&EPA
United States
Environmental Protection
Agency
Office of Pesticides
and Toxic Substances
Washington, D.C. 20460
EPA-560/2-83-001
March 1983
Toxic Substances
Preliminary Evaluations
of Initial TSCA
Section 8(e)
Substantial Risk
Notices
February 1, 1980 - December 31,1982
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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), Toxic Substances Control Act (1976)
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EPA 560/2-83-001
March 1983
PRELIMINARY EVALUATIONS OF INITIAL
TSCA SECTION 8(e) SUBSTANTIAL RISK NOTICES
FEBRUARY 1, 1980 TO DECEMBER 31, 1982
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, DC 20460
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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 Agency endorsement or recommendation.
ii
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Foreward
This volume contains, in ascending submission number order,
"sta tus reports" (i. e., prel im inary eval ua t ions) 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 February 1, 1980, and December 31, 1982,
pursuant to Section 8(e), the "substantial risk" information
reporting provision of the Toxic Substances Control Act (TSCA;
90 Stat. 2029, 15 U.S.C. 2607). Status reports are prepared by
OTS for all initial TSCA Section 8(e) submissions and reflect
only the initial phases of the OTS evaluation process for such
information.
This volume is being distributed through the Industry Assistance
Office (IAO) in OTS/OPTS. Those persons wishing to obtain a copy
of this volume of Section 8(e) status reports should telephone
IAO (toll-free: 800-424-9065 or, in Washington, D.C.: 554-1404),
or write to:
Industry Assistance Office (TS-799)
u.S. Environmental Protection Agency
401 "M" Street, s.w.
Washington, D.C. 20460
EPA plans to print a limited number of copies of this volume.
After the Agency's supply is exhausted, copies can be purchased
through the National Technical Information Service (NTIS), 5285
Port Royal Road, Springfield, Virginia 22161. Copies of the two
previously published Section 8(e) status report volumes (PB# 80-
221609 and PB# 81-145732) are currently available through NTIS.
The Agency welcomes submission of additional information for or
comments on the evaluations presented in this volume. The sub-
mission of unpublished information relating to biological/envi-
ronmental effects, production/importation volumes, use(s), and
worker, consumer, and environmental exposure to the subject chem-
ical substances and mixtures would be especially valuable. Such
information will be considered by OTS at subsequent steps in the
OTS chemical assessment process. Submission of additional infor-
mation for or comments on these evaluations should be directed to:
Mr. Frank D. Kover, Chief
Chemical Hazard Identification Branch
Assessment Division (TS-778)
Office of Toxic Substances/OPTS
u.S. Environmental Protection Agency
401 "M" Street, S.W.
Washington, D.C. 20460
All TSCA Section 8(e) submissions as well as EPA status reports
can be viewed in the OPTS public files (subject to claims of
confidentiality made by submitting companies). The OPTS public
iii
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files are located at EPA Headquarters (Room 107, East Tower),
401 II M" Street, S. W., Washington, D. C. Persons wishing to obta in
copies of actual TSCA Section 8(e) submissions should write to
EPA's Freedom of Information Office at the following address and
include the desired Section 8(e) submission numbers.
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 Section 8(e) status reports have
been published by EPA for two reasons. First, volumes of 8(e)
status reports will make reported information more accessible.
Second, such volumes may, by providing specific examples of sub-
mitted information and EPA's evaluation of it, help those persons
subject to Section 8(e) of TSCA to understand better the types of
information that should be submitted.
Joseph J. Merenda, Director
Assessment Division/OTS/OPTS
iv
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Contents
Fore ward. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Acknowledgment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
In trod u c t ion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Status Reports 8EHQ-0280-0331 S through 8EHQ-1282-0467....
Appendix A.
"Statement of Interpretation and Enforcement
Policy: Notification of Substantial Risk"
{43 FR 11110, March 16, 1978)................
Appendix B. Status Reports Listed by CAS Number..........
Appendix C. Status Reports Listed by Chemical Name.......
Appendix D. Status Reports Listed by Information Type....
Appendix E. Status Reports Listed by Submission Number...
v
iii
vii
1
5
419
427
455
491
497
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Acknowledgment
In preparing the status reports contained in this volume, staff
of EPA's Office of Pesticides and Toxic Substances (OPTS) have
frequently found it necessary to request further information
about or clarification of the submitted data. OPTS appreciates
the effort and cooperation of the following companies and organi-
zations that have submitted the information evaluated in this
volume:
3 lYJ COMPANY
A. B. DICK COMPANY
AIR PRODUCTS AND CHEMICALS, INC.
ALLIED CHEMICAL CORPORATION
AMCHEM PRODUCTS, INC.
AMERICAN CYANAMID COMPANY
ARMAK COMPANY
ASARCO INCORPORATED
ATLANTIC RICHFIELD COMPANY
B. F. GOODRICH COMPANY
BORG-WARNER CHEMICALS, INC.
BUCKMAN LABORATORIES, INC.
BUFFALO COLOR CORPORATION
CALLERY CHEMICAL COMPANY
CELANESE CORPORATION
CIBA-GEIGY CORPORATION
DIAMOND SHAMROCK CORPORATION
DOW CHEMICAL COMPANY
DOW CORNING CORPORATION
E. I. DUPONT DE NEMOURS & COMPANY, INC.
EASTMAN KODAK COMPANY
ETHYL CORPORATION
EXXON CHEMICAL AMERICAS
FMC CORPORATION
GAF CORPORATION
GENERAL ELECTRIC COMPANY
GLIDDEN COATINGS AND RESINS
GLYCO CHEMICALS, INC.
GREAT LAKES CHEMICAL CORPORATION
GULF MINERAL RESOURCES CO.
GULF OIL COMPANY - U.S.
GULF OIL EXPLORATION AND PRODUCTION COMPANY
GULF REFINING AND MARKETING COMPANY
HENKEL CORPORATION
HERCULES INCORPORATED
HOOKER CHEMICALS AND PLASTICS CORPORATION
IBM CORPORATION
INTERNATIONAL COAL REFINING COMPANY
INTERNATIONAL LEAD ZINC RESEARCH ORGANIZATION INC.
INTERNATIONAL MINERALS & CHEMICALS CORPORATION
KERR-MCGE8 CORPORATION
LEVER BROTHERS COMPANY (INCORPORATED)
LOCKHEED MISSILES & SPACE COMPANY, INC.
MARTIN MARIETTA CHEMICALS
vii
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MCB MANUFACTURING CHEMISTS, INC.
MOBIL RESEARCH AND DEVELOPMENT CORPORATION
MONTGOMERY ELEVATOR COMPANY
NALCO CHEMICAL COMPANY
OLIN CORPORATION
PENNWALT CORPORATION
PPG INDUSTRIES, INC.
PROCTER & GAMBLE COMPANY
R, T. VANDERBUILT COMPANY, INC.
S. C. JOHNSON & SON, INC.
SHELL OIL COMPANY
SHERWIN-WILLIAMS COMPANY
STANDARD OIL COMPANY (INDIANA)
STANDARD OIL COMPANY (SOHIO)
STAUFFER CHEMICAL COMPANY
STEPAN CHEMICAL COMPANY
SUN CHEMICAL CORPORATION
SUN REFINING AND MARKETING COMPANY
TENNECO CHEMICALS, INC.
TENNESSEE EASTMAN COMPANY
UNION CARBIDE CORPORATION
UNION OIL COMPANY OF CALIFORNIA
UPJOHN COMPANY
VELSICOL CHEMICAL CORPORATION
VULCAN CHEMICALS
WESTERN ELECTRIC
WILMINGTON CHEMICAL CORPORATION
WITCO CHEMICAL CORPORATION
viii
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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-effectuating and
required no implementing rules, manufacturers, processors, and
distributors of chemicals became subject to Section 8(e) report-
ing as of January 1, 1977, the effective data of TSCA. In order
to clarify the types of information to be submitted and the pro-
cedures 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 refer-
ral when using this volume, the March 16, 1978, 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 ;inew" information that "reasonably supports" the
conclusion that a chemical substance or mixture presents a sub-
stantial risk of injury to health or the environment but need not
necessarily conclusively indicate such risk. A determination of
"substantial risk" does not include an evaluation of economic or
social benefits of the use of the chemical and, therefore, is not
synonymous with the term "unreasonable risk" found in other sec-
tions 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
Section 8(e) does receive priority review and evaluation by EPA
in order to determine an appropriate course of Agency action.
Thus far, both EPA and the chemical industry have devoted signif-
icant efforts in fulfilling their respective responsibilities
under Section 8(e) of the Act. Since January 1, 1977, over 460
initial TSCA Section 8(e) notices covering a wide range of chem-
ical toxicity/exposure information have been received and given
priority evaluation and follow-up attention by the Office of
Toxic Substances (OTS). In general, each initial TSCA Section
8(e) submission is promptly reviewed and evaluated by OTS scien-
titic staff in order to determine both the degree of concern that
should be attached to the submitted information and the initial
course of any warranted OTS follow-up action. 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 current production and use of the
1
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subject chemical(s), and the recommendations for appropriate OTS
follow-up actions. Upon approval of the status report, the re-
commended follow-up actions are initiated. A letter containin~
the status report and any EPA requests for additional informatlon
is sent to the submitting company. In addition, copies of all
status reports are transmitted to the OPTS public files, othe~
designated EPA Offices and Federal Agencies, the Industry Ass7st-
ance Office (IAO/OTS/OPTS), and the Office of Toxics Integrat70n
(OTI/OPTS) for further distribution. Other OTS follow-up actlons
include consideration of further, more in-depth assessment of a
reported chemical hazard or risk. It should also be noted that
the Office of Toxic Substances immediately reviews, evaluates,
and initiates appropriate follow-up activities for all infor-
mation contained in "follow-up" and "supplemental" TSCA Section
8(e) notices. By definition, follow-up submissions are those
that contain information submitted directly in response to an EPA
request whereas supplemental submissions are those that contain
information not requested by EPA.
A Document Control Number is used by EPA to identify Section 8(e)
submissions and takes the following form: 8EHQ-OOOO-0000. Start-
ing at the left, the first four symbols identify the information
as a Section 8(e) submission received by EPA headquarters; the
next four digits identify the month and year (e.g., -0579-) of
EPA's receipt of the information; the final four digits identify
the submission's chronological number. In addition to the basic
numerical sequence, 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 Section 8(e) submission was sanitized
to remove information claimed by the submitting company
as "TSCA Confidential Business Information";
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 names or other identifiers);
* .
indicates that based on a preliminary evaluation, the
submission was considered by EPA to be unwarranted for
TSCA Section 8(e) reporting.
When reading the status reports contained in this compendium, one
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 docu-
ments and to any closely related information known by the OTS
reviewer. Neither a literature search to identify other reported
2
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effects nor an in-depth analysis of possible sources of exposure
to subject chemicals is part of the evaluation process. There-
fore, a status report should be viewed only as a preliminary
evaluation of the submitted information and not as a comprehen-
sive assessment of the chemical substance or mixture for which a
TSCA Section 8(e) notice has been filed.
3
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DAT!:
Ji2t8
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0280-0331S
8EHQ-0480-0336S
Page of 3
7/tIJC
Approved
'ROM:
Status Report *8EHQ-0280-0331S
8EHQ-0480-0336S I ;,(
~~:~~c~i ~~~:~d ~~;~~i~ f::!dlr
TO: Joseph J. Me7e~d~, Director
Assessment DIVISIon
Revision
Needed
SUaJICT:
Submission Description
In two separate submissions, the Henkel Corporation reports that
1,4-dioxane (CAS No. 123-91-1) has been detected by gas chroma-
tography in two of its polyalkoxylated polyamine products.
Although the exact chemical identities of the subject products
have been claimed confidential, the submitter states that the two
products are marketed under the tradenames POLYQUART@ Hand
STANAX@ 1166. POLYQUART@ H is reported to contain between 1.5%
to 2% (i.e. 15,000-20,000 ppm) dioxane and the STANAX@ 1166 is
reported to contain between 1.1% to 1.7% (i.e. 11,000-17,000 ppm)
dioxane.
Submission Evaluation
Like many polye~hylene glycols, 1,4-dioxane (an anhydride of
diethylene glycol) can produce toxic effects in the kidney and
liver (in humans). A characteristtc nephrosis of the kidney
tubules (hydropic degeneration) with associated liver cell
necrosis can occur regardless of the route of 1,4-dioxane
exposure (inhalation, oral ingestion, and/or skin application).
Because of this, there is definite concern about human exposure
to any product or material containing significant amounts of 1,4-
dioxane.
Based on the information provided in the submissions, 1,4-dioxane
levels as high as 200-1000 ppm could be present in certain
cosmetics formulated with POLYQUART@ H. The submitter states
that this particular end-use exposure to 1,4-dioxane "would be
brief in most cases as formulations are usually removed by water-
wash after use." In addition, undiluted textile finishing
products formulated with STANAX@ 1166 (antistatic agent) may
contain up to 2000 ppm 1,4-dioxane. The submitter reports in
this case, that the 1,4-dioxane would be removed from finished
*NOTE: This ~tatus report is the result of a preliminary
staff eva~uat10n of information submitted to EPA. Statements
made here1~ are not to be regarded as expressing final
Agen~y po11cy or intent with respect to this particular
chem7cal. ,Any ~eview of the status report should take into
7onfis1der~t10n tne fact that it may be based on incomplete
1n ormat1on.
.~A 1'0- I'''' ."EV. ..,11
5
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8EHQ-0280-033IS
8EHQ-0480-0336S
Page 2 of 3
textile fibers which are normally extracted and dried after
treatment. The submitter also reports that although the 1,4-
dioxane exposure to workers handling finished fibers and textile
products is not known, the exposure is expected to be minimal.
The subject polyalkoxylated polyamine products appear to be
sources for potentially significant dermal and, under certain
conditions, inhalation exposures to 1,4-dioxane. Depending on
duration, these exposures could lead to the serious human health
effects previously mentioned.
Current Production and Use
Due to the fact that confidentiality has been claimed by the
submitter for the exact chemical identities of both POLYQUART@ H
and STANAX@ 1166, a review of the non-confidential TSCA Inventory
(1977) production/importation ranges will not appear in this
status report.
A review of the production range (includes importation volumes)
statistics for 1,4-dioxane (CAS. No. 123-91-1) which is listed in
the initial TSCA Inventory has shown that between 2 million and
15 million pounds of this chemical were produced/imported in
1977.**/
According to the submitter, POLYQUART@ H is used as a component
in cosmestics and STANAX@ 1166 is used as an antistatic agent in
final formulated products used in textile treatment. No other
use information on either product was located in the secondary
literature sources consulted.
Comments/Recommendations
The Henkel Corporation reports that it is continuing the
investigation of this situation and will advise the EPA of newly
developed information. The submitting company also plans to
develop processes for reducing or eliminating the 1,4-dioxane
content in its products. The submitter reports that interim
steps have been taken to protect manufacturing employees. Henkel
is also notifying customers of the findings of 1,4-dioxane
contamination and providing them with recommendations for safe
handling and use.
**/ This production range information does not include any
production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it
include any information which would compromise Confidential
Business Information. The data submitted for the TSCA
Inventory, including production range information, are
subject to the limitations contained in the Inventory
Reporting Regulations (40 CFR 710).
6
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8EHQ-0280-0331S
8EHQ-0480-0336S
Page 3 of 3
In 1974, OSHA set the current occupational standard for 1,4-
dioxane exposure at an 8 hr. time-weighted average (TWA) of 100
ppm in air (39 CFR 23540). An evaluation of the carcinogenic
risk of 1,4-dioxane to man has been prepared by the International
Agency for Research on Cancer (IARC Monograph, Vol. 11, 1976).
In 1977. NIOSH recommended that the occupational exposure to 1,4-
dioxane be controlled so that workers are not exposed at airborne
concentrations greater than 1 ppm (3.6 mg/cu m) based on a 30-
minute sampling period (DHEW (NIOSH) Publication No. 77-226).
Based on the results of its bioassay of 1,4-dioxane for possible
carcinogenicity, the National Cancer Institute (1978) has
concluded that:
"Under the conditions of this bioassay, 1,4-dioxane induced
hepatocellular adenomas in female Osborne-Mendel rats. 1,4-
Dioxane was carcinogenic in both sexes of rats, producing
squamous-cell carcinomas of the nasal turbinates, and in both
sexes of B6C3Fl mice, producing hepatocellular carcinomas."
(DHEW (NIH) Publication No. 78-1330)
The Agency has recently received other 8(e) submissions (8EHQ-
1179-0320, 8EHQ-0979-0326S, and 8EHQ-0180-0326 Supplement) which
also reported the detection of 1,4-dioxane in other ethoxylated
products.
A Chemical Hazard Information Profile (CHIP) on 1,4-dioxane has
been prepared by the Chemical Hazard Identification Branch/AD.
The Chemical Review and Evaluation Branch/AD is now preparing an
indepth source and health/environmental effects assessment (Phase
I) for 1,4-dioxane.
a)
The Agency should transmit copies of these submissions
and status reports to NIOSH, OSHA, CPSC, FDA, OWWM, and
CREB/AD. In addition, the Industry Assistance Office
(IAO/OPII) should consider transmitting the same
information to the manufacturer(s)/importer(s) of the
subject polyalkoxylated polyamines listed in the master
TSCA Inventory.
7
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
4 1980
8EHQ-0280.0332
page 1 of
01/!p
JUN
Revisio
Needed
SU8JECT: Status Report *8EHQ-0280-0332
Frank D. Kover, Chief
"~:Chemical Hazard Identification Branch
Joseph Merenda, Director
TO'Assessment Division
Submission Description
The International Lead.Zinc Research Organization, Inc. (ILZRO)
has provided three progress reports from an ongoing epidemiology
study designed to determine the potential health risks of cadmium
(Cd, CAS No. 7440-43-9). This ILZRO-sponsored study is being
performed i~ Belgium.
The latest of the submitted progress reports (January 1979 to
June 1979) states that the investigation suggests that a group of
aged women who have lived in a cadmium-polluted area of Belgium
have higher cadmium body burden (which is reflected by an
increased excretion of cadmium in the urine and a higher
prevalence of signs of renal dysfunction) than the aged women
serving as the present control group.
The ILZRO states that although it is not a manufacturer,
processor, or distributor as defined by the Toxic Substances
Control Act (TSCA) and is not subject to the reporting
requirements of Section 8(e), it is providing the progress
reports from this epidemiology study under Section 8(e) because
it is felt that the "information concerning this study should be
included in EPA's body of knowledge of the potential health risks
of cadmium." .
Submission Evaluation
There is no doubt the provided data demonstrate that cadmium
cumulates in the human body and that the duration of exposure is
important. The proteinuria values indicate that the exposed
women's kidneys functioned less efficiently than those of the
unexposed women when measured by this parameter. The other
measures of kidney function do not show a major difference in
kidney performance between the two groups.
*NOTE: This ~tatus ~eport is the result of a preliminary
staff eva~uat~on of ~nformation submitted to EPA. Statements
made here~~ are n~t to be regarded as expressing final
Agency pol~cy or ~ntent with respect to this particular
chem~cal. .Any review of the status report should take into
7ons~der~t~on the fact that it may be based on incomplete
l.nforrna t~on.
E~A 'Ollttl 11211)04 ("E". )0111
8
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8EHQ-0280-0332
Page 2 of 3
Epidemiological studies on the renal toxicity of cadmium,
particularly as they relate to hypertension, will have to be
backed up by well designed studies in animals.
It appears that the final report may be useful to the Agency for
its ongoing assessment of the potential health risks of exposure
to cadmium. The progress reports which have been provided thus
far, however, are somewhat vague with respect to the
methodologies used in this study. The Agency should therefore
request the following additional information:
1.
A description of the analytical methods used for
determining the biological parameters reported.
2.
A description of the specific criteria and pollution
data used in selecting the industrial control, non-
industrial control, and cadmium polluted areas for this
study is needed. It should be noted that the
industrial control area contains steel industries,
which have been associated with cadmium pollution.
3.
More detail is needed regarding the criteria for
selection of the populations and individuals surveyed
in these three locations. Progress report no. 1
indicates that the women were institutionalized (i.e.
living in retirement homes). The levels of cadmium in
institutional diets have generally been reported as
higher than in average or typical diets.
4.
The Agency is interested to know why the measuring of
lead in the urine was discontinued.
5.
Copies of all subsequent progress reports and of the
final report as soon as they become available.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for cadmium (CAS No. 7440-43-9) which is listed in the
initial TSCA Inventory has shown that between 1.6 million and 16
million pounds of this chemical were produced/imported in
1977.**/
**/
This production range information does not include any
production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory; nor does it
include any information which would compromise Confidential
Business Information. The data submitted for the TSCA
Inventory, including production range information, are
subject to the limitations contained in the Inventory
Reporting Regulations (40 CFR 710).
9
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8EHQ-0280-0332
Page 3 of 3
Cadmium is used for electrodeposited and dipped coatings on
metals; bearing and low-melting alloys; electrical equipment;
brazing alloys; fire-protection systems; nickel-cadium storage
batteries; power transmission wire; TV phosphors; basis of
pigments used in ceramic glazes, machinery enamels, baking
enamels; Weston standard cell; control of atomic fission in
nuclear reactors; fungicides; photography and lithography; and in
selenium rectifiers.
Comments/Recommendations
The International Agency for Research on Cancer has evaluated the
carcinogenic risk to man from exposure to cadmium and other
selected inorganic and organometallic compounds (IARC Monograph
Vol. 2; 1973). NIOSH has published criteria for a recommended
standard for the occupational exposure to cadmium (August 1976).
The Chemical Review and Evaluation Branch (CREB/AD) has prepared
an indepth source and health/environmental effects assessment
(Phase I) for cadmium.
a)
The submitting organization should be requested to
provide all of the information specified in the
Submission Evaluation section of this status report.
b)
The Agency should transmit copies of the submission and
status report to OSHA, NIOSH, CPSC, OAQPS, OWWM, OPP,
and CREB/AD.
10
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OA TE:
SEP I 2 1980
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
8EHQ-0280-0333
8EHQ-0280-0333
Page 1 of 3
APproved~
Supplement
SUBJECT:
Status Report*
I"ROM.: 4-
~~;a~k_D. Kover, Chief
Chemical Hazard Identification Branch
BEHQ-02BO-0333
BEHQ-02BO-0,~~_3 Supplement
- Revision
Needed
TO:
Joseph J. Merenda, Director
Assessment Division (TS-792)
Submission Description
In its initial submission, the Kerr-McGee Corporation reported
that two of its marketed products, Kermac 600W (CAS No. 64742-46-
7) and Kermac 218a (CAS No. not provided), were found to be
mutagenic to selected Salmonella bacterial strains in the Ames
test.
Kerr-McGee reported that it produced and sold Kermac 600W. The
Kermac 21Ba product was reported to be bought for resale from
another company. The submitter also reported that "occasional
minor dermatitis from prolonged skin contact" was the only
adverse human health effect found in over 12 years of Kermac 600W
production. The submitter also provided a copy of the Kermac
600W "Material Safety Data Sheet" and that product's typical
chemical/physical specifications.
In the cover letter to the original submission, Kerr-McGee made
the following statement with regard to Ames testing in general:
"We recognize the controversial nature of the Ames test and its
imprecision for such determinations. We also understand that the
Salmonella strains used by [the performing laboratory] do not
have repair capability, which in the opinion of some authorities
makes the tests rather harsh. Additionally it is well known that
Ames test data are not translatable to human effects."
In the supplemental submission, the EPA was notified that Kerr-
McGee no longer produces or sells Kermac 600W. In its place,
Kermac 600 (CAS No. 64741-44-2) is now produced and sold.
Although the submitting company states that it does not have any
information on the Kermac 600 product that reasonably supports
the existence of a substantial risk, Kermac 600 is reported to be
similar to Kermac 600W in composition, constituents, and physical
properties, and is the petroleum feed-stock from which Kermac
600W was produced via hydrotreating.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agen~y policy or intent with respect to this particular
chem~cal. ,Any review of the status report should take into
7ons~der~t~on the fact that it may be based on incomplete
l.nforrna t~on.
11
I:~A '0- 1J~ ("E:V. )-711
-------
8EHQ-0280-0333
8EHQ-0280-0333 Supplement
Page 2 of 3
Submission Evaluation
In general, the EPA agrees with the performing laboratory
conclusions regarding the submitted Ames test results. Based on
the dose levels tested (10 to 200 microliters/plate), both Kermac
600W and 2l8a were demonstrated to be mutagenic in selected
bacterial strains in vitro.
Both with and without the rat liver metabolic activation system,
the Kermac 2l8a product was found to be mutagenic to Salmonella
bacterial strains TA 1535, TA 1537, and TA 98. Kermac 2l8a was
also found to be positive in the TA 1538 strain~ the addition of
metabolic activation eliminated this mutagenic response.
According to the performing laboratory. metabolic activation of
Kermac 2l8a was required to induce a mutagenic response in the TA
100 strain. However, without a description of the way in which
the normal number of spontaneous revertants was applied to the
reported revertant values for TA 100, the Agency considers the
mutagenic response in this particular bacterial strain to be at
most marginal.
In addition, the Kermac 600W.product was found to be mutagenic in
all tested bacterial strains (listed above), both in the presence
and absence of metabolic activation.
With regard to human toxicity, the attachment to the provided
"Material Safety Data Sheet" indicates that excessive inhalation
of Kermac 600W may cause "local irritation, drowsiness, collapse,
muscle twitching, coma, and later pneumonia." The data sheet
also warns that contact with the eyes will cause severe
irritation and that prolonged or frequent periodic skin contact
may lead to irritation and dermatitis.
Current Productions and Use
Kermac 600 is a straight-run middle distillate of petroleum crude
oil. Distillates of this type contain hydrocarbons predominantly
in the Cll-C20 range, and have a boiling range of 205°C to 345°C.
A review of the production range (includes importation volumes)
statistics for straight-run middle distillate of petroleum crude
oil (CAS. No. 64741-44-2) which is listed in the initial TSCA
Inventory, has shown that over 89 billion pounds were
produced/imported in 1977.**/
**/
This production range information does not include any
production/importation oata claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it
include any information which would compromise Confidential
Business Information. The data submitted for the TSCA
Inventory, including production/ importation range
information, are subject to the limitations contained in the
Inventory Reporting Regulations (40 CFR 710).
12
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8EHQ-0280-0333
8EHQ-0280-0333 Supplement
Page 3 6f 3
Kermac 600W, which is a hydrotreated middle distillate obtained
by treating a petroleum fraction with hydrogen in the presence of
a catalyst, consists of hydrocarbons predominantly in the CII-C25
range and has a boiling range of 205°C to 400°C. A review of tfie
production range (includes importation volumes) statistics for
hydrotreated middle distillate of petroleum oil (CAS No. 64742-
46-7) which is listed in the initial TSCA Inventory, has shown
that over 15 billion pounds were produced/imported in 1977.**/
The submitter states that the Kermac 600W is used as a mineral
seal oil and that one customer may use it in the formulation of
printing inks.
No information on the production and/or typical uses of Kermac
218a was provided or located. The CAS No. and uses of this
product should be requested from the submitter.
Comments/Recommendations
With regard to the submitter's statements concerning the Ames test,
the Agency believes that in vitro mutagenicity assays of this type
provide valuable data tha~can aid in assessing the possible risks
posed by chemicals to health and the environment. Although Ames
test results, when considered alone, may not be sufficient to
provide reasonable support for a conclusion of substantial risk,
the addition of information concerning high production of and/or
exposure to the chemical would suggest the need for further
testing.
The Kerr-McGee Corporation states that certain customers/suppliers
were advised of the original Section 8(e) notification on Kermac
600W and Kermac 218a. In addition, the submitter states that EPA
will be contacted should any other relevant information become
available.
The EPA has received and evaluated previous Section 8(e) submis-
sions (8EHQ-0879-0301 and 8EHQ-0879-0301 Supplement) on the muta-
genicity of Home Heating Oil Number 2, which contains straight-run
middle distillate of petroleum oil (CAS No. 64741-44-2).
a)
The Kerr-McGee Corporation should be requested to
provide the CAS No. and any available information on
the use(s) of the Kermac 218a product which is
reported to be bought for resale. In addition, the
submitting company should be asked if it has done or
plans to do toxicological tes~ onKermac 600.
b)
The Agency should transmit copies of the submissions
and status report to DOE, OSHA, NIOSH, OWWM, and ORD.
13
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0280-0334
Page 1 of 2
OAT!:
JUr~ II 1::JoJ
SUIJECT: Status Report*
'ROM~nk D. Kover,
. Chemical Hazard
8EHQ-0280-0334
Approved
,/
/1
RevisionV
(Ts-~~~ged
Chief
Identification Branch
TO:
Joseph J. Merenda, Director
Assessment Division (TS-793)
Submission Description
The BF Goodrich Company has submitted a summary of the results
from a battery in vitro mutagenicity tests on N-oxydiethylene
thiocarbamyl-N-oxydiethylene sulfenamide (CAS No. 13752-51-7) and
N-oxydiethylene-2-benzothiazyl sulfenamide (CAS No. 102-77-2).
The submitter reports that each compound was shown to give
positive results in several of the performed short-term assays.
In providing this toxicity information under Section 8(e) the
submitter states "these tests, which are verifiable and reliable,
may 'reasonably support the conclusion' that [both compounds] are
mutagenic and therefore may present substantial risk to health."
Submission Evaluation
As reported, the results from several of the performed in vitro
studies do indicate that both compounds have a mutageniC-
potential. Complete copies of the protocols and data from the
tests cited in the submission should be requested.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for CAS No. 13752-51-7 and CAS. No. 102-77-2, which
are listed in the initial TSCA Inventory, has shown that no 1977
production/importation was reported or that all of the production
range data reported were claimed as confidential by the
manufacturer(s) and importer(s) and cannot be disclosed.
(Section 14(a) of the TSCA, U.S.C. 2613 (a).**/
**/ The data submitted for the TSCA Inventory including produc-
tion range information, are subject to the limitations con-
tained in the Inventory Reporting Regulations (40 CFR 710).
*NOTE: This ~tatus report is the result of a preliminary
staff eva~uat~on of information submitted to EPA. Statements
made here~n are not to be regarded as expressing final
Agen~y policy or intent with respect to this particular
chem7cal. . Any review of the status report should take into
cons~derat~on the fact that it may be based on incomplete
information.
E~A '0- IJ~ (litE...,. )0111
14
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8EHQ-0280-0334
Page 2 of 2
BF Goodrich reports that the subject chemicals are solids which
are used in rubber processing.
Comments/Recommendations
The submitting company reports because the subject chemicals are
solids, dust control is necessary and normally used to minimize
exposure. The manufacture of both chemicals are reportedly
carried out in closed systems. The company believes that "low
risk use of these materials can be achieved through the applica-
tion of existing control practices."
a)
BF Goodrich should be requested to provide complete
copies of protocols and test data from all of the studies
cited in this submission.
b)
The company should also be requested to describe the
actions it has taken, in light of this toxicity data, to
warn workers and customers, and to further reduce and/or
eliminate exposure to the subject chemicals.
c)
The Agency should transmit copies of this submission and
status report to NIOSH, OSHA, CPSC, and FDA. The
Industry Assistance Office (IAO/OPII) should consider
transmitting the same information to the manufacturers of
the subject chemicals listed on the TSCA Inventory.
15
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
JUL I
" I
IVUV
8EHQ-0380-0335S
8EHQ-0680-0335 Supplement
8EHQ-0380-0335S :agerolv:: 2~ W3'
8EHQ-0680-0335 Supplement pp.. /
Chief Rev1s1ojf
Identification Branch (TS-7~ded
SUBJECT: Status Report*
~ank D. Kover,
Chemical Hazard
TO: Joseph J. Merenda, Director
Assessment Division (TS-792)
Submission Description
In its initial submission the Gulf oil Company-U.S. reported that
an undiluted, water-soluble cutting oil (Gulfcut Heavy Duty
Soluble Oil) had produced irreversible damage to the eyes
(irritation and corneal opacities) of several rabbits during a
standard test for eye irritation. The Company stated that
additional testing was planned at several representative
oil/water ratios in order to further define the observed eye
toxicity.
In a subsequent submission (8EHQ-0680-0335 Supplement) the
company reported the summarized results of the additional
testing. Based on those results, the company concluded that a
1:10 oil/water dilution did not produce any corneal opacities or
corneal involvement of any kind in the rabbit eyes. Inflammation
of the iris was reported to have cleared at 72 hours after
treatment. Although the 1:10 dilution is reported to be a
primary eye irritant according to the Federal Hazardous
Substances Act, the submitter states that the observed primary
eye irritation was completely reversible and was less severe than
that observed previously with the concentrated product.
Submission Evaluation
Several of the ingredients in this water-soluble cutting oil are
known to be mucous membrane and skin irritants. In addition, one
of the components has a structural relationship to compounds
which can exhibit anticholinesterase activity regardless of the
route of exposure. Several other ingredients may facilitate
absorption of toxic materials.
*NOTE: This status report is the result of a prelimina=y
staff eva~uation of information submitted to EPA. Statements
made here1n are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chem~cal. . Any review of the status report should take into
cons1derat10n the fact that it may be based on incomplete
information.
E~A 'QIIttII IJ~ I"EV. )on}
16
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8EHQ-0380-0335S
SEHQ-0680-0335 Supplement
Page 2 of 2
Exposure to a mist of the cutting oil product, regardless of
dilution with water, could still cause irritation of the ocular
and nasal mucous membranes. In addition, the product (via
inhalation of the mist) could find its way to the lung proper and
possibly produce a pneumonitis.
Current Production and Use
The submitter reports that under the TSCA Inventory reporting
regulations, this concentrated product is a "mixture" and is
listed by its brand name - Gulfcut Heavy Duty Soluble Oil. The
Gulf Oil Company-U.S. has claimed the identities and weight
percents of the chemical components of this mixture as
confidential.**/
The submitter states that the product is normally used as an oil-
water emulsion in the metalworking industry at concentrations of
one part oil to 10-100 parts water.
Comments/Recommendations
The submitter states that no further testing of Gulfcut Heavy
Duty Soluble Oil is planned at this time.
a) The submitting company should be requested to provide
complete copies of the protocols and data from the
studies cited in these submissions.
b) In addition, the company should be requested to
describe the actions it has taken, in light of the
submitted toxicity data, to warn workers and
customers, and to reduce or eliminate exposure to the
subject product.
c) The Agency should transmit copies of these submissions
and status report to NIOSH, OSHA, and CPSC.
**/ The data submitted for the TSCA Inventory including produc-
-- tion range information, are subject to the limitations con-
tained in the Inventory Reporting Regulations (40 CFR 710).
17
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
J1 2 f ISH)
SUBJECT:
Status Report 8EHQ-0480-0336 S
FROM: Frank D. Kover, Chief
Chemical Hazar~ Identification Branch
TO: Joseph J. Merenda, Director
Assessment Division
Please refer to the status report prepared for 8EHQ-0280-033l S
EPA FORM 1320-6 (REV. 3-76)
18
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
'1 :\' I
""Ul~ j
{ j.::;UtJ
8EHQ-0480-0337
Page 1 Of 3
Approved ~*/D
Revision 7
(T~_~d
SU8JECT:
Status Report* 8EHQ-0480-0337
. /1)1,-
!-:Kank D. Kover, Chie f
Chemical Hazard Identification Branch
"RO/oI:
TO:
Joseph J. Merenda, Director
Assessment Division (TS-792)
Submission Description
The Pennwalt Corporation has submitted the results from a long-
term carcinogenicity bisoassay on vinylidene fluoride (VDFi CAS
No. 75-38-7). The submitting company reports that it had
obtained the results from this study (Maltoni and Tovolii 1979)
from a recent Italian scientific journal. The published results
indicate that vinylidene fluoride had apparently produced an
increased incidence of fat tissue tumors (lipomas and
liposarcomas) at the highest dose (8.25 mg/kg) administered
orally to rats. The submitter points out that the Italian
authors state in their conclusion that "this report is the first
on the long-term effect of VDF and represents the first
indication of its potential carcinogenicity."
In providing this toxicity information under Section 8(e), the
Pennwalt Corporation states that although it" is not ready to
conclude that this report constitutes 'substantial risk
information''', the company does believe "that the public interest
is best served by assuming that the report may represent" such
information and that it is acting accordingly.
Submission Evaluation
The study by Maltoni and Tovoli (1979) establishes that
vinylidene fluoride is a carcinogen under the conditions
experiment. However, several issues should be addressed
the study is accepted as decisive.
of the
before
1. What was the purity of the VDF tested?
2. VDF boils at -84°C. How much VDF remained in solution in
the olive oil vehicle at a stomach temperature of 40°C?
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chem~cal. . Any review of the status report should take into
7ons~der~t~on the fact that it may be based on incomplete
J.nforma t~on.
E.-A '0"" 11»4 11111:". ~7I1
19
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8EHQ-0480-0337
Page 2 of 3
What assurances can be provided that the VDF was not
promptly exhaled or expelled as a gas?
3. What was the evidence that VDF actually entered the
body? VDF is known to release fluoride ions that can be
detected in blood and urine (Dilley et al.; 1974). Was
an attempt made to detect fluoride ions:rn these body
fluids?
4. A contemporary study (Stockle et al.; 1979) has been
performed in which VDF was administered by inhalation to
rats. VDF, in common with analogous chlorine and bromine
compounds, produced preneoplastic changes in liver.
Maltoni and Tovoli (1979) observed intra-abdominal
liposarcomas. This raises suspicion that VDF formed a
stable substance with something in the olive oil (oxide?,
peroxide?, unsaturated materials?). This stable complex
could have been transported to mesenteric and omental fat
depots where it was degraded to release fluoride ion.
Fluoride ion is known to inhibit enzymes involved in
lipid metabolism. Were fat depots analyzed for fluorine?
A study by Lester and Greenberg (1950) demonstrated that VDF is
an anesthetic in rats when inhaled. This indicates that inhaled
VDF can be absorbed into the body and taken up by brain and
possibly other tissues (also Stockle et al.; 1979). Excretion of
the fluoride ion (stripped from VDF bY-the liver) is via the
kidneys. The differences between oral and inhalation exposure is
that inhaled VDF would probably be elimin~ted unchanged to a
greater extent than ingested VDF. The latter exposure would
result in a more extensive degradation by the liver.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for vinylidene fluoride (Cas. No. 75-38-7) as listed
in the initial TSCA Inventory has shown that no 1977 production/
importation was reported or that all of the production range data
reported was claimed as confidential by the manufacturer(s) and
importer(s) and cannot be disclosed. (Section 14(a) of the TSCA,
U.S.C. 2613 (a».**/
The submitter reported however, that the 1977 U.S. production of
VDF was estimated to be approximately 10 million pounds.
Vinylidene fluoride is used as an intermediate in polymers (e.g.
polyvinylidene fluoride) and copolymers. To the submitter's
knowledge there are no consumer uses of VDF monomer as such.
**/ The data submitted for the TSCA Inventory including
production range information, are subject to the limitations
contained in the Inventory Reporting Regulations (40 CFR 710).
20
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8EHQ-0480-0337
Page 3 of 3
Comments/Recommendations
In light of the data presented in the 1979 Maltoni report,
Pennwalt states that it will advise all VDF customers and
Pennwalt employees, who have potential VDF inhalation exposure,
of the contents of the Section 8(e) submission and provide them
with copies of the Maltoni report.
In addition, the company reports that it will take necessary
steps in an attempt to further reduce the possibility of employee
exposure to inhalation of vinylidene fluoride.
Pennwalt also states that expert toxicologists will be retained
in order to analyze the Maltoni study, decide if additional tests
are necessary to determine whether VDF is a potential carcinogen
via inhalation and if so, determine further workplace changes
that may be necessary.
The Chemical Hazard Identification Branch (CHIB/AD) has an
existing Chemical Hazard Identification Profile (CHIP) on
vinylidene fluoride. NIOSH has an existing Criteria Document on
the recommended standard for exposure to vinyl halides.
a) In light of the toxicity information presented in this
submission, it is recommended that the existing CHIP on
vinylidene fluoride be updated to include a discussion of
these new data and any other additional relevant data.
b) The Agency should transmit copies of this submission and
status report to NIOSH, OSHA, CPSC, FDA, NCI, ORD, and
CAG. In addition the Industry Assistance Office
(IAO/OPII) should consider transmitting the same
information to all of the manufacturers of vinylidene
fluoride listed on the TSCA Inventory.
References
Maltoni and Tavoli; (1979); Med. Lavoro; Vol.2; pg. 363-368.
Dilley et al.; (1974); Tox. Appl. Pharmacol.; pg. 582-590.
Stockle et al.; (1979); Toxicol. Lett.; Vol. ~; pg. 337.
Lester and Greenberg
(1950); Arch. Ind. Hyg. Occ. Med.;
Vol. ~; pg. 335-344.
21
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DA TE:
JUL
7 /980
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0480-0338
Page 1 of 3
APproved~~?'~
Rev~s~on
Branch (TS-~~~~ed
SUBJECT: Status Report *8EHQ-0480-0338
FROM~nk D. Kover, Chief
Chemical Hazard Identification
TO:
Joseph J. Merenda, Director
Assessment Division (TS-792)
Submission Description
The Lockheed Missiles & Space Company, Inc. has reported that two
of its employees suffered "prolonged neurological damage"
possibly due to their exposure to the breakdown ~roduc~s of an
accidental exothermic reaction of HX999 - a chem1cal m1xture
reported to contain MY720 (tetraglycidyl methylenedianilinei CAS
No. 28768-32-3) and Eporal (diaminodiphenyl sulfone [DDS]i CAS
No. 80-08-0).
The company states that although a number of its workers were
exposed to unknown concentrations of the breakdown products
during the upset situation, "the symptoms displayed by most of
the exposed employees were temporary and typical of exposures to
such decomposition products."
Submission Evaluation
It is not surprising that some of the workers exposed to diamino-
diphenyl sulfone and tetraglycidyl methylenedianiline developed
neurological deficits.
Diaminodiphenyl sulfone is a drug (Dapsone) used in the treatment
of malaria and leprosy. Neuropathy has been reported to occur in
some patients undergoing treatments with this chemical.
The tetraglycidyl methylenedianiline has several structural
features which could result in toxic effects including carcino-
genicity (e.g. 4,4'-methylenedianiline is a suspected carcino-
gen). However, of particular interest to the present submission
is the somewhat similar structural relationship of tetraglycidyl
methylenedianiline to hemicholinium. Hemicholinium interferes
with the incorporation of choline into acetylcholine in motor
nerves. Such interference would result in muscle weakness.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
I:~A 'Q- IUI:~. C"[V. )-111
22
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8EHQ-0480-0338
Page 2 of 3
There are several issues which remain with regard to the
submitted information. Namely:
1. The submitter's statement concerning worker symptoms
"typical of exposure to such decomposition products"
needs further clarification. What are these typical
symptoms and their duration? Available medical diagnoses
of all affected employees is needed. What are the
chemical identities of the decomposition products? Has
any attempt been made to quantitate the amounts of these
materials? If so, what were the results and sensiti-
vities of such analyses?
2. In particular, a complete description (e.g. medical
diagnosis, if available) of the prolonged neurological
symptoms and damage experienced by the two workers is
needed.
Current Production and Use
No information on the production volumes or uses of the chemical
mixture HX999 was located in the secondary literature sources
consulted.
A review of the production range (includes importation volumes)
statistics for diaminodiphenyl sulfone (CAS No. 80-08-0) which is
listed in the initial TSCA Inventory has shown that between 10
thousand and 100 thousand pounds of this chemical were produced/
imported in 1977.**/
Diaminodiphenyl sulfone is used in medicine and as a curing agent
for epoxy resins.
A review of the production range (includes importation volumes)
statistics for tetraglycidyl methlyenedianiline (CAS No. 28768-
32-3) which is listed in the initial TSCA Inventory has shown
that between 1 thousand and 10 thousand pounds of this chemical
were produced/imported in 1977.**/
Information on the uses of tetraglycidyl methylenedianiline was
not located in the secondary literature sources consulted.
**/
This production range information does not include any
production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it
include any information which would compromise Confidential
Business Information. The data submitted for the TSCA
Inventory. including production range information, are
subject to the limitations contained in the Inventory
Reporting Regulations (40 CFR 710).
23
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8EHQ-0480-0338
Page 3 of 3
Comments/Recommendations
The submitting company states that as more conclusive information
is developed on this situation, it will be provided for the
Agency's consideration.
a) The submitting company should be requested to provide all
of the information specified in the Submission Evaluation
section of this status report.
b) In addition, the company should be requested to describe
the actions it has taken in response to the reported
toxicity to warn workers and others, and to reduce and/or
eliminate exposure to the subject chemicals.
c) The Chemical Hazard Identification Branch (CHIB/AD) will
review the requested information, revise this status
report as appropriate, and recommend further assessment
if warranted.
d) The Agency should transmit copies of this submission and
status report to NIOSH and OSHA. The Industry Assistance
Office (IAO/OPII) should consider sending the same
information to the manufacturers/importers of the subject
chemicals listed on the TSCA Inventory.
24
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
SUIJ~tatus Report*
~. Frank D. Kover,
IIROM: Chemical Hazard
8EHQ-0480-0339
8EHQ-0480-0339
Page 1 of 3;,/)
g . /:J.i)
Approved V/ /'
0/~
DATE:
APR 30 91)
Chief
Identification Branch
Revision!
Needed
TO:
Joseph J. Merenda, Director
Assessment Division
Submission Description
The IBM Corporation has reported that 2,4,7-trinitrofluorenone
(TNF: CAS No. 129-79-3), a component in charge-transfer complexes
in certain electrophotographic copiers and printers, had produced
positive results without metabolic activation in each of several
short-term mutagenicity assays. The tests performed include an
Ames Salmonella/microsomal mutation assay (his+/his-), a Chinese
hamster ovary cell sister chromatid exchange assay, and a
mammalian mutation assay with L5l78Y mouse cells.
In providing a summary of the results from these tests under TSCA
Section 8(e), the IBM Corporation states that based on the
results, it believes that under the actual conditions of use of
TNF in IBM products, "TNF does not pose a health hazard to
operating and service personnel."
In addition, IBM officials met with the EPA on April 25, 1980 to
discuss this submission and at that time expressed a willingness
to cooperate fully with the Agency in the further evaluation of
this situation.
Submission Evaluation
As reported, the summarized results do indicate that TNF is a
direct-acting mutagen (i.e. does not require metabolic
activation) in each of the performed bacterial and mammalian cell
assays. Complete copies of the test protocols and data obtained
from the studies cited in this submission should be requested in
order to evaluate the described mutagenic potential of TNF.
It should be noted that upon a single oral administration to
rats, Huggins and Yang (1962) found that TNF induced mammary
gland,tumors. The authors hypothesized that the strong electron-
accepting property of TNF may playa role in its potent
*NOTE: This 7tatus ~eport i7 the result of a preliminary
staff evaluat~on of ~nformat~on submitted to EPA. Statements
made herei~ are n?t to be regarded as expressing final
Agen~y pol~cy or ~ntent with respect to this particular
chem7cal. ,Any review of the status report should take into
~ons~der~t~on the fact that it may be based on incomplete
~nforrna t~on .
E~" ,.0- 11»4 ('-EV. ~"I
25
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8EHQ-0480-0339
Page 2 of 3
carcinogenicity. It is also important to point out that 2,4,7-
trinitrofluorenone is structurally related to both 2-
acetylaminofluorene (2-AAF), which is a potent multi-target
carcinogen in rodents, and benzidine, which is a well-known human
and animal carcinogen. It has been well-established that for
carcinogenicity, both 2-AAF and benzidine require metabolic
conversion to the hydroxamic acid form. Because nitroreductase
and N-hydroxylase enzymes are present in all mammalian liver (as
well as in some extrahepatic tissues) it is very likely that
trinitrofluorenone would also be converted to a mono- and/or di-
and/or tri-hydroxamic acid form via a similar metabolic pathway.
TNF might also be expected to cause toxic effects similar to
those caused by trinitrotoluene (TNT) and trinitrophenol (picric
acid). These effects include: methemoglobinemia, anemia,
formation of Heinz bodies in red blood cells, bone marrow injury,
and liver dysfunction. In addition, TNF has a 2,4-dinitrobenzene
moiety and, like 2,4-dinitrobenzene and TNT, would be expected to
produce skin sensitization and eczematous skin lesions. The
latter effect would probably be the most prevalent toxicity from
exposure to TNF during copying procedures.
At the April 25, 1980 meeting with EPA, the submitter reported
that TNF represents the photoelectrically active ingredient of
the coating mixture which is deposited on the Mylar plastic
lining of the printing drums in certain IBM copiers and
printers. Thus, the TNF-containing surface comes in direct
contact with the toner during the copying process. The
submitter also stated that some TNF is tranferred to the toner.
In order for the EPA to determine the nature and extent of the
possible exposure to TNF in copying processes, the following
information should also be requested from the submitter:
1.
A complete description of the processes and amounts in
which TNF is employed by IBM in their electrophoto-
graphic copiers and printers (including model types)
and an estimate of the total number of TNF-containing
machines presently in use.
2.
An estimate of "least-case" and "worst-case" TNF
exposure which should include the following
information: (a) the amount of TNF present in "spent"
toner (i.e. toner which has been in contact with the
TNF-containing printing surface), per unit weight of
toner; (b) the amount of "spent" toner released per
copy produced; and (c) the average amount of toner
adhering to the paper in an electrophotographic copy.
26
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-8EHQ-0480-0339
Page 3 of 3
Current Production and Use
A review of the production range (includes importation volumes)
statistics for 2,4,7-trinitrofluorenone (Cas. No. 129-79-3) which
is listed in the initial TSCA Inventory has shown that no 1977
production/importation was reported or that all of the production
range data reported was claimed as confidential by the
manufacturer(s) and importer(s) and cannot be disclosed.
(Section 14(a) of the TSCA, U.S.C. 2613 (a)).**/
Other than the use information provided by the submitting
company, no additional information was located in the secondary
literature sources consulted.
Comments/Recommendations
IBM reports that the submitted toxicity information is also being
provided to its employees, customers, and others who may use IBM
products containing TNF.
Trinitrofluorenone is currently listed on the proposed Section
8(a) "Preliminary Assessment Information Rule" (45 FR 13646).
a) The submitting company should be asked to provide all of
the information requested in the Submission Evaluation
section of this status report. In addition, IBM should
be requested to describe in detail any additional testing
it has done and/or planned to further define the toxicity
of trinitrofluorenone.
b) It is recommended that a production and use profile (PUP)
and a Chemical Hazard Information Profile (CHIP) be
prepared on 2,4,7-trinitrofluorenone.
c) The Chemical Hazard Identification Branch/AD
the additional information requested, revise
report as appropriate, and recommend further
assessment if warranted.
will review
this status
follow-up
d) The Agency should transmit copies of this submission and
status report to OSHA, NIOSH, CPSC, SAD/OPII, OAQPS, ORD,
and NCI.
Reference
Huggins, C., and Yang, N.C.: "Induction and Extinction of
Mammary Cancer," SCIENCE, Volume 137, pg. 257, (1962).
**/ The data submitted for the TSCA Inventory including
-- production range information, are subject to the limitations
contained in the Inventory Reporting Regulations (40 CFR
710).
27
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
Page 1 of 11
Chief
Identification Branch/AD
Revisio
Needed
AUG
7 1980
SUBJECT: Status Report*
'~;;nk D. Kover,
Chemical Hazard
8EHQ-0680-0339
Fo11owup Response "A"
Approved
TO: Joseph J. Merenda, Director
Assessment Division
Submission Description
In its original TSCA Section 8(e) submission (8EHQ-0480-0339),
the IBM Corporation reported that 2,4,7-trinitrofluorenone (TNF~
CAS No. 129-79-3) had been found to be a direct-acting mutagen in
several short-term in vitro bacterial and mammalian cell culture
assays.. IBM also reported that TNF is a component of charge-
transfer complexes in certain IBM electrophotographic copiers and
printers. The IBM Corporation stated in the original submission
that based on the reported short-term test results, it believes
that under the actual conditions of use of TNF in IBM equipment,
there is no health hazard posed to operating or service
personnel.
During a meeting at the EPA on April 25, 1980, IBM representa-
tives discussed the original submission with Agency scientists
and at that time indicated that some TNF is transferred to toner
during electrophotographic processes. At that meeting, IBM
expressed a willingness to cooperate fully with the Agency in the
further investigation and evaluation of the situation.
In the status report prepared for the initial IBM Section 8(e)
submission, the EPA provided its preliminary staff evaluation of
the submitted toxicity information. It was determined at that
time that additional TNF toxicity and exposure information was
needed from IBM in order for the EPA to better determine the
nature and extent of any possible risks of injury to human health
posed by exposure to TNF in photocopying/printing processes.
Per the Agency's request in a followup letter (dated May 1, 1980),
the IBM Corporation provided the following information on TNF:
A.
Complete copies of the final results, including
protocols and data, from the short-term in vitro
mutagenicity tests cited in the originallBubmission.
*NOTE: This ~tatus ~eport i~ the result of a preliminary
staff evaluat10n of 1nformat1on submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chem~cal. ,Any review of the status report should take into
cons1derat10n the fact that it may be based on incomplete
information.
28
E~A 'QMI 11»-6 fIIU:V. )07&1
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8EHQ-0680-0339
Followup Response A
Page 2 of 11
B.
Complete copies of the final results, including
protocols and data, from a number of in vivo acute and
chronic toxicity studies of TNF via several routes of
administration.
C.
Electrophotographic copying/printing process information
including affected product models, the number of TNF-
containing machines currently in use, the amounts of TNF
employed fn IBM equipment, and a "worst-case" TNF expo-
sure estimate.
It is the purpose of the present status report to provide the
Agency's preliminary evaluation of the above-listed information
provided by the IBM Corporation.
Submission Evaluation
a.
Mutagenicity (In Vitro)
The Ames Salmonella test results provided by IBM indicate that 4-
nitroquinoline N-oxide (4-NQO), benzo(a)pyrene (BP) and 2,4,7-
trinitrofluorenone (TNF) were mutagenic in this in vitro bacte-
rial assay. TNF was shown to be mutagenic for bacterial strains
TA 98 and TA 1538, both with and without metabolic activation.
However, this mutagenic activity was somewhat reduced following
the metabolic activation. 4-NQO was demonstrated to be mutagenic
in strains TA 98, TA 1538, and TA 100, both with and without
activation. Again the mutagenic response was reduced following
the enzyme treatment. BP was shown to be mutagenic for strains
TA 98 and TA 1538 following metabolic activation. The Agency
agrees with the IBM interpretations of the results from these in
vitro bacterial tests. Both TNF and 4-NQO are direct-acting --
bacterial mutagens (i.e. do not require metabolic activation for
inducing a mutagenic response) and BP is a bacterial mutagen
requiring metabolic activation.
The results from the mouse L5178Y lymphoma assay indicate that
TNF and 4-NQO induced dose-related increases in forward mutation
frequencies in mammalian cells in culture. It was found that
both compounds were direct-acting and that added 8-9 liver
homogenate (metabolic activation) was not necessary for activity
to be expressed. The Agency is again in agreement with the
submitter's interpretations of the provided data. As in the Ames
test, neither the TNF nor 4-NQO required metabolic activation for
inducing increases in mutations. The addition of the metabolic
activating system reduced both the cellular toxicity and the
mutagenicity of both TNF and 4-NQO in this assay.
4-NQO and TNF induced, without metabolic activation, dose-
related sister chromatid exchanges in Chinese hamster ovary cells
in culture. Here again, the addition of the metabolic activation
system was found to considerably reduce the toxicity of both
compounds. The Agency agrees with IBM's interpretation of the
data as provided. Both 4-NQO and TNF are active in this assay.
29
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8EHQ-0680-0339
Followup Response A
Page 3 of 11
The Agency believes that the following conclusions can be drawn
from the results of the in vitro mutagenicity assays as submitted
by the IBM Corporation:
1.
Without metabolic activation, TNF is approximately 10
times more potent than 4-NQO in the induction of muta-
genic effects in the TA 98 strain of Salmonella. It
should be noted that 4-NQO has been previously demon-
strated as a potent in vitro mutagen and animal carcino-
gen, and is used as one of many laboratory standards in
both mutagenicity and carcinogenicity testing.
Metabolic activation reduced but did not completely
eliminate the mutagenic activity of either 4-NQO or TNF
in the TA 98 bacteria in the Ames test.
2.
TNF produced a dose-related increase in the forward
mutation frequency in cultured mouse cells, both with
and without metabolic activation. This mutagenic
activity is diminished but not eliminated by the
addition of the metabolic activation system. 4-NQO
appears to be a more potent mutagen than TNF in this
assay.
3.
TNF increased the rate of sister chromatid exchanges
(SCEs) in cultured Chinese hamster ovary (CHO) cells by
approximately 2 times the incidence seen in untreated
cells. Metabolic activation is not required for TNF to
exert its effect in CHO cells. 4-NQO was also active in
this system but was more toxic for CHO cells than was
TNF. Direct comparisons of results with unactivated TNF
and 4-NQO are difficult to make because of differences
in toxicity. When tested with metabolic activation, 4-
NQO appears to be slightly more efficient as an inducer
of SCEs than is TNF.
Apparently. IBM did not conduct in vitro mutagenicty assays on
the charge-transfer complex (CTC~which is a combination of TNF
and a polyvinyl carbazole resin. This should be confirmed with
the submitter. (It should be noted that the Agency has previous-
ly prepared a status report for a Section 8(e) submission from
the Xerox Corporation on vinyl carbazole monomer (8EHQ-0579-
0286). In its submission, Xerox stated that the results from
several in vitro studies indicated that vinyl carbazole monomer
is a potential mutagen and carcinogen}.
b.
Carcinogenicity (In Vivo)
The initial evidence for the carcinogenic activity of 2,4,7-
trinitrofluorenone (TNF) stems from the report of Huggins and
Yang (Science, 137, 257 (1962}). TNF administered at a single
oral dose of 100 mg to 50-65 day old female Sprague-Dawley rats
induced a 35% mammary tumor incidence. At the same dose, the
well-known aryl hydrocarbon carcinogen, benzo(a}pyrene, induced
30
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8EHQ-0680-0339
Fo11owup Response A
Page 4 of 11
an 89% incidence in the same experiment. Although old Sprague-
Dawley females are known to show a low, spontaneous:m-arnrnary tumor
incidence, Huggins and Yang found that an oral dose of 200 mg of
a marginal carcinogen (benzo(a)anthracene) did not produce
tumors. The results of this 1962 study establish TNF as a
medium-potent mammary carcinogen in rats.
The in vivo toxicity data presented in the IBM follow-up
submTSsion of June 3, 1980, verify a TNF toxicity projection made
in the initial EPA status report, i.e. carcinogenicity.
In May 1968, a 6-month inhalation study was initiated by IBM to
test the carcinogenic potential of 2,4,7-trinitrofluorenone (TNF)
and the TNF-polyvinyl carbazole charge-transfer complex (CTC) in
mice. The study results indicate either a high normal incidence
of lung tumors or a low degree of tumorigenicity for both tested
materials. Because of the relatively short duration of the ex-
posure and the use of only the mouse as the test species, this
study does not provide an adequate basis to judge the carcino-
genic or tumorigenic potential of TNF or CTC via inhalation
exposure.
Another study was initiated by IBM in May 1968 to determine the
carcinogenicity of TNF and CTC by repeated skin application to
mice. The experimental procedure included 3 subcutaneous
injections followed by application to the skin for 15 months.
At the end of 6 months, there was a significant incidence of
fibrosarcomas and unspecified tumors at the site of application
of TNF and CTC. In addition, the TNF-treated mice had an
increased incidence (25%) of tumors at a distant site (adenomas
of the lung). It is significant that the positive control (2-
acetylaminofluorene7 2-AAF) also increased the incidence of lung
adenomas in the same experiment.
A second study on repeated skin application to mice was initiated
by IBM in December 1969. This study differed from the previous
study in that no injections of TNF or the CTC were made. The
final report concludes that neither TNF nor CTC increased
spontaneous tumor incidence. The positive control in this study,
benzo(a)pyrene, was reported to produce gross and microscopic
lesions which were consistent with the known carcinogenic actions
of this compound. It is assumed that IBM was attempting to
demonstrate that neither TNF nor CTC are absorbed through the
skin and that the carcinogenic action of these compounds occurs
only when they are injected subcutaneously. Although the results
of this study are reported to be negative, the Agency believes
that this study was inadequate and the results obtained do not
remove the EPA's concern for the potential carcinogenicity of
these chemicals. The Agency believes that the shortcomings of the
1969 IBM study are: 1) skin application was carried out for only
18 months7 and 2) the dose of TNF applied may have been
inadequate on a molar basis when compared to the doses of TNF
which produced significant internal toxicity after application to
the skin of rabbits (see c. Other Toxicity (In Vivo». The TNF
31
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8EHQ-0680-0339
Fo11owup Response A
Page 5 of 11
dose could also be considered inadequate on a molar basis with
regard to TNF biotransformation to the hydroxamic acid form. It
is suspected that only a small fraction of the absorbed
trinitrofluorenone compound will follow this pathway. If in this
series, it is the hydroxamic acid that is likely to be formed,
the only acceptable TNF dose would be the maximum tolerated dose
and the duration of application or administration would have to
be 2 years. This would be necessary to meet the concept that no-
effect doses do not apply to carcinogens. It would be helpful to
have data on the metabolites of TNF and the pathways of excre-
tion. It would also be helpful to have a pharmacokinetic study
on TNF absorption and its sojourn in the body. In the absence of
pharmacokinetic and biotransformation data on the CTC, the dose
applied may have also been inadequate.
The possibility that workers and users of the subject electro-
photographic copying/printing equipment could be exposed to TNF
via the skin and inhalation is sufficent to warrant a study of
the metabolism of this compound.
It should also be noted that the mouse may not be a truly
appropriate species to confirm the mammary tumorigenicity of
polynuclear hydrocarbon-type compounds. It is a well established
phenomenon that a single oral administration of certain
hydrocarbons induces mammary tumors predominantly in the rat. In
addition, the ICR Swiss mouse strain, which is randomly bred, is
not eminently suited for studying mammary tumor induction.
c.
Other Toxicity (In Vivo)
Additional in vivo TNF toxicity data provided by IBM also verify
several other toxicity projections made in the first EPA status
report, i.e. skin sensitization and irritation.
In two separate IBM-sponsored studies, TNF was tested for skin
sensitization using a modified Landsteiner technique in guinea
pigs. The criterion used by the performing laboratory to
determine sensitization was the comparison of the average skin
response (i.e. the degree of irritation and the area of skin
involvement) from nine (9) sensitizing injections with the
average skin response following a challenge injection. The
results from the studies showed that TNF was sensitizing to the
skin of 2/8 animals in the first test, and 1/8 animals in the
second test. The positive control 2,4-dinitro-l-chlorobenzene
(DNCB), which is a known skin sensitizer, did not cause
sensitization in any animals in either study. On a molar basis,
TNF appears to be a more potent skin sensitizer than DNCB because
the amount of TNF applied was 3-fold less than the amount of DNCB
applied. The CTC, which was tested in only one of the performed
studies, did not cause sensitization in any of the test
animals. However, the negative sensitization response with CTC
may not necessarily be valid in light of the failure of the
positive control to produce sensitization in the study.
32
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8EHQ-0680-0339
Fo11owup Response A
Page 6 of 11
The results from other IBM-sponsored tests indicate that TNF is
mildly irritating to rabbit skin and slightly irritating to
rabbit eyes. The oral LD50 for TNF was found to be in excess of
21 g/kg in rats. The dermal LD50 was found to be in excess of 2
g/kg when applied to intact or abraded skin of rabbits. The
principal toxic effects of TNF observed in this rabbit dermal
application study were transient soft feces at the lower dose (.2
g/kg) and diarrhea and soft feces at the higher dose (2 g/kg).
Although the laboratory report does not distinguish if these
effects were observed in animals with intact or abraded skin, the
results indicate that TNF may be absorbed through the skin,
excreted in the bile, and exert an irritant action on intestinal
mucous membranes.
The results from the above in vivo studies show that TNF is
capable of producing both mucoUSlmembrane and skin irritation,
and skin sensitization. The lack of an observed skin
sensitization response for the CTC might have been due to either
the injection of doses which were insufficient to exert such an
effect and/or the TNF contained in the CTC is biologically
unavailable to cause skin sensitization. The results also
indicate that TNF can be absorbed through the skin as evidenced
by the observed (and apparently dose-related) gastro-intestinal
toxicity. In order to determine whether TNF is absorbed more
efficiently through the skin than the g.i. tract, further studies
would need to be undertaken. However, based on the data provided
from the dermal versus oral LD50 studies, it appears that the
toxicity of TNF absorbed through the skin may be greater than the
toxicity of TNF absorbed through the gut.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for 2,4,7-trinitrofluorenone (CAS No. 129-79-3) which
is listed in the initial TSCA Inventory has shown that no 1977
production/importation was reported or that all of the production
range data reported was claimed as confidential by the manufac-
turer(s) and importer(s) and cannot be disclosed. (Section l4(a)
of the TSCA, U.S.C. 2613 (a». **/
However, an estimate of the U.S. production of 2,4,7-trinitro-
fluorenone for the years 1974-1979 is provided below (U.S.
International Trade Commission, 1976-1979):
Thousands of Pounds
1974
N.R.
1975
> 1
1976
> 5
1977
> 5
1978
N.R.
1979
N.A.
N.A.
N.R.
= Not Available
= Not Reported
33
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8EHQ-0680-0339
Followup Response A
Page 7 of 11
2,4,7-Trinitrofluorenone is most probably produced in the united
States by dry distillation of diphenic acid with calcium oxide to
form 9-fluorenone, which is then nitrated (The Merck Index, 1976;
Kirk-Othmer Encyclopedia of Chemical Technology, 1967).
2,4,7-Trinitrofluorenone is used as a component of charge-
transfer complexes, to extend the spectral sensitivity of such
complexes, which are used as the photoconductive coating in
electrophotographic copiers, and as the photoconductive layer in
photosensitive organic semiconductors and deformation recording
films (e.g., videotape) (Kirk-Othmer Encyclopedia of Chemical
Technology, 1978).
With regard to the use of TNF in electrophotographic copiers/
printers, IBM reports that there are two (2) basic types of
electrostatic copiers: DIRECT and TRANSFER. In the DIRECT
process, an image is formed directly on a specially treated
paper. In the TRANSFER process, the image is transferred to
plain paper following the formation of the image on an
intermediate substance.
The IBM Corporation reports that it markets the following four
(4) models of photocopy machines which employ a TRANSFER process
involving the use of TNF: the Model 3800 - IBM Printing
Subsystem; the Model 3896 - IBM Tape-Document Converter; the
Model 6800 - IBM Copier; and the Model 6801 - IBM Copier II.
(IBM states that according to a published industry source (not
cited), there were approximately 60,000 of these TNF-containing
models in use as of the end of 1979).
In general, the electrostatic photocopy TRANSFER process involves
the charging and exposure of a light-affected photoconductor
(PC), the developing and transfer of the image, and the fusing of
the image to the paper. It is the photoconductor (PC) which is
reported to contain the charge-transfer complex (i.e. TNF and
polyvinyl carbazole resin) embedded in an aluminized Mylar@
flexible plastic sheet.
The following briefly summarizes the basic steps involved in the
TRANSFER electrostatic photocopy process:
Image Formation - A charge apparatus places a negative
electrostatic charge on the PC surface where the image will
be formed. This charge is dissipated wherever light strikes
it. Exposure lamps reflect light from the original document
**/
The data submitted for the TSCA Inventory including produc-
tion range information, are subject to the limitations con-
tained in the Inventory Reporting Regulations (40 CFR 710).
34
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8EHQ-0680-0339
Followup Response A
Page 8 of 11
to the PC surface. Lighter areas of the document reflect
light to the PC surface and dissipate the electrostatic
charge. Darker areas of the document absorb light. The
unlighted areas of the PC therefore remain charged and
correspond to the printed areas of the document.
Image Development - The image is developed by bringing a
carrier loaded with toner into contact with the PC. The
toner consists of a finely powdered pigment and plastic
resin. The carrier consists of plastic coated beads. When
these two components are rubbed together, the toner becomes
positively charged and the carrier becomes negatively
charged. The carrier transports toner to the surface of the
PC via a magnetic brush. Toner clings to the charged areas
of the PC, forming a visible image.
Image Transfer and Fusion - The developed image is
transferred from the PC to the paper by placing a strong
negative charge on the back of the paper and bringing the
paper into contact with PC. This causes the majority of the
toner to be attracted away from the PC to make a copy. Heat
from fuser lamps then melts the toner onto the paper,
producing the photocopy product. The remaining toner is
removed from the PC by a cleaning apparatus and is then
deposited in a filter bag/cannister. It appears that this
toner is not re-used in the photocopy process.
The IBM Corporation reports that in 98.5% of the TNF-containing
copiers, the photoconductor (PC) film roll contains a maximum of
50 grams of TNF uniformly embedded throughout the coating, with
2-2.5% of the PC film being on the drum surface at any given
time. This would amount to between 1-1.25 grams of TNF actually
on the drum surface.
In the remaining 1.5% of the machines, IBM reports that the
maximum amount of TNF in the total PC film roll is 511 grams,
with 4.1% of that film being on the drum at any given time.
Therefore, the amount of TNF on the drum surface, in this case,
would be approximately 7 grams.
Per Agency's request, IBM provided an estimate of "worst-case"
exposure to TNF during photocopying procedures. It should be
noted that the following "worst-case" analyses reflect the
possible exposure to TNF from those photocopy machines reported
by IBM to contain a maximum of 511 grams of TNF.
1.
IBM has determined (via neutron activaton of doped
photoconductor) that "spent" toner contains an average
of 129 ppm (w/w) of TNF. IBM reports that although TNF
is present in "spent" toner, the virgin toner does not
35
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8EHQ-0680-0339
Fo11owup Response A
Page 9 of 11
contain any TNF. IBM should be requested to provide
complete protocols and data from this analysis. In
addition, IBM should be asked to provide its definitions
of "doped photoconductor" and "spent toner."
2.
Via a quantitative Ames test technique, IBM has found
that an average of .04 micrograms of TNF is present per
cubic meter of ambient air (8 hr. sample) at the opera-
tor position (i.e. breathing zone). The results from
this analytical technique indicate that a mutagen has
been detected in the ambient air near the photocopier.
Complete protocols and data from this study should be
requested.
3.
The average amount of toner thermally bonded to one
sheet of 8.5 x 11 inch plain paper (containing 1300
characters) is reported by IBM to be 20 milligrams.
Therefore, the amount of TNF physically bound to the
toner deposited on this typical printed page is
approximately 2.6 micrograms. This calculation is based
on the 129 ppm (w/w) of TNF in "spent" toner.
It is not clear from the submitted information whether the TNF
contained in "spent toner" exists as such or as a bound component
with the polyvinyl carbazole in the charge-transfer complex
(CTC). In addition no information was provided relative to the
nature of the binding of TNF or the CTC to the "spent" toner.
IBM should be requested to provide this type of information, if
available.
Comments/Recommendations
The Chemical Hazard Identification Branch (CHIB/AD) is preparing
a Chemical Hazard Information Profile (CHIP) on TNF.
With regard to IBM's mutagenicity/carcinogenicity potency
correlations (based upon the method Clive et al.: Mutation
Research, 59:61-108, 1979), the EPA believes that certain points
should be made. There is no disagreement with IBMls final
interpretation of the potency calculations (i.e. TNF is a more
potent bacterial mutagen than 4-NQO, while 4-NQO is more active
in cultured mammalian cells). However, the Agency believes that
the technique of potency estimation has not been sufficiently
validated at this time to be used routinely. Further, it is not
recommended that such calculations be used to estimate in vivo
carcinogenic/mutagenic potency from in vitro test results, or to
make comparative potency estimates between in vitro systems.
It is the Agency's preliminary determination with regard to the
submitted in vitro results, that trinitrofluorenone is a direct-
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Followup Response A
Page 10 of 11
acting mutagen which induces gene mutations in both bacterial and
mammalian cells in culture, and can cause an increase in sister
chromatid exchanges in cultured Chinese hamster ovary cells.
These mutagenic events can be shown in some instances to be dose-
related. It should also be noted that the mutagenicity of TNF
has been confirmed in a study which recently appeared in the
published literature (Levin et al.~ Mutation Research~ 63, 1
(1979». Based on the in vitrotest data provided by IBM, TNF
would be suspected of being a potential mutagen and/or carcinogen
in vivo.
In addition, it is the Agency.s preliminary determination that
TNF was shown in laboratory animals to be both sensitizing
(guinea pigs) and irritating to the skin (rabbits), and
irritating to mucous membranes (rabbit eyes and intestines).
With regard to carcinogenicity, it is the Agency's preliminary
determination that the studies in mice with TNF and CTC via
inhalation or dermal application alone appear to be inadequate to
assess the tumorigenic or carcinogenic potential of the two
substances by those routes of exposure. However, thus far both
TNF and CTC have demonstrated carcinogenic/tumorigenic potential
in laboratory animals via oral administration (rats~ TNF) and
combined subcutaneous injection/dermal application (TNF and CTC~
mice).
a)
In order to better determine the nature and extent of
any possible risks of injury to human health due to
exposure to TNF as used in certain photocopying pro-
cesses and equipment, the Agency should request that the
IBM corporation provide the following information:
1)
Definitions of "spent toner" and "doped
photoconductor."
2)
Complete copies of any and all results from neutron
activation studies performed by and for IBM to
detect TNF in "spent toner." This information
should include complete copies of the test protocols
and data, and the date(s) of performance and receipt
of results.
3)
Complete copies of any and all results from quanti-
tative Ames tests performed by and for IBM to detect
TNF in the ambient air surrounding electrophoto-
graphic copiers/printers. This information should
also include complete copies of the test protocols
and data, and the date(s) of performance and receipt
of results.
37
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b)
c)
d)
8EHQ-0680-0339
Followup Response A
Page 11 of 11
4)
Complete copies of the results from any and all
additional studies performed by and for IBM which
indicated the presence of TNF in any form in any
media (e.g. toner, paper, air, etc.) other than in
or on the photoconductor. This information should
include complete copies of the test protocols and
data, and the date(s) of performance and receipt of
results.
5)
The complete results including protocols and data,
from any and all studies performed by and for IBM to
determine the mutagenicity of the TNF-polyvinyl
carbazole CTC and/or polyvinyl carbazole alone.
Any available information on the form(s) in which
TNF and CTC exist as found in "spent toner", paper
copies, and air. Is TNF found as such, or always in
complex with other materials such as in the CTC? If
complexed, under what physical/biological conditions
can the complex disassociate to free TNF? If free
TNF exists, what are its binding properties to
"spent toner" and paper copies, and under what
physical/biological conditions can the TNF be
liberated? Do any machine functions/malfunctions
have any effect on the release of TNF and/or CTC
from the photoconductor? If so, what are those
functions/malfunctions and what are the effects?
These questions should be answered by IBM to the
extent possible based on available information.
6)
7)
What is the fate of
cleaned from the PC
bag/cannister? How
materials routinely
the "spent toner" which is
and deposited in the filter
and where are these "spent"
disposed?
The Chemical Hazard Identification Branch (CHIB/AD) will
review all requested information, revise this status
report as appropriate and recommend further assessment,
if warranted.
The Agency should transmit copies of the IBM followup
submission and EPA status reports to OSHA, NIOSH, CPSC,
NCI, SAD/OPII, and ORD. The Industry Assistance Office
(IAO/OPII) should transmit copies of the initial and
followup EPA status reports to the manufacturer(s)/
importer(s) of TNF listed in the master TSCA Inventory.
NIOSH and OSHA should be requested to review the
available toxicity and exposure information on TNF and
CTC and to recommend, if warranted, appropriate worker
health and safety protection measures. The EPA should
also offer to cooperate with those agencies in such
efforts.
38
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
SUBJECT: Status Report* 8EHQ-0480-0340S
~Frank D. Kover, Chief
Pf(OM:.~hemical Hazard Identification
Branch
8EHQ-0480-0340S
Page 1 of 2 ~ ~//O
Approved ~
Revision
(TS-~~~ded
DATE:
AUG
4 1980
TO:Joseph J. Merenda, Director
Assessment Division (TS-792)
Submission Description.
The Ciba-Geigy Corporation has reported summarized results from
several in vivo and in vitro acute toxicity studies on Chimassorb
944. Although the actual chemical identity of this product was
claimed confidential, the submitter stated that Chimassorb 944 is
a high molecular weight hindered amine which is imported from
Italy.
According to the summary provided, Chimassorb 944 has an acute
(4-hour) inhalation LCSO of approximately .112 mg/liter when
tested in Sprague-Dawley rats. The chemical was also reported to
be an eye irritant in rabbits. This effect was reported to be
non-reversible over a 14-day observation period. Although the
test species were not specified, Chimassorb 944 was not found to
be a skin sensitizer, but was found to be slightly irritating to
skin. The result of an in vitro bacterial mutagenicity study
(Ames test) was reported~o be negative.
Submission Evaluation
The chemical structure and molecular weight of Chimassorb 944
place it in the class of potential histamine liberators. This
class of chemicals produce their effect by degranulating mast
cells. These granules contain heparin and histamine. The
released histamine produces irritation or inflammatory
phenomena. The release of heparin could result in bleeding.
According to the submitter, a characterized Chimassorb 944 sample
will be tested in order to rule out the possibility that
impurities were responsible for the highly toxic action observed
via inhalation.
*NOTE: This status report is the result of a prelimina=y
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chem~cal. . Any review of the status report should take into
7ons~der~t~on the fact that it may be based on incomplete
~nforma t~on.
39
E ~ A , 0 IItM tJ2I)o.4, un: v. 1-711 I
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8EHQ-0480-0340S
Page 2 of 2
Complete copies of the results from the cited in vivo and in
vitro studies should be requested from the submitter.
Current Production and Use
Due to the fact that confidentiality has been claimed by the
submitter for the exact chemical identity of Chimassorb 944, a
review of the non-confidential TSCA Inventory (1977) importa-
tion/production range will not appear in this status report.**/
The submitter reports that Chimassorb 944 is a high molecular
weight (approximately 3000), polymeric light stabilizer which is
used to protect polymers from degradation, particularly
polyolefins such as polypropylene fibers and tape, and low-
density polyethylene and ethylene vinyl acetate films.
Comments/Recommendations
Ciba-Geigy Corporation states that the results from the planned
toxicity studies on Chimassorb 944 will be forwarded to the
EPA. However, as a consequence of the toxicity data provided in
the present submission, the company reports that it is in the
process of preparing an appropriate product warning label and is
updating the Chimassorb 944 Material Safety Data Sheet. In
addition, the submitter is notifying all Chimassorb 944 customers
of the toxicity findings submitted to the EPA and the modified
recommended handling precautions. The Ciba-Geigy Corporation
also states that it is actively engaged in the development of a
non-dusting granular form of Chimassorb 944. This is being done
in order to minimize any potential problems in handling the
product.
a)
The Ciba-Geigy Corporation should be requested to
provide complete copies of the results, including
protocols and data, from the studies cited in its
submission.
test
b)
The Chemical Hazard Identification Branch (CHIB/AD)
will review the additional information requested and/or
provided, revise this status report as appropriate, and
recommend further follow-up assessment if warranted.
c)
The Agency should transmit copies of this submission
and status report to NIOSH, OSHA, and CPSC. The
Industry Assistance Office (IAO/OPII) should consider
sending the same materials to manufacturer(s)/
importers(s) of the subject chemical listed in the
master TSCA Inventory.
**/ The data submitted for the TSCA Inventory, including
-- production/importation range information, are subject to the
limitations contained in the Inventory Reporting Regulations
(40 CFR 710).
40
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DATE:
JUN I 7 1980
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0580-0341
Page 1 of 2
::::::~ ~~
SUBJECT: Status Report* 8EHQ-0580-0341
FROW: ~ra""'nk D.
~~ Kover, Chief Needed
Chemical Hazard Identification Branch (TS-792)
TO: Joseph J. Merenda, Director
Assessment Division (TS-792)
Submission Description
The Union Carbide Corporation reports that several of its
maintenance workers experienced urinary dysfunction symptoms
(evidenced by bladder fullness, bladder pain, urgency, urinary
frequency, and low urine output) following a cleanup of spilled
propiophenone (CAS No. 93-55-0) at a production unit in South
Charleston, West Virginia. The company reports that in all cases
(2 male and 1 female) the urinary symptoms subsided after the
employees were removed from the working area.
The submitting company believes that inhalation was the route of
exposure during the clean-up as there was no ingestion of the
chemical and the maintenance workers involved were wearing
protective equipment (gloves, boots, etc.) to minimize skin
contact. In addition, the company reports that it has
manufactured propiophenone for five (5) years with no such
effects found or complaints made by their workers.
Submission Evaluation
The changes in urinary function as described in the submission
(urgency, frequency and small volume in addition to a feeling of
fullness and pain) suggest, at first consideration, direct
exposure of the groin area to the vapors of an irritant - in this
case propiophenone. If the vapors were actually inhaled the
symptoms would most likely be due to unmetabolized propiophenone
excreted via the kidney. The irritation would affect the kidney
proper, the ureters, bladder, and particularly the urethra.
Irritants that affect the kidney proper usually cause loss of
protein into the urine. Were the urines of the victims examined?
A more serious effect, though not likely in this case, would be
due to the ability of propiophenone to affect bladder control
through its action on the spinal cord. Phenones are known to act
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chem~cal. . Any review of the status report should take into
~ons~der~t~on the fact that it may be based on incomplete
~nforma t~on.
41
E~ I --
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8EHQ-0580-034l
Page 2 of 2
on the central nervous system. Acetophenone was used clinically
to produce sleep in humans and benzophenone was used to treat
epilepsy.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for propiophenone (CAS No. 93-55-0) which is listed in
the initial TSCA Inventory has shown that between 100 thousand
and 1 million pounds of this chemical were reported as
produced/imported in 1977.**/
Propiophenone (ethyl phenyl ketone) is used as a fixative in
perfumes, a starting material for the synthesis of ephedrine and
other pharmaceuticals and synthetic chemicals, and as a
laboratory reagent.
Comments/Recommendations
Union Carbide reports that company employees, customers, and
other concerned agencies including NIOSH, OSHA, and the ACGIH
have been advised of this situation. In addition, Union Carbide
states that studies will be initiated in order to determine
whether the reported urinary effects can be demonstrated in the
laboratory.
a)
The submitting company should be requested to
inform the Agency of the results obtained from the
laboratory studies planned to further define the
possible urinary system toxicity of propio-
phenone. The Agency should also request the
results of urinalyses (if performed) on the exposed
workers.
b)
The Agency should transmit copies of the submission
and status report to NIOSH, OSHA, and the ACGIH.
In addition, the Industry Assistance Office
(IAO/OPII) should consider sending the same
information to the manufacturers/importers of
propiophenone listed on the TSCA Inventory.
**/
This production range information does not include any
production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it
include any information which would compromise Confidential
Business Information. The data submitted for the TSCA
Inventory, including production range information, are
subject to the limitations contained in the Inventory
Reporting Regulations (40 CFR 710).
42
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U HITED STATES ENVIRONMENTAL PROTECTION AGENCY
OA TE;
JUL I
1980
8EHQ-0580-0342
Page 1 of 3
Approved ~~;l80
Revision~
Needed
Branch (TS-792)
SUBJECT:Status Report* 8EHQ-0580-0342
,. ~rank D.
~aI Kover, Chief
Chemical Hazard Identification
TOuoseph J. Merenda, Director
Assessment Division (TS-792)
Submission Description
ASARCO, Inc. has reported that lung tumors have been observed in
15/17 rats chronically exposed via inhalation to 4.2 milligrams
of antimony trioxide (CAS No. 1309-64-4) dust per cubic meter for
six hours per day, five days a week for one year. The submitter
reports that the animals at the low dose (1.6 mg per cubic meter)
and the control animals did not develop lung tumors. Liver and
mammary tumors were reported to have occurred in both the exposed
and control groups.
The submitting company reports that while it is unaware of any
prior information regarding the lung tumor effect of antimony
trioxide, it finds the occurrence of those tumors in the high
dose group puzzling. In addition, the submitter states that
because of the extremely high doses used in the study, it is
unclear as to the conclusions that can be drawn. ASARCO also
states that it believes that humans are not likely to be exposed
to doses as high as those used in the high dose group of study.
Submission Evaluation
Some researchers have suggested that a relationship exists be-
tween antimony (Sb) exposure and pulmonary carcinogenesis. This
submission appears to be the first authentic report of such an
activity. Although only two concentrations of antimony trioxide
were tested (with the highest dose alone reported as producing
tumors) the results establish that chemical as a carcinogen.
It is unclear from the submitted information, however, when the
lung tumors were first observed. Therefore, the duration of
exposure and latency to tumor formation cannot be surmised.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herei~ are n~t to be regarded as expressing final
Agency pol~cy or ~ntent with respect to this particular
chem~cal. ,Any review of the status report should take into
~ons~der~t~on the fact that it may be based on incomplete
lnforma t~on.
E~A '0l1l1I8 11»-6 fIllEV. ..761
43
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8EHQ-0580-0342
Page 2 of 3
Current Production and Use
A review of the production range (includes importation volumes)
statistics for antimony trioxide (CAS No. 1309-64-4) which is
listed in the initial TSCA Inventory has shown that between 10
million and 108 million pounds of this chemical were produced/
imported in 1977.**/
The uses of antimony trioxide
textiles, paper, and plastics
pigments; ceramic opacifiers;
and iron staining; phosphors;
include the flameproofing of
(mainly polyvinyl chloride); paint
catalysts; intermediates; copper
mordants; and glass decolorizers.
Comments/Recommendations
A contract report (hazard assessment) on antimony and antimony
compounds was prepared in 1976 for the Agency (EPA 560/2-76-002).
A dossier on antimony trioxide was prepared by a contractor for the
TSCA Interagency Testing Committee in 1978 (Contract No.
EQ8AC013). The National Institute for Occupational Safety and
Health (NIOSH) has prepared a criteria document on a recommended
standard for occupational exposure to antimony (September, 1978).
NIOSH recently (August 1978) published a technical report on the
environmental exposure to airborne contaminants in the antimony
industry (DHEW (NIOSH) Publication No. 79-140).
The Test Rules Development Branch (TRDB/AD), in conjunction with
the Environmental and Health Review Divisions, is currently
reviewing data received by the EPA pertaining to antimony trioxide
as designated by the Interagency Testing Committee (ITC).
a)
ASARCO, Inc. should be requested to provide complete
copies of the experimental results, including protocols
and data, from the in vivo chronic inhalation studies on
rats and swine citea-in this submission. In addition,
the submitter should be requested to provide the results
of the chemical analysis (if performed) on the tested
antimony trioxide.
b)
The submitting company should also be requested to
describe the actions it has taken in response to the
submitted toxicity data to warn workers and customers
and/or to eliminate or reduce exposure to the subject
chemical.
**/ This production range information does not include any
production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it
include any information which would compromise Confidential
Business Information. The data submitted for the TSCA
Inventory, including production range information, are
subject to the limitations contained in the Inventory
Reporting Regulations (40 CFR 710).
44
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8EHQ-0580-0342
Page 3 of 3
c)
The Chemical Hazard Identification Branch (CHIB/AD)
review the additional information requested, revise
status report as appropriate, and recommend further
follow-up assessment if warranted.
will
this
d)
It is recommended that a priority Chemical Hazard
Information Profile (CHIP) be prepared by CHIB/AD to
include a discussion of these new toxicological data
submitted on antimony trioxide.
e)
The Agency should transmit copies of the submission and
status report to NIOSH, OSHA, CPSC, NCI, ORD, and CAG.
The Industry Assistance Office (IAO/OPII) should
consider transmitting the same information to the
producers/importers of antimony trioxide listed on the
TSCA Inventory.
45
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OA TE:
AUG 2 5 1980
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0580-0343
page 1 of 2
Approved l/IJ );//0
Revision!'
Needed
SUIIJECT:
Status Report* 8EHQ-0580-0343
/tU-
FROW:~~~_nk D. Yover, Chief
Che~i~al Hazard Identification
Branch
TO:
Joseph J. Merenda, Director
Assessment nivision
Suhmission Description
Tre Gulf Oil ~xploration ano Production Company reported an
er1ergency incident of environmental contamination involving the
release of hydrogen sulfide (CAS No. 7783-06-4) frrnn a Gulf oil
Corporation-operated oil well in Dunn County. North Dakot_a. Due
to the level of hydrogen sulfide detected near tbe well (100 ppm~
maximUlu scale reaoing), rulf employees quickly evacuate
-------
8EHQ-0580-0343
Page 2 of 2
Current Production an~ Use
Base~ on the nature of this su~mission, a review of production
and uses of the su~ject che~ic~l is not necessary.
Ccmn1ent s /PecoImnenda t ion s
Gulf reports that tnE' actions taken hy its ewployees were in
accordance wi t11 its wri t,ten Hyclrogen f-:ulfic'Je Continsency Plan for
the Little Y-nife Field in which the incident occurred. ~he plan
reportedly provides for procedures to be followed for protecting
employees and other parties frOll1 hydroSE'n sulficle ane also
contains instructions on E'lIlerCTency evacui'1.tion s.
a)
..
':'he Agency shoulr:1 transmit a copy of tris statl1R report
and submission to the EPA's Region VIII Office.
47
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
OA TE:
.8'.
8EHQ-0680-0344P
Page 1 of 2
Approved ~~~
Revisiof'
(Ts-~ded
Status Report *8EHQ-0680-0344P
SUBJECT:
(I. -r-. '~,I / ,1
Frank D. Kover, Chief '~~~k
'R~:Chemical Hazard Identi6Acation BranCh
Joseph J. Merenda, Director
TO:Assessment Division (TS-792)
Submission Description
Western Electric has reported that certain of its employees are
experiencing "discomfort" (i.e. difficulty in breathing,
headaches, and burning in the nose) apparently during the purging
of ZYTEL@ molding presses. The submitting company reports that
ZYTEL@ is a nylon resin with the CAS No. 63428-83-1 and the
chemical formula (C6-HII-N-O)n.
Western Electric states that no information on any toxic or
hazardous decomposition products associated with nylon resin
could be found.
Submission Evaluation
Diamines could possibly be released during the heat purging of
the nylon molding presses. Many diamines can cause the release
of histamine from tissues or from the mast cells within
tissues. Histamine causes constriction of the smooth muscle in
the airways which would result in difficulty in breathing.
Histamine dilates blood vessels, including those within the
skull, which may cause the headaches. Histamine headache is a
recognized clinical entity- The burning in the nose could be
either a direct effect of a diamine or histamine release as
occurs in colds and some allergies.
Current Production and Use
ZYTEL@ is a trademark for nylon resins available as a molding
powders, extrusion powders, and soluble resins.
Due to the nature the information contained in this submission, a
review of the current production of the subject chemical does not
appear to be necessary at this time.
*NOTE: This ~tatus ~eport i~ the result of a preliminary
staff evaluat~on of ~nformat~on submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agen~y policy or intent with respect to this particular
chem~cal. ,Any review of the status report should take into
7ons~der~t~on the fact that it may be based on incomplete
~nforma t~on.
48
E~" ~Q- 11»-6 I~EV. ~711
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8EHQ-0680-0344P
Page 2 of 2
Comments/Recommendations
It is the Agency's preliminary determination that the acute
toxicity information, as presented in this submission, did not
warrant being reported under Section 8(e) of TSCA. The rationale
for this preliminary determination is as follows:
According to Part V of the March 16, 1978, "Statement of
Interpretation and Enforcement Policy; Notification of
Substantial Risk" (43 FR 11110), a substantial risk of
injury to health is a risk of considerable concern because
of (a) the seriousness of the effect... and (b) the fact or
probability of its occurrence." With regard to the
seriousness of the effect, the Agency considers the human
health effects for which substantial risk information must
be reported to include "any instance of cancer, birth
defects, mutagenicity, death, or serious or prolonged
incapacitation, including the loss of or inability to use a
normal bodily function with a consequent relatively serious
impairment of normal activities...." In addition, Part
VI(2) further states that it is possible that effects less
serious than those described above may be preliminary
manifestations of those more serious effects and together
with another triggering piece of information, constitute
reportable information.
Therefore, because the human health effects, as reported in this
submission, do not appear to be serious and did not produce a
prolonged incapacitation or serious impairment of normal
activities, the Agency believes that the provided acute human
toxicity information, when considered alone, did not warrant
reporting under section 8(e) of TSCA.
Western Electric states that it has urged its employees to report
any further difficulties to the company's medical department. In
addition, the submitting company states that its investigation of
the reported situation will continue in order to determine the
cause of the discomfort to its employees.
a)
The Agency should transmit a copy of this status report
and submission to OSHA and NIOSH.
49
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" ~ ". -, ,- -, ,
, II \, : .
r:
,I'
U '3 t~ ~ ~\ -
/: ':~ -; , ~ "
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8.EHQ-0680-0345
Page 1 of 3
APprove~0
'r~',:: :.-: ;
'l- '- I c.-.'-
, '.
OAT!: SEP I 6 1980
SUBJECT:Status Report* 8EHQ-0680-0345
".~nk D. Kover, Chief
-chemical Hazard Identification Branch
Revision
Needed
To~oseph J. Merenda, Director
Assessment Division
Submission Description
The SCM Corporation (Glidden Coatings and Resins Division) has
reported the results from a water sample analysis from a pump-out
well at a plant site in Charlotte, North Carolina. According to
the submission, the plant's previous owner (Celanese Corporation
prior to 1977).had constructed this well in order to collect
seepage from an underground release of approximately 50,000
gallons of vinyl acetate. The submitter reports that this
underground contamination, which had occurred in 1975, allegedly
resulted after a hydrochloric acid spill corroded a transfer line
connecting underground storage tanks of vinyl acetate. SCM also
reports that Ce1ansese indicated that this spill had been
reported to local and state authorities and the EPA in 1975.
In addition, the SCM corporation states that it (SCM) was cited
in early 1979 by the local utility district for low pH effluents
(pH not specified) from this plant site. As the problem was
traced to the vinyl acetate spill pump-out well, Celanese was
reported to have been notified of its continued responsibility
for the vinyl acetate spill.
The SCM Corporation reports that a tentative agreement for
remedying the low pH problem has been reached with the Celanese
Corporation. The actions to be taken, which include continuous
operation of the spill pump-out well and the addition of caustic,
are designed to lower the effluent pH, decontaminate the soil,
and confine the contaminated zone to the central area of the
plant site. These actions would thereby prevent the possible
spread of contaminated groundwater off site. The submitter also
states that, in addition to the maintainance of pH records, the
pump-out well and plant perimeter groundwater monitoring wells
*NOTE: This status report is the result of a prelimina=y
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agen~y policy or intent with respect to this particular
chem~cal. ,Any review of the status report should take into
~ons~der~t~on the fact that it may be based on incomplete
~nformat~on .
50
E~" 'OJlttt '.»-4 (~[v. ..711
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8EHQ-0680-0345
Page 2 of 3
will be analyzed on a monthly basis for organic contaminants and
the results forwarded to the North Carolina Department of Natural
and Economic Resources. The results of the first chemical
analysis of water from the pump-out well, provided by SCM in its
submission, indicated the presence of 10 volatile organics and 13
heavy metals (see Table I. below). However, the submitter has
raised questions concerning the validity of the sampling
technique used (i.e., the water sample was apparently withdrawn
from the pump-out well which had not been in operation for 9
months, and there was evidence of corrosion of the well's
galvanized steel casing). The submitter believes that because
this sampling technique did not allow for an adequate purge of
the well contents; the heavy metal content detected may have been
due to sedimentary corrosion products and not actual pump-out
well discharge. The submitter states that the detected organics
and metals currently appear on the EPA's list of 129 priority
pollutants and that some of the detected substances are in excess
of current Clean Water Standards.
TABLE I.
Results of Water Sample Analyses
for Priority Pollutants
ORGANICS
benzene
l,l-dichloroethane
l,2-trans-dichloroethylene
ethylbenzene
methylene chloride
dichlorodifluoromethane
tetrachloroethylene
toluene
trichloroethylene
vinyl chloride
PARTS
PER BILLION
7680
23
2295
24
570
50
25
5200
50
130
(ppb)
METALS (and other pollutants) PARTS PER MILLION (ppm)
Antimony 0.16
Arsenic 0.023
Beryllium <0.01*
Cadmium 0.018
Chromium 1.90
Copper 1.28
Lead 0.45
Mercury <0.001
Nickel 2.76
Selenium <0.01*
Silver <0.02*
Thallium <0.1*
Zinc 82.5
Total Cyanide 2.65**
Total Phenol O.lOt
* Higher detection limit due to interferences.
** Distillate highly colored; cyanide level measured on
original sample using ion-specific electrode.
t Interference suspected.
51
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8EHQ-0680-0345
Page 3 o~ 3
Submission Evaluation
Of obvious concern would be the potential for human, animal,
and/or plant exposure to water containing organic and heavy metal
pollutants, especially any found to be in excess of existing
standards. With regard to the low (acid) pH detected in the
effluents, there is a concern for potential harmful effects on
aquatic and plant life.
The submitter attributes the heavy metal content of the analyzed
water sample to a corrosive attack on the galvanized steel well
casing. This would not, however, readily account for the
detected chromium, lead, nickel, selenium, silver, thallium, and
cyanide. It is also difficult to conceive the conditions whereby
hydrochloric acid would react with vinyl acetate to yield
benzene, l,l-dichloroethane, methylene chloride, ethylbenzene,
dichlorodifluoromethane, tetrachloroethylene, toluene,
trichloroethylene, and l,2-trans-dichloroethylene. The presence
of these chemicals suggests another source of contamination.
Current production and Use
Based on the nature of this submission, a review of the current
production and uses of the subject chemicals is not necessary at
this time.
Comments/Recommendations
The Chemical Hazard Identification Branch (CHIB/AD) has
transmitted a copy of this submission to the EPA Region IV Office
in Atlanta, Georgia for appropriate fOllow-up actions.
a)
The Agency should transmit a copy of this status report
to the Region IV Office for inclusion in its files on
this reported groundwater contamination.
b)
The Agency should also transmit copies of the submission
and status report to OWWM for further EPA actions if
warranted.
52
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UNITED STATES ENV'IROHMENTAL PROTECTION AGENCY
SU8JECT: status Report*
8EHQ-0680-0346
8EHQ-0680-0346
Page I of 3
Approved ~ ~;to
Revisicf
Needed
(TS-792)
DJ. TE: JUl I
i9dO
fR~ank D. Kover, Chief
Chemical Hazard Identification Branch
TO: Joseph J. Merenda, Director
Assessment Division (TS-792)
Submission Description
The Ethyl Corporation has reported the results of a subchronic
rabbit dermal study on the zinc salt of O,O,bis(1,3-dimethyl-
butyl)phosphorodithioic acid (CAS No. 2215-35-2). The submitter
states that after "relatively large amounts" of the substance
were applied to rabbit skin (five days per week for three
consecutive weeks), microscopic examination of gonadal tissues
showed a decrease in or absence of sperm in 3/6 male rabbits at
the higher dose; 1/6 males in the lower dose group showed a
slight decrease in spermatogenic activity. In addition 1/6 males
at the higher dose reportedly exhibited testicular atrophy.
The Ethyl Corporation states that the above results were
suprising in light of negative spermatogenic effects obtained
from an earlier study (identical protocol) performed on the zinc
salt of the compound which was esterified with a mixture of
isobutanol and 2-ethylhexanol.
In addition, the submitter reports that as compounds of this type
are known to be highly irritating and corrosive to the skin,
"impervious gloves and facial protection are required" for
workers handling the materials. The submitter believes, however,
that inhalation of significant amounts of the chemical would be
most unlikely due to its low vapor pressure.
Submission Evaluation
The important finding is that O,O,bis(1,3-dimethylbutyl)phos-
phorodithioic acid was absorbed through the skin of male rabbits
in sufficient amounts to cause effects in the testes. Similar
application should be made to female rabbits to see if the
ovaries are affected.
*NOTE: This status report is the result of a preliminary
staff evaluation of. information submitted to EPA. Statements
made herei~ are n~t to be regarded as expressing final
Agency pol~cy or ~ntent with respect to this particular
chem~cal. ,Any review of the status report should take into
~ons~der~t~on the fact that it may be based on incomplete
~nforma t~on .
53
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8EHQ-0680-0346
Page 2 of 3
The reported failure of the esterified mix with isobutanol and 2-
ethyl-hexanol (the reaction gives rise to di-isobutyl, di-2-
ethylhexyl and iso-butyl-2-ethylhexylesters) to produce
testicular changes may have been due to inadequate water
solubility to allow penetration of the skin.
Although these zinc salt compounds are not likely to have potent
anti-cholinesterase action, in the absence of a more detailed
description of the clinical and pathological effects in the
rabbits it is not possible to rule out such action. What caused
the stress reaction with its subsequent involution of lymphoid
organs - skin necrosis or something else? What caused the
pneumonitis? Were the testicular changes related to the stress
reaction? Does not the stress (alarm) reaction produce changes
in the adrenal cortex (particularly if lymphoid involution is
still in progress)? Detailed toxicology data, including the
LDSO' are needed.
Current Production and Use
A review of the production range (including importation volumes)
statistics for the zinc salt of 0,0,bis(1,3-dimethylbutyl)
phosphorodithioic acid (CAS. No. 2215-35-2) which is listed in
the initial TSCA Inventory has shown that no 1977 production/
importation was reported or that all of the production range data
reported were claimed as confidential by the manufacturer(s) and
importer(s) and cannot be disclosed (Section 14(a) of the TSCA,
U.S.C. 2613 (a)).**/
The Ethyl Corporation reports that the subject chemical is
manufactured in a closed system and is diluted with oil before
transfer and shipment. The end-use of the compound is in
lubricating oils (generally closed systems) at concentrations of
less than 1%.
Comments/Recommendations
The Ethyl Corporation states that although it believes "that
under the conditions of manufacture and use this material poses
no threat to human health", it is notifying its customers and
employees of the results of the performed studies. In addition,
the company reports that additional testing will be undertaken in
order to verify the observed adverse spermatogenic effects.
a)
The Ethyl Corporation should be requested to provide the
complete report, including test protocols and data, from
the dermal study cited in this submission. In addition,
the complete results from the planned additional
toxicity testing should be requested from the submitter.
**/ The data submitted for the TSCA Inventory including
production range information, are subject to the limitations
contained in the Inventory Reporting Regulations (40 CFR 710).
54
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8EHQ-0680-0346
Page 3 of 3
b)
The Chemical Hazard Identification Branch (CHIB/AD)
review the additional information requested, revise
status report as appropriate, and recommend further
fOllow-up assessment if warranted.
will
this
c)
The Agency should transmit copies of this submission and
status report to NIOSH, OSHA, and CPSC. The Industry
Assistance Office (IAO/OPII) should consider sending the
same materials to manufacturer(s)/imports(s) of the
subject chemical listed in the master TSCA Inventory.
55
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DATE:
SEP I 9 1000
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0680-0347
Page 1 of __3
SU8JECT: Status Report * 8EHQ-0680-0347
'ROM~;ank D. Kover, Chief
ChemTcal Hazard Identification
Approved
/]\)
// '
1/.r/.
Revision
Needed
Branch
TO:
Joseph J. Merenda, Director
Assessment Division
Submission Description
The Dow Corning Corporation has submitted the summarized prelim-
inary results from a 28-day inhalation study of trimethoxysilane
(CAS No. 2487-90-3) in male and female rats. Exposures to the
chemical at chamber concentrations of 0.5, 5.0, and 10.0 parts
per million were reportedly carried out for five (5) days per
week, seven (7) hours per day for four (4) weeks. At the highest
dose, 60% of the animals had died after 2-3 weeks of exposure.
High dose exposure was terminated by the 21st day and the remain-
ing rats sacrificed in order to provide clinical and pathological
data. At the mid-dose, 40% of the animals had died by the end of
the fourth week. Neither the control (air) group nor the low-
dose group experienced any mortality in the experiment. The
submitter reports that significant decreases in both food
consumption and body weight,and general weakness with moderate to
severe lung congestion were observed in the high and mid-dose
animals of both sexes. Significant deviations from control
values were also found in hematological parameters (males and
females; mid and high dose) and blood biochemical parameters
(females; high dose). Subacute to chronic bronchitis and bron-
chiolitis were observed in all rats (male and female) exposed to
trimethoxysilane at 5 and 10 ppm; similar lesions were reportedly
not found in the 0.5 ppm dose group or in the control group.
In addition to submitting the summarized experimental results
described above, Dow Corning also provided a summary of the acute
toxicological properties of trimethoxysilane. According to the
data provided, trimethoxysilane has acute LD50s of 9.33 ml/kg
(oral; rats) and 6.3 ml/kg (dermal; rabbits) and a 4-hr LC50 of
approximately 125 ppm (inhalation; rats). The chemical is also
reported to be moderately irritating to rabbit eyes and slightly
irritating to rabbit skin.
*NOTE: This ~tatus ~eport is the result of a preliminary
staff eva~uat~on of ~nformation submitted to EPA. Statements
made here~~ are n~t to be regarded as expressing final
Agen~y pol~cy or ~ntent with respect to this particular
chem~cal. . Any review of the status report should take into
~ons~der~t~on the fact that it may be based on incomplete
~nformat~on .
56
I:~A '0- 11»-6 f~£V. )-711
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8EHQ-0680-0347
Page 2 of 3
With regard to human health, the submitter reports that
trimethoxysilane should be handled with great care and that
information available to the company indicates that health
incidents due to exposure to this chemical have been rare and of
a minor nature. The submitter also states that no adverse health
effects due to the chemical have been observed at Dow Corning.
Submission Evaluation
Trimethoxysilane may be considered to be an analog of tetraethyl-
silicate, which is known to produce capillary hemorrhages in the
lungs, regardless of the route of administration. Similar
changes occurred in the rats exposed to trimethoxysilane
vapors. The observed bronchiolitis is reminiscent of delayed
phosgene poisoning.
It is also of interest to note that the LD50 via dermal applica-
tion to rabbits is 2/3 of that by oral adm1nistration to rats.
It may be that following oral dosing, the stomach (via acid
hydrolysis) and the liver (via esterase and etherase activities)
metabolize this chemical, which would make less unaltered
compound available for systemic effects.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for trimethoxysilane (CAS. No. 2487-90-3), which is
listed in the initial TSCA Inventory, has shown that between 0
and 1000 pounds of this chemical were reported as produced/
imported in 1977.**/
Although no specific use information on trimethoxysilane was
located in the secondary literature sources consulted, silanes in
general, have been used to make water repellant textiles and
paper, and are the source of hyperpure silicon for use in
semiconductors.
Comments/Recommendations
The Dow Corning Corporation has reported that it is informing all
other manufacturers of organosilicon chemicals of these
toxicological findings on trimethoxysilane.
**/
This production range information does not include any
production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it
include any information which would compromise Confidential
Business Information. The data submitted for the TSCA
Inventory, including production range information, are
subject to the limitations contained in the Inventory
Reporting Regulations (40 CFR 710).
57
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8EHQ-0680-0347
Page 3 of 3
The EPA has recently received and evaluated other TSCA Section
B(e) submissions on silicon chemicals (BEHQ-06BO-0349 and BEHQ-
07BO-0354).
a)
The Chemical Hazard Identification Branch/AD should
review the additional information (i.e. final reports)
which the submitter has stated will be forwarded to the
EPA, revise this status report as appropriate, and
recommend further followup assessment if warranted.
b)
The Agency should transmit copies of this submission and
status report to OSHA and NIOSH. The Industry
Assistance Office (IAO/OTS) should consider sending the
same materials to the manufacturer(s)/importer(s) of
trimethoxysilane listed in the master TSCA Inventory.
58
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
OATE:
SEP 1 8 1980
8EHQ-0680-0348
PAa::r:V:; r;m9,. L
Revision ~
Needed ~
I
I
SUBJECT: Status Report* 8EHQ-0680-0348
'ROM:~;; D. Kover, Chief
. ChemiCal Hazard Identification Branch
TO:
Joseph J. Merenda, Director
Assessment Division
Submission Description
Amchem Products, Inc. has reported that certain chemical products
sold under the brand name Rodine@ (Rodine@ 50, 51, 85, 95, 96,
and 500) have been analyzed and found to contain residual amounts
(i.e. less than 0.5% by weight) of ortho-toluidine (CAS No. 95-
53-4). The methods(s) used for these analyses was not specified
by the submitter.
The submitter reports that the above listed Rodine@ products are
made from a Rodine Base which is an intermediate prepared from an
ortho-toluidine starting material. According to the analytical
data provided by the submitter, the Rodine Base, which comprises
less than 50% by weight of the final formulated Rodine@ products,
contains approximately 0.62% by weight (6200 ppm) ortho-toluidine.
Amchem states that the analyses of these products were prompted by
a report that an Italian company (which manufactures and distri-
butes Rodine@ products under license from Amchem) had been ordered
to discontinue the sale of Rodine@ products which utilize ortho-
toluidine as an ingredient.
The submitter states that during the time its Rodine@ products
have been manufactured and sold (more than 40 years), the company
has not received any reports of significant injury to health or
the environment resulting from use of these products. The
submitting company also provided technical data sheets for the
Rodine@ products listed above.
Submission Evaluation
O-toluidine can be absorbed through the lungs, skin and g.i. tract
and can cause methemoglobinemia, anemia, liver injury, kidney
injury and skin irritations. In addition, substituted anilines,
such as o-toluidine, are usually more potent carcinogens than is
aniline.
*NOTE: This status report is the result of a preliminary
staff evaluation of. information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chem~cal. ,Any review of the status report should take into
7ons~der~t~on the fact that it may be based on incomplete
~nformat~on .
59
E~A '0"" U~ IIU:". ~71i1
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8EHQ-0680-0348
Page 2 of 4
Although earlier studies of the carcinogenicity of o-toluidine
have had flaws, a recent National Cancer Institute carcinogenicity
study does not have such flaws and clearly demonstrates that 0-
toluidine is a potent and versatile carcinogen.
The NCI bioassay of o-toluidine hydrochloride was conducted by
administering the test chemical in feed to F344 rats and B6C3Fl
mice. Groups of 50 rats of each sex and 50 mice of each sex were
administered o-toluidine hydrochloride at one of several doses,
either 3,000 or 6,000 ppm for the rats and either 1,000 or 3,000
ppm for the mice, for 101 to 104 weeks. Matched controls consist-
ed of 20 untreated rats of each sex and 20 untreated mice of each
sex. All surviving rats and mice were killed at the end of
administration of the test chemical. Mean body weights of dosed
male and female rats and mice were lower than those of correspond-
ing matched controls and were dose related. Mortalities of the
male and female rats were dose related and were relatively high at
the end of the bioassay. Mortalities of the male and female mice
were not, however, significantly affected by administration of the
test chemical.
In rats, the administration of. the test chemical induced several
types of sarcomas of the spleen and other organs in both males and
females, i.e. mesotheliomas of the abdominal cavity or scrotum in
males, and transitional-cell carcinomas of the urinary bladder in
females. Administration of the 0- toluidine hydrochloride also
resulted in increased incidences of fibromas of the subcutaneous
tissues in the males and fibroadenomas or adenomas of the mammary
glands in the females.
In mice, hemangiosarcomas were induced at various sites in the
males, and hepatocellular carcinomas or adenomas were induced in
the females.
Current Production and Use
The submitter reports that the total amount of distributed Rodine~
products which may contain residual ortho-toluidine, was less than
1 million pounds in 1979. The company also reports that the 1980
figures are not expected to exceed those for 1979.
According to the technical data sheets provided, these Rodine~
products (i.e., Rodine@ 50,51,85,95,96, and 500) are used at
various dilutions as acid inhibitors in metal treatment (e.g.
pickling).
A review of the production range (includes importation volumes)
statistics for ortho-toluidine (CAS. No. 95-53-4), which is listed
in the initial TSCA Inventory, has shown that between 1 million
60
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8EHQ-0680-0348
Page 3 of 4
and 10 million pounds of this chemical were produced/imported in
1977.**/
Comments/Recommendation
Amchem Products, Inc. reports that it is reviewing this situation
involving the presence of residual ortho-toluidine in certain of
its Rodine@ products, and will take appropriate actions.
In 1974, OSHA set the current occupational standard for ortho-
toluidine exposure at an 8-hour time-weighted average (TWA) of 5
ppm in air (39 CFR 23540). An evaluation of the carcinogenic risk
of ortho-toluidine exposure to man has been prepared by the
International Agency for Research on Cancer (IARC Monograph, Vol.
16, 1978). A working draft dossier on ortho-toluidine was
prepared by a contractor on March 2, 1979, for the Interagency
Testing Committee (ITC).
Based on the results of its recent bioassay of ortho-toluidine
hydrochloride, the National Cancer Institute (1979) has concluded
that:
"Under the conditions of this bioassay, o-toluidine hydro-
chloride was carcinogenic in both male and female F344 rats
and B6C3Fl mice, producing a significant increased incidence
of one or more types of neoplasms." (DHEW Publication No.
(NIH) 79-1709)
a)
Amchem Products, Inc. should be requested to describe
those actions it states will be taken in response to the
detection of o-toluidine in certain of its Rodine@ pro-
ducts. The company should also be requested to describe
the actions it takes to warn workers and customers, and
to reduce and/or eliminate the exposure to o-toluidine in
the subject products.
b)
In this particular case, Amchem's direct submission of
this section 8(e) information to the Assistant Adminis-
trator's Office (OPTS) did not unduly burden the EPA's
processing of the notice. However, it should be brought
to the submitter's attention that the substantial risk
information reporting requirements (Part IX of the March
16, 1978, "Statement of Interpretation and Enforcement
**/ This production range information does not include any
-- production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor dges it
include any information which would compromise Confidential
Business Information. The data submitted for the TSCA
Inventory, including production range information, are
subject to the limitations contained in the Inventory
Reporting Regulations (40 CFR 710).
61
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8EHQ-0680-0348
Page 4 of 4
Policy: Notification of Substantial Risk" (43 FR 11110»
clearly specify that TSCA section 8(e) notices are to be
sent directly to the Document Control Officer, Management
Support Division, Office of Pesticides and Toxic
Substances (WH-557), Environmental Protection Agency, 401
M Street S.W., Washington, D.C. 20460. A copy of the
EPA's March 16, 1978, policy statement should be sent to
the submitter.
c)
It is recommended that a Chemical Hazard Information
Profile (CHIP) on ortho-toluidine be considered for
preparation.
d)
The Agency should transmit a copy of this submission and
status report to NIOSH, OSHA, and CPSC.
62
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0.01. TE;
U HITED STATES ENVIRONMENTAL PROTECTJON AGENCY
8EHQ-0680-0349
Page 1 of 3
SEP I 9 1980
SUBJECT: Status Report *8EHQ-0680-0349
F'~~:: D. Kover. Chief
Chemical Hazard Identification Branch
Approved
Revision
Needed
TO:
Joseph J. Merenda, Director
Assessment Division
Submission Description
The Union Carbide Corporation has reported the summarized results
from several acute toxicity tests on Silicone Y-6607 which was
reported for the TSCA Inventory as "Siloxanes and Silicones,
dimethyl, di(methylamino) terminated" (CAS No. 67762-92-9). The
submitter states that although "nothing remarkable or unusual"
was found during routine acute animal toxicity range finding
tests (oral: dermal: skin and eye irritation), the results from
subsequent short-term inhalation studies in rats showed an
unexpected level of toxicity-
The submitter reports that all test animals (6 rats per group)
died following timed exposures to "substantially saturated
vapors" of Silicone Y-6607 for periods of 195 seconds, 6.5
minutes, 13 minutes, or 26 minutes. At the shorter intervals,
some or all of the animals died between 1 to 6 days after their
removal from the exposure condition. An exposure for 97 seconds
resulted in the death of 50% of the test animals after exposure
was terminated. A 49 second exposure did not result in any
deaths, although toxic effects were reportedly observed. The
submitter states that the data from this inhalation study allows
the calculation of a median lethal time (LtsO) of 98 seconds in
"substantially saturated vapors" of Silicone Y-6607.
The submitter also reports that a 4-hour inhalation LCSO of 774
parts per million was determined from a metered vapor concentra-
tion study of Silicone Y-6607 in rats.
Union Carbide states that lung damage was observed in the rats
which died during both short-term inhalation studies. In addi-
tion, the submitter reports that eye opacities were found in the
animals exposed to "substantially saturated vapors" of Silicone
Y-6607.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Stateme~ts
ffiade herein are not to be regarded as expressinc final
A~e~~y policy or i~tent with respect to this pa~ticular
c.'1em~cal. ,Any reVlew of the status report should take into
~o~slder~tlon the fact that it may be based on incomplete
In!Ormatlon. 63
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8EHQ-0680-0349
Page 2 of 3
In providing these data, the Union Carbide Corporation states
that it has "no basis at present to suggest a mechanism regarding
the observed lethal effects, nor even to conclude that effects
are due directly to the chemical itself as opposed to conversion
products derived from the chemical. From evaluation of the
foregoing tests results, it is the conclusion of Union Carbide's
toxicologists that exposure to moderately high concentrations of
this chemical appears to present two hazards: namely, damage to
the respiratory tract leading to potentially lethal asphyxsia and
moderately severe eye irritation. Further, prolonged exposure to
saturated vapors may be fatal, either immediately or subsequent
to exposure~ shorter periods of exposure may initiate toxic
effects in the lungs which become progressive and ultimately
fatal."
Submission Evaluation
The Silicone Y-6607 product (dimethyl-, di(methylamino)-
terminated siloxanes and silicones) probably contains sufficient
amounts of low molecular weight components to yield (upon
hydrolysis) dimethylamine and finely divided dimethyl siloxane
diols. Low molecular weight compounds which contain the Si-N
linkage are not stable in aqueous environments, including the
lungs and eyes. The observed eye opacities in the exposed rats
suggest the presence of dimethylamine. Dimethylamine, like
ammonia, is a severe eye and upper respiratory tract irritant.
Such irritant action would also account for the acute rat deaths
observed during the 6.5 minute exposure to the "substantially
saturated vapors." Such deaths can be caused by cardiovascular
and respiratory inhibitory reflexes. In humans, the operation of
such reflexes for more than 60-80 seconds usually results in
death. If the exposure is less severe (as in the 90 second
chemical exposure to rats) recovery occurs but extensive damage
to the trachea, bronchi, bronchioles and the lungs may develop
and would result in bronchitis, bronchiolitis, and pneumonia
after several days (as was seen in the rats in 2-5 days following
exposure). The toxicity reportedly observed but not described
for the rats exposed to the saturated Silicone Y-6607 vapors for
49 seconds, also suggests the presence of an irritant.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for CAS. No. 67762-92-9 (dimethyl-, di(methylamino)-
terminated silicones and siloxanes) which is listed in the
initial TSCA Inventory. has shown that no 1977 production!
importation was reported or that all of the production range data
64
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8EHQ-0680-0349
Page 3 of 3
reported were claimed as confidential by the manufacturer(s) and
importer(s) and cannot be disclosed. (Section 14(a) of the TSCA,
U.S.C. 2613 (a)). **/
With the exception of one unspecified external use, the
reports that Silicone Y-6607 is used as an intermediate
manufacture of other chemicals within the Union Carbide
tion. No other information on the uses of this product
located in the secondary literature sources consulted.
submitter
in the
Corpora-
was
Comments/Recommendations
The Union Carbide Corporation states that the completed final
reports of the inhalation studies will be provided to the EPA.
In addition, the submitting company reports that all persons
potentially exposed to Silicone Y-6607 are being advised of this
toxicity information submitted to EPA under TSCA Section 8(e).
The company also reports that its workers are being advised of
safety and health protection measures to be implemented in the
event of spills or releases of Silicone Y-6607.
The EPA has recently received and evaluated other Section 8(e)
submissions on silicon chemicals (8EHQ-0680-0347 and 8EHQ-0780-
0354) .
a)
The Chemical Hazard Identification Branch (CHIB/AD)
will review the final reports from the cited studies
when received, revise this status report as
appropriate, and recommend further followup
assessment if warranted.
b)
The EPA should transmit copies of this submission
and status report to OSHA and NIOSH. The Industry
Assistance Office (IAO/OTS) should consider trans-
mitting the same materials to all manufacturer(s)/
importer(s) listed in the master TSCA Inventory.
**/
The data submitted for the TSCA Inventory, including produc-
tion range information, are subject to the limitations con-
tained in the Inventory Reporting Regulations (40 CFR 710).
65
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DATE:
NOV
I 3 :980
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8lliQ-0780-0350
Page 1 of 3
Approved ~
Revision I
Needed
~~"
SUBJECT:
Status Report* 8EHQ-0780-0350
'Ro./~k D.
.......... Chemical
Kover, Chief
Hazard Identification Branch
TO:
Joseph J. Merenda,
Assessment Di~ision
Director
Submission Description
The Procter and Gamble Company has provided the complete results
from a battery of mutagenicity tests on Acid Green 3 (CAS No.
4680-78-8). The submitter. reported that althou9h the results
from an in vivo cytogenetics test in rats were negative, Acid
Green 3 was demonstrated to be mutagenic in an in vitro mouse
lymphoma cell assay. The results from an in vitro bacterial cell
mutagenicity assay (Ames test) were reported to be equivocal.
Procter and Gamble also provided copies of several scientific
papers published between 1953 and 1966, which implicated Acid
Green 3 as a suspect animal carcinogen.
In evaluating the potential risk presented by the commercial use
of this dye, Procter and Gamble has reportedly taken the position
that "if a chemical can cause mutagenic response in animals or
living cells, and that exposure of unknown magnitude to humans
and the environment occurs, the information could be viewed as
subject to 8(e) reporting." However, the submitter also states
that the provided information "does not allow a firm conclusion
that Acid Green 3 presents a substantial risk to man...."
Submission Evalution
Acid Green 3 was tested in the Ames Salmonella/microsomal assay
using strains TA1535, TA1537, TA1538, TA98 and TAIOa both with
and without metabolic activation (liver enzyme prepared from rats
pretreated with Aroclor 1254). The results obtained with all
strains without metabolic activation were reported to be
uniformly negative. In addition, the results with strains
TA1537, TA1538, TA98, and TAIOO with metaholic activation were
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
66
r;~.. '0'"' U»-4 IIIIE". ..,11
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8E1IQ-0780-0350
Page 2 of 3
negative. When tested with strain TA1535 with metabolic
activation, Acid Green 3 produced neither a clearly negative nor
a clearly positive response. ~he Agency agrees with the
submitter's overall interpretation that the results obtained from
this in vitro test system with Acid Green 3 were equivocal.
Acid Green 3 was also tested for in vitro mutagenicity in Mouse
Lymphoma L5178Y cells. The assay was performed both with and
without enzyme activation by an 8-9 preparation from the livers
of male rats pretreated with Arocolor 1254. The EPA agrees with
the submitter's interpretation of the provided data. Acid Green
3 was shown to be mutagenic for L5178Y cells when tested without
enzyme activation: no activity was observed in the presence of
metabolic activation.
Acid Green 3 was tested for its ability to induce chromosomal
aberrations in the bone marrow of male and female albino rats.
The test material was administered by gavage once daily for 5
days. At the end of the treatment period, the animals were
sacrificed and slides prepared from femoral bone marrow were
stained with Giemsa stain. The slides were then analyzed for
chromosomal abnormalities such as deletions, exchanges, rings,
gaps and breaks. The submitter concluded that Acid Green 3 did
not induce chromosome aberrations in the femoral bone marrow of
treated rats. Based on a review of the experimental data
provided, the EPA agrees.
The Agency believes that the following overall statements can be
made about the mutagenicity test data submitted by Procter and
Gamble on Acid Green 3:
1. Acid Green 3 is a direct-acting mutagen which causes point
(gene) mutations in L5178Y mouse lymphoma cells in
culture. It is inactive in this same system when tested
with enzyme activation.
2. Acid Green 3 is at most marginally active in strain TA1535
when tested with enzyme activation in the Ames Salmonella/
microsomal assay. Strain TA1535 is reverted by agents
which cause base-pair mutations in the DNA.
3. Acid Green 3 does not cau&e chromosomal aberrations in rat
femoral bone marrow after five days of treatment. No
other conclusions about its mutagenic potential can be
drawn from this study.
With regard to the carcinogenicity of Acid Green 3, the
International Agency for Research on Cancer (IARC) has reviewed
and evaluated data which demonstrated this chemical to be
carcinogenic in rats, producing hepatic tumors after oral
administration, local sarcomas following subcutaneous injection,
and benign mammary tumors after continual (100 weeks) fur/skin
contact with the dye powder (IARC Monograph, Vol. 16, 1978).
67
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8EHQ-0780-0350
Page 3 of 3
Current production and Use
A review of the production range (includes importation volumes)
statistics for Acid Green 3 (CAS No. 4680-7R-8) which is listed
in the initial TSCA Inventory, has shown that between 1000 and
10,000 pounds of this chemical were reported as produced/imported
in 1977. **/
The Procter and Gamble Company reports that it is using Acid
Green 3 in an unspecified experimental product which may have
possible future commercial purposes. Acid Green 3 has been used
as a food coloring, in pigments, in paper, wood, wool, silk, and
leather dyes, and as a biological stain and indicator. It should
be noted, however, that in late 1966, the use of Acid Green 3 as
a colorant in foods, drugs, and cosmetics was forbidden by the
U.S. Food and Drug Administration (FDA).
Comments/Recommendations
In its development work, the Procter and Gamble Company reports
that it "has treated Acid Green 3 as a suspect carcinogen and has
severely restricted exposure to the chemical on the basis of this
assumption."
a) The Procter and Gamble Company should be requested to
describe the actions it has taken to warn workers and
others, and to reduce, "severely restrict", and/or
eliminate exposure to Acid Green 3.
b) Acid Green 3 is listed on the EPA's proposed TSCA section
8(a) Level A rule (45 FR 13646).
c) The Chemical Hazard Identification Branch (CHIB/AD) will
transmit copies of this status report to NIOSH, OSHA,
CPSC, FDA, NCI, and OWWM/EPA.
d) The Industry Assistance Office (IAO/OTS) should consider
sending copies of the status report to the manufac-
turer(s)/importer(s) of Acid Green 3 listed in the Master
TSCA Inventory.
**/ This production range information does not incl~de any
-- production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it
include any information which would compromise Confidential
Business Information. The data submitted for the TSCA
Inventory, including production range information, are
subject to the limitations contained in the Inventory
Reporting Regulations (40 CFR 710).
68
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0780-035l
OJ. TE: 8EHQ-0880-035l Supplement
'.OJECT, S~~U: °R~:rt *8EHQ-0780-0351 Page Al 0:0:t/1-. ~8/to
. /711Jt- 8EHQ-0880-035l Supplement pp e
FR~rank D. Kover, Chief Revisi
Chemical Hazard Identification Branch Needed
TO:
Joseph J. Merenda, Director
Assessment Division
Submission Description
In its initial submission, the A. B. Dick Company reported that
two of its electrophotographic copying toners (#62~2000
manufactured by DeSoto Inc. and #62-6100 manufactured by Agfa-
Gevaert of Belgium) were found to be mutagenic in the Ames Sal-
monella (bacteria) test. The submitter reported, however, that
due to manufacturing process changes made by DeSoto Inc., the
mutagenic activity of that particular toner had been eli~inated.
A. B. Dick also reported that Agfa-Gevaert had obtained results
of Ames tests which showed that its toner was negative for
mutagenicity. The submitter stated that the results of Agfa-
Gavaert's tests were requested for review and will be forwarded
to the EPA.
In the supplemental submission, the A. B. Dick Company provided
the complete results of the Ames tests performed with the
modified-process DeSoto toner.
Submission Evaluation
In the initial submission, DeSoto toner (#62-2000) was reported
to be mutagenic for S. ty~himurium strains TA1537 and TA98
without metabolic activatl0n and for strain TA1537 with metabolic
activation. Agfa-Gevaert toner (#62-6l00) was reported to be
mutagenic for strains TA1537, TAl538 and TA98, both with and
without metabolic activation. In addition, DeSoto toner (#62-
2000) induced a dose-related increase in the number of mutants
with strain TA98 with metabolic activation and with strain TAIOO
without metabolic activation. However, the absolute increase in
the number of induced mutants was less than 3x the control value
with strain TA98 and less than 3.5x the control value with strain
TAlOO. Therefore, this toner was not considered by the
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
ffiade herei~ are n~t to be regarded as expressing final
A~en~y pol~cy or l~tent with respect to this particular
cnem~cal. . Any reVlew of the status report should take into
~o~slder~tlon the fact that it may be based on incomplete
lD_ormatlon.
69
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8EHQ-0780-035l
8EHQ-0880-035l Supplement
Page 2 of 3
performing laboratory to be mutagenic for strain TA98 with
metabolic activation or for strain TAIOO without metabolic
activation. Agfa-Gevaert toner (#62-6100) also produced an
increase in the number of induced mutants in strain TAIOO both
with and without metabolic activation, but was not considered by
the performing laboratory to be mutagenic because the number of
induced mutants was less than 3.5x the number of mutants in the
control. In addition, nine (9) other A. B. Dick Company toners
were tested and reported to be non-mutagenic.
Based on a review of the provided in vitro data, the EPA believes
that the results as reported in the-initial submission were
correct. DeSoto toner (#62-2000) was mutagenic for S.
typhimurium strain TA1537 both with and without metabolic
activation and for strain TA98 without metabolic activation.
addition, Agfa-Gevaert toner (#62-6100) was mutagenic for S.
typhimurium strains TA1537, TA1538 and TA98 both with and without
metabolic activation. The results obtained with DeSoto toner
(#62-2000) in strain TA98 with metabolic activation and strain
TAIOO without metabolic activation, and Agfa-Gevaert toner (#62-
6100) in strain TAIOO both with and without metabolic activation
are equivocal. In addition, the nine (9) other tested A. B. Dick
toners were, as reported, without activity in the Salmonella/ mi-
crosome system.
In
According to data provided by the A. B. Dick Company in the
supplemental submission, DeSoto's modified-process toner
(#968X334) was tested for mutagenic activity with S. typhimurium
strains TA1535, TA1537, TA1538, TA98 and TAIOO. Toner #968X334
was reported to be nonmutagenic for those bacterial strains when
tested both with and without metabolic activation.
Based on a review of the data provided in the supplemental
submission, the EPA believes that the results are correct.
Modified-process DeSoto toner #968X334 was, as reported, without
activity in the Salmonella/Microsomal Assay for bacterial
mutagenicity-
Current production and Use
No information on the production volumes of the subject
electrophotographic copying toners was provided by the submitter
or located in the secondary literature sources consulted.
Comments/Recommendaitons
It is the A. B. Dick Company's stated opinion is that their
toners pose no health hazard to persons operating or servicing A.
B. Dick equipment using these toners under normal conditions.
The submitter reported that both DeSoto Inc. and Agfa-Gaevert
were advised of the original findings of in vitro mutagenicity.
Based on those initial findings, A. B. Dick informed DeSoto Inc.
that no additional toner product would be accepted until such
time as scientific evidence verifying the elimination of the
mutagenic element was received by the A.B. Dick Company.
70
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8EHQ-0780-035l
8EHQ-0880-035l Supplement
Page 3 of 3
The EPA is currently reviewing scientific data obtained (FYI-
0480-0070) from the Xerox Corporation relating to similar in
vitro findings and other in vivo toxicities of Xerox tonerS-and
toner materials. The EPA has also received information from the
University of Texas Medical Branch, Galveston, Texas (Connor,
1980, unpublished data) concerning the mutagenic and cell
transforming activities (in vitro) of organic solvent extracts of
a photocopying toner. --
NIOSH (DHEW, 1978) has published a Criteria Document which
addresses the recommended standard for the the occupational
exposure to carbon black.
The Chemical Hazard Identification Branch (CHIB/AD) is currently
updating its Chemical Hazard Information Profile (CHIP) on carbon
black to include a discussion of these new and other related
data.
The EPA has requested the Occupational Safety and Health
Administration (OSHA) and the Natonal Institute for Occupational
Safety and Health (NIOSH) to review and evaluate the information
obtained by the EPA concerning carbon black and electrophoto-
graphic toners and toner materials, and to recommend, if
warranted, appropriate worker safety and health protection
measures. The EPA has agreed to cooperate with NIOSH and OSHA in
such efforts.
a) The Chemical Hazard Identification Branch/AD will
transmit copies of this status report to NIOSH, OSHA,
CPSC, NCI, FDA, OANR/EPA, OWWM/EPA, and ORD/EPA.
71
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DAT!:
SEP I 6 1980
8EHQ-0780-0352
Page 1 of 4
-- ,\ /
Approved ,~~rV.,/" '1/7
SUBJECT:
Status Report* 8EHQ-0780-0352
"ROM?~~ank D. Kover, Chief
\ Chemical Hazard Identification Branch
Revision
Needed
TO:
Joseph J. Merenda, Director
Assessment Division
Submission Description
The Montgomery Elevator Company has reported that certain
elevators are powered by hydraulic systems which may contain
polychlorinated biphenyls(PCB)-contaminated fluids. This report
was prompted by the detection of 67 ppm PCBs in the hydraulic
fluids of an elevator located in the Food and Drug Administration
offices in Minneapolis, Minnesota. The subject elevator was manu-
factured by, but no longer owned by the submitting company- The
submitter believes that the detected PCBs are the result of the
elevator owner's use of a product called Wynn's Friction-Proofing
Fluid. The submitting company believes that although this
product was removed from the market in 1971, residual amounts of
the material may still remain in use.
The submitter also believes that because this type of hydraulic
powered elevator is typically found in small businesses and
apartment buildings, the owners. may not be fully aware of the
possible presence of PCBs in such systems, and in addition, may
be unaware of the EPA's current and proposed rules on PCBs.
Submission Evaluation
PCBs are among the most stable chemicals known. Once released
into the environment, they decompose very slowly over a period of
several decades. Due to this stability, they remain in the
environment and are taken up and accumulated in fatty tissues.
This accumulation in organisms is significant because PCBs are
hazardous to health at extremely low levels. Specifically, PCBs
have been shown to cause chronic toxic effects in many species at
less than 10 parts per million (ppm). There are well documented
tests on laboratory animals which show that PCBs can cause
reproductive failures, gastric disorders, skin lesions, tumors,
and other effects of concern.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
informa tion.
72
E~A '0'- II" fIllE\'. ~711
-------
8EHQ-0780-0352
Page 2 of 4
In man, PCBs can enter the body through the lungs, the gastroin-
testinal tract, and the skin. After absorption, PCBs are circu-
lated in the blood throughout the body and are stored in fatty
tissue and a variety of organs, including the liver, kidneys,
lungs, adrenal glands, brain, heart, and skin.
The submitter's finding of 67 ppm PCBs in an elevator hydraulic
fluid does indicate the opportunity for human exposure during
routine servicing and possibly during operation.
Current Production and Use
Polychlorinated biphenyls (PCBs; CAS No. 1336-36-3) are members
of a broad family of organic chemicals known as chlorinated
hydrocarbons. Although PCBs may be produced naturally in the
environment, almost all PCBs in existence today have been
synthetically manufactured.
Primary uses of PCBs were, and continue to be, electrical trans-
former cooling liquids and capacitor dielectric fluids. Most of
the PCBs marketed in the United States are still in service in
these applications. However, PCBs have also been used in a vari-
ety of other applications such as heat transfer systems and
hydraulic fluids; dye carriers in carbonless copy paper; plasti-
cizers in paints, adhesives, and caulking compounds; fillers in
investment casting wax; and as dust control agents, sealants, and
coatings on roads.
PCBs have heavy oil-like consistencies, have high boiling points,
and weigh approximately 10-12 pounds per gallon. Other important
properties include: a high degree of chemical stability, low
solubility in water, high solubility in fat, low flammability,
and low electrical conductivity. These physical/chemical
properties have made PCBs commercially attractive.
Legislative and Regulatory Actions on PCBs
A report by the President's Council on Environmental Quality in
May 1972, recommended that Congress enact the Toxic Substances
Control Act (TSCA) to provide regulatory authority required to
deal with PCBs and other chemicals. Before the passage of the
Toxic Substances Control Act, EPA could only regulate facilities
that discharged PCBs into navigable waterways. On July 23, 1976
(41 FR 30468), EPA proposed to ban the discharge of PCBs into
waterways by electrical transformer and capacitor
manufacturers. The final rule (42 FR 6532) was promulgated under
Section 307(a) of the Federal Water Pollution Control Act on
February 2, 1977.
At the time the Toxic Substances Control Act was passed (1976),
there was widespread recognition and concern regarding the
serious, adverse effects PCBs have on the environment and human
health. Congress responded to this problem by including a
73
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8EHQ-0780-0352
Page 3 of 4
special section in TSCA, Section 6(e),
facturing, processing, distribution in
and providing for adequate marking and
in use.
prohibiting future manu-
commerce, and use of PCBs
disposal of the PCBs still
Since then, EPA has implemented the provisions under Section 6(e)
of TSCA. The following is a summary of these actions:
On February 17, 1978, EPA promulgated the PCB Marking and Disposal
Rule (40 CFR 761). In this rule, EPA established specific require-
ments for the marking and disposal of PCBs according to the nature
and concentration of the PCBs in question.
On May 31, 1979, EPA promulgated the PCBs Manufacturing, Processing,
Distribution in Commerce, and Use Prohibitions (PCB Ban Rule) (40
CFR 761). Specifically. this rule:
1)
Prohibits all manufacturing of PCBs after July 2,
1979, unless specifically exempted by EPAj
2)
Prohibits the processing, distribution in commerce,
and use of PCBs, except in a totally enclosed manner
after July 2, 1979, unless specifically authorized by
EPAj
3)
Authorizes certain processing, distribution in
commerce, and use of PCBs in a non-totally enclosed
mannerj
4)
Prohibits all processing and distribution in commerce
of PCBs after July 1, 1979, unless specifically
exempted by EPA.
It should be noted that the regulatory scheme developed in the PCB
Marking and Disposal Rule and the PCB Ban Rule was designed to
minimize exposure to humans and the environment while allowing the
continued use of those PCBs which are totally enclosed or have been
granted authorizations or exemptions. "Totally enclosed manner" was
defined by Congress in TSCA to mean a manner which will ensure no
significant exposure of human beings or the environment to PCBs, as
determined by EPA by rule (Section 6(e)(2)(C)). The final ban rule
provides that human or environmental exposure to any detectable
quantities of PCBs shall be deemed significant.
The use of intact, non-leaking PCB transformers, PCB-contaminated
tranformers, electromagnets, and PCB capacitors and equipment con-
taining such capacitors is considered a "totally enclosed"
activity. However, servicing of such equipment is not considered a
totally enclosed activity.
Congress provided a mechanism to allow exceptions to the statutory
ban of non-totally enclosed activities (Section 6(e)) by permitting
EPA to authorize some activities which are not totally enclosed. In
order to authorize an activity, EPA must find that continuation of
74
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8EHQ-0780-0352
Page 4 of 4
the activity does not present an unreasonable risk of injury to
human health or to the environment.
Exceptions may also be made to the manufacturing ban or to the ban
on PCB processing and distribution in commerce. TSCA referred to
these exceptions as "exemptions" (Section 6(e)(3)(B)). Before an
exemption can be granted, there must be a determination that an
unreasonable risk is not present and that good faith efforts have
been made to develop substitutes for the PCBs.
The following non-totally enclosed activities have been granted
authorizations until July 1, 1984: the servicing of PCB-containing
transformers; the use of PCBs in heat transfer systems; the use of
PCBs in hydraulic systems; the servicing of PCB electromagnets; the
use of small quantities of PCBs for research and development; and
the use of PCBs as a microscopy mounting medium. The use of PCBs in
natural gas pipeline compressors was authorized until May 1, 1980.
Authorizations until January 1, 1982, have been granted for the use
of PCBs in mining equipment, the servicing of mining equipment, and
the use of PCBs in pigments. Finally, due to the significant
quantities of carbonless copy paper that contain small amounts of
PCBs in government, industry, and personal files, the rule
authorizes continued maintenance of such paper.
On May 9, 1980, the EPA, the Food and Drug Administration and the
Department of Agriculture, jointly published a proposed rule which
would ban the use of PCBs (including PCB use in hydraulic systems)
in facilities producing and/or storing agricultural chemicals, food,
feed, and food packaging (45 FR 30980).
Comments/Recommendations
Although PCBs remain in use, EPA carefully considers the circum-
stances and conditions of each remaining use. Most of the remaining
PCBs are in totally enclosed electrical equipment which will be
replaced in the next few years as this equipment is serviced or
retired. Most importantly, EPA has strict servicing, storage and
disposal requirements to protect against escape of the PCBs into the
environment. Further, authorization of each remaining use will
continue to be reviewed on a regular basis to ensure that they do
not present an unreasonable risk to human health and the
environment.
a)
The Agency should transmit copies of this submission and
status report to the PCB Team/CAD/OCC for appropriate
followup attention.
75
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DJ. T E:
OCT I 5 1980
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0780-0353
Page 1 of 3
:::::::~~~
Needed
SUBJECT: Status Report* 8EHQ-0780-0353
F'~ D. Kover, Chief
Chemical Hazard Identification Branch
TO: Joseph J. Merenda, Director
Assessment Division
Submission Description
The Standard Oil Company (SO HI 0) has provided the interim results
of a lifetime mouse skin-painting study of two grades of an
aromatic petroleum pitch (CAS No. 68187-58-6) which ~s derived
from an intermediate clarified oil solvent extract (CAS No.
64741-62-4). According to the provided summary, aromatic
petroleum pitch Grade 170 and Grade 290 were shown by the 59th
week of the study to be comparable in tumorigenic potential to
that of the positive control (benzo(a) pyrene). The submitter
reports that histopathological confirmation of the grossly-
diagnosed lesions has not been completed by the performing
laboratory, but will be provided upon completion to the EPA. The
submitter also reports that the results obtained "are corrobora-
tive of the generally known oncogenic activity of polynuclear
aromatic hydrocarbons". The submitter states that the uses of
this product and the methods of handling do not result in
substantial exposure under conditions which would make the
polynuclear hydrocarbons bioavailable.
Submission Evaluation
The average time for appearance of papillomas was approximately
the same for both grades of the aromatic petroleum pitch as that
observed for benzo(a)pyrene. The percent malignant and benign
tumors based on number of starting animals was 90% for
benzo(a)pyrene, 60% for Grade l70(a) (75% if the inadvertanly
killed animals are deducted), ~O% for Grade l70(b) and 80% for
Grade 290. Further evaluation of the potency of these grades
would require a quantitative analysis for known carcinogenic
polynuclear aromatic hydrocarbons.
*~OTE: This status report is the result of a prell' , r
..... <= f 1 ' f. . mlna. Y
s~a..... eva uatlon 0 lnformation submitted to EP~ St r t
rr-de h ro' - . a -eme:1 s
I.a ~ e__l~ are n?t to be regarded as expressing final
A?en~y fOllcy or l~tent with respect to this pa~ticular
c.'lerr.7ca_. . Any reVlew of the status report should tak '
~onslderatlon the fact that it may be based on in el lnto
lnEormation. 76 - comp ete
-------
8EHQ-0780-0353
Page 2 of 3
Although it may be true that the experimental application of the
test materials dissolved in toluene made them more bioavailable
than would occur under normal conditions of use, the possibility
exists for the pitch to dissolve, to some extent, in oily sweat
allowing some of the material to penetrate the pilosebaceous
glands. In addition, it would be of interest to know if the uses
of aromatic petroleum pitch (e.g. in foundry molds) results in
vaporization or dust generation giving rise to inhalation
exposure.
Current Production and Use
According to the TSCA Inventory, aromatic petroleum pitch is the
residue from the distillation of thermal cracked residuum and/or
catalytic cracked clarified oil with a softening point of 40GC to
l80GC. It is composed primarily of a complex combination of
three or more membered condensed ring aromatic hydrocarbons.
A review of production range (includes importation volumes)
statistics for aromatic petroleum pitcn (CAS No. 68187-58-6)
which is listed in the initial TSCA Inventory, has shown that no
1977 production/importation was reported or that all of the
production range data reported were claimed as confidential by
the manufacturer(s) and importer(s) and cannot be disclosed.
(Section 14 (a) of the TSCA, U.S.C. 2613 (a)). **/
The submitter reports that aromatic petroleum pitch is used as an
impregnant in cellulose fiber drainpipe and as a binder in the
manufacture of foundry molds and molded skeet targets. The
submitter also reports that aromatic petroleum pitch is a
preferred alternative to coal tar pitch in its applications.
Comments/Recommendations
The Agency has previously evaluated a TSCA Section 8(e) submis-
sion (8EHQ-1078-0253) from the Standard oil Company (SOHIO)
concerning the carcinogenic activity (lifetime mouse skin-paint-
ing study) of the intermediate clarified oil solvent extract
starting material (CAS No. 64741-62-4).
a)
The Standard oil Company (SOHIO) should be requested to
provide the EPA with complete copies of subsequent interim
reports and the final report from this lifetime mouse
skin-painting study of aromatic petroleum pitch. The
submitting company should also be requested to describe
the actions it has taken in light of the reported toxicity
data to warn workers, customers, and other producers, and
to reduce and/or eliminate exposure to aromatic petroleum
pitch.
**/ The data submitted for the TSCA Inventory including produc-
-- tion range information, are suhject to the limitations con-
tained in the Inventory Reporting Regulations (40 CFR 710).
77
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8EHQ-0780-0353
Page 3 of 3
b)
The Chemical Hazard Idenitification Branch (CHIB/AD will
transmit copies of this status report to OSHA, NIOSH,
CPSC, and DOE. The Industry Assistance Office (IAO/OTS)
should consider sending the same information to the
manufacturer(s)/importer(s) of aromatic petroleum pitch
listed in the master T$CA Invefltory.
78
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
SU8JECT:Status Report* 8EHQ-0780-0354
>{}f-
~R~'Frank D.
Chemical
Kover, Chief
Hazard Identification Branch
8EHQ-0780-0354
Page 1 of 3
Approved ~ ~
Revisionl
Needed
01. T E;
I\:OV I 2 lC1e., \
I'll I\..,-,Ci j
TO~oseph J. Merenda, Director
Assessment Division
Submission Description
MCB Manufacturing Chemists, Inc. submitted a recently obtained
copy of results from a subchronic in vivo study of silica gel
(CAS No. 63231-67-4) and quartz (crystalline silica; CAS No.
14808-60-7) dusts. This study, which was reported to have been
performed in Germany in 1967, involved intratracheal and
intraperitoneal injections of the test materials in rats.
According to the submitter, the results show that silica gel did
not cause silicosis, but may have caused a chronic inflamed
reaction in the test animals.
Submission Evaluation
It is well known that pulmonary exposure to quartz dust particles
of proper size can result in silicosis. This is confirmed in the
submitted study. In addition, silica gel has long been known to
be absorbed from the intestines and other membranes and excreted
rapidly yia the kidneys. The study submitted by MCB highlights
the fact that silica gel dust particles of proper size can elicit
the granulomatous and other pathological reactions of silicaceous
mat~rials. However, there is a difference between the
submitter's conclusion regarding silicosis and the conclusions
presented by the performing laboratory pathologist. According to
the statements of the performing laboratory pathologist, "...the
microscopic analysis and the determination of the organ weights
after intratrachea and intraperitoneum injections of quartz dust
and silica gel dust [make] the differences between silica gel
dust injection and quartz injection fairly meaningless." The
reconciliation of the differing conclusions would require an
indepth histopathological evaluation of the slides from the 1967
study and/or more definitive toxicological testing.
*NOTE: This ~tatus ~eport i~ the result of a prelimina=y
staff eva~uat~on of ~nformat~on submitted to EPA. Statements
made here~n are not to be regarded as expressing final
Agen~y policy or intent with respect to this particular
chem7~al. . Any review of the status report should take into
~onfis~ er~t~on the fact that it may be based on incomplete
~n ormat~on.
E~A '0- IJ~ I~EV. ~711
79
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8EHQ-0780-0354
Page 2 of 3
Current production and Use
A review of the production range (includes importation volumes)
statistics for silica gel (CAS No. 63231-67-4), which is listed
in the initial ~SCA Inventory, has shown that no 1977 production/
importation was reported or that all of the production range data
reported were claimed as confidential by the manufacturer(s) and
importer(s) and cannot be disclosed. (Section l4(a) of the TSCA,
U.S.C. 2613 (a). **/
Silica gel is a jelly-like precipitate obtained when sodium
silicate is acidified. Silica gel is used as a dehumidifying and
drying agent. It can also be used in the recovery of natural
gasoline from natural gas, the bleaching of petroleum oils, as a
catalyst and catalyst carrier, as an anticaking ingredient in
pharmaceuticals and cosmetics, and as a chromatographic agent.
A review of the production range (includes importation volumes)
statistics for crystalline silica (CAS No. 14808-60-7) which is
listed in the initial TSCA Inventory, has shown that between 10
million and 50 million pounds of this chemical was reported as
produced/imported in 1977. This production range information
does not include any production/impotation data claimed by the
person(s) reporting for the TSCA Inventory, nor does it include
any information which would compromise Confidential Business
Information. **/
Silica (silicon dioxide) occurs widely in nature as sand, quartz,
flint, and diatomite. It is used in the manufacture of glass,
water glass, ceramics, and abrasives. Silica is also used in
water filtration systems and as a component in hydraulic cements,
anticaking agent in foods, flatting agent in paints, filler in
cosmetics, pharmaceuticals, paper, and insecticides.
Comments/Recommendations
The National Institute for Occupational Safety and Health (NIOSH)
has prepared a "Criteria Document" which addresses the
recommended standard for occupational exposure to Crystalline
Silica (DHEW Publication No. 75-120 (NIOSH, 1974».
The EPA has recently received and evaluated other TSCA section
8(e) submissions on silicon chemicals (8EHQ-0680-0347 and 8EHQ-
0680-0349).
a) MCB Manufacturing Chemists, Inc. should be requested to
provide the basis for its contention that silica gel dust did
not cause silicosis. In addition, the submitter should be
**/ The data submitted for the TSCA Inventory, including
production range infomation, are subject to the limitations
contained in the Inventory Reporting Regulations (40 CRF 710).
80
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8EHQ-0780-0354
Page 3 of 3
requested to describe the actions it has taken, in
the provided toxicity information, to warn workers
customers, and to reduce and/or eliminate exposure
subject chemicals.
light of
and
to the
b) The Chemical Hazard Identification Branch (CHIB/AD) will
coordinate with NIOSH the need for further evaluation of the
submitted toxicity data on silica gel and quartz dusts. In
addition, CHIB will transmit copies of this status report to
OSHA, NIOSH, CPSC, FDA, and OWWM/EPA. The Industry
Assistance Office (IAO/OTS) should consider sending the same
information to the manufacturer(s) and importer(s) of the
subject chemicals listed in the Master TSCA Inventory.
81
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
NOV
I 2 \98r-j
8EHQ-0880-0355
Page 1 Of~
Approved 'I?
Revisio
Needed
SU8JECT: Status Report* 8EHQ-0880-0355
"ROM':~; D. Kover, Chief
Chemical Hazard Identification Branch
TO:
Joseph J. Merenda, Director
Assessment Division
Submission Description
Alli'ed Chemical has reported that several of its employees,
working with methylthioacetaldehyde oxime (MTAAO; CAS No. 10533-
67-2), had developed red splotches on the face and upper trunk,
headaches, and tachycardia following alcoholic beverage
consumption. The corporate physicians reported that the affected
employees do not appear to have any long-lasting adverse health
effects and that clinical laboratory findings are normal. The
submitter states that although the cause of these symptoms is not
known for certain, the workers' exposure to MTAAO or its
equilibrium decomposition products is suspected. The submitter
also states that the symptoms in the subject workers resemble
those observed following alcohol consumption by individuals being
treated with the anti-alcoholism drug Antabuse@
(tetraethylthiuram disulfide).
According to literature references obtained by Allied, the
following chemicals can produce symptoms similar to those
described above following alcohol consumption: n-butyraldoxime,
2-pyridine aldoxime, methyl chloride, metronidazole (FlagylR),
tolazamide, chlorpropamide, and certain chlorinated hydrocarbons.
Submission Evaluation
Many organic sulfur compounds inhibit the enzyme that oxidizes
acetaldehyde to acetic acid. The first step in oxidizing alcohol
in the body is the conversion to acetaldehyde. Therefore,
ingestion of alcohol during the presence of one of these sulfur
compounds will cause a piling up of acetaldehyde in the body.
This excess causes symptoms and signs related to heart, blood
vessels, respiration, liver function and nervous system
function. The symptoms reported by Allied Chemical could be
explained by accumulation of acetaldehyde following alcohol
consumption.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agen~y policy or intent with respect to this particular
chem~cal. ,Any review of the status report should take into
7ons~der~t~on the fact that it may be based on incomplete
~nformat~on .
E~" '0- 11»-4 fllU:V. ~711
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Page 2 of 3
It should be noted however, that not all of the compounds listed
by Allied produce reactions to alcohol by this same mechanism.
For instance, chlorpropamide may do so by releasing prostaglan-
dins in genetically susceptible individuals. The listed oximes
are largely weak anticholinesterases that are capable of dis-
placing stronger ones from the enzymes. It would be interesting
to dose appropriate test animals with MTAAO and then measure
blood levels of acetaldehyde after administering alcohol. One
could also administer prostaglandin synthetase inhibitors
(aspirin, indomethacin) to animals exposed to MTAAO and alcohol
in order to determine whether the oxime produces its effects by
the same mechanism as chlorpropamide. Information gathered by
such studies could be life-saving for the occasional person who
has an extreme reaction to the double exposure.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for MTAAO (CAS No. 10533-67-2) which is listed in the
initial TSCA Inventory, has shown that no 1977 production/
importation was reported or that all of the production range data
reported were claimed as confidential by the manufacturer(s) and
importer(s) and cannot be disclosed. (Section 14(a) of TSCA,
U.S.C. 2613 (a».**/
The submitter states that MTAAO is not a particularly high volume
chemical and is not widely used. No information on the use(s) of
MTAAO was provided by the submitter or was located in the
secondary literature sources consulted.
Comments/Recommendations
Allied Chemical states that it is advising the two other
companies known to produce or use MTAAO of both the toxicological
findings and Allied's actions. These reported company actions
include a review of the MTAAO production process and a revision
of the handling procedures in order to minimize employee exposure
to the chemical. MTAAO product labels and product hazard
communications are being reviewed by Allied in order to minimize
potential transportation problems. In addition, Allied reports
that it will continue its comprehensive medical surveillance
program for all employees involved in MTAAO operations and has
urged all employees to immediately report symptoms for prompt
medical observation. These medical-related actions are part of
the submitter's efforts to identify the specific causative
factor.
**/ The data submitted for the TSCA Inventory including
production range information, are subject to the limitations
contained in the Inventory Reporting Regulations (40 CFR 710).
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a)
MTAAO is listed in the EPA's proposed TSCA Section Sea)
Level A rule (45 FR 13646).
b)
The Chemical Hazard Identification Branch/AD will transmit
copies of this status report to NIOSH and OSHA.
The Industry Assistance Office (IAO/OTS) should consider
sending the same information to the manufacturer{s) and
importer{s) of MTAAO listed in the master TSCA Inventory.
c)
84
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
. Page 1 of 4
DAT!:
uL\.; - 4 1"':"'-')
~/~
SUIJECT, Status Report* 8EHQ-0880-0356 A d
8EHQ-0880-0357 pprove
~ 8EHQ-I080-0356/7 Supplements. .
( , Rev~s~on
'10116: nk D. Kover, Chief Needed
hemical Hazard Identification Branch
TO: J h J d.
osep. . Meren a, Dlrector
Assessment Division
Submission Description
In two seperate initial submissions, the Nalco Chemical Company
reported that preliminary results from a 13-week intraperitoneal
injection study (rats) of 2-hydroxyethylacrylate (CAS No. 818-61-
l~ 8EHQ-0880-0356) and methylene bis acrylamide (CAS No. 110-26-
9~ 8EHQ-0880-0357) indicated that both compounds have neurotoxic
properties. The initial submissions were based on preliminary
histopathologic examination of tissues which were reported to
show peripheral nerve damage. The submitter stated that these
toxicological findings were reported for 2-hydroxyethylacrylate
because it was the first indication (known to the company) that
the chemical had neurotoxic properties. With regard to its
methylene bis acrylamide submission, Nalco stated that the
obtained results were in direct contrast to the published
literature which indicates that this compound is non-neurotoxic.
In its supplemental submissions (8EHQ-I080-0356/7 Supplements),
Nalco provided the final report, including test protocols and
data, from the study which involved daily (5 days per week for 13
weeks) intraperitoneal injections of acrylamide (positive
control~ known neurotoxic agent), 2-hydroxyethylacrylate, methyl-
ene bis acrylamide, or a mixture of the latter two compounds.
According to the summary prepared by the performing laboratory,
no deaths occurred in the study. However, dose-related clinical
symptoms such as salivation, lacrimation, hunch-back position,
tip-toe walking, body tremors, piloerection, and weakening of the
hind legs were reported for the animals receiving the highest
doses (50 mg/kg) of either 2-hydroxyethylacrylate or methylene
bis acrylamide. The performing laboratory reported that some,
but not all, of the above clinical signs s~ggestive of
neurotoxicity were observed in the animals receiving lower doses
of the two compounds. The toxicity of the mixture was reported
to be minimal, with only a few "incidence" of lacrimation
observed.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submittec to EPA. Stateme~ts
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information. 85
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With regard to body weight, the highest doses (50 mg/kg) of 2-
hydroxyethylacrylate or methylene bis acrylamide were reported to
have caused a reduction in growth of the test animals. However,
the magnitude of reduction was greater in those animals receiving
methylene bis acrylamide. The mixture of the two compounds at 50
mg/kg was reported to have no apparent effect on the rate of
growth. Food consumption was reported to be considerably less in
the animals receiving 50 mg/kg doses of 2-hydroxyethylacrylate or
methylene bis acrylamide. Little adverse effect on food
consumption was observed at the lower doses of the two or in the
rats receiving 50 mg/kg of the mixture.
Histopathologic examination of the tissues from all treated
animals (including the acrylamide group) reportedly showed
varying degrees of peripheral nerve damage. According to the
performing laboratory, the extent of the nerve damage appeared to
be more compound-related than strictly dose-related. The 50
mg/kg dose of the 2-hydroxyethylacrylate/methylene bis acrylamide
mixture was rBported to have caused more pronounced overall
damage than the acrylamide control at a dose of 10 mg/kg. The
degenerative changes induced in the peripheral nerve tissues by
the individual compounds were reported to be less severe than
those found in the acrylamide treated animals.
Submission Evaluation
The acrylamide derivative (methylene bis acrylamide) and the
acrylate ester (2-hydroxyethylacrylate) both produced peripheral
neuropathy in the experiment. This neuropathy resembles that
produced by acrylamide. Both compounds were less toxic (less
potent) than the acrylamide under the conditions of the
experiment and for the nerve tracts that were examined histo-
logically by the performing laboratory. The reason for the
decreased food consumption and the resultant weight loss at the
50 mg/kg doses of methylene bis acrylamide or 2-hydroxyethyl-
acrylate is not readily apparent. It may have been due to lack
of appetite due to general malaise and/or an inability to reach
and handle food caused by the neuropathy. The dosing schedule
was inadequate to determine this.
Although no quantification for the severity of the lesions was
provided, there appears to be a dose-related incidence of
neurotoxicity for both methylene bis acrylamide and 2-
hydroxyethylacrylate. Considering that the two compounds are not
equally potent in toxicity, it is therefore not surprising that a
mixture of the two is not as potent as either component.
Methylene bis acrylaMide is an N-substituted acryLamide. The
size and nature of the substituent would not greatly (qualita-
tively) alter the action of the parent acrylamide. It is
therefore not surprising that the bis compound is also a
neurotoxic agent.
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The observation that 2-hydroxyethylacrylate causes the type of
peripheral neuropathy heretofore considered characteristic of
acrylamide is important. It establishes that the amide group
(-NH2) is not essential for the neurotoxic effect of acrylamide
(CH2=CH-C(=0)-NH2). The fact that in the 2-hydroxyethylacrylate
(CH2=CH-C(=0)-0-CH2-0H), the 2-hydroxyethyl group can replace the
-NH2 group suggests that other compounds with CH?=CH-C(=O)- may
also produce peripheral neuropathy. .
Current Production and Use
A review of the production range (includes importation volumes)
statistics for 2-hydroxyethylacrylate (CAS No. 818-61-1) and
methylene bis acrylamide (CAS No. 110-26-9), which are listed in
the initial TSCA Inventory, has shown that no 1977 production/
importation was reported or that all of the production range data
reported were claimed as confidential by the manufacturer(s) and
importer(s) and cannot be disclosed. (Section l4(a) of the TSCA,
U.S.C. 2613 (a)). **/
The Nalco Chemical Company reported in its initial submissions
that it has manufactured small quantities of methylene bis
acrylamide and processed small quantities of 2-hydroxyethyl-
acrylate at a facility in Chicago, Illinois.
2-Hydroxyethylacrylate is a functional monomer used in the
manufacture of thermosetting acrylic resins. Methylene bis
acrylamide is used as a chemical intermediate and as a cross-
linking agent.
Comments/Recommendations
In the cover letters to its supplemental submissions, the Nalco
Chemical Company stated that "as a result of this testing and
other factors, Nalco has decided to drop [its] activities" with
both methylene bis acrylamide and ?-hydroxyethylacrylate for the
particular uses it had planned.
a)
The Chemical Hazard Identification Branch will request
the Nalco Chemical Company to describe additional
actions it has taken, in light of the submitted toxicity
data, to warn workers and others, and to reduce and/or
eliminate exposure to the subject chemicals.
b)
2-Hydroxyethylacrylate is listed in the EPA's February
29, 1980 proposed TSCA Section 8(a) Level A rule (45 FR
13646). Methylene bis acrylamide should also be
considered for inclusion in Section 8(a) Level A
reporting.
**/
The data submitted for the TSCA Inventory including produc-
tion range information, are subject to the limitations con-
tained in the Inventory Reporting Regulations (40 CFR 710).
87
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c)
The Chemical Hazard Identification Branch will provide a
copy of the initial and supplemental submissions on
methylene bis acrylamide to the Test Rules Development
Branch/AD which is reviewing data obtained by the EPA on
acrylamide as recommended by the Interagency Testing
Committee (ITC).
d)
The Chemical Hazard Identification Branch will transmit
a copy of this status report to NIOSH, OSHA, CPSC, FDA,
NCI/NTP, OWWM/EPA, and TRDB/EPA. CHIB will also provide
a copy of the status report to the Office of Toxics
Integration (OTI/OPTS/EPA) for distribution to EPA
Regional Offices, State agencies, and to labor,
environmental, and selected citizen groups. The
Industry Assistance Office (IAO/OTS/EPA) should consider
sending the same information to the manufacturers and
importers of the subject chemicals as listed in the
Master TSCA Inventory, and to identified industry-
associated organizations.
88
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 5
OA TE:
FEB 2 5 1981
SUBJECT: Status Report* 8EHQ-0880-0358
8EHQ-0980-0358
8EHQ-1080-0358
F'~nk D. Kover, Chief
Chemical Hazard Identification Branch
TO:
Joseph J. Merenda, Director
Assessment Division
Approved -pz
Followup Response
Supplement R"
ev~s~on
Needed
-Yffl
Submission Description
An employee of E. I. DuPont de Nemours and Company, Inc. has
submitted a TSCA Section 8(e) notice concerning a possible hazard
posed by DuPont's ferric chloride, which the employee believes to
contain significant levels of radioactivity. The employee
reported that the DuPont ferric chloride, which is produced and
sold as a coagulant for use in water treatment facilities, is a
by-product from a titanium dioxide manufacturing process using
ilmenite ore as a starting material. The employee also reported
that the ilmenite ores contain small amounts of radioactive
substances which are subsequently concentrated in the ferric
chloride. As part of the employee's duties in preparing Material
Safety Data Sheets, the employee reported that attempts were made
to gather additional information from DuPont on this chemical.
The employee stated that DuPont "denied" the requests for data
and reportedly told the employee that the information concerned
"a highly sensitive subject." The employee stated that although
he had "no further information, DuPont's sensitivity about this
matter suggests that the ferric chloride solution introduces
significant amounts of radioactivity into drinking water
supplies, and that DuPont wishes to withhold this information
from water treatment customers who buy and use ferric chloride
solution and who are responsible for compliance
with EPA drinking water standards."
It should also be noted that the employee made a claim of
employer discrimination and requested protection as provided for
under Section 23 of TSCA. In light of this request, the EPA
forwarded a copy of the initial submission directly to the U.S.
Department of Labor which has responsibility for implementing
TSCA Section 23.
*NOTE: This status report is the result of a preliminary
staff eva~uation of information submitted to EPA. State~er.ts
made here~~ are not to be regarded as expressina final
Agency pol~cy or intent with respect to this pa;ticular
chem~cal. ,Any review of the status report should take into
cons~derat~on the fact that i~ may be based' 1
informa t l' on '- on ~ncomp ete
. . 89
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8EHQ-0880-0358
8ErIQ-0980-0358 Followup Response
8EHQ-l080-0358 Supplement
Page 2 of 5
In order for the EPA to determine the nature and extent of any
health hazards posed by such radioactivity, the Agency requested
(letter dated September 1, 1980) that E. I. DuPont de Nemours and
Company, Inc. address and respond to the following questions:
1.
Does DuPont's ferric chloride and/or ferric chloride
solution contain radioactive isotopes?
2.
If such isotopes are present, what are their specific
chemical identities and in what chemical form do they
exist? What is the actual source of these radioactive
isotopes? What is the fate of these isotopes upon the
end-use of ferric chloride in drinking water treat-
ment? What percent of the radioactivity is precipitated
during drinking water treatment? What percent remains
in any form in ferric chloride-treated drinking water?
3.
What are the maximum/minimum levels of the isotopes
detectable per mass of ferric chloride? What analytical
methods are used in that detection? What are the
sensitivities and/or lower limits of detection of such
analytical methods?
The Agency also requested that DuPont provide complete copies of
all analytical protocols and existing data, of which DuPont was
aware, that related to the above questions concerning ferric
chloride.
In its response to the above questions (8EHQ-0980-0358 Followup
Response), Dupont reported that 15% of its ferric chloride solu-
tion is sold for use in the treatment of drinking water (i.e. to
flocculate and precipitate impurities). DuPont also reported
that its ferric chloride solution does contain "low levels of
naturally occurring radioactive isotopes of the thorium and
uranium series." However, DuPont considers that radioactivity
"to be at a low and safe level." DuPont stated its belief that
the radioactive isotopes present in the ferric chloride solution
are in the form of metal chlorides of the thorium and uranium
series. DuPont also believes that the source of these isotopes
is the ilmenite ores used in the manufacture of titanium dioxide
pigments. DuPont stated that these naturally occurring
radioactive "impurities are chlorinated with the ilmenite ore
(Ti02-Feo or Tio2-Fe203) during titanium dioxide production and
leave the process wiEh the ferric chloride [by-product]."
with regard to the fate of the isotopes in the treated drinking
water, DuPont reported that the isotopes are precipitated with
the ferric ion and, as such, are separated from the water supply
and become a sludge component. DuPont also reported that the
results of sampling customers' drinking water supplies "indicate
that the [FeC13] water meets the standards for radioactivity
established by EPA under the Safe Drinking Water Act (40 CFR Sec.
141.15)."
90
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8lliQ-0880-0358
8EHQ-0980-0358 Followup Response
8EHQ-I080-0358 Supplement
Page 3 of 5
In response to the EPA questions relating to the maximum/minimum
levels of the isotopes detectable per mass of ferric chloride,
DuPont provided toe following information:
"Du Pont's ferric Ch;~~ide solution conta~~g 20-60 pCi/gm
gross 0(, 2-5 pCi/ gm Ra and 1-4 pCi/ gm Ra. A typical
potable surface water supply on the East C~~~t contains a
raw in~~6 of 1-2 pCi/l gross 0(, 0.5 pCi/l Ra and 0.5-1.0
pCi/l Ra. A typical FeC13 dose used in treating water
would be 15 ppm which in the case of Du pon~ ~eC13 would
contribute2~-3 pCi/l grosse(, 0.1-.3 pCi/l 2 Ra and 0.05-
0.2 pCi/l 6Ra. These requirements are near ~B below the
sensit~v~ty limits (1 pCi/l grosso(, 1 pCi/l 2 Ra and 0.3
pCi/l 2 Ra) using EPA-recommended test procedures."
DuPont stated that the above findings were confirmed in actual
tests performed in Philadelphia (Pa.), Wilmington (Del.),
Richmond (Va.). and Washington, D.C.
DuPont also reported that the EPA's Region II Office was informed
(by telephone) on May 1, 1978, of the presence of radioactive
isotopes in DuPont's waste ferric chloride solution and the
levels of radiation in the raw and processed materials. This
DuPont action was reportedly taken in light of the company's
barging of waste ferric chloride.
The EPA has also received additional information (8EHQ-I080-0358
Supplement) from the employee who had submitted the original
section 8(e) notice. The employee expressed concern with regard
to the DuPont followup response statement that "a typical FeC13
dose would be 15 ppm and would contribute 1-3 pCi/l grosse(" or,
as the employee stated "7-20% of the EPA drinking water standard
of 15 pCi/l." The employee reported that "Fifteen ppm (approxi-
mately 15 mg/l) is at the low end of the dose range for FeC13
according to DuPont's Ferric Chloride Dose Chart. The graph
gives addition rates to 140 mg/l (approximately 140 ppm), which
would contribute 9-28 pCi/l, or 65-187% of the EPA drinking water
limit." A copy of the subject dose chart was provided by the
employee.
Submission Evaluation
The evaluation of these submissions has been performed by the
Office of Drinking Water (ODW) of the Office of Water and Waste
Management '( OWWM/ EP A) .
The Office of Drinking Water is now developing a program which
will specify purity of direct additives (treatment chemicals) to
drinking water in order to assure that no risk to public health
will be involved. This program is centered around the
development, by the National Academy of Sciences, of a drinking
water treatment chemicals "codex", analogous to their Food
Chemicals Codex. The matter of radionuclide contamination of
ferric chloride, brought to the EPA's attention under TSCA
91
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Page 4 of 5
Followup Response
Supplement
Section 8(e), has been referred to the Academy for inclusion in
their study of coagulants and flocculants, as well as development
of an across-the-boar~policy on the contamination of direct
additives by radionucldes. However, in the opinion of the Office
of Drinking Water, the situation described in this case does not
indicate an imminent threat to public health. The Agency will
rely on the monitoring requirements of the Safe Drinking Water
Act to assure that the maximum contaminant levels (MCLs) for
radionuclides are not exceeded. When the direct additives
program is implemented, this opinion, and others issued by the
Office of Drinking Water will be subject to review based on the
recommendations of the Academy and on the procedures and criteria
developed by the Office of Drinking Water to deal with such
situations.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for ferric chloride (CAS No. 7705-08-0), which is
listed in the initial TSCA Inventory, has shown that between 62
million and 173 million pounds of this chemical were
produced/imported in 1977. **/
As stated previously in this status report, ferric chloride is
used to precipitate impurities in drinking water supplies.
DuPont reports that 15% of its ferric chloride is sold for this
purpose. The company did not provide any information on the use(s) of
the remaining 85%. According to secondary literature sources
consulted, ferric chloride is used in the dye industry and as a
styptic.
Comments/Recommendations
With regard to its employee's original TSCA Section 8(e) notice on
ferric chloride, DuPont stated that the original submission "should
not be treated as a report under Section 8(e), but rather as an
allegation of a possible adverse health or environmental effect."
DuPont also stated that the employee did "not have sufficient infor-
mation which reasonably supports the conclusion that the ferric
chloride presents a substantial risk of injury to health or the
environment as required for a matter to fall within the provisions of
Section 8 (e) . II
Following review and evaluation of the provided information, the EPA
believes that the DuPont employee did not have sufficient information
which would provide reasonable support for a conclusion of substantial
**/
This production range information does not include any
production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it
include any information which would compromise Confidential
Business Information. The data submitted for the TSCA
Inventory Reporting Regulations (40 CFR 710).
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Page 5 of 5
risk of injury to health or the environment as defined in the EPA's
March 16, 1978 "Statement of Interpretation and Enforcement PolicYi
Notification of Substantial Risk" (43 FR 11110). The employee's
concerns appear to have been based on a lack of, and/or inability to
obtain, information about a company product. It is important to note
that the March 16, 1978 policy statement (Appendix Bi EPA Response to
Comment 7) provides that Section 8(e) "applies to information which a
person possesses or of which he knows" which reasonably supports a
conclusion of substantial risk. The tone of the employee's statement
(i.e. [without] "further information, [the company's] sensitivity
suggests. . .") indicates that the employee did not possess, or have
actual knowledge of, information which reasonably supports a
conclusion that DuPont's ferric chloride, as used in treatment of
drinking water, poses a substantial risk of injury to health.
Therefore, it is the Agency's preliminary determination that the
information contained in 8EHQ-0880-0358 et seq. did not warrant
submission to the EPA pursuant to Section 8(e) of the Toxic Substances
Control Act.
Followup Response
Supplement
a)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, DOL, OWWM/EPA,
OANR/EPA, the submitting employee, and to DuPont. CHIB will
also provide a copy of the status report to the Office of
Toxics Integration (OTI/OTS/EPA) for distribution to EPA
Regional Offices and State agencies, and to labor, environ-
mental, and selected citizen groups.
93
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Pcp.ge 1 of 2
OAT!:
FEB 2 5 1981
Approved {/J;l ~I
Revis ioril
Needed
SU~!CT:Status Report* 8EHQ-0980-03S9
8EHQ-0181-0359 Supplement
~~ank D. Kover, Chief" .
~ Chemical Hazard Identlflcatl0n Branch
To:Joseph J. Merenda, Director
Assessment Division
Submission Description
In its initial submission, the FMC Corporation provided
summarized results from several in vitro mutagenicity and in vivo
acute toxicity studies on diallyY-tetrabromophthalate (DATBP; CAS
No. 49693-09-6). The submitter reported that DATBP was recently
found to be positive in an in vitro Yeast Mitotic Gene Conversion
assay and weakly positive in-an in vitro Mouse Lymphoma Forward
Gene Mutation assay. The submitter reported, however, that a
previous test for in vitro mutagenicity (Ames test performed in
1978) had demonstrated that DATBP was not mutagenic in bacteria
in the presence or absence of metabolic activation. The
submitter also reported that previously performed (1978) acute
toxicity studies had shown that DATBP was not corrosive or
irritating to the skin or eyes of rabbits. In addition, the
LDSOS for DATBP were reported to be in excess of 5 g/kg (oral;
rats) and in excess of 2 g/kg (dermal; rabbits). FMC Corporation
pointed out that the recently performed Yeast Mitotic Gene
Conversion assay fo~ primary DNA damage and the Mouse Lymphoma
Forward Gene Mutation Assay were both performed with a DATBP
sample which had been synthesized by a different route than the
sample of DATBP used in the studies done in 1978. The submitter
also stated that the recently synthesized and tested DATBP sample
was probably representative of that which would result from a
commercial process and was not as pure as the DATBP sample which
was tested in 1978. The submitting company stated that it was
not sure if the mutagenicity detected in the tests performed in
1980 was due to the DATBP itself or to some impurity in the
sample. The company reported that additional short-term
screening assays would be conducted on a highly purified DATB~
sample in order to clarify this issue.
In its supplemental submission, FMC provided summarized results
from its additional studies on "purified" DATBP. The company
reported that the purified DATBP did not induce mitotic gene
*NOTE: This status report is the result of a preliminary
staff eva~uation of information submitted to EPA. State;e~ts
made herel~ are n~t to be regarded as expressing final
Agen~y POllCY or lntent with respect to this particular
chem~cal. ,Any review of the status report should take into
7onslder~tlon the fact that it may be based on incomplete
lnforma tlon.
I:~.. '0- IJ~ I"E.... ),711
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Page 2 of 2
conversions in the in vitro Yeast Mitotic Gene Conversion Test,
and was not mutagenic in an in vivo Mouse Micronucleus Test. The
submitter reported, however,~hat the results of the Mouse
Lymphoma Forward Mutation Assay indicated that purified DATBP was
a weak mutagen. However, the submitter pointed out that the
performing laboratory did not use the FMC-specified vehicle
(DMSO) for this particular study and that the assay was being
repeated with purified DATBP in DMSO solvent. FMC reported that
the EPA would be advised of the results of the repeated Mouse
Lymphoma Forward Mutation Assay upon completion.
Submission Evaluation
The submitted information indicates that purified DATBP does not
have a high degree of acute in vivo toxicity. In addition, the
submitters suspicion that an impurity may have been responsible
for the detected mutagenicity may be correct. However, without
complete copies of the test protocols and data obtained from the
studies cited in these submissions, an evaluation of the reported
findings is not possible.
Current Production and Use
The FMC Corporation reported that DATBP is a research and
development chemical which has been distributed in small
quantities (one to four pounds) to several potential customers
for testing as a flame retardant co-monomer. A search of the
Master TSCA Inventory for diallyl tetrabromophthalate (CAS No.
49693-09-6) has shown that this chemical is not listed.
Comments/Recommendations
(a)
The Chemical Hazard Identification Branch/AD will request
the FMC Corporation to provide complete copies of the
final results, including test protocols and data, from
all of the laboratory studies cited in its submissions.
(b)
The Chemical Hazard Identification Branch will review and
evaluate the requested information, revise this status
report as appropriate, and recommend further assessment
if warranted.
(c)
The Chemical Hazard Identification Branch will transmit
copies of this status report to MSD/EPA and CCD/EPA.
95
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DATE:
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8Nlq-0980-0 360
Page 1 of 4
Revision
Needed
DEC - 4 i9GO
SUIJECT: Status Report* 8EHQ-0980-0360
,.........'.M.?-rank D.
~J?~n) Kover, Chief
Chemical Hazard Identification Branch
Approved
, TO: Joseph J. Merenda, Director
Assessment Division
Suhmission Descr'iption
The Hooker Chemicals and Plastics Corporation has submitted
information on the possible carcinogenicity of benzoyl chloride
(BC~ CAS No. 98-88-4), benzotrichloride (BTC~ CAS No. 98~07-7),
and para-chlorobenzotrichloride (PCBTC~ CAS No. 5216-25-1) in
mice. The submission consists of four Japanese scientific
articles, the respective English translations, and an evaluation
of the reported in vivo findings which was prepared by a Hooker
Corporation toxicologist.
According to the provided translations, benzoyl chloride was
found to induce tumors in mice following inhalation exposure~
benzotrichloride was shown to be carcinogenic following
inhalation, dermal application, and oral administration to mice~
para-chlorobenzotrichloride was found to be carcinogenic in mice
following eith~r oral administration or dermal application.
The submitting company stated that although this information has
been published, it was submitted pursuant to TSCA Section 8(e)
because the information was not, available through the literature
abstract services (i.e., Agricola, Biological Ahstracts, Chemical
Abstracts, Dissertation Abstracts, Index Medicus, and the
National Technical Information Service) which are listed in Part
VII(c) of the EPA's March 16, 1978 "Statement of Interpretation
and Enforcement Policy~ Notification of Substantial Risk" (43 FR
11110) .
Submission Evaluation
The submitter has concluded that the provided experimental data
indicate that BTC and PCBTC are chemical carcinogens. Although
the mice exposed to BC via inhalation rep9rtedly developed both
*NOTE: This status repo=t is the resul~ of a prelirni~a=;'
s~aff evaluation or informa~ion submittec to EPA. State~e~~s
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information. 96
E~A '0- II" I"EV. ~711
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8EHQ-0980-0360
Page 2 of 4
benign and malignant lung tumors, the submitter assumes these
particular data to be negative due to the lack of control animals
in the study which would not allow a determination of "what the
real increase over background is." The submitter's belief that
the observed level (3 of 7) of lung tumors in the BC-exposed mice
surviving to the 14th month "would be a reasonably, possibly low,
level background" cannot be verified in view of the missing
control data.
The submitter feels that the provided experimental evidence is
not sufficiently quantitative for risk assessment and expresses
concern that sub-irritant concentrations were not used in the
inhalation studies. These concerns may be valid from a
standpoint of risk assessment and/or mechanism of carcinogenesis,
but cannot undo the experimental findings of carcinogenicity for
BTC and PCBTC, and the tumorigenicity of BC. Although it may be
of interest to determine whether the lung tumors observed
following inhalation are the result of direct cellular injury or
mutation, such determinations cannot alter the findings of
carcinogenicity; nor will more precise techniques of vapor
exposure. Even if the inhalation and skin application studies
were dropped or discounted, which they should not be, the oral
administration studies do demonstrate the carcinogenicity of
PCBTC and BTC. The tumors resulting from the oral administration
of either compound were dose/response related and always higher
than in the control groups. The submitter's statement that the
technique of oral administration may have been inaccurate is not
reflected by the dose-response data which were obtained in two
studies.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for benzoyl chloride (CAS No. 98-88-4), which is
listed in the initial TSCA Inventory, has shown that between 10
million and 52 million pounds of this chemical were produced/
imported in 1977. **/
Benzoyl chloride is used as an intermediate for the introduction
of the benzoyl group in chemical syntheses. It has also been
used in medicines.
A review of the production range (includes importation volumes)
statistics for benzotrichloride (CAS No. 98-07-7), which is
listed in the initial TSCA inventory, has shown that between 10
million and 50 million pounds of this chemical were produced/
imported 'in 1977. * * /
Benzotrichloride is used in the manufacture of synthetic dyes and
in other organic chemical syntheses.
97
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8EHQ-0980-0360
Page 3 of 4
A review of the production range (includes importation volumes)
statistics for para-chlorobenzotrichloride (CAS No. 5216-25-1),
which is listed in the initial TSCA Inventory, has shown that
between 10 million and 51 million pounds of this chemical were
produced/imported in 1977. **/
Para-chlorobenzotrichloride is used as an intermediate in the
manufacture of pharmaceuticals, dyes, and other organic
chemicals.
Comments/Recommendations
with regard to a perceived need for further toxicological
information on the subject chemicals, the submitter's
toxicologist stated that "it seems reasonable that the
producer/user companies could get together and develop a
cooperative program to generate some data. "
a)
The Chemical Hazard Identification Branch (CHIB/AD) will
request the Hooker Chemicals and Plastics Corporation to
describe the actions it has taken, in light of the
provided toxicity data, to warn workers and others, and to
reduce and/or eliminate exposure to the subject
chemicals. In addition, the submitter will be informed of
the EPA's interest in receiving the results, including
test protocols and data, from the proposed cooperative
studies designed to further define the toxicities of the
subject chemicals.
b)
The Chemical Hazard Identification Branch/AD will consider
the preparation of Chemical Hazard Information Profiles
(CHIPs) on benzoyl chloride, benzotrichloride, and para-
chlorobenzotrichloride. The 1979 Carcinogen Assessment
Group (CAG/ORD/EPA) preliminary assessment on benzoyl
chloride will be considered in the CHIP review.
c)
Benzoyl chloride, benzotrichloride, and para-chlorobenzo-
trichloride are listed in the EPA's February 29, 1980,
TSCA Section 8(a) Level A rule (45 FR 13646).
d)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, FDA, NCI,
CAG/ORD/EPA, and OWWM/EPA. CRIB will also provide a copy
of the status report to the Office of Toxics Integration
**/ This production range information does not include any
production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it
include any information which would compromise Confidential
Business Information. The data submitted for the TSCA
Inventory, including production range information, are subject
to the limitations contained in the Inventory Reportinq
Regulations (40 CFR 710). -
98
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8EHQ-0980-0360
Page 4 of 4
(OTI/OPTS/EPA) for distribution to EPA Regional Offices,
State agencies, and to labor, environmental and selected
citizen groups. In addition, the Industry Assistance Office
(IAO/OTS/EPA) should consider providing a copy of this
status report to the manufacturers/importers of the subject
chemicals as listed in the Master TSCA Inventory, and to
identified industry-associated organizations.
99
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Branch
8EHQ-0980-0361 S
Page 1 of 2
APprove~
Revisio
Needed
7'f780
DATE:
OCT 3 0 1980
SU'JEC~:_~~~S Report* 8EHQ-0980-0361S
~~ D. Kover, Chief
'10M: Ch . 1 d d . f ' .
emlca Hazar I entl lcatl0n
TO: Joseph J. Merenda, Director
Assessment Division
Submission Description
The submitting company (company name claimed confidential; TSCA
CBI) provided the summarized results of in vitro Mouse Lymphoma
Forward Mutation Assays on cobalt phthalocyanine disulfonate (CAS
No. 29383-29-7) and cobalt phthalocyanine tetrasulfonate (CAS No.
14285-59-7). The submitter stated that the results indicate that
both chemicals were mutagenic only following metabolic
activation. In addition, the tetrasulfonate compound was
reported to be less Nutagenic than the disulfonate derivative.
Submission Evaluation
According to the provided summaries, both chemicals were found to
be mutagenic only in the presence of metabolic activation.
However; without complete copies of the test protocol and the
data obtained, a complete evaluation of the reported mutagenicity
is not possible at this time.
Current Production and Use
A review of the production range (includes importation volumes)
statistics fqr cobalt phthalocyanine disulfonate (CAS No. 29383-
29-7) which is listed in the initial TSCA Inventory, has shown
that between 100 thousand and 1 million pounds of this chemical
were produced/imported in 1977. This production range
information does not include any production/importation data
claimed as confidential by the person(s) reporting for the TSCA
Inventory, nor does it include any information which would
compromise Confidential Business Information. **/
A review of the production range (includes importation volumes)
statistics for cobalt phthalocyanine tetrasulfonate (CAS No.
14285-59-7) which is listed in the 'initial TSCA Inventory, has
shown that no 1977 production/importation was reported or that
all of the production range data reported were claimed as
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chem~cal. ,Any review of the status report should take into
conslderatlon the fact that it may be based on incomplete
information.
E~A "0"111 18»-6 t,,~v. "'"
100
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8EHQ-0980-036l S
Page 2 of 2
confidential by the manufacturer(s) and importer(s) and cannot be
disclosed. (Section 14(a) of the TSCA, U.S.C. 2613 (a)). **/
Information on the use(s) of the subject chemicals was claimed as
confidential (TSCA CBI) by the submitter. No information on the
use(s) of the chemicals was located in the secondary literature
sources consulted.
Comments/Recommendations
The Agency believes that in vitro mutagenicity assays of this
type provide valuable data-that can aid in assessing the possible
risks posed by chemicals to health and the environment. Although
Mouse Lymphoma Forward Mutation test results, when considered
alone, may not be sufficient to provide reasonable support for a
conclusion of substantial risk, the addition of information
concerning high production of and/or exposure to the chemicals
would suggest the need for further more definitive toxicological
testing.
The submitting company reported that the protective measures
(i.e. gloves, eye protection, respirators, etc.) in force at its
manufacturing operations ensure minimal chemical exposure to
employees. In addition, the submitter stated that steps are
being taken to inform and warn employees, customers, and others
known to have potential exposures to the subject chemicals.
(a)
(b)
(c)
(d)
The submitting company should be requested to provide
complete copies of the results, including the test
protocol and data, from the mutagenicity studies cited
in its submission.
The Chemical Hazard Identification Branch (CHIB/AD)
will review the requested information, revise this
status report as appropriate, and recommend further
assessment if warranted.
The Chemical Hazard Identification Branch will transmit
copies of this status report to NIOSH and OSHA. The
Industry Assistance Office/OTS should consider sending
the same information to the manufacturer(s)/importer(s)
of the subject chemicals listed in the Master TSCA
Inventory.
It is recommended that the subject chemicals be
considered for inclusion in TSCA section 8(a) Level A
reporting.
**/ The data submitted for the TSCA Inventory, including produc-
-- tion range information, are subject to the limitations con-
tained in the Inventory Reporting Regulations (40 CFR 710).
101
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATIE:
NOV
I 4 1980
8EHQ-0980-0362
Page I of 3
APproved~~~fD
Revision
Needed
SUSJECT: Status Report * 8EHQ-0980-0362
'R~~ D. Kover, Chief
C/'Chemical Hazard Identification Branch
TO:Joseph J. Merenda, Director
Assessment Division
Submission Description
The Nalco Chemical Company submitted a complete copy of the
final results of an acute inhalation study of the hydrochlo-
ride salt of a polymer of aniline and formaldehyde (CAS No.
57138-85-9) in albino rats. The submitter reported that a
single 4-hour inhalation exposu~e (nominal concentration of
3.3 mg/liter) of the vapors of the compound in a water
solution did not result in any clinical signs of intox-
ication or mortality. However, hydropic degeneration of the
liver was observed upon necropsy and histological examina-
tion. This degeneration, which was charac~erized by the
presence of vacoules in the cytoplasm of the hepatocytes
with subsequent dislocation of the nucleus to the periphery,
was considered by the performing laboratory to be
reversible.
Submission Evaluation
The purpose of the submitted inhalation study is not readily
apparent. In addition, the submitter stated that identity
of the chemical compound(s) to which the animals were expos-
ed was in question. In general, a single 4-hour exposure to
a vapor is of limited value, particularly if the concentra-
tion is low and no acute clinical signs are observable.
This type of study tells nothing about chronic toxicity.
The material tested was reported to be a "brown liquid"
no other properties recorded. It was reported that the
tested hydrochloride salt was in an aqueous solution.
Bubbling air through such a solution would most likely
vaporize only the water. If the vapors were not readily
analyzable, then the concentration of the polymer in the
with
solution
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitt~d to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
informa tion.
102
r;~" '0- u»-t I~["'. )-711
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8EHQ-0980-0362
Page 2 of 3
should have been determined at the start and at the end of the
exposure. Perhaps the rats were exposed to only water vapor.
addition, it is not clear from the submission whether the
solution generated during the exposure was as a mist or a true
vapor. If the material was generated as a mist it must have been
inhaled as such and also settled on the skin of the test
animals. It is not clear if precautions were taken to prevent
the animals from licking the compound from the skin.
In
If the inhaled material was irritating to the lungs, it was
mild. However, interpretation is complicated because the test
animals were diseased with mycoplasmosis. The grey foci which
were observed could have been due to endogenously aggregated
material such as white thrombi or precipitated exogenous material
such as the tested polymer. Either would be of concern.
Hydropic degeneration is a synonym for cloudy swelling of cells,
as is vacuolar degeneration. It is a non-specific lesion due to
inbibition of water (taking on of water) brought about by various
toxic suhstances and by the lack of oxygen. Its occurrence in
the liver of- the rats suggests that the "spray?" might have been
swallowed after licking from the skin. Its occurrence in the
kidney tubules could have been due to absorption via the lungs or
via the gut.
There is no evidence presented in the submission that the rats
were exposed to anything but water. This and the non-specificity
of the lesions, particularly in the rats with various disease
states, make further evaluation impossible.
Current production and Use
A review of the production range (includes importation volumes)
statistics for the hydrochloride salt of a polymer of aniline and
formaldehyde (CA.8 No. 57138-85-9), which is listed in the initial
TSCA Inventory, has shown that no 1977 production/importation was
reported or that all of the production range data reported were
claimed as confidential by the manufacturer(s) and importer(s)
and cannot be disclosed. (Section 14(a) of the TSCA, D.S.C. 2613
(a». **/
The Nalco Chemical Company reports that it has manufactured this
substance at two locations, one of which is a pilot plant. The
submitter did not provide any information on the use(s) of the
material. No information on the use(s) of the chemical substance
was located in the secondary literature sources consulted.
**/
The data submitted for the TSCA Inventory. including
production range information, are subject to the limitations
contained in the Inventory Reporting Regulations (40 CFR
710) .
103
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8EHQ-0980-0362
Page 3 of 3
Comments/Recommendations
The submitter stated that the provided inhalation study did give
an unexpected result which will require additional investigation
in order to determine the significance of the findings.
a)
The Nalco Chemical Company will be requested to address
the statements made in the Submission Evaluation section
of this status report. In addition, the submitter will
be requested to provide the results (including test
protocols and data) from the proposed additional toxicity
studies on the subject chemical.
b)
The Chemical Hazard Identification Branch/AD will trans-
mit a copy of this status report to OSHA and NIOSH.
104
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D.TE:
OCT 3 LJ .:~,,-,,,
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-09RO-03f33
Page 1 of 2
Approved ~ %[0
ReVisio/"
Needed
SUBJECT: Status Report * 8EHQ-0980-0363
no..:27'~k D. Kover, Chief
Chemical Hazard Identification Branch'
TO: Joseph J. Merenda, Director
Assessment Division
Submission Description
The International Coal Refining Company has provided a summary of
the preliminary results from an Ames Salmonella (bacteria) test
on Solvent Refined Coal (SRC) Recycle Solvent (CAS No. 68410-08-
2). The submitter states that SRC Recycle Solvent was found to
be mutagenic in that in vitro assay. The submitter also reports
that the positive result was expected based on the available
scientific literatu~e indicating the carcinogenic potential of
high boiling point, coal-derived materials.
Submission Evaluation
According to the summary information provided, SRC Recycle
Solvent was found to be mutagenic for Salmonella strains TA98 and
TAIOO. The submission does not indicate, however, whether the
mutagenic effects were observed in the presence or absence of a
metabolic activation system. without complete copies of the
experimental protocol and the data obtained, an evaluation of the
reported mutagenicity of SRC Recycle Solvent is not possible at
this time.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for SRC Recycle Solvent (CAS No. 68410-08-2) which is
listed in the initial TSCA Inventory, has shown that between 10
thousand and 100 thousand pounds of this chemical were
produced/imported in 1977. **/
According to the TSCA Inventory, SRC Recycle Solvent is the
liquid used to form the slurry for treating coal in the presence-
of hydrogen at high temperatures (over 800°F)~ the solvent boils
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herei~ are n?t to be regarded as expressing final
Agen~y pol1cy or 1ntent with respect to this particular
chem~cal. ,Any review of the status report should take into
~ons1der~t10n the fact that it may be based on incomplete
1nformat10n.
II~. '0"" 11»6 '''I:V. ..711
105
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8EHQ-0980-0363
Page 2 of 2
at temperatures ranging from 480° to 8500P. The submitter
reports that this process solvent is an internal, enclosed
stream, and that employee exposure is expected to be minimal.
comments/Recommendations
The Agency believes that in vitro mutagenicity assays of this
type provide valuable data that can aid in assessing the possible
risks posed by chemicals to health and the environment. Although
Ames test results, when considered alone, may not be sufficient
to provide reasonable support for a conclusion of substantial
risk, the addition of information concerning high production of
and/or exposure to the chemical would suggest the need for fur-
ther more definitive toxicological testing.
The EPA has received and evaluated other Section 8(e) submissions
on coal-derived and coal process materials: 8F.HQ-0778-0217, 8EHQ-
1078-0247, 8EHQ-I078-0252, 8EHQ-0779-0297, 8EHQ-0979-0306 and
8EHQ-1179-0316.
(a)
(b)
( c )
The International Coal Refining Company should be
requested to provide complete copies of the final
report, including the test protocol and data, from the
mutagenicity study cited in its submission. In addi-
tion, the company should be requested to describe the
actions it has taken in response to the submitted
toxicity information to warn workers and others, and to
reduce and/or eliminate exposure to SRC Recycle Solvent.
The Chemical Bazard Identification Branch (CRIB/AD) will
review the requested information, revise this status
report as appropriate, and recommend further assessment
if warranted.
The Chemical Hazard Identification Branch will transmit
copies of this status report to DOE, OSHA, NIOSH,
OWWM/EPA, and ORD/EPA. The Industry Assistance Office
(IAO/OTS) should consider sending the same information
to the manufacturers/importers of SRC Recycle Solvent
listed in the Master TSCA Inventory. CHIB will also
provide a copy of this status report and copies of the
above listed status reports to the OPTS Synfuels
Coordinator.
**/ This production range information does not include any
production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it
include any information which would compromise Confidential
Business Informaiton. The data submitted for the TSCA
Inventory, including production range information, are
subject to the limitations contained in the Inventory
Reporting Regulations (40 CPR 710).
106
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DATE:
NOV I 4 1980
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0980-0364
Page 1 of 3
~"
Approved
Revisio
Needed
SUBJECT:
Status Report* 8EHQ-0980-0364
fROM:,~"'-;;' D . Kove r , Ch i e f
~'Chemical Hazard Identification Branch
TO: Joseph J. Merenda, Director
Assessment Division
Submission Description
In a submission which was hand-delivered to the EPA Adminis-
trator's Office, Exxon Chemical Americas provided a summary
of preliminary results from the first phase of a 90-day
inhalation study of dicyclopentadiene (CAS No. 77-73-6) in
male and female Fisher 344 rats. According to the submis-
sion, male rats exposed to the chemical at 1, 5, and 50 ppm
were found to have varying degrees of anatomical and/or
functional kidney changes which'were apparently dose
related. The submitter reported that the observed changes
are non-specific and are those which are found in that
particular rat strain during the normal aging process and/or
following toxic insult.
Submission Evaluation
Dicyclopentad1ene is a highly reactive chemical and is pro-
bably an effective hapten. As such, and in common with
other hydrocarbons, it could produce antibodies which would
react with the dicyclopentadiene to precipitate in the mem-
branes of glomeruli in the kidneys. This process results in
hydrocarbon proliferative glomerulonephritis and approxi-
mates the descriptions of the observed effects noteq in the
provided summary. In addition, the diluted urine and cellu-
lar debris suggests that dicyclopentadiene produces typical
hydrocarbon tubular nephrosis of the kidney. The dilute
urine could also be due to ren?l diabetes insipidus.
It is doubtful that the kidney lesions observed in the test
animals were non-specific due to aging. It is aS$umed that
the rats used in the experiment were approximately 6 months
old which is ,not an age when changes in the kidneys (not due
to toxicity) typically occur.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made hexein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
inf"orma tion .
E~" '0,", U»4 uu:v. ..711
107
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8EHQ-0980-0364
Page 2 of 3
Current Production and Use
A review of the production range (includes importation volumes)
statistics for dicyclopentadiene (CAS No. 77-73-6), which is
listed in the initial TSCA Inventory, has shown that between 53
million and 282 million pounds of this chemical were
produced/imported in 1977. **/
Dicyclopentadiene is used as a chemical intermediate in the
manufacture of insecticides and other organic chemicals. It is
also used in the manufacture of certain paints, varnishes, and
flame retardants for plastics.
Comments/Recommendations
The submitting company reported that, upon completion, the final
results from this inhalation study will be forwarded to the EPA.
The submitter also reported that the results of the experiment
will provide preliminary information on the reversibility of the
observed kidney effects.
b)
a)
In this particular case, the Exxon Chemical Americas
submission of this section 8(e) information to the EPA
Administrator's Office did not unduly burden the EPA's
processing of the notice. However, it should be brought
to the submitter's attention that the substantial risk
information reporting requirements (Part IX of the EPA's
March 16, 1978, "Statement of Interpretation and Enforce-
ment Policy; Notification of Substantial Risk" (43 FR
11110» clearly specify that TSCA section 8(e) notices
are to be sent to the Document Control Officer, Manage-
ment Support Division, Office of Pesticides and Toxic
Substances (WH-557), Environmental Protection Agency, 401
M Street S.W., Washington, D.C. 20460. The Chemical
Hazard Identification Branch will provide a copy of the
March 16, 1978, policy statement to the submitter.
The submitting company should be requested to describe
the actions it has taken, in light of the provided
toxicity data, to warn workers and others, and to reduce
and/or eliminate exposure to dicyclopentadiene.
**/ This production range information does not include any
production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it
include any information which would compromise Confidential
Business Information. The data submitted for the TSCA
Inventory, including production range information, are subject
to the limitations contained in the Inventory Reporting
Regulations (40 CFR 710).
108
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BEHQ-0980-0364
Page 3 of 3
c)
The Chemical Hazard Identification Branch (CHIB/AD) will,
upon receipt, review the final results (which should
include test protocols and data) from the 90-day inhala-
tion study, revise this status report as appropriate, and
recommend additional assessment if warranted.
d)
CHIE will consider updating the draft Chemical Hazard
Information Profile (CHIP) on dicyclopentadiene to
include a discussion of these new and other relevant
data.
e)
Dicyclopentadiene is listed in the EPA's February 29,
1980 proposed TSCA Section 8(a) Level A rule (45 FR
13646).
f)
The Chemical Hazard Identification Branch will transmit
copies of this status report to NIOSH, OSHA, CPSC, and
OWWM/EPA. The Industry Assistance Office/OTS should
consider sending the same information to the manufac-
turers/importers of dicyclopentadiene listed in the
Master TSCA Inventory.
109
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
CATE:
tiGV - 6 :S',~"-:
8EHQ-0980-0365
Page I of 3
:::::::~ ~;;l60
Needed
SUBJECT:
Status Report* 8EHQ-0980-0365
'Ro.A:'1f'-
~Frank D. Kover, Chief
Chemical Hazard Identification Branch
TO: h d D . t
Josep J. Meren a, 1rec or
Assessment Division
Submission Description
S. C. Johnson & Son, Inc. has submitted a complete copy of the
the final results of an acute aspiration (intra-tracheal) test of
l;l,l-trichloroethane (methyl chloroform; CAS No. 71-55-6) in
rats. The submitting company stated that it had anticipated that
if death occurred, it would have been due to a chemical
pneumonitis. However, the submitter reported that death was
apparently due to "acute pulmonary hemorrhage."
Submission Evaluation
I,l, I-Trichloroethane is an irritant and an excellent solvent for
lipids. It is capable of blocking the conduction system in the
heart and can produce cardiac ventricular arrhthymias.
With regard to the submitted results, it should be noted that the
rat trachea has a volume of approximately 0.75 mI. Therefore,
the 0.2 ml of l,l,I-trichloroethane introduced directly into the
trachea is a relatively significant amount. The chemical would
immediately flow into the alveoli of the lung where it would
dissolve lipids in pulmonary and endothelial membranes which
could result in bleeding. It would also dissolve the
phospholipids of the lung surfactant.
The observed rapid deaths of the test animals suggests that the
chemical was absorbed rapidly from the lungs directly into the
left heart without dilution by the general circulation. This
would result in either a complete block of conduction or in
ventricular fibrillation. Either effect would cause a sudden
death.
*NOTE: This ~tatus report is the result of a preliminary
staff eva~uat10n of information submitted to EPA. Statements
made here1~ are n~t to be regarded as expressing final
Agen~y po11cy or 1ntent with respect to this particular
chem~cal. ,Any review of the status report should take into
7ons1der~t10n the fact that it may be based on incomplete
1nformat1on.
I:~" '0- 11»1 I!IIE". ~71)
110
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8EHQ-0980-0365
Pa
-------
8EHQ-0980-0365
Page 3 of 3
b) The Chemical Hazard Identification Branch (CHIB/AD) will
transmit copies of this status report to NIOSH, OSHA, CPSC,
and TRDB/AD/EPA. The Industry Assistance Office (IAO/OTS)
should consider sending the same information to the
manufacturers/importers of l,l,l-trichloroethane listed in
the Master TSCA Inventory.
c) In light of the fact that l,l,l-trichloroethane was listed
in the submission as "Insecticide 5198D72", CHIB will
transmit a copy of the submission and status report to the
Registration Division of tpe Office of pesticide Programs
(OPP/EPA) .
112
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U~UTED 5T A TES ENVIRONMENT AL PE:OTECTlm~ AGENCY
DA TE;
8EHQ-1080-0366
Page 1 of 3
APP~c~e~~ ~~ ~
Revisio
Needed
JAN 2 8 /98i
SUBJECT, Status Report* 8EHQ-1080-0366
FR~~:k D. Kover, Chief
Chemical Hazard Identification Branch
TO; Joseph J. Merenda, Director
Assessment Division
Submission Description
The Mobil Research anq Development Corporation has submitted
summarized results from several laboratory studies of dimethyl
hydrogen phosphite (CAS No. 868-85-9). According to the
submitter. the chemical was found to be positive in two of five
short-term mutagenicity screening tests. In addition, the
submitter report~d that cataracts and "other toxic effects" were
observed in rats exposed (subacutely) to dimethyl hydrogen
phosphite at bigh vapor concentrations (i.e., 119 and 198 ppm).
Milder forms of lens opacities were reportedly observed in rats
exposed to 12 and 35 ppm. The submitting company also reported
that although no clinical cataracts were found in a previously
performed ophthalmological study of plant employees, including
those involved with the manufacture of dimethyl hydrogen
phosphite, a reanalysis of the original data will be conducted
"to determine whether there may be a statistically significant
number of subclinical opacities among the dimethyl hydrogen
phosphite segment of the plant population."
Although the submitting company states that its laboratory find-
ings "suggest a potential hazard under conditions of excessive
long term exposure" to dimethyl hydrogen phosphite, the company
reports that the chemioal, which has a low vapor pressure (2.5 mm
Hg at 38°C and 25 mm Hg at 72°C) and is manufactured by Mobil in
small volumes in a closed system, "presents no significant
hazard" in its workplace.
Submission Evaluation
with regard to mutagenicity, dimethyl hydrogen phosphite was
reported to be positive in Drosophila tests and in an in vitro
mouse lymphoma assay (with metabolic activation). The submitter
reported that without metabolic activ~tion, the chemical was
negative for mutagenicity in the mouse lymphoma assay, and
*NOTE: This status reco=t is the result of a crelirni~a=v
staf: evaluation of i~formation submitted to EPA. Sta~e;e~ts
made he=ein a=e not to be regarded as ex~resS~DG fiDal
Agency policy or inten~ with respect to t~is particular
chem.lcal. . A.ny review or the status report should take into
co~s.lder~tlon t~e fact that it may be based on incom~:ete
.lD.o=mat.lon. .
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Fage 2 of 3
negative in the in vitro Ames test (both with and without
metabolic activation). The results of an in vitro DNA repair
test were reported to be inconclusive. As]?rovided, the
summarized test results do indicate that dimethyl hydrogen
phosphite has some degree of mutagenic activity. However,
without complete copies of all protocols and data obtained from
the cited studies, further evaluation of that activity is not
possible at this time.
With regard to the summarized results from the vapor exposure
studies in rats, the submitter did not provide any information on
the "other toxic effects" observed or on the types of cataracts
found. Subcapsular cataracts can result from chronic inflamma-
tion, while direct denaturation of lens proteins could give rise
to more rapid opaque changes. In addition, the phosphite could
be a weak alkylating agent as well as a weak anticholinesterase
agent. Either action could result in cataracts. Complete copies
of the rat study protocols and data should be requested for
further evaluation.
It should be noted that dimethyl hydrogen phosphite has bio-
logical properties similar to those previously reported for
trimethyl phosphite (TMP) by the Mobil Research and Development
Corporation pursuant to TSCA Section 8(e) (8EHQ-0679-029l et
seq.). Both compounds produced cataracts in rats and both were
negative in the Ames test but were positive in other short term
tests for mutagenicity. (It should also be noted that in light
of the submitted data on trimethyl phosphite, which also indi-
cated a teratogenic effect in rats (oral route), a Chemical
Hazard Information Profile (CHIP) was recommended for that
chemical and is now in preparation.)
Current production and Use
A review of the production range (includes importation volumes)
statistics for dimethyl hydrogen phosphite (CAS No. 868-85-9),
which is listed in the initial TSCA Inventory, has shown that
between 210 thousand and 2.1 million pounds of this chemical were
produced/imported in 1977.**/
The submitter reported that dimethyl hydrogen phosphite is
manufactured for chemical speciality use. Information on the
actual use(s) of the chemical was not provided by the submitter
nor located in the secondary literature sources consulted.
**/ This production range information does not include any pro-
-- duction/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it
include any information which would compromise Confidential
Business Information. The data submitted for the TSCA Inven-
tory, including production range information are subject to
the limitations contained in the Inventory Reporting
Regulations (40 CFR 710).
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Comments/Recommendations
The Mobil Research and Development Corporation reported that it
is informing its employees and customers of the submitted toxico-
logical findings for dimethyl hydrogen phosphite. In addition,
the submitter stated that any significant findings from the
reanalysis of the previous ophthalmological study of its workers
would be reported to the EPA.
b)
a)
The Chemical Hazard Information Branch (CHIB/AD) will
request the Mobil Research and Development Corporation to
provide complete copies of the results, including test
protocols and data obtained, from all of the laboratory
studies cited in its submission. In addition, the
submitting company will be asked if it plans to conduct
any further toxicological studies on dimethyl hydrogen
phosphite, especially with regard to teratogenicity.
It is recommended that dimethyl hydrogen phosphite be
considered for inclusion in TSCA Section 8(a) Level A
reporting.
c)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to OSHA and NIOSH. CHIB will
also provide a copy of the status report to the Office of
Toxics Integration (OTI/OPTS/EPA) for distribution to EPA
Regional Offices and State agencies, and to labor, envi-
ronmental, and selected citizen groups. The Industry
Assistance Office (IAO/OTS/EPA) should consider sending
the same information to the manufacturers and/or import-
ers of the subject chemical as listed in the Master TSCA
Inventory. and to identified industry-associated organi-
zations.
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DATE:
APR
6 198i
UNITED STATES ENVIRONMENTAL PROTECTIOH AGENCY
8EEQ-1080-0367
Page 1 of 5
Approved ~ ~~/
R " /.-
eVl.Sl.on .- ,
Needed ~/
SUaJECT: Status Report* 8EHQ-l080-0367
'~rank D. Kover, Chief
Chemical Hazard Identification Branch
TO:
Joseph J. Merenda, Director
Assessment Division
Submission Description
The Olin Corporation has submitted a copy of a Health Hazard
Evaluation Determination Report which was prepared by the
National Institute for Occupational Safety and Health (NIOSH) in
response to an employee representative's request for an .
evaluation of the Olin Chemical Company facility in Brandenburg,
Kentucky. According to the NIOSH summary, the evaluation was
requested by employees of the toluene diamine (TDA) manufacturing
area in that plant who had alleged that increased rates of
spontaneous abortions occurred in the wives of TOA workers.
According to Olin, the toluene diamine produced contains
approximately 80% 2,4-toluene diamine (CAS No. 95-80-7) and 20%
other TDA isomers including 2,6-toluene diamine. Olin also
provided a copy of a NIOSH Interim Report (No.2; April, 1980)
and a NIOSH Health Hazard Evaluation Medical Report (June, 1980)
concerning the Olin plant in Brandenburg, Kentucky.
In the initial employee request, which was received by NIOSH on
June 29, 1979, it was alleged that there was overexposure to the
chemicals used or produced in the TDA unit resulting in
"reproductive failures" among the workers. According to NIOSH,
the purpose of the initial study was to evaluate TDA and 2,4-
, dinitrotoluene (DNT; CAS No. 121-14-2) exposures and health
effects in the TDA unit. The NIOSH report states that the
results of an initial walk-through survey "revealed a history of
miscarriages, abnormal offspring, and semen abnormalities in the
TDA unit workers." Based on those findings, NIOSH scheduled a
fo11owup investigation (conducted January 14-18, 1980) which
included a detailed medical survey of the TDA workers and
monitoring of airborne levels of both TOA and ONT. Based on the
results of the studies conducted during their evaluation, NIOSH
has "determined that while this study cannot be interpreted as
*NOTE: This ~tatus report is the result of a prelimina=v
staff eva~uatlon of information submitted to EPA. State;e~ts
made herel~ are n~t to be regarded as expressing final
Agen~y pollCY or lntent with respect to t~is particular
chem~cal. ,Any review of the status report should take into
7onslder~tl.on the fact that it may be based on incomplete
lnrorma tl.on.
E~" '0"" 11»4 <"!:v. ~1"
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conclusive proof of TDA or DNT toxic effects on the male
reproductive system, it is strongly suggestive of a problem in
workers exposed to these agents. These effects were observed in
the presence of declining DNT and TDA exposures, none of which
exceeded current OSHA exposure limits during the survey."
A detailed discussion of the NIOSH findings and recommendations
are contained in the text of the submitted report. NIOSH reports
that based on the results of semen analyses, further studies will
be conducted on previously collected serum specimens. NIOSH also
plans to identify other plants using TDA in order to conduct
evaluations to find if similar problems exist among other TDA
workers. NIOSH reports that it will recommend that the National
Toxicology Program (NTP) conduct animal studies to determine if
reproductive effects can be demonstrated.
With regard to the NIOSH determinations that the subject studies
are "strongly suggestive of a problem in workers" exposed to TDA
and DNT, the Olin Corporation stated in the cover letter to its
submission that it disputes this and other NIOSH conclusions made
in the report and intends to comment directly to NIOSH. In
submitting the NIOSH study under Section 8(e), the company
reports that it has not concluded that the provided "information
supports or fails to support the conclusion that a certain
chemical substance(s) or mixture(s) presents a substantial risk
of injury to health or the environment."
Note:
On January 4, 1980, EPA scientists met with representa-
tives from the Olin Corporation and at that time received
information (PYI-OTS-0180-0055) from an interim (November,
1979) NIOSH report. At that meeting, the EPA was informed
that further information concerning this situation would
be forwarded to the Agency.
Submission Evaluation
The NIOSH epidemiologic study entailed a retrospective cohort
investigation primarily of reproductive effects among 30 male
workers. The study group size was very small and may limit the
overall interpretation of the study. These men were among a
larger group of individuals who volunteered to participate in the
study. Non-participation resulted from individuals' lack of
willingness to provide sperm specimens or pre-existing health
conditions thought to influence reproductive health.
The 30 men were assigned by job description information into
subgroups of exposed (9), or intermediate (12), or control (9).
Exposed group individuals were defined as those with the most
current continual contact to TDA, as well as to DNT.
Intermediate was defined as intermittent exposure for one or more
years, but not within the two years prior to the study. Control
group individuals were those who had no known exposure to TDA
during Olin employment. Many ambient samples of DNT and TDA
taken in the work environment at the time of the study were below
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the limit of detectio~. Although no measurements exceeded OSHA's
TLV for DNT (1.5 mg/M ), NIOSH believed that exposure had
diminished recently.
Medical and work histories were obtained, and physical and clini-
cal examinations were conducted among the cohort. In addition, a
questionaire on reproductive history was administered to the
workers' wives. No statistically significant differences (p >
.05) were observed between the three groups of workers regarding
history or physical examination. Although not statistically
significant, the NIOSH study found that more exposed than control
workers' wives reported spontaneous abortion. NIOSH reported two
statistically significant clinical findings. First, there was a
significant reduction in the number of large morphologic forms of
sperm in the exposed group when compared to controls(p = .015).
NIOSH stated in the report that the biological significance of
this finding is unknown. Second, there was a significant
reduction in sperm count in the exposed group compared to control
group (p = .03). This difference persisted when age of workers
was controlled.
The EPA believes that a number of experimental design and
statistical limitations in the provided study greatly influence
the overall interpretation of the obtained results. A selection
bias may have resulted from only a self-selected portion of the
exposed workers participating in the study, while reliance on
recall of the participating workers and their wives in
establishing medical and work histories and the failure to use
"blinded" investigators may have contributed observational bias
to the study. The EPA also believes that alternative statistical
procedures would have been more appropriate in analyzing some of
the obtained data. For example, in analyzing the incidence of
spontaneous abortions, congenital defects, and total pregnancies
before and after Olin employment, the investigators used the chi-
square and Fisher's exact tests. Because the groups before and
after Olin employment were not independent of one another (an
assumption required by the use of these tests), a non-parametric
analys~s, such as a sign test or McNemar's test for matched data,
would have been more appropriate. It should also be noted that
the study provides no direct evidence that either TDA or DNT had
passed through the bodies of the exposed workers. The workers'
blood could have been examined for Heinz bodies, methemoglobin-
emia, and anemia, and the urine could have been analyzed for
metabolites of the amino and nitro compounds. The study's
finding of a statistically significant reduction in sperm count
among the exposed workers provides a basis for concern about the
ability of TDA and/or DNT to cause reproductive effe~ts.
However, in view of the limitations of the study, the EPA
believes that further investigation is needed to confirm if such
effects are produced by TDA and/or DNT.
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Current Production and Use
A review of the production range (includes importation volumes)
statistics for 2,4-toluene diamine (CAS No. 95-80-7), which is
listed in the initial TSCA Inventory, has shown that between 130
million and 350 million pounds of this chemical were reported as
produced/imported in 1977. **/
2,4-Toluene diamine is a chemical intermediate for toluene
diisocyanate (used in the production of flexible and rigid
polyurethane foams~ polyurethane coatings~ cast elastomers
including fabric coatings~ polyurethane and other adhesives), and
for dyes used for textiles, leather, furs, and in hair-dye
formulations.
A review of the production range (includes importation volumes)
statistics for 2,4-dinitrotoluene (CAS No. 121-14-2), which is
listed in the initial TSCA Inventory, has shown that between 100
million and 500 milllion pounds of this chemical were reported as
produced/imported in 1977. **/
Manufacture of toluene diisocyanate consumes much of the 2,4-
dinitrotoluene produced. 2,4-Dinitrotoluene is also used as a
gelatinizing and waterproofing agent in explosives and as a dye
intermediate.
Comments/Recommendations
The International Agency for Research on Cancer (IARC) has
prepared a report on the carcinogenic risk of exposure to 2,4-
toluene diamine (IARC Monograph~ Vol 16, 1978). In addition, the
Chemical Hazard Identification Branch (CHIB/AD/EPA) has prepared
Chemical Hazard Information Profiles (CHIPs) on both 2,4-toluene
diamine and 2,4-dinitrotoluene.
The National Cancer Institute has tested both 2,4-toluene diamine
and 2,4-dinitrotoluene for carcinogenicity. According to the
1979 NIOSH Registry of Toxic Effects of Chemical Substances
(RTECS), 2,4-toluene diamine was found by NCI to be positive in
mice and rats, and 2,4-dinitrotoluene was found to be positive in
rats.
The existing Chemical Hazard Information Profile on 2,4-toluene
diamine recommends that the chemical be considered for inclusion
**/ This production range information does not include any
production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it include
any information which would compromise Confidential Business
Information. The data submitted for the TSCA Inventory including
production range information, are subject to the limitations
contained in the Inventory Reporting Regulations (40 CFR 710).
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in future TSCA Section 8(a) Level A reporting. 2,4-Dinitro-
toluene (CAS No. 121-14-2) is listed in the EPA's February 29,
1980 proposed TSCA Section 8(a) Level A rule (45 FR 13646). 2,4-
Dinitrotoluene is also included in the EPA's current list of 129
Priority Pollutants.
a)
The Chemical Hazard Identification Branch will ask the
Olin Corporation if it plans to conduct further
epidemiological and/or clinical studies of its workers
exposed to TDA and DNT. Olin will also be requested to
describe the actions it has taken, in light of the
submitted NIOSH report and the NCI findings, to warn
workers and others, and to reduce and/or eliminate
exposure to the subject chemical substances.
b)
The Chemical Hazard Identification Branch will transmit
a copy of this status report to NIOSH, OSHA, CPSC, FDA,
NCI/NTP, and OWWM/EPA. CHIB will also provide a copy of
the status report to the Office of Toxics Integration
(OTI/OPTS/EPA) for appropriate distribution. The
Industry Assistance Office (IAO/OTS/EPA) should consider
sending the same information to the manufacturers and/or
importers of the subject chemicals as listed in the
Master TSCA Inventory, and to industry-associated
organizations.
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-1080-0368
8EHQ-ll80-0368 Supplement
Page 1 of 2
-..!,-".J L 2 !~
Revisio
Needed
SUaJECT:
Status Report* 8EHQ-1080-0368
8EHQ-ll80-0368 Supplement
"Ro..,:/m'rik. D. Kover, Chief
Chemical Hazard Identification Branch
Approved
TO:
Joseph J. Merenda, Director
Assessment Division
Submission Description
In its initial submission, the Sodyeco Division of Martin
Marietta Chemicals reported that small quantities of certain
organic compounds (toluene, ethylbenzene, chlorobenzene, 1,2-
dichlorobenzene, and meta- and para-xylenes) had been detected in
the well water serving its plant site (and several nearby sites)
in Charlotte, North Carolina. The submitting company reported
that although the source of the contamination was not known, the
EPA was being advised because the compounds were in use by the
submitter. The submitter also reported that although it believed
that no substantial risk exists, it was expanding its analyses to
determine the extent of contamination and "taking all actions
that may be indicated to correct the situation expeditiously."
In the initial submission, Sodyeco provided the location of the
subject plant site and a map of that site giving the location of
the sampling stations. In addition, the submitter provided
copies of the sampling and analyses procedures and the laboratory
results keyed to the provided map. The submitter also included a
discussion of the company actions both taken and planned with
regard to this reported underground water contamination. Sodyeco
stated that it believes that its "actions to date will continue
to provide safe drinking water to all concerned." With regard to
planned activities, Sodyeco stated that its "plans are aimed at
eliminating any sources of these chemicals or pathways that lead
to groundwater supply systems."
In its supplemental submission, Sodyeco reported that it had
corrected the plant water system and had found that nearby
residences had not been exposed to significant concentrations of
toxic substances. The submitter also reported that every attempt
will be made to provide two commercial neighbors with a pure,
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agen~y policy or intent with respect to this particular
chem7cal. ,Any review of the status report should take into
~onslder~tlon the fact that it may be based on incomplete
lnforma tlon.
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Page 2 of 2
permanent water supply to replace the temporary filter systems
currently being used. In addition, Sodyeco stated that its
system of unlined treatment lagoons was believed to be the source
of the general inflitration (which was reportedly enhanced in
several locations by local ground conditions). The submitter
stated, however, that preliminary engineering had begun for an
effective containment system and that other minor potential
sources were being corrected. In conclusion, Sodyeco stated that
its "program is moving agressively toward a suitable solution..."
Submission Evaluation
Although all of the organic chemical contaminants reported are of
toxicologic concern, l,2-dichlorobenzene and chlorobenzene are of
greatest concern. These two compounds are irritants and are more
toxic when administered by mouth than by subcutaneous injection.
Both are capable of damaging the liver and affecting the bone
marrow.
The submitter's toxicology report suggests that no harm to health
occurred because of the short time of chemical exposure.
However, the report fails to take into account that synergistic
action, particularly between the two chlorobenzenes, may have
occurred. Toluene, ethylbenzene, and the xylenes are metabolized
by the liver to compounds that are readily excreted by the
kidney. At present, however, there are no studies that answer
the question of how low concentrations of hepatotoxic substances
(e.g. chlorobenzenes) affect the metabolism and elimination of
the three hydrocarbons.
Current Production and Use
Based on the nature of the submissions, a report on the current
production and uses of the subject chemical compounds does not
appear to be necessary at this time.
Comments/Recommendations
Upon receipt, the Chemical Hazard Identification Branch (CHIB/AD)
provided copies of both the initial and supplemental Section 8(e)
submissions to OWWM/EPA and to the EPA's Region IV Office in
Atlanta, Georgia for appropriate followup actions.
Toluene, ethylbenzene, chlorobenzene, and l,2-dichlorobenzene are
currently included in the EPA's list of 129 Priority Pollutants.
The Test Rules Development Branch (TRDB/AD/EPA) is currently
reviewing information received by the EPA pertaining to toluene,
xylenes, and chlorobenzenes.
a)
The Chemical Hazard Identification Branch will provide a
copy of the status report to TRDB/EPA, OWWM/EPA, and to
the EPA Region IV Office for inclusion in its files on
this reported ground water contamination.
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
6 : 1980
8EHQ-0780-0369
Page 1 o~ "~f'[rJ
:::::::d I~
Needed
OJ. TE: Revised (November 26, 1980)
SU8JECT: Status Report * 8EHQ-0780-0369
/1%-- (Previously FYI-OTS-0780-0075)
fR~~;ank D. Kover, Chief.
Chemical Hazard Identification Branch
TO: Joseph J. Merenda, Director
Assessment Div~sion
Submission Description
On May 12, 1980, several EPA scientists met with, and at the
requ~$t of, a past Director of Toxicology for the American
Cyanamid Company to discuss the results from certain in vivo
studies perf0rmed for the company prior to 1979. At tha~
meeting, the EPA was informed that high doses of two flame
retardant products had been found to produce neurotoxic effects
in laboratory animals. Specific?lly, the tested chemicals were
reported to be CYAGARD@ RF-l (ethylenebis[tris(2-cyanoethyl)]
phosphonium bromide) and PYROSET@ TKO (tetrakis(hydroxyrnethyl)
phosphonium sulfate). At that May 12 meeting, the EPA requested
(verbally) and was assured that complete copies of the American
Cyanamid toxicity files on both products would be forwarded to
the Agency for review and evaluation.
In response tO,this EPA request, the American Cyanamid Company
provided (FYI-OTS-0780-0075) the results from several short-term
in vivo studies on CYAGARD@ RF-l. The submission indicated that
neurotoxic effects (e.g. unsteady restricted gait, hind limb
paralysis) were observed in rats following oral administration of
the compound, either as part of the daily diet or by gavage.
However, CYAGARD@ RF-l did not appear to cause neurotoxic effects
in rats following dermal application. The submitter also
provided a CYAGARD@ RF-l technical data sheet which included
recommended handling precautions. -
Although specifically requested. by the EPA on May 12, 1980,
American Cyanamid did not provide any toxicity data on PYROSET@
TKO in its FYI submission.
*NOTE: This status report is the result of a prelimina=y
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
informa tion .
~./L ~Olll" u-.. IIU:V. "711
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Submission Evaluation
The ethylenebis[tris(2-cyanoethyl)]phosphonium bromide product
(CYAGARD~ RF-l) has two potentially neurotoxic chemical
configurations: 1) the compound is an analog of bisalkyl
quarternary ammonium compounds that can act at autonomic nervous
system ganglia or at neuromuscular junctions to produce blockade
or paralysis by preventing the release of acetylcholine; 2) the
compound is also an analog of polynitriles (e.g. iminodipropioni-
trile), which produce neurolathyrism resulting in muscle
paralysis such as that observed in the submitted feeding study in
rats. Nitriles of this type can produce degenerative changes
both to the spinal cord tracts that lead to the Purkinje cells of
the cerebellum and to the Purkinje cells themselves. It is of
interest to note that people in certain parts of the world (e.g.
India) may develop a wasting paralysis after eating plants in the
sweet pea family (lathyrus) that contain nitriles of this type.
The low oral LD50 observed (10 g/kg in rats) for
not highly signlficant in light of the fact that
nitrogen, phosphorous, and arsenic compounds are
absorbed from the intestine.
CYAGARD@ RF-l is
quarternary
not readily
Current Production and Use
A review of the production range (includes importation volumes)
statistics for ethylenebis[tris(2-cyanoethyl)]phosphonium bromide
(CAS. No. 10310-38-0) which is listed in the initial TSCA
Inventory, has shown that between 10 thousand and 100 thousand
pounds of this chemical were produced/imported in 1977.**/
American Cyanamid reported that CYAGARD@ RF-l is sold in limited
commercial quantities as a flame retardant in molded plastic
parts in certain types of electrical component and communication
equipment.
Comments/Recommendations
Following a review of the provided information on CYAGARD@ RF-l,
it was the EPA's preliminary determination that these neurotoxi-
city and exposure data should have been submitted to the Agency
at an earlier date pursuant to Section 8(e) of the Toxic
Substances Control Act (PL 94-469). The basis for this EPA
determination was as follows:
**/ This production range information does not include any
-- production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it
include any' information which would compromise Confidential
Business Information. The data submitted for the TSCA
Inventory, including production range information, are
subject to the limitations contained in the Inventory
Reporting Regulations (40 CFR 710).
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Page 3 of 5
The preface to Part V of the Agency's March 16, 1978,
"Statement of Interpretation and Enforcement PolicY7
Notification of Substantial Risk" (43 FR 11110) states that a
"substantial risk of injury to health or the environment is a
risk of considerable concern because of (a) the seriousness
of the effect... and (b) the fact or probability of its
occurrence." With regard to the seriousness of the effect,
Part V explains further 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... toxic effects resulting
in death, or serious or prolonged incapacitation." The
information respecting these effects can be obtained directly
or inferred from designed studies (e.g. in vivo experiments
and tests as described in Part VI of the]policy statement).
With regard to the "fact or probability of its occurrence"
criterion, Part V also provides that certain health effects
are so serious that relatively little weight should be given
to the chemical's exposure in determining whether a risk is
substantial. The mere fact that an implicated chemical is in
commerce constitutes sufficient evidence of exposure.
With regard to the reporting of substantial risk information,
Section 8(e) of the Toxic Substances Control Act (TSCA) (90
Stat. 2029, 15 D.S.C. 2607), states in part that a person who
obtains substantial risk information "must immediately inform
the Administrator...." Part IV of the EPA's Section 8(e)
policy statement of March 16, 1978, states that this
obligation to report "immediately" is fulfilled if the EPA
receives the information (via the reporting requirements
specified in Part IX) within 15 working days after the date a
subject manufacturer, processor, or distributor obtains such
information. With regard to information first obtained by a
subject person prior to the effective date of TSCA, Part VIII
of the Section 8(e) policy statement explains that any
substantial risk information possessed by a person prior to
January 1, 1977, of which that person is aware after that
date, shall be reported to the EPA within 60 days of March
16, 1978.
Because of the pattern and nature of the observed in vivo
neurotoxicological effects which can result in serious or
prolonged incapacitation, or death, and the fact that CYAGARD@
RF-l is and has been in commerce, the Agency believed that the
information contained in FYI-OTS-0780-0075 provided reasonable
support for a conclusion of substantial risk as defined in the
EPA's March 16, 1978, Section 8(e) policy statement. The Agency
also believed that the subject information should have been more
properly submitted by the ~~erican Cyanamid Company to the EPA at
an earlier date pursuant to TSCA Section 8(e).
125
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8EHQ-0780-0369
Page 4 of 5
The American Cyanamid Company stated that all of its customers
have been informed of the neurotoxicity findings on CYAGARD@ RF-
1. In addition, the submitter believes that this chemical can be
safely handled with a combination of good personal hygiene and
simple measures to avoid dust inhalation.
a)
On August 8, 1980, the American Cyanamid Company was
requested to provide its rationale as to why the
neurotoxicity and exposure data obtained by the company on
CYAGARD@ RF-l was not submitted to the EPA at an earlier
date pursuant to TSCA Section 8(e). American Cyanamid was
given an opportunity (20 working days) to rebut the
Agency's preliminary determination as to the Section 8(e)-
applicability of the information provided by the company
in FYI-OTS-C780-0075.
b)
In addition, the American Cyanamid Company was requested
to provide complete copies of any and all studies (other
than those already fully provided in FYI-OTS-0780-0075)
conducted for and by the American Cyanamid Company for the
purpose of assessing the biological activity of CYAGARD@
RF-l. This information was requested to include complete
test protocols, data obtained, conclusions drawn (if any)
and the date(s) of performance.
c)
As prevously stated in this status report, the Agency was
informed at the May 12, 1980 meeting that another flame
retardant product, PYROSET@ TKO, had also been found to be
neurotoxic in earlier laboratory studies performed for the
American Cyanamid Company- It was agreed (verbally) at
that meeting that complete copies of the company's
toxicity files on this product would be provided to the
EPA for review and evaluation. This requested information
on PYROSET@ TKO was not, however, provided to the EPA in
American Cyanamid's initial submission. The American
Cyanamid Company was therefore formally requested to
provide complete copies of any and all studies conducted
for and by the company for the purpose of assessing the
biological activity of PYROSET@ TKO. This information was
also to include complete test protocols, data obtained,
conclusions drawn (if any), and the date(s) of
performance.
d)
In its response (FYI-OTS-0980-0075 Followup Response) to
the EPA's August 8, 1980 letter, the American Cyanamid
Company stated that it had "reviewed the question of
reportability under Section 8(e) of TSCA in liqht of the
comments contained in [that EPA letter] and do not object
to the delivery of the information contained in either
submission to the OPTS Document Control Officer for ...
filing as Section 8(e) substantial risk information." The
company also stated that it would take the Agency's
comments into consideration in future determinations of
this type. Following a review of the company's response,
126
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8EHQ-0780-0369
Page 5 of 5
the Chemical Hazard Identification Branch delivered all
information contained in FYI-OTS-0780-0075 to the OPTS
Document Control Officer (DCO) for appropriate handling
and public filing as TSCA Section 8(e) substantial risk
information. The following substantial risk notice log
number was assigned by the DCO: 8EHQ-0780-0369.
e)
CHIB has reviewed and evaluated the additional information
requested and revised this status report as appropriate.
In addition, CHIB has prepared a status report on the
information which was provided by the American Cyanamid
Company on PYROSET@ TKO and other PYROSET@ flame retardant
products (8EHQ-0980-0369 Followup Response).
f)
It is recommended that ethylenebis[tris(2-cyanoethylJ
phosphonium bromide (CYAGARD@ RF-l) be considered for
inclusion in TSCA Section 8(a) Level A reporting.
g)
CHIB will transmit a copy of this revised status report to
OSHA, NIOSH, FDA, CPSC, OE/EPA, and the American Cyanamid
Company. CRIB will also provide a copy of the revised
status report to the Office of Toxics Integration (OTI/
OPTS/EPA) for distribution to EPA Regional Offices and
State agencies, and to labor, conservation, and selected
citizen groups. The Industry Assistance Office
(IAO/OTS/EPA) should consider sending the same information
to the manufacturers and importers of the subject chemical
listed in the Master TSCA Inventory, and to identified
industry-associated groups.
127
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DEC - 4 !980
SUBJECT: Status Report* 8EHQ-0980-0369
,m~
'.OWL-Frank D. Kover, Chief
Chemical Hazard Identification
Followup
Response
8EHQ-09BU~0369 FolIowup Response
Page 1 of 7
Approved ~ ~
Revision/
Needed
OAT!:
Branch
'TO: Joseph J. Merenda,- Director
Assessment Division
Submission Description
Per the Agency's requests in a followup letter (August 8, 1980),
the American Cyanamid Company provided additional toxicological
data (patch tests on human skin) on CYAGARD@ RF-l (ethylenebis-
tris(2-cyanoethyl)] .phosphonium bromide; CAS No. 10310-38-0) and
toxicity data (patch tests on humans and acute toxicity tests in
animals) on several tetrakis(hydroxymethyl) phosphonium salts
including PYROSET@ TKO (tetrakis(hydroxymethyl) phosphonium sul-
fate; CAS No. 55566-30-8). According to the submitted
information, several of the tested PYROSET@ flame retardants were
found to be neurotoxic in the performed animal experiments. A
list of the flame retardant compounds tested by the submitter is
shown below in Table 1.
Table 1. Flame Retardant Compounds Tested
PYROSET@
Tetrakis(hydroxymethyl)
phosphonium Salts
CAS Reg. No.
(None)
TKC
TKO
TKP
Acetate (1:1)
Chloride (1:1)
Sulfate (2:1)
Mixture of phosphate
and acetate salts
Oxalate (2:1)
Same as TKO
Condensat~on product of
oxalate salt and ammonia
758Q-37-2
124-64-1
,55566-30-8
-----
TKS
TK-115
PCA
52221-67-7
-----
-----
CYAGARD@
Ethylenebis[tris(2-cyano
ethyl)] phosphonium Salt
CAS Reg. No.
RF-l
Bromide
10310-38-0
*NOTE: This status reco=t is the result of a crelimina=v
staff evaluation of information submitted to EPA. State;er.~s
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
informa tion.
128
IE~A '0- 11»4 (I'IEV. ""I
-------
8EHQ-0980-0369 Fo110wup Response
Page 2 of 7
With regard to the use of the subject PYROSET@ flame retardants
in fabrics, American Cyanamid states that the tetrakis(hydroxy-
methyl) phosphonium salt flame retardants undergo significant
chemical changes during the course of application. In general,
fabric is passed through a bath containinq flame retardant which
has been pre-treated ("neutralized") with.J sodium hydroxide. The
submitter reports that this neutralization "converts about 70
mole/percent of the quaternary [tetrakis(hydroxymethyl)]
phosphonium compound to tris(hydroxymethyl) phosphine, formal-
dehyde, and the sodium salt of the counter-ion." The fabric,
which is reported to pick up "solids" from the bath, is next
substantially dried to a water content of 10-20 percent, and is
then treated with ammonia vapor, which the submitter reports
"converts adjacent hydroxymethyl groups to iminodimethylene
linkages." After the ammonia treatment, the fabric is treated
with hydrogen peroxide (or other oxidizing agent) which
reportedly "oxidizes the trivalent phosphorus to the pentavalent
state through the addition of an atom of oxygen." The material
is then washed in water/detergent and dried. The submitter
reports that although other types of treatment may be used on
occasion, these also result in similar chemical changes to the
flame retardant. The submitter states that following such treat-
ments, "the finish on the fabric is far different chemically from
the material that is applied." The submitter provided the
results from several sponsored studies which were performed to
determine the toxicity of flame retardant-treated fabrics which
were either "oxidized" or "unoxidized". According to the
provided results, neurotoxicity was observed only in rats which
were fed (1% in the daily diet for five weeks) pulverized flame
retardant-treated cotton cloth which was cured with ammonia but
had not received the hydrogen peroxide wash (i.e. unoxidized).
The Chemical Hazard Identification Branch/AD/EPA prepared an
earlier status report on acute in vivo neurotoxicity information,
provided by the American Cyanamid Company on a "For Your Infor-
,mation (FYI)" basis (originally FYI-OTS-0780-0075), concerning
its CYAGARD@ RF-l flame retardant product which is used in
plastics for electrical and communication equipment. Based on a
review and evaluation of that neurotoxicity data and the fact
that the subject chemical is and has been in commerce, it was the
Agency's preliminary determination that the information provided
reasonable support for a conclusion of substantial risk of injury
to health as defined in the Agency's March 16, 1978, "Statement
of Interpretation and Enforcement Policy; Notification of
Substantial Risk" (43 FR 11110) and should have been submitted by
the American Cyanamid Company to the Agency at an earlier date
pursuant to Section 8(e) of the Toxic Substances Control Act (PL
94-469). On August 8, 1980, American Cyanamid was requested to
provide its rationale as to why the subject data on CYAGARD@ RF-l
were not submitted earlier under Section 8(e) and was given an
opportunity to rebut the Agency's preliminary determination on
8(e)-applicability. The American Cyanamid Company was also
requested at that time to provide toxicological information on
129
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8EBQ-0980-0369 Fbllowup Response
Page 3 of 7
its PYROSET@ TKO flame retardant product. The requested
information was provided by American Cyanamid (FYI-OTS-0980-0369
Followup Response), and is the subject of the present status
report.
Submission Evaluation
The initial American Cyanamid submission dealt with the flame
retardant CYAGARD@ RF-I, a compound which had both a bisquater-
nary structure and an amino alkylcyano analog structure.
Bisquaternary compounds can cause skeletal muscle paralysis
either by preventing the release of acetylcholine presynaptically
at the neuromuscular junction or by the persistent depolarization
of the muscle end-plate at that junction. Amino alkylcyano com-
pounds also cause skeletal muscle paralysis, but by a different
mechanism: damage to the spinal cord and cerebellum. American
Cyanamid's followup response establishes that the tetrakis
(hydroxymethyl) phosphonium compounds are neurotoxic in
themselves and do not require the presence of an amino alkylcyano
analog group. The provided test data show that the subject
PYROSET@ compounds are absorbed from the skin of rabbits and in
some cases from the skin of rats and cats, and the gastroin-
testinal tract of rats. This absorption resulted in signs of
neurotoxicity in rabbits, rats, and/or cats. The oral route of
administration was 2 to 3 times as toxic as the dermal route.
However, in two instances, the dermal route was shown to be more
toxic than the oral. The differences 0etween the salts of the
tetrakis (hydroxymethyl) phosphoniums are quantitative rather
than qualitative, depending on the particular salt tested and the
route of exposure.
Most quaternary ammonium and bisquaternary ammonium compounds and
their P, As, Sb, B and other analogs are feeble cholinesterase
inhibitors. Therefore, it is not surpising that the
hydroxymethyl phosphonium was not an active anticholinesterase,
as demonstrated in the submitted studies.
With regard to human skin patch tests, neither the CYAGARD@ RF-I
nor the tested PYROSET@ compounds (which did not include PYROSET@
TKO) were found to be sensitizing to human skin.
According to the submitter's description of the flame retardant
application process, during the sodium hydroxide neutralization
step, not all of the initial quaternary phosphonium compound is
converted to the phosphine derivatives and by-products which
include formaldehyde. Considering that the cloth picks up
"solids" (undefined by the sUbmitter) from the neutralization
bath and is then only dried to a 10-20 percent water content, the
possibility exists that residual unaltered (i.e. un-neutralized)
quaternary phosphonium remains with the cloth at least to that
point. The subsequent treatment of that residual compound with
ammonia could lead to the formation of chemicals which are
irritating and could retain neurotoxic properties which possibly
may not be affected by the subsequent peroxide treatment. With
130
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8EHQ-0980-0369 Followup Response
Page 4 of 7
regard to the phosphine derivatives (i.e. neutralized flame
retardant) which are also picked up by the cloth, the ammonia
treatment would most likely generate compounds which may be
irritating but would not be expected to have neurotoxic
properties. The addition of peroxide treatment in this case
would be expected to bring about a further reduction in toxicity.
It should be noted that without a complete chemical analysis
performed during the steps in the application process, it is not
possible at this time to determine the actual chemical identities
and amounts of the various compounds which may be formed during
the process and are either discarded and/or are carried through
the process and remain with the finished flame retardant-treated
fabrics.
Current Production and Use
PYROSET@ Products
A review of the production range (includes importation volumes)
statistics for tetrakis(hydroxymethyl) phosphonium acetate (CAS
No. 7580-37-2) and tetrakis(hydroxymethyl) phosphonium oxalate
(PYROSET@ TKS7 CAS No.52221-67-7), which are listed in the
initial TSCA Inventory, has shown that no 1977 production/
importation was reported or that all of the production range data
was claimed confidential by the manufacturer(s) and importer(s)
and cannot be disclosed (Section 14(a) of the TSCA7 U.S.C. 2613
(a». **/
A review of the production range (includes importation volumes)
statistics for tetrakis(hydroxymethyl) phosphonium chloride
(PYROSET@ TKC7 CAS No. 124-64-1) which is listed in the initial
TSCA Inventory, has shown that between 100 thousand and 1 million
pounds of this chemical were produced/imported in 1977. **/
A review of the production range (includes importation volumes)
statistics for tetrakis(hydroxymethyl) phosphonium sulfate
(PYROSET@ TK07 CAS No. 55566-30-8) which is listed in the initial
TSCA Inventory, has shown that between 1.1 million and 11 million
pounds of this chemical were produced/imported in 1977. **/
American Cyanamid reports that, of the above PYROSET@ products,
only PYROSET@ TKO is currently a com~ercial product. According
to the submission, the tetrakis(hydroxymethyl) phosphonium salts
can be used as durable flame retardants in fabrics. The sub-
mitter also points out that it "sells otner flame retardants
under the PYROSET@ trademark whicr do not belong to this class of
compounds."
CYAGARD@ Product
A review of the production range (includes importation volumes)
statistics for ethylenebis[tris(2-cyanoethyl)1 phosphonium
bromide (CYAGARD@ RF-17 CAS No. 10310-38-0), which is listed in
131
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8EHQ-0980-0369 FolloWllp RespJnse
Page 5 of 7
the initial TSCA Inventory, has shown that between 10 thousand
and 100 thousand pounds of this chemical were produced/imported
in 1977.**/
American Cyanamid has reported that CYAGARD@ RF-l is sold in
limited commercial quantities as a flame retardant in molded
plastic parts in certain types of electrical component and
communication equipment.
Comments/Recommendations
Following a review of the toxicity information on the tetrakis
(hydroxymethyl) phosphonium salts, the EPA believes that the
provided information should have been submitted at an earlier
date pursuant to Section 8(e) of the Toxic Substances Control Act
(PL 94-469). The basis for the EPA's position is as follows:
The preface to Part V of the Agency's March 16, 1978,
"Statement of Interpretation and Fnforcement PolicYi Notifi-
cation of Substantial Risk" (43 FR 11110) states that a
substantial risk of injury to health or the environment is a
risk of considerable concern because of (a) the seriousness
of the effect. . . and (b) the fact or probability of its
occurrence." With regard to the seriousness of the effect,
Part V explains further 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. . . toxic effects
resulting in death, or serious or prolonged incapaci-
tation." The information respecting these effects can be
obtained directly or inferred from designed studies (e.g. in
vivo experiments and tests as described in Part VI of the
policy statement). With regard to the "fact or probability
of its occurrence" criterion, Part V also provides that
certain health effects are so serious that relatively little
weight should be given to the chemical's exposure in
determining whether a risk is substantial. The mere fact
that an implicated chemical is in commerce constitutes
sufficient evidence of exposure.
With regard to the reporting of substantial risk
information, Section 8(e) of the Toxic Substances Control
Act (TSCA) (90 Stat. 2029, 15 D.S.C. 2607), states in part
that a person who obtains substantial risk information "must
immediately inform the Administrator. "Part IV of the
EPA's Section 8(e) policy statement of March 16, 1978,
states that this obligation to report "immediately" is
fulfilled if the EPA receives the information (via the
reporting requirements specified in Part IX) within 15
working days after the date a subject manufacturer,
processor, or distributor obtains such information. With
regard to information first obtained by a subject person
prior to the effective date of TSCA, Part VIII of the
132
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BF.HQ-09BO-0369 Followup Response
Page 6 of 7
Section 8(e) policy statement
risk information possessed by
1977, of which that person is
be reported to the EPA within
explains that any substantial
a person prior to January 1,
aware after that date, shall
60 days of March 16, 1978.
In light of the in vivo neurotoxicological effects (which can
result in seriouS-or prolonged incapacitation or death) which
were observed following exposure to the tested PYROSET@ tetrakis
(hydroxymethyl) phosphonium salts including the sulfate salt
(PYROSET@ TKO), and considering that at least one of the subject
flame retardant compounds (PYROSET@ TKO) is and has been in
commerce, it is the Ag~ncy's preliminary determination that the
information contained in the American Cyanamid Company's followup
response provides reasonable support for a conclusion of substan-
tial risk as defined in the EPA's March 16, 1978, Section 8(e)
policy statement. In addition, it is the EPA's preliminary
determination that the subject information should have been more
properly submitted by the American Cyanamid Company to the EPA at
an earlier date pursuant to TSCA Section 8(e).
In the cover letter to its followup response, American Cyanamid
stated that it has reviewed the question of Section 8(e)-reporta-
bility in light of the Agency's comments on the data provided in
the initial FYI submission on CYAGARD@ RF-l and dOE:!s "not object
to the delivery of the information contained in either submission
[initial and followup] to the OPTS Document Control Officer
for... filing as Section 8(e) substantial risk information." The
submitting company also stated that it will take those EPA
comments "into consideration in futur determinations of this
type."
Following a review of the company's response and provided data,
the Chemical Hazard Identification Branch delivered all informa-
tion contained in FYI-OTS-0780-0075 anc FYI-OTS-0980-0075
Followup Response to the OPTS Document Control Officer (DCO) for
appropriate handling and public filing as TSCA Section 8(e)
substantial risk information. The following substantial risk
notice log numbers were assigned by the DCO: 8EHQ-0780-0369 and
8EHQ-0980-0369 Followup Response.
a)
The American Cyanamid Company will be requested to de-
scribe the actions it has taken, in light of the reported
toxicity data, to warn workers and others, and to reduce
and/or eliminate exposure to the subject flame retardant
chemicals.
b)
The Chemical Hazard Identification Branch has revised its
initial status report on CYAGARD@ RF-l to reflect the
assigned TSCA Section 8(e) log number.
c)
Tetrakis(hydroxymethyl) phosphonium sulfate (2:1)
(PYROSET@ TKO) is listed in the EPA's February 29, 1980
proposed TSCA Section 8(a) Level A rule (45 FR 13646).
In light of the reported toxicity data, it is recommended
133
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8EHQ-0980-0369 Followup Response
Page 7 of 7
that the other cheMicals referenced in this status report
be considered for inclusion in TSCA Section 8(a) Level A
reporting.
d)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to OSHA, NIOSH, FDA, CPSC,
OWVJM/EPA, and OE/EPA. CHIB will also provide a copy of
the status report to the Office of Toxics Integration
(OTI/OPTS/EPA) for distribution to EPA Regional Offices
and State agencies, and to labor, environmental, and
selected citizen groups. The Industry Assistance Office
(IAO/OTS/EPA) should consider sending the same
information to the manufacturers and/or importers of the
subject chemicals as listed in the Master TSCA Inventory,
and to identified industry-associated groups.
**/ This production range information does not include any
-- production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it
include any information which would compromise Confidential
Business Information. The data submitted for the TSCA
Inventory, including production range information, are
subject to the limitations contained in the Inventory
Reporting Regulations (40 CFR 710).
134
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
,.~ ~:nk D. Kover, Chief
Chemical Hazard Identification
Branch
8EHQ-1080-0370
Page 1 of ~
Approved ~*
Revisio/ .
Needed
OATf;:
JAN I 4 1981
Status Report* 8EHQ-1080-0370
SUBJECT:
TO:
Joseph J. Merenda, Director
Assessment Division
Submission Descriotion
.I:
Exxon Chemical Americas has submitted a summary of preliminary
results from a long term (lifetime) inhalation study of 1,3-
butadiene (CAS No. 106-99-0) in' male and female Sprague-Dawley
rats. The study, which was sponsored by the International
Institute of Synthetic Rubber Producers, involved inhalation
exposure to l,3-butadiene at concentrations of 0, 1000, and 8000
ppm for 6 hours/day, 5 days/week until the survival in any group
reached between 20% and 25%. The submitter reported that the
data obtained thus far indicate that there was an increase in
mortality for both sexes at the 1000 and 8000 ppm dose levels.
The submitter also reported that there appeared to be an
increased incidence in total mammary tumors (benign plus
malignant) in female rats exposed to 1000 or 8000 ppm. Male rats
exposed to 8000 ppm reportedly showed an increased incidence in
Leydig cell tumors (all benign) of the testes. The submitter
also reported that there was a suggestion of tumor increases in
several other orgari systems of the test animals.
Exxon Chemical Americas stated that although it is not possible
to draw definitive conclusions at present, "the data suggests
(sic) an association between l,3-butadiene exposure and increased
tumor incidence for the test animals."
Submission Evaluation
As submitted, the data show that l,3-butadiene is an oncogen.
The complete analysis of the final data will probably establish
l,3-butadiene to be a carcinogen. Although the preliminary data
indicate extensive organ distribution of tumors, it is of
interest that the supporti.ve or connective tissues appear to have
been the targets in the uterus and brain.
*NO~E: This ~tatus repo=t is the result of a prelimina=v
sta_f eva~uat10n of information submitted to EPA. State~ents
made here1~ are not to be regarded as expressing final
Agen~y po11cy or intent with respect to this oarticular
Chem~dcal. .Any review of the status report sh~uld take into
conS1 erat10n the fact that it may b b d .
information. ease on 1ncomplete
E~A '0'"" 11»-6 11'I£\'. ..711
135
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8EHQ-1080-G370
Page 2 of 3
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 Inventory, has shown that between 2.1 billion
and 7.3 billion pounds of this chemical were produced/imported in
1977. **/
1,3-Butadiene is used as a raw material in the manufacture of
synthetic rubber products and fibers.
Comments/Recommendations
The submitter reports that further results will be provided to
the EPA upon completion of the study.
In 1974, OSHA set the current occupational standard for 1,3-
butadiene exposure at an 8-hour time-weighted average (TWA) of
1000 ppm in air (39 CFR 23540). 1,3-Butadiene is listed in the
EPA's February 29, 1980 proposed TSCA Section 8(a) Level A rule
(45 FR 13546). l,3-Butadiene is currently being tested for
carcinogenicity (inhalation, mice) by the National Cancer
Institute (NCI)/National Toxicology Program (NTP).
a)
The Chemical Hazard Identification Branch (CHIB/AD) will
request the submitting company to describe the actions it
has taken, in light of the provided toxicity data, to warn
workers and others, and to reduce and/or eliminate
exposure to 1,3-butadiene.
b)
CHIB will consider the preparation of a Chemical Hazard
Information Profile (CHIP) on 1,3-butadiene. ("Butadiene
and Its Oligomers" was the subject of a previous (Decem-
ber, 1978) hazard assessment (EPA 560/2-78-008) which is
available through the National Technical Information
Service (NTIS) in Springfield, Va.).
c)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to OSHA, NIOSH, CPSC, FDA,
NCI/NTP, and OWWM/EPA. CHIB will also provide a copy of
the status report to the Office of Toxics Integration
(OTI/OPTS/EPA) for distribution to EPA Regional Offices.
**/ This production range information does not include any
production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it
include any information which would compromise Confidential
Business Information. The data submitted for the TSCA
Inventory, including production range information, are subject
to the limitations contained in the Inventory Reporting
Regulations (40 CFR 710).
136
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8EHQ-1080-0370
Page 3 of 3
and State agencies, and to labor, environmental, and
selected citizen groups. The Industry Assistance Office
(IAO/OTS/EPA) should consider sending the same information
to the manufacturers and/or importers of l,3-butadiene as
listed in the Master TSCA Inventory, and to identified
industry-associated organizations.
137
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D.\ TE:
JAN 2 2 I~~;!
Status Report* 8EHQ-1180-03?1
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-1l80-0371
Page I of 2
/J2G- .
'Ro,M' I K-~nk D. Kover, Ch~ef
~", Chemical Hazard Identification
Branch
APprove~ J'o/ft
Revisio
Needed
SU!JECT:
TO:
Joseph J. Merenda, Director
Assessment Division
Submission Description
Lever Brothers Company, Inc. has reported. that under the
conditions of a recently performed in vivo study, a commercial
product identified as VARISOFT 222(90%) was found to be a potent
skin sensitizer in guinea pigs. The submitter reported that this
product is supplied by the Sherex Chemical Corporation and is
described as being a complex difatty quaternary for use in liquid
fabric softener systems. Lever Brothers stated that its interest
in VARISOFT 222~90%) for use in household products could have
possibly constituted a new use by the public and therefore an
increase in the general exposure. In submitting this information
to the EPA under Section 8(e), Lever Brothers stated that it
believes that the preliminary data derived from the performed
study "reasonably supports our [the company's] contention that
this material could possibly pose a substantial risk to humans
upon repeated exposure."
Note:
In the initial submission, Lever Brothers reported that
the Sherex Chemical Corporation was a subsidiary of the
Ashland Chemical Corporation. However, the Ashland
Chemical Corporation has reported (8ERQ-0181-03?1
Supplement) that Sherex is a subsidiary of Schering A.G.
of West Germany.
Submission Evaluation
VARISOFT 222(90%), which is described as a "complex difatty
quaternary," may be related to the dialkyl cetyl ammonium
complexes which are used as cationic detergents. Some compounds
of this type are known to be skin irritants and sensitizers.
Efforts should be made to obtain the name(s) and amount(s) of the
actual chemical component(s) of VARISOFT 222(90%) from its
manufacturer.
*NOTE: This status report is the result of a preliminarv
staf: evaluation of information submitted to EPA. State~ents
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chem~cal. . Any review of the status report should take into
~o~s~der~t~on the fact that it may be based on incomplete
~n_ormat~on.
£~A '0- IJ~ II'IEV. "'''1
138
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8EHQ-1l80-0371
Page 2 of 2
Current Production and Use
VARISOFT 222(90%) is not listed as such in the initial TSCA
Inventory. The submitting company did not provide any
information on the current production/importation volumes of the
product nor was that information located in the secondary
literature sources consulted.
As previously stated, Lever Brothers reported that VARISOFT 222
(90%) is used in liquid fabric softener systems. No other
information on the use(s) of VARISOFT 222(90%) was located in
secondary literature sources consulted.
Comments/Recommendations
Lever Brothers reported that it had informed the Sherex Chemical
Corporation of the test results and also of Lever Brothers'
intention to submit a Section 8(e) notice. Lever Brothers also
reported that on the basis of those test data, the company will
probably not continue further development of a product containing
VARISOFT 222(90%).
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request the manufacturer of VARISOFT 222(90%) to
provide information concerning the actual identity
(including CAS Number(s)) and amount(s) of the chemical
component(s) of the product.
b)
CHIB will transmit a copy of this status report to both
the submitting company and the manufacturer of VARISOFT
222(90%). In addition, CHIB will transmit a copy of the
status report to NIOSH, OSHA, CPSC, and OWWM/EPA. CHIB
will also provide a copy of the status report to the
Office of Toxics Integration (OTI/OPTS/EPA) for distri-
bution to EPA Regional Offices and State agencies, and
to labor, environmental, and selected citizen groups.
139
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0... TE:
UNITED STATES E~VIRONMENTAL PROTECTION AGENCY
8EEQ-1l80-0372
Page] of 2
APproved~ J'1f1Y
Revision
Needed
JAN I 4 ,-
SUBJECT: Status Report* 8EHQ-1180-0372
,7)1:1'-
FR~: Frank D. Kover, Chief
Chemical Hazard Identification Branch
TO:
Joseph J. Merenda, Director
Assessment Division
Submission Description
The Callery Chemical Company has submitted a summary of results
from acute dermal toxicity and ocular irritation studies
(rabbits) of dimethylsulfide borane (CAS No. 13292-87-0).
According to the provided summary, a dose of 200 mg/kg body
weight applied to intact or abraded skin for 24 hours caused
death in 5/10 animals shortly after exposure. With regard to the
ocular irritation study, an 0.1 ml sample was placed into the
lower conjunctival sac in one eye of each of 6 rabbits. The eyes
were irrigated with water after 24 hours and the eyes were
examined. Signs of irritation/damage (i.e. corneal opacity.
injected iris, slight conjunctival redness and swelling) were
observed and were found to improve slightly by the seventh day of
post-exposure observation. The submitter stated that in "the
event of a spill or accident, dimethylsulfide borane can present
a risk to unprotected persons."
Submission Evaluation
Dimethylsulfide borane appears to be a highly toxic, lethal
chemical which is readily absorbed from the skin. It would be
important to have a description of the signs of intoxication that
preceded the death of the rabbits. The reported deaths could
have been due to either respiratory or cardiovascular failure.
Death could have also been due to central nervous system effects
such as occur with decaborane which releases norepinephrine in
the cerebral cortex.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for dimethylsulfide borane (CAS No. 13292-87-0), which
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
inxorma tion.
140
E~A '0- 11... (~r:v. )-7'"
-------
8EHQ-1l80-0372
Page 2 of 2
is listed in the initial TSCA inventory, has shown that no 1977
production/importation was reported or that all of the production
range data reported were claimed as confidential by the manu-
facturer(s) and importer(s) and cannot be disclosed. (Section
14(a) of the TSCA, U.S.C. 2613 (a».~
No information on the use(s) of dimethylsulfide borane was pro-
vided by the submitter nor located in the secondary literature
sources consulted.
comments/Recommendations
The Agency's interest in receiving the results of acute animal
toxicity studies pursuant to Section 8(e) of TSCA is, in general,
fairly limited. Under certain circumstances, however, the
results of such range finding studies can provide reasonable
support of a conclusion of substantial risk. Clarification of
this point can be found in the EPA's March 16, 1978 "Statement of
Interpretation and Enforcement POlicy: Notification of Substan-
tial Risk" (43 FR 11110), Appendix A, part D, Comment 14.
~
a)
~e Chemical Hazard Identification Branch (CHIB/AD) will
request the Callery Chemical Company to provide complete
copies of the test protocols, data, results of necropsy
(if performed), and cage-side observations (if any) from
the studies cited in its submission. The submitting
company will also be requested to describe the actions
it has taken, in light of the provided toxicity data, to
warn workers and others, and to reduce and/or eliminate
exposure to dimethylsulfide borane. In addition, the
company will be asked if it plans to conduct any addi-
tional testing in order to further define the toxicity
of dimethyl sulfide borane.
b)
The Chemical Hazard Identification Branch will transmit
a copy of this status report to NIOSH and OSHA. CHIB
will also provide a copy of the status report to the
Office of Toxics Integration (OTI/OPTS/EPA) for distri-
bution to EPA Regional Offices and State agencies, and
to labor, environmental, and selected citizen groups.
The Industry Assistance Office (IAO/OTS/EPA) should
consider sending the same information to the manufac-
turers and/or importers of the subject chemical as
listed in the Master TSCA Inventory, and to identified
industry-associated organizations.
The data submitted for the
duct ion range information,
contained in the Inventory
710) .
TSCA Inventory including pro-
are subject to the limitations
Reporting Regulations (40 CFR
141
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 7
DATE:
ADO 2 I .9"'"
J I \ I:~) I
Fa OM: /fI,;X,-
t//fank D.
Chemical
Status Report* 8EHQ-1180-0373S
8EHQ-1180-0374S
8EHQ-0281-0373S
8EHQ-0281-0374S
Kover, Chief'
Hazard Identification
Supplement
Supplement
Approved f"- ~fll
Re.vision
Needed
SU6JECi:
Branch
TO:
Joseph J. Merenda, Director
Assessment Division
Submission Description
The 3M Company has submitted preliminary reports with test
protocols and the final reports of a teratology study in rats
with 1) a mixture of N-ethyl perfluorooctylsulfonamido ethanol
and N-ethyl perfluoroheptylsulfonamido ethanol (8EHQ-1180-0373S:
8EHQ-0281-0373S Supplement) and 2) FC-95, a commercial mixture of
perfluoroalkylsulfonic acid potassium salts (8EHQ-1180-0374S and
8EHQ-0281-0374S Supplement). In addition, submission 8EHQ-1180-
0374S contains a 3M technical report entitled "Analysis of
Selected Decatur Employee Serum for Sulfonic and Carboxylic
Fluorochemicals".
According to the submitted protocols, the tested mixtures were
administered via oral intubation to sexually mature, time-mated
female rats on days 6 through 15 of gestation. Animals were
assigned to groups receiving 0, 1, 5 or 10 mg/kg/day of the
potassium salt derivative mixture or 0, 25, 37.5 or 75 mg/kg/day
of the perfluoroethanol derivative mixture.
The final teratology reports (8EHQ-028l-0373S Supplement and
8EHQ-028l-0374S Supplement) state that both test mixtures
produced a "developmental eye abnormality which appeared to be an
arrest in development of the primary lens fibers forming the
embryonal lens nucleus, followed by secondary aberrations of the
secondary lens fibers of the fetal nucleus". According to the
final reports, this effect was observed in all three dose groups
administered FC-95 (significant in the high dose group) and was
significantly higher than controls in all three dose groups
administered the mixture of perfluoroethanol derivatives. The
final reports further state that, while FC-95 did not produce an
increase in skeletal abnormalities, the mixture of
*NOTE: This ~tatus ~eport is the result of a preliminarv
staff eva~uatlon of lnformation submitted to EPA. State~ents
made herel~ are not to be regarded as expressing final
Agen~y POllCY or intent with respect to this particular
chern~~al. . Any review of the status report should take into
~O~Sl er~tlon the fact that it may be based On incomplete
In...orrnatlon.
E~A '0- U»-6 (~£v. "'II
142
-------
8EHQ-1180-Q373 Si 8EHQ-Q281-0373 S Supplement
8EHQ-1180-0374 Si 8EHQ-0281-Q374 S Supplement
Page 2 of 7
perfluoroethanol derivatives produced cleft palates in the high
and mid dose groups (significant in the high dose group), blood
in the fetal kidney parenchyma in all three dose groups
(significant in the high dose group), and malformations in fetal
sternebrae and other skeleton aberrations of varying significance
at the different dose levels. The final reports also state that
FC-95 at the high dose and the perfluoroethanol derivative
mixture at the high and mid doses were maternally toxic in
reducing weight gain during dosing, but did not affect the
ovaries or reproductive tract contents of the dams and were not
embryo toxic.
In the submitted 3M technical report, it is stated that fluoro-
chemicals have been detected in the blood of 3M employees.
According to that 3M report, the five highest fluorine-containing
serum samples among ten selected plant employees contained three
fluorochemicals with total levels ranging from 4.1 to 11.8 ppm.
The submitter also states that according to employee records and
a recent study conducted by the 3M Company which was published in
the American Industrial Hygiene Association Journal (Vol. 41:584-
589, August, 1980) "to date no human health problems have been
observed nor disease patterns detected which are attributable or
related to fluorochemical exposure". This published study,
entitled "Health Status of Plant Workers Exposed to Fluoro-
chemicals - A Preliminary Report," contains information on
fluorochemical levels both in the blood of fluorochemical plant
workers and in workplace ambient air. as well as the results of
employee health screening examinations and a retrospective
epidemiological investigation of plant employees. The published
study indicates that analysis of fluorine levels in the blood of
ammonium perfluorooctanoate production workers showed that
although inorganic fluorine levels were comparable to normal
human sera, organic fluorine levels ranged from 1.00 to 71.00
ppm, compared to 0.01 to 0.13 ppm for normal human sera. The
published report also states that one worker with elevated
organic fluorine in the blood was moved to a fluorochemical-free
plant location and monitored for blood and urine fluorine at
regular intervals. Over an 18 month period, the serum organic
fluorine levels in this worker reportedly decreased from 70 to 39
ppm, and levels of perfluorooctanoate in the urine (24 hour
collections) decreased from 387 to 80 micrograms over the first
14 months of this period. The report states that these blood and
urine values "suggest that some fluorochemicals are very slowly
eliminated in humans".
According to the same published 3M study, the results of 3M
employee medical examinations, which included liver function
profiles, showed no relationship between test result deviations
and blood levels of organic fluorine. The most frequently
encountered liver enzyme exceeding the normal range among a
143
-------
8EHQ-1l80-G373 S; 8EHQ-G28l-G373 S Supplement
8EHQ-ll80-G374 S; 8EHQ-G28l-G374 S Supplement
Page 3 of 7
sample of all plant employees was serum gamma-glutamyl-
transferase (SGGT). However the 3M study states that these
deviations "were most likely unrelated to plant work and are
compatible with the individuals' predisposition toward alcohol".
The 3M pub lis bed study also states that a retrospective cohort
mortality study of plant employees covering a 30 year period from
1948 to 1978 indicated no disagreement between observed and
expected mortality among employees in general or chemical workers
in particular. The report states further that this finding was
true for all causes of death and specific causes of death due to
cancer.
In the same publication, it is reported that ammonium perfluoro-
octanoate was negative in the Ames test both with and without
metabolic activation. The target organ of this same substance in
rodents was reported to be the liver, where a more pronounced
histopathological effect was observed in males than in females.
The published report also states that the major site of toxicity
in the rhesus monkey appeared to be the reticuloendothelial
system. The published report states that details of these
studies are presented in a separate publication. However, this
separate publication was not cited.
According to the 3M published report, air monitoring in the
operator'~ breathing zone indicated fluorochemical levels up to
3.27 mg/m during fluorochemical processing and packaging
operations, but that this level has been reduced to 0.47 mg/m3 by
instituting appropriate modifications which were described in the
report.
Submission Evaluation
The final reports provided in submissions 8EHQ-0281-0373S
Supplement and 8EHQ-0281-0374S Supplement furnish detailed
teratology data for the subject mixtures, both of which contain
organofluorine compounds and produce malformations during fetal
development, particularly failure of the eye lens to develop
normally. Such failure occurs rarely. These submissions report
for the first time that this type of teratogenic effect can be
induced by exogenous chemicals. Additional research with these
fluorochemical mixtures appears to be needed to determine the
mechanism of lens teratogenesis.
The 3M sponsored epidemiology study reported in the American
Industrial Hygiene Association Journal appears to be too general
for detecting slowly developing clinical toxicity resulting from
exposure to special classes of organic compounds. The interest-
ing data in this published report are that 1) workers exposed to
the perfluoro compounds can absorb them, as indicated by blood
144
-------
8EHQ-1180-o373 S; 8EHQ-0281-0373 S Supplement
8EHQ-1180-o374 S; 8EHQ-0281-o374 S Supplement
Page 4 of 7
and urine levels, and 2) the one worker studied for several
months after exposure had been terminated still had organic
fluorine in the blood at 18 months and was still excreting
perfluorooctanoate in the urine at 14 months. (It should be noted
that fecal elimination was not monitored). The blood level of
organic fluorine had decreased to approximately one half, and the
urine level of perfluorooctanoate by approximately 80%. This
finding indicates a blood half-life of at least one and one-half
years. The provided data do not permit a determinat~on of
whether there is firm bonding with plasma proteins or whether
there is continuous release from depot stores in the body. Firm
bonding is suggested by the increasing ratio of serum levels of
organic fluorine to urinary levels of perfluorooctanoate, as
though less and less of the amount in the blood can be excreted
by the kidneys. This ratio of organic serum in the blood to
perfluorooctanoate in the urine increased from 17 at one week
post-exposure to 55 at 14 months post-exposure. The data also
suggest that the perfluoroates are picked up by macrophages,
stored in the reticuloendothelial system (liver, spleen, lungs,
lymphatic structures and possibly the kidneys) and slowly
released into the blood. These suggestions can be answered only
by experiments on animals. The reported determinations on the
studied employee did not include blood and urine levels of
inorganic (ionized) fluorine.
It should be pointed out that although fluorine compounds affect
bone, teeth and enzymes involved in blood clotting and thyroid
gland functions, the published 3M report did not contain data
pertaining to these parameters. The consulting hepatologist
cited in this same published report may have been correct in
assuming that the slightly elevated SGGT reflected "dispositions
of the subjects to alcohol". However, no corroborating data were
presented, nor was the possibility of storage in the liver
considered. It appears that comprehensive animal studies on the
pharmacokinetics and tissue levels of the subject chemicals in
the reticulo-endothelial system are needed. Also, levels of
organic and inorganic fluoride in the blood and urine, dental
examinations and x-ray examination of bones for signs of
fluorosis for each exposed person would allow a more complete
evaluation of worker health status.
145
-------
8EHQ-1180-D373 S; 8EHQ-0281-0373 S Suppl~t
8EHQ-1180-0374 S; 8EHQ-0281-0374 S Supplement
Page 5 of 7
Current Production and Use
A review of the production range (includes importation volumes)
statistics for N-ethyl perfluorooctyl sulfonamido ethanol (CAS No.
1691-99-2), which is listed in the initIal TSCA Inventory, has
shown that between 100,000 and 1,000,000 pounds of this chemical
were produced/imported in 1977. **/
A review of the production range (includes importation volumes)
statistics for N-ethyl perfluoroheptylsulfonamido ethanol (CAS
No. 68555-73-7), which is listed in the initial TSCA Inventory
has shown that between 10,000 and 100,000 pounds of this chemical
were produced/imported in 1977 **/
The submitter states that the
is used as an intermediate in
fluorochemical products. The
diate has been claimed by the
Information" .
mixture of the above two chemicals
the production of various finished
actual identity of this interme-
submitter as "Confidential Business
FC-95 is identified by the submitter as FLUORAD@ Brand Fluoro-
chemical Surfactant, a mixture containing potassium salts of
homologous perfluoroalkyl sulfonates. The components of this
mixture and their combined production volume have been claimed by
the submitter as "Confidential Business Information".
The submitter states, in 8EHQ-l180-0374S, that this homologous
mixture (or the corresponding ammonium salts) is currently sold
as various products containing from 100 percent "solids" to 0.58
percent of the mixture. These products and their customer uses
are described in the submission as follows:
FLUORAD@ Brand Fluorochemical
Surfactant, FC-95
Chrome Plating
FLUORAD@ Brand Etching Bath Additive
FC-93 (corresponding ammonium salt of
the subject chemical)
Electronic
Manufacturing
FLUORAD@ Brand Fluorochemical
Surfactant, FC-99 (corresponding
amine salt of subject chemical)
Chrome Plating
**/ This production range information does not include any
production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it include
any information which would compromise Confidential Business
Information. The data submitted for the TSCA Inventory, includ-
ing production range information, are subject to the limitations
contained in the Inventory Reporting Regulations (40 CFR 710).
146
-------
8EHQ-1180-o373 S; 8EHQ-028l-o373 S Supplement
8EHQ-1180-o374 S; 8EHQ-028l-Q374 S Supplement
Page 6 of 7
LIGHT WATER@ Brand Aqueous Film
Forming Foam FC-203
Fire Suppression
LIGHT WATER@ Brand Aqueous Film
Forming Foam FC-203A
Fire Suppression
LIGHT WATER@ Brand Aqueous Film
Forming Foam, FC-206A
Fire Suppression
LIGHT WATER@ Brand Aqueous Film
Forming Foam Alcohol Type
Concentrate, FC-600
Fire Suppression
AFFF 6% Concentrate, FC-780B
Fire Suppression
No other information on current production volumes or uses of FC-
95 were located in the secondary sources consulted.
Comments/Recommendations
The 3M Company states that it plans to inform all customers and
employees with significant exposure potential to the subject
chemicals of the teratology study findings and to outline 3M's
recommendations for handling and using these products. The
submitter also states that copies of these submissions are being
transmitted to NIOSH and that the following work is planned for
initiation in the near future: 1) a second teratology study
designed to further evaluate these findings in both rats and
rabbits; 2) lifetime feeding studies in rats; 3) development of
industrial hygiene procedures designed to further reduce exposure
to plant employees.
The EPA has evaluated a previous 3M submission (8EHQ-1077-00ll)
in which it was reported that FC-70, a commercial product used as
an electronics vapor soldering fluid, decomposes to highly toxic
perfluoroisobutylene and an unidentified perfluoroimine when
overheated.
a)
The 3M Company will be asked if it plans to conduct
further monitoring studies (e.g., organic and inorganic
fluoride levels in the blood and urine, dental
examination and x-ray examinations of bones for signs of
fluorosis) of employees potentially exposed to the
subject chemicals.
b)
The 3M Company will be requested to provide biblio-
graphic citations for the mutagenicity and target organ
studies in rodents and monkeys cited and summarized in
the 3M report published in the American Industrial
Hygiene Association Journal which is referenced in the
original submissions.
147
-------
8EHQ-1180-o373 S; 8EHQ-0281-o373 S supplement
8ERQ-1180-0374 S; 8EHQ-0281-G374 S SUppleme~t
Page 7 of ]
c)
It is recommended that the chemicals referenced in this
status report be considered for inclusion in TSCA Sec-
tion 8(a) Level A reporting.
d)
The Chemical Hazard Identification Branch will consider
the preparation of Chemical Hazard Information Profiles
on selected chemicals within the class of perfluoro-
alkylsulfonates.
e)
The Chemical Hazard Identification Branch will transmit
a copy of this status report to OSHA, NIOSH, CPSC and
OWWM/EPA. CHIB will also provide a copy of the status
report to the Office of Toxics Integration (OTI/EPA) for
appropriate distribution. The Industry Assistance
Office (IAO/EPA) should consider sending the same infor-
mation to the manufacturers and/or importers of the sub-
ject chemicals as listed in the Master TSCA Inventory,
and to identified industry-associated organizations.
148
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
JAN I 5 198:
SU~ECT: Status Report* 8EHQ-1180-0375S
..~:~ D. Kover, Chief
Chem1cal Hazard Identification
Approved
8EHQ-1180-0375S
Page] of 2
~
DATI!:
Branch
Revision
Needed
TO:
Joseph J. Merenda, Director
Assessment Division
Submission Description
Tenneco Chemicals, Inc. submitted a summary of preliminary data
from a rat dermal application study of a mixture of the cadmium
salts of para-tertiary-butylbenzoic acid and-benzoic acid. (The
submitter has claimed the actual identities ~nd amounts of the
applieq mixture components to be Confidential Business
Information). According to the submitter, a single high level
dermal exposure to the mixture (in an appropriate vehicle)
produced testicular damage in the rats.
The submitting company stated that this dermal application study
in rats was undertaken following receipt of information that
para-tertiary-butyl benzoic acid caused testicular damage in
laboratory animals.
Submission Evaluation
It appears that th~ applied mixture of cadmium salts was absorbed
through the skin and resulted in damage to the testicles. This
observation confirms, in part, reports in the literature that
para-tertiary-butyl benzoic acid causes such damage when fed to
rats. It is also well established that acute cadmium poisoning
can cause testicular damage in rats.
Further evaluation of the submitter's findings will have
the EPA's receipt of complete copies of -the experimental
protocols(s) and data obtained from the cited rat dermal
application study.
to await
Current Production and Use
In light of the submitter's claim of confidentiality for the
actual chemi~al identities and amounts of the components in the
*NOTE: This status report is the result of a prelimina=v
staff eva~uation of information submitted to EPA. State~ents
made here~~ are n~t to be regarded as expressing final
Agen:y pol~cy or ~ntent with respect to this particular
chem7dcal. ,Any review of the status report should take into
cons~ erat~on the fact that it may b b d '
information. ease on ~ncomplete
149
-------
8EHQ-1180-0375S
Page 2 of 2
applied mixture, the review of the production volumes of the
mixture itself and its specific components will not appear in
this status report. The submitter did not provide any
information on the uses of the tested mixture, nor was such
information located in the secondary literature sources
consulted.
Comments/Recommendations
Tenneco Chemicals, Inc. reports that "steps are being taken to
insure elimination of workers' potential direct contact with this
chemical substance." (The exact nature of those steps have been
claimed as confidential by the sUbmitter).
The National Institute for Occupational Safety and Health (NIOSH)
has published a "Criteria Document" on cadmium. EPA's Carcinogen
Assessment Group (CAG/ORD) has also evaluated this chemical. In
addition, the Chemical Review and Evaluation Branch (CREB/AD/EPA)
has completed an in-depth source and health/environmental effects
assessment (Phase I) for cadmium. Cadmium is currently included
in the EPA's list of 129 Priority Pollutants.
a)
The Chemical Hazard Identification Branch (CHIB/AD) will
request the submitting company to provide a complete
copy of the final results, including test protocols and
data, from the rat dermal application study cited in its
submission.
b)
CHIB will transmit a copy of this status report to
NIOSH, OSHA, OWWM/EPA, ORD/EPA, and CREB/EPA. CHIB will
also provide a copy of the status report to the Office
of Toxics Integration (OTI/OPTS/EPA) for distribution to
the EPA Regional Offices and State agencies, and to
labor, environmental, and selected citizen groups.
150
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
8£8Q-1280-0376
P::p::~e: In In/W
Revision
Needed
JAN 2 7 /981
SUaJeC:T: Status Report * 8EHQ-1280-0376
,~k D. Kover, Chief
Chemical Hazard Identification Branch
To:Joseph J. Merenda, Director
Assessment Division
Submission Description
The Stepan Chemical Company has reported that two nitrosamines
have been identified as contaminants in an alkyl amine oxide.
Specifically, the submitter reports that by using a thermal
energy analysis (TEA) technique, a sample of lauryl dimethylamine
oxide (CAS No. 1643-20-5) was found to contain 2.1 ppm N-nitroso-
dimethylamine (CAS No. 62-75-9) and 6.1 ppm N-nitrosomethyldode-
cylamine (CAS No. 55090-44-3). The finding of N-nitrosodimethyl-
amine was reportedly confirmed by using another analytical
technique (GCMS).
The Stepan Chemical Company reports that lauryl dimethylamine
oxide is a surfactant used in formulated shampoos and household
detergent products. The submitter also reports that "the data
indicate that a product formulated with these materials at a
typical 4% level could contain 10 to 80 parts per billion of
dimethylnitrosamine. Since a representative usage concentration
of such a formulated product is in the range of 0.10%, the
exposure level of the ultimate consumer could be in the range of
0.010 to 0.080 parts per billion."
It is the submitter's stated belief that "the manufacture or use
of [lauryl dimethylamine oxide] or its use in cleaning products
at the levels determined" does not represent a substantial
risk. However, in making this report pursuant to TSCA Section
8(e). the Stepan Chemical Company states that it does understand
tha.t "certain ni trosamines, including N-ni trosodimethylamine,
have been recognized by the USEPA as suspected carcinogens...."
Submission Evaluation
Dimethylnitrosamine has been shown to be carcinogenic in all
animals species (over 20 species) tested to date, including the
guinea pig (which is refractory to the carcinogenic effect of
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. State;er.ts
made herein are not to be regarded as expressing final
Agen~y policy or intent with respect to this particular
chem~cal. ,Any review of the status report should take into
~ons~der~t~on the fact that it may be based on incomplete
~nforma t~on.
151.
t;,.. '0- 11»-4 ''lEV. ~711
-------
8EHQ-1280~0376
Page 2 of 4
highly potent azo dyes and aromatic amines), as well as sub-human
primates. The carcinogenic effects of higher dialkylnitrosamines
and more complex (e.g. cycloalkyl and alkyl aryl) nitrosamines are
also well known. However, these compounds have been far less
extensively studied than dimethylnitrosamine. (N-Nitrosomethyl-
dodecylamine belongs to the category of asymetric higher nitrosa-
mines). The target specificity of the various nitrosamines
covers a wide range of tissues and organs. As with other
carcinogens, the target tissues/organs for any particular
nitrosamine may vary from species to species.
Human tissues rapidly metabolize nitrosamines, in particular
dimethylnitrosamine, and have been shown to generate from the
latter compound an activated mutagenic agent. The discovery of
dimethylnitrosamine as a carcinogen has been linked to the
observation that the compound is a potent hepatotoxic agent in
humans at low exposure levels. It has also been established (in
rodents) that the hepatotoxicity is the preliminary stage of the
neoplastic transformation in the liver. Two recent forensic
cases have reaffirmed the potent hepatotoxicity of dimethylnitros-
amine in humans. Although there are no epidemiological data as
yet on the carcinogenicity of nitrosamines in humans, based on the
existing evidence, these chemical substances should be regarded as
potential human carcinogens.
There is experimentally-supported reason to conclude that no
threshold dose for carcinogenicity can be assumed, at least in the
cases of dimethyl- and diethylnitrosamine. In fact, the metabolism
of these two compounds consists of a one-step pathway which
represents an activation process for both mutagenicity and
carcinogenicity. It should also be pointed out that no
detoxification pathway for the above nitrosamines has been
discovered during 26 years of investigation. Consequently,
level of these less complex nitrosamines can be expected to
rise to an equimolar level of mutagenic/carcinogenic agents
humans.
any
give
in
In commercial products, nitrosamine contaminants may originate as
by-products formed during the manufacturing process or, as in the
case of complex mixtures (e.g. cutting fluids), nitrosamines may
arise and increase in concentration as the result of chemical
interaction of certain chemical components during storage. In the
case of single compounds, such as lauryl dimethylamine oxide, the
nitrosamine contaminants could represent by-products of the syn-
thesizing process or possibly impurities of the starting materials
used in that process. It is important to note that under these
circumstances, the levels of contaminating nitrosamines could be
very substantially reduced by appropriate change(s) in the
manufacturing process and/or careful monitoring (i.e. chemical
analysis) of the purity of the feedstocks used in the process.
152
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8FHQ-1280-0J76
Page 3 of 4
Current Production and Use
A review of the production range (includes importation volumes)
statistics for lauryl dimethylamine oxide (CAS No. 1643-20-5),
which is listed in the initial TSCA Inventory, has shown that
between 11 thousand and 112 thousand pounds of this chemical were
produced/imported in 1977.**/
The submitter reports that lauryl dimethylamine oxide is a
surfactant which is manufactured by a number of companies and is
used in shampoos and household detergent formulations. No further
information on the use(s) of the chemical was provided by Stepan
or was located in the secondary literature sources consulted.
A review of the production range (includes importation volumes)
statistics for N-nitrosodimethylamine (CAS No. 62-75-9), which is
listed in the initial TSCA Inventory, has shown that between 0 and
2 thousand pounds of this chemical were produced/imported in 1977.
**/
According to secondary literature sources, N-nitrosodimethylamine
was used (prior to 1976) in the United States as an intermediate
in the production of l,l-dimethylhydrazine liquid rocket fuel. The
chemical is apparently now only used for research purposes.
N-Nitrosomethyldodecylamine (CAS No. 55090-44-3) is not listed in
the initial TSCA Inventory. No information was located on the
use(s) of this chemical substance.
Comments/Recommendations
The International Agency for Research on Cancer (IARC) has found
that there "is sufficient evidence of a carcinogenic effect of N-
nitrosodimethylamine in many experimental animal species.
Similarities in its metabolism by human and rodent tissues have
been demonstrated. Although no epidemiological data were
available [to the IARC workgroup]...N-nitrosodimethylamine should
be regarded for practical purposes as if it were carcinogenic to
humans" (IARC Monograph~ Vol. 17 ~ May, 1978). Since 1974, N-
nitrosodimethylamine has been regulated by OSHA as a carcinogen
(39 CFR 3756). According to the NIOSH Registry of Toxic Effects
of Chemical Substances (RTECS~1979), N-nitrosomethyldodecylamine
has also been shown to be carcinogenic in laboratory animals.
**/
This production range information does not include any
production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it
include any information which would compromise Confidential
Business Information. The data submitted for the TSCA
Inventory, including production range information, are
subject to the limitations contained in the Inventory
Reporting Regulations (40 CFR 710).
153
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8EHQ-1280-0376
Page 4 of 4
Lauryl dimethylamine oxide and N-nitrosodimethylamine are listed
in the EPA's February 29, 1980 proposed TSCA Section 8(a) Level A
rule (45 FR 13646).
The Procter and Gamble Company recently informed (January 8, 1981)
the Chemical Hazard Identification Branch/AD that the company is
currently testing lauryl dimethylamine oxide and reported that the
information submitted by the Stepan Chemical Company under Section
8(e) of TSCA will be considered in the quality control program for
the conduct of that study. Procter and Gamble also reported that
the National Cancer Institute (NCI) is aware of the ongoing
testing and has reviewed the company's protocols.
The EPA has received and evaluated several other Section 8(e)
submissions on nitrosamines: 8EHQ-0012, 0133, and 0294. (These
numbers represent the last four digits of the EPA's Document
Control number assigned to the submission).
a)
The Chemical Hazard Identification Branch (CHIB/AD) will
request the Stepan Chemical Company to describe the
actions it has taken, in light of the provided informa-
tion on nitrosamines, to warn workers and others, and to
reduce and/or eliminate exposure to the subject chemical
substances.
b)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, CPSC, FDA,
NCI/NTP, OWWM/EPA, the Interagency Regulatory Liason
GrOup(IRLG) workgroup on nitrosamines, and to the Procter
and Gamble Company. CHIB will also provide a copy of the
status report to the Office of Toxics Integration
(OTI/OPTS/EPA) for distribution to EPA Regional Offices
and State agencies, and to labor, environmental, and
selected citizen groups. The Industry Assistance Office
(IAO/OTS/EPA) should consider sending the same
information to the manufacturers and/or importers of
lauryl dimethylamine oxide as listed in the Master TSCA
Inventory, and to identified industry-associated
organizations.
154
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
-/~-
FR~/ Frank D.
Chemical
Kover, Chief
Hazard Identification Branch
8EHQ-0181-0377
Page 1 of 4
Appyoved ~~I~/
Revision~
Needed
D.&. TE:
JAN 2 7 198\
SUBJECT:
Status Report* 8EHQ-Ol8l-0377
TO:
Joseph J. Merenda, Director
Assessment Division
Submission Description
The Atlantic Richfield Company has reported that upon repeated
dermal application to rabbits, Jet Fuel A, No.6 Heavy Fuel oil
(API Gravity 5.2/1.2%S). and No.6 Heavy Fuel Oil (API Gravity
23.1/0.2%S) each produced an apparent compound-related increase
in the incidence of hyperplasia of the urinary bladder
epithelium. The submitter reported that these studies (sponsored
by the American Petroleum Institute) involved the dermal applica-
tion of the test chemicals for five consecutive days followed by
a two day rest period with another five day application followed
by a two day rest period. According to the submitter, observa-
tions for mortality and local reactions were made during the 14-
day test period. Following the test period, microscopic examina-
tion of the urinary bladders reportedly revealed hyperplasia.
In reporting these toxicological findings under Section 8(e) of
TSCA, the submitter stated that there are several factors which
indicate that the increased incidence of urinary bladder
hyperplasia may not be due to the dermal application of the
tested chemicals. Specifically. the submitter stated that:
"I.
The small number of control animals used may not have
been indicative of the true incidence of bladder
hyperplasid in untreated animals.
2.
Because of the high doses used, many of the animals
died after only a few days exposure to the test
material. This limited time on test would appear to be
too short for the development of hyperplasia of the
bladder epithelium.
3.
The tissue sampling techniques used at necropsy were
not standardized. This difference in techniques may
have resulted in apparent increased thickness of normal
bladder epithelium. Examples of these non-standardized
*NOTE: This status recort is the result of a preliminary
staff evaluation of inforwation submitted to EPA. Sta~e~e~~s
made herein are not to be re~arded as ex~ressi~c :inal
A~ency policy or intent with~respect to t~is ?a;ticular
cnernlcal. . fu"y review of the status re?or~ should take into
~o~slder~tlor. the fact that it may be based on incom~~ete
:n_or~a~lon. '
155
.' .." ..,.... ..~~ . ~ ,.....
,.... -., . -,..,
-------
8EHQ-0181-0377
Page 2 of 4
techniques included: the site of the bladder from
which tissue was sampled was not the same in all
animals: and the fact that some bladders were inflated
with fixative before sampling, while others were not."
The Atlantic Richfield Company also pointed out that it had
previously submitted a Section 8(e) notice on Jet Fuel A (8EHQ-
1279-0323). In that earlier submission, Atlantic Richfield
provided a complete copy of the final results from a number of in
vitro and in vivo mutagenicity studies of Jet Fuel A. At that
time, the submitter reported that this fuel did not exhibit a
positive response in the Ames test either with or without
metabolic activation. However, Jet Fuel A was reportedly found
to induce mutations in the in vitro mouse lymphoma assay (in the
presence of metabolic activation), and found to produce bone
marrow cell mutations in an in vivo cytogenetics study.
Submission Evaluation
At an 8 ml/kg dose (only dose tested), Jet Fuel A produced
significant skin toxicity of some degree in all of the rabbits to
which it was applied derma11y. According to the laboratory
report, the compound also pro~uced hyperplasia of the
transitional epithelium in the urinary bladder of 3 of the 8
tested rabbits. Six of the 8 treated rabbits died during the
course of the experiment and 6 of the 8 animals were observed to
have some degree of liver injury. The performing laboratory
conclusion with regard to the experiment with Jet Fuel A was that
the effects observed were treatment related.
At an 8 ml/kg dose (only dose tested), No.6 Heavy Fuel oil (API
Gravity 23.1/0.2%S) resulted in the deaths of 2 of 8 rabbits to
which it was dermal1y applied. All of the treated animals were
observed to have severe skin changes. Four of 8 rabbits were
found to have proliferative changes in the transitional
epithelium of the urinary bladder and 7 of 8 had liver injury-
The performing laboratory reported the observed toxicological
effects to be treatment related.
No.6 Heavy Fuel oil (API Gravity 5.2/1.2%8) induced inflammatory
changes at the site of skin application at all doses tested (1.0,
2.0, and 2.5 ml/kg) in the rabbits. Fourteen of 16 animals
receiving the highest doses (2.0 and 2.5 ml/kg) were reported to
have mu1tifoca1 necrosis of the liver. One animal receiving the
highest dose was found to have hyperplasia of the transitional
epithelium of the urinary bladder.
Based on the findings of the performed studies, there is little
doubt that the three tested petroleum products result in severe
toxicity when applied to the skin. It is significant that
hyperplasia of the transitional epithelium of the urinary bladder
occurred only in the treated animals. The submitter's suggestion
156
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8EHQ-0181-0377
Page 3 of 4
that the observed toxicological effects were not compound
treatment related would require further experimentation in light
of the actual laboratory findings and the opinions expressed by
the performing laboratory. In addition, a more precise
characterization of the volume percent of polynuclear
hydrocarbons (some of which may be carcinogens) present in the
tested fuels would appear to be necessary.
Current Production and Use
In submission 8EHQ-1279-0323, the Atlantic Richfield Company
reported that Jet Fuel A is a complex petroleum product which is
sold to airline companies for use as jet airplane fuel. Although
there is no one CAS number used to identify the possible avail-
able mixtures and treatment processes for this product, the sub-
mitter did provide the results of a mass spectrometry analysis.
Jet Fuel A, as such, is not listed in the initial TSCA Inventory.
According to the TSCA Inventory, No.6 Fuel oils are petroleum
fuel oils having a minimum viscosity of 900 SUS and a maximum
viscosity of 9000 SUS at 100°F. A review of the production range
(includes importation volumes) statistics for No.6 Fuel Oils
(CAS No. 68553-00-4), which are listed in the initial TSCA Inven-
tory, has shown that over 1 billion pounds were produced/imported
in 1977. **1
Comments/Recommendations
Complete copies of the final results, including test protocols
and data, from the acute rabbit dermal application studies cited
by Atlantic Richfield in 8EHQ-0181-0377, were provided to the EPA
by the American Petroleum Institute (API).
The Agency has prepared status reports for a number of TSCA
Section 8(e) submissions received on synthetic and petroleum
fuels: 8EHQ-0029, 0030, 0044, 0082, 0083, 0117, 0148, 0212, 0215,
0216, 0217, 0238, 0240, 0247, 0252, 0253, 0297, 0301, 0306, 0316,
and 0323. (These numbers represent the last four digits of the
Document Control Officer assigned numbers).
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request the Atlantic Richfield Company to describe
**1
This production range information does not include any
production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it
include any information which would compromise Confidential
Business Information. The data submitted for the TSCA
Inventory, including production range information, are
subject to the limitations contained in the Inventory
Reporting Regulations (40 CFR 710).
157
-------
b)
8EHQ-0181-0377
Page 4 of 4
the actions it has taken, in light of the submitted
toxicity information, to warn workers and others, and
to reduce and/or eliminate exposure to the subject
fuels.
The Chemical Hazard Identification Branch will transmit
a copy of this status report to DOE, OSHA, NIOSH, OWWM/
EPA, ORD/EPA, and the American Petroleum Institute.
CHIB will also provide copy of the status report to the
Office of Toxics Integration (OTI/OPTS/EPA) for distri-
bution to EPA Regional Offices and State agencies, and
to labor, environmental, and selected citizen groups.
The Industry As.sistance Office (IAO/OTS/EPA) should
consider sending the same information to the manufac-
turers and/or importers of the subject chemicals listed
in the Master TSCA Inventory, and to industry-associated
organizations.
158
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UNITED S1 A TES EHVIROHMENT AL PROTECTION AGENCY
"R~.'tnk D.
. Chemical
Kover, Chief
Hazard Identification Branch
8EH~-0181-0378
Paae 1 of 2
A??~o~e~~'
Rev~s~o
Needed
OA TE:
JAN 3 0 I~Ji
Status Report* 8EHQ-018l-0378
SUoJECT,
TO: Joseph J. Merenda, Director
Assessment Division
Submission Description
Pursuant to TSCA Section 8(e), the International Minerals &
Chemical Corporation has submitted a written report concerning an
"Emergency Incident of Environmental Contamination" involving an
accidental release of sulfur dioxide (S02~ CAS No. 7446-09-5)
from one of its subsidiary's sulfuric aC1d manufacturing
facilities. In accordance with the EPA's March 16, 1978, Section
8(e) policy statement ("Statement of Interpretation and
Enforcement Policy~ Notification of Substantial Risk~ 43 FR
11110), the submitting company's written report follows its
telephoned Section 8(e) notification of EPA's Region IV Office in
Atlanta, Georgia. According to the provided written report, the
sulfur dioxide release (lasting 5 to 7 minutes) resulted from a
malfunctioning vibration monitoring device which caused an
emergency shutdown of the plant. The submitter reports that a
number of on-site construction workers were hospitalized and
subsequently released. The submitter also reports that restart
of the plant operation within 7 minutes corrected the sulfur
dioxide release situation immediately.
Submission Evaluation
Sulfur dioxide is a strong irritant to the mucous membranes of
the eyes, nose, and upper respiratory tract (trachea and
bronchi). However, the chemical rarely produces edema of the
glottis and lungs. Short term human exposure to high concen-
trations of sulfur dioxide from which escape is possible is
usually followed by prompt recovery (i.e. no after effects),
except in the case of asthmatics.
Current Production and Use
Based on the nature of this submission, a report on the current
production and uses of sulfur dioxide does not appear to
warranted at this time.
*NOTE: This status report is the result of a Drelirni~a=v
staff evaluation of i~forrnation submitted to EPA, State;'e~ts
mac2 he=ei~ are ~ot t~ be regarded as ex~ress:nc fi~al
Ase~cy policy or intent w:~h respect to t~is ~a;ticular
chemical. . .;r.y review of the stat'...lS report should ta::e into
cons~de=at~on the fact that it ~ay ~e based on incomp:ete
':':-l:o=-~a~ion.
159
-------
8EHQ-0181-0378
Page 2 of 2
Comments/Recommendations
In 1974, the Occupational Safety and Health Administration (OSHA)
established the current occupational standard for sulfur dioxide
exposure at an 8 hour time-weighted average (TWA) of 5 ppm (39
CFR 23540). In addition, the National Institute for. Occupational
Safety and Health (NIOSH) has prepared a "Criteria Document" on
sulfur dioxide.
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will provide a copy of this status report to OANR/EPA
and to the EPA's Region IV Office for inclusion in its
file on this reported release of sulfur dioxide.
b)
CHIB will also provide a copy of the status report to
the EPA's Office of Hazardous Emergency Response
(OHER/OWWM) .
160
-------
8EHQ-0181-0379
8EHQ-0381-0379 Supplement
Page 3 of 3
b)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, CPSC, the
Notice Review Branch (NRB/CCD/F.PA), the Initial Screen
and Profiles Team (ISPT/CHIB/AD/EPA) and to the Ethyl
Corporation. CRIB will also provide a copy of the status
report to the Office of Toxics Integration (OTI/OPTS/EPA)
for appropriate distribution. The Industry Assistance
Office (IAO/OTS/EPA) should consider sending the same
information to the manufacturers and/or importers of ZDDP
compounds as listed in the Master TSCA Inventory, and to
industry-associated organizations.
163
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DA TE:
FEB ' r:
I u ~.
8EHQ-0181-0380
Page 1 of 3
APprove~ *'
Revisio
Needed
SU&JECT: Status Report* 8EHQ-018l-0380
.~
, JIi 0..: Frank D. Kover, Chief
{/ . Chemical Hazard Identification Branch
TO: Joseph J. Merenda, Director
Assessment Division
Submission Description
R. T. Vanderbilt Company, Inc. has reported that'the results of
an acute study of 1,3,4-thiadiazolidine-2,5-dithione (CAS No.
1072-71-5) in rabbit eyes show the tested substance to be a
severe eye irritant. The submitter states that the study was
carried out according to a met~od described in the Federal
Hazardous Substances Act (16 CFR 125) and the results interpreted
according to the Draize scale for irritation (Draize et al.: J.
Pharm. Exp. Ther.: Vol. 82: 1944). The submitter reports tha~
although water washing reduces the degree of irritation, the
chemical (0.1 g instilled in the rabbit eye) is a severe irritant
in the unwashed eye. The submitter also reports, however, that
the overall results indicate the irritati0n effect to be
reversible.
Submission Evaluation
Thiazole derivatives are known irritants. Therefore, it is not
surprising that the subject thiadiazolidine compound, which is a
closely related substance, is also an irritant. It is important
to point out that animal corneas recover more readily from
opacity caused by irritation than do human corneas. With regard
to the submitted study, which involved a 30 second chemical
exposure to the eyes, it would be interesting to know what the
outcome of a 60 second chemical exposure to the eye followed by a
water wash would be.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for 1,3,4-thiadiazolidine-2,5-dithione (CAS No. 1072-
71-5), which is listed in the initial TSCA Inventory, has shown
that between 20 thousand and 202 thousand pounds of this chemical
*NOTE: This status repo=t is the result of a prelirnina=y
staff evaluation of information submitted to EPA. Stateme~ts
made herein are not to. be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
informa tion .
164
I:~A 'OIltM U~ I~!:V. ~711
-------
8EHQ-0181-0380
Pag9 2 of 3
were produced/imported in 1977. This production range informa-
tion does not include any production/importation data claimed as
confidential by the person(s) reporting for the TSCA Inventory. nor
does it include any information which would compromise Confidential
Business Information. The data submitted for the TSCA Inventory,
including production range information, are subject to the limita-
tions contained in the Inventory Reporting Regulations (40 CFR 710).
The submitting company did not provide any information on the use(s)
of the subject chemical substance, nor was such information located
in the secondary literature sources consulted.
Comments/Recommendations
Based on an initial review and evaluation of the toxicity infor-
mation contained in 8EHQ-0181-0380, the EPA believes that the
provided acute rabbit eye irritation study results did not
warrant submission to the Agency pursuant to Section 8(e) of the
Toxic Substances Control Act (PL 94-469). The basis for the
EPA's position 'is as follows:
The preface to Part V of the Agency's March 16, 1978, "State-
ment of Interpretation and Enforcement Policy; Notification
of Substantial Risk" (43 FR 11110) states that "a substantial
risk of injury to health or the environment is a risk of
considerable concern because of (a) the seriousness of the
effect... and (b) the fact or probability of its occur-
rence." With regard to the seriousness of the effect, Part V
explains further 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 mix-
ture can produce cancer, mutation, birth defects, or toxic
effects resulting in death, or serious or prolonged incapaci-
tation." The information respecting these effects can be
obtained directly or inferred from designed studies (e.g. in
vivo experiments and tests as described in Part VI of the --
policy statement). With regard to the "fact or probability
of its occurrence" criterion, Part V also provides that
certain health effects are so serious that relatively little
weight should be given to the chemical's exposure in deter-
mining whether a risk is substantial.
The EPA's response to Comment 14 in Appendix B of the March
16, 1978 policy statement provides guidance with regard to
the reportability of results obtained from routine acute in
vivo range finding tests such LD50 determinations, irritation
tests, etc. In its response, the EPA stated tha~ it believes
that "many routine tests are based on a knowledge of toxicity
associated with a chemical..." The EPA's response also
directs that unknown effects which occur and are observed
and/or determined during acute in vivo range tests may have
to be reported if those effects are serious and meet the
reporting requirements set forth in Parts V and VI of the
policy statement.
165
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8FHQ-0181-0380
Page 3 of 3
Thus when evaluating the results of acute animal toxicity
studies for submission under TSCA Section B(e), the Agency
believes that submitting companies should consider such
factors as the lethal dose, the route of administration, the
occurrence of unexpected effects (which could be obtained via
"cage-side" observations, during necropsy, etc.), and the
extent and pattern of the exposure of the subject chemical
substance(s). In general, when evaluating such information
for Section B(e) reporting, the greater the acute toxicity,
the less heavily companies should weigh the tested chemical's
exposure, and vice versa.
Based on the preceeding discussion, it is the EPA's preliminary
determination that the results from the acute rabbit eye
irritation study, as provided by Vanderbilt in the present
notice, did not warrant submission to the Agency pursuant to TSCA
Section B(e). However, in making this preliminary determination,
it must be understood that the EPA may not be aware of additional
pertinent information which may have been available to and/or
considered by the company in reporting the toxicity data under
Section B(e). Therefore, the Chemical Hazard Identification
Branch/AD will request the submitting company to provide its
rationale as to why the provided results offer reasonable support
for a conclusion of substantial risk of injury to health or the
environment, as defined in the EPA's March 16, 197B, Section B(e)
policy statement ("Statement of Interpretation and Enforcement
Policy; Notification of Substantial Risk"; 43 FR 11110).
a)
Considering the Agency's general interest in corporate
actions which are taken (on a voluntary basis) in
response to chemical toxicity/exposure information, the
~hemical Hazard Identification Branch (CHIB/AD/EPA) will
request the R. T. Vanderbilt Company, Inc. to describe
the actions it has taken, in light of the provided acute
toxicity data, to warn workers and others, and to reduce
and/or eliminate exposure to the subject chemical
substance.
b)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH and OSHA. CHIB will
also provide a copy of the status report to the Office of
Toxics Integration (OTI/OPTS/EPA) for distribution to EPA
Regional Offices and State agencies, and to labor,
environmental, and selected citizen groups. The Industry
Assistance Office (IAO/OTS/EPA) should consider sending
the same information to the manufacturers and/or
importers of the subject chemical as listed in the Master
TSCA Inventory.
166
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U~ITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
FEB - 9 :Sdi
8EHQ-0181-0381
Paae 1 of 4
APpro~e:r ~$fll
Revl.sl.o
Needed
SU&JEr:T:
Status Report* 8EHQ-0181-0381
~nk D. Kover, Chief
Chemical Hazard Identification Branch
-'.0lIl:
'TO: Joseph J. Merenda, Director
Assessment Division
Submission Description
PPG Industries, Inc. has provided summarized preliminary results
from an acute rabbit dermal application study of a by-product
stream composed mainly (98%) of a mixture of allyl alchol (CAS
No. 107-18-6) and diallyl carbonate (major constituent~ CAS No.
15022-08~9). According to the submitter, the results indicate
that a single application of the by-product stream (0.2 g/kg to
shaved, intact skin) resulted. in 100% mortality of the test
animals. In addition, the submitter reports that within 3 hours
of the sample application, the animals exhibited cyanosis, nasal
discharge, depressed respiration, and anesthesia. Necrospy find-
ings reportedly included lung and gastrointestinal hemorrhages.
In its submission, PPG Industries reported that the dermal LD50
of allyl alcohol is 0.05 g/kg in rabbits and that dermal toxicity
information on. the diallyl carb~ate could not be located in
available literature. The submitter also pointed out that the
acute dermal toxicity of the tested by-product stream "cannot be
explained satisfactorily by the quantity [unspecified] of allyl
alcohol present~ therefore, it is reasonable to suspect that
diallyl carbonate may be the primary toxic component of this
mixture."
with regard to the nature and extent of risk involved with
exposure to the by-product stream (which is reportedly generated,
collected, and periodically .incinerated at a PPG plant site in
Barberton, Ohio), the submitter stated that "an initial review of
the plant hospital daily log failed to reveal any reported cases
of skin or systemic effects associated with this by-product
stream. However, the animal test information would suggest this
by-product stream may represent a potentially high degree of risk
upon dermal.contact." In addition~ the submitter "believes that
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
'consideration the fact that it may be based on incomplete
-in forma tion .
167
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8EHQ-0181-0381
Page 2 of 4
the absence of previously reported employee illnesses associated
with this by-product, together with the containment and personal
protection practices employed within the workplace serve to
minimize the risk of harm to health or the environment. II
Submission Evaluation
Although it is clear why the submitter suspects that the primary
toxic component may have been diallyl carbonate, some doubt
remains because the submission did not indicate the percentages
of diallyl carbonate and other components in the mixture.
Allyl alcohol, acrolein, and allyl esters are known to be severe
irritants to many tissues including those of the respiratory
tract. Some allyl compounds produce liver injury. The signs of
toxicity mentioned in the submission are compatable with the
general toxicity of allyl compounds.
It is not clear whether the observed depressed respiration was a
result of direct irritation of the lungs or secondary to depres-
sion of the respiratory center in the medulla of the brain. It
is also not clear what signs of anesthesia were observed in the
study- Many esters and ketones are capable of producing anesthe-
sia. Diallyl carbonate, which boils at 100°C and is structurally
analogous to anesthetic ketones, could have remained on the skin
to be absorbed in significant quantities before evaporation
occurred. The latent period to death of the test animals could
have had several causes including slow transformation of the
diallyl carbonate to either allyl alcohol or acrolein.
Current Production and Use
PPG Industries, Inc. did not provide any information concerning
the actual amounts of the chemical components which are in the
tested by-product stream, nor did the company provide any infor-
mation on the industrial process(es) from which the subject by-
product stream is generated, or information on the amounts of the
by-product stream generated. No information on the production
volumes or use (if any) of the by-product stream was located in
the secondary literature sources consulted.
A review of the production range (includes importation volumes)
statistics for allyl alcohol (CAS No. 107-18-6). which is listed
in the initial TSCA Inventory, has shown that between 21 million
and 110 million pounds of this chemical were produced/imported in
1977. **/
Allyl alcohol is used in the manufacture of resins, plasticizers,
glycerol, acrolein, pharmaceuticals, herbicides, poison gases,
and other organic compounds.
A review of the production range (includes importation volumes)
statistics for diallyl carbonate (CAS No. 15022-08-9), which is
168
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8EHQ-0181-0381
Page 3 0-1= 4
listed in the initial TSCA Inventory, has shown that between 100
thousand and I million pounds of this chemical were produced/
imported in 1977 **/
No information on the use(s) of diallyl carbonate was located in
the secondary literature sources consulted.
comments/Recommendations
PPG Industries reported that all employees having potential
contact with the subject by-product stream have been informed of
the submitted acute rabbit dermal toxicity test results. In
addition, the submitter reports that existing work practices have
been reviewed and found to be generally satisfactory. PPG stated
that because "work practices were already based upon the handling
of allyl alcohol, a substance with similar hazardous qualities,
modifications to current work practices have been instituted
where necessary to reflect this new [submitted] information." In
addition, the submitting company reported that it is in the
process of conducting acute dermal LD50 tests on purified diallyl
carbonate and a typical by-product stream sample. PPG stated
that the results of the ongoing tests will be provided to the
EPA.
On August 29, 1~79 (44 FR 50766), the EPA Office of Water and
Waste Management (OWWM) designated allyl alcohol as a hazardous
substance; spills or releases of specified amounts are reportable
under Section 311 of the Clean Water Act (CWA). Under the
authority of the Federal Insecticide, Fungicide, and Rodenticide
Act (FIFRA; Section 3), the EPA Office of Pesticide Programs
(OPP/OPTS) has regulated certain FIFFA-related uses of allyl
alcohol.
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request the submitting company to provide a
complete copy of the results, including test protocol(s)
and data ohtained from the acute rabbit dermal study
which prompted the submission of this Section 8(e)
notice. In addition, the company will be requested to
provide a description of the process(es) from which the
tested by-product stream is generated, information on
the amount of by-product generated, and information on
the actual amounts and chemical ioentities of all of the
constituents in the by-product stream.
**/
This production range information does not include any
production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it
include any information which would compromise Confidential
Business Information. The data submitted for the TSCA
Inventory, including production range information, are
subject to the limitations contained in the Inventory
Reporting Regulations (40 CFR 710).
169
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8EHQ-0181-0381
Page 4 of 4
b)
It is recommended that allyl alcohol and dia1lyl
carbonate be considered for inclusion in TSCA Section
8(a) Level A reporting.
c)
The Chemical Hazard Identification Branch will transmit
a copy of this status report to NIOSH, OSHA, OPP/EPA,
and OWWM/EPA. CHIB will also provide a copy of the
status report to the Office of Toxics Integration
(OTI/OPTS/EPA) for distribution to EPA Regional Offices
and State agencies, and to labor, environmental, and
selected citizen groups. The Industry Assistance Office
(IAO/OTS/EPA) should consider sending the same
information to the manufacturers and/or importers of
allyl alcohol and dial1y1 carbonate as listed in the
Master TSCA Inventory, and to industry-associated
organizations.
170
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UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
8EHQ-0281-0382
Paae 1 of 3
DA TE:
FEB 2 3 /98/
Approved ~ ~I
ReviSion/
Needed
SU8JECT,
Status Report* 8EHQ-0281-0382
'R~~;;nk D. Kover, Chief
Chemical Hazard Identification Branch
TO: Joseph J. Merenda, Director
Assessment Division
Submission Description
Glyco Chemicals, Inc. has submitted summarized findngs from
several acute in vivo studies on three related halogenated
dimethylhydantoin derivatives: bromochlorodimethylhydantoin
(BCDMH; CAS No. 126-06-7); dichlorodimethylhydantoin (DCDMH; CAS
No. 118-52-5); and dibromodimethylhydantoin (DBDMHi CAS No. 77-
48-5). The submitter reported that BCDMH was found to be toxic
to mice and rats at oral doses of 690 and 600 mg/kg respectively.
BCDMH was also reported to be a moderately severe irritant and
corrosive to the skin (species not identified), and a severe
irritant to the eyes (species not identified), capable of causing
irreversible cellular damage to eye tissue. The submitter
reported that at higher oral doses (amounts not specified),
systemic effects (type of effects and species not identified)
were noted in the lungs and other organs. With regard to skin
absorption, Glyco reported that systemic effects observed
following dermal application of BCDMH were concluded to have been
due to entry of the compound to the general circulation through
corroded skin. Glyco also reported that earlier toxicological
studies performed with DCDMH and DBDMH had shown that these two
compounds produced similar effects. In addition, the submitter
reported that skin sensitization and inhalation toxicity studies
on BCDMH were now in progress.
In submitting these summarized results under TSCA Section 8(e),
Glyco stated that the proviqed toxicological findings "provide a
general assessment of the potential hazards of these materials
under the most unfavorable exposure circumstances." The
submitting company also stated that it does "not believe that the
data support the conclusion that BCDMH presents a substantial
risk to. human health and the environment." Glyco reported that
its conclusion is supported by over 25 years of continuous
experience in the manufacturing and marketing of the DCDMH
*NOTE: This status report is the result of a prelirni~a=:'
staff evaluation of information submittec to EPA. Stateme~~s
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
informa tion .
171
C~A "0- U~ (1'1:\1. ..711
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8EE~-0281-0382
Page 2 of 3
product, the results of a 1975 NIOSH Health Hazard Evaluation
Determination (Report No. 73-160-206), and the results of a 1979
Glyco-sponsored cross-sectional morbidity study. The submitting
company stated that, in combination, the above findings "all
confirm a total absence of occupationally related diseases in the
workplace where DCDMH and DBDMH are and were manufactured."
Submission Evaluation
It is not surprising that DCDMH, BCDMH, and DBDMH are
irritating. Although the submitter's supposition that the
compounds are not absorbable through intact skin may be valid,
pharmicokinetic data would be needed to confirm this theory.
The subject compounds are at the same time both haloamides and
dialkyl hydantoins. Halogenated amides have both oxidizing and
halogenating properties. The chlorinated amides are sufficiently
stable in water to be used as antiseptics (e.g. Halozone is used
to sterilize drinking water and Chloramine T is used as a topical
antiseptic for dressing wounds). Chlorinated amides can be
highly irritating to skin and mucous membranes and only those
with minimal irritating prop~rties have survived for medical
purposes.
5,5-Diphenyl hydantoin appears to have been established as a
teratogen in humans and has been reported to produce lymphatic
disease similar to Hodgkin's Disease (a lymphoid tumor), and a
number of other toxicities. 5-Phenyl,5-ethyl hydantoins have
produced severe toxicities in humans and are no longer
recommended as drugs. 5,5-diethyl hydantoins can produce sleep
in animals.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for BCDMH (CAS No. 126-06-7) and DCDMH (CAS No. 118-
52-5), which are listed in the initial TSCA Inventory, has shown
that no 1977 production/importation was reported or that all of
the production range data reported were claimed as confidential
by the manufacturer(s) and importer(s) and cannot be disclosed.
(Section 14{a) of the TSCA, U.S.C. 2613 (a». **/
A review of the production range (includes importation volumes)
statistics for DBDMH (CAS No. 77-48-5), which is listed in the
initial TSCA Inventory, has shown that between 20 thousand and
200 thousand pounds of this chemical were produced/imported in
1977. This production range information does not include any
**/
The data submitted for the TSCA Inventory including produc-
tion range information, are subject to the limitations
contained in the Inventory Reporting Regulations (40 CFR
710) .
172
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8EHQ-0281-0382
paqe 3 of 3
claimed as confidential by the
TSCA Inventory, nor does it include
compromise Confidential Business
production/importation data
person(s) reporting for the
any information which would
Information. **/
Glyco reported that BCDMH, which is currently in the R&D stage at
Glyco, is registered and sold as a pesticide by at least one
other U.S. company. Glyco also reported that it is attempting to
develop applications for BCDMH in the markets served by its DCDHH
product which has been produced and sold by Glyco for over 25
years. Other than the pesticide use of BCDMH, the submitter did
not provide any information on the proposed or actual use(s) of
the subject chemicals, nor was such information located in the
secondary literature sources consulted.
Comments/Recommendations
BCDMH (CAS No. 126-06-7) and DCDMH (CAS No. 118-52-5) are listed
in the EPA's February 29, 1980 proposed TSCA Section 8(a) Level A
rule (45 FR 13646).
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request the submitting company to provide complete
copies of the final results, including protocols and
data, from all of the studies cited in its submission,
with the exception of the NIOSH Health Hazard Evaluation
Determination report. Considering the Agency's general
interest in corporate actions taken on a voluntary basis
in response to chemical toxicity/ exposure information,
CHIB will also request Glyco Chemicals, Inc. to describe
the actions it has taken, in light of the provided
toxicity information, to warn workers and others, and to
reduce and/or eliminate exposure to the subject chemical
substances.
b)
The Chemical Hazard Identification Branch will transmit
a copy this status report to NIOSH, OSHA, and OPP/EPA.
CHIB will also provide a copy of the status report to
the Office of Toxics Integration (OTI/OPTS/EPA) for
distribution to EPA Regional Offices and State agencies,
and to labor, environmental, and selected citizen
groups. The Industry Assistance Office (IAO/OTS/EPA)
should consider sending the same information to the
manufacturers and/or importers of the subject chemicals
as -listed in the Master TSCA Inventory. and to industry-
associated organizations.
173
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
SU8JECT: Status Report* 8EHO-0281-0383
FR~a:k D. Kover, Chief
Chemical Hazard Identification
Branch
8EEQ-0281-0383
PaSTe 1 of 3
Approved ftf O/~I
Revisio/
Needed
DJ. T E:
FEB 2 3 1981
TO: Joseph J. Merenda, Director
Assessment Division
Submission Description
Note:
The submitting company has claimed its name to be
Confidential Business Information (CRI).
The submitter has reported that 7-chloro-4-nitrobenzo-2-oxa-l,3-
diazole (NBD Chloride; CAS No. 10199-89-0) ~as shown to be .
mutagenic in an in vitro Salmonella ~bacter~a) test. ~n prov~d-
ing this information under TSCA Sect~on 8(e), the subm~tter
stated that the results of the study from which this reported
information was derived had appeared in Chem. Biol. Interactions
(Vol. 19) in 1977. The company provided a copy of that article
and one other (Mutation Research; Vol. 48; 1977) which reportedly
indicates that analoqs of NBD Chloride are also mutagenic. In
addition, the submitter stated that the provided "articles have
probably been abstracted in widely available compilations, such
as Chem. Abstracts..."
Submission Evaluation
Given the known mutagenicity of chemicals which are structurally
related to NBD Chloride; one would also expect NBD Chloride to
have some degree of mutagenic activity. However, this cannot be
concluded from the data which were submitted. The only conclu-
sions that can be drawn from the submitted data are that 10 mg/ml
NBD Chloride produced a bigger transformed colony than did 1
mg/ml NBD Chloride, and the addition of enzyme activation appears
to have increased the size of the transformed colony produced at
the 1 mg/ml dose level. It should be pointed out that infor-
mation on transformed colony size, rather than actual transformed
colony count data, is of little value when attempting to
interpret mutagenicity data. This is especially true when
control data are lacking, as they were in the submitted articles.
*NOTE: This status report is the result of a prelimina=v
staff evaluation of information submitted to EPA. State~ents
made hereln are n~t to be regarded as expressing final
Agency pollcy or lntent with respect to this particular
chemlcal. . Any review of the status report should take into
~onslder~tlon the fact that it may be based on incomplete
lnrorrna tlon.
t:~A FOR1O 1J~ I~EV. )-7151
174
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8EH0-0281-0383
Page 2 of 3
Current Production and Use
A review of the production range (include importation volumes)
statistics for NBD Chloride (CAS No. 10199-89-0), which is listed
in the initial TSCA Inventory, has shown that between 0 and 1000
pounds of this chemical were produced/imported in 1977. **/
The submitter reported that the amount of NBD Chloride introduced
into commerce is probably less than one kilogram annually. The
submitting company also reported that NBD Chloride is used
principally as a highly fluorescent tag for proteins in
biochemical research. No other use information was located in
the secondary literature sources consulted.
Comments/Recommendations
Based on an initial review and evaluation of the information
contained in 8EHQ-028l-0383, the EPA believes that the provided
in vitro mutagenicity/exposure information did not warrant
submission to the Agency pursuant to Section 8(e) of the Toxic
Substances Control Act (PL 94-469). The basis for the EPA's
position is as follows:
The preface to Part V of the Agency's March 16, 1978,
"Statement of Interpretation and Enforcement PolicY7
Notification of Substantial Risk" (43 FR 11110) states that
"a substantial risk of injury to health or the environment
is a risk of considerable concern because of (a) the
seriousness of the effect... and (b) the fact or probability
of its occurrence." With regard to the "fact or probability
of its occurrence" criterion, Part V states that certain
health effects are so serious that relatively little weight
should be given to the chemical's exposure in determining
whether a risk is substantial. With regard to the serious-
ness of the effect, Part V explains further 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,
mutation, birth defects, or toxic effects resulting in
death, or serious or prolonged incapacitation." The
information respecting these effects can be obtained
directly or inferred from designed studies (e.g. in vivo and
in vitro experiments and tests as described in Part VI of
**/
This production range information does not include any
production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it
include any information which would compromise Confidential
Business Information. The data submitted for the TSCA
Inventory. including production range information, are
subject to the limitations contained in the Inventory
Reporting Regulations (40 CFR 710).
175
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8EHQ-0281-0383
Page 3 of 3
the policy statement). However, with regard to the circum-
stances under which the results of acute in vitro tests
should be reported, Part VI clarifies tha~the reporting of
positive results from such tests (e.g. Ames tests) will
depend upon the existence of corroborative information if
necessary to support the conclusion of substantial risk.
addition, Part VII of the policy statement states that
information need not be reported if the information has been
published in the scientific literature and referenced by
certain abstract services including Chemical Abstracts.
In
On the basis of the preceeding discussion, it is the Agency's
preliminary determination that the in vitro mutagenicity and
chemical exposure information contained in 8EHQ-028l-0383 does
not provide reasonable support for a conclusion that NBD Chloride
poses a substantial risk of injury to health or the environment
and therefore did not warrant submission to the EPA under Section
See) of the Toxic Substances Control Act.
176
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UNITED STATES ENYIROHMENTAL PROTECTION AGENCY
SU8JECT: Status Report* 8EHQ-028l-0384
'~~k D. Kover, Chief
Chemical Hazard Identification
Branch
8EH~-0281-0384
pase 1 of 3
APproved~ ~)fl
Revisior
Needed
0.. TE:
FEB 2 3 I~'. \i
TO: Joseph J. Merenda, Director
Assessment Division
Submission Description
The Dow Chemical Company has submitted summarized final and/or
preliminary results from several recently completed and ongoing
in vivo toxicity studies of ethylene glycol monomethyl ether
TEGME; 2-methoxyethanol; CAS No. 109-86-4). Dow reported that
two 9-day inhalation studies involving rats, mice, and rabbits
exposed to EGME at concentrations of 0, 100, 300, or 1000 ppm,
have been recently completed (unpublished Dow results; 1980).
According to the submitter, the highest level (1000 ppm) of EGME
was lethal to the rabbits, and caused hematological, testicular,
and lymphoid effects in rabbits, mice, and rats. Histopathologic
changes in the animals exposed to 1000 ppm reportedly included
"decreased bone marrow cellularity, degeneration of the
testicular germinal epithelium, and partial depletion of lymphoid
elements in the thymus, spleen and lymph nodes." Although
similar but. less pronounced changes were reportedly observed in
the animals exposed to 300 ppm EGME, Dow stated that no adverse
effects attributable to exposure to EGME were noted in the
animals at the 100 ppm dose level.
Dow reported that upon completion of the 9-day inhalation
studies, subchronic toxicity studies in rats and rabbits, and
reproduction and dominant lethal mutagenicity studies in rats
were initiated and are currently in progress. The submitter
reported that the animals in these studies have been exposed to
EGME at concentrations of 0, 30, 100, or 300 ppm for 6 hours/day,
5 days/week for 13 weeks. Although final results are not yet
available from these studies, Dow reported that the preliminary
fi'ndings can be'summarized as follows: "...exposure of rats and
rabbits to EGME at 300 ppm for 13 weeks resulted in hematologic
abnormalities, decreased testicular and thymus weights,
histopathologic changes in testes, and sterility in male rats.
At 100 ppm, histopathologic changes of the testes were found in 3
of 5 male rabbits. Slight testicular changes were detected
histopathologically in 1 of 5 male rabbits expo~ed to 30 ppm."
~NOTE: This status report is the resuit of a preliminary
staff evaluation of information submitted to EPA. State~e~ts
made herei~ are n?t to be regarded as expressing final
rlse:-~y pollCY or lntent with respect to this particular
chem~cal. . Any review of the status report should take into
~onslder~tlon the fact that it may be based on incomplete
...nforma tlon.
!:".. '0"''' 11~ 1"'£'1. )-751
177
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8EHQ-0281-0384
Page 2 of 3
In its submission, Dow also provided a synopsis of several pub-
lished scientific articles on EGME toxicity in laboratory animals
and humans. Dow also reported that, according to the published
literature, aberrations have been observed in the peripheral blood
of humans exposed to EGME in excess of 25-75 ppm. Dow stated that
those observed blood changes in humans exposed to EGME appear to
correlate well with the animal data. However, Dow also reported
that in its current l3-week studies, "testicular changes persisted
at lower concentrations than hematological changes in rabbits but
not rats." In considering these findings, Dow reported that
although the company is not aware of "any adverse testicular or
reproductive effects in "humans, the possibility exists that the
testes of man may be affected by exposure to lower levels of EGME
than needed to cause adverse hematological effects." Dowalso
reported that because systemic effects arising from human skin
contact with EGME has been reported in the published literature,
"skin absorption can be an additional potential route of signi-
ficant exposure." In addition, Dow reported that the "observed
testicular changes in rabbits at 100 and 30 ppm by the inhalation
route suggests that the current TLV (25 ppm) may not provide an
adequate margin of safety for workers exposed to EGME."
Submission Evaluation
The information contained in this submission suggests that the
test animals exposed to 300 and 1000 ppm EGME sustained an "alarm
reaction." This is indicated by the observed involution of the
lymphoid tissue, especially the thymus. However, microscopic
examination of the adrenal cortex would be needed to confirm this
suspicion. Frequently, an alarm reaction can result in adverse
effects on the testes due to cessation of gonadotrophic hormone
secretion by the anterior pituitary. The significance of the
reported findings may become more clear following the EPA's
receipt and evaluation of the actual data obtained from the
preliminary and subchronic Dow studies, including the results of
microscopic examinations (if performed) of the lymphoid organs,
adrenal cortex, and bone marrow.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for ethylene glycol monomethyl ether (CAS No. 109-86-
4), which is listed in the initial TSCA Inventory, has shown that
between 31 million and 162 million pounds of this chemical were
produced/imported in 1977. **/
**/ This production range information does not include any
production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it include
any information which would compromise Confidential Business
Information. The data submitted for the TSCA Inventory, includ-
ing production range information, are subject to the limitations
contained in the Inventory Reporting Regulations (40 CFR 710).
178
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8EHg-0281-0384
Page 3 of 3
According to secondary literature sources, ethylene glycol mono-
methyl ether is used as a solvent for nitrocellulose, cellulose
acetate, alcohol soluble dyes, and natural and synthetic resins.
The cheraical is also used in solvent mixtures, lacquers, enamels,
varnishes, leathers, perfume fixatives, wood stains, jet fuels
(de-icing additive), and in sealing moisture-proof cellophane.
Comments/Recommendations
The Dow Chemical Company reported that, in accordance with its
long-standing company policy, the provided toxicity information
on ethylene glycol monomethyl ether is being transmitted to Dow
employees, customers, and to other producers. Dow also reported
that the final reports from its ongoing studies will be provided
to the EPA.
Ethylene glycol monomethyl eth~r (CAS No. 109-86-4) is listed in
the EPA's February 29, 1980 proposed TSCA Section 8(a) level A
rule (45 FR 13646).
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request the Dow, Chemical Company to provide
complete copies of the results, including test protocols
and data, from the unpublished Dow 9-day studies cited
in its submission. Dow will also be requested to
provide complete copies of the results from microscopic
examinations (if performed) on the lymphoid organs,
adrenal cortex, and bone marrow from the animals in the
preliminary 9-day studies and the subchronic studies of
EGME.
b)
The Chemical Hazard Identification Branch will review
the requested information, revise this status report as
appropriate, and recommend further followup assessment
if warranted.
c)
The Chemical Hazard Identification Branch will transmit
a copy of this status report to NIOSH, OSHA, CPSC, and
OWWM/EPA. CHIB will also provide a copy of the status
report to the Office of Toxics Integration (OTI/OPTS/
EPA) for distribution to EPA Regional Offices and State
agencies, and to labor, environmental, and selected
citizen groups. The Industry Assistance Office (IAO/
OTS/EPA) should consider sending the same information to
the manufacturers and/or importers of EGME as listed in
the Master TSCA Inventory, and to industry-associated
organizations.
179
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
OATE:
MAR - 4 1981
8EEQ-0281-0385
Page 1 of 2
SU&JECT: Status Report* 8EHQ-0281-0385
Approved
r ¥+,It
, /1JCt-
"R~rank D. Kover, Chief
Chemical Hazard Identification Branch
Revision
Needed
TO: Joseph J. Merenda, Director
Assessment Division
Submission Description
The Gulf Oil Company - u.S. has submitted a summary of the final
results from two sets of short-term in vitro mammalian mutagen-
icity and cell transformation assays-of the following Gulf
products: Superquench 70, Process 65 (Gulf N.E.,61), Process 63
(Gulf N.E. 75), and 100 Texas oil. According to the submitter,
the Superquench 70 and Process 63 products were found to be
positive for mutagenicity in the presence of exogenous metabolic
activation and negative without activation in the Mouse Forward
Mutation Assay. Process 65 was also reported to be positive in
the presence of metabolic activation. However, the results
obtained with Process 65 were reported to be inconclusive in the
absence of activation. The submitter reported that inconclusive
results were also obtained with 100 Texas oil both in the
presence and absence of exogenous metabolic activation. With
regard to the results of the performed C3H/ lOT 1f2 Mouse Cell
Transformation Assays, the submitting company did not provide its
judgement as to whether the results obtained with the tested
products were considered negative, positive or equivocal.
Submission Evaluation
As presented, the summarized results of the in vitro Mouse
Lymphoma Forward Mutation Assays do indicate~hat the Superquench
70, Process 65, and Process 63 products have some degree of
mutagenic activity in cultured mammalian cells. In addition, the
provided summarized results from the performed in vitro C3H/IOT~2
Mouse Cell Transformation Assays, indicate that several of the
tested products may have some degree of cultured mammalian cell
transforming activity. However, without complete copies of the
test protocols and data, a more complete evaluation of the
reported in vitro findings is not possible at this time.
*NOTE: This status report is the result of a prelimina=v
staff eva~uation of information submitted to EPA. State~ents
made here~~ are not to be regarded as expressina final
Agency pol~cy or intent with respect to this pa;ticular
chem~cal. . Any review of the status report should take into
~ons~der~t~on the fact that it may be based on incomplet
~nformat~on. e
1[". 1'0- IJ~ I~EV. ..711
180
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8EHQ-0281-0385
Page 2 of 2
Current Production and Use
Gulf Oil Company - U.s. reported that Superquench 70, Process 65
(Gulf N.E. 61), Process 63 (Gulf N.E. 75), and 100 Texas oil are
listed under the Gulf Refining and Marketing Company in the
Initial TSCA Inventory-Reporting Company Section. Gulf Oil
Company - U.s. did not provide any information concerning the
identity of the chemical component(s) in the tested products, or
any information on the use(s) of those products. No information
on the production volumes or uses of the subject Gulf products
was located in the secondary literature sources consulted.
Comments/Recommendations
Gulf reported that it is evaluating the significance of the
provided in vitro assay results and plans to conduct further
testing o~the products. The submitter also reported that the
results of these additional tests would be provided to the EPA.
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request the submitter to provide complete copies of
the results, including test protocols and data, from the
in vitro studies cited in the submission. In addition,
the submitter will be requested to provide the actual
chemical identity (including CAS Numbers) and amount(s)
of the components in each of the tested Gulf products.
b)
Considering the Agency's general interest in corporate
actions which are taken (on a voluntary basis) in
response to chemical toxicity/exposure information, the
Chemical Hazard Identification Branch (CHIB/AD/EPA) will
request the Gulf Oil Company - U.s. to describe the
actions it has taken, in light of the provided toxicity
data, to warn workers and others, and to reduce and/or
eliminate exposure to the subject chemical substances.
c)
The Chemical Hazard Identification Branch will transmit
a copy of this status report to NIOSH and OSHA. CHIB
will also provide a copy of the status report to the
Office of Toxics Integration (OTI/OPTS/ EPA) for distri-
bution to EPA Regional Offices and State agencies, and
to labor, environmental, and selected citizen groups.
181
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OA TE:
APR 2 I 198i
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8fHQ-038l-0386
Page 1 of 4
APproved,1tl ~Ytl
RevisioV
Needed
SUBJECT: Status Report* 8EHQ-0381-0386
'R~;ank D. Kover, Chief
Chemical Hazard Identification
Branch
TO: Joseph J. Merenda, Director
Assessment Division
Submission Description
The Shell oil Company has submitted a copy of a NIOSH pre-
publication report (manuscript) containing the results from the
testing of 19 selected workplace chemicals for teratogenic
potential. The submitter stated that this information was being
submitted pursuant to TSCA Section 8(e) because of 1) the
experimental evidence of teratogenicity observed for 2-ethoxy-
ethanol (CAS No. 110-80-5) in rats and rabbits (via inhalation),
2) the widespread use of that chemical, and 3) the fact that the
established OSHA standard of 200 ppm for 2-ethoxyethanol is above
the lowest level of exposure which was found to cause teratogenic
effects in the NIOSH-sponsored experiments. Shell also provided
a copy of its Material Safety Data Sheet and Safety Notice for
OXITOL@ (2-ethoxyethanol).
In summary, the Shell oil Company reported that "at a 2-ethoxy-
ethanol inhalation level of 160 ppm [for rabbits and 200 ppm for
ratsJ for 7 hours/day on days 1-19 in rats, and 1-18 in rabbits,
teratogenic effects were observed. These effects were
characterized by skeletal and/or soft tissue abnormalities.
Fetal toxicity was significant in both species. At higher
exposure levels (615 ppm for rabbits and 765 for rats), severe
embryotoxicity was in evidence." Shell also reported that none
of the detailed information from the NIOSH study was available to
the company.
The submitted NIOSH report contained the following summary of the
experimental findings:
"The reproductive toxicity and teratogenic potential of 19
industrial chemicals have been investigated during the past 3
years. Preliminary studies in rats, utilizing intraperito-
neal treatments on days 1-15 of gestation, have been
conducted on 10 chemicals: allyl chloride, bisphenol A,
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. State~ents
made herein are not to be regarded as expressing final
Agen~y policy or intent with respect to t~is particular
chem~cal. . Any review of the status report should take into
cons~derat~on the fact that it may be based on incomplete
informa tion.
[~A '0- U~ I~[". )-711
182
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8EHQ-038l-0386
Page 2 of 4
copper naphthenate, ethylene dibromide, hexachlorobutadiene,
2-mercaptobenzothiazole, methyl styrene, naphthalene, 2-
nitropropane, and 1,2,3-trichloropropane. Studies in rats
and rabbits, utilizing inhalation exposure on days 1-19 and
1-24, respectively, of gestation, have been conducted on 9
chemicals: butylene oxide, carbon disulfide, 2-ethoxy-
ethanol, ethyl benzene, methyl bromide, nitrous oxide,
styrene oxide, tetrachloroethylene, and trichloroethylene.
In the preliminary studies, evidence of teratogenic potential
was seen with allyl chloride and bisphenol A, and fetal
toxicity was seen in the absence of maternal toxicity with
methyl styrene and 2-nitropropane. In the inhalation
studies, 2-ethoxyethanol was strongly embryotoxic at the
higher exposure levels employed, and was teratogenic at the
lower concentration."
Although the above NIOSH summary indicates that rabbits were
exposed to the chemicals via inhalation during days 1-24 of
gestation, the actual experimental protocol states(as does the
sUbmitter) that the rabbits' inhalation exposure to 2-ethoxy-
ethanol lasted only to the 18th day of gestation.
Submission Evaluation
The reported NIOSH study demonstrates that inhalation of 2-
ethoxyethanol vapors causes teratogenic effects at concentrations
which are not toxic (rats) or only slightly toxic (rabbits) to
dams. This particular finding raises questions about the
possible teratogenic actions of 2-methoxy-, 2-propoxy-, and 2-
butoxyethanols. It should also be noted that 2-ethoxyethanol can
be absorbed through the skin and from the gastrointestinal tract.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for 2-ethoxyethanol (CAS No. 110-80-5), which is
listed in the initial TSCA Inventory, has shown that between 62
million and 171 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 confidential by the
person(s) reporting for the TSCA Inventory, nor does it include
any information which would compromise Confidential Business
Information. The data submitted for the TSCA Inventory,
including production range information, are subject to the
limitations contained in the Inventory Reporting Regulations (40
CFR 710).
183
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8EHQ-0381-0386
Page 3 of 4
Shell reported that on a yearly industry-wide basis (based on
1977 data), between 75 and 80 million pounds of 2-ethoxyethanol
are used as a solvent for protective coatings. In addition,
Shell reported that many of the end uses of the chemical are in
proprietary coating formulations, largely in connection with
resin, marine, and industrial coatings, and in oil-based
lacquers. With regard to exposure, the company reported that the
cited uses are generally limited to industrial settings because
2-ethoxyethanol is too volatile to be used in household paints.
Shell also stated that it does not formulate protective coatings
or inks and has no knowledge of specific end use exposure data.
According to secondary literature sources, 2-ethoxyethanol is
used as a solvent for nitrocellulose and natural and synthetic
resins. The chemical is also used in the formulation of soluble
oils, lacquers and lacquer thinners, varnish removers, and
cleaning solutions. 2-Ethoxyethanol is also used in dyeing and
printing textiles, in leather processing, and as an anti-icing
additive for aviation fuels.
Comments/Recommendations
The Shell oil Company reported that although the company does not
have specific measurements of the presence of 2-ethoxyethanol in
the workplace, the company does recommend use of ventilation when
working with the chemical. Shell also reported that its 2-ethoxy-
ethanol production process is in a closed system which is located
in an outdoor setting. The company stated that monitoring
studies at Shell locations where the chemical is made and used
are being initiated on a "priority basis." In addition, Shell
reported that the information contained in its TSCA Section 8(e)
submission is being provided to OSHA, NIOSH, Shell's employees
and customers, and to other producers of 2-ethoxyethanol.
The National Cancer Institute/National Toxicology Program (NCI/
NTP) is currently testing 2-ethoxyethanol for carcinogenicity via
gavage in rats and mice. In addition, 2-ethoxyethanol is listed
in the EPA's February 29. 1980 proposed TSCA Section 8(a) Level A
rule (45 FR 13646).
a)
The Chemical Hazard Identification Branch (CHIB/AD) will
request the Shell oil Company to provide the results of
the company's planned 2-ethoxyethanol monitoring studies.
b)
The Chemical Hazard Identification Branch will consider
the preparation of a Chemical Hazard Information Profile
(CHIP) on 2-ethoxyethanol. In addition, the reported
NIOSH study will be screened in CHIB's Current Awareness
Program for additional chemical candidates for further
assessment.
184
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8EHQ-0381-0386
Page 4 of 4
c)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, CPSC, OWWM/EPA,
OANR/EPA, CREB/AD/EPA, TRDB/AD/EPA and to the "Solvents
Workgroup" of the EPA's Toxic Substances Priorities Com-
mittee (TSPC). CHIB will also provide a copy of the
status report to the Office of Toxics Integration (OTI/
OPTS/EPA) for appropriate distribution. The Industry
Assistance Office (IAO/OTS/EPA) should consider sending
the same information to the manufacturers and/or importers
of the subject chemicals as listed in the Master TSCA
Inventory, and to industry-associated organizations.
185
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
I'ih~ 2 6 I~,-,
Status Report* 8EHQ-0381-0387
8EHQ-0381-0387
Page 1 of 3:f!!- J~~ /
Approved' / -5 'I
Revisio
Needed
SUaJECT:
'~rank D. Kover, Chief
Chemical Hazard Identification Branch
TO:
Joseph J. Merenda, Director
Assessment Division
Submission Description
The Rthyl Corporation has reported that the results from a com-
pleted battery of mutagenicity tests of the O,O-dimethyl ester of
phosphorochloridothioic acid (DMCTP; CAS No. 2524-03-0) were
negative, with the exception of a dominant lethal test in rats.
The company submitted the results and discussion section from the
final report of the in vivo dominant lethal assay. Ethyl re-
ported that male rats were dosed (via gavage) with DMCTP for five
days and then bred with 2 virgin females per week for seven
weeks. The highest dose given (75 mg/kg/day) was reported to be
10% of the LD50. According to the submitter, the chemical was
found to increase the number of dead implants per pregnant female
rat in week five at doses of 25 and 75 mg/kg/day and in week six
at doses of 7.5 and 75 mg/kg/day. In addition, Ethyl reported
that significant pre implantation losses were found (week five) at
DMCTP doses of 7.5 and 75 mg/kg/day.
Ethyl stated that the obtained data has led the company to con-
clude that DMCTP produced a statistically significant level of
dominant lethality. The submitter pointed out, however, that the
fertility index (percent of fertile matings) was unaffected by
DMCTP treatment. This latter finding was reportedly consistent
with the results of a 90-day inhalation study of DMCTP which,
based on preliminary examinations, did not show any effect on
gonadal weights or histopathological appearance of the gonadal
tissues. The company did not provide any information on the
species or the DMCTP dose(s) tested in the cited 90-day inhala-
tion study, nor did the company provide any specific information
on the other performed mutagencity tests which were reportedly
negative.
*NOTE: This status report is the result of a preliminarv
staff eva~uation of information submitted to EPA. State~ents
made here~~ are n~t to be regarded as expressing final
Agen~y pol~cy or ~ntent with respect to this particular
chem~cal. ,Any review of the status report should take into
~ons~der~t~on the fact that it may be based on incomplete
l.nforma tl.on.
E~" "0- U~ I"EV. )0111
186
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8EHQ-0381-0387
Page 2 of 3
Submission Evaluation
Although dominant lethality is not a "heritable" event, it does
signify a serious adverse effect on the mammalian germ line
resulting in embryo lethality.
According to the information provided, the tested compound does
appear to have caused a significant level of dominant letha-
lity. However, without complete copies of the data, a more
complete evaluation of the reporteo test results is not possible
at Ulis time.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for phosphorochloridothioic acid, O,O-dimethyl ester
(CAS No. 2524-03-0), which is listed in the initial TSCA
Inventory. has shown that between 11 million and 60 million
pounds of this chemical were produced/imported in 1977.**/
The Ethyl Corporation reported that it does not produce DMCTP and
that the company is not in a position to judge exposure poten-
tial. Ethyl stated that it believes that the only use of DMCTP
is as an intermediate in pesticides manufacture. No other
information on the use(s) of DMCTP was located in the secondary
literature sources consulted.
Comments/PecoIDn1endations
The Ethyl Corporation reported that it does not plan to produce
DMCTP commercially, and does not have any plans to conduct
further toxicity studies of the chenical.
The O,O-dimethyl ester of phosphorochloridothioic acid (DMCTP~
CAS No. 2524-03-0) is listed in the BPA's February 29. 1980
proposed TSCA Section 8(a) Level A rule (45 FF 13646).
a)
The Chemical Hazard Identification Branch (CRIB/AD/BPA)
will request the Ethyl Corporation to provide complete
copies of the final results (including data and
protocols) from all of the laboratory studies cited in
its submission.
b)
The Chemical Hazard Identification Branch will consider
including a discussion of the submitted D~CTP toxicity
**/ This production range information does not include any pro-
duction/importation data claimed as confidential by the person(s)
reporting for the TSCA Inventory, nor does it include any infor-
mation which would compromise Confidential Business Information.
The data submitted for the TSCA Inventory, including production
range information, are subject to the limitations contained in
the Inventory Reporting Regulations (40 CFR 710).
187
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8EHQ-0381-0387
Page 3 of 3
data in the Chemical Hazard Information Profile (CHIP)
which is being prepared on the O,O-diethyl ester of
phosphorochloridothioic acid (DECTP~ CAS No. 2524-04-1).
c)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, and OPP/EPA.
CHIB will also provide a copy of the status report to the
Office of Toxics Integration (OTI/OPTS/EPA) for
appropriate distribution. The Industry Assistance Office
(IAO/OTS/EPA) should consider sending the same informa-
tion to the manufacturers and/or importers of the subject
chemical as listed in the Master TSCA Inventory, and to
industry-associated organizations.
188
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
SUIJECT: Status Report* 8EHQ-0381-0388 S
, ~rank D. Kover, Chief
~; ~~emical Hazard Identification
Branch
8FHQ-0381-0388 S
Page 1 of 3
Approved ~~~~
Revision
Needed
DATE:
APR 2 I 198i
TO: Joseph J. Merenda, Director
Assessment Division
submission Description
Exxon Chemical Americas has submitted preliminary results from a
28-day rabbit dermal application study of Paranox 52 which
reportedly contains the calcium salt of an alkylated phenol
sulfide. (The exact chemical identity and CAS Number of the
calcium compound has been claimed as Confidential Business
Information (CBI) by the company). The submitter pointed out
that the tested product is commonly referred to as a "calcium
phenate" in the lubricant additive industry. According to Exxon,
Paranox 52 at concentrations of 25% and 100% (medicinal white oil
vehicle) caused a decrease in testicular weights,
aspermatogenesis, and tubular hypoplasia in sexually immature
male rabbits. The company stated that following a 30-day post-
exposure period, the testicular toxicity was found to be
reversible in the low dose (25%) groups, but not in the groups
which had received 100% Paranox 52. The submitter noted,
however, that "the 30-day recovery period did not encompass a
complete spermatogenic cycle (approximately 43 days) during which
regeneration could take place."
Exxon Chemical Americas reported that all available data from the
rabbit dermal application study of Paranox 52 have been provided
and that the final pathology results (expected by June, 1981)
will be submitted to the EPA should the results differ
significantly from those reported in the present submission. In
addition, the submitter stated that the experimental results
obtained thus far from the study of Paranox 52 are similar to
those reported previously under TSCA Section 8(e) for the ZDDP
(zinc dialkyldithiophosphate) class of compounds (8EHQ-0680-0346
et seq., 'Ethyl Corporation; and 8EHQ-0181-0379 et seq., Exxon
Chemical Americas).
*NOTE: This ~tatus ~e~ort is the result of a preliminary
staff eva~uat~on of lnrormation submitted to EPA. Statements
made herel~ are not to be regarded as expressinc final'
Agen~y pol~cy or intent with respect to this pa~ticular
chem7~al. ,Any review of the status report should take into
70nfisl er~t~on the fact that it may be based on incomplete
ln ormatlon.
189
£~A "0'" IJ~ IIU:V. ..711
-------
8EJ~Q-0381-0388 S
Page 2 of 3
Submission Evaluation
It is important to note that the calcium salt compound should not
be confused with calcium phenate which is itself a unique
chemical substance. With regard to the observed toxicological
effects, the Paranox 52 product, as well as several of the
compounds within the referenced ZDDP class, have now been
observed to cause testicular degeneration and aspermatogenesis
in laboratory animals. It remains to be established whether the
observed toxic effects are produced through the pituitary,
thyroid, and/or adrenals, or by a direct effect on the tubules
or, more likely, on the testicular interstitial tissue (Leydig
cells) which governs testosterone synthesis and release.
Current Production and Use
Due to the fact that Exxon Chemical Americas has claimed the
actual chemical identity and CAS Number of the "calcium salt of
an alkylated phenol sulfide" as TSCA CBI, a review of the
production range statistics from the non-confidential TSCA
Inventory will not appear in this status report.
According to the submitter, Paranox 52 is used as a detergent
inhibitor in engine lubricating oils. No other information on
the production and use(s) of the product was located in the
secondary literature sources consulted.
Comments/Recommendations
Exxon Chemical Americas reported that the company is advising its
employees, customers, co-producers, and transporters of the sub-
mitted results. It is the submitter's medical judgment that "no
change in current industrial hygiene practices is warranted.
Present recommendations include avoidance of skin contact and
thorough washing after use." Exxon Chemical Americas also
reported that it will carefully monitor the efforts of the
Chemical Manufacturers Association (CMA)-sponsored ZDDP work-
group. The submitter reportedly plans to use the results of the
initial ZDDP studies as well as the final pathology results of
the present dermal application study of Paranox 52 to assess the
potential hazards, if any, posed by exposure to the product in
workplace settings. Exxon stated that the EPA will be informed
of the company's progress to that end.
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request Exxon Chemical Americas to provide a com-
plete copy of the final report, including test protocols
and data, from the 28-day rabbit dermal application study
of Paranox 52. In addition, the submitter will be
requested to provide the identity (i.e. actual chemical
name and CAS Number) and amount of each chemical com-
ponent of Paranox 52.
190
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8EEQ-0381-0388 S
Page 3 of 3
b)
The Chemical Hazard Identification Branch will consider
the preparation of a Chemical Hazard Information Profile
(CHIP) on the chemical referred to in this submission as
a calcuim salt of an alkylated phenol sulfide. In
addition, it is recommended that the chemical be
considered for inclusion in future TSCA Section 8(a)
Level A reporting.
c)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, CPSC, and
OWWM/EPA. CHIB will also provide a copy of the status
report to the Office of Toxics Integration (OTI/OPTS/EPA)
for appropriate distribution. The Industry Assistance
Office (IAO/OTS/EPA) should consider sending the same
information to industry-associated organizations.
191
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0381-0389
Page 1 of 3
DATE:
APR - 3 1981
SUBJECT: Status Report *8EHQ-0381-0389
..~ank D. Kover, Chief
Chemical Hazard Identification
Branch
APproved~~yll1
Revision
Needed
TO: Joseph J. Merenda, Director
Assessment Division
Submission Description
The Shell oil Company has submitted an interim report from a 2-
year mouse skin-painting study of composite samples of new and
used motor oil. According to the submitter, by the 72nd week of
this American Petroleum Institute-sponsored study, 3 of 50 mice
treated with used motor oil have malignant tumors and 6 have
benign tumors. Of the 6 mice with benign tumors, Shell stated
that 2 have been confirmed histologically and 4 animals are still
alive. Shell also reported that after 35 weeks, no tumors have
been found in the 50 mice exposed dermally to new motor oil.
Shell stated that because polynuclear aromatic hydrocarbon (PNA)
enrichment is known to occur in motor oils during normal engine
use, the test results are not unexpected. Shell provided the
results of an analysis for selected PNAs which shows a signifi-
cant increase in PNA concentration in the used versus new
composite oil samples.
The Shell Oil Company noted that the following points highlight
its areas of concern:
"1 )
The mice being exposed to used motor oil show
biologically significant effects. Statistical analysis
of the data confirms that the effects seen in the used
motor oil group are significantly different from the
control groups.
2 )
Analyses show that the used motor oil composite has
undergone PNA enrichment compared to the new motor oil
composite.
*NOTE: This ~tatus report is the result of a preliminary
staff eva~uat~on of information submitted to EPA. State;e~ts
made here~~ are not to be regarded as expressing final
Agen~y pol~cy or intent with respect to this part~cular
chem~cal. . Any review of the status report should take into
~ons~der~t~on the fact that it may be based on incomplete
lnforrna t~On.
192
It~A 'O~tI IJ~ '''[It'. ~7'1
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8EHQ-0381-0389
Page 2 of 3
3)
The potential exists for widespread exposure to used
motor oil, such as with service station and maintenance
garage personnel, automobile manufacturers and dealers,
and used oil reclaimers/dealers. Some persons in an
exposure situation may not use proper personal hygiene
and safe handling procedures as recommended."
In submitting this information under TSCA Section 8(e), Shell
stated that the "information forms a pattern which reasonably
supports the conclusion that used motor oil may present a sub-
stantial risk to persons not observing the necessary pre-
cautions."
Submission Evaluation
Based on the submitted information, the used motor oil sample has
demonstrated oncogenic and carcinogenic effects in the mice to
which it was de!mally applied. The cause appears to be poly-
nuclear aromatic hydrocarbon enrichment brought about during
engine use. The submission does not indicate either the type or
location of the benign and malignant tumors in the test animals.
Current production and Use
Based on the nature of this submission, a review of current
production and use of motor oils does not appear to be warranted
at this time.
Comments/Recommendations
The Shell oil Company stated that "petroleum based lubricants
(including used motor oil) present negligible health hazards to
the user when proper handling and personal hygiene procedures are
followed, even in light of this new information. To assist Shell
employees and customers alike in this regard, [Shell has] pre-
pared a safety notice on petroleum based lubricants. In addition
Shell Material Safety Data Sheets on such lubricants warn against
prolonged and repeated skin contact since this may lead to a
number of skin disorders including cancer."
The Agency has prepared status reports for a number of TSCA
Section 8(e) submissions received on synthetic and petroleum
fuels: 8EHQ-0029, 0030, 0044, 0082, 0083, 0117, 0148, 0212,
0215, 0216, 0217, 0238, 0240, 0247, 0252, 0253, 0297, 0301, 0306,
0316, 0323 and 0377. (These numbers represent the last four
digits of the EPA Document Control Officer assigned numbers).
a)
With regard to the 2-year mouse skin-painting study
cited in this submission, the Chemical Hazard
Identification Branch (CHIB/AD/EPA) will request the
Shell oil Company to provide all future interim reports
and the final report as that information becomes
available to the company.
193
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8EHQ-0381-0389
Page 3 of 3
b)
The Chemical Hazard Identification Branch will transmit
a copy of this status report to DOE, OSHA, NIOSH, OWWM/
EPA, ORD/EPA, and OMSAPC/OANR/EPA. CHIB will also
provide copy of the status report to the Office of
Toxics Integration (OTI/OPTS/EPA) for appropriate
distribution. The Industry Assistance Office
(IAO/OTS/EPA) should consider sending the same
information to industry-associated organizations.
194
-------
DATE:
APR - 2 1981
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0381-0390
Page 1 of 5
SUBJECT: Status Report*8EHQ-0381-0390
'~nk D. Kover, Chief
Chemical Hazard Identification
Branch
APprove~~1
Revision
Needed
TO: Joseph J. Merenda, Director
Assessment Division
Submission Description
The Dow Chemical Company has reported that a review of a subset
of Dow employee medical records has led to the discovery of a
reported diagnosis of a malignant fibrous histiocytoma in an
individual who had begun working in a trichlorophenol (TCP)
process area in 1951. Dow reported that "during late 1963 and
1964, there was an outbreak of chloracne in the employees of this
TCP process area apparently due to contamination of the process
area with 2,3,7,8-tetrachlorodibenzo-p-dioxin." Dowalso
reported that this plant had been shut down in 1966.
Dow reported that in 1979, the company began "the third of a
series of retrospective mortality cohort studies designed to
evaluate the employees involved in the 1963-1964 chloracne
outbreak." According to Dow, the above individual was one of 61
workers who had comprised the cohort study. Dow also reported
that this individual smoked cigarettes. Dow stated that
following the third study, "this currently active employee was
reportedly diagnosed by his personal physician in late 1979 or
early 1980 as having a malignant fibrous histiocytoma." Dowalso
stated that "the reported diagnosis came to Dow from an insurance
report and was apparently routinely entered in the employee's
medical record" and that the "entry was observed by the senior
author of Dow's TCP cohort study on February 18, 1981 during a
review of the records for other purposes."
Dow reported that the senior author is familiar with the results
of several retrospective cohort studies conducted on U.S. workers
presumably exposed to TCDD in which "three distinct histologi-
cally specific soft-tissue sarcomas have been reported." The
following citations and summaries were provided by the Dow
Chemical Company in its submission:
*NOTE: This ~tatus report is the result of a preliminarv
staff eva~uat~on of information submitted to EPA. State~er.ts
made here~~ are not to be regarded as expressing final
Agen~y pol~cy or intent with respect to this particular
chem7cal. .Any review of the status report should take into
cons~derat~on the fact that it may b b d .
information. ease on ~ncomplete
E~A '0'"" 1121)-6 flU:". )0111
195
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8EHQ-0381-0390
Page 2 of 5
"Zack (l980a) 1. A malignant fibrous histiocytoma. This
individual had chloracne. He was a cigarette smoker. First
exposure: 1948. This study of 121 men at Monsanto who were
substantially exposed to TCDD after a TCP plant explosion in
Nitro, West Virginia in 1949 found no excess of either total
deaths or deatns due to cancer."
"Ott (1980)2. No chloracne nor soft-tissue sarcomas
reported. This study of 204 men at Dow who worked in a
2,4,5-T [2,4,5-Trichlorophenoxy acetic acid] process area
from 1951 to 1971 found fewer than expected total deaths and
deaths due to cancer."
"Cook (1980)3. A fibrosarcoma. This individual developed a
facial dermatitis, but no definitive diagnosis of chloracne
was made. He was a cigarette smoker. First exposure 1964.
This study of 61 men at Dow who were substantially exposed to
TCDD in a TCP process area during 1963-1964 (this plant was
shut down in 1966) found fewer than expected total deaths and
no significantly greater than expected cancer deaths."
"Zack (1980b)4. A liposarcoma. Although the report does not
indicate whether this individual had chloracne, it does
mention that a number of men in his work area developed
chloracne. He was a cigarette smoker. First exposure
1950. This study of workers in the 2,4,5-T process area at
Monsanto's Nitro, West Virginia plant reported 58 deaths with
a lower percentage of cancer deaths among this cohort than in
another cohort of workers from the same plant who had not
worked in the 2,4,5-T area."
With regard to the cited studies, Dow stated that "it is note-
worthy that the information provided [above] involves, in all
cases, past workplace conditions" and that those "conditions do
not exist in today's workplace environment." In addition, Dow
pointed out that "none of the four cited studies found any in-
creased overall mortality, nor significantly increased mortality
due to cancer" and that "in aggregate, while the studies reveal
an apparent increase of soft-tissue sarcomas (albeit
histologically distinct), overall cancer was substantially less
than that expected in the general population."
with regard to studies conducted in Europe, Dow provided the
following literature citations and summary:
"Hardell et ale (1979, and in press)5,6,7. Three case-
control studies of Swedish males diagnosed with soft-tissue
sarcoma_or malignant lymphoma are interpreted by the authors
as demonstrating an association between these diseases and
prior exposure to phenoxy acids and/or chlorophenols but
there is sufficient question concerning the methodology and
alleged exposures that the studies are relatively
uninformative regarding the health hazards potentially
related to phenoxyacetic acid exposure."
196
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8EHQ-0381-0390
Page 3 of 5
In addition, Dow cited a recent article {Honchar; 1981)8 that
appeared in the British medical journal, Lancet, in which NIOSH
scientists reportedly called attention to the European studies
and noted that NIOSH is conducting both a retrospective cohort
study and a case-control study in order to investigate the
significance of the reported findings.
Dow reported that when the senior author of its TCP cohort study
had discovered the diagnosed malignant fibrous histiocytoma, the
author "considered it appropriate to report this information to
interested government agencies and to the scientific community in
order that this additional data point could be included in the
planned studies." In addition, Dow reported that although a
cause-effect relationship cannot be established at this time, the
data "suggest the hypothesis that smokers who exhibit chloracne
as a consequence of substantial TCDD exposure may be at increased
risk of developing fibrous soft-tissue sarcomas. Until the
hypothesis is tested and refined in a series of well-developed
and conducted epidemiologic studies, [Dow is] unable to make a
more definitive scientific judgment."
In conclusion, Dow stated that it no longer produces TCP in the
U.S.A. and that Dow's operations outside the U.S. "have been
modified over the years so that exposure to TCOD, a contaminant
of trichlorophenol, has been virtually eliminated."
Submission Evaluation
Based on the nature of the provided information, a copy of Dow's
submission was immediately transmitted to the EPA's "Chlorinated
Dioxins Workgroup" for evaluation and appropriate followup
attention.
Current Production and Use
The polychlorinated dibenzo-p-dioxins (PCDDs) are a series of
tricyclic aromatic compounds which exhibit similar chemical and
physical properties. The basic structure of the PCDDs has eight
possible points of chlorine substitution. From the monochloro to
the octachloro derivatives, a total of 75 different positional
isomers is possible. Polychlorinated dibenzo-p-dioxins are
impurities that may be formed as unwanted contaminants under
certain conditions during the production of chlorophenols and
certain other man-made chemicals. For example, 2,3,7,8-TCDD,
which is one of the most acutely toxic chemical substances known
to exist, has been identified as a contaminant produced during
the manufacture of 2,4,5,-trichlorophenol (2,4,5-TCP). Because
of this, the 2,4,5-trichlorophenoxy acetic acid (2,4,5-T)
pesticide derived from 2,4,5-TCP becomes contaminated with
2,3,7,8-TCDD from the TCP intermediate. Findings of TCDD resi-
dues in the environment have come from analyses of soils and
fish. In addition, TCDO residues have been detected in some
abandoned chemical dumpsites. Recent evidence also indicates
that TCODs may be associated with emissions from general
combustion processes.
197
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8EHQ-038l-0390
Pag8 4 of 5
Comments/Recommendations
In its submission, Dow stated that because the company considered
it "appropriate that the scientific community be aware of this
finding, only so that studies planned or underway may take this
information into account, [Dow is] concurrently reporting this
finding to the scientific community."
The Agency has received and evaluated several previous Dow
Section 8(e) submission~ on TCDDs and chlorophenols (8EHQ-0778-
209 et seq.). The following U.S. Government panels are currently
reviewing and evaluating information on dioxins: 1) U.S. EPA
Workgroup on Chlorinated Dioxins, 2) Interagency Regulatory
Liaison Group (IRLG) Dioxins Workgroup, and 3) Interagency
Workgroup on the Long-term Health Effects of Phenoxy Acids and
Their Contaminants. In addition, the EPA's Office of Research
and Development (ORD) recently published (November, 1980)
information on "DIOXINS" (EPA-600/2-80-197).
a)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to OSHA, NIOSH, CPSC, FDA, and
the EPA Chlorinated Dioxins Workgroup. CHIB will also
provide a copy of the status report to the Office of
Toxics Integration (OTI/OPTS/EPA) for appropriate dis-
tribution. The Industry Assistance Office (IAO/OTS/EPA)
should consider sending the same information to industry-
associated organizations.
References
1.
Zack, J. A. and
Workers Exposed
Trichlorophenol
(1980) .
R. R. Suskind, "The Mortality Experience of
to Tetrachlorodibenzo-Dioxin in a
Process Accident, "J. Occup. Med. 22:11
2.
Ott, M. G., Holder, B. B., Olson, R. D., "A Mortality
Analysis of Employees Engaged in the Manufacture of 2,4,5-
Trich10rophenoxyacetic Acid, "J. Occup. Med. 22:47-50 (1980).
3.
Cook, R. R., J. C. Townsend, M. G. Ott, and L. G.
Silverstein, "Mortality Experience of Employees Exposed to
2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD), "J. Occup. Med.
(in press).
4.
Zack, J. A., "Mortality Study of Workers Employed at the
Monsanto Company Plant in Nitro, West Virginia: (unpubished,
Sept. 10, 1980).
5.
Hardell, L. and A. Sandstrom, "Case-control Study: Soft-
tissue Sarcomas and Exposure to Phenoxyacetic Acids or
Chlorophenols," Br. J. Cancer 39:711-717 (1979).
198
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8EHQ-038l-0390
Fage 5 of 5
6.
Eriksson, M., Hardell, L., Berg, N. 0., Moller, T., and O.
Axelson, "Soft-tissue Sarcomas and Exposure to Chemical
Substances. A Case-reference Study," Fr. J. Ind. Medicine
(in press).
7.
Hardell, L., Eriksson, M., Lenner, P., and E. Lundgren,
"Malignant Lymphoma and Exposure to Chemical Substances
Especially Organic Solvents, Chlorophenols and Phenoxy
Acids. A Case-control Study," Br. J. Cancer (in press).
8.
Honchar,
(1981) .
P. A., Halperin, E. E., LANCET, Number One, 268
199
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
MAR 3 I 19B!
8IHQ-038l-039l
Page 1 of 2
f.d;k D.
Chemical
Kover, Chief
Hazard Identification Branch
Revision
Needed
~
~,+I
SUBJECT:
Status Report* 8EH0-038l-039l
Approved
TO: Joseph J. Merenda, Director
Assessment Division
Submission Description
Buckman Laboratories, Inc. has submitted the complete final
results, including test protocols and datal from two short-term in
vitro mutagenicity assays on 2'-hydroxyethyl-2,3-dibromo-
propionate (HEDBP; CAS No. 68479-77-6). According to the
submitting company, the chemical was found to be positive in the
Salmonella/Microsome Assay (Ames test) and the Mouse Lymphoma
Forward Mutation Assay. The submitter stated that the results
from both tests give corroborative evidence of the probable
mutagenicity of HEDBP.
Submission Evaluation
This submission presented oata on the mutagenic potential of 2'-
hydroxyethyl-2,3-dibromopropionate (HEDBP) in the Ames
Salmonella/Microsomal Assay and the mouse lymphoma L5178Y cell
culture assay. HEDBP was found to elicit a positive response in
both assays when tested with and without metabolic activation by
an 8-9 fraction from Aroclor 1254 induced male rats. In the
bacterial assay, mutagenic potential and cytotoxicity were re-
duced but not eliminated by S-9 treatment. In the cell culture
assay, cytotoxicity, but not mutagenicity, was reduced by
metabolic activation. There is no basic inconsistency in these
findings.
The protocols submitted indicate that these assays were performed
according to accepted procedures. However, page 2 of the
bacterial assay protocol indicated that the test agent was "a
dark viscous liquid"; page 3 indicated that the test article was
prepared by weighing 100 mg, The EPA questions whether "weigh"
is the correct term to use in this context. The submitted
protocol may be a "Standard Operating Procedure" (SOp) for solid
compounds which was not changed to reflect the liquid nature of
the test article.
*NOTE: This ~tatus ~e~ort is the result of a preliminary
staff eva~uatlon of lnrormation submitted to EPA. Statements
made herel~ are not to be regarded as expressing final
Agen~y POllCY or intent with respect to this particular
chem~cal. . Any review of the status report should take into
70nslder~tlon the fact that it may be based on incomplet
lnformatlon. e
r;~.. ,0"111 U~ (11£\1. ..711
200
-------
8E1'Q-0381-0391
Page 2 of 2
Current Production and Use
A review of the production range (includes importation volumes)
statistics for 2'-hydroxyethyl-2,3-dibromopropionate (CAS No.
68479-77-6), whic~ is listed in the initial ~SCA Inventory, has
shown that no 1977 production/importation was reported or that
all of the production range data reported were claimed as
confidential by the manufacturer(s) and importer(s) and cannot be
disclosed. (Section 14(a) of the TSCA, U.S.C. 2613 (a)). **/
In its submission, Buckman Laboratories, Inc. reported that it is
t~e sole manufacturer of HEDBP and that the amount produced is
between 10,000 to 100,000 pounds. The submitter also reported
that HEDBP is manufactureo for export only. No information on
the use(s) of HEDBP was provided by the sunmitting company, nor
was such information located in the secondary literature sources
consulted.
Comments/Recommendations
a)
The Chemical Hazard Identification Branch (CRIB/AD/EPA)
will request Buckman Laboratories, Inc. to describe the
actions it has taken, in light of the submitted toxicity
data, to warn workers and others, and to reduce and/or
eliminate exposure to HEDBP.
b)
2'-Hydroxyethy1-2,3-dibromopropionate will be considered
for inclusion in future TSCA Section 8(a) Level A
reporting.
c)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH and OSHA. CHIB will
also provide a copy of the status report to the Office of
~oxics Integration (OTI/OPTS/EPA) for appropriate
distribution.
**/ The data submitted for the TSCA Inventory including produc-
-- tion range information, are subject to the limitations con-
tained in the Inventory Reporting Regulations (40 CFR 710).
201
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
SUBJECT: Status Report* 8EHQ-0381-0392
~ank D. Kover, Chief
(~/~emical Hazard Identification
Branch
8EHQ-0381-0392
Page 1 of 2
Approved ~ %/h
Revisio/
Needed
0,," TE:
APR
8 19:.
TO: Joseph J. Merenda, Director
Assessment Division
Submission Description
The Union Carbide Corporation submitted a summary of the final
results from a series of acute and short-term inhalation studies
of methyl isocyanate (CAS No. 624-83-9) in rats. Although no
protocols or actual data were provided, the submitter reported
that toxic effects were observed at the highest dose tested (3.07
ppm) but not at two lower doses. Union Carbide stated that in
addition to irritation, histopathologic findings were noted and
included inflammation and squamous metaplasia of the upper
respiratory tract in some of the male and female rats studied. In
addition, polyp formation was reportedly observed in the lungs of
a few of the affected male rats. The submitter stated that the
effects, which were observed after only 8 days of exposure to the
highest dose, suggest that the experimental observations are
worthy of additional examination. Union Carbide also stated that
additional information will be provided to the EPA as planned
toxicity studies proceed. The submitter also reported that
"regular medical surveillance has shown no indication of any
adverse health effects to Union Carbide employees working with
this chemical."
Submission Evaluation
Methyl isocyanate is a highly active compound which is probably
capable of alkylating a variety of tissues that contain amino
(NH2-) and hydroxyl (OH-) groups. It is not suprising, there-
fore, that inhalation of this chemical could cause a variety of
lesions in the airways and lungs. Complete copies of the final
reports of the cited studies, including test protocols and data,
should be requested from the submitter.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for methyl isocyanate (CAS No. 624-83-9), which is
*NOTE: This ~tatus report is the result of a prelirninarv
staff evaluat~on of information submitted to EP' St t .
d h . .~ . a erne!'l ~ s
ma e ere1~ are not to be regarded as expressina final "'-
Agen~y po11cy or intent with respect to this pa~ticular
chem7cal. . Any review of the status report should take into
~onfis1der~t10n the fact that it may be based on incomplete
:Ln ormat:Lon.
202
I:~A '0""" 11»-4 (~EV. ~711
-------
8EHQ-0351-0392
Page 2 of 2
listed in the initial TSCA Inventory, has shown that between 10
thousand and 100 thousand pounds of this chemical were reported
as produced/imported in 1977- **/
According to secondary literature sources, methyl isocyanate is
used mainly as an intermediate in the manufacture of pesticides.
Comments/Recommendations
The Union Carbide Corporation stated that it "commenced the
manufacture of methyl isocyanate over 15 years ago, establishing
strict operating controls and handling procedures to minimize
risk of employee exposure." With regard to its Section 8(e)
submission, Union Carbide stated that it is informing its
employees and customers of the notice and will advise them of any
further available information.
a)
It is recommended that methyl isocyanate (CAS No. 624-
83-9) be considered for inclusion in future TSCA Section
8(a) Level A reporting.
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request the Union Carbide Corporation to provide
complete copies of the final reports, including test
protocols and data obtained, from the series of acute
and short-term laboratory studies of methyl isocyanate
cited in its submission.
b)
c)
The Chemical Hazard Identification Branch will transmit
a copy of this status report to NIOSH, OSHA, and OPP/
EPA. CHIB will also provide a copy of the status report
to the Office of Toxics Integration (OTI/OPTS/EPA) for
distribution. The Industry Assistance Office (IAO/OTS/
EPA) should consider sending the same information to the
manufacturers and/or importers of the subject chemical
as listed in the Master TSCA Inventory, and to industry-
associated organizations.
**/ This production range information does not include any production/
importation data claimed as confidential by the person(s) reporting for
the TSCA Inventory, nor does it include any information which would
compromise Confidential Business Information. The data submitted for
the TSCA Inventory, including production range information, are subject
to the limitations contained in the Inventory Reporting Regulations (40
CF 710).
203
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
0'" T E:
MAY I I 198!
8EHQ-038l-0393
Page 1 of 4
Approved ~~~
Revis ion fI
Needed
SU~JECT: Status Report* 8EHQ-038l-0393
FR~~;:nk D. Kover, Chief
Chemical Hazard Identification
Branch
TO: Joseph J. Merenda, Director
Assessment Division
Submission Description
The Dow Chemical Company has submitted a summary of preliminary
findings from a 2-year feeding study (Fischer 344 rats) of two
different compositions of FR651, which is reported to be a
mixture of hexahalocyclohexanes containing 1,2,3,4,5-pentabromo-
6-chlorocyclohexane (CAS No. 87-84-3) as the major constituent.
According to Dow, the study was designed to evaluate the chronic
toxicity and oncogenic potential of both "Compound A" (identified
only as a single isomer) and "Compound B" (identified only as a
mixture of isomers). Dow stated that the results of an interim
sacrifice which was conducted following one year of dietary
exposure indicated a slight, dose-related (higher doses only)
toxicity. primarily in the liver and kidneys. Dow reported these
findings to be consistent with those observed in a previously
conducted 13-week subchronic study. Dow also reported that "the
terminal sacrifice of all remaining rats was conducted after two
years of dietary treatment, followed by preparation of micro~
scopic slides of tissues and 0Fgans from all rats at all dose
levels (those dying early as well as those surviving to
termination)." Dow stated that the preliminary histopathologic
examination of the tissues and organs indicated an apparent
"increase in the incidence of proliferative. lesions originating
from the mucosal lining of the large intestine." Dow reported
that the majority of these particular lesiops have been tenta-
tively diagnosed as polypoid adenomas, which appear morpho-
logically identical to those obs~rved as spontaneously occurring
tumors noted at a background incidence rate of 0-3% in Fischer
344 rats in Dow's laboratory. Dow provided the following
summarized preliminary data on the incidence rates of these large
intestine tumors:
"In the study with "Compound A", the preliminary numbers
(percent) of male rats with a tumor of the large intestine
mucosa are as follows: control group has 1/86 (1.2%), low
dose group at 1 mg/kg/day has 1/50 (2%), the mid-dose group
*NOTE: This status reoort is the result of a oreliminarv
staff evaluation of information submitted to EPA. Sta~e~e~~s
made herein are not to be reaarded as exoressina final
Agency policy or intent with~res?ect to this pa~ticular
chemlcal. .~y review of the status report should taKe into
~o~sider~tior. the fact that it may be based on incomplete
In_ormatlon. 204
-------
8£HQ-0381-0393
Page 2 of 4
at 15 mg/kg/day has 0/50
mg/kg/day has 5/50 (10%)
female rats, the control
group at 1 mg/kg/day has
mg/kg/day has 3/50 (6%),
mg/kg/day has 8/50 (16%)
(0%), and high dose group at 50
affected. For the same tumor in the
group has 1/86 (1.2%), the low dose
0/50 (0%), the mid-dose group at 20
and the high dose group at 70
affected."
"In the study with "Compound B", the preliminary numbers
(percent) of male rats with a tumor of the large intestine
mucosa are as follows: contol group has 1/86 (1.2%), the low
dose group at 1 mg/kg/day has 0/50 (0%), the mid-dose group
at 15 mg/kg/day has 2/50 (4%), and the high dose group at 50
mg/kg/day has 2/49 (4%) affected. For the same tumors in the
female rats, the control group has 1/86 (1.2%), the low dose
group at 1 mg/kg/day has 0/50 (0%), the mid-dose group at 20
mg/kg/day has 2/50 (4%), and the high dose group at 70
mg/kg/day has 9/50 (18%) affected."
Dow reported that because the histopathologic evaluation of the
rats is not complete, the provided data are preliminary and are
subject to change as the result of additional pathologic
examination. Dow stated that its present interpretation is that
"these preliminary data suggest an increased incidence of
polypoid tumors of the large intestine in rats of the high dose
groups. The incidence at the low dose level is comparable to the
concurrent controls used in the studies and, therefore, appears
to be a "no observed effect" level for the large intestine tumor
response."
Dow reported that FR651 is known to have a low acute oral
toxicity and to be nonmutagenic in Salmonella (Ames bacter-
ial test). Dow also reported that this material, which has a
melting range of l80-197°C and a maximum vapor concentration at
ambient conditions of 0.05-0.06 ppm, is "slightly irritating to
skin and eyes and the dusts may cause respiratory irritation."
Dow stated that although FR651 does not appear on the Threshold
Limit Value (TLV) list prepared by the American Conference of
Governmental Industrial Hygienists (ACGIH), Dow's current
Industrial Fygi~ne Guide recommends a workplace air concentration
(TLV) of 5 mg/m for FR651.
Dow also reported that "the environmental behavior of this
material, as well as similar compounds, has been addressed in
several studies, and it appears that this material does not
persist in the environment. These data do not suggest a
substantial risk of injury to the environment." The submitter
provided literature citations for several of the mentioned
studies.
Dow stated that the company believes that its "employees are not
at increased risk as a result of these findings in laboratory
rats. First, the circumstances of the workplace are such that
employees are only intermittently working in the areas where the
potential for exposure exists; and second, dust respirators and
205
-------
BEEQ-038l-0393
Page 3 of 4
appropriate protective clothing (gloves, long-sleeved shirts,
pants, for example) are recommended for use by employees
intermittently working in work areas where exposures are likely
to exceed the [Dow] Industrial Hygiene Guide."
Submission Evaluation
The summarized preliminary data provided in this submission
appear to estahlish that Compounds A and Bare oncogens. With
regard to the submitter's statement that the lowest tested dose
appears to be a "no observed effect" level, the EPA agrees that
the reported incidence of intestinal tumors at the low dose is
comparable to that reportedly observed in the control animals.
However, the Agency does not at this time accept the concept of
no observed effect levels or threshold levels for oncogenicity.
It is possible that an increased tumor incidence might have
become apparent in time and/or in a larger population of exposed
animals. In order to further evaluate the reported findings, the
submitter should be requested to provide complete copies of the
interim and final reports including experimental protocols and
toxicological data.
It should be noted that although the tested compounds are analogs
of Lindane (gamma-hexachlorocyclonexane), their reported acute
toxicity does not resemble tnat of Lindane. The acute and
chronic toxicity of Compounds A and B appears to be more like
that seen with numerous other polyhalogenated hydrocarbons (e.g.
polybrominated biphenyls7 PBBs).
With regard to environmental persistence, although the scientific
articles cited by Dow provide information on a variety of
halogenated compou.nds including Lindane (gamma-hexachloro-
cyclohexane) and its isomers, the cited stu.dies do not contain
any information on the environmental effects, fate, or
persistence of l,2,3,4,S-pentabromo-6-chlorocyclohexane or FRnSl.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for l,2,3,4,5-pentahromo-6-chlorocyclohexane (CAS No.
87-84-3), which is listed in the initial TSCA Inventory, has
shown that between 1 million and 10 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 confidential by the
person(s) reporting for the TSCA Inventory, nor does it include
any information which would compromise Confidential Business
Information. The data submitted for the TSCA Inventory,
including production range information, are subject to the
limitations contained in the Inventory Reporting Regulations (40
CFR 710).
206
-------
8E'HQ-0381-0393
Fage 4 of 4
Dow reported that FR651 is a powder which is added to certain
plastics as an ignition suppressant. Protective clothing and
equipment are recommended by Dow in nonautomated operations in
which the FR651 powder is transferred by hand. No other use
information on FR651 or 1,2,3,4,5-pentahromo-6-chlorocyclohexane
was located in the secondary literature sources consulted.
Comments/Recommendations
Dow stated that in accorQance with its long-standing company
policy, the reported toxicity information is being transmitted to
employees and customers who hanole FP65l.
1,2,3,4,5-pentabromo-6-chlorocyclohexane (CAS No. 87-84-3) is
listed in the EPA's February 29, 1980 proposed TSCA Section 8(a)
Level A rule (45 FR 13646).
a)
b)
c)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request the Dow Chemical Company to provide the
following information:
1 )
complete copies of the final reports, including
protocols and data, which were the source of the
acute and 13-week subchronic toxicity findings cited
in the submission:
2)
complete copies of all interim reports and the final
report, including experimental protocols and data,
from the 2-year feeding study cited in the
submission:
3)
complete copies of results (including test
and data) from studies performed by and/or
or from studies in Dowis possession, which
environmental behavior of FR651 and/or its
components:
protocols
for Dow,
assess the
4)
the exact chemical identity and amount (if known) of
each of the isomer components in Compounds A and B.
The Chemical Hazard Identification Branch will consider
the preparation of a Chemical Hazard Information Profile
(CHIP) on 1,2,3,4,5-pentabromo-6-chlorocyclohexane and/or
FR65:J..
The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH and OSHA. CRIB will
also provide a copy of the status report to the Office of
Toxics Integration (OTI/OPTS/EPA) for appropriate dis-
tribution. The Industry Assistance Office (IAO/OTS/EPA)
should consider sending the same information to industry-
associated organizations.
207
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DA TE:
APR 27 1981
8IHQ-038l-0394 S
Page 1 of 4
:::::::~*"
Needed
SUBJECT, Status Report* 8EHQ-0381-0394 S
'R~:k D. Kover, Chief
Chemical Hazard Identification Branch
TO: Joseph J. Merenda, Director
Assessment Division
Submission Description
The 3M Company has submitted the final report of an oral
range finder study of T-2998CoC in pregnant rats. T-2998CoC is
referenced in the submitted report as FC-143, a homologous
mixture of perfluoroalkane ammonium carboxylates.
According to the submission, the oral range finder study was
conducted to determine the upper dose level of T-2998 CoC for a
subsequent oral teratology study in rats. The report states that
T-2998CoC was suspended in corn oil and administered daily by
gavage at doses of 150, 100, 75, 50 or 25 mg/kg/day to groups of
6 time-mated Sprague-Dawley derived female rats on days 6 through
15 of gestation. A control group of 6 rats reportedly received
only corn oil by oral intubation on the same days.
The report states that the animals were observed for abnormal
clinical signs and weight gain and that blood samples and liver
specimens were taken on day 20 of gestation. The report further
states that four fetuses from each of four dams in the 150 and 25
mg/kg/day dose groups were examined for eye abnormalities because
of teratogenic lens changes observed in earlier studies with
chemically related compounds. The 3M Company previously
submitted two final reports (8EHQ-0281-0373S Supplement and 8EHQ-
028l-0374S Supplement) of teratology studies in rats on
chemically related mixtures which reportedly produced a
"developmental eye abnormality which appeared to be an arrest
in development of the primary lens fibers forming the embryonal
lens nucleus, followed by secondary aberrations of the secondary
lens fibers of the fetal nucleus". The earlier submissions also
referenced a published study conducted by 3M which reported
elevated fluorochemical levels in the blood and urine of 3M
fluorochemical plant workers.
*NOTE: This ~tatus ~e~ort is the result of a preliminary
staff evaluat~on of ~nrormation submitted to EPA St t .
d h . . a eme'l1-s
ma e ere~r: are n'?t to be regarded as expressing final' -
Agency pol~cy or ~ntent with respect to this particular
chem~cal. . Any review of the status report should take i t
~onfis~der~t~on the fact that it may be based on incomp~et~ c
ln ormat~on.
~~A "0- IJ~ I~EV. ..7GI
208
-------
8EHQ-038l-0394 S
Page 2 of 4
According to the present submission, although oral administration
of T-2998CoC did not result in any deaths, a toxic effect of
reduced body weight gain occurred between days 6 and 9 of
gestation in the highest dose group. The submitted report also
states that this effect was more severe in the two non-pregnant
rats at 150 mg/kg level and that urinary incontinence was
observed in one of these two animals on days 11 to 13 of
gestation. No blood sample or liver specimen analyses were
reported.
The submitted report states that all examined fetuses "had eye
changes consisting of one or more of the following: large lens
clefts, dark streak running one-half to three-quarters of the way
through the lens or disorganized lens fibers." The report
further states that the same general morphological changes
occurred in the same location as those observed in the two
previously submitted 3M teratology studies. In addition, the
report states that the abnormalities seen in the present study
appeared to be more pronounced.
The submitted report concludes that the results of the
rangefinding study suggest that 150 mg/kg/day of T-2998CoC "would
be an appropriate high dose in a rat teratology study hecause of
the toxic effect of reduced body weight gain" and that the
observed teratogenic effect of lens abnormality "is likely to be
reproduced in a teratology study".
Submission Evaluation
The subject compounds resemble those previously reported by 3M
(8FHQ-1180-0373S, 8EHQ-1180-0374S, 8EFQ-0281-0373S Supplement and
8EHQ-0281-0374S Supplement) in that they are acidic perfluoro
compounds producing the same type of rare eye lens defect in the
developing embryo. These compounds, which are analogs of fatty
acids, may compete with fatty acids involved in growth and
development or, more likely, inhibit an enzyme system necessary
for organ development. For example, simple fatty acids such as
valproic acid and its amide produce toxicity by interfering with
GABA transaminase, carbamyl phosphate and cysteine synthesis.
Histological examination of the organs of both dams and fetuses
would be extremely valuable in the planned teratology studies
with FC-143 and/or other mixtures of perfluoroalkane ammonium
carboxylates. In general, subchronic studies to determine
toxicity, storage, and disposition of perfluoro compounds would
also provide useful information.
Current Production and Use
T-2998CoC is identified by the submitter as a homologous mixture
of perfluoroalkane ammonium carboxylates. The submitter states
that each of the homologs was reported on the TSCA Inventory, but
the chemical identities of these substances were claimed as
"Confidential Business Information" by 3M.
209
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9PHQ-038l-0394 S
Page 3 of 4
According to the submitter, various mixtures of homologous
ammonium carboxylates and the corresponding homologous carboxylic
acids are currently commercially available and used as follows:
"Fluorad@ Brand Fluorochemical
Surfactant FC-143
(ammonium carboxylates)
Emulsifier used in chemi-
cal processing and as an
additive in chemical
specialty products.
"Fluorao@ Brand Fluorochemical
Surfactant FC-126
(ammonium carboxylates)
Additive used in chemical
specialty products.
"3M Brand Fluorochemical
Acid FC-26
Emulsifier additive in
chemical specialty pro-
ducts (international
market only)".
The submitter states that the subject chemicals are manufactured
in a closed system from domestically produced and imported
perfluoroalkane carboxylic acids. According to the submitter,
perfluoroalkane carboxylates are exported annually, but export
volumes were claimed as "Confidential Business Information" by
3~-1.
No other information on current uses of FC-143, FC-l26 or FC-26
was located in the secondary literature sources consulted.
Comments/Recommendations
--
The 3M Company states that it plans to inform those customers and
3M employees who have, through uses and/or processing, potential
significant exposure to the subject chemicals. To inform these
customers and employees, 3M states that it will summarize the
findings of the submitted study and outline 3M's recommendations
. for handling and using the products referenced in this
submission. 3M also states that the company plans to advise
these customers and employees of additional information, as it
becomes available to 3M. The submitter further states that, in
view of the submitted preliminary findings, the following program
is planned for the ammonium carboxylate mixture: (1) a
teratology study in rats; (2) a subsequent teratology study in
rabbits; and (3) a continual industrial hygiene program to
improve and refine manufacturing and packaging processes which
have been developed to further reduce the exposure to plant
employees.
The Agency recently learned (The Free Lance-Star, Fredericksburg,
Virginia, Tuesday, April 7, 1981) that E. I. Du Pont de Nemours
and Company, Inc., a 3M customer and user of FC-143, has
reassigned 50 women employees of child-bearing age at one of its
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8ITQ-0381-0394 S
Page 4 of 4
plants. This was in response to information provided to DuPont
by 3M indicating that FC-143 had caused birth defects in rats in
the oral range-finding study which is the subject of this
submission.
The EPA has evaluated a previous 3M submission (8EHQ-1077-0011)
in which it was reported that FC-70, a commercial product used as
an electronics vapor soldering fluid, decomposes to highly toxic
perfluoroisobutylene and an unidentified perfluoroimine when
overheated. The EPA has also evaluated a series of 3M submis-
sions (8EHQ-1180-0373S~ 8EHQ-1180-0374S~ 8EHQ-0281-0373S
Supplement and 8EHQ-0281-0374S Supplement) on other perfluoro-
chemicals which reportedly produced a developmental eye lens
abnormality in rats.
a)
The Chemical Hazard Identification Branch (CHIB/AD) will
request the 3M Company to provide information on the amounts
of each perfluoro homolog present in the commercial mixtures
which are referenced in this submission. with reference to
the submitted oral rangefinder study, the Chemical Hazard
Identification Branch will request that 3M provide the
results of blood and liver sample analyses, if performed.
The 3M Company will also be asked if it plans to conduct
complete histological examination of the organs of dams and
fetuses in the planned teratology studies with the subject
perfluoro mixture, and will be asked if further studies are
planned to determine organ toxicity, storage, and disposition
of perfluoro compounds.
b)
The Chemical Hazard Identification Branch will consider the
preparation of Chemical Hazard Information Profiles on
selected chemicals within the class of perfluoroalkyl
compounds.
c) .
It is recommended that chemicals witnin the class of
perfluoroalkane ammonium carboxylates referenced in this
status report be considered for inclusion in future TSCA
Section 8(a) Level A reporting.
d)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to OSHA, NIOSH, CPSC, CCD/EPA and
OWWM/EPA. CHIB will also provide a copy of the status report
to the Office of Toxics Integration (OTI/EPA) for appropriate
distribution. The Industry Assistance Office (IAO/EPA)
should consider sending the same information to industry-
associated organizations.
211
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
SUBJECT:
Status Report 8EHQ-XXXX-0395
FROM: Frank D. Kover, Chief
Chemical Hazard Identification Branch
TO: Joseph J. Merenda, Director
Assessment Division
The Document Control Number 8EHQ-XXXX-0395 is VOID
EPA FORM 1320-6 (REV. 3-76)
212
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IviAY I 8 ISbl
Status Report* 8EHQ-0481-0396
SU~JECT:
~:nk D. Kover, Chief
1RCIl-: Chemical Hazard Identification
0.1. TE:
UNITED STATES ENY IRONMENT AL PROTECTION AGENCY
Branch
8EHQ-0481-0396
Page 1 of 4
~ $/PAl
APprov.ec
Revisio
Needed
TO:
Joseph J. Merenda, Director
Assessment Division
Submission Description
Martin Marietta Chemicals (Sodyeco Division) has reported that
two dyestuffs have been found positive for in vitro mutagenicity
in Ames (Salmonella) tests. The submitter stated that according
to an oral report received from Burlington Industries (the
sponsor of the performed tests), positive results were observed
with Martin Marietta's SODYECRON Blue GBL powder (also known as
Disperse Blue 291) and Eastman Blue RBS (manufactured by Eastman
Chemical). Martin Marietta provided the following summarized
findings from the performed Ames tests:
1.
SODYECRON Blue GBL Powder
Positive
2.
Yarn dyed with SODYECRON Blue GBL Powder
Negative
3.
Methylene chloride extract of yarn dyed
with SODYECRON Blue GBL Powder
positive
4.
Methylene chloride extract of yarn dyed
with SODYECRON Blue GBL Powder
and finished
positive
5.
Ethyl Acetate extract of yarn dyed with
SODYECRON Blue GBL Powder
Weakly positive
6.
Saline solution (synthetic perspiration)
extract of yarn dyed with-SODYECRON Blue
GBL Powder
Negative
7.
Eastman Blue.RBS dyestuff
positive
8.
Yarn dyed with Eastman Blue RBS dyestuff
Negative
9.
Ethyl acetate extract of yarn dyed with
Eastman Blue RBS dyestuff
Negative
*NOTE: This status ~eoo=t is the result of a crelirni~a=v
staff evaluation of information submitted to EPA. Sta~e;e",~s
made herein are not to be regarded as exoressinc final
Agency ~olicy or intent ~ith resoect to this oarticular
chem~cal. .Any review of the status report sh~ulc take in~o
~0r;.slder~tlo~ the fact that it may be based on incomplete
In-ormatl.on.
213
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8EHQ-0481-0396
Page 2 of 4
Martin Marietta stated that because correlations of results from
Ames tests and animal studies can vary substantially according to
both the reporter and the class of the compounds tested, the
cited Ames test results "do not prove that a substantial risk
exists."
According to Martin Marietta, 32 of its employees are exposed to
the concentrated dyestuff during the manufacturing process, 62
employees are exposed in Martin Marietta testing laboratories,
and an estimated 200 persons are exposed in its customer's
textile dyeing plants. Martin Marietta states that all of these
persons are exposed to low concentrations of the dyestuff for
short periods of time.
Submission Evaluation
Although the submission does not indicate if the performed tests
were carried out in the presence and/or absence of metabolic
activation, it is apparent from the provided summarized results
that both dyestuffs have some degree of in vitro mutagenic acti-
vity. However, without complete copies of the test protocols and
data from the performed studies, evaluation of the reported
results is not possible at this time. Complete copies of the
final reports from the cited tests should be requested from the
submitter.
Current production and Use
Martin Marietta reported that its SODYECRON Blue GBL c~ntains, in
addition to various additives, an azo dyestuff (not identified by
the submitter) which is also used in other Martin Marietta dye-
stuff products. No production information or specific use
information on SODYECRON Blue GBL or Eastman Blue RBS was
provided by Martin Marietta, nor was such information located in
the secondary literature sources consulted. The submitter did
not provide any information concerning the actual chemical
identity and amounts of the various components of the tested
dyestuffs.
Comments/Recommendations
Although the Agency agrees that a positive Ames test result is
not sufficient in itself to prove that a risk exists, the Agency
does believe that mutagenicity assays of this type provide
valuable data that can aid in assessing possible risks posed by
chemicals to health and the environment. In addition, the EPA
believes that knowledge of high production of and/or exposure to
the subject chemical would suggest the need for further more
definitive toxicological testing.
Based on an initial review of the information contained in 8EHQ-
0481-0396, the EPA believes that the submitted in vitro mutagen-
icity information alone does not appear to provide reasonable
support for a conclusion of substantial risk pursuant to Section
214
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8EHQ-0481-0396
Page 3 of 4
8(e) of the Toxic Substances Control Act (TSCA; PL 94-469).
basis for the EPA's position, at this time, is as follows:
The
The preface to Part V of the Agency's March 16, 1978,
"Statement of Interpretation and Enforcement Policy;
Notification of Substantial Risk" (43 FR 11110) states that "a
substantial risk of injury to health or the environment is a
risk of considerable concern because of (a) the seriousness of
the effect. ..and (b) the fact or probability of its
occurrence." With regard to the "fact or probability of its
occurrence" criterion, Part V states that certain health
effects are so serious that relatively little weight should be
given to the chemical's exposure in determining whether a risk
is substantial. With regard to the seriousness of the effect,
Part V explains further 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, mutation, birth defects, or
toxic effects resulting in death or serious or prolonged
incapacitation." The information respecting these effects can
be obtained directly or inferred from designed studies (e.g.
in vitro experiments and tests as described in Part VI of the
policy statement). However, with regard to the circumstances
under which the results of an in vitro test should be
reported, Part VI clarifies that the reporting of positive
results from such a test (e.g. Ames test) will depend upon the
existence of corroborative information if necessary to support
the conclusion of substantial risk.
In view of the preceeding discussion, it is the EPA's preliminary
determination that the in vitro Ames test results alone, as
provided by Martin Marietta in the present notice, do not appear
to have warranted submission to the Agency pursuant to TSCA
Section 8(e). However, in making this preliminary determination,
it must be understood that the EPA may not be aware of additional
pertinent information which may have been available to and/or
considered by the company in reporting the toxicity data under
Section 8 (e) .
a)
The Chemical Hazard Identification Branch will request
Burlington Industries (test sponsor) to provide complete
copies of the final results, including test protocols and
data, from the Ames tests cited in this submission. In
addition, CHIB will request both Martin Marietta and
Eastman Chemical to provide information on the actual
chemical identities (including CAS Numbers) and amounts of
the components of SODYECRON Blue GBL and Eastman Blue RBS.
215
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8EHQ-0481-0396
Page 4 of 4
b)
In view of the Agency's general interest in actions which
are taken on a voluntary basis by companies in response to
chemical toxicity/exposure information, CHIB will request
Martin Marietta, Eastman, and Burlington to describe their
actions taken to warn workers and others, and to reduce
and/or eliminate exposure to the tested dyestuffs. In
addition, CHIB will ask those companies if they plan to
conduct additional studies designed to further define the
toxicity of SODYECRON Blue GBL and/or Eastman Blue RBS.
c)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, CPSC, FDA,
Martin Marietta, Eastman, and Burlington. CHIB will also
provide a copy of the status report to the Office of
Toxics Integration (OTI/OPTS/EPA) for appropriate distri-
bution. The Industry Assistance Office (IAO/OTS/EPA)
should consider sending the same information to industry-
associated organizations.
216
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
OA TE:
. .. 1981
Page 1 of 6
SU&JECT, Status Report* 8EHQ-0481-0397
8EHQ-048l-0397 Supplement
'R~: Justine L. Welch, Team Leade~
Chemical Selection and profi~ Team/CHIB
TO: Frank D. Kover, Chief
Chemical Hazard Identification Branch/AD
Approvec
?J)t-
~1/~
Revision
Needed
Submission Description
The Wilmington Chemical Corporation has submitted (8EHQ-048l-
0397) a copy of an Oak Ridge National Laboratory (Tennessee)
draft report, entitled "Chronic [mouse] Dermal Toxicity of Epoxy
Resins. I. Skin Carcinogenic Potency and General Toxicity."
According to the Oak Ridge draft report, the study was an
extension and continuation of a u.S. Department of Energy (DOE)-
sponsored program to evaluate epoxy resins for potential
occupational health risks~
The concluding abstract of the Oak Ridge draft report stated in
part that "the skin carcinogenicity and systemic toxicity of six
commercial epoxy resins and two amine curing agents were
evaluated by continuous application of dilute acetone solutions
to the skin of C3H mice for two years. Applied separately, 2 of
the six resins were carcinogenic in mouse skin, with potency
ranging from 1/200 to 1/200,000 that of benzo[a]pyrene. Both
materials shown to be carcinogenic were previously untested in
experimental animals. positive synergism was noted between
resins that were either non-carcinogenic or weakly carcinogenic
under the prevailing assay conditions."
The epoxy resin and amine curing agent materials tested by Oak
Ridge were reported as follows:
1.
Epirez 508 (major component: 2,2'-[(1-Methylethylidene)
bis (4,l-phenyleneoxymethylene)] bis oxirane;
(CAS No. 1675-54-3).
II.
Epon 828 (major component: 2,2'-[(1-Methylethylidene) bis
(4,1-phenyleneoxymethylene)] bis oxirane; CAS No. 1675-54-
3 ).. (This product was reported to differ from I. with
respect to proprietary modifiers).
*NOTE: This status reoort is the result of a prelimi~a=;
staff evaluation of in~ormation submitted to EPA. Stateme~ts
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
inf"o!"ma tion.
217
[PO" '01'10 11~ IRtV. :-7GI
-------
III.
IV.
VI.
VII.
VIII.
IX.
8EH~0481-0397
8EH~0481-0397 Supplement
Page 2 of 6
Araldite 6010 (major component: 2,2'-[{1-Methylethylidene)
bis{4,I-phenyleneoxymethylene)] bis oxirane; CAS No. 1675-
54-3). (This product was reported to differ from I. with
respect to proprietary modifiers).
V.
ERE 1359 (major component: 2,2'-[1,3-Phenylenebis
(oxymethylene)] bis oxirane; CAS No. 101-90-6).
XB 2793 {major component: 5,5-Dimethyl-l,3-bis (oxiranyl-
methyl)-2,4-imidazolidenedione; CAS No. 15336-81-9).
Heloxy WC-68 (major component: 2,2'-[2,2-Dimethyl-l,3-
propanediyl) bis (oxymethylene)] bis oxirane; CAS No.
17557-23-2).
ERR 4205 (major component:
ether; CAS No. 2386-90-5).
Bis (2,3-epoxycyclopentyl)
Apco 2330 (major component:
108-45-2).
1,3-Benzenediamine; CAS No.
Menthane diamine {major component: 4-Amino -q~q-4-
trimethylcyclohexanemethanamine (CAS No. 80-52-4).
X.
Benzo[~]pyrene (positive control) (CAS No. 50-32-8).
In addition to the individual materials shown above, the various
combinations tested in this study were reported as follows:
A.
B.
C.
D.
a 50:50
a 70:30
a 50:50
a 50:50
mixture of
mixture of
mixture of
mixture of
III and VII
V and VI
I and VII
II and VII
The Oak Ridge draft report stated that "treatment related skin
neoplasms that were persistent, grew progressively and contri-
buted to mortality were induced with materials V, VI, VII, X
(positive control) and with all the resin mixtures {A,B,C,D)."
The Oak Ridge draft report also stated that material VII was not
applied separately in the present study because it had been
previously tested by Oak Ridge. {Published results from this
previous study (Holland et al., 1979) showed that test material
VII was an active skin carcinogen in mice via chronic dermal
application). In addition, the Oak Ridge report stated that
previously published animal carcinogenicity studies revealed that
material IV is capable of eliciting skin neoplasms in C57BL mice
(Mc Cammon et al., 1957), but not in Swiss ICR mice (Van Duuren
et al., 1965) following chronic dermal exposure. The Oak Ridge
report stated that these previous findings were consistent with
the present data which show that skin tumors were not induced by
material IV in C3H mice, a strain which is reportedly less
sensitive than C57BL mice to skin carcinogens. The draft report
further stated that by using the highest exposure levels
218
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8EHQ-0481-0397
8EHQ-0481-0397 Supplerrent
Page 3 of 6
permitted by local or systemic toxicity to estimate oncogenic
potential, the potencies of Jl1.aterials V and VI were an order of
magnitude greater toan that observed at the higoest permissible
dosages of material VII alone or in combination with material I,
II or III. Also, the combination of V and VI (mixture B) report-
edly induced a response comparable to that observed with V with
no indication of synergism.
The draft report stated that, in general, male mice were more
sensitive than female mice to skin tumor induction whereas female
mice were more sensitive to systemic toxicity. In addition, the
report stated that severe skin irritation induced by certain of
the test materials did not correlate with skin carcinogenicity.
According to the Oak Ridge draft report, clinical hematologic and
chemical analysis, as well as gross and microscopic evaluations,
were conducted on individual animals. The draft report stated
that correlations of clinical findings with gross and microscopic
pathologic changes will be included in future reports.
In its submission, Wilmington stated that it manufactures Heloxy
WC-68 (test material VI in the Oak Ridge study) and resorcinol
diglycidyl ether (reported by Oak Ridge to be the major component
of ERE 1359; test material IV). In a supplemental submission
(8EHQ-0481-0397 Supplement), toe CIBA-GEIGY Corporation stated
that "one of the coemicals studied, 2,2'-[(2,2-dimethyl-l,3-
propanediyl) bis (oxymethylene)l bis oxirane [the major
component of test material VIJ, which we [CIBA-GEIGY]
manufacture, was reported to be carcinogenic" in mice in the Oak
Ridge study. CIBA-GEIGY stated further that toe tested compound,
although chemically identical to one that CIBA-GEIGY
manufactures, was not manufactured nor supplied by CIBA-GEIGY for
the Oak Ridge study. CIBA GEIGY also stated that "the
epichlorohydrin content of the sample (batch) studied was
conspicuously absent". In addition, CIBA-GEIGY stated that it
was the company's experience" that epichlorohydrin impurities, if
present in appreciable amounts, can significantly affect
toxicological properties."
Submission Evaluation
The Oak Ridge study appears to be a substantial, well designed
carcinogenicity bioassay of seven structurally different epoxy
resins and various resin mixtures. There is no difficulty in
identifying fr~n the Oak Ridge draft report which two of the six
resins were found in the present study to be carcinogenic via
chronic dermal application to mice. These are test materials V
and VI. The criterion used by Oak Ridge to compare the carcino-
genic potencies of the different materials, i.e., the potencies
relative to benzo[~]pyrene (used as the reference carcinogen) at
the highest exposure level permitted by local or systemic toxic-
ity, appears to be reasonable. It is by this criterion that
compounds V and VI were judged by Oak Ridge to be carcinogenic.
Test material VI also attracts attention as a potential systemic
219
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8EHQ-048l-0:E 7
8EHQ-048l-0:E7 Supplement
Page 4 of 6
toxicant at levels of exposure that do not induce local
irritation.
The CIBA-GEIGY supplemental submission noted that epichlorohydrin
impurities, if present in appreciable amounts, can significantly
affect toxcicological properties and also noted that the presence
of epichlorohydrin was not indicated for test material VI in the
Oak Ridge study. It is of interest that of the five epoxy pro-
ducts for which the epichlorohydrin content was reported (i.e. I,
II, III, IV and V), the only product displaying carcinogenicity
in the present study was the one (material V) containing a 4-
digit ppm concentration of epichlorohydrin. However, other
observations in the present study seem to suggest that the
epichlorohydrin content may not have been the uniquely deter-
mining factor. Test material VII showed an equivalent degree of
synergism when tested in combination with I, II or III, despite
the fact that each of these latter products reportedly contained
low but differing levels of epichlorohydrin. As the Oak Ridge
report states, this "suggest(s} strongly that synergism is
between the principal components rather than reactive diluent or
trace contaminants." It should he noted, however, that the Oak
Ridge draft report did not contain any information on the
epichlorohydrin content of VII. This information should be
obtained, if available.
It is interesting that mixture B, the only mixture tested whose
principal components (materials V and VI) displayed carcinogeni-
city when tested separately, exhibited additivity rather than
synergism with respect to carcinogenic potential. In addition,
there was no indication from the data presented in the draft
report that clinical chemical or hematological irregularities
were correlated with skin carcinogenicity.
Current production and Use
.
Production statistics are reported below for the major components
of the test materials IV, V, VI, and VII which were reported to
be oncogenic either in the present Oak Ridge study or in previous
studies cited in the draft report.
A review of the production range (includes importation volumes)
statistics for 2,2'-[1,3-phenylenebis (oxymethylene)] bis oxirane
(CAS No. 101-90-6; the major component of test material IV),
which is listed in the initial 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 confidential by the person(s} reporting for the TSCA
Inventory, nor does it include any information which would
compromise Confidential Business Information. **/
A review of the production range (includes importation vOlumes)
statistics for 5,5-dimethyl-l,3-bis(oxiranylymethyl}-2,4-imidazo-
lidenedione (CAS No. 15336-81-9; the major component of test
220
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8EHQ-048 1-0 397
8EHQ-0481-0397 Supp1errent
Page 5 of 6
material V) and for bis(2,3-epoxycyc1opentyl) ether (CAS No. 2386-
90-5; the major component of test material VII), which are listed in
the initial TSCA Inventory, has shown that no 1977 production/
importation was reported or that all of the production range data
reported were claimed as confidential by the manufacturer(s) and
importer(s) and cannot be disclosed. (Section 14(a) of TSCA, U.S.C
2613 (a». **/
A review of the production range (includes importation volumes)
statistics for 2,2'-[(2,2-dimethyl-l,3-propanediyl) bis (oxymethy-
lene)] bis oxirane (CAS No.17557-23-2~ the major component of test
material VI), which is listed in the initial TSCA Inventory, has
shown that between 100 thousand and 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 confidential by the person(s) reporting
for the TSCA Inventory, nor does it include any information which
would compromise Confidential Business Information.**/
Epoxy resins constitute a broad group of chemical monomers that are
used to produce commercial products such as surface coatings for
household appliances, floors and wall panels, and adhesives for
metals, glass and ceramics. No information on the specific uses of
the tested materials was provided in the Oak Ridge draft report, in
the original submission by the Wilmington Chemical Corporation or in
the supplemental submission by the CIBA-GEIGY Corporation.
Comments/Recommendations
With regard to test material VI, in its supplemental submission
(8EHO-0481-0397 Supplement), the CIBA-GEIGY Corporation stated that
"if we [CIBA-GEIGY] determine that these carcinogenic results could
reasonably apply to our own product, we will advise our customers of
this finding and modify our labels to reflect the carcinogenicity
potential."
The National Institute for Occupational Safety and Health (NIOSH)
has prepared a "Criteria Document" on Glycidyl Ethers (DHEW (NIOSH)
Publication No. 78-166; June 1978). The Test Rules Development
Branch (TRDB/AD/EPA) is currently reviewing information pertaining
to "Glycidol and its Derivatives" as recommended by the Interagency
Testing Co~mittee (ITC).
The Agency has received and evaluated previous Section 8(e) submis-
sions (8EHQ-0180-0328S and 8EHQ-0681-03?8S Follow-up Response), in
wnich the CIBA-GEIGY Corporation reported that XB 2793 (in a
separate study) produced skin tumors in mice via chronic (life-time)
dermal application.
**/ The data submitted for the TSCA Inventory, including production
range information, are subject to the limitations contained in the
Inventory Reporting Regulations (40 CFR 710).
221
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References
BEHQ-0481-0 :E7
BEHQ-0481-0:E7 Supplerrent
Page 6 of 6
a)
The Chemical Hazard Identification Branch (CHIR/AD/EPA) will
request the Oak Ridge National Laboratory to provide, when
available, a copy of the final report of the present mouse
skin painting study and a copy of future reports concerning
this study. The Chemical Hazard Identification Rranch will
also request Oak Ridge to provide any available data on the
epichlorohydrin content of test materials VI and VII.
b)
The Chemical Hazard Identification Branch will request both
the Wilmington Chemical Corporation and the CIBA-GF.IGY
Corporation to descrihe the actions they have taken, in
light of the submitted toxicological information, to warn
workers and others, and to reduce and/or eliminate exposure
to epoxy materials found to exhibit oncogenic activity.
c)
The Chemical Hazard Identification Branch will consider the
preparation of Chemical Hazard Information Profiles (CHIPs)
on 2,2'-[1,3-phenylenebis(oxymethylene)]bis oxirane (CAS No.
101-90-6)i 5,5-dimethyl-l,3-bis (oxiranylmethyl)-2,4-
imidazolidenedione (CAS No. 15336-81-9)i 2,2'-[(2,2-
dimethyl-l,3-propanediyl) bis (oxymethylene)] bis oxirane
(CAS No.17557-23-2)i and bis(2,3-epoxycyclopentyl) ether
(CAS No. 2386-90-5), which were reported to be the principal
chemical components of test materials IV, V, VI and VII,
respectively- It also is recommended that these four
compounds be considered for inclusion in future TSCA Section
R(a) Level A reporting. In addition, the Oak Ridge draft
report will be screened in CRIB's Current Awareness Program
for additional chemical candidates for further assessment.
d)
The Chemical Hazard Ioentification Branch will transmit a
copy of this status report to OSHA, NIOSH, CPSC, TRDB/
AD/EPA, and the Oak Ridge National Laboratory. CHIB will
also provide a copy of the status report to the Office of
Toxics Integration (OTI/EPA) and the Industry Assistance
Office (IAO/EPA) for appropriate distribution.
Holland JM, Gosslee DG and Williams NJ. 197~. Epidermal carcino-
genicity of bis (2,3-epoxy cyclopentyl)ether, 1,1 bis(p-glycidyl-
oxyphenyl)propane, and m-phenylenediamine in male and female C3H
ano C57BL/6 mice. Cancer Res. 39:1718-1725.
HcCammon CJ, Kotin P and Fa1k HI.. 1957. The carcinogenic potency
of certain diepoxides. Proc. Amer. Assn. Cancer Res. 2:229-230.
Van Duuren, Orris L and Nelson N. 1965. Carcinogenicity of
expoxides, 1actones and peroxy compounds. II. J. Natl. Cancer
Inst. 35:707-717.
222
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OA TE:
MAY 2 6 /981
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0581-0398
"Page 1 of 2
Approvec ~ ~~J
Revision
Needed
SU!JECT: Status Report* 8EHQ-0581-0398
I'RQI.I: ~nk D. Kover, Chief
Chemical Hazard Identification Branch
TO:
Joseph~. Merenda, Director
Assessment Division
Submission Description
The Gulf Mineral Resources Company has provided the summarized
results of an acute aspiration toxicity test with Solvent Refined
Coal (SRC)-II Middle Distillate in rats. According to the
submitter, the tested substance was administered at a dose of 1.0
ml/kg of body weight into the oral cavity using a modified
Gerarde technique. In addition to mortality (2/5 males and 2/5
females during the 24-hour study period), the submitter reporteo
that the toxicity resulting from the SRC-II material included
"significant statistical differences in absolute and relative (to
body weight) lung weights and irritation 6f the lung tissue as
evidenced by macroscopic examination at necropsy." The company
also reported that "the mortality observed in the SRC-II [Vfiddle
Distillate group further indicates that the test article results
in lethal toxicity when administered in accordance with the
decribed protocol in the Fischer 344 rat." In conclusion, the
submitter stated that the observed effects are "well known and
similar to comparable petroLeum hydrocarbons", and that "there is
no employee hazard because this material [SRC-II Middle
Distillate] is not designed or intended to be ingested."
Submission Evaluation
Aspiration of hydrocarbon distillates of khis type can bring
about various adverse pulmonary changes ranging from pneumonitis,
pulmonary edema, pneumonia etc. The lung changes can occur
following exposure to the distillates via direct inhalation of
mists or via any other aspiration pathway, including vomiting
after oral ingestion.
Current production and Use
Although there are several SRC substances listed on the TSCA
Inventory, SRC-II Middle Distillate was not located. According
to the submitting company, the production of SRC-II Middle
*NOTE: This status report is the result of a prelimi~a=\.
staff evaluation of in~ormation submitted to E~A. State;e~~s
made herein are not to be reaarded as expressinc final
Agency ~olicy or intent with-respect to t~is pa~ticular
chemical. Any review of the status report shoul~ take i~to
consideration the fact that it may be based on incomplete
inf"orma tion . . .
223
t"A FO"''' t)~ IREV. ~-1GI
-------
8EHQ-OS81-0398
P~ge 2 of 2
Distillate is essentially limited to a Department of Energy (DOE)
pilot plant operated by The Pittsburg & Midway Coal Mining
Company at Ft. Lewis, Washington. No information on current
production was provided by the submitter or located in the
secondary literature sources consulted.
Comments/Recommendations
The Agency has prepared status reports for a number of TSCA
Section 8(e) submissions received on synthetic and petroleum
fuels: 8EHQ-0029, 0030, 0044, 0082, 0083, 0117, 0148, 0212,
0215, 0216, 0217, 0238, 0240, 0247, 0252, 0253, 0297, 0301, 0306,
0316, 0323, 0377 and 0389. (These numbers represent the last
four digits of the EPA Document Control numbers).
a)
The Chemical Hazard Identification Branch (CHIB/AD) will
request the submitter to provide a complete copy of the
final report, including protoco1(s) and data, from the
acute aspiration test cited in the submission. In
addition, CRIB will request the Gulf Mineral Resources
Company to describe the actions it has taken, in light of
the reported toxicity, to warn workers and others, and to
reduce and/or eliminate exposure to SRC-II Middle
Distillate. CHIB will also ask the submitting company if
it plans to conduct additional studies in order to
further define the toxicity of the material.
b)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to DOE, OSHA, NIOSH, OWWM/EPA,
ORD/EPA, OANR/EPA, the EPA Alternate Fuels Workgroup, and
the OTS Synfuels Workgroup. CRIB will also provide a copy
of the status report to the Office of Toxics Integration
(OTI/OPTS/EPA) for appropriate distribution. The
Industry Assistance Office (IAO/OTS/EPA) should consider
sending the same information to industry-associated
organizations.
224
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OA TE:
-.lUI~ - i 1::;,'1
UNITED 5T A TES ENV IRONMENT AL PROTECTION AGENCY
8EHQ-058l-0399 S
Page 1 of 3
SU~JECT:
Status Report* 8EHQ-058l-0399 S
Approved ~ ~~~I
" ,
Rev~s~on
Needed
FR~~~nk D. Kover, Chief
Chemical Hazard Identification Branch
TO: Joseph J. Merenda, Director
Assessment Division
Submission Description
Hercules Incorporated reported that a new high explosive was
found to cause teratogenic and other embryo/fetotoxic effects
following daily dermal applications to pregnant rats during the
period of organogenesis. Although the exact chemical identity of
the tested material was claimed by Hercules as TSCA Confidential
Business Information (CBI), the sanitized version of the notice
(which was provided by the company) indicates that the new high
explosive is a mixture. According to Hercules, "Ten daily doses
of 1850 mg (1 oral LD50)/kg/day/rat caused ectrodactyly
[congenital absence of all or of only part of a digit] (1 fetus
in each of 2 litters), late resorptions (35 in 18 litters),
multiple skeletal malformations and at least three characteristic
soft tissue defects - diaphragmatic hernia, major vascular
anomalies in the area of the aortic arch and delayed development
of kidney architecture (hydronephrosis)." The submitter also
stated that "Ten daily ooses'of 185 mg/kg/day/rat'did not cause
any late resorptions, skeletal deformities or delayed kidney
development in rats." However, the vascular anomaly was
reportedly observed in one rat at the lower dose. Hercules noted
that although the soft tissue examinations are not yet complete,
the company has tentatively concluded that the "lower dose is
marginally an effect level." Hercules also reported that the
company is "planning an additional study on the mixture to
determine a no-effect level."
Submission Evaluation
There are several types of explosives which can be absorbed
through the syin. 'In the absence of control data or any indi-
cation of maternal toxicity, it may be assumed that sufficient
amounts of the tested mixture component(s) were absorbed by the
pregnant mothers to cause teratogenic effects. It is possible
for chemicals to be of relatively low toxicity to the mother and
at the same time be highly injurious to the developing fetus.
*NOTE: This status ~eDo~t is the iesul~ of 1" ~
~ fF.~ ' ~,~, -~ a pre lrn~na_y
s~a_- eVcluat~on OL ~nrormat~on submit~ec ~o ED~ St ~ t-
o h r " '- ~ I... -...... a~eme;,-s
mace e-e~n are no~ to be regarded as expressinc final
Agency pol~cy or lntent with rQs~ec~ to ~, ' -~, 1
chemical' i . -" - l...:llS par~lcu ar
'd . ,Any rev-ew of the status repor~ should taKe in~o
~~~os~mae~~tlon the fact that it may be based on incomp'lete ~
...,,- -. --on.
225
r:,.. '0,"" IJ~ [R(V. ~-7CI
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8EHQ-0581-0399 S
Page 2 of 3
Although the submitter reports that an additional study will be
conducted to determine a no-effect level for the new explosive,
it should be noted that no-effect dose levels may vary
considerably between species. A teratogenicity study in another
species could provide valuable information for estimating safe
levels and safety factors for human exposure.
Current production and Use
Because the submitting company has claimed the actual chemical
identity of the components in the tested high explosive mixture
as CBI, a report based on production/importation range statistics
from the non-confidential TSCA Inventory will not appear in this
status report.
According to Hercules, the new explosive will replace certain
high explosives now used in many commercially available blasting
formulations and will be made in facilities which currently
produce explosives. The submitter also reported that blasting
agents, which usually contain approximately 25% high explosive,
are sold and used in sealed units which, in most cases, limits
user exposure to only that high explosive which may diffuse from
its absorbing material through the casing of the sealed unit.
Hercules stated that the company believes that the current
industrial hygiene practices which are observed for the manu-
facture and use of explosive products will provide adequate
protection of employees from the reported fetal effects.
Comments/Recommendations
In addition to the company's reported plans to conduct an
additional teratogenicity study, Hercules stated that its
employees and customers are being notified of the submitted
toxicological findings.
a)
The Chemical Hazard Identification Branch (CHIB/AD) will
request Hercules to provide, when available, a complete
copy of the final report, including test protocols and
data, from the unfinished teratogenicity study in rats
cited in its submission. CHIB will also request the
company to provide complete descriptions of the results
obtained from the other studies which have been
conducted during the company's reported "comprehensive
toxicological evaluation" of the new high explosive.
b)
The Chemical Hazard Identification Branch will consider
the preparation of a Chemical Hazard Information Profile
(CHIP) on the new high explosive and/or its chemical
components. The chemical components should also be
considered as candidates for future TSCA Section 8(a)
Level A reporting.
226
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8EHQ-0581-0399 S
Page 3 of 3
c)
~~e C~emical Razar~ I~entification Pranch wi].l transmit
a copy of this status report to ~IOSH, OSfIA, ~SPA,ana
CPSC. CPIB will also provide a copy of the status
report to t~e Office of ~oxics Integration (OTl/oP~~1
FPA) an~ to the Industry Assistance Office (I~n/o~s/pPA)
for appropriate distrihution.
227
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UNITED STATES ENVIRON.MENTAL PROTECTION AGENCY
8EHQ-0581-0400
Page 1 of 3
FR~;ank D.
Chemical
Kover, Chief
Hazard Identification Branch
Revisio
Needed
YNif
OA T E:
JUN - 4 /98/
SutoJECT:
Status Report* 8EHQ-058l-0400
Approvec
TO:
JosephJ. Merenda, Director
Assessment Division
Submission Description
In a submission sent directly to the EPA Acting Administrator,
the Upjohn Company reported that a squamous cell carcinoma has
been verified at the site of repeated application during a life-
time mouse skin-painting study of 2,2-diethoxyacetophenone (DEAPi
CAS No. 6175-45-7). According to the summarized information
contained in the submission, this chronic study was initiated in
April 1979, and involved the painting of undiluted DEAP (amount
not specified) three times per week for the lifetime of 40
mice. The submitter reported that the initial tumor was observed
on day 641 at which time there were 20 animals alive. The
squamous cell carcinoma was reportedly verified on day 667 with
12 animals remaining alive.
In its submission, Upjohn also provided a copy of an "Early
Warning Report" from the laboratory conducting the skin-painting
study of DEAP, a copy of the DEAP Material Safety Data Sheet, the
results of Ames Salmonella (bacteria) tests, and the summarized
final results of acute range-finding toxicity studies in rats and
rabbits. According to the provided summary toxicity reports,
DEAP was found to be non-toxic in the in vivo acute range finding
studies via ingestion (rats), skin penetrqtion (rabbits), and
inhalation (rats), and produced no acute eye injury (rabbits) and
only trace skin irritation (rabbits). In addition, DEAP was
reported to be negative both with and without metabolic
activation in the performed Ames mutagenicity tests.
In conclusion, Upjohn stated that the company "has no knowledge
of any toxic effects on its employees, customers, or others
attributable to the chemical, or of any literature reports of
such toxicological activity."
*NOTE: This status reoort is the result of a oreliminarv
staff evaluation of information submitted to EPA. State;e"ts
mace herein are not. to be reaarded as exoressinc final
Agency policy or intent with~respect to this pa~ticular
chemical. Any review of the status report should take into
consideration the fact that it ~ay be based on incomplete
inf"orma tion .
228
(~A '0"''' IJ~ [R(V. 1-7GI
-------
8lliQ-0581-0400
Page 2 of 3
Submission Evaluation
Although DEAP appears to have acute low toxicity, the compound is
absorbable through the skin and can cause malignant changes at
the site of repeated application. In reviewing the provided
information, it is not quite clear whether the one mouse showing
a tumor on day 641 is the same mouse that died with a squamous
cell carcinoma. Because DEAP is a photosensitive chemical, there
is an additional concern that exposure to the compound could
result in non-cancerous skin lesions. Also, the sites of
repeated skin application which showed no gross lesions could be
examined histologically for cellular changes. The submitter
should be requested to provide a complete copy of the final
results from this life-time mouse skin-painting study of DEAP for
further evaluation.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for DEAP (CAS No. 6175-45-7), which is listed in the
initial TSCA Inventory, has shown that between 10 thousand and
100 thousand pounds of this chemical were reported as produced/
imported in 1977. **/
The Upjohn Company reported that its Fine Chemicals Division has
been producing DEAP since early 197q at a plant site in North
Haven, Connecticut. Upjohn also reported that DEAP is
specifically designed for use as photosensitive initiator in
ultraviolet-cured inks, coatings and adhesives. The submitter
stated that previously developed information (not specified)
leads to the conclusion that a "significant portion" of the DEAP
is consumed during photo-cure processes. However, the submitter
also pointed out that a there is a remote possibility that trace
amounts of DEAP may remain in final products.
Comments/Recommendations
Upjohn reported that the company is notifying its DEAP customers
of the submitted results.
In this particular case, The Upjohn Company's submission of TSCA
Section 8(e) information to the EPA Acting Administrator's office
did not unduly burden the Agency's processing of the notice.
However, it will be brought to the submitter's attention that the
**/
This production range information does not include any
production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it
include any information which would compromise Confidential
Business Information. The data submitted for the TSCA
Inventory, including production range information, are
subject to the limitations contained in the Inventory
Reporting Regulations (40 CFR 710).
229
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8EHQ-0581-0400
Page 3 of 3
substantial risk information reporting requirements (Part IX of
the March 16, 1978, "Statement of Interpretation and Enforcement
Policy~ Notification of Substantial Risk" (43 FR 11110» clearly
specify that Section 8(e) notices are to be sent to the Document
Control Officer, Management Support Division, Office of Toxic
Substances (WH-557), Environmental Protection Agency, 401 M
Street, S.W., Washington, D.C. 20460.
a)
The Chemical Hazard Identification Branch (CHIB/AD) will
request Upjohn to provide a complete copy of the final
report, including protocols and data, from the life-time
mouse skin-painting study of DEAP cited in the sub-
mission. In addition, CHIB will request Upjohn to
provioe a complete description of the information which
was reportedly developed at an earlier date (including
results of chemical analyses for residual DEAP, if
performed) that forms the basis for the company's
conclusion that a "significant portion" of the DEAP is
consumed during photo-cure processes. CHIB will also
request Upjohn to describe other actions the company has
taken, in light of the reported toxicity information, to
warn its workers and to reduce and/or eliminate exposure
to DEAP.
b)
The EPA has received and evaluated previous Section 8(e)
submissions (Union Carbide Corporation~ 8EHQ-1078-025l et
seq.) which reported that skin tumors were found in mice
following repeated (life-time) dermal application of an
analogous photoinitiator chemical (DBAP~ 2,2-di(sec-
butoxy)acetophenone). In view of the oncogenic effects
reported in the present submission on DEAP, the Chemical
Hazard Identification Branch will consider preparing a
Chemical Hazard Information Profile (CHIP) on DEAP and
will reconsider the preparation of a CHIP on DBAP. It is
also recommended that both DEAP and DBAP he considered as
candidates for future TSCA Section 8(a) Level A
reporting.
c)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, CPSC and
OWWM/EPA. CHIB will also provide a copy of the status
report to the Office of Toxics Integration (OTI/OPTS/
EPA) and the Industry Assistance Office (IAO/OTS/EPA) for
appropriate distribution.
230
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UNITED STATES ENVIRONMENTAL PROTECTJON AGENCY
FROM:
-1{-
Frank D.
Chemical
Kover, Chief
Hazard Identification Branch
Page 1 of 8
hpprovec ~
ReVisionP~-
Needed
~J;il
DA T E:
AUG 1 3 1981
;U~JECT:
Status
Report* 8EHQ-1280-0401 S; and
Supplements A and B; and
Followup Responses A and B
TO
Joseph J. Merenda, Director
Assessment Division
Submission Description
In its initial submission (FYI-OTS-1280-0098 S), the Stauffer
Chemical company provided on a "For Your Information" basis, a
summarized preliminary report from a recently completed two-year
feeding study of Fyrol FR-2 (1,3-dichloro-2-propanol phosphate
(3:1); CAS No. 13674-87-8) in rats. Although Stauffer claimed
the actual preliminary data to be Confidential Business
Information (CBI), the company's cover letter stated that the
Fyrol FR-2 was administered in the rats' diet at dose levels of
0, 5, 20 and 80 mg/kg/day. Stauffer reported that neoplastic
changes were observed microscopically in the liver of the test
animals and that the incidence of hepatocellular carcinomas was
statistically significant at the 80 mg/kg dose but not at the
lower doses. The submitter also reported that benign testicular
interstitial cell tumors had been observed microscopically in the
test animals. The submitter stated, however, that these "tumors
are indigenous in the rat and are non-invasive." The submitting
company also reported that there was a substantial incidence of
interstitial cell tumors in both the control male rats and the
treated rat groups.
In addition to the above in vivo findings, Stauffer reported that
the results obtained from:personnel monitoring in the Fyrol FR-2
manufacturing facility indicated "very low worker exposure (less
than 10 ppb)" and that "medical surveillance programs of the
workers have not shown any findings that could be attributed to
exposure to Fyrol FR-2." In addition, Stauffer pointed out that
published National Institute of Environmental Health Sciences
(NIEHS) studies have shown that Fyrol FR-2 is "readily metabo-
lized and relatively non-persistent in experimental animals."
Stauffer also reported that it had previously provided Fyrol FR-2
scientific data, which apparently included negative results from
an in vitro cell transformation assay, to the EPA Administrator's
Toxic Substances Advisory Committee (ATSAC) in June, 1979.
*NOTE: T\-.. ....
;lis S\_2tuS ~epo~t is t}le result ~~ ,..
5 t co f:: e 'J (0 1" ,c"" " C:':: -~ ,-' - '-' cae r e J. l", 1 ;; 2,::~'
UJLJ_~.I 0- 1n..or,,,3L1on subm,,'-0r' '-c r:r:'\ c,-..
Tn ace her e 1 - - .-, r' - ...." - , .. - .. L '- ~ ~ ~ ,c, '-' ~ .:; ~ e :,', e '~ ~ :::
..... - n d.... e ;,......) l.. '- ~I b ere 0 2. r c e Cl 2. S f-~ '( ..-) or- 0 S ,..... l ~ C -= I n.. 1
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./ ~ ,-~I or llJl..ent 'w.'tn 'I-""",:::,s"1er+- ""1 .j....~-,-
C ;, em i c a 1 ;:, . ,- co , ' . - ... J.. - :- _.. L ~ L . . -'- 5 ~ 2. r t l C '-1.i ~ r
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con 5 1 d era t 1 0 nth c" f c' c .- t \" ; ~ ,\ : - - ~ ~.'. - -,-:l L 0
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~:l~ormc.t2.0n. - -..' ~_e~c:
231
!:?t... '0 RU I) 2...."-6 (Pt E v - ~- 7 G)
-------
Page 2 of 8
In its first supplemental submission (FYI-OTS-0181-0098
Supplement A), Stauffer provided a list of a number of in vitro
and in vivo toxicity studies which the company had previously
submitted to the Consumer Product Safety Commission (CPSC) and/or
the EPA AT SAC workgroup. Stauffer reported that complete copies
of all of the listed studies were being compiled and would be
provided to the EPA (FYI-OTS-0281-0098 Supplement B). Supplement
A also contained a copy of a Product Safety Information Sheet
which included a summary discussion of the in vitro and in vivo
toxicity of Fyrol FR-2. In addition, Stauffer provided a-copy of
a published scientific review article entitled "Flame-Retardant
Chemicals in Textiles" (Ulsamer et al.: Clinical Toxicology:
Vol.17: No.1: 1980).
Following a review of the reported preliminary oncogenicity/
carcinogenicity findings on Fyrol FR-2, it was the EPA's
preliminary determination that the subject information should
have been submitted pursuant to Section 8(e) of the Toxic
Substances Control Act (PL 94-469). Therefore, the Stauffer
Chemical Company was requested to provide its rationale as to why
the obtained carcinogenicity/oncogenicity data on Pyrol FR-2 was
not submitted to the EPA pursuant to TSCA Section 8(e). Stauffer
was informed that following an EPA review of the company's
response, the Chemical Hazard Identification Branch (CHIB/AD)
would, if warranted, deliver the subject information to the OTS
Document Control Officer for appropriate handling and public
filing as Section 8(e) substantial risk information.
With regard to the submitter's reported Fyrol FR-2 plant-site
personnel monitoring and medical surveillance studies, the
Stauffer Chemical Company was requested to provide complete
descriptions of the protocols and results from those performed
studies. In addition, Stauffer was requested to describe the
actions the company had taken, in light of the provided
carcinogenicity/oncogenicity information, to warn its workers and to
reduce and/or eliminate exposure to Pyrol FR-2. With regard to
the Fyrol FR-2 chronic feeding study, Stauffer was requested to
immediately provide complete copies of any and all preliminary
reports from that study which the company possessed and/or
obtained in the future. In addition, Stauffer was requested to
provide a complete copy of the final report, including protocols
and data, immediately upon receipt of that information by the
company.
In response to the Agency's requests, the Stauffer Chemical
Company provided (FYI-OTS-0381-0098 S Followup Response A) the
following documents, the contents of which were claimed by the
company as Confidential Business Information (CBI): 1) the
protocol for the two year rat chronic/oncogenic feeding study: 2)
a report on plant-site personnel monitoring studies: 3) a report
on the epidemiology study conducted at the manufacturing plant:
and 4) a report on a 90-day neurotoxicity study.
232
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Page 3 of 8
Stauffer's response also contained the company's rationale as to
why the previously described Fyrol FR-2 carcinogenicity/oncogen-
icity information was not submitted to the Agency pursuant to
TSCA Section 8(e). Stauffer stated that the company "used the
criteria outlined in EPA's March 16, 1978 "Statement of
Interpretation and Enforcement Policy" to determine whether or
not the FR-2 data are subject to the reporting mandates of
Section 8(e). We [Stauffer] concluded that the data do not meet
these criteria. We [Stauffer] disagree with EPA that the mere
fact that an implicated chemical is in commerce constitutes
sufficient evidence of exposure." In addition, Stauffer stated
that although the company believed that the substantial risk
criteria of the statute were not met, Stauffer had "voluntarily
complied with the intent of Section 8(e) by reporting pertinent
information to the EPA."
With regard to exposure, Stauffer reported that "measured
workplace exposures to airborne FR-2, the most common source of
occupational exposure, are extremely low. Data obtained by
monitoring personnel in the manufacturing plant show less than 10
parts per billion FR-2 in air as an 8-hour time weighted
average. These data are confirmed by workplace area samples
taken from a customer's plant showing no detectable amounts of
Fyrol FR-2." From this exposure data it is Stauffer's conclusion
that "the risk of human cancer from Fyrol FR-2 is extremely low
and that, based on the most conservative risk assessment models
that are currently used, Fyrol FR-2 does not present a
substantial risk of harm to human health or the environment."
With regard to the toxicity of Fyrol FR-2, Stauffer stated that
although the preliminary data provided to EPA from the chronic
feeding study "show a statistically significant incidence (10%)
of hepatocellular carcinoma, in one species (rat) and at the high
dose (80 mg/kg)", the "occurrence of tumors at the mid and low
doses was not statistically significant." Stauffer also stated
that the results of an in vitro malignant transformation test
showed that "Fyrol FR-idid not transform normal cells to
malignant cells in a study designed to predict carcinogenic po-
tential." Stauffer further stated that the results of in vitro
and in vivo mutagenicity tests were negative with Fyrol-PR-2.
With regard to human health, Stauffer reported that "an
epidemiology study conducted at the manufacturing plant shows no
finding of cancer or other disease that could be attributed to
Fyrol FR-2. While far from conclusive, the study is most
encouraging." Stauffer also stated that the preceeding toxicity
data "fail to demonstrate that FR-2 poses a substantial risk of
adverse health effects in humans." In addition, Stauffer stated
that "the occurrence of a significant incidence of tumors at only
the high dose level is indicative of a threshold response. This
is an important consideration in determining true carcinogenic
potential and this threshold appears to be far above the
extremely low levels of actual human exposure. In addition, the
carcinomas do not appear until late in the animal's life cycle.
This long time to tumor response at the high dose level is
233
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Page 4 of 8
further evidence that, at lower exposures, the threshold of tumor
occurrence can be pushed beyond the normal life span."
with regard to the environment, Stauffer again pointed out that
the NIEHS metabolism tests on Fyrol FR-2 show that the compound
"is metabolized quickly. is rapidly excreted and does not accumu-
late in test animals." Stauffer also stated that "the fact that
FR-2 does not bioaccumulate suggests that it is not persistent in
the environment and, thus, not an environmental hazard."
In summary, Stauffer stated that the company "disagrees with EPA
that the preliminary' data submitted are subject to TSCA Section
8(e). We [Stauffer] have adequate available data to judge that
the risk of human cancer to exposure to Fyrol FR-2 is extremely
low." In addition, Stauffer stated that the company "objects to
EPA's placing the submitted FR-2 data in the public file as
Section 8 (e) substantial risk information."
Pursuant to the Agency's request for additional preliminary
reports from the Pyrol FR-2 feeding study. Stauffer provided
(FYI-OTS-058l-0098 S Followup Response B) a copy of a letter from
the performing laboratory which contained a "preliminary,
unaudited summary of neoplastic findings in the renal tissues of
rats fed Pyrol FR-2 for two years." The actual information
contained in the summary was claimed by Stauffer as Confidential
Business Information (CBI). Stauffer reported that at the time
of the followup submission, no distinction could be made between
renal adenomas and renal carcinomas. In addition, Stauffer
stated that the company anticipates receiving the chronic feeding
study final report during the second quarter of 1981.
Submission Evaluation
In light of the reported preliminary toxicologic findings (i.e.
the statistically significant incidence of hepatocellular
carcinomas (malignancies) and the observed neoplastic changes),
Fyrol FR-2 must be viewed as having demonstrated carcinogenic/
oncogenic properties. Contrary to Stauffer's opinion, EPA does
not at this time believe that the available data support the
concept of a threshold for the carcinogenicity of Pyrol FR-2.
The summarized toxicity information contained in the provided
product safety data sheet indicates that Pyrol FR-2 can be
irritating to the skin and the eyes and is capable of being
absorbed both from the gastrointestinal tract and from the
skin. Fyrol FR-2 also appears to have some degree of neurotoxic
activity as indicated by the signs and symptoms which were
observed in laboratory animals and reported in both the provided
material safety data sheet and the review article on flam~
retardants (Ulsamer et al.; Clinical Toxicology; Vol.17; No.1;
1980). The final report from Stauffer's recently conducted 90-
day neurotoxicity study reports no clinical or histopathological
evidence of neurotoxic activity for Pyrol FR-2. However, due to
the restricted range of doses employed and the observed
234
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Page 5 of 8
pathologic changes in the controls, EPA believes the results of
this study to be indeterminate. EPA also believes that further
more definitive experimental evidence would be needed in order to
adequately characterize Fyrol FR-2's neurotoxic risk. With
regard to reproductive effects, the EPA believes that the
significance of fetotoxicity (reported in the product safety data
sheet) following oral dosing in pregnant rats is not clear in
light of the maternal toxicity which was also observed. In
addition, based on a review of the provided epidemiologic study,
the EPA believes that additional data and analyses would be
needed in order to support Stauffer's statement that there was
"no finding of cancer or other disease that could be attributed
to Pyrol FR-2."
with regard to mutagenicity, there is some disagreement between
the mutagenicity findings summarized in the provided Fyrol FR-2
product safety data sheet and the mutagenicity findings reported
in the open literature. The provided product safety data sheet
points out that Pyrol FR-2 does not induce gene (i.e. point)
mutations in bacteria (Salmonella; Ames Test), yeast
(Saccharomyces), fruit flies (Drosophila; sex-linked recessive
lethal test), or in cultureq mammalian cells (L5l78Y mouse
cells). The safety sheet also reports that urine from mice
treated with Fyrol FR-2 does not cause mutations in bacteria.
addition, Pyrol FR-2 reportedly does not induce chromosomal
aberrations in vivo (bone marrow assay; mice), does not induce
sister chromatid exchanges in cultured Mouse Lymphoma L5l78Y
cells, and does not cause in vitro cell transformation (Balb 3T3
mouse cells.) The product-Safety data sheet states that in vitro
chromosomal aberrations in mouse lymphoma cells (L5l78Y) can be
induced by Pyrol FR-2. According to the previously cited
scientific literature review article on flame retardants (Ulsamer
et al.; 1980), Pyrol FR-2 possesses weak (but significant)
mutagenic activity when tested in the Ames/Salmonella bacteria
assay in the presence of phenobarbital-induced mouse liver enzyme
preparations, PCB-induced mouse liver enzyme preparations, pheno-
barbital-induced rat liver enzyme preparations, or phenobarbital-
induced hamster liver enzyme preparations. The review article
also indicates that Pyrol FR-2 can induce both sister chromatid
exchanges and chromosomal aberrations in vitro (mouse L5l78Y
cells) .
In
Current production and Use
A review of the production range (includes importation volumes)
statistics for l,3-dichloro-2-propanol phosphate (3:1) (CAS No.
13674-87-8), which is listed in the initial TSCA Inventory, has
shown that no 1977 production/importation was reported or that
all of the production range data reported were claimed as
confidential by the manufacturer(s) and importer(s) and cannot be
disclosed. (Section 14(a) of the TSCA, U.S.C. 2613 (a». The
data submitted for the TSCA Inventory, including production range
information, are subject to the limitations contained in the
Inventory Reporting Regulations (40 CFR 710).
235
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Page 6 of 8
The submitter reported that Fyrol FR-2 is used as a flame
retardant. Additional information obtained by the Chemical
Hazard Identification Branch/AD indicates that Fyrol FR-2 is
recommended for use with cellulose acetate, ethyl cellulose,
epoxies, phenolics, polyurethanes, polyesters, polystyrene,
polyvinyl chloride, polyvinyl acetate, acrylics, other vinyls,
and rubber. According to an article which appeared in Chemical
and Engineering News (December 15, 1980), Fyrol FR-2 is used
"mainly in flexible polyurethane foams for cushions in
automobiles and in some furniture and also for mattresses."
comments/Recommendations
In its initial FYI report, the Stauffer Chemical Company stated
that in light of the preliminary scientific data from the Fyrol
FR-2 feeding study, the company was reviewing other data and
alerting its customers "to monitor their work environments and
use good industrial hygiene practices." The submitter also
reported that the Consumer Product Safety Commission (CPSC) had
been notified and that the EPA would be "apprised of additional
information as it becomes available." In Followup Response A,
Stauffer reported that letters had been transmitted to customers,
processors and users of Fyrol FR-2 notifying them of the report
to EPA, and that follow-up presentations were made to customers
by Stauffer's Director of Toxicology and Director of occupational
Medicine. Stauffer also reported that its Associate Director of
Occupational Medicine held meetings at Stauffer's manufacturing
facilities with workers involved in the manufacture of FR-2. In
addition, Stauffer stated that the company is "assisting and
cooperating with its customers to develop additional workplace
monitoring data." Finally, Stauffer stated that "preliminary data
have been collected which indicates no significant loss of FR-2
from end products such as urethane foam even at temperatures as
high as 240°F." Stauffer is reportedly "conducting more
extensive studies to confirm these preliminary findings."
Following a review of the Stauffer Chemical Company rationale
concerning the Section 8(e)-applicability of the preliminary
oncogenicity/carcinogenicity findings for Fyrol FR-2, it is the
EPA's position that the subject information should have been
formally submitted pursuant to Section 8(e), the substantial risk
information reporting provision of the Toxic Substances Control
Act (TSCA). The basis for the Agency's position is as follows:
The preface to Part V of the Agency's March 16, 1978 TSCA
Section 8(e) policy statement ("Statement of Interpretation
and Enforcement Policy~ Notification of Substantial Risk"~ 43
FR 11110), states that "a substantial risk of injury to
health or the environment is a risk of considerable concern
because of (a) the seriousness of the effect ...and (b) the
fact or probability of its occurrence." with regard to the
seriousness of the effect, Part V explains further that the
Agency considers the health effects for which substantial
risk information must be reported to include "any pattern of
236
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Page 7 of 8
effects or evidence which reasonably supports the conclusion
that the chemical substance or mixture can produce cancer..."
The information respecting these effects can be obtained
directly or inferred from designed studies (e.g. in vivo
experiments and tests as described in Part VI of the policy
statement). With regard to the "fact or probability of its
occurrence" criterion, Part V also provides that certain
health effects are so serious that relatively little weight
should be given to the chemical's exposure in determining
whether a risk is substantial. As stated in the policy
statement, "the mere fact that an implicated chemical is in
commerce constitutes sufficient evidence o£ exposure." That
is, for the purposes of TSCA Section S(e) reporting, a
chemical's presence in commerce is considered by EPA to be
presumptive evidence of sufficient potential for human
exposure to warrant formal reporting of new evidence that the
chemical is capable of causing a serious health effect such
as cancer. Although Stauffer has provided information which
indicates low (but measurable) worker exposure to Pyrol FR-2
and has reported that actions have been taken to further
evaluate and reduce occupational exposure to the chemical,
the available Fyrol FR-2 exposure data are both limited and
preliminary, and do not in EPA's view, provide an adequate
basis for rejecting the usual presumption that the chemical's
presence in commerce warrants reporting of the obtained Pyrol
FR-2 carcinogenicity data under Section S(e).
It is the Agency's position that the information provided by the
Stauffer Chemical Company offers reasonable support for a
conclusion of substantial risk as defined in the EPA's March 16,
1975, Section S(e) policy statement, and as such, should have
been formally submitted by the company to the EPA pursuant to
TSCA Section S(e). Therefore, the Chemical Hazard Identification
Branch has delivered Stauffer's FYI submissions on Fyrol FR-2 to
the OTS Document Control Officer for appropriate handling and
filing as TSCA Section S(e) information.
The Chemical Hazard Identification Branch is currently preparing
a Chemical Hazard Information Profile (CHIP) on 1,3-dichloro-2-
propanol phosphate (3:1). The subject chemical is listed in the
EPA's February 29, 19S0 proposed TSCA Section Sea) Level A rule
(45 FR 13646).
The Stauffer Chemical Company has been responding to requests
from the Management Support Division (MSD/OTS/EPA) that the
company substantiate its claims for confidential treatment of
information contained in several of the Stauffer submissions on
Fyrol FR-2. The Office of General Counsel (OGC/EPA) is currently
reviewing and. will rule on the Stauffer Chemical Company claims.
237
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Page 8 of 8
a)
The Chemical Hazard Identification Branch will again
request the Stauffer Chemical Company to ensure that a
complete copy of the final report from the chronic rat
feeding study of Fyrol FR-2 is transmitted to EPA
immediately upon the company's receipt of that report.
In addition, CHIB will request Stauffer to submit
complete copies of the actual data and analyses which
were the basis for Stauffer's provided epidemiology
report. Stauffer will also be requested to provide
copies of any other epidemiology findings/reports on
Fyrol FR-2, including protocols, underlying data, and
analyses.
b)
The Chemical Hazard Identification Branch will transmit
a copy of this status report to OSHA, NIOSH, FDA, CPSC,
OW/EPA, OSWER/EPA, ORD/EPA, OE/EPA, OGC/EPA, and the
Executive Secretary to the EPA Administrator's Toxic
Substances Advisory Committee (ATSAC). CHIB will also
provide a copy of the status report to the Office of
Toxics Integration (OTI/OPTS/EPA) and the Industry
Assistance Office (IAO/OTS/EPA) for appropriate
distribution.
238
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UNITED STATES ENY IRONMENT AL PROTECTION AGENCY
8FHQ- c [n- Cc, C:2
Pape 1 of 2
OJ. TE:
. .. 1981
SU&JECT:
Status Report* 8EHQ-0681-0402
Approved
,Z1Jt- -y;~
FROM:
, "'
Justine L. Welch, Te~~1y1
Chemical Selection a!~Ofiles
Frank D. Kover, Chief
Chemical Hazard Identification
Revision
Needed
Team/CHIB
TO:
Branch/AD
Submission Description
The Union Carbide Corporation has submitted a summary of
preliminary results from a nearly completed chronic mouse skin-
painting study of Silane A-186 (beta-(3,4-epoxycyclohexyl)
ethyltrimethoxy silane~ CAS No. 3388-04-3). Th~ submitter
reported that Silane A-186 has been applied undiluted to the skin
of 40 mice three times per week and that the study has been in
progress for over two years. Union Carbide also reported that
three of the starting 40 mice are still alive. Two of these
remaining animals reportedly have grossly diagnosed skin
carcinomas (malignant tumors) and the third mouse has a grossly
diagnosed skin papilloma (benign tumor). In addition, the
submitter reported that of the mice receiving Silane A-l86 that
died during the study, one had a histologically verified skin
squamous cell carcinoma, one had a histologically verified
fibrosarcoma near the application site, and three mice had
suspect skin lesions at the application site. Union Carbide
stated that the suspect lesions will undergo further examination
by light microscopy.
With regard to mortality, Union Carbide reported that the
mortality pattern for mice treated with Silane A-186 was similar
to that observed for the control group of 40 mice receiving
dermally applied acetone three times per week. The submitter
stated that no local skin tumors have been observed in the
acetone group. In addition, Union Carbide reported that all 40
mice treated (via dermal application) with 3-methylcholanthrene
(positive control) had died by the end of the ninth month of the
study and that all of the mice in that group developed malignant
tumors at the site of application.
Union Carbide stated that "this dermal carcinogenesis test was
undertaken after it was learned that Silane A-186 was mutageni-
cally active in Ames, sister chromatid exchange and mouse
*NOTE: This status re~ort is the result of a preliminary
staff evaluation of information submitted to EPA. Stateme"ts
made herein are not. to be regarded as expressing final
Agency ~olicy or intent with respect to this particular
chemical. .~y review of the status repor~ should take into
consideration the fact that it ~ay be based on. incomplete
information.
239
[PO" 'OR.. IJ~ IREV. :-7GI
-------
S::TQ-O f' 81-Ct: C;:2
PaITe 2 of 3
lymphoma assays and weakly active in an unscheduled DNA repair
test. We [Union Carbide] view these in vitro tests as corrobora-
tive of the chronic dermal carcinogenesis results." Union
Carbide also stated that the company "has no knowledge of reports
of any health hazards arising from the manufacturing and handling
of Silane A-186, either from customers or employees, during 15
years of manufacturing and marketing of Silane A-186."
Union Carbide reported that the chronic mouse skin-painting study
of Silane A-186 is expected to be completed and a full report
prepared by the last quarter of 1981. Union Carbide stated that
the full report, when issued, would be submitted to the EPA.
Submission Evaluation
Epoxide rings are highly reactive and are capable of binding to a
wide variety of chemical substances including many of those in
biological systems (e.g. proteins, nucleic acids and other
nucleophiles). In addition, many epoxides are known or are
suspected to have oncogenic and/or other serious toxic properties
in vivo. Beta-(3,4-epoxycyclohexyl)ethyltrimethoxy silane is an
aliphatic cyclic epoxide which appears to be absorbed through the
skin and can apparently react in epithelial cells to produce
squamous cell carcinomas and in fibroblasts to produce
fibrosarcomas. It should also be noted that the Silane A-186
molecule contains, in addition to the epoxide grouping, a second
reactive area (i.e. the oxygens within the -Si(-O-CH3)3 grouping)
which may also playa role in the reported oncogeniclty of Silane
A-186. Two structure/activity points provide the basis for this
suspicion: 1) epoxycyclohexane and l-ethyl-3,4-epoxycyclohexane
have not been found to be carcinogenic following chronic
application to the skin of mice, and 2) l-vinyl-3,4-
epoxycyclohexane, which contains both a reactive epoxide and a
reactive vinyl group, has displayed carcinogenicity in mice
following chronic dermal application (Arcos et al.~ Chemical
Induction of Cancer~ Volume IIIA~ In Press).
Further evaluation of the reported oncogenicity of Silane A-186
will have to await the receipt of other preliminary reports and
the final report from Union Carbide's chronic mouse skin-painting
study. In addition, Union Carbide should be requested to provide
more detailed information from the performed in vitro
mutagenicity studies of Silane A-186 which were viewed by the
company as "corroborative of the chronic dermal carcinogenesis
results."
Current Production and Use
Information concerning the use(s) of the subject chemical was not
provided in the Union Carbide submission nor located in the
secondary literature sources consulted.
240
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8E:-=Q-C681-0LfC2
PaLe 3 of 3
A review of the production range (includes importation volumes)
statistics for beta-(3,4-epoxycyclohexyl)ethyltrimethoxy silane
(CAS No. 3388-04-3), which is listed in the initial TSCA Inven-
tory, has shown that between 0 and 3 thousand pounds of this
chemical were reported as produced/imported in 1977. **/
Comments/Recommendations
The Union Carbide Corporation stated that the company.is advising
its Silane A-18G customers and Union Carbide employees who are
potentially exposed to Silane A-18G of the findings reported to
EPA. The company also stated that NIOSH, OSHA, NCI and the
American Conference of Governmental Industrial Hygienists (ACGIH)
were being informed. of the submitted information.
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request the Union Carbide Corporation to provide
complete copies of the final results, including protocols
and data, from all of the in vitro tests which were cited
in the submission.
b)
The Chemical Hazard Identification Branch will consider
the preparation of a Chemical Hazard Information Profile
(CHIP) on beta-(3,4-epoxycyclohexyl)ethyltrimethoxy
silane. In addition, it is recommended that this
chemical be considered for inclusion in future TSCA
Section 8(a) Level A reporting.
c)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, CPSC, NCI/NTP,
and ACGIH. CHIB will also provide a copy of the status
report to the Office of Toxics Integration (OTI/OPTS/EPA)
and the Indust~y Assistance Office (IAO/OTS/EPA) for
appropriate distribution.
**/This production range 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 Confidential Business Informa-
tion. The data submitted for the TSCA Inventory, including
production range information, are subject to the limitations
contained in the Inventory Reporting Regulations (40 CPR 710).
241
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DA T E:
Jl 2 I ( 1981
UNITED STATES ENV IRONMENT AL PR 0 I L.\.. nON AGENCY
SEHQ-0681-0403 S
Page 1 of 3
SUBJECT:
Status Report* 8EHQ-0681-0403 S
Approved
cJ7- :/~Y8(
~I!~:
Justine L. Welch, Team Leade~~tl
Chemical Selection and profi~~s Team/CHIB
.1
Revision
Needed
TO:
Frank D. Kover, Chief
Chemical Hazard Identification Branch/AD
Submission Description
The submitting company (name claimed as TSCA Confidential Busi-
ness Information (CBI)) reported that an approximate 1:1 mixture
of cobalt phthalocyanine monosulfonate and cobalt phthalocyanine
disulfonate (CAS Numbers 30638-08-5 and 29383-29-7, respectively)
was found to be positive in an in vitro mouse lymphoma cell for-
ward mqtation assay. According~o the submitter, the mutagenic
activity of this commercial product was observed only in the
presence of a rat liver S-9 microsomal fraction (i.e. metabolic
activation).
The submitting company stated that the subject mixture is in an
aqueous slurry and is not volatile, and that the major route of
human exposure is via dermal contact. The company estimates the
potential human exposure to the mixture to be of a limited nature
(i.e. approximately 900 persons). In making this estimate, the
submitting company has taken into consideration its own
employees, and those of its customers, and other persons such as
transporters.
Submission Evaluation
When tested for mutagenicity in the in vitro mouse lymphoma
L5178Y mammalian cell assay, the subject mixture was found to be
nonmutagenic in the absence of metabolic activation. However, in
the presence of metabolic activation, the mixture did demonstrate
mutagenic activity. The source of activation was reported to be
an S-9 prepa~ation from the livers of male rats pretreated with
Aroclor 1254. The assay results show that the tested mixture is
mutagenic in cultured mammalian cells and requires metabolic
activation in order to exert this activity. In addition, it
should be noted that in a previous Section 8(e) submission (8EHQ-
0980-0361 S et seq.), it was reported that cobalt phthalocyanine
*NOTE: This status report is the result of a Prell'm' -,
stafC e'"alu-t C' -, - ,lna_J
.-~ oj, c.1 lon oJ.. lnronnatlon submitted to EPi\ St-t" .-t-
mace hereln a-e "- t b . . C1 eme.I_S
'. -'- TlOL. 0 e regarded as expressina final
Kgency Do11CV or ~ t " . ~
C,--~', 1, - lnL.en Wltn respect to t21is particular
.Jemlca Anv rev'ew of th
consideration- the fact th te=tat~s report should take into
inrormation. a lL. maj be based on lncomplete
(P. rOFit> \)~ (REV. ~-7G1
242
-------
8EHQ-068l-0403 S
Page 2 of 3
disulfonate, when tested alone, displayed mutagenic activity in
the same mammalian cell assay and only in the presence of
metabolic activation. Considering this previously reported
result, it is possible that the mutagenic activity presently
reported for the mixture of the disulfonate and monosulfonate
compounds is due solely to the presence of the disulfonate
compound. However, the results obtained from an assay of cobalt
phthalocyanine monosulfonate alone would be necessary in order to
allow a definitive statement to be made.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for cobalt phthalocyanine monosulfonate (CAS No.
30638-08-5), which is listed in the initial TSCA Inventory, has
shown that between 10 thousand and 100 thousand pounds of this
chemical were reported as produced/imported in 1977. **/
A review of the production range (includes importation volumes)
statistics for cobalt phthalocyanine disulfonate (CAS No. 29383-
29-7), which is listed in the initial TSCA Inventory, has shown
that between 100 thousand and 1 million pounds of this chemical
were reported as produced/imported in 1977. **/
Use information on the chemicals was claimed as TSCA Confidential
Business Information (CBI) by the submitting company. No infor-
mation concerning the use(s) of the chemicals, either individual-
ly or as a mixture, was located in the secondary literature
sources consulted.
Comments/Recommendations
The submitting company reported that the safety measures which
are currently in force at its manufacturing facilities serve to
ensure only minimal employee exposure. In addition, the company
reported that steps are being taken to inform and warn its
employees, customers, and others who may have potential exposure
to the chemical mixture.
Although a positive in vitro test result, when considered alone,
may not be sufficien~to offer reasonable support for a
conclusion of substantial risk, the EPA believes that in vitro
studies do provide valuable data that can aid in assessing the
possible risks posed by chemicals to health and the environment.
The Agency also believes that a positive in vitro test result in
**/ This production range information does not include any
production/importation data claimed as confidential by the
person(s) reporting for the ~SCA Inventory, nor does it include
any information which would compromise Confidential Business
Information. The data submitted for the TSCA Inventory, includ-
ing production range information, are subject to the limitations
contained in the Inventory Reporting Regulations (40 CFR 710).
243
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8EHQ-0681-0ij03 S
Page 3 of 3
combination with additional information, such as knowledge of
exposure to or high production of the chemical substance or
mixture, would in many cases suggest the need for further, more
definitive toxicologic study- The results obtained from such
testing should also be reviewed and considered for possible
submission to the EPA pursuant to Section 8(e) of TSCA.
The EPA has received and evaluated previous Section 8(e) submis-
sions (8EHQ-0980-036l S et seq.) which reported that, when tested
separately, cobalt phthalocyanine disulfonate and cobalt phthalo-
cyanine tetrasulfonate (CAS No. 14285-59-7) were found to be
positive in mouse lymphoma forward mutation assays and only in
the presence of metabolic activation.
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request the submitting company to describe any plans
it has to conduct further, more definitive toxicological
studies on cobalt phthalocyanine sulfonate compounds.
b)
It is recommended that cobalt phthalocyanine monosulfon-
ate (CAS No. 30638-08-5) be considered for inclusion in
future TSCA Section 8(a) Level A reporting. The disul-
fonate and the tetrasulfonate compounds were previously
recommended for future 8(a) Level A reporting considera-
tion in the EPA status report prepared for submission
8EHQ-0980-0361 S.
c)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH and OSHA. CHIB will
also provide a copy of the status report to the Office of
Toxics Integration (OTI/OPTS/EPA) and the Industry
Assistance Office (IAO/OTS/EPA) for appropriate
distribution.
244
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0... TE:
n. 2 2 1981
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0681-0404
Page 1 of 2
SU&JECT:
Status Report* 8EHQ-0681-0404
Approved
{?1Jc '- '~?/ }B-1
FROM:
Justine L. Welch, Team Lead~Ai
Chemical Selection and prof~~-Team/CHIB
Frank D. Kover, Chief
Chemical Hazard Identification Branch/AD
Revision
Needed
TO:
Submission Description
The Gulf oil Company - u.S. reported that its paralux 70 product
had been found to display mutagenic activity or cell transforming
ability in two short-term in vitro studies. According to the
summarized information provided by the submitting company,
paralux 70 was found to be mutagenic in the Mouse Lymphoma
Forward Mutation Assay. However, this activity was reported to
have been observed only in the presence of exogenous metabolic
activation. In addition, Gulf reported that paralux 70 caused
mammalian cell transformation in a C3H/IOT V2 Cell Transformation
Assay.
Submission Evaluation
The provided summarized results from the in vitro Mouse Lymphoma
Forward Mutation Assay and C3H/IOT~2 Mouse-Cell Transformation
Assay indicate that paralux 70 has some degree of mutagenic
activity and transforming ability in cultured mammalian cells.
However, without complete copies of the final reports (including
protocols and data), a more complete evaluation of the reported
findings is not possible at this time.
Current Production and Use
The Gulf Oil Company - U.S. did not provide any information
concerning the actual chemical identity of the component(s) of
Paralux 70 or any information on the use(s) of the product. No
use information was located in the secondary literature sources
consulted.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. State~e~ts
made herei~ are not to be regarded as expressing final
Agen~y pollCY or intent with respect to this particular
chem~cal. . Any review of the status report should take into
~onslder~tlon the fact that it may be based on incomplete
lnrorma tJ.on.
(II'" FORt:! 1J2I)o.4 IREV. ~7C;1
245
-------
8EHQ-068l-0404
Page 2 of 2
Comments/Recommendations
The Gulf Oil Company - u.s. stated that the company is evaluating
the significance of the reported toxicological findings in order
to determine if any actions are warranted. In addition, the
company reported that the results of further testing of Para lux
70 would be provided to the EPA.
Although a positive in vitro test result, when considered alone,
may not be sufficien~to offer reasonable support for a
conclusion of substantial risk, the EPA believes that in vitro
studies do provide valuable data that can aid in assessing the
possible risks posed by chemicals to health and the environment.
The Agency also believes that a positive in vitro test result in
combination with additional information, such as knowledge of
exposure to or high production of the chemical substance or
mixture, would in many cases suggest the need for further, more
definitive toxicologic study. The results obtained from such
testing should also be reviewed and considered for possible
submission to the EPA pursuant to Section 8(e) of TSCA.
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request the Gulf oil Company - u.s. to provide
complete copies of the final reports, including test
protocols and data, from the cited in vitro studies of
paralux 70. In addition, the submitting company will be
requested to provide information on the actual identity
(including CAS Number) and amount of each chemical com-
ponent of Para lux 70. Considering the Agency's general
interest in company actions which are taken on a volun-
tary basis in response to chemical toxicity/exposure
information, CHIB will also request the submitter to
describe the nature of the additional toxicity studies
which are reportedly planned for Paralux 70 (or its
chemical components) and the nature of any other
health/safety-related actions taken.
b)
The Chemical Hazard Identification Branch will transmit
a copy of this status report to NIOSH, OSHA, CPSC, ORD,
and DOE. In addition, CHIB will provide a copy of the
status report to the Office of Toxics Integration
(OTI/OPTS/EPA) and to the Industry Assistance Office
(IAO/OTS/EPA) for appropriate distribution.
246
-------
UNITED STATES ENY IRONMENTAL PROTECTION AGENCY
0.1. TE:
U Z" 18'
8EHQ-0781-0405 S
Page 1 of 3
SUr-JECT:
Status Report* 8EHQ-0781-0405 S
Approvec
/;1;t- C/p/&l
C .
~,
FROM:
Justine L. Welch, Team Le~4er~
Chemical Selection and ProfIn~s Team/CHIB
~
Revision
Needed
TO:
Frank D. Kover, Chief
Chemical Hazard Identification Branch/AD
Submission Desc~iption
(Note: The submitting company has claimed both its identity and
the actual identity of the chemical substance as TSCA Confiden-
tial Business Information (CBI). However, the company did report
non-confidentially that the subject chemical was a zinc
dialkyldithiophosphate (ZDDP)).
The submitting company provided a summary of preliminary results
from a Chemical Manufacturers Association (CMA)-sponsored study
designed to evaluate the reproductive toxicity of a zinc
dialkyldithiophosphate (ZDDP). According to the submitter, the
ZDDP compound was applied as a 25% dilution in mineral oil to the
clipped, unabraded skin of rats and rabbits daily for five days
per week for three consecutive weeks. The following table was
provided and indicates the percent C%) change in mean values for
the ZDDP-treated versus control animals at the end of the
exposure:
Body Weight
Epididymides Weight
Testes Weight
RABBITS
Young
animals
-9
-35
-55
Mature
animals
-18
-28
-57
RATS
Young
animaLs
-27 -10 -1
-26 -5 -8
Mature
animals
*NOTE: This status report is the result of a prelirni~a=y
staff evaluation of information submitted to EFA. State~e;.~s
made herein are not to be reoarded"as exoressir.c final
Agency policy or intent with~respect to this pa~ticular
chemical. Any review of the status reoor~ should take i~t~
consideration the fact that it may be based on incomplete
inrormation. ~
[,. '0111" IJ~ IREV. )-7GI
247
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8EHQ-0781-0405 S
Page 2 of 3
The submitting company reported that it had not performed, nor
been apprised of, any statistical evaluations of the preceeding
data. The company also reported that the rats and rabbits which
were treated with the diluted ZDDP were subject to considerable
stress caused by severe skin irritation at the sample application
site. In addition, the submitter stated that the results of the
CMA-sponsored study were not expected because a previous 21 day
dermal application study of the undiluted ZDDP, (which was
performed by the Illinois Institute of Technology Research (IITR)
using a different protocol) did not show significant results with
regard to testes/body weight ratios.
Submission Evaluation
The subject compound appears to have the same toxicity (i.e. skin
irritation, reproductive system effects) as other chemicals
within the ZDDP class. Further evaluation of the reported
results will have to await the final report from the CMA-
sponsored study. In addition, the negative results reported by
the submitter from the IITR-performed ZDDP study cannot be
evaluated without a complete copy of the final report, including
test protocols and data. This information should be requested
from the submitter.
Current Production and Use
In view of the fact that the submitting company has claimed the
actual chemical identity of the subject ZDDP as TSCA Confidential
Business Information, a review of the production/importation
range statistics from the initial TSCA Inventory will not appear
in this status report.
In general, compounds within the ZDDP class are widely used in
lubricating oils and greases as anti-wear/anti-oxidant additives.
Comments/Recommendations
The submitting company stated that it does not believe that the
subject ZDDP, when handled with appropriate care, poses any human
health hazard. In addition, the company stated that its products
which contain ZDDPs are adequately labelled in view of the
currently available toxicity data to ensure proper handling. The
company also reported that it is currently providing its
customers of ZDDP-containing products with summaries of the
available toxicity information related to the apparent reproduc-
tive system effects. In addition, the company reported that it
plans to perform further studies in order to better evaluate the
observed reproductive system toxicity and plans to continue to
participate in the ongoing CMA-sponsored ZDDP study. The
submitter stated that the EPA will be informed of additional
findings from the latter study as they apply to the subject ZDDP
compound.
248
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8EHQ-0781-0405 S
Page 3 of 3
The EPA has received and evaluated two previous TSCA Section 8(e}
submissions on ZDDP compounds (8EHQ-0680-0346 et seq.; 8EHQ-018l-
0387 et seq.). In light of the reproductive effects information
provided in those submissions, the Chemical Hazard Identification
Branch, in conjunction with the Chemical Control Division
(CCD/OTS/EPA), is considering the preparation of a Chemical
Hazard Information Profile (CHIP) on selected chemicals within
the ZDDP class.
a}
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request the submitting company to provide complete
copies of the final reports, including protocols and
data, from both the CMA-sponsored and the IITR-performed
ZDDP studies cited in the submission.
b}
The Chemical Hazard Identification Branch will review the
information contained in the present submission and the
requested final reports in considering the preparation of
a Chemical Hazard Information Profile (CHIP) on selected
ZDDP compounds.
c}
It is recommended that the ZDDP compound which is the
subject of the present submission be considered as a
candidate for future TSCA Section 8(a} Level A reporting.
d}
The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, CPSC, OW/EPA,
OSWER/EPA, ORD/EPA, and CCD/OTS/EPA. A copy of the
status report will also be provided to the Office of
Toxics Integration (OTI/OPTS/ EPA) and to the Industry
Assistance Office (IAO/OTS/EPA) for appropriate
distribution.
249
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UNITED STATES ENY IRONMENT AL PROTECTION AGENCY
0"" TE:
N..G 21 1981
8EHQ-0781-0406 S
Page 1 of 3
SU&JECT: Status Report* 8EHQ-0781-0406 S
Approved
q/~/gl ,/1tf~
I' -
110/.1.: Justine L. Welchi,--1~. Leader
Chemical selectioj and Profiles
TO:Frank D. Kover, Chief
Chemical Hazard Identification
Team/CHIB
Revision
Needed
Branch/AD
Submission Description
The Celanese Corporation reported that a proprietary mixture
demonstrated mutagenicity in the following short-term in vitro
assays: the Ames Salmonella bacteria test, the L5178Y Mouse
Lymphoma assay, and the Chinese Hamster Ovary (CHO) Cell tests
for chromosomal aberrations and sister chromatid exchanges. With
regard to these mutagenicity findings, Celanese stated that it
is the company's judgment that the mutagenic activity displayed
by the proprietary mixture is due to the presence of an epoxy
resin identified as glycerol polyglycidyl ether (CAS No. 25038-
04-4). The submitter's judgment is reportedly based on negative
results obtained from a previously performed Ames test on the
other major mixture component (identity claimed as TSCA
Confidential Business Information (CBI», product literature and
other (unspecified) information obtained from the supplier of the
epoxy resin component, and a Celanese belief that the other minor
components (identities also claimed as TSCA CBI) would not be
responsible for the observed in vitro mutagenicity.
Submission Evaluation
The submitted final results do show that the proprietary mixture
is mutagenic both in the presence and absence of exogenous.
metabolic activation in all of the performed in vitro tests. In
the Ames test, Salmonella strains TA 100 and TA 1535 were found
to be positive while strains TA 98, TA 1537, and TA 1538 were
found to be negative. Although the submitter's judgment that the
epoxy resin component is the agent responsible for the mutagenic
activity may be valid, complete copies of the final report from
the previously performed Ames test on the other major component
should be requested for evaluation.
*NOTE: This status reoort is the result of a crelirnina=~
staff evaluation of information submitted to E?A. State;e;.~s
mace herein are not t8 be reoarded as excressinc final
Agency ~olicy or intent ~ith~respect to this pa~ticular
chemical. Any review of the status report should take i~t8
~o~sider~tion the fact that it may be based on incomplete
In_ormat~on.
250
r.,,, 'O~t2 11~ IA(V. }..7<;)
-------
8EHQ-0781-0406 S
Page 2 of 3
Current Production and Use
A review of the production range (includes importation volumes)
statistics for glycerol polyglycidyl ether (CAS No. 25038-04-4),
which is listed in the initial TSCA Inventory, has shown that
between 10 thousand and 100 thousand pounds of this chemical were
reported as produced/imported in 1977. **/
The Celanese Corporation did not provide any information on the
use(s) of the proprietary mixture (or its chemical components).
Use information was not located in the secondary literature
sources consulted.
Comments/Recommendations
The Celanese Corporation reported that copies of its TSCA Section
8(e) submission were being provided to NCI, OSHA, and NIOSH.
Although a positive in vitro test result, when considered alone,
may not be sufficien~to offer reasonable support for a
conclusion of substantial risk, the EPA believes that in vitro
studies do provide valuable data that can aid in assessing the
possible risks posed by chemicals to health and the environment.
The Agency also believes that a positive in vitro test result in
combination with additional information, such as knowledge of
exposure to or high production of the chemical substance or
mixture, would in many cases suggest the need for further, more
definitive toxicologic study. The results obtained from such
testing should also be reviewed and considered for possible
submission to the EPA pursuant to Section 8(e) of TSCA.
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request the Celanese Corporation to provide a com-
plete copy of the final report, including test protocol
and data, from the Ames test which was reportedly
performed on the other major chemical component of the
proprietary mixture. Considering the EPA's general
interest in company actions which are taken on a volun-
tary basis in response to chemical toxicity/exposure
information, the Celanese Corporation will also be asked
if it is conducting, or plans to conduct, additional
studies to further define the toxicity of the
proprietary mixture and/or its chemical components.
**/ This production range information does not include any
production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it include
any information which would compromise Confidential Business
Information. The data submitted for the TSCA Inventory, includ-
ing production range information, are subject to the limitations
contained in the Inventory Reporting Regulations (40 CFR 710).
251
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8EHQ-0781-0406 S
Page 3 of 3
b)
Glycerol polyglycidyl ether (CAS No. 25038-04-4) should
be considered as a candidate for future TSCA Section
8(a) Level A reporting.
c)
The Chemical Hazard Identification Branch will transmit
a copy of this status report to NIOSH, OSHA, CPSC,
NCI/NTP, OW/EPA, OSWER/EPA, ORD/EPA, and TRD~/AD/EPA.
CHIB will also provide a copy of the status report to
the Office of Toxics Integration (OTI/OPTS/EPA) and the
Industry Assistance Office (IAO/OTS/EPA) for appropriate
distribution.
252
-------
UNITED STA TES ENVIRONMENTAL PROTECTION AGENCY
01. Tf:
,~cp
-,
.'4 .1981
8EHQ-0881-0407
Page 1 of 2
SUUECT:
Status Report* 8EHQ-0881-0407
Approved
?J/Jt;- 1/8/8{
L.---- I ,
'R~: Justine L. Welch, Team LeadefhAJ
Chemical Selection and Profi~sTeam/CHIB
V
Revision
Needed
TO: Frank D. Kover, Chief
Chemical Hazard Identification Branch/AD
Submission Description
E. I. Du Pont de Nemours & Company, Inc. has submitted a written
report concerning an "Emergency Incident of Environmental
Contamination (EIEC)" which involved an accidental release of
approximately 4,000 gallons of fluorosulfonic acid (CAS No. 7789-
21-1) following a railroad car derailment in Bridgman, Michigan.
According to Du Pont, the accident occurred at 5 a.m. on
August 7, 1981, and was reported by phone to EPA's Region V
Office in Chicago, Illinois that same day. Du Pont reported that
a vapor cloud, which resulted from the chemical's reaction with
moisture in the atmosphere and estimated to be about 100 feet
high, drifted away from the population center of Bridgman. Du
Pont also reported that although the leaking tank car was sealed
and the residual spilled liquid neutralized with limestone, local
authorities did evacuate between 1,500 to 2,000 people near the
accident site. Approximately 12 people were reportedly treated
for skin and throat irritation but did not require
hospitalization. With regard to damage to the surrounding
environment, Du Pont stated that "some browning of the leaves has
been observed." Du Pont reported that a railroad company
coordinator has informed Du Pont that cleanup operations hpve now
been completed at the site.
Submission Evaluation
Fluorosulfonic acid, which is also known as fluorosulfuric acid,
is a colorless liquid which fumes when in contact with moist
air. Both the liquid and. fumes (depending on the concentration)
can be corrosive and highly irritating to eyes and mucous
membranes.
*NOTE: This status repo~t is the result of a ~relirnina=~
staff evaluation of information submitted to EP~. State~e~~s
made herein aze not to be reoarded as exoressir.c final
Agency policy or intent with~respect to t~is pa~ticular
chemical. Any review of the status repor~ should take i~to
70~sider~tion the fact that it may be based on incornplet~
In_ormat~on.
253
t~. "0111" IJ~ IREV. )01"
-------
8EHQ-0881-0407
Page-2 of 2
Current Production and Use
Fluorosulfonic acid is a fluorinating agent. The chemical can be
used as a catalyst in alkylation, acylation, polymerization, and
condensation reactions. Secondary literature sources indicate
that the compound is used in the hydro fluorination of ole fins and
in the production of substituted pyridines and certain petroleum
products.
In view of the nature of the submitted information, a review of
the production/importation statistics from the initial TSCA
Inventory (1977) does not appear to be warranted at this time.
Comments/Recommendations
The Chemical Hazard Identification Branch (CHIB/AD/EPA) will
forward a copy of this submission and status report to the EPA's
Office of Emergency and Remedial Response/Office of Solid Waste
and Emergency Response (OEER/OSWER) for review and any
appropriate and warranted Agency followup actions. A copy of the
submission and status report ~ill also be transmitted to DOT,
OW/EPA, ORD/EPA, OANR/EPA and to the EPA Region V Office in
Chicago, Illinois. In addition, a copy of the status report will
be provided to the Office of Toxics Integration (OTI/OPTS/EPA)
and the Industry Assistance Office for appropriate distribution.
254
-------
UNITED 5T A TES ENY IRONMENT AL PROTECTION AGENCY
OA TE:
ocr I 3i I98J
8EPQ-088l-0408 S
Page 1 of 3
SU!>JECT:
Status Report* 8EHQ-088l-0408 S
Approved
/1r--- iC/liB1
'....--' ~
FROI4.:
Justine L. Wei~Aieam Leader
Chemical selec~~n and Profiles
Frank D. Kover, Chief
Chemical Hazard Identification
Team/CHIB
Revision
Needed
TO:
Branch/AD
Submission Description
The submitting company (company name claimed as Confidential
Business Information (CBI» has provided the final reports from
acute primary eye and skin irritation studies of stearylphenyl-
ethyldimethyl ammonium p-toluene sulfonate in rabbits. According
to the submitter, the test results indicate that this quaternary
ammonium compound is "extremely irritating to the skin and
severely irritating/corrosive to the eyes of rabbits." In
addition, the company reported that the subject chemical is newly
synthesized and currently in research and development.
In the cover letter to its submission, the company stated its
view that this Section 8(e) notice did not need to be filed
"because it is merely corroborative of well established adverse
effects already documented in the scientific literature...." and
further stated that its notice was filed in order to avoid the
risk that the EPA may differ with the company on the need for
disclosure under TSCA Section 8(e). The company also provided a
list of 12 literature citations which reportedly indicate the
irritant action of quaternary ammonium compounds.
Submission Evaluation
Stearylphenylethyldimethyl ammonium p-toluene sulfonate closely
resembles several of the cationic detergents and antiseptics used
in medicine. The closest analog to the subject compound is cetyl
dimethyl benzyl ammonium chloride which is one of the benzalkon-
ium antiseptics. The 8(e) chemical differs mainly in that. it has
two additional -CH2- groups in the long chain alkyl group and one
additional -CH - group in the aralkyl group. The benzalkonium
compounds are ~nown irritants. It is 'therefore not unexpected
that the 8(e) compound is also severely irritating, probably by
virtue of its protein precipitant action.
"NOTE: This S~2 ~L1S reoo:::t is the resul ~ 0 f a 0:::21 ir.lir.2::-'.'
staff eVdluation of infor~atio~ submitted ~o E?A. State;e~~s
mace herein a:::e not to be rea2rded as exoressir.c final
Agency pOli:y or intent with-respect to this p2~ticular
chem~~al. .~ny rev~ew of the status repor~ should ta~e i~to
~o~slaer~tlQn the tact that it may be b~sed on incom?let2
In_ormatlon.
255
c-.. .,.......... t.~ lror... ._~"
-------
8EPQ-0881-0408 S
Page 2 of 3
Current Production and Use
As previously stated, the subject quaternary compound was re-
ported to be newly synthesized and in the research and
development (R&D) stage. The submitting company reported that
the CAS Number for the compound was unknown. The Chemical Hazard
Identification Branch (CHIB/AD/EPA) has transmitted a copy of the
sanitized submission to the Chemical Abstracts Service for
assistance in locating, or possibly assigning, a CAS Number for
the subject compound.
The company did not provide any information relating to the
planned or potential use(s) of the compound. No use information
was located in the secondary literature sources consulted.
Comments/Recommendations
Based on an initial review and evaluation of the toxicity
information contained in 8EHQ-0881-408 S, the EPA believes that
the provided acute rabbit eye and skin irritation study results
did not warrant submission to the Agency pursuant to Section 8(e)
of the Toxic Substances Control Act (PL 94-469). The basis for
the EPA's position is as follows:
The preface to Part V of the Agency's March 16, 1978, "State-
ment of Interpretation and Enforcement PolicYi Notification
of Substanitil Risk" (43 FR 11110) states that "a substantial
risk of injury to health or the environment is a risk of
considerable concern because of (a) the seriousness of the
effect... and (b) the fact or probability of its occurrence."
with regard to the seriousness of the effect, Part V explains
further 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, mutation, birth defects, or toxic
effects resulting in death, or serious or prolonged incapaci-
tation." The information respecting these effects can be
obtained directly or inferred from designed studies (e.g. in
vivo experiments and tests as described in Part VI of the--
policy statement). With regard to the "fact or probability
of its occurrence" criterion, Part V also provides that
certain health effects are so serious that relatively little
weight should be given to the chemical's exposure in
determining whether a risk is substantial.
The EPA's response to Comment 14 in Appendix B of the
March 16, 1978 policy statement provides guidance with regard
to the Section 8(e)-reportability of results obtained from
routine acute in vivo range finding tests such LDSO
determinations~irritation tests, etc. In its response, the
EPA stated that it believes that "many routine tests are
based on a knowledge of toxicity associated with a
chemical..." The EPA's response also directs that unknown
256
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8EPQ-0881-0408 S
Page 3 of 3
effects which occur and are observed and/or determined during
acute in vivo range tests may have to be reported if those
effectSiare-8erious and meet the reporting requirements set
forth in parts V and VI of the policy statement.
Thus when evaluating the results of acute animal toxicity
studies for submission under TSCA Section 8(e), the Agency
believes that submitting companies should consider such
factors as the lethal dose, the route of administration, the
occurrence of unexpected effects (which could be obtained via
"cage-side" observations, during necropsy, etc.), and the
extent and pattern of the exposure to the subject chemical
substance(s). In general, when evaluating such information
for Section 8(e) reporting, the greater the acute toxicity,
the less heavily companies should weigh the tested chemical's
exposure, and vice versa.
Based on the preceeding discussion and in light of the R&D status
of the compound and the type of expected and observed acute in
vivo effects (i.e. irritation), it is the EPA's preliminary--
determination that the results from the acute rabbit eye and skin
irritation studies, as reported, did not warrant submission to
the Agency pursuant to TSCA Section 8(e).
a)
Considering the Agency's general interest in corporate
actions which are taken on a voluntary basis in response
to chemical toxicity/exposure information, the Chemical
Hazard Identification Branch (CHIB/AD/EPA) will request
the submitting company to describe the actions it has
taken, in light of the provided acute toxicity data, to
warn workers and others, and to reduce and/or eliminate
exposure to the subject chemical substance.
b)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, ORD/EPA,
OSWER/EPA, OW/EPA, and CCD/OTS/EPA. A copy of this
status report will also be provided to the Office of
Toxics Integration (OTI/OPTS/EPA) and to the Industry
Assistance Office (IAO/OTS/EPA) for appropriate
distribution.
257
-------
UNITED 5T A TES ENY IRONMENT AL PROTECTION AGENCY
0.-. TE:
SfP 21 8M
8EHQ-098l-0409
Page 1 of 3
sur-JEeT:
Status Report* 8EHQ-098l-0409
Justine L. welcJjhklam Leader
Chemical select~r~nd Profiles
Approved
,iJ/t~ 1).)9
F R cu.:
Team/CHIB
Revision
Needed
TO: Frank D. Kover, Chief
Chemical Hazard Identification Brd(lC~l/i\D
Submission Descrip~~?~
The Velsicol Chemical Corporation has submitted two unpublished
manuscripts which concern 3,3',4,4'-tetrachloroazobenzene (TCABi
CAS No. 14047-09-7) and 3,3' ,4,4'-tetrachloroazoxybenzene (TCAOBi
CAS No. 21232-47-3). The first paper provides a literature
review of the toxic effects of TCAB and TCAOB and includes
information that the chloracnegenic and enzyme inducing potencies
of TCAB and TCAOB are as great or greater than that of 2,3,7,8-
tetrachIQrodibenzo-p-dioxin (2,3,7,8-TCDD). TI1e second paper
provides an update and review of information on chloracne froill
exposure to TCAB and TCAOB. Velsicol stated that "the similari-
ties between [TCAB and TCAOB] and TCDD are principally in the
area of chloracnegenic potential."
Velsicol reported that both TCAB and TCAOB are impurities in 3,4-
dichloroaniline (CAS No. 95-76-1), the pesticide methazole and
pesticide products that are formulated from 3,4-dichloroaniline
(diuron, linuron, and' propanil).
Submission Evaluation
Al though one of the submitted manusc.ci pi.>:; does not appear to
contain any new infor1natic)n, it is an excellent review of the
literature on the toxicities of 3,3',4,4'-tetrachlocoazobenzene
and its azoxy derivative. The other manuscript is an extension
of earlier observations (walle in 1974) and contains new data
'which appear to "clinch the case" for outbreaks of chloracne in
humans exposed to the TCAB and TCAOB. This manuscript also
suggests that some of the exposed humans may have sustained long-
term systemic effects, particularly photosensitization and
hyperpigmentation.
As with other polychlorinated and polybrominated aromatic
compounds, the acute toxicity of TCAB and TCAOB is low. roe
significant toxicologic effects are due to chronicity. The
enzyme inducing potency of the TCAOB is as great as that observed
for the chlorinated dibenzodioxins (TCDD) and dibenzofurans
-NOTE: This status reoo:-t is the result of a orelimir.a:-':
staff eV3luatio~ of infor~ation submitted to E?~. State~e~~s
mace herein are not to be reGarded as exoressinc final
Agency ?olicy or intent ~ith-res?ect to this ?a~ticular
chemlcal. hnY revie~ of the status report should ta%e i~to
~onsideration the fact that it may be based on incom?let2
1 i1 f'or7T\a t ion.
258
t,.. '0"" 11::)-4 IA(Y. 1-7t.1
-------
8EHQ-098 1-0 409
Page 2 of 3
(TCDF). The simple azo compound (TCAB) is one-fourth as
suggesting that the oxygen atom makes the azoxy compound
isoelectronically closer to TCDD and TCDF.
potent,
One of the submitted manuscripts also contains highly significant
information from an unpublished Du Pont 10 day sub-acute study in
which 20 mg of TCAB was applied daily to the skin of ten (10)
rabbits. After the 7th application, three (3) of the animals
died. It is apparent that TCAB is significantly absorbed via the
skin. In addition to the observed liver damage, the site of
application was reported to be "thickened, crusty, and necrotic."
These observations, in combination with other toxicologic
information (e.g. the potent enzyme-inducing capabilities and
chloracnegenic potentials of TCAB and TCAOB), indicate that TCAB
and TCAOB have substantial xenobiotic activities which may
include possible oncogenicity.
Current Production and Use
A review of the initial (1977) TSCA Inventory has shown that
3,3',4,4'-tetrachloroazobenzene (CAS No. 14047-09-7), 3,3',4,4'-
tetrachloroazoxybenzene (CAS No. 21232-47-3), methazole (2-(3,4-
dichlorophenyl)-4-methyl-l,2,4-oxadiazolidine-3,5-dionei CAS No.
20354-26-1), and propanil (N-(3,4-dichlorophenyl)propionamidei
CAS No. 709-98-8) are not listed. **/
A review of the production range (includes importation volumes)
statistics for 3,4-dichloroaniline (CAS No. 95-76-1), which is
listed in the initial TSCA Inventory, has shown that between 100
thousand and 1 million pounds of this chemical were reported as
produced/imported in 1977. **/
A review of the production range (includes importation volumes)
statistics for diuron (N'-(3,4-dichlorophenyl)-N,N-dimethylureai
CAS No. 330-54-1), which is listed in the initial TSCA Inventory,
has shown that between 100 thousand and 1 million pounds of this
chemical were reported as produced/imported in 1977. **/
A review of the production range (includes importation volumes)
statistics for linuron (N'-(3,4-dichlorophenyl)-N-methoxy-N-
methylureai CAS No. 330-55-2), which is listed in the initial
TSCA Inventory has shown that no 1977 production/importation was
reported or that all of the production range data reported were
claimed as confidential by the manufacturer(s) and/or importer(s)
and cannot be disclosed. (Section l4(a) of the TSCA, U.S.C.
2613(a)). **/
**/ This production range 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 Confidential Business Informa-
tion. The data submitted for the TSCA Inventory, including
production range information, are subject to the limitations
contained in the Inventory Reporting Regulations (40 CFR 710).
259
-------
8EHQ-098l-0409
Page 3 of 3
3,4-Dichloroaniline is used in the production of pesticides and
as an intermediate in the manufacture of certain dyes. Diuron,
linuron, propanil, and methazole are all registered pesticides.
Because diuron and linuron are 1 i.sb~d in the initial TSCA
Inventory, the possibility exists that these particular compounds
have uses other than as pesticides.
comments/Recommendations
Because both TCAB and TCAOB are impurities in the pesticide
product Technical Methazole (EPA Reg. No. 876-194), Velsicol
stated that a copy of its Section 8(e) submission and a report of
skin chloracne in workers exposed to Technical Methazole were
being submitted separately to the EPA's Office of Pesticide
Programs (OPP/OPTS/EPA) pursuant to Section 6(a)(2) of the
Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA).
The Test Rules Development Branch (TRDB/AD/EPA) is currently
reviewing chemical toxicity/exposure information on 3,4-
dichloroaniline as it pertains to the category "Aniline and
Chloro-, Bromo-I and/or Nitro- Anilines" "..,hich was recommended by
the Interagency Testing committee (ITC). In addition, 3,4-
dichloroaniline is listed in the EPA's February 29, 1980 proposed
TSCA Section 8(a) Level A rule (45 FR 13646).
a)
The Chemical Hazard Identification Branch will request
the Velsicol Chemical Corporation to describe the
actions it has taken on a voluntary basis in response to
the submitted information on TCAB and TCAOB, to warn
workers and others, and to reduce and/or eliminate
exposure to the subject chemicals.
b)
The Chemical Hazard Identification Branch will transmit
a copy of this status report to NIOSH, OSHA, CPSC, FDA,
OW/EPA, OSWER/EPA, ORD/EPA, OPP/OPTS/EPA, TRDB/AD/~PA,
and the EPA Chlorinated Dioxins Workgroup. A copy of
the status report will also be provided to the Office of
Toxics Integration (OTI/OPTS/EPA) and to the Industry
Assistance Office (IAO/OTS/EPA) for appropriate
distribution.
260
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UNITED 5T A TES ENY IRONMENT AL PROTECTION AGENCY
0... T f:
SEP 2 8 1981
8EH(-0981-0410/0411
Page 1 of 4
~- (DII
c
Approved
SU!JECT:
Status Report* 8EHQ-098l-04l0
and 8EHQ-098l-04ll
FR~: (\/L .
Justine L. Welch~~am Leader
Chemical selectit}! and Profiles Team/CHIB
TO: .
Frank D. Kover, Ch1ef
Chemical Hazard Identification Branch/AD
Revision
Needed
Submission Description
In two separat~ submissions, the Celanese Corporation has
provided a summary of preliminary results from a chronic mouse
dermal application study involving triethylene glycol diacrylate
(CAS No. 1680-21-3; 8EHQ-0981-04l0) and tetraethylene glycol
diacrylate (CAS No. 17831-71-9; 8EHQ-0981-041l). According to
Celanese, doses of 50 mg of 5% solutions of the test chemicals in
mineral oil were applied twice weekly for 18 months to the shaved
backs of " mice. The following table summarizes the preliminary
findings which were reported by Celanese and judged by the
company to indicate that the diacrylate compounds elicited weak
oncogenic responses:
Test Group
Number of Animals
Prelim. Findings
Control
100
Tumors at the
test site
(0 )
positive Control
(Benzo[a]pyrene)
50
Squamous Cell
Carcinomas (52)
Triethylene Glycol
Diacrylate
Not given
Squamous Cell
Carcinomas
Microscopic
Papillomas
Fibroma
(2)
(2 )
(1)
Tetraethylene Glycol
Diacrylate
Not given
Squamous Cell
Carcinomas
Microscopic
Papillomas
Gross Lesion
(3)
( 2 )
(1)*
* Tissue lost due to autolysis
*NOTE: This status report is the result of a p=elirni~a=~
staff evaluation of information submitted to E?A. State~e;.~s
mace herein are not to be regarded as expressi~g final
Agency policy or intent wit~ respect to this particular
chemical. ~~y review of the status report should ta~e i~to
consideration the fact that it may be based on incomplet~
ii1.formation. . .
261
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8EHQ-0981-0410/0411
Page 2 of 4
The Celanese corporation also reported that "preliminary and
partial histologic examination of the internal organs [of mice
treated with triethylene glycol diacrylateJ showed an excess of
I~TIphomas". The company also stated, however, that the
significance of these particular findings cannot be assessed until
histologic examination of all of the animals has been completed.
Submission Evaluation
Triethylene glycol diacrylate, tetraethylene glycol diacrylate, and
neopentyl glycol diacrylate (which was the subject of 8EHQ-0178-
0028 et seq.) should be 'considered together as a group. All three
are primary skin irritants (sometimes severe) which produce
neoplastic changes in the skin as well as skin malignancies. The
three diacrylate compounds appear to adsorb to the stratum corneum
of the skin and enter its reservoir. (The reservoir of the stratum
corneum serves as a fixation or holding site for numerous applied
drugs and chemicals which are subsequently removed in small amounts
via absorption). From the reservoir, the diacrylates may be
absorbed into the general blood circulation and distributed
throughout the body. In this respect, the three diacrylate esters
resemble the cellosolves and carbitols, some of which are skin
irritants and skin sensitizers. In addition, some of these analogs
with molecular weights in the range of triethylene glycol
diacrylate are readily absorbed from the skin to produce a lethal
outcome. The degree of systemic toxicity of the three diacrylate
esters is determined by the rate at which they are removed from the
reservoir into the blood. This rate is determined, in part, by the
n-octanol/water distribution.
The physico-chemical properties of the skin barrier to penetration
most closely resemble those of the chemical n-butanol. n-Butanol
and closely related compounds can penetrate the skin, enter the
reservoir and pass into the general circulation very readily.
Triethylene glycol diacrylate, with its isosteric bis-n-butanol
configuration comes the closest (of the three diacrylates) to n-
butanol and would be expected to be absorbed more readily to give
the highest blood and tissue levels. This could be verified by
actual determinations in blood and urine.
The following is a speculation with regard to the fate of the three
diacrylates following application to the skin:
1)
Following adsorption onto the skin, some of the
hydrolyzed by esterases from bacteria which are
resident on the skin surface. The acrylic acid
released is an irritant.
ester is
normally
which is
2)
The unhydrolyzed ester enters the reservoir where some is
further hydrolyzed by skin lipases. The acrylic acid and the
intact acrylate are epoxidized (the skin has metabolizing
enzymes) to compounds that can react with macromolecules in
cells of the germinal layer of the skin and thereby initiate
local oncogenesis.
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8EH(-0981-041010411
Page 3 of 4
3 )
The rapidly absorbed intact ester (i.e. triethylene glycol
diacrylate) reacts with blood plasma proteins and the
reaction product is either filtered by the lymphoid tissue
and/or brought to this tissue by phagocytes of the reticulo-
endothelial system. Lymphoid tissue is capable of producing
epoxides from compounds which contain -C=C- groups. These
epoxides would then initiate the oncogenic process.
4)
Diacrylates which leave the reservoir more slowly (i.e.
tetraethylene glycol diacrylate) would never reach a
sufficiently high concentration in the blood to overcome the
the normal capacity for neutralization by scavenging by cells
of the reticuloendothelial system. This could account for
the observation that triethylene glycol diacrylate produced
internal lymphomas and the apparent failure of tetraethylene
glycol diacrylate to do so.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for triethylene glycol diacrylate (CAS No. 1680-21-3),
which is listed in the initial TSCA Inventory, has shown that
between 110 thousand and 1.1 million pounds of this chemical were
reported as produced/imported in 1977. **/
A review of the production range (includes importation volumes)
statistics for tetraethylene glycol diacrylate (CAS No. 1783' -71-
9), which is listed in the initial TSCA Inventory, has shm.- that
between 200 thousand and 2 million pounds of this chemica' Here
reported as produced/imported in 1977. **/
The Celanese Corporation did not provide any information on the
use(s) of either triethylene glycol diacrylate or tetraethylene
glycol diacrylate. No use information was located in the secondary
literature sources consulted.
Comments/Recommendations
The Celanese Corporation reported that the company was providing
copies of its TSCA Section 8(e) submissions to the Occupational
Safety and Health Administration (OSHA), the National Institute for
Occupational Safety and Health (NIOSH), and the National Cancer
Institute (NCI). Celanese also stated that a copy of the final
results, when available, would be submitted to EPA.
**/ This production range information does not include any
production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it include
any information which would compromise Confidential Business
Information. The data submitted for the TSCA Inventory,
including production range information, are subject to the
limitations contained in the Inventory Reporting Regulations (40
CPR 710).
263
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8EHQ-0981-0410/0411
Page 4 of 4
The Agency has received and evaluated previous TSCA Section 8(e)
submissions (8EHQ-0178-0028 et seq.i Union Carbide Corporation)
concerning the oncogenicity (via skin application in mice) of
neopentyl glycol diacrylate (NPGDAi CAS No. 2223-82-7). A draft
Chemical Hazard Information Profile (CHIP) on NPGDA has been
prepared by the Chemical Hazard Identification Branch (CHIB/AD/EPA).
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request the Celanese Corporation to describe those
actions taken by the company on a voluntary basis in
response to the submitted toxicity information, to warn its
workers, and to reduce and/or eliminate exposure to
triethylene glycol diacrylate and tetraethylene glycol
diacrylate.
b)
The Chemical Hazard Identification Branch will consider the
preparation of Chemical Hazard Information Profiles (CHIPs)
on triethylene glycol diacrylate and tetraethylene glycol
diacrylate. In addition, both compounds should be
considered as candidates for future TSCA Section 8(a) Level
A reporting.
c)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, CPSC, NCI/NTP,
OW/EPA, OSWER/EPA, and ORD/EPA. A copy of this status
report will also be provided to the Office of Toxics
Integration (OTI/OPTS/EPA) and to the Industry Assistance
Office (IAO/OTS/EPA) for appropriate distribution.
264
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OA TE:
(X;f 21 .
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHC-098l-04l2
Page 1 of 4
SU~JECT:
Status Report* 8EHQ-098l-0412
Approvec
./~-
iig
FRou.:
Justine L. Wel~am Leader
Chemical selec~n~~nd Profiles
Team/CHIB
Revision
Needed
TO- Frank D. Kover, Chief
. Chemical Hazard Identification Branch/AD
Submission Description
The Ethyl Corporation has submitted the final reports from a
battery of short-term in vitro and in vivo genetic toxicology
assays of ethylphosphonothioic dichloride (EPTD~CAS No. 993-43-
1). According to the company, the potential genetic toxicity of
EPTD is difficult to interpret because of the conflicting data
obtained from the performed studies. The Ethyl Corporation also
stated that interpretation of the submitted data is further
confounded because there are no clear dose-responses in those
assays in- which EPTD demonstrated activity.
With regard to human toxicity, the Ethyl Corporation reported
that extreme eye irritation occurs as a delayed effect following
exposure to even minute concentrations (estimated by the company
to be less thanO.1 ppm) of EPTD vapor. The company also stated
that repeated exposure will not be tolerated because of the eye
irritation. Ethyl reported that in its manufacturing facilities
exposure to EPTD is essentially eliminated by the use of both
engineering controls and personal protection.
Submission Evaluation
EPTD was tested in the following assays: in vitro mammalian
specific locus mutation assay, with and without exogenous
metabolic activation~ in vitro mammalian cell transformation
assay, with and withou~metabolic activation~ in vitro Ames
Salmonella (bacteria) assay, with and without metabolic
activation~ and in vivo mouse micronucleus and rat dominant
--
lethal assays.
cell
In the in vitro mammalian cell mutation assay, the ability of
EPTD tomutate BALB/3T3 mouse cells to ouabain resistance was-
measured in the presence and absence of exogenous metabolic
activation. In the absence of metabolic activation, there was no
increase in the mutation frequency observed at any of the doses
tested. The assay was clearly negative.
*NOTE: This status reco=t is the result of a p=elimi~a=~
staff evaluation of information submitted to E?~. State~e~~s
mace herein are not to be reaarded as eXDressi~c final
Agency policy or intent with-respect to ~his pa;ticular
chemical. Any review of the status repor~ shoulc ta%e i::to
consideration the fact that it may be based on incomplet2
in.forma tion . 265
CI'
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8EHQ-0981-0412
Page 2 of 4
The in vitro mammalian cell mutation test in the presence of
exogenous metabolic activation was run twice. In the first test,
no mutant colonies were observed in the solvent control, or in
the two higher doses. However, at the lowest dose tested, there
was a statistically significant increase in the mutation
frequency. In the second test, although none of the
concentrations resulted in significant cell killing, all doses
resulted in a significant increase in the mutation frequency.
Although one is led to wonder about quality control in these
studies (because in the first test no mutant colonies were found
in the solvent control while in the rerun, seven colonies were
found in the solvent control), the performing laboratory was
correct in considering these test results positive.
In the in vitro mammalian cell transformation assay, the ability
of EPTD~o induce morphological transformation of BALB/3T3 mouse
cells was tested in the presence and in the absence of metabolic
activation. In the test in the absence of metabolic activation,
only the highest dose showed toxicity. There was no significant
increase in the transformation frequency at any of the doses
tested and the results were clearly negative.
As in the in vitro mammalian cell mutation assay, the in vitro
cell transformation assay in the presence of metabolic-activation
was run twice. In the first test, EPTD caused a dose related
increase in toxicity. The two lower doses and the solvent con-
trol gave no transformed foci while the highest dose produced two
foci. The difference, however, was not statistically signifi-
cant. In the repeat of this assay, the two lower doses caused no
cellular toxicity while the highest dose killed all the test
cells. The two lower doses (even in the absence of toxicity)
caused a four fold increase in the transformation frequency when
compared to the solvent control. While the induced transforma-
tion frequency at the highest dose was highly significant, the
value at the intermediate dose was just below significance. The
performing laboratory was correct in considering the results to
be positive.
The Ames test was also run both in the presence and absence of
exogenous metabolic activation. The results were clearly
negative. However, because no toxicity data were provided, it is
not known whether the compound was tested at high enough
concentrations. In addition, the range of doses tested in the
presence of metabolic activation was higher than that used for
the assay without activation. In most cases, the reverse is done
because added metabolic activation usually shows some toxicity.
In the in vivo mouse micronucleus test (MMT), two doses of EPTD
(150 andl200 mg/kg) were given (i.p.) twice in a 48 hour
period. The EPA finds this to be rather a poor choice of doses
because they are very close. Although the results of the test
were clearly negative, it should be remembered that the MMT is a
relatively insensitive test utilizing a limited endpoint.
266
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8FHQ-0981-0412
Page 3 of 4
The dominant lethal test was performed in rats receiving EPTD
orally at 100, 30 and 10 mg/kg/day for 5 consecutive days. The
following endpoints were examined: fertility index, implanta-
tions per pregnant female, corpora lutea per pregnant female,
pre-implantation losses per pregnant female, dead implants per
pregnant female, proportion of pregnant females with one or more
dead implants, proportion of pregnant females with two or more
dead implants, and live implants per pregnant female.
The following statistically positive events were observed: an
increase in pre-implantation losses on week 2 at 10 and 30 mg/kg
and on week 5 at 100 mg/kg~ an increase in dead implants per
pregnant female at 30 mg/kg on weeks 3 and 5 and at 10 mg/kg on
week 5; and a reduction in live implants at 10 mg/kg on week 5,
at 30 mg/kg on weeks 1 and 2, and at 100 mg/kg on weeks 3 and
5. The contract laboratory considered these results negative
because the positive events occurred in a seemingly random
fashion. If one simply looks at statistical significance this is
true. However, in many cases there were observed increases that
were not statistically significant. The Agency would prefer to
consider the outcome to be equivocal.
In general, the Agency agrees with the submitter that the genetic
toxicity of EPTD is somewhat difficult to interpret. However, it
is not unusual to have conflicting genetic toxicity data. This
is one of the reasons for performing a battery of tests instead
of just a single test.
With regard to the submitter's statement on dose response, it is
almost always true in mutagenicity testing that the mutation
frequency eventually plateaus with increasing concentration.
reason for this is unknown. Therefore, because only three
concentrations were tested in the specific in vitro mammalian
cell locus mutation test, the lack of an observed dose response
may have resulted from two concentrations being on the plateau
portion of the dose response curve.
The
With regard to the submitter's statements concerning eye irrita-
tion, it should be noted that a close analog to ethylphosphono-
thioic dichloride is thiophosphoryl trichloride (PSC13) which has a
low water solubility resulting in a slow release of hydrochloric
acid (HCl) via hydrolysis. The water solubility of ethylphos-
phonothioic dichloride would be expected to be even less and would
result in a slower release of HCl. This could account for the
delayed onset of eye irritation which was noted by the submitter.
The possibility also exists for ethylphosphonothioic dichloride to
react directly with -OH and -NH2 groups in proteins and thereby
cause irritation in tissues.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for ethylphosphonothioic dichloride (CAS No. 993-43-1),
which is listed in the initial TSCA Inventory, has shown that no
1977 production/importation was reported or that all of the
267
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8FEQ-Q981-Q412
Page 4 of 4
production range data reported were claimed as confidential by the
manufacturer(s) and/or importer(s) and cannot be disclosed. (Sec-
tion 14(a) of the TSCA, D.S.C. 2613(a)). The data submitted for
the TSCA Inventory, including production range information, are
subject to the limitations contained in the Inventory Reporting
Regulations (40 CFR 710).
The Ethyl Corporation reported that the company believes that it is
the only domestic producer of ethylphosphonothioic dichloride. The
Ethyl Corporation did not provide any information on the use(s) of
the subject compound. No use information was located in the
secondary literature sources consulted.
Comments/Recommendations
The Ethyl Corporation reported that in keeping with the company's
policies on health and safety, all Ethyl employees and EPTD
customers are being notified of the submitted information. In
addition, the company reported that its customers have been advised
to follow all protective measures that Ethyl uses in the
manufacture of EPTD.
Although a positive short-term genetic toxicity test result, when
considered alone, may not be sufficient to offer reasonable support
for a conslusion of substantial risk, the EPA believes that such
studies do provide valuable data that can aid in assessing the
possible risks posed by chemicals to health and the environment.
The Agency also believes that a positive short-term genetic
toxicity test result in combination with additional information,
such as knowledge of exposure to or high production of the chemical
substance or mixture, would in many cases suggest the need for
further, more definitive toxicologic study. The results obtained
from such testing should also be reviewed and considered for
possible submission to the EPA pursuant to Section B(e) of TSCA.
a)
Considering the Agency's general interest in company
actions which are taken on a voluntary basis in response to
chemical toxicity/exposure information, the Chemical Hazard
Identification Branch (CHIB/AD/EPA) will ask the Ethyl
Corporation if the company is conducting, or plans to
conduct, additional studies to better define the potential
toxicity of ethylphosphonothioic dichloride.
b)
This submission on ethylphosphonothioic dichloride (CAS No.
993-43-1) will undergo chemical screening by the Chemical
Hazard Identification Branch.
c)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, CPSC, OW/EPA,
OSWER/EPA, and ORD/EPA. A copy of this status report will
also be provided to the Office of Toxics Integration
(OTI/OPTS/EPA) and to the Industry Assistance Office
(IAO/OTS/EPA) for appropriate distribution.
268
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UNITED 5T A TE5 ENVIRONMENTAL PROTECTION AGENCY
0,1. TE:
_ocr
81981
8EHQ-0981-0413
Page 1 of 5
SUr-JECT:
Status Report* 8EHQ-0981-0413
Approved
, /1f:r--
,
/(;/-5/f!;1
fROW:
Justine L. Welc~~am Leader
Chemical selectvrn~~nd Profiles
Frank D. Kover, Chief
Chemical Hazard Identification
Revision
Needed
Te~/CHIB
TO:
Branch/AD
Submission Description
The Armak Company has reported that 2,2',4,4'-tetrachlorobiphenyl
(a polychlorinated biphenyl; PCB) was formed as a result of a
decomposition incident which occurred on September 1, 1981 at
Armak's N6ury Chemical company plant in Burt, New York.
According to Armak, a 600 pound mixture containing 2,'4-
dichlorobenzoyl peroxide, silicone oil, and dibutyl phthalate
"rapidly decomposed" and resulted in the release of fumes and
splattering of the reactants. The submitter reported that some
Noury employees were burned and exposed to the released fumes.
In addition, the submitter reported that some non-employees were
exposed to the decomposed reaction products and fumes.
Approximately one pound of 2,2',4,4'-tetrachlorobiphenyl was
estimated by Armak as having been generated during the
decomposition incident. Armak reported that the finding of the
-. subject PCB was first made on September 17, 1981, using electron
capture gas chromatography and confirmed on September 19, 1981,
using gas chromatography/mass spectroscopy (GCMS). The following
analytical results were provided by Armak in its submission:
Source of Sample
2,2',4,4'-Tetrachlorobiphenyl (PPM)
Weed sample with white
powder from decomposition
(Outside Building 2B)
125
Field earth with white
powder from decomposition
(Outside Building 2B)
20
Inside mixer change can
1760
External mixer sample
1480
Mixer vacuum vent sample
1810
*NOTE: This status reDo:-t is the result of a ~=elir.1ir.a=::'
staff evaluation of infor~ation submitted to EFA. State~e~~s
mace herein a:-e not to be regarded as expressir.g final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take i~t~
consideration the tact that it rnav be b~sed on incom?let2
in:ormation. -
269
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8EH~-0981-0413
Page 2 of 5
Submission Evaluation
PCBs are among the most stable chemicals known. Once released into
the environment, they decompose very slowly over a period of several
decades. Due to this stability, they remain in ~he environment and
can be taken up by organisms and accumulated in fatty tissues. This
accumulation in organisms is significant because PCBs are hazardous to
health at extremely low levels. Specifically, PCB's have been shown
to cause chronic toxic effects in many species at less than 10 parts
per million (ppm). There are well documented tests with laboratory
animals demonstrating that PCBs can cause reproductive failures,
gastric disorders, skin .lesions, tumors, and other health effects of
concern.
In man, PCBs can enter the body via the lungs, the gastrointestinal
tract, and the skin. Following absorption, PCBs are circulated in the
blood throughout the body and are stored in fatty tissue and a variety
of organs, including the liver, kidneys, lungs, adrenal glands, brain,
heart, and skin.
Based on the known reactivity (i.e. thermal instability) of benzoyl
peroxides as a class, it is not suprising that the PCB, 2,2',4,4'-
tetrachlorobiphenyl, was formed during the described decomposition
incident. Upon heating, the 2,4-dichlorobenzoyl peroxide would be
cleaved to the 2,4-dichlorobenzoyloxy radical which could then de-
carboxylate and couple to form 2,2'.4,4'-tetrachlorobiphenyl.
Current Production and Use
Polychlorinated biphenyls (PCBs; CAS No. 1336-36-3) are members of a
broad family of organic chemicals known as chlorinated hydrocarbons.
Although PCBs may be produced naturally in the environment, almost all
PCBs in existence today have been synthetically manufactured.
Primary uses of PCBs were, and continue to be, electrical transformer
cooling liquids and capacitor dielectric fluids. Most of the PCBs
marketed in the United States are still in service in these
applications. However, PCBs have also been used in a variety of other
applications such as heat transfer systems and hydraulic fluids; dye
carriers in carbonless copy paper; plasticizers in paints, adhesives,
and caulking compounds; fillers in investment casting wax; and as dust
control agents, sealants, and coatings on roads.
PCBs have heavy oil-like consistencies, have high boiling points, and
weigh approximately 10-12 pounds per gallon. Other important
properties include: a high degree of chemical stability, low
solubility in water, high solubility in fat, low flammability, and low
electrical conductivity. These physical/chemical properties have made
PCBs commercially attractive.
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Page 3 of 5
Legislative and Regulatory Actions on PCBs
A report by the president's Council on Environmental Quality (CEQ) in
May, 1972, recommended that Congress enact the Toxic Substances
Control Act (TSCA) to provide the regulatory authority required to
deal with PCBs and other chemicals. Before the passage of the Toxic
Substances Control Act, EPA could only regulate facilities that
discharged PCBs into navigable waterways. On July 23, 1976, EPA
proposed to ban the discharge of PCBs into waterways by electrical
transformer and capacitor manufacturers (41 FR 30468). The final rule
(42 FR 6532) was promulgated under Section 307(a) of the Federal Water
Pollution Control Act (FWPCA) on February 2, 1977.
At the time the Toxic Substances Control Act was passed (1976), there
was widespread recognition and concern regarding the serious, adverse
effects PCBs have on the environment and human health. Congress
responded to this problem by including a special section in TSCA (i.e.
Section 6(e)) prohibiting future manufacturing, processing,
distribution in commerce, and use of PCBs and providing for
marking and disposal of the PCBs still in use. Since then,
implemented the provisions under Section 6(e) of TSCA. The
is a summary of these actions:
adequate
EPA has
following
On February 17, 1978, EPA promulgated the PCB Marking and Disposal
Rule (40 CFR 761). In this rule, EPA established specific require-
ments for the marking and disposal of PCBs according to the nature
and concentration of the PCBs in question.
On May 31, 1979, EPA promulgated the PCBs Manufacturing, Processing,
Distribution in Commerce, and Use Prohibitions (PCB Ban Rule) (40
CFR 761). Specifically, this rule:
1 )
Prohibits all manufacturing of PCBs after July 2, 1979,
unless specifically exempted by EPAj
2)
Prohibits the processing, distribution in commerce, and
use of PCBs, except in a totally enclosed manner after
July 2, 1979, unless specifically authorized by EPAj
3)
Authorizes certain processing, distribution in commerce,
and use of PCBs in a non-totally enclosed mannerj
4)
Prohibits all processing and distribution in commerce of
PCBs after July 1, 1979, unless specifically exempted by
EPA.
It should be noted that the regulatory scheme developed in the
PCB Marking and Disposal Rule and the PCB Ban Rule was designed
to minimize exposure to humans and the environment while allowing
the continued use of those PCBs which are totally enclosed or
271
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8EPQ-098l-04l3
Page 4 of 5
have been granted authorizations or exemptions. "Totally
enclosed manner" was defined by Congress in TSCA to mean a manner
which will ensure no significant exposure of human beings or the
environment to PCBs, as determined by EPA by rule (Section 6(e)
(2)(C). The final ban rule provides that human or environmental
exposure to any detectable quantities of PCBs shall be deemed
significant.
The use of intact, non-leaking PCB transformers, PCB-contaminated
tranformers, electromagnets, and PCB capacitors and equipment
containing such capacitors is considered a "totally enclosed"
activity. However, servicing of such equipment is not considered
a totally enclosed activity.
Congress provided a mechanism to allow exceptions to the statutory
ban of non-totally enclosed activities (TSCA Section 6(e» by
permitting EPA to authorize some activities which are not totally
enclosed. In order to authorize an activity, EPA must find that
continuation of the activity does not present an unreasonable risk
of injury to human health or to the environment.
Exceptions may also be made to the manufacturing ban or to the
ban on PCB processing and distribution in commerce. TSCA refers
to these exceptions as "exemptions" (Section 6 (e) (3) (B). Before
an exemption can be granted, there must be a determination that
an unreasonable risk is not present and that good faith efforts
have been made to develop substitutes for the PCBs.
The following non-totally enclosed activities have been granted
authorizations until July 1, 1984: the servicing of PCB-
containing transformers; the use of PCBs in heat transfer
systems; the use of PCBs in hydraulic systems; the servicing of
PCB electromagnets; the use of small quantities of PCBs for
research and development; and the use of PCBs as a microscopy
mounting medium. The use of PCBs in natural gas pipeline
compressors was authorized until May 1, 1980. Authorizations
until January 1, 1982, have been granted for the use of PCBs in
mining equipment, the servicing of mining equipment, and the use
of PCBs in pigments. Finally, due to the significant quantities
of carbonless copy paper that contain small amounts of PCBs in
government, industry, and personal files, the rule authorizes
continued maintenance of such paper.
."
On May 9. 1980, the EPA, the Food and Drug Administration, and
the Department of Agriculture, jointly published a proposed rule
which would ban the use of PCBs (including PCB use in hydraulic
systems) in facilities producing and/or storing agricultural
chemicals, food, feed and food packaging (45 FR 30980). However,
based on a 1980 court decision involving an Environmental Defense
Fund (EDF) lawsuit, this proposed rule has been placed in
abeyance pending the outcome of court-imposed re-evaluation (by
EPA) of certain aspects of PCB regulations.
272
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8EEQ-098l-04l3
Page 5 of 5
Although PCBs remain in use, EPA carefully considers the
circumstances and conditions of each remaining use. Most of the
remaining PCBs are in totally enclosed electrical equipment which
will be replaced in the next few years as this equipment is
serviced or retired. Most importantly, EPA has strict servicing,
storage, and disposal requirements to protect against escape of
PCBs into the environment. Further, authorization of each of the
remaining uses will continue to be reviewed on a regular basis to
ensure that they do not present an unreasonable risk of injury to
human health and the environment.
CommentsjRecommendations
In its submission, the Armak Company reported that on Septem-
ber 2, 1981, the EPA Region II Office in New York had been
notified of the decomposition incident which had occurred the
previous day. According to the Region II Office, the notifica-
tion was received on September 14, 1981 pursuant to Subpart D of
Part 265 of the Resource Conservation and Recovery Act (RCRA).
Immediately upon receipt of Armak's TSCA Section 8(e) notice, the
Chemical Hazard Identification Branch (CHIBjADjEPA) contacted the
Region II Office by phone and informed appropriate personnel of
the reported PCB findings subsequent to the decomposition
incident.
The EPA has received several other TSCA Section 8(e) submissions
which have contained information on PCBs (8EHQ-0778-0209; 8EHQ-
1079-0319; 8EHQ-0180-0330; and 8EHQ-0780-0352).
a)
The Chemical Hazard Identification
transmit a copy of this submission
PCB TeamjCCDjOTSjEPA and the EPA's
warranted and appropriate followup
Branch (CHIBjADjEPA)
and status report to
Region II Office for
attention.
will
the
any
b)
The Chemical Hazard Identification Branch will also provide
copies of the status report to OWjEPA, OANRjEPA, OSWERjEPA,
and ORDjEPA, and to the Office of Toxics Integration
(OTIjOPTSj EPA) and the Industry Assistance Office
(IAOjOTSjEPA) for appropriate distribution.
273
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DA T!.
OCT 2 8 ' 1981
8EHQ-108l-04l4
Page 1 of 2
SUIJECT, Status Report*, 8EHQ-l08l-Q4l4
Approyed
zU-
/f~JI3(
r ~
'.~IJustine L. wel~'f~eam Leader
Chemical selec~~n and Profiles Team/CHIB
Revision
Needed
~'Frank D. Kover, Chief,
Chemical Hazard Identification Branch/AD
SubmissiQn Depcription
The wi tco Chemical Corporation has, provided a summary o,f the
results from a 28-day'dermal application study of Witco Hybase
M-400 (alkylbenzene magnesium sulfonate; CAS No. 6l789~87-5)
which is reported to be a detergent additive in engine
lubricating oi18. Adverse testicular and liver effects were
reported in rabbits e~posed dermally to 100% Hybase M-400 at a
dose of 2 ml/kg per day; 5 days per week for 4, weeks. The
submitter reported, however, 'that no 'toxicologically significant
effects were observed withHybaseM-:400 applied as a 25% solution
in mineral oil. ,In' addi tiori, Wi tco pointed out that the
potential 0ealth'hazard to users of lubricants containing Hybase
M-400 is '''extremely small because the observed 'no effect' level
is 8 times the concentration of Hy}:)ase M-400 at its hiqhest use
level in finished lubricants."
Submission Evaluation
The chemical structure, of the subject alkylbenzene magnesium
sulfonate is not exactly clear. The possibility exists that this
chemical is actually a complex micelle with a magnesium carbonate
core. 'If this is the case, the compound could not be considered
a simple magnesium salt. There is also the possibility that the
tested Hybase M-400 product contains other chemicals such as
carbitols or cellosolves which could explain the reported
toxicologic observations for the 100% product and not the 25%
dilution in mineral oil. Cellosolves and carbitols facilitate
penetration through the skin while mineral oil (USP liquid
petrolatum) may retard skin absorption.
Once the alkylbenzene magnesium sulfonate micelles are absorbed,
they would be expected to release Mg++ slowly. The micelles
would also be expected to be deposited in various organs,
particularly those of the reticulo-endothelial system. This
could explain the enlarged livers which were observed. The
micelles would also be taken up by the testes where the effects
could be two-fold: 1) deleterious effects of deposition; and 2)
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final Agency
pol~cy o~ intent with respect to this particular chemical. Any
reV1ew or the status report should take into consideration the
fact that it may be based on incomplete information.
274
£PA FOR'" 11~8 (REV. )-761
-------
8EHQ-108l-04l4
Page 2 of 2
slow release of Mg++ and subsequent effects of Mg++ excess on the
various enzyme processes involved in spermatogenesis in which
Mg++ is a cofactor as well as a binder of nucleic acids.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for alkylbenzene magnesium sulfonate (CAS No. 61789-
87-5), which is listed in the initial TSCA Inventory, has shown
that no 1977 production/importation was reported or that all of
the production range data reported were claimed as confidential
by the manufacturer(s) and/or importer(s) and cannot be disclosed
(Section 14(a) of the TSCA, U.S.C. 2613 (a)). The data submitted
for the TSCA Inventory, including production range information,
are subject to the limitations contained in the Inventory
Reporting Regulations (40 CFR 710).
witco reported that Hybase M-400 and materials like it are widely
used as detergent additives in engine lubricating oil. According
to the company, finished lubricating oils typically contain from
1% - 3% by weight of the Hybase M-400 additive.
Comments/Recommendations
witco Chemical Corporation stated that the only situations in
which 100% Hybase M-400 is likely to be found are during its
manufacture and the further preparation of finished lubricants.
In addition, the company stated that "any potential health hazard
is generaly well protected against by use of established good
hygiene practices for this type of product, and the use of
appropriate protective equipment." Witco also reported that its
customers and employees were being notified of the submitted
findings.
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request the Witco Chemical Corporation to provide
complete copies of the final report, including protocols
and data, from the 28-day rabbit dermal application study
of Hybase M-400. In addition, the submitter will be
requested to provide the chemical structure for the
alkylbenzene magnesium sulfonate identified in the
submission as having the CAS No. 61789-87-5. Witco will
also be requested to provide the chemical identity
(including CAS Number) and amount of each component in
witco Hybase M-400.
b)
Upon receipt of the requested information, the Chemical
Hazard Identification Branch will consider preparation of
a Chemical Hazard Information Profile (CHIP).
c)
The Chemical Hazard Identification Branch will transmit a
a copy of this status report to NIOSH, OSHA, CPSC, lTC,
OW/EPA, OSWER/EPA, ORD/EPA, and OANR/EPA. A copy of the
status report will also be provided to EPA's Office of
Toxics Integration (OTI/OPTS/EPA) and Industry Assistance
Office (IAO/OTS/EPA) for appropriate distribution.
275
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UNITED STATES ENVIRONMENTAL PROTECTJON AGENCY
DA T E:
OCT 2 8 1981
8F.HQ-I081-0415
Page I of 4
SU!JECT:
Status Report* 8EHQ-1081-04l5
Justine L. Welc~ ~Jam Leader
Chemical selecti11;~nd Profiles
Approved
;~:1?v- 11181
- ,
fR06I:
Team/CHIB
Revision
Needed
TO:
Frank D. Kover, Chief
Chemical Hazard Identification Branch/AD
Submission Description
The Atlantic Richfield Company has provided a summary of the
final results from several in vitro studies of 70% aqueous
tertiary-butyl hydroperoxidE!(TBHPi CAS No. 75-91-2). According
to the company, TBHP was found to be mutagenic both with and
without metabolic activation in an Ames test and a mouse lymphoma
cell mutation assay. Atlantic Richfield stated that the compound
was several times less active in the presence of the activation
mixture which "may indicate that TBHP can be readily metabolized
in a whole animal to a much less genotoxic material." In
addition, the company reported that TBHP did not induce trans-
formation in a cell transformation assay (cell line not
specified). Atlantic Richfield stated that this negative result
indicates that "TBHP is not considered to have the carcinogenic
potential of alkylating agents such as benzo(a)pyrene or 3-
methylcholanthrene."
Atlantic Richfield reported that its testing of TBHP was begun
because of two reports in the literature that. tne compound had
been shown to be mutagenic in Ames tests. The company also
reported that its TSCA Section 8(e) submission was based on its
recently obtained positive mouse lymphoma cell mutation assay
results.
Submission Evaluation
Without complete copies of the final reports from the performed
studies, evaluation of the reported findings is not possible at
the present time. There are, however, certain comments which can
be made with reference to the submitter's statements concerning
the reported results:
1.
The submitter's statement that TBHP may be metabolized
in vivo to a "much le.ss genotbxic material" cannot be
assessed in the absence of hard data. While in vitro
*NOTE: This status r2Dort is the result of a c=elirni~a:~
staff eV31uatio~ of information submitted to EFA. State;2~~S
mace herein are not ta be recarded as exoressir.c final
Agency ?olicy or intent ~ith~respect to this pa;ticular
chemical. hny review of the status repor~ should take i~to
consideration the fact that it may be based on incom?:et~
i j) .forma t ion.
276
... - .... - -
-------
8FHQ-I081-0415
Page 2 of 4
activity is an indication of the events which may occur
in vivo, reduction of activity in the presence of in
VTtro-enzyme activation does not in and of itself --
indicate reduced risk in vivo.
---
2.
The submitter refers to lack of activity in a cell
transformation assay and states that this implies that
TBHP lacks the carcinogenic potential of benzo(a)pyrene
(BP) and methylcholanthrene (MCA). This statement is
not justified by the information in the report. There
may be any number of reasons for negative results other
than lack of carcinogenic potential. These include poor
experimental design, insensitivity of the cell line used
in the assay and inadequacy of the activation system.
No mention is made of the cell line used in the study,
the use of metabolic activation or other experimental
details. It should also be noted that BP and MCA are
not alkylating agents as stated in the submission, but
are arylating agents which must always be metabolized to
active intermediates (in the case of BP to a diol
epoxide) to exert their mutagenic/carcinogenic effect.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for tertiary-butyl hydroperoxide (CAS No. 75-91-2),
which is listed in the initial TSCA Inventory, has shown that
over 1 billion pounds of this chemical were reported as
produced/imported in 1977. **/
The chemical has many industrial uses. A major use of TBHP is as
an intermediate in the production of propylene oxide and t-butyl
alcohol from isobutane and propylene. The free radicals that are
produced when TBHP undergoes reduction are highly reactive. TBHP
is used as an initiator and finishing catalyst in the solution
and emulsion polymerization methods of producing polystyrene and
polyacrylates. Another use of TBHP is in the emulsion
polymerization production of polyvinyl chloride. TBHP is an
initiator for the polymerization and copolymerization of vinyl
acetate. It is used as a curing agent in the thermoset of
polyesters. TBHP is used in the production of t-butyl peroxy-
esters, such as t-butyl peroxybenzoate. In bleaching and
deodorizing operations, TBHP is used as an oxidation and
sulfonation catalyst. Two other possible industrial uses are as
an anti-slime agent in cooling systems and as a settling agent in
**/ This production range information does not include any
production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it include
any information which would compromise Confidential Business
Information. The data submitted for the TSCA Inventory, includ-
ing production range information, are subject to the limitations
contained in the Inventory Reporting Regulations (40 CFR 710).
277
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8EHC-108l-04l5
Page 3 of 4
the precipitation of various mineral tailings in aqueous
slurries.
Comments/Recommendation
The Atlantic Richfield Company stated that it believes that the
"precautions taken to avoid skin and eye irritations as described
in the ARca Chemical Company material safety data sheet (MSDS)
for TBHP sufficiently limit exposure to prevent unreasonable
risks of the mutagenicity effects indicated by the mouse lymphoma
test results." The submitter also stated that the MSDS will be
revised to 'incorporate the new toxicity information. Atlantic
Richfield also reported that the ARca Chemical Company will be
notifying employees and customers of the submitted test results
and reminding them of proper precautionary procedures. With
regard to the summarized test results reported, Atlantic
Richfield stated that copies of the final reports will be
provided, when available, to EPA.
Although a positive in vitro test result, when considered alone,
may not be sufficientto of'fer reasonable support for a con-
clusion of substantial risk, the EPA believes that in vitro
studies do provide valuable data that can aid in assessing the
possible risks posed by chemicals to health and the environment.
The Agency also believes that a positive in vitro test result in
combination with additional information, such as knowledge of
exposure to or high production of the chemical substance or
mixture, would in many cases suggest the need for further, more
definitive toxicologic study- The results obtained from such
testing should also be reviewed and considered for possible
submission to the EPA pursuant to Section 8(e) of TSCA.
The Chemical Hazard Identification Branch (CHIB/AD/EPA) has an
existing draft Chemical Hazard Information Profile (CHIP) on
tertiary-butyl hydroperoxide. In addition, tertiary-butyl
hydroperoxide (CAS No. 75-91-2) is listed in the EPA's February
29, 1980 proposed TSCA Section 8(a) Level A rule (45 FR 13646).
a)
Considering the EPA's general interest in company actions
which are taken on a voluntary basis in response to
chemical toxicity/exposure information, the Chemical
Hazard Identification Branch will ask the Atlantic
Richfield Company if it is conducting, or plans to
conduct, additional studies to further define the
toxicity of TBHP.
b)
The Chemical Hazard Identification Branch will send a
copy of its existing draft Chemical Hazard Information
Profile (CHIP) on tertiary-butyl hydroperoxide to the
submitting company. The Chemical Hazard Identification
Branch will also consider updating the existing draft
CHIP to include a discussion of the in vitro findings
reported in the submitter's TSCA Section 8(e) notice on
the subject chemical.
278
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8EP0.-l08l-04l5
Page 4 of 4
c)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, CPSC, ORD/EPA,
OW/EPA, and OSWER/EPA. A copy of this status report will
also be provided to the Office of Toxics Integration
(OTI/OPTS/EPA) and to the Industry Assistance Office
(IAO/OTS/EPA) for appropriate distribution.
279
-------
UNITED 5T A TES ENVIRONMENTAL PROTECTJON AGENCY
OJ. TE:
OCT I 3 1981
8EE('-1081-0416
Page 1 of 2
SUr.JECT:
Status Report* 8EHQ-I081-0416
Approved
/\')f1
' ',/-
i ,/.
, , ", '!
'I' '
"iou':
Justine L. Wel~}~eam Leader
Chemical selectr9n and Profiles
Frank D. Kover, Chief
Chemical Hazard Identification
Team/CRIB
Revision
Needed
TO:
Branch/AD
Submission Description
The Great Lakes Chemical Corporation reported that a shipping
container, holding an estimated 500 5-gallon pails of
chloropicrin (CAS No. 76-06-2), was dropped on August 18,1981, as
it was being unloaded, from a ship at the Port of Long Beach in
California. According to Great Lakes, the accident resulted in
damage to several of the pails and leakage of chloropicrin onto
the dock. Great Lakes reported that the entire dock was shut
down and that 3 ships whi~h were being unloaded were evacuated
during the incident and the subsequent clean-up and disposal (in
a Class 1 dump site). The company also reported that 2 local
fireman and 9 longshoremen received medical attention at a'nearby
hospital. Great Lakes stated that of the 11 men affected, 10
were treated and released and the remaining individual left the
hospital on his own accord although it was recommended that he be
-- admi tted for abservation The Great Lakes Chemical Corporation
also reported that the chemical and biological properties of
chloropicrin are generally recognized and that the chemical leak
(estimated by the company to have been less than 50 gallons) was
quickly contained.
Submission Evaluation
ChloropicrIn is a highly irritating compound which can also cause
nausea and vomiting. Because the chemical is extremely efficient
in bringing about these latter effects, chloropicrin was used
during World War I as a chemical warfare agent. The toxicity of
chloropicrin itself is intermediate between that of chlorine and
phosgene. The more serious after-effects of exposure to
chloropicrin may be anemia, cardio-vascular changes, and, most
importantly, respiratory problems such as chronic bron~hitis or
asthma.
*NOTE: This status reoort is the result of a crelirni~a=~
staff evaluation of infor~ation submitted to EPA. State;e;.~s
mace herein are not to be reaarded as exoressir.c final
Agency policy or intent ~ith~respect to this pa;ticular
chemical. Any review of the status repor': should take i::to
~onsideration the fact that it may be based on incomplete
lilf"ormation.
C"" 'ORa IJ::>-6 IACV. 1-7(01
280.
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8EB~-1081-0416
Page 2 of 2
Current Production and Use
A review of the production range (includes importation volumes)
statistics for chloropicrin (CAS No. 76-06-2), which is listed in
the initial TSCA Inventory, has shown that no 1977 production/
importation was reported or that all of the production range data
reported were claimed as confidential by the manufacturer(s)
and/or importer(s) and cannot be disclosed. (Section 14(a) of
the TSCA, U.S.C. 2613 (a). **/
According to Great Lakes, chloropicrin is a currently registered
pesticide under the Federal Insecticide, Fungicide, and
Rodenticide Act (FIFRA). Secondary literature sources indicate
that the compound is also used in organic synthesis, in the
preparation of dye-stuffs, and as a poison gas.
Comments/Recommendations
Upon receipt of the Great Lakes Section 8(e) submission, the
Chemical Hazard Identification Branch (CHIB/AD/EPA) contacted the
EPA's Region IX Office (San Francisco, California) in order to
ensure that that Office was aware of the reported incident.
Region IX staff stated that their Office had been notified by the
U.S. Coast Guard on the day of the incident.
a)
The Chemical Hazard Identification Branch will transmit
a copy of the Great Lakes Section 8(e) submission and
this status report to the Office of Solid Waste and
Emergency Response (OSWER/EPA) and to EPA's Region IX
Office for any warranted and appropriate followup
attention.
b)
The Chemical Hazard Identification Branch will transmit
a copy of this status report to NIOSH, OSHA, ORD/EPA,
OANR/EPA, OW/EPA, and OPP/OPTS/EPA. A copy of this
status report will also be provided to the Office of
Toxics Integration (OTI/OPTS/EPA) and to the Industry
Assistance Office (IAO/OTS/EPA) for appropriate
distribution.
**/ The data submitted for the TSCA Inventory including
production range information, are subject to the limitations
contained in the Inventory Reporting Regulations (40 CFR 710).
281
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U HITED STATES ENY IRON~\ENT AL PROTECTION AGENCY
0... T f:
OCT 2 3 1981
8EP.C'-1081-0417
Page 1 of 2
SU!JECT:
Status Report* 8EHQ-I081-0417
Approved
/PlL- 1()/~6'
L, ,
FR~: Justine L. Wel~m Leader
Chemical selectier and Profiles
TO: Frank D. Kover, Chief
Chemical Hazard Identification
Team/CHIB
Revision
Needed
Branch/AD
Submission Description
The Union Oil Company of California has submitted the final
report from an in vitro Mouse Lymphoma Forward Mutation Assay of
L-ll, which is reported by the submitter to be a reduced syncrude
shale oil. According to the submitter, L-ll was found to be
mutagenic only in the presence of exogenous metabolic activation.
The company also provided the final report from an acute inhala-
tiontoxicity study of the vapor fraction of L-6 syncrude shale
oil in rats. According to the submitted report, LC50 values of
greater than 1.8 and 2.1 mg/liter (on a Time-Weighted Average
(TWA)) were estimated for male and female rats, respectively.
Submission Evaluation
With regard to mutagenicity, the provided final data demonstrate
that L-ll is capable 9f inducing a concentration-dependent
increase in the mutation frequency at the TK locus of cultured
L5178Y mouse lymphoma cells in the presence of an exogenous
source of metabolic activation. The data also demonstrate that
this mutagenic activity does not occur in the absence of
exogenous metabolic activation.
Although no data were presented for control animals, the acute in
vivo toxicity report indicates that inhalation of L-6 syncrude --
vapor results in some degree of lung, kidney. and liver toxicity.
Without histopathological examination, the exact nature of this
toxicity cannot be defined.
Current Production and Use
Union Oil reported that L-ll syncrude is a residual obtained
after distillation away of materials with boiling points of
6800 F or less, and that L-6 is a full range, dewaxed syncrude.
*NOTE: This status report is the result of a crelimi~a=~
staff evaluation of information submitted to EFA. State;e~:s
mace herein are not to be rea~rded as expressir.c final
Agency policy or intent with~respect to this pa~ticular
chemical. Any review of the status repor~ should take i~to
consideration the fact that it may be based on incomplete
lilf"orma tioD.
282
~. '0"" 11~ lACY. ~7c;\
-------
8EH~-1081-0417
Page 2 of 2
In general, crude shale oils are obtained from oil shale by
destructive distillation followed by hydrotreating. The company
did not provide any information on the current or planned
production volumes of L-ll or L-6. A review of the production
range (includes importation volumes) statistics for shale oils
having the CAS No. 68308-34-9 (which is listed in the initial
TSCA Inventory), has shown that between 11 million and 61 million
pounds were reported as produced/imported in 1977. **/
Comments/Recommendations
The Agency has prepared status reports for a number of TSCA
Section 8(e) submissions received on synthetic and petroleum
fuels: 8EHQ-0029, 0030, 0044, 0082, 0083, 0117, 0148, 0212,
0215, 0216, 0217, 0238, 0240, 0247, 0252, 0253, 0297, 0301, 0306,
0316, 0323, 0377, 0389, and 0398. (These numbers represent the
last four digits of the EPA Document Control numbers).
a)
In view of the EPA's general interest in company actions
which are taken on a voluntary basis in response to
chemical toxicity/exposure information, the Chemical
Hazard Identification Branch (CHIB/AD/EPA) will request
the Union Oil Company of California to describe its
actions to warn workers and others, and to reduce and/or
eliminate exposure to L-ll and L-6 syncrude shale oils.
The company will also be asked if it is conducting, or
plans to conduct, additional studies to further define
the toxicity of the subject shale oils.
b)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to DOE, OSHA, NIOSH, OW/EPA,
OSWER/EPA, OANR/EPA, ORD/EPA, the EPA Alternate Fuels Work-
group, and the OTS Synfuels Workgroup. A copy of this
status report will also be provided to the Office of Toxics
Integration (OTI/OPTS/EPA) and to the Industry Assistance
Office (IAO/OTS/EPA) for appropriate distribution.
**/ This production range information does not include any
production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it include
any information which would compromise Confidential Business
Information. The data submitted for the TSCA Inventory,
including production range information, are subject to the
limitations contained in the Inventory Reporting Regulations (40
CFR 710).
283
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DA n.
NOV
5 1981
8FF.Q-I08l-0418
Page 1.of 4
-& Ilfqft,
Approyed .,- ~
c...... .
SU8JICTI Status Report* 8EHQ-I081-04l8
'.~I Justine L. Wel~eam Leader
Chemical seleci1~n and Profiles
. TO. Frank D. Kover, Chief
- Chemical Ha~ard Identification
Revision
Needed
Team/ CHIB. .
Branch/AD
~ubmi~sion Description
The CIBA-GEIGY Corporation has provided a summary of recently
obtained final results from an' in. vitro BALB/3T3 mouse cell
transformation assay and an in vivo Chine'se hamster bone marrow
cytogenetic~ ~ssa.y of XU-238(5-ethyJ,-'5-methyl-l, 3-bis- (oxiranyl-
metr,yl)-'2,4-iriiidazolidinedionei CAS No. l5336-82-D). According
to the company. a significant dose-dependent. trend in transfor-
matiori- frequency with a highly significant di.fference between the
control and the highest dose tested was observed in the mouse
cell transformation assay~ With .regard to the hamster bone
marrow cytogenetics assay, ~IBA-GEIGY reported that a significant
difference in chromosomal aberration frequency was observed
between the con~rol animals and the animals receiving the highest
oral dose (2500 mg/kg.) of XU.,...238..'The company also reported that
other previously performe9 mutag~nicity tests, with the exception
of the .invi tro mouse lymphoma. assay, had given results which
were either negative or equivocal. In addi~ion, CIBA-GEIGY
reported that previous acute animal studies show that XU-238 is a
severe skin and eye irritant.
CIBA-GEIGY stated that the relevance of the in vitro cell
transformation assay "in assessing human hazard is unknown." The
company'also st?ted that. this particular assay "is currently
being evaluated in EPA's Gene Tox program to determine its
correlation with in vivo assays and, to date, it has been
coricluded that the-data base is so small that further validation
of the system is necessary." In addition, the company stated
that the other limitations of the assay "include the facts that
(a) the target cells utilized are from an established line and
therefore are not equivalent to normal cellsi and (b) that the
spontaneous background rate is susceptible to change unless
carefully controlled." With regard to the in vivo cytogenetics
assay, CIBA-GEIGY stated that the human significance of the
obtained positive results is doubtful because the experimental
conditions (i.e. high dose via an oral route) are "totally
irrelevant to human exposure."
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any
review of the status report should take into consideration the
fact that it may be based on incomplete information.
284
f:PA FOR'" u:<>-a (REI/, '-761
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8F.HQ-I081-0418
Page 2 of 4
Submission Evaluation
5-Ethyl-5-methyl-I,3-bis(oxiranylmethyl)-2,4-imidazolidinedione
(XU-238) has a very high degree of structural similarity (i.e. an
additional -CH2- group) to 5,5-dimethyl-I,3-bis(oxiranylmethyl)-
2,4-imidazolid1nedione, the major component of the epoxy
material, XB-2793. The potent irritant properties of XB-2793
have been reported previously in two separate TSCA Section 8(e)
notices (8EHQ-OI80-0328 et seq., CIBA-GEIGY Corporation; and
8EHQ-0481-0397 et seq., Wilmington Chemical Corporation) which
have been evaluated by the Agency. In addition to causing severe
irritation, XB-2793 was reported in those submissions to be onco-
genic, in that the material produced benign and malignant skin
tumors (including some with distant metastases) in mice chroni-
cally treated via dermal application. Submission 8EHQ-OI80-0328
also reported that XB-2793 in both the presence and absence of
exogenous metabolic activation demonstrated in vitro mutagenicity
in almost all Ames (Salmonella typhimurium (bacteria)) assays and
in a mouse lymphoma cell forward mutation assay. In the present
submission, CIBA-GEIGY stated that with the exception of the
mouse lymphoma assay, all tests other than the cultured cell
transformation and cytogenetics assays have been negative or
equivocal for XU-238. However, an attachment to the present
submission indicates that two Ames assays of XU-238 were
positive. Considering all of the above toxicologic findings and
XU-238's structural similarity to 5,5-dimethyl-I,3-bis(oxiranyl-
methyl)-2,4-imidazolidinedione, it is not at all surprising that
XU-238 can cause severe skin and eye irritation and also displays
mutagenic activity. One major question which remains to be
answered, however, is whether XU-238 is an oncogen.
In its submission, the CIBA-GEIGY Corporation made several
statements which the Agency believes should be addressed. The
submitter's comment that the Gene-Tox Program has concluded that
the Balb/c 3T3 data base is so small that further system
validation is necessary is incorrect. The Gene-Tox Program has
made no statement about either the size of the Balb/c 3T3 data
base or the need for further validation. This assay, along with
several other assays for cellular transformation, is currently
being evaluated by the Gene-Tox Program. Any statement about its
place in a screening program or need for further test system
development/validation must await the outcome of the evaluation
which will specifically address these issues. Apart from this
however, it should be pointed out that, in spite of the
limitations noted by the submitter, transformation assays are
generally regarded to be good predictors of in vivo activity when
the results are positive. The difficulty with these assays is
the proportion of false negatives detected because of the
insensitivity of the cell line(s) used in the assay, the lack of
adequate metabolic activation systems, poor experimental design
and/or technical difficulties associated with proper growth and
cell maintenance. It should also be noted that, strictly
speaking, positive results in the in vitro portion of a cell
transformation assay (morphologica~transformation) should be
confirmed by growth of the transformed cells in soft agar or by
285
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8FHQ-I081-0418
Page 3 of 4
inoculation into syngeneic or congenitally athymic animals.
However. because morphologic transformation is generally regarded
as being predictive of potential in vivo oncogenic activity and
because of technical difficulties associated with growing cells
in soft agar and the cost of animal inoculation, these confirma-
tory steps are sometimes omitted from a cell transformation
assay. In these instances, morphologic transformation alone,
because of its demonstrated correlation with in vivo oncogeni-
city, is used as a criterjonfor positive results and should be
viewed as reason for concern for the potential in vivo activity
--
of the test agent.
With regard to the in vivo cytogenetics assay, the submitter
stated that positive-results were observed following oral
administration and that this route bears no relationship to the
route of human exposure. One assumes, although it is not stated,
that the route of human exposure to XU-238 is by inhalation or
dermal contact. It is a well known toxicologic phenomenon
that inhaled material(s) may be expired from the respiratory
tract to the oral cavity where it is swallowed and then subject
to absorption from the gastrointestinal tract. Therefore,
positive results observed following oral administration can be
relevant when the expected route of human exposure is via
inhalation.
In general, the EPA believes that in vitro studies in themselves
do provide valuable data that can aid in assessing the possible
risks posed by chemicals to health and the environment. The
Agency also believes that positive in vitro test results in
combination with additional information, including knowledge of
exposure to or high production of the chemical substance or
mixture, would in many cases suggest the need for further, more
definitive toxicologic study. The results obtained from such
additional testing should also be reviewed and considered for
possible submission to the EPA pursuant to Section 8(e) of TSCA.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for 5-ethyl-5-methyl-I,3-bis(oxiranylmethyl)-2,4-
imidazolidinedione (CAS No. 15336-82-0), which is listed in the
initial TSCA Inventory, has shown that no 1977 production/
importation was reported or that all of the production range data
reported were claimed as confidential by the manufacturer(s) and/
or importer(s) and cannot be disclosed. (Section 14(a) of the
TSCA, U.S.C. 2613 (a)). The data submitted for the TSCA
Inventory, including production range information, are subject to
the limitations contained in the Inventory Reporting Regulations
(40 CPR 710).
CIBA-GEIGY reported that XU-238 is a partially water-soluble, low
viscosity liquid intended primarily for use as a component of
adhesion systems/formulations. No other use information was
located in the secondary literature sources consulted.
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Page 4 of 4
Comments/Recommendations
The CIBA-GEIGY Corporation provided a copy of its current XU-238
label and Material Safety Data Sheet containing recommended
handling precautions. The submitter also provided a copy of a
letter notifying its customers and those companies which have
been supplied samples of XU-238 of the product's toxicity. In
addition, the company stated that the reported mutagenicity
results were obtained on XU-238 which was manufactured abroad,
and has been imported for the past few years. CIBA-GEIGY also
stated that it does not have any analytical results on the
diglycidyl ether or epichlorohydrin content of the tested XU-238.
However, because the company has reportedly begun manufacture of
XU-238 domestically, the company stated that it plans to re-
evaluate the mutagenicity potential of a representative sample of
U.S. manufactured XU-238 of known diglycidyl ether and epichloro-
hydrin contents.
The National Institute for Occupational Safety and Health (NIOSH)
has prepared a "Criteria Document" on Glycidyl Ethers (DHEW
(NIOSH) Publication No. 78-166; June 1978). The Chemical Hazard
Identification Branch (CHIB/AD/EPA) has been considering the
preparation of Chemical Hazard Information Profiles (CHIPs) on
5,5-dimethyl-l,3-bis(oxiranylmethyl)-2,4-imidazolidinedione and
several other epoxy compounds. The Test Rules Development Branch
(TRDB/AD/EPA) is currently reviewing information pertaining to
"Glycidol and its Derivatives" as recommended by the Interagency
Testing Committee (ITC).
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request the CIBA-GEIGY Corporation to provide
complete copies of the final reports, including protocols
and data, from all of the in vitro and in vivo studies of
XU-238 which were cited in-rhe submission.--rn addition,
CHIB will request the CIBA-GEIGY Corporation to provide,
when available, complete copies of the final reports from
the planned studies designed to re-evaluate the mutagenic
activity of XU-238. The company will also be asked if it
is conducting, or plans to conduct, an in vivo study
designed to determine the oncogenic potential XU-238.
b)
The Chemical Hazard Identification Branch will screen the
requested toxicologic information and consider the need
for further assessment of 5-ethyl-5-methyl-l,3-
bis(oxiranylmethyl)-2,4-imidazolidinedione (XU-238).
c)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, CPSC, OW/EPA,
OSWER/EPA, ORD/EPA and TRDB/AD/EPA. A copy of this
status report will also be provided to the Office of
Toxics Integration (OTI/OPTS/EPA) and to the Industry
Assistance Office (IAO/OTS/EPA) for appropriate
distribution.
287
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DAn.
NOV
9 198/
8I'EQ-108l-04l9
Page 1 ()f 3
SuaJlCTI
Status Report* 8EHQ-I081-0419
Approyed
'/1;z-
'-
1,/"
. .
PI OM.
Justine L. Welch~am Leader
Chemical selectirn~:~d Profiles
Revision
Needed
Team/ CHIB.
TO.
Frank D. Kover, Chief
Chemical Hazard Identification Branch/AD
Submis~ion Description..
Exxon Chemica~Amer~cas has prbvided the following summarized
resul ts., from a recently completed 9-day irihalation study of
methy~cyclopentadiene dimer (MCPDi C~S No. 26472-00-4) in male
and female r~ts and mice:
"Male and female ,rats and mice were exposed to MCPD at.S,
50, a'nd 404 ppm for six hours a day over a two-week period
(9 exposure days). Kidney effects, evidenced by epithelial
cells and casts in the. urine along with protein accumulation
and hyperpla~ia of the ~ubular epithelial cells, were
observed only in male rats at all exposure levels. These
lesions were not found in female rats nor in male or female
mice. Hepatic mitotic figures were increased in male rats
at all exposure lev-els and in male mice exposed to SO and
404ppm. All high dose (404 ppm) animals of both species
and inte'rmediate dose (SO ppm) male mice had increased liver
weights. All animals with low exposure (S ppm) had organ
weights comparCible to. controls."
Exxon Chemical Americas reported that the above study was
performed be~ause MCPD is structurally similar to dicyclopenta-
diene and the company's interest was to determine any similarity
in the biological activity between the two compounds. The
~ubmitter stated that the observed kidney and liver toxicity for
MCPD was similar to that previously reported under Section 8(e)
by the company for dicyclopentadiene (8EHQ-0980-0364).
Submission Evaluation
Methylcyclopentadiene dimer (MCPD) does have a high degree of
structural analogy (i.e. MCPD contains two additional -CH3
substituents) to dicyclopentadiene. Dicyclopentadiene is highly
reactive and is known to cause a variety of systemic toxicities,
including kidney and liver toxicity. It is not unexpected,
therefore, that methylcyclopentadiene dimer, which is also highly
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any
review of the status report should take into consideration the
fact that it may be based on incomplete information.
£PA FORIoj U»-S (REV. )-761
288
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8rHQ-1081-04l9
Page 2 of 3
reactive, shows kidney and liver toxicity. The observed sex
difference in MCPD toxicity is not surprising because
dicyclopentadiene and many other organic compounds (e.g. carbon
tetrachloride) can display varying degrees of sex-specific
toxicity.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for methylcyclopentadiene dimer (CAS No. 26472-00-4),
which is listed in the initial TSCA Inventory, has shown that no
1977 production/importation was reported or that all of the
production range data reported were claimed as confidential by
the manufacturer{s)/importer{s) and cannot be disclosed.
(Section 14(a) of the TSCA, D.S.C. 2613 (a)). **/
Exxon Chemical Americas reported that methylcyclopentadiene dimer
is a cyclic diolefin which has limited uses as an intermediate in
the production of both high energy fuels and fuel additives.
According to secondary literature sources, however, MCPD can also
be used in manufacturing curing agents, plasticizers, resins,
surface-coatings, pharmaceuticals, and dyes.
Comments/Recommendations
Although Exxon Chemical Americas stated that the company has not
had an opportunity to fully evaluate the possible human health
implications of the observed toxic effects of MCPD in terms of
the current industrial hygiene/medical surveillance practices,
the company did state that "relevant information is being
compiled for a multidisciplinary review during which any need for
modification of current practices will be considered." Exxon
Chemical Americas also reported that the company has notified its
employees and DCPD and MCPD customers and co-producers about the
information contained in the Section 8(e) submission and has
urged continued adherence to the industrial hygiene practices
described in the current MCPD Material Safety Data Sheet.
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request Exxon Chemical Americas to provide a full
copy of the final report, including test protocols and
data, from the 9-day MCPD inhalation study cited in its
submission. In view of the Agency's general interest in
company actions which are taken on a voluntary basis in
response to chemical toxicity/exposure information, CHIB
will ask Exxon Chemical Americas if it is conducting, or
plans to conduct, other studies designed to further
define the toxicity of MCPD.
**/ The data submitted for the TSCA Inventory, including
production range information, are subject to the limitations
contained in the Inventory Reporting Regulations (40 CPR 719).
289
-------
8EHQ-I081-0419
rage 3 of 3
b)
The Chemical Hazard Identification Branch will screen
the requested toxicity information and consider the need
for further assessment of MCPD.
c)
The Chemical Hazard Identification Branch will transmit
a copy of this status report to NIOSH, OSHA, CPSC, DOE,
FDA, OW/EPA, OSWER/EPA, ORD/EPA, and OANR/EPA. A copy
of this status report will also be provided to the
Office of Toxics Integration (OTI/OPTS/EPA) and to the
Industry Assistance Office (IAO/OTS/EPA) for appropriate
distribution.
290
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DAn.
DEC I 4' 1981
UNITED STATES ENVIRONMENTAL PROTECTION AGEHCY
8EHC:-1281-o420
Page 1 of 2
Approved ?/jL iji:'J97
t .
Revision
Needed
SUIJECT,
Status Report* 8EHQ-1281-0420
'I~' Justine L. Welc~m Leader
Chemical selec~ and Profiles
TO. Frank D. Kover, Chief
Chemical Hazard Identification
Team/CHIB '
Branch/AD
Submission Description
Exxon Chemical Americas reported that dibromochloromethylpropane
(DBCMP) was detected in concentrations ranging from 50 to 100 ppm
in Exxon Bromobutyl 2244, a brominated butyl rubber (CAS No.
68441-i4-5). The submitter stated that although no toxicity data
were' found for'DBCMP, the compound is structurally similar to
dibromochloropropane (DBCPi CAS No. 96-12-8). In light of the
similarity~ the company decided to treat DBCMP as it treats DBCP
by observing the OSHA established exposure limit of 1 ppb on an 8
hour time-weighted average (TWA).
According ,to Exxon Chemical Americas, DBCMP is physically
entrapped in the rubber and exposure could only occur from the
release of DBCMP into air during pigh temperature processing
operations in rubber goods plani:;s. In addition', the submitter
stated that mixing operations have been carried out in an attempt
to simulate actual rubber plant operations., The company stated
that although the simulated conditions cannot be considered as
truly identical to those in the plant, DBCMP levels were found to
range from non-detectable to 1 ppb.
Submission Eva~uation
Although the submission does not contain the actual chemical
structure of DBCMP, the company's actions, which were taken in
the absence of specific toxicity data for DBCMP and were'
apparently based solely on a possible structure-activity
comparison to DBCP, should be viewed as sound. Based on a
general structure-activity relationship, it may be reasonable to
assume that DBCMP would be capable of causing irritation and
possibly kidney and liver toxicity. However, without specific
toxicity data for DBCMP, it can only be speculated at the present
time that DBCMP would produce the same toxic effects as DBCP,"a
compound which is capable of causing adverse human reproductive
effects (aspermatogenesis in males) and oncogenic effects (mice
and rats).
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any
review of the status report should take into consideration the
fact that it may be based on incomplete information.
291
£PA fORr.I 13:O-G :q[v. '-H)
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8EHQ-1281-0420
Page 2 of 2
Current Production and Use
A review of the production range (includes importation volumes)
statistics for brominated butyl rubber (CAS No. 68441-14-5),
which is listed in the initial TSCA Inventory, has shown that
between 13 million and 80 million pounds were reported as
produced/imported in 1977.**/
According to the submitter, Bromobutyl 2244 is an imported "low
unsaturation copolymer of isobutylene and isoprene brominated to
change its curing activity for increased compatibility with
highly unsaturated elastomers." No other use information was
located in the secondary literature sources consulted.
Comments/Recommendations
Based on information obtained from its simulated rubber plant
mixing operations, Exxon Chemical Americas believes that the
potential risk of adverse human health effects from exposure to
DBCMP is minimal. However, the company reported that its
customers have been notified and advised to 1) monitor their
plant operations~ 2) insure adequate ventilation~ and 3) observe
a 1 ppb exposure limit. In addition, Exxon Chemical Americas
reported that the considerble efforts undertaken to identify the
source of DBCP in manufacturing processes have been successful
and that corrective actions are planned which should eliminate
DBCMP in future runs.
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request Exxon Chemical Americas to provide the
exact chemical structure and CAS Registry Number (if
known) for dibromochloromethylpropane (DBCMP). In
addition, the submitter will be asked to provide
information relating to the source(s) of DBCMP in its
brominated butyl rubber product.
b)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will transmit a copy of this status report to NIOSH,
OSHA, CPSC, FDA, OW/EPA, OSWER/EPA, ORD/EPA, and
OANR/EPA. A copy of this status report will also be
provided to the Office of Toxics Integration
(OTI/OPTS/EPA) and to the Industry Assistance Office
(IAO/OTS/EPA) for appropriate distribution.
**/ This production range information does not include any
production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it include
any information which would compromise Confidential Business
Information. The data submitted for the TSCA Inventory,
including production range information, are subject to the
limitations contained in the Inventory Reporting Regulations (40
CFR 710).
292
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DAn.
DEC 1 I i 1981
8EHC:-128l-042l' S
Page 1 ~
APprove' . Iff: Ie #
,J!CT, Status Report*' 8EHQ-128l-042l S
'.~'Justine L. Wel~~am Leader
. Chemical selec~ and Profiles
TO. Frank D. Kover, Chief
. Chemical Hazard Identification
Revision
Needed
Team/CHIB
Branch/AD
Submission Des~ription
The submitter (company name claimed as TSCA Confidential Business
Information (CBI» reported that oral administration of p-tert-
butyl toluene (CAS No. 98-51-1) and p-tert-butyl benzal.dehyde (CAS
No. 939-97-9) to rats resulteq in a decrease in testis weights.
ahd .injury to .the seminiferous epithelium. The submitter stated
that the p-tert-butyltoluene and the p-tert-butyl benzaldehyde
were administered once per day for five consecutive days at doses
of 200mg/kg and 100 mg/kg, respectively.
According to the. submitter, both chemicals are manufactured on
site and are used exclusively as intermediates in the production
of a final' product (product identity claimed as TSCA CBI). In
addition, the submitter statedtha,t p-tert-butyl benzaldehyde is
sold to one other manufacturer f9r use as an intermediate. With
regard to exposure, the submitting company reported that less
than 200 ppm of p-tert~butyltoluene and p-tert-butylbenzaldehyde
are. present in its products and that the only other exposure to
the chemicals would be duriog their manufacture. However, the
submitter stated that there were not any steps in the company's
manufacturing processes which require direct dermal contact with
these chemicals. The company also reported that preliminary
atmospheric meaf?urements .at its manufacturing site indicate
exposure levels of less than 1 ppm to 3 ppm.
Submission Evaluation
Although p-tertbutylbenzaldehyde and p-tert-butyltoluene are
reported to cause adverse testicular effects in rats via oral
administration, the submitted information does not permit a
distinction to be made between adrenal, pituitary, or direct
effects on the testes. In addition, it should be noted that p-
tert-butylbenzoic acid (p-TBBA), a likely metabolite of both p-
tert-butyltoluene and p-tert-butylbenzaldehyde, is known to cause
testicular atrophy and adverse seminiferous tubule effects in
rats following oral administration.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any
review of the status report should take into consideration the
fact that it may be based on incomplete information.
293
, fOfll.1 11Z'~-6 IREY. )-7:,)
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8EEQ-1281-0421 S
Page 2 of 3
Current Production and Use
A review of the production range (includes importation volumes)
statistics for p-tert-butyltoluene (CAS No. 98-51-1), which is
listed in the initial TSCA Inventory, has shown that between 2
million and 20 million pounds of this chemical were reported as
produced/imported in 1977. **/
A review of the production range (includes importation volumes)
statistics for p-tert-butylbenzaldehyde (CAS No. 939-97-9), which
is listed in the initial TSCA Inventory, has shown that between
200 thousand and 2 million pounds of this chemical were reported
as produced/imported in 1977. **/
As noted previously, the submitting company has claimed its end-
use for the above compounds as TSCA CBI. According to secondary
literature sources, p-tert-butyltoluene is a stable, highly pure,
high~boiling solvent which can be used in resin production and as
an intermediate in certain organic syntheses. With regard to p-
tert-butylbenzaldehyde, no use information other than that
claimed as TSCA CBI by the submitter was located in the secondary
literature sources consulted.
Comments/Recommendations
The submitting company reported that its p-tert-butylbenzaldehyde
customer was being advised of the information contained in the
TSCA Section 8(e) notice. In addition, the company reported that
it plans to: 1) continue its toxicity test program to determine
the toxicologic hazard of p-tert-butyltoluene and p-tert-butyl-
benzaldehyde; 2) re-examine operational procedures to ensure
against any direct exposure of the workers to the chemicals; 3)
continue its environmental monitoring program; and 4) examine
available employee records for any significant incidence of
related health problems.
a)
The Chemical Hazard Indentification Branch (CHIB/AD/EPA)
will request the submitting company to provide a complete
copy of the final results, including test protocols and
data, from the cited toxicity study. In view of EPA's
general interest in voluntary company actions taken in
response to chemical toxicity/exposure information, CHIB
will ask the submitting company if its own workers have
been advised of the submitted toxicity information.
**/ This production range information does not include any
production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it include
any information which would compromise Confidential Business
Information. The data submitted for the TSCA Inventory~
including production range information, are subject to the
limitations contained in the Inventory Reporting Regulations (40
CPR 710).
294
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8EI:C:-1281-0421 S
Page 3 of 3
b)
The Chemical Hazard Identification Branch will consider
the preparation of Chemical Hazard Information Profiles
(CHIPs) on both p-tert-butylbenzaldehyde and p-tert-
butyltoluene. The Chemical Hazard Identification Branch
is currently considering the preparation of a CHIP on
p-tert-butylbenzoic acid (p-TBBA).
c)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, CPSC, FDA,
OW/EPA, OSWER/EPA, ORD/EPA, and OANR/EPA. A copy of this
status report will also be provided to the Office of
Toxics Integration (OTI/OPTS/EPA) and to the Industry
Assistance Office (IAO/OTS/EPA) for appropriate
distribution.
295
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
JAN 2 2 1982
8EHQ-1281-0422
Page 1 of 3
A / »jrdl
App:-oved />~'- I ,
L '
SU'JE~TI Stattl"S Report* 8EHQ-1281-0422
nOWIJustine L. welchl1T,Jm Leader
Chemical sel~ct~~and Profiles
Revision
Needed
Team/ qHB
TO:Frank D. Kover, Chief
Chemical Hazard Identification Branch/AD
Submission Description
The Atlantic Richfield Company submitted summarized preliminary
histopathologic findings from an ,American Petroleum Institute
(API)-sponsored ,chronic inhalation study of ualeaded gasoline
(CAS No. 8006-61-9) in rats and mice. The submitter reported
that the study involved 800 F344 rats and 800 B6C3Fl mice (equal
numbers per sex) exposed to unleaded gasoline at dose levels of
0, 67, 292, or 2056ppm for 6 hours per day, 5 days per week for
approximately 2 years. According to the information submitted by
the Atlantic Richfield Company and addi~ional histopathologic
findings provided by the American Petroleum Institute on a' II For
Your r'nforrnation" basis (FYI-AX-1181-0148 et seq.), significant
neoplastic lesions were not observed in control animals, exposed
mice of either sex, or in exposed female rats. However, the
histopathology performed on exposed male rats which had died
between the 18th and 24th months and those sacrificed at the end
of the 24th month was reported to indicate an increased incidence
of renal tubular epithelial neoplasms.
Submission Evaluation
Although the provided histopathological data leave no doubt that
the tested unleaded motor fuel is carcinogenic toward the kidney
of F344 rats, there is, however, considerable difference in sex~
dependent susceptibility, in that male rats were much more prone
to tumor induction than females.
Spontaneously occurring tumors of the renal tubular epithelium
are quite rare in aging F344 rats. The spontaneous tumor
incidence in the F344 strain ranges from 0.05 to 0.11% in males
and from 0 to 0.05% in females. The spontaneous incidence of
mixed histological types of malignant tumors of the kidney in
F344 rats is of a similar order (i.e., up to 0.17% in males and
0% in females).
*NOTE: T~is status reco=t is the result of a crelirnina:-v
staff evaluation of information submitted to EPA. Sta~e;e~ts
mace herein are no~ to be regarded as expressing final
Ase~~y policy or intent with res?ec~ to t~is particular
chem~cal. .~y review of the status report should take into
~onslderation the iact that it may be bas~d on incomplet~
lnformation.
~~, 'ORIf IJ~ IREV. ...,..
296
-------
8EHQ-1281-0422
Pa~e 2 of 3
The tumor incidences elicted by inhalatory administration of the
unleaded motor fuel should be considered against this very low
background of spontaneous tumor incidence. The results of two
histopathological examinations clearly indicate not only that the
tested unleaded motor fuel induced renal carcinogenesis, but also
that the tumor induction displayed an approximate dose-response
relationship in the males rats.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for unleaded (i.e., natural) gasoline (CAS No. 8006-
61-9), which is listed in the initial TSCA Inventory, has shown
that over 16 billion pounds were reported as produced/imported in
1977. **/
The Atlantic Richfield Company reported that based on information
obtained from API, the tested gasoline "was specially blended to
meet EPA reference fuel specifications for unleaded gasoline."
In addition, Atlantic Richfield reported that the tested blend
also "meets typical characteristics of commercial gasoline in the
DuPont Road Octane Survey of 1976."
Comments/Recommendations
The Atlantic Richfield Company reported its intention to request
the American Petroleum Institute to "pursue these preliminary
findings with in-depth statistical analyses, quality assurance
and a scientific assessment of these specific findings in light
of other results in the study." Atlantic Richfield also stated
that when a final evaluation of the data obtained from the study
has been completed, that evaluation, as well as the final report,
will be provided to EPA.
EPA has received/evaluated the following Section 8(e) submissions
on synthetic and petroleum fuels: (8ERQ) 0029, 0030, 0044, 0082,
0083, 0117. 0148, 0212, 0215, 0216, 0217. 0238, 0240, 0247, 0252,
0253, 0297, 0301, 0306, 0316, 0323, 0377, 0389, 0398, and 0417..
(Note: These numbers are the last four digits of the Section 8(e)
Document Control Numbers). EPA has also received/screened a
number of "For Your Information (FYI)" submissions on gasoline
and other petroleum and synthetic fuels. The Document Control
Numbers for FYI submissions which specifically involve gasoline
are FYI-AX-I081-0138, FYI-AX-I081-0143, and FYI-AX-1181-0148.
**/ This production range information does not include any
production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it include
any information which would compromise Confidential Business
Information. The data submitted for the TSCA Inventory,
including production range information, are subject to the
limitations contained in the Inventory Reporting Regulations (40
CFR 710).
297
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8EHQ-1281-0422
Page 3 of 3
a) In view of the Agency's general interest in company
actions which are taken on a voluntary basis in response
to chemical toxicity/exposure information, the Chemical
Hazard Identification Branch (CHIB/AD/EPA) will request
the Atlantic Richfield Company to describe the actions
it has taken in response to the submitted information on
unleaded gasoline to warn workers and others, and to
reduce and/or eliminate exposure.
b) The Chemical Hazard Identification Branch will transmit
a copy of this status report to NIOSH, OSHA, CPSC, DOE,
OW/EPA, OSWER/EPA, ORD/EPA, OANR/EPA, and to the EPA's
Alternate Fuels Workgroup. CHIB will also provide a
copy of the status report to the Office of Toxics
Integration (OTI/OPTS/EPA) and the Industry Assistance
Office (IAO/OTS/EPA) for appropriate distribution.
298
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UNITED 5T}, TES nlY IRONMEtfT'AL PROTECTION AGENCY
8EHQ-l28l-0423
Page 1 of 3
OJ. T E:
:"1
» /9R'>
APp=oved~
Revision
Needed
~~/&f
.
SU&JECT: Status Report* 8EHQ-1281-0423
I'Ro.&a Justine L. Wel~m Leader
Chemical selectitt and Profiles
TO: Frank D. Kover, Chief
Chemical Hazard Identification
Team/CHIB
Branch/AD
Submission Description
The Union Carbide Corporation provided summary results from a
chronic mouse dermal application study of two types of carbon
fibers. According to the submitter, the carbon fibers were
pulverized and suspended in benzene and applied via an automatic
pipette to the clipped backs of mice (40 animals per group) three
times per week over the course of the chronic study. Benzene
(negative control) and 3-methylcholanthrene (MC; positive
control) were reportedly applied to groups of 40 mice according
to the same schedule. Union Carbide stated that at the
conclusion of the study. histologically verified tumors were
found (see TABLE I. below) at the application site in three mice
treated with Type P (High modulus Thornel Type p) carbon fiber
suspension and three mice treated with MAT (Thornel MAT) carbon
fiber suspension.
TABLE I.
GROUP
HISTOLOGICAL FINDINGS
Type P
- skin, papilloma (1)
- skin, squamous cell carcinoma (1)
- subcutis, hemangiosarcoma (1)
MAT
- skin, fibrosarcoma (1)
- subcutis, squamous cell carcinoma (1)
- subcutis, hemangiosarcoma (1)
Benzene
- None
MC
- papillomas
- carcinomas
(3 )
(33) .
-NOTE: This status reoort is the result of a preliminary
staff eva~uation of i~forffia~ion submitt~c to EPA. State;e;.ts
mace hereln are nOL to be reaarded as exoressina final'
Ase~~y ?oli:y or i~tent with-res?ec~ to t~is ?3;ticular
chemlcal..~y reVlew of the status re?ort should take into
conslder~tlon the fact that it m3Y be based on incomolete
lntormatlon. .
299
." 'OR" IJ~ '11£"". ,..",
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8EHQ-l28l-0423
Page 2 of 3
Union Carbide reported that the mortality pattern for the carbon
fiber-treated mice was similar to that for the benzene (control)
group. The company also reported that the initial appearance
(visual detection) of tumors was 9-10 months and 19-20 months for
Type pand MAT carbon fiber-treated groups, respectively. The
first tumor in the positive control (MC) group was reported to
have appeared in the second month of the study.
Union Carbide stated that at the present time the company is
"unable to attribute the observed results strictly to the fibers
themselves, or to possible contaminants thereon, or to artifacts
introduced during preparation and transmission of the sample, to
experimental procedures, or other possible causes of the observed
biological effect." Union Carbide also stated that the company
"has no knowledge of any significant effects to people, chronic
or otherwise, arising from several years of manufacture,
processing and marketing products of this kind, other than skin
irritation. "
Submission Evaluation
Although it is conceivable that the carbon fibers themselves
could be carcinogenic based on actual or pseudo polycyclic
structure, the submitter should be requested to provide the
identity of the actual chemical source(s) of the tested carbon
fibers and a description of process(es) used in the manufacture
of those fibers.
Current Production and Use
Union Carbide reported that carbon fibers are "essentially 100%
carbon in a fibrous form suitable for industrial processing into
articles and materials in which the carbon is not chemically
altered." According to secondary literature sources, Thornel@ is
a tradename for graphite yarns. In addition, Thornel@ was
reported for the initial TSCA Inventory (1977) as graphite (CAS
No. 7782-42-5). Although some secondary literature sources point
out that the only fibers that should be called graphite are those
which are processed from coal tars or pitches, other secondary
literature sources report that high tensile-strength graphite
fibers can also be made from rayon or polyacrylonitrile.
Comments/Recommendations
The Union Carbide Corporation stated that its employees and
customers were being advised of the submitted information on
carbon fibers. In addition, Union Carbide stated that the final
report, which is expected to be issued in April, 1982, will be
provided to EPA as a supplement to the initial Section -8(e)
submission. The submitting company also reported that the EPA
would be advised of additional results from the subject chronic
mouse skin-painting study of carbon fibers, as well as the
results from further toxicologic and analytical studies which are
currently being considered.
300
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8EPQ-1281-0423
Page 3 of 3
a) The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request the Union Carbide corporation to provide the
identity of the actual chemical source(s) of the tested
carbon fibers and a description of the process(es) used in
the manufacture of those fibers.
b) The Chemical Hazard Identification Branch will transmit
a copy of this status report to NIOSH, OSHA, CPSC, OW/EPA,
OSWER/EPA, OANR/EPA, and ORD/EPA. A copy of this status
report will also be provided to the Office of Toxics
Integration (OTI/OPTS/EPA) and to the Industry Assistance
Office (IAO/OTS/EPA) for appropriate distribution.
301
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UNITED 5T A TES ENV IRONMENTAL PROTECTION AGENCY
8EE(-1281-0424
Page 1 of 3
OATE:
JAN 15 H2
APproved~
Revision
Needed
'/Jq/~~
.
SUaJECT.
Status Report* 8EHQ-1281-0424
'R~. Justine L. Wel~am Leader
Chemical selec~n and Pr~files Team/CHIB
TO: Frank D. Kover, Chief
Chemical Hazard Identification Branch/AD
Submission Description
The Velsicol Chemical Corporation submitted the following pre-
publication abstract from a manu;3cript containing toxicologic
results which are reported to "suggest" that both 3,3',4,4'-
tetrachloroazobenzene (TCAB; CAS No. 14047-Q9-7) and 3,3',4,4'-
tetrachloroazoxybenzene (TCAOB; CAS No. 21232-47-3) are
teratogenic in the chick embryo: .
"Abstract. The toxicity of 3,3' ,4, 4 '-tetrachloroazobenzene
(TCAB) and 3,3',4,4'-tetrachloroazaxybenzene (TCAOB) to chick
embryos was .examined. TCAB or TCAOB (0.1 I!g to 100 ng per
egg) was dissolVed in corn oil and injected into the air cell
of fertile chicken eggs. The time of injection had a major
effect on embryo mortality as eggs injected with TCAB or
TCAOB on the fourth day of incubation had a higher incidence
of embryo mortality than eggs injected on days 11-13. Both
TCAB and TCAOB were more toxic than all other chemicals that
have been tested in the chick embryo with the exception of
2,3,7,B-tetrachlQrodibenzo-£-dioxin (TCDD). Comparing the
potency of the two compounds, TCAOB was more potent than TCAB
in the chick embryo with an estimated LDSO of 12 ng and 44 ng
respectively. Rump edema was the major abnormality observed
in embryos treated with either TCAB or TCAOB. Other
malformations included altered feather pattern and lack of
down, hemorrhage, external viscera, reduced body size,
failure to withdraw the yolk sac, beak malformation,. dilation
of blood vessels and monomicropthalmia. The results o~ this
investigation suggest that both TCAB and TCAOB are
teratogenic' in the chick embryo."
Velsicol stated that the author of the paper has requested that
the paper (but not the results) be maintained as confidential
until the paper is accepted for publication. Velsicol also
stated that as soon as the company is notified of the acceptance,
a complete copy of the paper will be submitted to EPA.
.NOTE: T~is status ~eDo~t is the result of a Drelirnina=v
staff evaluation or i~forma~ion submitted to EPA. State;e~t3
made he~ein are not to be regarded as exc~essina final ..
Ase~~y policy or intent with respect to t~is ?articular
chem~cal. .~y review of the status report should take into
~onslderation the fact that it may be based on incomplet~
lnforma tion.
302
..
"JIll" "~.QtC t.~ '''.cc-'"f ~,--.
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8EP.(-1281-0424
Page 2 of 3
(Note: The Velsicol Chemical Corporation previously submitted
(8EHQ-098l-0409 et. seq.) two unpublished manuscripts which
concerned 3,3',4,4'-tetrachloroazobenzene (TCABi CAS No. 14047-
09-7) and 3,3',4,4'-tetrachloroazoxybenzene (TCAOBi Cas No.
21232-47-3). The first paper provided a literature review of the
toxic effects of TCAB and TCAOB and included information that the
chloracnegenic and enzyme inducing potencies of TCAB and TCAOB
are as great or greater than that of 2,3,7,8-tetrachlorodibenzo-
p-dioxin (2,3,7,8-TCDD). The second paper provided an update and
review of information on chloracne associated with exposure to
TCAB and TCAOB. In its submission, Velsicol stated that "the
similarities between [TCAB and TCAOB] and TCDD are principally in
the area of chloracnegenic potential.")
Submission Evaluation
According to the information contained in the submitted abstract,
both TCAB and TCAOB do appear to have some degree of teratogenic/
embryotoxic activity when tested in the chick embryo. However,
without complete copies of the test protocol and actual data
obtained, it is not possible at the present time to fully
evaluate the reported findings. It should be noted that in some
cases, chemical substances which have demonstrated teratogenic/
embryotoxic effects in the chick embryo have also displayed
teratogenic/embryotoxic activity when tested in mammalian
systems.
Current Production and Use
In TSCA Section 8(e) submission 8EHQ-098l-0409 et. seq., Velsicol
reported that both TCAB and TCAOB are impurities in 3,4-dichloro-
aniline (CAS No. 95-76-1), the pesticide methazole and pesticide
products that are formulated from 3,4-dichloroaniline (e.g.,
diuron, linuron, and propanil). According to secondary litera-
ture sources, 3,4-dichloroaniline is used both in the production
of pesticides and as an intermediate in the manufacture of
certain dyes. Diuron, linuron, propanil, and methazole are all
registered pesticides. Because diuron and linuron are listed in
the initial TSCA Inventory. however, the possibility exists that
these particular compounds have uses other than as pesticides.
A review of the initial (1977) TSCA Inventory has shown that
3,3'.4,4'-tetrachloroazobenzene (CAS No. 14047-09-7), 3,3' .4,4'-
tetrachloroazoxybenzene (CAS No. 21232-47-3), methazole (2-(3,4-
dichlorophenyl)-4-methyl-l,2,4-oxadiazolidine-3,5-dionei CAS No.
20354-26-1), and propanil (N-(3,4-dichlorophenyl)propionamidei
CAS No. 709-98-8) are not listed. **/
A review of the production range (includes importation volumes)
statistics for 3,4-dichloroaniline (CAS No. 95-76-1), which is
listed in the initial TSCA Inventory, has shown that between 100
thousand and 1 million pounds of this chemical were reported as
produced/imported in 1977. **/
303
-------
8EH(-1281-0424
Page 3 of 3
A review of the production range {includes importation vOlumes}
statistics for diuron {N'-{3,4-dichloropehnyl}-N,N-dimethylurea;
CAS No. 330-54-1}, which is listed in the initial TSCA Inventory,
has shown that between 100 thousand and 1 million pounds of this
chemical were reported as produced/imported in 1977. **/
A review of the production range {includes importation vOlumes}
statistics for linuron {N'-{3,4-dichlorophenyl}-N-methoxy-N-
methylurea; CAS No. 330-55-2}, which is listed in the initial
TSCA Inventory has shown that no 1977 production/importation was
reported or that all of the production range data reported were
claimed as confidential by the manufacturer{s} and/or importer{s}
and cannot be disclosed. {Section 14{a} of the TSCA, D.S.C. 2613
{a}}. **/
Comments/Recommendations
The Test Rules Development Branch {TRDB/AD/EPA} is currently
reviewing chemical toxicity/exposure information on 3,4-
dichloroaniline as it pertains to the category "Aniline and
Chloro-, Bromo-, and/or Nitro- Anilines" which was recommended by
the Interagency Testing Committee {ITC}.
a}
The Chemical Hazard Identification Branch {CHIB/AD/EPA}
will request the Velsicol Chemical Corporation to
describe the actions it has taken on a voluntary basis in
response to the submitted information on TCAB and TCAOB,
to warn workers and others, and to reduce and/or elimi-
nate exposure to the subject chemicals. In addition,
CHIB will ask the submitting company if it is conducting,
or plans to conduct, toxicologic studies designed to
assess potential mammalian reproductive hazards/risks
associated with exposure to TCAB, TCAOB and/or materials
which contain those substances.
b}
The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, CPSC, FDA, OANR/EPA,
OW/EPA, OSWER/EPA, ORD/EPA, OPP/OPTS/EPA, TRDB/AD/EPA and
the EPA Chlorinated Dioxins Workgroup. A copy of the
status report will also be provided to the Office of
Toxics Integration {OTI/OPTS/EPA} and to the Industry
Assistance Office {IAO/OTS/EPA} for appropriate
distribution.
**/ This production range 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 Confidential Business Informa-
tion. The data submitted for the TSCA Inventory, including
production range information, are subject to the limitations
contained in the Inventory Reporting Regulations (40 CFR 710).
304
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UNITED STATES ENY IRONMENTAL PROTECTION AGENCY
8EHQ-1281-0425 S
Page 1 of 3
DATE:
FEB
21982
APproved~ ~~;lB"
SUIJ£C:T,
Status Report* 8EHQ-1281-0425 S
'10016,
Justine L. wel~AJeam Leader
Chemical Sele9~tb~~~nd P-tofiles Team/CHIB
Revision
Needed
TO.
Frank D. Kover, Chief
Chemical Hazard Identification Branch/AD
Submission Description
Note: The submitting company claimed its identity, the identity
of the tested chemical, the CA~ Registry Number and the product
trade name as. TSCA CBI (Confidential Busine'ss Information).
The submitting company provided the protocol and a summary of
preliminary results from an ongoing 21-day skin-painting study
.designed to investigate the potential testicular~oxicity of the
subject chemical in male rats (Sprague-Dawley) and rabbits (New
Zealand white SPF).
Acc'ording to the 'submitted protocol, the chemical (diluted in
D.S.P. mineral oil) was being applied daily for a total of 21
days at doses of 0.25, 0.10, and 0.05 ml/kg to the skin (clipped
free of fur). In addition, the protocol indicated that the
following parameters would be ex'amined: body and testis weights,
gross and histopathology for a number of organs (including the
testes, seminal vesicles, prostate, epididymis), pharmacotoxic
observations for s~in and neurologic responses to treatment,
blood chemistry (e.g., testosterone levels), urine analysis, and
reversibility of observed effects.
With regard to the submitted preliminary results, the company
reported that irritation was observed after the first day of
dosing and that by the fourth day, rabbits receiving 0.25 and
0.10 ml/kg had developed severe skin irritation and 2 rabbits
receiving 0.25 ml/kg had died. 'Phe submitter reported that the
signs of the skin irritation included "edema, eschar, and
induration." Due to the severity of the irritation, 'the submitter
reported that dosing was terminated for rabbits receiving 0.25
and 0.10 ml/kg and that those animals were sacrificed. The
submitter reported, however, that the study was still in progress
with the rats (all doses) and the remaining rabbits (.05 ml/kg
group) .
*NOTE: T~is status recort is the result of a crelirninarv
staff evaluation or i~forma~ion submittec to EPA. State;e~ts
made herein are not to be reaarded as excressina final .,
Ase~cy policy or intent with~res?ect to t~is ?articular
chemical. .~y review of the status report should take into
consideration the tact that it may be based On incorn?let~
information. 305
E".-~"'D" I.~ '."U~ ...,al
-------
8EHQ-1281-0425 S
Page 2 of 3
The company stated its belief that its current safety precautions
observed during both manufacturing and use of the tested material
are sufficient for employee protection. The company also stated
that it had previously examined its employees and "found no
health effects that could be related to the manufacture or use of
the product."
Submission Evaluation
Although the subject study was designed, for the most part, to
determine if the submitter's product could cause testicular
toxicity, no such finding was reported in, or can be inferred
from, the provided information. The toxicologic findings which
were reported were severe skin irritation in rabbits at the two
highest doses and 2 deaths in the group of rabbits receiving the
highest dose. The submission did not indicate whether skin
irritation or lethality was observed in rats at any of the
applied doses. A more complete evaluation of the 21-day dermal
application study will be possible following EPA's receipt of the
final report which should include the data obtained for all of
the parameters specified in the provided protocol.
Current Production and Use
Due to the fact that the submitter has claimed the identity of
the subject chemical as TSCA CBI, information concerning current
production and use of the substance will not appear in this
status report. The chemical is, however, listed in the initial
TSCA Inventory.
Comments/Recommendations
The submitter reported that based on the new data, the Material
Safety Data Sheet and safety precautions for the product have
been revised and those revisions transmitted to all customers who
have purchased the product from the submitter within the past
year. The company also reported that a copy of the final results
from the ongoing dermal application study would be provided to
EPA.
In reporting acute in vivo toxicity results under Section 8(e),
most companies consider-BUch factors as the lethal dose, the
route of administration, the occurrence of unexpected serious
effects (which could also be obtained during necropsy, via "cage-
side" observations, etc.), and/or the extent and pattern of the
exposure to the subject chemical substance (e.g., the greater the
acute toxicity, the less heavily companies weigh the tested
chemical's exposure). With regard to the present submission, it
is possible that such pertinent information was available to
and/or considered by the company in submitting the summarized
acute toxicity results to EPA pursuant to Section 8(e) of the
Toxic Substances Control Act (TSCA; PL 94-469).
306
-------
8EHQ-1281-0425 S
Page 3 of 3
a)
In order to determine the need for further, more in-depth
assessment of the subject chemical substance, the Chemical
Hazard Identification Branch (CHIB/AD/EPA) will screen the
final results of the submitter's 2l-day dermal application
study.
b)
The Chemical Hazard Identification Branch will bring this
submission to the attention of both TRDB/AD/EPA and
CCD/OTS/EPA.
307
-------
UNITED STATES EHVIRONMENTAL PROTECTION AGENCY
'IOW&
Justine L. Welc~~m Leader
Chemical ~elect,i;ln~~~d Brofiles Team/CHIB
. '-
8EFC'-pSl-0426,
Page 1 of 3
APp=oved~-
Revision
Needed
'2/3ft?
DATE:
..IAN 2 1 1982
SUIJEtTL -: Status Report* 8EHQ-128l-0426
TO&
Frank D. Kover, Chief
Chemical Hazard Identification Branch/AD
Submission Description
The CIBA-GEIGY Corporation submitted complete copies of final
reports from a battery of shor,t-term in vitro and in vivo
mutagenicity ,screening studies of N-[4-(oxiranylmethoxy)phenyl]-
N-(oxiranylmethyl)-oxiranemethanamine (CAS No. 5026-74-4). ' CIBA-
GEIGY reported that positive results were obtained in each of the
following studies: Chinese Hamster (bone,'marrow) Sister Chroma-
tid Exchange Study, Chinese Hamster' (bone marrow)' Nucleus Anomaly
Test (Somatic Interphase Nuclei), Mouse Lymphoma Cell Point
Mutation Assay, and Ames Salmonella (bacteria) and Saccharomyces
D4 (yeast) Tests with and without metabolic~ctivation.' The
submitter also reported that the tested compound, as with other
epoxy resins, is capable of producing both skin irritation and
sensitization. '
The CIBA-GEIGY Corporation stated that the reported positive
mutagenicity results "are of limited relevance to human risk
since the most likely potential route of human exposure is
dermal." The subm~tter also stated that the tested chemical is
"a liquid with a ,vapor pressure of less than 0.1 rom Hg at
68°F." In addition, CIBA-GEIGY reported that its current
labeling/handling precautions minimize the possibility of skin
exposure to the tested substance and ,that the cured end products
which are made from the substance are "highly cross-linked, inert
and chemically resistant."
Submission Evaluation
As reported by CIBA-GEIGY, the subject compound did demonstrate
mutagenic activity in each of the performed assays. In the in
vivo studies, the compound (administered by gavage) did produce
highly significant dose-related increases in Sister Chromatid
Exchanges (SCE's) and interphase cell nucleus anomalies in the
bone marrow of Chinese hamsters. In the in vitro Mouse Lymphom~
Cell (L5l78Y) assay, the subject chemical~s weakly mutagenic in
*NOTE: T~is status report is the result of a preliminary
staff evaluation 0: i~formation submitted to EPA. State;e~t~
mace herein are not to be regarded as expressing final
Ase~cy policy or intent with respect to t~is particular
chemical. .~v review of the status report should take into
consideration-the fact that it may be bas~d on incomplet~
information. 308. .
I:~& '0"" IJ~ I"C:"'. ..,,,
-------
8EHQ-1281-0426
Page 2 of 3
that there was an increase over control in the number of mutant
colonies observed following an 18-hour incubation, but no detect-
able difference between treated and control following a 4-hour
incubation. In the in vitro microbial assays, the compound did
demonstrate mutagenic activity both in the presence and absence
of exogenous metabolic activation in bacteria (Salmonella
typhimurium strains TA-IOO and TA-1535) and in yeast (Saccharo-
myces D4), indicating that the chemical does not require
metabolic conversion in order to exert its mutagenic effect(s).
Current Production and Use
A review of the production range (includes importation volumes)
statistics for N-[4-(oxiranylmethoxy)phenyl]-N-(oxiranylmethyl)-
oxiranemethanamine (CAS No. 5026-74-4), which is listed in the
initial TSCA Inventory, has shown that no 1977 production/
importation was reported or that all of the production range data
reported were claimed as confidential by the manufacturer(s)/
importer(s) and cannot be disclosed. (Section 14(a) of the TSCA,
U.S.C. 2613 (a». **/
CIBA-GEIGY reported that the subject compound is a highly
reactive, low volatility liquid monomer used in certain adhesive
and laminate formulations.
Comments/Recommendations
As a result of the submitted toxicologic findings, CIBA-GEIGY
reported that its customers were being notified and that both the
label and Material Safety Data Sheet for the subject compound
were being modified "to more strongly emphasize proper handling
precautions."
Although a positive short-term genetic toxicity test result, when
considered alone, may not be sufficient to offer reasonable
support for a conclusion of substantial risk, EPA believes that
such studies do provide valuable data that can aid in assessing
the possible risks posed by chemicals to health and the
environment. The Agency also believes that a positive short-term
genetic toxicity test result in combination with additional
information, such as knowledge of exposure to or high production
of the chemical substance or mixture, would in many cases suggest
the need for further, more definitive toxicologic study. Should
the results obtained from such studies meet the reporting
criteria set forth in EPA's March 16, 1978, Section 8(e) policy
statement ("Statement of Interpretation and Enforcement Policy~
Notification of Substantial Risk"~ 43 FR 11110), appropriate
information should be submitted to EPA pursuant to TSCA Section
8(e). .
**/ The data submitted for the TSCA Inventory, including
production range information, are subject to the limitations
contained in the Inventory Reporting Regulations (40 CFR 710).
309
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8EE(-128l-0426
Page 3 of 3
The National Institute for Occupational Safety and Health (NIOSH)
has prepared a "Criteria Document" on Glycidyl Ethers (DHEW
(NIOSH ) Publication No. 78-166; June 1978). In addition, the
Test Rules Development Branch (TRDB/AD/EPA) is currently review-
ing information pertaining to "Glycidol and its Derivatives" as
recommended by the Interagency Testing Committee (ITC).
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will screen the submitted information and consider the
need for further assessment of N-[4-(oxiranylmethoxy)-
phenyl]-N-(oxiranylmethyl)-oxiranemethanamine (CAS No.
5026-74-4).
b)
Considering EPA's general interest in company actions
which are taken on a voluntary basis in response to
chemical toxicity/exposure information, the Chemical
Hazard Identification Branch (CHIB/AD/EPA) will ask the
CIBA-GEIGY Corporation if it is conducting, or plans to
conduct, further studies designed to better define the
toxicity of the subject chemical substance.
c)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, CPSC, OW/EPA,
OSWER/EPA, ORD/EPA and TRDB/AD/EPA. A copy of this
status report will also be provided to the Office of
Toxics Integration (OTI/OPTS/EPA) and to the Industry
Assistance Office (IAO/OTS/EPA) for appropriate
distribution.
310
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APR
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EH;r0282-0427 S
Page 1 of 3
OATI:
81982
~U'JtCTI Status Report* 8EHQ-0282-0427 S
App:'oved
'~- '1-//-3.
( ,
'1~IJustine L. Wel~eam Leader
Chemical select)hn and Profiles
TOIFrank D. Kover, Chief
Chemical Hazard Identification
Team/CHIB
Revision
Needed
Branch/AD
Submission Description
Note: The submitting company claimed its identity as TSCA CBI
(Confidential Business Information).
The submitting company provided a final report, including test
protocols and raw data, from a guinea pig maximization
(sensitization) study of V-50 (2,2'-azobis(2-amidinopropane)
dihydrochloride; CAS No. 2997-92-4). The submitter also provided
an account of several medical investigations, including
summarized results of human skin patch tests associating V-50
exposure to a skin rash problem identified in the workplace, as
well as final reports (supplied to the submitter by the Japanese
manufacturer of V-50) on the acute oral and dermal toxicity of V-
50 to rats, the irritant effects of V-50 to rabbit skin and the
results of Ames Salmonella (bacteria) tests with both V-50 and an
unidentified decomposition product of V-50. The submitter
pointed out that the data supplied by the manufacturer of V-50
gave no indication of the skin sensitization potential of the
compound.
In addition to the toxicity information, the submitting company
provided a letter from St. John's Hospital (London, England)
which contains a recommendation that maximization tests of V-50
be conducted. This recommendation was based on human "patch test
results [which] suggest with a high degree of probability that V-
50 may be the cause of the recent outbreak of dermatitis in the
plant."
The conclusion of the submitted guinea pig maximization study of
V-50 was that "based on the results obtained, the test material,
V-50, is considered a strong skin sensitizer in guinea pigs."
The submitted report stated that the test material was
administered to 15 male guinea pigs as a 50% w/w mixture in
petrolatum for the topical induction and as a 25% w/w mixture in
*NOTE: T~is status reco:'t is the result of a crelirnina:,v
staff evaluation of ir.formation submitted to EPA. State;e~ts
mace herein are not to be reaarded as ex~ressina final
Asen~y policy or i~tent with-r~s?ect to t~is particular
chem7cal. ..~Y rev:ew of the status report should take into
~ons~der~tlon the Iact that it may be based on incompleta
lnf?rmatlon. 311
- .
£,.
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8EHQ-0282-0427 S
Page 2 of 3
petrolatum for the challenge application. According to the
sub~itted report, all surviving aniMals (13) in the test group
exhibited a reaction to the test material at 24 and 48 hours
following the challenge apFlication. 'l'he submitted report also
stated that two animals in the test group were found dead on day
11 of the study. According to the suhmitted report:
"Eypoacti vi ty and ataxia were seen in [one animal J for tvlO
days prior to death. No phan71acotoxic signs were observed in
[the second animal] prior to death. No visible lesions were
observed during the gross patholosdcal examination. The
death~ of these two animals are considered treatment
related."
The report also stated that one surviving animal in the test
group exhibited hypoactivity on ~ay 14 of the study but appeared
normal at all other observations.
with regard to the other submitted toxicoloqical results, the
reported acute median oral lethal dose (LDSO) of V-50 to rats was
0.41 g/kg bodyweight; the acute median lethal dermal dose (LDSO)
of V-50 to rats was found to be greater than 5.9 g/kg bodyweight;
and V-50 was considered to be "mildly irritating" to rabbit skin.
In addition, the submitted Ames Salmonella report concluded that
under the conditions of the study, both V-50 and its decomposi-
tion product (tested separately) were non-mutagenic to Saln,onella
strains TA-1535, TA-1537, TA-1538, TA-9R and TA-IOO with and
without exogenous netabolic activation.
Submission Evaluation
Based on positive patch test results among workers exposed to V-
50 and positive results in guinea pig maxi~ization tests, V-50
does appear to be a strong skin sensitizer. In addition to the
positive skin reaction reported in guinea pigs, two of the
fifteen animals in the V-50 treated group exhibited delayed
ataxia and/or hypoactivity at nine to fourteen days following
topical application and two (including one hypoactive aniLlal)
died. These findings suggest dermal absorption of V-50. In
addition, there is a possibility that peripheral nerve, spinal
cerd, and/or brain injury occ~rred, despite the absence of
visible lesions during gross pathological examination.
It should be pointecl out that the effects of dermal sensitization
are not limited to skin reactions. In contrast to simple skin
irritation, sensitization involves immune rnechanisr0.s that can
cause immediate or delayed systemic reactions, including adverse
effects on the central nervous system.
With regarc to the reported ffi~es test results, V-50 as well as
its unidentified decomposition product appear to be nonmutagenic
to Salmonella typ1)irrur i un. However, there are questions wi th
resrect to test performance and data presentation which qualify
this conclusion. There was no indication in the report that a
cytotoxicity assay was perforued to provide a rationale for dose
312
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8EHQ-0282-0427 S
Page 3 of 3
selection. If the test chemicals are nontoxic, they should have
been tested in the Ames assay to the limits of solubility or to
an upper limit of 5 mg/plate. Also, the report did not provide
data on the numbers of revertants per plate, standard deviations
from the mean number of revertants per plate, or the number of
plates per dose.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for 2,2'-azobis(2-amidinopropane) dihydrochloride (CAS
No. 2997-92-4), which is listed in the initial TSCA Inventory,
has shown that between 2,000 and 20,000 pounds of this chemical
were reported as produced/imported in 1977.**/
No information on use patterns of V-50 was found in the secondary
literature sources consulted.
Comments/Recommendations
The submitting company stated that protective measures in the
workplace have been instituted, including the use of respirators,
rubber gloves, coveralls and eye protection. In addition,
employees are reportedly instructed to wash their hands well
after contact with V-50. According to the submitter, there have
been no skin problems with new workers since the changes were
instituted. The submitter also stated that there have been no
reports of skin problems at two of its other plant locations
where V-50 is used. In conclusion, the submitting company stated
that it believes that V-50 can be handled without substantial
risk when proper hygienic procedures and working conditions are
utilized.
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will screen 2,2'-azobis(2-amidinopropane) dihydrochloride
and consider the need for further assessment.
b)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, CPSC, ORD/EPA,
OW/EPA and OSWER/EPA. A copy of this status report will
also be provided to the Office of Toxics Integration
(OTI!OPTS/EPA) and to the Industry Assistance Office
(IAO/OTS/EPA) for appropriate distribution.
**/ This production range information does not include any
production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it include
any information which would compromise Confidential Business
Information. The data submitted for the TSCA Inventory,
including production range information, are subject to the
limitations contained in the Inventory Reporting Regulations (40
CFR 710).
313
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UNITED 5T A TES nlY IRONMENT Al PROTECTION AGENCY
Page 1 of 6
OJ. T E:
M.AR I I' 19R2
SU~JECT: St.atus Report* 8EHQ-0282-0428; -0429; -0430;App:-oved
-0431; -0432; -0433; and -0436
""014, Justine L. wel!;;)JA:;iam Leader
Chemical selec~-and Profiles Team/CHIB
TO: Frank D. Kover, Chief
Chemical Hazard Identification Branch/AD
-~- 3?' p;
L ,
.. tI I
Revision
Needed
Submission Description
In seven separate submissions, the Buffalo Color Corporation
reported summarized final results from acute toxicity studies
(oral LDSO and/or 4-hour inhalation LCSO determinations) of seven
different chemicals in rats.
In submission 8EHQ-0282-0428, the company reported that N,N-
dimethylaniline (CAS No. 121-69-7) was tested in three separate
4-hour inhalation studies using three different geometric mean
particle sizes, nominal (estimated) chamber concentrations, and
time-weighted measured concentrations at the breathing zone. The
reported lethalities for both male and female rats are summarized
as follows:
Mean Particle Nominal Concen- Measured conce~- Mortality/14 days
Size (..urn) tration (mg/m3) tration (mg/m) Males Females
4.8 5100 1900 2/5 0/5
5.2 4600 2000 2/5 2/5
5.8 4900 1000 0/5 0/5
In submission 8EHQ-0282-0429, the company reported that followlag
a single 4-hour inhalation exposure to N-ethylaniline (CAS No.
103-69-5), the LCSO for rats ~combined sexes) was determined to
be between 2600 and 3800 mg/m based on nominal (estimated)
chamber input. When based on actual measured concentrations at
the breathing zone, however, the LCSO for combined sexes was
reported to'be between 1130 and 1480 mg/m3.
The company reported in submission 8EHQ-0282-0430 that the LCSO
for rats (combined sexes) exposed via inhalation f~r 4-hours to
N,N-diethylaniline (CAS No. 91-66-7) was 4300 mg/m based on
nominal chamber concentr~tion. The LCSO for combined sexes was
reported to be 1920 mg/m when based on measured concentration at
the breathing zone.
*NO~~: ThlS status re~ort is the result of a creliminarv
sta!! evaluation 0: informa~ion submitt~c to EFA. State;e:.ts
mace hereln are no~ to be regarded as excressino final'
Ase~cy ~olicy or intent with r~s?ec~ to t~is ?a;ticular
chemlcal. .;'J1Y review of the status re~or';: should tak~ into
con51d~ratlon the fact that it m3Y be based on lncomc~ete
lntorma tlon. 314 '
[~. '0"" IJ~ '''£'.'. )-HI
-------
Page 2 of 6
In submission 8EHQ-0282-0431, the submitter provided the results
of a 4-hour inhalation toxicity study and an oral (single dose)
toxicity study of Nadic Methyl Anhydride (Tradename for
3A,4,7,7A-tetrahydromethyl-4,7-methanoisobenzofuran-l,3-dionei
CAS No. 25134-21-8) in rats. According to the company, the oral
LD50 for the compound was determined to be 914 mg/kg for males,
1006 mg/kg for females, and 958 mg/kg for the combined sexes.
With regard to the 4-hour inhalation study, the submitter
reported jhat at a nominal chamber concentration of 4900 mg/m3
(750 mg/m measured at the breathing zone), 5/5 female rats died
by the 5th day and 3/5 male rats died by the 14th day of post-
exposure observation. The company stated that the tested aerosol
was comprised of 90% Nadic Methyl Anhydride/10% ethyl alcohol and
had a geometric mean particle size of approximately 3.2 ~.
In submission 8EHQ-0282-0432, the Buffalo Color Corporation
reported the final results of a 4-hour inhalation study of
dodecenylsuccinic anhydride (CAS No. 25377-73-5) in rats. The
subm~tter stated that at a nominal chamber concentration of 5300
mg/m (time-weighted measured concentration of 1220 mg/m3), 2/5
female rats died by the 2nd day post-exposure and 2/5 male rats
died by the 5th day. The company also reported that no further
deaths were observed by the 15th day post-exposure. In addition,
the submitter reported that the administered aerosol consisted of
90% dodecenylsuccinic anhydride/10% ethyl alcohol and had a
geometric mean particle size of 2.3~m.
The Buffalo Color Corporation also reported (8EHQ-0282-0433) the
results of an acute oral (single dose) toxicity study of succinic
anhydride (CAS No. 108-30-5) in rats. According to the company,
the observed LD50 was 2157 mg/kg for male rats, 1510 mg/kg for
female rats, and 1795 mg/kg for the combined sexes.
Finally, the submitter reported (8EHQ-0282-0436) the final
results of two acute oral (single dose) toxicity studies of C. I.
Basic Violet 1 (CAS No. 8004-87-3) in rats. According to the
company, the compound was tested as a 93% pure powder and as a
45% solution in 15% acetic acid. The submitter reported that the
LD50's observed for the combined sexes were 413 mg/kg and 815
mg/kg for the powder and the solution, respectively.
In submitting
Buffalo Color
substances ~o
environment.
the preceding acute in vivo toxicity data, the
Corporation stated its belief that the subject
not pose a significant hazard to health or the
Submission Evaluation
N,N-Dimethylaniline is known to be toxic via both acute and
chronic exposure. The compound can produce skin irritation,
methemoglobinemia, anemia, and liver and possible kidney
toxicity. The compound is used as a standard for determining N-
oxygenation of aromatic arnipesi several tissues from a variety of
species have been investigated thus far including human liver and
315
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Page 3 of 6
kidney. Although N-ethylaniline and N,N-diethylaniline are
probably less toxic than N,N-dilnethylaniline, these compounds are
expected to bring about similar pathologic changes.
The 4-hour inhalation exposure of rats to approximately 500 ppm
Nadic Methyl Anhydride or approximately 600 ppm dodecenylsuccinic
anhydride (both compounds in aerosol form) resulted in delayed
lethality. It is suspected that animals exposed to Nadic Methyl
Anhydride died from some type of pulmonary inflammation most
likely due to hydrolysis of the anhydride to the parent dibasic
acid. Dodecenylsuccinic anhydride could interact with and/or
displace phospholipoprotein surfactants in the lung (thereby
decreasing elasticity) and could also provoke a macrophage
response in the lung. With regard to the reported succinic
anhydride toxicity, the compound appears to be more toxic and
more irritating than certain alkali metal or alkaline-earth metal
succinates which have been administered in 10 gram doses to
humans for laxative action.
The toxicity of C. I. Basic Violet 1 appears to be similar to
that of other rosaniline dyes which have been used in medicine
for at least 50 years and whos~ biological activities and
toxicities are fairly well known. For example, gentian violet
has been used on burned areas of the skin where the compound
promotes the formation of a tough scab which is antiseptic and
prevents the loss of body fluid. Gentian violet has also been
administered (orally) to humans in order to treat various types
of worms. The minimal oral lethal dose for gentian violet in
rabbits is 22 mg/kg.
Current Production and Use
The following table contains approximate production/importation
range information for the subject chemicals from the initial
(1977) TSCA Inventory. (Note: This production/importation range
information does not include any data claimed as confidential by
the person(s) reporting for the TSCA Inventory, nor does it
include any information which would compromise Confidential
Business Information. The data submitted for the TSCA Inventory,
including production/importation range information, are subject
to the limitations contained in the Inventory Reporting
Regulations (40 CFR 710)).
N,N-Dimethylaniline
N-Ethylaniline
N,N-Diethylaniline
3A,4,7,7A-Tetrahydromethyl-
4,7-methanoisobenzo-
furan-l,3-dione
Dodecenylsuccinic Anhydride
Succinic Anhydride
C. I. Basic Violet 1
121-69-7
103-69-5
91-66-7
Approx. prod./Imp. Range
2.0X106 to 2.0X107 lbs.
1.lX105 to 1.lX106 lbs.
3.1X105 to 3.1X106 lbs.
Chemical
CAS Number
25134-21-8
25377-73-5
108-30-5
8004-87-3
2.2X105
2.0X105
5.2X105
2.6X105
to 2.2X106
to 2.0X106
to 5.2X106
to 2.6X106
lbs.
lbs.
lbs.
lbs.
316
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Page 4 of 6
According to secondary literature sources, N,N-dimethylaniline is
used in the synthesis of dyes and dye intermediates, and in the
manufacture of vanillin. The compound is also used as an acid-
accepting stabilizer, as a solvent, and as a reagent. N,N-Di-
ethylaniline is used in the manufacture of dyestuffs, in the
synthesis of dyestuff and other intermediates, and in the
manufacture of pharmaceuticals. N-Ethylaniline is used mainly as
an intermediate in organic synthesis.
As reported in secondary literature, Nadic Methyl Anhydride is
used as a curing agent for epoxy resins and as an intermediate in
the synthesis of alkyd resins, polyesters, and plasticizers. The
compound is also used in laminating (electrical) and filament-
winding processes. Succinic anhydride is used in the manufacture
of organic esters (and other chemicals) and pharmaceuticals. The
compound is also used as a resin hardener. Dodecenylsuccinic an-
hydride is used in preparing resins (e.g. alkyd, epoxy), plasti-
cizers, corrosion inhibitors, and wetting agents.
According to the secondary literature, C. I. Basic violet 1 was
used at one time as a disinfectant. One of the primary current
uses of the colorant is as a biological stain in microscopy.
comments/Recommendations
Based on an initial review and evaluation of the reported acute
toxicity results, it does not appear that the provided data
warranted submission to the Agency pursuant to Section 8(e) of
the Toxic Substances Control Act (PL 94-469). The basis for
EPA's initial position is as follows:
The preface to Part V of the Agency's March 16, 1978,
"Statement of Interpretation and Enforcement Policy;
Notification of Substantial Risk" (43 FR 11110) states that
"a substantial risk of injury to health or the environment is
a risk of considerable concern because of (a) the seriousness
of the effect... and (b) the fact or probability of its
occurrence." With regard to the seriousness of the effect,
Part V explains further 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, mutation, birth
defects, or toxic effects resulting in death, or serious or
prolonged incapacitation." The information respecting these
effects can be obtained directly or inferred from designed
studies (e.g., in vivo experiments and tests as described in
Part VI of the policy statement). With regard to the "fact
or probability of its occurrence" criterion, Part V also
provides that certain health effects are so serious that
relatively little weight should be given to the chemical's
exposure in determining whether a risk is substantial.
317
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Page 5 of 6
The EPA's response to Comment 14 in Appendix B of the March
16, 1978, policy statement provides guidance with regard to
the Section 8(e)-reportability of results obtained from
routine acute in vivo range finding tests such LDSO or LCSO
determinations:-irritation tests, etc. In its response, EPA
stated that it believes that "many routine tests are based on
a knowledge of toxicity associated with a chemical..." The
EPA's response also directs that unknown effects which occur
and are observed and/or determined during acute in vivo range
finding tests may have to be reported if those effects are
serious and meet the reporting requirements set forth in
Parts V and VI of the policy statement.
Thus, when evaluating acute in vivo toxicity results for
possible submission to EPA under Section 8(e), EPA believes
that companies should consider such factors as the lethal
dose, the route of administration, the occurrence of
unexpected serious effects (which could be observed during
necropsy, via "cage-side" observations, etc.), and/or the
extent and pattern of the exposure to the subject chemical
substance. In addition, the greater the acute toxicity, the
less heavily companies should weigh the tested chemical's
exposure.
Based on the preceding discussion, it is EPA's preliminary
determination that the acute LCSO/LDSO data, as provided, did not
warrant submission to the Agency pursuant to TSCA Section 8(e).
In making this preliminary determination, however, it must be
understood that EPA may not be aware of additional pertinent
information (such as the factors previously mentioned) which may
have been available to and/or considered by the company in
reporting the toxicity data under Section 8(e).
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request the Buffalo Color Corporation to provide
its rationale as to why the reported results offer
reasonable support for a conclusion of substantial risk
of injury to health or the environment as defined the
EPA's March 16, 1978, Section 8(e) policy statement
("Statement of Interpretation and Enforcement Policy;
Notification of Substantial Risk"; 43 FR 11110).
b)
Considering the Agency's general interest in corporate
actions which are taken on a voluntary basis in response
to chemical toxicity/exposure information, the Chemical
Hazard Identification Branch will request the Buffalo
Color Corporation to describe the actions it has taken,
in light of the provided acute toxicity data, to warn
workers and others, and to reduce and/or eliminate
exposure to the chemical substances which were cited in
the submissions.
318
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Page 6 of 6
c}
The Chemical Hazard Identification Branch will transmit
a copy of this status report to NIOSH, OSHA, CPSC, FDA,
OWjEPA, OSWERjEPA, and ORDjEPA. A copy of this status
report will also be provided to the Office of Toxics
Integration (OTIjOPTSjEPA) and to the Industry
Assistance Office (IAOjOTSjEPA) for appropriate
distribution.
319
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0282-0434
Page 1 of 3
CAT£:
MAR
1'1982
SUaJE~TI
Status Report* 8EHQ-0282-0434
App=oved
{JJ?- ~J1.
'10M,
(£- Z-, /
Justine L. Wel ,- /rfeam Leader
Chemical Sele on and Profile£
Team/CHIB
Revision
Needed
TO. Frank D. Kover, Chief
. Chemical Hazard Identification Branch/AD
Submission Description
The Sun Chemical Corporation provided a summary of preliminary
,results from a Cosmetic, Toiletry and Fragrance Association
(CTFA)-sponsored chronic feeding study of D&C Red No. 19 (Basic
Violet 10~ Rhodamine B~ CAS No. 81-88-9) in mice and rats. The
submitting company stated that it has learned that there was an
"increased incidence of mice with hepatic neoplasms" and an'
"increased incidence of rats with thyroid tumors." The company
also stated that CTFA has informed the U. S.Food ~nd Drug
Administration (FDA) of the preliminary findings~nd that a final
report would be submitted, by CTFA to FDA in early 1982.
The Sun Chemical Corporation stated that D&C,Red No. 19 is a
bluish red colorant provisionally listed by the FDA for use, in
drugs and cosmetics and that the CTFA has petitioned FDA for
permanent listing of the substance as a color additive. The
company also stated that FDA regulations "required CTFA to notify
FDA immediately of any findings that indicate potential for D&C '
Red No. 19 to cause adverse effects. 21 <;.F.R. ~81.27(d)(4)."
The Sun Chemical Corporation reported that a,maximum of 25
personnel (production and laboratory) are directly involved at
the company's Staten Island, N.Y. plant in the "manufacture,
filtration, drying, pulverizing, packaging, evaluation and
analysis of D&C Red No. 19" for ultimate use by the cosmetic and
toiletry industry in lipsticks, soaps, and other products. The
Sun Chemical Corporation also reported that a maximum of 10
personnel (production and laboratory) are directly involved at
the company's manufacturing plants' in the handling and reaction
of the colorant as Basic Violet 10 (Rhodamine B) which is used by
the pigment industry in the manufacture of organic pigments.
In conclusion, the Sun Chemical Corporation stated that its
Section 8(e) notice was filed based on "knowledge of preliminary
results predicated upon incomplete studies..." The company also
stated that, at the present time, "insufficient information
exists to enable a determination to be made as to whether a
"substantial risk" exists with D&C Red No. 19."
-NOTE: T~is status recort is the result of a crelirninarv
staff evaluation 0: i~forma~ion submittec to EPA. Sta~e;e~t~
mace herein are no~ to be regarded as expressing final
Asency policy or intent with respect to t~is particular
chemical. .~y review of the status report should take into
consideration the fact that it may be based on incomolete
information. 320. .
-'
[~, 'OR" 11::0.-6 '''EV. ..,.,
-------
8EHQ-0282-0434
Page 2 of 3
Submission Evaluation
The published scientific literature indicates that D&C Red No. 19
is readily absorbed when administered via the oral route and is
extensively biotransformed. The literature also indicates that
the chemical is hepatotoxic and suggests that the compound may be
carcinogenic. Of particular concern in the present submission is
the reported increased incidence of thyroid tumors in rats. This
finding suggests that the effect(s) of D&C Red No. 19 on the
following parameters may deserve further attention:
1) Effect(s) on incorporation of iodine by the thyroid.
2) Effect(s) on thyroid hormone levels.
3) Effect(s) on thyrotropic hormone.
4) Effect( s) on the general histology of the thyroid.
The above effects would be expected to manifest themselves long
before the development of thyroid tumors.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for D&C Red No. 19 (CAS No. 81-88- 9), which is listed
in the initial TSCA Inventory, has shown that between 110 thou-
sand and 1.1 million pounds of this chemical were reported as
produced/imported in 1977. **/
In its submission, the Sun Chemical Corporation reported that
16,000 pounds of D&C Red No. 19 were produced in the U.S. in 1980
and also reported that 247,000 pounds of Basic violet 10 were
imported to the U.S. during 1980.
According to secondary literature sources, the subject colorant
can be used to dye a wide variety of synthetic and natural fibers
(e.g., wool, cotton, nylon), paper, feathers, leather, wax, wood,
soap, ink, and lacquer. In addition, the color has uses in drugs
and cosmetics (e.g., tablets, capsules, toothpaste, lipstick,
rouge). The chemical has also been used as a "tracing agent" in
water pollution studies and as an analytical reagent for
detecting a variety of metals (e.g., gold, antimony. mercury).
**/ This production range information does not include any
production/importation data claimed as 'confidential by the
person(s) reporting for the TSCA Inventory, nor does it include
any information which would compromise Confidential Business
Information. The data submitted for the TSCA Inventory,
including production range information, are subject to the
limitations contained in the Inventory Reporting Regulations (40
CFR 710).
321
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8EHQ-0282-0434
Page 3 of 3
Comments/Recommendations
In 1978, the International Agency for Research on Cancer (IARC)
evaluated the possible carcinogenic risk due to exposure to
Rhodamine B (IARC Monograph; Vol. 16; January 1978). Based on
the information available at that time, IARC stated that
"Rhodamine B has been tested in mice and rats by subcutaneous
injection and, in inadequate studies, by oral administration. It
was carcinogenic in rats when injected subcutaneously. producing
local sarcomas."
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request the Sun Chemical Corporation to describe the
actions it has taken on a voluntary basis in reponse to
the submitted chemical toxicity/exposure information to
warn workers and others and to reduce and/or eliminate
exposure to the subject colorant.
b)
The U.S. Food and Drug Administration has been requested
to provide EPA with a complete copy of the final report,
including data and. protocols, from the CTFA-sponsored
chronic feeding study of D&C Red No. 19 in rats and mice.
c)
The Chemical Hazard Identification Branch will consider
the preparation of a Chemical Hazard Information Profile
(CHIP) on the subject colorant.
d)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, CPSC, FDA,
NTP, NCI, OW/EPA, OSWER/EPA, and ORD/EPA. A copy of this
status report will also be provided to the Office of
Toxics Integration (OTI/OPTS/EPA) and to the Industry
Assistance Office (IAO/OTS/EPA) for appropriate
distribution.
322
-------
UNITED 5T A TES OIY IRONMOfTAL PR OT~CTION AGENCY
OA TE:
_19.
8EHQ-0282-0435
Page 1 of 3
SU6JECT:Status Report* 8EHQ-0282-0435
I'Row,Justine L. Wel (Me am Leader
Chemical select7o~'l'and Profiles
App.:::-oved
,?j/J0 7/~f
/ I
Team/CHIB
Revision
Needed
To:Frank D. Kover, Chief
Chemical Hazard Identification Branch/AD
Submission Description
The FMC Corporation reported preliminary results from an acute
rabbit dermal application toxicity study of sodium sulfide (CAS
No. 1313-82-2). The following summary of the observed
experimental findings was submitted by the company:
"A sample of sodium sulfide 60% flake was subjected to dermal
toxicity testing at a single dose level of 340 mg/kg. The
test was performed as specified in the FIFRA proposed guide-
lines (FR 43: 37356-37357). Briefly, moistened 60% sodium
sulfide flakes on a gauze pad were placed in contact with the
skin of 10 albino rabbits (5 males, 5 females). All animals
appeared normal at 1 and 3 hours after dosing. At 6 hours, 7
out of 10 animals were dead. At 24 hours, 9 out of 10
animals were dead. The remaining animal is likely to survive
the duration of the study. The material also causes skin
corrosion. The above data indicate that this material has a
dermal LD50 of less than 340 mg/kg."
The FMC corporation reported that although the corrosive
properties of sodium sulfide are well documented in the
scientific literature, no references were located on lethality
due to dermal application of sodium sulfide. In addition, the
company reported that it does not know the actual mechanism for
the observed lethality, but believes that it is "reasonable to
conjecture that the skin of the rabbit is penetrated by the
corrosive action of sodium sulfide permitting its entry into the
blood stream... [where] the sodium sulfide can be hydrolyzed to
hydrogen sulfide which is known to be highly toxic." The company
also reported that the conditions of the test in rabbits are
unlikely to be duplicated in humans, because sodium sulfide is
corrosive and gives painful burns. The FMC Corporation stated
that "a person would not willingly permit sodium sulfide to
remain in contact with the skin but would take action to wash it
off or otherwise remove it" and that "the rabbit under test
*NOTE: This status reDo-t is the resu'~ Of 1,'
f f' ' - ": '- . . j - '- - a pre 1 Till Ii a:- '/
st2- eva~uatloIi 0: l~rormation submitted to EPA. State:e~r
made hereln are not to be re0arded ,",.'" oj _5.
A enc Dolicv' " as eXpresslng Llnal
hs ' ,Y 1, - or lntent wlth reS;Ject to t'1is "articular
c emlca. .~v revi 'f h' .!'"
consideration- the i:~tOth t e,~tatus repo.:::-t should take into
information at l~ may be basQd on lncomolet2
" 323 .
--
r.rA .,..-- I.~ IlIrv L..'IlIt
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8EHQ-0282-0435
Page 2 of 3
conditions is
addition, the
believe there
test result."
physically restrained from such relief." In
submitting company stated that it has "no reason to
is undue hazard to humans because of this observed
Submission Evaluation
Both alkali and alkaline-earth metal sulfides (e.g., K, Na, Ca)
have been used to treat a variety of human skin diseases and have
also been used as depilatories. These types of compounds are
known to be irritating (sometimes severely) to the skin. When
swallowed, the sulfides, in addition to their alkaline corrosive
action in the gastrointestinal tract (mainly the esophagus and
stomach), release hydrogen sulfide. In addition, it is known
that human death has occurred following application (to the head)
of permanent-wave solutions containing ammonium sulfide.
Therefore, it is not totally surprising that lethality was
observed in rabbits treated dermally with sodium sulfide. As the
submitter stated, the corrosive action of sodium sulfide would
permit absorption of the compound directly into the bloodstream
where hydrogen sulfide would be released. It should also be
noted that hydrogen sulfide itself can be absorbed through the
skin. Therefore, some of the hydrogen sulfide released via
hydrolysis beneath the gauze pad would also be absorbed at the
site of application to the rabbits.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for sodium sulfide (CAS No. 1313-82-2), which is
listed in the initial TSCA Inventory. has shown that approxi-
mately 2.5 million to 8.8 million pounds of this chemical were
reported as produced/imported in 1977.**/
The FMC Corporation reported that its sodium sulfide, which is
sold in the form of a 60% flake, contains the equivalent of
approximately 3 molecules of water per molecule of sodium sul-
fide. According to the secondary literature sources consulted,
sodium sulfide is used in the manufacture of various organic
chemicals and sulfur dyes. The compound has also been reported
for use as depilatory agent for leather, as a solvent for gold
(from gold ores), and as a photographic and analytical reagent.
Sodium sulfide has also been used in sheep dips, and in paper
pulping, engraving, and lithography processes.
**/ This production range information does not include any
production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it include
any information which would compromise Confidential Business
Information. The data submitted for the TSCA Inventory,
including production range information, are subject to the
limitations contained in the Inventory Reporting Regulations (40
CFR 710).
324
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8EHQ-0282-0435
Page 3 of 3
Comments/Recommendations
The FMC Corporation reported that the company's current sodium
sulfide product labels warn that the chemical is corrosive, can
cause severe skin burns, and is harmful if absorbed through the
skin. The submitter also reported that those people handling
sodium sulfide are "admonished to avoid skin contact and to wear
gloves and protective clothing." The FMC Corporation stated that
the company is now considering whether its current sodium sulfide
product label "gives sufficient warning to users or whether it
should be modified in light of this new [reported] information."
a}
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request the FMC Corporation to provide a complete
copy of the final report, including protocols and data,
from the acute toxicity study of sodium sulfide which was
cited in its submission.
b}
The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, CPSC, FDA,
OW/EPA, OSWER/EPA, and ORD/EPA. A copy of this status
report will also be provided to the Office of Toxics
Integration (OTI/OPTS/EPA) and to the Industry Assistance
Office (IAO/OTS/EPA) for appropriate distribution.
325
-------
UNITED STATES ENV'IRONMENTAL PROTECTION AGENCY
DATE:
.1,.
SUBJECT: Status Report 8EHcr0282-0436
FROM: Justine L. Welch, Team Leader
Chemical Selection and Profiles Team/CRIB
TO: Frank D. Kover, Chief
Chemical Hazard Identification Branch/AD
please refer to the status report prepared for 8EHQ-0282-0428
EPA FORM 1320-6 (REV. 3-76)
326
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0282-0437
Page 1 of 3
0..1&:
MAA 2 5 1982
5UIJICT. S-tatus Report* 8EHQ-0282-0437
Approved
~ ,H~7
,IOM. Justine L. Welc~m Leader
Chemical selec~n and Profiles
TO. Frank D. Kover, Chief
Chemical Hazard Identification
Revision
Needed
Team/CHIB
Branch/AD
Submission Description
The Lever Brothers Company (Incorporated) provided a copy of the
protocol and final pathology report from an acute inhalation
study of C. I. Direct Violet 9 (CAS No. 6227-14-1) in male and
female rats. Five (5) male and 5 female rats were exposed to the
dye powder via inhalation at a nominal (estimated) chamber
concentration of 6.5 mg/l for a single 4-hour period followed by
a 14-day observation period, sacrifice, and necropsy. Control
animals (2 males and 2 females) were exposed to room air under
the same test conditions as the treated animals.
According to the submitted pathology report, clonic convulsions
were observed in 2 dye-exposed female rats and corneal lesions
were observed in 6 dye-exposed rats (sex not given) during the
test. At necropsy, 1/5 males and 3/5 females rats were reported
to have had ocular lesions "primarily due to inflammation and/or
edema of the corneal stroma." One eye of one of the affected
female rats was reported to be "shrunken, and had retinal
displacement and was generally inflamed (panophthalmitis)."
Although the pathology report stated that microscopic examination
of kidney, lung, liver, cervical lymph node, and ovary tissue did
not reveal any evidence of effects attributable to dye exposure,
histomorphologic changes observed in the testes, epididymis, and
brain were considered by the submitter's pathologist as
suggestive of being treatment related. The testes of one of the
treated rats were reported to have degeneration of the germinal
epithelium. In addition, this particular animal was found to
have abundant cellular debris from the seminiferous tubule
epithelium in the ducts of the epididymis. Although the testes
of the other 4 male rats were reported to be within normal
limits, 3 of the 4 were reported to have cellular debris in the
ducts of the epididymis. These findings were considered by the
pathologist as being "suggestive of an earlier testicular
lesion." - The testes and epididymis from both control animals
were reported to be normal.
.NOTE: T~is status reoort is the result of a orelirninarv
staff evaluation of information submittec to EPA. State;'e~ts
mace herein are no~ to be re~arded as eXDressino final
Agency policy or intent with~res?ec~ to t~is particular
chemical. .~y review 6f the status repor~ should tak~ into
consideration the iact that it may be based on incomplet~
information. 327
f"."'~I'\-"" ..~ ,..u -...
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8EHQ-0282-0437
Page 2 of 3
With regard to the "suggestive" findings in the brain, the
cerebellum of 7/10 treated and 1/4 control rats was reported to
contain subtle histomorphological alterations (i.e., multiple
foci of separated nerve fibers and/or vacuolated glial cells) in
the gray matter of the folia. The pathology report stated that
"due to the subtle nature of these changes it was difficult to
determine whether they were pathological alterations or possibly
artifacts associated with processing."
In its submission, the Lever Brothers Company stated that the
provided data "may suggest that this material [C. 1. Direct
Violet 9J may pose a substantial risk to human health under
certain manufacturing or processing conditions." Although the
company stated that "a degree of risk may be associated with
worker safety upon repeated exposure to the raw material when
supplied as a powder," the company noted that "th):re is no
evidence [that] this material when formulated in a commercial
household liquid product poses any health risk to the general
public."
Worker exposure at the Lever Brothers' manufacturing facilities
was reported to be minimal. The company stated that C. I. Direct
Violet 9 is "formulated at a 0.00025% level in the final product
in batch operations at two facilities." Lever Brothers estimated
that "human exposure at these facilities is approximately 0.10
hours/worker/shift over a range of 60-90 days yearly." The
company also reported that "handling of the dye by plant workers
is clearly defined in a Material Safety Data Sheet minimizing
exposure through inhalation."
Submission Evaluation
It is possble that an analog of p-phenylenediamine would be
released from C. I. Direct Violet 9 in the body via the Ji1etabolic
action of azoreductase. The p-phenylenediamine analog could
cause an intense release of histamine and could also cause
sensitization. With regard to the adverse ocular effects
observed in the rats, it should be noted that p-phenylenediamine
itself is known to have caused blindness in women who applied the
compound to their eyelashes. It is not possible to determine the
validity of the adverse effects noted in the cerebellar gray
matter unless behavioral observations indicated motor dysfunction
or Purkinje cell involvement. Likewise, the relationship between
exposure to the dye and the observed adverse male reproductive
system effects cannot be determined on the basis of the provided
information.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for C. I. Direct Violet 9 (CAS No. 6227-14-1), which
is listed in the initial TSCA Inventory, has shown that between 1
thousand and 10 thousand pounds of this chemical were reported as
328
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8EHQ-0282-0437
Page 3 of 3
produced/imported in 1977. This production range information
does not include any production/importation data claimed as
confidential by the person(s) reporting for the TSCA Inventory,
nor does it include any information which would compromise
Confidential Business Information. The data submitted for the
TSCA Inventory, including production range information, are
subject to the limitations contained in the Inventory Reporting
Regulations (40 CFR 710).
According to secondary literature sources, C. I. Direct Violet 9
can be used to dye leather, paper, and natural and synthetic
fibers (e.g., wool, silk, nylon). As previously stated, the
submitter reported that C. I. Direct Violet 9 is formulated in a
commerical household liquid product which was not identified in
the submission.
Comments/Recommendations
The Lever Brothers Company stated that "due to the inconclusive
results of the current animal inhalation study [the company]
would normally consider conducting a follow-up "head only"
inhalation study." Hqweveri because the submitting company has
decided (based on marketing considerations) to discontinue its
particular use of C. I. Direct Violet 9, no further testing of
the dye is being considered. The Lever Brothers Company reported
that the current handling procedures (outlined in a submitted
Material Safety Data Sheet) would be strictly enforced during the
phase-out period and that all "remaining dye at the plants will
either be returned to the supplier or disposed of as a hazardous
material." The Lever Brothers Company also stated that the
supplier of C. I. Direct Violet 9 was being informed of this TSCA
Section 8(e) notice.
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will screen the submitted information on C. I. Direct
Violet 9 in order to determine the need for any further
assessment.
b)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will transmit copies of this status report to NIOSH,
OSHA, CPSC, FDA, OW/EPA, OSWER/EPA, and ORD/EPA. A copy
of this status report will also be provided to the Office
of Toxics Integration (OTS/OPTS/EPA) and to the Industry
Assistance Office (IAO/OTS/EPA) for appropriate
distribution.
329
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0382-0438 S
Page 1 of 3
CAU:
,.
6 1982
SUIJEtT, Status Report* 8EHQ-0382-0438 S
'IOM, Justine L. welQ..4~m Leader
Chemical select;6~L:~d Profiles
TOI Frank D. Kover, Chief
Chemical Hazard Identification
Approved
,/J)t~
l
~/7
I
Revision
Needed
Team/CHIB
Branch/AD
Submission Description
The submitting company (name claimed as TSCA Confidential
Business Information (CBI)) provided summarized results from
several short-term in vivo inhalation toxicity studies of the
particulate form of-a partial aluminum potassium salt of
polyacrylic acid in rats. The submitter also provided summarized
results from several in vitro mammalian (mouse) macrophage
studies of a partial aluminum potassium salt of polyacrylic acid
(differing particle sizes), a partial sodium salt of polyacrylic
acid, a partial sodium salt of an acrylic acid-starch graft
polymer, and polyacrylic acid.
with regard to the provided in vivo inhalation toxicity studies,
the submitter reported that rats were exposed to respirable
particles (i.e., particle sizes less than 3.5 microns average
diameter) of a partial aluminum potassium salt of polyacrylic
acid. The exposure conditions (reported to be equivalent to 0.1,
0.3, and 1.0 of the current Threshold Limit Value (TLV) for
respirable nuisance particulate dusts i.e., 5.0 mg/M3/8 Hours),
were as follows:
1 )
One 6-hour exposure with sacrifices at 1 day, 2 weeks, 4
weeks, and 13 weeks post-exposure;
2)
Five 6-hour exposures with sacrifices at 1 day, 4 weeks,
and 13 weeks following the last exposure; and
3 )
Twenty 6-hour exposures with sacrifices at 1 day, 4 weeks
and 13 weeks following the last exposure.
-NOTE: T~is status recort is the result of a preliminary
staff evaluation of i~formation submitted to EPA. Sta~eme~ts
mace herein are no~ to be regarded as expressing final
Ase~cy policy or intent with respec~ to t~is particular
chemical. .~y review of the status report should tak~ into
consideration the fact that it may be based on incomplete
information. 330
.-
I:~. '0"" ..~ 1111£'0'. ~,.'
-------
8EHQ-0382-0438 S
Page 2 of 3
The submitting company provided the following summary of the
results obtained from the performed inhalation studies:
"In all tests (but not in all animals of the lower dose
concentrations and shorter exposures) macrophage cell and
lung tissue damage was observed. The effect was dose
related. At the lowest dose levels only small portions of
lung were affected if any lesions were found in the animal,
but the nature of the change was consistent. There was much
resolution during the recovery periods, but it was not
complete, and even after 13 weeks there were focal
aggregations of mononuclear cells and some deposition of
reticulin."
with regard to the performed in vitro mouse macrophage studies,
the submitter reported that all substances were tested either as
an "ultrasonicated gel" or as a "homogenized aqueous dilution of
an ethanolic suspension." According to the submitter, all
partial aluminum potassium polyacrylic acid samples of differing
particle sizes (i.e., regular, fine, or milled fine) were found
to be "moderately to highly toxic to cultured mouse peritoneal
macrophages." The submitter also stated that "the results
indicated that there was a selective toxic action for
macrophages." In addition, the submitter reported that poly-
acrylic acid and the partial sodium salts of either polyacrylic
acid or acrylic acid-starch graft were found to be toxic to
cultured macrophages. The company reported that although the in
vitro macrophage toxicity screening test predicts two in vivo --
responses to inhaled materials (i.e., macrophage toxicity and the
potential for fibrogenesis), the in vitro study "does not remove
the need for animal studies."
Submission Evaluation
The provided information indicates that the partial alumimum
potassium salt of polyacrylic acid provoked an inflammatory
reaction in the lungs. Even following a single 6-hour exposure,
some rats still had lesions at 13 weeks. The severity of such
pathological lesions depends on both the concentration of
particles in the inspired air and the duration of exposure.
observed tissue response involved monocytes and fibroblasts.
Therefore, some of the lesions would not be expected to resolve
completely without necessarily producing symptoms. The reported
lung lesions appear to resemble granulomas that occur following
inhalation or certain microorganisms or some types of non-living
particulates such as beryllium ores.
The
Current Production and Use
Wi th the
provided
accurate
exception of polyacrylic acid, the chemical names
by the submitting company were not sufficient to allow
indentification of the tested chemical substances.
.
331
-------
8EHQ-0382-0438 S
Page 3 of 3
A review of the production range (includes importation volumes)
statistics for polyacrylic acid (CAS No. 9003-01-4), which is
listed in the initial TSCA Inventory, has shown that between 11.3
million and 63.8 million pounds of this chemical were reported as
produced/imported in 1977. **/
The submitting company did not provide any use information for
any of the compounds which were cited in the submission.
According to secondary literature, polyacrylic acid is used as a
tackifier and a flocculant, and in co-polymeric form as a binder
for non-woven fabrics.
Comments/Recommenoations
The submitting company stated that due to a lack of commercial
success, its manufacture of a partial aluminum potassium salt of
polyacrylic acid has been discontinued. The company also stated
that no further animal toxicity studies involving any of the
subject substances are planned.
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request the submitting company to provide complete
copies of the final reports, including test protocols and
data, from all of the in vivo and in vitro toxicity
studies cited in the submission. The Chemical Hazard
Identification Branch will also request the submitting
company to provide additional information which will
permit adequate identification of the tested chemical
substances. In addition, the submitting company will be
requested to describe the actions it has taken on a
voluntary basis in response to the submitted toxicity
information to warn workers and others and to reduce
and/or eliminate exposure to polyacrylic acid and the
partial sodium salts of both polyacrylic acid and acrylic
acid-starch graft.
b)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, CPSC, FDA,
OW/EPA, OSWER/EPA and ORD/EPA. A copy of this status
report will also be provided to the Office of Toxics
Integration (OTI/OPTS/EPA) and to the Industry Assistance
Office (IAO/OTS/EPA) for appropriate distribution.
**/ This production range information does not include any
production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it
include any information which would compromise Confidential
Business Information. The data submitted for the TSCA
Inventory, including production range information, are
subject to the limitations contained in the Inventory
Reporting Regulations (40 CFR 710).
332
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0282-439
Page 1 of 3
DATE:
APR
61982
SUIJICT.Status Report* 8EHQ-0282-0439
Approved
.tfI- ~fT
,.~Justine L. Wel~eam Leader
Chemical selecttFn and Profiles
TD.Frank D. Kover, Chief
Chemical Hazard Identification
Team/CHIB
Revision
Needed
Branch/AD
Submission Description
The Dow Chemical Company submitted a summary of interim results
from a chronic inhalation study of propylene oxide (PO; CAS No.
75-56-9) in male and female rats. According to Dow, the study is
being conducted in the Netherlands and is co-sponsored by several
European propylene oxide producers including one of Dow's
subsidiaries. Dow reported that Wistar rats (European strain)
had been exposed via inhalation to propylene oxide vapors at
concentrations of 0, 30, 100, or 300 parts per million (ppm) for
6 hours/day, 5 days/week for approximately 28 months. The
submitter stated that all remaining animals in all groups were
sacrificed when mortality reached 50% in the control group. Dow
also stated that the histopathology on the terminally sacrificed
animals was in progress.
With regard to the results obtained from interim sacrifices
conducted at 12, 18, and 24 months, Dow reported that the only
unusual findings were "microscopically-detectable degenerative
changes in the olfactory portions of the nasal mucosa of both
male and female rats exposed to 100 or 300 ppm PO [propylene
oxide]." In addition to these microscopic findings, Dow reported
that the preliminary information which has been received thus far
from the study co-sponsors included summarized findings from the
gross pathology for all animals from the chronic portion of the
study and summarized histopathologic findings from animals which
died spontaneously or had been killed moribund prior to the
terminal sacrifice.
Dow reported that although the company has not yet received any
statistical analyses or interpretive comments from the European
investigators, it is Dow's opinion that the interim results (as
received by Dow) support the following preliminary conclusions:
"1) There appears to be an increased mortality in both male
and female rats associated with chronic inhalation
exposure to 300 ppm of PO.
-NOTE: T~is status recort is the result of a preliminary
staff evaluation of information submitted to EPA. Stateme~ts
mace herein are not to be regarded as expressing final
Agency policy or intent with res?ec~ to t~is ?articular
chemical. .~y review of the status report should take into
consideration the fact" that it may be based on incomolet~
information. 333" .
I~. ~"'-- ..~ ....0 -....
-------
8EHQ-0282-0439
Page 2 of 3
"2) There appears to be an increased number of female rats
with a grossly-observed mammary tumor (or mass suggestive
of a mammary tumor) in groups exposed to 100 or 300 ppm
PO.
3) Based on the limited histopathologic examination of rats
dying spontaneously or killed moribund prior to the
terminal sacrifice, there are indications of an increased
incidence of benign mammary tumors, as well as increased
numbers of benign mammary tumors per animal with a
mammary tumor, in the groups exposed to 100 or 300 ppm
PO. "
Dow stated that due to the preliminary nature of the data
received and Dow's unfamiliarity with the test conditions and the
strain of rats used in the study, "additional interim conclusions
from the data available would not be scientifically supported."
In addition, Dow stated that "subsequent developments in the
course of this study may modify current interim conclusions" and
that "final conclusions must await the completion of all phases
of this study."
Submission Evaluation
The significance of the observed degenerative changes in the
olfactory portions of the nasal mucosa of rats exposed to 100 or
300 ppm propylene oxide may become more clear when additional
histopathology findings are submitted. It is possible that the
observed lesions could be metaplasia resulting from chronic
irritation. At the present time, however, the reported mortality
following inhalation exposure to PO appears to be dose-related,
with female rats probably somewhat more susceptible. In
addition, the increased incidence of mammary tumors in female
rats also appears to be dose related.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for propylene oxide (CAS No. 75-56-9), which is listed
in the initial TSCA Inventory, has shown that between 710 million
and 1.75 billion pounds of this chemical were reported as
produced/imported in 1977. **/
~/ This production range information does not include any
production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it
include any information which would compromise Confidential
Business Information. The data submitted for the TSCA
Inventory. including production range information, are
subject to the limitations contained in the Inventory
Reporting Regulations (40 CFR 710).
334
-------
8EHQ-0282-0439
Page 3 of 3
According to secondary literature sources, the major use of
propylene oxide is as an intermediate in the manufacture of
polyether polyols, which are used primarily to produce
polyurethane foams. The chemical is also used to make propylene
glycol, dipropylene glycol, glycol ethers, and synthetic
glycerin. Propylene oxide has also been used as an insecticidal
and fungicidal fumigant for sterilizing a wide variety of
materials including medical equipment and foodstuffs.
comments/Recommendations
The Dow Chemical Company stated that in accordance with the
company's longstanding policy, Dow's employees and propylene
oxide customers and other producers of the chemical were being
notified of the interim results from the subject study. Dow also
stated that a copy of the final report from the study would be
provided to EPA when that report is received by the company.
In 1976, the International Agency for Research on Cancer (IARC)
conducted an evaluation of the carcinogenic risk from exposure to
propylene oxide (IARC Monograph; Volume 11; 1976). According to
that evaluation, propylene oxide was determined to be carcino-
genic (i.e., produced local sarcomas via subcutaneous injection)
in a "limited" study in rats. The National Cancer Institute/
National Toxicology Program (NCI/NTP) is currently testing
propylene oxide for carcinogenicity via inhalation in rats and
mice. In addition, the Test Rules Development Branch (TRDB/AD/
EPA) is currently reviewing chemical toxicity/exposure data on
propylene oxide as it pertains to the Interagency Testing
Committee (ITC) recommended class of "Alkyl Epoxides."
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request the Dow Chemical Company to provide complete
copies of all interim reports/data which the company has
received thus far and may receive in the future that
pertain to the cited co-sponsored chronic inhalation
study of propylene oxide in rats.
b)
The Chemical Hazard Identification Branch will consider
the preparation of a Chemical Hazard Information Profile
(CHIP) on propylene oxide.
c)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, CPSC, FDA,
NCI/NTP, OW/EPA, OSWER/EPA, OANR/EPA, ORD/EPA, OPP/OPTS
and TRDB/AD. A copy of this status report will also be
provided to the Office of Toxics Integration (OTI/OPTS/
EPA) and to the Industry Assistance Office (IAO/OTS/EPA)
for appropriate distribution.
335
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0382-0440 S
Page 1 of 4
01.1&:
APR 2 0 1982
Approved .~
Revision
Needed
f/'T
.
SuaJ£CT. Status Report* 8EHQ-0382-0440 S
'10M. Justine L. welS;~1/~am Leader
Chemical sele~~~ and Profiles Team/CHIB
TO: Frank D. Kover, Chief
Chemical Hazard Identification Branch/AD
Submission Description
The Shell oil Company provided summarized results from two acute
inhalation toxicity studies of para-tertiary-butyl benzoic acid
(ptBBA; CAS No. 98-73-7) dust in rats. Specifically, the company
provided: (1) final results from a study involving a single 4-
hour inhalation exp~sure to ptBBA at concentrations of 0, 0.57,
0.7, 1.0 or 1.9 g/m air; and (2) preliminary results from a
study involving 6-hour repeated (7-days) inhalati~n exposures to
ptBBA at concentrations of 12.5, 106, or 525 mg/m air.
The conclusions drawn from the 4-hour inhalation study were
reported as follows:
"1. Single 4-hour exposure of Fischjr 344 rats to ptBBA dust
at concentrations up to 1.9 g/m did not result in
extensive mortality; the acute 4-hour LC50 for ptBBA dust
was greater than 1.9 g/m3.
"2. Single 4-hour exposure of Fischer 343 rats to ptBBA
at concentrations of 0.52 to 1.9 g/m resulted in
significant treatment-related toxic effects which
included:
dust
"a. Decreased rate of body weight gain in both male and
female rats of all dose groups during days 0-7 and 0-
14 post-exposure.
"b. A CNS lesion characterized grossly by forelimb
neuropathy and described as multifocal poliomyelo-
pathy at the microscopic level; females developed
this lesion more frequently than males.
"c. Testicular effects in males characterized grossly by
approximately 50% reduction in testes weight in all
treated groups and accompanied by consistent
pathological changes at the microscopic level.
*NOTE: T~is status recort is the result of a crelimina=y
staff evaluation or information submitted to EPA. Sta~ements
mace herein are no~ to be regarded as expressing final
Ase~cy policy or intent wi~h respect to t~is particular
chemical. .~y review of the status report should take into
consideration ~he tact that it maY be based on incamclete
information. . .
- .
336
I:~" '0"" 11::1)0.6 "'!tv. ..,.,
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8EHQ-0382-0440 S
Page 2 of 4
"3. A no-effect level was not established in this study for
any of the three cranges listed in 2 above which followed
exposure to ptBBA dust."
with regard to the results of the 7-day inhalation study, the
mortality observed during that study was reported to be greater
for male rats than for the females (i.ej' 7/8 males versus 2/8
females died at the high dose (525 mg/m ) and 2/8 males versus
1/8 females died at the middle dose (1~6 mg/m3); no deaths were
observed at the lowest dose (12.5 mg/m ) administered). The
following information was provided on other toxicologic effects
observed in the 7-day study:
"Toxicological effects similar to those seen following a
single 4-hour exposure to ptBBA were also seen following
repeated exposures at lower concentrations; these included
testicular effects, forelimb neuropathy and ~ecreased rate of
body weight gain. In addition, there were apparent effects
seen in livers of females at all treatment levels, and in
males in the mid and high levels. Other effects included
changes seen at the high level and occasionally at the mid
level in other parameters not examined in the acute study
(hematology, clinical chemistry and histopathology)."
With regard to the above preliminary findings, the submitting
company stated that "statistical analysis of all data has not yet
been completed, and histopathological examinations are still in
progress."
In its submission, the Shell oil Company reported that adverse
testicular effects and neuropathy in rats exposed to ptBBA are
well known. In addition, the company stated that the cadmium
salt of ptBBA has been reported to cause adverse testicular
effects via dermal exposure and that two ptBBA precursors (i.e.,
para-tert-butyl toluene and para-tert-butyl benzaldehyde) have
been reported to produce testicular atrophy and damage via the
oral route of administration. The Shell Oil Company also
reported that based on a previous epidemiology study (conducted
by an independent research group) it was concluded that ptBBA, at
the levels of exposure experienced by male workers at a Shell
ptBBA production site, "did not have an apparent clinical or
epidemiologic effect on testicular function." Shell reported,
however, that "after careful consideration of this human study as
well as the preliminary data from the rat inhalation study, the
question of substantial risk remains, primarily because of the
rat's sensitivity to ptBBA at the levels tested."
Submission Evaluation
Para-tertiary-butyl benzoic acid (ptBBA) is toxic to rats and is
known to cause at least four significant types of adverse
effects: 1) lesions in the kidney tubules, 2) lesions in the
testes, 3) lesions in the liver, and 4) lesions in the spinal
cord and perhaps in the brain stem. The compound has been shown
337
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8EHQ-0382-0440 S
Page 3 of 4
to be toxic via ingestion, skin application and inhalation. When
inhaled, ptBBA can also produce lesions in the lung. The most
significant lesions, so far as survival is concerned, appear to
be those in the kidney tubules. Such lesions can cause severe
electrolyte and pH changes in the tissues.
The central nervous system lesions appear to involve only the
gray matter, mostly in the spinal cord and perhaps the medulla.
The observed lesions resemble those of neurolathyrism rather than
those of anterior poliomyelitis.
The observed liver lesions are probably due to a direct effect on
hepatocytes as evidenced by the numerous enzyme changes. The
increased liver weight may be a reflection of enzyme induction or
deposition of ptBBA or fat. It is possible that most of the
toxici"ty caused by ptBBA is due to a high lipid/water partition
coefficient for the compound.
With regard to the cited epidemiology study at the Shell plant,
it would be of interest to know if the workers exposed to ptBBA
were examined for kidney, liver and pulmonary function.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for para-tertiary-butyl benzoic acid (CAS No. 98-73-
7), which is listed in the initial TSCA Inventory, has shown that
between 1 million and 10 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 confidential by the person(s) reporting for the TSCA
Inventory, nor does it include any information which would
compromise Confidential Business Information. The data submitted
for the TSCA Inventory, including production range information,
are subject to the limitations contained in the Inventory
Reporting Regulations (40 CFR 710).
Para-tertiary-butyl benzoic acid is used as a resin modifier and
regulator for alkyd resins which are used in automobile enamels,
implement enamels, and aerosol finishes. The chemical is also
used in cutting fluids and as a raw material in the manufacture
of unsaturated polyester resins, as an intermediate for
speciality organic chemicals, and as a corrosion inhibitor.
Comments/Reco~nendations
The Shell oil Company reported that a copy of its submission had
been provided to both NIOSH and OSHA. The Material Safety Data
Sheet (MSDS) which was provided by the company in its submission
states in part that overexposure to ptBBA via ingestion, inhala-
tion, or absorption through the skin may result in adverse
effects on the testes, kidneys, liver, and lungs. In addition,
the MSDS recommends that ptBBA not be used in cutting fluids.
338
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8EHQ-0382-0440 S
Page 4 of 4
EPA has received and evaluated TSCA Section 8(e) submissions on a
mixture of the cadmium salts of ptBBA and benzoic acid (8EHQ-
1180-0375 S et seq.), and p-tert-butyl benzaldehyde and p-tert-
butyl toluene (8EHQ-1281-0421 S et seq.). EPA has also received
(on a "For Your Information (FYI)" basis) and evaluated the re-
sults from the study of testicular functions of Shell workers
exposed to ptBBA (FYI-OTS-0780-0081 et seq.). The Chemical
Hazard Identification Branch (CHIB/AO/EPA) is currently preparing
Chemical Hazard Information Profiles (CHIPs) on ptBBA, p-tert-
butyl benzaldehyde, and p-tert-butyl toluene.
a)
The Chemical Hazard Identification Branch (CHIB/AO/EPA)
will request the Shell oil Company to provide, when
available, complete copies of the final reports,
including protocols and data, from the two in vivo
inhalation studies of ptBBA which were cite~in the
submission. The submitting company will also be asked if
it has tested or plans to test kidney, liver, and/or
pulmonary functions of workers exposed to ptBBA. In
addition, the company will be requested to describe the
actions it has taken on a voluntary basis in response to
the submitted information to reduce and/or eliminate
exposure to ptBBA.
b)
The Chemical Hazard Identification Branch will include a
discussion of the findings reported in the present
submission in the Chemical Hazard Information Profile
(CHIP) on ptBBA which is currently in preparation.
c)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, CPSC, FOA,
OW/EPA, OSWER/EPA, OANR/EPA, and ORO/EPA. A copy of this
status report will also be provided to the Office of
Toxics Integration (OTI/OPTS/EPA) and to the Industry
Assistance Office (IAO/OTS/EPA) for appropriate
distribution.
339
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0382-0441
Page 1 of 3
DATI:
" OQ I 1 \00')
Approved, "<~- f'l
Revision
Needed
SUaJ£C:T.
Status Report* 8EHQ-0382-0441
nOM,
Justine L. \"]el~eam Leader
Chemical selecVon and Profiles 'I'eam/ClIIE
TO.
Frank D. Yover, Chief
Chemical Hazard Icentification Eranch/A~
SulITiseicn Description
The Dm'.' Chemical Company provided the sumn,arized results of an
inhalation teratology study of l,3-butadiene (CAS Ro. 106-99-0)
in rats. This study was reportedly sponsored by the Intei-
national Institute of Synthetic :8ubber Producers an(~ conducted in
Ensland.
The subni t ter stated that groups of rrlated fewale Sprague-Dm/ley
rats were eXf,osec1 to 0,200, 1,000 or 8,000 ppm of l,3-butadiene
via inl:alation for 6 hours 'per day from days 6-15 of gestation,
the period of major organogenesis for rats. According to the
submitter, t~e final laboratory report concluded that:
"I.
l..clrdnistration of butadiene toy the inhalation route, in
whole body exposure chambers, during the period of
organogenesis elicited naternal toxicity and, as a
result, embryonic growth retardation and slight
ernLryolethality at all dose levels (200-8,000 ppm
v Iv). The ftlagni tude of the effect was dose-related.
"2.
At the highest exposure level (8,000 ppm v/v) there was
also an indication of teratogenicity due to the presence
of [,'ajor fetal defects vlhich could not be attributed to
any other factor. There was no evidence of teratogeni-
city at the lower exposure levels (200 and 1,000 ppm
v/v) ."
The Dow Chemical Company stated that following a detailed
analysis and evaluation of the data by its scientific staff, the
company concluded that "exposure of rats to 8,000 ppm [1,3-
~utadieneJ during days 6-15 of gestation resulted in D
significant increase in major skeletal anomalies." However, Cow
also stated that the company disasreed. with the conclusions of
the study with respect to the effect of 1,3-butadiene on post-
implantation losses because the rates of these losses among dose
groups \~re not significantly different from the control group
-NOTE: T~is status recort is the result of a crelirnina=y
staff evaluation of ir.formation submitted to EPA. Sta~eme~ts
mace herein are not to be re~arded as ex~ressina final
Agency policy or intent wi~h-r~s?ec~ to t~is particular
chemical. .~v review of the status repor~ should take into
consideration-the fact- that it mav be based on incomolete
information. 340. .
- ,
t~. '011118 1J:D-4 ."I:Y. ..".
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8EHQ-0382-0441
Page 2 of 3
(i.e., 3.6, 6.0, 4.9, and 7.3% at O. 200, 1,000, and B,OGC Pf~,
respectivel~'). Tl,e suL1:1itter furtber stated that post-implanta-
tion losses of up to 10% have ~een observed historically in
control Sprague-Dawley rats in Dow's la~oratory. According to
DOVi, based on these reasons, the cOli1pany believes tljat the post-
implantation 10Eses ol:served in all eXf'osure grouf's were not a
direct result of 1,3-butadiene exposure.
[.uh.lission Evaluation
Tte rerorted teratogenicity of 1,3-hutadiene is not necessarily
suqrising-. It is known that 1, 3-butadiene can adversely affect
the central nervous system followinS inhalation exposure. Other
volatile hydrocarbons causing sin'ilar effects '...'hen inhaler1 or
ingested by hUMans can also produce teratogenic effects e.g.,
alcohol-fetal sync'1rone.
The subrni ttin~.; company disa9reed vii th the oonclusion of the
rerforming laboratory that embryonic growth retardation anc~
P-lTtcryolethali ty \Jere dose related. To sUPFort this position, the
sur-wi tting company provided percentages of post-ir:lplantation
losses in the stuCiy cowpared tq tlle rate of such losses in
historical control Sprague-Lawley rats at its own laboratory.
However, in order to perform a meaningful statistical analysis
and evaluation of the study, the Agency needs a full copy of the
final report, including test protocols and actual data on post-
implantation losses, ~aternal toxicity. growth retardation, and
all other experim.ental Farameters.
It should also be pointed out that the rate cf post-implantation
loss in historical controls at the laboratory of the submitter
may not necessarily represent rates at other laboratories ~here
conditions may vary. No data on historical controls at the
rerforwing laboratory in England were frovided by the submitter.
Current Production and Use
11. revievi of the production range (includes importation volumes)
statistics for l,3-butadiene (CAS No. 106-99-0), which is listed
in the initial TSCA Inventory, has shown that between 2.1 billion
and 7.3 billion ~ounds of this ch8rnical were reported as
Froduced/ irllported in 1977. ~/
**/ This production range information does not include any
- production/importation data claimed as confidential by the
person(~) reporting for the TSCA Inventory, nor dces it
include any information which would compromise Confidential
Business InforDation. The data submitted for the TSCA
Inventory. including production range information, are
sutject to the limitations contained in the Inventory
Reporting Regulations (40 CFR 710).
341
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8EHQ-0382-0441
Page 3 of 3
Accordins to secondary literature sources and a recently
cor:\r::leted draft Chemical Hazard Inforuation Frofile (Cf-lIP) on
1,3-cute.diene, the subject chemical is used as a polYEler
cOMfonent in the manufacture of styrene-butadiene and nitrile
rutber .rroducts, in the J'1anU facture of polybutadiene, neoprene
and ot11er elastor:1ers, in the nanufacture of resins, and as a
chemical intermediate.
COInr-ent s/ Recor'l}nen9ati~~
The Agency previously received and evaluated another TSCA Section
E(e) Bubnission on 1,3-butadiene (8EIT(;-1080-0370 et seq.). The
Chel;~ica 1 Hazard Icenti fication Branch (CHIB/ 1',D/EPA) has completed
Cl draft CheLiical Hazard Inforrdation Profile (CHIP) on 1,3-
butadiene (09/18/81).
a)
In order for EP1". to properly evaluate the results of the
inhalation teratology study of 1,3-butadiene cited in
this subL1ission, the Cher:lical Hazard Identification
Branch will request the Cow Ch.erl1ical Company to provide a
complete copy of the final report, including protoccls
and data.
t)
rI'he Chemical Hazard Identification Branch will request
the DoVi Chemical Company to describe the actions it has
taken on a voluntary basis in response to the submitted
inforiJation on 1, 3-butadiene, to warn workers and ot.hers,
and to reduce and/or eliminate exposure to the subject
chemical.
c)
T~ne Cher.lical I-Iazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, CPSC, FDA,
NCI /NTP, OA};R/EPA, m7/EFA, OSHER/EPA and ORD/EPI~. "A copy
of the status report will alse be provided to the Office
of Toxics Integration (OTI/OPTS/EPA) and to the Industry
Assistance Office (IAO/OTS/EPA) for appropriate
distribution.
342
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0482-0442
Page 1 of 3
DA u: APR 2 2 1982
'1~.Justine L. Wel~eam Leader
Chemical selec~on and Profiles
TO. Frank D. Kover, Chief
Chemical Hazard Identification
Team/CHIB
App:oved ~
Revision
Needed
flf/f'~
I
SUIJ£CT. Status Report* 8EHQ-0482-0442
Branch/AD
Submission Description
The Stepan Chemical Company reported that dimethyl sulfate (CAS
No. 77-78-1) had been identified as an impurity in one of the
company's products (Stepan Agent 291-83). According to the
submitter, Stepan Agent 291-83 contains the following sulfonated
methyl esters: tetradecanoic acid, 2-sulfo-, I-methyl ester (CAS
No. 29454-23-7); hexadecanoic acid, 2-sulfo-. I-methyl ester (CAS
No. 58849-75-5); octadecanoic. acid, 2-sulfo-, I-methyl ester (CAS
No. 3076-26-4). The submitter reported that the dimethyl sulfate
impurity was discovered during air sampling of the "head space"
of a retained product sample. The company stated that the method
of analysis was qualitative and sensitive to levels of dimethyl
sulfate ranging from 1 to 50 parts per million. The submitter
also stated that air samples from the processing area where the
sulfonated methyl esters were being synthesized did not have any
detectable levels of dimethyl sulfate.
The Stepan Chemical Company stated that dimethyl sulfate is
formed at temperatures greater than 100GC under anhydrous condi-
tions. In addition, the company reported that it appears that
the dimethyl sulfate impurity can be eliminated by digestion of
Stepan Agent 291-83 with small volumes of water. The company
also reported that "neutralization of sulfo methyl esters with
caustic is effective in destroying dimethyl sulfate." The
submitting company reported that it believes that the "risk of
exposure to the impurity is limited to workers who may process
the acid in open reaction vessels."
Submission Evaluation
Dimethyl sulfate is known to be irritating to the skin, mucous
membranes and lungs. Following absorption, the compound can
adversely affect various internal organs - the most serious tox-
icity being in the kidneys. The use of dimethyl sulfate as a war
gas showed it to have immediate blistering actions like those of
mustard gas and delayed pulmonary effects like those of phosgene.
*NOTE: This status reoo~t is the resul: of a crelimina:v
staff evaluation of information submitteci to EPA. Stace;ents
mace herein are not to be re~arded as eXDressina final
Agency policy or intent with~res?ec~ to t~is particular
chemical. .'ny review of the status repor~ should take into
consideration the tact that it mav be based on incomoleta
information. 343. .
I:~" '0." 1J:m-.I1.~V. ~'.I
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8EHQ-0482-0442
Page 2 of 3
The presence of dimethyl sulfate as an impurity as described in
the present submission is not likely to invoke any of the above
effects with the possible exception of mild irritation of skin,
eyes, throat and bronchi. What is of concern, however, would be
chronic exposure to dimethyl sulfate, an alkylating agent which
has been shown to be a carcinogen in animals and possibly humans.
In 1974, the International Agency for Research on Cancer (IARC)
conducted an evaluation of the carcinogenic risk to humans from
exposure to dimethyl sulfate (IARC Monograph; Volume 4; 1974).
With regard to the animal data available at that time, IARC found
that dimethyl sulfate was "carcinogenic in the rat, the only
species tested, by inhalation, subcutaneous injection, and fol-
lowing pre-natal exposure....and carcinogenic to the rat in a
single-dose exposure." With regard to available human data, IARC
stated that certain case reports raised "suspicion as to the
possible carcinogenicity of dimethyl sulfate in man, but good
epidemiological evidence [was] not available to confirm this."
Current Production and Use
According to Stepan, its current manufactured volume of sulfon-
ated methyl esters is less than 1 million pounds per year. A
review of the production range (includes importation volumes)
statistics for the cited sulfonated methyl esters (CAS No. 29454-
23-7, 58849-75-5, and 3076-26-4), which are listed in the initial
TSCA Inventory, has shown that between 10 thousand and 100 thou-
sand pounds of each of these chemicals were reported as produced/
imported in 1977. **/
The Stepan Chemical Company reported that "sulfonated methyl
esters are chemical process intermediates which are used to
manufacture surfactants and other specialty chemicals by neu-
tralization or by further processing." The submitter also
reported that the company does not know of any commercial use(s)
for the acid form of the types of materials in which dimethyl
sulfate was detected.
A review of the production range (includes importation volumes)
statistics for dimethyl sulfate (CAS No. 77-78-1), which is
listed in the initial TSCA Inventory, has shown that between 20
million and 100 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 confidential by the
person(s) reporting for the TSCA Inventory, nor does it include
any information which would compromise Confidential Business
Information. The data submitted for the TSCA Inventory,
including production range information, are subject to the
limitations contained in the Inventory Reporting Regulations (40
CFR 710).
344
-------
8EHQ-0482-0442
Page 3 of 3
According to secondary literature sources, the main use of
dimethyl sulfate is as a methylating agent in the synthesis of
organic chemicals, including certain pharmaceuticals.
Comments/Recommendations
The Stepan Chemical Company reported that it has notified its
customer of the potential problem and that investigations of
certain process alterations are underway which the company ex-
pects will eliminate dimethyl sulfate from the product. In
addition, the submitting company reported that it plans to
continue monitoring for dimethyl sulfate in process areas.
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will screen the reported information in order to
determine the need for further assessmentv
b)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, CPSC, FDA,
NCI/NTP, OW/EPA, OSWER/EPA, OANR/EPA, and ORD/EPA. A
copy of this status report will also be provided to the
Office of Toxics Integration (OTI/OPTS/EPA) and to the
Industry Assistance Office (IAO/OTS/EPA) for appropriate
distribution.
345
-------
"ATE: MAY 3
\982
UNITED STATES ENVIRONMENTAL PROTECTIOH AGENCY
8EHQ-0482-0443
Page 1 of 2
Approved .m-
L-
Revision
Needed
tJ/t
UIiJECT'Status Report*' 8EHQ-0482-0443
nOM,Justine L. welcWam Leader
Chemical selec~;-and Profiles
Team/CHIB
TOr Frank D. Kover, Chief
Chemical Hazard Identification Branch/AD
Submission Description
The CIBA-GEIGY Corporation provided a full copy of the final re-
port of a two-year rat inhalation (snout only) study of Irgastab@
2002 (nickel-bis-[ethyl(3,5-di-tert-butyl-4-hydroxybenzyl)phos-
phonate]; CAS No. 30947-30-9) which was conducted by CIBA-GEIGY
Limited of Basel, Switzerland. According to the submitter,
groups of 40 rats (20 animals per sex) were exposed to I~gastab@
2002 dust at target concentrations of 0, 10, or 100 mg/m for 2
hours per day, 5 days per week for 105 weeks. The following
results summary was provided by the submitter:
"Results indicated poor survival at the high dose since, by
18 months, there was 80% mortality in females and 50% morta-
lity in males, with only 3 males and two females available
at final sacrifice. No survival differences were seen
between control and low dose animals. The respiratory tract
was the target organ. Two of the three males surviving to
final sacrifice each developed a well differentiated
squamous cell carcinoma of the lung. From the available
histopathology results, no mention of preneoplastic changes
were evident in the lungs of male animals surviving up to
682 days or in any female up to final sacrifice."
In its submission the CIBA-GEIGY Corporation stated that it does
not believe that Irgastab@ 2002 "represents a substantial risk of
injury to human health during manufacture, processing, use or
disposal..." and also stated that the company's "currently recom-
mended handling precautions already protect against inhalation
exposure by specifying the use of local ventilation and a NIOSH
approved dust respirator or organic vapor respirator in heated
operations."
Submission Evaluation
The carcinogenic, irritant (skin, pulmonary), and sensItizing
effects of nickel salts are well known. This well designed and
-NOTE: T~is status reDo~t is the result of a prelimina:y
staff evaluation or ir.formation submitt~c to EPA. Statements
mace herein are no~ to be regarded as expressing final
Ase~cy policy or intent with respect to t~is ?articular
chemical. .~y review of the status report should taKe into
consideration the iact that it may be based on incompleta
information. 346
- .
t~. , 0"'88 11:1>1 lacy. ~"I
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8EHQ-0482-0443
Page 2 of 2
executed study further establishes the carcinogenicity and pul-
monary irritation. The low dose had sufficient time to produce
methemoglobinemia with typical reticulocyte and erythrocyte
responses. The high doses produced sufficient pulmonary capil-
lary changes to cause hemoconcentration (i.e., increased blood
cell concentrations and hematocrit).
Current Production and Use
A review of the production range (includes importation volumes)
statistics for the subject chemical (CAS No. 30947-30-9), which
is listed in the initial TSCA Inventory, has shown that between
100 thousand and 1 million pounds were reported as produced/
imported in 1977.**/
The CIBA-GEIGY Corporation reported that Irgastab@ 2002 is used
as a light stabilizer for plastics~ The submitter also reported
that Irgastab@ 2002 contains approximately 8% nickel and is com-
mercially available as a dihydrate.
Comments/Recommendations
In order to re-emphasize the necessity for handling Irgastab@
2002 in a safe manner"the CIBA-GEIGY Corporation reported that
the Material Safety Data Sheet for Irgastab@ 2002 "has been re-
vised to more strongly emphasize the danger of inhalation
exposure" and that the Irgastab@ 2002 container label was being
revised for reprinting. CIBA-GEIGY also reported that its
"laboratory and plant personnel handling this product have been
advised orally of the submitted findings and will receive copies
of the revised Safety Data Sheet, label and Toxicology Bulle-
tin." In addition, the company stated that its customers, as
well as those persons who have requested samples, are being
notified by letter of the new toxicity findings and the re-
emphasized proper handling precautions.
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will consider the preparation of a Chemical Hazard
Information Profile (CHIP) on nickel-bis-[ethyl(3,S-di-
tert-butyl-4-hydroxybenzyl)phosphonate].
b)
The Chemical Hazard Identification Branch will transmit
a copy of this status report to NIOSH, OSHA, CPSC, ORD/
EPA, OW/EPA and OSWER/EPA. A copy of this status report
will also be provided to the Office of Toxics Integra-
tion (OTI/OPTS/EPA) and to the In~ustry Assistance
Office (IAO/OTS/EPA) for appropriate distribution.
**/ This production range information does not include any pro-
duction/importation data claimed as confidential by the person(s)
reporting for the TSCA Inventory, nor does it include any inform-
ation which would compromise Confidential Business Information.
The data submitted for the TSCA Inventory, including production
range information, are subject to the limitations contained in
the Inventory Reporting Regulations (40 CFR 710)
347
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0582-0444
Page 1 of 4
DAft:
JJ4 2 8 1982
Approved .~ ~~
Revision
Needed
SuaJ!CT. Status Report* 8EHQ-0582-0444
,.01&. Justine L. Wel~am Leader
Chemical sele~on and Profiles Team/CHIB
TO, Frank D. Kover, Chief
Chemical Hazard Identification Branch/AD
Submission Description
The Velsicol Chemical Corporation submitted a copy of a manu-
script entitled: "Mortality and Benzotrichloride [BTC] Exposure:
A Study of Mortality in a Factory Manufacturing Chlorinated
Toluenes Involving Exposure to Benzotrichloride, Including an
Analysis by the Method of Regression Models in Life-Tables," by
T. Sorahan and J. Waterhouse, Cancer Epidemiology Research Unit,
University of Birmingham, Birmingham, England. Specifically, the
performed epidemiologic study involved worker exposure to various
chemical substances, including benzal chloride (CAS No. 98-87-3),
benzoyl chloride (CAS No. 98-88-4), benzyl chloride (CAS No. 100-
44-7), and benzotrichloride (BTCi CAS No. 98-07-7), in the
chlorinated toluenes manufacturing process. In its submission,
Velsicol stated that although the company was not sure of the
exact status or date of the provided manuscript, the company had
determined that EPA was not aware of the document or its content.
Due to the fact that both the Velsicol and EPA copies of the
submitted manuscript were of very poor quality, the Chemical
Hazard Identification Branch (CHIB/AD/EPA) requested a better
copy directly from the lead English author. In response to EPA's
request, the author provided the most recent manuscript which had
a new title: "A Mortality Study of Workers in a Factory Manu-
facturing Chlorinated Toluenes" by T. Sorahan, J. Waterhouse, M.
Cooke, E. Smith, J. Jackson, and L. Temkin. The author stated
that the manuscript had been submitted to the Journal of Applied
Toxicology for publication and that EPA would receive a-copy of
the published version as soon as it becomes available.
In the cover letter to its Section 8(e) submission, Velsicol
pointed out that the authors concluded that "despite [certain]
reservations and bearing in mind the results of other epidemio-
logical and toxicological studies, the most reasonable inter-
pretation of this study is that BTC is a potential human
carcinogen." However, in the copy of the more recent manuscript
*NOTE: T~is status recort is the resul~ of a orelirninarv
staff evaluation of information submitted to EPA. State;e~ts
mace herein are no~ to be regarded as expressing final
Ase~cy ?olicy or intent with r~s?ec~ to t~is ?articular
chem~cal. .~y review of the status repor~ should take into
~onslderation the fact that it may be based on incomplete
J.nforma tion.
348
- .
t~& ~Olt. 11:1>-6 "II:V. ~"I
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8EHQ-0582-0444
Page 2 of 4
which EPA obtained directly from England, the authors concluded
that "despite [certain] reservations and bearing in mind other
reports and the results of toxicological studies, a reasonable
interpretation of this study is that BTC should be considered to
be a potential human carcinogen."
In its TSCA Section 8(e) submission, Velsicol stated that the
company is treating benzotrichloride as a potential .human
carcinogen. The submitting company also reported that although
it has industrial hygiene monitoring data, no precise estimate of
worker exposure to BTC can be made at the present time because
the analytical method of detection has not been validated.
Velsicol reported, however, that it is attempting to develop a
valid method for detecting BTC and that when such a method
becomes available monitoring studies would be conducted.
Submission Evaluation
The following evaluation pertains to the author-supplied revision
of the manuscript which was initially submitted by the Velsicol
Chemical Corporation.
Sorahan et al. examined the 'patterns of deaths among 953 workers
employed at an English chlorinated toluenes manufacturing
facility at some time between January 1, 1961 and December 31,
19.70. The vital status of each of these workers, 163 of whom
were known only to have been exposed to a variety of chlorinated
toluenes, was determined after exposure classification. This may
have introduced a bias by including more deaths among the so-
called exposed group.
Two types of
performed by
standardized
than for all
statistical analyses of the obtained data were
the investigators. One type, which focused on
mortality ratios (SMRs), showed greater death rates
England and Wales in the following three instances:
1. among all workers, for all causes and for all cancer
causes,
2. among workers said to have been exposed, for all causes,
for all cancer causes, for cancers of the digestive system
and of the respiratory system, and
3. among unexposed workers, only for cancers of the mouth and
throat.
The above increases were diminished when compared to mortality in
the local (Merseyside) area, but remained elevated, significantly
so for the exposed workers for all cancer causes of death, can-
cers of the digestive system, and all causes of death.
The other type of statistical analysis used was the method of
regression models in life tables which was a means of using
exposure status within the worker group to look for associations
349
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8EHQ-0582-0444
Page 3 of 4
with mortality, while controlling for age at entry to the survey
and the year of first employment. By this method, when length of
post-1937 employment was taken as a surrogate for cumulative
exposure magnitude, only cancer deaths as a whole were considered
statistically significantly affected by exposure status. The
observed cancers were almost all digestive or respiratory, but
neither category individually showed significant effect of
exposure. Mortality differences were almost entirely attibutable
to those workers first employed prior to 1951.
The conduct of the performed epidemiologic study limits the
interpretations of its results. While acknowledging this
reservation, the authors used animal toxicological evidence to
infer that, among the variety of chlorinated toluenes present,
benzotrichloride was the substance most likely associated with
the increased cancer mortality- However, based solely on the
results of the epidemiologic study and the limitations of the
study, a reasonable interpretation of the findings would be that
they are suggestive of an association between cancer mortality
and exposure to one or more of the chemicals in the chlorinated
toluenes manufacturing process at the facility.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for the subject substances, which are listed in the
initial 1977 TSCA Inventory, has shown that the following
production/importation ranges were reported:
Chemical Name CAS Number Approximate Prod./Import. Range
Benzal Chloride 98-87-3 2 million to 20 million pounds
Benzoyl Chloride 98-88-4 10 million to 52 million pounds
Benzyl Chloride 100-44-7 52 million to 110 million pounds
Benzotrichloride 98-07-7 10 million to 50 million pounds
The above ranges do not include any production/importation data
claimed as confidential by the person(s) reporting for the TSCA
Inventory, nor do they include any information which would com-
promise Confidential Business Information. The data submitted
for the TSCA Inventory, including production range information,
are subject to the limitations contained in the Inventory Report-
ing Regulations (40 CPR 710).
Benzal chloride is used as a chemical intermediate in the
manufacture of benzaldehyde and cinnamic acid. Benzoyl chloride
is used as a chemical intermediate in the acylation of alcohols,
phenols, and amines, and in the manufacture of benzoyl peroxide
and dye intermediates. Benzyl chloride is used as a chemical
intermediate in the manufacture of benzyl compounds, perfumes,
pharmaceuticals, dyes, synthetic tannins and artificial resins.
Benzotrichloride is used mainly in the manufacture of synthetic
dyes and other organic chemicals, including some pesticides.
350
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8EHQ-0582-0444
Page 4 of 4
Comments/Recommendations
In addition to its reported treatment of BTC as a potential human
carcinogen and its efforts to develop a valid analytical method
for detecting and monitoring BTC exposure in the workplace, the
Velsicol Chemical Corporation reported that its workers and cus-
tomers had been notified of the submitted information. The
company also reported that it planned to meet with staff of the
National Institute for Occupational Safety and Health (NIOSH) to
discuss benzotrichloride. In addition, the company reported that
it was in the process of developing a total benzotrichloride
strategy which may possibly include an epidemiologic study.
EPA has received and evaluated several other TSCA Section 8(e)
and "For Your Information (FYI)" submissions on benzotrichloride,
benzyl chloride, benzal chloride, and/or benzoyl chloride (8EHQ-
0777-0001; 8EHQ-0178-0041; 8EHQ-0478-0138 P; 8EHQ-0678-0180; and
8EHQ-0980-0360; FYI-OTS-1180-0107; and FYI-OTS-0981-0122). In
addition, the Chemical Hazard Identification Branch (CHIB/AD/EPA)
is currently preparing and/or evaluating Chemical Hazard Informa-
tion Profiles (CHIPs) on benzotrichloride, benzal chloride, and
benzoyl chloride; a CHIP on benzyl chloride was completed in
1977.
a) The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request the Velsicol Chemical Corporation to keep EPA
apprised of the results of the company's BTC monitoring
efforts and clinical/epidemiologic studies (if performed)
involving human exposure to BTC in the workplace.
b) The Chemical Hazard Identification Branch will consider
including a discussion of the submitted information in the
Chemical Hazard Information Profiles on benzotrichloride,
benzal chloride, and benzoyl chloride which are currently
in preparation or undergoing evaluation.
c) The Chemical Hazard Identification Branch will transmit a
copy of this status report to OSHA, NIOSH, CPSC, FDA,
NCI/NTP, OPP/OPTS/EPA, ORD/EPA, OW/EPA, and OSWER/EPA. In
addition, a copy of the status report will be provided to
the Industry Assistance Office (IAO/OTS/OPTS/EPA) and to
the Office of Toxics Integration (OTI/OPTS/EPA) for
appropriate distribution.
351
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHq-0582-0445
::-P~ge 1 of 3
DATI:
JM t 6 1&
APprove~
Revision
Needed
6Jlb
,
SUIJECT. Status Report* 8EHQ-0582-0445
,.01&. Justine L. welb:1lAleam Leader
Chemical selec~nand Profiles Team/CHIB
T~ Frank D. Kover, Chief
Chemical Hazard Identification Branch/AD
Submission Description
The Sherwin-Williams Company submitted summarized preliminary
results from a 3-week rabbit dermal exposure study of 2-dodecyl-
9-H-thioxanthen-9-one (DTX; no known CAS Registry Number).
According to the submitter, oral reports received from the
pertorming laboratory indicated that DTX both bioaccumulated and
caused dose-dependent severe internal hemorrhaging in all
animals. Sherwin-Williams reported that a workup of retained
tissue samples and an analysis of blood samples were currently
underway.
In its submission, Sherwin-Williams noted that the 3-week dermal
application study of DTX was conducted based on the results of
acute toxicity tests which were submitted by the company to EPA
in a "premanufacturing Notice" (PMN #81-500) pursuant to Section
5 of the Toxic Substances Control Act (TSCA).
Submission Evaluation
As previously stated, the 3-week rabbit dermal application study
of DTX was initiated by the Sherwin-Williams Company to more
clearly define certain acute toxicity test results which were
submitted to EPA as part of PMN-81-500. The post-mortem findings
from those acute toxicity tests included internal hemorrhaging in
rabbits following a single high dose (2g/kg) of DTX applied to
the skin.
If the proposed and previously provided protocol for the 3-week
rabbit dermal application study was followed by the performing
laboratory, the reported preliminary findings that dermally
applied DTX both bioaccumulated and caused dose-dependent severe
internal hemorrhaging could be cause for concern depending on the
degree of human exposure to DTX and especially if such exposure
occurs via the dermal route. In addition, the reported finding
that DTX bioaccumulates is consistent with EPA's prediction which
was based on a log P value which was calculated for the compound.
-NOTE: T~is status reoo~t is the result of a creliminarv
staff evaluation of ir.formation submitted to EPA. State;e~ts
mace herein are no~ to be regarded as ex?ressing final
Age~cy policy or intent with res?ect to t~is ?articular
chemical. .~y review of the status report should take into
consideration the fact that it mav be based on incomolete
information. .. .
352
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8EHQ-0582-0445
Page 2 of 3
A more complete evaluation of the results of the 3-week study of
DTX is not possible without a complete copy of the final labora-
tory report which should include the final study protocol and all
data obtained at necropsy and from the post-mortem analyses of
retained tissue and blood samples.
Current Production and Use
In its TSCA Section 8(e) submission, Sherwin-Williams reported
that DTX is not a commercial product and that only 500 pounds of
DTX have been manufactured and sold under a Test Market Exemption
(TME #81-17) and extension. The company also reported in its
TSCA Section 8(e) submission that approximately 20 customers have
received samples of DTX.
In its application for a Test Market Exemption (TME #81-17), the
Sherwin-Williams Company reported that dodecylthioxanthone
(synonyms: DTX, UCI-200, Ultra-CureTM 1-200) was a yellow-brown
liquid composed mainly of mixed alkylthioxanthones with alkyl
side-chains varying in length from 10 to 14 carbon atoms with the
C12 alkyl component (dodecylthioxanthone) being the most
a5undant. The company also reported that the total alkylthio-
xanthone content was approximately 89%.
With regard to possible use patterns, Sherwin-Williams reported
in its DTX Test Market Exemption application that "the intended
use of this product is as a photoinitiator additive in UV light
cured inks and coatings" and that "conceivable application might
include notebook covers; brochures; display boards; signs; mirror
decoration; bottle, can and plastic cup exteriors; electrical
circuitry; wall coverings; and other areas that are traditionally
decorated with inks, coatings and paints."
In its Test Market Exemption application, Sherwin-Williams also
reported that in the use of this material in cured films,
concentrations of approximately 1% may exist and that dermal
exposure is possible. The company also reported, however, that
proper industrial hygiene observed during handling would insure
"zero or negligible exposure."
Comments/Recommendations
a) The Chemical Hazard Identitication Branch (CHIB/AD/EPA)
will request the Sherwin-Williams Company to provide a
complete copy of the final report including the final
study protocol and all data obtained from its 3-week
rabbit dermal application study of DTX. In addition, the
company will be requested to describe the actions it has
taken on a voluntary basis in response to the submitted
toxicity information to warn workers and others and to
reduce and/or eliminate exposure to DTX. The Sherwin-
Williams Company will also be asked about its plans to
conduct additional studies designed to further define the
toxicity of DTX.
353
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8EHQ-0582-0445
Page 3 of 3
b) The Chemical Hazard Identification Branch will screen
available information on DTX in order to determine the
need for further assessment.
c) The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, CPSC, FDA,
OSWER/EPA, OW/EPA, ORD/EPA, and CCD/OTS/EPA. A copy of
this status report will also be provided to the Industry
Assistance Office (IAO/OTS/EPA) and the Office of Toxics
Integration (OTI/OPTS/EPA) for appropriate distribution.
354
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0682-0446 S
Page 1 of 5
DAn:
JJt 2. .
APp::oved~
Revision
Needed
~P1
,
SUIJECT. Status Report* 8EHQ-0682-0446 S
nOM.
Justine L. wel\:>nAJeam Leader
Chemical sele~n~~nd Profiles
Team/CHIB
TO. Frank D. Kover, Chief
Chemical Hazard Identification Branch/AD
Submission Description
The Standard oil Company (Indiana), on behalf of the Amoco Oil
Company (a wholly owned subsidiary), submitted summarized pre-
liminary results from several sub-acute/sub-chronic in vivo (rat)
inhalation studies of selected naphtha refinery streams and a
hydrocarbon blend reported to contain one of those streams. Spe-
cifically, the tested substances were: 1) a full-range alkylate
naphtha (CAS No. 64741-64-6), 2) a light straight run naphtha
(CAS No. 64741-46-4), 3) a light catalytic cracked naphtha (CAS
No. 64741-55-5), and 4) a hydrocarbon blend containing approxi-
mately 22% full-range alkylate naphtha. The exact chemical
composition of the blend was claimed by the company as TSCA
Confidential Business Information.
The submitting company reported that a 21-day inhalation toxicity
study was conducted with the full-range alkylate naphtha. Accord-
ing to the company, groups (10 animals/sex/group) of mature
Sprague-Dawley rats were exposed to the test substance at graded
concentrations of 15.0, 5.0, or 1.5 mg/l in whole-body exposure
chambers for six hours per day for a total of 15 exposures in 21
days. Two other groups were exposed to either filtered or "en-
vironmental" air and served as controls. The company reported
that all of the animals were sacrificed at the end of the 21-day
period. The following table contains the reported preliminary
histopathology findings for degeneration/necrosis and regenera-
tion in the renal proximal tubules.
Exposure Level
Degeneration/Necrosis
Males Females
Regeneration
Males Females
15.0 mg/l
5.0 mq/l
1.5 mg/l
Filtered Air Control
Environmental Air Control
10/10
10/10
10/10
0/10
0/10
0/10
0/10
0/10
0/10
0/10
10/10
9/10
2/10
2/10
0/10
0/10
0/10
0/10
0/10
0/10
*NOTE: This status reco::t is the result of a crelirnina::v
staff evaluation of ir.formation submitted to EPA. State;ents
mace herein are not to be recrarded as eXDressinc final
Agency policy or intent with~res?ec~ to this particular
chemical. .~y review of the status report should take into
consideration the tact that it may be based on incomolet~
information. .. .
355
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8EHQ-0682-0446 S
Page 2 of 5
In a similar 21-day inhalation study on light straight run naph-
tha, the submitting company reported that although "nephropathic
effects in male rats were also observed," the results of the
study were "questionable due to a high incidence of respiratory
problems in all animals, including controls."
With regard to the results obtained from a 21-day inhalation
study conducted with light catalytic cracked naphtha, the sub-
mitter reported that "at the tested concentration levels of 0.2,
2.0, and 20.0 mg/l, no evidence of any treatment-related lesions
were observed."
The Standard oil Company (Indiana) also reported that a 90-day
inhalation study was conducted with groups (20 animals/sex/group)
of Sprague-Dawley rats exposed to a hydrocarbon blend containing
approximately 22% full-range alkylate naphtha. The company re-
ported that in this study, three groups of rats were exposed
(whole-body) to the blend at graded concentrations of 15.0, 1.5,
or 0.5 mg/l for six hours per day, five days per week for the 90
day period. As in the previous 21-day studies, two additional
groups of rats exposed to filtered or "environmental" air served
as controls. The submitter reported that at the end of the 90-
day period, 10 males and 10 females from each group were sacri-
ficed for histopathologic examination and the remaining rats held
for a recovery period of one month then sacrificed and examined.
The following table shows the reported preliminary histopathology
results for renal proximal tubular degeneration/necrosis observed
at the end of 90 days and following the I-month recovery period.
End of Exposure I-Month Recovery
Exposure Level Males Females Males Females
15.0 mg/l 5/10 0/10 4/10 0/10
1.5 mg/l 7/10 0/10 5/10 0/10
0.5 mg/l 1/10 0/10 1/10 0/10
Filtered Air Control 0/10 0/10 0/10 0/10
Environmental Air Control 0/10 0/10 0/10 0/10
Finally, the submitting company reported that a 21-day inhalation
study (similar to the other 21-day studies cited) of the hydro-
carbon blend "produced no evidence of kidney damage in rats
exposed to the same concentrations employed in the 90-day study."
Based on its reported data, the Standard Oil Company (Indiana)
stated that "there is reason to believe that certain naphtha
streams may be responsible for the degene'rative kidney effects
seen in males rats" and cited a previous TSCA Section 8(e) sub-
mission (8EHQ-I079-0312 et seq.; Exxon Company, U.S.A.) in which
similar adverse kidney effects in male rats exposed to ISOPAR C
(a light alkylate naphtha) were reported. The Standard Oil
Company (Indiana) also stated that "although highly speculative,
these effects might also be related to the kidney effects in male
rats reported [under TSCA Section 8(e)] by ARCO (8EHQ-1281-0422)
on studies performed by the American Petroleum Institute on a
356
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8EHQ-0682-0446 S
Page 3 of 5
reference unleaded gasoline." According to the draft final
report from the API's 2-year inhalation study of unleaded gaso-
line, kidney tumors (renal carcinomas) were found in male rats at
all dose levels tested (i.e., 67, 292, and 2056 ppm). Similar
lesions in female rats were reportedly not observed in the study.
Submission Evaluation
Although the Standard Oil Company (Indiana) submission does not
indicate the actual in-chamber test substance concentrations (the
tested concentrations reported are assumed to be estimated or
"target" levels), the provided information does indicate that the
observed nephrotoxic effect in male rats is real, in that the
observed adverse effect is both reproducible and dose-related.
Although the numbers of affected animals were reported in the
submission, neither the extent nor the severity of the renal
proximal tubule degeneration/necrosis or the extent of regen-
eration were indicated. In addition, the reportedly "question-
able" results of the 21-day inhalation study of light straight
run naphtha may not necessarily be that questionable, but may
actually tend to increase concern. The concern is due to the
reported observation of male-specific kidney toxicity despite the
presence of respiratory problems. Such problems would imply less
than normal alveolar ventilation resulting in lower than expected
doses. In general, all of the reported observations of degenera-
tion, necrosis, and regeneration should become more clear when
EPA receives complete copies of the final reports containing the
actual protocols and data obtained from the performed studies.
It should be noted that the dramatically greater sensitivity of
the male rat kidney to certain chemical substances is not a new
finding. As the submitter pointed out, Isopar C (which is a
light alkylate naphtha) is known to cause adverse kidney effects
in male but not female rats. In addition, other chemical sub-
stances (e.g., carbon tetrachloride, dicyclopentadiene, methyl-
dicyclopentadiene dimer, medium aliphatic solvent naphtha) have
also been reported (under TSCA Section 8(e) for the latter three
substances) to cause male-specific kidney toxicity in rats.
With regard to the submitter's speculation that the male-specific
kidney toxicity observed with exposure to certain of the tested
naphtha streams/blends might be related to the findings in the
API's chronic inhalation study of unleaded gasoline, it should be
noted that the Discussion and Conclusion section in the draft fi-
nal report of the latter study contains the following statement:
"Renal carcinomas were found in male rats at all three
[unleaded gasoline] exposure levels. Similar lesions
were not observed in the female rats. Simple explana-
tions for this difference, e.g., lower minute ventilation
rates for females than males, are probably not adequate
since the response was observed over a large concentra-
tion range. More probably, the difference is due to a
more fundamental difference between male and female rats."
357
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8EHQ-0682-0446 S
Page 4 of 5
In light of the previous statement, additional studies could be
conducted to examine the kidney effects of known male(rat)-
specific kidney toxicants in castrated or estrogen-treated male
and ovarectomized or androgen-treated female rats. The results
of such studies may help to clarify the observed male-specific
kidney toxicity in rats exposed to certain chemical substances.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for the CAS Registry Numbers 64741-64-6, 64741-46-4,
and 64741-55-5 (which are listed in the initial TSCA Inventory)
shows that in excess of 26, 64, and 64 billion pounds, respect-
ively, were reported as produced/imported in 1977. **/
The following definitions for the subject refinery streams were
obtained from the initial TSCA Chemical Substance Inventory:
Naphtha (petroleum), full range alkylate (CAS# 64741-64-6)
A complex combination of hydrocarbons produced by distillation
of the reaction products of isobutane and monoolefinic hydro-
carbons usually ranging in carbon number from C3 through C6.
It consists of predominantly branched chain saturated hydro-
carbons having carbon numbers predominantly in the range of C7
through C12 and boiling in the range of approximately 90°C to
220°C (194°P to 428°P).
Naphtha (petroleum), light straight-run (CAS# 64741-46-4)
A complex combination of hydrocarbons produced by distillation
of crude oil. It consists predominantly of aliphatic hydro-
carbons having carbon numbers predominantly in the range of C4
through CIO and boiling in the range of approximately -20°C to
180°C (-4°P to 356°P).
Naphtha (petroleum), light catalytic cracked (CAS# 64741-55-5)
A complex combination of hydrocarbons produced by the distil-
lation of products from a catalytic cracking process. It con-
sists of hydrocarbons having carbon numbers predominantly in
the range of C4 through Cll and boiling in the range of
approximately -20°C to 190°C (-4°P to 374°P). It contains a
relatively large proportion of unsaturated hydrocarbons.
**/ This production range information does not include any
production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it include
any information which would compromise Confidential Business
Information. The data submitted for the TSCA Inventory,
including production range information, are subject to the
limitations contained in the Inventory Reporting Regulations (40
CPR 710).
358
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8EHQ-0682-0446 S
Page 5 of 5
Comments/Recommendations
In its submission, the Standard Oil Company (Indiana) reported
its intention to request the American Petroleum Institute (API)
to pursue the preliminary findings of adverse kidney effects in
male rats. In addition, the company reported that due to the
unreliable results obtained in the 2l-day inhalation study of the
light straight run naphtha, another study is scheduled and that
the results, when available, would be provided to the Agency.
The Agency has received and evaluated an American Petroleum
Institute "For Your Information" submission (FYI-OTS-0382-0l71 et
seq.) containing final results from several acute in vivo
toxicity studies and preliminary results from an in-v~chronic
toxicity study of light catalytic cracked petroleum naphtha (CAS
No. 64741-55-5). The Agency has also received and reviewed many
other TSCA Section 8(e) and "FYI" submissions which have
contained both toxicity and/or exposure information on a variety
of synthetic fuel and petroleum process streams.
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request the Standard Oil Company (Indiana) to
provide, when available, complete copies of the final
reports including the test protocols and data from each
of the in vivo inhalation studies cited in its submis-
sion. In addition, the company will be requested to
describe the actions it has taken or plans to take on a
voluntary basis in response to the submitted data to warn
workers and others and to reduce or eliminate exposure to
the subject naptha streams.
b)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to OSHA, NIOSH, CPSC, DOE,
NCI/NTP, ORD/EPA, OANR/EPA, OW/EPA, OSWER/EPA, the OTS
Synfuels Workgroup, and the EPA Alternate Fuels Work-
group. In addition, a copy of this status report will
also be provided to the Office of Toxics Integration
(OTI/OPTS/EPA) and to the Industry Assistance Office
(IAO/OTS/EPA) for appropriate distribution.
359
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0682-0447
Page 1 of 3
DAT!;
11 It\) 2 8 19~
SUIJICT'Status Report* 8EHQ-0682-0447
App:oved
?J/XL
lij ~i
,
nOM. Justine L. we(~~/~am Leader
Chemical selectV0n and Profiles
TOr Frank D. Kover, Chie f
Chemical Hazard Identification
Revision
Needed
Team/CHIB
Branch/AD
Submission Description
The Sun Refining and Marketing Company provided the following
summarized final results from a chronic mouse skin-painting study
of 60 SUS @ 100°F viscosity grade light naphthenic distillate
(CAS No. 64741-52-2). The test material was reported to have
been applied at doses of 30 milligrams, three times per week for
2 years to 25 male and 25 female Charles River CD-l mice.
60 SUS @ 100° F VISCo GRADE
LIGHT NAPHTHENIC DISTILLATE
USP WHITE
MINERAL OIL
Epidermal Hyperplasia
Grade 1
Grade 2
7 of 50 (14%)
3 of 50 ( 6%)
2 of 50 (4%)
Epidermal Dysplasia
Grade 2
1 of 50 ( 2%)
11 of 50 (22%)
2 of 50 (4%)
According to the submitter, the obtained results indicate that
the tested distillate induced a statistically significant in-
crease in benign epidermal tumors when compared to USP white
mineral oil (control).
(NOTE: In a previous TSCA Section 8(e) submission (8EHQ-0278-
0044), the Sun Petroleum Products Company (now a part of the Sun
Refining and Marketing Company) reported that an extended 100°F
naphthenic oil product (a blend of four (4) petroleum distillate
streams) displayed tumorigenic activity (i.e., produced skin
tumors) in mice following chronic dermal application. The 60 SUS
@ 100°F viscosity grade light naphthenic distillate which is the
subject of the present 8(e) submission was reported in 8(e) sub-
mission 8EHQ-0278-0044 to be one of the four petroleum distillate
streams in the tested extended oil product).
-NOTE: T~is status reoo:t is the resul~ of a orelimina:v
staff evaluation of ir.forma~ion submitted to EPA. State;ents
mace herein are not to be recrarded as eXDressina final
Agency policy or intent with~res?ec~ to t~is ?articular
chemical. .~y review of the status repor~ should take into
consideration the fact that it may be based on incomplete
information.
360
- .
I:~& '01'. "" IJU:V. ~"I
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8EHQ-0682-0447
Page 2 of 3
Submission Evaluation
Based on the provided summarized information, it is unclear as to
the relationship which exists between the reported gradations of
epidermal hyperplasia/dysplasia and the reported induction of a
statistically significant level of benign skin tumors. This may
be clarified when the Agency receives a complete copy of the
final report including protocols and data from the chronic skin-
painting study.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for light naphthenic petroleum distillates (CAS No.
64741-52-2), as listed in the initial TSCA Inventory, has shown
that over 4.3 billion pounds were reported as produced/imported
in 1977. This production range 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 Confidential Business Informa-
tion. The data submitted for the TSCA Inventory, including
production range information, are subject to the limitations
contained in the Inventory Reporting Regulations (40 CFR 710).
The following definition for the subject petroleum distillate was
obtained from the initial TSCA Chemical Substances Inventory:
Distillates (petroleum), light naphthenic
(CAS# 64741-52-2)
A complex combination of hydrocarbons produced by vacuum dis-
tillation of the residuum from atmospheric distillation of
crude oil. It consists of hydrocarbons having carbon numbers
predominantly in the range of C15 through C30 and produces a
finished oil with a viscosity of less than 100 SUS at 100°F
(19cSt at 40°C). It contains relatively few normal paraffins.
Comments/Recommendations
The Sun Refining and Marketing Company reported that its employ-
ees had been notified of the "potential skin hazards associated
with prolonged or repeated contact with this oil and have attend-
ed educational sessions informing them how to protect themselves
when handling this oil." In addition, the submitting company
reported that it was eliminating 60 SUS @ 100°F viscosity grade
light naphthenic distillate from its product line. It should
also be noted that the Sun Petroleum Products Company reported
(in TSCA Section 8(e) submission 8EHQ-0278-0044) that the tested
extended oil product had been discontinued.
The Agency has received and reviewed many other TSCA Section 8(e)
and "For Your Information (FYI)" submissions which have contained
toxicity and/or exposure data on a variety of coal, shale, and
petroleum crude and distillate streams.
361
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8EHQ-0682-0447
Page 3 of 3
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request the Sun Refining and Marketing Company to
provide a complete copy of the final report including
protocols and data from its chronic mouse skin-painting
study of 60 SUS @ 100°F viscosity grade light naphthenic
distillate.
b)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to OSHA, NIOSH, CPSC, NCI/NTP,
DOE, ORD/EPA, OANR/EPA, OW/EPA, OSWER/EPA, the OTS Syn-
fuels Workgroup, and the EPA Alternative Fuels Workgroup.
A copy of this status report will also be provided to the
Office of Toxics Integration (OTI/OPTS/EPA) and to the
Industry Assistance Office (IAO/OTS/EPA) for appropriate
distribution.
362
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DAn:
J1 30 9J2
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0682-0448 S
Page 1 of 3
Approved {)J.r '0( ~
SUIJ£CT. Status Report* 8EHQ-0682-0448 S
'IOM. Justine L. Welcp~am Leader
Chemical select~nand Profiles
TO. Frank D. Kover, Chief
Chemical Hazard Identification
Revision
Needed
Team/CHIB
Brpnch/AD
Submission Description
The GAF Corporation submitted summarized results from several
short-term in vitro assays of 1-(2-hydroxyethyl)-2-pyrrolidinone
(CAS No. 3445-11-2). According to the submitter, the subject
compound demonstrated a positive mutagenic response in an 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/c-3T3 (mouse) Cell Transformation assays. With regard
to acute in vivo toxicity, the company reported that the chemical
shows "a very low potential for acute effects" as evidenced by an
acute oral LD50 (rats) of greater than 14 g/kg, negative results
obtained from primary rabbit skin irritation and guinea pig
sensitization studies, and observed mild conjunctivitis (clearing
on the second day) in a primary rabbit eye irritation study.
Submission Evaluation
1-(2-Hydroxyethyl)-2-pyrrolidinone was tested for reverse muta-
tion in the Ames (Salmonella typhimurium (bacteria)) test; for
specific locus mutation, sister chromatid exchange, and chromo-
somal aberrations in cultured Chinese hamster ovary (CHO) cells;
and for neoplastic transformation in cultured mouse cells.
According to the provided summarized information, 1-(2-hydroxy-
ethyl)-2-pyrrolidinone gave a positive response in the Ames test
and the activity was reduced by purification of the chemical.
However, because test data and protocols were not provided for
review, the validity of the latter interpretation is open to
question.
Although the results obtained from the CHO specific locus muta-
tion and sister chromatid exchange assays could be considered as
suggestive of positive, no conclusions can be drawn without a
review of the actual test data and protocols. In addition, there
was no indication in the submission that either of these assays
*NOTE: T~is status report is the resul~ of a oreliminarv
staff evaluation of ir.forma~ion submitted to EPA. State;e~ts
mace herein are not to be reaarded as ex~ressinc final
Agency policy or intent with.respect to t~is particular
chemical. .~y review 6f the status report should take into
consideration the fact" that it may be based on incomolete
information. .. .
363
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8EHQ-0682-0448 S
Page 2 of 3
were performed in the presence of metabolic activation. Before
any statement can be made about the chemical's activity or lack
thereof, it would be essential to review data from these assays
performed in the presence and absence of exogenous metabolic
activation.
The submitter stated that 1-(2-hydroxyethyl)-2-pyrrolidinone did
not induce chromosome aberrations in CHO cells and did not induce
neoplastic transformation in Balb/c-3T3 (mouse) cells. However,
no data were submitted to support this claim nor was there any
evidence presented in the submission that these assays were con-
ducted in the presence of metabolic activation. Again, it would
be necessary to perform these particular studies both in the ab-
sence and presence of metabolic activation. Therefore, in the
absence of data and information on the protocols used to test 1-
(2-hydroxyethyl)-2-pyrrolidinone, no conclusions can be drawn
about this chemical's ability to induce chromosomal aberrations
in cultured Chinese hamster ovary cells or its ability to induce
neoplastic transformation of cultured mouse cells.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for 1-(2-hydroxyethyl)-2-pyrrolidinone (CAS No. 3445-
11-2), which is listed in the initial TSCA Inventory, has shown
that no 1977 production/importation was reported or that all the
production range data reported were claimed as confidential by
the manufacturer(s)/importer(s) and cannot be disclosed. (See
Section 14(a) of TSCA, U.S.C. 2613 (a». **/
Although the GAP Corporation did not provide any information
concerning the uses of the subject chemical substance, the
company did report that because most of the uses of 1-(2-hydroxy-
ethyl)-2-pyrrolidinone are still being developed to full poten-
tial, the field volume of the chemical is low and its use is
being directed by technically qualified people. No information
on the use(s) of 1-(2-hydroxyethyl)-2-pyrrolidinone was located
in the secondary literature sources consulted.
Comments/Recommendations
Although a positive in vitro test result, when considered alone,
may not be sufficien~to offer reasonable support for a conclu-
sion of substantial risk, EPA believes that in vitro studies do
provide valuable data that can aid in assessIng possible risks
posed by chemicals to health and the environment. EPA also
believes that positive in vitro test results in combination with
additional information (e.g., knowledge of exposure to or high
**/The data submitted for the initial TSCA Inventory, including
production range information, are subject to the limitations
contained in the Inventory Reporting Regulations (40 CPR 710).
364
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8EHQ-0682-0448 S
Page 3 of 3
production of the chemical substance or mixture) would in many
cases suggest the need for further, more definitive toxicologic
study and the results considered for possible submission to EPA
pursuant to Section 8(e) of TSCA.
The GAF Corporation stated that the company is evaluating its
worker safety practices in the light of the submitted data in
order to assure continued compliance with the best current
practices. The company also reported that it plans to update its
literature and inform its customers of the submitted information.
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request the GAF Corporation to provide complete cop-
ies of the final reports including protocols and data
from all of the in vitro studies on 1-(2-hydroxyethyl)-2-
pyrrolidinone whTCh were cited in its submission. In
view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure information, CHIB will ask the GAF
Corporation if it is conducting, or plans to conduct,
additional studies designed to further define the
toxicity of 1-(2-hydroxyethyl)-2-pyrrolidinone.
b)
The Chemical Hazard Identification Branch will screen the
submitted information on l-(2-hydroxyethyl)-2-pyrrolidin-
one to determine the need for further assessment.
c)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, CPSC, ORD/EPA,
OW/EPA, and OSWER/EPA. In addition, a copy of the status
report will also be provided to the Office of Toxics In-
tegration (OTI/OPTS/EPA) and to the Industry Assistance
Office (IAO/OTS/EPA) for appropriate distribution.
365
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ~0682~0449 S
Page 1 of 3
DAU:
~~
I 5 198'2
Approved '{i1t--
Revision
Needed
1fjq
5UIJ£CT'Status Report* 8EHQ-0682-0449 S
flOMuustine L. Welch07~am Leader
Chemical select~~-~nd Profiles Team/CHIB
TOFrank D. Kover, Chief
Chemical Hazard Identification Branch/AD
Submission Description
Buckman Labortories, Inc. reported that 1,4-dioxane (CAS No. 123-
91-1) had been detected by gas chromatography-mass spectroscopy
in technical grade dichloroethyl ether (DCEE; CAS No. 111-44-4).
The submitter stated that the amounts of 1,4-dioxane found in two
separate lot~ of DCEE were 0.42 percent and 0.55 percent.
Submission Evaluation
In 1976, the International Agency for Research on Cancer (IARC)
concluded (IARC Mongraph, Vol. 11, 1976) that 1,4-dioxane was
"carcinogenic in rats and guineapigs" via oral administration in
that the compound "produced malignant tumors of the nasal cavity
and liver in rats and tumors of the liver and gall bladder in
guinea pigs." IARC also stated that 1,4-dioxane was "active as a
promoter" in a 2-stage mouse skin carcinogenicity study but was
not found to be carcinogenic in an inhalation study in rats.
Based on the results of a bioassay (DHEW (NIH) Publication No.
78-1330), the National Cancer Institute (NCI) concluded that 1,4-
dioxane, administered via the drinking water, "induced hepato-
cellular adenomas in female Osborne-Mendel rats." From the same
study, NCI also concluded that the compound "was carcinogenic in
both sexes of rats, producing squamous cell carcinomas of the
nasal turbinates, and in both sexes of B6C3Fl mice, producing
hepatocellular carcinomas." In addition, like many polyethylene
glycols, 1,4-dioxane (an anhydride of diethylene glycol) can
produce toxic effects in the kidney and liver (in humans). A
characteristic nephrosis of the kidney tubules (hydropic degener-
ation) with associated liver cell necrosis can occur regardless
of the route of 1,4-dioxane exposure (i.e., via inhalation, oral
ingestion, and/or skin application).
It should also be noted that an evaluation of data on dichloro-
ethyl ether (which is structurally related to the known carcino-
gen bis(chloromethyl)ether) was conducted by the International
Agency for Research on Cancer (IARC Monograph, Vol. ~, 1975).
-NOTE: T~is status recort is the result of a crelimina:v
staff evaluation of ir.formation submittec to EPA. Stace;ents
mace herein are not to be regarded as expressing final
Agency policy or intent with respect to t~is particular
chemical. .~y review 6f the status repor~ should take into
consideration the fact" that it may be based on incomolete
information. . ..
366
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8EHQ-0682-0449 S
Page 2 of 3
According to IARC, orally administered dichloroethyl ether "pro-
duced an increased incidence of liver-cell tumours in male mice
of two strains" and subcutaneously injected dichloroethyl ether
"produced a low incidence of sarcomas at the injection site." In
addition, it is known that dichloroethyl ether and its vapors are
highly irritating to skin, eyes, and mucous membranes; acutely
toxic amounts of dichloroethyl ether have been shown to penetrate
rabbit skin. '
With regard to the present submission, it should be noted that
the possibility exists that there may be some degree of synergism
or antagonism between DCEE and 1,4-dioxane which may affect the
ultimate oncogenic (or other toxic) activity of the two chemicals
in combination.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for dichloroethyl ether (CAS No. 111-14-4), which is
listed in the initial TSCA Inventory, has shown that between 2.4
million and 24 million pounds of this chemical were reported as
produced/imported in 1977. **/
Dichloroethyl ether is a general
bricating oils; textile scouring
paints, varnishes, lacquers, and
fumigant.
solvent used in high grade lu-
and cleaning; organic syntheses;
finish removers; and as a soil
A review of the production range (includes importation volumes)
statistics for 1,4-dioxane (CAS No. 123-91-1), which is listed in
the initial TSCA Inventory has shown that between 2 million and
15 million pounds of this chemical were reported as produced/
imported in 1977. **/
The main use of 1,4-dioxane is as a stabilizer in chlorinated
solvents. The chemical is also used as a solvent for cellulose
acetate, ethyl and benzyl cellulose, resins, oils, waxes, and
certain dyes; as a solvent for electrical, agricultural, and
biochemical intermediates, and as a solvent for adhesives,
sealants, cosmetics, pharmaceuticals, rubber chemicals, and
surface coatings.
**/This production range information does not include any
production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it include
any information which would compromise Confidential Business
Information. The data submitted for the TSCA Inventory,
including production range information, are subject to the
limitations contained in the Inventory Reporting Regulations (40
CFR 710).
367
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8EHQ-0682~0449 S
Page 3 of 3
Comments/Recommendations
Buckman Laboratories, Inc. reported that its employees and cus-
tomers were being notified of the presence of 1,4-dioxane in di-
chloroethyl ether. In addition, the company reported that its
current safety precautions include "body-protective clothing and
boots, eye protection, and monitoring of air levels of dichloro-
ethyl ether."
In 1974, the Occupational Safety and Health Administration (OSHA)
set the current occupational standard for exposure to dichloro-
ethyl ether at ceiling level of 15 ppm and established the cur-
rent occupational standard for 1,4-dioxane exposure at an 8-hour
time-weighted average (TWA) of 100 ppm in air (39 CFR 23540). In
1977, the National Institute for Occupational Safety and Health
(NIOSH) recommended that the occupational exposure to 1,4-dioxane
be controlled so that workers are not exposed at airborne concen-
trations greater than 1 ppm based on a 30-minute sampling period
(DHEW (NIOSH) Publication No. 77-226).
EPA has received and evaluated several other TSCA Section 8(e)
submissions concerning 1,4-dioxane contamination (8EHQ-1179-0320
et seq., Sherex Chemical Company; 8EHQ-0979-0326 S et seq., Shell
Oil Company; 8EHQ-0280-0331 S et seq./8EHQ-0380-0336 S et seq.,
Henkel Corporation). In addition, the Chemical Hazard Identifi-
cation Branch (CHIB/AD/EPA) has prepared a Chemical Hazard Infor-
mation Profile (CHIP) on 1,4-dioxane.
a)
The Chemical Hazard Identification Branch will
transmit a copy of this status report to NIOSH,
OSHA, CPSC, FDA, OW/EPA, OSWER/EPA, OANR/EPA, and
ORD/EPA. A copy of this status report will also be
provided to the Office of Toxics Integration (OTI/
OPTS/EPA) and to the Industry Assistance Office
(IAO/OTS/EPA) for appropriate distribution.
368
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UNITED STATES ENV IROHMEHTAL PROTECTION AGENCY
8EHQ-0682-0450
Page 1 of 3
DATI:
JUL 3 0 1982
SUUECT.
Status Report* 8EHQ-0682-0450
App::oved
, ~-8lo
\...' ..
nOM.
Justine L. wei~/vfeam Leader
Chemical Sele~tAon and Profiles
)
Frank D. Kover, Chief
Chemical Hazard Identification
Revision
Needed
Team/CHIB
TOI
Branch/AD
Submission Description
The Tennessee Eastman Company, a Division of the Eastman Kodak
Company, submitted summarized results extracted from a draft
paper entitled, "Comparative Inhalation Teratogenicity of Three
Glycol Ether Solvents in Rats" (B.K. Nelson et al.i National
Institute for Occupational Safety and Health (NIOSH)). The
submitting company stated that its TSCA 8(e) notification
pertains to 2-ethoxyethanol acetate (CAS No. 111-15-9), referred
to in the submission as 2-ethoxyethyl acetate, and that Eastman
manufactures and markets this chemical under the trade name
EKTASOLVE@ EE Acetate Solvent.
The following summary was provided by the Tennessee Eastman
Company:
"Pregnant rats were exposed to 2-ethoxyethyl acetate at 130,
390, or 600 ppm, 7 hours/day, on gestation days 7-15, and
were sacrificed on day 20. At 600 ppm, there was total embryo
lethality. At 390 ppm, there was increased embryo lethality,
fetotoxicity as shown by reduced fetal weight, and several
cardiac malformations. At 130 ppm, one fetus had a cardiac
malformation which was of the same type as one of those
observed at 390 ppm. Cardiac malformations rarely occur
spontaneously and none were observed in control fetuses. In
addition, the incidence of visceral and skeletal variations
was increased in exposed groups compared to controls."
The Tennessee Eastman Company also provided information on the
physical and chemical properties of EKTASOLVE@ EE Acetate
Solvent, as well as current production and employee exposure
data.
Submission Evaluation
The submitted summarized results indicate that 2-ethoxyethanol
acetate is teratogenic in rats dosed via inhalation for 7 hours/
.NOTE: This status recort is the result of a crelirnina::v
staff evaluation of ir.formation submitted to EPA. State;'e~ts
mace herein are not to be regarded as expressing final
Agency policy or intent with respec~ to t~is particular
chemical. .~y review of the status report should take into
consideration the fact that it mav be based on incomcletB
infC?rmation. 369" .
. .
I:~" '0". 11:0-. ."£Y. ..,.,
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8EHQ-0682-0450
Page 2 of 3
day with 600, 390 or 130 ppm of the chemical on gestation days 7-
15. The author of the paper (B.K. Nelson of NIOSH), stated in a
telephone conversation on July 15, 1982, that no maternal toxi-
city was apparent in this study at any dose level. However, the
author also stated that although animal weight data had been
collected, statistical analysis of these data had not yet been
performed. Because there was total embryo loss reported at 600
ppm, weight data for this dose group may not reflect maternal
toxicity. Embryo/fetal toxicity: including cardiac malforma-
tions, occurred at 390 ppm, while one cardiac malformation
occurred at 130 ppm. This dose level (130 ppm) is probably close
to the no-observed-effect level in rats.
Although the current OSHA standard for 2-ethoxyethanol acetate is
100 ppm as an 8-hour time-weighted average (TWA), the submitting
company stated that it has recommended a maximum workplace
exposure level of 5 ppm (TWA).
An additional consideration in the evaluation of
acetate toxicity is the teratogenic potential of
a hydrolysis product of 2-ethoxyethanol acetate.
could occur in the mucosa of the gastrointestinal
esterases in the liver and red blood cells.
2-ethoxyethanol
2-ethoxyethanol,
Hydrolysis
tract and from
Current Production and Use
A review of the production range (includes importation volumes)
statistics for 2-ethoxyethanol acetate (CAS No. 111-15-9), which
is listed in the initial TSCA Inventory, has shown that between
20 million and 100 million pounds of this chemical were reported
as produced/imported in 1977. **/
The Tennessee Eastman Company stated that 2-ethoxyethanol acetate
is currently manufactured in closed systems at two of its plant
sites, with a combined approximate annual production of 60
million pounds involving 90 employees. According to the
submitter, approximately 225 thousand pounds of 2-ethoxyethanol
acetate are handled at a third site in semi closed or open systems
by eight employees who may experience brief, limited exposures.
The submitter also reported that the Photographic Division of the
Eastman Kodak Company handles approximately 66 thousand pounds of
2-ethoxyethanol acetate annually in the formulation of its
photoresist products and for laboratory use. According to the
submitter, 12 employees are involved in these operations and
exposures are limited.
**/ This production range information does not include any
production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it includ€
any information which would compromise Confidential Business
Information. The data submitted for the TSCA Inventory,
including production range information, are subject to the
limitations contained in the Inventory Reporting Regulations (40
CFR 710).
370
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8EHQ-0682-0450
Page 3 of 3
According to secondary literature sources, the major uses of 2-
ethoxyethanol acetate include: a blush retardant in lacquers; a
solvent for oils, nitrocellulose, and resins; a component of wood
stains and varnish removers; and an ingredient in products for
the treatment of textiles and leather.
Comments/Recommendations
The Tennessee Eastman Company stated that it was notifying its
customers and employees of the 2-ethoxyethanol acetate toxicity
findings from the cited NIOSH study and provided the Agency with
a copy of its revised Material Safety Data Sheet on EKTASOLVE@ EE
Acetate Solvent. The company also stated that product labels
would be revised as soon as possible to reflect the new toxicity
findings. As previously mentioned, Eastman stated that it has
established a company industrial hygiene guideline for EKTASOLVE@
EE Acetate Solvent of 5 ppm as an 8-hour time-weighted average
(TWA). The company also reported that the Chemical Manufacturers
Association plans a teratology study to begin in mid-1982 and to
be complete by mid-1983.
The Chemical Hazard Identification Branch (CHIB/AD/EPA) has
prepared Chemical Hazard Information Profiles (CHIP's) on 2-
ethoxyethanol acetate and 2-ethoxyethanol. The Office of Toxic
Substances (OTS/OPTS/EPA) is currently conducting a detailed
assessment of 2-ethoxyethanol.
a)
The Chemical Hazard Identification Branch will request a
complete copy of the final report entitled "Comparative
Inhalation Teratogenicity of Three Glycol Ether Solvents
in Rats" directly from NIOSH in order to more completely
evaluate the findings reported by the Tennessee Eastman
Company. The requested report and its evaluation will be
considered during the review of the CHIP on 2-
ethoxyethanol acetate.
b)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, CPSC, OW/EPA,
OANR/EPA, HERD/OTS/EPA, TRDB/AD/EPA and to the "Solvents
Workgroup" of the EPA Toxic Substances Priorities
Committee (TSPC). CHIB will also provide a copy of this
status report to the Industry Assistance Office
(IAO/OTS/EPA) and to the Office of Toxics Integration
(OTI/OPTS/EPA) for appropriate distribution.
371
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0682-045l
Page 1 of 3
DAn:
J1 16 9rl
APproved?:fJL 7!J; r
I
SUIJICT. Status Report* 8EHQ-0682-045l
nOM. Justine L. Wel. ~m Leader
Chemical selec~nT:~d Profiles Team/CHIB
Revision
Needed
TO. Frank D. Kover, Chief
Chemical Hazard Identification Branch/AD
Submission Description
Borg-Warner Chemicals, Inc. reported that it had been verbally
informed by a laboratory in England that triphenyl phosphite (CAS
No. 101-02-0), dermally applied at doses of 500 and 5,000 mg/kg,
had been found to produce neurotoxic effects in chickens. The
company also reported that no effects had been observed thus far
at the 50 mg/kg dose level. According to the submitter, Tenneco
Chemicals, Synthetic Products Company, and Borg-Warner Chemicals,
Inc. are co-sponsors of the subject study.
In its submission, Borg-Warner stated that "it has been known for
many years and reported in the open literature that triphenyl
phosphite can produce neurotoxic effects in animals when taken
orally" and cited the following reference: "The Pharmacologic
Action of the Phosphorous Acid Esters of the Phenols", M. Smith
et al., J. Pharmacol. Exp. Ther., Vol. 49, 78-99 (1933).
In addition, Borg-Warner Chemicals, Inc. stated that the company
has "never observed any neurotoxic effects in ... [its employees
at its manufacturing] plant that could be attributed to triphenyl
phosphite" and also stated that the company has never received
information from customers claiming human neurotoxic effects due
to exposure to the chemical.
Submission Evaluation
Many organophosphorous chemicals (e.g., certain aryl phosphates)
are known to be absorbed dermally and pose a risk of neurotox-
icity via that route of exposure. As reported by the submitter
(and as demonstrated by Smith et ale (1933», triphenyl phosphite
is neurotoxic. The known symptoms of triphenyl phosphite neuro-
toxicity consist of early onset motor signs of acetylcholinester-
ase inhibition and delayed onset motor signs of neurotoxic target
protein (formerly referred to as neurotoxic esterase (NTE» inhi-
bition accompanied by axonal degeneration in both peripheral and
*NOTE: This status reco::t is the result of a crelirninarv
staff evaluation of ir.formation submittec to EPA. State;ents
mace herein are not to be re~arded as ex~ressina final
Agency policy or intent with~res?ec~ to t~is particular
chemical. .~y review 6f the status report should take into
consideration the iact that it may be based on incomolete
information. .
E~' '0". U::Dot IIU:V. ~'"
372
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8EHQ-0682-0451
Page 2 of 3
central neurons. While Smith et al. observed these types of ef-
fects in chickens exposed to triphenyl phosphite via the oral
route, these effects were also seen in rats and cats following
subcutaneous injection of the chemical.
In general, dermal exposure of hens to organophosphorus chemicals
is usually accomplished by application of the test substance to
the comb or to a patch of skin under the wing. Knowledge of the
relationship between the dermally applied doses/effects and oral-
ly administered doses/effects would help to estimate the degree
of the dermal absorption and also help to evaluate the relative
hazard/risk of dermal versus oral exposure to triphenyl phos-
phite. Although the duration of the ongoing study was not re-
ported, it is speculated that study most probably involves acute
or subacute dermal exposure. It should also be noted that a 90-
day delayed neurotoxicity study in hens would be appropriate for
establishing a no-observed-effect-level (NOEL) for the compound.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for triphenyl phosphite (CAS No. 101-02-0), which is
listed in the initial TSCA Inventory, has shown that between 10
million and 51 million pounds of this chemical were reported as
produced/imported in 1977. **/
Borg-Warner Chemicals, Inc. reported that it is the major U.S.
manufacturer of triphenyl phosphite and that the company has
produced the chemical since 1959. The submitter also reported
that the major use of triphenyl phosphite is as a stabilizer in
plastics. According to secondary literature sources, triphenyl
phosphite is also used as a chemical intermediate, a diluent for
epoxy resins, and as a metal scavenger.
Comments/Recommendations
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request Borg-Warner Chemicals, Inc. to provide a
complete copy of the final report, including test proto-
cols and data, from the co-sponsored neurotoxicity study
of triphenyl phosphite. In addition, Borg-Warner will
be requested to clarify its statement that no neurotoxic
effects that could be attributed to triphenyl phosphite
had been observed in company employees.
**/ This production range information does not include any
production/importation data claimed as con.fidential by the
person(s) reporting for the TSCA Inventory, nor does it include
any information which would compromise Confidential Business
Information. The data submitted for the TSCA Inventory,
including production range information, are subject to the
limitations contained in the Inventory Reporting Regulations (40
CFR 710).
373
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8EHQ-0682-0451
Page 3 of 3
b)
In light of EPA's general interest in company actions
that are taken on a voluntary basis in response to
submitted information, each of the study co-sponsors
will be requested to describe their actions taken to
warn workers and others, and to reduce and/or eliminate
exposure to triphenyl phosphite. In addition, the co-
sponsors will be asked if they are conducting or plan to
conduct other studies designed to further define the
neurotoxic potential of triphenyl phosphite.
c)
The Chemical Hazard Identification Branch will consider
the preparation of a Chemical Hazard Information Profile
(CHIP) on triphenyl phosphite.
d)
The Chemical Hazard Identification Branch will transmit
a copy of this status report to NIOSH, OSHA, CPSC, OW/-
EPA, OSWER/EPA, ORD/EPA and TRDB/AD/EPA. A copy of this
status report will also be provided to the Office of
Toxics Integration (OTI/OPTS/EPA) and to the Industry
Assistance Office (IAO/OTS/EPA) for appropriate distri-
bution.
374
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DAUI
ALG 3 1! f982
8EHQ-0882-0452
Page 1 of 3
APp:oved4,-
V
1f/er
SUIJIC:T. Status Report* 8EHQ-0882-0452
flOM. Justine L. Wel~am Leader
Chemical selec~n and Profiles
T~ Frank D. Kover, Chief
Chemical Hazard Identification
Revision
Needed
Team/CHIB
Branch/AD
Submission Description
The Eastman Kodak Company provided the following summarized
results from a 14-day feeding study of 4-chloro-3-nitroaniline
(CAS No. 635-22-3) in rats:
"Four groups of five male Sprague-Dawley rats were
fed ground feed containing 1% corn oil and 1%, 0.1%,
0.01%, and 0% 4-chloro-3-nitroaniline. Dosage rates
were calculated as 698, 87, 8.7 or 0 mg/kg/day, re-
spectively, for 14 days. There was a severe decrease
in the absolute and relative weights of the testes
for rats in the 1% dose group. Histopathology re-
vealed severely degenerated sperm in the testes and
epididymides and moderate atrophy of the semini-
ferous epithelium with minimal presence of multi-
nucleated giant cells. A single small area of clear
cells observed in the liver of a single rat mayor
may not be compound related since similar changes
are observed in unexposed older rats. These effects
were not observed for animals in the control group
or in the 0.1% or 0.01% dose groups."
In submitting this information to EPA, the Eastman Kodak Company
stated that no data were found in the literature that describe
the reported toxic effects for 4-chloro-3-nitroaniline. The
company did point out, however, that Bond et al. (Fundamental and
Applied Toxicology 1:389-394, 1981) observed similar lesions in
Fischer 344 male rats following single 200, 300, or 450 mg/kg
oral doses of nitrobenzene in corn oil. The lesions observed by
Bond et al. were characterized as "necrosis of spermatogenic
cells and the presence of multinucleated giant cells in the
testes with the replacement of spermatozoa in the epididymides
with necrotic debris."
,-
*NOTE: This status recort is the result of a crelirnina:v
staff evaluation of ir.formation submitted to EPA. State;e~ts
mace herein are no~ to be re~arded as exoressino final
Agency policy or intent with~res?ec't to t~is particular
chem~cal. .'~Y review 6f the status repor~ should take into
conslderatlon the fact that it may be based on incomo'ete
information. 375" . -
I:~A '0". ..... 'REV. ..",
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8EHQ-0882-0452
Page 2 of 3
Submission Evaluation
Although a complete evaluation of the seriousness of the reported
testicular toxicity is not possible due to the summary nature of
the submitted information, the provided data do indicate that the
observed adverse effects may be reversible. However, it should
be noted that because the study was not carried out for a full
spermatogenic cycle in the rat (60 to 70 days), it is possible
that more chronic testicular effects would not be reversible.
In view of the fact that the only other reported pathologic
effect was a small area of clear cells in the liver of a single
rat exposed to the chemical, it may be that the observed
testicular effects are among the more sensitive indicators of
exposure to 4-chloro-3-nitroaniline.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for 4-chloro-3-oitroaniline (CAS No. 635-22-3), which
is listed in the initial TSCA Inventory, has shown that between
100 thousand and 1 million pounds of this chemical were reported
as produced/imported in 1977. **/
With regard to its own production and use of 4-chloro-3-nitro-
aniline, Eastman Kodak stated that the chemical is manufactured
by the Tennessee Eastman Company and shipped to the Arkansas
Eastman Company where the compound is used solely as a reaction
intermediate. According to the submitter, 4-chloro-3-nitro-
aniline is insoluble in water and release to the environment is
"minimal to non-existent." In addition, Eastman Kodak reported
that the chemical is always handled as a "water wet solid" and
that the maximum air concentration is expected to be "less than 1
mg/m3." The Eastman Kodak Company also reported that although it
does not presently sell 4-chloro-3-nitroaniline, the chemical may
be sold in the future.
According to secondary literature sources, 4-chloro-3-nitro-
aniline is used as an intermediate in the manufacture of certain
azo dyes, pharmaceuticals, and other organic chemicals.
**/ This production range information does not include any pro-
duction/importation data claimed as confidential by the person(s)
reporting for the TSCA Inventory, nor does it include any infor-
mation which would compromise Confidential Business Information.
The data submitted for the TSCA Inventory, including production
range information, are subject to the limitations contained in
the Inventory Reporting Regulations (40 CFR 710).
376
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8EHQ-0882-0452
Page 3 of 3
Comments and Recommendations
In its submission, Eastman Kodak stated that the company had
taken the following actions in response to the reported toxicity
data: 1) company personnel handling 4-chloro-3-nitroaniline were
notified of the laboratory findings; 2) handling procedures were
reviewed to assure maximum safety in working with the chemical;
and 3) the product label for the chemical was updated to
incorporate the new toxicologic findings.
The Test Rules Development Branch (TRDB/AD/EPA) is currently
evaluating available toxicity/exposure data on 4-chloro-3-nitro-
aniline as it pertains to the Interagency Testing Committee
(ITC)-designated class of aniline and halogen/nitro-substituted
anilines (44 FR 31866). In addition, 4-chloro-3-nitroaniline is
listed in the EPA's June 22, 1982 TSCA Section 8(a) chemical
exposure information-gathering final rule (47 FR 26992).
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will screen the information contained in both the
initial submission and the recently received final
report from the 14-day feeding study of 4-chloro-3-
nitroaniline in rats (8EHQ-0882-0452 Supplement).
b)
In view of the Agency's general interest in company
actions that are taken on a voluntary basis in response
to submitted chemical toxicity/exposure information, the
Eastman Kodak Company will be asked if it is conducting,
or plans to conduct, additional studies designed to
further define the toxicity of 4-chloro-3-nitroaniline.
c)
The Chemical Hazard Identification Branch will transmit
a copy of this status report to NIOSH, OSHA, CPSC, FDA,
ORD/EPA, OW/EPA, OSWER/EPA, and TRDB/AD/EPA. A copy of
the status report will also be provided to the Industry
Assistance Office (IAO/OTS/EPA) and to the Office of
Toxics Integration (OTI/OPTS/EPA) for appropriate
distribution.
377
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0882-0453
;Page 1 of 3
DAn:
ALG 3 I 1982
App:oved tJJ- qM~o
Revision
Needed
SUIJECT. Status Report* 8EHQ-0882-0453
nOM. Justine L. welWwam Leader
Chemical sele~~-~nd Profiles Team/CHIB
TO. Frank D. Kover, Chief
Chemical Hazard Identification Branch/AD
Submission Description
The Union Carbide Corporation reported that the company had
received a preliminary and limited oral report from scientific
staff of the National Institute for Occupational Safety and
Health (NIOSH) concerning the incidence of gliomas in male rats
chronically exposed via inhalation to ethylene oxide (ETO; CAS
No. 75-21-8). According to Union Carbide, the following glioma
incidence data from the study were furnished by NIOSH:
Group Gliomas/Male Rats
o (Control) 0/38
50 ppm ETO 2/77
100 ppm ETO 5/79
According to NIOSH, the subject study involved Fischer 344 male
rats exposed to E10 via inhalation at the above doses for 7
hours/day, 5 days/week for 24 months. Further, NIOSH indicated
that a full final report (which is expected to be released in
early 1983) would be provided to EPA.
In its submission, Union Carbide reported that the company had
also submitted the glioma incidence data to EPA's Office of
Pesticide Programs pursuant to the Section 6(a)(2) and Rebuttable
Presumption Against Registration (RPAR) provisions of the Federal
Insecticide, Fungicide and Rodenticide Act (FIFRA). In providing
this information to EPA, Union Carbide stated that neither the
biological nor statistical validity of the subject data had been
determined.
-NOTE: T~is status reco~t is the result of a crelirninarv
staff evaluation of ir.formation submittec to EPA. State;e~ts
mace herein a~e not to be recrarded as ex~ressir.a final
Agency policy or intent with-respect to t~is ?articular
chemical. .~y review 6f the status report should take into
~onsideration the fact that it may be based on incomplet~
1nforma tion.
- .
I:~A "0". 11»4 UIII:V. ..",
378
-------
8EHQ-0882-0453
rage 2 ox 3
Submission Evaluation
Although the oncogenicity data contained in the present submis-
sion are both preliminary and limited in nature, there does
appear to be a relationship between the level of ethylene oxide
exposure and the glioma incidence. It should be noted that
gliomas, which are tumors of the supporting structures of nervous
tissue, are not considered common tumors in Fischer 344 rats.
Further evaluation of the submitted (and other) findings should
be possible when the full final report is released by NIOSH in
early 1983.
In general, human and animal exposure to ethylene oxide can re-
sult in irritation to eyes, skin, and respiratory tract, central
nervous system (CNS) depression, and possibly peripheral neuro-
pathy. Degenerative changes in the lungs, liver, and kidneys of
animals have been observed following acute exposures to ETO at
high concentrations. Adverse reproductive system effects due to
ETO exposure have been detected in rats (embryo/fetotoxicity),
mice (teratogenicity), and humans (decreased sperm counts).
Ethylene oxide has been shown to be mutagenic in in vitro and in
vivo studies. The chemical has also been found to-induce clas~
togenic effects (chromosomal aberrations) and increased numbers
of Sister Chromatid Exchanges (SCEs) in peripheral lymphocytes in
both humans and animals. In addition, ethylene oxide has been
found to be carcinogenic via inhalation in rats causing periton-
eal mesotheliomas and mononuclear cell leukemia and via sub-
cutaneous injection in mice causing injection-site sarcomas.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for ethylene oxide (CAS No. 75-21-8), which is listed
in the initial TSCA Inventory, -has shown that between 1.46
billion and 5.36 billion pounds of this chemical were reported as
produced/imported in 1977. This production range information
does not include any production/importation data claimed as
confidential by the person(s) reporting for the TSCA Inventory,
nor does it include any information which would compromise
Confidential Business Information. The data submitted for the
TSCA Inventory, including production range information, are
subject to the limitations contained in the Inventory Reporting
Regulations (40 CFR 710).
According to the July 5, 1982 issue of Chemical & Engineering
News, annual U.S. ethylene oxide production is expected to remain
stable at approximately 5.2 billion pounds until at least 1983.
The major use of ethylene oxide is as an intermediate in the
production of ethylene glycol, acrylonitrile, ethanolamine,
glycol ether, and non-ionic surfactants. The chemical is also
used as a sterilant and fumigant.
379
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8EHQ-0882-0453
Page 3 of 3
Comments/Recommendations
In 1974, the Occupational Safety and Health Administration (OSHA)
set the current occupational standard for ethylene oxide exposure
at an 8 hour time-weighted average (TWA) of 50 ppm in air (39 CFR
23540). In 1977, the National Institute for Occupational Safety
Health (NIOSH) prepared a Special Occupational Hazard Review with
control recommendations for the use of ethylene oxide as a steri-
lant in medical facilities (DHEW (NIOSH) Publication No. 77-200).
In that review NIOSH recommended (based on the results of tests
for mutagenicity) that exposure be controlled so that workers
would not be exposed to ethylene oxide at a concentration greater
than 75 ppm (determined during a 15 minute sampling period) as a
ceiling occupational exposure limit and with the provision that
the TWA concentration limit of 50 ppm for a workday not be ex-
ceeded. Based primarily on the results of an industry-sponsored
study showing ethylene oxide to be carcinogenic rn rats, NIOSH
further recommended (Current Intelligence Bulletin #35; May 22,
1981) that ethylene oxide be regarded in the workplace as a
potential occupational carcinogen and recommended that appropri-
ate controls be implemented to reduce worker exposure to the
chemical. At present, the Occupational Safety and Health Admin-
istration (OSHA) is re-evaluating the existing current occupa-
tional health standard which regulates employee exposure to
ethylene oxide. OSHA is currently reviewing comments received on
its January 26, 1982, Advance Notice of Proposed Rulemaking for
Occupational Exposure to Ethylene Oxide (ANPR; 47 FR 3566). In
addition, the EPA's Office of Pesticide Programs (OPP/OPTS/EPA)
is currently evaluating (via its RPAR process) toxicity/exposure
data on ethylene oxide.
The EPA's Office of Toxic Substances (OTS/OPTS/EPA) has received
and evaluated other TSCA Section 8(e) submissions on ethylene
oxide (8EHQ-I078-0248 et seq. and 8EHQ-0979-0305 et seq.). In
addition, OTS has received and reviewed two "For Your Information
(FYI)" submissions on ethylene oxide (FYI-OTS-0280-0058 et seq.
and FYI-OTS-0981-0123 et seq.). The Chemical Hazard Identifi-
cation Branch (CHIB/AD/OTS/OPTS/EPA) has completed a draft
Chemical Hazard Information Profile (CHIP) on ethylene oxide and
the Test Rules Development Branch (TRDB/AD/OTS/OPTS/EPA) is
currently evaluating toxicity/exposure data on alkyl epoxides as
recommended by the Interagency Testing Committee (42 FR 55026).
In addition, ethylene oxide is listed in the EPA's June 22, 1982,
TSCA Section 8 (a) chemical exposure information-gathering final
rule (47 FR 26992).
a)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, CPSC, FDA,
NCI/NTP, ORD/EPA, OW/EPA, OSWER/EPA, OANR/EPA, OPP/OPTS/-
EPA, and TRDB/AD/EPA. A copy of this status report will
also be provided to the Office of Toxics Integration
(OTI/OPTS/EPA) and to the Industry Assistance Office
(IAO/OTS/EPA) for appropriate distribution.
380
-------
DATIl
SEP 20m2
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0882-0454
Page 1 of 3
SUIJICT'Status Report* 8EHQ-0882-0454
Approved
~ ?/;2?
'.~Justine L. wel~~iam Leader
Chemical sele~-;nd Profiles
Revision
Needed
Team/CHIB
TOrFrank D. Kover, Chief
Chemical Hazard Identification Branch/AD
Submission Description
The Celanese Corporation submitted the final results of a chronic
(lifetime) mouse skin-painting study of pentaerythritol triacryl-
ate (PETA; CAS No. 3524-68-3) which was reported to contain vary-
ing amounts of pentaerythritol diacrylate (CAS No. 53417-29-1)
and pentaerythritol tetraacrylate (CAS No. 4986-89-4).
According to Celanese, "the shaved backs of 50 mice were painted
twice per week for 18 months with 50 mg of a 5% solution of the
test chemical [PET A] in mineral oil. A positive control group of
50 mice was treated with benzo-a-pyrene. There were two control
groups of 50 mice each. One of the control groups received no
treatment; the other was painted with mineral oil only. Each was
held for the duration of the experiment to observe background
tumor rates. Six of 43 surviving animals in the test group
developed lymphomas primarily of the spleen, compared to none of
48 animals in the "no treatment" control group and one of 49
animals in the mineral oil control group." Further, Celanese
reported that the following conclusions were drawn from the
results obtained from the performed study:
"1. )
The incidence of lymphomas seen in animals treated with
PETA is most likely treatment related.
2. )
The data suggest the PETA is absorbed through the skin
and may act as an internal carcinogen to lymphoid
systems."
Submission Evaluation
The performed mouse skin-painting study results show that PETA
causes slight dermal toxicity and can adversely affect several
internal organ systems. Such results indicate absorption through
the skin. Considering the slight dermal toxicityc however, it is
impossible to determine whether intact skin serves as a barrier.
-NOTE: T~is status report is the resul~ of a preliminary
staff evaluation of ir.formation submittec to EPA. Statements
mace herein are not to be re~arded as exoressina final
Age~cy policy or intent with-res?ec~ to t~is particular
chemical. .~y review 6f the status repor~ should take into
consideration the fact that it may be based on incomplete
inf~rmation. 381
.
,,,,,- ;0"'. ..~ 'Rey. ~,..
-------
8EHQ-0882-0454
Page 2 of 3
Following 18 months of twice weekly dermal PETA exposure, there
was not only an increase in lymphomas of the spleen, but toxic
effects in the kidney, including degeneration and pyelonephritis
(not observed in the controls), adrenal inflammation, and prosta-
titis. There was also a number of cases of prostatic hyperplasia
which did not correspond with those animals having prostatitis.
In addition, about 30% of the PETA-treated animals had atrophic
gonads, compared with approximately 1-2% of the controls. Al-
though the degree of gonadal atrophy was described as +1 to +2,
the numbering system was not more specifically defined. With
this percentage of animals affected, however, reproductive tox-
icity may be considered a possibility from extended exposure to
the test material.
It should also be noted that there seems to be some discrepancy
concerning the number of animals in_the PETA-treated group.
Although the submitter's cover letter referred to 43 survivors,
Table 1 of the final report indicated that the final effective
number was 35, whereas Table 5 listed 41 as the number of mice
examined. No explanation for these differences was given in the
submission.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for the. subject chemicals, which are listed in the
initial TSCA Inventory, has shown that the following ranges were
reported for 1977: **/
Chemical Name CAS No. Approx. Prod./Import.
Pentaerythritol triacrylate 3524-68-3 lXl05 to lXl06 pounds
Pentaerythritol diacrylate 53417-29-1 lXl03 to lXl04 pounds
Pentaerythritol tetraacrylate 4986-89-4 lXl05 to lXl06 pounds
Although no specific information was provided by the Celanese
Corporation concerning specific end-use(s) of PETA, it should be
noted that the material is a reactive monomer. No specific end-
use information for PETA was located in the secondary literature
sources consulted.
**/ The above production range 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 Confidential Business Informa-
tion. The data submitted for the TSCA Inventory, including
~roduction range information, are subject to the limitations
contained in the Inventory Reporting Regulations (40 CFR 710).
382
-------
8EHQ-0882-0454
Page 3 of 3
Comments/Recommendations
The Celanese Corporation reported that based on a review of its
current recommended handling and industrial hygiene procedures,
the company had concluded that those procedures afford adequate
protection from PETA exposure. The recommended handling/indus-
trial hygiene procedures reported by Celanese include avoiding
eye and skin contact via the use of impervious gloves and over-
shoes, protective clothing, and chemical safety goggles. The
Celanese Corporation also reported that copies of its submission
had been sent to the Occupational Safety and Health Administra-
tion (OSHA), the National Institute for Occupational Safety and
Health (NIOSH), and the National Cancer Institute (NCI).
The Agency has received and evaluated the following Section 8(e)
submissions containing the results of chronic mouse skin-painting
studies of compounds structurally related to pentaerythritol tri-
acrylate: 8EHQ-Ol78-0028 et seq., neopentyl glycol diacrylate,
Union Carbide Corporation; 8EHQ-098l-04l0 et seq., triethylene
glycol diacrylate, Celanese Corporation; and 8EHQ-098l-04ll et
seq., tetraethylene glycol diacrylate, Celanese Corporation. The
Chemical Hazard Identification Branch (CHIB/AD/OTS/EPA) has pre-
pared a Chemical Hazard Information Profile (CHIP) on neopentyl
glycol diacrylate and is currently considering the preparation of
CHIPs on triethylene glycol diacrylate and tetraethylene glycol
diacrylate.
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request the Celanese Corporation to provide, if
available, analytical data on the amount(s) of penta-
erythritol diacrylate and pentaerythritol tetraacrylate
typically found in PETA.
b)
The Chemical Hazard Identification Branch will consider
the preparation of a Chemical Hazard Information Profile
(CHIP) on pentaerythritol di-, tri-, and tetraacrylate.
c)
The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, CPSC, NCI/NTP,
OW/EPA, OSWER/EPA and ORD/EPA. A copy of thIS status
report will also be provided to the Office of Toxics
Integration (OTI/OPTS/EPA) and to the Industry Assistance
Office (IAO/OTS/EPA) for appropriate distribution.
383
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UNITED STATES E1-!VIRONMENTAL PROTECTION AGENCY
CIA 11:
OCT 2 I 1982
8EHQ-0982-0455
Page 1 of 3
Approved /~~J;{.-- k)J'/ -
SUIJECT, Stat us Report * 8EHQ-098 2-04 55
~
flOI6'Justine L. Wel earn Leader
Chemical Sele~ on and Profiles
Revision
Needed
Team/CHIB
TOr Frank D. Kover, Chief
Chemical Hazard Identification Branch/AD
Submission Description
The Celanese Corporation submitted complete copies of the final
reports from several short-term in vitro genetic screening assays
of the following commercial dyes:- Oil Yellow E190 (CAS No. 2481-
94-9) and Solvent Red 19 (CAS No. 6368-72-5). According to
Celanese, Oil Yellow E190 was found to be mutagenic in an Ames
(bacteria)' test in the presence of metabolic activation and in a
mouse lymphoma cell test both with and without metabolicactiva-
tion; Solvent Red 19 was reported to be active in the Ames and
mouse lymphoma cell tests only in the presence of metabolic
activation. In addition, Celanese reported that neither dye was
found to be active in cultured mammalian cell transformation
tests. In submitting these findings to EPA, Celanese stated that
the company had "made no assessment of the risks presented by
these dyes other than to determine their genotoxic potential."
Submission Evaluation
Oil Yellow E190 and Solvent Red 19 were tested for their ability
to induce gene mutations in bacteria (Salmonella typhimurium) and
mammalian cells in culture (mouse lymphoma L5178Y cells) and for
their ability to induce morphologic transformation in Balb/c 3T3
mouse cells in culture.
Oil Yellow E190 induced gene mutations in S. typhimurium strains
TA 98 and TA 100 when tested in the presence of an exogenous
source of metabolic activation. In addition, a dose related
increase in the number of revertant colonies was observed with
strain TA 1538 in the presence of metabolic activation. Although
the testing laboratory that performed this assay considered Oil
Yellow E190 to be nonmutagenic for this particular strain because
the induced mutation rate was not 3X background, this is an
arbitrary designation of a positive response. A review of the
data shows a dose related increase in revertant colonies which is
jUdged tQ constitute a positive response in TA 1538.
-NOTE: This status recort is the resul~ of a preliminary
staff evaluation of ir.formation submitteci to EPA. Sta~e;ents
mace herein are no~ to be re~arded as exoressina final
Age~cy policy or intent with~res?ec~ to t~is particular
chemical. .~y review 6f the status repor~ should take into
consideration the iac~ that it may be based on incomplete
information. 384
.-
E~' '0'''' 11::1)-& ""CY. ~'"
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8EHQ-0982-0455
Page 2 of 3
As reported, Solvent Red 19 did induce gene mutations in S.
typhimurium strains TA 1538, TA 98 and TA 100 when tested:ln the
presence of an exogenous source of metabolic activation.
In cultured mouse lymphoma L5178Y cells, Oil Yellow E190 induced
gene mutations when tested both with and without metabolic acti-
vation, while Solvent Red 19 induced mutation in these cells only
in the presence of an exogenous source of metabolic activation.
Although neither chemical induced morphologic transformation of
c~ltured Balb/c 3T3 mouse cells, the assays were not conducted
with metabolic activation. In the absence of such tests, no
conclusions can be drawn about the ability of either Oil Yellow
E190 or Solvent Red 19 to transform mammalian cells in culture.
It should be noted that in 1975, the International Agency for
Research on Cancer (IARC) conducted an evaluation of the carcino-
genic risk to humans from exposure to Solvent Red 19 (IARC Mono-
graph; Volume 8; 1975). Although IARC found that the existing
animal studies (performed via the oral route in rats) did not
demonstrate a significant increase in tumor incidence, the
studies were considered- by IARC to be inadequate for evaluation.
It should also be noted that Oil Yellow E190 (N,N-diethyl-4-
(phenylazo)benzenamine) is highly related structurally to the
known potent rat liver carcinogen, N,N-dimethyl-4-(phenylazo)-
benzenamine ("Butter Yellow"). Although the oral studies per-
formed to date have not shown Oil Yellow E190 to possess tumor-
igenic activity toward the rat liver, further studies of more
sophisticated design (e.g., using partially hepatectomized rats)
would need to be conducted in order to remove a continuing
suspicion that Oil Yellow E190 is also an oncogene
Current Production and Use
A review of the production range (includes importation volumes)
statistics for Oil Yellow E190 (CAS No. 2481-94-9), which is
listed in the initial TSCA Inventory, has shown that between 1
thousand and 12 thousand pounds of this chemical were reported as
produced/imported in 1977. **/ A review of the production range
(includes importation volumes) statistics for Solvent Red 19 (CAS
No. 6368-72-5), which is listed in the initial TSCA Inventory,
has shown that between 1 thousand and 11 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 confidential by the
person(s) reporting for the TSCA Inventory, nor does it include
any information which would compromise Confidential Business
Information. The data submitted for the TSCA Inventory,
including production range information, are subject to the
limitations contained in the Inventory Reporting Regulations (40
CFR 710).
385
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8EHQ-0982-0455
Page 3 of 3
According to secondary literature sources, Solvent Red 19 can be
used to color solvents, vegetable oils, fats, waxes, printing
inks, candles, mineral oils, synthetic resin lacquers, cellulose,
and plastics. Secondary literature sources indicate that Oil
Yellow E190 can be used to color hydrocarbon solvents, oils, fats
and waxes/polishes.
Comments/Recommendations
The Celanese Corporation reported that the manufacturers of both
dyes, the Occupational Safety and Health Administration (OSHA),
the National Institute for Occupational Safety and Health
(NIOSH), and the National Cancer Institute (NCI) had been
notified of the results of the performed in vitro genetic
screening studies. In addition, Celanese:reported that the
company is no longer considering the use of the tested dyes.
It should be noted that although a positive in vitro test result,
when considered alone, may not be sufficient-ro offer reasonable
support for a conclusion of substantial risk, EPA does believe
that in vitro studies do provide valuable data that can- aid in
assessing possible risks posed by chemicals to health and the
environment. EPA also believes that positive in vitro test
results in combination with additional information (e.g.,
knowledge of exposure to or high production of the chemical
substance or mixture) would, in many cases, suggest the need for
further, more definitive toxicologic study with the results of
such studies considered for possible submission to EPA pursuant
to Section 8(e) of TSCA.
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will screen the reported findings in order to determine
the need for further assessment of Oil Yellow E190 and
Sol vent Red 19.
b)
The Chemical Hazard Identification Branch will transmit a,
copy of this status report to NIOSH, OSHA, CPSC, FDA,
NCI/NTP, OW/EPA, OSWER/EPA, and ORD/EPA. A copy of this
status report will also be provided to the Office of
Toxics Integration (OTI/OPTS/EPA) and to the Industry
Assistance Office (IAO/OTS/EPA) for appropriate
distribution.
386
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0982-0456 S
Page 1 of 3
CI" TE:
nr,r ? 2 198'?
SIJIJ£CT'Status Report* 8ERQ-0982-0456 S
App:-oved (~ - /(.!~v~)-
, .
PlOM'Justine L. w~eam Leader
Chemical se~ion and Profiles
TO'Frank D. Kover, Chief
Chemical Hazard Identification
Revision
Needed
Team/CRIB
Branch/AD
Submission Description
The Gulf Refining and Marketing Company provided summarized
results from an acute rabbit eye irritation (Draize) test of Gulf
TS-905-HWCF. Although Gulf described the product as being a high
water content fluid, the chemical identities and weight per cent
of the fluid's ingredients were claimed by the company as TSCA
Confidential Business Information (CBI). According to Gulf, the
obtained results indicated that 0.1 ml of concentrated TS-905-
HWCF produced irreversible damage in unwashed eyes and damage of
a less severe nature in eyes rinsed with water 20-30 seconds
following instillation of 0.1 ml of the concentrated product.
The submitter reported that 0.1 ml of a 1 to 20 dilution of the
product in water was not considered to be a primary eye irritant.
According to Gulf, TS-905-HWCF is sent to customers in concen-
trated form and is diluted with 20 parts water by the customer
for use.
Submission Evaluation
Considering that TS-950-HWCF contains several chemical substances
which are known to be irritating and in some cases corrosive to
mucous membranes (and skin), it is not necessarily surprising
that the product in concentrated form was found to cause severe
eye damage. Although the 1 to 20 dilution was not considered by
the submitter to be a primary irritant, the concentrated product
appears to react avidly with corneal tissue. It should also be
noted that rinsing the eye shortly after exposure to the concen-
trated product was not completely effective in preventing
permament damage. The observed infiltration of the affected
corneas with blood vessels is a part of the healing process that
unfortunately causes serious and lasting impairment of vision.
An additional concern would be the possibility that following
dilution of TS-905-HWCF with 20 parts water; evaporation of the
aqueous phase could take place under the conditions of typical
use and/or storage thereby concentrating the product.
-NOTE: T~is status reco:-t is the resul: of a orelimina:-v
staff evaluation of ir.forma:ion submitted to EPA. State;e~ts
mace herein are not to be recrarded as eXDressir.c final
Asency policy or intent with~res?ec~ to t~is particular
chemical. .~y review 6f the status repor~ should take into
consideration the fact that it mav be based on incomotete
information. 387. .
E~& '0". u:z>...t '''C:Y. ~'"
-------
8EHQ-0982-0456 S
Page 2 of 3
Current Production and Use
In view of the submitter's claim of confidentiality, production/
importation range statistics from the TSCA Inventory for the
chemical ingredients of TS-905-HWCF will not appear in this
report.
According to Gulf, TS-905-HWCF contains water and a soluble
additive package comprised of corrosion inhibitors, antiwear
agents, and emulsifying agents. Gulf also reported that when
diluted with 20 parts water, TS-905-HWCF can be used in hydraulic
equipment operation at relatively high pressures.
Comments/Recommendations
Gulf Refining and Marketing Company reported that it plans to
alert (via product labelling) all potential handlers and users
about the observed TS-905-HWCF toxicity. In its submission, Gulf
provided EPA with a copy of the proposed product label containing
warnings and handling/first aid instructions.
Based on a preliminary review and evaluation of the chemical
toxicity/exposure information contained in 8EHQ-0982-0456 S, it
is EPA's preliminary determination that the provided acute rabbit
eye irritation results did not warrant submission to the Agency
under Section 8(e) of the Toxic Substances Control Act (PL 94-
469). The basis for EPA's position is as follows:
The preface to Part V of EPA's March 16, 1978, "Statement of
Interpretation and Enforcement Policy; Notification of
Substantial Risk" (43 FR 11110) states that "a substantial
risk of injury to health or the environment is a risk of
considerable concern because of (a) the seriousness of the
effect...and (b) the fact or probability of its occurrence."
With regard to the seriousness of the effect, Part V explains
that the Agency considers the health effcts 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, or toxic effects resulting
in death, or serious or prolonged incapacitation." The
information respecting these effects can be obtained directly
or inferred from designed studies (e.g. in vivo experiments
and tests as described in Part VI of the-Policy statement).
With regard to the "fact or probability of its occurrence"
criterion, Part V also explains that certain types of health
effects are so serious that relatively little weight should
be given to a chemical's exposure in determining whether a
risk is substantial.
EPA's response to Comment 14 in Appendix B of the March 16,
1978, policy statement provides additional guidance with
regard to the Section 8(e)-reportability of results obtained
from routine acute in vivo range finding tests such LD50
--
388
-------
8EHQ-0982-0456 S
Page 3 of 3
determinations, skin/eye irritation tests, etc. In its
response, EPA stated its belief that "many routine tests are
based on a knowledge of toxicity associated with a
chemical..." EPA's response also directed that unknown
effects which occur and are observed and/or determined during
acute in vivo range-finding tests may have to be reported if
those effects are serious and meet the reporting requirements
set forth in Parts V and VI of the policy statement.
Thus, when evaluating the results of acute animal toxicity
studies for submission to EPA under TSCA Section 8(e), the
Agency believes that submitting companies should consider
such factors as the lethal dose, pH, route of adminstration,
the occurrence of unexpected effects (which could be obtained
via "cage-side" observations, during necropsy, etc.), and the
extent and pattern of the exposure of the s~bject chemical
substance(s). In general, when evaluating such information
for Section 8(e) reporting, the greater the acute toxicity,
the less heavily companies should weigh the tested chemical's
exposure, and vice versa.
Based on the preceeding discussion, it is EPA's preliminary
determination that the results from the acute rabbit eye irrita-
tion study, as provided by the Gulf Refining and Marketing
Company in the present notice, did not warrant submission to the
Agency pursuant to TSCA Section 8(e). In making this determi-
nation, however, it must be understood that EPA may not be aware
of additional pertinent information which may have been available
to and/or considered by the company in reporting the subject
information under TSCA Section 8(e).
a)
The Chemical Hazard Identification Branch/AD will
request the Gulf Refining and Marketing Company to
provide its rationale as to why the reported results
offer reasonable support for a conclusion of substantial
risk of injury to health or the environment, as defined
in EPA's March 16, 1978, Section 8(e) policy statement
("Statement of Interpretation and Enforcement Policy;
Notification of Substantial Risk"; 43 FR 11110). The
company will also be requested to provide a complete
copy of the final report, including protocols and data,
from the rabbit eye irritation test cited in the notice.
b)
The Chemical Hazard Identification Branch will transmit
a copy of this status report to NIOSH and OSHA. A copy
of the status report will also be provided to the Office
of Toxics Integration (OTI/OPTS/EPA) and to the Industry
Assistance Office (IAO/OTS/EPA) for appropriate distri-
bution.
389
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0982~0457
Page 1 of 2
DAU:
OCT
5 1982
Approved ~ k>/~/ptr
SUIJ£CTI Stat us Report * 8EHQ-0 982-045 7
flOM'Justine L. ~Team Leader
Chemical sele(7i0n and Profiles Team/CHIB
TO'Frank D. Kover, Chief
Chemical Hazard Identification Branch/AD
Revision
Needed
Submission Description
The General Electric Company reported preliminary analytical
results from a study of groundwater flow and quality at the
company's capacitor manufacturing facility in Ft. Edward, New
York. According to General Electric, a groundwater sample taken
from a well near the southern boundary of the facility was found
to contain 2500 ppb (parts per billion) trichloroethylene, 4000
ppb trans-l,2-dichloroethylene, and 60 ppb l,l,l-trichloroethane;
a water sample taken from another well at the facility was
reported to contain 220 ppb trichloroethylene.
In addition, the General Electric Company reported that the New
York State Department of Health had recently sampled about twenty
(20) domestic water supply wells near the Ft. Edward facility and
that three (3) wells near the plant's southern boundary were
found to contain certain volatile synthetic organic chemicals in
excess of New York State Department of Health guidelines.
General Electric reported that in addition to the chemicals
mentioned above, vinyl chloride was detected by the State.
It should also be noted that the summarized supporting data
provided by General Electric indicate that trichlorobenzene, di-
2-ethylhexyl phthalate (DEHP), and polychlorinated biphenyls
(PCBs) were also detected in water samples taken by the company
from certain wells at its Ft. Edward facility.
Submission Evaluation
One of the most obvious concerns with regard to this type of
contamination would be the potential for human, animal, and/or
plant exposure to water containing toxic levels of chemical
pollutants. At sufficient doses and lengths of exposure, the
chemical substances cited in the present submission are known to
cause adverse mammalian and/or environmental effects.
*NOTE: T~is status report is the result of a crelimina=v
staff evaluation of ir.formation submitted to EPA. State;ents
mace herein are not to be regarded as ex?ressing final
Agency policy or intent with res?ect to t~is particular
chemical. .~y review of the status report should take into
consideration the fact that it may be based on incomplete
information.
390
. .
r~" '0". 11=>-4 '''C:Y. to,.,
-------
8EHQ-0982-0457
PC\ge 2 of 2
Current Production and Use
Due to the nature of this TSCA Section 8(e) submission, a review
of the production/importation ranges and use(s) of the subject
chemicals does not appear to be necessary at this time.
Comments/Recommendations
The General Electric Company stated that its groundwater study is
continuing and that the results will be reviewed with the appro-
priate New York State authorities.
a)
Immediately upon receipt of the General Electric Company
TSCA Section 8(e) submission, the Chemical Hazard Ident-
ification Branch (CHIB/AD/EPA) transmitted copies of the
notice to EPA's Region II Office, the Office of Water
(OW/EPA), the Office of Solid Waste and Emergency
Response (OSWER/EPA), the "Solvents Workgroup" of EPA's
Toxic Substances Priorities Committee (TSPC) and the PCB
Team in the Chemical Control Division (CCD/OTS/OPTS/EPA)
for any warranted and appropriate followup attention.
b)
The Chemical Hazard Identification Branch will provide
copies of this status report to the previously mentioned
EPA Offices/Workgroups/Teams and to the Office of Toxics
Integration (OTI/OPTS/EPA) and the Industry Assistance
Office (IAO/OTS/EPA) for appropriate distribution.
391
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0982-0458
Page 1 of 3
CIA n: ocr I 2 1982
flOMa.Justine L. Welcld)~m Leader
Chemical selec~~n and Profiles
TO. Frank D. Kover, Chief
Chemical Hazard Identification
APproved~
Revision
Needed
k>/>
S"'IJttTa Status Report * 8EHQ-0982-0458
Team/CHIB
Branch/AD
Submission Description
The Great Lakes Chemical Corporation reported the final results
from several Ames (bacteria) mutagenicity tests of the bis(2,3-
dibromopropyl ether) of tetrabromobisphenol A (CAS No. 21850-44-
2). According to the submitting company, although the results of
an earlier (1976) Ames test were negative, three purified samples
of the chemical were recently tested for mutagenicity (Ames test)
and found "to induce base-pair substitution mutation and. to show
detoxification to a large extent by the addition of S-9 activa-
tion mix." In a customer notification letter attached to the
submission, Great Lakes stated that the negative 1976 Ames test
was performed at a dose of 250 micrograms/plate whereas the
recently conducted Ames tests were performed at doses of 500
micrograms/plate or greater and yielded a dose-response for muta-
genicity. In that letter, Great Lakes also pointed out that the
dose level used in the 1976 Ames test was chosen on the basis of
toxicity range-finding protocols.
The Great Lakes Chemical Corporation reported that the bis(2,3-
dibromopropyl ether) of tetrabromobisphenol A has been a devel-
opmental chemical at the company for several years and a com-
mercial product in Europe during the last ten years. Great Lakes
also reported that European manufacturers had been questioned
about their mutagenicity findings with the subject chemical and
that the one European company responding thus far reported
negative results.
Submission Evaluation
Although Great Lakes indicated that its submission contained
complete copies of the final reports from the subject Ames tests
and copies of certain correspondence with the performing labor-
atory, these documents were not attached to the notice. Without
complete copies of those final reports (which should include data
-NOTE: T~is status report is the resul~ of a prelirninarv
staff evaluation of ir.formation submitted to EPA. Sta~e;e~ts
mace herein are no~ to be regarded as expressing final
Agen~y policy or intent with r~spec~ to t~is ?articular
chem~cal. .~y review of the status repo=~ should taK~ into
~ons1deration the iact tha~ it may be based on incomplete
lnforma tion.
392
..
E.-a '0". ..~ '"CV. ~"I
-------
8EHQ-0982-..0458
Page 2 of 3
and protocols), an evaluation of the reported in vitro mutagen-
icity is not possible. When Great Lakes was informed (by phone)
about the missing attachments, the company stated that the mis-
sing reports and correspondence would be transmitted to EPA as
soon as possible.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for the bis(2,3-dibromopropyl ether) of tetrabromo-
bisphenol A (CAS No. 21850-44-2), which is listed in the initial
TSCA Inventory, has shown that no 1977 production/importation was
reported or that all of the production range data reported were
claimed as confidential by the manufacturer(s) and importer(s)
and cannot be disclosed. (Section 14(a) of the TSCA, U.S.C. 2613
(a)). **/
In its submission, the Great Lakes Chemical Corporation stated
that "approximately 25,000 pounds of the compound have been sold
in the United States in the last several years with increased
volume expected in the next few years" and that the company
"presently manufactures the compound in Europe with the transfer
of manufacturing to the United States contingent on increased
sales volume."
In addition, Great Lakes reported that the major use of the
bis(2,3-dibromopropyl ether) of tetrabromobisphenol A is as "a
flame retardant in the insulation of electrical cable" and that
"some use may occur as a flame retardant in other polyolefin
applications in the future." With regard to exposure, the
company reported that "there will be negligible contact with the
material after installation, and the potential for significant
exposure during manufacturing and incorporation into the final
product is small."
Comments/Recommendations
The Great Lakes Chemical Corporation stated that its current and
known potential customers had been notified of the reported
positive mutagenicity results. In its submission, Great Lakes
provided a copy of both the customer notification letter and an
amended material safety data sheet for the subject chemical.
It should be noted that although a positive in vitro test result,
when considered alone, may not be sufficient~o offer reasonable
support for a conculsion of substantial risk, EPA does believe
that in vitro studies do provide valuable data that can aid in
assessing possible risks posed by chemicals to health and the
environment. EPA also believes that positive in vitro test
**/ The data submitted for the TSCA Inventory, including
production range information, are subject to the limitations
contained in the Inventory Reporting Regulations (40 CFR 710).
393
-------
8EHQ-0982-0458
Page 3 of 3
results in combination with additional information (e.g., know-
ledge of exposure to or high production of the chemical substance
or mixture) would, in many cases, suggest the need for further,
more definitive toxicologic study with the results of such
studies considered for possible submission to EPA pursuant to
Section 8(e) of TSCA.
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will ask the Great Lakes Chemical Corporation if it is
conducting or plans to conduct further studies designed
to better define the toxicity of the bis(2,3-dibromo-
propyl ether) of tetrabromobisphenol A.
b)
Upon receipt of the final reports and correspondence
cited in the initial submission, the Chemical Hazard
Identification Branch will screen the reported mutagen-
icity findings in order to determine the need for any
further assessment of the bis(2,3-dibromopropyl ether)
of tetrabromobisphenol A.
c)
The Chemical Hazard Identification Branch will transmit
a copy of this status report to NIOSH, OSHA, CPSC, OW/-
EPA, OSWER/EPA,' and 'ORD/EPA. In addition, copies of
this status report will be provided to the Office of
Toxics Integration (OTI/OPTS/EPA) and to the Industry
Assistance Office (IAO/OTS/EPA) for appropriate
distribution.
394
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-1082-0459/0460
Page 1 of 3
DAn:
ocr 2 5 1982
APproved~ 1~/~1~r
SUIJECT, *-8EHQ-I082-0459 & 8EHQ-I082-0460
,,01&, Justine L. Wel~eam Leader
Chemical selecet~n and Profiles Team/CHIB
TOIFrank D. Kover, Chief
Chemical Hazard Identification Branch/AD
Revision
Needed
Submission Description
In two separate submissions, the Atlantic Richfield Company pro-
vided summary results from acute animal eye/skin irritation
studies and a battery of short-term in vitro tests of dipropyl-
eneglycol diacrylate (DPGDAi 8EHQ-I082-0459) and pentaerythritol
monooleate triacrylate (PEMOTAi 8EHQ-I082-0460). The reported
results are summarized in the following table:
Type of Test
DPGDA
PEMOTA
Ames Test (bacteria)
Negative
Negative
Mouse Lymphoma Assay
(without activation)
Positive
Positive
Mouse Lymphoma Assay
(with activation)
Equivocal
Positive
Chinese Hamster Ovary (CHO) Cell
Sister Chromatid Exchange (SCE)
Assay (with/without activation)
Positive/
Positive
Nega ti vel
Negative
Eye/Skin Irritation Studies
(species not specified)
Severe
Severe
Atlantic Richfield reported that both DPGDA and PEMOTA were shown
to be "extremely toxic" to cultured mouse lymphoma and Chinese
Hamster ovary cells in the absence of exogenous metabolic activa-
tion and that the inclusion of metabolic activation resulted in a
several-fold reduction in the chemicals' toxicity in both assays.
Atlantic Richfield also reported that excess numbers of chromo-
somal breaks were noted in the cultured Chinese Hamster Ovary
(CHO) cells treated with PEMOTA and DPGDA. With regard to the
observed chromosomal breaks, Atlantic Richfield reported that
such breaks are not normally seen in the CHO cell Sister Chrom-
atid Exchange assay with other chemicals and further stated:
-NOTt: T~is status report is the result of a preliminary
staff evaluation of information submitted to tPA. Stateme~ts
mace herein are no~ to be recrarded as exoressinc final
Agency policy or intent with.respect to t~is ?articular
chemical. .~y review of the status report should take into
consideration the fact that it may be based on incomolete
informa tion. 395" .
E~'- ;0111. 11»-& ""::\1. ~"I
-------
8EHQ-I082-0459/0460
Page 2 of 3
"In the usual SCE assay, the CHO cells are allowed to go
through the two cell cycles which result in Hetaphase II
cells predominating. The toxicity of DPGDA [and PEMOTA]
evidently resulted in delaying the cell cycling time which
allowed some Metaphase I cells to be visualized. The chromo-
somal breaks mentioned above were noted in these Metaphase I
cells. However, in the SCE assay the chromosomal breaks
cannot be quantified due to the limitations of the test."
According to Atlantic Richfield, the performed studies were
initiated as part of the company's "continuing effort to develop
toxicological information on new chemicals which may be of
commercial value."
Submission Evaluation
Although the submitted summarized information indicates that both
DPGDA and PEMOTA are severely irritating to the eyes/skin and
possess some degree of in vitro cytogenic, mutagenic, and/or
clastogenic activity, an-evaluation of the reported findings is
not possible without complete copies of the final reports in-
cluding test protocols and data. According to the Atlantic
Richfield Company, these reports are now in preparation and upon
completion will be transmitted to EPA for review.
Current production and Use
In its submission, the Atlantic Richfield Company stated that
DPGDA and PE!1OTA are "novel" chemicals that are under development
as multifunctional acrylates designed to serve as cross-linking
agents in inks and coatings.
Neither dipropyleneglycol diacrylate (DPGDA; CAS Numbet 57472-68-
1) nor pentaerythritol monooleate triacrylate (PEMOTA; no CAS
Number assigned) were found to be listed in the non-confidential
portion of the Master TSCA Inventory File.
Comments/Recommendations
The Atlantic Richfield Company reported that R&D personnel "had
been advised to use caution and proper skin and eye protection
when handling [DPGDA and PEMOTA] to preclude any unnecessary ex-
posure." In addition, Atlantic Richfield stated that the "ARCO
Chemical Company has decided to postpone further development of
[DPGDA and PEMOTA] until the ramifications of the in vitro
results can be analyzed."
It should be noted that although a positive in vitro result, when
considered alone, may not be sufficient to offer reasonable
sup~ort for a conclusion of substantial risk, EPA does believe
that in vitro studies do provide valuable data that can aid in
396
-------
8EHQ-1082-0459j0460
Page 3 of 3
assessing possible risks posed by chemicals to health andjor the
environment. EPA also believes that positive in vitro test
results in combination with additional information (e.g.,
knowledge of potential exposure to or high production of the
chemical substance or mixture) would, in many cases, suggest the
need for further more definitive toxicologic study with the
results considered for possible submission to EPA pursuant to
Section 8(e) of TSCA.
EPA has received and evaluated the following TSCA Section 8(e)
submissions on acrylic acid esters of various glycolsjpolyols:
(neopentylglycol diacrylate, 8EHQ-0178-0028 et seq.; triethyl-
eneglycol diacrylate, 8EHQ-098l-04l0 et seq.; tetraethyleneglycol
diacrylate, 8EHQ-098l-04ll et seq.; and pentaerythritol di-, tri-
and tetra- acrylates, 8EHQ-0882-0454 et seq.). In addition, the
Chemical Hazard Identification Branch has prepared a Chemical
Hazard Information Profile (CHIP) on neopentylglycol diacrylate
and is currently considering the preparation of additional CHIPs
on acrylic acid esters of glycolsjpolyols.
a)
The Chemical Hazard Identification Branch (CHIBjADjEPA)
will request the Atlantic Richfield Company to ensure
that when submitted, the final reports of the cited
studies include complete copies of the test protocols
and data obtained. In addition, Atlantic Richfield will
be asked if the company is conducting or plans to con-
duct additional studies designed to further define the
toxicity of DPGDA and PEMOTA.
b)
The Chemical Hazard Identification Branch will screen
the information submitted by the Atlantic Richfield
Company on PEMOTA and DPGDA in order to determine the
need for further assessment of those particular chemical
substances. In addition, the Chemical Abstract Service
will be requested to assign a CAS Registry Number to
pentaerythritol monooleate triacrylate (PEMOTA).
c)
The Chemical Hazard Identification Branch will transmit
a copy of this stat~s report to NIOSH, OSHA, CPSC, FDA,
CCDjOTSjEPA, OWjEPA, OSWERjEPA, and ORDjEPA. A copy of
this report will also be provided to both the Office of
Toxics Integration (OTIjOPTSjEPA) and Industry Assist-
ance Office (IAOjOTSjEPA) for appropriate distribution.
397
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-l082-0461
Page 1 of 2
DAn:
SUIJECT. Status Report* 8EHQ-I082-0461
App:oved
/~
/.;/./1.
I
n"T
,.~ Justine L. Wel~am Leader
Chemical sele~n-~nd Profiles
Revision
Needed
Team/CHIB
TOt Frank D. Kover, Chief
Chemical Hazard Identification Branch/AD
Submission Description
Air Products and Chemicals, Inc. reported that it was recently
informed (via a private communication from E. I. du Pont de
Nemours & Company, Inc.) of the results of a chronic (IS-month)
feeding study of "chlorinated toluenediamine" in 'rats. According
to Air Products and Chemicals, Inc., the IS-month study was con-
ducted by Du Pont prior to 1976 and involved chlorinated toluene-
diamine dose levels of 1000 and 2000 ppm in the feed. The sub-
mitting company stated that although it does not have the actual
report(s) from the Du Pont study, liver tumors were reportedly
observed in animals at both dose levels with a higher incidence
of liver tumors observed in animals receiving the higher dose.
In its submission, Air Products and Chemicals, Inc. stated that
"chlorinated toluenediamine, because of its similiarity in
structure to toluenediamine which has been shown to cause cancer
in laboratory animals, has been treated in [the company's]
laboratory with the same cautions as those which are applied to
toluenediamine, itself." Air Products and Chemicals, Inc.
further stated that the Du Pont findings were not surprising
because "a number of phenylenediamines have been shown to cause
cancer in laboratory animals, and further validates th€ precau-
tions taken in [the Air Products and Chemicals, Inc.] laboratory
in the handling of chlorinated toluenediamine."
Submission Evaluation
Assuming (based on the submitter's chemical terminology) that the
ring is the site of chlorination, it is not necessarily surpris-
ing, as indicated by the the submitter, that some chlorinated
toluenediamines may possess oncogenic activity toward the rat
liver. In order to properly evaluate the significance of the
reported oncogenicity, however, a complete copy of the IS-month
-NOTE: This status reco:t is the result of a crelirnina:v
staff evaluation of ir.formation submittec to EPA. Sta~e;ents
mace herein are no~ to be regarded as expressing final
Ase~~y policy or intent with res?ec~ to t~is ?3rticular
chem~cal. ..~Y review 6f the status repor~ should take into
~onslderatlon the iact that it m3Y be based on incompleta
l.nformation.
398
.'
£~, '0". ..~ UII:V. ..,,,
-------
8EHQ-l082-0461
Page 2 of 2
chlorinated toluenediamine feeding study final report, including
the protocols, data, and results of statistical analyses (if
performed), is needed. Considering the fact that there are many
possible isomeric configurations for chlorinated toluenediamines,
the exact identity of the subject chemical(s) is also needed.
Current Production and Use
Air Products and Chemicals, Inc., reported that it "has been con-
ducting a research and development activity involving the synthesis
[and purification] of small quantities of chlorinated toluene-
diamine." The submitter also reported that "although some samples
of chlorinated toluenediamine have been utilized in experimental
polymers, their distribution has been very restricted, and the
amounts of chlorinated toluenediamine so utili7ed would be less
than 10 lbs."
A formal search ot the Master TSCA Inventory File for the subject
chlorinated toluenediamine(s) will be requested upon EPA's receipt
of the exact identity of the chemical substance(s).
Comments/Recommendations
In its submission, Air Products and Chemicals, Inc. stated that E.
I. du Pont de Nemours & Company, Inc. had been advised of the sub-
mitter's intention to report the subject oncogenicity findings to
EPA under Section 8(e) of TSCA.
The Test Rules Development Branch (TRDB/AD/EPA) is currently eval-
uating toxicity and exposure data for certain phenylenediamines as
recommended by the Interagency Testing Committee (ITC).
a)
E. I. du Pont de Nemours & Company, Inc. recentl~' Lnformed
EPA (by phone) that Du Pont will provide EPA with a copy of
the final report from the IS-month chlorinated toluene-
diamine feeding study in rats. The Chemical Hazard Identi-
fication Branch (CHIB/AD/EPA) will request Du Pont to en-
sure that EPA receives a complete copy of that final
report, including experimental protocols, data, and the
results of statistical analyses (it performed). In add-
ition, both Du Pont and Air Products and Chemicals, Inc.
will be requested to provide the exact identity of the
subject chlorinated toluenediamine(s).
b)
The Chemical Hazard Identification Branch will screen the
reported information in order to determine the need for
further assessment of the subject chemical substance(s).
c)
The Chemical Hazard Identification Branch will transmit
copies of this status report to NIOSH, OSHA, CPSC, OW/EPA,
OSWER/EPA, OANR/EPA, ORD/EPA, CCD/OTS/EPA, and TRDB/AD/-
EPA. Copies will also be sent to the Office of Toxics
Integration (OTI/OPTS/EPA) and Industry Assistance Office
(IAO/OTS/EPA) for appropriate distribution.
399
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-1182-0462
Page 1 of 6
DATE:
~,:=-("
8 19R?
SUIJ;;CTa sta tus Repo rt* 8EHQ-1182-0462
Justine L. Wel~~eam Leader
flowaChemical Se lectQ?n and Prof iles
App:oved
~- I)-I 1
Team/CHIB
Revision
Needed
Frank D. Kover, Chief
TOIChemical Hazard Ident i f ication Branch/AD
Submission Description
The Eastman Kodak Company provided summarized final results from
a 16-day male rat feeding study and several other acute/subacute
in vivo toxicity studies of p-nitrobenzamide (CAS No. 619-80-7).
With regard to the results obtained from the performed 16-day
feeding study, Eastman Kodak reported:
"The compound was added to rat chow at levels of 1.0%, 0.1%
or 0.0% with 1.0% corn oil and fed to 3 groups of five male
rats. The 1.0% group ate less feed and gained less weight
than the controls. The mean daily dose of compound was 426
mg/kg/day. The 0.1% group ate and gained weight normally:
the mean daily intake of the compound was 78 mg/kg/day. On
day 14 of the study four of the five rats on the 1.0% diet
developed unusual gaits. The animals walked with hyperex-
tension of the hindlimbs and overstepping with the hindpaws.
The tails were held unusually high while walking. Visual and
tactile placing, vestibular drop, and flexor reflexes were
normal. Weakness was not evident. Bowel and bladder control
was unaffected. The study was extended by two days for fur-
ther observation. On the fifteenth day, all rats in the 1.0%
group were equally affected. No progression of neurological
impairment was observed. The 0.1% group remained unaffected.
At autopsy, day 17, the clinical condition of the 1.0% group
was unchanged or slightly improved."
Eastman Kodak reported further that "compound-related histologic
abnormalities occurred in the brain, adrenal glands, testes,
epididymides, male accessory sex organs, pituitary, and adipose
tissue." The company also reported that renal hyaliri droplet
degeneration occurred in both the 1.0% and 0.1% groups. The
submitter stated, however, that because "the frequency of
degeneration was not dose-related and was similar to that which
occurs spontaneously in male rats...hyalin droplet degeneration
was not considered a compound-related effect." Eastman Kodak
also stated that "rats consuming the 0.1% diet showed no
compound~related effects."
.NOTE: This status report is the resul: of a prelimina:y
staff evaluation of ir.formation submittec to EPA. Stacements
mace herein are not to be re~arded as e~~ressina final
Agency policy or intent with~res?ect to this particular
chemical. .~y review of the status report should take into
~onsider~tion the fact that it may be based on incomplete
.lnforma t.lon.
400
. .
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8EHQ-1182-0462
Page 2 of 6
The following excerpts from the submission pertain to histopatho-
logic abnormalities observed in specific organs/tissues of the
male rats in the l6-day feeding study of p-nitrobenzamide:
Brain: "Brain lesions consisted of bilaterally sYmmetrical areas
of malacia [morbid softening] in the cerebellum and pons. Mala-
cia was limited to nuclear groups including the deep cerebellar
nuclei, ventral cochlear nucleus, lateral and superior vestibular
nuclei, and a nuclear group adjacent but dorsolateral to the
superior olivary nucleus. Vascular changes within affected areas
included perivascular hemosiderin [insoluble iron] deposition,
perivascular hemorrhage, and prominent vascular walls. Infil-
trating mononuclear phagocytic cells heavily cuffed occasional
vessels and were present within vacuolated areas."
Specifically with regard to the observed brain lesions, Eastman
Kodak noted that although a computerized search of the scientific
literature for toxicity data on p~nitrobenzamide was negative,
"similar areas of malacia have been described following single
oral doses of 450 mg/kg of nitrobenzene" and that "the descrip-
tions of lesion morphology and location suggest that the brain
lesions caused by nitrobenzene and p-nitrobenzamide may be
identical." In addition, the company pointed out:
"The cerebral lesions produced by nitrobenzene and p-nitro-
benzamide have a prominent vascular component and are located
in nearly the same transverse plane through the brain stem.
This particular region of the brain stem is at the distal end
of two arterial systems supplying the cerebellum and pons.
These systems include the basilar artery and the internal
carotid artery through the circle of Willis. This region of
the brain is thus in or near a "watershed" area which is
potentially susceptible to changes in arterial perfusion."
Adrenal glands: "Adrenal glands from all five rats in the 1.0%
group were altered. The most common effects were vascular
congestion in the zona fasciculata and zona reticularis and
cytoplasmic vacuolization of zona fasciculata. Fasciculata cells
also appeared diffusely enlarged or hypertrophied. Diffuse
necrosis of the zona reticularis was observed in [one rat] and
karyopyknosis [shrinkage of the nuclei] was observed in the same
region in [two other rats]. [One other rat] showed congestion
and hemorrhage in all areas of the cortex."
Reproductive System: "Reproductive effects included atrophy of
accessory sex organs in four rats, severe atrophy of testicular
spermatogenic epithelium, and near compiete absence of spermato-
zoa in the epididymides. A spermatic granuloma was also present
in an epididymis from [one] rat. In the testes, there was a
total absence of spermatozoa and spermatids. Spermatocytes and
spermatogonia were reduced but present. The most severely
affected tubules contained only Sertoli cells."
401
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8EHQ-ll82-0462
Page 3 of 6
Adipose Tissue: "All rats in the 1.0% group developed atrophy of
body adipose tissue."
Pituitary Gland:
acidophiles."
"[Two rats] showed degranulation of pituitary
With regard to the results obtained from other in vivo acute/-
subacute studies of p-nitrobenzamide, Eastman Kodak reported that
the L050 for male rats was 673 mg/kg and 476 mg/kg for female
rats with deaths occurring within two days of dosing. According
to the submitter, the clinical signs exhibited by the rats in-
cluded slight to severe weakness, shallow breathing, and decreas-
ed food consumption. The company also reported that the dermal
L050 (test species not identified) was in excess of 1000 mg/kg
with only slight skin irritation noted. In addition, the sub-
mitter reported that "only slight exacerbation of the original
minimal dermal effect" was observed following 10 daily applica-
tions (test species not identified) of p-nitrobenzamide as a 50%
weight/volume suspension in ethanol:glycerol (1:9). The company
also stated that p-nitrobenzamide was found to be only slightly
irritating to the eyes (test species not identified) and "did not
elicit an allergic contact dermatitis reaction in 10 guinea pigs
tested."
Finally, the Eastman Kodak Company reported that no adverse human
effects related to p-nitrobenzamide exposure have been observed.
Submission Evaluation
With regard to the reported neurotoxicity: the provided descrip-
tions of functional signs in exposed animals and central nervous
system (CNS) lesions were of a high quality and are, therefore,
most likely valid. The performed feeding study identified signs
of motor system dysfunction and widespread midbrain cell loss in
areas subserving a variety of functions. Effects were reported
after dietary exposure (1.0%) that also produced significant
decreases in food intake (a calculated dose of only 426 mg/kg)
but no effects were seen after the smaller dose (0.1%; 78
mg/kg). It is not clear what effects intermediate doses of
relatively short duration would have or what effects subchronic
doses (at least 90 days) would have.
The reported similarity of the obtained results to the neurotoxic
effects of nitrobenzene is generally valid and supported by the
existing literature on nitrobenzene both with respect to the
neurotoxic signs and pathology and their likely dependence on
cardiovascvlar and hematologic effects. It is well known that
nitrobenzene as well as many other amino- and nitroaromatics
produce methemoglobinemia, resulting in the deprivation of brain
tissue of oxygen (Smith, 1975). In addition, Smith noted that
"some aromatic amino and nitro compounds, such as aniline and
nitrobenzene, have central and prominent cardiac effects that in
some species, including man, appear to be the proximal cause of
death."
402
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8EHQ-1182-0462
Page 4 of 6
It should also be noted that there are "marked species differ-
ences in response to methemoglobin formers~ (Beard and Noe,
1981). Beard and Noe reported that man is about 10 times as
sensitive as the rat, although the relative contribution of
methemoglobinemia to observed toxic effects is unknown. In
addition, it has been suggested (Jacobs, 1978) that sensory
systems (including the visual system) are particularly sensitive
to changes in vascular permeability. Optic nerve pathology has
also been associated with nitrobenzene exposure (Yoshida, 1962)
and might well be expected for p-nitrobenzamide.
In general, the reported neurotoxicity and some of the other
reported toxic effects of p-nitrobenzamide are consistent with
those observed in humans and many animal species following
exposure to nitrobenzene (USEPA, 1980). Further evaluation of
the results obtained from the performed 16-day p-nitrobenzamide
feeding study will be possible following EPA's receipt of the
final report which should include the test protocol and data.
Current Production and Use
A review of the product~on range (includes importation volumes)
statistics for p-nitrobenzamide (CAS No. 619-80-7), which is
listed in the initial TSCA Inventory, has shown that between 2
thousand and 21 thousand pounds of this chemical were reported as
produced/imported in 1977. **/ In its submission, Eastman Kodak
stated that its annual production volume of p-nitrobenzamide is
expected to be approximately 50 thousand to 100 thousand pounds.
Eastman Kodak reported that p-nitrobenzamide is manufactured at
one plant site and then shipped to another plant site where the
chemical is used as an intermediate. Although the submitter
reported that the chemical is not found in the final product, the
nature of that product was not indicated in the submission.
With regard to potential occupational exposure to p-nitrobenz-
amide, Eastman Kodak reported that such exposure could occur at
the isolation step during the manufacturing process and during
unloading of the drummed chemical into a reactor for use as an
intermediate. According to the company, a total of eight people
(two people at a time) wearing organic vapor cartridge equipped
respirators, rubber aprons, and gloves are involved in the
manufacturing process and forty people (two people at a time)
wearing gloves are involved in dumping the drummed chemical into
**/ This production range information does not include any
-- production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it
include any information which would compromise Confidential
Business Information. The data submitted for the TSCA
Inventory, including production range information, are
subject to the limitations contained in the Inventory
Reporting Regulations (40 CFR 710).
403
-------
8EHQ-1182-0462
Page 5 of 6
the reactor. Eastman Kodak reported that the potential exposure
time for the forty individuals involved in the unloading opera-
tion would be approximately one hour per year.
with regard to actual measurements of occupational exposure to
p-nitrobenzamide, Eastman Kodak reported that two workplace air
monitoring studies conducted at the manufacturing facility have
show~ airborne p-nitrobenzamide concentrations r~nging from 2
mg/m to 40 mg/m3 with a median value of 18 mg/m (the length of
air sampling time was not given in the submission). The company
stated that professional review of the unloading operation indi-
cated that p-nitrobenzamide exposure at this stage should be very
low but did not indicate the nature of the information that
served as the basis for this judgment.
With regard to environmental release of p-nitrobenzamide, Eastman
Kodak stated that "approximately 3% of this material will be lost
in the waste water during manufacture and drained into the indus-
trial waste water treatment facility."
Comments/Recommendations
In its submission, Eastman Kodak stated that the previously
described routine handling procedures are expected to adequately
protect against the reported toxic effects. The company also
stated that a summary of the reported findings was being added to
information sheets for distribution to employees. In addition,
Eastman Kodak reported that aquatic toxicity tests of p-nitro-
benzamide were underway-
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request Eastman Kodak to provide complete copies of
the final reports, including test protocols and data,
from all of the mammalian toxicity studies cit'ed in the
initial submission. In addition, Eastman Kodak will be
requested to provide, when available, complete copies of
the final reports, including test protocols and data,
from the company's ongoing aquatic toxicity studies of p-
nitrobenzamide.
b)
The Chemical Hazard Identification Branch will screen the
reported information on p-nitrobenzamide in order to
determine the need for further assessment.
c)
The Chemical Hazard Identification Branch will transmit
copies of this status report to NIOSH, OSHA, CPSC, FDA,
OW/EPA, OSWER/EPA, ORD/EPA, and TRDB/AD/EPA. Copies will
also be provided to the Office of Toxics Integration
(OTI/OPTS/EPA) and to the Industry Assistance Office
(IAO/OTS/EPA) for appropriate distribution.
404
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8EHQ-1182-0462
Page 6 of 6
References
Beard RR, Noe JT. 1981. Aromatic Nitro and Amino Compounds.
In: Patty's Industrial Hygiene and Toxicology. 3rd edition.
Clayton GD, Clayton FE, eds. New York: Wiley. 2413-2490.
Jacobs JM. 1978. Vascular Permeability and Neurotoxicity-
In: Environmental Health Perspectives. 26; 107-116.
Smith RP. 1975. Toxicology of the Formed Elements of the
Bloods. In: Toxicology - The Basic Science of Poisons.
Casarett LJ, Doull J, eds. New York: Macmillian. 225-243.
USEPA.
1980.
TSCA Section 4 Nitrobenzene Support Document 8/80.
Yoshida T. 1962. Experimental Studies on the Pathohistological
Changes in Optic Nerves of Rabbits Administered Aniline or
Nitrobenzene. Japanese Journal of Industrial Health. 4; 12-29.
405
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-1l82-0463
Page 1 of 4
DAU:
DEC I 0 1982
S\.IIJ£C:T. Status Report* 8EHQ-1182-0463
App=oved
~ p-jJe
'101&. Justine Hel~eam Leader
Chemical se{fction and Profiles Team/CHIB
Revision
Needed
TOr Frank D. Kover, Chief
Chemical Hazard Identification Branch/AD
Submission Description
The Diamond Shamrock Corporation provided a translation of a
German draft summary from a report of a chronic (30-month) study
of sodium bichromate and calcium chromate administered at varying
doses via intratracheal instillation to groups containing 40 male
and 40 female Sprague-Dawley rats. In its submission, Diamond
Shamrock stated that although EPA is "aware of historic infor-
mation on the toxicologica~ properties of chrome and chrome com-
pounds, particularly in relation to Chrome VI compounds and lung
cancer," the company believed that its submission contained new
information about sodium bichromate.
The provided summary stated that it could be assumed that the
slightly soluble inorganic chromium VI compounds are carcinogenic
but that the carcinogenicity of the easily soluble chromium VI
compounds was still in question at least to the point that the
carcinogenic potential appears lower in the case of the more sol-
uble chromates. The stated purpose of the performed study was to
provide an answer to that question by comparing the tumorigenic
potential of calcium chromate (which is slightly water soluble)
to that of the more easily soluble sodium bichromate (dihydrate).
With regard to the test animals' appearance, behavior, food con~
sumption, and the results of clinical examinations, the summary
stated that there was no indication of toxic effects other than a
30 minute period of continuous and pronounced breathing difficul-
ty observed after the 415th day of the study in almost all rats
receiving a dose of 1.25 mg/kg sodium bichromate once per week.
With regard to carcinogenicity, the summary stated that "a car-
cinogenic effect was only produced by both chromates in the lung"
and that "there was no differences in intensity of effect between
the sodium dichromate and the dissolved calcium chromate."
-NOTE: T~is status reco=t is the resul~ of a crelirnina=v
staff evaluation of information submitted to EPA. Sta~e;e~ts
mace herein are not to be regarded as expressing final
Ase~cy policy or intent wi~h res?ec~ to t~is particular
chemical. .~y review 6f the status repor~ should take into
consideration the fact" that it may be based on incornoleta
information. .
406
- "
f~' ~o'n. .,:0-. IJlI:V. ~'"
-------
8EHQ-1182-0463
Page 2 of 4
The reported pathological results (excluding those from the posi-
tive and negative controls) are contained in the following table:
Chemical Lung Tumors
Test Dose Regimen Benign Mal ignan t
Sodium Bichromate 5 X 0.01 mg/kg/week 0 0
(dihydrate)
" 5 X 0.05 mg/kg/week 0 0
" 5 X 0.25 mg/kg/week* 0 0
" 1 X 0.05 mg/kg/week 0 0
" 1 X 0.25 mg/kg/week 1 0
" 1 X 1. 25 mg/kg/week 12 7t
Calcium Chromate 5 X 0.25 mg/kg/week 5 1
" 1 X 1. 25 mg/kg/week 11 3t
* previously determined max imum tolerated dose (MTD)
t includes one (1) doubtful lung tumor
with regard to the above results, the summary stated that for
"both chromates - on the same weekly dose - loading-dose treat-
ment (1 x /week) was more effective than when the same dose was
distributed between 5 administrations (5 x /week)," and that
"from this, it can be deduced that an even more uniform distribu-
tion (inhalation in man) possibly reveals an even weaker effect."
In conclusion, the performing laboratory stated that the obtained
results could be summarized in the following way:
"The very water-soluble sodium dichromate and dissolved cal-
cium chromate have a weak carcinogenic effect, when toxic
loading doses or massive doses lying within the maximal
tolerable dose range are absorbed over a very long period of
time~ The potential carcinogenic effect of water-soluble
dichromates is, as a result, slight. A uniform distribution
of the doses over the period has a weaker effect than mas-
sive doses. According to the rules of general carcinogen-
esis, rather would the opposite have been expected. The
results support the view that defence mechanisms, which can
be overcome by massive loading doses, are involved in the
case of the chromate investigated. The question remains of
how slightly soluble chromates behave under similar test
conditions."
407
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8EHQ-1182-0463
Page 3 of 4
Submission Evaluation
In general, the carcinogenic and genotoxic potential of chromium
compounds has been well established. Although carcinogenicity
has so far only been clearly established in animal bioassays with
hexavalent chromium, both hexa- and trivalent chromium are known
to be genotoxic. In addition, epidemiological evidence indicates
that chromium is carcinogenic in humans.
In view of this background, the observed induction of lung tumors
in rats by intratracheal instillation of sodium bichromate and
calcium chromate is not unexpected. Although the submitted data
are suggestive of a dose-response relationship with sodium bi-
chromate, the tumor incidences are so low that it is unlikely
that this relationship is statistically significant. It is also
highly unlikely that the difference between the malignant tumor
incidences of the 5 x 0.25 mg/kg/week and 1 x 1.25 mg/kg/week
groups receiving calcium chromate is statistically significant.
Moreover, in addition to the likely lack of statistical signif-
icance, the group sizes are too low to solidly establish the
findings in a way relevant to humans. It should also be noted
that the presented results are inadequate to support the conclu-
sion by the performing laboratory that "...defence mechanisms,
which can be overcome by massive loading doses, are involved in
the case of the chromates investigated."
Current Production and Use
A review of the production range (includes importation volumes)
statistics for sodium bichromate (CAS No. 10588-01-9), which is
listed in the initial TSCA Inventory, has shown that between 300
million and 1.2 billion pounds of this chemical were reported as
produced/imported in 1977. **/ A review of the production range
(includes importation volumeS) statistics for calcium chromate
(CAS No. 13765-19-0), which is listed in the initial TSCA Inven-
tory, has shown that between 14 thousand and 146 thousand pounds
of this chemical were reported as produced/imported in 1977. **/
According to secondary literature sources, sodium bichromate can
be used in the manufacture of pigments, in leather tanning, and
in electroplating operations; as a corrosion inhibitor, defol-
iant, catalyst, wood preservative, and a reactant in oxidative
reactions. Secondary literature sources report that calcium
chromate can be used as a pigment, corrosion inhibitor, battery
depolarizer, and oxidizing agent; and used in the preparation of
coatings for light metal alloys.
**/ This production range information does not include any pro-
duction/importation data claimed as confidential by the person(s)
reporting for the TSCA Inventory, nor does it include any infor-
mation which would compromise Confidential Business Information.
The data submitted for the TSCA Inventory, including production
range information, are subject to the limitations contained in
the Inventory Reporting Regulations (40 CFR 710).
408
-------
8EHQ-1l82-0463
Page 4 of 4
Comments/Recommendations
In the cover letter to its submission, the Diamond Shamrock
Corporation stated that although the company "has not concluded
that qualitatively or quantitatively there is any increase in
risk to health or the environment indicated by the preliminary
results of this study" the company believes that "work practice
and safety measures employed during the production of chrome
chemicals, training sessions given to employees, and information
supplied to customers on the safety precautions in use of chrome
chemicals minimize the potential of exposure to these products."
In 1974 and again in 1980, the International Agency for Research
on Cancer (IARC) evaluated the carcinogenic risk to humans posed
by exposure to chromium and chromium compounds (IARC Monographs;
Volume 2 (1974) and Volume 23 (1980)). The National Institute
for Occupational Safety and Health (NIOSH) published "Criteria
Documents" containing recommended standards for occupational ex-
posure to chromic acid (1973) and other chromium IV compounds
(1975). NIOSH has also published (1976) a "Current Intelligence
Bulletin" pertaining to chrome pigments. In addition, according
to a recently published National Toxicology Program (NTP) review
of the status of government-sponsored research, there are a
number of ongoing toxicologic studies of chromium and chromium
compounds.
A number of TSCA Section 8(e) and "For Your Information (FYI)"
submissions pertaining to chromium and chromium compounds have
been received and reviewed by EPA's Office of Toxic Substances.
In addition, a number of health and evironmental assessments of
chromium and chromium compounds have been prepared or are being
prepared by various Program Offices within EPA. Also, chromium
and/or certain chromium compounds are covered by authorities
(e.g., Clean Water Act) administered by EPA.
a) According to the Diamond Shamrock Corporation, the full
final report from the chronic intratracheal instillation
study will not be available until 1983. The Chemical Hazard
Identification Branch (CHIB/AD/EPA) will request Diamond
Shamrock to ensure that EPA receives a complete copy of the
final report including protocols and data as soon as that
report is received by the company.
b) The Chemical Hazard Identification
screen the reported information in
need for further OTS assessment of
substances.
Branch (CHIB/AD/EPA) will
order to determine the
the subject chemical
c) The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, CPSC, OW/EPA,
OSWER/EPA, OANR/EPA, and ORD/EPA. A copy of this report
will also be provided to the Office of Toxics Integration
(OTI/OPTS/EPA) and the Industry Assistance Office (IAO/OTS/-
EPA) for appropriate distribution.
409
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
BEHQ-1l82-0464
Page 1 of 2
DA TE: DEC I
J982
SUIJtCT. Status Report* 8EHQ-1182-0464
App:.-oved
~
/;./ I
nOM. Justine L. Welc~m Leader
Chemical selectL~n~~~d Profiles
Revision
Needed
Team/CHIB
TOI Frank D. Kover, Chief
Chemical Hazard Identification Branch/AD
Submission Description
Vulcan Chemicals (a division of the Vulcan Materials Company)
provided summarized results from two in vivo toxicologic studies
of chloromethane (methyl chlroride; CAS ~74-87-3) that were
carried out by CIIT (Chemical Industry Institute of Toxicology).
According to Vulcan Chemicals, male Fischer 344 rat reproduction
was "totally impaired" following inhalation exposure to 1500 ppm
chloromethane for 6 hours per day, 5 days per week for 10 weeks.
The submitter further stated that "histopathological evaluation
of 10 males in the exposed group confirmed a 100 percent inci-
dence of testicular atrophy and a 20 percent incidence of sperm
granuloma formation." In addi tion, Vulcan Chemicals reported
that a B6C3Fl mouse inhalation teratogenicity study conducted at
250, 500, or 750 ppm chloromethane "revealed a dose-dependent and
statistically significant increase in the incidence of heart
defects at the mid and high dose exposures."
Submission Evaluation
In its submission, Vulcan Chemicals stated that the Test Rules
Development Branch/Assessment Division/Office of Toxic Substances
(OTS) had received the subject studies directly from CIIT. The
evaluation of the reported and other toxic effects of chloro-
methane is being conducted by scientists in the Test Rules Devel-
opment Branch in conjunction with scientists in the Health and
Environmental Review Division/OTS. Chloromethane was initially
recommended in October 1977 by the Interagency Testing Committee
(ITC) to EPA for testing consideration under Section 4 of the
Toxic Substances Control Act. On July 18, 1980, the Test Rules
Development Branch/AD published (45 FR 48524) a proposed "test
rule" for carcinogenicity and teratogenicity testing of chloro-
methane. In.addition, the Office of Toxic Substances is current-
ly gathering additional exposure and toxicity information on
chloromethane under TSCA Sections 8(a) and 8(d), respectively.
..
.NOTE: This status reoo:.-t is the resul: of a orelimina:.-v
staff evaluation of ir.formation submittec to EPA. State;ents
mace herein are not to be regarded as expressing final
Agen~y policy or intent with respect to t~is ?articular
chem7cal. .~y review of the status report should take into
~onslderation the fact that it may be based on incomplete
J.nforma tion.
410
f~' '0". 1J:D-6 'RCV. ~,.,
-------
8EHQ-1l82-0464
Page 2 of 2
Current production and Use
-------
A review of the production range (includes importation volumes)
statistics for chloromethane (methyl chloride; CAS No. 74-87-3),
which is listed in the initial TSCA Inventory, has shown that
between 281 million and 960 million pounds were reported as
produced/imported in 1977. **/ The July 14, 1982 issue of
Chemical & Engineering News reported a preliminary figure of 362
million pounds for U.S. chloromethane production in 1981.
According to secondary literature sources, chloromethane can be
used as a catalyst carrier in certain types of polymerization
reactions. Chloromethane can also be used in the manufacture of
silicones, tetramethyl lead, synthetic rubber, methyl cellulose,
refrigerants, fumigants, and certain organic chemicals (e.g.,
chloroform, carbon tetrachloride, methylene chloride). In addi-
tion, the chemical can be used as an extractant, a propellant and
an herbicide.
Comments/Recommendations
In 1974, the Occupational Safety and Health Administration (OSHA)
set the current occupational standard for chloromethane exposure
at an 8 hour time-weighted average (TWA) of 100 parts per million
(ppm) in air with a 200 ppm ceiling level (39 CFR 23540). In
1980, the ACGIH (American Conference of Governmental Industrial
Hygienists) recommended a threshold limit value (TLV) for chloro-
methane at 50 ppm in air. In addition, chloromethane is current-
ly considered by EPA as a priority water pollutant under Section
307 of the Clean Water Act (CWA).
a) In view of EPA's general interest in company actions taken
on a voluntary basis in response to chemical toxicity/ex-
posure information, the Chemical Hazard Identification
Branch (CHIB/AD/EPA) will request Vulcan Chemicals to
describe its actions taken in light of the reported toxicity
information on chloromethane to warn workers and others and
to reduce and/or eliminate exposure to the subject chemical.
b) The Chemical Hazard Identification Branch will provide a
copy of this status report to NIOSH, OSHA, CPSC, FDA, OW/-
EPA, OSWER/EPA, OANR/EPA, ORD/EPA, and TRDB/AD/EPA. In
addition, a copy will be transmitted to the Office of Toxics
Integration (OTI/OPTS/EPA) and to the Industry Assistance
Office (IAO/OTS/EPA) for appropriate distribution.
**/ This production range information does not include any pro-
duction/importation data claimed as confidential by the person(s)
reporting for the TSCA Inventory, not does it include any infor-
mation which would compromise Confidential Business Information.
The data submitted for the TSCA Inventory, including production
range information, are subject to the limitations contained in
the Inventory Reporting Regulations (40 CFR 710).
411
-------
UNITED STA TES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-1l82.,.,0465
Page 1 of 2
SUI.lICT. status Report* 8EHQ-1182-0465
Justine L. wel~,Vtleam Leader
nOM. Chemical selecvon and Profiles
Frank D. Kover, Chief
To.Chemical Hazard Ident if icat ion
App:oved,
~--- II;.
DAn:
..IAN
4 1983
Team/CHIB
Revision
Needed
Branch/AD
~~bm is s i on__De ~_~~~i 0 n
The Celanese Corporation provided complete copies of the final
reports, including test protocols and data, from several 2~~~tro
genetic screening assays of two commercial dyes: Calco Oil Bronze
Y and Calco oil Red YM. According to Celanese, Calco Oil Bronze
Y displayed mutagenic activity in an Ames Salmonella typhimurium
(bacteria) assay both with and without exogenous metabolic acti-
vation, and mutagenic activity in cultured mouse lymphoma cells
without activation. Calco Oil Red YM was reported by Celanese to
have exhibited mutagenic activity in both the Ames and mouse lym-
phoma cell assays only in the presence of metabolic activation.
Submission Evaluation
As reported by Celanese, Calco Oil Bronze Y was shown to possess
mutagenic activity in Salmonella typhimurium (bacteria) when
tested with and without exogenous metabolic activation. Although
the submitter's cover letter stated that Calco Bronze Y was found
to be positive in cultured mouse lymphoma cells when tested
without metabolic activation, a review of the data contained in
the provided final reports revealed that Calco Bronze Y induced
specific gene locus mutation in mouse lymphoma (L5178Y) cells
only in the presence of exogenous metabolic activation. In addi-
tion, a 'review of the provided data on Calco oil Red YM confirmed
the submitter's statement that this particular azo dye mixture
was mutagenic only in the presence of metabolic activation in
both _~almonella ~himurium and cultured mouse lymphoma cells.
It should be noted that although the performed Ames Salmonella
typhimurium assays on Calco Oil Bronze Y and Calco Oil Red YM did
provide data that could be used in evaluating mutagenicity, these
bacterial assays were not conducted in accordance with U.S. EPA
or Organization for Economic Cooperation and Development (OECD)
guidelines. Both the EPA and OECD guidelines recommend the use
of two (2) plates per dose point and the confirmation of all
results in an independent assay.
'.
.NOTE: T~is status reco:t is the resul~ of a crelimina:v
staff evaluation of information submitted to EPA. State;ents
mace herein are not to be re~arded as exoressir.a final
Agency policy or intent with-res?ec~ to this ?articular
chemical. .~y review 6f the status repor~ should take into
consideration the fact that it may be based on incompleta
information.
412
. .
~~. '0". 11:1)06 'ltCY. ~".
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8EHQ-1l82~0465
Page 2 of 2
Current production and Use
---. ---~-- - .-- ----- ----.
According to the Celanese Corporation, there are no specific
Chemical Abstract Service (CAS) Registry Numbers assigned to
either Calco oil Bronze Y or Calco Oil Red YM as they are azo dye
mixtures. Celanese did not, however, identify the chemical
constituents of either of the tested dye mixtures.
In its submission, Celanese reported that although both Calco Oil
Bronze Y and Calco oil Red YM were used at one time for tinting
industrial polyester yarn, these dye mixtures are not being used
by the company at the present time. No other information on the
specific use(s) of Calco oil Bronze Y or Calco Oil Red YM was
located in the secondary literature sources consulted.
Comments/Recommendations
In the cover letter to its submission, the Celanese Corporation
reported that it had provided copies of the submitted in vitro
mutagenicity test reports to the supplier of both dyes~ The
Celanese cover letter also indicated that the subject reports had
been transmitted to the National Institute for Occupational
Safety and Health (NIOSH), the Occupational Safety and Health
Administration (OSHA), and the National Cancer Institute (NCI).
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request the Celanese Corporation to provide the exact
chemical identity (including CAS Numbers, if known) and
amount of each constituent in Calco Oil Bronze Y and Calco
Oil Red YM.
b)
The Chemical Hazard Identification Branch will screen the
reported information in order to determine the need for
further assessment of Calco oil Bronze Y, Calco Oil Red YM
or any of the chemical components of those dye mixtures.
c)
The Chemical Hazard Identification Branch will transmit
copies of this status report to NIOSH, OSHA, CPSC, FDA,
NCI/NTP, OW/EPA, OSWER/EPA, and ORD/EPA. In addition,
copies will be sent to the Office of Toxics Integration
(OTI/OPTS/EPA) and Industry Assistance Office (IAO/OTS/-
EPA) for appropriate distribution.
413
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-1l82-0466
Page 1 of 2
DAn:
JAN
4 1983
App:oved Of;t.-
Revision
Needed
'NG ~
SUIJtCT'Status Report* 8EHQ-1182-0466
,IOM.Justine L. welcCbJeam Leader
Chemical select~'n and Profiles
TO.Frank D. Kover, Chief
Chemical Hazard Identification
Team/CHIB
Branch/AD
Submission Description
Pursuant to Section 8(e) of TSCA, E. I. du Pont de Nemours &
Company, Inc. submitted a written followup report concerning an
accidental atmospheric release of approximately 1100 pounds of
chlorine gas (CAS No. 7782-50-5) from the company's plant at
Niagara Falls, New York According to Du Pont, 76 people (most
of whom were attending an evening football game) were affected
and reported to nearby hospitals for observation. The company
reported that although most of the affected people were examined
and released immediately, 3 individuals were held overnight for 1
or 2 nights. Du Pont also reported that the company was not
aware of any person suffering serious or prolonged incapacitation
due to the chlorine release. In addition, Du Pont stated that
there was no evidence of any chlorine release-related adverse
environmental effects.
Submission Evaluation
It is generally well known that chlorine gas is highly irri-
tating, especially to the mucous membranes of the eyes and
respiratory tract. Inhalation of sufficient amounts of chlorine
gas may lead to serious human health effects such as bronchitis,
pulmonary edema, bronchopneumonia, tachycardia (increased heart
beat), and possibly death.
Current Production and Use
Due to the nature of this submission, a review of the current
production and uses of chlorine does not appear to be warranted
for this status report.
*NOTE: T~is status reco~t is the result of a crelirnina:v
staff evaluation of information submittec to EPA. State;e~ts
mace herein are no~ to be regarded as expressing final
Agen:y policy or intent with respect to t~is particular
chem~cal. ..~Y review of the status report should take into
~onslder~tlon the fact that it may be based on incomplete
~nforma t~on.
414
."
E~. '0". ..~ CIIIC:Y. ..".
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8EHQ-1l82-0466
Page 2 of 2
Co~~~nts/~~~~~~endations
In its submission, Du Pont stated that when the company learned
of the chlorine gas release, it immediately notified appropriate
local/state authorities and EPA pursuant to the mandatory report-
ing provisions of the Comprehensive Environmental Response, Com-
pensation, and Liability Act (CERCLA; "Superfund").
According to Part V(c) of EPA's March 16, 1978, TSCA Section 8(e)
policy statement ("Statement of Interpretation and Enforcement
Policy; Notification of Substantial Risk" 43 FR 11110), an
emergency incident of environmental contamination is considered
reportable to EPA pursuant to Section 8(e) if the incident in-
volves "any environmental contamination by a chemical substance
or mixture to which any... [serious] adverse effects [have] been
ascribed and which because of the pattern, extent, and amount of
contamination (1) seriously threatens humans with cancer, birth
defects, mutation, death, or serious or prolonged incapacitation,
or (2) seriously threatens non-human organisms with large scale
or ecologically significant population destruction." Part VII of
the policy statement directs, however, that such information need
not be reported under TSCA Section 8(e) if the information has
already been formally reported to EPA pursuant to mandatory
reporting requirements contained in other authorities administer-
ed by EPA (e.g., "Superfund"). It should be noted, however, that
chemical release-related reporting requirements contained in such
other authorities are, for the most part, triggered by incidents
involving releases of specified amounts (i.e., reportable quanti-
ties (RQs» of specific (i.e., listed) chemical substances. In
those cases involving a release of less than the reportable
quantity of a listed chemical or a release of a chemical not
listed in such other authorities, companies should consider the
need for reporting pursuant to Section 8(e) of TSCA.
In view of the above discussion and considering that 1) the Du
Pont chlorine gas release involved a release of a reportable
quantity of a listed chemical substance, and 2) the incident was
immediately reported by the company to EPA pursuant to the
notification provisions of CERCLA ("Superfund"), there was no
need for Du Pont to also notify EPA under TSCA Section 8(e).
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will transmit a copy of this status report to NIOSH,
OSHA, OANR/EPA, and OSWER/EPA. A copy of this status
report will also be provided to the Office of Toxics
Integration (OTI/OPTS/EPA) and to the Industry Assist-
ance Office (IAO/OTS/EPA) for appropriate distribution.
415
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UNITED STATES E~IVIRONMENTAL PROTECTION AGENCY
8EHQd282-046J
Page 1 of 3
DATE:
JAN 2 0 1983
APproved{/t~ ,1;;,1 f 3
SUIJICT. .
Status Report* 8EHQ-1282-0467
(\
Justine L. wel~1Aieam Leader
nOMa Chern ical selection and Prof iles
Frank D. Kover, Chief
TO'Chemical Hazard Identitication
Team/CHIB
Revision
Needed
Branch/AD
Submission Description
Following receipt and review of a National Toxicology Program
(NTP) draft report containing the results of an NTP bioassay of
ethyl acrylate (CAS Number 140-88-5) administered chronically by
gavage to male and female mice and rats, the Union Carbide.
Corporation submitted a summary of certain toxioologic findings
presented in that report. According to Union Carbide, "compound-
related increases in the incidence of inflammation; hyperplasia,
and hyperkeratosis of the forestomach were observed in the
treated animals." In addition, the submitter stated that "for
animals of each sex, incidences of squamous cell papillomas,
squamous cell carcinomas, or, either papillomas or carcinomas
occurred with statistically significant positive trends, and the
incidences in the treated groups were significantly higher than
in the vehicle (corn oil) controls." .
Submission Evaluation
Although the submitted summarized results indicate that ethyl
acrylate demonstrated oncogenic activity in the performed study,
a copy of the actual draft bioassay report should be obtained
directly from NTP in order for EPA to more properly evaluate the
obtained toxicologic findings.
Current Production and Use
A review of the production range (includes Importation volumes)
statistics for ethyl acrylate (CAS Number 140-88-5), which is
listed in the initial TSCA Inventory, has shown that between 70
million and 200 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 con-
fidential by those persons reporting for the TSCA Inventory, nor
does it include any information which would compromise Confiden-
tial Business Information. The data submitted for the TSCA In-
ventory, including production range information, are subject to
the limitations contained in the Inventory Reporting Regulations.
-NOTt: This status recort is the result of a crelimina=v
staff evaluation of information submitted to tPA. State;e~ts
mace herein are no~ to be regarded as expressing final
Agen~y policy or intent with res?ec~ to t~is ?articular
chem~cal. .~y review of the status repor~ should take into
~onsidcration the iact that it may be based on incomplet~
~nIormation.
- .
416
I:~& '0'''' 1J::&>ot I"ey. ~"I
-------
8EHQ-1282-0467
Page 2 of 3
According to secondary literature sources, ethyl acrylate is used
mainly in the manufacture of polymers and acrylic paints, and as
a chemical intermediate.
COE1m~!l_t sj~ecom~~_r:!~_a t ions
In its submission, Union Carbide stated that the company does
"not plan any actions involving notifying employees, customers,
other government agencies, etc. of the information, but will
consider that question when the final report is in hand and the
official opinion of the significance of the information by the
scientists in the National Toxicology Program can be reviewed."
It should be noted that EPA believes that the toxicologic
information on ethyl acrylate which was obtained by the Union
Carbide Corporation was appropriate for reporting pursuant to
Section 8(e), the substantial risk information r~porting pro-
vision of the Toxic Substances Control Act (TSCAi PL 94-469).
The Agency's position is based on the following discussion.
TSCA Section 8(e) states that "any person who manufactures,
processes, or distributes in commerce a chemical substance or
mixture and who obtains information which reasonably supports the
conclusion that such substance or mixture presents a substantial
risk of injury to health or the environment shall immediately
inform the [EPA] Administrator of such information unless such
person has actual knowledge that the Administrator has been
adequa tely informed of such information." The types of informa-
tion that need not be reported (i.e., that information about
which subject persons can automatically assume the EPA to be
"adequately informed") are clearly defined in Part VII of EPA's
March 16, 1978, Section 8(e) policy statement ("Statement of
Interpretation and Enforcement PolicYi Notification of Substan-
tial Risk" 43 FR 11110). Part VII of the Section 8(e) policy
statement states in part for example that information need not be
reported to EPA under Section 8(e) if the information has been
published in the open scientific literature referenced by certain
abstracting services or submitted in writing to EPA pursuant to
mandatory reporting requirements under TSCA or any other author-
ity administered by EPA. In addition to the various types of
"non- reportable" informa tion wh ich are cited in Part VI I of the
8(e) policy statement, one can automatically assume that EPA has
been "adequately informed" about the results of carcinogenesis
bioassays conducted under the auspices of the National Toxicology
proyram (NTP) once the NTP formally releases copies of the draft
technical reports from those bioassays for peer review by the
Technical Report Peer Review Subcommittee of the NTP's Board of
Scfent[{ic Counselors. This assumption can be made automatically
-because-EPA's Office of Toxic Substances routinely receives com-
plete copies of all draft NTP carcinogenesis bioassay technical
reports which are formally released by NTP for peer review.
It cannot be automatically assumed, however, that EPA has been
"adequately informed" about the results (includin~ preliminary
results) of: 1) NTP carcinogenesis bioassays for which the NTP
has not formally released draft technical reports for peer re-
417
-------
8EHQ-1282-0467
Page 3 of 3
view, and 2) other toxicity studies (i.e.. other than carcino-
genesis bioassays) performed under the auspices of the NTP or
toxicity studies conducted by or for other Federal Agencies.
Therefore, a chemical company's receipt of results from toxico-
logic studies of the types listed in 1) and 2) above should and
in most cases does trigger immediate evaluation with considera-
tion then given for reporting appropriate information to EPA
pursuant to TSCA Section 8(e). It should be noted that EPA has
correctly received many Section 8(e) submissions (usually com-
prised of a maximum of 1 to 2 pages) that have been filed by
companies who have obtained toxicologic information from studies
conducted by or for other Federal Agencies. It should also be
noted that in those situations involving such TSCA Section 8(e)
submissions, EPA's Office of Toxic Substances has immediately
initiated appropriate followup activities directly with those
other Agencies. These BPA followup actions have minimized and in
most cases eliminated any further TSCA Section 8(e) reporting
obligation on the part of the submitting companies to provide
items such as complete copies of supporting data or actual
technical reports.
Therefore, considering that 1) the NTP draft report on ethyl
acrylate that was received by the Union Carbide Corporation had
not been formally released by National Toxicology Program for
peer review by the Technical Report Peer Review Subcommittee of
NTP's Board of Scientific Counselors, and 2) the toxicologic
(e.g., oncogenicity) information on ethyl acrylate as presented
by Union Carbide does provide reasonable support for a conclusion
of substantial risk of injury to health as defined in EPA's March
16, 1978, Section 8(e) policy statement, the obtained information
was appropriate for submission pursuant to TSCA Section 8(e).
Several TSCA Section 8(e) and "For Your Information (FYI)" sub-
missions on ethyl acrylate and other acrylate compounds have been
received and reviewed by EPA. In addition, the Chemical Hazard
Identification Branch has prepared Chemical Hazard Information
Profiles (CHIPs) on several acrylates including ethyl acrylate.
At the present time, the OTS Existing Chemicals Task Force (ECTF)
is considering the need for further OTS activities on certain
acrylate compounds.
a) The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request the National Toxicology Program to provide
EPA with a copy of the subject draft NTP bioassay report
on ethyl acrylate. Both the Union Carbide Corporation
submission and the draft NTP bioassay report on ethyl
acrylate will be provided to the OTS Existing Chemicals
Task Force (ECTF).
b) A copy of this status report will be transmitted to OSHA,
N IOSH, CPSC, r.LJA, NTP, OANR/EPA, ORD/EPA., OW/EPA, OSWER/-
EPA, and to the OTS Existing Chemicals Task Force. In
addition, the status report will be provided to the Office
of Toxics Integration (OTI/OPTS/EPA) and Industry Assist-
ance Office (IAO/OTS/EPA) for appropriate distribution.
418
-------
-
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APPENDIX A,
THURSDAY, MARCH 16, 1978
PART V
ENVIRONMENTAL
PROTECTION
AGENCY
.
TOXIC SUBSTANCES
CONTROL ACT
Statement of Interpretation and
Enforcement Policy; Notification
of Substantial Risk
419
-------
11110
[ 6560-0 1]
ENVIRONMENTAL PROTECTION
AGENCY
[FRL 84~2]
TOXIC SUBSTANCES CONTROL ACT
Notification of Substantial Risk Under
Section 8( e)
AGENCY: Environmental Protection
Agency.
ACTION: Statement of interpretation
and enforcement policy.
SUMMARY: This action states EPA's
interpretation of, and enforcement
policy concerning, section 8(e) of the
Toxic Substances Control Act (TSCA)
(90 Stat. 2029, 15 U.S.C. 2607). The
provisions of that section went into
effect 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
Administrator has been adequately in-
formed of such information."
DATES: The policy expressed in this
document is in effect as of the date of
publication.
FOR FURTHER INFORMATION
CONTACT:
Frank D. Kover, Assessment Divi-
sion, Office of Toxic 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, 1977 (42 FR
54857). On November 4, 1977, a supple--
mental notice to the proposed guid-
ance was published (42 FR 57744), de-
leting the November 15 date for re-
porting certain information obtained
before 1977 and stating that a new
date would be established in the final
guidance.
In developing this policy statement,
two meetings have been held (Febru-
NOTICES
ary I, 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 significant issues raised in
these comments and the Agency's re-
sponse to them.
The major modifications to the Sep-
tember 9 proposal are summarized in
points 1 through 7 below.
(1) Pursuant to some question over
the definition and nature of "guid-
ance," this document is now described
more accurately as a "policy state-
ment." It is exempt from the notice
and public comment provisions of the
Administrative Procedure Act, as well
as provisions concerning delayed effec-
tive dates.
(2) Many commenters expressed the
view that to apply these requirements
to officers and employees of a business
organization would result in ill-consid-
ered, premature reports and would un-
fairly subject employees to conflicting
responsibilities as individual respon-
dents and as corporate agents. Other
commenters expressed support for the
view that certain employees have a re-
sponsibility to report pertinent infor-
mation, and felt that the phrase "ca-
pable of appreciating pertinent infor-
mation" appropriately described those
employees.
The September 9 proposal would
have applied section 8(e) requirements
to commercial establishments as well
as to employees capable of appreciat-
ing pertinent information, but 'stipu-
lated enforcement priorities intended
to encourage corporate processing and
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 i11-considered
submissions.
The Agency now feels that these ob-
jectives would best be served by allow-
ing commercial establishments-under
certain conditions designed to ensure
full disclosure-to assume exclusive re-
sponsibility for reporting to EPA any
substantial-risk information obtained
by individual officers or employees.
Accordingly, this policy statement
stipulates that individual officers and
employees wi11 have fully discharged
their section 8(e) obligations once they
have notified the designated responsi-
ble company supervisor or official of
pertinent information, provided, that
the employing company or firm has
established, internally publicizes, and
affirmatively implements procedures
governing such notifications. These
procedures, at a minimum, must: (1)
Specify the information that must be
reported; (2) indicate how the notifica-
tions are to be prepared and submit-
ted; (3) note the Federal penalties for
failing to report; and (4) provide a
mechanism for promptly notifying of.
ficers and employees who have submit-
ted reports of the company's disposi-
tion of those reports, including wheth-
er or not they were submitted to EPA
(and if not, informing employees of
their right to report to EPA, as pro-
tected by TSCA section 23). EPA be-
lieves these four criteria wi11 ensure
prompt and appropriate processing of
pertinent information.
Establishment of such procedures
notwithstanding, all officials responsi-
ble and having authority for the orga-
nization's execution of its section 8(e)
obligations retain personal liability for
ensuring that 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 consti-
tutes a "substantial risk". The Agency
continues to focus in this policy state-
ment on the effects set forth in the
September 9 proposal, but clarifies
that the substantiality of a 'risk is a
function of both the seriousness-of the
effect and the probability of its occur-
rence (see Part V).
(5) Numerous commenters main-
tained that section 8( e) only applies
prospectively to information obtained
after January I, 1977. The Agency dis-
agrees, as explained in the preamble
to the September 9 proposal. This
policy statement continues to apply
section 8(e) to information obtained
before 1977 of which a person has
FEDERAL REGISTER, VOL. 43, NO. 52-THURSDAY, MARCH 16, 1978
420
-------
been aware since January I, 1977, In
response to requests for clarification,
the statement defines what constitutes
such awareness. In this manner, EPA
intends to iimit the need for searches
of historical records and files.
(6) This policy statement now pro-
vides that any information pUblished
in scientific literature, in any lan-
guage, is exempt if it is referred to in
abstracts published by specified ab-
stracting services.
(7) This policy statement describes
in a new Part X how to submit claims
of confidentiality.
Accordingly, the Administrator's in-
terpretation of and policy towards sec-
tion 8(e) is set forth below.
Dated: February 24, 1978.
DOUGLAS COSTLE
Administrator.
I. DEFINITIONS
The definitions set forth in TSCA
section 3 apply to these requirements.
In addition, the following definitions
are provided for purposes of this
policy statement:
The term "manufacture or process
'for commercial purposes' " means to
manufacture or process: (1) For distri-
bution in commerce, including for test
marketing purposes, (2) for use as a
catalyst or an intermediate, (3) for the
exclusive use by the manufacturer or
processor, or (4) for product research
and development.
The term "person" includes any nat-
ural person, corporation, firm, com-
pany, joint-venture, partnership, sole
proprietorship, association, or any
other business entity, any State or po-
litical subdivision thereof, any munici-
pality, any interstate body and any de-
partment, agency, or instrumentality
of the Federal Government.
The term "substantial-risk informa-
tion" means information which rea-
sonably supports the conclusion that a
chemical substance or mixture pre-
sents a substantial risk of injury to
health or the environment.
II. PERSONS SUBJECT TO THE
REQUIREMENT
Persons subject to section 8(e) re-
quirements include both natural per-
sons and business entities engaged 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-
ecutive officer, and any other officers
responsible and having authority for
the organization's execution of its sec-
tion 8(e) obligations must ensure that
the organization reports substantial-
risk information to EPA. The business
organization is considered to have ob-
tained any information Which any of-
ficer or employee capable of appreciat-
ing the significance of that informa-
tion has obtained. It is therefore in-
NOTICES
cumbent upon business organizations
to establish procedures for expedi-
tiously processing pertinent informa-
tion in order to comply with the
schedule set forth in Part IV.
Those officers and employees of
business organizations who are capa-
ble of appreciating the significance of
pertinent information are also subject
to these reporting requirements. An
employing organization may relieve its
individual officers and employees of
any responsibility for reporting sub-
stantial-risk information directly to
EPA 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 failing to report; and (4)
provide a mechanism for promptly ad-
vising officers aDd employees in writ-
ing of the company's disposition of the
report, including whether or not the
report was submitted to EPA (and if
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 has
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 its section
8
-------
11112
spondent has actual knowledge that
the Administrator is already Informed
of them.
(Ii) Information respecting these ef-
fects can be obtained either directly,
by observation of their occurrence, or
inferred from designed studies as 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 effects-(1) Any
instance of cancer, birth defects, mu-
tagenicity, death, or serious or pro-
longed incapacitation, including the
loss of or inability to use a normal
bodily function with a consequent rel-
atively serious impairment of normal
activities, if one (or a few) chemical(s)
is strongly implicated.
(2) Any pattern of effects or evi-
dence which reasonably supports the
conclusion that the chemical sub-
stance or mixture can produce cancer,
mutation, birth defects or toxic effects
resulting in death, or serious or pro-
longed incapacitation.
(b) Environmental effects-(1) Wide-
spread and previously unsuspected dis-
tribution in environmental media, as
indicated in studies (excluding materi-
als contained within appropriate dis-
posal facilities).
(2) Pronounced bioaccumulation..
Measurements and indicators of pro-
nounced bioaccumulation heretofore
unknown to the Administrator (includ-
ing bioaccumulation in fish beyond
5,000 times water concentration in a
30-day exposure or having an n-oc-
tanol/water partition coefficient
greater than 25,000) should be report-
ed when coupled with potential for
widespread exposure and any non-triv-
ial adverse effect.
(3) Any non-trivial adverse effect,
heretofore unknown to the Admillis-
trator, associated with a chemical
known to have bloaccumulated to a
pronounced degree or to be wide-
spread In environmental media.
(4) Ecologically significant changes
in species' interrelationships; that is,
changes in population behavior,
growth, survival, etc. that in turn
affect other species' behavior, growth,
or survival.
Examples include: (i) Excessive stim-
ulation of primary producers (algae,
macrophytes) in aquatic ecosystems,
e.g., resulting in nutrient enrichment,
or eutrophication, of aquatic ecosys-
tems.
(Ii) Interference with critical biogeo-
chemical cycles, such as the nitrogen
cycle.
(5) Facile transformation or degra-
dation to a chemical having an unac-
ceptable risk as defined above.
(c) Emergency incidents of environ-
mental contamination-Any environ-
mental contamination by a chemical
substance or mixture to which any of
NOTICES
the above adverse effects has been as-
cribed and which because of the pat-
tern, extent, and amount of contami-
nation (1) seriously threatens humans
with cancer, birth defects, mutation,
death, or serious or prolonged inca-
pacitation, or (2) seriously threatens
non-human organisms with large-scale
or ecologically significant population
destruction. .
VI. NATURE AND SOURCES OF INFORMA-
TION WHICH "REASONABLY SUPPORTS
THE CONCLUSION" OF SUBSTANTIAL
RISK
Information attributing any of the
effects described in Part V above to a
chemical substance or mixture is to be
reported if it is one of the types listed
below and if it is not exempt from the
reporting requirement by reason of
Part VII of this policy statement. A
person is not to delay reporting until
he obtains conclusive information that
a substantial risk exists, but is to im-
mediately report any evidence which
"reasonably supports" that conclusion.
Such evidence will generally not be
conclusive as to the substantiality of
the risk; it should, however, reliably
ascribe the effect to the chemical.
Information from the following
sources concerning the effects de-
scribed in Part V will often "reason-
ably support" a conclusion of substan-
tial risk. Consideration of corrobora-
tive information before reporting can
only occur where it is indicated below.
(1) Designed, controlled studies. In
assessing the quality of information,
the respondent is to consider whether
it contains reliable evidence ascribing
the effect to the chemical. Not only
should final results from such studies
be reported, but also preliminary re-
sults from incomplete studies where
appropriate. Designed, controlled stud-
ies include:
(i) In vivo experiments and tests.
(Ii) In vitro experiments and tests.
Consideration may be given to the ex-
istence of corroborative information, if
necessary to reasonably support the
conclusion that a chemical presents a
substantial risk.
(Iii) Epidemiological studies.
(Iv) Environmental monitoring stud-
ies.
(2) Reports concerning and studies
of undesigned, uncontrolled circum-
stances. It is anticipated here that re-
portable effects will generally occur in
a pattern, where a significant common
feature is exposure to the chemical.
However, a single instance of cancer,
birth defects, mutation, death, or seri-
ous incapacitation in a human would
be reportable if one (or a few)
chemical(s) was strongly implicated.
In addition, it is possible that effects
less serious than those described in
Part V(a) may be preliminary manifes-
tations of the more serious effects
and, together with another triggering
piece of information. constitute repor-
table information; an example would
be a group of exposed workers experi-
encing dizziness together with prelimi-
nary experimental results demonstrat-
ing neurological dysfunctions.
Reports and studies of undesigned
circumstances include:
(i) Medical and health surveys.
(Ii) Clinical studies.
(Iii) Reports concerning and evi-
dence of effects in consumers, workers,
or the environment.
VII. INFORMATION WHICH NEED NOT BE
REPORTED
Information need not be reported if
it:
(a) Has been published by EPA in re-
ports;
(b) Has been submitted in writing to
EP A pursuant to mandatory reporting
requirements under TSCA or any
other authority administered by EPA
(Including the Federal Insecticide,
Fungicide and Rodenticide Act, the
Clean Air Act, the Federal Water Pol-
lution Control Act, the Marine Protec-
tion, Research, and Sanctuaries Act,
the Safe Drinking Water Act, and the
Resource Conservation and Recovery
Act), provided that the information:
(1) Encompasses that required by Part
IX (c) through (f); and (2) is from now
on submitted within the time con-
straints set forth in Part IV and iden-
tified as a section 8(e) notice in accor-
dance with Part IX(b);
(c) Has been published in the scien-
tific literature and referenced by the
following abstract services: (1) Agric-
ola, (2) Biological Abstracts, (3)
Chemical Abstracts, (4) Dissertation
Abstracts, (5) Index Medicus, (6) Na-
tional Technical Information Service.
(d) Is corroborative of well-estab-
lished adverse effects already docu-
mented in the scientific literature and
referenced as described in (c) above,
unless such information concerns
emergency incidents of environmental
contamination as described in Part
V(c), or
(e) Is contained in notification of
spills under section 311
-------
(b) Any information the contents of
which a person has been alerted to by
date received after January I, 1977, in-
cluding any information concerning a
chemical for which the person is pres-
ently assessing health and environ-
mental effects;
(c) Any other information of which
the person has actual knowledge.
IX. REPORTING REQUIREMENTS
Notices shall be delivered to the
Document Control Officer. Chemical
Information Division. Office of Toxic
Substances (WH-557). Environmental
Protection Agency, 401 M Street SW.,
Washington, D.C. 20460.
A notice should:
(a) Be sent by certified mail. or in
. any other way permitting verification
of its receipt by the Agency,
(b) State that it 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
mime and address of the manufactur-
ing, processing, or distributing estab-
lishment with which he is associated,
(d) Identify the chemical substance
or mixture (including, if known. the
CAS Registry Number).
(e) Summarize the adverse effects
being reported, describing the nature
and the extent of the risk involved,
and
(f) Contain the specific source of the
information together with a summary
and the source of any available sup-
porting technical data.
For emergency incidents of environ-
mental contamination (see Part V(c»,
a person shall report the incident to
the Administrator by telephone as
soon as he has knowledge of the inci-
dent (see below for appropriate tele-
phone contacts). The report should
contain as much of the information re-
quired by instructions (b) through (f)
above as possible. A wrjtten report. in
accordance with instructions (a)
through (f) above, is to be submitted
within 15 days. Twenty-four hour
emergency telephone numbers are:
Region I (Maine. Rhode Island, Connecti-
cut, Vermont. Massachusetts, New Hamp-
shire), 617-223-7265.
Region II (New York, New Jersey, Puerto
Rico, Virgin Islands), 201-548-8730.
Region III (Pennsylvania, West Virginia.
Virginia, Maryland, Delaware, District of
Columbia), 215-597-9898.
Region IV (Kentucky, Tennessee, North
Carolina, South Carolina, Georgia, Ala-
bama, Mississippi, florida), 404-881-4062.
Region V (Wisconsin, Illinois, Indiana,
Michigan, Ohio, Minnesota), 312-353-
2318.
Region VI (New Mexico, Texas, Oklahoma,
Arkansas, Louisiana), 214-749-3840.
Region VII (Nebraska, Iowa, Missouri,
Kansas), 816-374-3778.
Region VIII (Colorado, Utah, Wyoming,
Montana, North Dakota, South Dakota),
303-837-3880.
Region IX (California, Nevada, Arizona,
HawaII, Guam), 415-556-6254.
NOTICES
Region X (Washington, Oregon, Idaho,
Alaska),206-442-1200.
X, CONFIDENTIALITY CLAIMS
(a) Any person submitting a notice
to ~PA under section 8(e) of TSCA
may assert a business confidentiality
claim covering all or part of the infor-
mation contained in the notice. Any
information covered by a claim will be
disclosed by EPA only to the extent.
and by means of the procedures, set
forth in 40 CFR Part 2 (41 FR 36902,
September I, 1976).
(b) If no claim accompanies the
notice at the time it is submitted to
EPA, the notice will be placed in an
open file to be available to the public
without further notice to the submit-
ter.
(c) To assert a claim of confidential-
ity for information contained in a
notice, the submitter must submit two
copies of the notice.
(1) One copy must be complete. In
that copy the submitter must indicate
what information. if any, is claimed as
confidential by marking the specified
information on each page with a label
- such as "confidential," "proprietary,"
or "trade secret."
(2) If some information in the notice
is claimed as confidential. the submit-
ter must submit a second copy. The
second copy must be complete except
that all information claimed as confi-
dential in the first copy must be de-
leted.
(3) The first copy of the notice will
be disclosed by EP A only to the
extent, and by means of the proce-
dures, set forth in 40 CFR Part 2. The
second copy will be placed in an open
file to be available to the public.
(d) Any person submitting a notice
containing information for which they
are asserting a confidentiality claim
should send the notice in a double
envelope.
(1) The outside envelope should bear
the same address outlined in section
IX of this policy'statement.
(2) The inside envelope should be
clearly marked "To be opened only by
the OTS Document Control Officer."
XI. FAILURE To REPORT INFORMATION
Section 15(3) of TSCA makes it un-
lawful for any person to fail or refuse
to submit information required under
section 8(e). Section 16 provides that a
violation of section 15 renders a
person liable to the United States for
a civil penalty and possible criminal
prosecution. Pursuant to section 17,
the Government may seek judicial
relief to compel submittal of section
8(e) information and to otherwise re-
strain any violation of section 8(e).
11113
ApPENDIX A.-QUICK REFERENCE SUMMAHY
FOR EMERGENCY INCIDENTS OF ENVIRONMEN-
TAL CONTAMINATION
A. WHAT SHOULD BE REPORTED AS AN
EMERGENCY INCIDENT
An emergency incident of environmental
contamination is "any environmental con-
tamination by a chemical substance or mix-
ture ... which, because of the pattern.
extent and amount of contamination, (1) Se-
riously threatens humans with cancer, birth
defects, mutation, death, or serious or pro-
longed incapacitation, or (2) seriously
threatens non-human organisms with large
scale or ecologically significant population
destruction". (See Part V(c) for complete
description. )
B. WHAT NEED NOT BE REPORTED AS AN
EMERGENCY INCIDENT
Information contained in notification of
spills under section 311< b)( 5) of the Federal
Water Pollution Control Act (FWPCA).
(For a complete list of exemptions to report-
ing, see Part VII.)
C. WHEN AND WHERE TO REPORT EMERGENCY
INCIDENTS
Emergency incidents of environmental
contamination are to be reported Immedi-
ately by telephone to the appropriate EPA
Regional 24-hour telephone emergency line
listed below.
Region I (Maine, Rhode Island, Connecti-
cut, Vermont, Massachusetts, New Hamp-
shire). 617-223-7265.
Region II (New York, New Jersey, Puerto
Rico, Virgin Islands), 201-548-8730.
Region III (Pennsylvania, West Virginia,
Virginia, Maryland, Delaware, District of
Columbia), 215-597-9898.
Region IV (Kentucky. Tennessee, North
carolina, South Carolina, Georgia, Ala-
bama, Mississippi, Florida). 404-881-4062.
Region V (Wisconsin, Illinois, Indiana,
Michigan, Ohio. Minnesota). 312-353-
2318.
Region VI (New Mexico, Texas, Oklahoma,
Arkansas, Louisiana), 214-749-3840.
Region VII (Nebraska. Iowa, Missouri,
Kansas), 816-374-3778.
Region VIII (Colorado. Utah, Wyoming,
Montana, North Dakota, South Dakota).
303-837 -3880.
Region IX (California, Nevada, Arizona,
Hawaii. Guam), 415-556-6254.
Region X (Washington, Oregon, Idaho,
Alaska), 206-442-1200,
In addition, a written report. in accord-
ance with instructions (a) through (f) of
Part IX. is to be submitted within 15 days to
the Document Control Officer. Chemical In-
formation Division, Office of Toxic Sub-
stances (WH-557), 401 M Street SW., Wash.
ington. D.C. 20460.
ApPENDIX B-SIGNIFICANT COMMENTS AND
RESPONSES
A. PERSONS SUBJECT TO THESE REQUIREMENTS
Comment 1: Employees cannot be held
subject to these requirements, since: (n)
They only have a partial role in the manu-
facture, processing, or distribution of chemi-
cals, (b) in other sections of TSCA, the term
"person who manufactures, processes. or
distributes" chemicals clearly refers to busi-
ness organizations; "persons" should be con.
slstently defined. and (c) the application of
criminal penalties mandates a stricl inter-
pretation of this word.
FEDERAL REGISTER, VOL. 43, NO. 52-THURSDAY, MARCH 16, 1978
423
-------
11114
Regponse: The Agency considers that dif-
ferent sections of TSCA. having different
purposes, are appropriately directed to dif-
ferent respondents. In the case of section
8(e), officers and employees who are capable
of appreciating the signiflcancc of informa-
tion have a legitimate responsibility to be
alert to and report substantial-risk informa-
tion. The guidance has been modified so
that natural persons and business entities
can fulfill their section 8(e) obligations in
different ways. Most officers and employees
can discharge their section 8(e) obligations
by submitting pertinent information to cor-
porate superiors, provided that the com-
pany has established the risk-evaluation
procedures characterized in Part II. In the
case of a business organization, its presi-
dent, chief executive officer, and other offi-
cials responsible and having authority for
the business organization's execution of its
section 8(e) obligations must ensure that
the organization reports substantial-risk in-
formation to EPA. .
Comment 2: Even if employees can be held
subject to these requirements, they should
not be. To do so would force employees and
employers into conflicting positions, inviting
internal corporate dissension and over- re-
porting. Further, individuals often do not
have the overview necessary to reach con-
sidered, well-supported decisions. Corporate
reporting by designated officials will pro-
vide EPA with more reliable data.
Response: The Agency considers that em-
ployees have a legitimate role in risk report-
ing; It is Imperative that risk information
obtained by employees be appropriately
considered. Officers and employees can ful-
fill their role in the reporting of substantial-
risk information, without the disadvantages
described above, by reporting information
to superiors for corporate consideration.
and, having done so, will have discharged
their obligation to EPA. This Is contingent
upon the establishment by the business or-
ganization of certain procedures for rlsk-
evaluation, thereby assuring the appropri-
ate consideration of such reports. Those of-
ficers responsible and having authority for
the organization's execution of Its section
8(e) obligations must ensure that the orga-
nization reports substantial-risk informa-
tion to EP A.
Comment 3: Clarify which employees are
covered, and the extent of their obligation.
Are employees "capable of appreciating per-
tinent information" by virtue of rank, or
knowledge? Are rank and file employees
subject to these requirements, or just super-
visory and managerial personnel, company
toxicologists. etc.? Is an employee absolved
of further responsibility If he reports to his
supervisor?
Response: The Agency considers that the
phrase "capable of appreciating the signifi-
cance of pertinent information" appropri-
ately describes those officers and employees
who have a responsibility to be alert to and
report substantial-risk information. includ-
ing not only relatively senior corporate offi-
cers but also many corporate employees.
The policy statement modifies the Septem-
ber 9 proposal, in response to the concerns
expressed in Comments 2 and 3. to permit
most officers and empioyees to discharge
their obligation by submitting information
to corporate superiors, subject to the condi-
tions described in Part II.
Comment 4: Consultants and independent
labs should not be subject to these require-
ments.
Response: Contractors and independent
labs are not responsible for reporting infor-
NOTICES
matlon they have obtained directly to EPA;
rather, their client manufacturers, proces-
sors and distributors are responsible for
reporting such information.
B, THE "OBTAINING" OF INFORlllATION
Comment 5: The "may suggest" criterion
in Part 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 language calling for
"reasonable suppon" does not support this.
Further. risk assessment often requires any-
where from months to several years of
study after preliminary results "suggest"
risk, far exceeding the 15-day compliance
period.
Response: The Agency does. not intend to
compel under section 8(e) examination of
information that by itself Is not subject to
section 8(e) requirements and has deleted
the "may suggest" provision, providing Its
interpretation of what constitutes evidence
that "reasonably supports the conclusion"
of substantial risk in anew Paf't VI.
Comment 6: Section 8(e) obligations are
incurred upon obtaining conclusory substan-
tial-risk information.
Response: The Agency. disagrees, and con-
siders that "reasonable support" of a con-
clusion of. substantial risk is not Identical to
the conclusion itself. The former typically
occurs, and must be reported. at an earlier
stage.
Comment 7: The statement. in Part III of
the proposal that a person has obtained in-
formation If he ". . . should know of the ex-
Istence of such information not in his pos-
session but which would be delivered to him
on request," tends to compel an active
search for substantial-risk information
rather than the reporting of substantial-risk
information a person "obtains." This is of
particular concern to Importers with limited
access to information possessed by their
suppliers.
Resp01Ule: The Agency considers that sec-
tion 8(e) applies to information which a
person possesses or of which he knows. It Is
not intended to compel searches for infor-
mation or extraordinary efforts to acquire
information. The Agency further considers.
however, that "known" information in-
cludes information which a prudent person
similarly situated could reasonably be ex-
pected to know. Negligence or intentional
avoidance of information does not absolve a
person of his section 8(e) obligation. Part
III has been modified to express these in-
tentions-
Comment 8: Circumstances can exist when
coming "into possession" of risk Informa-
tion does not correspond to an understand-
ing of the implications of the information;
"obtains" should be defined in terms of pos-
session of information and awareness of its
import-
Respo1Ule: The "obtaining" of Information
occurs via persons who are "capable of ap-
preciating the significance of pertinent in-
formation." There will likely be circum-
stances in which the evaluation of informa-
tion clarifies its full Import; the establish-
ment of corporate procedures for processing
risk-information prescribed in Part II will
expedite this.
C. TIME ALLOWED FOR COMPLIANCE
Comment 9: Fifteen calendar days Is insuf-
ficient to determine whether information
which "may suggest" substantial risk should
be reported; it Is even insufficient to accom-
modate normal procedural time constraints
(corporate processing, mailing, holidays,
etc.).
Regp01Ule: The Agency has changed the
compliance period to 15 business days. It Is
imperative that procedures be established to
expedite the reporting of substantial-risk in-
formation, not that reporting conform to
existing procedures.
Comment 10: Allow from 30 to 90 days for
the second. phase of reporting; alternatively,
do not prescribe a time limit for additional
reporting.
Response: Having deleted the "may sug-
gest" criterion. the Agency sees no need to
provide a second phase to the reporting
period. Supplemental information that Is
generated after a section 8(e) notification
should, if appropriate, be Immediately reo
ported.
Comment 11: Allow from 30 to 120 days to
report pre-1977 information: this period
should commence: (a) upon final publica-
tion. (b) January I, 1978, (c) following the
inventory reporting period since many of
the same" corporate personnel will be imple-
menting both requlrements.
RegpofUJe: The policy statement prescribes
a. 60 da.y reporting period. commencing Im-
mediately,upon publication. Section 8(e) has
been in effect since January 1. 1977; post-
ponement in reporting substantial-risk in-
formatlon'ls not warranted.
D. EFFECTS AND INFORMATION nuT MUST BE
REPORTED
Comment 12: The reporting of "any in-
stance" of cancer. birth defects, etc.. in
humans Is too broad and such Information
will be of little use; chemical workers. like
the general population. develop cancers and
other ailments of uncertain etiology.
RegpOfUJe: This policy statement clarifies
that the reporting of single occurrences of
human cancer or other serious effects will.
depend upon evidence strongly implicating
one (or a few) chemical(s).
Comment 13: Dermal ailments and nausea
are poorly chosen examples of preCUIsor
symptoms. Deleting these examples will
avoid unduly emphasizing them when other
symptoms may be more Important, yet will
not eliminate the obligation to report them
if they are suspected precursol'5.
Regponse: The Agency agrees.
Comment 14: How are reportable data dis-
tinguished from routine tests including
range tests such as LD..'s?
Respo1Ule: This policy' statement directs
the reporting of specified effects when WJ-
known to the Administrator. Many ,-ouUne
tests are based on a knowledge of toxicity
associated with a chemical; unknown effects
occurring during such a range test may have
to be reported if they are those of concern
to the Agency and If the information meets
the criteria set forth in Parts V and VL
Comment 15: The most widespread "In
vitro" test Is the Ames test. which Is subject
to considerable debate. Clarify the circum-
stances under which positive results of In
vitro tests must be reported.
Regponse: Part VI clarifies that the re-
porting of in vitro tests will depend upon
the existence of corroborative information
if necessary to reasonablY support the con-
clusion of substantial risk.
Comment 16: The description of "extreme
persistence" as a substantial risk is an exam-
ple of the need to redefine Part V(C) ("Envi-
ronmental Effects"). Persistence and bio-
accumulation should be considered risks
only when coupled with toxicity and signifi-
cant exposure.
FEDERAL REGISTER, VOL 43, NO. 52-THuaSDAY, MARCH 16, 1978
424
-------
Response: Part V now clarifies those ef-
fects for which reporting depends upon a
significant exposure potential. Persistence
by itself Is no longer itemized as a report-
able eff~ct but rather Is conslder~ to be a
component of exposure potential; it may
also underlie the measurements described in
Part V(b)(1). Laboratory Indicators of pro-
nounced bioaccumulation are to be reported
when coupled with potential for widespread
exposure and any non-trivial adverse effect.
Comment 17: The n-octanol/water parti-
tion coefficient addresses a physico-chemi-
cal property, not biological effects, and Is
not alone an indicator of substantial risk;
further, the values stated for the coefficient
and the bioaccumuIation factor In fish do
not correspond.
Response: The Agency acknowledges the
numerical error and has amended the values
to correspond. This policy statement now
directs the reporting of an experimental
measurement of bloaccumulation 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
supports".
Response: The Agency has provided In a
new Part VI its interpretation of "reason-
ablY supports". '
Comment 19: A determination that infor-
mation "reasonably supports the conclu-
sion" of substantial risk cannot be made in-
dependently of considerations of use since
the method and manner of using a chemical
may Influence the occurrence of an effect;
In particular, the criteria should reflect a
distinction between normal and abnormal
uses of chemicals.
Response: The Agency considers that the
appropriate components of a "substantial
risk" with respect to a chemical are (a) the
seriousness of the effect, and (b) total expo-
sure potential. The method and manner of
using a chemical Is one of several factors de-
termining Its exposure potential. As de-
scribed in Part V, the importance of expo-
sure potential as a component of "substan-
tial risk" depends upon the kind of effect of
concern. Thus, the effects described In Part
Via) are so serious that relatively little
weight Is given to exposure; the effects de-
scribed In Parts V (b) and (c) involve a sig-
nificant exposure or exposure potential.
The Agency further considers that a defi-
nition of "normal" use for a particular
chemical will often depend upon a knowl-
edge of the risks associated with the
chemical.
E. INFORMATION THAT NEED NOT BE 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?
Response: This policy statement now pro-
vides that information published in scien-
tific literature, whether in English or an-
other language, is exempt from reporting If
published in summary form by certain
specified abstract services.
Comment 21: Information exchange sys-
tems with other Federal agencies should be
immediately established so that respondents
need not report to EPA information already
reported to other Agencies, and vice versa.
Such duplicative reports are unduly burden-
some.
NOTICES
Response: EP A Is coordinating this pro-
gram with other agencies now. When this
coordination Is successfully completed, the
poUcy 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
EP A; such a report does not discharge any
reporting obUgation to other agencies.
F. INFORMATION FIRST RECEIVED PRIOR TO THE
EFFECTIVE DATE OF TSCA
Comment 22: The tense of the verb "ob-
tains" reveals that section 8(e) was Intended
to be applied prospectively to information
newly acquired after January I, 1977. Utilize
section 8(d) or other rules to acquire infor-
mation obtained before then.
Response: As discussed In the preamble to
the September 9 proposal, the Agency con-
siders section 8(e) to apply to risk informa-
tion possessed by or known to a person
before, on, or after January I, 1977. Con-
cerning information first obtained before
1977, this poUcy statement continues to re-
Quire reporting of Information received if a
person has been aware of it since January I,
1977, for the reasons discussed In the Sep-
tember 9 preamble.
Comment 23: The term "aware" Is too
vague to be of any help in responding to
these requirements. Since many corporate
employees are potentially subject to these
requirements, and given uncertainty over
the extent to which they ought to be aware
of pre-1977 information, this provision tends
to compel the very file search it was intend-
ed to avoid. The term "aware" should be
further defined, possibly in terms of actual
knowledge. .
Response: The Agency in Part VIII of this
policy statement now defines the pre-1977
information of which a person is considered
to be aware.
G. CONFIDENTIAL INFORMATION
Comment 24: EPA should delay guidance
until procedures are published governing
the treatment of confidential submissions.
Comment 25: EPA should treat all submis-
sions as confidential until the information is
verified.
Comment 26: EPA should automaticallY
publish section 8(e) notices.
Response to Comments 24 through 26:
EPA has included a new Part X which de-
scribes how to submit a claim of confiden-
tiality and states that any or all of the in-
formation submitted may be claimed as con-
fidential. Such information will be disclosed
by EPA only to the extent, and by means of
the procedures, set forth in 40 CFR Part 2.
H. MISCELLANEOUS
Comment 27: What Is the statutory basis
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). As 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 will 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 longer manufactured, processed, or
distributed in commerce by a person.
Response: Information obtained before
1977 must be reported If the person has
been aware of it since January I, 1977, as
prescribed by Part VIII. Concerning chemi-
cals which a person has discontinued manu-
facturing, processing, or distributing since
January I, 1977, information obtained
before the time of discontinuation Is subject
to these requirements.. It Is expected that
the acquisition of information after that
time will be minimal; however, should addi-
tional information be acquired, it may trig-
ger the reporting described in Part VIII.
Comment 29: Clarify the meaning of "sub-
stantial risk" relative to other risks ad-
dressed by TSCA.
Response: A substantial risk is defined in
Part Via) of this policy statement as a risk
of considerable concern because of (a) the
seriousness of the effect, and (b) the fact or
probability of Its occurrence. As opposed to
other risks addressed by TSCA. economic or
social benefits of use, or costs of restricting
use, are not to be considered in determining
whether a risk is "substantial".
Comment 30: To what extent are "users"
of chemicals subject to these requirements?
Response: The Agency considers that
many industrial uses of chemicals actually
fall within the scope of "processing" chemi-
cals. A manufacturer, processor, or distribu-
tor who obtains substantial-risk information
concerning chemicals he handles should be
alert to the possibility he may have to
report it.
Comment 31: Are chemicals manufac-
tured, processed and distributed in com-
merce In small Quantities sOlely for purposes
of research and development subject to
these requirements?
Response: In general, the Agency consid-
ers that much manufacturing, processing,
and distribution In commerce of chemicals
in small Quantities solely for purposes of re-
search and development Is conducted for
"commercial pUlJ)oses". Such purposes
would include the sale and distribution of
such materials, as well as their use by the
maqufacturer or processor in activities (for
example, product research and development
and studies assessing the feasibility and
safety of using chemicals) preceding his or a
client's commercial use of such materials or
others on a larger scale.
As described in Part V, the Agency consid-
ers that "substantial risks" depend in part
upon an exposure potential. Thus, the oc-
currence of the effects described In Part
Via) presuppose exposure to the chemical
and must be reported; reporting of the
other effects will depend upon a potential
for significant levels of exposure.
Comment 32: Are raw materials, interme-
diates, and Inert ingredients produced or
used in the manufacture of a pesticide sub-
ject to TSCA?
Response: The Administrator considers
that raw materials, intermediates and inert
ingredients produced or used in the manu-
facture of a pesticide are substances or mix-
tures which can be regulated under TSCA.
In order to be considered a pesticide, a
substance must be intended for use as a pes-
ticide. Raw materials, intermediates, and
Inert ingrE'dients produced or used in the
manufacture of a pesticide are not them-
selves regulated under FIFRA (unless they
happen to be pesticides themselves) and,
therefore, are subject to TSCA. The pesti-
FEDERAL REGISTER, VOl. 43, NO. 52-THURSDAY, MARCH 16, 1978
425
-------
11116
cide r~gulations at 40 Cl'"'R 162.4 are consis-
tent with this view.
Comment 33: Are Intermediates and cata-
lysts intended solely for use in the produc-
tion of a food, food additive, drug, cosmetic,
or device subject to TSCA?
Response: The Administrator considers
that Intermediates -and catalysts intended
solely for use in the production of a food,
food additive, drug, cosmetic, or device are
excluded from regulation under TSCA. The
definitions of the FFDCA provide that
chemical substances which are intended for
use as a component of a food, food additive,
drug, cosmetic, or device are encompassed
",;thin the meaning of such terms, respec-
tively. The FDA considers intermediates
and catalysts to be such components. There-
fore, they are subject to regulation under
the FFDCA. Any such substance is excluded
from regulation under TSCA Insofar as it is
aclually manufactUred, processed, or dis-
tributed in commerce solely for use in the
NOTICES
production of a food, food additive, drug,
cosmetic, or device.
Comment 34: Employees should have the
option to submit reports anonymouslY.
Re8ponse: EP A considers that any person
may report information to EPA under
TSCA. Those who are required to do so
under section 8(e) are persons who manu-
facture, process, or distribute In commerce
chemical substances or mixtures, including
not only business entities but also such em-
ployees as described in Part II. In order to
establish that such persons have discharged
their obligations, and in order to encourage
responsible review of the quality of informa-
tion and the substantiality of risks, EPA be-
lieves that notlfiers should identify them-
selves. Section 23 will adequately protect
employees from discrimination pursuant to
notifications they have made under section
8(e).
[FR Doe. 78-7064 Filed 3-15,'18: 8:45 am]
FEDERAL REGISTER. VOL. 43, NO. 52-THURSDAY, MARCH 16. 1978
4?6
-------
APPENDIX B:
STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 62-75-9 CHEMICAL NAME: METHANAMINE, N-METHYL-N-NITROSO-
SUBMISSION #: 8EHQ-1280-0376
CAS NUMBER: 67-63-0 CHEMICAL NAME: 2-PROPANOL
SUBMISSION #: 8EHQ-1l80-0371
CAS NUMBER: 71-43-2 CHEMICAL NAME: BENZENE
SUBMISSION #: 8EHQ-0680-0345
CAS NUMBER: 71-55-6 CHEMICAL NAME: ETHANE, lil,l-TRICHLORO-
,I::. SUBMISSION #: 8EHQ-0980-0365 8EHQ-0982-0457
N
-...J
CAS NUMBER: 74-87-3 CHEMICAL NAME: METHANE, CHLORO-
SUBMISSION It: 8EHQ-1l82-0464
CAS NUMBER: 75-01-4 CHEMICAL NAME: ETHENE, CHLORO-
SUBMISSION #: 8EHQ-0680-0345 8EHQ-0982-0457
CAS NUMBER: 75-01-4 CHEMICAL NAME: VINYl CHLORIDE
SUBMISSION It: 8EHQ-0680-0345 8EHQ-0982-0457
CAS NUMBER: 75-09-2 CHEMICAL NAME: METHANE, DICHLORO-
SUBMISSION #: 8EHQ-0680-0345
-------
APPENDIX B:
STATUS ~EPORTS BY CAS NUMBER (CONT.)
CAS NUMBER:
75-09-2
CHEMICAL NAME: METHYLENE CHLORIDE
SUBMISSION #: 8EHQ-0680-0345
CAS NUMBER:
75-21-8
CHEMICAL NAME: ETHYLENE OXIDE
SUBMISSION #: 8EHQ-t832-0453
CAS NUMBER: 75-21-8 CHEMICAL NAME: OXIRANE
SUBMISSION #: 8EHQ-0882-0453
CAS NUMBER: 75-34-3 CH.EMICAL NAME: ETHANE, 1,1-DICHLORO-
SUBMISSION #: 8EHQ-0680-0345
*'"
tV CAS NUMBER: 75-38-7 CHEMICAL NAME: ETHENE, 1,1-DIFLUORO-
00
SUBMISSION #: 8EHQ-0480-0337
CAS NUMBER: 75-56-9 CHEMICAL NAME: OXIRANE, METHYL-
SUBMISSION I: 8EHQ-0282-0439
CAS NUMBER: 75-56-9 CHEMICAL NAME: PROPYL ENE OXIDE
SUBMISSION #: 8EHQ-0282-0439
CAS NUMBER: 75-71-8 CHEMICAL NAME: METHANE, DICHLORODIFLUORO-
SUBMISSION #: 8EHQ-0680-0345
CAS NUMBER: 75-91-2 CHEMICAL NAME: HYDROPEROXIDE, 1,I-DIMETHYLETHYL
SUBMISSION #: 8EHQ-1081-0415
-------
APPENDIX B:
CAS NUMBER: 76-06-2 CHEMICAL NAME: METHANE, TRICHlORONITRO-
SUBMISSION #: 8EHQ-I081-0416
CAS NUMBER: 77-48-5
SUBMISSION #: 8EHQ-0281-0382
CAS NUMBER: 77-73-6
SUBMISSION It: 8EHQ-0980-0364
CAS NUMBER: 77-73-6
SUBMISSION I: 8EHQ-0980-0364
,j::.
!\.)
I.D CAS NUMBER: 77-78-1
SUBMISSION It: 8EHQ-0482-0442
STATUS REPORTS BY CAS NUMBER (CONT.)
CHEMICAL NAME: 2,4-IMIDAZOlIDINEDIONE, 1,3-DIBROMO-5,5-DIMETHYl-
CHEMICAL NAME: DICYClOPENTADIENE
CHEMICAL NAME: 4,7-METHANO-IH-INDENE, 3A,4,7,7A-TETRAHYDRO-
CHEMICAL NAME: SULFURIC ACID, DIMETHYL ESTER
CAS NUMBER: 79-01-6 CHEMICAL NAME: ETHENE, TRICHlORO-
SUBMISSION I: 8EHQ-0680-0345 8EHQ-0982-0457
CAS NUMBER: 79-01-6 CHEMICAL NAM!::: TRICHLOROETHYLENE
SUBMISSION #: 8EHQ-0680-0345 8EHQ-0982-0457
CAS NUMBER: 80-08-0 CHEMICAL N~.ME: BENZENAMINE, 4,4'-SUlFONYlBIS-
SUBMISSION It: 8EHQ-0480-0338
CAS NUMBER: 80-08-0 CHEMICAL NAME: DDS
SUBMISSION It: 8EHQ-0480-0338
-------
APPENDIX B:
CAS NUMBER: 80-08-0 CHEMICAL NAME: EPORAL
SUBMISSION It: 8EHQ-0480-0338
CAS NUMBER: 81-88-9 CHEMICAL NAME: C. 1. BASIC VIOLET 10
SUBMISSION It: 8EHQ-0282-0434
CAS NUMBER: 81-88-9
SUBMISSION I: 8EHQ-0282-0434
CAS NUMBER: 81-88-9
~ SUBMISSION It: 8EHQ-0282-0434
w
0
CAS NUMBER: 81-88-9
SUBMISSION I: 8EHQ-0282-0434
CAS NUMBER:
86-28-2
SUBMISSION I: BEHQ-1080-036B
CAS NUMBER:
87-84-3
SUBMISSION It: 8EHQ-0381-0393
CAS NUMBER:
91-66-7
SUBMISSION It: BEHQ-0282-0430
STATUS REPORTS BY CAS NUMBER (CONT.)
CHEMICAL NAME: ETHANAMINIUM, N-[9-(2-CARBOXYPHENYl)-6-(DIETHYlAMINO)-3H-XAN
THEN-3-YlIDENEJ-N-ETHYl-, CHLORIDE
CHEMICAL NAME: D&C RED NO. 19
CHEMICAL NAME: RHODAMINE B
CHEMICAL NAME: 9H-CARBAZOlE, 9-ETHYL-
CHEMICAL NAME: CYClOHEXANE, 1,2,3,4,5-PENTABROMO-6-CHLORO-
CHEMICAL NAME: BENZENAMINE, N,N-DIETHYl-
3(
-------
APPENDIX B:
STATUS REPORTS BY CAS NUMBER (CONT.)
CAS NUMBER: 93-55-0 CHEMICAL NAME: I-PROPANONE, I-PHENYL-
SUBMISSION #: 8EHQ-0580-0341
CAS NUMBER: 95-50-1 CHEMICAL NAME: BENZENE, 1,2-DICHLORO-
SUBMISSION #: 8EHQ-1080-0368
CAS NUMBER: 95-53-4 CHEMICAL NAME: BENZENAMINE, 2-METHYL-
SUBMISSION #: 8EHQ-0680-0348
CAS NUMBER: 95-53-4 CHEMICAL NAME: TOLUIDINE (ORTHO)
SUBMISSION #: 8EHQ-0680-0348
*'"
w
I-' CAS NUMBER: 55-76-1 CHEMICAL NAME: BENZENAMINE, 3,4-DICHLORO-
SUBMISSION #: 8EHQ-0981-0409
CAS NUMBER: 95-80-7 CHEMICAL NAME: 1,3-BENZENEDIAMINE, 4-METHYL-
SUBMISSION #: 8EHQ-I080-0367
CAS NUMBER: 98-07-7 CHEMICAL NAME: BENZENE, (TRICHLOROMETHYL)-
SUBf'1ISSION #: 8EHQ-0980-0360 8EHQ-0582-0444
CAS NUMBER: 98-51-1 CHEMICAL NAME: BENZENE, 1-(1,I-DIMETHYlETHYL)-4-METHYL-
SUBMISSION #: 8EHQ-1281-0421 S
CAS NUMBER: 98-51-1 CHEMICAL NAME: TOLUENE, P-TERT-BUTYL-
SUBMISSION #: 8EHQ-1281-0421 S
-------
APPENDIX B:
STATUS REPORTS BY CAS NUMBER (CONT.)
CAS NUMBER:
98-73-7
CHEMICAL NAME: BENZOIC ACID, P-TERT-BUTYl-
SUBMISSION I: 8EHQ-0382-0440 S
CAS NUMBER: 98-73-7 CHEMICAL NAME: BENZOIC ACID, 4-(1,1-DIMETHYlETHYl)-
SUBMISSION I: 8EHQ-0382-0440 S
CAS NUMBER: 98-87-3 CHEMICAL NAME: BENZENE, (DICHlOROMETHYl)-
SUBMISSION I: 8EHQ-0582-0444
CAS NUMBER: 98-88-4 CHEMICAL NAME: BENZOYL CHLORIDE
SUBMISSION I: 8EHQ-0980-0360 8EHQ-0582-0444
*'"
w CAS NUMBER: 100-41-4 CHEMICAL NAME: BENZENE, ETHYl-
N
SUBMISSION I: 8EHQ-0680-0345 8EHQ-1080-0368
CAS NUMBER: 100-44-7 CHEMICAL NAME: BENZENE, (CHLOROMETHYl)-
SUBMISSION I: 8EHQ-0582-0444
CAS NUMBER: 101-02-0 CHEMICAL NAME: PHOSPHOROUS ACID, TRIPHENYl ESTER
SUBMISSION I: 8EHQ-0682-0451
CAS NUMBER: 102-77-2 CHEMICAL Nf.ME: MORPHOLINE, 4-(2-BENZOTHIAZOLYLTHIO)-
SUBMISSION I: 8EHQ-(l2~0-0334
CAS NUMBER:
102-77-2
CHEMICAL NAME: OBTS
SUBMISSION I: 8EHQ-0280-0334
-------
APPENDIX B: STATUS REPORTS BY CAS NUMBER (CONT.)
CAS NUMBER: 103-69-5' CHEMICAL NAME: BENZENAMINE, N-ETHYl-
SUBMISSION #: 8EHQ-0282-0429 *
CAS NUMBER: 106-42-3 CHEMICAL NAME: BENZENE, 1, 4-DIMETHYl-
SUBMISSION #: 8EHQ-I080-0368
CAS NUMBER: 106-99-0 CHEMICAL NAME: 1,3-BUTADIENE
SUBMISSION #: 8EHQ-I080-0370 8EHQ-0382-0441
CAS NUMBER: 107-18-6 CHEMICAL NAME: 2-PROPEN-I-0l
SUBMISSION I: 8EHQ-0181-0381
.J:>,
w
w CAS NUMBER: 108-30-5 CHEMICAL NAME: 2,5-FURANDIONE, DIHYDRO-
SUBMISSION I: 8EHQ-0282-0433 *
CAS NUMBER: 108-38-3 CHEMICAL NAME: BENZENE, 1, 3-DIMETHYl-
SUBMISSION I: 8EHQ-I080-0368
CAS NUMBER: 108-88-3 CHEMICAL NAME: BENZENE, METHYl-
SUBMISSION #: 8EHQ-0680-0345 8EHQ-I080-0368
CAS NUMBER: 108-88-3 CHEMICAL NAME: TOLUENE
SUBMISSION I: 8EHQ-0680-0345 8EHQ-I080-0368
CAS NUMBER: 108-90-7 CHEMICAL NAME: BENZENE, CHLORO-
SUBMISSION It: 8EHQ-I080-0368
-------
APPENDIX B:
CAS NUMBER: 110-26-9 CHEMICAL NAME: 2-PROPENAMIDE, N,N'-METHYLENEBIS-
SUBMISSION It: 8EHQ-0880-0357
CAS NUMBER: 110-80-5 CHEMICAL NAME: ETHANOL, 2- ETHOXY-
SUBMISSION It: 8EHQ-0381-0386
CAS NUMBER: 111-15-9 CHEMICAL NAME: ETHANOL, 2-ETHOXY-, ACETATE
SUBMISSION I: 8EHQ-0682-0450
.t:>o
W CAS HUMBER: 111-44-4 CHEMICAL NAME: ETHANE, 1,1'-OXYBIS[2-CHLORO-
.t:>o
SUBMISSION It: 8EHQ-0682-0449 S
CAS NUMBER: 117-81-7
SUBMISSION It: 8EHQ-0982-0457
CAS NUMBER: 118-52-5
SUBMISSION #: 8EHQ-0281-0382
CAS NUMBER: 121-14-2
SUBMISSION ,: 8EHQ-1080-0367
CAS NUMBER:
109-86-4
SUBMISSION ,: 8EHQ-0281-0384
CAS NUMBER:
121-69-7
SUBMISSION It: 8EHQ-0282-0428
STATUS REPORTS BY CAS NUMBER (CONT.)
CHEMICAL NAME: ETHANOL, 2-METHOXY-
CHEMICAL NAME: 1,2-BENZEHEDICARBOXYLIC ACID, BIS(2-ETHYLHEXYL) ESTER
CHEMICAL NAME: 2,4-IMIDAZOLIDINEDIONE, 1,3-DICHLORO-5,5-DIMETHYL-
CHEMICAL NAME: BENZENE, 1-METHYL-2,4-DINITRO-
CHEMICAL NAME: BENZEHAMINE, N,N-DIMETHYL-
*
-------
APPENDIX B:
STATUS REPORTS BY CAS NUMBER (CONT.)
CAS NUMBER:
123-91-1
CHEMICAL NAME: 1,4-DIOXANE
8EHQ-0380-0336 S
8EHQ-0682-0449 S
SUBMISSION #: 8EHQ-0280-0331 S
CAS NUMBER:
126-06-7
CHEMICAL NAME: 2,4-IMIDAZOlIDINEDIONE, 3-BROMO-1-CHlORO-5,5-DIMETHYl-
SUBMISSION #: 8EHQ-0281-0382
CAS NUMBER: 127-18-4 CHEMICAL NAME: ETHENE, TETRACHlORO-
SUBMISSION #: 8EHQ-0680-0345
CAS NUMBER: 127-18-4 CHEMICAL NAME: TETRACHLOROETHYLENE
SUBMISSION #: 8EHQ-0680-0345
~
w CAS NUMBER: 129-79-3 CHEMICAL NAME: 9H-FlUOREN-9-0NE, 2,4, 7-TRINITRO-
V1
SUBMISSION #: 8EHQ-0480-0339
CAS NUMBER:
129-79-3
CHEMICAL NAME: 2,4,7-TRINITROFlUORENONE
SUBMISSION #: 8EHQ-0480-0339
CAS NUMBER:
140-88-5
CHEMICAL NAME: 2-PROPENOIC ACID, ETHYL ESTER
SUBMISSION #: 8EHQ-1282-0467
CAS NUMBER:
156-60-5
CHEMICAL hAME: ETHENE, 1,2-DICHlORO-, (E)-
8EHQ-0982-0457
SUBMISSION #: 8EHQ-r6~O-0345
CAS NUMBER:
330-54-1
CHEMICAL NAME: DIURON
SUBMISSION #: 8EHQ-0981-0409
-------
APPENDIX B:
CAS NUMBER: 330-54-1
SUBMISSION I: 8EHQ-0981-0409
CAS NUMBER: 330-55-2
SUBMISSION I: 8EHQ-0981-0409
CAS NUMBER: 330-55-2
SUBMISSION ,: 8EHQ-0981-0409
CAS NUMBER: 619-80-7
SUBMISSION I: 8EHQ-1l82-0462
A
W CAS NUMBER: 624-83-9
'"
SUBMISSION ,: 8EHQ-0381-0392
CAS NUMBER: 635-22-3
SUBMISSION I: 8EHQ-0882-0452
CAS NUMBER:
709-98-8
SUBMISSION I: 8EHQ-0981-0409
CAS NUMBER:
709-98-8
SUBMISSION I: 8EHQ-0981-0409
CAS NUMBER:
818-61-1
SUBMISSION I: 8EHQ-0880-0356
STATUS REPORTS BY CAS NUMBER (CONT.)
CHEMICAL NAME: UREA, N'-(3,4-DICHlOROPHENYl)-N,N-DIMETHYl-
CHEMICAL NAME: lINURON
CHEMICAL NAME: UREA, N'-(3,4-DICHLOROPHENYL)-N-METHOXY-N-METHYl-
CHEMICAL NAME: BENZAMIDE, 4-NITRO-
CHEMICAL NAME: METHANE, ISOCYANATO-
CHEMICAL NAME: BENZENAMINE, 4-CHlORO-3-NITRO-
CHEMICAL NAME: PROPANIl
CHEMICAL NAME: PROPIONAMIDE, N-(3,4-DICHlOROPHENYl)-
CHEMICAL NAME: 2-PROPENOIC ACID, 2-HYDROXYETHYl ESTER
-------
APPENDIX B:
CAS NUMBER: 823-40-5
SUBMISSION #: 8EHQ-10JO-0367
CAS NUMBER: 868-85-9
SUBMISSION #: 8EHQ-l080-0366
CAS NUMBER: 939-97-9
SUBMISSION #: 8EHQ-128l-042l S
CAS NUMI\ER: 939-97-9
SUBMISSION #: 8EHQ-128l-042l S
w:::.
w CAS NUMBER: 99-3-43-1
-...]
SUBMISSION #: 8EHQ-098l-04l2
CAS NUMBER: 1072-71-5
SUBMISSION #: 8EHQ-018l-0380
CAS NUMBER:
13 0 9-6 4-4
SUBMISSION #: 8EHQ-0580-0342
CAS NUMBER:
1313-82-2
SUBMISSION #: 8EHQ-0282-0435
CAS NUMBER:
1336-36-3
SUBMISSION #: 8EHQ-0780-0352
STATUS REPORTS BY CAS NUMBER (CONT.)
CHEMICAL ~AME: 1,3-BENZENEDIAMINE, 2-METHYL-
CHEMICAL NAME: PHOSPHONIC ACID, DIMETHYL ESTER
CHEMICAL NAME: BENZALDEHYDE, P-TERT-BUTYL-
C~EMICAL NAME: BENZALDEHYDE, 4-(1,1-DIMETHYLETHYL)-
CHEMICAL NAME: PHOSPHONOTHIOIC DICHLORIDE, ETHYL-
CHEMICAL NAME: 1,3,4-THIADIAZOLIDINE-2,5-DITHIONE
*
CHEMICAL NAME: ANTIMONY OXIDE
CHEMICAL NAME: SODIUM SULFIDE
CHEMICAL NAME: l,l'-BIPHENYL, CHLORINATED
8EHQ-098l-0413
8EHQ-0982-0457
-------
APPENDIX B:
CAS NUMBER:
1336-36-3
SUBMISSION ,: 8EHQ-0780-0352
CAS NUMBER: 1643-20-5
SUBMISSION #: 8EHQ-1280-0376
CAS NUMBER: 1680-21-3
SUBMISSION #: 8EHQ-0981-0410
CAS NUMBER: 1691-99-2
*'" SUBMISSION #: 8EHQ-1180-0373 S
w
CD
CAS NUMBER: 1746-01-6
SUBMISSION #: 8EHQ-0381-0390
CAS NUMBER: 2215-35-2
SUBMISSION #: 8EHQ-0680-0346
CAS NUMBER: 2481-94-9
SUBMISSION #: 8EHQ-G9~2-0455
CAS NUMBER:
2481-94-9
SUBMISSION #: 8EHQ-0982-0455
STATUS REPORTS BY CAS NUMBER eCONT.)
CHEMICAL NAME: POLYCHLORINATED BIPHENYLS epCB)
8EHQ-0981-0413
8EHQ-0982-0457
CHEMICAL NAME: 1-DODECANAMINE, N,N-DIMETHYL-, N-OXIDE
CHEMICAL NAME: 2-PROPENOIC ACID, 1,2-ETHANEDIYLBISeOXY-2,1-ETHANEDIYL) ESTE
R
CHEMICAL NAME: 1-0CTANESULFONAMIDE, N-ETHYL-1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8
,8-HEPTADECAFLUORO-N-e2-HYDROXYETHYL)-
CHEMICAL NAME: DIOXIN, 2,3,7,8-TETRACHLORODIBENZO-P-
CHEMICAL NAME: 2-PENTANOL, 4-METHYL-, HYDROGEN PHOSPHORODITHIOATE, ZINC SAl
T
CHEMICAL ~AME: BENZENAMINE, N,N-DIETHYL-4-ePHENYLAZO)-
CHEMICAL NAME: OIL YELLOW E190
-------
APPENDIX B:
STATUS REPORTS BY CAS NUMBER (CONT.)
CAS NUMBER:
2481-94-9
CHEMICAL NAME: C. I. SOLVENT YELLOW 56
SUBMISSION #: 8EHQ-0982-0455
CAS NUMBER: 2487-90-3 CHEMICAL NAME: SILANE, TRIMETHOXY-
SUBMISSION #: 8EHQ-0680-0347
CAS NUMBER: 2524-03-0
SUBMISSION #: 8EHQ-0381-0387
CAS NUMBER: 2997-92-4
SUBMISSION #: 8EHQ-0282-0427 S
*"
W
\.0 CAS NUMBER: 2997-92-4 CHEMICAL NAME: V-50
SUBMISSION #: 8EHQ-0282-0427 S
CHEMICAL NAME: PHOSPHOROCHLORIDOTHIOIC ACID, O,O-DIMETHYl ESTER
CHEMICAL NAME: PROPANIMIDAMIDE, 2,2'-AZOBIS£2-METHYl-, DIHYDROCHLORIDE
CAS NUMBER:
3076-26-4
CHEMICAL NAME: OCTADECANOIC ACID, 2-SULFO-, I-METHYL ESTER
SUBMISSION #: 8EHQ-0482-0442
CAS NUMBER:
3388-04-3
CHEMICAL NAME: SILANE A-186
SUBMISSION #: 8EHQ-0681-0402
CAS NUMBER:
3388-04-3
CHEMICAL NAME: SILANE, TRIMETHOXY£2-(7-0XABICYClO£4.1.0JHEPT-3-YL)ETHYlJ-
SUBMISSION #: 8EHQ-0681-0402
CAS NUMBER:
3445-11-2
CHEMICAL NAME: 2-PYRROlIDINONE, 1-(2-HYDROXYETHYl)-
SUBMISSION #: 8EHQ-0682-0448 S
-------
APPENDIX B:
CAS NUMBER: 3524-68-3
SUBMISSION It: 8EHQ-0882-0454
CAS NUMBER: 4680-78-8
SUBMISSION I: 8EHQ-0780-0350
CAS NUMBER: 4680-78-8
SUBr.ISSION It: 8EHQ-0780-0350
.t:-
.t:-
o
CAS NUMBER:
4986-89-4
SUBMISSION It: 8EHQ-0882-0454
CAS NUMBER: 5026-74-4
SUBMISSION It: 8EHQ-1281-0426
CAS NUMBER: 5216-25-1
SUBMISSION It: 8EHQ-0980-0360
CAS NUMBER: 6175-45-7
SUBMISSION It: 8EHQ-0581-0400
CAS NUMBER: 6175-45-7
SUBMISSION It: 8EHQ-0581-0400
STATUS REPORTS BY CAS NUMBER CCONT.)
CHEMICAL NAME: 2-PROPENOIC ACID, 2-(HYDROXYMETHYL)-2-[[C1-0XO-2-PROPENYL)OX
YJMETHYLJ-1,3-PROPANEDIYL ESTER
CHEMICAL NAME: C. I. ACID GREEN 3
CHEMICAL NAME: BENZENEMETHANAMINIUM, N-ETHYL-N-14-[14-IETHYL[C3-SULFOPHENYL
)METHYLJAMINOJPHENYLJPHENYLMETHYLENEJ-2,5-CYCLOHEXADIEN-1-YL
IDENEJ-3-SULFO-, HYDROXIDE, INNER SALT, SODIUM SALT
CHEMICAL NAME: 2-PROPENOIC ACID, 2,2-BISIIC1-0XO-2-PROPENYL)OXYJMETHYLJ-1,3
-PROPANEDIYL ESTER
CHEMICAL NAME: OXIRANEMETHANAMINE, N-14-COXIRANYLMETHOXY)PHENYLJ-N-COXIRANY
LMETHYL) -
CHEMICAL NAME: BENZENE, 1-CHLORO-4-CTRICHLOROMETHYL)-
CHEMICAL NAME: ETHANONE, 2,2-DIETHOXY-1-PHENYL-
CHEMICAL NAME: U-2352
-------
CAS NUMBER: 6227-14-1 CHEMICAL NAME: C. 1. DIRECT VIOLET 9
SUBMISSION I: 8EHQ-0282-0437
CAS NUMBER: 6227-14-1
SUBMISSION I: 8EHQ-0282-0437
CAS NUMBER: 6368-72-5
SUBMISSION #: 8EHQ-0982-0455
CAS NUMBER: 6368-72-5
~ SUBMISSION I: 8EHQ-0982-0455
~
f-J
CAS NUMBER: 7439-92-1
SUBMISSION I: 8EHQ-0680-0345
CAS NUMBER: 7439-97-6
SUBMISSION I: 8EHQ-0680-0345
APPENDIX B:
CAS NUMBER:
7440-02-0
SUBMISSION #: 8EHQ-r.6~0-0345
CAS NUMBER:
7440-22-4
SUBMISSION I: 8EHQ-0680-0345
STATUS REPORTS BY CAS NUMBER (CONT.)
CHEMICAL NAME: 2-NAPHTHALENESULFONIC ACID, 4-HYDROXY-3-[[2-METHOXY-5-METHYL
-4-[(4-SULFOPHENYL)AZOIPHENYLIAZOI-7-(PHENYLAMINO)-, DISODIU
M SALT
CHEMICAL NAME: 2-NAPHTHALENAMINE, N-ETHYL-1-[[4-(PHENYLAZO)PHENYLIAZOI-
CHEMICAL NAME: C. I. SOLVENT RED 19
CHEMICAL NAME: LEAD
CHEMICAL NAME: MERCURY
CHEMICAL ~AME: NICKEL
CHEMICAL NAME: SILVER
-------
APPENDIX B: STATUS REPORTS BY CAS NUMBER CCONT.)
CAS NUMBER: 7440-28-0 CHEMICAL NAME: THALLIUM
SUBMISSION I: 8EHQ-0680-0345
CAS NUMBER: 7440-36-0 CHEMICAL NAME: ANTIMONY
SUBMISSION I: 8EHQ-0680-0345
CAS NUMBER: 7440-38-2 CHEMICAL NAME: ARSENIC
SUBMISSION I: 8EHQ-0680-0345
CAS NUMBER: 7440-41-7 CHEMICAL NAME: BERYlLIUM
SUBMISSION I: 8EHQ-0680-0345
.1:>0
.1:>0
N CAS NUMBER: 7440-43-9 CHEMICAL NAME: CADMIUM
SUBMISSION I: 8EHQ-0280-0332 8EHQ-0680-0345
CAS NUMBER: 7440-47-3 CHEMICAL NAME: CHROMIUM
SUBMISSION ,: 8EHQ-0680-0345
CAS NUMBER: 7440-50-8 CHEMICAL NAME: COPPER
SUBMISSION ,: 8EHQ-0680-0345
CAS NUMBER: 7440-66-6 CHEMICAL NAME: ZINC
SUBMISSION I: 8EHQ-0680-0345
CAS NUMBER: 7446-09-5 CHEMICAL NAME: SULFUR DIOXIDE
SUBMISSION I: 8EHQ-0181-0378
-------
APPENDIX B: S T A H'S REPORTS BY CAS NUMBER (CONT.)
CAS NUMBER: 7705-08-0 CHEMICAL NAME: IRON CHLORIDE
SUBMISSION #: 8EHQ-0880-0358 *
CAS NUMBER: 7782-49-2 CHEMICAL NAME: SELENIUM
SUBMISSION #: 8EHQ-0680-0345
CAS NUMBER: 7782-50-5 CHEMICAL NAME: CHLORINE
SUBMISSION #: 8EHQ-1l82-0466 'E
CAS NUMBER: 7783-06-4 CHEMICAL NAME: HYDROGEN SULFIDE
SUBMISSION #: 8EHQ-0580-0343
~
~ CAS NUMBER: 7789-21-1 CHEMICAL NAME: FLUOROSULFURIC ACID
w
SUBMISSION #: 8EHQ-0881-0407
CAS NUMBER: 8004-87-3 CHEMICAL NAME: C. 1. BASIC VIOLET 1
SUBMISSION #: 8EHQ-0282-0436 *
CAS NUMBER: 8006-61-9 CHEMICAL NAME: GASOLINE, NATURAL
SUBMISSION #: 8EHQ-1281-0422
CAS NUMBER: 8006-61-9 CHEMICAL NAME: GASOLINE, UNLEADED
SUBMISSION ~t: 8EHQ-1281-0422
CAS NUMBER: 9003-01-4 CHEMICAL NAME: POLYACRYLIC ACID
SUBMISSION #: 8EHQ-0382-0438 S
-------
APPENDIX B:
CAS NUMBER:
9003-01-4
SUBMISSION I: 8EHQ-0382-0438 S
CAS NUMBER:
10199-89-0
SUBMISSION I: 8EHQ-0281-0383 S
CAS NUMBER:
10310-38-0
SUBMISSION I: 8EHQ-0780-0369
CAS NUMBER: 10310-38-0
SUBMISSION I: 8EHQ-0780-0369
~
~
~
CAS NUMBER: 10533-67-2
SUBMISSION #: 8EHQ-0880-0355
CAS NUMBER: 10588-01-9
SUBMISSION #: 8EHQ-1l82-0463
CAS NUMBER: 12002-48-1
SUBMISSION #: 8EHQ-(,9~2-0457
CAS NUMBER: 13292-87-0
SUBMISSION #: 8EHQ-1180-0372
STATUS R~PURrS BY CAS NUMBER (CONT.)
CHEMICAL NAME: 2-PROPENOIC ACID, HOMOPOLYMER
CHEMICAL NAME: BENZOFURAZAN, 4-CHLORO-7-NITRO-
*
CHEMICAL NAME: CYAGARD RF-1
CHEMICAL NAME: PHOSPHONIUM, 1,2-ETHANEDIYLBIS[TRIS(2-CYANOETHYL)-, DIBROMID
E
CHEMICAL NAME: ACETALDEHYDE, (METHYLTHIO)-, OXIME
CHEMICAL NAME: CHROMIC ACID, DISODIUM SALT
CHEMICAL NAME: BENZENE, TRICHLORO-
CHEMICAL NAME: BORANE, COMPD. WITH THIOBIS[METHANEJ (1:1)
-------
APPENDIX B:
CAS NUMBER:
13674-87':'8
SUBMISSION I: 8EHQ-1280-0401 S
CAS NUMBER: 13674-87-8
SUBMISSION I: 8EHQ-1280-0401 S
CAS NUMBER: 13752-51-7
SUBMISSION I: 8EHQ-0280-0334
CAS NUMBER: 13752-51-7
SUBMISSION I: 8EHQ-0280-0334
,j::o,
,j::o, CAS NUMBER: 13765-19-0
U1
SUBMISSION I: 8EHQ-1l82-0463
CAS NUMBER: 14047-09-7
SUBMISSION I: 8EHQ-0981-0409
CAS NUMBER: 14285-59-7
SUBMISSION I: 8EHQ-0980-0361 S
CAS NUMBER:
14808-60-7
SUBMISSION I: 8EHQ-0780-0354
STATUS REPORTS BY CAS NUMBER (CONT.)
CHEMICAL NAME: FYROl FR-2
CHEMICAL NAME: 2-PROPANOL, 1,3-DICHlORO-, PHOSPHATE (3:1)
CHEMICAL NAME: CURE-RITE 18
CHEMICAL NAME: MORPHOlINE, 4-[(4-MORPHOlINYlTHIO)THIOXOMETHYLJ-
CHEMICAL NAME: CHROMIC ACID, CALCIUM SALT (1:1)
CHEMICAL NAME: BENZENE, 3,3',4,4'-TETRACHlOROAZO-
8EHQ-1281-0424
CHEMICAL NAME" C~3AlTATE(4-), [29H,31H-PHTHAlOCYANINE-2,9,16,23-TETRASUlFON
ATO(6-)-N29,N30,N31,N32J-, TETRAHYDROGEN, (SP-4-l)-
CHEMICAL NAME: QUARTZ
-------
APPENDIX B:
CAS NUMBER:
15022-08-9
SUBMISSION #: 8EHQ-0181-0381
CAS NUMBER:
15336-81-9
SUBMISSION #: 8EHQ-0481-0397
CAS NUMgER:
15336-82-0
SUBMISSION #: 8EHQ-1081-0418
CAS NUMBER: 15336-82-0
oJ::> SUBMISSION #: 8EHQ-1081-0418
oJ::>
0)
CAS NUMBER: 17557-23-2
SUBMISSION #: 8EHQ-0481-0397
CAS NUMBER: 17831-71-9
SUBMISSION #: 8EHQ-0981-0411
CAS NUMBER:
20354-26-1
SUBMISSION #: 8EHQ-0981-0409
CAS NUMBER:
20354-26-1
SUBMISSION #: 8EHQ-0981-0409
STATUS REPORTS BY CAS NUMBER (CaNT.)
CHEMICAL NAME: CARBONIC ACID, DI-2-PROPENYL ESTER
CHEMICAL NAME: 2,4-IMIDAZOLIDINEDIONE, 5,5-DIMETHYL-1,3-BIS(OXIRANYLMETHYL)
CiiEMICAl NAME: 2.4-IMIDAZOLIDINEDIONE, 5-ETHYl-5-METHYl-1,3-BIS(OXIRANYLMET
HYL) -
CHEMICAL NAME: XU-238
CHEMICAL NAME: OXIRANE, 2,2'-[(2.2-DIMETHYl-1,3-PROPANEDIYl)BIS(OXYMETHYLEN
E>JBIS-
CHEMICAL NAME: 2-PROPENOIC ACID. OXYBIS(2,1-ETHANEDIYLOXY-~,1-ETHANEDIYL) E
STER
CHEMICAL NAME: METHAZOLE (TECHNICAL)
CHEMICAL NAME: 1,2,~-OXADIAZOLIDINE-3.5-DIONE,
-------
APPENDIX B:
CAS NUMBER: 21232-47-3
SUBMISSION #: 8EHQ-0981-0409
CAS NUMBER: 21850-44-2
SUBMISSION #: 8EHQ-0982-0458
CAS NUMBER: 25038-04-4
SUBMISSION #: 8EHQ-0781-0406 S
CAS NUMBER: 25134-21-8
~ SUBMISSION #: 8EHQ-0282-0431
~
-....J
CAS NUMBER: 25134-21-8
SUBMISSION #: 8EHQ-0282-0431
CAS NUMBER:
25167-82-2
SUBMISSION #: 8EHQ-0381-0390
CAS NUMBER:
25321-14-6
SUBMISSION #: 8EHQ-I080-0367
CAS NUMBER:
25376-45-8
SUBMISSION #: 8EHQ-I080-0367
STATUS REPORTS BY CAS NUMBER (CONT.)
CHEMICAL NAME: BENZENE. 3.3',4,4'-TETRACHlOROAZOXY-
8EHQ-1281-0424
CHEMICAL NAME: BENZENE. 1.1'-(1-METHYlETHYlIDEHE)BIS£3.5-DIBROMO-4-(2.3-DIB
ROMOPROPOXn -
CHEMICAL NAME: 1,2,3-PROPANETRIOl. POLYMER WITH (CHlOROMETHYl)OXIRANE
CHEMICAL NAME: 4.7-METHANOISOBENZOFURAN-l,3-DIONE, 3A.4.7.7A-TETRAHYDROMETH
Yl-
*
CHEMICAL NAM~: NADIC METHYL ANHYDRIDE
*
CHEMICAL NAME: PHENOL, TRICHlORO-
CHEMICAL NAME: BENZENE. METHYlDINITRO-
CHEMICAL NAME: BENZENEDIAMINE. AR-METHYl-
-------
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
"'-
"'-
00
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
APPENDIX B:
25377-73-5
SUBMISSION #: 8EHQ-0282-0432
26472-00-4
SUBMISSION #: 8EHQ-I081-0419
26472-00-4
SUBMISSION #: 8EHQ-I081-0419
28768-32-3
SUBMISSION #: 8EHQ-0480-0338
28768-32-3
SUBMISSION #: 8EHQ-0480-0338
29383-29-7
SUBMISSION #: 8EHQ-0980-0361 S
29454-23-7
SUBMISSION #: 8EHQ-0482-0442
30638-08-5
SUBMISSION I: 8EHQ-0681-0403 S
STATUS REPORTS BY CAS NUMBER (CONT.)
CHEMICAL NAME: 2.5-FURANDIOHE. 3-(DODECEHYl)DIHYDRO-
1(
CHEMICAL NAME: 4.7-NETHANO-IH-INDENE. 3A.4.7.7A-TETRAHYDRODIMETHYl-
CHEMICAL NAME: METHYlCYClOPENTADIENE DIMER
CHEMICAL HAME: MY 720
CHEMICAL NAME: OXIRAHEMETHAHAMIHE. N,N'-(METHYlEHEDI-4.1-PHENYlENE)BISrN-(O
XI RANYlMETHYl)-
CHEMICAL NAME: COBALTATE(2-), r29H,31H-PHTHAlOCYANINEDISULFONATO(4-)-N29,N3
O,N31,N32)-. DIHYDROGEN
8EHQ-0681-0403 S
CHEMICAL NAME: TETRADECANOIC ACID. 2-SULFO-, I-METHYL ESTER
CHEMICAL NAME: COBAlTATE(l-), [29H.31H-PHTHAlOCYANINESUlFONATO(3-)-H29,H30,
N31,N32J-, HYDROGEN
-------
APPENDIX B:
CAS NUMBER:
30947-30-9
SUBMISSION I: 8EHQ-0482-0443
CAS NUMBER:
30947-30-9
SUBMISSION I: 8EHQ-0482-0443
CAS NUMBER:
53417-29-1
SUBMISSION I: 8EHQ-0882-0454
CAS NUMBER: 57138-85-9
~ SUBMISSION I: 8EHQ-0980-0362
~
\.0
CAS NUMBER: 57472-68-1
SUBMISSION I: 8EHQ-I082-0459
CAS NUMBER: 58849-75-5
SUBMISSION I: 8EHQ-0482-0442
CAS NUMBER: 61789-87-5
SUBMISSION I: 8EHQ-I081-0414
CAS NUMBER:
63231-67-4
SUBMISSION I: 8EHQ-0780-0354
STATUS REPORTS BY CAS NUMBER eCONT.)
CHEMICAL NAME: IRGASTAB 2002
CHEMICAL NAME: PHOSPHONIC ACID, [(3,5-BISel,I-DIMETHYLETHYL)-4-HYDROXYPHENY
LJMETHYLJ-, MONO ETHYL ESTER, NICKELe2+) SALT e2:1)
CHEMICAL NAME: PENTAERYTHRITOL DIACRYLATE
CHEMICAL NAME: BENZENAMINE, POLYMER WITH FORMALDEHYDE, HYDROCHLORIDE
CHEMICAL NAME: 2-PROPENOIC ACID, OXYBISeMETHYL-2,I-ETHANEDIYL) ESTER
CHEMICAL NAME: HEXADECANOIC ACID, 2-SULFO-, I-METHYL ESTER
CHEMICAL NAME: SULFONIC ACIDS, PETROLEUM, MAGNESIUM SALTS
CHEMICAL NAME: SILICA GEL
-------
APPENDIX B:
CAS NUMBER:
64741-46-4
SUBMISSION I: 8EHQ-0682-0446 S
CAS NUMBER:
64741-52-2
SUBMISSION #: 8EHQ-0682-0447
CAS NUMBER:
64741-55-5
SUBMISSION #: 8EHQ-0682-0446 S
J
CAS NUMBER: 64741-64-6
SUBMISSION #: 8EHQ-0682-0446 S
,j:>,
U1
0 CAS NUMBER: 64741-67-9
SUBMISSION #: 8EHQ-0280-0333
CAS NUMBER: 64741-67-9
SUBMISSION #: 8EHQ-0280-0333
CAS NUMBER: 64742-04-7
SUBMISSION #: 8EHQ-n~n-0385
CAS NUMBER: 64742-04-7
SUBMISSION #: 8EHQ-0281-0385
CAS NUMBER: 64742-11-6
SUBMISSION I: 8EHQ-0281-0385
STATUS REPORTS BY CAS NUMBER (CONT.)
CHEMICAL NAME: NAPHTHA (PETROLEUM), LIGHT STRAIGHT-RUN
CHEMICAL NAME: DISTILLATES (PETROLEUM), LIGHT NAPHTHENIC
CHEMICAL NAME: NAPHTHA (PETROLEUM), LIGHT CATALYTIC CRACKED
CHEMICAL NAME: NAPHTHA (PETROLEUM), FULL-RANGE ALKYLATE
CHEMICAL NAME: KERMAC 218A
CHEMICAL NAME: RESIDUES (PETROLEUM), CATALYTIC REFORMER FRACTIONATOR
CHEMICAL NAME: EXTRACTS (PETROLEUM), HEAVY PARAFFINIC DISTILLATE SOLVENT
CHEMICAL NAME: GULF N.E. 75 (PROCESS 63)
CHEMICAL NAME: EXTRACTS (PETROLEUM), HEAVY NAPHTHENIC DISTILLATE SOLVENT
-------
APPENDIX B:
STATUS REPORTS BY CAS NUMBER (CONT.)
CAS NUMBER:
64742-11-6
CHEMICAL NAME: GULF N.E. 61 (PROCESS 65)
SUBMISSION #: 8EHQ-0281-0385
CAS NUMBER:
64742-16-1
CHEMICAL NAME: PETROLEUM RESINS
SUBMISSION #: 8EHQ-0281-0385
CAS NUMBER: 64742-46-7 CHEMICAL NAME: DISTILLATES (PETROLEUM), HYDROTREATED MIDDLE
SUBMISSION #: 8EHQ-0280-0333
CAS NUMBER: 64742-46-7 CHEMICAL NAME: KERMAC 600W
SUBMISSION #: 8EHQ-0280-0333
.::.
lJ1
I-' CAS NUMBER: 64742-52-5 CHEMICAL NAME: DISTILLATES (PETROLEUM), HYDROTREATED HEAVY NAPHTHENIC
SUBMISSION #: 8EHQ-0281-0385
CAS NUMBER: 64742-52-5 CHEMICAL NAME: GULF 100 TEXAS OIL
SUBMISSION #: 8EHQ-0281-0385
CAS NUMBER: 64742-55-8 CHEMICAL NAME: DISTILLATES (PETROLEUM), HYDROTREATED LIGHT PARAFFINIC
SUBMISSION #: 8EHQ-0281-0385 8EHQ-0681-0404
CAS NUMBER: 64742-55-8 CHEMICAL NAME: GULF PARALUX 70
SUBMISSION #: 8EHQ-0681-0404
CAS NUMBER: 67762-92-9 CHEMICAL NAME: SILICONE Y-6607
SUBMISSION #: 8EHQ-0680-0349
-------
APPENDIX B:
CAS NUMBER: 67762-92-9
SUBMISSION #: 8EHQ-0680-0349
CAS NUMBER: 68153-35-5
SUBMISSION #: 8EHQ-1l80-0371
CAS NUMBER: 68187-58-6
SUBMISSION #: 8EHQ-0780-0353
CAS NUMBER: 68308-34-9
SUBMISSION #: 8EHQ-1081-0417
~
U1
IV
CAS NUMBER: 68410-08-2
SUBMISSION It: 8EHQ-0980-0363
CAS NUMBER: 68441-14-5
SUBMISSION #: 8EHQ-1281-0420
CAS NUMBER: 68441-14-5
SUBr'lISSION I: 8EHQ-1281-0420
CAS NUMBER: 68441-14-5
SUBMISSION It: 8EHQ-1281-0420
STATUS REPORTS BY CAS NUMBER (CONT.)
CHEMICAL NAME: SILOXANES AND SILICONES, DI-ME, DIMETHYL AMINO-TERMINATED
CHEMICAL NAME: ETHANAMINIUM, 2-AMINO-N-(2-AMINOETHYL)-N-(2-HYDROXYETHYL)-N-
METHYL-, N,N'-DITALLOW ACYL DERIVS., ME SULFATES (SALTS)
CHEMICAL NAME: PITCH, PETROLEUM, CONDENSED-RING AROM.
CHEMICAL NAME: SHALE OILS
CHEMICAL NAME: DISTILLATES (COAL), SOLVENT-REFINING (SRC), RECYCLE
CHEMICAL NAME: BROMOBUTYL 2244
CHEMICAL NAME: 1,3-BUTADIEHE, 2-METHYL-, POLYMER WITH 2-METHYL-1-PROPEHE, B
ROMINATED
CHEMICAL NAME: RUBBER, BROMINATED BUTYL-
-------
APPENDIX B:
STATUS REPORTS BY CAS NUMBER (CONT.)
CAS NUMBER:
68442-22-8
CHEMICAL NAME: PHOSPHORODITHIOIC ACID, MIXED 2-ETHYlHEXYl AND 2-METHYlPROPY
l ESTERS, ZINC SALTS
SUBMISSION It: 8EHQ-0680-0346
CAS NUMBER: 68479-77-6 CHEMICAL NAME: Bl-4420
SUBMISSION It: 8EHQ-0381-0391
CAS NUMBER: 68479-77-6
SUBMISSION #: 8EHQ-0381-0391
CAS NUMBER: 68555-73-7
""
IJ1 SUBMISSION It: 8EHQ-1l80-0373 S
w
CHEMICAL NAME: PROPANOIC ACID, 2,3-DIBROMO-, 2-HYDROXYETHYl ESTER
CHEMICAL NAME: I-HEPTANESUlFONAMIDE, N-ETHYl-l,l,2,2,3,3,4,4,5,5,6,6,7,7,7-
PENTADECAFlUORO-N-(2-HYDROXYETHYl)-
* Based on a preliminary evaluation, EPA believes that the submitted information did not warrant reporting pursuant to
Section 8(e) of TSCA. In some cases, a submitting company was requested to provide the basis for its contention that
the reported information offered reasonable support for a conclusion of substantial risk of injury to health and/or
the environment as defined in EPA's March 16, 1978, TSCA Section 8(e) policy statement (Appendix A of this volume).
-------
454
-------
APPENDIX C:
CAS NUMBER: 10533-67-2
SUBMISSION #: 8EHQ-0880-0355
CAS NUMBER: 4680-78-8
SUBMISSION #: 8 EHQ-O 780-0 350
CAS NUMBER: UNKNOWN
SUBMISSION #: 8EHQ-0382-0438 S
CAS NUMBER: 7440-36-0
*'" SUBMISSION #: 8EHQ-0680-0345
U1
U1
CAS NUMBER: 1309-64-4
SUBMISSION #: 8EHQ-0580-0342
CAS NUMBER:
7440-38-2
SUBMISSION I: 8EHQ-0680-0345
CAS NUMBER:
8004-87-3
SUBMISSION I: 8EHQ-0282-0436
CAS NUMBER:
81-88-9
SUBMISSION #: 8EHQ-0282-0434
STATUS REPORTS BY CHEMICAL NAME
CHEMICAL NAME: ACETALDEHYDE, (METHYLTHIO)-, OXIME
CHEMICAL NAME: C. I. ACID GREEN 3
CHEMICAL NAM~: ACRYLIC ACID-STARCH GRAFT, PARTIAL SODIUM SALT
CHEMICAL NAME: ANTIMONY.
CHEMICAL NAME: ANTIMONY OXIDE
CHEMICAL NAME: ARSENIC
CHEMICAL NAME: C. I. BASIC VIOLET 1
1E
CHEMICAL NAME: C. I. BASIC VIOLET 10
-------
CAS NUMBER:
CAS HUMBER:
CAS HUMBER:
CAS NUMBER:
~
Vl CAS NUMBER:
0'\
CAS NUMBER:
CAS HUMBER:
CAS NUMBER:
CAS NUMBER:
APPENDIX C:
939-97-9
SUBMISSION I: 8EHQ-1281-0421 S
939-97-9
SUBMISSION #: 8EHQ-1281-0421 S
619-80-7
SUBMISSION #: 8EHQ-1182-0462
103-69-5
SUBMISSION #: 8EHQ-0282-0429
91-66-7
SUBMISSIOH #: 8EHQ-0282-0430
2481-94-9
SUBMISSION #: 8EHQ-0982-0455
121-69-7
SUBMISSION #: 8EHQ-0282-0428
57138-85-9
SUBMISSION #: 8EHQ-0980-0362
95-53-4
SUBMISSION #: 8EHQ-0680-0348
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CHEMICAL NAME: BENZALDEHYDE, P-TERT-BUTYL-
CHEMICAL NAME: BENZALDEHYDE, 4-(1,1-DIMETHYLETHYL)-
CHEMICAL NAME: BENZAMIDE, 4-NITRO-
CHEMICAL HAME: BEHZEHAMINE, N-ETHYL-
*
CHEMICAL NAME: BEHZEHAMIHE, H,N-DIETHYL-
*
CHEMICAL NAME: BENZENAMINE, H,N-DIETHYL-4-{PHENYLAZO)-
CHEMICAL NAME: BENZEHAMIHE, N,N-DIMETHYL-
*
CHEMICAL NAME: BENZENAMINE, POLYMER WITH FORMALDEHYDE, HYDROCHLORIDE
CHEMICAL NAME: BENZENAMINE, 2-METHYL-
-------
APPENDIX C:
CAS NUMBER:
95-76-1
SUBMISSION I: 8EHQ-0981-0409
CAS NUMBER: 635-22-3
SUBMISSION I: 8EHQ-0882-0452
CAS NUMBER: 80-08-0
SUBMISSION I: 8EHQ-0480-0338
CAS NUMBER: 71-43-2
SUBMISSION I: 8EHQ-0680-0345
"""
U1 CAS NUMBER: 108-90-7
-.J
SUBMISSION I: 8EHQ-1080-0368
CAS NUMBER:
100-44-7
SUBMISSION #: 8EHQ-0582-0444
CAS NUMBER:
25376-45-8
SUBMISSION #: 8EHQ-1080-0367
CAS NUMBER:
UNKNOWN
SUBMISSION #: 8EHQ-1082-0461
CAS NUMBER:
823-40-5
SUBMISSION I: 8EHQ-I080-0367
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CrlEMICAL NAME: BENZENAMINE, 3,4-DICHLORO-
CHEMICAL NAME: BENZENAMINE, 4-CHLORO-3-NITRO-
CHEMICAL NAME: BENZENAMINE, 4,4'-SULFONYLBIS-
CHEMICAL NAME: BENZENE
CHEMICAL NAME: BENZENE, CHLORO-
CHEMICAL NAME: BENZENE, (CHLOROMETHYL)-
CHEMICAL NAME: BENZENEDIAMINE, AR-METHYL-
CHEMICAL NAME: BENZENEDIAMINE(S), CHLORINATED, AR-METHYL-
CHEMICAL NAME: 1,3-BENZENEDIAMINE, 2-METHYL-
-------
APPEtmIX C:
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CAS NUMBER: 95-80-7
SUBMISSION 1t: 8EHQ-1080-0367
CAS NUMBER: 117-81-7
SUBMISSION 1t: 8EHQ-0982-0457
CAS NUMBER: UNKNOWN
SUBMISSION t: 8EHQ-0980-0359
CAS NUMBER: 98-87-3
"'" SUBMISSION t: 8EHQ-0582-0444
V1
co
CAS NUMBER: 100-41-4
SUBMISSION t: 8EHQ-Ot,80-0345
CAS NUMBER: 4680-78-8
SUBMISSION t: 8EHQ-0780-0350
CAS NUMgER:
108-88-3
SUBMISSION t: 8EHQ-0680-0345
CAS NUMBER:
25321-14-6
SUBMISSION #: 8EHQ-1080-0367
CHEMICAL NAME: 1,3-BENZENEDIAMINE, 4-METHYL-
CHEMICAL NAME: 1,2-BENZENEDICARBOXYLIC ACID, BIS(2-ETHYLHEXYL) ESTER
CHEMICAL NAM~: 1,2-BENZENEDICARBOXYLIC ACID, 3,4,5,6-TETRABROMO-, DI-2-PROP
ENYL ES T ER
CHEMICAL NAME: BENZENE, (DICHLOROMETHYL)-
CHEMICAL NAME: BENZENE, ETHYL-
8EHQ-1080-0368
CHEMICAL NAME: BENZENEMETHANAMINIUM, N-ETHYL-N-[4-[[4-[ETHYL[(3-SULFOPHENYL
)METHYLJAMIHOJPHEHYLJPHENYLMETHYLEHEJ-2,5-CYCLOHEXADIEN-I-YL
IDENEJ-3-SULFO-, HYDROXIDE, INNER SALT, SODIUM SALT
CrlEMICAL NAME: BENZENE, METHYL-
8EHQ-I080-0368
CHEMICAL NAME: BENZENE, METHYLDINITRO-
-------
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
*'"
~ CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
APPENDIX C:
12002-48-1
SUBMISSION #: 8EHQ-0982-0457
98-07-7
SUBMISSION #: 8EHQ-0980-0360
5216-25-1
SUBMISSION #: 8EHQ-0980-0360
121-14-2
SUBMISSION #: 8EHQ-1080-0367
98-51-1
SUBMISSION #: 8EHQ-1281-0421 S
21850-44-2
SUBMISSION #: 8EHQ-0982-0458
95-50-1
SUBMISSION #: 8EHQ-1080-0368
108-38-3
SUBMISSION #: 8EHQ-1080-0368
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CHEMICAL NAME: BENZENE, TRICHLORO-
CHEMICAL NAME: BENZENE, (TRICHLOROMETHYL)-
8EHQ-0582-0444
CHEMICAL NAME: BENZENE, 1-CHLORO-4-(TRICHLOROMETHYL)-
CHEMICAL NAME: BENZENE, 1-METHYL-2,4-DINITRO-
CHEMICAL NAME: BENZENE, 1-(1,1-DIMETHYLETHYL)-4-METHYL-
CHEMICAL NAME: BENZENE, 1,1'-(1-METHYLETHYLIDENE)BIS[3,5-DIBROMO-4-(2,3-DIB
RONOPROPOXn -
CHEMICAL NAME: BENZENE. 1.2-DICHLORO-
CHEMICAL NAME: BENZENE, 1.3-DIMETHYL-
-------
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME CCONT.)
CAS NUMBtR: 106-42-3
SUBMISSION #: 8EHQ-1080-0368
CAS NUMBER: 14047-09-7
SUBMISSION #: 8EHQ-0981-0409
CAS NUMBER: 21232-47-3
SUBMISSION It: 8EHQ-0981-0409
CHEMICAL NAME: BENZENE, 1,4-DIMETHYL-
CHEMICAL NAME: BENZENE, 3,3',4,4'-TETRACHLOROAZO-
8EHQ-1281-0424
CHEMICAL NAME: BENZENE, 3,3',4,4'-TETRACHLOROAZOXY-
8EHQ-1281-0424
CAS NUMBER: NONE CHEMICAL NAME: BENZOFURAZANS, NITRO-
SUBMISSION #: 8EHQ-0281-0383 S *
*"" CAS NUMBER: 10199-89-0 CHEMICAL NAME: BENZOFURAZAN, 4-CHLORO-7-NITRO-
0)
a
SUBMISSION #: 8EHQ-0281-0383 S *
CAS NUMBER:
NONE
SUBMISSION #: 8EHQ-0281-0383 S
CAS NUMBER:
98-73-7
SUBMISSION #: 8EHQ-0382-0440 S
CAS NUMBER:
98-73-7
SUBMISSION #: 8EHQ-0382-0440 S
CAS NUMBER:
98-88-4
SUBMISSION It: 8EHQ-0980-0360
CHEMICAL NAME: BENZOFUROXANS, NITRO-
*
CHEMICAL NAME: BENZOIC ACID, P-TERT-BUTYL-
CHEMICAL NAME: BENZOIC ACID, 4-C1,1-DIMETHYLETHYL)-
CHEMICAL NAME: BENZOYL CHLORIDE
8EHQ-0582-0444
-------
APPENDIX C:
CAS NUMBER:
7440-41-7
SUBMISSION I: 8EHQ-0680-0345
CAS NUMBER:
1336-36-3
SUBMISSION I: 8EHQ-0780-0352
CAS NUMBER:
UNKNOWN
SUBMISSION I: 8EHQ-0981-0413
CAS NUMBER: 68479-77-6
SUBMISSION I: 8EHQ-0381-0391
~
0'1 CAS NUMBER: 13292-87-0
f-'
SUBMISSION I: 8EHQ-1l30-0372
CAS NUMBER: 68441-14-5
SUBMISSION I: 8EHQ-1281-0420
CAS NUMBER: 106-99-0
SUBMISSION I: 8EHQ-1080-0370
CAS NUMBER: 68441-14-5
SUBMISSION It: 8EHQ-1281-0420
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CHEMICAL NAME: BERYLLIUM
CHEMICAL NAME: 1,1'-BIPHENYL, CHLORINATED
8EHQ-0981-0413
8EHQ-0982-0457
CHEMICAL NAME: 1,1'-BIPHENYL, 2,2',4,4'-TETRACHLORO-
CHEMICAL NAME: BL-4420
CHEMICAL NAME: BORANE, COMPD. WITH THIOBIS[METHANE] (1:1)
CHEMICAL NAME: BROMOBUTYL 2244
CHEMICAL NAME: 1,3-BUTADIENE
8EHQ-0382-0441
CHEMICAL NAME: 1,3-BUTADIENE, 2-METHYL-, POLYMER WITH 2-METHYL-1-PROPEHE, B
ROMINATED
-------
APPENDIX C:
CAS NUMBER:
7440-43-9
SUBMISSION #: 8EHQ-0280-0332
CAS NUMBER:
UNKNOWN
SUBMISSION #: 8EHQ-1180-0375 S
CAS NUMBER: NONE
SUBMISSION #: 8EHQ-1l82-0465
CAS NUMBER: NONE
SUBMISSION I: 8EHQ-1l82-0465
*'"
0'1 CAS NUMBER: 86-28-2
IV
SUBMISSION #: 8EHQ-1D8D-D368
CAS NUMBER: UNKNOWN
SUBMISSION I: 8EHQ-1281-0423
CAS NUMBER: 15022-08-9
SUBMISSION #: 8EHQ-0181-0381
CAS NUMBER: UNKNmJN
SUBMISSION I: 8EHQ-0480-0340
CAS NUMBER:
7782-50-5
SUBMISSION #: 8EHQ-1182-0466
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CHEMICAL NAME: CADMIUM
8EHQ-068D-0345
CHEMICAL NAME: CADMIUM SALTS OF P-TERT-BUTYL BENZOIC ACID ~ND BENZOIC ACID
CHEMICAL NAME: CAlCO OIL BRONZE Y
CHEMICAL NAME: CALCO OIL RED YM
CHEMICAL NAME: 9H-CARBAZOLE, 9-ETHYL-
CHEMICAL NAME: CARBON (FIBERS)
CHEMICAL NAME: CARBONIC ACID, DI-2-PROPENYL ESTER
CHEMICAL NAME: CHIMASSORB 944
CHEMICAL NAME: CHLORINE
14:
-------
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CAS NUMBER:
13765-19-0
CHEMICAL NAME: CHROMIC ACID, CALCIUM SALT (1:1)
SUBMISSION #: 8EHQ-1182-0463
CAS NUMBER:
10588-01-9
CHEMICAL NAME: CHROMIC ACID, DISODIUM SALT
SUBMISSION #: 8EHQ-1182-0463
CAS NUMBER:
7440-47-3
CHEMICAL NAME: CHROMIUM
SUBMISSION #: 8EHQ-0680-0345
CAS NUMBER:
NONE
CHEMICAL NAME: COAL, SOLVENT-REFINING CSRC) PROCESS/PRODUCTS
8EHQ-0581-:-0398
SUBMISSION #: 8EHQ-0980-0363
oJ:>. CAS NUMBER: 30638-08-5 CHEMICAL NAME:
0"\
w
SUBMISSION #: 8EHQ-0681-0403 S
CAS NUMBER: 29383-29-7 CHEMICAL NAME:
SUBMISSION #: 8EHQ-0980-0361 S
CAS NUMBER: 14285-59-7 CHEMICAL NAME:
COBALTATEC1-), [29H,31H-PHTHALOCYANINESULFONATOC3-)-N29,N30,
N31,N32)-, HYDROGEN
COBALTATE(2-), [29H,31H-PHTHALOCYANINEDISULFONATOC4-)-N29,N3
0,N31,N32)-, DIHYDROGEN
8EHQ-0681-0403 S
COBALTATEC4-), [29H,31H-PHTHALOCYANINE-2,9,16,23-TETRASULFON
ATO(6-)-N29,N30,N31,N32J-, TETRAHYDROGEN, (SP-4-1)-
SUBMISSION #: 8EHQ-0980-0361 S
CAS NUMBER:
7440-50-8
CHEMICAL NAME: COPPER
SUBMISSION #: 8EHQ-0680-0345
-------
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CAS NUMBER:
13752-51"7
CHEMICAL NAME: CURE-RITE 18
SUBMISSION #: 8EHQ-0280-0334
CAS NUMBER:
NONE
CHEMICAL NAME: CUTTING FLUID
SUBMISSION #: 8EHQ-0380-0335 S
CAS NUMBER:
10310-38-0
CHEMICAL NAME: CYAGARD RF-l
SUBMISSION #: 8EHQ-0780-0369
CAS NUMBER:
NONE
CHEMICAL NAME: CYClOHEXANES, HEXAHAlOGENATED-
SUBMISSION I: 8EHQ-v3JI-0393
~
~ CAS NUMBER:
87-84-3
CHEMICAL NAME: CYClOHEXANE, 1,2,3,4,5-PENTABROMO-6-CHlORO-
SUBMISSION I: 8EHQ-0381-0393
CAS NUMBER: 80-08-0 CHEMICAL NAME: DDS
SUBMISSION #: 8EHQ-0480-0338
CAS NUMHR: UNKNOWN C;iEMICAl NAME: V-50 DECOMPOSITION PRODUCT
SUBMISSION #: 8EHQ-0282-0427 S
CAS NUMBER: NONE CHEMICAL NAME: DIBENZOFURANS, CHLORINATED
SUBMISSION I: 8EHQ-0981-0409
CAS NUMBER: 77-73-6 CHEMICAL NAME: DICYClOPENTADIENE
SUBMISSION #: 8EHQ-0980-0364
-------
APPENDIX C:
CAS NUMBER:
123-91-1
SUBMISSION #: 8EHQ-0280-0331 S
CAS NUMI3ER: NONE
SUBMISSION #: 8EHQ-0381-0390
CAS NUMBER: 1746-01-6
SUBMISSION #: 8EHQ-0381-0390
CAS NUMBER: 6227-14-1
SUBMISSION #: 8EHQ-0282-0437
,j:>.
0"1 CAS NUMBER: UNKNOL.JN
V1
SUBMISSION #: 8EHQ-0481-0396
CAS NUMBER: UNKNOWN
SUBMISSION #: 8EHQ-0581-0398
CAS NUMBER: 68410-08-2
SUBMISSION #: 8EHQ-0980-0363
CAS NUMBER: 64742-52-5
SUBMISSION #: 8EHQ-0281-0385
CAS NUMBER: 64742-55-8
SUBMISSION #: 8EHQ-0281-0385
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CHEMICAL NAME: 1,4-DIOXANE
8EHQ-0380-0336 S
8EHQ-0682-0449 S
CHEMICAL NAME: DIOXINS, CHLORINATED
8EHQ-0981-0409
CHEMICAL NAME: DIOXIN, 2,3,7,8-TETRACHLORODIBENZO-P-
CHEMICAL NAME: C. I. DIRECT VIOLET 9
CHEMICAL NAME: DISPERSE BLUE 291
*
CHEMICAL NAME: DISTILLATES (COAL), SOLVENT-REFINING (SRC), MIDDLE
CHEMICAL NAME: DISTILLATES (COAL), SOLVENT-REFINING (SRC), RECYCLE
CHEMICAL NAME: DISTILLATES (PETROLEUM), HYDROTREATED HEAVY NAPHTHENIC
CHEMICAL NAMf: DISTILLATES (PETROLEUM), HYDROTREATED LIGHT PARAFFINIC
8EHQ-0681-0404
-------
APPENDIX C:
CAS NUMBER: 64742-46-7
SUBMISSION #: 8EHQ-0280-0333
CAS NUMBER: 64741-52-2
SUBMISSION #: 8EHQ-0682-0447
CAS NUMBER: 330-54-1
SUBMISSION #: 8EHQ-0981-0409
CAS NUMBER: UNKNOWN
SUBMISSION #: 8EHQ-1280-0376
~
~ CAS NUMBER: 1643-20-5
~
SUBMISSION #: 8EHQ-1280-0376
CAS NUMBER: UNKNOWN
SUBMISSION I: 8EHQ-0481-0396
CAS NUMBER: 80-08-0
SUBMISSION #: 8EHQ-0480-0338
CAS NUMBER: NONE
SUBMISSION #: 8EHQ-0481-0397
CAS NUMBER: 81-88-9
SUBMISSION #: 8EHQ-0282-0434
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CHEMICAL NAME: DISTILLATES (PETROLEUM), HYDRO TREATED MIDDLE
CHEMICAL NAME: DISTIllATES (PETROLEUM), LIGHT NAPHTHENIC
CHEMICAL NAME: DIURON
CHEMICAL NAME: DODECANAMINE, N-METHYl-N-NITROSO-
CHEMICAL NAME: I-DODECANAMINE, N,N-DIMETHYL-, N-OXIDE
CHEMICAL NAME: EASTMAN BLUE RBS
*
CHEMICAL NAME: EPORAL
CHEMICAL NAME: EPOXY RESINS
CHEMICAL NAME: ETHANAMINIUM, N-[9-(2-CARBOXYPHENYL)-6-(DIETHYLAMINO)-3H-XAN
THEN-3-YLIDENE]-N-ETHYl-, CHLORIDE
-------
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
,!:::.
0'\
-....J
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
APPENDIX C:
68153-35-5
SUBMISSION #: 8EHQ-1180-0371
75-34-3
SUBMISSION #: 8EHQ-0680-0345
71-55-6
SUBMISSION I: 8EHQ-0980-0365
111-44-4
SUBMISSION I: 8EHQ-~682-0449 S
110-80-5
SUBMISSION I: 8EHQ-0381-0386
111-15-9
SUBMISSION I: 8EHQ-0682-0450
109-86-4
SUBMISSION I: 8EHQ-0281-0384
6175-45-7
SUBMISSION I: 8EHQ-0581-0400
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CHEMICAL NAME: ETHANAMINIUM, 2-AMINO-N-(2-AMINOETHYl)-N-(2-HYDROXYETHYl)-N-
METHYl-, N,N'-DITAllOW ACYL DERIVS., ME SULFATES (SALTS)
CHEMICAL NAME: ETHANE, 1,I-DICHlORO-
CHEMICAL NAME: ETHANE, 1,1,I-TRICHlORO-
8EHQ-0982-0457
CHEMICAL NAME: ETHANE, 1,1'-OXYBISI2-CHlORO-
CHEMICAL NAME: ETHANOL, 2-ETHOXY-
CHEMICAL NAME: ETHANOL, 2-ETHOXY-, ACETATE
CHEMICAL NAME: ETHANOL, 2-METHOXY-
CHEMICAL NAME: ETHANONE, 2,2-DIETHOXY-I-PHENYl-
-------
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CAS NUMBER:
75-01-4
CHEMICAL NAME: ETHENE. CHlORO-
8EHQ-0982-0457
SUBMISSION I: 8EHQ-0680-0345
CAS NUMBER: 127-18-4 CHEMICAL NAME: ETHENE. TETRACHLORO-
SUBMISSION I: 8EHQ-0680-0345
CAS NUMBER: 79-01-6 CHEMICAL NAME: ETHENE. TRICHLORO-
SUBMISSION I: 8EHQ-0680-0345 8EHQ-0982-0457
I
CAS NUMBER: 75-38-7 CHEMICAL NAME: ETHENE. 1.1-DIFLUORO-
SUBMISSION I: 8EHQ-0480-0337
~
0'1 CAS NUMBER: 156-60-5 CHEMICAL NAME: ETHENE. 1.2-DICHLORO-. (E)-
co
SUBMISSION It: 8EHQ-0680-0345 8EHQ-0982-0457
CAS NUMBER:
75-21-8
CHEMICAL NAME: ETHYLENE OXIDE
SUBMISSION I: 8EHQ-0882-0453
CAS NUMBER:
64742-11-6
CHEMICAL NAME: EXTRACTS (PETROLEUM). HEAVY NAPHTHENIC DISTILLATE SOLVENT
SUBMISSION I: 8EHQ-0281-0385
CAS NUMBER:
64742-04-7
CHEMICAL NAME: EXTRACTS (PETROLEUM). HEAVY PARAFFINIC DISTILLATE SOLVENT
SUBMISSION I: 8EHQ-0281-0385
CAS NUMBER:
129-79-3
CHEMICAL NAM~: 9H-FLUOREN-9-0NE. 2.4.7-TRINITRO-
SUBMISSION I: 8EHQ-0480-0339
-------
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CAS NUMBER:
HONE
CHEMICAL HAME: FlUORORAD FC-143
SUBMISSION 3: 8EHQ-0381-0394 S
CAS NUMBER:
NONE
CHEMICAL NAME: FlUORORAD FC-95
SUBMISSION I: 8EHQ-1180-0374 S
CAS NUMBER:
7789-21-1
CHEMICAL NAME: FlUOROSUlFURIC ACID
SUBMISSION I: 8EHQ-0881-0407
CAS NUMBER:
NONE
CHEMICAL NAME: FR651
SUBMISSION I: 8EHQ-0381-0393
,j:::.
"" CAS HUMBER: 108-30-5 CHEMICAL NAME: 2.5-FURANDIONE. DIHYDRO-
1.0
SUBMISSION 3: 8EHQ-0282-0433 *
CAS HUMBER: 25377-73-5 CHEMICAL NAME: 2, 5-FURANDIONE, 3-(DODECEHYl)DIHYDRO-
SUBMISSION It: 8EHQ-0282-0432 *
CAS NUMBER: 13674-87-8 CHEMICAL NAME: FYROl FR-2
SUBMISSION 3: 8EHQ-1280-0401 S
CAS NUMBER: 8006-61-9 CHEMICAL NAME: GASOLIHE. NATURAL
SUBMISSION 3: 8EHQ-1281-0422
CAS HUMBER: 8006-61-9 CHEMICAL NAME: GASOLINE, UNLEADED
SUBMISSION I: 8EHQ-1281-0422
-------
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CAS NUMBER:
NONE
CHEMICAL NAME: GULFCUT HEAVY DUTY SOLUBLE OIL
SUBMISSION #: 8EHQ-0380-0335 S
CAS NUMBER:
64742-11-6
CHEMICAL NAME: GULF N.E. 61 (PROCESS 65)
SUBMISSION #: 8EHQ-0281-0385
CAS HUMBER:
64742-04-7
CHEMICAL NAME: GULF N.E. 75 (PROCESS 63)
SUBMISSION #: 8EHQ-0281-0385
CAS NUMBER:
64742-55-8
CHEMICAL NAME: GULF PARALUX 70
SUBMISSION #: 8EHQ-068l-0404
*"
-..J CAS NUMBER:
o
NONE
CHEMICAL NAME: GULF SUPERQUEHCH 70
SUBMISSION #: 8EHQ-028l-0385
CAS NUMBER: NONE CHEMICAL NAME: GULF TS-905-HWCF
SUBMISSION #: 8EHQ-0982-0456 S ~
CAS NUMBER: 6't742-52-5 CHEMICAL NAME: GULF 100 TEXAS OIL
SUBMISSION #: 8EHQ-028l-0385
CAS NUMBER:
NONE
CHEMICAL HAME: HELOXY WC-68
SUBMISSION #: 8EHQ-048l-0397
CAS NUMBER:
68555-73-7
CHEMICAL NAME: l-HEPTANESULFONAMIDE, N-ETHYL-l,1,2,2,3,3,4,4,5,5,6,6,7,7,7-
PEHTADECAFLUORO-N-(2-HYDROXYETHYL)-
SUBMISSION #: 8EHQ-1180-0373 S
-------
CAS HUMBER:
CAS HUMBER:
CAS HUMBER:
CAS HUMBER:
0+=-
~ CAS HUMBER:
CAS HUMBER:
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME (CONT.)
58849-75-5
SUBMISSION #: 8EHQ-0482-0442
NONE
SUBMISSION #: 8EHQ-0581-0399 S
HONE
SUBMISSION #: 8EHQ-0480-0338
HONE
SUBMISSION #: 8EHQ-I081-0414
NONE
SUBMISSION #: 8EHQ-0780-0352
7783-06-4
SUBMISSION #: 8EHQ-0580-0343
CAS NUMBER: 75-91-2
SUBMISSION #: 8EHQ-I081-0415
CAS NUMBER: 77-48-5
SUBMISSION #: 8EHQ-0281-0382
CAS NUMBER: 118-52-5
SUBMISSION #: 8EHQ-0281-0382
CHEMICAL NAME: HEXADECANOIC ACID, 2-SULFO-, I-METHYL ESTER
CHEMICAL NAME: HIGH EXPLOSIVE (MIXTURE)
CHEMICAL NAME: HX 999
CHEMICAL NAME: HYBASE M-400
CHEMICAL NAME: HYDRAULIC FLUIDS
CHEMICAL NAME: HYDROGEN SULFIDE
CHEMICAL NAME: HYDROPEROXIDE, 1,I-DIMETHYLETHYL
CHEMICAL NAME: 2,4-IMIDAZOLIDINEDIONE, 1,3-DIBROMO-5,5-DIMETHYL-
CHEMICAL NAME: 2,4-IMIDAZOLIDINEDIONE, 1,3-DICHLORO-5,5-DIMETHYL-
-------
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CAS NUMBER:
126-06-7
CHEMICAL NAME: 2,4-IMIDAlOLIDINEDIONE, 3-BROMO-I-CHLORO-5,5-DIMETHYL-
SUBMISSION #: 8EHQ-0281-0382
CAS NUMBER:
15336-82-0
CHEMICAL NAME: 2,4-IMIDAlOlIDINEDIONE, 5-ETHYl-5-METHYL-1,3-BIS(OXIRANY1MET
HYL)-
SUBMISSION #: 8EHQ-1081-0418
CAS NUMBER:
15336-81-9
CHEMICAL NAME: 2,4-IMIDAlOlIDINEDIONE, 5,5-DIMETHYL-1,3-BIS(OXIRANYlMETHYl)
SUBMISSION #: 8EHQ-0481-0397
CAS NUMBER: 30947-30-9 CHEMICAL NAME: IRGASTAB 2002
,j:>. SUBl'lISSION #: 8EHQ-D482-0443
-.....J
I'J
CAS NUMBER: 77 05-08-0 CHEMICAL NAME: IRON CHLORIDE
SUBMISSION #: 8EHQ-0880-0358 *
CAS NUMBER: NONE CHEMICAL NAME: 1-122
SUBMISSION #: 8EHQ-1l80-D375 S
CAS NUMBER: NONE CHEMICAL NAME: JET FUEL A
SUBMISSION #: 8EHQ-0181-0377
CAS NUMBER: 64741-67-9 CHEMICAL NAME: KERMAC 218A
SUBMISSION #: 8EHQ-D28D-0333
-------
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CAS HUMBER:
64742-46-7
CHEMICAL NAME: KERMAC 600W
SUBMISSION #: 8EHQ-0280-0333
CAS NUMBER:
7439-92-1
CHEMICAL NAME: LEAD
SUBMISSION #: 8EHQ-0680-0345
CAS NUMBER:
330-55-2
CHEMICAL NfME: LINURON
SUBMISSION #: 8EHQ-09'1-0409
CAS NUMBER:
7439-97-6
CHEMICAL NAME: MERCURY
SUBMISSION #: 8EHQ-0680-0345
~
-..J
W
CAS NUMBER:
62-75-9
CHEMICAL NAME: METHANAMINE, N-METHYL-N-NITROSO-
SUBMISSION I: 8EHQ-1280-0376
CAS NUMBER: 74-87-3 CHEMICAL NAME: METHANE, CHLORO-
SUBMISSION I: 8EHQ-1l82-0464
CAS NUMBER: 75-09-2 CHEMICAL NAME: METHANE, DICHLORO-
SUBMISSION I: 8EHQ-0680-0345
CAS NUMBER: 75-71-8 CHEMICAL NAME: METHANE, DICHLORODIFLUORO-
SUBMISSION #: 8EHQ-0680-0345
CAS NUMBER: 624-83-9 CHEMICAL NAME: METHANE, ISOCYANATO-
SUBMISSION I: 8EHQ-0381-0392
-------
CAS NUMBER: 26472-00-4 CHEMICAL NAME:
SUBMISSION I: 8EHQ-1081-0419
~
~
~
CAS NUMBER: 20354-26-1
SUBMISSION #: 8EHQ-0981-0409
CAS NUMBER: 26472-00-4
SUBMISSION #: 8EHQ-1081-0419
CAS NUMBER: 75-09-2
SUBMISSION #: 8EHQ-0680-0345
CAS NUMBER: NONE
SUBMISSION #: 8EHQ-0680-0344 P
8EHQ-0981-0409
APPENDIX C:
CAS NUMBER:
76-06-2
SUBMISSION #: 8EHQ-1081-0416
CAS NUMBER:
25134-21-8
SUBMISSION #: 8EHQ-0282-0431
CAS NUMBER:
77-73-6
SUBMISSION #: 8EHQ-0980-0364
STATUS REPORTS BY CHEMICAL NAME
-------
APPENDIX C:
CAS NUMBER: 102-77-2
SUBMISSION It: 8EHQ-0280-0334
CAS NUMBER: 13752-51-7
SUBMISSION It: 8EHQ-0280-0334
CAS NUMBER: 28768-32-3
SUBMISSION It: 8EHQ-0480-0338
CAS NUMBER: 25134-21-8
SUBMISSION It: 8EHQ-0282-0431
t/:>.
-..J CAS NUMBER: 6368-72-5
U1
SUBMISSION It: 8EHQ-0982-0455
CAS NUMBER: 6227-14-1
SUBMISSION It: 8EHQ-0282-0437
CAS NUMBER: 64741-64-6
SUBMISSION It: 8EHQ-0682-0446 S
CAS NUMBER: 64741-55-5
SUBMISSION It: 8EHQ-0682-0446 S
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CHEMICAL NAME: MORPHOLINE, 4-(2-BENZOTHIAZOLYLTHIO)-
CHEMICAL NAME: MORPHOLINE, 4-[(4-MORPHOLINYLTHIO)THIOXOMETHYLJ-
CHEMICAL NAME: MY 720
CHEMICAL NAME: NADIC METHYL ANHYDRIDE
*'
CHEMICAL NAME: 2-NAPHTHALENAMINE, N-ETHYL-1-[[4-(PHENYLAZO)PHENYLJAZOJ-
CHEMICAL NAME: 2-NAPHTHALENESULFONIC ACID, 4-HYDROXY-3-[[2-METHOXY-5-METHYL
-4-[(4-SULFOPHENYL)AZOJPHENYLJAZOJ-7-(PHENYLAMINO)-, DISODIU
M SALT
CHEMICAL NAME: NAPHTHA (PETROLEUM), FULL-RANGE ALKYLATE
CHEMICAL NAME: NAPHTHA (PETROLEUM), LIGHT CATALYTIC CRACKED
-------
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
"'"
~ CAS NUMBER:
CAS NUMi3ER:
CAS NUMBER:
CAS NUMBER:
APPENDIX C:
64741-46-4
SUBMISSION #: 8EHQ-0682-0446 S
7440-02-0
SUBMISSION #: 8EHQ-0680-0345
NONE
SUBMISSION #: 8EHQ-12~0-0376
CONFIDENT
SUBMISSION #: 8EHQ-0280-0331 S
102-77-2
SUBMISSION #: 8EHQ-0280-0334
3076-26-4
SUBMISSION #: 8EHQ-0482-0442
UNKNOWN
SUBMISSION #: 8EHQ-I082-0460
1691-99-2
SUBMISSION #: 8EHQ-1180-0373 S
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CHEMICAL NAME: NAPHTHA (PETROLEUM), LIGHT STRAIGHT-RUN
CHEMICAL NAME: NICKEL
CHEMICAL NAME: NITROSAMINES
CHEMICAL NAME: NONAX 1166
CHEMICAL NAME: OBTS
CHEMICAL NAME: OCTADECANOIC ACID, 2-SULFO-, I-METHYL ESTER
CHEMICAL NAME: 9-0CTADECENOIC ACID, (l)-, 3-[(1-0XO-2-PROPENYL)OXYJ-2,2-BIS
[[(1-OXO-2-PROPENYL)OXYJMETHYLJPROPYL ESTER
CHEMICAL NAME: 1-0CTANESULFONAMIDE, N-ETHYL-l,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8
,8-HEPTADECAFLUORO-N-(2-HYDROXYETHYL)-
-------
APPENDIX C:
CAS NUMBER:
NONE
SUBMISSION It: 8EHQ-0380-0335 S
CAS NUMBER:
NONE
SUBMISSION I: 8EHQ-0381-0389
CAS NUMBER: UNKNm~N
SUBMISSION It: 8EHQ-0181-0377
CAS NUMBER: NONE
SUBMISSION It: 8EHQ-0381-0389
,j::.
-..J CAS NUMBER: NONE
-..J
SUBMISSION I: 8EHQ-1081-0417
CAS NUMBER: NONE
SUBMISSION It: 8EHQ-1081-0417
CAS NUMBER:
2481-94-9
SUBMISSION It: 8EHQ-0982-0455
CAS NUMBER:
20354-26-1
SUBMISSION #: 8EHQ-0981-0409
CAS NUMBER:
75-21-8
SUBMISSION It: 8EHQ-0882-0453
STATUS REPORTS BY CHEMICAL NAME (CO NT.)
CHEMICAL NAME: OIL, GULFCUT HEAVY DUTY SOLUBLE
CHEMICAL NAME: OIL (PETROLEUM), NEW MOTOR
CHEMICAL NAME: OIL (PETROLEUM), NUMBER 6 HEAVY FUEL
CHEMICAL NAME: OIL (PETROLEUM), USED MOTOR
CHEMICAL NAME: OIL (SHALE), FULL-RA~GE DEWAXED SYNCRUDE
CHEMICAL NAME: OIL (SHALE), REDUCED SYNCRUDE
CHEMICAL NAME: OIL YELLOW E190
CHEMICAL NAMt: 1,2,4-0XADIAZOLIDINE-3,5-DIONE,
CHEMICAL NAME: OXIRANE
-------
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CAS NUMBER:
28768-32-3
CHEMICAL NAME: OXIRANEMETHANAMINE, N,N'-(METHYlENEDI-4,1-PHENYlENE)BIS[N-(O
XIRANYlMETHYl )-
SUBMISSION I: 8EHQ-0480-0338
CAS NUMBER:
5026-74-4
CHEMICAL NAME: OXIRANEMETHANAMINE, N-[4-(OXIRANYlMETHOXY)PHENYll-N-(OXIRANY
lMETHYl )-
SUBMISSION I: 8EHQ-1281-0426
CAS NUMBER: 75-56-9 CHEMICAL NAME: OXIRANE, METHYl-
SUBMISSION I: 8EHQ-0282-0439
CAS NUMBER: 17557-23-2 CHEMICAL NAME: OXIRANE,
E>lBIS-
~
-...J SUBMISSION I: 8EHQ-0481-0397
co
CAS NUMBER: NONE CHEMICAL NAME: PARANOX 52
SUBMISSION II: 8EHQ-0381-0388 S
CAS NUMBER: 53417-29-1 CHEMICAL NAME: PENTAERYTHRITOl DIACRYlATE
SUBMISSION II: 8EHQ-0882-0454
2,2'-[(2,2-DIMETHYl-1,3-PROPANEDIYl)BIS(OXYMETHYlEN
CAS NUMBER:
UNKNOWN
CHEMICAL NAME: PENTAERYTHRITOl MONOOlEATE TRIACRYlATE
SUBMISSION II: 8EHQ-1082-0460
CAS NUMBER:
2215-35-2
CHEMICAL NAME: 2-PENTANOl, 4-METHYl-, HYDROGEN PHOSPHORODITHIOATE, ZINC SAl
T
SUBMISSION II: 8EHQ-0680-0346
-------
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
"'"
-..J
~
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
APPENDIX C:
CONFIDENT
SUBMISSION #: 8EHQ-0381-0394 S
CONFIDENT
SUBMISSION #: 8EHQ-0381-0394 S
NONE
SUBMISSION #: 8EHQ-1180-0373 S
CONFIDENT
SUBMISSION #: 8EHQ-1180-0374 S
64742-16-1
SUBMISSION #: 8EHQ-0281-0385
CONFIDENT
SUBMISSION #: 8EHQ-0381-0388 S
25167-82-2
SUBMISSION #: 8EHQ-0381-0390
868-85-9
SUBMISSION #: 8EHQ-1080-0366
30947-30-9
SUBMISSION #: 8EHQ-0482-0443
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CHEMICAL NAM[: PERFLUOROALKYL CARBOXYLIC ACID, AMMONIUM SALTS
CHEMICAL NA~E: PERFLUOROALKYL CARBOXYLIC ACIDS
CHEMICAL NAME: PERFLUOROALKYL COMPOUNDS
8EHQ-1180-0374 S
8EHQ-0381-0394 S
CHEMICAL NAME: PERFLUOROALKYL SULFONATES, POTASSIUM SALTS
CHEMICAL NAME: PETROLEUM RESINS
CHEMICAL NAME: PHENOL SULFIDE, ALKYLATED-, CALCIUM SALT
CHEMICAL NAME: PHENOL, TRICHLORO-
CHEMICAL NAME: PHOSPHONIC ACID, DIMETHYL ESTER
CHEMICAL NAME: PHOSPHONIC ACID, 113,5-BIS(1,1-DIMETHYLETHYL)-4-HYDROXYPHENY
LJMETHYL]-, MONO ETHYL ESTER, NICKEL(2+) SALT (2:1)
-------
APPENDIX C:
CAS NUMBER:
10310-38-0
SUBMISSION It: 8EHQ-0780-0369
CAS NUMBER: 993-43-1
SUBMISSION It: 8EHQ-0981-0412
CAS NUMBER: 2524-03-0
SUBMISSION It: 8EHQ-0381-0387
CAS NUMBER: CONFIDENT
SUBMISSION It: 8EHQ-0781-0405 S
~
00
a
CAS NUMBER: 68442-22-8
SUBMISSION It: 8EHQ-0680-0346
CAS NUMBER: CONFIDENT
SUBMISSION I: 8EHQ-1281-0425 S
CAS NUMBER: UNKNOWN
SUBMISSION It: 8EHQ-0181-0379
CAS NUMBER:
UNKNOWN
SUBMISSION It: 8EHQ-0181-0379
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CHEMICAL NAME: PHOSPHONIUM, 1,2-ETHANEDIYLBISITRIS(2-CYANOETHYL)-, DIBROMID
E
CHEMICAL NAME: PHOSPHONOTHIOIC DICHLORIDE, ETHYL-
CHEMICAL NAME: PHOSPHOROCHLORIDOTHIOIC ACID, O,O-DIMETHYL ESTER
CHEMICAL NAME: PHOSPHORODITHIOIC ACID, DIALKYL ESTERS, ZINC SALT
CHEMICAL NAME: PHOSPHORODITHIOIC ACID, MIXED 2-ETHYLHEXYL AND 2-METHYlPROPY
l ESTERS, ZINC SALTS
CHEMICAL NAME: PHOSPHORODITHIOIC ACID, O,O'-DIAlKYl ESTER, ANTIMONY SALT
CHEMICAL NAME: PHOSPHORODITHIOIC ACID, O,O'-DI(ISOHEXYL, ISOHEPTYl, ISOOCTY
l, ISONONYL, ISODECYL)MIXED ESTERS, ZINC SALT
CHEMICAL NA~E: PHOSPHORODITHIOIC ACID, (SECONDARY BUTYL AND ISOOCTYL)MIXED
ESTERS, ZINC SALT
-------
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CAS NUMBER:
101-02-0
CHEMICAL NAME: PHOSPHOROUS ACID, TRIPHENYL ESTER
SUBMISSION I: 8EHQ-0682-0451
CAS NUMBER:
NONE
CHEMICAL NAME: PHOTOCOPYING PRODUCTS/PROCESS
8EHQ-0780-0351
SUBMISSION I: 8EHQ-0480-0339
CAS NUMBER:
68187-58-6
CHEMICAL NAME: PITCH, PETROLEUM, CONDENSED-RING AROM.
SUBMISSION I: 8EHQ-0780-0353
CAS NUMBER:
9003-01-4
CHEMICAL NAME: POLYACRYLIC ACID
SUBMISSION I: 8EHQ-0382-0438 S
,I:>.
co
......
CAS NUMBER:
UNKNOWN
CHEMICAL NAME: POLYACRYLIC ACID, PARTIAL ALUMINUM POTASSIUM SALT
SUBMISSION I: 8EHQ-0382-0438 S
CAS NUMBER:
UNKNOWN
CHEMICAL NAME: POLYACRYLIC ACID, PARTIAL SODIUM SALT
SUBMISSION I: 8EHQ-0382-0438 S
CAS NUMBER: NONE CHEMICAL NAME: POLYALKOXYLATED POLYAMINES
SUBMISSION I: 8EHQ-0280-0331 S 8EHQ-0380-0336 S
CAS NUMBER: 1336-36-3 CHEMICAL NAME: POLYCHLORINATED BIPHENYLS (PCB)
SUBMISSION I: 8EHQ-0780-0352 8EHQ-0981-0413 8EHQ-0982-0457
CAS NUMBER:
UNKNOWN
CHEMICAL NAME: POLY ,[N,N'-BIS(2,2,6,6-TETRAMETHYLPIPERID-4-YL)-N-(4-(I,I,3
3-TETRAMETHYLBUTYLAMINO)-1,3,5-TRIAZINE-2,6-DIYL)HEXAMETHYLE
NEDIAMINE
SUBMISSION I: 8EHQ-0480-0340
-------
APPENDIX C:
CAS NUMBER:
NONE
SUBMISSION I: 8EHQ-0381-0389
CAS NUMBER:
CONFIDENT
SUBMISSION t: 8EHQ-0280-0331 S
CAS NUMBER:
UNKNOWN
SUBMISSION #: 8EHQ-1281-0420
CAS NUMBER:
25038-04-4
~
co
IV
SUBMISSION t: 8EHQ-0781-0406 S
CAS NUMBER:
709-98-8
SUBMISSION t: 8EHQ-0981-0409
CAS NUMBER: 2997-92-4
SUBMISSION #: 8EHQ-0282-0427 S
CAS NUMBER: 68479-77-6
SUBMISSION t: 8EHQ-0381-0391
CAS NUMBER: 67-63-0
SUBMISSION t: 8EHQ-1l80-0371
'.
CAS NUMBER: 13674-87-8
SUBMISSION #: 8EHQ-1280-0'.01 S
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CHEMICAL NAME: POLYNUCLEAR, AROMATIC HYDROCARBONS
CHEMICAL NAME: POLYQUART H
CHEMICAL NAME: PROPANE, DIBROMOCHLOROMETHYL-
'CHEMICAL NAME: 1,2,3-PROPANETRIOL, POLYMER WITH (CHLOROMETHYL)OXIRANE
CHEMICAL NAME: PROPANIL
CHEMICAL NAME: PROPANIMIDAMIDE, 2,2'-AlOBIS[2-METHYL-, DIHYDROCHLORIDE
CHEMICAL NAME: PROPANOIC ACID, 2,3-DIBROMO-, 2-HYDROXYETHYL ESTER
CHEMICAL NAME: 2-PROPANOL
CHEMICAL NAME: 2-PROPANOL, 1,3-DICHLORO-, PHOSPHATE (3:1)
-------
APPENDIX C:
CAS NUMBER: 93-55-0
SUBMISSION I: 8EHQ-0580-0341
CAS NUMBER: 110-26-9
SUBMISSION I: 8EHQ-0880-0357
CAS NUMBER: 140-88-5
SUBMISSION I: 8EHQ-1282-0467
CAS NUMBER: 9003-01-4
SUBMISSION I: 8EHQ-0382-0438 S
~
co
w CAS NUMBER: 57472-68-1
SUBMISSION I: 8EHQ-1082-0459
CAS NUMBER: 17831-71-9
SUBMISSION I: 8EHQ-0981-0411
CAS NUMBER: 1680-21-3
SUBMISSION I: 8EHQ-0981-0410
CAS NUMBER: 818-61-1
SUBMISSION I: 8EHQ-0880-0356
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CHEMICAL NAME: 1-PROPANONE, 1-PHENYl-
CHEMICAL NAME: 2-PROPENAMIDE, N,N'-METHYlENEBIS-
CHEMICAL NAME: 2-PROPENOIC ACID, ETHYL ESTER
CHEMICAL NAME: 2-PROPENOIC ACID, HOMOPOLYMER
CHEMICAL NAME: 2-PROPENOIC ACID, OXYBISCMETHYl-2,1-ETHANEDIYl) ESTER
CHEMICAL NAME: 2-PROPENOIC ACID, OXYBIS(2,1-ETHANEDIYlOXY-2,1-ETHANEDIYl) E
STER
CHEMICAL NAME: 2-PROPENOIC ACID, 1,2-ETHANEDIYlBIS(OXY-2,1-ETHANEDIYl) ESTE
R
CHEMICAL NAME: 2-PROPENOIC ACID, 2-HYDROXYETHYl ESTER
-------
APPENDIX C:
CAS NUMBER:
3524-68-3
SUBMISSION I: 8EHQ-0882-0454
CAS NUMBER:
4986-89-4
SUBMISSION I: 8EHQ-0882-0454
CAS NUMBER:
107-18-6
SUBMISSION I: 8EHQ-0181-0381
CAS HUMBER: 709-98-8
01::>
00 SUBMISSION I: 8EHQ-0981-0409
01::>
CAS NUMBER: 75-56-9
SUBMISSION I: 8EHQ-0282-0439
CAS NUMBER: 3445-11-2
SUBMISSION I: 8EHQ-0682-0448 S
CAS NUMBER:
14808-60-7
SUBMISSION I: 8EHQ-0780-0354
CAS NUMBER:
NONE
SUBMISSION I: 8EHQ-0880-0358
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CHEMICAL NAME: 2-PROPENOIC ACID. 2-(HYDROXYMETHYL)-2-[[(1-0XO-2-PROPENYL)OX
YIMETHYLI-1,3-PROPANEDIYl ESTER
CHEMICAL NAME: 2-PROPENOIC ACID. 2.2-BIS[[(1-0XO-2-PROPENYl)OXYIMETHYll-1.3
-PROPANEDIYL ESTER
CHEMICAL NAME: 2-PROPEN-1-0l
CHEMICAL NAME: PROPIONAMIDE, N-(3.4-DICHLOROPHENYL)-
CHEMICAL NAME: PROPYLENE OXIDE
CHEMICAL NAME: 2-PYRROLIDINONE, 1-(2-HYDROXYETHYL)-
CHEMICAL NAME: QUARTZ
CHEMICAL NAME: RADIOACTIVE MATERIALS
*
-------
APPENDIX C:
CAS NUMBER:
81-88-9
SUBMISSION #: 8EHQ-0282-0434
CAS NUMBER: 64741-67-9
SUBMISSION #: 8EHQ-0280-0333
CAS NUMBER: 81-88-9
SUBMISSION #: 8EHQ-0282-0434
CAS NUMBER: NONE
SUBMISSION #: 8EHQ-0680-0348
~
co
lJ1 CAS NUMBER: NONE
SUBMISSION #: 8EHQ-0680-0348
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CHEMICAL NAME: D&C RED NO. 19
CHEMICAL NAME: RESIDUES (PETROLEUM), CATALYTIC REFORMER FRACTIONATOR
CHEMICAL NAME: RHODAMINE B
CHEMICAL NAME: RODINE 50
CHEMICAL NAME: RODINE 500
CAS NUMBER: NONE CHEMICAL NAME: RODINE 51
SUBMISSION #: 8EHQ-0680-0348
CAS NUMBER: NONE CHEMICAL NAME: RODINE 85
SUBMISSION #: 8EHQ-0680-0348
CAS NUMBER: NONE CHEMICAL NAME: RODINE 95
SUBMISSION #: 8EHQ-0680-0348
CAS NUMBER: NOt~E CHEMICAL NAME: RODINE 96
SUBMISSION #: 8EHQ-0680-0348
-------
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CAS NUMBER:
68441-14-5
CHEMICAL NAME: RUBBER, BROMINATED BUTYL-
SUBMISSION I: 8EHQ-1281-0420
CAS NUMBER:
7782-49-2
CHEMICAL NAME: SELENIUM
SUBMISSION I: 8EHQ-0680-0345
CAS NUMBER: 68308-34-9 CHEMICAL NAME: SHALE OILS
SUBMISSION I: 8EHQ-1031-0417
CAS NUMBER: 3388-04-3 CHEMICAL NAME: SILANE A-186
SUBMISSION I: 8EHQ-0681-0402
01>-
co
0'\ CAS NUMBER: 2487-90-3 CHEMICAL NAME: SILANE, TRIMETHOXY-
SUBMISSION ,: 8EHQ-0680-0347
CAS NUMBER: 3388-04-3 CHEMICAL NAME: SILANE, TRIMETHOXY[2-(7-0XABICYClO[4.1.0JHEPT-3-Yl)ETHYlJ-
SUBMISSION I: 8EHQ-0681-0402
CAS NUMBER: 63231-67-4 CHEMICAL NAME: SILICA GEL
SUBMISSION It: 8EHQ-0780-0354
CAS NUMBER: 67762-92-9 CHEMICAL NAME: SILICONE Y-6607
SUBMISSION It: 8EHQ-0680-0349
CAS NUMBER: 67762-92-9 CHEMICAL NAME: SIlOXANES AND SILICONES, DI-ME, DIMETHYlAMINO-TERMINATED
SUBMISSION ,: 8EHQ-0680-0349
-------
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CAS NUMBER:
7440-22-4
CHEMICAL NAME: SILVER
SUBMISSION I: 8EHQ-0680-0345
CAS NUMBER:
1313-82-2
CHEMICAL NAME: SODIUM SULFIDE
SUBMISSION I: 8EHQ-0282-0435-
CAS NUMBER: UNKNOWN CHEMICAL NAME: SODYECRON BLUE GBL
SUBMISSION I: 8EHQ-0481-0396 *
CAS NUMBER: 6368-72-5 CHEMICAL NAME: C. 1. SOLVENT RED 19
SUBMISSION I: 8EHQ-0982-0455
,j:>.
C':)
--J CAS NUMBER: 2481-94-9 CHEMICAL NAME: C. 1. SOLVENT YELLOW 56
SUBMISSION I: 8EHQ-0982-0455
CAS NUMBER: NONE CHEMICAL NAME: SRC PROCESS/PRODUCTS
SUBMISSION I: 8EHQ-0980-0363 8EHQ-0581-0398
CAS NUMBER: CONFIDENT CHEMICAL NAME: STANAX 1166
SUBMISSION I: 8EHQ-0380-0336 S
CAS NUMBER:
UNKNOWN
CHEMICAL NAME: STEARYLPHENYLETHYLDIMETHYL AMMONIUM P-TOLUENE SULFONATE
SUBMISSION I: 8EHQ-0881-0408 S
*
CAS NUMBER:
NONE
CHEMICAL NAME: STEPAN AGENT 291-83
SUBMISSION #: 8EHQ-C4~2-0442
-------
APPENDIX C:
CAS NUMBER:
61789-87,-5
SUBMISSION #: 8EHQ-I081-0414
CAS NUMBER:
7446-09-5
SUBMISSION #: 8EHQ-0181-0378
CAS NUMBER:
77-78-1
SUBMISSION #: 8EHQ-0482-0442
CAS NUMBER: 127-18-4
SUBMISSION #: 8EHQ-0680-0345
.c:.
00
00 CAS NUMBER: 29454-23-7
SUBMISSION #: 8EHQ-0482-0442
CAS NUMBER: 7440-28-0
SUBMISSION #: 8EHQ-0680-0345
CAS NUMBER:
1072-71-5
SUBMISSION #: 8EHQ-0181-0380
CAS NUMBER:
UNKNOWN
SUBMISSION #: 8EHQ-0582-0445
CAS NUMBER:
UNKNOWN
SUBMISSION #: 8EHQ-1281-0423
STATUS REPORTS BY CHEMICAL NAME
-------
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
APPENDIX C:
UNKNOWN
SUBMISSION ,: 8EHQ-1281-0423
108-88-3
SUBMISSION ,: 8EHQ-C6dO-0345
98-51-1
SUBMISSION I: 8EHQ-1281-0421 S
CAS NUMBER: 95-53-4
SUBMISSION ,: 8EHQ-0680-0348
~
co
I..D CAS NUM3ER: 79-01-6
SUEMISSION ,: 8EHQ-0680-0345
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
129-79-3
SUBMISSION ,: 8EHQ-0480-0339
330-55-2
SUBMISSION ,: 8EHQ-0981-0409
330-54-1
SUBMISSION .: 8EHQ-0981-0409
6175-45-7
SUBMISSION .: 8EHQ-0581-0400
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CHEMICAL NAME: THORNEL TYPE P (HIGH MODULUS)
CHEMICAL NAME: TOLUENE
8EHQ-I080-0368
CHEMICAL NAME: TOLUENE, P-TERT-BUTYL-
CHEMICAL NAME: TOLUIDINE (ORTHO)
CrlEMICAL NAME: TRICHLOROETHYLENE
8EHQ-0982-0457
CHEMICAL NAME: 2,4,7-TRINITROFLUORENONE
CHEMICAL NAME: UREA, N'-(3,4-DICHLOROPHENYL)-N-METHOXY-N-METHYL-
CHEMICAL NAME: UREA, N'-(3,4-DICHlOROPHENYL)-N,N-DIMETHYL-
CHEMICAL NAME: U-2352
-------
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CAS NUMBER:
NONE
SUBMISSION #: 8EHQ-1180-0371
CAS NUMBER:
75-01-4
SUBMISSION #: 8EHQ-0680-0345
CAS NUMBER:
2997-92-4
SUBMISSION #: 8EHQ-0282-0427 S
CAS NUMBER:
NONE
SUBMISSION I: 8EHQ-0780-0352
tI:>o
~
0 CAS NUMBER: NONE
SUBMISSION t: 8EHQ-0481-0397
CAS NUMBER: 15336-82-0
SUBMISSION t: 8EHQ-1081-0418
CAS NUMBER: 7440-66-6
SUBMISSION t: 8EHQ-0680-0345
CAS NUMBER: NONE
SUBMISSION I: 8EHQ-0680-0346
CAS NUMBER:
NONE
SUBMISSION t: 8EHQ-0680-0344 P
CHEMICAL NAME: VARISOFT 222 (90~)
CHEMICAL NAME: VINYL CHLORIDE
8EHQ-0982-0457
CHEMICAL NAME: V-50
CHEMICAL NAME: WYNN'S FRICTION PROOFING FLUID
CHEMICAL NAME: XB 2793
CHEMICAL NAME: XU-238
CHEMICAL NAMl: ZINC
CHEMICAL NAME: ZINC DIALKYL DITHIOPHOSPHATES (ZDDP)
8EHQ-0181-0379
8EHQ-0781-0405 S
CHEMICAL NAME: ZYTEL NYLON RESIN PURGING PROCESS
*
* Based on a preliminary evaluation, EPA believes that the submitted information did not warrant reporting pursuant to
Section 8(e) of TSCA. In some cases, a submitting company was requested to provide the basis for its contention that
the reported information offered reasonable support for a conclusion of substantial risk of injury to health and/or
the environment as defined in EPA's March 16, 1978, TSCA Section 8(e) policy statement (Appendix A of this volume).
-------
APPENDIX D: STATUS REPORTS BY INFORMATION TYPE
ACUTE TOXICITY (ANIMAL)
SUBMISSION I: 8EHQ-0380-0335 S 8EHQ-0480-0340 8EHQ-0680-0347
8EHQ-0680-0349 8EHQ-0980-0359 8EHQ-0980-0362
8EHQ-0980-0365 8EHQ-0780-0369 8EHQ-1l80-0372
8EHQ-0181-0380 * 8EHQ-0181-0381 8EHQ-0281-0382
8EHQ-0381-0392 8EHQ-0581-0398 8EHQ-0581-0400
8EHQ-0881-0408 S * 8EHQ-0981-0409 8EHQ-I081-0417
8EHQ-I081-0418 8EHQ-0282-0427 S 8EHQ-0282-0428 *
8EHQ-0282-0429 * 8EHQ-0282-0430 * 8EHQ-0282-0431 *
8EHQ-0282-0432 * 8EHQ-0282-0433 * 8EHQ-0282-0435
,j::"
~ 8EHQ-0282-0436 * 8EHQ-0282-0437 8EHQ-0382-0438 S
f-J
8EHQ-0382-0440 S 8EHQ-0682-0448 S 8EHQ-0982-0456 S *
8EHQ-I082-0459 8EHQ-I082-0460 8EHQ-1l82-0462
ACUTE TOXICITY (HUMAN)
SUBMISSION I: 8EHQ-0280-0333 8EHQ-0480-0338 8EHQ-0580-0341
8EHQ-0680-0344 P * 8EHQ-0880-0355 8EHQ-0881-0407
8EHQ-0981-0409 8EHQ-1l82-0466 *
ALLERGENICITY (ANIMAL)
SUBMISSION #: 8EHQ-0480-0340 8EHQ-1l80-0371 8EHQ-0281-0382
8EHQ-0282-0427 S 8EHQ-0682-0448 S 8EHQ-1l82-0462
ALLERGENICITY (HUMAN)
SUBMISSION #: 8EHQ-0880-0355 8EHQ-0282-0427 S
-------
APPENDIX D: STATUS REPORTS BY INFORMATION TYPE
SUBMISSION #:
CEll TRANSFORMATION (IN VITRO)
BEHQ-02BO-0334
BEHQ-06BI-0404
BEHQ-02BI-0385
BEHQ-0981-0412
BEHQ-IOBI-041B
8EHQ-0982-0455
SUBMISSION #:
CHEMICAL/PHYSICAL PROPERTIES
8EHQ-0480-0340
8EHQ-0280-0333
8EHQ-0382-0440 S
CHRONIC TOXICITY (ANIMAL)
SUBMISSION #: 8EHQ-0580-0342
*'"
~
~ CHRONIC TOXICITY (HUMAN)
SUBMISSION #: 8EHQ-0981-0409
DNA REPAIR (IN VITRO)
SUBMISSION #:
8EHQ-0282-0439
8EHQ-0280-0334
SUBMISSION #:
ECOTOXICITY/AQUATIC TOXICITY
8EHQ-0881-0407
SUBMISSION #:
EMERGENCY INCIDENT OF ENV. CONTAMINATION
8EHQ-0181-0378
8EHQ-0580-0343
8EHQ-1l82-0466
*
SUBMISSION It:
ENV. OCCURRENCE/RELEASE/FATE
BEHQ-0680-0345
8EHQ-0580-0343
(CONT.)
8EHQ-1280-0401 S
8EHQ-I081-0415
8EHQ-06BO-0348
8EHQ-1282-0467
8EHQ-0881-0407
8EHQ-0880-0358
*
-------
APPENDIX D: STATUS REPORTS BY INFORMATION TYPE
SUBMISSION #:
ENV. OCCURRENCE/RELEASE/FATE (CONT.)
EPIDEMIOLOGY/CLINICAL
SUBMISSION #:
GROUNDWATER CONTAMINATION
*'"
1.0
W
SUBMISSION #:
HUMAN EXPOSURE (ACCIDENTAL)
SUBMISSION #:
HUMAN EXPOSURE (MONITORING)
SUBMISSION #:
8EHQ-I080-0368
8EHQ-0981-0413
8EHQ-0881-0407
8EHQ-I081-0416
8 EHQ-1l82- 0 46 2
8EHQ-1182-0466
8EHQ-0280-0332
8EHQ-I080-0367
8EHQ-0580-0341
8EHQ-0381-0390
8EHQ-0282-0427 S
8EHQ-0382-0440 S
8EHQ-0680-0345
8EHQ-I080-0368
8EHQ-0480-0338
8EHQ-0381-0390
8EHQ-0580-0341
8EHQ-0981-0413
8EHQ-1l82-0466
*
8EHQ-0280-0331 S
8EHQ-0680-0345
8EHQ-0380-0336 S
8EHQ-0680-0348
8EHQ-I080-0368
8EHQ-0482-0442
8EHQ-1280-0401 S
8EHQ-0982-0457
SUBMISSION #:
HUMAN EXPOSURE (PRODUCT CONTAMINATION)
8EHQ-0380-0336 S
8EHQ-0280-0331 S
(CONT.)
8EHQ-0981-0409
8EHQ-0982-0457
*
8EHQ-1080-0366
8EHQ-1280-0401 S
8EHQ-0582-0444
8EHQ-0982-0457
8EHQ-0580-0343
8EHQ-I081-0416
8EHQ-0580-0343
8EHQ-I080-0367
8EHQ-0382-0440 S
8EHQ-1l82-0462
8EHQ-0680-0348
-------
APPENDIX D: STATUS REPORTS BY INFORMATION TYPE
(CONT.)
SUBMISSION #:
HUMAN EXPOSURE (PRODUCT CONTAMINATION) (CONT.)
*
8EHQ-0780-0352
8EHQ-0381-0390
8EHQ-0880-0358
8EHQ-0981-0409
8EHQ-1280-0376
8EHQ-1281-0420
8EHQ-0482-0442
8EHQ-0682-0449 S
SUBMISSION #:
METABOLISM/PHARMACOKINETICS (ANIMAL)
8EHQ-1280-0401 S
MUTAGENICITY (IN VITRO)
SUBMISSION #:
"'"
1.0
"'"
MUTAGENICITY (IN VIVO)
SUBMISSION #:
8EHQ-0780-0350
8EHQ-0280-0333
8EHQ-0480-0340
8EHQ-0280-0334 8EHQ-0480-0339
8EHQ-0780-0350 8EHQ-0780-0351
8EHQ-0980-0361 S 8EHQ-0980-0363
8EHQ-0281-0383 S * 8EHQ-0281-0385
8EHQ-0481-0396 * 8EHQ-0581-0400
8EHQ-0681-0403 S 8EHQ-0681-0404
8EHQ-0981-0412 8EHQ-I081-0415
8EHQ-I081-0418 8EHQ-1281-0426
8EHQ-0682-0448 S BEHQ-0982-0455
8EHQ-I082-0459 8EHQ-IOB2-0460
BEHQ-09BO-0359
BEHQ-I080-0366
8EHQ-03BI-0391
8EHQ-06BI-0402
BEHQ-0781-0406 S
8EHQ-IOBI-0417
BEHQ-02B2-0427 S
BEHQ-0982-0458
BEHQ-llB2-0465
8EHQ-0780-0350
BEHQ-03BI-03B7
8EHQ-I080-0366
BEHQ-0981-0412
BEHQ-02BI-0384
8EHQ-I081-0418
8EHQ-12BI-0426
-------
NEUROTOXICITY (ANIMAL)
SUBMISSION I:
NEUROTOXICITY (HUMAN)
SUBMISSION I:
ONCOGENICITY (ANIMAL)
SUBMISSION I:
~
\.D
V1
ONCOGENICITY (HUMAN)
SUBMISSION I:
APPENDIX D: STATUS REPORTS BY INFORMATION TYPE
(CONT.)
8EHQ-0880-0356
8EHQ-0382-0440 S
8EHQ-0880-0357
8EHQ-0682-0451
8EHQ-0780-0369
8EHQ-1182-0462
8EHQ-0480-0338
8EHQ-0480-0337
8EHQ-0780-0353
8EHQ-0580-0342 8EHQ-0780-0350
8EHQ-0980-0360 8EHQ-I080-0370
8EHQ-0381-0393 8EHQ-0481-0397
8EHQ-1280-0401 S 8EHQ-0681-0402
8EHQ-0981-0411 8EHQ-1281-0422
8EHQ-0282-0434 8EHQ-0282-0439
8EHQ-0682-0447 8EHQ-0882-0453
8EHQ-I082-0461 8EHQ-1182-0463
8EHQ-0381-0389
8EHQ-0581-0400
8EHQ-0981-0410
8EHQ-1281-0423
8EHQ-0482-0443
8EHQ-0882-0454
8EHQ-1282-0467
8EHQ-0582-0444
SUBMISSION I:
PRODUCT COMPOSITION/CHEMICAL IDENTITY
8EHQ-0280-0331 S
8EHQ-0380-0336 S
8EHQ-0280-0333
8EHQ-0780-0350
8EHQ-0380-0335 S
8EHQ-1180-0375 S
8EHQ-0581-0399 S
8EHQ-0781-0406 S
8EHQ-0482-0442
-------
APPENDIX D: STATUS REPORTS BY INFORMATION TYPE
(CONT.)
PRODUCT COMPOSITION/CHEMICAL IDENTITY
(CONT.)
SUBMISSION I:
8EHQ-0682-0446 S
8EHQ-0882-0454
8EHQ-0 982-0456 S
*
REPRODUCTIVE TOXICITY/TERATO. (ANIMAL)
SUBMISSION ft:
8EHQ-0680-0346
8EHQ-1l80-0375 S
8EHQ-1l80-0373 S
8EHQ-0181-0379
8EHQ-1l80-0374 S
8EHQ-0281-0384
8EHQ-0381-0386
8EHQ-0581-0399 S
8EHQ-0381-0388 S
8EHQ-0781-0405 S
8EHQ-0381-0394 S
8EHQ-I081-0414
8EHQ-1281-0421 S.
8EHQ-0382-0441
8EHQ-1281-0424
8EHQ-0682-0450
8EHQ-0382-0440 S
8EHQ-0882-0452
~
I.D
0'\
8EHQ-1l82-0462
8EHQ-1l82-0464
REPRODUCTIVE TOXICITY/TERATO. (HUMAN)
SUBMISSION I:
8EHQ-I080-0367
8EHQ-0382-0440 S
SUBACUTE TOXICITY (ANIMAL)
SUBMISSION I:
8EHQ-0680-0346
8EHQ-0181-0377
8EHQ-I080-0366
8EHQ-0281-0384
8EHQ-0780-0369
8EHQ-0381-0392
8EHQ-I081-0419
8EHQ-0582-0445
8EHQ-1281-0425 S
8EHQ-0682-0446 S
8EHQ-0382-0438 S
8EHQ-1182-0462
SUBCHRONIC TOXICITY (ANIMAL)
SUBMISSION #:
8EHQ-0680-0347
8EHQ-0281-0384
8EHQ-0780-0354
8EHQ-0682-0446 S
8EHQ-0980-0364
* Based on a preliminary evaluation, EPA believes that the submitted information did not warrant reporting pursuant to
Section B(e) of TSCA. In some cases, a submitting company was requested to provide the basis for its contention that
the reported information offered reasonable support for a conclusion of substantial risk of injury to health and/or
the environment as defined in EPA's March 16, 1978, TSCA Section 8(e) policy statement (Appendix A of this volume).
-------
8EHQ-0280-0331 S
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
8EHQ-0280-0332
CAS NUMBER:
8EHQ-0280-0333
CAS NUMBER:
,j::.
~
'-.J
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
8EHQ-0280-0334
CAS NUMBER:
CAS NUMBER:
CA S NU1'1B ER:
CAS NUMBER:
8EHQ-0380-0335 S
CAS NUMBER:
CAS NUMBER:
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER
SUBMITTER: HENKEL CORPORATION
CONFIDENT CHEMICAL NAME: NONAX 1166
CONFIDENT CHEMICAL NAME: POLYQUART H
NONE CHEt'lICAL NAME: POLYALKOXYLATED POLYAMINES
123-91-1 CHEMICAL NAME: 1,4-DIOXANE
SUBMITTER: INTERNATIONAL LEAD ZINC RESEARCH ORGANIZATION INC.
7440-43-9
CHEMICAL NAME: CADMIUM
SUBMITTER: KERR-MCGEE CORPORATION
64741-67-9 CHEMICAL NAME: KERMAC 218A
64741-67-9 CHEMICAL NA1'1E: RESIDUES (PETROLEUM), CATALYTIC REFORMER FRACTIONATOR
64742-46-7 CHEMICAL NAME: DISTILLATES (PETROLEUM), HYDROTREATED MIDDLE
64742-46-7 CHEMICAL NAME: KERMAC 600W
SUBMITTER: B. F. GOODRICH COMPANY
102-77-2 CHEMICAL NAME: MORPHOLINE, 4-(2-BENZOTHIAZOLYLTHIO)-
102-77-2 CHEMICAL NAME: OBTS
13752-51-7 CHEMICAL NAME: CURE-RITE 18
13752-51-7 CHEMICAL NAME: MORPHOLINE, 4-[(4-MORPHOLINYLTHIO)THIOXOMETHYLJ-
NONE
NONE
SUBMITTER: GULF OIL COMPANY - U.S.
CHEMICAL NAME: CUTTING FLUID
CHEMICAL NAME: GULFCUT HEAVY DUTY SOLUBLE OIL
-------
8EHQ-0380-0335 S
CAS NUMBER:
APPENDIX E:
STATU~ REPORTS BY SUBMISSION NUMBER (CONT.)
(CONT.)
SJBMITTER: GULF OIL COMPANY - U.S.
CHEMICAL NAME: OIL, GULFCUT HEAVY DUTY SOLUBLE
NONE
8EHQ-0380-0336 S SUBMITTER: HENKEL CORPORATION
CAS NUMBER: CONFIDENT CHEMICAL NAME: ST ANAX 1166
CAS NUMBER: NONE CHEMICAL NAME: POLYALKOXYLATED POLYAMINES
CAS NUMBER: 123-91-1 CHEMICAL NAME: 1,4-DIOXANE
8EHQ-0430-0337
CAS NUMBER:
*'"
I.D
00
8EHQ-0480-0338
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
8EHQ-0480-0339
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
SUBMITTER: PENNWALT CORPORATION
75-38-7
CHEMICAL NAME: ETHENE, 1,1-DIFlUORO-
SUBMITTER: LOCKHEED MISSIL ES & SPACE COMPANY, INC.
NONE CHEMICAL NAME: HX 999
80-08-0 CHEMICAL NAME: BENZENAMINE, 4,4'-SULFONYLBIS-
80-08-0 CHEMICAL NAME: DDS
80-08-0 CHEMICAL NAME: EPORAL
28768-32-3
28768-32-3
CHEMICAL NAME: MY 720
CHEMICAL NAME: OXIRANEMETHANAMINE, N,N'-CMETHYLENEDI-4,1-PHENYLENE)BIS[N-(O
XIRANYLMETHYL )-
NONE
SUBMITTER: IBM CORPORATION
CHEMICAL NAME: PHOTOCOPYING PRODUCTS/PROCESS
129-79-3
129-79-3
CHEMICAL NAME: 9H-FLUOREN-9-0NE, 2,4,7-TRINITRO-
CHEMICAL NAME: 2,4,I-TRINITROFLUORENONE
-------
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER CCONT.)
8EHQ-0480-0340
CAS NUMBER:
SUBMITTER: CIBA-GEIGY CORPORATION
CAS NUMBER:
UNKNOWN
UNKNOWN
CHEMICAL NAME: CHIMASSORB 944
CHEMICAL NAME: POLY ,IN,N'-BISC2,2,6,6-TETRAMETHYLPIPERID-4-YL)-N-C4-C1,1,3
3-TETRAMETHYLBUTYLAMINO)-1,3,5-TRIAZINE-2,6-DIYL)HEXAMETHYLE
NEDIAMINE
8cHQ-0580-0341
CAS NUMBER:
SUBMITTER: UNION CARBIDE CORPORATION
93-55-0
CHEMICAL NAME: 1-PROPANONE, 1-PHENYL-
8EHQ-0580-0342 SUBMITTER: ASARCO INCORPORATED
CAS NUMBER: 1309-64-4 CHEMICAL NAME: ANTIMONY OXIDE
~
'" 8EHQ-0580-0343 SUBMITTER: GULF OIL EXPLORATION AND PRODUCTION COMPANY
'"
CAS NUMBER: 7783-06-4 CrlEMICAL NAME: HYDROGEN SULFIDE
8EHQ-0680-0344 P
CAS NUMBER:
CAS NUMBER:
NONE
NONE
SUBMITTER: WESTERN ELECTRIC
CHEMICAL NAME: MISC. CHEMICALS
*
CHEMICAL NAME: ZYTEL NYLON RESIN PURGING PROCESS
8EHQ-0680-0345 SUBMITTER: GLIDDEN COATINGS AND RESINS
CAS NUMBER: 71-43-2 CHEMICAL NAME: BENZENE
CAS NUMBER: 75-01-4 CHEMICAL NAME: ETHENE, CHLORO-
CAS NUMBER: 75-01-4 CHEMICAL NAME: VINYL CHLORIDE
CAS NUMBER: 75-09-2 CHEMICAL NAME: METHANE, DICHLORO-
CAS NUMBER: 75-09-2 CHEMICAL NAME: METHYLENE CHLORIDE
-------
APPENDIX E: STATUS REPORTS BY SUBMISSION NUMBER (CONT.)
8EHQ-0680-0345 (CONT.) SUBMITTER: GLIDDEN COATINGS AND RESINS
CAS NUMBER: 75-34-3 CHEMICAL NAME: ETHANE, 1,1-DICHLORO-
CAS NUMBER: 75-71-8 CHEMICAL NAME: METHANE, DICHLORODIFLUORO-
CAS NUMBER: 79-01-6 CHEMICAL NAME: ETHENE, TRICHLORO-
CAS NUMBER: 79-01-6 CHEMICAL NAME: TRICHLOROETHYLENE
CAS NUMBER: 100-41-4 CHEMICAL NAME: BENZENE, ETHYL-
CAS NUMBER: 108-88-3 CHEMICAL NAME: BENZENE, METHYL -
CAS NUMBER: 108-88-3 CHEMICAL NAME: TOLUENE
CAS NUMBER: 127-18-4 CHEMICAL NAME: ETHENE, TETRACHLORO-
lJ1 CAS NUMBER: 127-18-4 CHEMICAL NAME: TETRACHLOROETHYLENE
0
0 CAS NUMBER: 156-60-5 CHEMICAL NAME: ETHENE, 1,2-DICHLORO-, (E)-
CAS NUMBER: 7439-92-1 CHEMICAL NAME: LEAD
CAS NUMBER: 7439-97-6 CHEMICAL NAME: MERCURY
CAS NUMBER: 7440-02-0 CHEMICAL NAME: NICKEL
CAS NUMBER: 7440-22-4 CHEMICAL NAME: S IL V ER
CAS NUMBER: 7440-28-0 CHEMICAL NAME: THALLIUM
CAS NUMBER: 7440-36-0 CHEMICAL NAM~: ANTIMONY
CAS NUMBER: 7440-38-2 CHEMICAL NAME: ARSENIC
CAS NUMBER: 7440-41-7 CHEMICAL NAME: BERYLLIUM
CAS NUMBER: 7440-43-9 CHEMICAL N~,ME: CADMIUM
CAS NUMBER: 7440-47-3 CHEMICAL NAME: CHROMIUM
CAS NUMBER: 7440-5(;-3 CHEMICAL NAME: COPPER
-------
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CONT.)
8EHQ-0680-0345
(CONT.)
SUBMITTER: GLIDDEN COATINGS AND RESINS
CAS NUMBER:
CAS NUMBER:
7440-66-6
7782-49-2
CHEMICAL NAME: ZINC
CHEMICAL NAME: SELENIUM
8EHQ-0680-0346
CAS NUMBER:
NONE
SUBMITTER: ETHYL CORPORATION
CHEMICAL NAME: ZINC DIALKYL DITHIOPHOSPHATES (ZDDP)
CAS NUMBER:
2215-35-2
CHEMICAL NAME: 2-PENTANOL. 4-METHYL-. HYDROGEN PHOSPHORODITHIOATE, ZINC SAL
T
CHEMICAL NAME: PHOSPHORODITHIOIC ACID. MIXED 2-ETHYLHEXYL AND 2-METHYLPROPY
L ESTERS. ZINC SALTS
CAS NUMBER:
68442-22-8
U1 8EHQ-0680-0347 SUBMITTER: DOW CORNING CORPORA TI ON
0 (
I-' CAS NUMBER: 2487-90-3 CHEMICAL NAME: SILANE. TRIMETHOXY-
8EHQ-0680-0348 SUBMITTER: AMCHEM PRODUCTS. INC.
CAS NUMBER: NONE CHEMICAL NAME: RODINE 50
CAS NUMBER: NONE CHEMICAL NAME: RODINE 500
CAS NUMBER: NONE CHEMICAL NAME: RODINE 51
CAS NUMBER: NONE CHEMICAL NAME: RODINE 85
CAS NUMBER: NONE CHEMICAL NAME: RODINE 95
CAS NUMBER: NONE CHEMICAL NAME: RODINE 96
CAS NUMBER: 95-53-4 CHEMICAL NAME: BENZENAMINE, 2-METHYL-
CAS NUMBER: 95-53-4 CHEMICAL NAME: TOLUIDINE (ORTHO)
-------
8EHQ-0680-0349
CAS NUMBER:
CAS NUMBER:
8EHQ-0780-0350
CAS NUMBER:
CAS NUMBER:
lJ1
a
IV
8EHQ-0780-0351
CAS NUMBER:
8EHQ-0780-0352
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
8EHQ-0780-0353
CAS NUMBER:
8EHQ-0780-0354
CAS NUMBER:
CAS NUMBER:
APPENDIX E:
STATUS ~EPORTS BY SUBMISSION NUMBER (CONT.)
SUBMITTER: UNION CARBIDE CORPORATION
67762-92-9
67762-92-9
CHEMICAL NAME: SILICONE Y-6607
CHEMICAL NAME: SILOXANES AND SILICONES, DI-ME, DIMETHYLAMINO-TERMINATED
SUBMITTER: PROCTER & GAMBLE COMPANY
4680-78-8
4680-78-8
CHEMICAL NAME: C. I. ACID GREEN 3
CHEMICAL NAME: BENZENEMETHANAMINIUM, N-ETHYL-N-[4-[[4-[ETHYL[(3-SULFOPHENYL
)METHYLJAMINOJPHENYLJPHENYLMETHYLENEJ-2,5-CYCLOHEXADIEN-I-YL
IDENEJ-3-SULFO-, HYDROXIDE, INNER SALT, SODIUM SALT
NONE
SUBMITTER: A. B. DICK COMPANY
CHEMICAL NAME: PHOTOCOPYING PRODUCTS/PROCESS
NONE
NONE
SUBMITTER: MONTGOMERY ELEVATOR COMPANY
CHEMICAL NAME: HYDRAULIC FLUIDS
CHEMICAL NAME: WYNN'S FRICTION PROOFING FLUID
CHEMICAL NAME: l,l'-BIPHENYL, CHLORINATED
1336-36-3
1336-36-3
CHEMICAL NAME: POLYCHLORINATED BIPHENYLS (PCB)
SUBMITTER: STANDARD OIL COMPANY (SOHIO)
68187-58-6
CHEMICAL NAME: PITCH, PETROLEUM, CONDEMSED-RING AROM.
SUBMITTER: MCB MANUFACTURING CHEMISTS, INC.
14808-60-7
63231-67-4
CHEMICAL NAME: QUARTZ
CHEMICAL NAME: SILICA GEL
-------
8EHQ-0880-0355
CAS NUMBER:
8EHQ-0880-0356
CAS NUMBER:
8EHQ-0880-0357
CAS NUMBER:
8EHQ-0880-0358
U1
o
w
CAS NUMBER:
CAS NUMBER:
8EHQ-0980-0359
CAS NUMBER:
8EHQ-0980-0360
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
8EHQ-0980-0361 S
CAS NUMBER:
CAS NUMBER:
10533-67-2
818-61-1
110-26-9
*
NONE
7705-08-0
UNKNOWN
98-07-7
98-88-4
5216-25-1
14285-"9-7
29383-~9-7
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CONT.)
SUBMITTER: ALLIED CHEMICAL CORPORATION
CHEMICAL NAME: ACETALDEHYDE, (METHYLTHIO)-, OXIME
SUBMITTER: NALCO CHEMICAL COMPANY
CHEMICAL NAME: 2-PROPENOIC ACID, 2-HYDROXYETHYL ESTER
SUBMITTER: NALCO CHEMICAL COMPANY
CHEMICAL NAME: 2-PROPENAMIDE, N,N'-METHYLENEBIS-
SUBMITTER: EMPLOYEE SUBMISSION
CHEMICAL NAME: RADIOACTIVE MATERIALS
CHEMICAL NAME: IRON CHLORIDE
SUBMITTER: FMC CORPORATION
CHEMICAL NAME: 1,2-BENZENEDICARBOXYLIC ACID, 3,4,5,6-TETRABROMO-, DI-2-PROP
ENYl ES TER
SUBMITTER: HOOKER CHEMICALS AND PLASTICS CORPORATION
CHEMICAL NAME: BENZENE, (TRICHLOROMETHYL)-
CHEMICAL NAME: BENZOYL CHLORIDE
CHEMICAL NAME: BENZENE, 1-CHLORO-4-(TRICHLOROMETHYL)-
SUBMITTER: CONFIDENTIhL
CHEMICAL NAME: COBALTATE(4-), 129H,31H-PHTHALOCYANINE-2,9,16,23-TETRASULFON
ATO(6-)-N29,N30,N31,N32]-, TETRAHYDROGEN, (SP-4-1)-
CHEMICAL NAME: COBALTATE(2-), 129H,31H-PHTHALOCYANINEDISULFONATO(4-)-N29,N3
O,N31,N32]-, DIHYDROGEN
-------
8EHQ-0980-0362
CAS NUMBER:
8EHQ-0980-0363
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
8EHQ-0980-0364
CAS NUMBER:
U1
a
~
CAS NUMBER:
8EHQ-0980-0365
CAS NUMBER:
8EHQ-1080-0366
CAS NUMBER:
8EHQ-1080-0367
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS HUMBER:
57138-85-9
NONE
NONE
68410-08-2
77-73-6
77-73-6
71-55-6
868-85-9
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CONT.)
SUBMITTER: NALCO CHEMICAL COMPANY
CHEMICAL NAME: BENZENAMINE, POLYMER WITH FORMALDEHYDE, HYDROCHLORIDE
SUBMITTER: INTERNATIONAL COAL REFINING COMPANY
CHEMICAL NAME: COAL, SOLVENT-REFINING (SRC) PROCESS/PRODUCTS
C~EMICAL NAME: SRC PROCESS/PRODUCTS
CHEMICAL NAME: DISTILLATES (COAL), SOLVENT-REFINING (SRC), RECYCLE
SUBMITTER: EXXON CHEMICAL AMERICAS
CHEMICAL NAME: DICYClOPENTADIENE
CHEMICAL NAME: 4,7-METHANO-1H-INDENE, 3A,4,7,7A-TETRAHYDRO-
SUBMITTER: S. C. JOHNSON & SON, INC.
CHEMICAL NAME: ETHANE, 1,1,1-TRICHLORO-
SUBMITTER: MOBIL RESEARCH AND DEVELOPMENT CORPORATION
CHEMICAL NAME: PHOSPHONIC ACID, DIMETHYL ESTER
SUBMITTER: OLIN CORPORATION
95-80-7 CHEMICAL NAME: 1,3-BENZENEDIAMINE, 4-METHYL-
121-14-2 CHEMICAL NAME: BENZENE, 1-METHYl-2,4-DINITRO-
823-40-5 CHEMICAL NAME: 1,3-BENZENEDIAMIHE, 2-METHYL-
25321-14-6 CHEMICAL NAr1E: BENZENE, METHYLDIIHTRO-
25376-45-8 CHEMICAL NAME: BENZENEDIAMINE, AR-METHYL-
-------
8EHQ-1080-0368
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
V1
o
V1
8EHQ-0780-0369
CAS NUMBER:
CAS NUMBER:
8EHQ-1080-0370
CAS NUMBER:
8EHQ-1l80-0371
CAS NUMBER:
CAS NUt1BER:
CAS NUMBER:
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CONT.)
SUBMITTER: MARTIN MARIETTA CHEMICALS
86-28-2 CHEMICAL NAI'1E: 9H-CARBAZOLE, 9-ETHYl-
95-50-1 CHEMICAL NAME: BENZENE, 1,2-DICHLORO-
100-41-4 CHEMICAL NAME: BENZENE, ETHYl-
106-42-3 CHEMICAL NAI'1E: BENZENE, 1, 4-DIMETHYl-
108-38-3 CHEMICAL NAME: BENZENE, 1,3-DIMETHYl-
108-88-3 CHEMICAL NAME: BENZENE, METHYl-
108-88-3 CHEMICAL NAME: TOLUENE
108-90-7 CHEMICAL NAME: BENZENE, CHLORO-
SUBMITTER: AMERICAN CYA~AMID COMPANY
10310-38-0
10310-38-0
CHEMICAL NAME: CYAGARD RF-1
CHEMICAL NAME: PHOSPHONIUM, 1,2-ETHANEDIYLBISrTRIS(2-CYANOETHYL)-, DIBROMID
E
SUBMITTER: EXXON CHEMICAL AMERICAS
106-99-0
CHEMICAL NAME: 1,3-BUTADIENE
NONE
SUBMITTER: LEVER BROTHERS COMPANY (INCORPORATED)
CHEMICAL NAME: VARISOFT 222 (90~)
67-63-0
68153-35-5
CHEMICAL NAME: 2-PROPANOL
CHEMICAL NAME: ETHANAMINIUM, 2-AMINO-N-(2-AMINOETHYL)-N-(2-HYDROXYETHYL)-N-
METHYL-, N,N'-DITALLOW ACYL DERIVS., ME SULFATES (SALTS)
-------
8EHQ-1l80-0372
CAS NUMBER:
8EHQ-1180-0373 S
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
13292-87-0
NONE
1691-99-2
68555-73-7
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CONT.)
SUBMITTER: CALLERY CHEMICAL COMPANY
CHEMICAL NAME: BORANE. COMPO. WITH THIOBIS[METHANEJ (1:1)
SUBMITTER: 3M COMPANY
CHEMICAL NAME: PERFlUOROAlKYl COMPOUNDS
CHEMICAL NAME: 1-0CTANESUlFONAMIDE. N-ETHYl-1,1,2,2,3,3,~,4,5,5,6,6,7,7,8,8
,8-HEPTADECAFlUORO-N-(2-HYDROXYETHYL)-
CHEMICAL NAME: 1-HEPTANESUlFONAMIDE, N-ETHYl-l.1,2,2,3,3,4.4,5,5,6,6,7,7.7-
PENTADECAFlUORO-N-(2-HYDROXYETHYl)-
8EHQ-1180-0374 S SUBMITTER: 3M COMPANY
CAS NUMBER: CONFIDENT CHEMICAL NAME: PERFlUOROAlKYl SUlFONATES. POTASSIUM SALTS
LJ1
0 CAS NUMBER: NONE CHEMICAL NAME: FLUORORAD FC-95
0"\
CAS NUMBER: NONE CHEMICAL NAME: PERFlUOROAlKYl COMPOUNDS
8EHQ-1180-0375 S
CAS NUMBER:
CAS NUMBER:
8EHQ-1280-0376
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
NONE
UNKNOWN
NONE
UNKNOWN
62-75-9
1643-20-5
SUBMITTER: TENNECO CHEMICALS, INC.
CHEMICAL NAME" r-122
CHEMICAL NAME: CADMIUM SALTS OF P-TERT-BUTYl BENZOIC ACID AND BENZOIC ACID
SUBMITTER: STEPAN CHEMICAL COMPANY
CHEMICAL NAME: NITROSAMINES
CHEMICAL NAME: DODECANAMINE. N-METHYl-N-NITROSO-
CHEMICAL NAME: METHANAMINE, N-METHYl-N-NITROSO-
CHEMICAL NAME: 1-DODECANAMINE, N,N-DIMETHYl-. N-OXIDE
-------
8EHQ-0181-0377
CAS NUMBER:
CAS NUMBER:
8EHQ-0181-0378
CAS NUMBER:
8EHQ-0181-0379
CAS NUMBER:
CAS NUMBER:
V1
o
~
CAS NUMBER:
8EHQ-0181-0380
CAS NUMBER:
8EHQ-OUn-0381
CAS NUMBER:
CAS NUMBER:
8EHQ-0281-0382
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CONT.)
NONE
SUBMITTER: ATLANTIC RICHFIELD COMPANY
CHEMICAL NAME: JET FUEL A
UNKNOWN
CHEMICAL NAME: OIL (PETROLEUM), NUMBER 6 HEAVY FUEL
SUBMITTER: INTERNATIONAL MINERALS & CHEMICAL CORPORATION
7446-09-5
CHEMICAL NAME: SULFUR DIOXIDE
NONE
SUBMITTER: EXXON CHEMICAL AMERICAS
CHEMICAL NAME: ZINC DIALKYL DITHIOPHOSPHATES (ZDDP)
UNKNOWN
CHEMICAL NAME: PHOSPHORODITHIOIC ACID, O,O'-DI(ISOHEXYL, ISOHEPTYL, ISOOCTY
L, ISONONYL, ISODECYL)MIXED ESTERS, ZINC SALT
CHEMICAL NAME: PHOSPHORODITHIOIC ACID, (SECONDARY BUTYL AND ISOOCTYL)MIXED
ESTERS, ZINC SALT
UNKNOWN
*
SUBMITTER: R. T. VANDERBILT COMPANY, INC.
1072-71-5
CHEMICAL NAME: 1,3,4-THIADIAZOLIDINE-2,5-DITHIONE
SUBMITTER: PPG INDUSTRIES, INC.
107-18-6
15022-08-9
CHEMICAL NAME: 2-PROPEN-1-0L
CHEMICAL NAME: CARBONIC ACID, DI-2-PROPENYL ESTER
SUBMITTER: GLYCO CHEMICALS, INC.
77-48-5
118-52-5
CHEMICAL NAME: 2,4-IMIDAZOLIDINEDIONE, 1,3-DIBROMO-5,5-DIMETHYL-
CHEMICAL NAME: 2,4-IMIDAZOLIDINEDIONE, 1,3-DICHLORO-5,5-DIMETHYL-
126-06-7
CHEMICAL NAME: 2,4-IMIDAZOLIDINEDIONE, 3-BROMO-1-CHLORO-5,5-DIMETHYL-
-------
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CONT.)
CAS NUMBER:
CAS NUMBER:
NONE
NONE
SUBMITTER: CONFIDENTIAL
CHEMICAL NAME: BENZOFURAZANS, NITRO-
8EHQ-0281-0383 S
*' .
CAS NUMBER:
10199-89-0
CHEMICAL NAME: BENZOFUROXANS, NITRO-
CHEMICAL NAME: BENZOFURAZAN, 4-CHLORO-7-NITRO-
8EHQ-0281-0384 SUBMITTER: DOW CHEMICAL COMPANY
CAS NUMBER: 109-86-4 CHEMICAL NAME: ETHANOL, 2-METHOXY-
8EHQ-0281-0385 SUBMITTER: GUL F OIL COMPANY - U.S.
CAS NUMBER: NONE CHEMICAL NAME: GULF SUPERQUENCH 70
CAS NUMBER: 64742-04-7 CHEMICAL NAM[: EXTRACTS (PETROLEUM), HEAVY PARAFFINIC DISTILLATE SOLVENT
lJ1
a CAS NUMBER: 64742-04-7 CHEMICAL NAME: GULF N.E. 75 (PROCESS 63)
OJ
CAS NUMBER: 64742-11-6 CHEMICAL NAI'1E: EXTRACTS (PETROLEUM), HEAVY NAPHTHENIC DISTILLATE SOLVENT
CAS NUMBER: 64742-11-6 CHEMICAL NAME: GULF N.E. 61 (PROCESS 65)
CAS NUMBER: 64742-16-1 CHEI'HCAL NAME: PETROLEUM RESINS
CAS NUMBER: 64742-~2-5 CHEMICAL NAME: DISTILLATES (PETROLEUM), HYDROTREATED HEAVY NAPHTHENIC
CAS NUMBER: 64742-52-5 CHEMICAL NAME: GULF 100 TEXAS OIL
CAS NUMBER: 64742-55-8 CHEMICAL NAME: DISTILLATES (PETROLEUM), HYDROTREATED LIGHT PARAFFINIC
8EHQ-0381-0386 SUBMITTER: SHELL OIL COMPANY
CAS NUMBER: NONE CHEMICAL NAME: MISC. CHEMICALS
CAS NUMBER: 110-80-5 CHEMICAL NAME: ETHANOL, 2-ETHOXY-
-------
8EHQ-0381-0387
CAS NUMBER:
8EHQ-0381-0388 S
CAS NUMBER:
CAS NUMBER:
8EHQ-0381-0389
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
lJI
o
1.0
8EHQ-0381-0390
CAS NUMBER:
CAS NU~'BER:
CAS NUMBER:
8EHQ-0381-0391
CAS NUMBER:
CAS NUMBER:
8EHQ-0381-0392
CAS NUMBER:
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CO NT.)
SUBMITTER: ETHYL CORPORATION
2524-03-0
CHEMICAL NAME: PHOSPHOROCHLORIDOTHIOIC ACID, O,O-DIMETHYL ESTER
SUBMITTER: EXXON CHEMICAL AMERICAS
CONFIDENT
NONE
CHEMICAL NAME: PHENOL SULFIDE, ALKYLATED-, CALCIUM SALT
CHEMICAL NAME: PARANOX 52
NONE
NONE
SUBMITTER: SHELL OIL COMPANY
CHEMICAL NAME: OIL (PETROLEUM), NEW MOTOR
NONE
CHEMICAL NAME: OIL (PETROLEUM), USED MOTOR
CHEMICAL NAME: POLYNUCLEAR AROMATIC HYDROCARBONS
SUBMITTER: DOW CHEMICAL COMPANY
NONE CHEMICAL NAME: DIOXINS, CHLORINATED
1746-01-6 CHEMICAL NAME: DIOXIN, 2,3,7,8-TETRACHLORODIBENlO-P-
25167-82-2 CIoiEMICAL NAME: PHENOL, TRICHLORO-
SUBMITTER: BUCKMAN LABORATORIES, INC.
68479-77-6
68479-77-6
CHEMICAL NAME: BL-4420
CHEMICAL NAME: PROPANOIC ACID, 2,3-DIBROMO-, 2-HYDROXYETHYL ESTER
SUBMITTER: UNION CARBIDE CORPORATION
624-83-9
CHEMICAL NAME: METHANE, ISOCYANATO-
-------
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CaNT.)
8EHQ-0381-0393 SUBMITTER: DOW CHEMICAL COMPANY
CAS NUMBER: NONE CHEMICAL NAME: CYCLOHEXANES, HEXAHALOGENATED-
CAS NUMBER: NONE CHEMICAL NAI'1E: FR651
CAS NUMBER: 87-84-3 C'iEMICAL NAME: CYCLOHEXANE, 1,2,3,4,5-PENTABROMO-6-CHLORO-
8EHQ-0381-0394 S
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
U1
f-'
o
8EHQ-0481-0396
CAS NUt.1BER:
CAS HUMBER:
CAS NUMBER:
8EHQ-0481-0397
CAS NUMBER:
CAS NUMBER:
CAS NUt'1B ER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
SUBMITTER: 3M COMPANY
CONFIDENT CHEMICAL NAME: PERFLUOROALKYL CARBOXYLIC ACID, AMMONIUM SALTS
CONFIDENT CHEMICAL N Ar1 E: PERFLUOROALKYL CARBOXYLIC ACIDS
NONE CHEMICAL NAME: FLUORORAD FC-143
NONE CHEMICAL NAME: PERFLUOROALKYL COMPOUNDS
*
SUBMITTER: MARTIN MARIETTA CHEMICALS
UNKNOWN CHEMICAL NAME: DI5PERSE BLUE 291
UNKNOWN CHEMICAL NAME: EASTMAN BLUE RBS
UNKNOl-JN CHEMICAL NAME: SODYECRON BLUE GBL
SUBMITTER: WILMINGTON CHEMICAL CORPORATION
NONE CHEMICAL NAME: EPOXY RESINS
NONE CHEMICAL NAME: HELOXY WC-68
NONE CHEMICAL NAME: MISC. CHEMICALS
NONE
CHEMICAL NAME: XB 2793
CHEMICAL NAME: 2,4-IMIDAlOlIDINEDIONE, 5,5-DIMETHYL-1,3-BIS(OXIRANYLMETHYL)
15336-81-9
17557-23-2
CHEMICAL NAME: OXIRANE, 2,2'-[(2,2-DIMETHYL-1,3-PROPANEDIYl)BIS(OXYMETHYLEN
E))BIS-
-------
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CONT.)
8EHQ-0581-0398 SUBMITTER: GULF MINERAL RESOURCES CO.
CAS NUMBER: NONE CHEmCAL NAME: COAL SOLVENT-REFINING (SRC) PROCESS/PRODUCTS
CAS NUMBER: NONE CHEf'HCAL NAME: SRC PROCESS/PRODUCTS
CAS NUMBER: UNKNOWN CHEMICAL NAME: DISTILLATES (COAL>, SOLVENT-REFINING (SRC), MIDDLE
8EHQ-0581-0399 S SUBMITTER: HERCULES INCORPORATED
CAS NUMBER: NONE CHEMICAL NAME: HIGH EXPLOSIVE (MIXTURE)
8EHQ-0581-0400
CAS NU~'B ER:
U1
~
........
CAS NUMBER:
8EHQ-1280-0401 S
CAS NUMBER:
CAS NUMBER:
8EHQ-0681-0402
CAS NUMBER:
CAS NUMBER:
8EHQ-0681-0403 S
CAS NUMBER:
CAS NUMBER:
SUBMITTER: UPJOHN COMPANY
6175-45-7
6175-45-7
CHEMICAL NAMF: ETHANONE, 2,2-DIETHOXY-1-PHENYL-
CHEMICAL NAME: U-2352
SUBMITTER: STAUFFER CHEMICAL COMPANY
13674-87-8
13674-87-8
CHEMICAL NAME: FYROL FR-2
CHEMICAL NAME: 2-PROPANOL, 1,3-DICHLORO-, PHOSPHATE (3:1)
SUBMITTER: UNION CARBIDE CORPORATION
3388-04-3
3388-04-3
CHEMICAL NAME: SILANE A-186
CHEMICAL NAME: SILANE, TRIMETHOXYI2-(7-0XABICYCLOI4.1.0]HEPT-3-YL)ETHYL1-
SUBMITTER: CONFIDENTIAL
29383-29-7
CHEMICAL NAME: COBALTATE(2-), 129H,31H-PHTHALOCYANINEDISULFONATO(4-)-N29,N3
0,N31,N32]-, DIHYDROGEN
CHEMICAL NAME: COBALTATE(l-), 129H,31H-PHTHALOCYANINESULFONATO(3-)-N29,N30,
N31,N32]-, HYDROGEN
30638-08-5
-------
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CONT.)
8EHQ-0681-0404
CAS NUMBER:
SUBMITTER: GULF OIL COMPANY - U.S.
CAS NUMBER:
64742-55-8
64742-55-8
CHEMICAL NAME: DISTILLATES (PETROLEUM), HYDROTREATED LIGHT PARAFFINIC
CHEMICAL NAME: GULF PARALUX 70
8EHQ-0781-0405 S
CAS NUMBER:
SUBMITTER: CONFIDENTIAL
CAS NUMBER:
CONFIDENT
NONE
CHEMICAL NAME: PHOSPHORODITHIOIC ACID, DIALKYL ESTERS, ZINC SALT
CHEMICAL NAME: ZINC DIALKYL DITHIOPHOSPHATES (ZDDP)
8EHQ-0781-0406 S
CAS NUMBER:
SUBMITTER: CELANESE CORPORATION
25038-04-4
CHEMICAL NAME: 1,2,3-PROPANETRIOL, POLYMER WITH (CHLOROMETHYL)OXIRANE
Ul
I-'
rv
8EHQ-0881-0407
CAS NUMBER:
SUBMITTER: E. I. DUPONT DE NEMOURS & COMPANY, INC.
7789-21-1
CHEMICAL NAME: FLUOROSULFURIC ACID
8EHQ-0881-0408 S
)(
SUBMITTER: CONFIDENTIAL
CAS NUMBER:
UNKNOWN
CHEMICAL NAME: STEARYLPHENYLETHYLDIMETHYL AMt10NIUM P-TOlUENE SULFONATE
8EHQ-0981-0409 SUBMITTER: VELSICOl CHEMICAL CORPORATION
CAS NUMBER: NONE CHEMICAL NAME: DIBENZOFURANS, CHLORINATED
CAS NUMBER: NONE CHEMICAL NAME: DIOXINS, CHLORINATED
CAS NUMBER: NONE CHEMICAL NAME: MISC. CHEMICALS
CAS NUMBER: 95-76-1 CHEMICAL NAME: BENZENAt'1INE, 3,4-DICHLORO-
CAS NUMBER: 330-54-1 CHEmCAL NAME: DIURON
CAS NUMBER: 330-54-1 CHEMICAL NAME: UREA, H'-(3,4-DICHlOROPHENYL)-N,N-DIMETHYL-
-------
8EHQ-0981-0409
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
U1
......
LV
8EHQ-0981-0410
CAS NUMBER:
8EHQ-0981-0411
CAS NUMBER:
8EHQ-0981-0412
CAS NUMBER:
8EHQ-0981-0413
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CONT.)
(CONT.)
SUBMITTER: VELSICOL CHEMICAL CORPORATION
330-55-2
330-55-2
CHEMICAL NAME: LINURON
CHEMICAL NAME: UREA, N'-(3,4-DICHLOROPHENYL)-N-METHOXY-N-METHYL-
709-98-8
709-98-8
CHEMICAL NAME: PROPANIL
CHEMICAL NAME: PROPIONAMIDE, N-(3,4-DICHLOROPHENYL)-
CHEMICAL NAME: BENZENE, 3,3',4,4'-TETRACHLOROAZO-
CHEMICAL NAME: METHAZOLE (TECHNICAL)
CHEMICAL NAME: 1,2,4-0XADIAZOLIDINE-3,5-DIONE,
CHEMICAL NAME: BENZENE, 3,3',4,4'-TETRACHLOROAZOXY-
14047-09-7
20354-26-1
20354-26-1
21232-47-3
SUBMITTER: CELANESE CORPORATION
1680-21-3
CHEMICAL NAME: 2-PROPENOIC ACID, 1,2-ETHANEDIYLBIS(OXY-2,1-ETHANEDIYL) ESTE
R
SUBMITTER: CELANESE CORPORATION
17831-71-9
CHEMICAL NAME: 2-PROPENOIC ACID, OXYBIS(2,1-ETHANEDIYLOXY-2,1-ETHANEDIYL) E
STER
SUBMITTER: ETHYL CORPORATION
993-43-1 CHEMICAL NAME: PHOSPHONOTHIOIC DICHLORIDE, ETHYL-
SUBMITTER: ARMAK COMPANY
UNKNOWN CHEMICAL NAME: 1,1'-BIPHENYL, 2,2',4,4'-TETRACHLORO-
1336-36-3 CHEMICAL NAME: 1,1'-BIPHENYL, CHLORINATED
1336-36-3 CHEMICAL NM1E: POLYCHLORINATED BIPHENYLS (PCB)
-------
8EHQ-1081-0414
CAS NUMBER:
CAS NUMBER:
8EHQ-1081-0415
CAS NUMBER:
8EHQ-I081-0416
CAS NUMBER:
lJ1
t-'
of'>
8EHQ-1081-0411
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
8EHQ-I081-0418
CAS NUMBER:
CAS NUMBER:
8EHQ-1081-0419
CAS NUMBER:
CAS NUMBER:
NONE
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CONT.)
SUBMITTER: WITCO CHEMICAL CORPORATION
CHEMICAL NAME: HYBASE M-400
61189-81-5
CHEMICAL NAME: SULFONIC ACIDS, PETROLEUM, MAGNESIUM SALTS
75-91-2
76-06-2
NONE
NONE
SUBMITTER: ATLANTIC RICHFIELD COMPANY
CHEMICAL NAME: HYDROPEROXIDE, 1,1-DIMETHYlETHYl
SUBMITTER: GREAT lAKES CHEMICAL CORPORATION
CHEMICAL NAME: METHANE, TRICHlORONITRO-
SUBMITTER: UNION OIL COMPANY OF CALIFORNIA
CHEMICAL NAME: OIL (SHALE), FUll-RANGE DEWAXED SYNCRUDE
68308-34-9
CHEMICAL NAME: OIL (SHALE), REDUCED SYNCRUDE
CHEMICAL ~AME: SHALE OILS
15336-82-0
SJBMITTER: CIBA-GEIGY CORPORATION
CHEMICAL NAME: 2,4-IMIDAZOlIDINEDIONE, 5-ETHYL-5-METHYL-l,3-BIS(OXIRANYLMET
HYU -
CHEMICAL NAME: XU-238
15336-82-0
SUBMITTER: EXXON CHEMICAL AMERICAS
26472-00-4
26472-00-4
CHEMICAL NAME: 4,7-METHANO-IH-INDENE, 3A,4,7,7A-TETRAHYDRODIMETHYL-
C,EMICAL NAME: METHYlCYCLOPENTADIENE DIMER
-------
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CONT.)
8EHQ-1281-0420
CAS NUMBER:
SUBMITTER: EXXON CHEMICAL AMERICAS
CAS NUMBER:
CAS NUMBER:
UNKNOWN
68441-14-5
CHEMICAL NAME: PROPANE, DIBROMOCHLOROMETHYL-
CHEMICAL NAME: BROMOBUTYL 2244
68441-14-5
CHEMICAL NAME: 1,3-BUTADIENE, 2-METHYL-, POLYMER WITH 2-METHYL-1-PROPENE, B
ROMINATED
CHEMICAL NAME: RUBBER, BROMINATED BUTYL-
CAS NUMBER:
68441-14-5
8EHQ-1281-0421 S SUBMITTER: CONFIDENTIAL
CAS NUMBER: 98-51-1 CHEMICAL NAME: BENZENE, 1-(1,1-DIMETHYLETHYL)-4-METHYL-
CAS NUMBER: 98-51-1 CHEtUCAL NAME: TOLUENE, P-TERT-BUTYL-
CAS NUMBER: 939-97-9 CHEMICAL NAME: BENZALDEHYDE, P-TERT-BUTYL-
U1
I-' CAS NUMBER: 939-97-9 CHEMICAL NAME: BENZALDEHYDE, 4-(1,1-DIMETHYLETHYL)-
U1
8EHQ-1281-0422 SUBMITTER: ATLANTIC RICHfIELD COMPANY
CAS NUMBER: 8006-61-9 CHEMICAL NAME: GASOLINE, NATURAL
CAS NUMBER: 8006-61-9 CHEMICAL NAME: GASOLINE, UNLEADED
8EHQ-1281-0423 SUBMITTER: UNION CARBIDE CORPORATION
CAS NUMBER: UNKNOWN CHEf'1ICAL NAME: CARBON (FIBERS)
CAS NUMBER: UNKNOL.JN CHEf'1ICAL NAME: THORNEL MAT
CAS NUMBER: UNKNOWN CHEMICAL NAME: THORNEL TYPE P (HIGH MODULUS)
-------
8EHQ-1281-0424
CAS NUMBER:
CAS NUMBER:
BEnQ-1281-0425 S
CAS NU~1BER:
8EHQ-1281-0426
CAS NUMBER:
U1
f-'
~
8EHQ-0282-0427 S
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
8EHQ-0282-0428
CAS NUMBER:
8EHQ-0282-0429
CA S NUr1B ER:
8EHQ-0282-0430
CAS NUMBER:
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CONT.)
SUBMITTER: VELSICOL CHEMICAL CORPORATION
14047-09-7
21232-47-3
CHEMICAL NAME: BENZENE. 3.3'.4.4'-TETRACHLOROAZO-
CHEMICAL NAME: BENZENE. 3.3'.4.4'-TETRACHLOROAZOXY-
SUBMITTER: CONFIDENTIAL
CONFIDENT
CHEMICAL NAME: PHOSPHORODITHIOIC ACID. O.O'-DIALKYL ESTER. ANTIMONY SALT
SUBMITTER: CIBA-GEIGY CORPORATION
5026-74-4
CHEMICAL NAME: OXIRANEMETHANAMINE. N-[4-(OXIRANYLMETHOXY)PHENYLJ-N-(OXIRANY
U'lETHYU -
SUBMITTER: CONFIDENTIAL
UNKNOL.JN
2997-92-4
CHEMICAL NAME: V-50 DECOMPOSITION PRODUCT
CHEMICAL NAME: PROPANIMIDAMIDE. 2.2'-AZOBIS[2-METHYL-. DIHYDROCHLORIDE
2997-92-4
CHEMICAL NAME: V-50
*
SUBMITTER: BUFFALO COLOR CORPORATION
121-69-7
CHEMICAL NAME: BENZENAMINE. N.N-DIMETHYL-
*
SUBMITTER: BUFFALO COLOR CORPORATION
103-69-5
CHEMICAL NAME: BENZENAMINE. N-ETHYL-
*
SUBMITTER: BUFFALO COLOR CORPORATION
91-66-7
CHEMICAL NAME: BENZENAMINE. N.N-DIETHYL-
-------
8EHQ-0282-0431
CAS NUMBER:
CAS NUMBER:
8EHQ-0282-0432
CAS NUMBER:
8EHQ-0282-0433
CAS NUMBER:
U1
t--'
-...J
8EHQ-0282-0434
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
8EHQ-0282-0435
CAS NUMBER:
8EHQ-0282-0436
CAS NUMBER:
*
25134-21-8
25134-21-8
*
25377-73-5
*
108-30-5
81-88-9
81-88-9
81-88-9
81-83-9
1313-82-2
*
8004-87-3
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CONT.)
SUBMITTER: BUFFALO COLOR CORPORATION
CHEMICAL NAME: 4,7-METHANOISOBENZOFURAN-l,3-DIONE, 3A,4,7,7A-TETRAHYDROMETH
Yl-
CHEMICAL NAME: NADIC METHYL ANHYDRIDE
SUBMITTER: BUFFALO COLOR CORPORATION
CHEMICAL NAME: 2,5-FURANDIONE, 3-(DODECENYl)DIHYDRO-
SUBMITTER: BUFFALO COlOP CORPORATION
CHEMICAL NAME: 2,5-FURANDIONE, DIHYDRO-
SUBMITTER: SUN CHEMICAL CORPORATION
CHEMICAL NAME: C. I. BASIC VIOLET 10
CHEMICAL NAME: ETHANAMINIUM, N-[9-(2-CARBOXYPHENYl)-6-(DIETHYlAMINO)-3H-XAN
THEN-3-YLIDENEJ-N-ETHYL-, CHLORIDE
CHEMICAL NAME: D&C RED NO. 19
CHEMICAL NAME: RHODAMINE B
SUBMITTER: FMC CORPORATION
CHEMICAL NAME: SODIUM SULFIDE
SUBMITTER: BUFFALO COLOR CORPORATION
CHEMICAL NAME: C. I. BASIC VIOLET 1
-------
8EHQ-0282-0437
CAS NUMBER:
CAS NUr1BER:
8EHQ-0382-0438 S
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
lT1
f-'
00
CAS NUMBER:
CAS NUMBER:
8EHQ-0282-0439
CAS NUMBER:
CAS NUMBER:
8EHQ-0382-0440 S
CAS NUMBER:
CAS NUMBER:
8EHQ-0382-0441
CAS NUMBER:
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CONT.)
SUBMITTER: LEVER BROTHERS COMPANY (INCORPORATED)
6227-14-1
6227-14-1
CHEMICAL NAME: C. I. DIRECT VIOLET 9
CHEMICAL NAME: 2-NAPHTHALENESULFONIC ACID, 4-HYDROXY-3-[[2-METHOXY-5-METHYL
-4-[(4-SULFOPHENYL)AZOJPHENYLJAZOJ-7-(PHENYLAMINO)-, DISODIU
M SALT
SUBMITTER: CONFIDENTIAL
UNKNOWN CHEMICAL NAME: ACRYLIC ACID-STARCH GRAFT, PARTIAL SODIUM SALT
UNKNOWN CHEMICAL NAME: POLYACRYlIC ACID, PARTIAL ALUMINUM POTASSIUM SALT
UNKNOWN CHEMICAL NAME: POL YACRYl IC ACID, PARTIAL SODIUM SALT
9003-01-4 CHEMICAL NAME: POLYACRYLIC ACID
9003-01-4 CHEMICAL NAME: 2-PROPENOIC ACID, HOMOPOLYMER
SUBMITTER: DOW CHEMICAL COMPANY
75-56-9
75-56-9
CHEMICAL NAME: OXIRANE, METHYL-
CHEMICAL NAME: PROPYLENE OXIDE
SUBMITTER: SHELL OIL COMPANY
98-73-7 CHEMICAL NAME: BENZOIC ACID, P-TERT-BUTYl-
98-73-7 CHEMICAL NAME: BENZOIC ACID, 4-(1,1-DIMETHYLETHYL)-
SUBMITTER: DOW CHEMICAL COMPANY
106-99-0
CHEMICAL NAME: 1,3-BUTADIENE
-------
8EHQ-0482-0442
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
8EHQ-0482-0443
CAS NUMBER:
CAS NUMBER:
U1
I--'
\.D
8EHQ-0582-0444
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
8EHQ-0582-0445
CAS NUMBER:
8EHQ-0682-0446 S
CAS NUMBER:
CAS NUMBER:
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CONT.)
SUBMITTER: STEPAN CHEMICAL COMPANY
NONE CHEMICAL NAME: STEPAN AGENT 291-83
77-78-1 CHEMICAL HAr1E: SULFURIC ACID, DIMETHYL ESTER
3076-26-4 CHEMICAL NAME: OCTADECANOIC ACID, 2-SULFO-, I-METHYL ESTER
29454-23-7 CHEMICAL NAME: TETRADECANOIC ACID, 2-SULFO-, I-METHYL ES T ER
58849-75-5 CHEMICAL NAME: HEXADECANOIC ACID, 2-SULFO-, I-METHYL ESTER
SUBMITTER: CIBA-GEIGY CORPORATION
30947-30-9
30947-30-9
CHEMICAL NAME: IRGASTAB 2002
CHEMICAL NAME: PHOSPHONIC ACID, [[3,5-BIS(I,I-DIMETHYLETHYL)-4-HYDROXYPHENY
LJMETHYLJ-, MONO ETHYL ESTER, NICKEL(2+) SALT (2:1)
SUBMITTER: VELSICOL CHEMICAL CORPORATION
98-07-7 CHEMICAL NAME: BENZENE, (TRICHLOROMETHYL)-
98-87-3 CHEMICAL NAME: BENZENE, (DICHLOROMETHYL)-
98-88-4 CHEMICAL NAME: BENZOYL CHLORIDE
100-44-7 CHEMICAL NAME: BENZENE, (CHLOROMETHYL)-
SUBMITTER: SHERWIN-WILLIAMS COMPANY
UNKNOWN
CHEMICAL NAME: THIOXANTHEN-9-0NE, 2-DODECYL-9-H-
SUBMITTER: STANDARD OIL COMPANY (INDIANA)
64741-46-4
64741-55-5
CHEMICAL NAME: NAPHTHA (PETROLEUM), LIGHT STRAIGHT-RUN
CHEMICAL NAME: NAPHTHA (PETROLEUM), LIGHT CATALYTIC CRACKED
-------
8EHQ-0682-0446 S
CAS NUMBER:
8EHQ-0682-0447
CAS NUMBER:
8EHQ-0682-0448 S
CAS NUMBER:
8EHQ-0682-0449 S
CAS NUMBER:
Vl
N
a
CAS NUMBER:
8EHQ-0682-0450
CAS NUMBER:
8EHQ-0682-0451
CAS NUMBER:
8EHQ-0882-0452
CAS NUMBER:
8EHQ-0882-0453
CAS NUMBER:
CAS NUMBER:
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CONT.)
(CONT.)
SUBMITTER: STANDARD OIL COMPANY (INDIANA)
64741-64-6
CHEMICAL NAME: NAPHTHA (PETROLEUM), FUll-RANGE AlKYlATE
SUBMITTER: SUN REFINING AND MARKETING COMPANY
64741-52-2
CHEMICAL NAME: DISTIllATES (PETROLEUM), lIGHT NAPHTHEHIC
SUBMITTER: GAF CORPORATION
3445-11-2
CHEMICAL NAMt: 2-PYRROlIDINONE, 1-(2-HYDROXYETHYl)-
SUBMITTER: BUCKMAN lABORATORIES. INC.
111-44-4
123-91-1
CHEMICAL NAME: ETHANE, 1,1'-OXYBIS[2-CHlORO-
CHEMICAL HPME: 1.4-DIOXANE
SJBMITTER: TENNESSEE EASTMAN COMPANY
111-15- 9
CHEMICAL NAME: ETHANOL. 2-ETHOXY-. ACETATE
SUBMITTER: BORG-WARNER CHEMICALS. INC.
101-02-0
CHEMICAL NAME: PHOSPHOROUS ACID, TRIPHENYl ESTER
SUBMITTER: EASTMAN KODAK COMPANY
635-22-3
CHEMICAL NAME: BENZENAMINE, 4-CHlORO-3-NITRO-
SUBMITTER: UNION CARBIDE CORPORATION
75-21-8
75-21-8
CHEMICAL NAME: ETHYLENE OXIDE
CHEMICAL NAME: OXIRANE
-------
8EHQ-0882-0454
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CONT.)
SUBMITTER: CELANESE CORPORATION
3524-68-3
CHEMICAL NAME: 2-PROPENOIC ACID. 2-(HYDROXYMETHYL)-2-[[(1-0XO-2-PROPENYL)OX
YJMETHYLJ-1,3-PROPANEDIYL ESTER
CHEMICAL NAME: 2-PROPENOIC ACID, 2.2-BIS[[(1-0XO-2-PROPENYL)OXYJMETHYLJ-1,3
-PROPANEDIYL ESTER
4986-89-4
53417-29-1
CHEMICAL NAME: PENTAERYTHRITOL DIACRYLATE
8EHQ-0982-0455 SUBMITTER: CELANESE CORPORATION
CAS NUMBER: 2481-94-9 CHEMICAL NAME: BENZENAMINE, N,N-DIETHYL-4-(PHENYLAZO)-
CAS NUMBER: 2481-94-9 CHEMICAL NAME: OIL YELLOW El90
CAS NUMBER: 2481-94-9 CHEMICAL NAt'1E: C. 1. SOLVENT YELLOW 56
lJ1 CAS NUMBER: 6368-72-5 CHEMICAL NAME: 2-NAPHTHALENAMINE. N-ETHYL-1-[[4-(PHENYLAZO)PHENYLJAZOJ-
tV
f-' CAS NUMBER: 6368-72-5 CHEMICAL NAME: C. 1. SOLVENT RED 19
8EHQ-0982-0456 S
CAS NUMBER:
8EHQ-0982-0457
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
*
SUBMITTER: GULF REFINING AND MARKETING COMPANY
CHEMICAL NAME: GULF TS-905-HWCF
NONE
SUBMITTER: GENERAL ELECTRIC COMPANY
71-55-6 CHEMICAL NAME: ETHANE, l,l,l-TRICHLORO-
75-01-4 CHEMICAL NAME: ETHENE. CHLORO-
75-01-4 CHEmCAL NAME: VINYl CHLORIDE
79-01-6 CHEMICAL NAME: ETHENE, TRICHLORO-
79-01-6 CHEMICAL NAME: TRICHLOROETHYLENE
117-81-7
CHEMICAL NAME: l,2-BENZENEDICARBOXYLIC ACID, BIS(2-ETHYLHEXYL) ESTER
-------
8EHQ-0 982-0457
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
8EHQ-0982-0458
CAS NUMBER:
lJ1
N
N
8EHQ-I082-0459
CAS NUMBER:
8EHQ-I082-0460
CAS NUMBER:
CAS NUMBER:
8EHQ-I082-0461
CAS NUMBER:
8EHQ-1l82-0462
CAS NUMBER:
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CONT.)
(CONT.)
SUBMITTER: G=NERAL ELECTRIC COMPANY
156-60-5 CHEMICAL NAME: ETHENE, 1,2-DICHLORO-, (E)-
1336-36-3 CHEMICAL NAME: 1,1'-BIPHENYL, CHLORINATED
1336-36-3 CHEMICAL NM1E: POLYCHLORINATED BIPHENYLS (PCB)
12002-48-1 CHEMICAL NAME: BENZENE. TRICHLORO-
SUBMITTER: GREAT LAKES CHEMICAL CORPORATION
21850-44-2
CHEMICAL NAME: BENZENE, 1,1'-(1-METHYLETHYLIDENE)BIS[3,5-DIBROMO-4-(2,3-DIB
RO~1OPROPOXy)-
SUBMITTER: ATLANTIC RICHFIELD COMPANY
57472-68-1
CHEMICAL NAnE: 2-PROPENOIC ACID, OXYBIS(METHYL-2,1-ETHANEDIYL) ESTER
SUBMITTER: ATLANTIC RICHFIELD COMPANY
UNKNOWN
CHEMICAL NAME: 9-0CTADECENOIC ACID, (Z)-, 3-[(1-0XO-2-PROPENYL)OXYJ-2,2-BIS
[[(1-0XO-2-PROPENYL)OXYJMETHYLJPROPYL ESTER
CHEMICAL NAME: PENTAERYTHRITOL MONOOLEATE TRIACRYLATE
UNKNOWN
SUBMITTER: AIR PRODUCTS AND CHEMICALS, INC.
UNKNOWN
CHEMICAL NAME: BENZENEDIAMINECS), CHLORINATED, AR-METHYL-
SUBMITTER: EASTMAN KODAK COMPANY
619-80-7
CHEMICAL NAME: BENZAMIDE, 4-NITRO-
-------
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CONT.)
8EHQ-1l82-0463
CAS NUMBER:
SUBMITTER: DIAMOND SHAMROCK CORPORATION
CAS NUMBER:
10588-01-9
13765-19-0
CHEMICAL NAME: CHROMIC ACID, DISODIUM SALT
CHEMICAL NAME: CHROMIC ACID, CALCIUM SALT (1:1)
8EHQ-1l82-0464 SUBMITTER: VULCAN CHEMICALS
CAS NUMBER: 74-87-3 CHHlICAL NM1E: METHANE, CHLORO-
8EHQ-1l82-0465 SUBMITTER: CELANESE CORPORATION
CAS NUMBER: NONE CHEMICAL NAME: CALCO OIL BRONZE Y
CAS NUMBER: NONE CHEMICAL NM1E: CALCO OIL RED YM
V1
N
W
8EHQ-1l82-0466
1(
SUBMITTER: E. I. DUPONT DE NEMOURS & COMPANY, INC.
CAS NUMBER:
7782-5(-5
CHEMICAL NAME: CHLORINE
8EHQ-1282-0467
CAS NUMBER:
3UBMITTER: UNION CARBIDE CORPORATION
140-88-5
CHEMICAL NAME: 2-PROPENOIC ACID, ETHYL ESTER
* Based on a preliminary evaluation, EPA believes that the submitted information did not warrant reporting pursuant to
Section 8(e) of TSCA. In some cases, a submitting company was requested to provide the basis for its contention that
the reported information offered reasonable support for a conclusion of substantial risk of injury to health and/or
the environment as defined in EPA's ~arch 16, 1978, TSCA Section 8(e) policy statement (Appendix A of this volume).
-------
524
-------
50272'J 01
REPORT DOCUMENTATION 1.1,-REPORT NO.
PAGE EPA 56ill2-83-001
4. Title and Subtitle "PRELIMINARY EVALUATIONS OF INITIAL
TSCA SECTION 8(E) SUBSTANTIAL RISK NOTICES!!
(FEBRUARY 1, 1980 - DECEMBER 31, 1982)
12.
3. Recipient's Accession No.
5. Report Date
.
1983
6.
----
--_._-~-_.......-------~
7. Author(s)
8. Performine Oreanization Rept. No.
9. Performlne Oreanlution Name and Address
Office of Pesticides and Toxic Substances (TS-788)
U.S. Environmental Protection Agency (EPA)
401 "M" Street, S.W.
Washington, D.C.
20460
.10. Project/Task/Work Unit No.
U. Contract(C) or Grant(G) No.
(C)
(G)
U. Sponsoring Organization Name and Address
.13. Type of Report & Period Covered
02/01/80 to 12/31/82
------
.14.
15. Supplementary Notes
--
..----
--
----- - ---
--
-- ---<
-I&. Abstract (Limit: 200 words)
This volume contains, in ascending submission number order, "status reports" (i.e.,
preliminary evaluations) prepared by staff of the Office of Toxic Substances in the
Office of Pesticides and Toxic Substances for initial submissions received by EPA
from chemical manufacturers, processors, and distributors between February 1, 1980,
and December 31, 1982, pursuant to Section 8(e), the "substantial risk" information
reporting provision of. the Toxic Substances Control Act (TSCA, 90 Stat. 2029, 15
U.S.C. 2607). The status reports contained in this volume reflect only the initial
phases of EPA's evaluation process for the submitted information.
This TSCA Section 8(e) status report volume has been published by EPA for two reasons.
First, a volume of 8(e) statu~,reports will make the submitted information more
accessible. Second, this volume may, by providing specific examples of submitted
information and EPA's preliminary evaluation of that information, help those persons
subject to Section 8(e) of TSCA to understand better the types of information that
should be submitted.
17. Documant Analyeis a. Dascrlptors
Toxic Substances
TSCA
Substantial Risk
Section 8(e)
Control Act
Information
b. Identlfiers/0gen.Ended Terms
c. COSATI Field/Group
18. Availability Statement
.19. Security Class (This Report)
2.1. No. of Paees
525 pages_-
--
20. Security Class (This Paee)
22. Price
(See ANSI-Z39..18)
See Instructions on Reverse
525
OPTIONAL FORM 272 (4-77)
(Formerly NTIS-35)
Department of Commerce
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