPA was
in the process of preparing a statement outlining the Agency's
initial position on the Section 8(e)-applicability/reportability
of the findings from the teratology study cited by the company in
FYI-OTS-1o85-0407 S Supplement. It is appropriate, therefore,
that this status report will serve as the forum for EPA to pre-
sent its position.
Following an EPA review of FYI-OTS-l085-0407 S Supplement, it is
EPA's initial position that the teratological findings presented
therein should have been reported to EPA under Section 8(e), the
"substantial risk" inforrnation reporting provision of TSCA. The
basis for EPA's position is as follows:
TSCA Section 8(e) states that "any person who manufac-
tures, [imports,] processes, or distributes in commerce
a chemical substance or mixture and who obtains informa-
tion which reasonably supports the conclusion that such
substance or mixture presents a substantial risk of in-
jury to health or the environment shall immediately in-
form the Administrator of such information unless such
person has actual knowledge that the Administrator has
been adequately informed of such information."
314
-------
8EHQ-0986-0626 S
Page 5 of 6
The preface in Part V of EPA' s March 16, 1978 Section
8(e) policy statement (" Statement of Interpretation and
Enforcement policy; Notification of Substantial Risk"
43 FR 11110) states that lIa substantial risk of injury
to health. is a risk of considerable concern be-
cause of (a) the seriousness of the effect. . . and (b)
the fact or probability of its occurrence. II With regard
to the seriousness of the effect, Part V explains that
EPA considers the types of health effec~s for which sub-
stantial risk information must be reported to include
lIany pattern of effects or evidence which reasonably
supports the conclusion that the chemical substance or
mixture can produce. . birth defects. . II The
information concerning these effects can be obtained
directly or inferred from designed studies (e.g., in
vivo animal studies) as described in Part VI of the
Section 8(e) policy statement.
With regard to the IIfact or probability of its [i.e.,
the serious effect's] occurrence" criterion, part V of
the Section 8 (e) policy statement explains that certain
type s of heal th ef fects (e. g ., bi rth de fects, cancer)
are considered by EPA to be so serious that relatively
little weight should be attached to the chemical's
exposure in determining whether a risk is substantial.
Further, EPA's response to Comment 31 (see Appendix B of
the TSCA Section 8(e) policy document) states that the
occurrence of serious effects such as those described in
Part V(a) of the policy statement (e.g., birth defects)
presupposes exposure to the tested chemical or mixture
and must be submitted to EPA pursuant to Section 8(e) of
TSCA.
Wi th regard to when to report information to EPA under
Section 8(e), Part VI of the policy statement explains
that a subject IIperson is not to delay reporting until
he obtains conclusive information that a substantial
risk exists, but is to immediately report any evidence
which reasonably supports that conclusion. II Part VI
explains also that IInot only should final resul ts from
such studies be reported, but also preliminary results
from incomplete studies where appropriate. II
In light of the preceding discussion and EPA's review of the
informa tion presented in the submi tting company's supplemental
FYI notice (FYI-OTS-I085-0407 S Supplement), EPA believes that
the teratologic findings contained therein can IIstand alone" in
their abili ty to offer reasonable support for a conclusion that
this TSCA-covered substance can cause birth defects and as such
should have been submitted formally to EPA under Section 8(e) of
the Toxic Substances Control Act.
315
-------
8EHQ-0986-0626 S
Page 6 of 6
a)
The Chemical Screening Branch (CSB/ECAD) will ask the
submi tting company to provide its rationale as to why
the results from the oral teratology study cited in FYI-
OTS-I085-0407 S Supplement were not provided formally to
EPA under TSCA Section 8(e). Following a review of the
submi tting company's response, the Chemical Screening
Branch (CSB/ECAD/OTS) will, if appropriate, deliver all
information contained in the submitter's supplemental
FYI notice to the OTS Document Control Officer (DCO) for
proper handling and filing under Section 8(e) of TSCA.
In addition, the Chemical Screening Branch will ask the
submitting company to provide full copies of the final
reports from all studies ci ted in FYI-OTS-0585-0407 S
Ini tial, FYI-OTS-I085-0407 S Supplement and 8EHQ-0986-
0626 S Initial.
In view of EPA' s general interest in corporate actions
taken on a voluntary basis in response to chemical toxi-
city or exposure information, the submitting company
will be asked also to describe the nature and results,
if available, from all studies (other than those that
have been reported already to EPA) about which the com-
pany is aware or that the company has conducted, is con-
ducting or plans to conduct to determine the toxicity of
or the exposure to this halogenated pyridine.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of this halogenated pyridine.
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, NTP, FDA, OSWER/EPA,
OAR/EPA, OW/EPA, ORD/EPA and OPP/OPTS/EPA. Copies of
this report will be provided also to the TSCA Assistance
Office (TAO/OTS/EPA) for further distribution.
316
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
SEP 3 0 1986
Status Report* 8EHQ-0986-0627 Approved: ~ l~o::.- /~ "kJ,.?r-~'L
k t/4 ~ (j q 3L)/i'," ~
James F. Darr, Sect ion Head :1 f lJo..-//L.-
Chemical Risk ldentificatio Section/CSB
Page 1 of 4
UBJECT:
FROM:
TO:
Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Note
In reporting the following information under Section 8 (e) of
TSCA, the CIBA-GEIGY Corporation stated that Tinuvin@ 1130 (the
reaction product of the methyl ester of beta-[3-(2H-benzotriazol-
2-yl) -4-hydroxy-5-tert-butylphenyl] propionic acid and polyethyl-
ene glycol) was the subject of a TSCA Section 5 Premanufacture
Notice (PMN 85-812) for which EPA's PMN review period had expired
and for which the company had submitted (on December 17, 1985) a
Notice of Commencement (NOC) of manufacture.
Submission Description
The CIBA-GEIGY Corporation submitted a complete copy of the final
report from a 28-day oral gavage study of Tinuvin@ 1130 in rats.
In the cover letter to its submi ss ion, CIBA-GEIGY presented the
following information with regard to the conduct and results of
this 28-day study:
"The test mate1:lial was administered by gavage for a
period of 28 days to [groups (5 males and 5 females/
group) of Crl CD (SD) Br] rats. The dose levels were 0,
10, 50, 200 and 1000 mg/kg/BW. The major findings were
foci of liver necrosis, focal liver hemorrhages, and
marked renal tubular degeneration. The renal effects
were only seen in the high dose males, and the 1 iver
effects had a NOEL [( no-observed-effect-level)] of 10
mg/kg. "
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
317
-------
8EHQ-0986-0627
Page 2 of 4
In its submission, CIBA-GEIGY stated also that "a substituted
benzotriazole, CG-571, that was the subject of 8EHQ-0486-0597 S,
is an impurity in Tinuvin@ 1130 «1%)." It should be noted that
in that previous Section 8(e) notice, the submitter reported that
this substituted benzotriazole (identified non-confidentially as
a "benzotriazole-2-yl substituted hydroxyphenylpropionate ester")
had been found to cause hepatotoxici ty, as well as other serious
toxic effects, in male and female rats in a 28-day oral gavage
stud Y .
In the present Section 8(e) submission, CIBA-GEIGY also provided
copies of the Tinuvin@ 1130 Material Safety Data Sheet (MSDS) and
product label. According to the submi tted MSDS, Tinuvin@ 1130
has an oral (rat) LD50 in excess of 5 grams/kg and a dermal (rat)
LD50 in excess of 2 grams/kg. In addition, the MSDS reports that
Tinuvin@ 1130 is non-irri tating to non-abraded rabbi t skin and
only slightly irritating to rabbit eyes. The MSDS does report,
however, that Tinuvin@ 1130 has a "strong grade of sensitizing
potential" based on resul ts obtained from a maximization test in
guinea pigs (70% of the treated animals became sensitized to the
product). With regard to genotoxicity, the submitted MSDS states
that Tinuvin@ 1130 was negative in an Ames Salmonella typhimurium
(bacteria) test, a nucleus anomaly test in Chinese hamsters, and
a micronucleus test in Chinese hamsters.
Submission Evaluation
Although the information received to date on Tinuvin@ 1130 does
indicate that the chemical is not particularly acutely toxic, the
data from the 28-day repeated oral (gavage) exposure shOt/I that
Tinuvin@ 1130 induces liver and kidney toxicity, as well as other
organ toxicities. Specifically, the 28-day study shows that when
rats of both sexes were given oral dose levels of 0, 10, 50, 200
or 1000 mg/kg/day for 28 days, there was an observed increase in
liver weights in a dose-responsive manner. For liver toxicity
the no-observed-effect-level (NOEL) was 10 mg/kg/day and the
hepatic findings included liver foci and focal liver hemorrhages.
Wi th regard to kidney toxici ty, male rats receiving 1000 mg/kg
dose had renal tubular degeneration (the NOEL was 200 mg/kg/day).
In terms of mortali ty, the treated animals experienced a high
death rate at the highest dose level. Five of 10 treated animals
died with males appearing to be more susceptible (4/5 died) than
females (1/5 died). \Vi th regard to other toxicolog ic findings,
the submitted data show that at 200 and 1000 mg/kg/day, the male
rats had a decrease in size or weight of the seminal vesicles;
females receiving 200 and 1000 mg/kg/day showed a decrease in
spleen weights and females receiving 1000 mg/kg/day showed a de-
crease in thymus gland weights. The submitted data indicate,
however, that the thymus and spleen weight decreases observed in
the higher dose females were not accompanied by any microscopic
abnormalities.
318
-------
8EHQ-0986-0627
Page 3 of 4
Current Production and Use
In the cover letter to its Section 8(e) submission, CIBA-GEIGY
stated that Tinuvin@ 1130 "is a relatively low volume product in
an early stage of commercialization." According to the provided
MSDS, Tinuvin@ is an ultraviolet (UV) light absorber; according
to EPA's public file (non-confidential) records for PMN 85-812,
Tinuvin@ 1130 is a light stabilizer imported as an additive for
coatings. CIBA-GEIGY stated in its Section 8(e) submission that
Tinuvin@ 1130 "is alight yellow liquid wi th a boilin1 point of
greater than 300°C and a vapor pressure of 6.8 X 10- mm Hg at
25°C." The provided MSDS reports also that Tinuvin@ 1130 has "no
discernible odor."
In its TSCA Section 8(e) submission on Tinuvin@ 1130, CIBA-GEIGY
also provided the following information concerning the potential
for exposure to this product:
"There is little likelihood of exposure by vapor inhala-
tion because of the high boiling point and the very low
vapor pressure of the liquid substance. Dermal exposure
will be mitigated because the product has a strong der-
mal sensitizing potential, and protective equipment, im-
pervious gloves, are already recommended in the MSDS.
Based on theoretical considerations of the high molecu-
lar weight and chemical structure/properties of the test
substance, dermal absorption would be expected to be
negligible."
Comments/Recommendations
In the cover letter to its Section 8(e) submission, CIBA-GEIGY
reported that based on the submitted toxicologic findings, the
company has 1) revised the Tinuvin@ 1130 MSDS and label, and 2)
notified the company's laboratory staff and customers about the
toxicologic findings.
a)
In view of EPA' s general interest in corporate actions
taken on a voluntary basis in response to chemical tox-
icity or exposure information, CIBA-GEIGY will be asked
to describe the nature and results, if available, from
all studies (other than those submitted already to EPA)
about which the company is aware or that the company has
conducted, is conducting or plans to conduct to deter-
mine the toxicity of or the exposure to Tinuvin@ 1130.
b)
The Chemical Screening Branch will review the submitted
information in order to determine the need for further
OTS assessment of the subject chemical substance.
319
-------
8EHQ-0986-0627
Page 4 of 4
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OWl EPA, OAR/BPA, ORD/EPA, OPP/OPTS, and CCD/OTS/OPTS.
Copies of this status report will be provided also to
the TSCA Assistance Office (TAO/OTS/OPTS) for further
distribution.
320
-------
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
Page 1 of 5
DATE:
OCT
9 1986
JBJECT:
status Report*
8EHQ-0886-0628
APproved:~ Iq!~b
FROM:
James F. Darr, Section Head d~L1~bt~L-
Chemical Risk Identificatio~;:ction/CSB
TO:
Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Union Carbide Corporation provided a full copy of a pre-
publ ication manuscript enti tIed" Behavioral Toxici ty of Nitrous
Oxide in Rats Following Prenatal Exposure." According to the
provided manuscript, the results of this study (which was con-
ducted independently by investigators from the Forsyth Dental
Center (Boston, MA) and the University of Pittsburgh (pittsburgh,
PA») "emphasize the fact that exposure to . . . [nitrous oxide] in
utero during a period beyond major organogenesis can result in
permanent al terations in brain function." The submi tted manu-
script states also that previously conducted "teratological
studies have focused on the physical malformations associated
with early prenatal exposure [to nitrous oxide], leaving the
false impression that no serious consequences occur as a result
of exposure late in gestation. The submitted manuscript states
further that "neurobehavioral deficits unaccompanied by physical
deformities, such as those [behavioral deficits] induced by . . .
[nitrous oxide] in this study, are lasting effects in need of
further consideration."
According to the submitted draft manuscript, the performed study
involved 40 timed-pregnant Sprague-Dawley rats of which 15 were
exposed to a 75% nitrous oxide/25% oxygen mixture for 8 hours on
day 15 of gestation; 15 were exposed to air only for 8 hours on
day 15 of gestation (sham air control); 5 were exposed to the 75%
nitrous oxide/25% oxygen mixture for 8 hours on both days 14 and
15 of gestation; and 5 were exposed to air only for 8 hours each
on both days 14 and 15 of gestation (sham air control).
====================================================================================
* NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
321
-------
8EHQ-0886-0628
Page 2 of 5
The submitted manuscript reports that "at parturition, all
litters were reduced to eight pups; 4 males and 4 females were
randomly selected whenever possible'. for use in studies involving
1) exploratory, diurnal and nocturnal locomotor activity in a
residential maze, and 2) spontaneous di urnal primary behaviors
(e.g., lying down, standing, walking, rearing) and secondary be-
haviors (e.g., grooming, sniffing, scratching) as measured by
time-lapse photography of rats exposed to a novel environment.
The Resul ts section of the manuscript presents the
information regarding the findings of the maze study:
following
". In 1 month old males and females exposed [to
75% nitrous oxide] only on gestational day 15, no sig-
nificant changes in group activity were detected. By 5
months of age, however, the females had developed s ig-
nificant hypoactivity during the exploratory period.
Males, in contrast, displayed significant diurnal acti-
vity. Extending the prenatal [nitrous oxide] treatment
to include gestational day 14 as well as day 15 resulted
in significant exploratory and diurnal hyperactivity in
the females at both ages tested. Hyperact ivi ty also
appeared in the males receiving two days of [ni trous
oxide] exposure in utero, but it was detectable in the
residential mazeonly at the early age and not at 5
months."
The Resul ts section of the submi tted manuscript provided the
following information regarding behavioral activi ty as measured
by time-lapse photography in the male rats:
"Examination of ni trous ox ides's effect on behavior in
one month-old males revealed little change. Whether ex-
posure lasted one or two days, no significant changes in
the frequency, duration or distribution of the primary
motor acts. were found. Only a few secondary or
modifier acts were affected in males at this age, and
these changes were specific to the day/days of exposure
Males exposed on gestational day 15 exhibited
fewer occurrences and a shorter duration. . of snif-
f ing, marg inally fewer occurrences of scratching and a
greater frequency of looking. The average duration of
turning in these young . males. tended to be
shorter than in the simultaneously filmed controls. . .,
but the difference [observed] was not statistically sig-
nificant. Males exposed on gestational days 14
and 15 did not show any significant changes in their
motor acts, although they too showed slight tendencies
of change in turning (frequency) and sniffing (frequency
and duration).
322
-------
8EHQ-0886-0628
Page 3 of 5
"Altered male behavior was most obvious in the five
month-old rats exposed [to nitrous oxide on days 14 and
15 of gestation]. In that group, changes in body posi-
tion were detected, consisting of a decreased frequency
of standing and a corresponding increase in the
average duration of rearing. . .. In addition to [the]
changes in body posi tion, there were fewer incidences
when no secondary. . . [motor acts were observed]. All
[nitrous oxide-]treated males displayed effects on face
washing behavior; males exposed for one day did not wash
their faces as often, whereas males exposed for two days
displayed face washing more randomly over time.
In general, all of these changes make the adul t males
appear slightly hyperactive, especially those exposed
for two days in utero. II
The Resul ts section of the manuscript presented the following
information with regard to behavioral activi ty as measured by
time-lapse photography of the female rats:
"Induction of hyperactivity by prenatal [nitrous oxide]
exposure is demonstrated clearly in data from females.
Even at one month, evidence for hyperactivity could be
found. The females exposed [to nitrous oxide] in utero
on days 14 and 15 had increased reari ng and walking
frequencies. . . that accompanied significantly shorter
durations of standing. . and sitting. At five
months of age, hyperactivi ty in the females was even
more evident. The frequencies of turning and smelling
increased, whereas those of sitting, washing face and
grooming decreased. . .. The average durations of sit-
ting, grooming, looking and rearing were more randomly
distributed in time. In contrast, [the observed] occur-
rences of sitting and face washing were more clustered
in time. . . .
"Females exposed [to nitrous oxide] on only gestational
day 15 did not exh ibi t the same behavioral abnormal i-
ties, although they too had been affected. At one month
of age, [the females] exhibited more occurrences of head
turning. and a more random. . distribution of
body turning. . . when compared to air controls. . . ."
At five months [of age], these females displayed a ten-
dency toward hypoactivity as indicated by a greater
nmaber of instances when no secondary [motor] acts. . .
were performed and the duration of rearing was
shortened. . . . II
The Discussion section of the submitted manuscript presented the
following statements with regard to the overall interpretation of
the data obtained from the performed studies:
323
-------
8EHQ-0886-0628
Page 4 of 5
"The time-lapse photographic and residential maze data
demons tra ted that prenatal expos ure [of rats] to 75 [%]
ni trous oxide for 8 hours can permanently al ter the
neurobehavioral output of the CNS. This [nitrous oxide]
effect was easier to detect in mature, 5 month old rats
than it was in younger animals only one month old.
F'emales exh ib i ted more changes than males, and two day
exposures spanning gestational days 14 and 15 al tered
behavior more than a one day exposure on gestational day
15. vVf1en hyperact i vi ty was the clearcut outcome, it was
typically characterized by the grooming behaviors (sit,
wash face, groom) decreasing in frequency, shortening in
duration and clustering in distribution in time. Con-
currently, exploratory and attentive acts increased in
frequency (turn and smell) and become more randomly
distributed in time (stand, smell, look and rear)."
Submission Evaluation
Al though there are several limi tations of the performed study,
the submitted findings do suggest that prenatal exposure to
nitrous oxide results in a pattern of hyperactivity postnatally.
(It should be noted that the reported resul ts are supported by
published studies, the results of which indicate that altered
behavior occurred in mice following prenatal exposure to nitrous
oxide.) Some of the limi tations of the present behavioral tera-
tology study include, for example: 1) use of too few animals; 2)
use of the pup as opposed to the litter as the statistical unit;
and 3) use of a technique (t ime-lapse photography) that is not
as yet well establshed for assessment purposes (the results ob-
tained using this technique do appear to support, however, the
findings of the maze study). Further, it is quite difficult to
interpret some of the reported findings because the experimental
methodology was not described in sufficient detail. For example,
there was no indication as to whether the same rats were tested
at 1 month and 5 months of age. Also, the residential maze study
findings were presented for only 4 or 5 Ii tters al though there
were 15 litters exposed to nitrous oxide on day 15 of gestation.
In addition, there is no way to determine how many different lit-
ters were analysed in the time-lapse photography portion of the
study because the data are presented only in terms of numbers of
animals. Finally, the informa tion presented in the manuscript
does not allow for a determination of whether the rats tested in
the residential maze were the same as those tested via time-lapse
photography.
In conclusion, while there are a number of limitations regarding
study design and presentation of the findings, the submitted data
suggest that altered post-natal behavior occurred as the result
of exposure to ni trous oxide in utero. In order to reach a firm
conclusion regarding this apparent toxicity, however, additional
research is clearly necessary.
324
-------
8EHQ-0886-0628
Page 5 of 5
Current Production and Use
A review of the production range (includes importa tion volumes)
statistics for nitrous oxide (CAS Number 10024-97-2), which is
listed in the initial TSCA Chemical Substance Inventory, shows
that between 101 million and 211 million pounds of this chemical
were reported as being manufactured and/or imported in 1977.
This production range information does not include any data that
were claimed as TSCA Confidential Business Information (TSCA CBI)
by the person( s) reporting for the initial 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).
Accord ing to secondary 1 i tera ture sources, ni trous oxide (which
is known also as laughing gas) is a colorless, non-combustible
gas with a "sweet" odor/taste. The applications of nitrous oxide
include its use as a general anesthetic in dentistry/medicine, as
a propellant in certain types of aerosol food products, as a leak
detector, as a component in carbon disulfide-containing rocket
fuels, and as an oxidizing agent.
Comments/Recommendations
In its Section 8(e) submission, Union Carbide provided EPA with
the name, address and phone number of the lead author of the
submi tted manuscript in order for the Agency to obtain further
information directly from the investigator(s).
a)
The Chemical Screening Branch will contact the lead
investigator in order to obtain additional information
wi th regard to the Gonduct/resul ts of this behav ioral
teratology study of nitrous oxide in rats.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of nitrous oxide.
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, OAR/EPA, ORD/EPA and OPP/OPTS/EPA. Copies of
this status report will be provided also to the TSCA
Assistance Office (TAO/OTS) for further distribution.
325
-------
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
Page 1 of 4
DATE:
OCT I 4 1986
Status Report* 8EHQ-0986-0629 Approved :~
James F. Darr, Section Head ~-~~
Chemical Risk Identificatiog~~;~tion/CSB
10/1'1 /~
SUBJECT:
FROM:
TO:
Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Union Carbide Corporation submi tted a copy of draft final
report enti tIed" Epidemiologic Study of vinyl Chloride Horkers."
(According to Union Carbide, the study had been conducted for the
Chemical Manufacturers Association (CMA).) The "Summary" section
of the submitted report presented the following information with
regard to the conduct and results of the performed epidemiologic
stud y :
"The cohort consisted of 10,173 men who had worked for
at least one year in jobs involving exposure to vinyl
chloride pr ior to January 1, 1973. These men were em-
ployed at 37 plants in the U. S. belonging to 17 com-
panies. Observation of the mortality experience of the
cohort was extended to December 31, 1982. A total of
1536 cohort members were identified to have died. The
ooserved mortality, by cause, was compared with the ex-
pected based on U.S. mortality rates, standardized for
age, race and calendar time. Analyses by length of ex-
posure, latency, age at first exposure, calendar year of
first exposure and type of products were performed. The
[performed epidemiologic] study confirmed that the vinyl
chloride workers [had] experienced significant mortality
excesses in ang iosarcoma (15 deaths), cancer of the
1 iver and biliary tract (SMR = 641), and cancer of the
brain and other central nervous system (SMR = 180). In
addition, the study also found a significant mortality
excess in emphysema (SMR = 179). On the other hand, the
study did not find any excess in either respiratory
cancer or lymphatic and hematopoietic cancer."
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
326
-------
8FHO-0986-0629
Page 2 of 4
In submitting this report to EPA, union Carbide stated that nthe
information on excess emphysema observed in [the] vinyl chloride
\mrkers is not reliably ascribed in the report to exposure to
vinyl chloride because of: (1) potential problems involved in the
cause of death coding for emphysema; (2) the manner in which the
diagnosis of emphysema was made (clinically or patholog ically;
(3) the possible contribution of other factors such as smoking
and geographical variation; and (4) the absence of precedents in
experimental animals." In addition, Un.ion Carbide stated that
the apparent excess of biliary tract cancer "may be explained by
failure to diagnose angiosarcoma properly."
Submission Evaluation
The submitted epidemiological study continued the follow-up of
10,173 workers who were exposed to vinyl chloride for 1 year or
more between 1942 (or on initiation of complete recordkeeping
systems at the studied plant) and December 31, 1972. The vital
status of 9200 members was characterized as of December 31, 1982.
Within the period of the study, 1536 (16.7% of the cohort) died.
When compared to the mortality experience of u.S. white males,
this cohort had a statistically significant deficit in total mor-
tality. statistically significant increases in mortality were
observed from neoplasms of the liver and biliary tract (Standard
Mortality Ratio (Sr1R)=641.2; p
-------
8EHQ-0986-0629
Page 3 of 4
In conclusion, this epidemiolog ical study appears to have been
conducted carefully and the results are presented in an unbiased
fashion. The excesses in liver and brain cancers observed in the
cohort could be used possibly to estimate low-level human cancer
risks. The observed excess in emphysema deaths is a findin'J that
deserves further attention. For example, an in-depth evaluation
of the existing epidemiologic information on vinyl chloride could
be conducted in order to determine the ability of previously per-
formed studies to detect emphysema excesses.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for vinyl chloride (CAS NO. 75-01-4), which is listed
in the initial TSCA Chemical Substance Inventory, has shown that
between 3.8 and 10 billion pounds of this chemical were reported
as manufactured and/or imported in 1977. This produc tion range
information does not include any manufacturing/importation data
claimed as TSCA Conf idential Business Information (TSCA CBI) by
the person(s) reporting for the initial TSCA Inventory, nor does
it include any informa tion that would compromise TSCA CBl. All
information reported for the initial TSCA Inventory, inc lud ing
the production range information, is subject to the limitations
that are contained in the TSCA Inventory Reporting Regulations
(40CFR710).
According to Chemical & Engineering News (June 9, 1986 issue),
u.S. production of vinyl chloride was 6.09 billion pounds and
7.78 billion pounds in 1984 and 1985, respectively.
According to secondary literature sources, applications of vinyl
chloride include the chemical's use in the production of poly-
vinyl chloride, as a refrigerant, and as a plastics adhesive.
Comments/Recommendations
In its Section 8(e) submission, Union Carbide stated that any
questions concerning the submitted report should be addressed to
the Chemical Manufacturers Association.
It should be noted that the Office of Toxic Substances (OTS) has
received several Section 8(e) and "For Your Information" (FYI)
notices on vinyl chloride. It should be noted also that several
EPA program Offices (e.g., Office of Air and Radiation (OAR))
have evaluated or are currrently evaluating available toxicologic
and exposure data on vinyl chloride.
a)
In view of EPA' s general interest in corporate actions
taken on a voluntary basis in response to toxicologic or
exposure data, the Chemical Screening Branch (CSB/ECAD)
will request Union Carbide to describe the actions the
company has taken or plans to take to notify workers or
others about the reported epidemiologic findings.
328
-------
8F.HQ-0986-0629
Page 4 of 4
b)
The Chemical Screening Branch will review the reported
information in greater detail in order to determine the
need for further OTS assessment of vinyl chloride.
c)
The Chemical Screening Branch will send copies of this
status report to OSHA, NIOSH, CPSC, FDA, NTP, OS~mR/EPA,
OW/EPA, OAR/EPA, ORD/EPA and OPP/OPTS/EPA. Copies of
this report will be sent also to the TSCA Assistance
Office (TAO/OTS) for further distribution.
329
-------
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
Page 1 of 3
DATE:
SEP 24 1986
status Report* 8EHQ-0986-0630 APproved:~h i 0;;, ~"Ip;..I{:t;..'L
0- 'I J'Iltt, j
James F. Darr, Section Head ~"f ZX;;1.--
Chemical Risk IdentificatioP~ec~ion/CSB
SUBJECT:
FROM:
TO:
Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Celanese Corporation provided the following information with
regard to the conduct and preliminary results of two genotoxicity
studies on pentaerythritol-tris-(B-(N-aziridinyl)propionate) (CAS
No. 57116-45-7:
"The tests conducted were in vitro chromosome aberration
and in vi tro cell transformation assays. Both [of the]
testS-were positive. The chromosome aberration test was
positive with and without metabolic activation. These
resul ts are from an oral report, and full reports will
be available shortly.. [and will be sent to EPA]."
Submission Evaluation
The submi tted summarized information indicates that the tested
chemical does possess some degree of genotoxic activity. In
order for the Agency to evaluate the overall significance of the
reported findings, however, full copies of the final reports (in-
cluding the actual experimental protocols, data, resul ts of any
statistical analyses, etc.) from the cited studies are needed.
Current production and Use
A review of the production range (includes importation volumes)
statistics for CAS No. 57116-45-7, which is listed in the initial
TSCA Chemical Substance Inventory, has shown that between 10,000
and 100,000 pounds of this chemical were reported as manufactured
and/or imported in 1977. This production range information does
------------------------------------------------------------------------------------
------------------------------------------------------------------------------------
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
330
-------
8EHQ-0986-0630
Page 2 of 3
not contain any manufacturing or importation data claimed as TSCA
Confidential Business Information (TSCA CBI) by the person(s) re-
porting for the ini tial TSCA Inventory, nor does it include any
information that would compromise TSCA CBI. All of the data re-
ported for the ini tial TSCA Inventory, includ ing the production
range data, are subject to the limitations contained in the TSCA
Inventory Reporting Regulations (40 CFR 710).
According to the Celanese Corporation, this chemical is being
manufactured in Japan and is imported for commercial purposes by
virginia Chemicals, Inc., a Celanese subsidiary. In addition,
Celanese stated that the chemical's "primary end use appl ication
is as a cross-linker in coating systems."
Comments/Recommendations
Although a positive in vitro genotoxicity test finding, when
considered by itself, may not be sufficient to offer reasonable
support for a conclusion of substantial risk (as 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 a finding is
of value in assessing the possible risk( s) posed by exposure to
the chemical or mixture. Also, the Agency believes that a posi-
tive genotoxici ty test resul t, in combination wi th addi tional
information (e.g., the knowledge of potential exposure to and/or
high production of the tested chemical or mixture), would suggest
the need, in many case s, to conduct other stud ies des ig ned to
determine better the toxicity of or the exposure to that chemical
or mixture. The results of such additional studies should be
considered also for submission to EPA under Section 8(e) of TSCA.
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will ask
the Celanese Corpora-tion to ensure that EPA receives a
full copy of the final report (including the actual ex-
perimental protocol, data, resul ts of any statistical
analyses, etc.) from each study cited in the company's
TSCA Section 8(e) notice.
In view of EPA' s general interest in corporate actions
taken on a voluntary basis in response to chemical toxi-
city or exposure information, Celanese will be requested
also to describe the actions that the company has taken
or plans to take to notify workers or others about the
reported toxicologic findings. In addition, Celanese
will be requested to describe the nature and results, if
available, of all studies (other than those cited in the
open scientific literature or those submitted already to
EPA) about which Celanese is aware or that Celanese has
conducted, is conducting, or plans to conduct to deter-
mine the toxicity of or the exposure to this chemical.
331
-------
8EHQ-0986-0630
Page 3 of 3
b)
The Chemical Screening Branch will review the reported
findings 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, OAR/EPA, ORD/EPA, and OPP/OPTS/EPA. Copies of
this status report will be transmitted also to the TSCA
Assistance Office (TAO/OTS) for further distribution.
332
-------
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
Page 1 of 3
DATE:
SEP 2 9 1986
Status Report* 8EHQ-0986-0631 S Approved: ~r C;;7rI f.;'\ ~~O:-Kn~
-- ~ U 9/:J.9/Pi-
James F. Darr, Section Head ~1 T al/"Y'l----
Chemical Risk IdentificatioJ/~e.ction/CSB
UBJECT:
FROM:
TO:
Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
NOTE
The submi t ting company claimed its company name and the exact
identities of the subject chemicals to be TSCA Confidential
Business Information (TSCA CBI); the Information Management
Division (IMD/OTS) will request the submitter to substantiate
these claims. In its submission, the company did state non-
confidentially that the subject chemicals, which were tested as a
mixture in mineral spirits, were perfluoroalkyl resins that had
been the subject of the following TSCA Section 5 premanufacture
Notifications: (PMN 85-1053 and PMN 85-1054). According to the
non-confidential versions of these PMNs (which were obtained from
the Agency's public TSCA Section 5 files), the tested resins are
"perfluoroalkyl methacrylate copolymers."
Submission Description
The submi tting company provided summarized preliminary findings
from acute inhalation studies in rats exposed for 4 hours to a
respirable aerosol (1 urn mass medium aerodynamic diameter or
less) of mineral spirits alone (solvent control) or a mixture
consisting of 0.5% perfluoroalkyl resins (total content), 4.5%
chlorofluorocarbon 113, and 95% mineral spirits. According to
the submitter, these acute inhalation studies showed the mixture
to be more toxic than mineral spirits alone (10/10 deaths were
observed following exposure to 544 parts per million (ppm) of the
mixture while no deaths were observed following exposure to 488
ppm of mineral spirits (the published 4-hour rat inhalation LC50
value for mineral spirits is 3400 ppm). The submitter reported
also that no deaths were observed for rats exposed for 4 hours
via inhalation to 102 ppm of the mixture. According to the non-
CBI versions of PMN 85-1053 and PMN 85-1054, the subject resins
have acute oral LD50's of approximately 15 grams/kg each in mice.
------------------------------------------------------------------------------------
------------------------------------------------------------------------------------
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
=33
-------
8EHQ-0986-0631 S
l?age 2 of 3
Submission Evaluation
Immediately upon receipt of this TSCA Section 8(e) submission,
the Chemical Screening Branch (CSB/ECAD/OTS) pro v ided copies of
the submission to the Premanufacture Notice Management Branch
(PNMB/CCD/OTS) and the Risk Analysis Branch (RAB/ECAD/OTS) for
review. It should be noted that EPA's Office of Toxic Substances
(OTS) has received a number of TSCA Section 8(e) submissions on
perfl uoroalkyl compounds. It should be noted also that the Ri sk
Analysis Branch is currently reviewing available toxicologic and
exposure data on this class of chemicals. Finally, it should be
noted that EPA's 90-day PMN review period for PMN 85-1053 and PMN
85-1054 has been halted to date due to the company's voluntary
testing of the subject perfluoroalkyl methacrylate copolymers.
Current Production and Use
According to the non-CBI versions of PMN 85-1053 and PMN 85-1054,
the subject perfluoroalkyl methacrylate copolymers are imported.
In addition, the non-CBI PMN's state that the substances are for
use as "fabric stain repellents." In its Section 8(e) notice,
the submi tting company stated that because lithe resins tested in
the mixture are not commercial products, only very small nlliobers
of people have been potentially exposed in development work."
The submitter stated further that this development work "has been
carried out with the usual safeguards employed in the conduct of
research act i vi ties" and it is the corapany' s bel ie£ II that the
risk to these individuals has been minimal."
Comments/Recommendations
In its Section 8(e) notice, the submitting company stated that
the company I s development program employees and the overseas
supplier of the resins have been notified about the reported
toxicologic findings.
a)
The Chemical Screening Branch will ask the subrai tting
company to ensure that EPA receives complete copies of
the final report (including the actual experimental pro-
tocol, results of gross and histopathologic examination,
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 corporate actions
taken on a voluntary basis in response to chemical toxi-
city or exposure data, the submitting company will be
requested also to describe the nature and results, if
available, from all studies (other than those submitted
already to EPA) about which the company is aware or that
the company has conducted, is conducting, or is planning
to conduct to determine the toxicity of or the exposure
to the subject resins alone or in combination with other
chemical substances.
334
-------
8EHQ-0986-063l S
Page 3 of 3
b)
As in the case of the initial Section 8(e) submission,
all reported information will be transmitted immediately
to RAB/ECAD/OTS and PNMB/CCD/OTS for evaluation.
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSHEH/EPA,
OW/EPA, OAR/EPA, ORD/EPA, OPP/OPTS/EPA, PNMB/CCD/OTS,
and RAB/ECAD/OTS. In addition, copies of this report
will be sent to the TSCA Assistance Office (TAO/OTS) for
further distribution.
335
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 2
DATE:
OCT 2 2 1986
status Report* 8EHQ-0986-0632 Approved :t:Jf-
James F. Darr, Section Head ~r-~
Chemical Risk IdentificatioW-sectionjCSB
~/~/1~
SUBJECT:
FROM:
TO:
Frank D. Kover, Branch Chief
Chemical Screening BranchjECADjOTSjOPTS
Submission Description
Hercules Incorporated reported that the company received letters
in which two physicians indicated that a Hercules employee's sus-
ceptibility to ear infections was increased due to the inhalation
of siliceous muscovite mica dust. In its notification, Hercules
stated that its decision to submit this information to EPA under
Section 8(e) of TSCA was based on 1) the possible sequelae of ear
infections leading to serious impairment of normal activities, 2)
the widespread environmental occurrence of mica dust, and 3) the
concurrence by two doctors that exposure to mica dust resulted in
the employee's ear infections.
In its TSCA Section 8(e) submission, Hercules reported that it
reviewed the available toxicological literature, including the
supplier's Material Safety Data Sheet (MSDS), and did not locate
any information that links mica dust exposure and ear infections.
In addition, Hercules stated that although the affected employee
has been exposed to mica dust only on an intermittent basis in
the workplace, the employee is "now wearing a respirator during
his worktime when he might be exposed to mica dust."
Submission Evaluation
The information provided to the Agency by Hercules does indicate
that the affected employee's ear infections are the result of or
are at least exacerbated by the employee's exposure to mica dust
in the workplace. Hercules should be asked to keep EPA apprised
of any further significant developments regarding this matter.
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
336
-------
8EHQ-0986-0632
Page 2 of 2
Current Production and Use
In its TSCA Section 8(e) submission, Hercules reported that it
processes mica as that term is defined in TSCA Section 3(10)(B).
According to secondary li terature sources, mica can be obtained
from natural sources (muscov i te, phlogopi te, and pegma ti te) as
well as from synthetic routes (i.e., single mica crystals can be
"grown" by an electrothermal process). Synthetic or naturally
occurring micas are used in a variety of applications including a
number of electr ical and build ing appl ica tions (e. g., elec tr ical
equipment; vaCU~l tubes; incandescent lights; lubricants; dusting
agents; exterior paint filler; roofing and insulation materials;
wallboard/wallpaper cement). Also, mica is reportedly used in
cosmetics, drilling muds, and rubber products.
Comments/Recommendations
Hercules reported that the company is re-analyzing the air in the
affected employee's work area and will forward the results to the
Agency.
It is not completely clear that the information provided by
Hercules is of the type required for submission to the Agency
under Section 8(e), the substantial risk information reporting
provision of TSCA. It is quite probable, on the other hand, that
the subject information is of the type required to be maintained
by the company under Section 8 (c), the 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 toma in tain records of significant
adverse reactions alleged to have been caused by a TSCA-covered
chemical subs tance or mix ture. Th is TSCA Section 8 (c) rule also
requires that allegations involving significant adverse reactions
in workers be maintained for 30 years and that other recordable
allegations be kept for 5 years. It should be noted that EPA is
empowered to both inspect and require submission of Section 8(c)
records and has done so on a number of occasions to date.
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will ask
Hercules to ens ure that the Agency is appr ised of any
further developments concerning the reported adverse
effects.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of mica dust.
c)
The Chemical Screening Branch will send copies of this
status report to OSHA, NIOSH, CPSC, FDA, NTP, OSHER/EPA,
OH/EPA, OAR/EPA, ORD/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.
337
-------
DATE:
SU8JECT:
FRO"':
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 3
OCT 3 1986
Status Report' 8EHQ-0986-0633 S Approved: (j"HU(,T. ~ ~!J./i.
1: .; 'r-. (j I/Jh/;, '
~ {,;rtrv-
James F. Darr, section Head ~ n~
Chemical Risk Identificatio Section/CSB
TO:
Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Note
E. 1. Du pont de Nemour s & Company, Inc. has cla imed the exact
identity of the subject chemical to be TSCA Confidential Business
Inforrna tion (TSCA CBI). The Inforrna tion Management Di vi sion/OTS
will request the submitter to substantiate this TSCA CBI claim.
In its submission, Du Pont reported non-conf identially that l)
the tested chemical is a haloalkyl substituted cyclic ether, and
2) the chemical was the subject of a premanufacture Notification
(PMN 85-367) submitted to EPA under Section 5 of TSCA. According
to EPA's public file for PMN 85-367, the Agency has issued a TSCA
Section 5(e) "Consent Order" for the haloalkyl substituted cyclic
ethers cited in PMN 85-367, PMN 85-368 and PMN 85-369.
Submission Description
under TSCA Section 8(e), E. I. Du Pont de Nemours & Company, Inc.
provided the following information with regard to the conduct and
preliminary results from a 2-week inhalation study of a haloalkyl
substituted cyclic ether in male rats:
"Groups of 25 male rats were exposed by inhalation to
concentrations of the haloalkyl substituted cyclic ether
of 0, 10, 50 or 250 ppm for six hours a .day, five days a
week. The concentrations selected for this repeated ex-
posure study were lower than those that would have been
selected normally for a material wi th a 4-hour lethal
concentration of 4300 ppm because preliminary work indi-
cated that the rats would probably not survive repeated
exposure to higher concentrations. The planned exposure
period was two weeks followed by a l4-day recovery peri-
od. In each exposure group [(25 rats/group)), 10 rats
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
338
-------
8EHQ-0986-0633 S
Page 2 of 3
per group were designated for toxicological assessment;
the other 15 rats were used to assess ef fects on motor
activi ty. Following six exposures to 250 ppm, severe
losses in body we igh t, cl inical signs of tox ici ty and
mortality were observed and exposures at this level were
discontinued. Rats exposed to 50 and 250 ppm had signi-
ficantly depressed testes weights immediately following
the last exposure and at the end of the recovery period.
Microscopic examination revealed degeneration of the
germinal cells in the testes and epididymides in rats
from all exposure groups. The incidence and severity of
the lesions were dose-dependent. These lesions were
still present after the 14-day recovery period, although
some evidence of regeneration was observed. No signifi-
cant effects on motor activity were observed except for
reduced activity noted on the day after termination of
expos ures in rats exposed to 250 ppm."
In its Section B(e) submission, Du Pont reported also that 1) "an
addi tional inhalation study will be conducted using male
and female rats to better define the toxic effects on the repro-
ductive system" and 2) "exposure concentrations will overlap the
10 pprn level used in the present [2-week inhalation] study- II
Submission Evaluation
In view of the fact that the Agency issued a TSCA Section 5 (e)
Consent Order covering the tested chemical, copies of this TSCA
Section 8 (e) notice were immediately delivered by the Chemical
Screenin<] Branch/ECAD/OTS to the Premanufacture Notice Hanagement
Branch/CCD/OTS for review and disposition.
Current Production and Use
According to the public file copy of PMN 85-367, this haloalkyl
substi tuted cyclic ether is used as an intermediate and a sol-
vent. In its Section 8(e) submission, Du Pont stated that the
chemical II is currently employed as a research and development
material and is used captively within Du pont, thus there are few
employees working with this material. II In addition, Du Pont
provided the following informa tion regarding the potential for
worker exposure to this haloalkyl substituted cyclic ether:
liThe haloalkyl substituted cyclic ether has been treated
by Du Pont as a no-contact chemical and therefore respi-
ratory protection and other protective equipment is em-
ployed in all manufacturing operations where there is a
potential for exposure. Industrial hyg iene data [that
have been] obtained at the facility where this chemical
is made indicate that in most operations sampled, the
chemical is non-detectable (detection limit of 0.5 ppm)
but occasional peaks of 2-3 ppm have been observed.
Workers have not been exposed to these concentrations
since they wear airline respirators in the area where
339
-------
8EHQ-0986-0633 S
Page 3 of 3
these concentrations have been measured. Du Pont plans
to continue its practice of treating this chemical as a
non-contact chemical until more definitive toxicologic
information is available."
Comments/Reca~mendations
In its section 8(e) submission, Du pont stated that the company
plans to notify all employees who work with the tested chemical
substance about the reported toxicologic findings. In addition,
Du Pont stated that copies of the final report from the current
2-week study, as well as the interim and final reports from the
planned follow-up studies, would be sent to EPA as soon as the
reports become available.
a)
The Chemical Screening Branch (CSB/ECAD/OTS) \vill ask Du
Pont to ensure that EPA receives complete copies of the
final reports (including the actual experimental proto-
cols, results of gross and histopathologic examinations,
results of statistical analyses, etc.) from the current
2-week study and the planned follow-up studies on this
haloalkyl substituted cyclic ether.
In view of EPA I S general interest in corporate actions
taken on a voluntary basis in response to chemical toxi-
city or exposure data, the Chemical Screening Branch
will request Du Pont to describe the nature and results,
if available, of all studies (other than those studies
submitted already to EPA) about which Du Pont is aware
or that Du Pont has conducted, is conducting, or plans
to conduct to determine the toxicity of or the exposure
to this haloalkyl substituted cyclic ether.
b)
As in the case of the initial Section 8(e) notice, the
Chemical Screening Branch will immediately send all of
the reported informa tion to the Premanufacture Notice
Management Branch/CCD for review and disposition.
c)
The Chemical Screening Branch will send copies of this
status report to OSHA, NIOSH, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, OAR/EPA, ORD/EPA, OPP/OPTS and PNMB/CCD/OTS. In
addition, copies of this status report will be provided
to the TSCA Assistance Office (TAO/OTS/OPTS) for further
distribution.
340
-------
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
DATE:
ocr I 4 1986
Page
1 of 4
UBJECT:
status Report* 8EHQ-0986-0634 Approved :-b--
8EHQ-I086-0634 SUPP.
James F. Darr, Section Head ~AA.AA r ~
Chemical Risk Identificatio~~~~~ion/CSB
lojltPjrh
.
FROM:
TO:
Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The American Hoechst Corporation submitted an English translation
of a letter (received recently by the company from Hoechst AG in
Germany) regarding new epidemiological findings of bladder cancer
among workers exposed chronically to 4-chloro-2-methyl aniline
(CAS No. 95-69-2). The following excerpts are from the submitted
translation of the letter received by American Hoechst:
"Dur ing the last year, [Hoechst AG] had undertaken and
published a retrospective mortality study as to the po-
tential causation of cancer of the bladder by 4-chloro-
2-methyl aniline. Wi thin the framework of this study,
which had a data collection closing date of December 31,
1982, there was no indication of respective malignant
neoplastic activ i ty. However, after the closing date,
[Hoechst AG] learned of five cases of bladder cancer
within the [epidemiologic] study cohort. One person of
the five affected has died in the meantime.
"In consideration of the cause/effect relationship in
the above mentioned cases, [Hoechst AG] cannot any more
exclude the possibil i ty that 4-chloro-2-methyl anil ine
has contributed to the above findings."
In its Section 8(e) submission, American Hoechst also provided a
copy of the company's 4-chloro-2-methyl aniline Material Safety
Data Sheet (MSDS) as well as additional information regarding the
importation volumes and uses of the chemical.
::===========~=======================================================================
* NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
341
-------
8EHQ-0986-0634 INIT.
8EHQ-I086-0634 SUPP.
Page 2 of 4
Submissio~ Evaluation
An EPA evalua tion of the overall significance of the reported
epidemiologic findings should be possible upon EPA's receipt of
more in-depth information regarding the conduct and resul ts of
the performed study.
It is important to note that in 1978, the International Agency
for Research on Cancer (IARC) published a review of available
da ta on 4-chloro-2-methyl anil ine (IARC Monograph; Volume 16;
pages 277-285). In this 1978 review, IARC stated that the only
data available to the workgroup at that time was from a 1972 ab-
stract of results of a lifetime feeding study of of 4-chloro-2-
methyl aniline hydrochloride in male and female mice. According
to IARC, although this particular abstract stated that 4-chloro-
2-methyl aniline hydrochloride induced 40 haemangiosarcomas in
various organs in 82 mice (no tumors were reportedly found in
control mice), the summary nature of the abstract (no further
information concerning the study was available to IARC at that
time) did not allow for an evaluation of the carcinogenicity of
the chemical. IARC stated further in its 1978 Monograph on 4-
chloro-2-methyl aniline hydrochloride that insufficient human
data were available at that time to allow the IARC workgroup to
evaluate the potential carcinogenicity of the chemical. In 1983,
however, IARC published (IARC Monograph; Volume 30; pages 61-72)
its review of available data on the pesticide, chlordimeform. In
that 1983 Monograph, IARC noted that 4-chloro-2-methyl aniline is
an intermediate in the production of, an impurity (as the hydro-
chloride salt) in, and a metabolite of chlordimeform, which is an
insecticide, acaricide and ovicide. IARC reported also that the
results of chronic feeding studies in mice and rats conducted at
the National Cance~ Institute (NCI) showed that 4-chloro-2-methyl
aniline hydrochloride induced haemangiosarcomas in two strains of
mice; the NCI feeding studies conducted in two strains of rats
were negative although IARC did note certain limitations in the
design of those studies. In the 1983 Monograph on chlordimeform,
IARC stated further that the ability of 4-chloro-2-methyl aniline
to cause urinary tract injury in humans was known and pointed to
the results of a 1933 study of 4-chloro-2-methyl aniline-exposed
workers in an English chemical factory. with regard to this 1933
study, IARC stated that the investigator had detected 11 workers
with urinary tract problems and that the follow-up examination (3
years later) of 3 of the affected workers showed that 1 of those
3 workers had developed a bladder carcinoma.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for 4-chloro-2-methyl aniline (CAS No. 95-69-2), which
is listed in the initial TSCA Chemical Substance Inventory, shows
that 10,000 to 100,000 pounds of this chemical were reported as
manufactured and/or imported in 1977. This production range in-
formation does not include any data claimed as TSCA Confidential
Business Information (TSCA CBI) by the person(s) who reported for
342
-------
8EHQ-0986-0634 IN IT.
8EHQ-I086-0634 SUPP.
Page 3 of 4
the initial TSCA Inventory, nor does it include any information
that would compromise TSCA CBI. All of the information reported
for the ini tial TSCA Inventory, includ ing the production range
information, is subject to the limitations contained in the TSCA
Inventory Reporting Regulations (40 CFR 710).
In its submission, the A.rnerican Hoechst Corporation stated that
it imports 4-chloro-2-methyl aniline from Hoechst AG and resells
approximately 15,000 to 30,000 pounds/year for use in pigment
manufacture. As stated previously, 4-chloro-2-methyl aniline is
used also in the production of the pesticide, chlordimeform.
with regard to product handling, American Hoechst reported that
4-chloro-2-methyl aniline is imported in 55 gallon drums with
bungs and because of the chemical's low melting point (26.8°C),
filling and emptying of the drums is performed above the melting
point with the product in liquid form.
comments/Recommendations
It should be noted that American Hoechst has updated the "Health
Information" section of the company's 4-chloro-2-methyl aniline
MSDS to include the following information:
"Based on data from a recent Hoechst AG epidemiological
study, newly discovered cases of human bladder cancer
may be linked to chronic exposure to 4-chloro-2-methyl
aniline."
It should be noted also that based on the new epidemiolog ical
findings, Hoechst AG has 1) decided to immediately cease all 4-
chloro-2-methyl aniline production, shipping and marketing, and
2) communicated the new findings to several European commissions.
In a letter dated september 29, 1986 (8EHQ-I086-0634 Supplement),
American Hoechst provided 'a copy of a letter by which the company
informed its customers about the new epidemiolog ical find ings.
In that letter, kTIerican Hoechst also told its customers that due
to the Hoechst AG decision to cease the production, r:Iarketing and
shipping of 4-chloro-2-methyl aniline, &~erican Hoechst would no
longer be able to supply the chemical.
a)
The Chemical Screening Branch will ask A.rnerican Hoechst
to ensure that EPA receives full copies of all documents
(including correspondence, reports, transcripts, etc.)
in the company's possession now or that the company ob-
tains in the future that relate to the epidemiologic
findings cited in the company's Section 8(e) submission.
In view of EPA' s general interest in corporate actions
that are taken on a voluntary basis in response to chem-
ical toxicity or exposure data, American Hoechst will be
asked to describe the nature and results, if available,
from all studies (other than those published in the open
343
-------
8EHQ-0986-0634
8EHQ-1086-0634
Page 4 of 4
scientific literature or submitted already to EPA) about
which American Hoechst is aware or that the company has
conducted, is conducting, or is planning to conduct to
determine the toxicity of or the exposure to 4-chloro-2-
methyl aniline. American Hoechst will be asked also to
describe the actions that the company has taken or plans
to take 1) to notify its own workers about the reported
epidemiological findings, and 2) to reduce or eliminate
exposure to 4-chloro-2-methyl aniline that remains in
the company's current inventory.
INIT.
SUPP.
b)
The Chemical Screening Branch will review the reported
infor:nation in order to determine the need for further
OTS assessment of 4-chloro-2-methyl aniline.
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, OAR/EPA, ORD/EPA, and OPP/OPTS/EPA. Copies of
this status report will be provided also to the TSCA
Assistance Office (TAO/OTS) for further distribution.
344
-------
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
DATE:
NOV
7 1986
Page 1 of 4
SUBJECT,
status Report*
Approved:
~ r~
Darr, Section Head !1.-#IL-J f/. LA.(1i~
Risk Identificatio SectionjCSB
8EHQ-I086-0635
ZfJt- "/1/1(,
FROM:
James F.
Chemical
TO:
Frank D. Kover, Branch Chief
Chemical Screening BranchjECADjOTS!OPTS
Note
In this TSCA Section 8(e) notice, the Union Carbide Corporation
stated that "UCON 50-HB Polyethers are homologous members of a
series of butanol-initiated co-polymers of 50% ethylene oxide and
50% propylene oxide. . . [and] differ only in degrees of polymer-
ization as indicated by the final numbers which reference their
viscosities in SUS (Saybolt Universal Seconds)."
Submission Description
The Union Carbide Corporation submitted the following summarized
information concerning the conduct and prel iminary resul ts of a
14-week aerosol inhalation study of UCON Lubricant 50-HB-5100
(CAS No. 9038-95-3) in rats:
"The effects of inhalation of aerosols of UCON Lubricant
50-HB-5100 were investigated in Fischer 344 rats. Four
groups of 30 animals of each sex were exposed to aerosol
concentrations of 0, 0.3, 1.1 or 5.2 mgjm3 of the test
material. The aerosols were generated from dilute (5%)
water solutions of the UCON fluid, and the particle
sizes were in the respirable range (1. 6 microns wi th a
geometric standard deviation of 1.6 microns). Animals
were exposed for 6 hours a day, 5 days a week for 14
weeks. At the end of this exposure regimen, animals in
each group were sacrificed and examined to determine
potential toxic effects of the exposure. Additional
animals in each group were maintained wi thout further
exposure for an additional 5 week recovery interval
after which they were sacrificed and examined.
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
345
-------
8EHQ-I086-0635
Page 2 of 4
"The principle and essentially only effects noted were
on the lungs of the [DeON Lubricant 50-HB-5100-]exposed
animals. The findings included increased lung weights
in the 1.1 and 5.2 mg/m3 exposure groups, grey and tan
foci on the surface of lungs from animals of all expo-
sure groups, and microscopic evidence of lung tissue
injury in all exposure groups, described as hemorrhage,
alveolar histiocytosis, interstitial pneumonia and focal
or multifocal fibrosis of the pulmonary interstitium.
"Both absolute and relative (lung weight as a percent of
body we igh t) lung we igh ts were increased in male and
female rats exposed to 5.2 mg/m3 and in females exposed
to 1.1 mg/m3, wh ile relative lung we igh t was increased
in males exposed to 1.1 mg/m3. There was a slight, but
not statistically significant, increase in lung weights
of males and females exposed to 0.3 mg/m3. The inc i-
dence of the macroscopic lesions in the lungs increased
with increasing exposure concentrations as did the inci-
dence and severity of the histopathological lesions.
"The lung weights of male and female rats in the 5.2
mg/m3 recovery group and males in the 1.1 mg/m3 recovery
group remained statistically significantly heavier than
those of control recovery animals. In addition, mean
lung weights of the 0.3 m~m3 recovery group, and those
of females in the 1.1 mg/m recovery group were slightly
but not significantly greater than those of the control
group. The magni tude of increased lung we igh t in the
recovery animals was less than that seen in animals sac-
rificed immediately after the 14 weeks of [inhalation]
exposure, demonstrating a degree of recovery possibly
from associated pulmonary edema. 'l'here was some evi-
dence for repair of the lung injury upon recovery,
particularly with respect to alveolar histiocytosis and
hemorrhage. Generally, the pulmonary fibrosis seen upon
microscopic examination of lung tissue in this study is
considered to be a permanent type of injury.
"The injury to lung tissue observed in this 14-week
subchronic study is believed to be a natural progression
of the injury noted in two short-term repeated (9 expo-
sures in 11 days) studies which have been previously
submi tted to the Agency. [These short-term inhalation
studies were provided to EPA on "For Your Information"
(FYI) basis, FYI-OTS-0784-0335 et seq.] The injury ob-
served in the present [14-week inhalation] study was of
a slight, to at most, moderate degree of severity, even
at the highest exposure concentration employed, 5 mg/m3.
The impairment of pulmonary function from this degree of
injury would likely be minimal if detectable at all.
Although the test data showed minimal injury, continued
exposure beyond 14 weeks might lead to impairment of
pulmonary function."
346
-------
8EHQ-I086-0635
Page 3 of 4
In a supplemental FYI submission (FYI-OTS-I084-0335 Supplement
Seq. C), the Union Carbide Corporation reported that "extensive
testing by other routes of exposure (swallowing, skin absorption,
etc.) have demonstrated [that] these copolymeric materials do not
constitute a health hazard by these routes of exposure." In ad-
dition, Union Carbide stated that no adverse human health effects
have been observed during manufacture or use of these copolymers.
Submission Evaluation
In order for EPA to evaluate the overall significance of the
observed lung toxici ty, Union Carbide should be asked to ensure
that the Agency receives a complete copy of the final report
(including the actual experimental protocol, results of gross and
histopathologic examinations, resul ts of statistical analyses,
etc.) from the l4-week inhalation study cited in the company's
TSCA Section 8(e) submission.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for CAS No. 9038-95-3, which is listed on the initial
TSCA Chemical Substance Inventory, has shown that 2 million to 20
million pounds were reported as manufactured and/or imported in
1977. This production range information does not contain any in-
formation claimed as TSCA Confidential Business Information (TSCA
CBI) by the persons reporting for the TSCA Inventory, nor does it
include any information that would compromise TSCA CBL 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 E. 1. Du Pont de Nemours & Company, Inc. (the sub-
mi tter of the ini tial FYI notice (FYI-OTS-0784-0335 Seq. A) on
UCON Lubricant 50-HB-5100), this chemical is a component in a
textile finish formulation.
Comments/Recommendations
In its Section 8(e} notice, Union Carbide stated that the company
is l} notifying its employees and customers about the reported
findings, and 2) revising the UCON Lubricant 50-HB-5100 label and
Material Safety Data Sheet to reflect the reported findings.
a}
The Chemical Screening Branch (CSB/ECAD/OTS) will ask
the Union Carbide Corporation to ensure that the Agency
receives a complete copy of the final report (including
the actual exper imental protocol, resul ts of gross and
histopathological examinations, resul ts of statistical
analyses, etc.) from the 14-week inhalation study cited
in the company's TSCA Section 8(e} submission.
347
-------
8EHO-I086-0635
Page 4 of 4
In view of EPA I S general interest in corporate actions
taken on a voluntary basis in response to chemical toxi-
city or exposure data, Union Carbide will be requested
to describe nature and results, if available, of all
studies (other than those published in the open scien-
tific literature or those submitted already to EPA)
about which the company is aware or that the company has
conducted, is conducting or plans to conduct to deter-
mine the toxici ty of or the exposure to UCON Lubricant
50-HB-5l00.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS evaluation 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, OAR/EPA, ORD/EPA, and OPP/OPTS/EPA. Copies of
this status report will be provided also to the TSCA
Assistance Office (TAO/OTS) for further distribution.
348
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 3
DATE:
NOV
7 1986
SUBJECT: status Report*
8EHQ-1086-0636 S
Approved: {Jlj- j//?cP
II ----
FROM: James F. Darr, Section Head ~.~J r [klllr
Chemical Risk Identificatio~-Section/CSB
roo Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Note
PPG Industries, Inc. claimed the exact identities of the tested
chemical substances to be TSCA Confidential Business Information
(TSCA CBI). In the non-CBI version of the submission, PPG pro-
vided the following generic names for the chemicals: 1) chloride
capped alcohol ethoxyla tes (BSF-O 2), and 2) qua ternary ammoni urn
chloride (BSC-57). Staff of the Information Management Division
(IMD/OTS) will ask PPG to substantiate the company's CBI claims.
Submission Description
PPG Industries, Inc. submitted summarized preliminary findings
from acute eye irritation studies of two research and development
(R&D) chemicals (BSF-02 and BSC-57 (see Note above» in rabbits.
According to PPG, these R&D materials were found to be severe eye
irritants. In addition, PPG reported that BSF-02 and BSC-57 pro-
duced corneal opacity in 1/6 and 6/6 rabbits, respectively, at
day 21 following eye application.
Submission Evaluation
In order for the Agency to evaluate the overall significance of
the reported eye toxicity, PPG should be asked to submit complete
copies of the final reports from the acute eye irritation studies
cited in the company's Section 8(e) notice.
====================================================================================
* NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
349
-------
8EHQ-I036-0636 S
Page 2 of 3
Current Production and Use
In view of PPG's TSCA CBI claims, no information concerning the
TSCA Chemical Substance Inventory status of the tested materials
will appear in this report.
In its submission, PPG provided the following information wi th
regard to the potential for exposure to the chemicals:
"The extent of risk was and is currently limited by the
fact that only developmental amounts. . . are available
and the synthesis has been performed on site of the sub-
mi tter by technically qual ified staf f. The evaluation
of the materials has been conducted by a limited number
of personnel outside of PPG who are normally involved in
R&D evaluation. Personnel wi th potential for exposure
are protected by use of protective facilities, equipment
and clothing, e.g., laboratory hoods, impervious gloves,
coveralls or lab coats, and eye protective equipment.
The most likely route of exposure would be dermal. . ,
with inhalation a less likely route because of the phys-
ical properties of the materials, particularly
[the] low vapor pressure."
Comments/Recommendations
In its Section 8(e) subfilission, PPG reported that the company's
"safety procedures call for establishing and updating whatever
guidelines for safe handling are appropriate as data on the
potential toxici ty of new materials are rece ived." In add i tion,
PPG stated that "all personnel with potential exposure to the
materials will be informed of the findings and guidelines for
handling." Finally, PPG reported that "the Experimental Product
Data Sheets will be modified to include a statement about the
severe eye irritation."
Based on EPA' s ini tial evaluation of the summarized information
presented in PPG's submission, it is not entirely clear that the
provided information is of the type required for reporting to EPA
under Section 8(e), the "substantial risk" information reporting
provision of TSCA. As further information is received from PPG
concerning the perfonned studies, PPG's rationale for submi tting
the findings to EPA under Section 8(e) may become more apparent.
a)
The Chemical Screening Branch (CSB/ECAD) will ask PPG to
submi t complete copies of the final reports (includ ing
the actual experimental protocols, results of gross and
histopathological examinations, resul ts of statistical
analyses, etc.) froHl the acute eye irritation studies
cited in the company's TSCA Section 8(e) submission.
350
-------
8EHQ-I086-0636 S
Pa ge 3 of 3
In view of EPA's general interest in corporate actions
taken on a voluntary basis in response to chemical toxi-
city or exposure data, PPG will be requested to describe
the nature and results, if available, from all stud ies
(other than those published in the scientific literature
or those submitted already to EPA) about which PPG is
aware or that PPG has conducted, is conducting, or plans
to conduct to determine the toxicity of or the exposure
to the subject chemical substances. .
b)
The Chemical Screening Branch will review the reported
information in order to determine the neea for further
OTS assessment of the tested chemicals.
c)
The Chemical Screening Branch will send copies of this
status report to OSHA, NIOSH, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, OAR/EPA, ORD/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.
351
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 3
DATE:
NOV 'A 1986
SUBJECT:
status Report*
8EHQ-l086-0637
Approved:
tJ;t-
II /17 frc,
FROM:
James F. Darr, Section Head ~ ~t~
Chemical Risk Identificatio~~e;~ion/CSB
TO:
Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Chevron Chemical Company submitted the following information
concerning the cond uct and prel iminary findings from a 28-day
dermal application study of trans-l-chloro-3-oxyaminopropene
hydrochloride (CAS No. 82244-86-8) in rats:
"preliminary evaluation of the data from a 28-day dermal
toxicity study of this substance in male and female rats
indicates that this substance produced methemoglobinemia,
macrocytic anemia (characterized by decreased erythrocyte
count, hemoglobin, and mean cell hemoglobin concentration
and increased reticulocyte count, mean cell hemoglobin
and mean cell volume) and histopathological changes in
the spleen (described as dilated sinusoidal spaces packed
with erythrocytes) in a dose-related pattern in both
sexes. ... Animals were treated dermally six hours
per day, seven days per week, for four weeks with a 1.0
ml/kg solution of 5.0 mg/kg, 20.0 mg/kg or 80.0 mg/kg of
. . .an aqueous solution containing 47.4% trans-l-chloro-
3-oxyaminopropene hydrochloride. Compound related effects
were noted at all dose levels."
In its submission, Chevron stated that trans-l-chloro-3-oxyamino-
propene hydrochloride is a research and development compound that
is an isolated intermediate used in the manufacture of a candi-
date pesticide. Chevron stated also that the manufacture of the
candidate pesticide involves reacting the isolated intermediate
with the trione that was the subject of a previous Section 8(e)
submission (8EHQ-0186-0584 et seq.).
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
352
-------
8EHQ-I086-0637
Page 2 of 3
Submission Evaluation
.
Noblithstandiny the brief and preliminary nature of the reported
findings, the observed adverse effects do appear to be related to
deDnal a?plication of the test material. The observed adverse
effects with the most serious toxicological consequences are the
fonnation of methemoglobinemia and macrocytic anemia.
The formation of methemoglobinemia should be viewed in light of
the fact that the test material is a derivative of hydroxylamine,
a chemical substance known to induce methemoglobinemia in animals
and man. It is important to note that sufficient Qffiounts of the
test chemical were absorbed through the skin to produce a dose-
related and statistically significant methemoglobinemia response.
In addition, it should be noted that humans have lower levels of
the enzyme (methemoglobin reductase) that reduces methemoglobin.
It is likely, therefore, that humans would be more susceptible
than rats to methemoglobinemia induced by the test material.
Further, the adverse effects on the spleen (i.e., sinusoidal
dilatation and increase in absolute and relative spleen weight)
are most likely secondary to methemoglobinemia and due to the
sequestration of methemoglobin-containing red blood cells in the
spleen. Finally, if exposure to the test material had been
continued for a longer period of time or if higher doses were
used, both major structural/functional spleen damage might occur.
Another adverse effect of concern is the induction of macrocytic
anemia, especially in combination with methemoglobinemia. In the
absence of detailed information on histopathology, particularly
on the bone marrow and 1 iver, an explanation of this effect is
speculative. If the test compound causes liver damage, the red
cell membrane may take up excess cholesterol to increase the
membrane surface area and may "spread out" upon smearing to form
what appears to be a thin JllaCrocyte; it was not clear from the
submi tted informa tion whether or not serum cholesterol levels
were determined.
Current production and Use
According to Chevron, the company's "current development plans
call for the submission of a [TSCA Section 5] premanufacturing
notification and subsequent importation of . [trans-l-chloro-
3-oxyaminopropene hydrochloride] and the trione as well during
1987 for pilot plant manufacture of the pesticide." In addition,
Chevron reported that "it is known that if . [trans-l-chloro-
3-oxyaminopropene hydrochloride] appears in the final product at
all, it will be at less than 0.1% (w/w)."
Comments/Recommendations
Chevron reported that the Material Safety Data Sheet for trans-l-
chloro-3-oxyaminopropene hydrochloride was revised to reflect the
reported effects and sent to Chevron employees and potential toll
}?roducers.
353
-------
8EHQ-I086-0637
Page 3 of 3
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, results of
gross and histopathologic examinations, results of any
statistical analyses, etc.) from the 28-day skin appli-
cation study cited in the company's TSCA Section 8(e)
submission.
In view of EPA's general interest in corporate actions
taken on a voluntary basis in response to chemical toxi-
city or exposure information, Chevron will be asked to
describe the nature and results, if available, of all
other studies that Chevron has conducted, is conducting,
or is planning to conduct to determine the toxici ty of
or the exposure to trans-l-chloro-3-oxyaminopropene
hydrochlor ide.
b)
The Chemical Screening Branch wi 11 rev iew the reported
information in order to determine the need for further
OTS assessment of trans-l-chloro-3-oxyaminopropene
hydrochloride at the present time.
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, NTP, FDA, OSWER/EPA,
OW/EPA, OAR/EPA, ORD/EPA, and OPP/OPTS/EPAi copies of
this status report will be provided also to the TSCA
Assistance Office (TAO/OTS) for further distribution.
354
-------
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
DATE:
NOV I 3 1986
Page 1 of 3
SUBJECT:
status Report*
8EHQ-I086-0638
Approved:
Zfbt-- /I1/~/1&
FROM:
James F. Darr, Section Head f),~1 rL~vL,..---
Chemical Risk Identificatio6!section/CSB
TO:
Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The AZS Corporation submitted final reports from several acute in
vivo studies of Coronate EH (hexamethylene diisocyanate trimer;
CAS No. 28182-81-2). According to the submitted information, the
chemical is moderately irritating to rabbit skin and eyes, is not
corrosive to rabbit skin, has an oral LD50 in excess of 5.0 g/kg
in rats, has a I-hour median lethal inhalation concentration of
approximately 18.5 mg/l in rats, and has a dermal LD50 greater
than 2.0 g/kg in rats.
Submission Evaluation
Immediately upon receipt of this Section 8 (e) submission, the
Chemical Screening Branch (CSB/ECAD/OTS) delivered copies of the
notice to the Risk Analysis Branch (RAB/ECAD/OTS) for inclusion
in the ongoing review of available data on diisocyanates.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for CAS No. 28182-81-2, which is listed in the initial
TSCA Inventory, has ,shown that no 1977 manufacture or importation
was reported or that all manufacture/ importation data reported
were claimed as TSCA Confidential Business Information (TSCA CBI)
by the person( s) reporting for the TSCA Inventory and cannot be
disclosed (Section 14(a) of TSCA, U.S.C. 2613(a)). All of the
data submitted for the TSCA Inventory, including the production
range data, are subject to the limitations contained in the TSCA
Inventory Reporting Regulations (40 CFR 710).
AZS did not submit any information regarding current production,
importation, or use(s) of Coronate EH, nor was such information
located in the secondary literature sourc~s consulted by EPA.
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
355
-------
8EHQ-I086-0638
Page 2 of 3
Comments/Recommendations
It has been EPA' s longstanding posi tion that certain types of
acute animal toxici ty data may not warrant submission to EPA
under Sect ion 8 (e), the subs tantial risk informa tion reporting
provision of TSCA. The basis for EPA's position in this matter
is as follows:
The preface to Part V of EPA's TSCA Section 8(e) policy
statement ("statement of Interpretation and Enforcement
policy; Notif ication of Substantial Risk" 43 FR 11110;
March 16, 1978) explains that "a substantial risk of in-
jury to [human] health or the environment is a risk of
considerable concern because of (a) the seriousness of
the [adverse] effect and (b) the fact or proba-
bility of its [(i.e., the effect's)] occurrence."
With regard to the seriousness of the effect, Part V of
the Section 8(e) policy statement explains that EPA
considers the health effects for which substantial risk
infor:nation must be reported to include "any pattern of
effects or evidence which reasonably supports the con-
clusion that the [tested] chemical substance or mixture
can produce cancer, mutation, birth defects, or toxic
effects resulting in death, or serious or prolonged in-
capaci tation." Informa tion wi th respect to these types
of effects can be obtained directly or inferred from
studies of a designed or undesigned nature (see Part VI
of the TSCA Section 3(e) policy statement).
v-Jith regard to the criterion concerning the "fact or
probability" of the occurrence of such serious effects,
Part V as well as other portions of the Section 8 (e)
pol icy statement explain that certain types of heal th
effects are so serious that relatively 1 i t tIe or, in
some cases, no weight should be given to the subject
chemical's exposure in determining whether a risk is
substantial. In the case of cancer, for example, the
mere fact that the implicated chemical or mixture is in
commerce would constitute sufficient evidence that there
is potential exposure to the substance(s).
EPA's response to Comment 14 in Append ix B of the TSCA
Section 8(e) policy statement provides guidance with
regard to the 8(e)-reportability of results obtained
from acute in vivo toxicity range finding studies (e.g.,
LD50 determinations, skin/eye irritation studies, etc.).
In its response, EPA stated that unknown effects that
occur and are observed/determined during such routine
tests may have to be reported under Section 8(e) if the
effects are serious and meet the reporting criteria set
forth in Part V of the Section 8 (e) policy statement.
Thus, when evaluating the results of acute animal tests
for possible submi ss ion to EPA under Section 8 (e), EPA
356
-------
8EHQ-I086-0638
Page 3 of 3
believes that a subject company should consider such
factors as lethal dose, pH of the test material, the
route(s) of administration, occurrence of unexpected
serious effects (which could be determined via "cage-
s ide" observation or dur ing necropsy), and the extent
and pattern of the actual or potential exposure to the
tested material (s) . In general, when evaluating such
information for 8 (e) reporting, the following factors
should be kept in mind: the greater the acute toxicity,
the less heavily one should weigh the actual/potential
exposure to the test material(s) and vice versa.
In light of the preceding discussion, it does not appear that the
acute toxicity information, as presented in the AZS Corporation's
submission, warranted reporting under Section 8 (e) of TSCA. In
making this initial determination on Section 8(e)-reportability,
however, it must be understood that the Agency is not aware of
any additional pertinent information that was available to and/or
considered by AZS in deciding to report under Section 8(e).
a)
In view of the Agency's initial position with regard to
TSCA Section 8(e)-reportability, the Chemical Screening
Branch will request the AZS Corporation to provide its
rationale (in I ight of the discussion at the beginning
of the Comments/Recommendations section of this status
report) as to why the the subioi tted information vias be-
lieved to have warranted reporting under Section 8(e).
In view of EPA' s general interest in corporate actions
taken on a voluntary basis in response to chemical toxi-
city or exposure data, the Chemical Screening Branch
will ask the AZS Corporation to describe the actions the
company has taken or plans to take 1) to notify workers
and others about the reported findings, and 2) to reduce
or eliminate exposure to Coronate ER. In addition, AZS
will be requested to describe the nature and results, if
available, from all studies (other than those reported
in the open scientific literature or those submitted
already to EPA) about which the company is aware or that
the company has conducted, is conducting, or plans to
conduct to determine the toxicity of or the exposure to
Coronate EH.
b)
As in the case of the initial TSCA section 8(e) notice,
the Chemical Screening Branch will transmit copies of
all further information received on Coronate EH to the
Risk Analysis Branch/ECAD for inclusion in the ongoing
review of diisocyanates.
c)
The Chemical Screening Branch will send copies of this
status report to OSHA, NIOSH, CPSC, FDA, NTP, OSHER/EPA,
OW/EPA, OAR/EPA, ORD/EPA, OPP/OPTS, and RAB/ECAD/OTS;
copies of this report will be sent also to the TSCA
Assistance Office (TAO/OTS) for further distribution.
357
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 3
DATE:
tDI '1 1986
SUBJECT:
Status Report*
8EHQ-I086-0639 S
Approved: ~ /I /11/f?f,
FROM:
James F. Darr, Section Head LlAr~
Chemical Risk IdentificatioJ7~~~~ion/CSB
TO:
Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Note
PPG Industries, Inc. has claimed the exact identity and use of
the tested chemical substance to be TSCA Confidential Business
Information (TSCA CBI); the Information Management Division
(IMD/OTS) will request the submitting company to substantiate
these TSCA CBI claims. In the non-conf iden tial vers ion of the
submission, PPG reported that the chemical is a chlorinated acid.
Submission Description
PPG Industries, Inc. submi tted prel iminary resul ts of several
acute in vivo toxicity studies of a chlorinated acid. According
to PPG~although this chlorinated acid was found to have an oral
LD50 of approximately I g/kg (male/female rats), the chemical was
found to be corrosive to rabbit skin and to have a 4-hour inhala-
tion LC50 of .39 mg/l (male/female rats) and a I-hour inhalation
LC50 of approximately I mg/l (male/femal~ rats). In addition, it
should be noted that this chlorinated acid was reported in PPG's
Section 8(e) submission to be similar in structure to a chemical
substance found to cause cancer in laboratory animals.
Submission Evaluation
In order for EPA to evaluate the overall significance of the
reported toxicologic findings, PPG should be asked to provide to
EPA full copies of the final reports from all stud ies ci ted in
the company's TSCA Section 8(e) submission.
====================================================================================
*
NOTE: This status report ;s the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
358
-------
8EHQ-I086-0639 S
Page 2 of 3
Current Production and Use
In view of PPG' s TSCA CBI claims, no information concerning the
TSCA Chemical Substance Inventory status or use(s) of the tested
chemical will appear in this report.
In the non-confidential version of PPG's submission, the
stated that 1) this chlorinated acid has a vapor pressure
mm Hg at 20°C, and 2) the following production procedures
chemical are in place at the present time:
company
of 11. 2
for the
"NIOSH approved category 19C air supplied positive pres-
sure respirator[s are] required for persons who might be
exposed to this product during manufacturing, processing
and use.
"Any person who may be reasonably expected to be exposed
dermally to this product are required to wear a) imper-
vious gloves [and] b) protective clothing.
"The product is labeled: Warning - avoid all contact.
A chemical similar in structure has been found to cause
cancer in laboratory animals. The required use of res-
pirators, protective clothing and impervious gloves will
help protect you.
"All persons who work with this product
trained. Persons with possible exposure to
are PPG employees engaged in manufacture
of the contract manufacturer.
are properly
this material
and employees
"Distribution of the product is limited to the contract
manufacturer."
Comments/Recommendations
In its Section 8(e) submission, PPG reported that the company's
"safety procedures call for establishing and updating guidelines
for safe handling as appropriate based on the new data." In ad-
dition, PPG stated that the company willI) notify all persons
potentially exposed to the tested chemical about the submi tted
findings, 2) update the product label and i>1aterial Safety Data
Sheet (MSDS) to reflect the reported toxicologic findings, and 3)
ensure that all shipping containers comply wi th U. S. Department
of Transportation (DOT) requirements.
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will ask
PPG to submit to EPA full copies of the final reports,
including the actual experimental protocols, results of
gross and histopathologic examinations, resul ts of any
statistical analyses, etc.) from all studies cited in
the company's TSCA Section 8(e) notice.
359
-------
8EHQ-I086-0639 S
Page 3 of 3
In view of EPA's general interest in corporate actions
taken on a voluntary basis in response to chemical toxi-
ci ty or exposure informa tion, PPG will be requested to
describe the nature and results, if available, from all
studies (other than those reported already to the Agency
or those published in the open scienti f ic Ii terature)
about which PPG is aware or that PPG has conducted, is
conducting, or is planning to conduct to determine the
toxicity of or the exposure to this chlorinated acid.
b)
The Chemical Screening Branch will ensure that all of
the reported information is forwarded immediately to ap-
propriate offices within OTS to determine the need for
further assessment of this chlorinated acid.
c)
The Chemical Screening Branch will send copies of this
status report to OSHA, NIOSH, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, OAR/EPA, ORD/EPA, and OPP/OPTS/EPA. Copies of
this report will be provided also to the TSCA Assistance
Office (TAO/OTS/OPTS) for further distribution.
360
-------
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
DATE:
NOV I 9 1986
Page 1 of 2
SU8JECT:
Status Report*
8EHQ-I086-0640 S
Approved: ~~
lI/f9/Tfo
FROM:
James F. Darr, Section Head t1AA.."'A 1 C
Chemical Risk Identificatio~~~~tion/CSB
TO:
Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Note
The submitting company claimed its identity as TSCA Confidential
Business Information (CBI). The Information Managemen t Division
will request the submitting company to substantiate this claim.
Submission Description
In its TSCA Section 8(e) submission, the company reported that
"diethylethoxymethyleneoxalacetate, when placed in one eye of
each of three rabbi ts at a dose of 0.1 cc, caused persistent
severe corneal opacity, severe iritis, and severe conjuncti-
vitis." In addition, the submitting company reported that the
tested material was a mixture of two isomeric forms wi th the
following CAS Registry Numbers: 55130-49-9 and 55130-39-7. Ac-
cording to the company, CAS Number 52942-64-0 has been "assigned
to this compound wi thou t reference to isomeric form." Finally,
the submitter reported that "the proportions of the two isomers
in the mixture have not been determined."
Submission Evaluation
In order for EPA to evaluate the overall significance of the
reported findings, the submi tting company should be requested to
provide complete copies of the final report from the cited rabbit
eye irritation study.
Current Production and Use
None of the CAS Numbers provided by the submi t ting company we re
located in the computerized version of the non-confidential TSCA
Chemical Subs tance Inventory. Accord ing to the submi t ting com-
pany, the tested material is a "non-isolated intermediate in the
manufacture of a pesticide that is in the research and develop-
ment stage." The submitting company reported also that "less
than 750 kilograms of the intermediate have been manufactured."
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
361
-------
8EHQ-I086-0640 S
Page 2 of 2
Comments/Recommendations
The submitting company stated that company personnel who may work
wi th this chemical mixture have been noti f ied about the reported
toxicologic findings. In addition, the submitter stated that the
reported findings will be reflected in the product manufacturing
instructions. Finally, the submi tting company stated that "eye
protection will be provided to workers, if it becomes necessary
to isolate any more. . . [diethylethoxymethyleneoxalacetate]."
Based on a preliminary review of the provided information, it is
not clear that the information warranted submission to EPA under
Section 8(e), the "substantial risk" information reporting pro-
vision of TSCA. The submitting company's rationale for reporting
the information under Section 8(e) may become apparent upon EPA's
receipt of a complete copy of the final report from the performed
study.
a)
The Chemical Screening Branch will ask the submi tting
company to provide to EPA a complete copy of the final
report (including the actual experimental protocol,
results of gross/histopathological examinations, pH of
the tested material (if known), etc.) fr~n the acute eye
irritation study that was cited in the company's TSCA
Section 8(e) notification.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of the tested mixture and/or its isomers.
c)
The Chemical Screening Branch will send copies of this
status report to OSHA, NIOSH, CPSC, FDA, NTP, OSHER/EPA,
OH/EPA, OAR/EPA, ORD/EPA and OPP/OPTS/EPA. Copies of
this status report will be provided also to the TSCA
Assistance Office (TAO/OTS) for further distribution.
362
-------
SUBJECT:
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
Page 1 of 5
DATE:
OEe
3 1986
Approved:~ JzJ'f/('(P
FRO"':
Status Report* 8EHQ-I086-0641
8EHQ-1186-0641 SUPP.
James F. Darr, Section Head 11lNt..1VI r ~
Chemical Risk IdentificatioriJs~tion/CSB
TO:
Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
In its in i t ial TSCA Sec t ion 8 (e) submission, the Union Carbide
Corporation provided a copy of an abstract entitled liThe Neuro-
logical Manifestations of Chronic Ethylene Oxide Exposure" that
had appeared in the July 1986 issue of the Annals of Neurology
(Vol. 20, No.1, pg. 136, Abstract No. P51). The following ex-
cerpt is from the submitted abstract:
II . [The investigators, G. Ristow and D. Cornelius of
Michigan State University, studied] 14 persons chronical-
ly exposed to . . . [ethylene oxide (EO)] over a period of
18 months. Sensory symptoms were present in 93 % (13 of
14), motor symptoms were present in 79% (11 of 14), and
in addition, disturbances in cognitive function were pre-
sent in 79% (11 of 14). The cogni ti ve defec ts included
memory disturbancet mood change, and language and speech
disturbance. Additional symptoms [reported] in-
cluded seizures (29%, 4 of 14) and headache (43%, 6 of
14) . . . [The performed study included] 9 women and
5 men wi th ages rang ing from 18 to 55 years. Follow-up
after 12 to 18 months revealed marked improvement in
motor function and sensory symptoms and significant im-
provement in mood and memory, although some patients
continue to complain of cogni tive problems and pares-
thesias. . [The investigators believe] there is
significant risk for the development of neurological
symptoms associated with both intimate and prolonged
casual contact with EO."
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
363
-------
Page 2 of 5
In the supplemental notice, Union Carbide reported that the
results of the study were "presented by the authors as a Poster
Presentation at a recent meeting of the American Neurologic
Association." In the supplemental submission, Union Carbide pro-
vided a copy of the manuscript which (according to Union Carbide)
contains the text of the authors' presentation. The submitted
manuscript contains the following background information:
"At a small town bulk medical supply sterilization plant,
two large industrial sterilizers for hospi tal material
were in frequent use dur ing the per iod in wh ich sever al
workers were exposed. At this plant, the sterilant used
was 12% [ethylene oxide (ETa)] mixed with 88% fluorocar-
bon (FREON) and the sterilizers operated at about 300,000
parts per million [(ppm)] during sterilization. At the
time employees became symptomatic, there was no dedicated
external exhaust equipment for the sterilizers. The ste-
rilizer exhaust fumes had to pass into plant air and the
fumes were ventilated through adjacent preparation and
sewing areas where non-sterilizer workers were stationed.
In addition, the standard three air-wash procedure after
sterilization had often been reduced to two or one air-
washes and the sterilization equipment was frequently in
operation day and night. Material to be sterilized was
loaded and unloaded into the sterilizers on wooden pal-
lets which were later stacked and stored in the shipping
area, presumably saturated with ETa residue. The sterili-
zer operators did not wear protective clothing or equip-
ment (e.g., masks, gloves, or self-contained ventilation
equipment) and were not cautioned about potential hazards
of the gas.
"Persons loading and unloading the sterilizers frequently
reported smelling the characteristic odor of the gas, in-
dicating a level of above 700 ppm and could at all times
feel a slippery, oily residue on handled materials which
had been sterilized. Packers in the preparation area at
times had to repack items for resterilization and report-
ed occasional odor and feeling of residue. In mid-1984,
the plant resumed the three air-wash procedure, installed
a dedicated ventilation system at the sterilizers and in-
structed sterilizer operators not to enter the chambers
for loading and unloading. Other additional safety pre-
cautions were instituted at this time.
"[The study involved] nine males and five females who
were exposed and symptomatic. The age range was 18 to 55
years. None had a history of alcohol abuse or diabetes.
None were taking prescription medications and none were
exposed to other tox ins. During the time of the ir em-
ployment, none of them described any episodes of acute
ETO intox ica tion. The range of employment time from
hiring to the development of the first symptom was 0.4 to
8.0 years with an average in this series of 3.9 years.
364
-------
Page 3 of 5
"Fifteen workers were exposed to increased ambient con-
cen tra t ions of ETO dur ing 1983 and early 1984. Fourteen
of the 15 became symptomatic. Several of these workers
had intimate contact with the gas and sterilization
equip;nent while others worked at some distance from the
sterilizers. Those in close contact included persons who
loaded and unloaded the sterilizers and emptied and
stacked the wooden pallets used to hold large quantities
of material during sterilization. Those working at a
further distance from the sterilization equipment in-
cluded persons stacking and packing material to be
sterilized as well as unwrapping and repacking items
which required re-sterilization.
"Eleven persons who became symptomatic noticed a gradual
and insidious progression of various mood change, memory
and speech disturbance. Thirteen patients noted acral
numbness, paresthesias and dysesthesias. Distal weakness
was noted in 11 patients. In 7 patients, the symptoms
led to domestic difficulties including impotence in all 5
males. A peculiar feeling of persistent fatigue occurred
in 12 patients. Muscle cramps and spasms were noted in
10 patients and new and persistent headaches occurred in
6 patients. Seven patients complained of chest pain or
discomfort. Four patients noted tachycardia and 6 noted
visual disturbance (blurred or double vision).
"Six patients had an electroencephalogram [(EEG)] during
the ir course of exposure, 3 of these were abnormal wi th
the presence of nonfocal sharp activity or increased
generalized slow activity- Three patients had a seizure
dur ing the per iod of exposure although 1 of the 3 had a
his tory of se izures in childhood. The EEG was abnormal
in 2 of these patients and normal in 1.
"Ten patients described a speech disturbance during the
course of [the] symptoms, described variously as slurred
or mushy speech, slow speech, problems with word substi-
tution or word finding difficulty.
"The first patient seeking medical attention did so
because of progressive difficulty with coordination of
the feet. The majority of patients who were bothered by
disturbances in higher cort ical and cogni tive function
indicated that these symptoms did not diminish or change
significantly over weekends, holidays or vacations and
only diminished when the persons were removed from the
workplace or after the sterilization procedure had been
changed. Most patients were not aware that the ethylene
oxide exposure might account for their symptoms of mood
change, behavior change and cognitive difficulties.
"In a one year follow-up, some patients continued to
complain of persistent but mild cognitive problems
365
-------
Page 4 of 5
including decreased concentration, poor memory, ,episodic
blurring of vision and slurred speech. One patIent con-
tinues having headaches and several of the patients most
severely affected with the polyneuropathy continue to
complain of pain, dysesthesias and paresthesias although
the distal weakness has resolved. As of mid 1986, 10 of
the patients continue to work at the same facility. II
Submission Evaluation
The submitted information has been forwarded for inclusion in the
Chemical Screening Branch's ongoing review of ethylene oxide.
The purpose of this review is to determine the need for further
OTS assessment of ethylene oxide and/or transmi ttal of the sub-
mitted information to other EPA Offices and/or other appropriate
Federal agencies for consideration in any ongoing assessments of
the potential risks posed by exposure to ethylene oxide.
Immediately upon receipt of the Union Carbide Corporation's
ini tial and supplemental TSCA Section 8 (e) notices on ethylene
oxide, the Chemical Screening Branch sent copies of the notices
to the Occupational Safety and Health Administration (OSHA), the
Na t ional Insti tu te for Occupational Safety and Heal th (NIOSH),
the Food and Drug Administration (FDA) and to EPA's Office of
pesticide Programs. It should be noted that on June 22, 1984,
OSHA promulgated (49 FR 25734) a final standard for occupational
exposure to ethylene oxide. OSHA's permissible Exposure Level
(PEL) for occupa tional exposure to ethylene ox ide was set at 1
ppm as an 8-hour Time Weighted Average (TWA).
It should be noted that the Office of Toxic Substances (OTS) has
received a number of TSCA Section 8(e) and "For Your Information"
not ices on ethylene ox ide. In add i tion, the Chemical Screening
Branch prepared (in 1982) a Chemical Hazard Information Profile
(CHIP) on ethylene oxide. EPA has also promulgated TSCA Section
8(a) and 8(d) information gathering rules on ethylene oxide.
Current Production and Use
According to Chemical & Engineering News (July 9, 1986 issue),
5.7 billion and 5.8 billion pounds of ethylene oxide were manu-
factured in the United States in 1984 and 1985, respectively.
Ethylene ox ide is used ma inly as a chemical intermed ia te (e. g. ,
in the production of ethylene glycol) and as a chemosterilant/
fumigant (e.g., for medical and surgical equipment and devices,
packaging materials, dried foods). According to EPA's Office of
Pesticide Programs (OPP/OPTS) ethylene oxide is present as the
active ingred ient in 38 pesticide products registered under the
Federal Insecticide, Fungicide and Rodenticide Act (FIFRA).
366
-------
Page 5 of 5
Comments/Recommendations
It should be noted that a search of several publicly available
computerized data bases (including those listed in 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» did not reveal any references to the sub-
mitted study. It appears, therefore, that Union Carbide was
correct (in the strictest interpretation of EPA's Section 8(e)
policy statement) in submitting the information to the Agency
pursuant to Section 8(e) of TSCA.
The Chemical Screening Branch will transmit copies of this status
report to OSHA, NIOSH, CPSC, FDA, NTP, OPP/OPTS/EPA, OSWER/EPA,
OAR/EPA, ORD/EPA and OW/EPA. Copies of this status report will
be sent also to the TSCA Assistance Office (TAO/OTS) for further
d i s tr i but io n .
367
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 3
DATE:
NOV I 9 1986
SUBJECT:
Status Report*
8EHQ-I086-0642
Approved: OU- 11/19 J?(p
, I
FROM:
James F. Darr, Section Head ah'MEA r~
Chemical Risk IdentificatioN'~~~tion/CSB
TO:
Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
On behalf of the union Carbide Corporation, the U.S. Industrial
Chemicals Company, the Celanese Corporation and E. 1. DuPont de
Nemours & Company, Inc., the society of the plastics Industry,
Inc. (SPI) submitted the following information regarding the con-
duct and preliminary results of a two-year inhalation study of
vinyl acetate (CAS No. 108-05-4) in mice:
"Groups of 90 CD-l mice were exposed to concentrations
of vinyl acetate of 0, 50, 200 and 600 ppm for six hours
a day, five days a week, for two years. The preliminary
pathology review. indicated that the only adverse
effects observed were in the respiratory tract. i"lice
exposed to the 600 ppm level exhibited bronchiolar epi-
thelial lesions in the lung which included one animal
with one squamous cell nodule of a terminal bronchial
airway and another animal wi th one squamous cell car-
cinoma in a major airway. NO such tumors were observed
at the other exposure [concentrations] or in the
control animals. The 50 ppm concentration appeared to
be a no observable effect level."
In submitting these findings on behalf of the above mentioned
companies (who are the primary co-sponsors of the cited chronic
inhalation study), SPI stated that the provided information is
"preliminary and not all tissues from all the mice in the control
or the treatment groups have been reviewed." SPI stated also
that the conducting laboratory, which is located in the united
Kingdom, expects to complete the pathology by the end of 1986.
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
368
-------
8EHQ-I086-0642
Page 2 of 3
Submission Evaluation
Immediately upon receipt of this TSCA Section 8(e) submission,
the Chemical Screening Branch (CSB/ECAD/OTS) provided copies of
the notice to the Risk Analysis Branch (RAB/ECAD/OTS) for inclu-
sion in the ongoing review of available toxicologic and exposure
data on vinyl acetate.
It should be noted that the Agency has received a number of TSCA
Section 8 (e) and" Fo r Your Information" (FYI) not ices on vinyl
aceta te. It should be noted also that in 1984, the Chemical
Screening Branch prepared a Chemical Hazard Information Profile
(CHIP) on vinyl acetate.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for vinyl acetate (CAS No. 108-05-4), which is listed
in the initial TSCA Chemical Substance Inventory, has shown that
521 million to 2.6 billion pounds of this chemical were reported
as manufactured/imported in 1977. This production range informa-
tion does not include any data claimed to be TSCA Confidential
8usiness Informa tion (CBI) by the person( s) reporting for the
ini tial TSCA Inventory, nor does this production range informa-
tion include any data that would compromise TSCA C8I. All of the
information reported for the initial TSCA Inventory, including
the production range data, is subject to the limitations con-
tained in the TSCA Inventory Reporting Regulations (40 CFR 710).
According to Chemical & Engineering News (June 9, 1986 issue),
2.02 billion and 2.11 billion pounds of vinyl acetate were pro-
duced in the U.S. during 1984 and 1985, respectively. According
to secondary literature sources, the major use of vinyl acetate
is in the production of polymers (e.g., poly(vinyl acetate),
poly(vinyl alcohol), vinyl chloride copolymer, ethylene-vinyl
acetate copolymers).
Comme n t s / Re c omme nd a t ion s
Thus far, EPA has received a number of Section 8(e) submissions
from trade associations on behalf of their member companies. In
the Comments/Recommendations section of the status report that
was prepared by EPA in response to Section 8(e) submission 8EHQ-
0185-0543, the Agency reiterated its position with regard to the
TSCA Section 8(e) reporting obligations of trade associations and
their member companies.
369
-------
8EHQ-I086-0642
Page 3 of 3
a)
The Chemical Screening Branch will ask SPI to ensure
that copies of the status report EPA has prepared for
the present TSCA Section 8(e) notice are distributed to
the u. S. co-sponsors of the cited two-year inhalation
study of vinyl acetate in mice. In addition, SPI will
be requested to ensure that EPA receives full copies of
all future interim reports as well as the final report
from this chronic vinyl acetate inhalation study.
b)
As in the case of the initial Section 8(e) submission,
the Chemical Screening Branch will immediately transmit
all reported informa tion on vinyl acetate to the Risk
Analysis Branch for inclusion in the ongoing review of
available toxicologic and exposure data on this chemical
substance.
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, OAR/EPA, ORD/EPA, OPP/OPTS and RAB/ECAD/OTS. In
addition, copies of this report will be sent to the TSCA
Assistance Office (TAO/OTS) for further distribution.
370
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 3
DATE:
DEC
5 1986
SUBJECT:
Status Report*
8EHQ-1186-0643
Approved: ~ Iz,J~/?:v
FROM:
James F. Darr, Section Head (~rk
Chemical Risk Identificatio~~~c~ion/CSB
TO:
Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Dow Corning Corpora tion reported that the company recently
discovered that low molecular weight ni trosamines (see TABLE 1.
below) are produced and liberated during the foaming of 2 (two)
Dow Corning silicone elastomer foams (Silastic@ Q4-4682 Silicone
Rubber and Silastic@ Q4-4683 Silicone Rubber) used in applica-
tions such as foam rubber gaskets. In its Section 8(e) notice,
Dew Corning stated that the company assumes that the nitrosamines
form as the result of thermal decomposition of the blowing agent
(Nitropore@ ATA, a product of the Olin Corporation). Dow Corning
also submitted a copy of the Nitropore@ ATA Material Safety Data
Sheet (MSDS) that states that Nitropore@ ATA is a proprietary
mixture identified simply as an "azotetramine derivative."
TABLE 1. NITROSAMINES IDENTIFIED CAS Number
N-Nitrosodimethylamine (NDMA) 62-75-9
N-Nitrosodiethylamine (NDEA) 55-18-5
N-Nitrosodibutylamine (NDBA) 924-16-3
N-Nitrosomorpholine (NMOR) 59-89-2
Dow Corning reported that its testing procedures were based on
actual fabrica tion cond i tions used by a Dow Corning customer.
According to Dow Corning, this customer uses curing times of 10
to 20 minutes at temperatures ranging from 275°F to 325°F. Dow
Corning reported also that certain articles are cured at 392°F
for 4 hours. Dow Corning reported further tha t the analyses
involved volatiles (collected during curing) and extractables
(collected via solvent extraction of cured foam). The results of
Dow Corning's analyses are shown in TABLE 2. on the next page.
====================================================================================
* NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
371
-------
8EHQ-1186-0643
Page 2 of 3
TABLE 2.
"REsuurs 1
VOLATILE EXTRACTED
SAMPLE CURE TEMP ./TIME NITROSOAMINES NITROSOAMINES
Q4-4682 2750F/10 min. 61 ng* (NDMA) 450 ppbu (NDMA)
29 ng (NDEA) 85 ppb (NMOR)
12 ng (NMOR)
Q4-4682 3250F/20 min. 3600 ng (NDM.\) 720 ppb (NDMA)
790 ng (NDBA) 48 ppb (NDBA)
Q4-4682 & 275~/10 min. 32 ng (NDMA) 1100 ppb (NDMA)
Flame Retardant 110 ppb (NDBA)
Q4-4682 & 3250F/10 min. 5200 ng (NDMA) 450 ppb (NDMA)
Flame Retardant 800 ng (NDBA) 46 ppb (NDBA)
Q4-4682 392oF/4 hrs. 17,600 ng (NDMA) 80 ppb (NDMA)
350 ng (NDBA)
Q4-4683 3250F/20 min. 4200 ng (NDMA) 327 ppb (NDMA)
460 ng (NDBA) 24 ppb (NMOR)
24 ppb (NDBA)
Q4-4683 392oF/4 hrs. 60,200 ng (NDMA) 18 ppb (NDMA)
1500 ng (NDMA)
*Nanograms
**parts per billion
lMethod of Analysis - GC-TEA (Gas Chromatography - Thermal Energy Analyzer)
- HPLC-TEA (High Pressure Liquid Chromatography - Thermal
II
Energy Analyzer)
Submission Evaluation
EPA's concern about human exposure to nitrosamines is well known
and is based mainly on a large number of animal studies in which
nitrosamine exposure by a variety of routes resulted in cancer.
It should be noted that EPA's Office of Toxic Substances (OTS)
has received a number of Section 8(e) and "For Your Information"
submissions on nitrosamines. In addition, the Chemical Screening
Branch (CSB/ECAD/OTS) has prepared Chemical Hazard Information
Profiles (CHIPs) on several nitrosamines.
372
-------
8EHQ-1186-0643
Page 3 of 3
Immed iately upon rece ipt of this TSCA Sect ion 8 (e) submission,
the Chemical Screening Branch provided copies of the notice to
the Risk Analysis Branch (RAB/ECAD/OTS) and the Existing Chemical
Control Branch (ECCB/CCD/OTS) for inclusion in the OTS evaluation
of available tox icolog ic and exposure data on ni trosamines. It
should be noted also that in September 1984, EPA published two
"Chemical Adv isories" tha t outl ine the Agency's concerns about
ni trosamines in metalworking fluids. Copies of these advisories
may be obtained by calling (202)-554-1404, or by writing to:
Ed Klein, Director
TSCA Assistance Office (TS-799)
Office of Toxic Substances (OTS)
Environmental Protection Agency
401 "M" Street, S.W.
Washington, D.C. 20460
Comments/Recommendations
Dow Corning stated that the company "has temporarily suspended
the manufacture of silicone elastomer products." In addition,
Dow Corning stated that the submitted findings were communicated
to Dow Corning personnel as well as Dow Corning's customer who
has also suspended the manufacture of foamed elastomer. Dow
Corning stated also that the reported findings have been sent to
the "Olin Corporation and Kenrich Petrochemicals Inc., a contract
formulator." Finally, Dow Corning reported that the company is
still investigating this matter and will inform the Agency about
any further pertinent findings.
The Chemical Screening Branch will send copies of this status
report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA, ORD/EPA,
OW/EPA, OAR/EPA, RAB/ECAD/OTS and ECCB/CCD/OTS. Copies of this
status report will be provided also to the TSCA Assistance Office
(TAO/OTS/OPTS) for further distibution.
373
-------
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
Page 1 of 3
DATE:
DEC
5 1986
I t-f'6 !re,
SUBJECT:
Status Report* 8EHQ-1186-0644 Approved: ~
James F. Darr, Section Head L~~ ~~
Chemical Risk Identificationa~~~~ion/CSB
FROM:
TO:
Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Dow Corning Corporation reported that the company discovered
recently that 3,3, 3-tr ifluoropropionaldehyde (CAS No. 460-40-2)
"is prod uced when fluorosil icone fluids and greases are held at
elevated temperatures for extended periods of time." According
to Dow Corning, the company "exposed fluorosilicone fluids,
greases and elastomers [(listed below)] to elevated temperatures
and analyzed the chemical substances produced." Dow Corning
reported that "trace quantities of trifluoropropionaldehyde were
detected [by Fourier Transform Infra-Red (FTIR) spectroscopy]
when fluorosilicone fluids and greases were heated at tempera-
tures of 400°F - 500°F in air for several hours." The company
also reported, however, that "trifluoropropionaldehyde was not
produced when the fluorosilicone elastomer was exposed to these
same cond i t ions. " The company noted also that" in certa in ap-
plications, fluorosilicone fluids and greases may reach these
temperatures."
Dow Corning Materials Analyzed
DOW CORNING@ FS-1265 Fluid
DOW CORNING@ FS-1265 Fluid
DOW CORNING@ FS-1265 Fluid
MOLYKOTE@ FS-3451 Grease
MOLYKOTE@ FS-3452 Valve Lubricant
SILASTIC@ LS-2860 Fluorosilicone Rubber
( 300 CS)'
(1,000 CS)
(10,000 CS)
In its submission, Dow Corning reported that all of the products
listed above "are based on polymers that contain trifluoropropyl
substitution. "
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
374
-------
8EHQ-1186-0644
Page 2 of 3
Dow Corning stated that because the company could not locate any
tox icolog ic information on tr ifluoropropionaldehyde and was not
able to find a commercial supplier for the chemical, Dow Corning
synthesized a small amount of trifluoropropionaldehyde to verify
chemical structure and to conduct toxicologic testing. According
to Dow Corning, "an initial rangefinding acute oral toxicity
study with rats was conducted. . . and indicates the material to
be highly toxic, [with an] ALD50 < 25 mg/Kg body weight."
Submission Evaluation
In order for EPA to evaluate the overall significance of the
reported information, Dow Corning should be asked to submit a
full copy of the final report from the acute oral toxicity test
ci ted in the company's TSCA Sect ion 8 (e) not ice. In add it ion,
DOW Corning should be asked to report the levels of trifluoro-
propionaldehyde detected by the company.
Current Production and Use
3,3,3-Trifluoropropionaldehyde (CAS No. 460-40-2) was not located
during a search of the non-confidential computerized version of
the initial TSCA Chemical Substance Inventory.
Comments/Recommendations
In its TSCA Section 8(e) submission, the Dow Corning Corporation
reported that the company has 1) revised ~'laterial Safety Data
Sheets (MSDSs), labels, and literature to reflect the reported
data; 2) notified affected Dow Corning personnel and customers;
and 3) notified the General Electric Company (a U.S. producer of
fluorosilicone materials) as well as "other global fluorosilicone
producers." Dow Corning reported also that the company will con-
tinue to investigate the matter and will report to the Agency any
further pertinent information obtained by the company.
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will ask
the Dow Corning Corporation to submit a complete copy of
the final report (including the actual experimental pro-
tocol, results of gross/histopathological examinations,
results of statistical analyses (if performed), etc.)
from the acute rat oral toxicity study that was cited in
the company's TSCA Section 8(e) submission.
In view of EPA' s general interest in corporate actions
taken on a voluntary basis in response to chemical toxi-
city or exposure data, Dow Corning will be requested to
describe the nature and results, if available, of all
studies that Dow Corning has conducted, is conducting or
is plann ing to conduct to determine the tox ic i ty of or
the exposure to trifluoropropionaldehyde.
375
-------
8EHQ-1186-0644
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 trifluoropropionaldehyde.
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, OAR/EPA, ORD/EPA, and OPP/OPTS/EPA. Copies of
this status report will be provided also to the TSCA
Assistance Office (TAO/OTS) for further distribution.
376
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
DEC I I 1986
Page 1 of 3
SUBJECT:
Status Report*
8EHQ-1286-0645
Approved :;:;JJi- I z./J ( (g"~
FROM:
James F. Darr, Section Head ~ T ~
Chemical Risk Identificatioll~~ction/CSB
TO:
Frank D. Koverj Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Lever Brothers Company provided summarized results of an Ames
test of C.I. (Color Index) Direct Yellow 28 (CAS No. 8005-72-9).
Accord ing to the submission, C. I. Direct Yellow 28 was found to
induce a n\veakn mutagen ic effect when tested wi th and wi thout
exogenous metabolic activation in two strains (TA 98 and TA 1538)
of Salmonella typhimurium (bacteria).
Submission Evaluation
In order for the Agency to evaluate the overall significance of
the reported genotox icolog ic find ings, Lever Brothers should be
asked to submit a complete copy of the final report from the Ames
test cited in the company's TSCA Section 8(e) submission.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for C.L Direct Yellow 28 (CAS No. 8005-72-9), which
is 1 isted in EPA' s ini tial TSCA Chemical Substance Inventory,
showed that between 12 thousand and 120 thousand pounds of this
chemical were reported as manufactured/imported in 1977. This
production range information does not include any information
claimed to be TSCA Confidential Business Information (TSCA CBI)
by the person(s) reporting for the initial TSCA Inventory, nor
does it include any information that would compromise TSCA CBL
All of the data reported for the initial TSCA Chemical Substance
Inventory, including the production range data, are subject to
the limitations contained in the initial TSCA Inventory Reporting
Regulations (40 CFR 710).
====================================================================================
* NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
377
-------
8EHQ-1286-0645
Page 2 of 3
According to secondary literature sources, C.I. Direct Yellow 28
is a thiazole derivative used to dye/stain a variety of natural
and synthetic materials. In its TSCA Section 8(e) submission,
Lever Brothers reported that this dye "is not being used in any
Lever Brothers' products but was being investigated for possible
use." (Lever Brothers did not disclose, however, the nature of
the company's possible use of this dye.)
Comments/Recommendations
In its Section 8(e) notice, Lever Brothers stated that a company
"decision to conduct additional mutagenicity testing will be made
after further discussions with. [Tricon Colors Incorporated
(the supplier of C.I. Direct Yellow 28)] and after assessment of
Lever's continued interest in this material."
It should be noted that although a positive in vitro genotoxicity
finding, when considered alone, may not besufficient to offer
reasonable support for a conclusion of substantial risk (as de-
fined in EPA's TSCA Section 8(e) policy statement ("Statement of
Interpretation and Enforcement Policy; Notification of Substan-
tial Risk" 43 FR 11110; March 16, 1978), EPA does believe that a
single positive genotoxicity finding is of value in assessing the
possible risk(s) posed by exposure to the tested chemical or mix-
ture. In addition, EPA believes that a positive genotoxicity
result, in combination with other information (e.g., knowledge of
real or potential exposure to and/or high production of the sub-
ject chemical or mixture) would suggest the need, in many cases,
to conduct further studies to determine better the toxicity of or
the exposure to tha t chemical or mixture. The resul ts of such
additional testing should be considered also for submission to
EPA under Section 8(e) of TSCA.
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will ask
the Lever Brothers Company to submit to EPA a full copy
of the final report (including the actual experimental
protocol, data, results of statistical analyses (if per-
formed), etc.) from the Ames test cited in the company's
TSCA Section 8(e) submission.
In addition, the Chemical Screening Branch will ask
Tr icon Colors Incorpora ted to prov ide to EPA the exac t
chemical identity of C.!. Direct Yellow 28, a dye that
is supplied by Tricon as Yellow Shade 18569.
In view of EPA's general interest in corporate actions
taken on a voluntary basis in response to chemical tox-
icity or exposure data, Lever Brothers and Tricon will
be asked to describe the actions the companies have
taken or plan to take 1) to notify workers/others about
the reported findings, and 2) to reduce or eliminate
exposure to C.I. Direct Yellow 28. In addition, Tricon
and Lever Brothers will be asked to describe the nature
378
-------
8EHQ-1286-0645
Page 3 of 3
and results, if available, from all studies (other than
those that have been published in the open scientific
literature or those that have been submitted already to
EPA) about wh ich the companies are aware or that the
companies have conducted, are conducting or plan to con-
duct to determine the toxicity of or the exposure to
C.l. Direct Yellow 28.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of C.l. Direct Yellow 28.
c)
The Chemical Screening Branch will send copies of this
status report to NlOSH, OSHA, CPSC, NTP, FDA, OSWER/EPA,
OW/EPA, OAR/EPA, ORD/EPA and OPP/OPTS/EPA. Copies of
this report will be provided also to the TSCA Assistance
Office (TAO/OTS) for further distribution.
379
-------
DA TE:
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 3
DEC I 2 1986
I qU/f(P
SUBJECT: Status Report* 8EHQ-1186-0646 S Approved: (~
FROM: James F. Darr, Section Head ~~f~
Chemical Risk IdentificationU~~c~~ion/CSB
TO:
Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Note
The submitting company has claimed its company name and the exact
identi ties and use (s) of the tested ma terial and its components
to be TSCA Confidential Business Information (TSCA CBI). The
Information Management Division (IMD/OTS) will be reviewing the
adequacy of the submitter's substantiation of these CBI claims.
In the non-confidential version of this TSCA Section 8(e) notice,
the tested material was identified as an acrylate mixture.
Submission Description
The submitting company provided summarized preliminary results
from a number of in vitro and in vivo genotoxicty studies of an
acryla te mixture. -Accord ing tothe submi tted information, this
acrylate mixture was found to be:
o
negative at all dose levels tested with and without
exogenous metabolic activation in a "modified" Ames
Salmonella .typhimurium (bacteria) assay;
o
positive at all, dose levels tested in the absence of
exogenous metabolic activation in an in vitro Chinese
hamster ovary (CHO) cell Sister Chromatid Exchange (SCE)
assay (a positive response was reportedly observed only
at the highest dose tested in the presence of metabolic
activation) ;
o
posi tive (in a dose-related manner) in a micronucleus
assay conducted in vivo using Swiss CD-I mice;
o
negative at all dose levels tested in an Unscheduled DNA
Synthesis (UDS) assay in cultured rat hepatocytes; and
====================================================================================
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
380
-------
8EHQ-1186-0646 S
Pag e 2 of 3
o
negative at all dose levels tested in the presence of
exogenous metabolic activation in an in vi tro CHO cell
mutagenici ty as say (an increase in mutation frequency
was reportedly observed only at the highest dose level
tested in the absence of metabolic activation.)
Submission Evaluation
In order for EPA to evaluate the overall significance of the
reported genotoxicologic findings, the submitting company should
be asked to ensure that EPA receives complete copies of the final
reports from all studies cited in the company's submission.
Current Prod uct ion and Use
In light of the submitter's TSCA CBI claims, no information
concerning the use (s) or TSCA Inventory status of the subject
mixture or its components will appear in this report.
Comments
EPA's Office of Toxic Substances (OTS) has received a number of
TSCA Section 8(e), TSCA Section 5 and "For Your Information"
s ubmis sions on acryla tes . In addition, the Chemical Screening
Branch (CSB/ECAD/OTS) has prepared Chemical Hazard Information
Profiles (CHIPs) on several acrylates. Further, OTS is assessing
available toxicologic and exposure data on acrylates as a class.
Finally, the reader's attention is directed to a notice in 51 FR
43785 (December 4, 1986) which announces a public meeting to held
at EPA Headquarters in Washington, D.C. on February 3, 1987 from
9:00 AM to 5:30 PM. The focus of this public meeting will be to
identify and discuss the potential health risk issues associated
with chemicals in the acrylate category.
a)
The Chemical Screening Branch will ask the submi tter to
ensure that EPA receives a full copy of the final report
(including the actual experimental protocol(s), data,
results of statistical analyses (if performed), etc.)
fr om e ac h as say cited in the company's subm is sion. In
addition, the submitter will be requested to report the
amount of each component in the tested mixture.
In view of EPA' s general interest in corporate actions
taken on a voluntary basis in response to chemical toxi-
ci ty or exposure data, the submi tting company will be
asked to describe the actions the company has taken or
plans to take 1) to reduce or eliminate exposure to the
381
-------
8EHQ-1l86-0646 S
Page 3 of 3
tested mixture and/or its components, and 2) to notify
workers and others about the reported genotox icolog ic
findings. In addition, the submitting company will be
asked to describe the nature and results, if available,
of all studies (other than those cited in the published
scientific literature or those submitted already to EPA)
about which the company is aware or that the company has
conducted, is conducting or plans to conduct to deter-
mine the tox ici ty of or the exposure to this acrylate
mixture and/or its components.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for separate
OTS assessment of the subject acrylate mixture (or its
components) and/or referral of the data for inclusion in
the ongoing OTS assessment of acrylates as a class.
c)
The Chemical Screening Branch will send copies of this
status report to OSHA, NIOSH, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, OAR/EPA, ORD/EPA, OPP/OPTS/EPA, RAB/ECAD/OTS and
ECCB/CCD/OTS. In addition, copies of this status report
will be sent to the TSCA Assistance Office (TAO/OTS) for
further distribution.
382
-------
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
DATE:
JAN 1 2 1987
Page 1 of 3
SUBJECT:
Status Report * 8EHQ-1186-0 64 7 Approved:
James F. Darr, Section Head c1,A....#A r ~
Chemical Risk Identificatio~/~~:~ion/CSB
~ j/'l?7
FROM:
TO:
Frank D. Kove~. Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
.Submission Description
Allied-Signal Inc. prov ided summar i zed resul ts from a series of
acute in vivo and in vitro studies of a tetraoximinosilane (TOS)
and methyloximinosilane (MaS) mixture. Allied-Signal stated non-
confidentially by phone on January 6, 1987 that the composition
of the mixture was 15% TOS (CAS No. 34206-40-1) and 85% MaS (CAS
No. 22984-54-9). According to the submitted information, the
TOS/MOS mixture was found to be a severe irri tant in a primary
dermal irritancy test in rabbits. Based on these results,
Allied-Signal stated that the TOS/MOS mixture was not tested in
an acute rabbit eye irritancy study, although the material was
expected to be severely irritating to the eyes. Allied-Signal
stated further that the TOS/r10S mixture was found to be an ex-
treme skin sensitizer in guinea pigs. In addition, Allied-Signal
reported that although no deaths occurred among rats dosed once
orally with the mixture at levels of 0.1, 0.75 or 2.0 ml/kg,
"reversible neurological effects (narcosis) were apparent at all
dose levels." Allied-Signal also provided the following informa-
tion regarding the findings from an acute rabbit dermal toxicity
study in which the TOS/MOS mixture was appl ied to the skin (5
male and 5 female rabbits/group) for 24 hours at doses of 0.05,
1.0 or 2.0 ml/kg:
"The tes t substance caused 9 deaths at the 2.0 ml/kg
level and 1 death at the 1.0 ml/kg level. The mortali-
ties were associated with either severe methemoglobin-
emia or erythrolysis and resultant hemoglobinuria. Both
hepatic and renal lesions appeared to have occurred
secondarily to hypoxia associated with the erythrocytic
tox ici ty induced by the test substance. Eight/nine sur-
viving rabbits at the 1.0 ml/kg level had increased
hemosiderin pigment of the spleen indicating a sublethal
====================================================================================
* NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
383
-------
8EHQ-1l86-0647
Page 2 of 3
test substance effect had occurred in these animals. A
microscopic no effect level occurred in rabbits dosed at
the 0.05 ml/kg level."
With regard to in vitro genotoxicity, Allied-Signal reported that
the TOS/r10S mix-ture was negative wi th and wi thout exogenous meta-
bolic activation in 1) an Ames Salmonella typhimurium (bacteria)
assay, and 2) cuI tured mammalian cell mutation and chromosomal
aberra tion as says. In addi tion, Allied-Signal reported that an
in vitro mammalian cell Sister Chromatid Exchange assay was nega-
tive with activation, and, without activation, "the highest dose
level was significantly elevated, causing a positive trend test."
Finally, Allied-Signal's submission contained a memorandum in
which the findings from acute rat oral toxicity studies of the
TOS/HOS mixture and MaS alone were compared. Accord ing to this
memorandum, the TOS/MOS mixture "produces nearly the same quali-
tative and quantitative effects" as MOS. The memorandum states
further that "based on mortality patterns, the presence of TOS in
the mixture. . . seems to have had a diluent effect and produced
less acute lethality for similar dose levels." In addition, the
memorandum states that effects other than lethality were similar
for both the TOS/MOS mixture and MaS alone.
Submission Evaluation
The submitted information has been provided to the Risk Analysis
Branch (RAB/ECAD/OTS) for inclusion in their recently initiated
review of organosilanes.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for t10S (CAS No. 22984-54-7), which is listed in the
initial TSCA Chemical Substance Inventory, has shown that no 1977
manufacture/importation was reported or that all of the reported
data was claimed as TSCA Confidential Business Information (CBI)
by the person(s) reporting for the TSCA Inventory and cannot be
disclosed (see Section 14(a) of TSCA; U.S.C. 2613(a». 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).
~etraoximinosilane (TOS; CAS No. 34206-40-1) was not found in the
current non-confidential versions of ei ther the printed or com-
puterized TSCA Inventory. According to staff of the Information
Management Division (IMD/OTS), however, this chemical substance
is included in the non-confidential TSCA Inventory.
Allied-Signal did not submit any information with regard to the
actual/planned use(s) of TOS and/or MaS nor was such information
located in the secondary literature sources consulted by EPA.
384
-------
8EHQ-1186-0647
Page 3 of 3
~omments/Recommendations
EPA I s Office of Tox ic Substances (OTS) has rece i ved a number of
TSCA Section 5 and 8(e) submissions as well as several "For Your
Information" (FYI) submissions on organosilanes. The Chemical
Screening Branch recently prepared a Chemical Hazard Information
profile (CHIP) on organosilanes and did prepare (in 1982) a CHIP
on 3,4-epoxycyclohexylethyltrimethoxysilane (TMOHS). As stated
previously, staff of the Risk Analysis Branch/ECAD/OTS recently
initiated a review of organosilanes.
a)
The Chemical Screening Branch will request Allied-Signal
to provide full copies of the final reports (including
the actual experimental protocols, results of gross and
histopathologic examinations, results of any statistical
analyses, etc.) from all studies cited in the company's
TSCA Section 8(e) submission.
In view of EPA's general interest in corporate actions
taken on a voluntary basis in response to chemical toxi-
city or exposure data, Allied-Signal will be asked to
descr ibe the act ions the company has taken or plans to
take 1) to notify workers and others about the reported
toxicologic findings, and 2) to reduce or eliminate the
exposure to '1'08 and/or }\WS. In addition, Allied-Signal
will be requested to describe the nature and results, if
available, from all studies (other than those submitted
already to EPA or those cited in the open scientific
literature) about which Allied-Signal is aware or that
the company has conducted, is conducting, or plans to
cond uct to determine the tox ic i ty of or the exposure to
TOS and/or MOS.
b)
The Chemical Screening Branch will transmi t all of the
reported information immediately to the Risk Analysis
Branch/ECAD/OTS for inclusion in their ongoing review of
organosilanes.
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, OAR/EPA, ORD/EPA, OPP/OPTS/EPA, RAB/ECAD/OTS and
CCD/OTS. In addition, copies of this status report will
be provided to the TSCA Assistance Office (TAO/OTS) for
further distribution.
385
-------
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
Page 1 of 3
DATE:
JAN I 6 1987
SUBJECT:
Status Report*
8EHQ-1286-0648
Approved:
ZJr {1~/rt7
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 Ethyl Corporation provided summarized findings from a sub-
chronic feeding study of diethyltoluenediamine (DETDA; CAS No.
68479-98-1) in rats. According to the submission, DETDA (which
is a mixture comprised mainly of 3,5-diethyltoluene-2,4-diamine
(CAS No. 2095-02-5) and 3,5-diethyltoluene-2,6-diamine (CAS No.
2095-01-4)) was incorporated into the diet and fed ad libitum to
4 groups (20 males and 20 females per group) of Sprague-Dawley
rats at dose levels of 0, 50, 125 or 320 parts per million (ppm)
per day for 90 days. The Conclusions section of the submitted
pathology report presented the following information regarding
the results of this sub-chronic feeding study:
"Administration of diethyltoluenediamine (DETDA) to rats
by repeated oral exposure for a period of ninety days at
levels of 50, 125, and 320 ppm resulted in a high mor-
tality rate in the high dose animals. Treatment-related
microscopic changes were present in all of the male and
female rats receiving 320 ppm. In these high dose rats,
there was a high incidence of bilateral cataractous
change in the eyes, diffuse atrophy of the acinar cells
of the pancreas, ,bone marrow depletion, tubular vacuola-
tion (hydropic change) of the kidneys and vacuolation of
the islet cells of the pancreas, atrophy of many organs
[including the genital organs of both sexes], lymphoid
deplet ion of the spleen, thymus and mesen ter ic lymph
nodes, and [an] increased pigmentation of the liver and
spleen. A minimal to moderate multifocal degeneration of
the acinar cells of the pancreas and increased splenic
pigmentation in the females were present in the tissues
examined from the rats receiving 50 and 125 ppm DETDA in
the diet."
------------------------------------------------------------------------------------
------------------------------------------------------------------------------------
*
NOTE: This status report is the result of a preliminary evaluation of
information submitted to EPA pursuant to Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Control
Act (TSCA). The statements made in this 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
the fact that the report may be based on incomplete information.
386
-------
8EHQ-1286-0648
Page 2 of 3
In its Section 8(e) submission, the Ethyl Corporation stated that
the doses used in the 90-day study were expected to cause toxic
effects in order to set the dose levels for a 2-year bioassay of
DETDA. In addition, Ethyl reported non-confidentially by phone
on December 31, 1986 that DETDA has the following composition:
74% to 80% of 3,5-diethyltoluene-2,4-diamine;
18% to 24% of 3,5-diethyltoluene-2,6-diamine;
a maximum of 1% 2,4,6-triethylberlzene-l,3-diamine; and
o to 4% of other polyalkylated m-phenylenediamines.
Submission Evaluation
The draft summary report from this 90-day feeding study of DETDA
in rats indicates that the highest dietary DETDA dose (320 ppm)
produced a high rate of mortality (27 deaths/40 exposed rats) and
severe toxic manifestations in both sexes. The observed adverse
ef fects inc luded: bila teral degenera tive changes in the lens of
the eye; diffuse atrophy of the pancreatic acinar cells, vacuola-
tion ;:md reduction in the quantity of pancreatic islet cells;
bone marrow hypocellularity; hydropic changes in the kidney;
lymphoid depletion in the thymus, spleen and mesenteric lymph
nodes; thymic involution; atrophy of the salivary gland, thymus,
stomach, and reprod uct ive organs; and increased pigmentation in
the liver and spleen which, in combination with the decreased
hemoglobin content in the blood, is undoubtedly hemosiderosis.
A considerable number of these serious toxic effects were noted
in male and female rats at the mid-dose level (125 ppm). In view
of the fact that 1) the low-dose (50 ppm) females demonstrated a
modera tely severe splenic pigmentation in 8/20 rats as compared
to 0/20 control rats, and 2) the low-dose (50 ppm) males were
found to have varying degrees of pancreatic acinar cell degenera-
tion in 12/20 rats as compared to 5/20 control rats wi th less
severe degeneration, a "no-observed-adverse-effect-level" (NOAEL)
was not determined in this 90-daY DETDA feeding study.
Current Prod uct ion and Use
A review of the production range (includes importation volumes)
statistics for diethyltoluenediamine (CAS No. 68479-98-1), which
is 1 is ted in the in i t ial TSCA Chemical Substance Inventory, has
shown that no 1977 manufacture/importation was reported or that
all of the prod uction range 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
(TSCA Section l4(a), U.S.C. 26l3(a». All of the information
reported for the initial TSCA Inventory, including the production
range information, is subject to the limitations contained in the
TSCA Inventory Reporting Regulations (40 CFR 710).
Accord ing to secondary Ii terature sources,
ex tender /curing agent for polyurethane, as
epoxy resins, and as a chemical intermediate.
DETDA is used as an
a curing agent for
387
-------
8EHQ-1286-0648
Page 3 of 3
With regard to worker exposure to DETDA, the Ethyl Corporation
stated that "industrial hygiene monitoring [(minimum detection
limit of 50 parts per billion)] of Ethyl employees engaged in the
manufacture of DETDA has shown no detectable airborne DETDA in
the workplace. II Ethyl reported also that "DETDA has a very low
vapor pressure and is handled in a closed system. II In addition,
Ethyl stated that its "workers wear full body protective clothing
to prevent skin contact [with DETDA]. II
Comments/Recommendations
In its TSCA Section 8(e) submission, the Ethyl Corporation stated
that the company is notifying its workers and customers about the
reported toxicologic findings. In addition, Ethyl stated that a
copy of the final report from the 90-day DETDA feeding study will
be sent to EPA as soon as that report is received by the company.
Finally, Ethyl reported that the company plans to conduct further
studies (in addition to the 2-year bioassay) in an attempt to
"elucidate the mechanism of DETDA's toxic effect in the pancreas
and determine if this effect is species specific or reversible. II
It should be noted that EPA's Office of Toxic Substances (OTS)
received previously a Section 8(e) submission (8EHQ-0883-0489 et
seq.) in which Lonza Inc. reported that DETDA caused a dose-
dependent mutagenic response in the presence of metabolic
activation in an Ames Salmonella _typhimurium (bacteria) assay.
a)
The Chemical Screening Branch will request the Ethyl
Corporation to ensure that the Agency receives a full
copy of the final report (including the actual experi-
mental protocol, results of gross and histopathological
examinations, results of any statistical analyses, etc.)
from the company's 90-day DETDA feeding study.
In light of EPA's general interest in corporate actions
taken on a voluntary basis in response to chemical toxi-
ci ty or exposure data, the Chemical Screening Branch
will ask the Ethyl Corporation to descr ibe the nature
and results, if available, from all studies (other than
those reported already to EPA or those cited in the open
scientific literature) about which the company is aware
or that the company has conducted, is conducting, or is
planning to cond uct to determine the tox ic i ty of DETDA
or its constituents.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of DETDA or its constituents.
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
ORD/EPA, OAR/EPA, OW/EPA and OPP/OPTS/EPA. In addition,
copies of this report will be transmitted to the TSCA
Assistance Office (TAO/OTS) for further distribution.
388
-------
-:..~
-=
---
== 51 -=
==-==
~A
--~
~-
~ .a::=
A
~
m
-===- s;:=-'
- -
~ ::..
-=a,
===~
~
..
-~---
-~-.-
----
--
--
~==.
====-=
=== = ===
:.:=.. 55 ==
=== --====-
= =
- -
8fffNIUX A
THURSDAY, MARCH 16, 1978
PART V
ENVIRONMENT AL
PROTECTION
AGENCY
.
TOXIC SUBSTANCES
CONTROL ACT
Statement of Interpretation and
Enforcement Policy; Notification
of Substantial Risk
389
-------
11110
[ 6560-0 1 ]
ENVIRONMENT AL PROTECTION
AGENCY
[FRL 849-21
TOXIC SUISTANaS CONTIOl ACT
Notlf\cetlen of Sub.tontl" Rlak Undo,
SoctIon I( 0)
AGENCY: Environmental Protection
Mency.
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. 2607>. The
provisions of that section went Into
eUect on January I, 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
AdminiBtrator has been adequately in-
formed of such information."
DATES: The policy expressed In this
document is In eUect as of the date of
publication.
FOR FURTHER INFORMATION
CONTACT:
Frank D. Kover, Assessment Divi-
sion, OUlce of Toxic Substances
(WH-557), Environmental Protec-
tion Agency, 401 M Street SW.,
Washington, D.C. 20460, 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, 1'977 (42 FR
54857). On November 4. 1977. a supple-
mental notice to the proposed guid.
ance was published (42 FR 57744). de-
letlI1&' the November 15 date for re-
porting certain Information obtained
before 1977 and stating that a new
date would be established In the final
l11idance.
In developing this policy statement.
two meetings have been held (FE:,bru-
NOTICES
ary 1. 1977, and October 26. 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 sign1!lcant Issues raised In
these comments and the Agency's re-
sponse to them.
The major mod1!lcatlona 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 empl01ees of a business
organization would result In 1ll-consid-
ered, premature reports and would un.
fairly subject employees to conflicting
responsib1lIties as individual respon-
dents and as corporate agents. Other
commenters expressed support for the
view that certain employees have are.
sponsib1l1ty 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-
Inr pertinent information, but stipu-
lated enforcement priorities Intended
to encourage corporate processing and
centralized 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-
mizing 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 reo
sponslb1l1ty for reportlnr to EPA any
substantial-risk Information obtained
by Individual oUicers or employees.
Accordlnrly, this poltley statement
stipulates that individual o!!1cers and
employees will have fully discharged
their section 8(e) obligations once they
have notified the designated responsi-
ble company supervisor or oUlclal 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
faiUng to report; and (4) provide a
mechanism for promptly notifying of-
ficers and employees who have submit-
ted reports of the company's dlsposl.
tlon of those reports, including whE'th-
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 proc/;'dures
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 substantial-risk informa-
tion Is reported to EP A.
(3) The September 9 proposal stated,
In Part III. that a person obtains In-
formation when he Is aware that it
"may suggest" substantial 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 Substantial
Risk"). particularly concerning envi-
ronmental effects, and suggested dif.
ferent interpretations of what constl.
tutes a "substantial risk" The Agency
continues to focus in this polley 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
poUcy statement continues to apply
section 8(e) to Information obtained
before 1977 of which a person hM
feDERAL REGISTER. VOL 43, NO. 52-THUISDAY, MARCH 16, 197.
390
-------
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.
vldes that any Information published
In scientific literature, In any Ian.
guage, Is exempt If It is referred to In
abstracta published by specified ab-
stracting services.
(7) This policy statement describes
In a nfW Part X how to submit claims
of confidentiality.
Accordingly, the Administrator's In.
terpretatlon of and policy towards sec.
tion 8(e) is set forth below.
Dated: February 24, 1978.
DOUGLAS COSTLE
Adminutrator.
I. DEFINITIONS
The definitions set forth in TSCA
section 3 apply to these requirements.
In addition, the following definitions
are provided for purposes of this
polley statement:
The term "manufacture or process
'for commercial purposes' " means to
manufacture or process: (1) For dlstrl.
butlon 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
propriftorshlp. assoclaUon, or any
other business entity, any State or po-
litical subdivision thereof, any munlcl.
pallty, 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 SUB.JJ:CT TO THE
REQUIREMENT
Persons subject to section 8(e) reo
Qulrements Include both natural per.
sons and business entities engaged in
manufacturing. processing. or distrib-
uting In commerce a chemical sub-
stance or mixture. In the case of busi-
ness entities, the president. chief ex.
ecutlve oUicer. 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.
flcer or employee capable of appreclat.
Ing the significance of lhat Informa-
tion has obtained. It Is therefore in.
HOTIaS
cumbent upon business organizations
to establish procedures for expedl.
tlously 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 requlrementa. An
employing organization may relieve Its
Individual officers and employees of
any responslbllIly for reporting sub.
stantlal-rlsk Information directly to
~PA by establishing. Internally publi-
cizing, and affirmatively Implementing
procedures for employee submission
and corporate processing of pertinent
Information. These procedures, at a
minimum. must: (1) Specify the Infor-
mation that officers and employees
must submit; (2) indicate how such
submissions are to be prepared and
the company official to whom they are
to be submitted; (3) note the Federal
penalties for falling to report; and (4)
provide a mechanism for promptly ad.
vising officers and employees in writ-
ing of the company's disposition of the
report, including whether or not the
report was submitted to EPA (and 11
not Informing employees of their right
to report to EP A. as protected by
TSCA section 23). An employee of any
company that has established and
publicized such procedures, who haa
internally submitted pertinent infor-
mation in accordance with them, shall
have discharged his section 8(e) obli-
gation. Establishment of such proce-
dures notwithstanding, all officials re-
sponsible and having authority for the
organization's execution of Ita section
8(e) obligations retain personal liabil-
ity for ensuring that the appropriate
substantlal.rlsk information Is report-
ed to EPA.
Business organizations that do not
establish such procedures cannot re-
Heve their individual officers and em-
ployees of the responslbllty for ensur.
Ing that substantlal.rIsk Information
they obtain Is reported to EP A. While
officers and employees of such organi.
zatlons may also elect to submit sub-
stantial-risk Information to their supe-
riors for corporate processing and re-
porting, rather than to EPA directly.
they have not discharged their Ind1vtd-
ual section 8(e) obligation untl1 EPA
has received the information.
NOTZ.-Irrespective of a business orpnlza-
tlon's decision to establish and publicize the
procedures descrlbE;d above, It Is responsible
for becoming cognizant of any substantlal-
risk Information obtained by Its officers and
employees, and for elUiurlng that such infor-
mation Is reported to EPA within 15 work-
Ing days.
III. WHEN A PERSON WILL BE REGARDED
AS HAVING OBTAINED INFORMATION
A person obtains substantlal.risk in-
formation at the time he first comes
11111
Into possession of or knows of such in-
formation.
Non.-Thla Includes Information of
which a prudent person similarly situated
could reuonably be expected to possess or
have knowledge.
An establishment obtains Informa-
tion at the time any officer or em-
ployee capable of appreciating the sig-
nificance of such information obtains
it.
IV. REQUIREMENT THAT A PERSON "1M.
MEDIATELY INFORM" THE ADMINISTRA-
TOR
With the exception of Information
on emergency Incidents of environ-
mental contamination [see Part V(C)]
a person has "immediately Informed"
the Administrator If information Is re-
ceived by EPA not later than the 15th
working day after the date the person
obtained such Information. Supple-
mentary Information generated after a
section 8(e) notification should. If ap-
propriate, be immediately reported.
For emergency Incidents of environ-
mental contamination, a person shall
report the incident to the Administra-
tor by telephone as soon as he haa
knowledge of the Incident (see Part IX
for appropriate telephone contacts).
The report should contain as much of
the information required by Part IX
aa possible. A written report in accor-
dance with Part IX (a) through (f) Is
to be submitted within 15 days.
Information currently In the posses-
sion of a person who Is subject to re-
porting must be reported within 60
days of publication of this policy state.
ment.
V. WHAT CONSTITUTES StJBSTAKTIAL
RISKS
A "substantial risk of Injury to
health or the environment" Is a risk of
considerable concern because of (a)
the seriousness of the effect [see Sub-
parts (a), (b). and (c) below for an il-
lustrative list of effects of concern].
and (b) the fact or probability of Its
occurrence. (Economic or social bene-
flta of use, or costs of restricting use.
are not to be considered in determin.
Ing whether a risk Is "substantial".)
These two criteria are differentially
weighted for different types of effects.
The human health effects listed in
Subpart (a) below, for example. are so
serious that relatively little weight Is
liven to exposure; the mere fact the
implicated chemical Is In commerce
constitutes sufficient evidence of expo-
sure. In contraat. the remaining ef.
fects listed in Subparts (b> and (c)
below must Involve, or be accompanied
by the potential for. significant levela
of exposure (because of general pro-
duction levels, persistence, typical
uses, common means of disposal, or
other pertinent factors>.
Note that: (j) The effects outlined
below should not be reported if the re-
fiDEIAL IEGISTEI, VOL 43, NO. 52-THUISDAY, MAICH 16, 1978
391
-------
1111%
spondent haa actual knowledle that
the Administrator Is already informed
of them.
(Ii) Information respectlne these ef-
fects e&n be obtained either directly,
by observation of their occurrence. or
inferred from designed studies aa 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 ef/ecu-(1) Any
instance of e&ncer. birth defects, mu-
tagenicity. death. or serious or pro-
longed incapacitation. includina the
loss of or inabUity to use a normal
bodily function with a consequent rel-
atively serious impairment of normal
activities. if one (or a few) chemicaHs)
Is strongly implicated.
(2) Any pattern of effects or evi-
dence which reasonablY supports the
conclusion that the chemical sub-
stance or mixture e&n produce e&ncer,
mutation, birth defects or toxic effects
resultini in death. or serious or pro-
10Died incapacitation.
(b) Environmental ef/ecu- Wide-
spread and previously unsuspected dis-
tribution in environmental media. u
indicated in studies (excludina materi-
als contained within appropriate dis-
posal facUitles).
(2) Pronounced bioaccumulatlon.
Measurements and indicators of pro-
nounced bioaccumulatlon heretofore
unknown to the Administrator (includ-
ini bloaccumulatlon in fish beyond
5.000 times water concentration in a
30-day exposure or havlni 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-
Ial adverse effect.
(3) Any non. trivial adverse effect.
heretofore unknown to the Admin!8-
trator. associated with a chemical
known to have bloaccumulated to a
pronounced degree or to be wide-
spread in environmental media.
(4) Ecoloi1C&lly significant ch&niea
in species' interrelationshiP8: that 18.
chanies in population behavior.
growth, survival, etc. that in turn
affect other species' behavior, growth.
or survival.
Examples include: m Excessive stim-
ulation of primary producers (ali&e,
macrophytes) in aquatic ecosystems.
e.g.. resulting in nutrient enrichment.
or eutrophication. of aquatic ecosys-
tems.
(Ii) Interference with critical bioleo-
chemical cycles, such as the nitroien
cycle.
(5) Facile transformation or degra-
dation to a chemical havlni an unac-
ceptable risk as defined above.
(c) Emergency incidenu 0/ environ-
mental contamination-Any environ-
mental contamination by a chemical
substance or mixture to which any of
Nonas
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 ecoloi1cally slgnifie&nt population
destruction.
VI. NATURE Aim SoURCES OF INFORMA-
TION WHICH "REASONABLY SUPPORTS
TIm 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 18 one of the types listed
below and if It is not exempt from the
reportini requirement by reason of
Part VII of thla policy statement. A
person 18 not to delay reporting until
he obtalns 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 &I to the substantlallty of
the risk: it should. however, reliably
ascribe the effect to the chemical.
Information from the followtni
sources concernlni the effects de-
scribed in Part V will often "reason-
ably support" a conclusion of substan-
tial risk. Consideration of corrobora-
tive information before reportlni can
only occur where It Is indicated below.
(1) Dengned, controlled .tudtu. In
assesslni the quality of information.
the respondent Is to consider whether
It contalns reliable evidence ascribini
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-
lea include:
m In vivo experiments and teats.
(ti) In vitro experiments and tests.
Consideration may be i1ven to the ex-
Istence of corroborative information. if
necessary to reasonably support the
conclusion that a chemical presents a
substantial risk.
(111) Epldemioloi1cal studies.
Clinical studies.
-------
(b) Any information the contents of
which a person has been alerted to by
date received after January I, 1977, in-
cludinr any Information concerning a
chemical for which the person is pres-
ently assessinr health and environ-
mental effects;
(c) Any other information of which
the person has actual knowledge.
IX. REPORTING REQUlREKEJfTS
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.,
Washlniton, D.C. 20460.
A notice should:
(a) Be sent by certified mail. or in
any other way pennittini verification
of its receipt by the Aiency,
(b) State that it is 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, processine, or distributing estab-
lishment with which he is associated,
(d) Identify.the chemical substance
or mixture (Including. if known, the
CAS Regtstry Number),
(e) Summarize the adverse effects
beinr 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-
portlni technical data.
. For emerrency incidents of environ-
mental contam1n&tlon (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) throuih . 312-353-
2318.
Rerlon VI (New Mexico. Texas. Oklahoma,
Arkansu, Louisiana). 214-749-3840.
ReClon VII (Nebraska. Iowa. Mlaaourl,
Kansu>, 818-374-3778.
ReClon VIII (Colorado, Utah, Wyoming.
Montana. North Dakota. South Dakota).
303-837 -3880.
Rerton IX (California, Nevada. Arizona.
HawaII. Guam). 415-556-6254.
NOTICES
Region X (Washington. Oreron. Idaho,
Alaska), 208-442-12<>0.
X. CONFIDENTIALITY CUIII8
(a) Any person submittinr a notice
to EPA under section 8
.. WHAT IfEED IfOT BE REPORTED AS Alf
IDOIIODCY UfCIDDT
information contained In notUication of
apilla under section 311(b)(6) ot the Federal
Water Pollution Control Act (FWPCA).
(For a complete list ot exemptions to report-
tnr. see Part VII.>
C. WBD Alf1) WHDJ: TO RJ:POIIT DO:IIODeT
mCmDTI
Emergency Incidents of environmental
contamination are to be reported immedi-
ately by telephone to the appropriate EP A
Rertonal 24-hour telephone emergency line
ILsted below.
Recton I (Maine, Rhode Island, Connecti-
cut. Vermont. Mus&chusetta, New Hamp-
shlre),817-223-7266.
Rerton II (New York. New Jersey, Puerto
Rico. VLrctn Islanda). 201-1148-8730.
Rerlon III (Pennsylvania. West Vlrrln1&.
Vlra1n1a. Maryland, Delaware, District of
Columbla),215-11117-9898.
Rerlon IV (Kentucky, Tennessee, North
Carolina. South Carolina. Georrta. Ala-
bama, Mlaalaalppl, Florida). 404-881-4062.
Rerton V (Wisconsin, illinois, indiana.
Mlchlpn. Ohio, MInnesota). 312-363-
2318.
Rerton VI (New Mexico. Texaa. Oltlahoma.
Arkanau, Loulalana). 214-749-3840.
Rerton VII (NebrL'k&, Iowa. MIaaow1.
~), 818-374-3778.
Rerton VIII (Colorado. Utah, Wyomlnr,
Montana. North Dakota, South Dakota).
303-837-3880.
Rerton IX (California. Nevada, ArIzona.
Hawaii, Guam), 415-558-8254.
Region X (Wu..bJn&ton, Or~ Idaho.
~442-12<>O.
In addition, a written report. In accord-
ance with instructions (a> throurh (t) ot
Part IX. fa to be submitted within 111 days to
the Document Control Offlcer. Chemical In.
tormation Division. Offlce ot Toxic Sub-
stance.s (WH-557J. 401 M Street SW.. Wash-
Ineton. D.C. 20460.
,ApPEmlIX B-SIGlfIPICAKT COIiOlDTS AlfD
RESPONSES
A. PDSOlfS SUBJECT TO THESE REQUIRDaJn'8
c.~ 1: Employees cannot be hp.ld
subject to these requlrementa, since: (a)
They only have a partial role In the manu-
facture. processing. or distribution ot chem!-
cala. (b) In other sections ot TSCA. the term
"person who manufactures. processes. or
distributes" chemicals clearly refers to busl.
ness organizations; "persons" should be con-
sistently defined, and (c) the application of
criminal penalties mandate.s a strict inter-
pretation of th Is word.
FEDERAL IEGISTEI, VOL 43, NO. 52-THUISDAY. MAICH 16, 197.
393
-------
11114
R~8fJOn8~: The Agency considers that dU-
ferent sections of TSCA. havtn&' d1lferent
purposes, are appropriately directed to dif-
ferent respondents. In the case of section
8rue: Contractors and Independent
labs are not responsible for relX>rtlng Infor-
NOTICES
matlon they have obtained directly to EPA;
rather, their cl1ent manufacturers. proces-
sors and distributors are responsible for
reporting such information.
.. no: "OnAIJfII'O" or mroRMATIolf
ComllU11t 5: The "may SUggest" criterion
In Pt.rt III of the proposal serves to compel
further examination of Information that by
Itself Is not subject to section 8(e) require.
ments. The statutory laneuaae calling for
"reasonable support." does not support this.
Further. risk &88eIIment often requires any.
where from monthl to Rver&l years of
Itudy &fter preliminary results "SUgeNt"
risk. far exceed1n8 the 15-d&y compliance
period.
RuponH.' The .uency does not Intend to
compel under section 8
-------
IU'JI01I$e: Part V now clarifies those ef-
fecta for which reporting depends upon a
.lrniflcant eXpollure potential. Persistence
by Itlelf Is no longer Itemized as a report-
able effect but rather Is considered to be a
component of exposure, potential; It m&¥
al80 underlie the measurementa described in
Part V(b)(l>. Laboratory indicators of pro-
nounced bloaccumulatlon 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 physlco-cheml-
cal property. not blololic&l effects. and Is
not alone an indicator of substantial risk;
further. the values stated for the coefficient
and the bloaccumulatlon factor In fish do
not correspond.
RUponae: The Agency acknowledges the
numertcal error and has amended the values
to correspond This policy statement now
c\lreCta the reporting of an experimental
meuurement of bloaccumulatlon when
coupled with an adverse effect and potential
for widespread exposure.
Comment 18: 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
IUPporta".
Rupome: The Agency has provided In a
new Part VI Ita interpretation of "reason-
ablY supporta".
Comment 19: A determination that infor-
mation "reasonably supports the conclu-
sion" of substantial rIBk cannot be made in-
dependently of considerations of use since
the method and manner of using a chemical
may tnnuence the occurrence of an effect;
In particular. the criteria should reflect a
distinction between normal and abnormal
uses of chemicals.
Ruponae: The Agency considers that the
approprtate componenta of a "substantial
rIak" with respect to a chemical are (a) the
sertoumess of the effect. and (b) total expo-
lUre potential. The method and manner of
IIIin& a chemical Is one of several factors de-
tennlnlnc Ita exposure potential. As de-
scribed In Part V. the importance of expo-
sure potential &8 a component of "substan-
tial rIak" depends upon the kind of effect of
concern. Thus. the effects descrtbed In Part
V(a) are 80 sertous that relativelY little
wellht Is liven to expollure; the effects de-
scribed In Parts V (b) and (c) Involve a si,-
nlflcant exposure or eXpollure 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.
L 11IPOlUlATIOlf THAT IfDI) IfOT 81: REPORTED
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?
Rupon,e: 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 rE'spondents
need not report to EPA Information already
reported to other Agencies. and vice versa.
Such duplicative reports are unduly burden-
some.
NOTICES
Re,pome: 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 agenclea.
r. IIfFORllATIOIf FIRST RECUVJ:D PUOR TO TID
U'n:criVJ: DATa or TSCA
Com7rU!!nt 22: The tense of the verb "ob-
tains" reveals that section 8(e) wu Intended
. to be applied prospectively to information
newly acquired after January 1. 11177. Utilize
section 8(d) or other rulea to 'acquire infor-
mation obtained before then.
Re,ponae: As discussed In the preamble to
the September 9 proposal, the Agency con-
siders section 8(e) to apply to rIak informa-
tion poase.ued by or known to a penon
before. on. or after January 1. 11177. Con-
cemlnr information first obtained before
1977. this policy statement continues to re-
Quire reportlnc 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" 18 too
vague to be of any help In respond1nc to
these requirements. Since many corporate
employees are potentially subject to these
requirements. and riven uncertainty over
the extent to which they ourht 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.
Rupome: The Arency In Part VIII of thl8
policy statement now defines the pre-1977
information of which a penon Is conaldered
to be aware.
G. COIfFIDElfTIAL IIfFORllATIOIf
Comment 24: EP A should delay guidance
until procedures are published governing
the treatment of confidential submlaslona.
Comment 25: EPA should treat allsubm18-
slons as confidential until the information 18
verified
Comment 26: EPA should automatically
publish section 8(e) notices.
Respome to Commentl 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. IIISCJ:LlAlfl:Ot7S
Comment 27: What Is the statutory bul8
or need for guidance? What Is Its exact
status under the Administrative Procedure
Act?
Response: This policy statement sets forth
EPA's Interpretation of and policy concern-
Ing TSCA section 8(e). A3 an Interpretive
rule and statement of policy It Is not subject
to the comment period and delayed effec-
tive date provisions of the Administrative
Procedure Act (5 U.S.C. 553). Although
TSCA does not mandate a policy statement.
the Agency of necessity must develop the
criteria which wtll govern enforcement ac-
tivities. Trade associations and businesses
were among those who previously expressed
Interest In such a statement to guide their
compliance.
11115
Comment 28: Clarify whether these re-
Quirements apply to chemicals previously
but no lonrer manufactured. processed. or
dl8trtbuted In commerce by a penon.
Rupome: Information obtained before
1977 must be reported If the person has
been aware of It since January 1. 1977. u
prescribed by Part VIII. Concernlnr chemi-
cals which a penon has discontinued manu-
facturing. proce.ulnr. or dlstrtbutlnC since
January 1. 11177. information obtained
before the time of discontinuation 18 subject
to these requlrementa. It Is expected that
the acqul8lt1on of information after that
time will be minimal; however. should addl-
tlonal information be acquired. It may trlc-
ger the reporting described In Part VIII.
Comment 29: Cl&rIfy the meanlnr of "sub-
stantial rIak" relative to other rt.sk8 ad-
dre88ed by TSCA.
Ruponae: A substantial risk 18 defined In
Part V(a) of thla policy statement u a rIak
of conaiderable concern becauae of (a) the
serioume81 of the effect. and (b) the fact or
probability of Its occurrence. As oppoeed to
other rIBk8 &ddreued by TSCA. economic or
social beneflta of uae. or costs of restrictlnr
use. are not to be considered In detel'lJlinlnc
whether a risk 18 "substantial".
Comment 30: To what extent are "uaers"
of chemicals subject to these requirements?
Rupcnue.' The Agency considers that
many Industrial uses of chemicals actually
fall within the scope of "processinr" chemi-
cals. A manufacturer. proceasor. or distribu-
tor who obtains substantial-riak 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 'dlstrtbuted In com-
merce In small quantities solely for purposes
of research and development subject to
these requirements?
Re,ponae: In reneral. the Agency consid-
ers that much manufacturing. processing.
and dlstrtbutlon In commerce of chemicals
In small quantities solely for purposes of re-
search and development Is conduc~ for
"commercial purposes". Such purposes
would Include the sale and distribution of
such materiala. &8 well &8 their uae by the
manufacturer or proceasor In activities (for
example. product research and development
and studies assessing the feasibility and
safety of uslnC chemicals) precedinr his or a
client's commercial uae of such materials or
others on a l&r1fer 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; reportlnr of the
other effects will depend upon a potential
for significant level8 of exposure.
Comment 32: Are raw matertal.!. Interme-
diates. and Inert Ingredients produced or
used In the manufacture of a pesticide sub-
Ject to TSCA?
Re,ponae: The Administrator considers
that raw matertals. Intermediates and Inert
ingredients produced or used In the manu-
facture of a pesticide are substances or mix-
tures which can be regulated under TSCA.
In order to be considered a pesticide. a
substance must be Intended for use &8 a pes-
ticide. Raw materiala. intermediates. and
Inert ingredients produced or used In the
manufacture of a pesticide are not them-
selves rell'Ulated under FIFRA (unless they
happen to be pesticides themselves) and.
therefore. are subject to TSCA. The pestl-
fEDERAL REGIS TEl, VOL 43. NO. 52-THURSDAY, MAICH 16, 1971
395
-------
11111
ctde rerulatlonl at 40 CPR 182.4 are cona!8-
tent with thl8 view.
Comment 33: Are intermediates and cata-
lysts Intended solely for I18e In the produc-
tion of a food. food additive. dru,. coametlc.
or device subject to TSCA?
Ruponu: The Admlnlatrator considers
that "intermediates and catalyata Intended
solely for uae In the production of a food.
food additive. drur. cosmetic.. or device are
excluded from reruIation under TSCA. The
definitions of the FFDCA provide that
chemlcalsubstancea which are Intended for
uae as a component of a food. food additive.
drur. C08D1etlc. or device are encompaaaed
within the meantna of such tenDII. respec-
tively. The FDA considers intermediates
and catalyata to be such component&. There-
fore. they are subject to rerulatlon under
the FFDCA. Any such substance 18 excluded
from reruIatlon under TSCA Inaofar as It 18
actuall)' manufactured. proceued. or dI8-
trtbuted In commerce solely for use In the
Nonas
production of a food. food additive. druc.
COIIIDetic. or device.
Comment 34: Employ- should have the
option to submit reports anonymously.
Ruponu: EPA considers that any person
may report information to EPA under
TSCA. Those who are required to do 10
under section 8
-------
APPENDIX B:
STATUS REPORTS BY CAS NUMBER
CAS NUMBER:
55-18-5
CHEMICAL NAME: ETHANAMINE, N-ETHYl-N-NITROSO-
SUBMISSION #: 8EHQ-1186-0643
CAS NUMBER:
55-18-5
CHEMICAL NAME: N-NITROSODIETHYlAMINE
SUBMISSION I: 8EHQ-1186-0643
CAS NUMBER: 59-89-2 CHEMICAL NAME: MORPHOLINE, N-NITROSO-
SUBMISSION #: 8EHQ-0885-0564 S 8EHQ-1l86-0643
CAS NUMBER: 59-89-2 CHEMICAL NAME: N-NITROSOMORPHOlINE
SUBMISSION I: 8EHQ-0885-0564 S 8EHQ-1l86-0643
CAS NUMBER: 60-01-5 CHEMICAL NAME: BUTANOIC ACID, 1,2,3-PROPANETRIYl ESTER
SUBMISSION I: 8EHQ-0486-0600
w
\.D CAS NUMBER: 60-12-8 CHEMICAL NAME: BENZENEETHANOL
....,J
SUBMISSION II: 8EHQ-0186-0587
CAS NUMBER: 62-75-9 CHEMICAL NAME: METHANAMINE, N-METHYl-N-NITROSQ-
SUBMISSION !: 8EHQ-0885-0564 S 8 EHQ-1l86-0643
CAS NUMBER: 62-75-9 CHEMICAL NAME: N-NITROSODIMETHYLAMINE
SUBNISSION I: 8EHQ-0885-0564 S 8EHQ-1l86-0643
CAS NUMBER: 64-17-5 CHEMICAL NAME: ETHANOL
SUBMISSION I: 8EHQ-0786-0617
CAS NUMBER: 64-19-7 CHEMICAL NAME: ACETIC ACID
SUBMISSION #: 8EHQ-0486-0600
-------
APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 64-67-5 CHEMICAL NAME: SULFURIC ACID, DIETHYl ES TER
SUBMISSION It: 8EHQ-0585-0554 S
CAS NUMBER: 67-63-0 CHEMICAL NAME: 2-PROPANOl
SUBMISSION It: 8EHQ-0985-0566
CAS NUMBER: 68-12-2 CHEMICAL NAME: FORMAMIDE, N,N-DIMETHYl-
SUBMISSION It: 8EHQ-0486-0598
CAS NUMBER: 75-01-4 CHEMICAL NAME: ETHEl'lL CHlORO-
SUBMISSION It: 8EHQ-0986-0629
CAS NUMBER: 75-01-4 CHEMICAL NAME: VINYL CHLORIDE
SUBMISSION It: 8EHQ-0986-0629
w
\.D CAS NUMBER: 75-21-8 CHEMICAL NAME: ETHYl EN E OXI DE
ro
SUBMISSION It: 8EHQ-0786-0611 8EHQ-1086-0641
CAS NUMBER: 75-21-8 CHEMICAL NAME: OXIRANE
SUBMISSION It: 8 EHQ-0786-0611 8EHQ-1D86-0641
CAS NUMBER: 76-13-1 CHEMICAL NAME: ETHANE, 1,1,2-TRICHlORO-1,2,2-TRIFlUORO-
SUBMISSION It: 8EHQ-0986-0631 S
CAS NUMBER: 79-06-1 CHEMICAL NAME: ACRYlAMIDE
SUBMISSION It: 8EHQ-0785-0560
CAS NUMBER: 79-06-1 CHEMICAL NAME: 2-PROPENAMIDE
SUBMISSION It: 8EHQ-0785-0560
-------
APPENDIX B:
CAS NUMBER: 79-09-4
SUBMISSION I: 8EHQ-0486-0600
CAS NUMBER: 79-10-7
SUBMISSION #: 8EHQ-0386-0592
CAS NUMBER: ]9-10-7
SUBMISSION I: 8EHQ-0386-0592
CAS NUMBER: 84-74-2
SUBMISSION I: 8EHQ-0886-0620
CAS NUMBER:
88-12-0
SUBMISSION I: 8EHQ-0785-0561 S
w
\.0
\.0
CAS NUMBER:
88-12-0
SUBMISSION I: 8EHQ-0785-0561 S
CAS NUMBER: 95-69-2
SUBMISSION I: 8EHQ-0986-0634
CAS NUMBER: 97-00-7
SUBMISSION I: 8EHQ-0485-0552
CAS NUMBER: 101-77-9
SUBMISSION I: 8EHQ-1285-0577
CAS NUMBER: 106-99-0
SUBMISSION I: 8EHQ-0786-0615
STATUS REPORTS BY CAS NUMBER
CHEMICAL NAME: PROPANOIC ACID
CHEMICAL NAME: ACRYLIC ACID
CHEMICAL NAME: 2-PROPENOIC ACID
CHEMICAL NAME: 1,2-BENZENEDICARBOXYLIC ACID, DIBUTYL ESTER
CHEMICAL NAME: PYROL
CHEMICAL NAME: 2-PYRROLIDINONE, 1-ETHENYL-
CHEMICAL NAME: BENZENAMINE, 4-CHLORO-2-METHYL-
CHEMICAL NAME: BENZENE, 1-CHLORO-2,4-DINITRO-
CHEMICAL NAME: BENZENAMIHE, 4,4'-METHYLEHEBIS-
CHEMICAL NAME: 1,3-BUTADIENE
-------
APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 107-13-1 CHEMICAL NAME: ACRYlONITRILE
SUBMISSION It: 8EHQ-0486-0598
CAS NUMBER: 107-13-1 CHEMICAL NAME: 2-PROPENENITRILE
SUBMISSION I: 8EHQ-0486-0598
CAS NUMBER: 107-21-1 CHEMICAL NAME: 1, 2-ETHANEDIOL
SUBMISSION ;: 8EHQ-0485-0552
CAS NUMBER: 107-92-6 CHEMICAL NAME: BUTANOIC ACID
SUBMISSION #: 8EHQ-0486-0600
CAS NUMBER: 108-05-4 CHEMICAL NAME: ACETIC ACID ETHENYL ESTER
SUBMISSION I: 8EHQ-0185-0543 8EHQ-1086-0642
*" CAS NUMBER: 108-05-4 CHEMICAL NAME: VINYl ACETATE
0
0
SUBMISSION #: 8EHQ-0185-0543 8EHQ-1086-0642
CAS NUMBER: 108-30-5 CHEMICAL NAME: 2,5-FURANDIONE, DIHYDRO-
SUBMISSION I: 8EHQ-0885-0565 S
CAS NUMBER: 108-30-5 CHEMICAL NAME: SUCCINIC ANHYDRIDE
SUBMISSION It: 8EHQ-0885-0565 S
CAS NUMBER: 108-45-2 CHEMICAL NAME: 1,3-BENZENEDIAMINE
SUBMISSION #: 8EHQ-1285-0577
CAS NUMBER: 108-65-6 CHEMICAL NAME: 2-PROPANOL, 1-METHOXY-, ACETATE
SUBMISSION I: 8EHQ-0585-0572
-------
APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 109-52-4 CHEMICAL NAME: PENTANOIC ACID
SUBMISSION I: 8EHQ-0486-0600
CAS NUMBER: 110-69-0 CHEMICAL NAME: BUTANAl, OXIME
SUBMISSION II: 8EHQ-1185-0S73
CAS NUMBER: 110-69-0 CHEMICAL NAME: EXKIN NO. 1 ANTI-SKINNING AGENT
SUBMISSION I: 8EHQ-1185-0573
CAS NUMBER: 110-69-0 CHEMICAL NAME: EXKIN 1
SUBMISSION #: 8EHQ-1185-057 3
CAS NUMBER: 111-15-9 CHEMICAL NAME: ETHANOL, 2-ETHOXY-, ACETATE
SUBMISSION I: 8EHQ-0386-0593
,j::.
0 CAS HUMBER: 111-86-4 CHEMICAL HAME: 1-0CTANAMINE
f-'
SUBMISSION .: 8EHQ-1085-0569
CAS NUMBER: 115-07-1 CHEMICAL NAME: i-PROPENE
SUBMISSION #: 8EHQ-0985-0566
CAS NUMBER: 115-07-1 CHEMICAL NAME: PROPYlENE
SUBMISSION #: 8EHQ-0985-0566
CAS NUMBER: 123-38-6 CHEMICAL NAME: PROPANAl
SUBMISSION #: 8EHQ-0985-0566
CAS NUMBER: 123-38-6 CHEMICAL NAME: PROPIONAlDEHYDE
SUBMISSION #: 8EHQ-0985-0566
-------
APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 123-54-6 CHEMICAL NAME: 2,4-PENTAHEDIONE
SUBMISSION It: 8EHQ-0386-0595
CAS NUMBER: 123-72-8 CHEMICAL NAME: BUTANAL
SUBMISSION #: 8EHQ-0786-0617
CAS NUMBER: 128-85-8
SUBMISSION II: 8EHQ-1285-0580
CAS NUMBER: 128-85-8
SUBMISSION .: 8EHQ-1285-0580
CAS NUMBER: 128-85-8
SUBMISSION .: 8EHQ-1285-0580
.I'>
a
N
CAS NUMBER: 131-11-3
SUBMISSION .: 8EHQ-0886-0620
CAS NUMBER: 137-29-1
SUBMISSION I: 8EHQ-0786-0616
CAS NUMBER: 137-40-6
SUBMISSION II: 8EHQ-0486-0600
CAS NUMBER: 142-62-1
SUBMISSION II: 8EHQ-0486-0600
CAS NUMBER: 409-21-2
SUBMISSION II: 8EHQ-1185-0574
CHEMICAL NAME: 9,10-ANTHRACENEDIONE, 1-(METHYLAMINO)-4-[(4-METHYLPHENYL)AMI
NO]-
CHEMICAL NAME: C. I. SOLVENT BLUE 11
CHEMICAL NAME: SUDAN BLUE GA
CHEMICAL NAME: 1,2-BENZENEDICARBOXYLIC ACID, DIMETHYL ESTER
CHEMICAL NAME: COPPER, BIS(DIMETHYLCARBAMODITHIOATO-S,S')-, (SP-4-1)-
CHEMICAL NAME: PROPANOIC ACID, SODIUM SALT
CHEMICAL NAME: HEXANOIC ACID
CHEMICAL HAME: SILICON CARBIDE FIBERS
-------
APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 409-21-2
SUBMISSION #: 8EHQ-1l85-0574
CAS NUMBER: 460-40-2
SUBMISSION It: 8EHQ-1l86-0644
CAS NUMBER: 460-40-2
SUBMISSION #: 8EHQ-1186-0644
CAS NUMBER: 598-62-9
SUBMISSION It: 8EHQ-0286-0588
CAS NUMBER: 681-84-5
SUBMISSION It: 8EHQ-0785-0563
~
0 CAS NUMBER: 756-80-9
w
SUBMISSION It: 8EHQ-0385-0547
CAS NUMBER: 764-41-0
SUBMISSION It: 8EHQ-0985-0567
CAS NUMBER: 924-16-3
SUBMISSION It: 8EHQ-1l86-0643
CAS NUMBER: 924-16-3
SUBMISSION #: 8EHQ-1l86-0643
CAS NUMBER: 999-21-3
SUBMISSION It: 8EHQ-0786-0612
CHEMICAL NAME: SILICON CARBIDE, (SIC)
CHEMICAL NAME: PROPANAL, 3,3,3-TRIFLUORO-
CHEMICAL NAME: PROPIONALDEHYDE, 3,3,3-TRIFLUORO-
CHEMICAL NAME: CARBONIC ACID, MANGANESE(2+) SALT (1:1)
*
CHEMICAL NAME: SILICIC ACID, (H4SI04), TETRAMETHYL ESTER
CHEMICAL NAME: PHOSPHORODITHIOIC ACID, O,O-DIMETHYL ESTER
CHEMICAL NAME: 2-BUTENE, 1,4-DICHLORO-
CHEMICAL NAME: 1-BUTANAMINE, N-BUTYL-N-NITROSO-
CHEMICAL NAME: N-NITROSODIBUTYLAMINE
CHEMICAL NAME: 2-BUTENEDIOIC ACID (Z)-, DI-2-PROPENYL ESTER
-------
APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 1116-54-7 CHEMICAL NAME: ETHANOL, 2,2'-(NITROSOIMINO)BIS-
SUBMISSION II: 8EHQ-0185-0542 S 8EHQ-0885-0564 S
CAS NUMBER: 1116-54-7 CHEMICAL NAME: N-NITROSODIETHANOLAMINE
SUBMISSION II: 8EHQ-0185-0542 S 8EHQ-0885-0564 S
CAS NUMBER: 1271-55-2 CHEMICAL NAME: FERROCENE, ACETYL-
SUBMISSION It: 8EHQ-1285-0578
CAS NUMBER: 1306-19-0 CHEMICAL NAME: CADMIUM OXIDE (CDO)
SUBMISSION #: 8EHQ-0886-0618 S
CAS NUMBER: 1306-23-6 CHEMICAL NAME: CADMIUM SULFIDE, (CDS)
SUBMISSION It: 8EHQ-0886-0618 S
*'" CAS NUMBER: 1310-73-2 CHEMICAL NAME: SODIUM HYDROXIDE, (NA(OH»
o
*'"
SUBMISSION #: 8EHQ-0485-0552
CAS NUMBER: 1313-13-9 CHEMICAL NAME: MANGANESE OXIDE, (MN02)
SUBMISSION #: 8EHQ-0286-0588 *
CAS NUMBER: 1332-21-4 CHEMICAL NAME: ASBESTOS
SUBMISSION ". 8EHQ-0586-0601
"..
CAS NUMBER: 1569-01-3 CHEMICAL NAME: 2-PROPANOL, 1-PROPOXY-
SUBMISSION II: 8EHQ-0686-0603
CAS NUMBER: 1569-01-3 CHEMICAL NAME: PROPASOL SOLVENT P
SUBMISSION 11: 8EHQ-0686-0603
-------
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
*"
o
U1
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
APPENDIX B:
1825-62-3
SUBMISSION #: 8EHQ-0985-0568 S
2095-01-4
SUBMISSION #: 8EHQ-1286-0648
2095-02-5
SUBMISSION #: 8EHQ-1286-0648
2386-90-5
SUBMISSION #: 8EHQ-1285-0577
2386-90-5
SUBMISSION #: 8EHQ-1285-0577
2564-83-2
SUBMISSION #: 8EHQ-0786-0607 S
2628-17-3
SUBMISSION #: 8EHQ-1285-0579 S
2831-60-9
SUBMISSION #: 8EHQ-0485-0552
3091-25-6
SUBMISSION ~: 8EHQ-0786-0614 S
3542-36-7
SUBMISSION #: 8EHQ-0786-0614 S
STATUS REPORTS BY CAS NUMBER
CHEMICAL NAME: SILANE, ETHOXYTRIMETHYL-
CHEMICAL NAME: 1,3-BENZENEDIAMINE, 4,6-DIETHYL-2-METHYL-
CHEMICAL NAME: 1,3-BENZENEDIAMINE, 2,4-DIETHYL-6-METHYL-
CHEMICAL NAME: ERR 4205
CHEMICAL NAME: 6-0XABICYCLO[3.1.0]HEXANE, 2,2'-OXYBIS-
CHEMICAL NAME: 1-PIPERIDINYLOXY, 2,2,6,6-TETRAMETHYL-
CHEMICAL NAME: PHENOL, 4-ETHENYL-
CHEMICAL NAME: ETHANOL, 2-(2,4-DINITROPHENOXY)-
CHEMICAL NAME: STANNANE, TRICHLOROOCTYL-
CHEMICAL NAME: STANNANE, DICHLORODIOCTYL-
-------
APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 3734-48-3 CHEMICAL NAME: CHlORDENE
SUBMISSION If: 8EHQ-1085-0570
CAS NUM3E~: 3734-48-3
SUBMISSION #: 8EHQ-1085-0570
CAS NUMBER: 3852-09-3
SUBMISSION #: 8EHQ-0486-0599
CAS NUMBER: 4075-81-4
SUBMISSION #: 8EHQ-0486-0600
CAS NUMBER: 5538-94-3
SUBMISSION #: 8EHQ-0386-0591
.p.
0
(J) CAS NUMBER: 6320-14-5
SUBMISSION II: 8EHQ-1285-0581
CAS NUMBER: 6320-14-5
SUBMISSION It: 8EHQ-1285-0581
CAS NUMBER: 6320-14-5
SUBMISSION #: 8EHQ-1285-0581
CAS NUMBER: 7439-92-1
SUBMISSION II: 8EHQ-0285-0546
CAS NUMBER: 7439-96-5
SUBMISSION #: 8EHQ-0286-0588
CHEMICAL NAME: 4,7-METHANO-1H-INDENE, 4,5,6,7,8,8-HEXACHlORO-3A,4,7,7A-TETR
AHYDRO-
CHEMICAL NAME: PROPANOIC ACID, 3-METHOXY-, METHYL ESTER
CHEMICAL NAME: PROPANOIC ACID, CALCIUM SALT
CHEMICAL NAME: 1-0CTANAMINIUM, N,N-DIMETHYl-N-OCTYl-, CHLORIDE
CHEMICAL NAME: C. I. BASIC RED 12
CHEMICAL NAME: CAlCOZINE RED BG
CHEMICAL NAME: 3H-INDOLIUM, 2-[3-(!,3-DIHYDRO-!,3,3-TRIMETHYL-2H-INDOL-2-YL
IDENE)-!-PROPENYL]-!,3,3-TRIMETHYL-, CHLORIDE
CHEMICAL NAME: lEAD
8EHQ-0286-0588
*
8EHQ-0586-0601
CHEMICAL NAME: MANGANESE
*
-------
APPENDIX B: STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 7439-97-6 CHEMICAL NAME: MERCURY
SUBMISSION #: 8EHQ-0286-0588 * 8EHQ-0586-0601
CAS NUMBER: 7440-02-0 CHEMICAL NAME: NICKEL
SUBMISSION #: 8EHQ-0586-0601
CAS NUMBER: 7440-38-2 CHEMICAL NAME: ARSENIC
SUBMISSION II: 8EHQ-0586-0601
CAS NUMBER: 7440-43-9 CHEMICAL NAME: CADMIUM
SUBMISSION #: 8EHQ-0286-D588 )( 8EHQ-0586-0601
CAS NUMBER: 7440-50-8 CHEMICAL NAME: COPPER
SUBMISSION ;: 8EHQ-0586-0601
01:> CAS NUMBER: 7440-66-6 CHEMICAL NAME: ZINC
0
-..J
SUBMISSION #: 8EHQ-0286-0588 * 8EHQ-0586-0601
CAS NUMBER: 7446-09-5 CHEMICAL NAME: SULFUR DIOXIDE
SUBMISSION It: 8EHQ-0586-0601
CAS NUMBER: 7664-93-9 CHEMICAL NAME: SULFURIC ACID
SUBMISSION It: 8EHQ-0985-0566
CAS NUMBER: 7785-87-7
SUBMISSION It: 8EHQ-0286-0588
CAS HUMBER: 8005-72-9
SUBMISSION II: 8EHQ-1286-0645
CHEMICAL NAME: SULFURIC ACID, MANGANESE(2+) SALT (1:1)
*
CHEMICAL NAME: 7-BENZOTHIAZOLESUlFONIC ACID, 6-METHYL-2-(4-(4-(6-METHYL-7-S
ULFOBENZOTHIAZOL-2-Yl)PHEHYlAZO)PHENYL)-
-------
APPENDIX B:
CAS NUMBER: 8005-72-9
SUBMISSION II: 8EHQ-1286-0645
CAS NUMBER: 8005-72-9
SUBMISSION II: 8EHQ-1286-0645
CAS NUMBER: 9003-13-8
SUBMISSION II: 8EHQ-0985-0566
CAS NUMBER: 9003-13-8
SUBMISSION II: 8EHQ-0985-0566
CAS NUMBER: 9038-95-3
SUBMISSION ~: 8EHQ-1086-0635
*'"
0
CD CAS NUMBER: 9038-95-3
SUBMISSION I: 8EHQ-1086-0635
CAS NUMBER:
9046-10-0
SUBMISSION II: 8EHQ-0885-0565 S
CAS NUMBER:
9046-10-0
SUBMISSION II: 8EHQ-0885-0565 S
CAS NUMBER:
9080-79-9
SUBMISSION I: 8EHQ-0485-0549 S
CAS NUMBER:
9080-79-9
SUBMISSION I: 8EHQ-0485-0549 S
STATUS REPORTS BY CAS NUMBER
CHEMICAL NAME: C.I. DIRECT YELLOW 28
CHEMICAL NAME: YELLOW SHADE 18569
CHEMICAL NAME: POLY[OXYCMETHYL-1,Z-ETHANEDIYL)], .ALPHA.-BUTYL-.OMEGA.-HYDR
OXY-
CHEMICAL NAME: UCON LUBRICANT LB-Z50
CHEMICAL NAME: OXIRANE, METHYL-, POLYMER WITH OXIRANE, MONOBUTYL ETHER
CHEMICAL NAME: UCON lUBRICANT 50-HB-5100
CHEMICAL NAME: JEFFAMINE D-2000
CHEMICAL NAME: POLY[OXYCMETHYL-1,2-ETHANEDIYl)], .AlPHA.-C2-AMINOMETHYlETHY
l)-.OMEGA.-CZ-AMINOMETHYlETHOXYJ-
CHEMICAL NAME: BENZENESUlFONIC ACID, ETHENYl-, HOMOPOLYMER, SODIUM SALT
CHEMICAL NAM=: VERSA-Tl 600
-------
APPENDIX B:
STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 10024-97-2 CHEMICAL NAME: NITROGEN OXIDE (N20)
SUBMISSION I: 8EHQ-0886-0628
CAS NUMBER: 10024-97-2 CHEMICAL NAME: NITROUS OXIDE
SUBMISSION I: 8EHQ-0886-0628
CAS NUMBER: 10124-36-4 CHE:"IICAL NAME: SULFURIC ACID, CADMIUM SALT (1:1)
SUBMISSION II: 8EHQ-0886-0618 S
CAS NUMBER: 10606-42-5 CHEMICAL NAME: PROPANOIC ACID, 3-METHOXY-, ETHYL ESTER
SUBMISSION II: 8EHQ-0486-0599
CAS NUMBER: 12001-26-2 CHEMICAL NAME: MICA (DUST>, SILICEOUS MUSCOVITE
SUBMISSION It: 8EHQ-0986-0632
*"
0 CAS NUMBER: 12001-26-2 CHEMICAL NAME: SILICATE, MICA
\.0
SUBMISSION II: 8EHQ-0986-0632
CAS NUMBER:
12225-84-2
CHEMICAL NAME: C. I. REACTIVE ORANGE 12
SUBMISSION I: 8EHQ-0386-0589 S
CAS NUMBER:
15112-89-7
CHEMICAL NAME: SILANETRIAMINE, N,N,N',N',N",N"-HEXAMETHYL-
SUBMISSION II: 8EHQ-0685-0559 S
CAS NUMBER:
15571-58-1
CHEMICAL NAME: 8-0XA-3,5-DITHIA-4-STANNATETRADECANOIC ACID, 10-ETHYL-4,4-DI
OCTYL-]-OXO-, 2-ETHYLHEXYL ESTER
SUBMISSION #: 8EHQ-0386-0594 S
CAS NUMBER:
2129]-]2-3
CHEMICAL NA:"IE: I-SILA-2-AZACYCLOPENTANE, 1,I-DIETHOXY-2-TRIMETHYLSILYL-
SUBMISSION II: 8EHQ-0985-0568 S
-------
APPENDIX B:
CAS NUMBER: 22984-54-9
SUBMISSION #: 8EHQ-1l86-0647
CAS NUMBER: 22984-54-9
SUBMISSION #: 8EHQ-1l86-0647
CAS NUMBER: 23209-59-8
SUBMISSION #: 8EHQ-0386-0619
CAS NUMBER: 23676-09-7
SUBMISSION #: 8EHQ-0585-0554 S
CAS NUMBER: 25068-38-6
SUBMISSION #: 8EHQ-1285-0577
*" CAS NUMBER: 25068-38-6
i-'
0
SUBMISSION #: 8EHQ-1285-0577
CAS NUMBER: 25646-77-9
SUBMISSION #: 8EHQ-1l85-0575
CAS NUMBER: 25646-77-9
SUBMISSION #: 8EHQ-1l85-0575
CAS NUMBER: 26538-44-3
SUBMISSION #: 8EHQ-0485-0551
CAS NUMBER: 26538-44-3
SUBMISSION #: 8EHQ-0485-0551
STATUS REPORTS BY CAS NUMBER
CHEMICAL NAME: 2-BUTANONE, O,O',O"-(METHYLSILYLIDYNE)TRIOXIME
CHEMICAL NAME: SILANE, METHYlOXIMINO-
CHEMICAL NAME: METAPHOSPHORIC ACID, (HP03), CALCIUM SODIUM SALT
CHEMICAL NAME: BENZOIC ACID, 4-ETHOXY-, ETHYL ESTER
CHEMICAL NAME: ARAlDITE 6010
CHEMICAL NAME: PHENOL, 4,4'-(1-METHYlETHYlIDENE)BIS-, POLYMER WITH (CHLOROM
ETHYL) OXI RAN E
CHEMICAL NAME: ETHANOL, 2-[(4-AMINO-3-METHYLPHENYL)ETHYLAMINO]-, SULFATE (1
:1) (SALT)
CHEMICAL NAME: KODAK COLOR DEVELOPING AGENT (CD-4)
CHEMICAL NAME: IH-2-BENZOXACYCLOTETRADECIN~1-0NE, 3,4,5,6,7,8,9,10,11,12-DE
CAHYDRO-7,14,16-TRIHYDROXY-3-METHYL-, (3S-(3R*,7S*)]-
*
CHEMICAL NAME: ZERANOL
*
-------
APPENDIX B:
CAS NUMBER: 52942-64-0 CHEMICAL
SUBMISSION ;: 8EHQ-I086-0640 S '"
CAS NUMBER: 55130-39-7 CHEMICAL
SUBMISSION I: 8EHQ-I086-0640 S '"
CAS NUMBER: 55130-49-9 CHEMICAL
SUBMISSION I: 8EHQ-1086-0640 S '"
CAS NUMBER: 28182-81-2
SUBMISSION I: 8EHQ-1086-0638
CAS NUMBER: 28182-81-2
SUBMISSION II: 8EHQ-1086-0638
CAS NUMBER: 32536-52-0
SUBMISSION I: 8EHQ-0585-0555
CAS NUMBER: 34206-40-1
SUBMISSION II: 8EHQ-1186-0647
CAS NUMBER: 34206-40-1
SUBMISSION II: 8EHQ-1186-0647
01'> CAS NUMBER: 36483-60-0
f-'
f-' SUBMISSION I: 8EHQ-0585-0555
CAS NUMBER:
57116-45-7
SUBMISSION II: 8EHQ-0986-0630
STATUS REPORTS BY CAS NUMBER
CHEMICAL NAME: CORONATE EH
'"
CHEMICAL NAME: HEXANE, 1,6-DIISOCYANATO-, HOMOPOLYMER
*
CHEMICAL NAME: BENZENE, l,l'-OXYBIS-, OCTABROMO DERIV.
CHEMICAL NAME: 2-BUTANONE, O,O',O",O"'-SIlANETETRAYlTETRAOXIME
CHEMICAL NAME: SILANE, TETRAOXIMINO-
CHEMICAL NAME: BENZENE, 1,1'-OXYBIS-, HEXABROMO DERIV.
NAME: BUTANEDIOIC ACID, (ETHOXYMETHYlENE)OXO-, DIETHYl ESTER
NAME: BUTANEDIOIC ACID, (ETHOXYMETHYlENE)OXO-, DIETHYl ESTER, (E)-
NAME: BUTANEDIOIC ACID, (ETHOXYMETHYlENE)OXO-, DIETHYl ESTER, (Z)-
CHEMICAL NAME: l-AZIRIDINEPROPANOIC ACID, 2-[[3-(1-AZIRIDINYl)-1-OXOPROPOXY
JMETHYlJ-2-(HYDROXYMETHYl)-l,3-PROPANEDIYL ESTER
-------
APPENDIX B:
CAS NUMBER:
63843-89-0
SUBMISSION I: 8EHQ-0186-0585 S
CAS NUMBER:
63843-89-0
SUBMISSION I: 8EHQ-0186-0585 S
CAS NUMBER: 63936-56-1
SUBMISSION It: 8EHQ-0585-0555
CAS NUMBER: 63936-56-1
SUBMISSION I: 8EHQ-0585-0555
CAS NUMBER: 64741-62-4
~ SUBMISSION I: 8EHQ-1l85-0576
I-'
N
CAS NUMBER: 64741-62-4
SUBMISSION II: 8EHQ-1l85-0576
CAS NUMBER: 64742-80-9
SUBMISSION II: 8EHQ-0786-0610
CAS NUMBER: 64742-80-9
SUBMISSION II: 8EHQ-0786-0610
CAS NUMBER: 64742-94-5
SUBMISSION II: 8EHQ-0686-0604
CAS NUMBER: 68479-98-1
SUBMISSION II: 8EHQ-1286-0648
STATUS REPORTS BY CAS NUMBER
CHEMICAL NAME: PROPANEDIOIC ACID, [[3,5-BIS(1,1-DIMETHYLETHYL)-4-HYDROXYPHE
NYL]METHYL]BUTYL-, BIS(1,2,2,6,6-PENTAMETHYL-4-PIPERIDINYL)
ESTER
CHEMICAL, NAME: TINUVIN 144
CHEMICAL NAME: BENZENE, PENTABROMO(TETRABROMOPHENOXY)-
CHEMICAL NAME: BENZENE, 1,1'-OXYBIS-, NONABROMO DERIV.
CHEMICAL NAME: CLARIFIED OILS (PETROLEUM), CATALYTIC CRACKED
CHEMICAL NAME: OIL (PETROLEUM), CLARIFIED SLURRY
CHEMICAL NAME: DISTILLATES (PETROLEUM), HYDRODESULFURIZED MIDDLE
CHEMICAL NAME: OIL (PETROLEUM), MINERAL SEAL
CHEMICAL NAME: SOLVENT NAPHTHA (PETROLEUM), HEAVY AROM.
CHEMICAL NAME: BENZENEDIAMINE, AR,AR-DIETHYL-AR-METHYL-
-------
APPENDIX B:
CAS NUMBER: 68928-80-3
SUBMISSION I: 8EHQ-OS85-0555
CAS NUMBER: 70657-70-4
SUBMISSION II: 8EHQ-OS8S-0572
CAS NUMBER: 76714-88-0
SUBMISSION II: 8EHQ-0485-0548
CAS NUMBER: 80387-97-9
SUBMISSION II: 8EHQ-028S-0S44
CAS NUMBER: 80387-97-9
01'> SUBMISSION II: 8EHQ-0285-0544
f--'
W
CAS NUMBER: 82244-86-8
SUBMISSION II: 8EHQ-I086-0637
STATUS REPORTS BY CAS NUMBER
CHEMICAL NAME: BENZENE, l,l'-OXYBIS-, HEPTABROMO DERIV.
CHEMICAL NAME: I-PROPANOL, 2-METHOXY-, ACETATE
CHEMICAL NAME: I-PENTEN-3-0L, CE)-1-C2,4-DICHLOROPHENYL)-4,4-DIMETHYL-2-(1,
2,4-TRIAZOL-I-YL)-
CHEMICAL NAME: ACETIC ACID, [[[3,S-BISCl,1-DIMETHYLETHYL)-4-HYDROXYPHENYL]M
ETHYL]THIO]-, 2-ETHYLHEXYL ESTER
CHEMICAL NAME: IRGANOX 1192
CHEMICAL NAME: HYDROXYLAMINE, O-(3-CHLORO-Z-PROPENYL)-, HYDROCHLORIDE
-------
CAS NUMBER: CONFIDENT
SUBMISSION I: 8EHQ-0186-0586 S
CAS NUMBER: 64-19-7
SUBMISSION I: 8EHQ-0486-0600
CAS NUMBER: 108-05-4
SUBMISSION I: 8 EHQ-O 185-0543
CAS NUMBER: 80387-97-9
SUBMISSION I: 8EHQ-0285-0544
CAS NUMBER: 79-06-1
SUBMISSION I: 8EHQ-0785-0560
~
I-' CAS NUMBER: 79-10-7
~
SUBMISSION I: 8EHQ-0386-0592
CAS NUMBER:
CONFIDENT
SUBMISSION #: 8EHQ-0586-0602 S
CAS NUMBER:
NONE
SUBMISSION I: 8EHQ-0585-D556 S
CAS NUMBER:
107-13-1
SUBMISSION I: 8EHQ-0486-0598
CAS NUMBER:
CONFIDENT
SUBMISSION I: 8EHQ-1086-0636 S
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: ACETAMIDE, Z-CHLORO-N-METHYL-N-SUBSTITUTED
CHEMICAL NAME: ACETIC ACID
CHEMICAL NAME: ACETIC ACID ETHENYL ESTER
8EHQ-1086-0642
CHEMICAL NAME: ACETIC ACID, [[[3,5-BIS(1,1-DIMETHYLETHYL)-4-HYDROXYPHENYL]M
ETHYL]THIO]-, 2-ETHYLHEXYL ESTER
CHEMICAL NAME: ACRYLAMIDE
CHEMICAL NAME: ACRYLIC ACID
CHEMICAL NAME: ACRYLIC ACID DERIVATIVES
8EHQ-1186-0646 S
CHEMICAL NAME: ACRYLIC ACID, 2-METHYL-, (COMPLEX MONOMER MIXTURE)
CHEMICAL NAME: ACRYLONITRILE
CHEMICAL NAME: ALCOHOL ETHOXYLATES, CHLORIDE CAPPED
-------
CAS NUMBER: NONE
SUBMISSION I: 8EHQ-0485-0553
CAS NUMBER: 128-85-8
SUBMISSION #: 8EHQ-1285-0580
CAS NUMBER: 25068-38-6
SUBMISSION It: 8EHQ-1285-0577
CAS HUMBER: 7440-38-2
SUBMISSION It: 8EHQ-0586-0601
CAS NU:':BER: 1332-21-4
SUBMISSION It: 8EHQ-0586-0601
~
f-'
(Jl
CAS NUMBER:
NONE
SUBMISSION #: 8EHQ-0885-0564 S
CAS NUMBER:
57116-45-7
SUBMISSION #: 8EHQ-0986-0630
CAS NUMBER:
6320-14-5
SUBMISSION I: 8EHQ-1285-0581
CAS NUMBER:
CONFIDENT
SUBMISSION II: 8EHQ-0886-0621 S
CAS NUMBER:
95-69-2
SUBMISSION II: 8EHQ-0986-0634
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: AlUMINOSIlICATE FIBERS
CHEMICAL NAME: 9,10-ANTHRACENEDIONE, l-CMETHYlAMINO)-4-[C4-METHYlPHENYl)AMI
NO]-
CHEMICAL NAME: ARALDITE 6010
CHEMICAL NAME: ARSENIC
CHEMICAL NAME: ASBESTOS
CHEMICAL NAME: AUTOMOTIVE COOLANTS
CHEMICAL NAME: 1-AZIRIDINEPROPANOIC ACID, 2-[[3-C1-AZIRIDINYL)-1-0XOPROPOXY
]METHYL]-2-CHYDROXYMETHYL)-1,3-PROPANEDIYL ESTER
CHEMICAL NAME: C. I. BASIC RED 12
CHEMICAL NAME: BENZENAMINE, ALKYLATED
CHEMICAL NAME: BENZEHAMINE, 4-CHLORO-2-METHYL-
-------
CAS NUMBER: 101-77-9
SUBMISSION II: 8EHQ-1285-0577
CAS NUMBER: 108-45-2
SUBMISSION II: 8EHQ-1285-0577
CAS NUMBER: 68479-98-1
SUBMISSION I: 8EHQ-1286-0648
CAS NUMBER: 2095-02-5
SUBMISSION II: 8EHQ-1286-0648
CAS NUMBER: 2095-01-4
SUBMISSION II: 8EHQ-1286-0648
.!:>
I--'
01 CAS NUMBER: 84-74-2
SUBMISSION II: 8EHQ-0886-0620
CAS NUMBER: 131-11-3
SUBMISSION II: 8EHQ-0886-0620
CAS NUMBER: 60-12-8
SUBMISSION It: 8EHQ-0186-0587
CAS NUMBER: 63936-56-1
SUBMISSION It: 8EHQ-0585-0555
CAS NUMBER: 9080-79-9
SUBMISSION II: 8EHQ-0485-0549 S
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: BENZENAMINE, 4,4'-METHYlENEBIS-
CHEMICAL NAME: 1,3-BENZENEDIAMINE
CHEMICAL NAME: BENZENEDIAMINE, AR,AR-DIETHYl-AR-METHYl-
CHEMICAL NAME: 1,3-BENZENEDIAMINE, 2,4-DIETHYl-6-METHYl-
CHEMICAL NAME: 1,3-BENZENEDIAMINE, 4,6-DIETHYl-2-METHYl-
CHEMICAL NAME: 1,2-BENZENEDICARBOXYlIC ACID, DIBUTYl ESTER
CHEMICAL NAME: 1,2-BENZENEDICARBOXYlIC ACID, DIMETHYL ESTER
CHEMICAL NAME: BENZENEETHANOl
CHEMICAL NAME: BENZENE, PENTABROMOCTETRABROMOPHENOXY)-
CHEMICAL NAME: BENZENESUlFONIC ACID, ETHENYl-, HOMOPOLYMER, SODIUM SALT
-------
CAS NUMBER: 97-00-7
SUBMISSION #: 8EHQ-0485-0552
CAS NUMBER: NONE
SUBMISSION #: 8EHQ-0585-0555
CAS NUMBER: 68928-80-3
SUBMISSION #: 8EHQ-0585-0555
CAS NUMBER: 36483-60-0
SUBMISSION #: 8EHQ-0585-0555
CAS NUMBER: 63936-56-1
SUBMISSION II: 8EHQ-0585-0555
~ CAS NUMBER: 32536-52-0
f-'
-..J 8EHQ-0585-0555
SUBMISSION II:
CAS NUMBER: 23676-09-7
SUBMISSION II: 8EHQ-0585-0554 S
CAS NUMBER: 8005-72-9
SUBMISSION II: 8EHQ-1286-0645
CAS NUMBER: CONFIDENT
SUBMISSION #: 8EHQ-0486-0597 S
CAS NUMBER: 26538-44-3
SUBMISSION II: 8EHQ-0485-0551
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: BENZENE, l-CHLORO-2,4-DINITRO-
CHEMICAL NAME: BENZENE, 1,1'-OXYBIS-, BROMINATED DERIV.
CHEMICAL NAME: BENZENE, 1,1'-OXYBIS-, HEPTABROMO DERIV.
CHEMICAL NAME: BENZENE, l,l'-OXYBIS-, HEXABROMO DERIV.
CHEMICAL NAME: BENZENE, 1,1'-OXYBIS-, NONABROMO DERIV.
CHEMICAL NAME: BENZENE, 1,1'-OXYBIS-, OCTABROMO DERIV.
CHEMICAL NAME: BENZOIC ACID, 4-ETHOXY-, ETHYL ESTER
CHEMICAL NAME: 7-BENZOTHIAZOLESULFONIC ACID, 6-METHYL-2-(4-(4-(6-METHYL-7-S
ULFOBENZOTHIAZOL-2-YL)PHENYLAZO)PHENYL)-
CHEMICAL NAME: BENZOTRIAZOLE-2-YL SUBSTITUTED HYDROXYPHENYLPROPIOHATE ESTER
CHEMICAL NAME: 1H-2-BENZOXACYCLOTETRADECIH-1-0NE, 3,4,5,6,7,8,9,10,11,12-DE
CAHYDRO-7,14,16-TRIHYDROXY-3-METHYL-, [3S-(3R*,7S*)]-
*
-------
CAS NUMBER: 106-99-0
SUBMISSION I: 8EHQ-0786-0615
CAS NUMBER: 123-72-8
SUBMISSION I: 8EHQ-0786-0617
CAS NUMBER: 110-69-0
SUBMISSION I: 8EHQ-1185-0573
CAS NUMBER: 924-16-3
SUBMISSION I: 8EHQ-1186-0643
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: 1,3-BUTADIENE
CHEMICAL NAME: BUTANAL
CHEMICAL NAME: BUTANAL, OXIME
CHEMICAL NAME: 1-BUTANAMINE, N-BUTYL-N-NITROSO-
CAS NUMBER: 52942-64-0 CHEMICAL NAME: BUTANEDIOIC ACID, CETHOXYMETHYLENE)OXO-, DIETHYL ESTER
SUBMISSION I: 8EHQ-1086-0640 S 1(
""
I-' CAS NUMBER: 55130-39-7 CHEMICAL NAME: BUTANEDIOIC ACID, (ETHOXYMETHYLENE)OXO-, DIETHYL ESTER, CE)-
(J)
SUBMISSION I: 8EHQ-1086-0640 S *
CAS NUMBER: 55130-49-9 CHEMICAL NAME: BUTANEDIOIC ACID, (ETHOXYMETHYLENE)OXO-, DIETHYL ESTER, CZ)-
SUBMISSION I: 8EHQ-1086-0640 S 1(
CAS NUMBER:
107-92-6
SUBMISSION I: 8EHQ-0486-0600
CAS NUMBER:
60-01-5
SUBMISSION I: 8EHQ-0486-0600
CAS NUMBER:
22984-54-9
SUBMISSION I: 8EHQ-1186-0647
CHEMICAL NAME: BUTANOIC ACID
CHEMICAL NAME: BUTANOIC ACID, 1,2,3-PROPANETRIYL ESTER
CHEMICAL NAME: 2-BUTANONE, O,O',O"-CMETHYLSILYLIDYNE)TRIOXIME
-------
CAS NU:-:3ER: 34206-40-1
SUBMISSION #: 8EHQ-1186-0647
CAS NUMBER: 999-21-3
SUBMISSION II: 8EHQ-0786-0612
CAS NUMBER: 764-41-0
SUBMISSION #: 8EHQ-0985-0567
CAS NUMBER: 7440-43-9
SUBMISSION #: 8EHQ-0286-0588
CAS NUMBER:
1306-19-0
SUBMISSION II: 8EHQ-0886-0618 S
~
I--'
\.0
CAS NUMBER:
1306-23-6
SUBMISSION #: 8EHQ-0886-0618 S
CAS NUMBER:
6320-14-5
SUBMISSION #: 8EHQ-1285-0581
CAS NUMBER:
NONE
SUBMISSION I: 8EHQ-1185-0576
CAS NUMBER:
598-62-9
SUBMISSION #: 8EHQ-0286-0588
CAS NUMBER:
CONFIDENT
SUBMISSION #: 8EHQ-0486-0596 S
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: 2-BUTANONE, O,O',O",O"'-SILANETETRAYLTETRAOXIME
CHEMICAL NAME: 2-BUTENEDIOIC ACID (Z)-, DI-2-PROPENYL ESTER
CHEMICAL NAME: 2-BUTENE, 1,4-DICHLORO-
CHEMICAL NAME: CADMIUM
*
8EHQ-0586-0601
CHEMICAL NAME: CADMIUM OXIDE (CDO)
CHEMICAL NAME: CADMIUM SULFIDE, (CDS)
CHEMICAL NAME: CALCOZINE RED BG
CHEMICAL NAME: CARBAZOLES
CHEMICAL NAME: CARBONIC ACID, MANGANESE(2+) SALT (1:1)
*
CHEMICAL NAME: CARBOXANILIDE, HALOGENATED ALIPHATIC
-------
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME
CAS NUMBER:
CONFIDENT
CHEMICAL NAME: CGA-143686
SUBMISSION I: 8EHQ-0685-0583 S
CAS NUMBER:
CONFIDENT
CHEMICAL NAME: CGA-149071
SUBMISSION #: 8EHQ-0285-0545 S
CAS NUMBER: UNKNOWN CHEMICAL NAME: CGA-18809
SUBMISSION #: 8EHQ-0786-0613
CAS NUMBER: 3734-48-3 CHEMICAL NAME: CHlORDENE
SUBMISSION .: 8EHQ-1085-0570
CAS NUMBER: CONFIDENT CHEMICAL NAME: CHLORINATED ACID
SUB:-IISSION .: 8EHQ-1086-0639 S
~
[\.)
a
CAS NUMBER: CONFIDENT CHEMICAL NAME: CHlOROBENZENE, SUBSTITUTED
SUBMISSION #: 8EHQ-0986-0625 S
CAS NUMBER: NONE CHEMICAL NAME: CIBACRON BLACK GR-D
SUBMISSION .: 8EHQ-0386-0589 S
CAS NUMBER: NONE CHEMICAL NAME: CIBACRON BLACK GR lQ 40
SUBMISSION #: 8EHQ-0386-0589 S
CAS NUMBER: NONE CHEMICAL NAME: CIBACRON GOLDEN YEllOW 2R
SUBMISSION #: 8EHQ-0386-0589 S
CAS NUMBER: NONE CHEMICAL NAME: CIBACRON GOLDEN YEllOW 2R-A
SUBMISSION #: 8EHQ-0386-0589 S
-------
CAS NUMBER:
NONE
SUBMISSION It: 8EHQ-0386-0589 S
CAS NUMBER:
64741-62-4
SUBMISSION #: 8EHQ-1185-0576
CAS NUMBER:
NONE
SUBMISSION I: 8EHQ-0586-0601
CAS NUMBER:
CONFIDENT
SUBMISSION I: 8EHQ-0585-0554 5
8EHQ-1186-0646 S
CAS NUMBER: 7440-50-8
SUBMISSION It: 8EHQ-0586-0601
*"
I\) CAS NUMBER: 137-29-1
~
SUBMISSION It: 8EHQ-0786-0616
CAS NUMBER: 28182-81-2
SUBMISSION It: 8EHQ-1086-0638
CAS NUMBER:
NONE
SUBMISSION It: 8EHQ-0185-0542 5
CAS NUMBER:
99422-01-2
SUBMISSION It: 8EHQ-0186-0584
CAS NUMBER:
CONFIDENT
SUBMISSION It: 8EHQ-I085-0571 S
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: CIBACRON GOLDEN YELLOW 2R LQ 25
CHEMICAL NAME: CLARIFIED OILS CPETROLEUM), CATALYTIC CRACKED
CHEMICAL NAME: COAL DUST
CHEMICAL NAME: CONFIDENTIAL
8EHQ-0386-0594 S
8EHQ-0586-0602 S
CHEMICAL NAME: COPPER
CHEMICAL NAME: COPPER, BISCDIMETHYLCARBAMODITHIOATO-S,S')-, CSP-4-1)-
CHEMICAL NAME: CORONATE EH
*
CHEMICAL NAME: CUTTING FLUID
CHEMICAL NAME: 1,3-CYCLOHEXANEDIONE, 5-[2-CETHYLTHIO)PROPYL]-2-C1-0XOPROPYL
)-
CHEMICAL NAME: DIAMINE, AROMATIC
-------
CAS NUMBER:
CONFIDENT
SUBMISSIOX :: 8EHQ-0785-0562 S
CAS NUMBER:
UNKNOWN
SUBMISSION .: 8EHQ-0786-0613
CAS NUMBER:
CONFIDENT
SUBMISSION .: 8EHQ-0986-0623 S
CAS NUMBER: 8005-72-9
SUB:-1ISSION .: 8EHQ-1286-0645
CAS NUMBER: 64742-80-9
SUBMISSION I: 6EHQ-0786-0610
01:> CAS NUMBER: NONE
rv
rv SUBMISSION I: 8EHQ-0585-0557
CAS NUMBER: NONE
SUBMISSION I: 8EHQ-1186-0644
CAS NUMBER: NONE
SUBMISSION .: 8EHQ-1186-0644
CAS NUMBER: NONE
SUBMISSION It: BEHQ-1186-0644
CAS NUMBER: NONE
SUBMISSION It: BEHQ-0586-0601
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: DICHLOROPHENYLALKOXYALKYLOXOHETEROMONOCYCLE
CHEMICAL NAME: O,O-DIMETHYL-S-(6-CHLOR-OXAZOLO(4,5.B)PYRIDIN-2(3H)-ON-3-YL-
METHYL)-THIOPHOSPHATE
CHEMICAL NAME: DIPHENYL ETHER. SUBSTITUTED
CHEMICAL NAME: C.I. DIRECT YELLOW 28
CHEMICAL NAME: DISTILLATES (PETROLEUM). HYDRODESULFURIZED MIDDLE
CHEMICAL NAME: DISTILLATES (PETROLEUM). REFINERY STREAMS
CHEMICAL NAME: DOW CORNING FS-1265 FLUID (1.000 CS)
CHEMICAL NAME: DOW CORNING FS-1265 FLUID (10.000 CS)
CHEMICAL NAME: DOW CORNING FS-1265 FLUID (300 CS)
CHEMICAL NAME: DUST. COAL
-------
CAS NUMBER: NONE
SUBMISSION It: 8EHQ-1285-0577
CAS NUMBER: NONE
SUBMISSION ;: 8EHQ-1285-0577
CAS NUMBER: 2386-90-5
SUBMISSION It: 8EHQ-1285-0577
CAS NUMBER: 55-18-5
SUBMISSION 11: 8EHQ-1186-0643
CAS NUMBER: 107-21-1
SUBMISSION 11: 8EHQ-0485-0552
Ii» CAS NUMBER: 76-13-1
I\.J
W SUBMISSION It: 8EHQ-0986-0631 S
CAS NUMBER: 64-17-5
SUBMISSION It: 8EHQ-0786-0617
CAS NUMBER: 111-15-9
SUBMISSION I: 8EHQ-0386-0593
CAS NUMBER:
1116-54-7
SUBMISSION I: 8EHQ-0185-0542 S
CAS NUMBER:
2831-60-9
SUBMISSION II: 8EHQ-0485-0552
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: EPOXY RESINS
CHEMICAL NAME: ERL-2258
CHEMICAL NAME: ERR 4205
CHEMICAL NAME: ETHANAMINE, N-ETHYL-N-NITROSO-
CHEMICAL NAME: 1,2-ETHANEDIOL
CHEMICAL NAME: ETHANE, 1,1,2-TRICHLORO-1,2,2-TRIFLUORO-
CHEMICAL NAME: ETHANOL
CHEMICAL NAME: ETHANOL, 2-ETHOXY-, ACETATE
CHEMICAL NAME: ETHANOL, 2,2'-(NITROSOIMINO)BIS-
8EHQ-0885-0564 S
CHEMICAL NAME: ETHANOL, 2-(2,4-DINITROPHENOXY)-
-------
CAS NUMBER: 25646-77-9
SUBMISSION #: 8EHQ-1185-0575
CAS NUMBER: 75-01-4
SUBMISSION #: 8EHQ-0986-0629
CAS NUMBER: CONFIDENT
SUBMISSION I: 8EHQ-0986-0633 S
CAS NUMBER: 75-21-8
SUBMISSION #: 8EHQ-0786-0611
CAS NUMBER: 110-69-0
SUBMISSION #: 8EHQ-1185-0573
~
tV
~ CAS NUMBER: 110-69-0
SUBMISSION I: 8EHQ-1l85-0573
CAS NUMBER: 1271-55-2
SUBMISSION It: 8EHQ-1285-0578
CAS NUMBER: NONE
SUBMISSION #: 8EHQ-0485-D553
CAS NUMBER: 68-12-2
SUBMISSION #: 8EHQ-0486-D598
CAS NUMBER:
108-30-5
SUBMISSION #: 8EHQ-0885-D565 S
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: ETHANOL, 2-[(4-AMINO-3-METHYLPHENYL)ETHYLAMINO]-, SULFATE (1
:1) (SALT)
CHEMICAL NAME: ETHENE, CHLORO-
CHEMICAL NAME: ETHER (CYCLIC), HALOALKYL SUBSTITUTED
CHEMICAL NAME: ETHYLENE OXIDE
8EHQ-1086-0641
CHEMICAL NAME: EXKIN NO.1 ANTI-SKINNING AGENT
CHEMICAL NAME: EXKIN 1
CHEMICAL NAME: FERROCENE, ACETYL-
CHEMICAL NAME: FIBERFRAX
CHEMICAL NAME: FORMAMIDE, N,N-DIMETHYL-
CHEMICAL NAME: 2,5-FURANDIONE, DIHYDRO-
-------
CAS NUMBER: 28182-81-2
SUBMISSION 11: 8EHQ-1086-0638
CAS NUMBER: 142-62-1
~ SUBMISSION 11: 8EHQ-0486-0600
N
V1
CAS NUMBER: 82244-86-8
SUBMISSION 11: 8EHQ-1086-0637
CAS NUMBER: 6320-14-5
SUBMISSION 11: 8EHQ-1285-0581
CAS NUMBER: 80387-97-9
SUBMISSION 11: 8EHQ-0285-0544
CAS NUMBER: 9046-10-0 CHEMICAL NAME: JEFFAMINE D-2000
SUBMISSION 11: 8EIiQ-0885-0565 S
CAS NUMBER: UNKNOWN CHEMICAL NAME: KEVLAR
SUBMISSION 11: 8EHQ-0485-0550
CAS NUMBER:
CONFIDENT
SUBMISSION 11: 8EHQ-0786-0609 S
CAS NUMBER:
CONFIDENT
SUBMISSION 11: 8EHQ-0186-0582 S
CAS NUMBER:
CONFIDENT
SUBMISSION 11: 8EHQ-0285-0545 S
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: HETEROCYCLIC DERIVATIVE
CHEMICAL NAME: HETEROMONOCYCLIC HETEROMONOCYCLE, CHLOROPHENOXY CHLOROPHEHYL
ALKYL SUBSTITUTED
CHEMICAL NAME: HETEROMONOCYCLIC HETEROMOHOCYCLE, HALOPHENOXY HALOPHEHYL SUB
STITUTED
CHEMICAL NAME: HEXANE, 1,6-DIISOCYANATO-, HOMOPOLYMER
1(
CHEMICAL NAME: HEXANOIC ACID
CHEMICAL NAME: HYDROXYLAMINE, O-(3-CHLORO-2-PROPENYL)-. HYDROCHLORIDE
CHEMICAL NAME: 3H-INDOLIUM, 2-[3-(1,3-DIHYDRO-1,3.3-TRIMETHYL-2H-INDOL-2-YL
IDENE)-1-PROPENYL]-1.3.3-TRIMETHYL-. CHLORIDE
CHEMICAL NAME: IRGANOX 1192
-------
CAS NUMBER: 25646-77-9
SUBMISSION I: 8EHQ-1185-0575
CAS NUMBER: 7439-92-1
SUBMISSION II: 8EHQ-0285-0546
CAS NUMBER: 7439-96-5
SUBMISSION II: 8EHQ-0286-0588
CAS NUMBER: 1313-13-9
SUBMISSION II: 8EHQ-0286-0588
CAS NUMBER: 7439-97-6
SUBMISSION I: 8EHQ-0286-0588
,j::.
N CAS NUMBER: NONE
0"\
SUBMISSION ". 8EHQ-0286-0588
".
CAS NUMBER: 23209-59-8
SUBMISSION II: 8EHQ-0386-0619
CAS NUMBER:
62-75-9
SUBMISSION II: 8EHQ-0885-0564 S
CAS NUMBER:
3734-48-3
SUBMISSION #: 8EHQ-1085-0570
CAS NUMBER:
12001-26-2
SUBMISSION II: 8EHQ-0986-0632
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: KODAK COLOR DEVELOPING AGENT (CD-4)
CHEMICAL NAME: lEAD
8EHQ-0286-0588
j(
8EHQ-0586-0601
CHEMIC~L NAME: MANGANESE
'I(
CHEMICAL NAME: MANGANESE OXIDE, (MN02)
'I(
CHEMICAL NAME: MERCURY
j(
8EHQ-0586-0601
CHEMICAL NAME: MERCURY/ZINC AlMALGAM
'I(
CHEMICAL NAME: META PHOSPHORIC ACID, (HP03), CALCIUM SODIUM SALT
CHEMICAL NAME: METHANAMINE, N-METHYL-N-NITROSO-
8EHQ-1186-0643
CHEMICAL NAME: 4,7-METHANO-1H-INDENE, 4,5,6,7,8,8-HEXACHLORO-3A,4,7,7A-TETR
AHYDRO-
CHEMICAL NAME: MICA (DUST), SILICEOUS MUSCOVITE
-------
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
"'"
~
-....J
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
UNKNOWN
SUBMISSION I: 8EHQ-0986-0631 S
NONE
SUBMISSION I: 8EHQ-0985-0566
NONE
SUBMISSION #: 8EHQ-1186-0644
NONE
SUBMISSION #: 8EHQ-1186-0644
NONE
SUBMISSION #: 8EHQ-0585-0556 S
NONE
SUBMISSION #: 8EHQ-0585-0556 S
NONE
SUBMISSION #: 8EHQ-0585-0556 S
NONE
SUBMISSION #: 8EHQ-0585-0556 S
59-89-2
SUBMISSION #: 8EHQ-0885-0564 S
7440-02-0
SUBMISSION ;: 8EHQ-0586-0601
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: MINERAL SPIRITS
CHEMICAL NAME: MISC. CHEMICALS
CHEMICAL NAME: MOLVKOTE FS-3451 GREASE
CHEMICAL NAME: MOLYKOTE FS-3452 VALVE LUBRICANT
CHEMICAL NAME: MONOMER PCM-200
CHEMICAL NAME: MONOMER PCM-400
CHEMICAL NAME: MONOMER QM-867
CHEMICAL NAME: MONOMER QM-928
CHEMICAL NAME: MORPHOLINE, N-NITROSO-
8EHQ-1186-0643
CHEMICAL NAME: NICKEL
-------
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME
CAS NUMBER:
CONFIDENT
CHEMICAL NAME: NITROBENZENE, SUBSTITUTED
SUBMISSION I: 8EHQ-0986-0624 S
CAS NUMBER: 10024-97-2 CHEMICAL NAME: NITROGEN OXIDE (N20)
SUBMISSION I: 8EHQ-0886-0628
CAS NUMBER: NONE CHEMICAL NAME: NITROPORE ATA
SUBMISSION I: 8EHQ-1186-0643
CAS NUMBER: NONE CHEMICAL NAME: NITROSAMINES
SUBMISSION I: 8EHQ-0185-0542 S 8EHQ-0885-0564 S 8EHQ-1186-0643
CAS NUMBER: 924-16-3 CHEMICAL NAME: N-NITROSODIBUTYlAMINE
SUBMISSION I: 8EHQ-1186-0643
~
N CAS NUMBER: 1116-54-7 CHEMICAL NAME: N-NITROSODIETHANOLAMINE
CD
SUBMISSION I: 8EHQ-0185-0542 S 8EHQ-0885-0564 S
CAS NUMBER: 55-18-5 CHEMICAL NAME: N-NITROSODIETHYLAMINE
SUBMISSION #: 8EHQ-1186-0643
CAS NUMBER: 62-75-9 CHEMICAL NAME: N-NITROSODIMETHYlAMINE
SUBMISSION I: 8EHQ-0885-0564 S 8EHQ-1186-0643
CAS NUMBER: 59-89-2 CHEMICAL NAME: N-NITROSOMORPHOLINE
SUBMISSION II: 8EHQ-0885-0564 S 8EHQ-1186-0643
CAS NUMBER: 10024-97-2 CHEMICAL NAME: NITROUS OXIDE
SUBMISSION #: 8EHQ-0886-0628
-------
CAS NUMBER: 111-86-4
SUBMISSION It: 8EHQ-1085-0569
CAS NUMBER: 5538-94-3
SUBMISSION It: 8EHQ-0386-0591
CAS NUMBER: 64741-62-4
SUBMISSION It: 8EHQ-1185-0576
CAS NUMBER: 64742-80-9
SUBMISSION It: 8EHQ-0786-0610
CAS NUMBER: NONE
SUBMISSION It: 8EHQ-0585-0557
~
IV CAS NUMBER: 2386-90-5
\.0
SUBMISSION It: 8EHQ-1285-0577
CAS NUMBER: 15571-58-1
SUBMISSION I: 8EHQ-0386-0594 S
CAS NUMBER:
CONFIDENT
SUBMISSION I: 8EHQ-0685-0558 S
CAS NUMBER:
75-21-8
SUBMISSION :: 8EHQ-0786-0611
CAS NUMBER:
9038-95-3
SUBMISSION It: 8EHQ-1086-0635
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: 1-0CTANAMINE
CHEMICAL NAME: 1-0CTANAMINIUM, N,N-DIMETHYL-N-OCTYL-, CHLORIDE
CHEMICAL NAME: OIL (PETROLEUM), CLARIFIED SLURRY
CHEMICAL NAME: OIL (PETROLEUM), MINERAL SEAL
CHEMICAL NAME: OIL (PETROLEUM), REFINERY STREAMS
CHEMICAL NAME: 6-0XABICYCLO[3.1.0]HEXANE, 2,2'-OXYBIS-
CHEMICAL NAME: 8-0XA-3,5-DITHIA-4-STANNATETRADECANOIC ACID, 10-ETHYL-4,4-DI
OCTYL-7-0XO-, 2-ETHYLHEXYL ESTER
CHEMICAL NAME: OXIMIDOALKANE, SUBSTITUTED
CHEMICAL NAME: OXIRANE
8EHQ-1086-0641
CHEMICAL NAME: OXIRANE, METHYL-, POLYMER WITH OXIRANE, MONOBUTYL ETHER
-------
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME
CAS HUMBER:
123-54-6
CHEMICAL NAME: 2,4-PEHTAHEDIOHE
SUBMISSION II: 8EHQ-0386-0595
CAS NUMBER:
109-52-4
CHEMICAL NAME: PENTANOIC ACID
SUBMISSION II: 8EHQ-0486-0600
CAS NUMBER:
76714-88-0
CHEMICAL NAME: 1-PENTEN-3-0L, (E)-1-(2,4-DICHLOROPHENYL)-4,4-DIMETHYL-2-(1,
2,4-TRIAZOL-1-YL)-
SUBMISSION 11: 8EHQ-0485-0548
CAS NUMBER: NONE CHEMICAL NAME: PERFLUOROALKYL COMPOUNDS
SUBMISSION It: 8EHQ-0986-0631 S
CAS NUMBER: CONFIDENT CHEMICAL NAME: PERFLUOROALKYL RESIN
SUBMISSION It: 8EHQ-0986-0631 S
"'"
w CAS NUMBER: 2628-17-3 CHEMICAL NAME: PHENOL, 4-ETHENYl-
o
SUBMISSION #: 8EHQ-1285-0579 S
CAS NUMBER:
25068-38-6
CHEMICAL NAME: PHENOL, 4,4'-(1-METHYLETHYLIDENE)BIS-, POLYMER WITH (CHLOROM
ETHYl)OXIRANE
SUBMISSION 11: 8EHQ-1285-0577
CAS NUMBER:
NONE
CHEMICAL NAME: PHOSPHATE FIBERS
SUBMISSION 11: 8EHQ-0386-0619
CAS NUMBER:
CONFIDENT
CHEMICAL NAME: PHOSPHINE, ALKYL ARYL
SUBMISSION I: 8EHQ-0386-0590 5
CAS NUMBER:
CONFIDENT
CHEMICAL NAME: PHOSPHORIC ACID ESTER, METAL SALT
SUBMISSION It: 8EHQ-0786-0608 5
-------
CAS NUMBER: 756-80-9
SUBMISSION II: 8EHQ-0385-0547
CAS NUMBER: 2564-83-2
SUBMISSION II: 8EHQ-0786-0607 S
CAS NUMBER: NONE
SUBMISSION 11: 8EHQ-0585-0572
CAS NUMBER: 9003-13-8
SUBflISSION 11: 8EHQ-0985-0566
CAS NUMBER: 9046-10-0
~ SUBMISSION It: 8EHQ-0885-0565 S
w
i-'
CAS NUMBER: UNKNOWN
SUBMISSION II: 8EHQ-0485-0550
CAS NUMBER: UNKNOWN
SUBMISSION 11: 8EHQ-0485-0550
CAS NUMBER: 123-38-6
SUBMISSION II: 8EHQ-0985-0566
CAS NUMBER: 460-40-2
SUBMISSION It: 8 EHQ-1186 -0 6 44
CAS NUMBER: 63843-89-0
SUBMISSION It: 8EHQ-0186-0585 S
APPENDIX c:
STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: PHOSPHORODITHIOIC ACID, O,O-DIMETHYl ESTER
CHEMICAL NAME: 1-PIPERIDINYLOXY, 2,2,6,6-TETRAMETHYL-
CHEMICAL NAME: PM ACETATE
CHEMICAL NAME: POlY[OXY(METHYl-l,2-ETHANEDIYl»), .AlPHA.-BUTYl-.OMEGA.-HYDR
OXY-
CHEMICAL NAME: POlY[OXY(METHVl-l,2-ETHANEDIYl»), .AlPHA.-(2-AMIHOMETHYLETHY
L)-.OMEGA.-(2-AMINOMETHVlETHOXY)-
CHEMICAL NAME: POLY P-PHENYlENE TEREPHTHAlAMIDE ARAMID FIBER
CHEMICAL NAME: PPD-T ARAMID FIBER
CHEMICAL NAME: PROP ANAL
CHEMICAL NAME: PROPANAL, 3,3,3-TRIFLUORO-
CHEMICAL NAME: PROPANEDIOIC ACID, [[3,5-BIS(1,1-DIMETHYLETHYL)-4-HYDROXYPHE
NYL)METHYL)BUTYL-, BIS(1,2,2,6,6-PENTAMETHYL-4-PIPERIDINYL)
ESTER
-------
CAS NUMBER: 79-09-4
SUBMISSION #: 8EHQ-0486-0600
CAS NUMBER: 4075-81-4
SUBMISSION #: 8EHQ-0486-0600
CAS NUMBER: 137-40-6
SUBMISSION #: 8EHQ-0486-0600
CAS NUMBER: 10606-42-5
SUBMISSION I: 8EHQ-0486-0599
CAS NUMBER: 3852-09-3
SUBMISSION #: 8EHQ-0486-0599
"'" CAS NUMBER: 67-63-0
w
IV
SUBMISSION I: 8EHQ-0985-0566
CAS NUMBER: 108-65-6
SUBMISSION I: 8EHQ-0585-0572
CAS NUMBER: 1569-01-3
SUBMISSION I: 8EHQ-0686-0603
CAS NUMBER: 70657-70-4
SUBMISSION I: 8EHQ-0585-0572
CAS NUMBER: 1569-01-3
SUBMISSION I: 8EHQ-0686-0603
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: PROPANOIC ACID
CHEMICAL NAME: PROPANOIC ACID, CALCIUM SALT
CHEMICAL NAME: PROPANOIC ACID, SODIUM SALT
CHEMICAL NAME: PROPANOIC ACID, 3-METHOXY-, ETHYL ESTER
CHEMICAL NAME: PROPANOIC ACID, 3-METHOXY-, METHYL ESTER
CHEMICAL NAME: 2-PROPANOL
CHEMICAL NAME: 2-PROPANOL, 1-METHOXY-, ACETATE
CHEMICAL NAME: 2-PROPANOL, 1-PROPOXY-
CHEMICAL NAME: 1-PRO?ANOL, 2-METHOXY-, ACETATE
CHEMICAL NAME: PROPASOL SOLVENT P
-------
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
01'>
w
w
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
79-06-1
SUBMISSION .: 8EHQ-0785-0560
115-07-1
SUBMISSION :: 8EHQ-0985-0566
101-13-1
SUBMISSION #: 8EHQ-0486-0598
19-10-7
SUBMISSION #: 8EHQ-0386-0592
CONFIDENT
SUBMISSION #: 8EHQ-0586-0602 S
NONE
SUBMISSION #: 8EHQ-0585-0556 S
123-38-6
SUBMISSION #: 8EHQ-0985-0566
460-40-2
SUBMISSION I: 8EHQ-1186-0644
115-07-1
SUBMISSION #: 8EHQ-0985-0566
CONFIDENT
SUBMISSION #: 8EHQ-0986-0626 S
APPENDIX C:
~TATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: 2-PROPENAMIDE
CHEMICAL NAME: I-PROPENE
CHEMICAL NAME: 2-PROPENENITRILE
CHEMICAL NAME: 2-PROPENOIC ACID
CHEMICAL NAME: 2-PROPENOIC ACID DERIVATIVES
8EHQ-1186-0646 S
CHEMICAL NAME: 2-PROPENOIC ACID, 2-METHYL-, (COMPLEX MONOMER MIXTURE)
CHEMICAL NAME: PROPIONALDEHYDE
CHEMICAL NAME: PROPIONALDEHYDE, 3,3,3-TRIFLUORO-
CHEMICAL NAME: PROPYLENE
CHEMICAL NAME: PYRIDINE, HALOGENATED
-------
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
..,..
!..oJ
..,..
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
88-12-0
SUBMISSION #: 8EHQ-0785-0561 S
88-12-0
SUBMISSION #: 8EHQ-0785-0561 S
CONFIDENT
SUBMISSION #: 8EHQ-1086-0636 S
NONE
SUBMISSION #: 8EHQ-0485-0551
UNKNOWN
SUBMISSION #: 8EHQ-0986-0627
CONFIDENT
SUBMISSION #: 8EHQ-0386-0589 S
12225-84-2
SUBMISSION #: 8EHQ-0386-0589 S
NONE
SUBMISSION #: 8EHQ-0485-0553
NONE
SUBMISSION #: 8EHQ-0585-0555
1825-62-3
SUBMISSION #: 8EHQ-0985-0568 S
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: PYROL
CHEMICAL NAME: 2-PYRROLIDINONE, l-ETHENYL-
CHEMICAL NAME: QUATERNARY AMMONIUM CHLORIDE
CHEMICAL NAME: RALGRO
*
CHEMICAL NAME: REACTION PRODUCT OF BETA-[3-(2H-BENZOTRIAZOL-2-YL)-4-HYDROXY
-5-TERT-BUTYLPHENYLJPROPIONIC ACID, METHYL ESTER AND POLYETH
YLENE GLYCOL 300
CHEMICAL NAME: C. I. REACTIVE ORANGE 12
CHEMICAL NAME: C. I. REACTIVE ORANGE 12
CHEMICAL NAME: REFRACTORY CERAMIC FIBERS
CHEMICAL NAME: SAYTEX 111
CHEMICAL NAME: SILANE, ETHOXYTRIMETHYL-
-------
CAS NUMBER:
22984-54-9
SUBMISSION #: 8EHQ-1186-0647
CAS NUMBER:
CONFIDENT
SUBMISSION I: 8EHQ-0686-0605 S
CAS NUMBER: NONE
SUBMISSION II: 8EHQ-0686-0605 S
CAS NUMBER: 34206-40-1
SUBMISSION II: 8EHQ-1186-0647
CAS NUMBER: 15112-89-7
SUBMISSION II: 8EHQ-0685-0559 S
"" CAS NUMBER: NONE
w
Ln SUBMISSION II: 8EHQ-1186-0644
CAS NUMBER: UNKNOWN
SUBMISSION II: 8EHQ-1186-0643
CAS NUMBER: UNKNOWN
SUBMISSION II: 8EHQ-1186-0643
CAS NUMBER: 21297-72-3
SUBMISSION II: 8EHQ-0985-0568 S
CAS NUMBER:
UNKNOWN
SUBMISSION II: 8EHQ-0985-0568 S
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: SILANE, METHYLOXIMINO-
CHEMICAL NAME: SILANE (ORGANa) OLIGOMER
CHEMICAL NAME: SILANE (ORGANO) OLIGOMERS, MIXTURE OF COMPLEX
CHEMICAL NAME: SILANE, TETRAOXIMINO-
CHEMICAL NAME: SILANETRIAMINE, N,N,N',H',H",H"-HEXAMETHYL-
CHEMICAL NAME: SILASTIC LS-2860 FLUOROSILICONE RUBBER
CHEMICAL NAME: SILASTIC Q4-4682 SILICONE RUBBER
CHEMICAL NAME: SILASTIC Q4-4683 SILICONE RUBBER
CHEMICAL NAME: 1-SILA-2-AZACYCLOPENTANE, 1,1-DIETHOXY-2-TRIMETHYLSILYL-
CHEMICAL NAME: 1-SILA-2-AZACYCLOPENTAHE, 1,1-DIETHOXY-2-TRIMETHYLSILYL-, DI
MER
-------
CAS NUMBER: 12001-26-2
SUBMISSION #: 8EHQ-0986-0632
CAS NUMBER: 681-84-5
SUBMISSION #: 8EHQ-0785-0563
CAS NUMBER: 409-21-2
SUBMISSION II: 8EHQ-1185-0574
CAS NUMBER: 409-21-2
SUBMISSION II: 8EHQ-1185-0574
CAS NUMBER: 1310-73-2
SUBMISSION II: 8EHQ-0485-0552
01:>
w CAS NUMBER: 128-85-8
0"\
SUBMISSION It: 8EHQ-1285-0580
CAS NUMBER: 64742-94-5
SUBMISSION It: 8EHQ-0686-0604
CAS NUMBER:
3542-36-7
SUBMISSION II: 8EHQ-0786-0614 S
CAS NUMBER:
3091-25-6
SUBMISSION It: 8EHQ-0786-0614 S
CAS NUMBER:
108-30-5
SUBMISSION #: 8EHQ-0885-0565 S
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: SILICATE, MICA
CHEMICAL NAME: SILICIC ACID, (H4SI04), TETRAMETHYL ESTER
CHEMICAL NAME: SILICON CARBIDE FIBERS
CHEMICAL NAME: SILICON CARBIDE, (SIC)
CHEMICAL NAME: SODIUM HYDROXIDE, (NACOH»
CHEMICAL NAME: C. I. SOLVENT BLUE 11
CHEMICAL NAME: SOLVENT NAPHTHA (PETROLEUM), HEAVY AROM.
CHEMICAL NAME: STANNANE, DICHLORODIOCTYl-
CHEMICAL NAME: STANNANE, TRICHLOROOCTYL-
CHEMICAL NAME: SUCCINIC ANHYDRIDE
-------
APPENDIX C: STATUS REPORTS BY CHEMICAL NAME
CAS NUMBER: 128-85-8 CHEMICAL NAME: SUDAN BLUE GA
SUBMISSION #: 8EHQ-1285-0580
CAS NUMBER: 7446-09-5 CHEMICAL NAME: SULFUR DIOXIDE
SUBMISSION II: 8EHQ-0586-0601
CAS NUMBER: 7664-93-9 CHc:1ICAL NAME: SULFURIC ACID
SUBMISSION II: 8EHQ-0985-05S6
CAS NUMBER: 10124-36-4 CHEMICAL NAME: SULFURIC ACID, CADMIUM SALT 0:1)
SUBMISSION II: 8EHQ-0886-0618 S
CAS NUMgER: 64-67-5 CHEMICAL NAME: SULFURIC ACID, DIETHYL ESTER
SUBMISSION .: 8EHQ-0585-0554 S
~ CAS NUMBER: 7785-87-7 CHEMICAL NAME: SULFURIC ACID, MANGANESE(2+) SALT (1: 1)
w
-..J SUBMISSION #: 8EHQ-0286-0588 *
CAS NUMBER: UNKNOWN CHEMICAL NAME: TINUVIN 1130
SUBMISSION #: 8EHQ-0986-0627
CAS NUMBER: 63843-89-0 CHEMICAL NAME: TINUVIN 144
SUBMISSION II: 8EHQ-0186-0585 S
CAS NUMBER: 9003-13-8 CHEMICAL NAME: UCON LUBRICANT LB-250
SUBMISSION II: 8EHQ-0985-0566
CAS NUi"':3ER: 9038-95-3 CHEMICAL NAME: UCON LUBRICANT 50-HB-5100
SUBMISSION #: 8EHQ-1086-0635
-------
CAS NUMBER:
NONE
SUBMISSION #: 8EHQ-0886-0622 S
CAS NUMBER:
CONFIDENT
SUBMISSION ;: 8EHQ-0786-0606 S
CAS NUMBER:
9080-79-9
SUBMISSION #: 8EHQ-0485-0549 S
CAS NUMBER: 108-05-4
SUBMISSION #: 8EHQ-0185-0543
CAS NUMBER: 75-01-4
SUBMISSION #: 8EHQ-0986-0629
""
w CAS NUMBER: 8005-72-9
CD
SUBMISSION #: 8EHQ-1286-0645
CAS NUMBER: 26538-44-3
SUBMISSION #: 8EHQ-0485-0551
CAS NUMBER: 7440-66-6
SUBMISSION #: 8EHQ-0286-0588
CAS NUMBER: NONE
SUBMISSION I: 8EHQ-0286-0588
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: UNKNOWN CHEMICALCS)
CHEMICAL NAME: UREA, HETEROMONOCYCLIC CARBOMONOCYCLIC
CHEMICAL NAME: VERSA-TL 600
CHEMICAL NAME: VINYL ACETATE
8EHQ-1086-0642
CHEMICAL NAME: VINYL CHLORIDE
CHEMICAL NAME: YELLOW SHADE 18569
CHEMICAL NAME: ZERANOL
*
CHEMICAL NAME: ZINC
*
8EHQ-0586-0601
CHEMICAL NAME: ZINC/MERCURY ALMALGAM
*
-------
ACUTE TOXICITY (ANIMAL>
SUBMISSION #: 8EHQ-0485-0548
8EHQ-0585-0556 S
8EHQ-0885-0565 S
8EHQ-I085-0571 5
8EHQ-1285-0578
8EHQ-1285-0581
8EHQ-0386-0589 S
8EHQ-0486-0599
8EHQ-0786-0616
8EHQ-I086-0636 5
8EHQ-I086-0640 5 *
.t>
w ACUTE TOXICITY (HUMAN)
~
SUBMISSION II: 8EHQ-0485-0552
8EH~-0886-0622 S
All ERGENICITY (ANIMAL>
SUBMISSION 11: 8EHQ-0485-0550
8EHQ-0386-0589 S
AllERGENICITY (HUMAN)
SUBMISSION 11: 8EHQ-0485-0550
8EHQ-0786-0612
CELL TRANSFORMATION (IN VITRO)
SUBMISSION #: 8EHQ-0685-0558 S
APPENDIX
D : STATUS REPORTS BY INFORMATION TYPE
8EHQ-0485-0549 5 8EHQ-0485-0550
8EHQ-0685-0559 S 8EHQ-0785-0563
8EHQ-0985-0568 S 8EHQ-I085-0569
8EHQ-1l85-0573 8EHQ-1l85-0575
8EHQ-1285-0579 S 8EHQ-1285-0580
8EHQ-0186-0584 8EHQ-0186-0585 5
8EHQ-0486-0596 S 8EHQ-0486-0597 S
8EHQ-0786-0607 S 8EHQ-0786-0609 S
8EHQ-0886-0621 S 8EHQ-0986-0631 5
8EHQ-I086-0638 * 8EHQ-I086-0639 S
8EHQ-1186-0644 8EHQ-1186-0647
8EHQ-0985-0566
8EHQ-0986-0632
8EHQ-0186-0585 5
8EHQ-1285-0580
8EHQ-0486-0597 S
8EHQ-0186-0585 5
8EHQ-1186-0647
8EHQ-Ol86-0585 S
8EHQ-0886-0622 S
8EHQ-0386-0589 S
8EHQ-0785-0561 S
8EHQ-0786-0610
-------
CELL TRANSFORMATION (IN VITRO)
SUBMISSION I: 8EHQ-0786-0613
8EHQ-0986-0630
CHEMICAL/PHYSICAL PROPERTIES
SUBMISSION t: 8EHQ-0185-0542 S
8EHQ-0485-0549 S
8EHQ-0585-0554 S
8EHQ-0685-0559 S
8EHQ-I085-0569
8EHQ-1l85-0576
8EHQ-0186-0584
01::>
01::>
o
8EHQ-0486-0597 S
8EHQ-0786-0614 S
8EHQ-0986-0627
8EHQ-I086-0635
8EHQ-1186-0643
CHRONIC TOXICITY (ANIMAL)
SUBMISSION #: 8EHQ-0285-0545 S
8EHQ-0785-0562 S
8EHQ-0386-0592
8EHQ-0786-0606 S
8EHQ-0386-0619
8EHQ-I086-0642
APPENDIX
D : STATUS REPORTS BY INFORMATION TYPE
8EHQ-0886-0620
8EHQ-0886-0621 5
8EHQ-0285-0544 8EHQ-0485-0548
8EHQ-0485-0550 8EHQ-0485-0553
8EHQ-0585-0555 8EHQ-0585-0556 5
8EHQ-0885-0564 S 8EHQ-0985-0568 5
8EHQ-I085-0571 S 8EHQ-1l85-0574
8EHQ-1285-0577 8EHQ-1285-0579 S
8EHQ-0186-0585 S 8EHQ-0386-0589 S
8EHQ-0786-0609 5 8EHQ-0786-0610
8EHQ-0786-0616 SEHQ-0386-0619
8EHQ-0986-0632 8EHQ-0986-0634
8EHQ-I086-0636 5 8EHQ-I086-0639 5
8EHQ-1l86-0644 8EHQ-1286-0648
8EHQ-0485-0550
8EHQ-0985-0567
8EHQ-0485-0553
8EHQ-0685-0583 5
8EHQ-0486-0600
8EHQ-0786-0614 5
8EHQ-0636-0604
8EHQ-0886-0618 5
8EHQ-0986-0624 S
8EHQ-0986-0625 S
-------
CHRONIC TOXICITY (HUMAN)
SUBMISSION #: 8EHQ-0285-0546
8EHQ-0586-0601
8EHQ-0986-0634
CLASTOGENICITY (ANIMAL)
SUBMISSION #: 8EHQ-0486-0597 S
8EHQ-0986-0627
CLASTOGENICITY (IN VITRO)
SUBMISSION #: 8EHQ-0685-0558 S
8EHQ-0586-0602 S
8EHQ-0886-0621 S
>I'>
>I'>
f-'
8EHQ-1l86-0647
DNA ADDUCT (IN VITRO)
SUBMISSION #: 8EHQ-0386-0592
DNA DAMAGE/REPAIR
SUBMISSION #: 8EHQ-0785-0561 S
8EHQ-0886-0621 S
ECOTOXICITY/AQUATIC TOXICITY
SUBMISSION #: 8EHQ-0486-0597 S
EMERGENCY INCIDENT OF ENV. CONTAMINATION
SUBMISSION #: 8EHQ-0985-0566
APPENDIX
D : STATUS REPORTS BY INFORMATION TYPE
8EHQ-0585-0557
8EHQ-0786-0615
8EHQ-0486-0598
8EHQ-0986-0629
8EHQ-0586-0602 S
8EHQ-1l86-0646 S
8EHQ-0786-0613
8EHQ-1285-0580
8EHQ-0786-0608 S
8EHQ-0386-0595
8EHQ-0786-0610
8EHQ-0986-0630
8EHQ-1l86-0646 S
8EHQ-0586-0602 S
8EHQ-1l86-0646 S
8EHQ-0786-0613
8EHQ-0386-0593
8EHQ-0786-0617
-------
APPENDIX D : STATUS REPORTS BY INFORMATION TYPE
ENV. OCCURRENCE/RELEASE/FATE
SUBMISSION II: 8EHQ-0985-0566 8EHQ-0386-0593 8EHQ-0486-0597 S
8EHQ-0786-0617
EPIDEMIOLOGY/CLINICAL
SUBMISSION II: 8EHQ-0285-0546 8EHQ-0485-0551 * 8EHQ-0485-0552
8EHQ-0585-0557 8EHQ-0985-0567 8EHQ-0186-0585 S
8EHQ-0286-0588 * 8EHQ-0386-0589 S 8EHQ-0486-0598
8EHQ-0586-0601 8EHQ-0786-0611 8EHQ-0786-0612
8EHQ-0786-0615 8EHQ-0986-0629 8EHQ-0986-0632
8EHQ-0986-0634 8EHQ-I086-0641
,j:>.
,j:>.
N HUMAN EXPOSURE (ACCIDENTAL>
SUBMISSION I: 8EHQ-0985-0566 8EHQ-0786-0617
HUMAN EXPOSURE (MONITORING)
SUBMISSION II: 8EHQ-0185-0542 S 8EHQ-0285-0546 8EHQ-0385-0547
8EHQ-0485-0550 8EHQ-0485-0551 * 8EHQ-0485-0553
8EHQ-0585-0554 S 8EHQ-0985-0566 8EHQ-0286-0588 *
8EHQ-0586-0601 8EHQ-0986-0633 S 8EHQ-1286-0648
HUMAN EXPOSURE (PRODUCT CONTAMINATION)
SUBMISSION I: 8EHQ-0185-0542 S 8EHQ-0585-0554 S 8EHQ-0885-0564 5
8EHQ-1186-0643 8EHQ-1186-0644
-------
IMMUNOTOXICITY (ANIMAL)
SUBMISSION .: 8EHQ-0186-0585 S
METABOLISM/PHARMACOKINETICS (ANIMAL)
SUBMISSION .: 8EHQ-0585-0572
8 EH.Q- 0 386 - 0 5 91
METABOLISM/PHARMACOKINETICS (HUMAN)
SUBMISSION .: 8EHQ-0285-0546
MUTAGENICITY (IN VITRO)
SUBMISSION 8: 8EHQ-0685-0558 S
,j::.
,j::.
LV
8EHQ-1285-D579 S
8EHQ-0186-D585 S
8EHQ-0786-D606 S
8EHQ-D786-D613
8EHQ-0986-0627
BEHQ-1186-D647
MUTAGENICITY (IN VIVO)
SUBMISSION .: 8EHQ-0785-0560
NEUROTOXICITY (ANIMAL)
SUBMISSION .: 8EHQ-0585-0556 S
8EHQ-0386-0590 S
APPENDIX
D : STATUS REPORTS BY INFORMATION TYPE
8EHQ-(!386-0594 S
8EHQ-1185-0576
8EHQ-0486-060D
BEHQ-0186-0587
8EHQ-D386-D619
8EHQ-0485-0551
*
8EHQ-0486-0600
8EHQ-0785-0561 S
8EHQ-1285-D58D
8EHQ-1085-0571 S
8EHQ-0186-0584
8EHQ-0486-0597 S
8EHQ-0786-D608 S
8EHQ-0586-0602 S
8EHQ-0786-0610
8EHQ-0886-0620
8EHQ-1286-0645
8EHQ-0886-0621 S
8EHQ-1186-0646 S
8EHQ-1285-0577
8EHQ-D786-0613
8EHQ-ID85-0571 S
8EHQ-D486-D599
8EHQ-0186-D584
8EHQ-D886-D628
-------
NEUROTOXICITY (HUMAN)
SUBMISSION #: 8EHQ-0786-0611
ONCOGENICITY (ANIMAL)
SUBMISSION ~: 8EHQ-0485-0550
8EHQ-0785-0562 S
8EHQ-0386-0592
8EHQ-0786-0606 S
8EHQ-0386-0619
ONCOGENICITY (HUMAN)
SUBMISSION I: 8EHQ-0285-0546
>10>
>10>
>10>
8EHQ-0586-0601
8EHQ-0986-0634
PRODUCT COMPOSITION/CHEMICAL IDENTITY
SUBMISSION #: 8EHQ-0185-0542 S
8EHQ-0485-0551
8EHQ-0585-0555
8EHQ-0885-0564 S
8EHQ-0585-0572
8EHQ-0186-0582 S
8EHQ-0386-0594 S
8EHQ-0586-0602 S
8EHQ-0786-0608 S
8EHQ-0786-0614 S
APPENDIX
D : STATUS REPORTS BY INFORMATION TYPE
8EHQ-I086-0641
8EHQ-0485-0553
8EHQ-0985-0567
8EHQ-0785-0561 S
8EHQ-0685-0583 S
8EHQ-0486-0600
8EHQ-0786-0614 S
8EHQ-0686-0604
8EHQ-0886-0618 S
8EHQ-I086-0642
8EHQ-0585-0557
8EHQ-0786-0615
8EHQ-0486-0598
8EHQ-0986-0629
*
8EHQ-0285-0545 S 8EHQ-0485-0548
8EHQ-0485-0553 8EHQ-0585-0554 S
8EHQ-0585-0556 S 8EHQ-0785-0562 S
8EHQ-0985-0568 S 8EHQ-I085-0571 5
8EHQ-1185-0 576 8EHQ-1285-0577
8EHQ-0685-0583 5 8EHQ-0386-0589 5
8EHQ-0486-0596 5 8EHQ-0486-0597 5
8EHQ-0686-0605 5 8EHQ-0786-0606 S
8EHQ-0786-0609 5 8EHQ-0786-0610
8EHQ-0886-0621 5 8EHQ-0986-0623 5
-------
PRODUCT COMPOSITION/CHEMICAL IDENTITY
SUBMISSION #: 8EHQ-0986-0624 S
8EHQ-0986-0627
8EHQ-0986-0633 5
8EHQ-I086-0639 S
8EHQ-1l86-0644
PRODUCTION/USE/PROCESS
SUBMISSION #: 8EHQ-0185-0542 S
8EHQ-0285-0546
8EHQ-0485-0549 S
8EHQ-0485-0552
8EHQ-0585-0555
01'>
01'>
U1
8EHQ-0685-0558 S
8EHQ-0785-0562 S
8EHQ-0885-0565 S
8EHQ-I085-0569
8EHQ-0585-0572
8EHQ-1l85-0575
8EHQ-1285-0578
8EHQ-1285-0581
8EHQ-0186-0584
8EHQ-0286-0588
8EHQ-0386-0594 S
8EHQ-0486-0599
8EHQ-0586-0602 S
APPENDIX
D : STATUS REPORTS BY INFORMATION TYPE
8EHQ-0986-0625 S
8EHQ-0986-0631 S
8EHQ-D986-0626 5
8EHQ-D986-D632
8EHQ-I086-0636 5
8EHQ-I086-0640 5
*
8EHQ-ID86-D637
8EHQ-1l86-D643
8EHQ-1l86-0646 S
*
8EHQ-0285-0544 8EHQ-0285-0545 S
8EHQ-D385-0547 8EHQ-D485-0548
8EHQ-0485-D550 8EHQ-D485-0551 *
8EHQ-0485-0553 8EHQ-0585-0554 S
8EHQ-0585-0556 5 8EHQ-D585-D557
8EHQ-0685-0559 S 8EHQ-0785-0561 S
8EHQ-0785-0563 8EHQ-0885-0564 5
8EHQ-0985-0566 8EHQ-0985-0568 5
8EHQ-I085-0570 8EHQ-I085-0571 5
8EHQ-1l85-0573 8EHQ-1l85-0574
8EHQ-1l85-D576 8EHQ-1285-0577
8EHQ-1285-0579 S 8EHQ-1285-0580
8EHQ-0l86-0582 S 8EHQ-0685-D583 S
8EHQ-0186-0585 S 8EHQ-D186-0586 5
8EHQ-0386-0589 S 8EHQ-0386-0591
8EHQ-D486-0596 5 8EHQ-D486-0597 S
8EHQ-0486-0600 8EHQ-0586-0601
8EHQ-0686-0603 8EHQ-0786-0606 5
-------
PRODUCTION/USE/PROCESS
SUBMISSION #: 8EHQ-0786-0607 S
8EHQ-0786-0613
8EHQ-0786-0616
8EHQ-0986-0624 S
8EHQ-0986-0629
8EHQ-0986-0633 S
8EHQ-1086-0636 S
8EHQ-1086-0640 S
8EHQ-1l86-0643
8EHQ-1286-0648
.to>
.to>
())
REPRODUCTIVE TOXICITY/TERATO. (ANIMAL)
SUBMISSION #: 8EHQ-0185-0543
8EHQ-0485-0548
8EHQ-0785-0562 S
8EHQ-1285-0577
8EHQ-0986-0626 S
REPRODUCTIVE TOXICITY/TERATO. (HUMAN)
SUBMISSION #: 8EHQ-0286-0588
SUBACUTE TOXICITY (ANIMAL)
SUBMISSION #: 8EHQ-0385-0547
8EHQ-0585-0556 S
8EHQ-1085-0571 S
APPENDIX
D : STATUS REPORTS BY INFORMATION TYPE
*
8EHQ-0786-0608 S 8EHQ-0786-0609 S
8EHQ-0786-0614 S 8EHQ-0786-0615
8EHQ-0886-0622 S 8EHQ-0986-0623 S
8EHQ-0986-0625 S 8EHQ-0986-0627
8EHQ-0986-0630 8EHQ-0986-0631 S
8EHQ-0986-0634 8EHQ-1086-0635
8EHQ-1086-0637 8EHQ-1086-0639 S
8EHQ-1086-0641 8EHQ-1086-0642
8EHQ-1l86-0644 8EHQ-1286-0645
8EHQ-0285-D544
8EHQ-0585-0555
8EHQ-0385-0547
8EHQ-0785-0560
8EHQ-1085-0570
8EHQ-0186-0587
8EHQ-0585-0572
8EHQ-0986-0623 S
8EHQ-0886-0628
8EHQ-0986-0633 S
*
8EHQ-0485-0549 S
8EHQ-0785-0561 S
8EHQ-0485-0550
8EHQ-0785-0562 S
8EHQ-0186-0585 S
8EHQ-0386-0590 S
-------
SUBACUTE TOXICITY (ANIMAL)
SUBMISSION #: 8EHQ-0386-0591
8EHQ-0686-0605 S
8EHQ-0986-0633 S
SUB CHRONIC TOXICITY (ANIMAL)
SUBMISSION I: 8EHQ-0785-0561 S
8EHQ-1l85-0576
8EHQ-0386-0594 S
8EHQ-1286-0648
TSCA 8(C) ALLEGATION
.t:>
.t:>
-..J
SUBMISSION I: 8EHQ-0386-0589 S
8EHQ-0986-0632
APPENDIX
D : STATUS REPORTS BY INFORMATION TYPE
8EHQ-0486-0597 S
8EHQ-0786-0608 S
8EHQ-0686-0603
8EHQ-0986-0627
8EHQ-I086-0637
8EHQ-0785-0562 S
8EHQ-0186-0582 S
8EHQ-1l85-0574
8EHQ-0186-0586 S
8EHQ-0486-0600
8EHQ-I086-0635
8EHQ-0786-0612
8EHQ-0886-0622 5
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-0185-0542 S
CAS NUMBER: NONE
SUBMITTER: CONFIDENTIAL
CHEMICAL NAME: CUTTING FLUID
CAS NUMBER: NONE
CAS NUMBER: 1116-54-7
CHEMICAL NAME: NITROSAMINES
CHEMICAL NAME: ETHANOL, 2,2'-(NITROSOIMINO)BIS-
CAS NUMBER: 1116-54-7
CHEMICAL NAME: N-NITROSODIETHANOLAMINE
8EHQ-0185-0543
SUBMITTER: SOCIETY OF THE PLASTICS INDUSTRY, INC.
CAS NUMBER: 108-05-4
CAS NUMBER: 108-05-4
CHEMICAL NAME: ACETIC ACID ETHENYL ESTER
CHEMICAL NAME: VINYL ACETATE
8EHQ-0285-0544
SUBMITTER: CIBA-GEIGY CORPORATION
CAS NUMBER: 80387-97-9
CHEMICAL NAME: ACETIC ACID, [[[3,5-BIS(l,l-DIMETHYLETHYL)-4-HYDROXYPHENYL]M
ETHYL]THIO)-, 2-ETHYLHEXYL ESTER
CHEMICAL NAME: IRGANOX 1192
CAS NUMBER: 80387-97-9
~
~
00
8EHQ-0285-0545 S
SUBMITTER: CIBA-GEIGY CORPORATION
CAS NUMBER: CONFIDENT
CAS NUMBER: CONFIDENT
CHEMICAL NAME: CGA-149071
CHEMICAL NAME: HETEROMONOCYCLIC HETEROMONOCYCLE, HALOPHENOXY HALOPHENYL SUB
STITUTED
8EHQ-0285-05~S
SUBMITTER: INTERNATIONAL LEAD ZINC RESEARCH ORGANIZATION INC.
CAS NUMBER: 7439-92-1
CHEMICAL NAME: LEAD
8EHQ-0385-0547
SUBMITTER: MONSANTO COMPANY
CAS NUMBER: 756-80-9
CHEMICAL NAME: PHOSPHORODITHIOIC ACID, O,O-DIMETHYL ESTER
8EHQ-0485-0548
SUBMITTER: CHEVRON CHEMICAL COMPANY
CAS NUMBER: 76714-88-0
CHEMICAL NAME: 1-PENTEN-3-0L, (E)-1-(2,4-DICHLOROPHENYL)-4,4-DIMETHYL-2-(l,
2,4-TRIAZOL-1-YL)-
8EHQ-0485-0549 S
SUBMITTER: NATIONAL STARCH AND CHEMICAL CORPORATION
CAS NUMBER: 9080-79-9
CHEMICAL NAME: BENZENESULFONIC ACID, ETHENYL-, HOMOPOLYMER, SODIUM SALT
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-0485-0549 S
SUBMITTER: NATIONAL STARCH AND CHEMICAL CORPORATION
CAS NUMBER: 9080-79-9
CHEMICAL NAME: VERSA-Tl 600
8EHQ-0485-0550
SUBMITTER: E. I. DUPONT DE NEMOURS & COMPANY, INC.
CAS NUMBER: UNKNOWN
CAS NUMBER: UNKNOWN
CHEMICAL NAME: KEVlAR
CHEMICAL NAME: POLY P-PHENYlENE TEREPHTHAlAMIDE ARAMID FIBER
CAS NUMBER: UNKNOWN
CHEMICAL NAME: PPD-T ARAMID FIBER
8EHQ-0485-0551
*
SUBMITTER: INTERNATIONAL MINERALS & CHEMICAL CORPORATION
CHEMICAL NAME: RALGRO
CAS NUMBER: NONE
CAS NUMBER: 26538-44-3
CHEMICAL NAME: 1H-2-BENZOXACYClOTETRADECIN-1-0NE, 3,4,5,6,7,8,9,10,11,12-DE
CAHYDRO-7,14,16-TRIHYDROXY-3-METHYl-, [3S-(3R*,7S*)]-
CHEMICAL NAME: ZERANOl
CAS NUMBER: 26538-44-3
~ 8EHQ-0485-0552 SUBMITTER: OLIN CORPORATION
~
\.0 CAS NUMBER : 97-00-7 CHEMICAL NAME: BENZENE, 1-CHlORO-2,4-DINITRO-
CAS NUMBER : 107-21-1 CHEMICAL NAME: 1,2-ETHANEDIOL
CAS NUMBER : 1310-73-2 CHEMICAL NAME: SODIUM HYDROXIDE, (NA(OH»
CAS NUMBER : 2831-60-9 CHEMICAL NAME: ETHANOL, 2-(2,4-DINITROPHENOXY)-
8EHQ-0485-0553 SUBMITTER: SOHIO ENGINEERED MATERIALS COMPANY
CAS NUMBER : NONE CHEMICAL NAME: AlUMINOSILICATE FIBERS
CAS NUMBER : NONE CHEMICAL NAME: FIBERFRAX
CAS NUMBER : NONE CHEMICAL NAME: REFRACTORY CERAMIC FIBERS
8EHQ-0585-0554 S
SUBMITTER: CONFIDENTIAL
CAS NUMBER: CONFIDENT
CAS NUMBER: 64-67-5
CHEMICAL NAME: CONFIDENTIAL
CHEMICAL NAME: SULFURIC ACID, DIETHYL ESTER
CAS NUMBER: 23676-09-7
CHEMICAL NAME: BENZOIC ACID, 4-ETHOXY-, ETHYL ESTER
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-0585-0555
CAS NUMBER: NONE
SUBMITTER: ETHYL CORPORATION
CHEMICAL NAME: BENZENE, 1,1'-OXYBIS-, BROMINATED DERIY.
CAS NUMBER: NONE
CHEMICAL NAME: SAYTEX 111
CAS NUMBER : 32536-52-0 CHEMICAL NAME: BENZENE, 1,1'-OXYBIS-, OCTABROMO DERIY.
CAS NUMBER : 36483-60-0 CHEMICAL NAME: BENZENE, 1,1'-OXYBIS-, HEXABROMO DERIV.
CAS NUMBER : 63936-56-1 CHEMICAL NAME: BENZENE, PENTABROMO(TETRABROMOPHENOXY)-
CAS NUMBER : 63936-56-1 CHEMICAL NAME: BENZENE, 1,1'-OXYBIS-, NONABROMO DERIV.
CAS NUMBER : 68928-80-3 CHEMICAL NAME: BENZENE, 1,1'-OXYBIS-, HEPTABROMO DERIV.
8EHQ-0585-o556 S SUBMITTER: ROHM AND HAAS COMPANY
CAS NUMBER : NONE CHEMICAL NAME: ACRYLIC ACID, 2-METHYL-, (COMPLEX MONOMER MIXTURE)
CAS NUMBER : NONE CHEMICAL NAME: MONOMER PCM-2oo
.1'0 CAS NUMBER : NONE CHEMICAL NAME: MONOMER PCM-400
LT1
0
CAS NUMBER : NONE CHEMICAL NAME: MONOMER QM-867
CAS NUMBER : NONE CHEMICAL NAME: MONOMER QM-928
CAS NUMBER : NONE CHEMICAL NAME: 2-PROPENOIC ACID, 2-METHYL-, (COMPLEX MONOMER MIXTURE)
8EHQ-0585-0557 SUBMITTER: AMOCO CORPORATION
CAS NUMBER : NONE CHEMICAL NAME: DISTILLATES (PETROLEUM), REFINERY STREAMS
CAS NUMBER : NONE CHEMICAL NAME: OIL (PETROLEUM), REFINERY STREAMS
8EHQ-0685-0558 S
SUBMITTER: CONFIDENTIAL
CAS NUMBER: CONFIDENT
CHEMICAL NAME: OXIMIDOALKANE, SUBSTITUTED
8EHQ-0685-0559 S
SUBMITTER: CONFIDENTIAL
CAS NUMBER: 15112-89-7
CHEMICAL NAME: SILANETRIAMINE, N,N,N',N',N",H"-HEXAMETHYL-
8EHQ-0785-0560
SUBMITTER: NALCO CHEMICAL COMPANY
CAS NUMBER: 79-06-1
CHEMICAL NAME: ACRYLAMIDE
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-0785-0560
SUBMITTER: NALCO CHEMICAL COMPANY
CAS NUMBER: 79-06-1
CHEMICAL NAME: 2-PROPENAMIDE
8EHQ-0785-0561 S
SUBMITTER: BASF WYANDOTTE CORPORATION
CAS NUMBER: 88-12-0
CAS NUMBER: 88-12-0
CHEMICAL NAME: PYROL
CHEMICAL NAME: 2-PYRROLIDINONE, 1-ETHENYL-
8EHQ-0785-0562 S
SUBMITTER: CONFIDENTIAL
CAS NUMBER: CONFIDENT
CHEMICAL NAME: DICHLOROPHENYLALKOXYALKYLOXOHETEROMONOCYCLE
8EHQ-0785-0563
SUBMITTER: DOW CORNING CORPORATION
CAS NUMBER: 681-84-5
CHEMICAL NAME: SILICIC ACID, CH4SI04), TETRAMETHYL ESTER
8EHQ-0885-0564 S SUBMITTER: CONFIDENTIAL
~ CAS NUMBER NONE CHEMICAL NAME: AUTOMOTIVE COOLANTS
IJ1 :
f--'
CAS NUMBER : NONE CHEMICAL NAME: NITROSAMINES
CAS NUMBER : 59-89-2 CHEMICAL NAME: MORPHOLlNE, N-NITROSO-
CAS NUMBER : 59-89-2 CHEMICAL NAME: N-NITROSOMORPHOLINE
CAS NUMBER : 62-75-9 CHEMICAL NAME: METHANAMINE, N-METHYL-N-NITROSO-
CAS NUMBER : 62-75-9 CHEMICAL NAME: N-NITROSODIMETHYLAMINE
CAS NUMBER : 1116-54-7 CHEMICAL NAME: ETHANOL, 2,2'-CNITROSOIMINO)BIS-
CAS NUMBER : 1116-54-7 CHEMICAL NAME: N-NITROSODIETHANOLAMINE
8EHQ-0885-0565 5
SUBMITTER: CONFIDENTIAL
CAS NUMBER : 108-30-5 CHEMICAL NAME: 2,5-FURANDIONE, DIHYDRO-
CAS NUMBER : 108-30-5 CHEMICAL NAME: SUCCINIC ANHYDRIDE
CAS NUMBER : 9046-10-0 CHEMICAL NAME: JEFFAMINE D-2000
CAS NUMBER : 9046-10-0 CHEMICAL NAME: POLY[OXYCMETHYL-1,2-ETHANEDIYL)], .ALPHA.-C2-AMINOMETHYLETHY
L)-.OMEGA.-C2-AMINOMETHYLETHOXY)-
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-0985-0566
CAS NUMBER: NONE
SUBMITTER: UNION CARBIDE CORPORATION
CHEMICAL NAME: MISC. CHEMICALS
CAS NUMBER: 67-63-0
CHEMICAL NAME: 2-PROPANOl
CAS NUMBER : 115-07-1 CHEMICAL NAME: I-PROPENE
CAS NUMBER : 115-07-1 CHEMICAL NAME: PROPYl ENE
CAS NUMBER : 123-38-6 CHEMICAL NAME: PROP ANAL
CAS NUMBER : 123-38-6 CHEMICAL NAME: PROPIONAlDEHYDE
CAS NUMBER : 7664-93-9 CHEMICAL NAME: SULFURIC ACID
CAS NUMBER : 9003-13-8 CHEMICAL NAME: POlY[OXY(METHYl-l,2-ETHANEDIYl)], .AlPHA.-BUTYl-.OMEGA.-HYDR
OXY-
CAS NUMBER : 9003-13-8 CHEMICAL NAME: UCON lUBRICANT LB-250
8EHQ-0985-0567
SUBMITTER: E. I. DUPONT DE NEMOURS & COMPANY, INC.
*"
V1
N
CAS NUMBER: 764-41-0
CHEMICAL NAME: 2-BUTENE, 1,4-DICHlORO-
8EHQ-0985-0568 S
SUBMITTER: CONFIDENTIAL
CAS NUMBER: UNKNOWN
CHEMICAL NAME: I-SIlA-2-AZACYClOPENTAHE, 1,1-DIETHOXY-2-TRIMETHYLSILYL-, DI
MER
CHEMICAL NAME: SILANE, ETHOXYTRIMETHYl-
CAS NUMBER: 1825-62-3
CAS NUMBER: 21297-72-3
CHEMICAL NAME: I-SIlA-2-AZACYCLOPENTANE, 1,1-DIETHOXY-2-TRIMETHYLSILYL-
8EHQ-I085-0569
SUBMITTER: CELANESE CORPORATION
CAS NUMBER: 111-86-4
CHEMICAL NAME: 1-0CTANAMINE
8EHQ-I085-0570
SUBMITTER: VElSICOl CHEMICAL CORPORATION
CAS NUMBER: 3734-48-3
CAS NUMBER: 3734-48-3
CHEMICAL NAME: CHlORDENE
CHEMICAL NAME: 4,7-METHANO-IH-INDENE, 4,5,6,7,8,8-HEXACHlORO-3A,4,7,7A-TETR
AHYDRO-
8EHQ-I085-0571 S
SUBMITTER: E. I. DUPONT DE NEMOURS & COMPANY, INC.
CAS NUr.3ER : CONFIDENT
CHEMICAL NAME: DIAMINE, AROMATIC
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION HUMBER
8EHQ-I085-0571 S
SUBMITTER: E. I. DUPONT DE NEMOURS & COMPANY, INC.
8EHQ-0585-0572
CAS NUMBER: NONE
SUBMITTER: UNION CARBIDE CORPORATION
CHEMICAL NAME: PM ACETATE
CAS NUMBER: 108-65-6
CAS NUMBER: 70657-70-4
CHEMICAL NAME: 2-PROPANOL, 1-METHOXY-, ACETATE
CHEMICAL NAME: I-PROPANOL, 2-METHOXY-, ACETATE
8EHQ-1185-0573 SUBMITTER: NUODEX INC.
CAS NUMBER : 110-69-0 CHEMICAL NAME: BUTANAL, OXIME
CAS NUMBER : 110-69-0 CHEMICAL NAME: EXKIN NO. 1 ANTI-SKINNING AGENT
CAS NUMBER : 110-69-0 CHEMICAL NAME: EXKIN 1
8EHQ-1185-0574 SUBMITTER: ATLANTIC RICHFIELD COMPANY
CAS NUMBER : 409-21-2 CHEMICAL NAME: SILICON CARBIDE FIBERS
""
U1
w CAS NUMBER : 409-21-2 CHEMICAL NAME: SILICON CARBIDE, (SIC)
8EHQ-1185-0575
SUBMITTER: EASTMAN KODAK COMPANY
CAS NUMBER: 25646-77-9
CHEMICAL NAME: ETHANOL, 2-[(4-AMINO-3-METHYLPHENYL>ETHYLAMINO]-, SULFATE (1
:1) (SALT>
CHEMICAL NAME: KODAK COLOR DEVELOPING AGENT (CD-4)
CAS NUMBER: 25646-77-9
8EHQ-1185-0576
CAS NUMBER: NONE
SUBMITTER: MOBIL RESEARCH AND DEVELOPMENT CORPORATION
CHEMICAL NAME: CARBAZOLES
CAS NUMBER: 64741-62-4
CAS NUMBER: 64741-62-4
CHEMICAL HAME: CLARIFIED OILS, (PETROLEUM), CATALYTIC CRACKED
CHEMICAL NAME: OIL (PETROLEUM), CLARIFIED SLURRY
8EHQ-1285-0577 SUBMITTER: U. S. DEPARTMENT OF ENERGY
CAS NUMBER : NONE CHEMICAL NAME: EPOXY RESINS
CAS NUMBER : NONE CHEMICAL NAME: ERL-2258
CAS NUMBER : NONE CHEMICAL NAME: ZZL-0820
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-1285-0577
SUBMITTER: U. S. DEPARTMENT OF ENERGY
CAS NUMBER : 101-77-9 CHEMICAL NAME: BENZENAMINE, 4,4'-METHYLENEBIS-
CAS NUMBER: 108-45-2 CHEMICAL NAME: 1,3-BENZENEDIAMINE
CAS NUMBER: 2386-90-5 CHEMICAL NAME: ERR-4205
CAS NUMBER : 2386-90-5 CHEMICAL NAME: 6-0XABICYCLO[3.1.0]HEXANE, 2,2'-OXYBIS-
CAS NUMBER : 25068-38-6 CHEMICAL NAME: ARALDITE 6010
CAS NUMBER : 25068-38-6 CHEMICAL NAME: PHENOL, 4,4'-(1-METHYLETHYLIDENE)BIS-, POLYMER WITH (CHLOROM
ETHYL )OXIRANE
8EHQ-1285-0578
SUBMITTER: SYNTEX (U.S.A.) INC.
CAS NUMBER: 1271-55-2
CHEMICAL NAME: FERROCENE, ACETYL-
8EHQ-1285-0579 S
SUBMITTER: CONFIDENTIAL
l:>
lJ1
l:>
CAS NUMBER: 2628-17-3
CHEMICAL NAME: PHENOL, 4-ETHENYL-
8EHQ-1285-0580
SUBMITTER: IBM CORPORATION
CAS NUMBER : 128-85-8 CHEMICAL NAME: 9,10-ANTHRACENEDIONE, 1-(METHYLAMINO)-4~[(4-METHYLPHEHYL)AMI
NO]-
CAS HUMBER : 128-85-8 CHEMICAL NAME: C. I. SOLVENT BLUE 11
CAS NUMBER : 128-85-8 CHEMICAL NAME: SUDAN BLUE GA
8EHQ-1285-0581
SUBMITTER: AMERICAN CYANAMID COMPANY
CAS NUMBER: 6320-14-5
CAS NUMBER: 6320-14-5
CHEMICAL NAME: C. I. BASIC RED 12
CHEMICAL NAME: CALCOZINE RED BG
CAS NUMBER: 6320-14-5
CHEMICAL NAME: 3H-INDOLIUM, 2-[3-(1,3-DIHYDRO-1,3,3-TRIMETHYL-2H-INDOL-2-YL
IDENE)-1-PROPENYL]-1,3,3-TRIMETHYL-, CHLORIDE
8EHQ-0186-0582 S
SUBMITTER: CIBA-GEIGY CORPORATION
CAS NUMBER: CONFIDENT
CHEMICAL NAME: HETEROMONOCYCLIC HETEROMONOCYCLE, CHLOROPHENOXY CHLOROPHENYL
ALKYL SUBSTITUTED
8EHQ-0685-0583 S SUBMITTER: CIBA-GEIGY CORPORATION
CA~ NUM~tK : CUN~lUtNI CHtMICAL NAMt: CuA-l~~b~b
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-0685-0583 S
SUBMITTER: CIBA-GEIGY CORPORATION
8EHQ-0186-0584
SUBMITTER: CHEVRON CHEMICAL COMPANY
CAS NUMBER: 99422-01-2
CHEMICAL NAME: 1.3-CYCLOHEXANEDIONE. 5-[2-CETHYLTHIO)PROPYL]-2-C1-0XOPROPYL
)-
8EHQ-0186-0585 S
SUBMITTER: CIBA-GEIGY CORPORATION
CAS NUMBER: 63843-89-0
CHEMICAL NAME: PROPANEDIOIC ACID, [[3.5-BISC1,1-DIMETHYLETHYL)-4-HYDROXYPHE
NYL]METHYL]BUTYL-, BISC1.2.2.6.6-PENTAMETHYL-4-PIPERIDINYL)
ESTER
CHEMICAL NAME: TINUVIN 144
CAS NUMBER: 63843-89-0
8EHQ-0186-0586 S
SUBMITTER: CONFIDENTIAL
CAS NUMBER: CONFIDENT
CHEMICAL NAME: ACETAMIDE. 2-CHLORO-N-METHYL-N-SUBSTITUTED
~
~
~
8EHQ-0186-0587
SUBMITTER: FRAGRANCE MATERIALS ASSOCIATION CU.S.)
CAS NUMBER: 60-12-8
CHEMICAL NAME: BENZENEETHANOL
8EHQ-0286-0588
*
SUBMITTER: UNION CARBIDE CORPORATION
CHEMICAL NAME: MERCURY/ZINC ALMALGAM
CAS NUMBER: NONE
CAS NUMBER: NONE
CAS NUMBER: 598-62-9
CAS NUMBER: 1313-13-9
CHEMICAL NAME: ZINC/MERCURY ALMALGAM
CHEMICAL NAME: CARBONIC ACID, MANGANESEC2+) SALT C1:1)
CAS NUMBER: 7439-92-1
CAS NUMBER: 7439-96-5
CHEMICAL NAME: MANGANESE OXIDE. (MN02)
CHEMICAL NAME: LEAD
CAS NUM3ER : 7439-97-6
CAS NUMBER: 7440-43-9
CHEMICAL NAME: MANGANESE
CHEMICAL NAME: MERCURY
CAS NUMBER: 7440-66-6
CAS NUMBER: 7785-87-7
CHEMICAL NAME: CADMIUM
CHEMICAL NAME: ZINC
CHEMICAL NAME: SULFURIC ACID, MANGANESEC2+) SALT C1:1)
8EHQ-0386-0589 S
SUBMITTER: CIBA-GEIGY CORPORATION
~A~ NUM~~K : ~UNrlU~NI
~H~Ml~Al NAM~: ~. 1. K~A~11V~ UKANu~ l~
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-0386-0589 S SUBMITTER: CIBA-GEIGY CORPORATION
CAS NUMBER : NONE CHEMICAL NAME: CIBACRON BLACK GR-D
CAS NUMBER : NONE CHEMICAL NAME: CIBACRON BLACK GR LQ 40
CAS NUMBER : NONE CHEMICAL NAME: CIBACRON GOLDEN YElLOW 2R
CAS NUMBER : NONE CHEMICAL NAME: CIBACRON GOLDEN YELLOW 2R-A
CAS NUMBER : NONE CHEMICAL NAME: CIBACRON GOLDEN YElLOW 2R LQ 25
CAS NUMBER : 12225-84-2 CHEMICAL NAME: C. 1. REACTIVE ORANGE 12
8EHQ-0386-0590 S
SUBMITTER: CONFIDENTIAL
CAS NUMBER: CONFIDENT
CHEMICAL NAME: PHOSPHINE, ALKYL ARYL
8EHQ-0386-0591
SUBMITTER: PROCTER & GAMBLE COMPANY
CAS NUMBER: 5538-94-3
CHEMICAL NAME: 1-0CTANAMINIUM, N,N-DIMETHYL-N-OCTYL-, CHLORIDE
>Po
U1
0'1
8EHQ-0386-0592 SUBMITTER: CELANESE CORPORATION
CAS NUMBER : 79-10-7 CHEMICAL NAME: ACRYlIC ACID
CAS NUMBER: 79-10-7 CHEMICAL NAME: 2-PROPENOIC ACID
8EHQ-D386-0593 SUBMITTER: UNION CARBIDE CORPORATION
CAS NUMBER: 111-15-9
CHEMICAL NAME: ETHANOL, 2-ETHOXY-, ACETATE
8EHQ-0386-0594 S
SUBMITTER: CONFIDENTIAL
CAS NUMBER: CONFIDENT
CAS NUMBER: 15571-58-1
CHEMICAL NAME: CONFIDENTIAL
CHEMICAL NAME: 8-QXA-3,5-DITHIA-4-STANNATETRADECANOIC ACID, 1D-ETHYl-4,4-DI
OCTYL-7-0XO-, 2-ETHYLHEXYL ESTER
8EHQ-D386-0595
SUBMITTER: UNION CARBIDE CORPORATION
CAS NUMBER: 123-54-6
CHEMICAL NAME: 2,4-PENTANEDIONE
8EHQ-0486-D596 S
SUBMITTER: ELI LILLY AND COMPANY
CAS NUMBER: CONFIDENT
CHEMICAL NAME: CARBOXANILIDE, HALOGENATED ALIPHATIC
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION HUMBER
8EHQ-0486-0596 S
SUBMITTER: ELI LILLY AND COMPANY
8EHQ-0486-0597 S
SUBMITTER: CIBA-GEIGY CORPORATION
CAS NUMBER: CONFIDENT
CHEMICAL NAME: BENZOTRIAZOLE-2-YL SUBSTITUTED HYDROXYPHENYLPROPIOHATE ESTER
8EHQ-0486-0598
SUBMITTER: E. I. DUPONT DE NEMOURS & COMPANY, INC.
CAS NUMBER: 68-12-2
CAS NUMBER: 107-13-1
CHEMICAL NAME: FORMAMIDE, N,N-DIMETHYL-
CHEMICAL NAME: ACRYLONITRILE
CAS NUMBER: 107-13-1
CHEMICAL NAME: 2-PROPENENITRILE
8EHQ-0486-0599
SUBMITTER: EASTMAN KODAK COMPANY
CAS NUMBER : 3852-09-3 CHEMICAL NAME: PROPANOIC ACID, 3-METHOXY-, METHYL ESTER
CAS NUMBER : 10606-42-5 CHEMICAL NAME: PROPANOIC ACID, 3-METHOXY-, ETHYL ESTER
*'"
V1 8EHQ-0486-0600 SUBMITTER: UNION CARBIDE CORPORATION
--.J
CAS NUMBER : 60-01-5 CHEMICAL NAME: BUTANOIC ACID, 1,2,3-PROPANETRIYL ESTER
CAS NUMBER : 64-19-7 CHEMICAL HAME: ACETIC ACID
CAS NUMBER : 79-09-4 CHEMICAL NAME: PROPANOIC ACID
CAS NUMBER : 107-92-6 CHEMICAL NAME: BUTANOIC ACID
CAS NUMBER : 109-52-4 CHEMICAL NAME: PENTANOIC ACID
CAS NUMBER : 137-40-6 CHEMICAL NAME: PROPANOIC ACID, SODIUM SALT
CAS NUMBER : 142-62-1 CHEMICAL NAME: HEXANOIC ACID
CAS NUMBER : 4075-81-4 CHEMICAL NAME: PROPANOIC ACID, CALCIUM SALT
8EHQ-0586-0601
CAS NUMBER: NONE
SUBMITTER: SMELTER ENVIRONMENTAL RESEARCH ASSOCIATION
CHEMICAL NAME: COAL DUST
CAS NUMBER: NONE
CAS NUMBER: 1332-21-4
CHEMICAL NAME: DUST, COAL
CHEMICAL NAME: ASBESTOS
CAS NUMBER: 7439-92-1
CHEMICAL NAME: LEAD
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-0586-0601
SUBMITTER: SMELTER ENVIRONMENTAL RESEARCH ASSOCIATION
CAS NUMBER : 7439-97-6 CHEMICAL NAME: MERCURY
CAS NUMBER : 7440-02-0 CHEMICAL NAME: NICKEL
CAS NUMBER : 7440-38-2 CHEMICAL NAME: ARSENIC
CAS NUMBER : 7440-43-9 CHEMICAL NAME: CADMIUM
CAS NUMBER : 7440-50-8 CHEMICAL NAME: COPPER
CAS NUMBER : 7440-66-6 CHEMICAL NAME: ZINC
CAS NUMBER . 7446-09-5 CHEMICAL NAME: SULFUR DIOXIDE
8EHQ-0586-0602 S SUBMITTER: CONFIDENTIAL
CAS NUMBER : CONFIDENT CHEMI CAL NAME: ACRYLIC ACID DERIVATIVES
CAS NUMBER : CONFIDENT CHEMICAL NAME: CONFIDENTIAL
*" CAS NUMBER : CONFIDENT CHEMICAL NAME: 2-PROPENOIC ACID DERIVATIVES
U1
CD
8EHQ-0686-0603 SUBMITTER: UNION CARBIDE CORPORATION
CAS NUMBER : 1569-01-3 CHEMICAL NAME: 2-PROPANOL, 1-PROPOXY-
CAS NUMBER : 1569-01-3 CHEMICAL NAME: PROPASOL SOLVENT P
8EHQ-0686-0604
SUBMITTER: AMOCO CORPORATION
CAS NUMBER: 64742-94-5
CHEMICAL NAME: SOLVENT NAPHTHA, (PETROLEUM), HEAVY AROM.
8EHQ-0686-0605 S
SUBMITTER: CONFIDENTIAL
CAS NUMBER: CONFIDENT
CAS NUMBER: CONFIDENT
CHEMICAL NAME: SILANE (ORGANO) OLIGOMER
CHEMICAL NAME: SILANE (ORGANO) OLIGOMER
CAS NUMBER: NONE
CHEMICAL NAME: SILANE (ORGANO) OLIGOMERS, MIXTURE OF COMPLEX
8EHQ-0786-0606 S
SUBMITTER: CIBA-GEIGY CORPORATION
CAS NUMBER: CONFIDENT
CHEMICAL NAME: UREA, HETEROMONOCYCLIC CARBOMONOCYCLIC
8EHQ-0786-0607 S
SUBMITTER: CONFIDENTIAL
~A~ NU~tltK : ~~b~-~~-~
~Ht~l~AL NA~t:
1-~1~tK1V1NTLUXT, ~,~,b,b-ltIKAMtIHTL-
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-0786-0607 S
SUBMITTER: CONFIDENTIAL
8EHQ-0786-0608 S
SUBMITTER: CONFIDENTIAL
CAS NUMBER: CONFIDENT
CHEMICAL NAME: PHOSPHORIC ACID ESTER, METAL SALT
8EHQ-0786-0609 S
SUBMITTER: R. T. VANDERBILT COMPANY, INC.
CAS NUMBER: CONFIDENT
CHEMICAL NAME: HETEROCYCLIC DERIVATIVE
8EHQ-0786-0610
SUBMITTER: TOTAL PETROLEUM, INC.
CAS NUMBER: 64742-80-9
CAS NUMBER: 64742-80-9
CHEMICAL NAME: DISTILLATES, (PETROLEUM), HYDRODESULFURIZED MIDDLE
CHEMICAL NAME: OIL (PETROLEUM), MINERAL SEAL
8EHQ-0786-0611
SUBMITTER: UNION CARBIDE CORPORATION
~
~
~
CAS NUMBER: 75-21-8
CAS NUMBER: 75-21-8
CHEMICAL NAME: ETHYLENE OXIDE
CHEMICAL NAME: OXIRANE
8EHQ-0786-0612
SUBMITTER: ALCOLAC
CAS NUMBER: 999-21-3
CHEMICAL NAME: 2-BUTENEDIOIC ACID (Z)-, DI-2-PROPENYL ESTER
8EHQ-0786-0613
SUBMITTER: CIBA-GEIGY CORPORATION
CAS NUMBER: UNKNOWN
CAS NUMBER: UNKNOWN
CHEMICAL NAME: CGA-18809
CHEMICAL NAME: O,O-DIMETHYL-S-(6-CHLOR-OXAZOLO(4,5,B)PYRIDIN-2(3H)-ON-3-YL-
METHYL)-THIOPHOSPHATE
8EHQ-0786-0614 S
SUBMITTER: CONFIDENTIAL
CAS NUMBER: 3091-25-6
CAS NUr.3ER : 3542-36-7
CHEMICAL NAME: STANNANE, TRICHLOROOCTYL-
CHEMICAL NAME: STANNANE, DICHLORODIOCTYL-
8EHQ-0786-0615
SUBMITTER: TEXACO INC.
CAS NUMBER: 106-99-0
CHEMICAL NAME: 1,3-BUTADIENE
8EHQ-0786-0616
SUBMITTER: R. T. VANDERBILT COMPANY, INC.
~A~ NUMH~K : 1~/-~~-1
~H~M~~Al NAM~: ~U~~~K, Hl~lVlM~IHTlCAKHAMUUlIHlUAIU-~,~')-, l~~-~-l)-
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-0786-0616
SUBMITTER: R. T. VANDERBILT COMPANY, INC.
8EHQ-0786-0617
SUBMITTER: UNION CARBIDE CORPORATION
CAS NUMBER: 64-17-5
CAS NUMBER: 123-72-8
CHEMICAL NAME: ETHANOL
CHEMICAL NAME: BUTANAL
8EHQ-0886-0618 S
SUBMITTER: CONFIDENTIAL
CAS NUMBER : 1306-19-0 CHEMICAL NAME: CADMIUM OXIDE, (CDO)
CAS NUMBER : 1306-23-6 CHEMICAL NAME: CADMIUM SULFIDE. (CDS)
CAS NUMBER : 10124-36-4 CHEMICAL NAME: SULFURIC ACID, CADMIUM SALT (1:1)
8EHQ-0386-0619 SUBMITTER: MONSANTO COMPANY
CAS NUMBER : NONE CHEMICAL NAME: PHOSPHATE FIBERS
.J'>
()I
o
CAS NUMBER: 23209-59-8
CHEMICAL NAME: METAPHOSPHORIC ACID, (HP03), CALCIUM SODIUM SALT
8EHQ-0886-0620
SUBMITTER: CHEMICAL MANUFACTURERS ASSOCIATION
CAS NUMBER: 84-74-2
CAS NUMBER: 131-11-3
CHEMICAL NAME: 1,2-BENZENEDICARBOXYLIC ACID, DIBUTYL ESTER
CHEMICAL NAME: 1,2-BENZENEDICARBOXYLIC ACID, DIMETHYL ESTER
8EHQ-0886-0621 S SUBMITTER: CONFIDENTIAL
CAS NUMBER : CONFIDENT CHEMICAL NAME: BENZENAMINE, ALKYLATED
8EHQ-0886-0622 S SUBMITTER: CONFIDENTIAL
CAS NUMBER : NONE CHEMICAL NAME: UNKNOWN CHEMICAL(S)
8EHQ-0986-0623 S
SUBMITTER: CONFIDENTIAL
CAS NUMBER: CONFIDENT
CHEMICAL NAME: DIPHENYL ETHER, SUBSTITUTED
8EHQ-0986-0624 S
SUBMITTER: CONFIDENTIAL
CAS NUMBER: CONFIDENT
CHEMICAL NAME: NITROBENZENE, SUBSTITUTED
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-0986-0625 S SUBMITTER: CONFIDENTIAL
CAS NUMBER: CONFIDENT CHEMICAL NAME: CHLOROBENZENE, SUBSTITUTED
8EHQ-0986-0626 S SUBMITTER: CONFIDENTIAL
CAS NUMBER: CONFIDENT CHEMICAL NAME: PYRIDINE, HALOGENATED
8EHQ-0986-0627
SUBMITTER: CIBA-GEIGY CORPORATION
CAS NUMBER: UNKNOWN
CHEMICAL NAME: REACTION PRODUCT OF BETA-[3-C2H-BENZOTRIAZOL-2-YL)-4-HYDROXY
-5-TERT-BUTYLPHENYL]PROPIONIC ACID, METHYL ESTER AND POLYETH
YLENE GLYCOL 300
CHEMICAL NAME: TINUVIN 1130
CAS NUMBER: UNKNOWN
8EHQ-0886-0628
SUBMITTER: UNION CARBIDE CORPORATION
,j::.
(J\
f-'
CAS NUMBER: 10024-97-2
CAS NUMBER: 10024-97-2
CHEMICAL NAME: NITROGEN OXIDE, CN20)
CHEMICAL NAME: NITROUS OXIDE
8EHQ-0986-0629
SUBMITTER: UNION CARBIDE CORPORATION
CAS NUMBER: 75-01-4
CAS NUMBER: 75-01-4
CHEMICAL NAME: ETHENE, CHLORO-
CHEMICAL NAME: VINYL CHLORIDE
8EHQ-0986-0630
SUBMITTER: CELANESE CORPORATION
CAS NUMBER: 57116-45-7
CHEMICAL NAME: 1-AZIRIDINEPROPANOIC ACID, 2-[[3-C1-AZIRIDINYL)-1-0XOPROPOXY
]METHYL]-2-CHYDROXYMETHYL)-1,3-PROPANEDIYL ESTER
8EHQ-0986-0631 S
SUBMITTER: CONFIDENTIAL
CAS NUMBER : CONFIDENT CHEMICAL NAME: PERFLUOROALKYL RESIN
CAS NUMBER : CONFIDENT CHEMICAL NAME: PERFLUOROALKYL RESIN
CAS NUMBER : NONE CHEMICAL NAME: PERFLUOROALKYL COMPOUNDS
CAS NUMBER : UNKNOWN CHEMICAL NAME: MINERAL SPIRITS
CAS NUMBER : 76-13-1 CHEMICAL NAME: ETHANE, 1,1,2-TRICHLORO-1,2,2-TRIFLUORO-
8EHQ-0986-0632
SUBMITTER: HERCULES INCORPORATED
~A~ NUMtl~K : l~UUl-~b-~
~H~Ml~AL NAM~: Ml~A lUU~IJ, SlLl~~UUS MUS~UVll~
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-0986-0632
SUBMITTER: HERCULES INCORPORATED
CAS NUMBER: 12001-26-2
CHEMICAL NAME: SILICATE, MICA
8EHQ-0986-0633 S
SUBMITTER: E. I.. DUPONT DE NEMOURS & COMPANY, INC.
CAS NUMBER: CONFIDENT
CHEMICAL NAME: ETHER (CYCLIC), HALOALKYL SUBSTITUTED
8EHQ-0986-0634
SUBMITTER: AMERICAN HOECHST CORPORATION
CAS NUMBER: 95-69-2
CHEMICAL NAME: BENZENAMINE, 4-CHLORO-2-METHYL-
8EHQ-1086-0635
SUBMITTER: UNION CARBIDE CORPORATION
CAS NUMBER: 9038-95-3
CAS NUMBER: 9038-95-3
CHEMICAL NAME: OXIRANE, METHYL-, POLYMER WITH OXIRANE, MONOBUTYL ETHER
CHEMICAL NAME: UCON LUBRICANT 50-HB-5100
8EHQ-1086-0636 S
SUBMITTER: PPG INDUSTRIES, INC.
..,.
(1\
N
CAS NUMBER: CONFIDENT
CAS NUMBER: CONFIDENT
CHEMICAL NAME: ALCOHOL ETHOXYLATES, CHLORIDE CAPPED
CHEMICAL NAME: QUATERNARY AMMONIUM CHLORIDE
8EHQ-1086-0637
SUBMITTER: CHEVRON CHEMICAL COMPANY
CAS NUMBER: 82244-86-8
CHEMICAL NAME: HYDROXYLAMINE, O-(3-CHLORO-2-PROPENYL)-, HYDROCHLORIDE
8EHQ-1086-0638
*
SUBMITTER: AZS CORPORATION
CAS NUMBER: 28182-81-2
CAS NUMBER: 28182-81-2
CHEMICAL NAME: CORONATE EH
CHEMICAL NAME: HEXANE, 1,6-DIISOCYANATO-, HOMOPOLYMER
8EHQ-1086-0639 S
SUBMITTER: PPG INDUSTRIES, INC.
CAS NUMBER: CONFIDENT
CHEMICAL NAME: CHLORINATED ACID
8EHQ-1086-0640 S * SUBMITTER: CONFIDENTIAL
CAS NUMBER : 52942-64-0 CHEMICAL NAME: BUTANEDIOIC ACID, (ETHOXYMETHYLENE)OXO-, DIETHYL ESTER
CAS NUMBER : 55130-39-7 CHEMICAL NAME: BUTANEDIOIC ACID, (ETHOXYMETHYLENE)OXO-, DIETHYL ESTER, (E)-
CAS NUMBER: 55130-49-9 CHEMICAL NAME: BUTANEDIOIC ACID, (ETHOXYMETHYLENE)OXQ-, DIETHYL ESTER, (Z)-
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-1086-06~0 S
*
SUBMITTER: CONFIDENTIAL
8EHQ-1086-0641
SUBMITTER: UNION CARBIDE CORPORATION
CAS NUMBER: 75-21-8
CAS NUMBER: 75-21-8
CHEMICAL NAME: ETHYLENE OXIDE
CHEMICAL NAME: OXIRANE
8EHQ-1086-06~2
SUBMITTER: SOCIETY OF THE PLASTICS INDUSTRY, INC.
CAS NUMBER : 108-05-~
CAS NUMBER: 108-05-4
CHEMICAL NAME: ACETIC ACID ETHENYL ESTER
CHEMICAL NAME: VINYL ACETATE
8EHQ-1l86-0643 SUBMITTER: DOW CORNING CORPORATION
CAS NUMBER : NONE CHEMICAL NAME: NITROPORE AT A
CAS NUMBER : NONE CHEMICAL NAME: NITROSAMINES
~ CAS NUMBER : UNKNOWN CHEMICAL NAME: SILASTIC Q4-4682 SILICONE RUBBER
0'\
w CAS NUMBER: UNKNOWN CHEMICAL NAME: SILASTIC Q4-4683 SILICONE RUBBER
CAS NUMBER : 55-18-5 CHEMICAL NAME: ETHANAMINE, N-ETHYL-N-NITROSO-
CAS NUMBER : 55-18-5 CHEMICAL NAME: N-HITROSODIETHYlAMINE
CAS NUMBER : 59-89-2 CHEMICAL NAME: MORPHOLINE, N-NITROSO-
CAS NUMBER: 59-89-2 CHEMICAL NAME: N-NITROSOMORPHOLINE
CAS NUMBER : 62-75-9 CHEMICAL NAME: METHANAMIHE, N-METHYL-H-NITROSO-
CAS NUMBER : 62-75-9 CHEMICAL NAME: H-NITROSODIMETHYLAMINE
CAS NUMBER : 924-16-3 CHEMICAL NAME: I-BUTANAMINE, N-BUTYL-N-NITROSO-
CAS NUMBER : 924-16-3 CHEMICAL NAME: N-NITROSODIBUTYLAMINE
8EHQ-1l86-0644 SUBMITTER: DOW CORNING CORPORATION
CAS NUMBER : NONE CHEMICAL NAME: DOW CORNING FS-1265 FLUID (1,000 CS)
CAS NUMBER : HONE CHEMICAL NAME: DOW CORNING FS-1265 FLUID 00,000 CS)
CAS NUMBER : NONE CHEMICAL NAME: DOW CORNING FS-1265 FLUID (300 CS)
CAS NUMBER : NONE CHEMICAL NAME: MOLYKOTE FS-3451 GREASE
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER
8EHQ-1l86-0644
CAS NUMBER: NONE
SUBMITTER: DOW CORNING CORPORATION
CHEMICAL NAME: MOLYKOTE FS-3452 VALVE LUBRICANT
CAS NUMBER: NONE
CAS NUMBER: 460-40-2
CHEMICAL NAME: SILASTIC LS-2860 FLUOROSILICONE RUBBER
CAS NUMBER: 460-40-2
CHEMICAL NAME: PROPANAL, 3,3,3-TRIFLUORO-
CHEMICAL NAME: PROPIONALDEHYDE, 3,3,3-TRIFLUORO-
8EHQ-1286-0645
SUBMITTER: LEVER BROTHERS COMPANY (INCORPORATED)
CAS NUMBER : 8005-72-9 CHEMICAL NAME: 7-BENZOTHIAZOLESULFONIC ACID, 6-METHYL-2-(4-(4-(6-METHYL-7-S
ULFOBENZOTHIAZOL-2-YL)PHENYLAZO)PHENYL)-
CAS NUMBER : 8005-72-9 CHEMICAL NAME: C.!. DIRECT YEllOW 28
CAS NUMBER : 8005-72-9 CHEMICAL NAME: YELLOW SHADE 18569
8EHQ-1186-0646 S SUBMITTER: CONFIDENTIAL
CAS NUMBER : CONFIDENT CHEMICAL NAME: ACRYLIC ACID DERIVATIVES
.J::>
(j\
.J::> CAS NUMBER : CONFIDENT CHEMICAL NAME: CONFIDENTIAL
CAS NUMBER : CONFIDENT CHEMICAL NAME: 2-PROPENOIC ACID DERIVATIVES
8EHQ-1186-0647 SUBMITTER: ALLIED-SIGNAL INC.
CAS NUMBER : 22984-54-9 CHEMICAL NAME: 2-BUTANONE, O,O',O"-(METHYLSILYLIDYNE)TRIOXIME
CAS NUMBER : 22984-54-9 CHEMICAL NAME: SILANE, METHYLOXIMINO-
CAS NUMBER : 34206-40-1 CHEMICAL NAME: 2-BUTANONE, O,O',O",O"'-SILANETETRAYLTETRAOXIME
CAS NUMBER : 34206-40-1 CHEMICAL NAME: SILANE, TETRAOXIMINO-
8EHQ-1286-0648
SUBMITTER: ETHYL CORPORATION
CAS NUMBER: 2095-01-4
CAS NUMBER: 2095-02-5
CHEMICAL NAME: 1,3-BENZENEDIAMINE, 4,6-DIETHYL-2-METHYL-
CHEMICAL NAME: 1,3-BENZENEDIAMINE, 2,4-DIETHYL-6-METHYL-
CAS NUMBER: 68479-98-1
CHEMICAL NAME: BENZENEDIAMINE, AR,AR-DIETHYL-AR-METHYL-
-------
~0272' 101
REPORT DOCUMENTATION 11. REPORT NO.
PAGE EPA 560/2 87 001
.. Title and Subtitle
12.
3. Recipient's Acceuion No.
"Prel:i.minary Evaluations of Initial TSCA
Section 8(e) Substantial Risk Notices"
January 1, 1985 to December 31, 1986
7, Author(s) Off ice of Toxic Substances/OPTS
U.S. Environmental Protection Agency (SPA)
9. Performlna Oraanizatlon Name and Addre55
Office of Pesticides and Toxic Substances (TS-788)
U.S. Environmental Protection Agency (ErA)
401 "~1" Street, S.H.
Washington, D.C. 20460
5. Report Date
~.l
------- |