f/EPA
United States
Environmental Protection
Agency
Office of Pesticides
and Toxic Substances
Washington DC 20460
March 1985
EPA 560/2-85-001
Toxic Substances
Preliminary Evaluations
of Initial TSCA
Section 8(e)
Substantial Risk Notices
February 1, 1983 - December 31,1984
-------
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)
-------
EPA 560/2-85-001
March 1985
PRELIMINARY EVALUATIONS OF INITIAL
TSCA SECTION 8(e) SUBSTANTIAL RISK NOTICES
JANUARY 1, 1983 TO DECEMBER 31, 1984
Office of Toxic Substances
Office of pesticides and Toxic Substances
Washington, D.C. 20460
-U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF PESTICIDES AND TOXIC SUBSTANCES
WASHINGTON, D.C. 20460
-------
Disclaimer
This volume has been reviewed by the Office of pesticides and
Toxic Substances (OPTS), U.S. Environmental Protection Agency,
and approved for publication. The status reports contained in
this volume present the Agency's preliminary evaluations of the
submitted information and do not represent final Agency policy
or intent with respect to the submissions or subject chemicals.
Mention of company names, trade names, or commercial products
does not constitute an Agency endorsement or recommendation for
or against use.
ii
-------
Foreward
This volume contains, in ascending submission number order,
"status reports" (i.e., preliminary evaluations) prepared by
staff of the Office of Toxic Substances (OTS) in the Office of
pesticides and Toxic Substances (OPTS) for initial submissions
received by EPA from chemical manufacturers, processors, and
distributors between January 1, 1983, and December 31, 1984,
pursuant to Section 8(e), the "substantial riskh information
reporting provision of the Toxic Substances Control Act (TSCA;
90 Stat. 2029, 15 U.S.C. 2607(e)). Status reports are prepared
by OTS for all initial TSCA Section 8(e) submissions and reflect
only part of the initial phase of the OTS evaluation process for
such information.
This volume is being distributed through the TSCA Assistance
Office (TAO) in OTS/OPTS. Persons wishing to obtain a copy of
this volume of Section 8(e) status reports should telephone TAO
(toll-free: 800-424-9065 or, in Washington, D.C.: 554-1404), or
write to:
TSCA Assistance Office (TS-799)
u.S. Environmental Protection Agency
401 "M" Street, S.W.
Washington, D.C. 20460
The Agency plans to print a limited number of copies of this
volume. After the Agency's supply is exhausted, copies can be
purchased through the National Technical Information Service
(NTIS), 5285 Port Royal Road, Springfield, virginia 22161.
Copies of the three previously published Section 8(e) status
report volumes (PB# 80-221609, PB# 81-145732 and PB #83-187815)
are currently available through NTIS.
The Agency welcomes the submission of additional information for,
or comments on, the evaluations presented in this volume. The
submission of unpublished information relating to biological or
environmental effects, production/importation volumes, use(s),
and worker, consumer, and environmental exposure to the subject
chemical substances and mixtures would be especially valuable.
Such information will be considered at subsequent steps in the
OTS chemical assessment process. The submission of additional
information for, or comments on, these evaluations should be
directed to:
Mr. Frank D. Kover, Chief
Chemical Screening Branch
Existing Chemical Assessment Division
Office of Toxic Substances/OPTS
U.S. Environmental Protection Agency
401 "M" Street, S.W.
Washington, D.C. 20460
(TS-778)
iii
-------
All TSCA,Secti?n 8(e) submissi?ns ~s 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
files are located at EPA H~adquarters (Room 107, East Tower),
401 "M" Street, S.W., Washington, D.C. Persons wishing to obtain
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 that information help
those persons subject to Section 8(e) to understand better the
types of information that should be submitted.
~~e ~ J. Merenda, Director
~' ting Chemical Assessment Division
fice of Toxic Substances/OPTS/EPA
iv
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Contents
Foreward [[[ i i i
Acknowledgment.............................................. vii
Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1
Status Reports 8EHQ-0183-0468 through 8EHQ-1284-0541 S
Appendix A.
Appendix B.
Appendix C.
Appendix D.
Appendix E.
5
"Statement of Interpretation and Enforcement
policy; Notification of Substantial Riskh
(43 FR 11110, March 16, 1978) .................. 260
Status Reports Listed by CAS Number ............ 268
Status Reports Listed by Chemical Name ......... 285
Status Reports Listed by Information Type ...... 306
-------
Acknowledgment
In preparing the status reports contained in this compendium,
EPA's Office of Toxic Substances (OTS) has frequently found it
necessary to request additional information about, or clarifi-
cation of, the submitted data. OTS appreciates the efforts and
cooperation of the following companies and organizations that
have submitted the information reflected in this volume:
3M COMPANY
AIR PRODUCTS AND CHEMICALS, INC.
ALLIED CORPORATION
AMERICAN CYANAMID COMPANY
ANGUS CHEMICAL COMPANY
CELANESE CORPORATION
CHEVRON CHEMICAL COMPANY
CHLORINATED PARAFFIN PRODUCERS TESTING CONSORTIUM
ClBA-GEIGY CORPORATION
DOW CHEMICAL COMPANY
E. I. DU PONT DE NEMOURS & COMPANY, INC.
EASTMAN KODAK COMPANY
EMHART CORPORATION
EXXON COMPANY, U.S.A.
FERRO CORPORATION
GENERAL MOTORS CORPORATION
GULF OIL PRODUCTS COMPANY
HALOGENATED SOLVENTS INDUSTRY ALLIANCE
IBM CORPORATION
INTERNATIONAL COAL REFINING COMPANY
LONZA INC.
MALLINCKRODT, INC.
NOR-AM CHEMICAL COMPANY
PHILLIPS PETROLEUM COMPANY
PPG INDUSTRIES, INC.
R.I\CON INC.
RIO BLANCO OIL SHALE COMPANY
ROHM N~D HAAS COMPANY
SHELL OIL COMPANY
STANDARD OIL COMPANY (INDIANA)
TENNESSEE EASTMAN COMPANY
UNION CARBIDE CORPORATION
VELSICOL CHEMICAL CORPORATION
VULC.I\N CHEMICALS
W. R. GRACE & CO.
WITCO CHEMICAL CORPORATION
vii
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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-implementing
(i.e., required no implementing rules), chemical manufacturers,
processors, and distributors became subject to the Section 8(e)
reporting provision as of January 1, 1977, the effective date of
TSCA. In order to clarify the types of information to be sub-
mitted and the procedures for doing so, EPA (following receipt
and review of public comments) published its March 16, 1978 TSCA
Section 8(e) policy statement ("Statement of Interpretation and
Enforcement policy; Notification of Substantial Risk" 43 FR
11110). For easy referral when using this volume, EPA's TSCA
Section 8(e) policy statement has been reproduced as Appendix A
in the back of this volume.
The March 16, 1978 TSCA Section 8(e) policy statement expresses
the Agency's policy that the information subject to Section 8(e)
reporting is any "new" information that "reasonably supports" a
conclusion that a chemical substance or mixture presents a sub-
stantial risk of injury to health or the environment but need not
necessarily 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" which is found in
other sections of the Act. Although EPA's receipt of information
under Section 8(e) of TSCA does not necessarily trigger immediate
regulatory action, the information which is submitted under TSCA
Section 8(e) does receive priority review and evaluation by EPA
in order to determine an appropriate course of Agency action.
Thus far, EPA and the chemical industry have devoted significant
efforts in fulfilling their respective responsibilities under
Section 8(e) of TSCA. Since January 1, 1977, over 540 initial
TSCA Section 8(e) notices covering a broad range of toxicity and
exposure-related information on a wide variety of chemicals have
been received and given priority evaluation and follow-up atten-
tion by the Office of Toxic Substances (OTS) in EPA's Office of
Pesticides and- TOxic-Substances (OPTS). In general, each initial
TSCA Section 8(e) submission is promptly reviewed and evaluated
by OTS scientific staff in order to determine both the degree of
1
-------
concern that should be attached to the submitted information and
the initial course of any warranted OTS follow-up action(s). A
"status report" is prepared which contains a brief description of
the submitted information, the results of the OTS preliminary
evaluation, a statement with respect to the production and use of
the subject chemical(s), and the recommendations for appropriate
follow-up actions. opon approval of the status report, recom-
mended follow-up actions are initiated. A letter containing the
status report and any Agency requests for additional information
is sent to the submitting company. In addition, copies of all
status reports are transmitted to the OPTS public files, other
designated EPA Program Offices and Federal Agencies, and to the
TSCA Assistance Office (TAO/OTS/OPTS) for further distribution.
Other OTS follow-up actions include the consideration of further,
more in-depth assessment of the reported chemical hazard or risk.
It should be noted also that the OTS immediately reviews, evalu-
ates, and initiates appropriate follow-up actions/activities for
all information 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 specifically requested by EPA.
A DOcument Control Number is used by EPA to identify TSCA Section
8(e) submissions and takes the following form: 8EHQ-OOOO-0000.
Starting at the left, the first four symbols identify the infor-
mation as a Section 8(e) submission received by EPA headquarters;
the next four digits identify the month and year (e.g., -0579-)
of the Agency's receipt of the information; the final four digits
identify the submission's chronological number. In addition to
the basic numerical sequence, additional characters may be added
to the right end of the Document Control Number to convey other
information. These additional characters and their meaning are
as follows:
S:
indicates that the TSCA Section 8(e) submission was
sanitized to delete information that was claimed by the
submitting company to be "TSCA Confidential Business
Information."
P:
indicates that the Section 8(e) submission contained
names or other identification (e.g., Social Security
Numbers) of individuals, the release of which may
violate the privacy Act (such documents are sanitized
to remove an individual's name or other identifiers).
* .
indicates that, based on a preliminary evaluation, the
submission was considered by EPA to be unwarranted for
reporting under Section 8(e) of TSCA.
2
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When reviewing the status reports contained in this volume, the
reader should realize that the purpose of the OTS preliminary
evaluation is to determine the significance of the submitted
information in terms of a need for possible follow-up action by
the Agency- This determination involves a critical analysis of
the submitted data to assess the extent that the reported hazard
or risk is supported by the provided information. The scope of
this initial evaluation, however, is generally limited to the c
submitted documents and to any closely related information known
by the OTS reviewer. Neither a literature search to identify
other reported effects nor an in-depth analysis of possible
sources of exposure to subject chemicals is part of the evalua-
tion process. Therefore, a status report should be v~ewed only
as a preliminary evaluation of the submitted information and not
as a comprehensive assessment of the chemical substance or mix-
ture for which a TSCA Section 8(e) notice has been filed.
3
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0183-0468
Page 1 of 3
CIA TE;
:::cn 2 8 !SQ,)
SUlnCTI St- t R t*
a us epor
8EHQ-0183-0468
App:oved
/1:- ~ J / 1 t:' J.
nOM'Justine L. welc~am Leader
Chemical selectton and Profiles
TO'Frank D. Kover, Chief
Chemical Hazard Identification
Revision
Needed
Team/CHIB
Branch/AD
Submission Descrip~ion
The Phillips Petroleum Company provided summarized final results
from several acute in vivo toxicity studies and final reports
from two in vitro mutagenicity assays of carbon black feedstock
(Residual-oil Solvent Extracts (Petroleum); CAS No. 64742-10-5).
According to the company, the carbon black feedstock displayed
mutagenic activity with exogenous metabolic activation in both
an Ames/Salmonella typhimurium (bacteria) Assay and a Mouse Lym-
phoma Forward Mutation Assay; without activation the carbon black
feedstock was reported to be negative in both assays. With re-
gard to the results of the acute in vivo carbon black feedstock
toxicity studies, Phillips reported that the oral (rat) LD50 was
in excess of 5 g/kg and the inhalation (rat) LC50 was in excess
of 49.3 parts per million. In addition, Phillips reported that
short-term inhalation (mice, head only) exposure to 46.3 ppm
vaporized carbon black feedstock did not result in upper respira-
tory tract irritation. Phillips also reported that no erythema,
edema, or other dermal effects were observed at either 24 or 72
hours following carbon black feedstock application to the clipped
abra ided or unabra ided sk i n of rabb i ts. (See note on pg. 3 of
this status report)
Submission Evaluation
A review of the submitted in vitro data shows that the subject
carbon black feedstock, when tested in the presence of exogenous
metabolic activation, induced increased mutation frequencies in
Salmonella typhimurium bacterial strains TA 98 and TA 1538. In
the absence of metabolic activation, although the carbon black
feedstock (at the highest dose tested) induced increased mutation
frequencies (i.e., 3X and 2.7X background for strains TA 98 and
TA 1538, respectively), the observed activity was considerably
less than that seen in the bacterial assay conducted in the
presence of metabolic activation. Although only summary final
data were submitted for the in vitro mouse lymphoma cell assay,
it is apparent that the feedstock was mutagenic only in the
.NOTE: This status recort is the result of a orelirnina:v
staff evaluation of information submitted to EPA. State;'ents
mace herein are not to be re~arded as exoressino final
Agency policy or intent with.res?ec~ to ~his ?a~ticular
chem~cal. .~y review 6f the status report should take into
7ons~der~tion the iact- that it may be based on incomplete
1nformat1on.
. -
5
E~A ro.... "'" .8ICY. ~,..
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8EHQ-0183-0468
Page 2 of 3
presence of metabolic activation. Overall, the submitted in
vitro mutagenicity results are not necessarily surprising in
light of the likely presence of various polynuclear aromatic
hydrocarbons (PAH) in the tested carbon black feedstock.
It can be inferred from the summarized acute in vivo toxicity
information that the tested carbon black feedstock does not
possess serious acute oral toxicity in that no animals died in
the 14 days following oral administration. With regard to the
results of the acute inhalation test in rats, however, it is not
clear if the carbon black feedstock vapor concentration of 49.3
ppm was 1) the maximum attainable concentration and 2) a measured
or nominal (i.e., estimated) vapor concentration. Although the
summary results of the mouse head-only inhalation exposure study
indicate that the tested carbon black feedstock is not an acute
upper respiratory tract irritant, there was no rationale given
for the dose selected (46.3 ppm) and no indication of whether
this concentration was monitored or nominal. In addition, there
was no information presented that pertained to the appearance of
the eyes or the incidence or duration of eye closure in the mice
in the acute head-only inhalation exposure test. with regard to
the reported acute rabbit dermal irritation results, although it
appears that the carbon black feedstock is not a primary skin
irritant, it should be noted that long-term or repeated dermal
exposure to the feedstock could result in dissolution and removal
of oils that are normally present in the skin. Chronic dermal
(or other) exposure to petroleum products containing PAH (some of
which are known to possess mutagenic and/or oncogenic activity)
would also be of concern. Finally, the inhalation of mists or
aspiration of liquid hydrocarbons that might accompany their
ingestion and/or regurgitation could result in a chemical pneumo-
nitis. Considering this and the reported lack of toxicity by
gavage, the company's Material Safety Data Sheet (MSDS) recom-
mendation that vomiting not be induced following accidental
ingestion appears pruden~
Current Production and Use
The tested carbon black feedstock (Residual Oil Solvent Extracts
(Petroleum); CAS No. 64742-10-5) is defined by the TSCA Chemical
Substances Inventory as "a complex combination of hydrocarbons
obtained as the extract from a solvent extraction process. It
consists of aromatic hydrocarbons having carbon numbers predom-
inantly higher than C25."
A review of the production range (includes importation volumes)
statistics for carbon black feedstock (CAS No. 64742-10-5), which
is listed in the initial TSCA Inventory, has shown that over 2.65
billion pounds were reported as produced/imported in 1977. This
production range information does not include any production/im-
portation data claimed as confidential by the person(s) reporting
for the TSCA Inventory, nor does it include any information that
6
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8EHQ-0183-0468
Page 3 of 3
would compromise Confidential Business Information (CBI). The
data submitted for the TSCA Inventory, including production range
information, are subject to the limitations contained in the TSCA
Inventory Reporting Regulations (40 CFR 710).
Phillips reported that the company does not market carbon black
feedstock but either burns the material to produce carbon black
or recycles the material back into petroleum refinery streams for
further processing. In addition, the company reported that the
potential for human exposure to carbon black feedstock is minimal
because the feedstock is produced, transported, and consumed in
enclosed systems.
Comments/Recommendations
In its submission, the Phillips Petroleum Company stated that
based on the submitted test data and the company's knowledge that
the carbon black feedstock contains polynuclear aromatic hydro-
carbons (PAH), Phillips has classified the feedstock as an
indirect-acting mutagen. In addition, Phillips stated that al-
though there is no history of adverse health effects among its
employees, the company had revised (and submitted) its carbon
black feedstock Material Safety Data Sheet (MSDS) to reflect the
submitted information and believes that adherence to the recom-
mended precautions will prevent adverse health effects among
those people working with the material. Phillips also reported
that the results of a [lanned in vitro Sister Chromatid Exchange
(SCE) assay of carbon black feedstock will be submitted to EPA
upon receipt of those results by the company.
EPA has received and evaluated many TSCA Section 8(e) and "For
Your Information (FYI)" submissions containing toxicologic and/or
exposure information on many petroleum refinery process streams,
carbon black, and certain chemical substances (including PAH) as-
sociated with petroleum refinery streams and carbon black and/or
its production. In addition, the Chemical Hazard Identification
Branch has prepared a Chemical Hazard Information Profile (CHIP)
on carbon black.
a) The submitted information on carbon black feedstock will
be screened by the Chemical Hazard Identification Branch
(CHIB/AD/EPA) in order to determine the need for further
OTS assessment.
b) The Chemical Hazard Identification Branch will transmit
copies of this status report to NIOSH, OSHA, CPSC, FDA,
OW/EPA, OSWER/EPA, OANR/EPA and ORD/EPA. Copies of this
status report will also be sent to the Industry Assistance
Office (IAO/OTS/EPA) and the Office of Toxics Integration
OTI/OPTS/EPA) for appropriate distribution.
NOTE: On April 7, 1983 (8EHQ-0483-0468 Supplement), Phillips
notified EPA that the tested carbon feedstock was a mixture of
light, intermediate, and heavy catalytic cracked petroleum dis-
tillates (CAS No.'s: 64741-59-9, 64741-60-2, and 64741-61-3,
respectively) and not residual oil solvent.petroleum extracts
(CAS No. 64742-10-5) as reported in the initial submission.
7
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UNITED STATES ENV IRONMENT AL PROTECTION AGENCY
8EHQ-0283-0469 S
Page 1 of 2
DATE:
- .-,~ ? 8 In~~
SUaJICT.
Status Report*
8EHQ-0283-0469 S
Approved
, ~1ft- 7/{/ ~!J
l- I
'10M.
Justine L. Welc~eam Leader
Chemical select1~n and Profiles Team/CHIB
Frank D. Kover, Chief
Chemical Hazard Identification Branch/AD
Revision
Needed
TO.
Submission Description
(NOTE: The submitting company has claimed its identity and the
identities of the subject chemical products to be Confidential
Business Information (TSCA CBI)).
The submitting company provided summary results from a lifetime
mouse skin-painting study (conducted by the National Institute
for Occupational Safety and Health (NIOSH)) involving eleven (11)
undiluted metalworking fluid products. The submitting company
reported that two of the tested metalworking fluid products were
found to be oncogenic to the mouse liver in that higher than
chance scores were obtained when the liver data was subjected to
two different types of statistical analyses (Chi Square and
Fisher Exact Tests). The submitter identified one of the two
products as a nitrite/amine synthetic fluid containing a high
level of nitrosodiethanolamine (NDELAj CAS No. 1116-54-7)j the
other product was identified as a non-nitrite synthetic fluid
containing no detectable nitrosamines. In addition, the company
reported that "none of the other nitrite/amine products in the
test gave positive results."
With regard to the observed oncogenic activity, the submitting
company stated that:
"It is important to emphasize that these products were tested
in the concentrated form. In normal practice, they would be
diluted with water before use and human exposure would be
limited to the diluted form only- The nitrite/amine product
is recommended for use at a dilution of 1 part of concentrate
to 180 parts of water. The non-nitrite product is normally
diluted with 20 to 50 parts of water, depending on the
application. since the effect of exposure to the concen-
trated products was on~y suggestive, it would be expected
that exposure to the diluted product would not involve a
significant risk."
*NOTE: T~is status reoort is the result of a oreliminarv
staff evaluation of ir.formation submitted to EPA. Sta~e;e~ts
mace herein are no~ to be re~arded as ex~ressino final
Agency policy or intent with~res?ec~ to t~is particular
chem~cal. .~y review 6f the status report should take into
cons~deration the fact that it may be based on incomplete
information.
. -
8
I:~A '0'''' 11:0-4 I"'EV. "'"
-------
8EHQ-0283-0469 S
Page 2 of 2
Submission Evaluation
In addition ~o the observed oncogenic activity of a nitrite/amine
synthetic ~etalworking fluid containing a high level of NDELA (a
demonstrated animal carcinogen), it is of interest that a non-
nitrite synthetic metalworking fluid containing no detectable
level of nitrosamines also displayed oncogenic activity. EPA
should obtain a copy of the actual study report directly from
NIOSH in order to more properly evaluate the reported findings.
Current Production and Use
Metalworking fluids (also known as cutting/grinding fluids) are
applied to cutting tools to aid in machine operation by serving
as lubricants and/or coolants and by washing away metal chips.
Comments/Recommendations
EPA has received and evaluated several TSCA section 8(e) and "For
Your Information (FYI)" submissions concerning cutting fluids
and/or various nitrosamines. In addition, the Chemical Hazard
Identification Branch (CHIB/AD/OTS) has prepared Chemical Hazard
Information Profiles (CHIPs) on cutting fluids and certain N-
nitroso compounds, including nitrosodiethanolamine (NDELA). The
OTS "Existing Chemicals Task Force (ECTF)" is currently reviewing
toxicity and exposure information on cutting fluids.
a)
The Chemical Hazard Identification Branch has requested
the National Insitute for Occupational Safety and Health
to provide EPA with a complete copy of the final report,
including test protocol(s) and data, from the subject
lifetime skin-painting study of eleven (11) metalworking
fluid products.
b)
The Chemical Hazard Identification Branch will transmit
copies of this status report to NIOSH, OSHA, CPSC, FDA,
OW/EPA, OSWER/EPA, ORD/EPA, OANR/EPA, and to the OTS
"Existing Chemicals Task Force (ECTF)." Copies of this
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.
9
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0283-0470
Page 1 of 3
DAn:
;~AR
8 1983
SUIJEC:T, Status Report*
8EHQ-0283-0470
Approved
7f/;i- 1ft
'--- .
'.~,Justine L. wel~vvfeam Leader
Chemical Sele~on and Profiles
Revision
Needed
Team/CHIB
TO, Frank D. Kover, Chief
Chemical Hazard Identification Branch/AD
Submission Description
The Angus Chemical Company submitted complete copies of the final
reports, including test protocols and data, from two in vitro ge-
netic toxicity screening assays of 4,4-dimethyl-l,3-oxazolidine
(CAS No. 51200-87-4). According to the submitted information,
4,4-dimethyl-l,3-oxazolidine caused a significant dose-dependent
increase in the chromosomal aberration frequency in cultured
Chinese Hamster Ovary (CHO) cells both in the presence and ab-
sence of exogenous metabolic activation. In addition, the sub-
ject chemical was reported to cause a dose-dependent mutagenic
response both in the absence and presence of metabolic activation
in cultured Mouse Lymphoma L5l78Y TK+/- cells.
Submission Evaluation
The submitted data show that 4,4-dimethyl-l,3-oxazolidine induced
a dose-related increase in chromosomal aberrations in CHO cells
when tested both with and without metabolic activation. Although
metabolic activation reduced cellular toxicity, it had no effect
upon the chemical's ability to induce chromosomal aberrations.
Both in the presence and absence of activation, the highest dose
tested increased the number of aberrations per cell approximately
5X over that seen in the untreated control culture. In addition,
the highest dose tested was as active as the positive control
chemical for that particular assay (i.e., 0.11 ul/ml test agent
was as active as 0.5 ug/ml triethylenemelamine in the assay with-
out activation and 0.28 ul/ml test agent was as active as 35
ug/ml cyclophosphamide in the assay with activation).
The submitted data also show that 4,4-dimethyl-l,3-oxazolidine
induced a dose-related increase in the number of TK locus muta-
tions in a population of cultured mouse lymphoma L5l78Y cells.
Without metabolic activation, an increase in mutation frequency
*NOTE: T~is status recort is the result of a crelimina:v
staff evaluation of ir.formation subrnitt~ci to EPA. State;e~t5
mace herein are no~ to be re~arded as eXDressina final
Ase~cy policy or intent with.res?ec~ to this particular
chemical. .~y review of the status repor~ should take into
consideration the tact that it mav be based on incomolete
. - ....
~ntorrnation.
10
£~& '0"111 u:o-. UII:V. ~,.,
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8EHQ-0283-0470
Page 2 of 3
ranging from 2X to 18X that of the untreated control cultures was
observed at test material concentrations of 0.010 ul/ml to 0.032
ul/ml. When tested with activation, concentrations of 0.075 ul/-
ml and 0.10 ul/ml induced mutation frequencies of about 3X to 4X
over that seen in the untreated control cultures. The metabolic
activation also reduced both cellular toxicity and mutagenic po-
tency. In the presence and absence of activation, the highest
dose tested was approximately as active as the positive control
compound (i.e., 0.032 ul/ml of test agent was approximately as
active as 0.5 ul ethyl methanesulfonate in the assay without met-
abolic activation and 0.1 ul/ml was approximately as active as 5
ug/ml 7,12-dimethyl-benzanthracene in the assay with activation).
Current Production and Use
A review of the production range (includes importation volumes)
statistics for 4,4-dimethyl-l,3-oxazolidine (CAS No. 51200-87-4),
which is listed in the initial TSCA Inventory, has shown that no
1977 production/importation was reported or that all of the pro-
duction 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 Toxic Substances Control Act, 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).
Although the Angus Chemical Company's submission did not contain
any information pertaining to the use(s) of 4,4-dimethyl-l,3-
oxazolidine, the chemical is listed in the Third Edition (1982)
of the Cosmetics, Toiletries, and Fragrances Association (CTFA)
Cosmetics Ingredient Dictionary. No further information on the
use(s) of the subject chemical was located in the secondary
literature sources consulted.
Comments/Recommendations
It should be noted that although a positive in vitro result, when
considered alone, may not be sufficient to offer reasonable sup-
port for a conclusion of substantial risk, EPA does believe that
in vitro studies provide valuable data that can aid in assessing
possible risks posed by chemicals to health and/or the environ-
ment. EPA also believes that positive in vitro test results in
combination with additional information~e.g., knowledge of po-
tential 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 tests
considered for possible submission pursuant to TSCA Section 8(e).
a) Considering the Agency's general interest in those company
actions that are taken on a voluntary basis in response to
chemical toxicity/exposure information, the Chemical Haz-
ard Identification Branch (CHIB/AD/EPA) will request the
11
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8EHQ-0283-0470
Page 3 of 3
Angus Chemical Company to describe the voluntary actions
it has taken in response to the submitted genotoxic data
to warn workers and others and to reduce or eliminate ex-
posure to 4,4-dimethyl-l,3-oxazolidine. The company will
also be asked if it is conducting, or plans to conduct~
further studies designed to better define the toxicity of
the subject chemical. In addition, the Angus Chemical
Company will be informed that EPA would welcome the sub-
mission of information pertaining to current production/-
importation volumes, use(s), and worker, consumer, and
environmental exposure to 4,4-dimethyl-l,3-oxazolidine.
b) The Chemical Hazard Identification Branch will screen the
submitted information on 4,4-dimethyl-l,3-oxazolidine in
order to determine if further OTS assessment is warranted.
c) The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, CPSC, FDA, NTP,
OW/EPA, OSWER/EPA, and ORD/EPA. In addition, copies will
be sent to the Industry Assistance Office (IAO/OTS/EPA)
and the Office of Toxics Integration (OTI/OPTS/EPA) for
appropriate distribution.
12
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Page 1 of 5
DATE;
APR
4 1983
SUa.lECT1Sta tus Report * 8EHQ-028 3-0 4 71 Sand
8EHQ-0383-0471 Supplement
'I~ustine L. we~eam Leader
Chemical selec6fon and Profiles Team/CHIB
To.Frank D. Kover, Chief
Chemical Hazard Identification Branch/AD
Approved
uPC01~
Revision
Needed
Submission Description
In its initial submission, the Ferro Corporation notified EPA
that the company had been recently informed by certain customers
that several incidents of contact dermatitis had occurred among
workers exposed to metalworking chemicals and products including
Ferro's industrial lubricant additive. product, Klarus 1717. In
addition, the submitter reported that Klarus 1717 (major chemical
component reported to be bis(2-chlorooctyl) disulfide; CAS No.
70776-26-0) had recently been found to exhibit "moderate to ex-
treme potential to produce dermal sensitization in the guinea
pig." In the initial submission, the Ferro Corporation also pro-
vided the summarized final results from several other acute in
vivo toxicity and two in vitrb genotoxicity tests of Klarus 1717
With regard to the reported incidents of contact dermatitis among
metalworkers using lubricating fluids containing Klarus 1717, the
Ferro Corporation stated that an informal investigation initially
showed that "in each case, the worker involved used kerosene to
wash parts and came into contact with the kerosene" and "other
workers at the same sites who came into contact with lubricants
containing Klarus 1717, but who did not come into contact with
kerosene, did not develop any reported cases of contact derma-
titis." In its supplemental submission, however, Ferro stated
that further investigation indicated that "not every case of
dermatitis alleged to be connected with metalworking fluids con-
taining Klarus 1717 also involved exposure to kerosene." In
addition, the submitter reported that "while it appears that all
cases involved exposure to both a Klarus-containing fluid and a
solvent degreaser, in some cases the solvent degreaser was 1,1,1-
trichloroethane, in some it was stoddard solvent, and in some
(most) cases it was kerosene."
With regard to the acute in vivo toxicity of Klarus 1717, the
Ferro Corporation reportedin the i ni t ial submiss ion tha t KIa rus
1717 was found to have an acute oral (rat) LD50 greater than 5.0
g/kg and an acute dermal (rabbit) LD50 greater than 2.0 g/kg.
*NOTE: This status reco=t is the result of a creliminarv
staff evaluation of ir.formation submitted to EPA. Sta~e;ents
mace herein are not to be reaarded as ex~ressina 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 mav be based on incompleta
information. .
13
I:~' '0- 18:1)04 .REV. ..".
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8EHQ-0283-0471 S
8EHQ-0383-047l Supplement
Page 2 of 5
In addition, the submitter reported that Klarus 1717 "produced
generally mild irritation persisting for seven days to the eyes
of all animals [rabbits] and mild transient corneal opacity
observed after fluorescein staining in the eyes of two of nine
New Zealand white rabbits." With regard to the performed in
vitro studies, it was reported that Klarus 1717 was non-mutagenic
in Ames Salmonella typhimurium (bacteria) assays conducted in the
presence and absence of exogenous metabolic activation. In a
Saccharomyces cerevisiae (yeast) Mitotic Gene Conversion Assay,
Klarus 1717 was reported to be mutagenic in the absence of exog-
enous metabolic activation and caused increased numbers of ~
cerevisiae mutants in the presence of metabolic activation. Ac-
cording to the submitter, not all of the criteria for a positive
test were met in the yeast assay conducted in the presence of
metabolic activation.
Submission Evaluation
Based on the provided information, Klarus 1717 does appear to
have only slight oral and dermal medium lethality. There was no
indication in the submission that an acute inhalation LC50 study
was performed on the product. Although the product was not found
to be a severe eye irritant, in terms of irreversible eye tissue
damage, it did cause (reversible) corneal opacity and effects
persisted for seven (7) days. Such observations suggest that the
eye irritancy of Klarus 1717 is not trivial.
Dernlatitis (skin inflammation) can be the result of, among other
things, the repeated defatting of the skin by frequent dermal
contact with various chemicals. Dermal exposure to kerosene
and/or other solvents probably plays more of a role in additive
defatting (thereby facilitating absorption of other chemicals
through the skin) than in the actual induction of sensitization
reactions (e.g., contact dermatitis).
Contact dermatitis is a delayed type of induced allergy of the
skin with varying degrees of redness, swelling, and blistering
resulting from dermal contact with a specific antigen. Chemical
substances and/or their metabolites can be antigenic on the basis
of their molecular structure and can also combine with endogenous
proteins in the body to form antigenic complexes. Allergic reac-
tions are of concern because they 1) can be evoked in response to
a small amount of antigen, 2) can be manifested at or around the
site of exposure and/or away from the site of exposure, 3) can
range in intensity from mild to severe, and 4) can be evoked upon
exposure to other antigens (cross-reactivity). In some cases,
allergic reactions-can be life-threatening should they involve
symptoms such as swelling in the tissues of the respiratory
tract. In the absence of specific evidence (e.g., bronchial
constriction), however, there is no basis to conclude that a sub-
stance that can induce dermal sensitization will also induce
asthmatic or anaphylactic-type sensitization reactions.
14
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8EHQ-0283-0471 S
8EHQ-0383-047l Supplement
Page 3 of 5
Integumentary (skin) hazard is judged by at least four criteria:
1) degree or intensity of effect, 2) reversibility of effect, 3)
duration of effect, and 4) incidence of the observed effect among
those exposed. Intensity would include the continuum from no
effect through redness and edema to corrosion and scarring to,
ultimately, lethality. The classification of dermal sensitizers
is based upon incidence rather than intensity in that a "potent"
dermal sensitizer will affect a substantial fraction (though not
necessarily a majority) of those exposed, although the individual
reactions may range from relatively mild to severe. It should be
noted that dermatitis is not necessarily a sensitization reaction
as it is possible to find both responses in the same individual
at the same time. It should also be noted that irritation, which
usually occurs early following exposure to an irritant, can be
prolonged and may in some cases seem to have a latent period.
Dermal sensitization reactions, on the other hand, may not
develop until several days have elapsed since exposure to the
causative agent(s); asthmatic or anaphylactic-type sensitization
reactions can occur promptly (usually within an hour or two
following exposure). There is, therefore, some overlap in time
of onset between the effects of sensitizers having an early onset
and irritants having a late onset. This overlap may, in some
cases, hinder the diagnosis of dermal ailments and attempts to
determine their causative agent(s).
In view of the above discussion, and considering 1) the labora-
tory evidence that Klarus 1717 exhibited "moderate to extreme
potential to produce dermal sentization in guinea pigs," 2) the
fact that certain metalworkers are exposed to Klarus 1717, and 3)
the preliminary evidence that the reported incidents of contact
dermatitis occurred among workers exposed to Klarus 1717 and
other metalworking chemicals, the possibility that Klarus 1717
may be the (or one of the) causative agent(s) should be investi-
gated further. Such an investigation is now being conducted by
the Ferro Corporation.
In order for EPA to evaluate more properly the reported toxicity
information, the Ferro Corporation should be requested to provide
a complete copy of the final report (including test protocol(s)
and data) from each of the in vitro and in vivo studies cited in
--
the company's initial submission.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for bis(2-chlorooctyl) disulfide (CAS No. 70776-26-0),
which is listed in the initial TSCA Inventory, has shown that be-
tween 100 thousand and 1 million pounds of the subject chemical
were reported as produced and/or imported in 1977. This produc-
tion range information does not include any production/importa-
tion data claimed as confidential by the person(s) reporting for
the TSCA Inventory, nor does it include any information that
would compromise Confidential Business Information. The data
15
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8EHQ-0283-047l S
8EHQ-0383-047l Supplement
Page 4 of 5
submitted for the TSCA Inventory, including production range
information, are subject to the limitations contained in the
Inventory Reporting Regulations (40 CFR 710).
In general, metalworking fluids (also known as cutting/grinding
fluids) are applied to cutting tools to aid in machine operation
by serving as lubricants and/or coolants and by washing away
metal chips. Although the Ferro Corporation reported that bis(2-
chlorooctyl) disulfide was the major component of Klarus 1717,
the submitter did not provide any information concerning the
identity and amount of the other chemical constituent(s) of
subject lubricant additive product.
Comments/Recomnendations
In its supplemental submission, the Ferro Corporation stated that
the company is in the process of transmitting copies of the sub-
mitted information to each Klarus 1717 customer and to persons
who have received research samples of the product. In addition,
the submitter stated that an investigation of the reported inci-
dents of contact dermatitis is continuing and that EPA will be
advised of any significant conclusions that are reached.
With regard to in vitro genotoxicity studies, EPA believes that
such studies provide valuable data that can aid in assessing pos-
sible hazards/risks posed by chemical substances or mixtures to
health and/or the environment. In addition,. EPA believes that
positive in vitro test results in combination with additional
information (e.g., knowledge of high production/importation of
and/or potential for exposure to the chemical substance or mix-
ture) would, in many cases, suggest the need for further more
definitive toxicologic study with the results of such testing
considered for possible submission to EPA pursuant to Section
8(e) of TSCA.
EPA's Office of Toxic Substances (OTS) has received and evaluated
several TSCA Section 8(e) and "For Your Information (FYI)" sub-
missions concerning the toxicity of and/or exposure to cutting
fluids, kerosene, stoddard solvent, and l,l,l-trichloroethane.
In~addition, the Chemical Hazard Identification Branch (CHIB/AD/-
OT~) has prepared a Chemical Hazard Information Profile (CHIP) on
cutting fluids. At present, the OTS "Existing Chemicals Task
Force (ECTF)" is reviewing toxicity and exposure data on cutting
fluids and the Test Rules Development Branch (TRDB/AD/OTS) is
reviewing toxicity and exposure data on l,l,l-trichloroethane.
a)
The Chemical Hazard Identification Branch will request
the Ferro Corporation to provide information pertaining
to the exact identity and amount of each chemical con-
stituent (including known contaminants) of Klarus 1717.
In view of EPA's general interest in voluntary corporate
actions taken in response to chemical toxicity/exposure
information, the Ferro Corporation will be asked if it is
-------
8EHQ-0283-047l S
8EHQ-0383-047l Supplement
Page 5 of 5
conducting, or plans to conduct, any further laboratory
studies (e.g., mammalian cell genotoxicity) designed to
define better the tox~city of Klarus 1717 and/or~the
chemical components of~Klarus 1717.
b)
The Chemical Hazard Identification Branch will transmit
copies of this status report to NIOSH, OSHA, CPSC, NTP,
OW/EPA, OSWER/EPA, OANR/EPA, ORD/EPA, TRDB/AD/EPA, and
the "Existing Chemicals Task Force (ECTF)." In addition,
copies of this status-report will be provided to the
Industry Assistance Office (IAO/OTS/EPA) and the Office
of Toxics Integration (OTI/OPTS/EPA) for appropriate
distribution.
17
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
SUIJICTI Sta tus Report *
8EHQ-0283-0472 S
8EHQ-0283-0472 S
Page 1 of 3
APp:oved71?c- 7i jr:J
1)1. Tt;
FEB 2 8 \983
-'
fa 0161
Justine L. weld} ~am Leader
Chemical select~n and Profiles Team/CHIB
Revision
Needed
T~ Frank D. Kover, Chief
Chemical Hazard Identification Branch/AD
Submission Description
(See NOI'E on Page 3 of this status report)
The submitting company (company name claimed as Confidential Bus-
iness Information (CBI)) provided summarized preliminary results
from a lifetime mouse skin-painting study of heavy catalytic re-
formed petroleum naphtha (CAS No. 64741-68-0) both alone and ad-
mixed 3:1 with kerosene (CAS No. 8008-20-6). According to the
submitter, fifty (50) microliters of the materials were applied
directly to the skin of the back of fifty (50) male mice, two (2)
times per week for the lifetime of the mice.
With regard to those mice treated with heavy catalytic reformed
naphtha alone, the submitter reported that:
"Two mice developed one tissue mass each at the application
site, with a mean latency period of 67.5 weeks. Histopath-
ology examinations of these masses has not yet been done.
Masses not located at the site of application occurred in 28
animals. These are not considered to be treatment related as
such masses occurred in 41 and 45 animals in the 2 control
groups which were run with the study."
For those mice treated with the 3:1 heavy catalytic reformed
naphtha/kerosene mixture, the submitter reported that:
"Five mice developed one mass each at the site of applica-
tion, with a mean latency period of 95.8 weeks. Based on
gross observations, [the performing laboratory] reports two
benign tumors and three advanced tumors. Histopathology for
these masses is not yet completed and therefore it is not
known whether malignant tumors were present."
with regard to the reported preliminary results, the submitting
company stated that "although the long latency period and the
small number of tumors indicates that the [tested materials] are
weak animal carcinogens," the company believes that the materials
"are not likely to present a carcinogenic risk to employees or
-NOTE: This status reco~t is the result of a prelimina~v
staff evaluation of ir.forrnation submitted to EPA. State;e~ts
mace herein are not to be re~arded as ex~ressino final
Agency policy or intent withdrespect to t~is particular
chem~cal. .~y review of the status repo~~ should tak~ into
cons~deration the fact that it ffi3V be based on incomoletG
informationo .. ~
18
r~A '0"1:1 IJ~ '''CY. ..,.,
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8EHQ-0283-0472 S
Page 2 of 3
users." The submitter also stated that due to the fact that the
tested materials are "skin irritants causing dryness and dermati-
tis upon prolonged exposure, both employees and customers avoid
skin contact to prevent these acute effects." Finally, the sub-
mitter reported that prolonged skin contact to the materials is
not a normal occurrence in that exposure in the workplace is
"minimized by standard industrial hygiene control measures and
good work practices."
Submission Evaluation
(See NOTE on Page 3 of this status report)
Although the submitted preliminary information suggests that the
heavy catalytic reformed petroleum naphtha when tested alone or
admixed 3:1 with kerosene does possess some degree of oncogenic
activity toward mouse skin, this observation is clouded by the
apparent 80% and 90% incidences of non-application site masses
(tumors?) reportedly found in the two control groups. It would
not be surprising, however, that the tested material is oncogenic
in light of the likely presence of polynuclear aromatic hydro-
carbons. A complete copy of the final report from this study
should be obtained in order for the Agency to evaluate more
properly the reported toxicologic findings.
Current Production and Use
(See NOI'E on Page 3 of this status report)
According to the TSCA Chemical Substances Inventory, heavy cata-
lytic reformed petroleum naphtha (CAS No. 64741-68-0) is defined
as a "complex combination of hydrocarbons produced from the dis-
tillation of products from a catalytic reforming process. It
consists of predominantly aromatic hydrocarbons having carbon
numbers predominantly in the range of C7 through C12 and boiling
in the range of approximately 90°C to 230°C (194°F to 446°F)."
A review of the production range (includes importation volumes)
statistics for heavy catalytic reformed petroleum naphtha (CAS
No. 64741-68-0), which is listed in the initial TSCA Inventory,
has shown that over 60 billion pounds were reported as produced/-
imported in 1977. **/
**/ 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 WGuld 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).
lq
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8EHQ-0283-0472 S
Page 3 of 3
comments/Recorrimend~t ions 0
EPA's Office of Toxic Substances (OTS) has received and evaluated
many TSCA Section 8(e) and "For Your Information (FYI)" submis-
sions ~ertaining to the toxisologic properties of and/or exposure
to various petroleum refinery, process streams.
NOTE:
a)
The Chemical Hazard Identification Branch (CHIB/AD) will
request the submitter to provide, when available, a com-
plete copy of the final report (including protocol(s) -
and histopathology data) from the subject lifetime mouse
skin-painting study of heavy catalytic reformed naphtha~
b)
The Chemical Hazard Identification Branch will screen
the reported information to determine if further OTS
assessment of heavy catalytic reformed petroleum naphtha
is warranted.
c)
The Chemical Hazard Identification Branch will transmit
a copy of this status report to NIOSH, OSHA, CPSC, DOE,
OW/EPA, OSWER/EPA, OANR/EPA, ORD/EPA, and to the EPA's
"Alternate Fuels Workgroup." A copy of this status
report will also be provided to the Office of Toxics
Integration (OTI/OPTS/E,PA) and to the Industry Assis-
tance Office (IAO/OTS/EPA) for appropriate distribution.
In a supplemental submission dated January 30, 1985,
(8EHQ-0285-0472 S Supplement), the submitting company
reported that the test material that was identified in
the initial Section 8(e) submission as a heavy catalytic
reformed petroleum naphtha (CAS No. 64741-68-0) could be
more accurately described as a low-boiling catalytic
reformer fractionator residue petroleum distillate (CAS
No. 68477-31-6).
A review of the production range (includes importation
volumes) statistics for CAS No. 68477-31-6, which- is
listed in the initial TSCA Inventory, has shown that
between 10 thousand and 100 thousand pounds of this
material were reported as produced/imported in 1977.
This production range information does not include any
production or importation data that were claimed as TSCA
Confidential Business Information (TSCA CBI) by those
person(s) reporting for the TSCA Inventory, nor does it
contain any data that would compromise TSCA CBI. The
data submitted for the TSCA Inventory, including produc-
tion range information, are subject to the limitations
contained-in the TSCA Inventory Reporting Regulations
(40 CFR 710).
z[J!!.i /J, ~ 2/12/85
20
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0383-0473
Page 1 of 5
DATE:
APR 2 0 /983
SUIJECT'Status Report*
8EHQ-0383-0473
App=oved
CJt- 1.;25"
nOM,Justine L. wel01.A./eam Leader
Chemical sele~lf;~~nd Profiles Team/CHIB
Revision
Needed
TO.Frank D. Kover, Chie f
Chemical Hazard Identification Branch/AD
Submission Description
W. R. Grace & Co. (Grace) provided preliminary results of an
ongoing company epidemiology study of past/present workers at the
Grace vermiculite mining and milling operation in Libby, Montana.
According to the submitter, the Libby vermiculite deposit has
been long known to be contaminated with tremolite, an asbestiform
mate~ial. W. R. Grace & Co. also reported that in addition to
its own epidemiology study, the "National Institute for Occu-
pational Safety and Health (NIOSH), acting at the request of the
Mine Safety and Health Administration (MSHA), began a study in
March 1982 of the effects of tremolite exposure upon present and
past employees at Libby." The submitter stated that the NrOSH
study is a "cooperative effort" and stated further that Grace has
made its data available to NIOSH. The submitting company also
reported that it has "developed estimates of historical individ-
ual worker exposure levels" ar.d has recently startpd to compile
other employee data with these estimates of individual worker
exposure levels. In addition, W. R. Grace & Co. reported that
NIOSH is now in the process of developing its own exposure esti-
mates so that NIOSH and the company will be able to use the
other's estimates for cross-comparison purposes, an activity
which Grace hopes will "provide a more precise final product."
In its submission, W. R. Grace & Co. reported that the Libby
vermiculite mining and milling facility, which has been in
operation since the 1930's, was purchased by Grace in 1963 and
currently employs 170 people. The submitting company stated that
although "dust exposure levels" at Libby were "very high" prior
to 1963, "conditions gradually improved" following the company's
acquisition of the operation. The submitter also reported that a
1971 study (conducted by the U. S. Bureau of Mines) showed fiber
exposures at Libby ranging from 13 to 71 fibers/cubic centimeter
(cc) of air. W. R. Grace. & Co. stated, however, that following
"time-consuming research" in ov~rcoming unique technical design
problems, "a new wet milling facility was placed into operation
[in 1974] followed by further major process and operational
-NOTE: This status reoo=t is the resul: of a crelirnina=v
staff evaluation of ir.formation subrnitt~d to EPA. State;e~ts
made herein are not to be re~arded as ex~ressino final
Agency policy or intent with-respect to t~is particular
chemical. .~y review of the status repor~ should take into
70nsider~tion the fact that it may be based on incomplet~
J.nforma t10n.
21
EPA "0". 11:1).4 .ncy. ..".
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8EHQ-0383-0473
Page 2 of 5
improvements in the mine, mill and other areas which improved
working conditions significantly." The submitting company also
reported that since 1974/1975, fiber "exposures have been drama-
tically lowered and at present average less than 0.2 fibers/cc
(0.01-0.9 fibers/cc range)."
With regard to the preliminary results of its own ongoing study,
W. R. Grace & Co. reported that the company's "information indi-
cates that of 109 known deaths of former Libby employees, the
cause of death for 16 was listed in death certificates or insur-
ance claim forms as lung cancer, and for two others the cause was
listed as mesothelioma." The company stated that it did not have
"sufficient medical information or sufficient occu~ational and
personal history data in these cases to make a judgment as to the
cause of these illnesses." The submitting company also reported
that based upon "individual exposure estimates, it appears that
certain [Grace] employees whose work history predates the new
mill and who have a cumulative exposure of less than 100 fiber
years show signs of asbestos-related disease" and that "all of
these employees had exposure levels of more than 2.0 fibers per
cc for varying periods of time prior to the new mill."
W. R. Grace & Co. pointed out "several methodological problems
which have prevented [the company] from making any preliminary
judgments" based on the reported preliminary information. First,
the company pointed out that the information pertains to condi-
tions which "do not exist in today's workplace environment" and
that "all of the employees who show signs of asbestos-related
disease were employed prior to 1976 when fiber levels were sig-
nificantly higher than they are today." The company noted that
in contrast, its "preliminary data [show that] none of the cur-
rent employees hired since 1975 have asbestos-related disease."
Second, the company pointed out that "there are those who ques-
tion the validity of using cumulative exposures (averaging
periods of significantly high exposure with later low exposure
periods) and the fiber year concept as a proper basis for eval-
uating the effects of asbestiform material exposure." Finally,
the company pointed out that "the Libby employee population has a
history of both a large number of smokers (about 75%) and rela-
tively heavy individual smoking histories (most employees smoked
a pack or more per day)."
W. R. Grace & Co. stated the company believes that the submitted
preliminary information "corroborates written scientific opinion
on the effects of exposure to asbestiform material and that it is
within the realm of expectation for a mining and milling popula-
tion having exposures at the levels which prevailed at Libby in
the past." In addition, the submitting company stated that "in
some respects, the data are similar to what has been reported in
studies of talc mining and milling operations in which the talc
contained tremolite and other forms of asbestos." Finally, Grace
stated that "despite the uncertainty as to the meaning of the
data," the company had submitted the subject preliminary findings
pursuant to Section 8(e) for the following reasons: "(1) the
22
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8EHQ-0383-0473
Page 3 of 5
expressed interest of EPA, NIOSH, OSHA and MSHA in determining
whether the various asbestiform materials induce different
medical effects, and (2c) ongoing agency investigations as to
whether current asbestos exposure standards are adequate."
Submission Evaluation
It is agreed that the reported serious health effects (i.e., l~
lung cancers/l09 deaths and 2 mesotheliomas/l09 deaths) are
corroborative of written scientific opinion on the effects of
exposure to asbestiform materials and that the effects are, as
the submitter stated, "within the realm of expectation for a
mining and milling population having exposures at the levels
which prevailed...in the past."
In the submitter's study cohort, the proportion of men having
smoked was estimated to be 75%, a figure that is consistent with
other estimates of the proportion of males who have smoked in the
past.(l) For lung cancer, the estimated probability of death due
to lung cancer in males in the U.S. from age 35 until age 74 is
.062 or 6.2%.(2) Because this was a working population, it is
assumed that the deaths due to lung cancer did not occur before
age 35 and the population was followed to at least age 74. The
observed proportion of deaths due to lung cancer was 16/109 or
.147 (14.7%). Therefore, the calculated relative risk would be
approximately 2.4, which is statistically significant at p < 0.01
and is consonant with the known synergistic effects of asbestos
in smokers.
For mesothelioma, there is no established background incidence
for this disease. However, the rate estimates for asbestos-
related mesothelioma in North ~TIerica in the mid-1970's were
8.0/106 for males and about 2.5/106 for females.(3) If the
incidence of mesothelioma observed in the deceased Libby employ-
ees (i.e., 2 mesotheliomas/l09 deaths) is projected to a popu-
lation of 106, the rate would be equivalent to 18,349 cases of
mesothelioma. This finding is quite significant even though the
exposure levels between the two groups (i.e., the North American
males/females versus the studied Libby population) are not com-
parable. In addition, the finding is not necessarily surprising
in light of the 13-71 fibers/cc found by the U.S. Bureau of Mines
during the 1971 survey of the Libby facility. In addition, W. R.
Grace & Co. stated in the submission that exposure levels at the
Libby operation were even higher prior to 1970.
It would be of interest to know the actual past/present exposure
levels for the current Libby employees who reportedly show signs
of asbestos-related disease{s), the number of current employees
affected, and the nature of the asbestos-related disease(s) that
are occurring. In addition, it should be noted that the submit-
ter's finding that none of the current employees hired since 1975
show signs of asbestos-related disease is not surprising because
inadequate time has passed for the potential asbestos-related
diseases to be significantly expressed.
23
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8EHQ-0383-0473
Page 4 of 5
The submitter's final comment that W. R. Grace & Co. has "no
reason to believe there is any risk associated with the current
uses of Libby vermiculite-containing products" remains to be
determined and is dependent upon the potential exposure of users
to asbestos from the Libby vermiculite-containing products and
the inherent risk such uses impose.
Current Production and Use
Vermiculite is a naturally occurring hydrated magnesium-iron-
aluminum silicate (CAS No. 1318-00-9) that when heated (2000°F)
can expand (exfoliate) from 6-20 times its original size. The
known major vermiculite deposits are located in South Africa,
~vyoming, Colorado, Montana, North Carolina, and South Carolina.
Vermiculite uses include: insulating and packing materials; fil-
ler for paints, plastics, and rubber; removal of strontium-90
from milk and phosphates from wastewater; animal feed and fer-
tilizer additive; insecticide carrier; plant bedding; and general
absorbant.
Tremolite (CAS No. 14567-73-8) is a variety of asbestos which is
used particularly in paints, ceramics, and acid-resisting appli-
cations.
Comments/Recommendations
W. R. Grace & Co. reported that its medical surveillance program
at the Libby facility includes annual chest X-rays (since 1964),
annual pulmonary function tests (since 1974), and health status
questionnaires (since 1978). The company stated that the results
of these tests are made available to individual Libby employees
and/or their personal physicians. In addition, the company re-
ported that "based upon the recognition that smoking and asbestos
exposure can increase the incidence of disease, Grace, in 1978,
banned smoking at all Company facilities in Libby." W. R. Grace
& Co. also reported that it has initiated a program designed to
"help employees stop smoking, and the smoking population has been
reduced to 25% of the staff." In addition, the company stated
that "all new hires are required to be nonsmokers." W. R. Grace
& Co. reported that because of the difficulties in interpreting
the submitted information, the company plans to retain Drs. J. C.
McDonald and A. D. McDonald (McGill University, Montreal, Canada)
to "undertake a thorough analysis of the Libby data" in order to
allow Grace "to reach a scientifically sound conclusion based
upon [the company'sl historical data." W. R. Grace & Co. also
reported that the company does plan to continue to cooperate with
NIOSH and has sent a copy of the company's 8(e) notice to NIdsH.
The National Toxicology Program (NTP) recently completed a life-
time carcinogenesis bioassay of blocky (nonfibrous) tremolite
administered at a 1% concentration in the pelleted diet of male
and female Fischer 344 rats (starting with the dams of the test
animals). According to the DRAFT NTP Technical Report, "Under
the conditions of this bioassay, nonfibrous tremolite was not
24
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-
8EHQ-0383-0473
Page 5 of 5
" "
toxic anp did riot cause a carcinogenic response when ingested at
a level of 1% in the diet of male and female Fischer 344 rats for
their lifetime.~ .
References
1
2
3
NOTE:
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA}
will request W. R. Grace & Co. to report the actual past
and present exposure levels for the Libby employees who
are reportedly experiencing asbestos-related disease(s),
the number of employees affected by such disease(s), and
the nature of those asbestos-related disease(s). The
company will also be requested to submit, when available,
a complete copy of the results (including methodologies
and data) of the Libby data analysis which is to be per-
formed by Dr. A. D. McDonald and Dr. J. C. McDonald at
McGill University in Montreal, Canada.
b)
The Chemical Hazard Identification Branch will provide
copies of this status report to NIOSH, OSHA, CPSC, MSHA,
OW/EPA, OSWER/EPA, OANR/EPA, ORD/EPA, and the "Asbestos
Team" (CCD/OTS/EPA). Copies of this status report will
also be transmitted to the Industry Assistance Office
(IAO/OTS/EPA) for appropriate distribution.
Preventive Medicine.
1980.
Vol. 9, pp. 747-759.
SEER Report, NCI Monograph 57, June 1981.
McDonald JC and McDonald AD. Mesothelioma as an index of
asbestos impact. In: Peto R, Schneiderman M (ed), Banbury
Report 9, Quantification of Occupational Cancer, Cold Spring
Harbor Laboratory, 1981, pg. 73-82.
In a supplemental submission dated June 7, 1983 (8EHQ-0683-0473
Supplement), R. T. Vanderbilt Company, Inc. reported that the
asbestiform (i.e., fibrous) variety of tremolite is correctly
termed "tremolite asbestos" (CAS No. 77536-68-6), whereas the
non-fibrous (i.e., non-asbestiform) variety is correctly termed
"tremolite" (CAS No. 14567-73-8).
25
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0383-0474
Page 1 of 4
DATEI
APR 2 5 \983
SUIJICT, Status Report*
8EHQ-0383-0474
Approved. zjJ0- 4{;z, '"
Revision
Needed
nQIU Justine L. wel~ieam Leader
Chemical select&bn and Profiles
TO, Frank D. Kover, Chief
Chemical Hazard Identification
Team/CHIB
Branch/AD
Submission Description
The Celanese Corporation provided the experimental protocol and a
"poster" summarizing the preliminary findings from the first 15
months of an ongoing chronic rat inhalation study of acetaldehyde
(CAS No. 75-07-0) which is being conducted in the Netherlands.
Celanese also provided a January 6, 1983 cover letter from the
Institute CIVO - Toxicology and Nutrition TNO (Netherlands) to
the National (U.S.) Center for Toxicological Research (NCTR) and
one of that letter's two enclosures (an NCTR/EPA Formaldehyde
Clearing House Data Form on acetaldehyde). The other enclosure
(a Data Form on formaldehyde) was not included in the submission.
According to the submitted acetaldehyde Data Form, the Institute
CIVO - Toxicology and Nutrition TNO, the Netherlands Ministry of
Health and Environment, and the Netherlands Cancer Foundation are
co-sponsors of the subject study ("Lifespan Inhalation Carcino-
genicity Study of Acetaldehyde in Rats"). The January 6, 1983,
cover letter states that the chronic inhalation study and several
short-term inhalation studies in rats were initiated to verify
previously reported oncogenic effects of acetaldehyde in Syrian
Golden hamsters following long-term inhalation exposure. The
short-term studies in rats reportedly revealed "severe degenera-
tive, hyperplastic and metaplastic epithelial changes in the nose
at levels of 1000, 2200, and 5000 ppm; similar changes were also
found in the larynx at the two highest exposure levels."
According to the "poster" summary, the ongoing chronic study,
which has been underway for 21 months as of January, 1983, in-
volves 4 grol.ps of Wistar rats, each group consisting of 105
males and 105 females, exposed via inhalation to acetaldehyde
vapor concentrations of 0, 750, 1500, or 3000 parts per million
(ppm) for 6 hours per day, 5 days per week for at most 30 months.
The "poster" summary stated that interim sacrifices have been
carried out at 3, 6, and 12 months and further stated that
"recovery groups" have been included in the study.
-NOTE: This status reDo:t is the result of a Drelirninarv
staff evaluation of information submitted to EPA. State;ents
mace herein are not to be re~arded as eXDressina final
Asency policy or intent with~res?ect to t~is particular
chem~cal. .~y review of the status repor~ should take into
conslderation the tact that it may be based on incomoleta
information. .
26
I:~. '0111" 1I;t)-& IJlEY. ..",
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8EHQ-0383-0474
Page 2 of 4
With regard to the preliminary results of the ongoing chronic
acetaldehyde inhalation study in rats, the submitted "poster"
summary stated that:
"Mortality was significantly increased in males and females
of the top-dose group as compared to controls. Growth retar-
dation was observed in males at each treatment level and in
females at the mid- and top-dose levels. The histopatho-
logical examination of rats killed after 3, 6, or 12 months
revealed hyper- and metaplastic epithelium with massive
keratini[z]ation in the nose, and similar, but less severe
changes in the larynx at the highest exposure level. Less
severe degenerative and hyper/metaplastic changes in the nose
were also found at the lower exposure levels. The first
nasal carcinoma (a squamous cell carcinoma from the respira-
tory epithelium) was found in a top-dose rat in week 44. A
considerable number of top-dose rats found dead or killed in
extremis during the first 15 months of the study had a nasal
carcinoma (7/35 males and 13/31 females). Both squamous cell
carcinomas and adenocarcinomas of the olfactory epithelium
were observed. A few lower dose rats had also developed a
nasal carcinoma. So far, no laryngeal tumors were detected."
The "poster" summary also contains the following conclusion:
"It is concluded that under the conditions of the present
study, acetaldehyde is capable of inducing nasal carcinomas
in rats."
In addition, the submitted January 6, 1983, cover letter discus-
sed the possible role of cytotoxicity in both formaldehyde and
acetaldehyde carcinogenicity and the perceived need for further
study. The cover letter also addressed the question of risk of
human lung and laryngeal cancer posed by exposure to formaldehyde
and/or acetaldehyde.
Submission Evaluation
The submitted summary information clearly indicates that inhaled
acetaldehyde vapors are carcinogenic toward the respiratory tract
of rats. The provided information also indicates the existence
of a dose-response relationship. Further evaluation of the re-
ported carcinogenic findings in rats will be possible upon EPA's
receipt of future interim reports as well as a complete copy of
the final report (expected in the summer of 1984).
Current Production and Use
A review of the production range (includes importation volumes)
statistics for acetaldehyde (CAS No. 75-07-0), which is listed in
the initial TSCA Inventory, shows that between 771 million and
2.2 billion pounds of this chemical were reported as produced
and/or imported in 1977. This production range information does
not include any production/importation data claimed confidential
27
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8EHQ-0383-0474
Page 3 of 4
bi the person(s) reporting for the TSCA Inventory, nor does it
include any information that would compromise Confidential
Business Information. The data submitted for the initial TSCA
Inventory, including production range information, are subject to
the limitations contained in the TSCA Inventory Reporting Regula-
tions (40 CFR 710).
The major use of acetaldehyde is as an intermediate in the manu-
facture of a wide variety of chemical substances (e.g., acetic
acid and peracetic acid, pyridine and pyridine bases, pentaery-
thritol', glyoxal, 1,3-butylene glycol, paraldehydes, acetic
anhydride, butyl alcohol, butyraldehyde, chloral). In addition,
acetaldehyde is used to manufacture perfumes, polyester resins,
and basic dyes. The chemical has also been used as a fruit and
fish preservative, as an alcohol denaturant, as an additive in
certain foodstuffs and alcoholic beverages, and as a solvent in
the paper, rubber, and tanning industries. Some of the other
applications of acetaldehyde include its use in fuel composi-
tions, in preventing mold growth on leather goods, in silvering
of mirrors, and in producing certain types of thermoset resins.
Comments/Recommendations
The Celanese Corporation's submission indicated that the company
had provided copies of the reported information to NIOSH, OSHA,
and NCI. In addition, Celanese has reported that the company is
attempting to obtain additional information from the laboratory
investigators and plans to forward that information to EPA. The
provided NCTR/EPA Data Form on acetaldehyde indicates that the
projected date for the final report of the chonic inhalation
study in rats is July, 1984.
The Chemical Hazard Identification Branch (CHIB/AD) is currently
preparing a Chemical Hazard Information Profile (CHIP) on acet-
aldehyde. In addition, the National Toxicology Program has been
conducting other toxicologic studies of the subject chemical.
a) The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request the Celanese Corporation to immediately sub-
mit (upon receipt by the company) copies of all future
interim reports and a copy of the final report from the
ongoing chronic acetaldehyde inhalation study in rats. In
view of EPA's general interest in corporate actions which
are taken on a voluntary basis in response to chemical
toxicity/exposure information, Celanese will be requested
to describe the actions it has taken to warn workers and
to reduce and/or eliminate exposure to acetaldehyde.
b) The Chemical Hazard Identification Branch will ensure that
the oncogenicity findings in rats are incorporated in the
acetaldehyde Chemical Hazard Information Profile (CHIP)
which is now in preparation.
28
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8EHQ-0383-0474
Page 4 of 4
c) The Chemical Hazard Identification Branch will transmit
copies of this status report to NIOSH, OSHA, FDA, CPSC,
NTP, OW/EPA, OSWER/EPA, OANR/EPA, ORD/EPA, and OPP/EPA.
Copies of this status report will also be sent to the
'Industry Assistance Office (IAO/OTS/OPTS) for additional
distribution.
29
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
SUIJEC:T. Sta t us Report *
8EHQ-0483-0475
8EHQ-0483-0475
A:;:::e:f ~~~
Revision
Needed
DATE:
APR 2 9 \983
" '\
nOM. Justine L. We c);f, earn Leader
Chemical Sele . ion and Profileb Team/CHIB
TOI Frank D.
Chemical
Chief
Identification Branch/AD
Submission Description
The Eastman Kodak Company submitted a March 2, 1983, interim
summary report entitled "Inhalation Teratological Potential of
Ethylene Glycol Monobutyl Ether [EGBE; 2-butoxyethanol] in -the
Rat." Eastman Kodak reported that the study is being conducted
under contract for the Chemical Manufactures Association (CMA)
and is being sponsored by the Glycol Ether Program (GEP) of which
the Tennessee Eastman Company (a division of the Eastman Kodak
Company) is a member. In its submission, Eastman Kodak noted
that the data contained in the interim report "have not been
subjected to Quality Assurance and are incomplete since fetal
skeletal examination and statistics have not been finished~"
According to the submitted interim report, 4 groups of 30 mated
female Fischer 344 rats were exposed via inhalation to EGBE vapor
concentrations of 0, 100, 200, or 300 ppm for 6 hours per day on
gestation days (GD) 6 through 15. In addition, the interim
report presented the following summarized clinical observations
and results of examinations performed as of March 2, 1983:
"Gestation Body Weight Changes: Gestational body weight gains
of animals exposed to 300 ppm were significantly depressed
(compared to controls) from GD 6-21. Significant reductions
in body weight gains (compared to controls) were also present
in the 200 ppm group from GD 6-15 and in the 100 ppm group
from GD 6-12."
Gestational Food Consumption: Food consumption was reduced
during the dosing period in all groups exposed to EGBE. Sig-
nificant reductions in food consumption (compared to controls)
were noted in the 300 ppm group from GD 6-15, in the 200 ppm
group from GD 6-12, and in the 100 ppm group from GD 6-12.
Animals in the 300 and 200 ppm groups had a significant in-
crease in their food consumption (compared to controls) from
the end of exposures (GD 15) until sacrifce (GD 21).
-NOTE: T~is status repo~t is the result of a prelirnina~v
staff evaluation of information submitt~d to EPA. Stace;ents
mace herein are not to be re~arded as eXDressir.o final
Asen~y policy or intent wiCh-res?ec~ to t~is ?articular
chem~cal. ..~y review of the status report should take into
~onslderatlon the fact thac it may be based on incomplete
lnforma tion.
30
E~. '0"'18 11:0-. IJlC..,. ..,.,
-------
8EHQ-0483-0475
Page 2 of 4
Gestational Water Consumption: Only animals exposed to 300
and 200 ppm had significant reductions in water consumption.
Those exposed to 300 ppm consumed less water than controls
from GD 6-12. Animals in the 200 ppm group consumed less
water than controls in the periods GD 6-9 and GD 12-15.
Water consumption prior to the exposure segment of the study
and following exposures were similar in all groups.
Maternal Clinical Observations: Exposures to EGBE resulted
in a dose-related increase in -the frequency of signs indica-
tive of hematuria. These signs included red fluid on cage
trays, and urogenital wetness, discharges and encrustations
of red and/or black color. In addition, animals exposed to
EGBE were hypoactive during the exposure segment of the study
when compared with controls.
Maternal Organ Weights: The weight of the uteri of animals
exposed to 300 ppm was significantly lower than those of con-
trols. This reduction in uterine weight is associated with
the high degree of embryo and fetal lethality present at this
exposure level.
Maternal Uterine and Ovarian Examinations: Exposures to
EGBE, particularly at the 300 ppm level, resulted in a marked
increase in embryo and fetal lethality manifested by resorp-
tions of concepti. Exposures to 200 ppm produced a more
moderate increase in resorption when compared to controls.
Fetal Visceral Examinations: Exposures to EGBE resulted in a
dose-related increase in fetal atelectasis [the incomplete
expansion of the lung(s) at birth]. In addition, fetuses
from groups exposed to EGBE had ventricular septal defects,
absent innominate arteries, and severely shortened innominate
arteries."
In addition to the March 2, 1983, interim report, the Eastman
Kodak Company provided the following background information:
"Nelson et al at the National Institute for Occupational
Safety andlHealth (NIOSH) studied the teratogenic potential
of three glycol ethers in rats; 2-butoxyethanol (EB), 2-meth-
oxyethanol (EM), and 2-ethoxyethyl acetate (EEA). They found
that EM and EEA were teratogenic, while 2-butoxyethanol did
not produce significant embryofetotoxicity. The exposure
concentrations of 2-butoxyethanol were 150 to 200 ppm and
Nelson et al reported that these concentrations were diffi-
cult to-generate (vapor pressure of EB = 0.6 mm Hg at 20°C).
Maternal toxicity was evident at both dose levels and consis-
ted of hematuria only after the first exposure. No other ad-
verse effects were seen in the darns exposed to either level.
No major skeletal or soft tissue malformations were seen at
150 or 200 ppm of 2-butoxyethanol and the incidence of common
skeletal variants and minor soft tissue anomalies seen in the
treated groups were comparable to the controls. Potential
31
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8HQ-0483-0475
Page 3 of 4
.
reproductive effects of 2-butoxyethanol and other glycol
ethers were studied in male rats in [the submitter's] labora-
tory and in male mice by Nagano et al in Japan. Administra-
tion was by gavage five times per-week. In the former, doses
from 222 tc 885 mg/kg/day, and in the latter, doses from 250
to 1000 mg/kg/day, did not produce testicular effects."
Finally, Eastman Kodak noted that the following factors should be
considered by EPA in assessing the CMA/GEP-sponsored inhalation
teratology study of 2-butoxyethanol in rats: "the severe maternal
toxicity produced, the lack of a dose-related response and the
low incidence of. effects seen in the [CMA/GEP] study, as well as
the negative results from the NIOSH study, the known toxicity of
2-butoxyethanol in adult male and non-pregnant female rats, and
[the chemical's] vapor pressure."
Submission Evaluation
Although the submitted findings indicate that 2-butoxyethanol did
produce some degree of maternal toxicity in the CMA/GEP-sponsored
teratology study, EPA does not believe that 2-butoxyethanol pro-
duced "severe" maternal toxicity in the study. One of the most
common major manifestations of severe maternal toxicity in this
type of study is a significant weight change (usually seen as a
decrease) in exposed versus controL dams. The summarized data
that are presented in Table 4 (which contains measured maternal
organ weights and "corrected" maternal body weights (i.e., the
maternal body weight minus the weight of the uterus and its
contents)), indicate that there were no significant changes in
the corrected body weights of exposed dams when compared to the
corrected body weights of control dams. There was, however, a
significant decrease found in the uterine weights of dams exposed
to 300 ppm 2-butoxyethanol when compared to controls. Stated in
another way, the apparent decreases in maternal body weights of
dams exposed to 300 ppm 2-butoxyethanol are due primarily to the
decrease in the weight of the uterus and its contents.
In order for EPA to more properly evaluate the significance of
the embryo/fetotoxic effects (including abnormalities) observed
in the CMA/GEP-sponsored inhalation study of 2-butoxyethanol, a
complete copy of the final report (including protocol(s), data
and the results of performed statistical analyses) should be ob-
tained. It should be noted at the present time, however, that
the embryo/fetotoxic effects observed in the CMA/GEP-sponsored
study (although in apparent contrast to previous findings), are
consistent with the adverse developmental effects found in labor-
atory animals exposed to two structurally related chemicals: 2-
methoxyethanol and 2-ethoxyethanol.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for 2-butoxyethanol (CAS No. 111-76-2), which is
listed in the initial TSCA Inventory, has shown that between 31
32
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8EHQ-0483-0475
Page 4 of 4
million and 161 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 the person(s) reporting for the TSCA Inventory, nor
does it include any information which would compromise Confiden-
tial Business Information (CBI). 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).
2-Butoxyethanol is used as a solvent for nitrocellulose resins,
spray and quick-drying lacquers, varnish and varnish removers,
enamels, and drycleaning compounds. The chemical is also used
for preventing spotting during the printing and/or dyeing of
textiles and as an ingredient in certain pesticides.
Comments/Recommendations
EPA's Office of Toxic Substances (OTS) has received and evaluated
several Section 8(e) and "For Your Information (FYI)" submissions
concerning various glycol ethers. The Chemical Hazard Identifi-
cation Branch (CHIB/AD/OTS) has prepared CHIPs (Chemical Hazard
Information Profiles) on 2-methoxyethanol, 2-ethoxyethanol, and
their acetates. In addition, Priority Review Level-l (PRL-l)
documents on 2-methoxyethanol and 2-ethoxyethanol have been pre-
pared by the Health and Environmental Review Division (HERD/OTS).
At present, the OTS "Existing Chemicals Task Force (ECTF)" is
considering various EPA options with regard to chemicals within
the class of glycol ethers.
a) The Chemical Hazard Identification Branch will request the
Eastman Kodak Company to submit, when available, a complete
copy of the final report from the CMA/GEP-sponsored inhala-
tion teratology study of 2-butoxyethanol in rats. The sub-
mitter will also be requested to provide a complete copy of
the final report (including test protocols and data) from
the Eastman Kodak study reportedly conducted to determine
potential reproductive system effects of 2-butoxyethanol
administered to male rats by gavage five (5) times per week
at doses ranging from 222 to 885 mg/kg/day.
b) In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical tox-
icity/exposure information, the Chemical Hazard Identifica-
tion Branch will request the Eastman Kodak Company to des-
cribe the actions it has taken to warn workers and others
and to reduce and/or eliminate exposure to 2-butoxyethanol.
c) The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, CPSC, FDA, NTP,
OANR/EPA, ORD/EPA, OSWER/EPA, OW/EPA, OPP/OPTS/EPA, and the
OTS "Existing Chemicals Task Force (ECTF)." A copy of this
report will also be provided to EPA's Industry Assistance
Office (IAO/OTS) for further distribution.
33
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UNITED STATES ENV IRONMENT AL PROTECTION AGENCY
8EHQ-0483-0476 S
Page 1 of 4
DATE:
MAY 2
1983
SIJIJUTI S-tatus Report*
8EHQ-0483-0476 S
App:'oved
zJI- ~/¥
,.0... Justine L. welchl~am Leader
Chemical Selection and Profiles Team/CHIB
vi
TO,Frank D. Kover, Chief
Chemical Hazard Identification Branch/AD
Revision
Needed
Submission Description
Note: The identity of the submitting company has been claimed as
Confidential Business Information (CBI).
The submitting company provided summary results of two recently
conducted genotoxicity studies of hexafluoroisobutylene (HFIB;
CAS No. 382-10-5). The submitter reported that in the first
study, sex-linked recessive lethal mutations were observed in
fruit flies (Drosophila melanogaster) following a 2-hour exposure
to HFIB at a concentration of 10,000 ppm (vol/vol). The second
study reportedly involved rabbits exposed via inhalation to BFIB
at concentrations of 6, 30, or 100 ppm for 6 hours per day for 9
exposure days. The submitter stated that analyses for induced
sister chromatid exchanges (SCEs) in peripheral lymphocytes "did
not indicate consistent statistically significant differences
from control animals" or "a cumulative dose response." The
submitter did state, however, that "there were several individual
data points (4/38) that were significantly elevated above the
overall mean control value" and that these differences were
observed in the 10 and 100 ppm HFIB exposure groups, but not in
the 30 ppm HFIB exposure group.
The submitter reported that the above studies were conducted due
to the company's "renewed [but not reported] commercial interest"
in hexafluoroisobutylene. In addition, the company stated that
although previously conducted studies yielded "inconclusive re-
sults," the findings in the recent studies "suggest that it is
reasonable to conclude that this chemical is a weak mutagen."
With regard to the previously performed studies on HFIB, the
submitter reported that in an Ames Salmonella typhimurium (bac-
teria) assay conducted in the presence of exogenous metabolic
activation and using an exposure time of 1 hour in an enclosed
chamber containing a high HFIB gas concentration, the chemical
caused an increase in the reversion of strain TA-1538, a slight
.NOTE: This status report is the result of a prelimina:,v
staff evaluation of information submitt~d to EPA. State;ents
mace herein are not to be regarded as eXDressir.o final
Asen~y policy or intent with respect to t~is particular
chem~cal. .'~Y review of the status report should take into
~onslderatlon the fact that it may be based on incomplete
lnformation.
34
I:~' '0." ..~ IIIIC'II. ..,,,
-------
8EHQ-0483-0476 S
Page 2 of 4
response in TA-1537, and no response in TA-1535. The submitter
also reported that when HFIB was tested in suspension, reversion
frequencies were increased in TA-1538, slightly increased in TA-
1537, and not increased in TA-1535. The submitting company did
not state whether these particular studies were also conducted in
the absence of exogenous metabolic activation.
In another Ames assay, although HFIB reportedly induced a 2 to 3-
fold "increase in histidine revertents per plate over background
levels in strain TA-IOO in the range of 6.4 to 22.8 percent gas
in air mixture," the submitter stated that "there was no linear
dose response." The submitter also stated that the observed
mutagenic activity was "consistently higher" in the presence of
exogenous (rat liver) metabolic activation and that there were no
increases in reversion frequencies in strains TA-1538, TA-1537,
TA-1535 and TA-98.
The submitting company reported that HFIB was found to be
mutagenic in an in vitro L5178Y mouse lymphoma cell forward
mutation assay conducted in the presence of exogenous (mouse
liver) metabolic activation. The submitter did not provide any
information on the levels of HFIB tested in this study and did
not indicate whether the study was also conducted in the absence
of exogenous metabolic activation.
The submitter reported that no effects were noted when HFIB was
tested in a yeast (Saccharomyces cerevisiae (strain D4)) gene
conversion mutagenicity study. The submitter did not report
whether this study was conducted in the absence and/or presence
of exogenous metabolic activation.
With regard to previously performed in vivo studies, the company
stated that there was a slight, but not statistically signifi-
cant, increase over controls in the observed frequency of struc-
tural chromosomal aberrations in the cells (unspecified) of rats
exposed to 7,500 ppm HFIB for 1 hour. The submitting company
stated that "there was no increase in the frequency of structural
chromosomal aberrations observed in rats exposed to 5,000 ppm."
In addition, the company reported that the I-hour LC50 was found
to be 7,000 ppm in this study.
The submitting company reported that the 4-hour LC50 for HFIB was
found to be 1425 ppm in rats. In addition, the submitter
reported that HFIB had been tested in rats via inhalation at 0,
53, or 215 ppm for 6 hours per day, 5 days per week for 2 weeks.
The company stated that "all animals in the 215 ppm group either
died or were killed in moribund condition after 4 exposures" and
"in the 53 ppm exposure group, while all the animals survived the
exposures, signs of probable respiratory tract irritation were
seen, as well as an increase in kidney weight."
Finally, the submitting company stated its belief that, based on
the currently available information, hexafluoroisobutylene is
"moderately toxic and weakly mutagenic."
35
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8EHQ-0483-0476 S
Page 3 of 4
Submission Evaluation
Based on a review of the summarized experimental findings that
were presented in this submission, it does appear that HFIB is,
at minimum, moderately toxic in vivo and does possess some degree
of in vitro/in vivo mutagenic-and in vivo clastogenic activity.
Further evaluation of the reported-rindings must await EPA's
receipt of complete copies of the final reports (including data
and protocols) from all of the toxicologic studies cited in the
submission.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for hexafluoroisobutylene (CAS No. 382-10-5), which is
listed in the initial TSCA Inventory, has shown that no 1977 pro-
duction/importation was reported or that all of the production
range data reported were claimed as Confidential Business Infor-
mation by the manufacturer(s) and/or importer(s) and cannot be
disclosed (Section 14(a) of TSCA; U.S.C. 2613(a». All of 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).
No information concerning past, current, or proposed use(s) of
hexafluoroisobutylene was provided by the submitting company or
located in the secondary literature sources consulted.
Comments/Recommendations
The submitting company reported that an internal hexafluoroiso-
butylene exposure limit of 1 ppm has been established because the
company has not as yet determined a no observed effect level in
laboratory animals. In addition, the company reported that when
hexafluoroisobutylene commercial activity is resumed, "process
controls and personal protective equipment, including respirators
and medical surveillance, will be utilized to limit the potential
for exposure and to protect workers."
EPA's Office of Toxic Substances (OTS) has received and evaluated
TSCA Section 8(e) submissions containing toxicity and/or exposure,
information on structural analogs of hexafluoroisobutylene (e.g.,
8EHQ-I077-0011 and 8EHQ-0278-0042). The Test Rules Development
Branch (TRDB/AD/OTS) is currently reviewing toxicity and exposure
data on various fluoroalkenes as recommended by the Interagency
Testing Committee (ITC).
a) The Chemical Hazard Identification Branch (CHIB/AD/OTS)
will request the submitting company to provide complete
copies of the final reports (including protocols and data)
from each of the in vitro and in vivo toxicologic studies
cited in its submission. In view-or-the Agency's general
interest in company actions that are taken on a voluntary
basis in response to chemical toxicity/exposure informa-
36
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8EHQ-0483-0476 S
Page 4 of 4
tion, the submitting company will also be askecl if it is
conducting, or plans to conduct, additional studies de-
signed to further define the toxicity of hexafluoroiso-
butylene and to describe the nature of such studies. In
addition, the company will be informed that EPA would
welcome the submission of the following types of informa-
tion on hexafluoroisobutylene: 1) current and/or projected
production/importation volumes, 2) past, current and/or
proposed use(s), and 3) actual and/or potential consumer
and environmental exposure.
b) The Chemical Hazard Identification Branch will screen the
reported information in order to determine the need for
further OTS assessment of hexafluoroisobutylene.
c) The Chemical Hazard Identification Branch will transmit
copies of this status report to NIOSH, OSHA, CPSC, FDA,
NTP, OW/EPA, OSWER/EPA, OANR/EPA, ORD/EPA and TRDB/AD/~PA.
A copy will also be sent to EPA's Industry Assistance
Office (IAO/OTS) for further distribution.
37
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
SU'JECTI Status Report *
8EHQ-0583-0477 S
8TI1Q-0583-0477 S
Page 1 of 4
Approved /
[/
Revision
Needed
'01
DAn:
JUN
1 1983
,.01&1 Justine L. Wel~eam Leader
Chemical selec~~nand profiles Team/CHIB
TOr Frank D. Kover, Chief
Chemical Hazard Identification Branch/AD
Note
The submitting company has claimed its identity and the identity
of each of the subject chemical substances as TSCA Confidential
Business Information (CBI).
Submission Description
The submitting company provid~d summarized final results from a
battery of short~terrn in vitro and in vivo tests on the subject
chemical substances, three of which-Were reported to be inter-
mediates. According to the submitter, all of the chemicals pro-
duced varying results in Ames Salmonella typhimurium (bacteria)
tests. In addition, the submitter reported that three of the
chemicals were tested in an in vitro Mouse Lymphoma Cell Forward
Gene Mutation Assay. The submitter stated, however, that the
positive results obtained from this in vitro assay were "scien-
tifically questionable," because guidelines for performing the
test were not rigorously followed. The submitter also reported
that these three chemicals were found to be negative when tested
in an in vivo cytogenetics assay and an "oncogenic [cell] trans-
formation~say. In addition, the submitter reported that due
to the fact that previously obtained Unscheduled DNA Synthesis
(UDS) test results were declared invalid by the performing labor-
atory, the tests were re-run and the three chemicals were found
to give negative results.
The submitter stated that on the basis of the test data, which
were received by the company in "(mostly verbal, some in draft
form)," the submitter does not know "if the source of the muta-
genic response derives from the compounds themselves or from
impurities in the. . . r.aw material."
.NOTE: This status reoort is the result of a oreliminarv
staff evaluation of information submitted to EPA. Sta~e;ents
mace herein are not to be recrarded as ex~ressina final
~sen:y policy or intent with~res?ec~ to t~is particular
chem~cal. .~y review 6£ the status report should take into
consideration the fact that it may be based on incomolete
information. ..
38
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---
8EHQ-0583-0477 S
Page 2 of 2
Submission Evaluatio~
The submitted summarized information indicates that the tested
substances may possess some degree of mutagenic activity. Com-
plete copies of the final reports (includ ing test protocols 'and'
data) from the cited studies should be obtained in order to
properly evaluate the reported findings.
Current Production and Use
Due ~o the fact that the submitter has claimed the identities of
the subject chemical substances as TSCA CBI, no production or use
information will appear in this status report.
Comments/Recommendations
It should be noted that although a positive in vitro result, when
considered alone, may not be sufficient to offer reasonable sup-
port for a conclusion of substantial risk, EPA does believe that
in vitro studies do provide valuable data that can aid in asses-
sing possible hazards/risks posed by chemicals to health and/or
the environment. EPA also believes that a positive in vitro test
result in combination with additional information (e.g., know-
ledge 9f actual or potential exposure to or high production of
the subject 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 under
Section 8(e) of TSCA.
In its submission, the company stated that further in vitro Mouse
Lymphoma Cell Forward Gene Mutation Assays were being conducted
with some of the subject chemicals. The company stated that EPA
would be informed about the results of these additional tests.
a) The Chemical Hazard Identification Branch (CHIB/AD) will
request the submitting company to provide complete copies
of the final reports (including test protocols and data)
from each of the in vitro and in vivo studies cited in its
--
submission.
b) The Chemical Hazard Identification Branch will screen the
reported information in order to determine if further OTS
assessment of the subject chemicals is warranted.
c) The Chemical Hazard Identification Branch will provide a
copy of this status report to the TSCA Assistance Office
(TAO/OTS/OPTS/EPA).
39
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DATE:
JM
81983
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0583-0478 S
Page 1 of 3
App:oved ~ ~I~\~~
SUIJ£CT. Status Report* 8EHQ-0583-0478 S
Justine L. Wel~eam Leader
nOM'Chemical selec(}on and Profiles
Frank D. Kover, Chief
TO'Chemical Hazard Identification
Team/CHIB
Revision
Needed
Branch/AD
Submission Description
The Shell Oil Company submitted a copy of a draft report of a
recently completed 14-day rat skin-application study of EPON
Curing Agent@D (2-ethyl hexanoic acid compounded with 2,4,6-
tris[(dimethylamino)methyl]phenol; CAS No. 51365-70-9). Shell
reported that signs of central nervous system (CNS) effects at
doses of 0.1 ml/kg/day and above, and a dose-related incidence of
mortality and time to death at doses of 1 and 5 ml/kg/day had
been observed in the 14-day study. The submitter also reported
that the provided preliminary information had not yet been sub-
jected to a quality assurance review or a complete statistical
analysis. With regard to the significance of the results from
the 14-day rat skin-application study, the Shell Oil Company
stated that:
"The signs of CNS effects were observed at all levels tested
(0.1, 1.0 and 5.0 ml/kg/day) and were seen in some animals as
early as the first day of exposure. Comparable human exposure
would be 5 to 7 ml/day, an unlikely but possible occupational
exposure. In our consideration, this possibility and the ab-
sence thus far of a demonstrated no effect level, reasonably
supports a conclusion of substantial risk. Animal mortality
was observed at the two higher levels of exposure; comparable
exposure in man would be 70 to 350 ml/day. The animal deaths
were unexpected, particularly at the mid-range dose because 0f
the low [previously] observed acute [rat] oral toxicity (7.1
g/kg), and contribute to our perception of substantial risk."
With regard to the toxicity observed in previously conducted
studies, Shell submitted a copy of a 1951 report containing the
final results of several acute in vivo toxicity studies of EPON
Curing Agent@D administered via-the following routes of exposure:
oral (mice and rats), inhalation (rats), dermal (intact rabbit
skiri) , or ocular (rabbits). The results contained in the 1951
report can be summarized as follows: 1) the LD50 for mice exposed
to a single oral dose was found to be in excess of 9 g/kg; 2) the
ALD (approx. lethal dose) for rats exposed to a single oral dose
-NOTE: This status recort ~s the result of a crelirninarv
staff evaluation of ir.formation submitted to EPA. Sta~e;ents
mace herein are no~ to be re~arded as ex~ressir.a final
Agen:y policy or intent with~res?ec~ to t~is particular
chem~cal. .'~Y review 6f the status repor~ should take into
conslderatlon the tact that it may be based on incomolete
information. .
40
I:~& "0"" 11:01 UICY. ~,.,
-------
8EHQ-0583-0478 S
Page 2 of 3
was determined to be 7.1 g/kg; 3) the ALD for rabbits exposed via
a single skin application was found to be greater than 10 g/kg;
4) repeated (4 hours daily for 9 days) inhalation exposures to
saturated vapor did not produce death or any toxic symptoms in
rats; 5) no signs of irritation were found following a single
application of the test material to the intact skin of rabbits;
and 6) progressive severe eye damage was observed in rabbits
following instillation of one drop of the test material.
In its submission, the Shell Oil Company reported that it was not
aware of any adverse effects having occurred as the result of
using EPON Curing Agent@D. In addition, Shell stated that the
existing Material Safety Data Sheet (MSDS) "recommends skin pro-
tection in the use of the product." Shell's submission also
contained a copy of the existing MSDS for EPON Curing Agent@D.
Submission Evaluation
The submitted animal data indicate that EPON Curing Agent@D
causes death by CNS activity at very high acute doses as evi-
denced by the rapidity of death (5-30 minutes) and the observed
signs (clonic and epileptiform convulsions). At lower lethal
doses in both the acute oral and 14-day dermal studies, CNS signs
were also observed. However, the actual cause of death was prob-
ably not CNS toxicity because the time-frame is more consistent
with other organ toxicity (e.g., the observed hepatotoxicity).
At non-lethal doses, reversible CNS signs of lesser magnitude
were observed.
Although the submitted data do not allow a complete determination
of direct neurotoxic action of EPOl1 Curing Agent@D at any dose
(because no neuropathology was attempted), there is clear evi-
dence of direct CNS activity at very high doses. Many of the CNS
signs observed at the lower doses may be secondary to the other
types of systemic toxicity observed.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for CAS No. 51365-70-9, which is listed in the TSCA
Inventory, has shown that no 1977 production/importation was re-
ported 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)). All of the data submitted for the Inventory, including
production range information, are subject to the limitations
contained in the Inventory Reporting Regulations (40 CFR 710).
Shell reported that EPON Curing Agent@D has been used for over 30
years as an epoxy resin hardener and that the "the major uses for
this curing agent are directed toward electronic and electrical
encapsulation, embedment, and insulation." No additional infor-
mation on the uses of the subject substance was located in the
secondary literature sources consulted.
41
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8EHQ-0583-047~ S
Page 3 of 3'
Com~ents~Recommendations
In 'the cover letter to its Section See) submission, Shell stated
that the reported information was being transmitted to NIOSH and
OSHA, Shell employees and customers, and other companies who cur-
rently produce or have produced the product. Shell also stated
that the existing EPON Curing Agent@D "Material Safety Data Sheet
is being revised to reflect these new animal test data" and that
a complete copy of the 14-day rat skin-application study report,
upon completion, will be provided to EPA.
a)
The Chemical Hazard Identification Branch (CHIB/AD/OTS)
will screen the submitted information in order to deter-
mine if further OTS assessment of EPON Curing Agent@D is
warranted.
b)
The Chemical Hazard Identification Branch will transmit
copies of this status report to NIOSH, OSHA, CPSC, NTP,
FDA, OW/EPA, OSWER/EPA, OANR/EPA, and ORD/EPA. A copy of
this status report will also be transmitted to the TSCA
Assistance Office (TAO/OTS/EPA) for further distribution.
42
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DATE:
JUN 2 1 1983
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
,;8EHQ-0583-0479 S
Page 1 of 6
SUIJICT'Status Report*
8EHQ-0583-0479 S
ApproveC'
,tftr t,!;-V
flOM,Justine L. welcrt:0.Neam Leader
Chemical select~-and Profiles Team/CHIB
T~Frank D. Kover, Chief
Chemical Hazard Identification Branch/AD
Revision
Needed
Note
The submitting company has claimed its name and specific product
names as TSCA Confidential Business Information (CBI). For ease
in reviewing this status report, the reader's attention is direc-
ted first to the information contained in the Current Production
and Use section that begins on page 4 of this report.
Submission Description
The submitting company provided the results of three acute
inhalation toxicity studies involving rats exposed to vapors gen-
erated by heating/melting the chemical substances and mixture
listed below. The submitter reported that these studies were
conducted in response to customer concerns about possible effects
of worker exposure to vapors observed during the cooling phase of
plastic products manufacturing processes. The submitter also
pointed out that although "no complaints or problems have been
recorded in the workplace," the company "decided that an inhal-
ation study on the vapors would be appropriate."
TEST MATERIALS
A) polypropylene (CAS No. 9003-07-0);
B) Bis-2-hydroxyethyl-tallow amine (CAS No. 61791-44-4); or
C) Mixture (1 part A / 3 parts B)
According to the submitter, the first study involved groups of
rats (10 rats/group) exposed via inhalation for 4 hours to vapors
generated during the heating/melting of polypropylene (A) alone,
bis-2-hydroxyethyl-tallow amine (B) alone, or C (mixture of A/B)
to temperatures of 240°C, 185°C, and 235°C, respectively. With
regard to the observed overall mortality, the submitter reported
that 10/10, 3/10, and 9/10 rats died within the first few days
following exposure to A, B, and C vapors, respectively. The'
*NOTE: This status recort is the result of a orelirnina:v
staff evaluation of ir.formation submitted to EPA. Sta~e;e~ts
mace herein are not to be regarded as expressing final
Agency policy or intent with respect to t~is particular
chemical. .~y review of the status repor~ should take into
considerati~n the fact" tha~ it mav b~ based on incomolete
information. - .
43
I:~A '0". .... '''£Y. ..,..
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8EHQ-0583-0479 S
Page 2 of 6
submitting company stated that although these results indicated
that polypropylene vapors alone or mixed with vapors of bis-2-
hydroxyethyl-tallow amine were "extremely toxic to the test ani-
mals," there was great uncertainty as to whether the observed
mortality was due to simple asphyxiation or due to the toxicity
of certain heat decomposition products of the tested materials.
The submitter also reported that due to several serious experi-
mental deficiencies that were detected during review of the final
report, it was decided that the study was not conducted by the
performing laboratory in accordance with the TSCA inhalation
testing guidelines and needed to be repeated.
The submitter reported that prior to repeating the inhalation
study, a quantitative analytical study (not involving animal
exposure) was performed on vapors generated by heating/melting
polypropylene. The company stated that in order to prevent the
loss of low boiling compounds, the heating/melting process was
performed without venting to the outside and further stated that
this procedure was the same as that used to generate the vapors
in the first acute inhalation study. The submitter reported that
the analytical study showed that carbon monoxide (over 1800 ppm
(detection limit» and acetaldehyde (over 1000 ppm) were present
in the polypropylene vapor. Specifically with regard to the car-
bon monoxide level detected in the p~lypropylene vapor, the sub-
mitter stated that such a level would "represent a very toxic
concentration to test animals."
With regard to the repeated 4-hour inhalation study, the company
stated that a revised protocol was employed that included "con-
stant oxygen monitoring and measurement of certain polypropylene
breakdown products such as carbon monoxide, carbon dioxide, pro-
pylene, and short-chain aldehydes." In addition, the submitter
stated that the method used to generate the test vapors involved
heating the test material in a flask that was vented to a scrub-
ber to remove vapor and low boilers." The submitter also stated
that once the test material had melted and was at the desired
temperature, the container was removed from the hood and con-
nected to the test animal exposure chamber. The heating/melting
was reportedly performed this way for the following reasons: 1)
the animals would not be exposed to decomposition products formed
while the test materials were being initially heated/melted and
brought up to the desired temperature (240°C in the case of poly-
propylene); and 2) this vapor "generation method more closely
resembles the type [of] exposure that would occur in the work-
place, where the reactors in which the polymer resins are melted
are basically closed systems with vents that lead to either a
scrubber or directly to the outside of the building."
. -
With regard to the results of the repeated study, the submitter
reported that although no deaths were observed for rats exposed
to A or B vapors alone, 10/10 rats died over a five day period
following exposure to vapors of the mixture (C). The submitter
stated, however, that due to evidence that showed that the test
mixture was "heated to well over 210°C with even auto-ignition
44
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8EHQ-0583-0479 S
Page 3 of 6
occcuring at one point," the results of the second study were
considered "invalid or at least inconclusive." The submitter
also stated that the second study, as performed, was "not
representative of the actual conditions of use" in that the
submitter's workers "are not exposed to oxidized product" and
customers' workers "are not exposed to [the solid product] heated
more than 1 or 2 minutes."
The submitter stated that considering the experience gained from
the first two studies, a third and final inhalation study was
conducted under conditions that would "more closely duplicate
conditions employed during actual manufacture..." The company
stated that the third study, which involved a 4-hour rat inhala-
tion exposure to vapors of the heated mixture (C) only, was con-
ducted with the following modifications to the protocol: "(1) all
heating procedures were performed under a nitrogen gas atmosphere
to minimize oxidation; (2) the ethoxylated amine was heated to
temperature while being stirred; (3) after the amine had reached
the correct temperature, the polypropylene pellets were added to
the flask, the mix was continuously stirred throughout the exper-
iment and the mix temperature was continuously monitored and kept
at 200°-210°C; (4) low boiling compounds produced during the
initial heating and melting procedure were not directed into the
test chamber." The submitter stated that "during the course of
the inhalation study, at no time was the mix observed to be dis-
colored, indicating that oxidation of the material was being min-
imized". In addition, the submitter stated that "gravimetric and
particle size analysis performed during the exposure period both
indicated that the chamber concentration of the test article was
.4 mg/l, suggesting that very little vapor was present, but
rather condensed droplets of test article."
With regard to the results of the third study, the submitting
company reported that each of the 10 exposed animals exhibited
salivation, nasal discharge, and labored breathing during the 4-
hour exposure period. With regard to mortality, the submitter
reported that although all rats survived the 4-hour exposure, 1
male rat and 1 female rat died on days 3 and 7, respectively of
the 14-day post-exposure observation period. The remaining 8
animals were reported to have lost weight during the first few
days and gained weight over the last few days of the 14-day post-
exposure observation period. The submitting company reported
that other than "some darkened areas of the lungs" of one of the
exposed rats, nothing remarkable was observed during necropsy
performed on all rats, including those that died on days 3 and 7.
The submitter stated that a chemical analysis that was performed
during the third study "indicated that the chamber concentrations
of the amine was 0.25 mg/l, which was very close to the level
measured during the second inhalation study (i.e., 0.3 mg/l) and
which caused the death of 100% of the test animals following a 4-
hour exposure period." It was also stated that "the precautions
taken during the third inhalation study to minimize oxidation
significantly reduced the toxicity of the resultant atmosphere."
45
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8EHQ-0583-0479 S
Page 4 of 6
With regard to the results of previously performed toxicicologic
studies, the submitter stated that polypropylene resin (powdered
form, room temperature) is non-toxic via acute oral administra-
tion to rats (LD50 in excess of 5 g/kg), is not a primary rabbit
skin irritant, and is slightly to moderately irritating to the
eyes of rabbits. The submitter also noted that "it has been well
documented in the literature that the heating of polypropylene in
air to greater than 350°C will form lethal concentrations of
toxic gases, including carbon monoxide and short-chain, highly
irritating aldehydes such as acrolein and crotonaldehyde." In
addition, the submitting company reported that the ethoxylated
tallow amine and a 75% ethoxylated tallow amine/25% polyethylene
resin mixture were shown in previous studies to be "toxic by
ingestion (oral LD50 in rats is approximately 1-2 g/kg)~ and are
severe eye and skin irritants, with probable corrosive effects."
The 'company also submitted a copy of a paper entitled "Further
Investigations into the Relative Toxicity of Decomposition Pro-
ducts Given Off from Smoldering Plastics" (Hofmann, H. Th. and
Sand, H.; JFF/Combustion Toxicology; Vol. 1; pg. 250-8; 1974).
In conclusion, the submitting company stated that the results of
the acute inhalation toxicity testing of the polypropylene/bis-2-
hydroxyethyl-tallow amine mixture "show that highly irritating
compounds become airborne when the test material is heated to
190°-210°C" and hypothesized that "some form of hydrocarbon is
carrying [bis-2-hydroxyethyl-tallow amine], a known, severe irri-
tant, into the lungs of the test animals." The submitter also
stated that "decreasing the oxidation and degradation of the mix
was shown to decrease the toxicity of the generated atmosphere."
Submission Evaluation
Based on a review of the submitted summarized results, it is
apparent that, as the submitter stated, oxidation/degradation of
the mixture of polypropylene and bis-2-hydroxyethyl-tallow amine
renders the heat-generated vapors extremely toxic upon inhala-
tion. It should be noted that the darkened areas of the lungs
observed in one of the rats in the final acute inhalation study
may have represented hemorrhage or focal congestion and may not
have been the result of the heat-generated vapor of the mixture;
such areas are often observed during necropsy of rats. Complete
copies of the final reports from the three inhalation studies,
including test protocols and data, should be obtained in order to
evaluate better the reported toxicologic findings.
Current Production and Use
The submitting company stated that it currently manufactures
several products grouped under a single product name (name was
claimed as TSCA CBI) which are sold for use as antistatic agents
in formed plastic articles (e.g., bottles and films). The sub-
mitter reported that these "antistat" products are composed of
either an ethoxylated amine (e.g., ethoxylated tallow amine or
ethoxylated cocoamine), or a combination of such ethoxylated
amines and a plastic resin (e.g., polypropylene or polyethylene).
46
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8EHQ-0583-0479 S
Page 5 of 6
The submitting company stated that the mixed product is prepared
by beating 1 part polypropylene and 3 parts ethoxylated tallow
amine to l80-210°C (220°C maximum) for 4 hours under a carbon
dioxide or nitrogen "blanket" in order to reduce oxidation and
degradation. The submitter reported that during this process, a
homogeneous melt is formed, cooled, and "converted to pellets
that are added to the plastics to be antistat treated."
The submitter reported that in molding operations, the antistat
products are mixed (in an extruder) with melted plastic resins at
200°C "to levels ranging from 0.1% to 0.3% ethoxylated amine
relative to total batch size" for 1 to 2 minutes prior to the
molding and cooling phases of the process. The submitter stated
that the extruder is basically considered to be a closed system.
The use of the antistat product in plastic film production is re-
ported to be similar to the above described molding operation ex-
cept that the final plastic product is a thin plastic sheet as
opposed to a molded plastic article.
A review of the production range (includes importation volumes)
statistics for polypropylene (CAS No. 9003-07-0), which is listed
in the initial TSCA Inventory, has shown that between 704 million
and 2.94 billion pounds were reported as produced and/or imported
in 1977. A review of the production range (includes importation
volumes) statistics for bis-2-hydroxyethyl-tallow amine (CAS No.
61791-44-4), which is also listed in the initial TSCA Inventory,
has shown that between 11 thousand and 111 thousand pounds were
reported as produced and/or imported in 1977. It should be noted
that this production range information does not include any pro-
duction/importation data claimed as confidential by the person(s)
reporting for the initial TSCA Inventory, nor does it include any
information which would compromise TSCA Confidential Business In-
formation. The data submitted for the TSCA Inventory, including
production range information, are subject to the limitations con-
tained in the Inventory Reporting Regulations (40 CFR 10).
Comments/Recommendations
In its submission, the company stated that alth~ugh its current
Material Safety Data Sheet (MSDS) contains a warning to "Avoid
Inhalation of Vapors Generated During Processing," plant person-
nel and customers were being notified about the reported findings
in order to re-emphasize "the need to minimize exposure to any
vapors generated during manufacture and processing."
The Chemical Hazard Identification Branch (CHIB/AD/OTS) recently
prepared a DRAFT Chemical Hazard Information Profile (CHIP) on
acetaldehyde. The acetaldehyde monitoring information presented
in this submission will be considered for inclusion in that CHIP.
a) The Chemical Hazard Identification Branch will request the
submitting company to provide complete copies of the final
reports (including protocols and data) from each of the
acute rat inhalation studies cited in the submission.
47
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8EHQ-0583-~419 S
Page 6 of 6
b) The Chemical Hazard Iaentification Branch-will screen tl~
submitted ~nformation in order to determine. if further OTS
assessment of the reported findings is warranted.
c) The Chemical Hazard Identification Branch will transmit a
copy of this status report to NIOSH, OSHA, CPSC, OW/EPA,
OSVJER/EPA, OANR/EPA, and ORD/EPA... A copy Gf this report
will also be sent to the TSCA Assistance Office (TAO/OTS)
for appropriate distribution.
48
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
SUIJ£CT. Status Report*
8EHQ-0683-0480
8EHQ-0683-0480
Page 1 of 3
App:-oved f:1fi~ '7fi:r
DATE:
!!t
6 rqr.n
,.01& Justine L. welQuJam Leader
'Chemical select~n-and Profiles
TDPrank D. Kover, Chief
'Chemical Hazard Identification
Team/CHIB
Revision
Needed
Branch/AD
Submission Description
Exxon Company, U.S.A. provided summarized interim results from an
ongoing chronic mouse skin-painting study of a mineral seal oil
product (Mentor@28). The submitter reported (by phone) that
Mentor@28 is a chemically neutralized middle petroleum distillate
(CAS No. 64742-30-9). According to Exxon, 25 microliters of the
product have been applied 3 times per week for over two years to
the skin of 50 C3H male mice. The company reported that as of
May 16, 1983 (756th day of th~ study), only 6 Mentor@28-treated
mice remained alive. Exxon stated that the study is expected to
continue for another 10 to 12 weeks or until the last animal has
died. Exxon Company, U.S.A. reported that as of May 16, 1983,
8/50 Mentor@28-treated mice had been observed (grossly) to have a
skin tumor (a total of 3 papillomas and 5 carcinomas). In addi-
tion to the summarized interim results, the company submitted
physical/chemical data, ultraviolet (UV) inspection data, and
product information for Mentor@28.
Submission Evaluation
Although Exxon Company, U.S.A. did not submit any information
about negative (or positive) controls, it can be inferred from
the summarized information that was provided that the tested
material does possess some degree of oncogenic activity toward
mouse skin. According to Exxon, the final report (which should
contain the study protocol(s) and data) will be completed and
submitted to EPA in the latter part of 1984.
Current Production and Use
According to the TSCA Inventory, a chemically neutralized middle
petroleum distillate (CAS No. 64742-30-9) is defined as a complex
combination of hydrocarbons produced via a treating process to
remove acidic materials. The hydrocarbons have carbon numbers
predominantly in the range of Cll through C20 and boil in the
range of "approximately 4010p to 653°p (205°C to 345°C).
*NOTE: This status reDo~t is the result of a Drelirnina~v
staff evaluation of information submitted to EPA. State;ents
made herein are not to be re~arded as ex~ressinc final
Agency policy or intent with.res?ec~ to t~is particular
chemical. .~y review of the status report should take into
consideration the fact that it mav be based on incomolete
information. . -
49
E~& '0". 11»-6 UICY. ..",
-------
".
8EHQ-0683-0480
Page 2 of 3
. , , : . - .'
/~':3[-iil{Gt~VJi~- dil2-:-dfhe production range (includes importation volumes)
'~€h~i~~ for chemically neutralized middle petroleum distil-
lates (CAS No. 64742-30-9), which are listed in the initial TSCA
Inventory, has shown that over 6.7 billion pounds 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 that would compromise TSCA Con-
fidential 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 provided product information, Mentor@28 can be
used in a variety of industrial and household products. The in-
dustrial applications of Mentor@28 were reported to include its
use as a base oil in tanning liquors for leather, as a vehicle
for colored inks (e.g., heat-set inks) in newspaper printing, as
a medium for chemical and vapor recovery systems, as a cordage
oil for spraying and coating of light-colored twine and rope, as
an instrument standardization oil, as a plasticizer for certain
specialty resins, and as a replacement for diesel fuel (and other
hydrocarbon streams) in oil drilling mud formulations. Household
applications of Mentor@28 were reported to include the product's
use as a base or diluent in disinfectants, germicides, polishes,
cleaning compounds and cleaning solvents.
In addition, Exxon Company, U.S.A. reported that some of the
chemically neutralized middle petroleum distillate is marketed as
Somentor@43, a product which is used principally as a base oil
for surface lubrication in the rolling of aluminum sheets into
foil stock that may come into contact with foods.
Comments/Recommendations
Exxon Company, U.S.A. reported that all Mentor@28 and Somentor@43
customers of record and the U.S. Food and Drug Administration
(FDA) are being notified about the interim chronic mouse skin-
painting results.
EPA's Office of Toxic Substances (OTS) has received and
many other TSCA Section 8(e) and "For Your Information"
sions that have contained toxicity/exposure information
variety of petroleum process streams/products.
evaluated
submis-
on a wide
a) The Chemical Hazard Identification Branch (CHIB/AD/OTS)
will request the Exxon Company, U.S.A. to ensure that the
Agency is ~pprised of any new and/or significant toxico-
logic results from the company's ongoing chronic mouse
skin-painting study of Mentor@28 and to ensure that the
final report, when submitted, contains complete copies of
the study protocol(s) and all data obtained. In view of
EPA's general interest in company actions that are taken
on a voluntary basis in response to toxicity/exposure
50
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8EHQ-Q683-Q48Q
Page 3 of 3
infqrmation, Exxon Company, U.S.A. wili also be requested
to describe the actions it has taken to warn Exxonoworkers
and to reduce and/or eliminate expos~~e ,to the chemically
neutralized middl~ petroleum distillate.
b) The Chemical Hazard Identification Branch will screen the
reported information in order to determine if further OTS
assessment of the chemically neutralized middle petroleum
~-distillate is warranted at tne present time.
c) The Chemical Hazard Identification Branch will provide a
copy of this status report to NIOSH, OSHA, CPSC, FDA, NTP,
OW/EPA, OSWER/EPA, OANR/EPA, ORD/EPA, and OPP/OPTS/EPA. A
copy of this report will also be sent to the TSCA Assis-
tance Office (TAO/OT5/EPA) for appropriate distribution.
51
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
JlIL I 5 1983
8EHQ-0683-048l
Page 1 of 3
SUIJICTI
Status Report*
8EHQ-0683-0481
Approved
01fl- "/11/
nOMa
Justine L. Wel~~m Leader
Chemical selecyY6n and Profiles
Frank D. Kover, Chief
Chemical Hazard Identification
Revision
Needed
Team/CHIB
TOI
Branch/AD
Submission Description
(Se~ ~ on Page 3 of this report)
The Phillips Petroleum Company submitted copies of Standard
Operating Procedures (SOPs) and results from several in vitro
genotoxicity studies of 1,2-ethanedithiol (CAS NO., 26914-40-9).
According to the submitter, the chemical was found to be negative
in an Ames Salmonella typhimurium (bacteria) assay both in the
presence and absence of exogenous metabolic activation. The
submitter also reported that 1,2-ethanedithiol was found to be
positive (without metabolic activation) and negative (with
metabolic activation) in a Mouse Lymphoma Cell Forward Mutation
Assay. In addition, the company reported that the chemical was
found to cause an increased incidence of Sister Chromatid
Exchanges (SCEs) in cultured Chinese Hamster Ovary (CHO) cells.
Submission Evaluation
Considering that Standard Operating Procedures (SOPs) do not
detail actual observations or protocol changes made during the
performance of toxicologic tests, the submitted SOPs are of only
limited value for evaluating the reported in vitro findings. In
the absence of complete copies of the fina~reports (including
the actual study protocols and all data), it is not possible at
this time to verify the accuracy of the reported results. It
should be noted that the Phillips Petroleum Company submission
did not contain any experimental details for the performed SCE
assay in cultured Chinese Hamster Ovary (CHO) cells. The sub-
mission also contained a detailed SOP, but no experimental data,
for an Escherichia coli (bacteria) microsuspension assay for DNA
damage.
According to a provided Material Safety Data Sheet (MSDS), i,2-
ethanedithiol is a clear, combustible liquid with a pungent,
nauseating odor. The MSDS indicates that over-exposure to vapors
of the chemical can cduse "generalized weakness, diarrhea, clonic
*NOTE: This status report is the result of a preliminary
staff evaluation of ir.forrnation submitted to EPA. Stacements
mace herein are not to be regarded as expressing final
Agency policy or intent with res?ec~ to t~is particular
chemical. .~y review of the status repor~ should take into
consideration the fact that it may be based on incomplete
informa tion.
52
E~' '0"'. IIZI)o.6 '''cv. ~'"
-'
-------
8EHQ-0683-048l
J?ag~ 2 of 3
convulsions, lacrymation, tremors, narcosis, [and] increased res-
piratory rate." It should be noted that 1,2-ethanedithiol is a
very close structural analog to ethanethiol (ethyl mercaptan), a
highly toxic chemical with a very strong, penetrating odor which
is used as an odorant in natural gas..
Current Production and Use
(S~ NOTE on Page 3 of this report)
A review of the production range (includes importation volumes)
statistics for ethanedithiol (CAS No. 26914-40-9), which if>
listed in the initial TSCA Inventory~ has shown that no 1977 pro-
duction/importation was reported or that'all 'of the production
range data reported were claimed as TSCA Confidential Business
Information (CBI) by the manufacturer(s) and/or importer(s) and
cannot be disclosed (Section 14(a) of TSCA, U.S.C. 2613(a». All
of the data submitted for the initial TSCA Inventory, including
the production range information, are subjec~ to the limitations
contained in the Inventory Reporting Regulations (40 CPR 710).
Although the Phillips Petroleum Company did not provide any use
information for 1,2-ethanedithiol, the company did state that the
chemical is not marketed to the public. The submitting company
also stated that exposure to the chemical is minimal because the
"odor mandates that it be produced, stored, transported, and con-
sumed in enclosed systems." No information concerning the use of
1,2-ethanedithiol was located in the secondary literature sources
consulted.
Comments/Recommendations
The Phillips Petroleum Company stated that the 1,2-ethanedithiol
Material Safety Data Sheet (MSDS) had been revised to reflect the
reported in vitro findings and had been transmitted to all 1,2-
ethanedithiol customers and to all of the submitter's facilities
that handle the chemical.
It should be noted that although a positive in vitro result, when
considered alone, may not be sufficient to offer reasonable sup-
port for a conclusion of substantial risk, EPA does believe that
in vitro studies do provide valuable data that can aid in the as-
sessment of possible hazards/risks posed by chemicals to health
and/or 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 studies with the re-
sults of such studies considered for possible submission to EPA
pursuant to Section 8(e) of TSCA.
a) The Chemical Hazard Identification Branch (CHIB/AD/OTS)
will request the Phillips Petroleum Company to provide EPA
with complete copies of ~he full final reports (includi~g
actual experimental protocols and all data) from the in
vitro Ames, Mouse Lymphoma, Bacterial DNA Damage, and:SCE
53
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8EHQ-0683-048l
Page 3 of 3
assays cited in its submission. In view of the Agency's
general interest in company actions that are taken on a
voLuntary basis in response to chemical toxicity/exposure
information, the Phillips Petroleum Company will also be
asked if it is conducting, or plans to conduct, additional
studies designed to further define the toxicity of 1,2-
ethanedi thiol.
b) The Chemical Hazard Identification Branch will screen the
reported information in order to determine if further OTS
assessment of 1,2-ethanedithiol is warranted.
c) The Chemical Hazard Identification Branch will transmit
copies of this status report to NIOSH, OSHA, CPSC, FDA,
NTP, OW/EPA, OSWER/EPA, OANR/EPA, ORD/EPA, and OPP/OPTS/-
EPA. A copy will also be sent to the TSCA Assistance
Office (TAO/OTS/OPTS) for appropriate distribution.
NOTE: In a supplemental submission dated November 22, 1983, the
Phillips Petroleum Company stated that the CAS Registry Number
for 1,2-ethanedithiol was 540-63-6 and not 26914-40-9 as had been
reported by the company in its initial TSCA Section 8(e) sub-
mission. A review of the production range (includes importation
volumes) statistics for l,2-ethanedithiol (CAS No. 540-63-6),
which is listed in the initial TSCA Inventory, has shown that no
1977 production/importation was reported or that all the produc-
tion range data reported were claimed as Confidential Business
Information (CBI) by the manufactu~er(s) and/or importer(s) and
cannot be disclosed (Section 14(a) of TSCAi D.S.C. 2613(a». All
of the data submitted for the initial TSCA Inventory, including
the production range information, are subject to the limitations
contained in the Inventory Reporting Regulations (40 CFR 710).
In its November 22, 1983 submission, the Phillip Petroleum
Company also s~ated that the company was going to correct the 2AS
Registry Numbe~ in its 1,2-ethanedithiol Material Safety Data
Sheet (MSDS) and any other company information relating to this
substance.
54
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UNITED STATES ENY I~ONMENTAL PROTECTION AGENCY
DAn:
JUL 2 0 {g8~
8EHQ-0683-0482
Page 1 of '-'4
'IOMI
Justine L. Wel~am Leader
Chemical selec~on and Profiles
Frank D. Kover, Chief
Chemical Hazard Identification
Team/CHIB
~ pproved t:Jht-- "1/ ,;z..,t
Revision
Needed
IUIJIC:T,
Status Report*
8EHQ-0683-0482
TO:
Branch/AD
Submission Description
The International Coal Refining Company (ICRC) submitted complete
copies of the final reports (including experimental protocols and
data) from a series of short-term in vitro genotoxicity and acute
in vivo toxicity studies of severar-solvent-refined coal (SRC-I)
products, process intermediates, and/or wastes produced by U.S.
Department of Energy (DOE) pilot plants in Ft. Lewis, Washington
and Wilsonville, Alabama. ICRC reported that it is und€r a DOE
contract to develop the SRC-I technology and to design an SRC-I
"demonstration" plant. The company also reported that the SRC-I
technology program includes an ongoing and comprehensive toxicity
testing program which includes short-term in vitro genotoxicity
studies and acute, sub-chronic, and chroniC-in vivo studies of
the SRC-I materials. The results of the short-term in vitro and
acute in vivo studies that were reported in the present submis-
sion are summarized in Tables 1. and 2., respectively of this
status report.
The International Coal Refining Company stated that both "ICRC
and DOE are aware of the hazards that may be associated with
coal-derived materials and, as a matter of routine practice, use
and insist on the use of stringent precautions in their manufac-
ture, transportation and testing." In addition, ICRC provided
copies of several SRC-I Material Safety Data Sheets and SRC-I
product shipping labels.
In the cover letter to its submission, ICRC stated that the
results obtained from the ongoing/planned SRC-I toxicity testing
studies "are expected to be useful in future process/product
safety optimization work, in the design of worker health protec-
tion programs, and in the preparation of needed premanufacturing
notifications (PMN'sypursuant to the provisions of Section 5(a)(1)
of TSCA." ICRC also stated that both the company and DOE are com-
mitted to insure that the SRC-I process technology "is developed
in an environmentally responsible manner."
-NOTE: T~is status report is the result of a Drelirninarv
staff eva~uatior. of i~fo~ation submittec to EPA. State;'ents
mace here~n are no~ to be regarded as e~~ressir.o final
Agen:y poli~y or intent with res?ec~ to t~is particular
chem~cal. ..~y rev~ew of the status report should take into
~ons~de~~t~on the tact that it may be based on incomo'et~
1nformat1on. .- ~
55
EP. '0"''' II~ uu:v. ..,,,
-------
TABLE 1. SHORT-TERM IN VITRO RESULTS
TEST MATERIAL AMES TEST MOUSE LYMPHOMA ASSAY
ACTIVATION WIO ACTIVATION ACTIVATION WIO ACTIVATION
SRC Middle Distillate Negative Negative positive Negative
(CAS No. 68911-57-9)
TSL* Middle Distillate NR** NR** positive positive
(CAS No. Unknown)
SRC Solid Fuel positive Negative positive positive
(CAS No. 68409-94-9)
U1 (DMSO Extract)
CJ'\
TSL* Solid Fuel positive Negative Positive positive
(CAS No. Unknown)
(DMSO Extract)
Ash Concentrate NR** NR** positive Negative
(CAS No. 68131-74-8)
(Saline Extract)
Ash Concentrate NR** NR** positive Negative
(CAS No. 68131-74-8)
(DMSO Extract)
co
'UtrJ
Pi ::r:
\.010
(1) I
o
tV CJ'\
co
o W
HlI
o
~~
co
tV
*
ICRC reported (by phone) that TSL pertains to "Two Stage Liquefaction"
**
No results reported
-------
TABLE 2.
ACUTE IN VIVO RESULTS
TEST MATERIAL
ORAL LD50
SENSITIZATION
SKIN IRRITATION
EYE IRRITATION
(RATS)
(RABBITS)
(GUINEA PIGS)
(RABBITS)
SRC Middle Distillate
(CAS No. 689ll-57-9)
NR**
probable
4-5 gjkg
moderate (washed)
severe (unwashed)
TSL* Middle Distillate 4-7 gjkg NR** NR** probable
(CAS No. unknown)
Ul
--.J SRC Light Oil (Naphtha) NR** (washed) moderate (intact) marked
severe
(CAS No. 68476-79-9) severe (unwashed) moderate (abraded)
TSL* Solid Fuel
(CAS No. Unknown)
NR**
NR**
NR**
positive
* ICRC reported (by phone) that TSL pertains to "Two-Stage Liquefaction"
** No results reported
co
1iJM
PJ ::r:
lQIQ
(!) I
o
W0'
co
o Lv
}-f11
o
01::- 01::-
co
tV
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8EHQ-0683-0482
Page 4 of 4
Submission Evaluation
In general, the submitted short-term in vitro results show that
the tested SRC-I materials possess varying degrees of mutagefiic
activity in bacteria and in mammalian (mouse) cells in culture.
The results of the acute in vivo toxicity studies indicate that
the tested SRC-I materialS-can be toxic (although not extremely
toxic) upon oral administration, can be irritating (in some sases
severely) to the eyes, can be moderately irritating to the skin,
and can provoke varying degrees of skin sensitization reactions.
Further evaluation of the toxic properties of these (and possibly
other) SRC-I products, process intermediates, and wastes will be
possible when EPA receives complete copies of the final reports
(including protocols and data) from the ongoing/planned short-
term in vitro genotoxicity and acute, sub-chronic, and chronic
in vivo studies.
--
Current Production and Use
In its submission, the International Coal Refining Company stated
the "current use of SRC-I materials, in addition to being care-
fully controlled, is limited to research and testing purposes at
a limited number of research and testing facilities."
Comments/Recommendations
In the cover letter to its TSCA Section 8(e) submission, the
International Coal Refining Company stated that positive results
that may be obtained as the SRC-I toxicity testing program con-
tinues will be submitted to EPA to supplement the toxicologic
data already provided. The submitter also stdted that "in late
1983 and early 1984, ICRC expects to publish for DOE a series of
reports on the short-term portions of the overall program."
EPA's Office of Toxic Substances (OTS) has received and evaluated
a number of TSCA Section 8(e) and "For Your Information (FYI)"
submissions containing toxicologic and/or exposure information on
a variety of coal, shale, and petroleum oil products, process in-
termediates, and/or waste materials.
a)
The Chemical Hazard Identification Branch (CHIB/AD/OTS)
will screen the reported information in order to deter-
mine if further OTS assessment of the subject coal-
derived materials is warranted at the present time.
b)
The Chemical Hazard Identification Branch will transmit
copies of this status report to NIOSH, OSHA, CPSC, NTP,
DOE, OW/EPA, OSWER/EPA, OANR/EPA, ORD/EPA, CCD/OTS, and
HERD/OTS. A copy of this status report will also be
provided to the TSCA Assistance Office (TAO/OTS/OPTS)
for appropriate distribution.
58
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
SUIJ£C:T. Status Report *
8EHQ-0683-0483 S
8EHQ-0683-0483 S
Page 1 of 8
App=ove~ ~
8-/"
,
DAT£.
JlLG I 9 1983
fiOM. Just~ne~Aielc~, Team Lead~r
ChemlCa~<31ectlon and Proflles Team/CHIB
Revision
Needed
Frank D. Kover, Chief
TOI Chemical Hazard Identification Branch/AD
Note
The submitting company has claimed its name and the name of the
company sponsoring the reported studies to be TSCA Confidential
Business Information (CBI). Although the submitter originally
claimed the actual identities of the two tested chemicals to be
TSCA C8I, the company later reported non-contidentially that one
of the tested chemicals was ethylene diamine tetra (methylene
phosphonic ac id). According to Volume I I of EPA' s 'TSCA Chemical
Substances Inventory, ethylene diamine tetra (methylene phos-
phonic acid) has the following CAS Registry Number: 1429-50-1.
For the purposes of this status report, ethylene diamine tetra
(methylene phosphonic acid) will be referred to as EDTMPA. In
addition, it should be noted that in two of the submitted tox-
icity studies (one range-finding study and one chronic study),
EDTMPA was tested in combination with the second chemical, the
identity of which remains confidential (TSCA CB1). For the pur-
,?oses of this status report, the second chbldcal will be referred
to a6 Chemical X.
Submission Description
The submitting company provided the final reports from four 1-
month range-finding studies (two in rats and two in mice) and
interim reports with protocols from three ongoing chronic gavage
studies (two in rats and one in mice). In addition, the company
submitted several memoranda that present additional information
with regard to the ongoing chronic studies. The submitter stated
that the subject studies were sponsored by a company that was
considering th~ purchase of EDTMPA from the submitter for use in
a new application. According to several of the submitted experi-
mental protocols, an oral (gavage) route of exposure was selected
for the performed studies because this route will approximate
human exposure to the chemical(s).
-NOTE: This sta~us reco=t is the resul~ of a prelimina=v
... ..
staff- eva lua tior. of ir: forma tion submi tt~c to EPA. 5 ta t:e!:1e!'lt:s
mace herein are no~ to be regarded as ex?ressing final
Agen~y policy or intent with res?ec~ to ~his particular
chemical. .~v review 6f the status recor~ should take into
-consideration-the fact that it mav be based on incomclet~
information. - .
59
E~& '0". IJ~ '''EY. ~'"
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8EHQ-06'83-0483 S
Page 2 of 8
The four I-month range-finding studies were conducted in order to
determine the appropriate dose levels to be used in the chronic
studies. In the first I-month study in rats, Sprague-Dawley rats
(5 animals/sex/group) were reported to have been dosed by gavage
(gastric intubation) for 28 consecutive days with EDTMPA (aqueous
solution) at doses of 0 (distilled water), 15, 150, 350, or 500
mg/kg body weight. The abstract contained in the final report of
this I-month study in Sprague-Dawley rats presented the following
information:
"No deaths occurred during the course of the study, nor were
there any daily observations which indicated toxicity related
to administration of [EDTMPA]. There were no changes in body
weights, food consumption, or mean hematological and urine
parameters which indicated any test article-related toxicity.
A statistically significant increase in alkaline phosphatase
levels was noted in male rats dosed at a level of 500 mg/kg
body weight. Alkaline phosphatase levels were also increased
in female rats at the same dosage level, however, the in-
crease was not statistically significant when compared to the
control level. No test article-related gross pathological
effects were observed in any animal. A subtle difference in
the histological appearance of the femur was evident between
control animals and those exposed to the test article at the
high-dose level (500 mg/kg BW), however, the variation was
not considered a definite pathological effect related to ex-
posure to the test compound."
In the second I-month range-finding study in rats, Charles River
CD rats (5 animals/sex/group) were reported to have been dosed by
gavage for 27 consecutive days with an aqueous solution of EDTMPA
in combination with Chemical X. The tested EDTMPA:Chemical X
dose ratios were reported to be: 0:0 (distilled water controT)i
15:1.2 mg/kg/day (Group T-I)i 75:5.7 mg/kg/day (Group T-II)i
150:11.4 mg/kg/day (Group T-III)i or 350:26.6 mg/kg/day (Group T-
IV). The following information was contained in the abstract of
the final report of the I-month study in Charles River CD rats:
"Histopathology studies performed on the femur and costochon-
dral junction revealed an osteodystrophy of the rachitic type
in all rats in the T-IV group, four of five female T-III rats
and three of four male T-III rats sacrificed at the termina-
tion of the study. No histopathologic lesions were detected
in the femur or costochondral junctions of T-II, T-I and Ve-
hicle Control rats. These dystrophic lesions were interpre-
ted as related to the test article administration. Gross
lesions in other organs were of the naturally occurring type
and of a severity normally expected in laboratory rats of
this age."
[According to the Clinical Chemistry Determinations section
of the final report, "no noteworthy or statistically signifi-
cant differences were observed in the alkaline phosphatase
da ta . II ] .
60
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8EHQ-0683-0483 S
Page 3 of 8
With regard to the first I-month study in mice, it was reported
that EDTMPA "was administered orally via gavage to 80 B6C3Fl mice
(lU/sex/group) at dose levels of [0 (distilled water)], 25, 75,
150 and 300 mg/kg/day." The following information was contained
in the abstract of the submitted final report:
"Alkaline phosphatase measurements at termination in control
and high-dose (Group V) animals revealed a 36%-45% increase
in Group V animals of both sexes as compared to their respec-
tive control groups. These data suggest a treatment-related
effect on this enzyme, although insufficient data are avail-
able to make a firm conclusion.... Chostochondral osteodys-
trophy was observed in treated males and females from Groups
III [7~ mg/kg] (3/10 males; 2/9 females), IV [150 mg/kg] (6/-
10 males; 4/10 females) and V [300 mg/kg] (9/10 males; 6/9
females). This finding was considered to be minimal in af-
fected animals from Group III and minimal to moderate in
those from Groups IV and V. One male from Group IV and two
males and two females from Group V which showed chostochon-
dral osteodystrophy also showed mild femoral osteodystrophy."
In the second I-month range-finding study conducted in mice, it
was reported that EDTMPA "was administered orally via gavage to
40 B6C3Fl mice (lO/sex/group) at dose levels of [0 (distilled
water vehicle control)], 500 and 750 mg/kg/day." The following
information was contained in the abstract of the final report:
"Dose-related elevations in serum alkaline phosphatase val-
ues, considered attributable to test material administration,
were seen at Week 4. Values for treated animals of both
sexes were 34-41% (low dose) and 74-77% (high dose) higher
than control values. Microscopic examination of bone (femur
and costochondral junction) from [EDTMPA]-treated animals
revealed osteodystrophy, which was attributed to test materi-
al administration and was characterized by variable increases
in the thickness of the epiphysial plate, persistent carti-
lage in the underlying spongiosa, osteoid deposition and per-
iosteal hyperosteosis. Femoral osteodystrophy occurred in 4
of 10 males and 3 of 7 females in the low-dose group and 8 of
10 males and 9 of 10 females in the high-dose group; [the]
changes were considered minimal at the low dose and minimal
to moderate at the high dose. Costochondral osteodystrophy
occurred in 9 of 10 males and 8 of 8 females in the low-dose
group and 9 of 9 males and 9 of 9 females in the high-dose
group; [the] changes were considered to be minimal to mild at
the low dose and mild to moderate at the high dose."
The charts on the following page summarize the dose levels that
were selected (based on the toxicity observed in the I-month
range-finding studies) for the ongoing 24-month and 30-month
gavage studies in rats and the ongoing 18-month gavage study in
mice. It should be noted that EDTMPA is being administered in
combination wi th Chemical. X in the ongoing 24-month study in
Charles River CD rats.
61
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8EHQ-0683-0483 S
Page 4 of 8
Ongoing Chronic Gavage Studies in Rats and Mice
A.
24-Month Gavage Study (Charles River CD Rats)
Group - Dose
o (Distilled Water Control)
15 mg EDTMPA : 1.2 mg X/kg/day
75 mg EDTMPA : 5.7 mg X/kg/day
150 mg EDTMPA :11.4 mg X/kg/day
Males
45
40
40
40
Females
45
40
40
40
B.
3D-Month Gavage Study (Sprague-Dawley Rats)
Group - Dose
o (Distilled Water Control)
15 mg EDTMPA /kg/day
50 mg EDTMPA /kg/day
150 mg EDTMPA /kg/day
C.
18-Month Gavage Study (B6C3F, Mice)
Group - Dose
o (uistilled Water Control)
15 mg EDTMPA /kg/day
75 mg EDTMPA /kg/day
Males
60
60
60
60
Males
85
85
85
Females
60
60
60
60
Females
85
85
85
The 6-month interim report from the 30-month gavage study in
Sprague-Dawley rats stated that no toxicologically significant
effects had been observed following 26 weeks of dosing. The 6-
month interim report from the 24-month gavage study in Charles
River CD rats stated that osteodystrophy had been observed
microscopically in the high dose groups. However, according to
memoranda dated approximately twelve months after the starting
dates of the two chronic gavage studies in rats, osteogenic sar-
comas were reported to have been observed in the rats in both the
24- and 3D-month studies. The charts on the following page sum-
marize the incidences of osteogenic sarcomas reportedly observed
approximately one year into the ongoing chronic gavage studies in
rats.
62
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8EHQ-0683-0483 S
Page 5 of 8
Re~orted Incidence of Osteogenic Sarcoma in Rats
A.
24-Month Gavage Study (Charles River CD Rats)
Group - Dose
Males
o (Distilled Water Control)
15 mg EDTMPA: 1.2 mg X/kg/day
75 mg EDTMPA: 5.7 mg X/kg/day
150 mg EDTMPA:ll.4 mg X/kg/day
0/45
0/40
1/40
6/40
Females
0/45
0/40
0/40
0/40
B.
30-Month Gavage Study (Sprague-Dawley Rats)
Group - Dose
Males
o (Distilled Water Control)
15 mg EDTMPA /kg/day
5U mg EDTMPA /kg/day
150 mg EDTMPA /kg/day
(330 mg/kg*)
0/60
0/60
1/60
5/60
Females
0/60
0/60
0/60
1/60
* The 15U mg/kg daily dose was increased to 330 mg/kg on
February 14, 1983 (approximately 10 months into study)
In one of the submitted memoranda concerning the 30-month chronic
gavage study, it was stated that EDTMPA was believed to be the
most likely causative agent of the observed osteosarcomas.
According to the submitted 6-month interim report of the 18-month
EDTMPA gavage study in mice, no osteosarcomas had been observed.
In addition, the submitter provided a memorandum stating that
there was no evidence of osteogenic sarcoma observed in mice by
the eleventh month ot the study.
Submission Evaluation
In view of the fact that EDTMPA reportedly induces osteogenic
sarcomas (as discussed below) in both Sprague-Dawley and Charles
River CD rats, it is of particular interest that in the I-month
range-finding study using Sprague-Dawley rats, EDTMPA at a dose
of 500 mg/kg was found to bring about a statistically significant
increase in the serum alkaline phos~hatase levels in male rats.
Alkaline phosphatase plays a key role in the deposition of phos-
phorus in bone metabolism. Increased alkaline phosphatase levels
were also seen at the same EDTMPA dose level in female Sprague-
Dawley rats, but the increase was not statistically significant.
Paralleling this lesser effect on alkaline phosphatase in the fe-
males, EDTMPA (at the highest dose tested) was reported to show
63
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8EHQ-0683-0483 8
Page 6 of 8
some (albeit very weak) tumorigenic effect toward the bone in one
of the female Sprague-Dawley rats in the ongoing 30-month gavage
study. The observed disturbance of bone metabolism by EDTMPA is
consistent with the histopathologic observation of osteodystrophy
(i.e., defective de novo bone formation) in Charles River CD and
Sprague-Dawley rats of both sexes, as well as with the tissue-
s~ecific tumorigenic effect.
EDTMPA was also reported to bring about a dose-related elevation
of serum alkaline phosphatase levels, as well as osteodystrophy,
in mice in both I-month range-finding studies. Although no con-
clusion can be made at this time relative to the tumorigenic
~otential of EDTMPA toward mouse bone, it should be noted that
there is a consistency in both rats and mice for the observed
enzymological (alkaline phosphatase) and histopathological
(osteodystrophy) effects. Due to the tact that the latency per-
iod for tumorigenesis by a given chemical agent may be notably
different in different species, it is possible that EDTMPA may
possess tumorigenic potential toward mouse bone. However, this
potential may become manifest only after a sufficiently prolonged
period of administration and/or by using other inbred strains of
mice. It should also be borne in mind that the actual observa-
tion periods (11-12 months) at this stage of the studies corres-
pond to only about one-half of the life span of the two species.
The preliminary results provided thus far for the ongoing 24-
month and 30-month rat studies indicate that the incidence of
EDTMPA-induced osteogenic periosteal sarcomas is dose-dependent.
Furthermore, the bone tumor incidence does not appear to be in-
fluenced by combination with Chemical X (in the 24-month study).
This dose-dependence lends support to the reliability of the
ongoing studies, although it would also be useful to know the
purity of the tested materials and the chemical identity of any
impurities. Considering that the reported tumor incidences re-
sulted from actual administration periods corresponding to only
about one-halt of each species life-span, the possibility exists
that EDTMPA may represent a significant carcinogenic hazard.
However, a more complete evaluation of the carcinogenic potential
of ~DTMPA and the EDTMPA:Chemical X mixture must await EPA's
receipt of complete copies of the final reports from each of the
chronic gavage studies. It would also be of interest to know the
effect (if any) of EDTMPA exposure on fetal bone development.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for EDTMPA (CAS No. 1429-50-1), which is listed in the
initial TSCA Inventory, has shown that no 1977 production/impor-
tation was reported or that all of the production range data re-
ported were claimed as confidential by the manufacturer(s) and/or
importer(s) and cannot be disclosed (Section 14(a)i T8CAi U.8.C.
2613 (a)). The data submitted for the TSCA Inventory, including
production range information, are subJect to the limitations con-
tained in the TSCA Inventory Reporting Regulations (40 CPR 710).
64
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8EHQ-0683-0483 S
Page 7 of 8
According to the submitter, EDTMPA is manufactured by another
company (identity claimed as TSCA CBI) and is marketed by the
submitter in wet cake form. Although recent production/sales
data were claimed as TSCA CBI, the submitter did report that "in
1983, sales are expected to be lower [than in 1982]." The sub-
mitter also reported that "of the material sold in the United
States, approximately one-third is used as a stabilizer in hydro-
gen peroxide, one-third is used by the precious metals industry
in plating applications, and one-third is used in miscellaneous
applications principally in metal chelating applications."
Other than the statements contained in several of the submitted
experimental protocols that the oral route would approximate
human exposure, the submission did not present any information
with r~gard to the sponsoring company's actual or proposed use of
EDTMPA. According to the information obtained from a publicly
available on-line computerized data base (TOXLINE), EDTMPA may
have a variety of actual/potential medical and dental applica-
tions. The TOXLINE citations (which EPA obtained by using the
EDTMPA CAS Registry Number) indicate that EDTMPA has been evalu-
ated for use as an antidote in certain types of metal poisoning
and as a component of oral/dental hygiene formulations.
Comments/Recommendations
The submitter stated that the two chronic rat studies were begun
in March and April 1982 and are expected to end in September and
April 1984, respectively, with final reports expected in June and
January 1985, respectively. The submitter also reported that the
chronic study in mice "was begun in May 1982 and is expected to
be terminated in November 1983, with a final report anticipated
in July 1984."
Although the submitter's cover letter emphasized that "there are
no known adverse effects from the use of [EDTMPA] in any of its
applications, or from workplace handling of the product," the
company reported that "letters are being transmitted to all cus-
tomers of the product, recommending that they take appropriate
steps to minimize exposure to their employees" and "similar let-
ters will be sent to other known manufacturers of the product."
a)
The Chemical Hazard Identification Branch (CHIB/AD/OTS)
will request both the submitting and sponsoring companies
to ensure that EPA immediately receives, when available,
complete copies of further interim reports and complete
copies of the final reports from the ongoing rat and
mouse chronic EDTMPA gavage studies. In view of EPA's
general interest in company actions that are taken on a
voluntary basis in response to chemical toxicity/expo-
sure information, both companies will also be asked to
describe the nature of all other studies that they are
now conducting/sponsoring, or plan to conduct/sponsor,
that are designed to further define EDTMPA toxicity.
65
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8EHQ-0683-0483 S
Page 8 of 8
In addition, both companies will be informed that the
Agency would appreciate receiving additional available
information pertaining to actual/potential human and/or
environme~tal exposure to EDTMPA.
b)
The Chemical Hazard Identification Branch will consider
. the preparation of a Chemical Hazard Information Profile
(CHIP) on ethylene diamine tetra (methylene phosphonic
acid).
c)
The Chemical Hazard Identification Branch will transmit
a copy of this status report to NIOSH, OSHA, CPSC, FDA,
NTP, OW/EPA, OSWER/EPA, OANR/EPA, ORD/EPA, CCD/OTS and
HERD/OTS. A copy of this report will also be sent to
the TSCA Assistance Office (TAO/OTS/OPTS) for further
distribution.
66
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UNITED STATES EHYIRONMENTAL PROTECTION AGENCY
DAU:
Jl 2 0 f983
8EHQ-0683-0484 S
Page 1 of 4
SUIJEC:TI
Status Report*
8EHQ-0683-0484 S
Approved ;:;J1t-
Revision
Neeoed
,j?-,
'10161
Justine L. Wel~eam Leader
Chemical selece)Pri and Profiles Team/CHIB
Frank D. Kover, Chief
Chemical Hazard Identification Branch/AD
TOI
Submission Description
(See NOTE on Page 4 of this status report)
The Rohm and Haas Company provided summarized final results from
a sub-acute inhalation toxicity study of a polymer dust in male
and female Crl:CD(SD)BR rats. Although the submitting 'company
claimed the actual chemical identity/composition of the subject
polymer to be TSCA Confidential Business Information (CBI), the
company did report that the polymer has a molecular weight of
approximately 1,000,000 and contains a significant amount (ap-
proximately 35%) of respirable dust particles (5 microns or
less). The Rohm and Haas Company reported that "the lack of
toxicological data to confirm that finely divided organic
polymers are truly nuisance dusts prompted initiation" of this
study.
According to the submitted summary, 5 groups of rats were expo~ed
to polymer dust concentrations of 0, 4.9, 48, 259, or 950 mg/m
for 6 hours per day, 5 days per week for two weeks. On the day
after the last exposure, 8 males and 8 females from each group
were sacrificed while 8 males and 8 females from both the control
group and the highest dose group were held for a 3-week post-
exposure observation/recovery period. The submitter reported
that the obtained results indicated the induction of pneumonitis
in those rats exposed to the two higher concentrations. The
submitter also reported that although a reversible pneumonitis
would normally be expected to result from inhalation exposure to
a "nuisance dust," the pneumonitis observed in the performed
study was "neither progressive nor reversible within a three week
recovery periOd." Rohm and Haas stated that "nuisance dusts, in
contrast to fibrogenic dusts which cause scar tissue to be formed
in the lungs when inhaled in excessive amounts, have little
adverse effect on lungs and do not produce organic disease or
toxic effect." The submitter also stated that the following lung
observations would be expected to be made following inhalation of
nuisance dusts: "I) the architecture of the air spaces ~emains
intact; 2) collagen (scar tissue) is not formed to a significant
extent; and 3) the tissue reaction is potentially r.eversible."
-NOTE: This status reDort is the result of a crelirninarv
staff evaluation of i~forma~ion submitt~c to EPA. State;e~ts
mace herein are nOt to. be re~arded as ex~ressinc final
Agency p~licy or intent with~res?ect to t~is particular
chemical. .~y review of the status report should take into
consideration the tact that it mav be based on incomclet~
information. . .
67
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8EHQ-0683-0484 S
Page 2 of 4
The following summarized information was provided with regard to
the general pathologic findings from the two-week inhalation
study:
"No effects were observed in the two lowest treatment groups
compared to the controls. Inhalation of 258.6 mg/m3 produced
minimal to mild multi-focal pneumonitis. Inhalation of 949.6
mg/m3 produced slight to moderate diffuse pneumonitis. There
was no evidence of foreign body giant cells or early fibro-
sis. What necrosis did occur was very slight. There was no
damage to the architecture of the air spaces, nor was there
collagen formation. There were not enough animals at 250
mg/m3 to hold for observation for post-ex~osure resolution of
pneumonitis. Animals exposed at 950 mg/m were held for
three weeks without either progression or resolution of pneu-
monitis observed. Despite the adverse effects observed on
deep lung tissue, no effects were observed in the upper
bronchial tree where non-respirable dust would be expected to
deposit."
With regard to the interpretation of the obtained results, Rohm
and Haas stated that the company's internal Technical Review
Committee had reached the following conclusions:
"Pneumonitis is the expected early stage reaction to high
dust concentrations, that is, concentrations which exceed the
normal clearance capacity of the lung. For nuisance dusts,
our [the company's] toxicologist generally expects to observe
initiation of the resolution of pneumonitis within a two-week
exposure period. For non-nuisance dusts, resolution may take
longer or it may never occur. Failure of the pneumonitis in-
duced by the polymer product to begin resolution within three
weeks is a concern. It is possible that further investiga-
tion will establish reversibility of the induced pneumonitis
over a longer period of time. Acting on the evidence in
hand, however, it was concluded that the polymeric product
cannot be considered just a nuisance dust."
In addition to the provided summarized toxicologic results, Rohm
and Haas noted that the company's "workplace exposure limit for
the respirable portion of this [polymer] material had been set at
5 mg/m3, the same limit established by the American Conference of
Governmental Industrial Hygienists [ACGIH] for the respirable
portion of nuisance dusts."
Submission Evaluation
Although no adverse effects were found at 50 (47.8) mg/m3 and
below, pneumonitis was observed at the two highest concentrations
tested. Both the severity of reaction and extent of the lung
affected were dose related, and the effects persisted for three
weeks after exposure had ceased. Therefore, the Agency is
inclined to agree with the submitter that the observed effects
are real and that the tested material is not simply a nuisance
68
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8EHQ-0683-0484 S
Page 3 of 4
dust. It should be noted, however, that further studies would
need to be performed in order to confirm this initial impression.
Whether and how the breathing-zone concentration and particle
sizes were verified were not reported in the submission. In
addition, it does not appear that unreacted feedstock(s) would be
present in large quantity in the polymeric material that was
tested. Due to the fact that no test data were reported on the
feedstock(s), however, there is a chance that unreacted feed-
stock(s) may accompany the polymer at some (probably low) concen-
tration. The possibility of an unreacted substance contributing
in a major or minor way to the observed or potential toxicity
cannot, therefore, be ruled out at this time.
Although the submission described the observed biological effects
only in general terms, it did indicate that the inhaled particles
reached the deep lung and caused necrosis, but did not alter the
normal architecture of the airspaces of the lung. These observa-
tions raise several questions. What cells or tissues were
necrotic? How extensive was the necrosis? How was the necrosis
resolved? What was the fate of the sloughed cells that were
observed in the airways? What effect did the inhaled particles
have on the lung clearance ability or on resident macrophages?
The submitted summary report stated that "...alveolar septal
epithelial cells and macrophages... frequently had sloughed into
the lumen of the airways....macrophage necrosis was not severe."
This statement suggests that there was at least a noticeable
amount of macrophage necrosis. This statement also suggests that
the observed pneumonitis may be complicated by a weakening of the
host defense mechanisms and lung clearance, and raises questions
about the possible adverse effects on immune competence due to
chronic exposure. Macrophage necrosis is also important because
it may lead to pulmonary fibrosis following the release of lytic
enzymes in th~ lung by the killed macrophages. Fibrosis was not,
however, detected in the three weeks following inhalation expo-
sure to the polymeric material.
It should be noted that macrophage necrosis has been observed
following inhalation of other polymeric materials. For example,
in TSCA Section 8(e) submission 8EHQ-0382-0438 S et seq., respir-
able particulates (in vivo) and a gel or suspension of polymeric
particles (in vitro); were reported to be lethal to marcrophages.
Therefore, it would be of interest to see the full histopathology
report upon which the present Section 8(e) submission is based,
and to know what effect the subject polymeric material has on
macrophages in cell culture. The present submission also raises
a question concerning the potential for the inhaled polymeric
material to bring about progressive and ultimately profound
respiratory embarrassment with impaired lung clearance,
macrophage necrosis leading to fibrosis, intercurrent infections,
and bronchiectasis.
69
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8EHQ-0683-0484 S
Page 4 of 4
Current Production and Use
Due to the fact that the Rohm and Haas Company claimed the actual
chemical identity/composition of the subject polymer to be TSCA
Confidential Business Information (CBI), no production or use'
information for the polymer will appear in this status report.
Comments/Recommendations
NOTE:
a)
The Chemical Hazard Identification Branch (CHIB/AD/EPA)
will request the Rohm and Haas Company to provide EPA
with a complete copy of the final report (including
protocol(s) and data) from the company's two-week
inhalation study of the subject polymer dust in rats.
In view of EPA's general interest in company actions
that are taken on a voluntary basis in response to
chemical toxicity/exposure information, the Chemical
Hazard Identification Branch will also ask the Rohm and
Haas Company if it is conducting, or plans to conduct,
additional studies designed to further define the
toxicity of the subject polymer. In addition, Rohm and
Haas will be requested to describe the actions the
company has taken to warn workers and others and to
reduce and/or eliminate exposure to the polymer.
b)
The Chemical Hazard Identification Branch will screen
the reported information to determine if further OTS
assessment of the subject polymer is warranted.
c)
The Chemical Hazard Identification Branch will provide a
copy of this status report to NIOSH, OSHA, CPSC, FDA,
NTP, OW/EPA, OSWER/EPA, OANR/EPA, ORD/EPA, CCD/OTS, and
HERD/OTS. A copy will also be provided to the TSCA
Assistance Office (TAO/OTS/OPTS) for appropriate
distribution.
In further correspondence with EPA regarding this submission,
the Rohm and Haas Company provided the following generic name
for the tested polymeric material: "Acrylic Polymer"
70
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OA1£:
AUG I 2' 1983
UNITED STATES ENVIRONMEHTAL PROTECTION AGENCY
8EHQ-0783-0485 S
Page 1 of 3
sua.lEtT.
Stat.us Report*
8EHQ-0 783-04 85 S
Approved
~ &({J--
,. OM.
Justine L. Wel~am Leader
Chemical selec~n and Profiles ~eam/CHIB
Frank D. Kover, Chief
Chemical Hazard Identification Branch/AD
Revision
Needed
TOt
Submission Description
The CIBA-GEIGY Corporation provided a copy of a cover letter from
a recent CIBA-GEIGY submission on terbuthylazine (CAS No. 5915-
41-3) that had been formally sent to EPA's Office of Pesticide
Programs (OPP/OPTS) pursuant to Section 6(a)(2) of the Federal
Insecticide, Fungicide and Rodenticide Act (FIFRA). The provided
cover letter contained a listing of the final reports of several
acute and sub-acute in vivo terbuthylazine toxicity studies that
had been submitted to-OPP;-certain terbuthylazine production and
use information, and the following summary of the toxicologic
findings:
"...the data from a 28-day repeat dermal study in rabbits
showed specific effects involving lymphoreticular organs at
the lowest dose tested (500 mg/kg/day) and at higher levels
which reversed during a 14-day observation period. In another
study, repeated oral exposure for 13 days in pregnant rabbits
(pilot toxicity study prior to teratogenicity evaluation) re-
sulted in a no observable effect level (NOEL) of 2 mg/kg/day.
This NOEL is considerably lower than that previously deter-
mined in other species including rats, mice, and dogs. The
significance of these findings for humans is unknown. II
Submission Evaluation
The submitted terbuthylazine toxicity informati9n is currently
under review by staff of the Hazard Evaluation Division of the
Office of Pesticide Programs.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for terbuthylazine (CAS No. 5915-41-3), which is
liSted in the initial TSCA Inventory, has shown that between 1
million and 10 million pounds were reported as produced and/or
-
-NOTE: T~is status reoo:-t is the result of a orelimina:-v
staff evaluation of i~formation submittec to EPA. State;e~ts
mace herein are no~ to be re~arded as ex~ressino final
Agency policy or intent with-r~s?ec~ to t~is ?arti~ular
chemical. .~y review 6f the status report should take into
consideration the iact that it may be based on incomolete
information. .
71
E~& '0". n:>4 nutv. ~'.I
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8EHQ-0783-0485 S
Page 2 of 3
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 TSCA Confidential
Business Information (C8I). The data submitted for the TSCA In-
ventory, including production range information, are subject to
the limitations contained in the Inventory Reporting Regulations
(40 CFR 710).
The followin~ terbuthylazine production/use information was
provided by CIBA-GEIGY in the submitted cover letter:
"Only one pesticide product containing this chemical, CIBA-
GEIGY Technical Terbuthylazine, is registered in the United
States. No end-use products are registered in this country.
CIBA-GEIGY discontinued development of terbuthylazine in the
United States in the mid-1970's for economic reasons. How-
ever, prior to the company's withdrawal on November 6, 1980
of the application for end-use registration (EPA File Symbol
lOU-LRA), tolerances were established in corn grain, corn
fodder and forage, and sorghum forage and grain (P.P. Nos.
IFl154 and 3F1409, 4U CFR 180.333)."
"At [the company's) St. Gabriel, Louisiana production facil-
ity (BPA Est. 100-LA-l), CIBA-GEIGY manufactures technical
terbuthylazine for export to its parent organization, CIBA-
GEIGY Limitea, in Switzerland. CIBA-GEIGY also makes this
cheIT.ical at St. Gabriel for use as an intermediate in certain
triazine herbicides manufactured at its plant in McIntosh,
Alabama (EPA Est. lOO-AL-l)....CIBA-GEIGY Limited has regis-
tered end-use products in foreign countries for use as a
herbicide in sorghum, pome fruits, grapes, citrus and
forests, and for use as an algicide in swimming pools."
No further informatio~ on the use(s) of terbuthylazine was
located in the secondary literature sources consulted.
Comments/Recommendations
It is EPA's initial determination that the reported information
on terbuthylazine, once formally submitted to the Agency pursuant
to Section 6(a)(2) of FIFKA, need not have been also reported to
the Agency under TSCA Section ~(e). According to Part VII(b) of
EPA's March 16, 1978, TSCA Section 8(e) policy statement ("State-
ment ot Interpretation and Enforcement Policy; Notification of
Substantial Risk" 43 FR 11110), information need not be reported
under Section 8(e) if the information "has been submitted in
writing to EPA pursuant to mandatory reporting requirements under
TSCA or any other authority administered by BPA (including the
Federal Insecticide, Fungicide and Rodenticide Act...)."
In its submission, CIBA-GEIGY stated that the company is in-
torming its plant personnel about the reported toxicologic
findings. In addition, ClbA-GEIGY stated that the dompany plans
72
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8EHQ-0783-0485 S
P~ge 3 of 3
to "re-evaluate its personnel protection procedures to ensure
that the work force is adequately protected from over-exposure to
terbuthylazine." The submitter also stated that "additional
rabbit studies [on terbuthylazine] have been initiated' and are
expected to be available in late 1983."
a)
In view of EPA's general interest in company actions
that are taken on a voluntary basis in response to '
chemical toxicity/exposure information, the Chemical
Hazard Identification Branch (CHIB/AD/OTS) will request
the CIBA-GEIGY Corporation to describe the actions it
has taken to notify non-CIBA-GEIGY personnel about t0e
reported toxicologic findings on terbuthylazine. The
submitter will also be requested to describe the actions
the company has taken or plans to take to reduce and/or
eliminate exposure to terbuthylazine.
b)
The Chemical Hazard Identification Branch will tLansmit
a copy of this status report to the Office of Pesticides
Programs. Copies of this status report will also be
provided to NIOSH, OSHA, CPSC, FDA, OW/EPA, OSWER/EPA,
OANR/EPA, ORD/EPA and to the TSCA Assistance Office
(TAO/OTS/OPTS/EPA) for appropriate distribution.
73
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DAn:
rm t.6 1983
UNITED STAT~S ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0783-0486
Page 1 of 4
SUIJtCT.
Status Report*
8EHQ-0783-0486
1\pp:oved
~
'~8
/
'10M.
Justine L. Wel~m Leader
Chemical selec~n and Profiles
Frank D. Kover, Chief
Chemical Hazard Identification
Team/CHIB
Revision
Needed
TO,
Branch/AD
Submission Description
The Allied Corporation submitted summarized results of two acute
rabbit dermal toxicity studies of hydroxylamine sulfate (CAS No.
lU039-54-0). In the first study, hydroxylamine sulfate was re-
portedly applied as a solution under a gauze patch to the skin of
New Zealand white rabbits (5 males and 5 females/group) at doses
of 2.U, 1.5, 1.0, or 0.5 g/kg. Allied reported that the length
ot exposure was 24 hours and that the post-exposure observation
period was 14 days. The fol19wing summarized information was
presented by the company with regard to the results obtained from
the first acute dermal exposure study:
"The LD50 of the material in this test was found to be
between 1.5 and 2.0 g/kg. Absorption through the skin was
confirmed as seen by the following effects: cyanosis and
hypothermia for the first several days post exposure. Re-
ductions in red blood cell counts, increases in reticulocyte
counts and enlarged spleens were observed at sacrifice 14
days post exposure. These effects suggest that the hemato-
poietic system is the primary systemic target organ. It was
also noted that these effects may have extended down to the
lowest dose level tested (0.5 g/kg), but ,the results at this
level are not clearly defined."
The Allied Corporation reported that another acute rabbit dermal
toxicity study was conducted in order to determine whether the
adverse effects observed in the first study would occur at lower
dose levels of hydroxylamine sulfate. The following information
was presented by the company with regard to the second study:
"The rabbits were divided into four groups consisting of two
animals each. Hydroxylamine sulfate, moistened with an equi-
valent weight of distilled water, was applied to the shaved
backs of-the test animals at dose levels of 0.1, U.05, and
0.01 g/kg. The two control rabbits were treated with distil-
led water alone (0.1 g/kg). Because of the small quantities
-NOTE: T~is status reco:t is the resu2t of a crelirnina:v
staff evaluation of ir:format:ion" subrnitt~c to EPA. Stat.e;'e~ts
mace herein are no~ to be re~arded as ex~ressinc final
Agency policy or intent wit.h.res?ec~ to t~is particular
chemical. .~v review of the status recort should take into
- .
consideration the fact that it mav be based on incomolete
information. .. .
74
E"" "0l1li111 ..~ ,"'ty. ~"I
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8EHQ-0783-0486
Page 2 of 4
of hydroxylamine sulfate, the test material was held in place
with an inverted plastic cover rather than gauze to prevent
loss of material in the mesh of the gauze. Exposure was for
24 hours. Four days after dosing, blood was collected from
the marginal ear vein for hematological analyses. The re-
sults of this study indicate that hydroxylamine sulfate in-
duced a hemolytic anemia in a dose responsive manner. A
severe hemolytic crisis was apparent in the two animals dosed
at 0.1 g/kg. One of these animals died during the bleeding
procedure. A no-effect level was not established in this
probe [study] since a slight hematological effect may have
been present at the lowest dose level (0.01 g/kg)."
Allied stated that the results of the performed studies "indicate
that dermal absor~tion of hydroxylamine sulfate in rabbits may
occur at low exposure levels and that this absorption can lead to
blood dyscrasia." In addition, the submitter stated that "these
blood effects are well documented in the ~ublished literature,
but they may result from different routes of exposure."
The Allied Corporation also reported that hydroxylamine sulfate
is a "lJotential sensitizer upon dermal exposure." with regard to
the potential for sensitization, Allied stated that the company
"recommends minimum contact either by dermal or inhalation expo-
sure routes." Allied stated that the precautions taken to avoid
sensitization "will be more than sufficient to also avoid hemo-
lytic effects from potential dermal absorption and, therefore,
Allied believes that there should not be a substantial risk of
hemolytic effects from proper use of this material."
Submission Evaluation
The unique information contained in this notice is reported to be
the route (dermal) of hydroxylamine sulfate exposure and the low
dosage (down to lU mg/k~) that caused dose-related reproducible
adverse hematologic effects in rabbits. In addition, the rabbit
dermal LD5U that was reported is an improvement over the minimal
information contained in the published (1':180) NIOSH Registry of
Toxic Effects of Chemical Substances (RTECS) for this chemical.
The spectrum oY-the adverse effects noted in the acute rabbit
dermal toxicity studies is indeed interesting, even though some
or all of the effects have been observed at higher doses in other
slJecies.
Due to the fact that hydroxylamine sulfate can decompose to
hydroxylamine and sulfuric acid, the effects of hydroxylamine it-
self need to be considered. Both hydroxylamine and sulfuric acid
can be corrosive to mucous membranes and skin. Dermal corrosion
would facilitate the uptake of hydroxylamine (and its sulfate)
through the skin, allowing greater systemic toxicity. hydroxyl-
amine has been reported in the scientific literature to cause
hematuria (possibly the result of red blood cell (RBC) lysis
and/or renal damage), proteinuria (possibly the result of renal
damage), and methemoglobinemia. It has also been reported that
75
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8EHQ-0783-0486
Page 3 of 4
hydroxylamine possesses some degree of clastogenic (and muta-
~enic) activity. The possibility exists, therefore, that there
may be an adverse effect on hematopoiesis. It should also be
noted that reticulocyte formation and an enlarged spleen both may
be caused by hemolysis and hemolysis may be a function of direct
RBC lysis or methemoglobin formation.
The observed hemolytic effects were reported to be severe in
those rabbi~s exposed dermally to hydroxylamine sulfate for 24
hours at a dose of 0.1 g/kg, and there were "slight" but other-
wise undefined hematologic effects observed at the 0.01 g/kg (10
my/kg) dose level. Due to the fact that the latter dose was the
lowest dose tested in the two experiments, a no-observed-effect
level (NOEL) could not be determined.
One of the more interesting adverse health effects reported in
this submission may be the potential for hydroxylamine sulfate to
cause sensitization. Although no test data were presented for
sensitization, it is possible that if both hemolysis and sensi-
tization were part of a single pathologic entity, such as the
human disease, acquired hemolytic anemia, it might yield a model
tor the study of such diseases.
It should also be noted that the Allied Corporation provided a
copy of the company's hydroxylamine sulfate Product Safety Data
Sheet in which it was reported that the chemical had been found
to possess in vitro mutagenic activity, had been shown not to be
carcinogeniC-in long-term animal studies (animal species and dose
not svecified), and had been shown in one in vitro study to pos-
sess spermicidal effects. It would be of interst to know the
literature (or other source) citations for these findings.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for hydroxylamine sulfate (CAS No. 10039-54-0), which
is listed in the initial TSCA Inventory, has shown that between
110 million and 551 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 the person(s) reporting for the TSCA Inventory, nor
does it include any information which would compromise TSCA Con-
fidential 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).
Secondary literature sources indicate that hydroxylamine sulfate
is used as a reducing agent, as a dehairing agent for hides, as a
purification agent for aldehydes and ketones, in making oximes
for paints and varnishes, in rustproofing operations, as a non-
discoloring short-stopper for synthetic rubbers, as an oxidation
inhibitor for fatty acids and as a photographic developer.
76
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8EHQ-0783-0486
Page 4 of 4
Comments/Recommendations
The submitted Product Safety Data
safety glasses, impervious gloves
working or coming in contact with
regard to respiratory protection,
recommends that a "full-face high
ator" be used if dusty conditions
Sheet recommends the use of
and disposable work cloths when
hydroxylamine sulfate. with
the Product Safety Data Sheet
efficiency particulate respir-
exist.
a)
The Chemical Hazard Identification Branch (CHIB/AD/OTS)
will request the Allied Corporation to submit complete
copies of the final reports (including actual test pro-
tocols and data) from the two acute dermal toxicity
studies that were cited in the submission. In addition,
Allied will be requested to provide literature (or other
source) citations for the summarized toxicity findings
presented in the Chronic Toxicity section of Allied's
Product Safety Data Sheet on hydroxylamine sulfate.
b)
The Chemical Hazard Identification Branch will screen the
submitted information in order to determine if further
OTS assessment of hydroxylamine sulfate is warranted.
c)
The Chemical Hazard Identification Branch will transmit
copies of this status report to NIOSH, OSHA, CPSC, FDA,
NTP, OW/EPA, OSWER/EPA, OANR/EPA and ORD/EPA. A copy of
this report will also be transmitted to the Industry
Assistance Office (IAO/OTS/OPTS).
77
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
85HQ-0783-CI487 S
Page 1 of 3
DAU:
ALG 2 4 1983
SUIJECT. Status Report *
8EHQ-0783-0487 S
Approved
:-jk-
, '
8?'f
nOAt, Justine L. wel~A.jeam Leader ,
Chemical selec~~-~nd Profiles Team/CHIS
Revision
Needed
TOI Fran~ D. Kover, Chief
Chemlcal Hazard Identification Branch/AD
Submission Description
The American Cyanamid Company submitted a one-page letter that
stated that the results of a Draize test had shown that a deriva-
tive of nicotinic acid was corrosive to rabbit eyes. The exact.
identity of the tested chemical was claimed by the submitter to
be TSCA Confidential Business Information (CBI).
Submission Evaluation
Due to the fact that the submission did not contain any data from
the performed Draize test, an evaluation of the reported rabbit
eye toxicity is not possible at this time. According to the sub-
mitting company, a full report of the subject study will be sent
to EPA in the near future.
Current Production and Use
Although the exact identity of the nicotinic acid derivative was
claimed to be TSCA CBI, American Cyanamid did report that the
"status of this compound is that of a research chemical." The
submitter did not provide any information concerning the actual
or proposed use(s) of the chemical nor was any use information
located in the secondary literature sources consulted.
Comments/Recommendations
It should be noted that it has been EPA's longstanding policy
that c&rtain types of acute toxicity information may not warrant
submission to EPA pursuant to Section 8(e), the substantial risk
information re~orting provision of the Toxic Substances Control
Act (TSCA). The basis for the Agency's position is as follows:
The preface to Part V of EPA's March 16, 1978, TSCA
8(e) policy statement ("Statement of Interpretation
forcement Policy; Notification of Substantial Risk~
11110) states that "a substantial risk of injury to
Section
and En-
43 FR
health or
-NOTE: This status reeo:t is the result of a ereliminarv
staff evaluation of information submittec to EPA. Sta~e;ents
mace herein are no~ to be regarded as expressing final
~se~cy policy or intent wi~h res?ec~ to t~is ?articula~
chemical. .~v review 6f the status reeor: should take into
consideration-the tact that it may be based on incomDlete
informa tion. 78 .. .
r~. '011111 1J::D-4 IJII:\'. ~"I
-------
8EHQ-0783-0487 S
Page 2 of 3
the environment is a risk of considerable concern because of
(a) the seriousness of the effect...and (b) the fact or prob-
ability of its occurrence." With regard to the seriousness
of the effect, Part V exvlains 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." Information with respect to 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 8(e,-pGlicy 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 sub-
stantial.
EPA's response to Comment 14 in Appendix B of the March 16,
1978, Section 8(e) policy statement provides additional
guidance with regard to the Section 8(e)-reportability of
results obtained from routine acute in vivo range finding
tests (e.g., LD50 determinations, skin/eye irritation tests,
etc). In its response, the Agency stated that "many routine
tests are based on knowledge of toxicity associated with a
chemical..." BPA's response also directed that unknown ef-
fects which occur and are observed and/or determined during
acute in vivo range-finding tests may have to be reported if
such 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 pursuant to TSCA Section 8(e), the
Agency believes that submitting companies should consider
such factors as the lethal dose, pH, 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 actual/potential exposure to the
tested chemical substance(s). In general, when evaluating
such information for Section 8(e) reporting, the greater the
acute toxicity, the less heavily a company should weigh
exposure to the subject chemical(s), and vice versa.
In light of the preceeding discussion, it would appear that the
results of the acute rabbit eye irritation study of the nicotinic
acid derivative (as presented by the American Cyanamid Company)
are not of the type warranted for submission to EPA pursuant to
oection 8(e) of TSCA. In making this statement, however, it must
be understood that EPA may not be aware of additional pertinent
information that may have been available to and/or considered by
the American Cyanamid Company in reporting the subject informa-
tion to EPA under ToCA Section 8(e).
79
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8EHQ-0783-0487 S
Page 3 of 3
a)
The Chemical Hazard Identitication Branch (CHIB/AD/OTS)
will request the American Cyanamid Company to ensure that
the Agency receives a complete copy of the final report
(including test protocol(s) and data) of the acute rabbit
eye irritation study/of the nicotinic acid derivative.
In addition, American Cyanamid will be asked to provide
the company's rationale as to why the acute eye toxicity
findinys warranted submission to EPA pursuant to Sectio~
8(e) of TSCA. In view of the Agency's general interest
in company actions that are taken on a voluntary basis in
response to chemical toxicity/exposure information, the
submitting company will also be requested to describe the
actions it has taken to warn workers and others and to
reduce or eliminate exposure to the subject: chemical.
b)
The Cheluical Hazard Identification Branch will transmi t
copies 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 sent to the TSCA Assistance
Office (TAO/OTS/OPTS/EPA) for further distribution.
80
-------
UNITED STATES EHYIROHMEHTAL PROTECTION AGENCY
DAT£:
U26r003
8EHQ-0783-0488
Page 1 of 3
SUIJ£C:T, Status Report*
8EHQ-0783-0488
Approved (JJJt.-- ~/')4
'10it Justine L. wel'qbA1eam
'Chemical select1~~land
J
Leader
Profiles Team/CHIB
Revision
Needed
TO Frank D. Kover, Chief
'Chemical Hazard Identification Branch/AD
Submission Description
The Dow Chemical Company provided interim results from a chronic
toxicity/oncogenicity study of acrylamide (CAS No. 79-06-1) that
is being sponsored by the Dow Chemical Company, the American
Cyanamid Company, the Nalco Chemical Company, and the Standard
Oil Company (Ohio). This 2-year study (which is being conducted
at the Dow Toxicology Research Laboratory) involves groups of
Fischer 344 rats (9U rats/sex/group) exposed via the drinking-
water to acrylamide at dose levels of U, U.Ol, 0.1, 0.5, or 2.0
mg/kg/day. Sacrifices of lU rats/sex/grou~ were performed at 6,
12, and 18 months with 60 rats/sex/group scheduled for sacrifice
at termination of the study.
In its submission, Dow provided the following summarized informa-
tion with regard to the histopathologic results for female rats
exposed to acrylamide at the 2.0 mg/kg/day dose level:
1 )
"Neoplasms were statistically significantly increased in
female rats at the 2.0 mg/kg/day dose level for the fol-
lowing organs: central nervous system (brain and spinal
cord), mammary gland, clitoral gland, uterus, oral ca-
vity, pituitary gland, thyroid gland.
2 )
The degree of tibial nerve degeneration was statistically
significantly increased in female rats at the 2.0 mg/kg/-
day dose level. (Anticipated result per previously pub-
lished report: Burek, J.D.; Albee, R.R.; Beyer, J.E.;
Bell, T.J.; Carreon, R.M.; Morden, D.C.; Wade, C.E.;
Hermann, E.A.; Gorzinski, ~.J.; 1980 "~ubchronic Toxicity
of Acrylamide Administered to Rats in the Drinking Water
Followed by Up to -144 Days of Recovery," Journal of
Environmental Patho~ogy and Toxicology, 4:157-182)."
Dow also reported that an analysis of the male rat mortality data
showed a statistically significant increase in mortality at the
2.0 mg/kg/day dose level.
-NOTE: T~is status recort is the resul~ of a prelirnina:-v
staff evaluation of i~formation submitted to EPA. State;e~ts
mace herein are no~ to be regarded as.ex?ressing final
Agency policy or intent with res?ec~ to t~is particular
chemical.> .'!u1\" review of the status repo!'~ should take into
consideration-the iact that it mav be based on incomo'ete
information. 81 - .-
E~. 'OAIII 11:0-6 IJU:V. ~tI'
-------
8EHQ-0783-0488
Page 2 of 3
It should be noted that Dow previously reported ("For Your Infor-
mationh submission number FYI-OTS-1282-0223) that there was "in-
creased mortality for female rats at the 2.0 mg/kg/day dose level
of acrylamide and an increased number of female rats with a gros-
sly observed mass in the mammary region (suggestive of a mammary
tumor) at the 2.0 mg/kg/day dose level of acrylamide."
In the cover letter to its Section 8(e) submission, Dow reported
that "upon completion of the remaining portions of this study in-
cluding light microscopic examination of the tissues from male
rats and the electron microscopic examination of the tibial
nerves from male rats, final conclusions will be reported and
submitted to the Agency."
Submission Evalulation
The interim chronic toxicity/oncogenicity findings for acrylamide
that were re~orted in this submission are currently under review
by both the Test Rules Development Branch (TRDB/AD/OTS) and the
"Existing Chemicals Task Force" (ECTF/OTS).
Current Production and Use
A review ot the production range (includes importation volumes)
statistics for acrylamide (CAS No. 79-06-1), which is listed in
the initial TSCA Inventory, has shown that between 10 million and
51 million pounds were reported as produced and/or imported in
1977. This production range information does not include any
production/im~ortation data that were claimed as confidential by
the person(s) reporting for the TSCA Inventory, nor does it in-
clude any information which would compromise TSCA Confidential
Business Information. The data submitted for the TSCA Inventory,
including production range information, are subject to the limi-
tations contained in the Inventory Reporting Regulations (40 CFR
71U ) .
The major applications of acrylamide include the chemical's
as a cross-linking agent, in certain adhesive formulations,
paper and textile sizes, as a soil conditioning agent, as a
culant, and in sewage and waste treatment.
use
in
floc-
Comments/Recommendations
In its submission, the Dow Chemical Company reported that in ac-
cordance with longstanding corporate policy, Dow is immediately
notifying its employees, its acrylamide customers, and other
acrylamide ~roducers. The Dow Chemical Company also reported
that it is "recommending that work situtations where acrylamide
is encountered be reviewed to make sure the current ACGIH TLV of
U.3 mg/cubic meter - skin (U.6 mg/cubic meter short-term exposure
limit) is not beiny exceeded."
82
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8EHQ-0783-0488
Page 3 of 3
In 1976, NIOSH (National Institute for Occupational Safety and
Health) published a "Criteria Document" relating to occupational
exposure to acrylamide. In April 1978, acrylamide was designated
by the Interagency Testing Committee (ITC) for certain types of
health and environmental effects testing pursuant to Section 4 of
TSCA. In addition, TSCA Section 8(a) and 8(d) chemical informa-
tion reporting rules for acrylamide have been published by EPA.
EPA has also received and reviewed several "For Your Information
(FYI)" submissions containing toxicity and/or exposure data on
acrylamide.
a)
The Chemical Hazard Identification Branch (CHIB/AD/OTS)
will request the Dow Chemical Company to ensure that EPA
receives complete copies of all future interim reports
and a complete copy of the final report (including actual
study protocol(s) and data) from the 2-year drinking-
water study of acrylamide in rats.
b)
The Chemical Hazard Identification Branch will transmit
copies of this status report to NIOSH, OSHA, CPSC, FDA,
NTP, OW/EPA, OSWER/EPA, OANR/EPA, ORD/EPA, TRDB/AD/OTS,
and to the OTS "Existing Chemicals Task Force (ECTF)." A
copy will also be provided to the TSCA Assistance Office
(TAO/OTS/OPTS/EPA) for further distribution. (Copies of
the submission itself were provided (by CHIB) to TRDB and
ECTF immediately upon CHIB's r~ceipt of the information.)
83
-------
UNITED STATES ENV IRONMENTAL PROTECTION AGENCY
8EHQ-0883-0489
Page 1 ot 2
DAT£;
~261933
SUIJ£C:T. Status Report*
8EHQ-0 883-0489
App=oved
~
~/~
nOM. Just~ne L. wel~~am
Chemlcal selec~j~n and
Leader
Profiles Team/CHIS
Revision
Needed
TO Frank D. Kover, Chief
'Chemical Hazard Identification Branch/AD
Submission Description
Lonza, Inc. submitted summarized final results from a series of
Ames Salmonella typhimurium (bacteria) mutagenicity assays with
diethyl toluene diamine (CAS No. 68479-98-1). According to the
submitter, the results of these short-term in vitro ~ests (which
were conducted both with and without exogenous metabolic activa-
tion) show that diethyl toluene diamine causes a dose-dependent
mutagenic response in the presence of metabolic activation.
Submission Evaluation
Although the submitted information does indicate that diethyl
toluene diamine possesses some degree of mutagenic activity in
bacteria, complete copies of the tinal reports (including the
actual test protocols and data) should be requested in order to
evaluate the reported in vitro findings more properly-
Current Production and Use
A review of the production range (includes importation volumes)
statistics for diethyl toluene diamine (CAS No. 68479-98-1), as
listed in the initial TSCA Inventory, has shown that no 1977 pro-
duction/importation was reported or that all of the production
range data re~orted were claimed as confidential by the manufac-
turer(s) and/or importer(s) and cannot be disclosed (TSCA Section
14(a), D.S.C. 2613 (a)). All of 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 information contained in a recent American
Chemical Society publication (CHEMCYLOPEDIA; 1982-1983), diethyl
toluene diamine has the following applications: as an extender
and curing agent for polyurethane, as a curing agent for epoxy
resins, and as a chemical intermediate.
-NOTE: T~is status reDort is the result of a creliminarv
staff evaluation of ir.formation submitted to EPA. Sta~e;ents
mace herein are no~ to be recrarded as ex~ressinc final
Asency policy or intent with-res?ec~ to this particular
chemical. .~y review of the status report should take into
consideration ~he tact that it mav be bas~d on incomolete
informa tion. . 84 . .
E~' '0". 11=>-4 IJIIEV~ ~,..
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8EHQ-0883-0489
Page 2 of 2
Comments/Recommendations
Although a positive ~ vitro genotoxicity test result, when
considered alone, may not be sufficient to 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 hazards/risks posed by chemicals to health
.
and/or the environment. The Agency 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 suggest, in many cases,
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/OTS)
will request Lonza, Inc. to provide complete copies of
the final reports (including actual test protocols and
data) from the Ames assays cited in the submission. In
view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure information, Lonza, Inc. will be asked
to describe those actions the company has taken to warn
workers and others and to reduce or eliminate exposure
to diethyl toluene diamine. Lonza, Inc. will also be
asked to describe the studies that the company is now
conducting/sponsoring, or plans to conduct/sponsor, that
are designed to further define the toxicity of diethyl
toluene diamine. .
b)
The Chemical Hazard Identification Branch will screen
the submitted information in order to determine if fur-
ther OTS assessment of diethyl toluene diamine is war-
ranted at the present time.
c)
The Chemical Hazard Identification Branch will transmit
a copy of this status report to NIOSH, OSHA, CPSC, FDA,
NTP, OW/EPA, OSWER/EPA, OANR/EPA, ORD/EPA and TRDB/AD/OTS.
A copy of this status report will also be transmitted to
the TSCA Assistance Office (TAO/OTS/OPTS) for further
distribution.
85
-------
UNITED STATES EHVIROHMEHTAL PROTECTION AGENCY
- Justine L. Wel~m Leader
'1~'Chemical selec~n-~~d Profiles
Team/CHIB
8EHQ-0883-0490
Page 1 of 4
App=oved ~
Revision
Needed
1/lq
01.1£;
SEP I A .
SuaJECT, Status Report *
8EHQ-O 883 -0 4 90
Frank D. Kover, Chief
TO'Chemical Hazard Identification Branch/AD
Submission Description
The CIBA-GEIGY Corporation submittpd complete copies of the final
reports from several short-term in vitro and in vivo genotoxicity
studies of Araldite PT-810 (1,3,5-tris(oxiranylmethyl)-1,3,5-tri-
azine-~,4,6(lH,3h,5H)-trione; CAS No. 2451-62-9). According to
the submitter, positive results were obtained in an in vitro Ames
Salmonella typhimurium (bacteria) assay and in in vivo nucleus
anomaly and Sister Chromatid Exchange (SCE) assays of the bone
marrow cells of Chinese hamsters treated orally with Araldite PT-
810. The CIBA-GEIGY Corporation also reported that the results
of two other short-term in vitro assays (a Balb-c/3T3 mouse cell
transformation assay and-an Escherichia coli (bacteria) WP2 uvrA
point mutation assay) were negative. With regard to the positive
in vivo genotoxicity results, the submitter reported that the
"relative concentrations and [oral] route employed are totally
irrelevant to human exposure."
In addition to the provided genotoxicity information, CIBA-GEIGY
submitted an Araldite PT-810 Material Safety Data Sheet (MSDS)
that states that the chemical is toxic via oral and dermal ex-
posure and may cause eye, skin, and respiratory tract irritation;
dermatitis; nosebleeds; and loss of appetite. The submitted MSDS
also provides the following summarized acute animal toxicity
information for Araldite PT-810:
LD50 (oral): 400 mg/kg (rats)
LD50 ( de rma I ) : >3 g/kg (rats)
Irritation ( d e rma 1 ) : Mild (rabbits)
Irritation (eye): Severe (rabbits)
Sensitization ( de rma 1 ) : Mild (guinea pigs)
-NOTE: T~is status reco~t is the result of a crelirninarv
. ..
staff evaluation of i~forma~ion submitted to EPA. Sta~eme~ts
mace herein are no~ to be regardeq as ex?ressing final
Asency policy or intent wi~h res?ec~ to t~is part~cu~ar
chemical .~v review 6f the status recort should take -into
consideration-the iact tha~ it mav be based on incomolete
information. . .
86
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8EHQ-0883-0490
Page 2 of 4
Submission Evaluation
The submitted data show that Araldite PT-810 is mutagenic in
Salmonella typhimurium (bacteria) strains TA 98, TA 100, and TA
1535 when tested with and without exogenous metabolic activation.
The chemical did not produce a mutagenic response in Escherichia
coli WP2 uvrA (bacteria) when tested under the same conditions.
s. typhimurium strain TA 98 detects frameshift mutagens; strain
TA 100 detects both base-pair and frameshift mutagens; strain TA
1535 and ~ coli WP2 uvrA detect base-pair mutagens. Araldite
PT-810 was most active when tested with s. typhimurium stain TA
98 (the peak activity with this strain was 8.3 times the number
of mutant colonies seen in control cultures). The peak activity
with ~ typhimurium strains TA 100 and TA 1535 was 3.8 and 3.6
times background, respectively. These findings indicate that
Araldite PT-810 is primarily a frameshift mutagen. Due to the
fact that ~ typhimurium strains TA 100 and TA 1535 detect muta-
tion at the same site in the genome, it is reasonable that the
tested chemical is equally active in these strains. Although
~ coli and ~ typhimurium are closely related Gram negative
bacteria, there are sufficient differences in their genomes that
differences in mutagenic activity observed following exposure to
the same chemical agent are not unexpected. For example, a chem-
ical that affects histidine biosynthesis in ~ typhimurium need
not necessarily be expected to affect tryptophan synthesis in E.
coli. Therefore, the negative response observed in E. coli does
not lessen the significance of the positive mutageniC-response
observed in ~ typhimurium.
The submitted data also show that Araldite PT-810 can induce both
Sister Chromatid ~xchanges (SCEs) and nuclear anomalies in the
femoral bone marrow of Chinese hamsters following oral admini-
stration of the chemical at doses of 14U, 280, or 560 mg/kg in
the SCE assay and 280, 560, or 1120 mg/kg in the assay for
nuclear anomalies. These results demonstrate that Araldite PT-
810 is capable of inducing chromosomal alterations in vivo.
Although Araldite PT-810 was not found to induce morphological
transformation in cultured Balb-c/3T3 (mouse) cells when tested
without metabolic activation, the results of the Ames Salmonella
typhimurium (bacteria) assay show that the chemical is a direct-
acting mutagen (i.e., does not require metabolic activation in
order to exert a mutagenic effect). Therefore, there is no
reason to believe that the addition of metabolic activation in
the in vitro Balb-c/3T3 cell transformation assay would have
significantly affected the observed negative results. It should
also be noted that while the correlation between positive results
obtained in in vitro cellular transformation assays and in vivo
carcinogenicity studies are generally well correlated, there is a
false negative rate which in the Balb-c/3T3 system can approach
5U% (Heidelberger et al., Mutation Research 114:283-385; 1983).
Due to the fact that the number of known noncarcinogens tested in
the Balb-c/3T3 cell transformation assay is limited, nothing can
be said about the ability of this in vitro assay to accurately
87
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8EHQ-0883-0490
Page 3 of 4
identify noncarcinogens. The observed negative response in the
cultured Balb-c/3T3 mouse cell transformation assay, therefore,
does not outweigh the positive responses observed in the Ames
Salmonella typhimurium assay and the in vivo SCE and nuclear
anomaly assays.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for Araldite PT-810 (CAS No. 2451-62-9), which is
listed in the initial TSCA Inventory, has shown that between 20
thousand and 200 thousand pounds of this chemical were reported
as produced/imported in 1977. This production range information
does not include any production/importation data claimed to be
confidential by the person(s) reporting for the TSCA Inventory,
nor does it include any information which would compromise TSCA
Confidential Business Information. The data submitted for the
TSCA Inventory, including the production range information, are
subject to the limitations contained in the Inventory Reporting
Regulations (40 CFR 710).
The CIBA-GEIGY Corporation reported that Araldite PT-8l0 is a
trifunctional solid epoxy resin which is used only in industrial
applications. The following industrial applications were listed
in a submitted Araldite PT-810 Product Information Sheet: powder
coatings, casting/potting, molding compounds, structural lamin-
ates, and adhesives. CIBA-GEIGY stated that in these industrial
aplications, Araldite PT-810 "becomes a highly crosslinked, high
molecular weight, insoluble and inert material."
Comments/Recommendations
In the cover letter to its submission, the CIBA-GEIGY Corporation
reported that the company "plans to review its MSDS, label, and
technical product bulletin with a view to supplying current safe-
ty information." In additio~, CIBA-GEIGY reported that customer
notification letters were being considered.
Although a positive genotoxicity test result, when considered
alone, may not be sufficient to offer reasonable support for a
conclusion of substantial risk, the Agency believes that such
results are of value in assessing possible risks posed by chem-
icals to health and/or the environment. EPA also believes that
positive genotoxicity test results in combination with additional
information (e.g., knowledge of potential exposure to, or high
production of, the chemical substance or mixture), would suggest,
in many cases, the need to conduct additional toxicologic studies
with the results of such testing considered for possible submis-
sion to ~PA pursuant to Section 8(e) of TSCA.
88
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8EHQ-0883-0490
Page 4 of 4
a)
In light of EPA's general interest in company actions
that are taken on a voluntary basis in response to
chemical toxicity/exposure information, CIBA-GEIGY will
be asked to describe the studies that the company is now
conducting/sponsoring, or plans to conduct/sponsor, that
are designed to further define Araldite PT-8l0 toxicity.
b)
The Chemical Hazard Identification
the submitted information in order
further OTS assessment of Araldite
at the present time.
Branch will screen
to determine if
PT-8l0 is warranted
c)
The Chemical Hazard Identification Branch will transmit
copies of this status report to NIOSH, OHSA, CPSC, FDA,
NTP, OW/EPA, OSWER/EPA, OANR/EPA, ORD/EPA, and the Test
Rules Develo~ment Branch (TRDB/AD/OTS). A copy of this
status report will be sent to the TSCA Assistance Office
(TAO/OTS/OPTS/EPA) for further distribution.
89
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
5UIJ£C:T. Status Report*
8EHQ-0983-049l S
8EHO-0983-0491 S
\
Page 1 of 2
Approved D/1tr /o/' j
Revision
Needed
DAn:
OCT-5~
Justine L. Wel~eam Leader
'IOM'Chemical select~~-and Profiles'Team/CHIB
Frank D. Kover, Chief
TO'Chemical Hazard Identification Branch/AD
Submission Description
The U.S. members of the International Chlorinated Paraffin Pro-
ducers Testing Consortium submitted the results from acute and
chronic toxicity studies of chlorinated ,paraffin in Daphnia magna
and Chironomous tentans (midge). In the cover letter, it was
stated that these two studies, as well as assessments of the
ready and inherent biodegradability of chlorinated paraffin and
chlorinated paraffin toxicity studies in mussels (GO-day study),
rainbow trout (GO-day study), and marine alga, had been conducted
in accordance with a "Negotiated Testing Agreement" under Section
4 of TSCA. The cover letter also stated that the decision to
submit the results under Section 8(e) was "not based upon any
individual study but results from cummulative assessment of data
received to date." With the submission of the reports of the
Daphnia magna and Chironomous tentans studies, the Agency has now
received copies of the results from each of the above referenced
studies/assessments. According to the submitter, the adverse
biologic activity observed in the performed studies "was limited
to a short chain length highly clorinated paraffin." It was also
reported that non-biodegradability was found and that bioconcen-
tration had been observed in trout and mussels. The submitter
stated that an "assessment of [chlorinated paraffin] levels
present in the environment is a key to interpreting the meaning
of these data."
Submission Evaluation
Although the finding of serious toxicity to aquatic species due
to exposure to low concentrations of a chemical substance is in
and of itself of considerable concern, the level of concern is
raised significantly when such toxicity is caused by a chemical
that bioaccummulates and/or is not readily biodegradable. All of
the cited chlorinated paraffin studies/assessments are under re-
view by staff of the Test Rules Development Branch (TRDB/AD/OTS)
and "Existing Chemicals Task Force" (ECTF/AD/OTS) in conjunction
with staff of the Environmental Effects Branch (EEB/HERD/OTS).
-NOTE: T~is status reco~t is the result of a prelimir.a~v
staff eval~atior. of i~formation submitteci to EPA. State;ents
mace herein are no~ to be regarded as ex?ressing final
Ase~cy policy or intent with r~s?ect to t~is ?articular
chemical. .;nv review of the status report should take into
- .
consideration the iact that it mav be bas~d on incomolete
information. .. .
90
[~. 'O"a ":1)04 1"1:"". ~'"
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8EHQ-0983-0491 S
page 2 of 2
Current Production and Use
The chlorinated paraffins are a family of chlorinated compounds
that are derived from primarily saturated, straight-chain hydro-
carbons. The maximum amount of chlorination that is achievable
is 70% by weight. In general, the chloroparaffins are viscous
liquids, with viscosity increasing as the percent chlorine in-
creases. These compounds are considered to be soluble in oils
and oil solvents, insoluble in water; readily emulsifiable, and
nonflammable. Chlorinated paraffins are used as fire retardants,
as ~lacticizers and as additives in extreme pressure lubricants.
It should be noted that chlorinated paraffins are used in some
applications as substitutes for polychlorinated biphenyls (PCBs),
a class ot chemical substances that are strictly regulated.
Comments/Recommendations
The U.S. members of the International Chlorinated Paraffin Pro-
ducers Testing Consortium reported that they are planning to
conduct a field study "to determine the levels of chlorinated
paraffin present in various aqueous environments." It was also
reported that this study will be started as soon as possible and
that the results will be submitted to EPA.
a)
The Chemical Hazard Identification Branch (CHIB/AD/OTS)
will send a copy of this status report to NIOSH, OSHA,
CPSC, FDA, NTP, OW/EPA, OSWER/EPA, OANR/EPA, ORD/EPA,
TRDB/AD and the "Existing Chemicals Task Force." A copy
will also be transmitted to the TSCA Assistance Office
(TAO/OTS/OPTS) for further distribution.
91
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DAn:
OCT 2 0 1983
8EHQ-0983-0492 S
Page I of 3
SUIJECT. Status Report
8EHQ-0983-0492 S
App=oved
~/f
Justine L. wel~ieam Leader
nOli. Chemical select!.f~.;: and Profiles Team/CHIB
Revision
Needed
Frank D. Kover, Chief
TOr Chemical Hazard Identification Branch/AD
Submission Description
Although the submitting company claimed its name and the exact
identity of the subject chemical to be TSCA Confidential Business
Information (CBI), the company did report nonconfidentially that
the subject chemical was an aliphatic carbamate. According to
the submission, an acute rat inhalation study was conducted with
the residue obtained from an aerosol of aliphatic carbamate. The
following summarized information was submitted by the company
with regard to this study:
"The aerosol was aspirated with sufficient air to vaporize
substanti~lly all of the water. The remaining material was
classified by particle $ize and a stream containing 99% res-
pirable solid particles having an aerodynamic mass mean di-
ameter of 1-2 [microns] was separated for the test. These
particles were introduced into an exposure chamber containing
six rats. At an airborne concentration of about 0.06 mg/L
administered for 4 hours, all 6 test rats died within 24
hours of administration. At an airborne concentration of
about 0.04 mg/L, 3 of 6 test rats died within 24 hours and
the remaining rats recovered wi thout .apparent ill effects.
At levels of about 0.03mg/L and below no mortality was ob-
$erved. Pathological examination of the rats is underway,
but at this time [the submitting company] is not in a posi-
tion to further characterize or interpret the test results."
The submitter stated that "in view of the above results, a por-
t'ion of the sample used in the inhalation test was administered
intravenously to rats." It was reported that "no ettects were
noted until doses high enough to produce emboli were reached" and
that the "high doses resulted in death." The submitter stated,
however, that the "doses which approximated those which produced
inhalation toxicity (assuming 100% absorption) produced no mor-
tlity." In addition, the company stated that "the aliphatic
carbamate had previously been found to have low oral toxicity
(ALD greater than 25 g/kg) and only slight skin irritation and
mild eye irritation."
-NOTE: This status recort is the result of a crelimina=v
staff evaluation of i~£o~.ation submittec to EPA. State;e~ts
mace herein are not to be regarded as ex?ressir.~ final
Agency policy or intent with r~s?ec~ to t~is ?articular
chemical. .;ny review of the status repor~ should take into
consideration the iact that it may be based on incomplete
informa tion.
92
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8EHQ-0983-0492 S
Page 2 of 3
Submission Evaluation
Although the reported acute rat inhalation study results are
preliminary and only a few animals were used in the study, the
observed lethality was found to be dose-related. Other than the
lethality, no other adverse effects were reported as being noted
during the course of exposure or during the post-exposure period.
In order to interpret the significance of the reported findings,
EPA should request a complete copy of the final report and a com-
plete copy of the results from the pathologic examination which
is reported by the submitter to be underway. It is apparent that
the submitting company was attempting to assess a "worst-case"
exposure by testing a dust that was 99% respirable. The company
reported that the typical exposure to the chemical would not be
expected to involve dust particles that small.
It is of particular interest that the aliphatic carbamate was
found to be more toxic (i.e., lethal) via the inhalation route
than by intravenous administration. Without a complete copy of
the final report (including test protocols and data) from the
intravenous study, however, the validity of the results from the
study cannot be determined.
If one assumes that the results of both the acute inhalation and
intravenous studies are in fact valid, there are at least two
hypotheses that may explain why the aliphatic carbamate was found
to be more lethal via the inhalation route than when administered
intravenously: 1) the inhaled material may have induced a rapid
chemical pneumonitis resulting in pulmonary edema and/or may have
affected pulmonary surfactant resulting in impaired oxygen uptake
and/or carbon dioxide removal; and/or 2) the inhaled material may
have caused bronchial constriction thereby shutting the airways.
The second hypothesis is less tenable, however, unless the ali-
phatic carbamate and/or one of its metabolites reacted with the
blood or its constituents. The results of the postmortem exam-
ination of the rats from the acute inhalation study should help
to determine the validity of the above hyphotheses.
Current Production and Use
Due to the fact that the submitter has claimed the exact chemical
identity of the tested material to be TSCA CBI, no information
relating to production or use will appear in this status report.
The submitting company did report, however, that a dust similar
to that which was tested in the acute rat inhalation study would
not be generated during the manufacture or end-use of the ali-
phatic carbamate.
Comments/Recommendations
The submitting company stated that although "a {"eview of exposu.re
during [aliphatic carbamate] manufacture indicates no exposure by
the inhalation route," the company's employees were being advised
about the submitted toxicologic findings. The submitting company
93
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8EHQ-0983-0492 S
Page 3 of 3
also reported that it plans to conduct the following studies: 1)
an industrial hygiene survey to "investigate the potential for
inhalation exposures that could occur during manufacture, distri-
bution and use of products containing aliphatic carbamate" and 2)
other studies designed to define better the relationship between
aliphatic carbamate particle size and possible toxicity. The
submitting company stated that EPA would be notified about the
status of the company's "scientific investigation of this problem
and [about] any decisions as to changes, if any, in recommended
industrial hygiene practices."
a)
The Chemical Hazard Identification Branch (CHIB/AD/OTS)
will request the submitting company to provide complete
copies of the final reports (including test protocol(s)
and data) from all of the toxicity studies cited in the
company's submission.
b)
The Chemical Hazard Identification Branch will screen
the reported information to determine if further OTS
assessment of the aliphatic carbamate is warranted.
c)
The Chemical Hazard Identification Branch will send 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 sent to the TSCA Assistance Office
(TAO/OTS/OPTS/EPA) for further distribution.
94
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UNITED STATES EHYIROHMENTAL PROTECTION AGENCY
SUIJICT, Status Report*
8EHQ-0983-0493 S
8EHQ-0983-0493 S"
Page I of 3
App=oved ~JA..
C/ '
JI/'
.
DATE:
to
91!m
Justine L. Wel~eam Leader
'1C*'Chemical selecfon and Profiles Team/CSB
Frank D. Kover, Chief
TO'Chemical Screening Branch/ECAD/OTS
Revision
Needed
Submission Description
The submitting company (name claimed to be TSCA Confidential
Business Information (CBI)) reported that it was recently in-
formed by one of its customers that three (3) of the customer's
workers had exhibited "flu-like symptoms" after they had handled
new and spent lots of a product identified non-confidentially by
the submitter as a "mixture of metallic oxides." According to
the submission, the submitting company "received no verification
as to whether those symptoms were caused by exposure to [the sub-
mitter's] material nor as to whether the material was handled
properly."
Submission Evaluation
Other than the statement that three workers had exhibited "flu-
like symptoms" after handling new and used lots of the subject
product, the submission did not present any further information
about the actual condition of the affected workers. F~r example,
the submission did not indicate whether the observed symptoms
were serious, long-lasting, or incapacitating to any degree. In
addition, no information was provided concerning the duration of
the worker's exposure to the product, the time to onset of the
observed symptoms, or the identity of other chemical substances
to which the affected worker's were exposed that could have
caused "flu-like symptoms." It should also be noted that the
submitter did not report the chemical identity of the metallic
oxide components of the subject mixture.
Current Production and Use
Considering the fact that the submitting company has claimed the
exact chemical identity of the subject product to be TSCA CBI and
diq not report the actual chemical identity of the consituents of
the product, no information concerning production or use of the
product or its constituents will appear in this status report.
-NOTE: This status reco=t is the result of a orelirnina=v
staff evaluation 0: i~fo~.ation submittec to EPA Sta~e;'e~ts
mace herein are no~ to be regarded as ex?ressing final
As~n~y policy or intent with res?ect to t~is ?articular
chemical. .~v review of the status report should take into
consideration-the tact that it mav be based on incomolete
information. - .
95
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8EHQ-0983-0493 S
Page 2 of 3
Comments/Recommendations
It is the Agency's initial position that the acute human toxicity
information, as presented in this submission, did not warrant
reporting under section 8(e) of TSCA. The basis for the Agency's
position is as follows:
According the Part V of EPA's March 16, 1978 TSCA section
8(e) policy statement ("Statement of Interpretation and
Enforcement Policy; Notification of Substantial Risk" 43 FR
11110), 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 seriouness of the effect, EPA considers
the human health effects for which substantial risk informa-
tion 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 if one (or a few) chemical(s)
is strongly implicated. In addition, Part VI(2) of the 8(e)
policy document states that it is possible that effects less
serious than those described above may be preliminary mani-
festations of those more serious effects and together with
another triggering piece of information, constitute section
8(e)-reportable information.
Therefore, because the human health effects reported in this
submission do not appear to be serious and do not appear to have
resulted in a prolonged incapacitation or a serious impairment of
normal bodily functions/activities, the Agency believes that the
reported acute human toxicity information, when considered alone,
did not warrant submission under section 8(e) of TSCA. It must
be emphasized, however, that EPA's position with regard to the
8(e)-reportability of the submitted information is based solely
on the provided information and not on pertinent information that
may have been available to and/or considered by the submitter in
deciding to report the observed symptoms under section 8(e).
It is also important to point out that although EPA does not
believe that the human health effects information, as presented
in this submission, was required for reporting pursuant to TSCA
section 8(e), EPA does believe that as of November 21, 1983 (as
explained below), such information may constitute an "allegation
of a significant adverse reaction" as defined under TSCA section
8(c). Section 8(c) requires that "any person who manufactures,
processes, or distributes in commerce any chemical substance or
mixture" must keep "records of significant adverse reactions to
health or the environment, as determined by the Administrator by
rule, alleged to have been caused by the substance or mixture."
Section 8(c) also requires that allegations of adverse reactions
to the health of employees be kept for 30 years, and all other
allegations be kept for five years. ,In addition, the Agency is
empowered to inspect and/or require submission of 8(c) records.
96
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8EHQ-0983-0493 S
Page 3 of 3
On August 22, 1983, the Agency published (48 FR 38178) the final
rule implementing section 8(c) of TSCA. Subject persons will be
required to be in full compliance with section 8(c) of TSCA as of
November 21, 1983.
a)
In light of the preceeding discussion, the Chemical
Screening Branch (CSS/ECAD/OTS/OPTS) will transmit a
copy of the August 22, 1983 Federal Register (48 FR
38178) notice on TSCA section 8(c) to the submitting
company. In addition, the Chemical Screening Branch
will request the submitting company to provide its
rationale as to why the provided human health effects
information was reported to the Agency under section
8(e) of TSCA. The Chemical Screening Branch will also
request the submitter to provide the exact identity
(including the CAS Registry Number if known) of each of
the chemical components in the "mixture of metallic ox-
ides." Considering EPA's general interest in company
actions that are taken in response to chemical toxicity
and exposure information, the Chemical Screening Branch
will ask the submitter to describe the actions that have
been taken or are planned by the submitter's company to
determine the severity of the reported human toxicity
and to determine the cause(s) of that toxicity.
NOTE: The submitter has been requested in writing by the
OTS Document Control Officer to substantiate all of the
company's confidentiality claims.
b)
Copies of this status report will be sent to NIOSH and
OSHA and to the TSCA Assistance Office (TAO/OTS/OPTS)
for further distribution.
97
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-l083-0494
pa.ge 1 of 4
DAn:
tD/211Ei
5UaJ£CT, Sta tus Report *
8EHQ-l083-0494
APP::oved~-
Revision
Needed
i j/(
nOM Justine L. Wel£~ection Chief
'Chemical Risk ~ntification Section/CSB
TO Frank D. Kover, Branch Chief
'Chemical Screening Branch/ECAD
Submission Description
Pursuant to Section 8(e) of TSCA, PPG Industries, Inc. provided
to EPA's Office of Toxic Substances the summarized results of
several in vivo toxicity studies of sodium azide (CAS No. 26628-
22-8) an~potassium azide (CAS No. 20762-60-1) According to
PPG, the preliminary and final reports of the subject studies
were previously submitted (in 1981) to the Office of Pesticide
Programs (OPP/OPTS/EPA) under Section 6(a)(2) of the Federal
Insecticide, Fungicide, and Rodenticide Act (FIFRA) because the
company had obtained a "registration for a formulating use of
sodium azide." The following information was contained in the
cover letter to, PPG's April 14,. 1981 FIFRA Section 6(a)(2) sub-
mission on sodium azide:
"PPG Industries, Inc. has been pursuing the development of
sodium azide for use as a soil fungicide. Several Exper.imen-
tal Use Permits have been obtained for its use on peanuts,
rice, Florida vegetables and ornamentals. In 1974, a regis-
tration for a 15% granular formulation of sodium azide ~as
issued (748-219) for formulating use only. Although this
registration and these permits have had the effect of limi-
ting environmental exposure to sodium azide to a minimum,
nevertheless [PPG feels] compelled under Section 6(a)(2) of
fIFRA to bring the following facts to [EPA's] attention:
1 )
There are several literature references to observed
effects on the central nervous system due to'exposure to
sodium azide via intravenous or intraperitoneal injection
in species such as rats and monkeys. (Casarett, L. J. and
Doull J., Toxicology, The Basic Science of Poisons, pp
152-167 Macmillan (1975))
2 )
In 1970, as part of PP I-GI066, PPG submitted a 125-Day
Subacute Oral Toxicity Study of Potassium Azide [KN] on
Beagle Dogs...In this study, animals were dosed with 0.1,
-NOTE: T~is status reDo=t is the result of a crelimina=v
staff evaluation of i~forma~ion subrnit~~c to EPA. State;e~ts
mace herein are nOt to be re~arded as ex~ressir.o final
Ase~cy policy or intent witp.res?ec~ to t~is particular
chemical. .~y review of the status report should take into
consideration the iact that it may be based on incom?let~
information.
98
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8EHQ-l083-0494
P~ge 2 of 4
1.0 and 10.0 mg KN per Kg of body weight per day. At the
high dose rate, symptoms of motor ataxia were observed in
four of the eight treated animals. Two of these animals
had to be sacrificed in extremis (a male after 60 days
and a female after ll~days). However, no histopatho-
logical or other abnormalities were noted in this study.
Subsequently, PPG has not been able to validate this
study, largely because of [the company's] inability to
track the individual animals in the raw data.
3 )
In 1980, PPG commissioned another subchronic oral feeding
study in dogs...using [sodium azide] treatment rates of
1, 3 and 10 mg/Kg/day. In the 27th and last week of this
study, ataxia was again observed in two high-dose females
and one mid-dose male. However, unlike the earlier study,
a draft report...indicates that compound-related histo-
morphologic changes were found in the two ataxic high-
dose females. Lesions were detected in both the anterior
and middle cerebral sections, and consisted of one or
more of the following alterations: gliosis, vascular
prominence due to endothelial cell swelling and conden-
sation of the neuropil, demyelination and degenerative
changes in the caudate nucleus. To the best of [PPG1s]
knowledge, this is the first time that CNS lesions have
been found in animals treated by oral ingestion of sodium
azide.
[The performing laboratory scientists] also reported
possibly [sodium azide] treatment-related clinical chem-
istry findngs, including: decreased alkaline phosphatase
in all male treated groups and in most female groups, de-
creased LDH levels in all male treated groups and de-
creased serum glutamic oxalocetic transaminase levels in
most treated groups....
Other than the above, there were no distinct treatment-
related trends evident in any of the body weight and food
consumption data, opthalmologic and neurologic examina-
tions, or the hematology, urinanalysis, gross pathology,
terminal body weight and absolute and relative organ
weight data."
In the cover letter to its Section 8(e) notice, PPG Industries,
Inc. gave the following rationale for its decision to re-submit
the toxicity information at this time under Section 8(e) of TSCA:
" [PPG has] noted from recent press accounts that there are
renewed plans for the production of air bag restraint systems
for automobiles. [PPG] information in past years was that
sodium azide is used as a propellant for air bags. In view
of this poss ible expanded use, [PPG] thought it appropriate
to make sure that the Office of Toxic Substances was aware of
the information previously provided and [is] resubmitting the
correspondence pursuant to Section 8(e)..."
99
-------
8EHQ-I083-0494
~e3cl4
Submission Evaluation
The results of the subchronic sodium azide feeding study in dogs
are consistent with the results of other sodium azide studies in
other species by other routes of exposure. The potency of sodium
azide via the oral route appears to be similar to that found by
either intraperitoneal or intramuscular injection. Although no
histopathological abnormalities were observed in dogs exposed to
potassium azide, the ataxia which was found is consistent with
sodium azide toxicity; further potassium azide dosing might have
resulted in overt pathology. Finally, the changes observed in
both subchronic studies appear to be treatment related.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for sodium azide (CAS No. 26628-22-8), which is listed
in the initial TSCA Inventory, has shown that between 20 thousand
and 200 thousand pounds were reported as produced and/or imported
in 1977. This production range information does not include any
production/importation data claimed as confidential by those per-
son(s) reporting for the TSCA Inventory, nor does it include any
information that would compromise TSCA Confidential Business
Information. **/
A review of the production range (includes importation volumes)
statistics for potassium azide (CAS No. 20762-60-1), which is
listed in the initial TSCA Inventory, has shown that no 1977 pro-
duction/importation was reported or that all of the production
range data reported were claimed as confidential by the manufac-
turer(s) and/or importer(s) and cannot be disclosed (see Section
14(a) of TSCA, U.S.C. 26l3(a)). **/
In addition to the fungicidal applications cited in the Section
8(e) notice, sodium azide is used as an intermediate in organic
syntheses and explosives manufacture, as a laboratory reagent for
preserving solutions, and in preparing hydrazoic acid, lead azide
and pure sodium. No information on the use(s) of potassium azide
was located in the secondary literature sources consulted.
Comments/Recommendations
Technically, the provided toxicity information on sodium azide,
once formally submitted to EPA under Section 6(a)(2) of FIFRA,
need not have been submitted pursuant to Section 8(e) of TSCA.
According to Part VII (b) 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), information need not be reported under TSCA Section 8(e)
**/ All data submitted for the TSCA Inventory, including the
production range information, are subject to the limitations
contained in the Inventory Reporting Regulations (40 CFR 710).
100
-------
8EHQ-1083-0494
PAge 4 pI; 4
if it "has been submitted in writing to EPA pursuant to mandatory
reporting requirements under TSCA or any other authority adminis-
tered by EPA (including the Federal Insecticide, Fungicide and
Rodenticide Act...)."
A Chemical Hazard Information Profile (CHIP) on sodium azide was
prepared by OTS staff on August 1, 1977.
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will screen
the reported information in order to determine if further
OTS assessment of sodium azide and/or potassium azide is
warranted.
b)
Considering the issue relating to the use of sodium azide
as an air bag propellant, the Chemical Screening Branch
will provide a copy of this status report to the Office
of Motor Vehicle Safety Standards/National Highway Traf-
fic Safety Administration/Department of Transportation
(DOT). In addition, copies of this status report will be
sent to NIOSH, OSHA, CPSC, FDA, DOT, OW/EPA, OSWER/EPA,
OANR/EPA, ORD/EPA, and OPP/OPTS/EPA. A copy of this re-
port will also be provided to the TSCA Assistance Office
(TAO/OTS/OPTS) for further distribution.
101
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UNITED ST A.TES ENYIR"ONMENTAL PROTECTION AGENCY
DAn:
NW 28 ~
8EHQ-I083-0495
Page I of 3
SuaJ£CTI
Status Report*
8EHQ-I083-0495
1\pprOvedOJt<-
Revision
Needed
/(/~~
'IOMI
Justine L. Wel~ction Chief
Chemical Risk t1entification Section/CSB
Frank D. Kover, Branch Chief
Chemical screening Branch/ECAD/OTS/OPTS
TOI
Submission Description
The Eastman Kodak Company submitted the final results/reports
from an in vitro mammalian cell transformation assay and three in
vitro Ames Salmonella typhimurium (bacteria) assays of 2-amino-4-
phenylphenol (CAS No. 1134-36-7). Eastman Kodak provided the
following summary of .resul ts in its submission:
"On October 4, 1983, 2-amino-4-phenylphenol was reported to
be positive in an In Vitro Mammalian Cell Transformation
Assay by the Health; Safety, and Human Factors Laboratory of
Eastman Kodak Company. The c~ll line was Balb 3T3 clone ~31-
1-13. This material induced foci of transformed cells over a
concentration range of 1.2 ug/mL to 12 ug/mL. The relative
cell survival covered by this concentration range was 99.5%
to <1%. A statistically significant (p
-------
8EHQ-l083-0495
Page 2 of 3
Submission Evaluation
The provided in vitro genotoxicity results show that 2-amino-4-
phenylphenol induces cellular transformation in Balb/c-3T3 cells
when tested without metabolic activation. Although it was stated
in the report that the chemical also induced gene mutation in
Salmonella typhimurium strain TA 100 when tested both with and
without metabolic activation in an S. typhimurium/mammalian
microsomal assay (Ames test), no data were presepted to support
this claim. In light of this statement, and in the absence of
evidence to the contrary, 2-amino-4-phenylphenol should be con-
sidered to be a bacterial mutagen. The negative results reported
for this agent in the 1975 Ames assay must be discounted because
strain TA 100 was not yet available for use in the assay and
because only one minimal dose was tested.
In its submission, the Eastman Kodak Company also provided a
Toxicity and Health Hazard Summary, Environmental Safety Data
Sheet, and a report entitled, "Basic Toxicity of 2-Amino-4-
Phenylphenol." According to the these reports, the acute oral
LD50 for 2-amino-4-phenylphenol was found to be 2262 mg/kg in
both rats and mice, and the acute dermal LD50 was found to be in
excess of 1000 mg/kg in guinea pigs. In addition, the chemical
was reported to be only slightly irritating to the skin (guinea
pigs) and eyes (rabbits). The sensitization potential in guinea
pigs was reportedly found to be moderate and the results of an
II-day feeding study in rats showed that the kidney and red blood
cells were the major sites of toxicity.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for 2-amino-4-phenylphenol (CAS No. 1134-36-7), which
is listed in the initial TSCA Inventory, has shown that between 1
thousand and 10 thousand pounds of this chemical substance were
reported as produced/imported in 1977. This production range in-
formation does not include any production or importation data
claimed as confidential by the person(s) reporting for the TSCA
Inventory, nor does it 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 TSCA Inventory
Reporting Regulations (40 CFR 710).
The following exposure/use information for 2-amino-4-phenylphenol
was presented by Eastman Kodak in its submission:
"Essentially all of the small amount of 2-amino-4-phenyl-
phenol manufactured is used as a site-limited chemical
intermediate by Eastman Kodak Company. This chemical is
manufactured in closed equipment with potential for dermal
and inhalation exposure only during a rotary drying opera-
tion. During this operation four operators are potentially
exposed for 20 minutes/day up to 10 times/year. Their 8-hr
103
-------
TWA exposure
minimized by
glasses, and
dered by the
8EHQ-I083-0495
~~3cl3
would be less than 1 mg/m3 Worker exposure is
local exhaust, use of neoprene gloves, safety
dust masks, and clothing is supplied and laun-
corporation.
During on site use in closed equipment, dermal and inhalation
exposure may occur for one to three people for 30 minutes/day
up to 3 times/year. Local and general exhaust, dust masks,
gloves, safety glasses, and protective clothing are used to
minimize ex~osure. Potential exposure is estimated at less
than 1 mg/m 8-hr TWA.
Less than 0.1% of the small amount manufactured is sold for
laboratory use in 25 g bottles. One employee is involved in
bottling. The operation occurs with local exhaust. Poten-
tial exposure may be 15 minutes/day, 1 day/year and is expec-
ted to be less than 1 mg/m3 for the 15 minute operation.
Wastes from manufacture, use, and bottling are incinerated on
site or treated in an on site activated sludge wastewater
treatment facility; therefore, there is minimal risk to the
environment from the manufact~re, use, and processing of this
chemical."
Comments/Recommendations
Although Eastman Kodak stated that the
any adverse health problems associated
4-phenylphenol, the company did report
current label and recommended handling
company was not aware of
with exposure to 2-amino-
that it is reviewing the
procedures.
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will screen
the reported toxicity and exposure information in order
to determine the need for further OTS assessment of 2-
amino-4-phenylphenol.
b)
The Chemical Screening Branch will send a copy of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OW/EPA,
OSWER/EPA, OANR/EPA and ORD/EPA. A copy of this status
report will also be provided to the TSCA Assistance
Office (TAO/OTS/OPTS/EPA) for further distribution.
104
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UNITED ST A TE.S EHY IRONMENTAL "pROTECTION AGENCY
5UIJECT.
Status Report *
8EHQ-I083-0496
8EHQ-I083-0496
Page 1 of 3
App=oved ;;JJ.-
1(c28
DATE:
NOV 2 3 .f983
fiOM.
Justine L. wel~AJection Chief
Chemical Ri sk tIe'i1-ti f icat ion Sect ion/CSB
Revision
Needed
TO.
Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Eastman Kodak Company submitted the final results from three
in vitro mouse cell transformation assays, an in vitro mouse cell
mutagenicity assay and two Ames/Salmonella typhlmurium (bacteria)
assays of 4-methyl-2-nitroaniline (CAS No. 89-62-3). Eastman
Kodak provided the following summarized information in the cover
letter to the company's submission:
"On October 4, 1983, 4-methyl-2-nitroaniline was reported to
be positive in an In Vitro Mammalian Cell Transformation
Assay by the Health, Safety, and Human Factors Laboratory of
Eastman Kodak Company. The cell line was Balb 3T3 clone A31-
1-13. The three highest doses of 4-methyl-2-nitroaniline in-
duced a statistically significant increase (p-4 uu:v. ~'II
-------
8EHQ-l083-0496
Page 2 of 3
In August, 1980, [the contract laboratory] reported that the
test material did not induce transformed foci in the In Vitro
Balb 3T3 Cell Transformation Assay (clone 113 C14) over the
applied concentration range of 0.1 ug/mL to 25.0 ug/mL. This
range corresponded to approximately 50% to 80% survival in
the cytotoxicity test. The test material was considered to
be inactive in the In vitro Balb 3T3 Cell Transformation
Assay.
A mutagenicity evaluation of 4-methyl-2-nitroaniline in the
Mouse Lymphoma Forward Mutation Assay, completed by [the con-
tract laboratory] in October, 1979, resulted in a significant
increase in the mutation frequency at the TK locus in L5178Y
Mouse Lymphoma cells only in the presence of rat liver S-9
microsomal activation. Concentrations from 31.3 ug/mL to 250
ug/mL were moderately toxic and induced dose-dependent in-
creases in mutation frequency while 500 ug/mL was lethal.
without activation, concentrations up to the highly toxic le-
vel of 500 ug/mL were not detectably mutagenic. The compound
was considered to be active in the presence of microsomal
metabolism in the Mouse Lymphoma Forward Mutation Assay.
The material was found to be negative in the Bacterial
Mutagenesis Assay (Ames Test) by [the contract laboratory]
and by Eastman Kodak Company."
Submission Evaluation
There is no evidence from the submitted test data that 4-methyl-
2-nitroaniline is a bacterial mutagen when tested in the Ames
Salmonella typhimurium assay.
4-Methyl-2-nitroaniline was tested for its ability to induce
morphologic transformation of Balb/c-3T3 cells on three occa-
sions; once by Eastman Kodak and twice by a contract labora-
tory. The assay conducted by Eastman Kodak and one of the two
assays conducted by the contract laboratory was positive; the
other cell transformation assay conducted by the contract labor-
atory was negative. A review of the submitted data revealed no
apparent reasons for this discrepancy. In light of the two pos-
itive responses, however, 4-methyl-2-nitroaniline should be con-
sidered to induce morphologic transformation in Balb/c-3T3 cells.
4-Methyl-2-nitroaniline was also tested for its ability to induce
gene mutation in cultured mouse lymphoma L5178Y cells. Under the
conditions of this test, the chemical was shown to be mutagenic
for L5178Y cells when tested with metabolic activation. Although
there is a discrepancy in the requirement for metabolic activa-
tion in the Balb/c-3T3 and mouse lymphoma L5178Y cell systems, it
may be a reflection of the different inherent metabolic capabili-
ties of these tw~ cell lines. 3-Methylcholanthrene, for example,
which requires metabolic activation when tested in the Ames assay
and L5l78Y cells, is a direct-acting transformant for Balb/c-3T3
cells.
106
-------
8EHQ-l083-0496
Page 3 of 3
In addition to the in vitro genotoxicity data, the Eastman Kodak
Company also submitted a "Toxicity and Health Hazard Summary" for
4-methyl-2-nitroaniline. According to provided in vivo toxicity
information, the acute oral LD50 for the compoun~was found to be
approximately 1900 mg/kg in rats and in excess of 3200 mg/kg in
mice. In addition, the chemical was found to cause slight eye
irritation in rabbits and slight skin irritation (with no evi-
dence of skin absorption) in guinea pigs. The provided informa-
tion also indicates that 4-methyl-2-nitroaniline did not produce
significant methemoglobinemia in rats dosed orally at 1000 mg/kg.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for 4-methyl-2-nitroaniline (CAS No. 89-62-3), 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. This production range information
does ~ot 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 TSCA
Confidential Business Information. The data submitted for the
TSCA Inventory, including production range information, are sub-
ject to the limitations contained in the Inventory Reporting
Regulations (40 CPR 710).
The Eastman Kodak Company reported that because the company does
"not manufacture, process, or distribute [4-methyl-2-nitroani-
line] in commerce...there is no employee exposure and no environ-
mental release." Eastman Kodak also reported that "the chemical
was last purchased and used in 1981 and there are no plans for
future use."
Comments/Recommendations
In its submission, Eastman Kodak stated that although the company
was "not aware of any adverse health problems associated with [4-
methyl-2-nitroaniline] ...any future use would be after careful
review of the laboratory findings and handling procedures to as-
sure maximum safety to personnel and the environment before
working with the chemical."
a)
The Chemical Screening Branch will screen the reported
toxicity and exposure information in order to determine
if further OTS assessment of 4-methyl-2-nitroaniline is
warranted.
b)
The Chemical Screening Branch will send a copy of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OW/EPA,
OSWER/EPA, OANR/EPA and ORD/EPA. A copy of this status
report will also be provided to the TSCA Assistance
Office (TAO/OTS/OPTS/EPA) for further distribution.
107
-------
UNITED STATES EHVIROHMENTAL PROTECTION AGENCY
SuaJ£CT, Status Report*
8EHQ-IO 83-04 97
8EH<;}-1083-0497
,Page 1 of 4
App"oved ;:JL
Revision
Needed
"(;3
DA1£:
trN 2 3 1003
Justine L. Wel~ction Chief
'IOM'Chemical Risk -~~tification Section/CSB
Frank D. Kover, Chief
TOrChemical Screening Branch/ECAD
Submission Description
E. I. Du Pont de Nemours & Company, Inc. submitteo summarized
preliminary findings from a two-year rat inhalation study of
titanium dioxide (CAS No. 13463-67-7) conducted at Du Pont's
Haskell Laboratory for Toxicology and Industrial Medicine.
According to Du Pont, 100 male and 100 female Charles River-CD
rats were exposed to respirable titanium dioxide dust levels of
0, 10, 50 or 250 mg/m3 for six hours per day, five days per week
for 104 weeks. The titanium dioxide particles in the exposure
chamber were reported to have had an estimated mass median dia-
meter of approximately 1.6 microns. Du Pont reported that there
were no effects on survival and no clinical signs of any adverse
effect at any dose for rats exposed for 104 weeks. Du Pont also
stated that no tumors were observed at any dose among the small
number of rats sacrificed at three months, six months and one
year. With regard to the remaining animals, Du Pont presented
the following information:
"The remaining rats were sacrificed at the end of the 104-
week exposure period. All major tissues and organs were
studied. All except the respiratory system were normal. In
the lungs a preliminary diagnosis indicated a statistically
sign if icant incidence ot' microscop ic tumors identi f ied as
squamous cell carcinoma (in about 10% of the rats) and bron-
chiolalveolar adenoma (in abqut 15% of the rats) at the 250
mg/m3 .level. No increased inc idence of these tumors was ob-
served at lower dose levels. In addition, although upon
gross examination the rats appeared normal, the tissues
lining the nasal cavity and the trachea" showed microscopic
evidence of irritation. Minute areas of lung fibrosis were
also noted at the two higher exposure levels."
Du Pont reported that the titanium dioxide respirable dust level
of 250 mg/m3 (i.e., the dose level producing tumors in rats) is
well above that which could be obtained in an occupational set-
ting. Du Pont also reported that a survey of personal monitoring
data from Du Pont plants indicated "that in the job with the
-NOTE: T~is status reco=t is the result of a crelirnina=v
staff evaluation of i~fo~.ation submitted to EPA. State;e~ts
mace herein are nOt to be re~arded as ex~ressino final
Agency policy or intent with'res?ec~ to t~is particular
chemical. .;ny review 6f the status repor~ should take into
consideration the fact that it ~av be based on incomolete
information. . .
108
E~' ':01'''' 1J:1)-6 u'£v. ~"I
-------
8EHcrl083-0497
Page 2 of 4
highest potential for exposure, the highest mean ex~osure was 3.1
mg/m3 of total dust with a range of 0.7 to 3.1 mg/m." Based on
these preliminary measurements, Du Pont stated that "the maximum
respirable fraction is 42% of the total dust."
As background information, Du Pont reported that titanium dioxide
"is essentially nontoxic on an acute basis, as its approximate
lethal oral dose is greater than 25 g/kg." Du Pont also reported
that titanium dioxide was tested by the National Cancer Institute
(NCI) at 25,000 or 50,000 ppm in the diets of Fisher 344 rats and
B6C3Fl mice for 103 weeks and was not found to be carcinogenic in
either species (DHEW Publication No. 79-1347 (NIH».
In conclusion, Du Pont stated that the information presented in
its submission does "not suggest that existing manufacturing
practices in the titanium dioxide industry or use by customers
poses risk of adverse health effects."
Submission Evaluation
Titanium is not known to be a carcinogenic metal. As reported by
the submitter, the NCI 2-year feeding study with rats and mice
showed that titanium dioxide was non-carcinogenic under the con-
ditions of the bioassay. The findings of this NCI bioassay are
consistent with the results of earlier studies in which titanium
itself failed to display tumorigenicity. The small percentage of
pulmonary squamous cell carcinomas and bronchioalveolar adenomas
observed at the high dose (i.e., 250 mg titanium dioxide pigment
dust/m3) in Du Pont's 2-year rat inhalation study may be ascribed
to the pneumoconiosis-inducing properties of hard mineral dusts.
Silicosis is the most extensively studied type of pneumoconiosis
and it is known that in a small percentage of cases, the resul-
ting fibrotic tissue may give rise to malignant lung tumors.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for titanium dioxide (CAS No. 13463-67-7), which is
listed in the initial TSCA Inventory: shows that between 500
million and 1.8 billion pounds were reported as produced/imported
in 1977. This production range information does not include any
production/importation data claimed as confidential by those per-
sons reporting for the TSCA Inventory, nor does it include any
information which would compromise TSCA Confidential Business
Information. The data submitted for the TSCA Inventory, inclu-
ding production range information, are subject to the limitations
contained in the Inventory Reporting Regulations (40 CFR 710).
According to secondary literature sources, titanium dioxide can
be used in the production of white pigment in paints, paper,
rubberi and plastics; as an opacifying agent; in cosmetics;
radioactive decontamination of skin; floor coverings; glassware
and ceramics; er.amel fri ts; delusteri ng synthetic fibers,
printing inks and welding rods.
109
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8EHQ-l083-0497
Page 3 of 4
Comments/Recommendations
In its submission, Du Pont stated that the current OSH~ Standard
for titanium dioxide (as a "nuisance dust") is 15 mg/m and the
American Conference of Governmental Industrial Hygienists (ACGIH)
has rec~mmended a titanium dioxide Threshold Limit Value (TLV)30f
10 mg/m. According to Du Pont, the high dose level (250 mg/m )
of titanium dioxide respirable dust which was tested in the com-
pany's two-year rat inhalation study, in addition to being well
above both the OSHA Standard and ACGIH TLV, is also well above
that which could be obtained in an occupational setting. Never-
theless, Du Pont stated that in view of the reported oncogenicity
findings, the company plans to:
1.
communicate the test results and Du Pont's assessment of
their meaning to employees, competitors and customers,
and to other Federal agencies (OSHA, NIOSH, FDA and
MSHA) ;
2.
conduct an epidemiology or detailed employee health
study; and
3.
assess the need for furth~r toxicity studies.
With regard to its plans to conduct an epidemiology or employee
health study, Du Pont stated that although preliminary indica-
tions are that the employees in Du Pont's titanium dioxide manu-
facturing plants have experienced no statistically significant
increase in incidence of mortality from lung cancer, the company
plans to confirm these findings. Du Pont also reported that the
company will advise EPA of the results of further Du Pont studies
and will provide to EPA a final report of the 2-year rat inhala-
tion study with titanium dioxide as soon as that report becomes
available.
There a number of titanium dioxide-related actions/activities
that are underway within and/or completed by the other EPA
Program Offices under such authorities as the Clean Water Act
(CWA), the Clean Air Act (CAA), and the Resource Recovery and
Conservation Act (RCRA).
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will request
E. I. Du Pont de Nemours & Company, Inc. to ensure that
EPA receives a complete copy of the final report from Du
Pont's 2-year titanium dioxide inhalation study including
test protocols and data. In addition, Du Pont will be
requested to provide to EPA any available information
with regard to the job or job categories with the highest
potential for occupational exposure to titanium dioxide.
b)
The Chemical Screening Branch will screen the submitted
information on titanium dioxide in order to determine the
need for further OTS assessment.
no
-------
8EHQ-1083-0~97
Page 4 of 4
c)
The Chemical Screening Branch will transmit copies of
this status report to NIOSH, OSHA, MSHA, CPSC, FDA, NTP,
OW/EPA, OSWER/EPA, OANR/EPA, ORD/EPA, and OPP/OPTS/EPA.
In addition, a copy of the report will be sent to the
TSCA Assistance Office (TAO/OTS/OPTS/EPA) for further
distribution.
111
-------
UNITED 5T A TES EHYIROHMENTAL PROTECTION AGENCY
suanC:T. Status Report
8EHQ-I083-0498
8EHQ-I083-0498
Page 1 of 4
App:oved {J1t-
Revision
Needed
Jl?-7
I
DAn:
tfN 2 5 1983
, OM Justine L. wel~Askction Chief
. . Chemical Risk I~~tification Section/CSB
TO Frank D. Kover, Branch Chief
tChemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Gulf Oil Chemicals Company submitted final results/reports
from a two-week repeated dose rat dermal toxicity study and a
nine-day repeated dose rat inhalation toxicity study of Gulf
Aromatic Pyrolysis Oil (CAS No. 64742-90-1). The submitter's
cover letter presented the following summarized results:
"There were no animal deaths reported in either study;
however, there were several toxicological effects. In the
two-week dermal toxicology study on rats, the material was
applied to the backs of the rats at 2 dose levels, either
2 g/kg (undiluted) or 1 g/kg (diluted with corn oil) for 9
daily applications during a 14-day period. The test material
was' wiped from the backs of the animals approximately 6 hours
after application. Findings related to dermal exposure to the.
test material included moderate to severe erythema with es-
char formation, alopecia, peeling skin arid dermal fissures.
Hair loss was not seen in the low dose animals. Histological
evaluation of the skin of the high dose animals showed hyper-
plasia, acanthosis and hyperkeratosis. Possible treatment-
related effects included: depression of body weight gain and
food consumption, and increased liver weight. .,There were no
changes in the liver function as reflected in ~he blood chem-
istry profile nor were there any histopathological changes
reported in the liver.
In the inhalation studj' rats were exposed .to airborne con-
centrations of 0.5 g/M or 2.0 g/M3 of Aromatic Pyrolysis
Oil, 6 hours/day for a total of 9 days during a 12-day per-
iod. Treatment-related effects resulting from inhalation ex-
posure included body weight loss, yellow discoloration of the
'.ungs, and hyperplas ia of the alveolar macrophages. S igni f i-
cant changes occurred in several organ weights: liver and
lung weights were increased, while spleen and heart weights
were decreased. There were no biologically significant
changes in the hematology or blood chemistry values."
-NOTE: T~is status repo~t is the result of a prelirnina~y
staff evaluation of i~forma~ion submitted to EPA Stateme~ts
mace herein are no~ to be re~arded as ex~ressino final
.. . . .,
Ase~cy policy or intent with respect to t~is particular
chemical .;nv review of the status report should take into
consideration-the fact that it may be based on incomolete
informa tion. - .
112
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8EHQ-I083-0498
Page 2 of 4
With regard to the relevance of the performed subacute toxicity
studies toward human health, the submitter stated that the com-
pany considered the following two items to be significant:
"Firstly, in the dermal study, there was no attempt made to
wash the material off the skin following exposure, as would
occur in the workplace. Thus, the animals were exposed over
a 6-hour period to a high concentration of the test material
which covered approximately 10 percent of the body surface
area. Secondly, in the inhalation study, the dose levels
were 100-400 times the oil mist standard which would be used
for an upper exposure limit in the workplace and does provide
a reasonably high margin of safety."
In addition to the subacute in vivo toxicity studies, the company
stated that a draft report oY-an-Tn vitro BALB/3T3 Mouse Cell
Transformation Test concluded tha~Gulf Aromatic Pyrolysis Oil
was positive under the conditions of the test.
Submission Evaluation
The reported two-week repeated dose dermal toxicity and nine-day
repeated dose inhalation toxicity studies indicate that Aromatic
Pyrolysis Oil is toxic but not unusually so. Although exposures
were reliably associated with various toxic symptoms/signs, in-
cluding weight loss, ocular and nasal discharge, hair loss and
skin reactions, the brain and lungs were only minimally affected;
such is not the case with many hydrocarbon exposures. There was
no mortality reported by either the dermal or inhalation routes
of exposure. The observed skin fissuring and pulmonary alveolar
macrophage hyperplasia are to be expected as similar adverse
effects have been reported with dermal and inhalation exposures
to other petroleum process steams. It is probably significant
that microscopic examination of the lungs did not yield reports
of macrophage necrosis or of polymorphonuclear infiltration in
the lung. The skin effects resulting from inhalation exposure
illustrate well that whole-body inhalation exposure involves der-
mal exposure. Apparently, inhalation exposure was more effective
than dermal administration in eliciting a depression of spleen
weight and an elevation of serum glutamic-pyruvic transaminase
(SGPT), the latter in the high-dosage group. Although these
changes were not dramatic and their biological importance is not
clear, the SGPT observation does tend in a small way to weaken
the conclusion in the Gulf cover letter that there were "...no
changes in...liver function as reflected in the blood chemistry
profile...." The increase seen in liver weights with exposure
was probably reactive or adaptive, rather than pathological.
The submitted inhalation study highlights the importance of
measuring the actual concentration of the test material in the
exposure chamber, and preferably in the animals' breathing zone.
In the low-dose group, the actual concentration measured in the
chamber was only one-quarter of the nominal or estimated concen-
tration (i.e., 0.54 g/M3 actually present, compared with 2.2 g/M3
113
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8EHQ-I083-0498
Page 3 of 4
calculated to be the nominal concentration).
even more pronounced in the high dose group,
concentration was less than one-tenth of the
tion (i.e., 2.0 g/M3 actual versus 22.4 g/M3
The difference was
in which the actual
nominal concentra-
nominal).
Current Production and Use
A review of the production range (includes importation volumes)
statistics for Gulf Aromatic Pyrolysis Oil (CAS No. 64742-90-1),
which is listed in the initial TSCA Inventory, has shown that
over 1.39 billion pounds were reported as produced/imported in
1977. This production range information does not include any
production/importation data claimed as confidential by those
person(s) reporting for the TSCA Inventory, nor does it include
any information which would compromise TSCA 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).
According to the definitions section of the TSCA Inventory, CAS
No. 64742-90-1 pertains to steam-cracked petroleum residues which
are defined as follows:
"A complex combination of hydrocarbons obtained as the
residual fraction from the distillation of the products of a
steam cracking process (including steam cracking to produce
ethylene). It consists predominantly of unsaturated hydro-
carbons having carbon numbers predominantly greater than C14
and boiling above approximately 260°C (500°F). This stream
is likely to contain 5 wt. % or more of 4- to 6-membered
condensed ring aromatic hydrocarbons."
In its submission, the Gulf Oil Chemicals Company stated that its
"Aromatic Pyrolysis oil is an intermediate process stream from an
ethylene/quench oil pyrolyis unit which is used for supplementary
fuel for [Gulf's] olefins operations." With regard to exposure
to this oil, the submitting company reported:
"Generally, the material will be totally contained within
piping, instruments, and process equipment. The only time the
material is not totally enclosed is when filters and furnace
burners are cleaned, or when drain lines are opened from sam-
pling ports, pump seals, valve packings, and heat exchangers.
The material also has negligible vapor pressure under normal
operating temperature which minimizes the formation of air-
borne concentrations. Potential exposure to [company] employ-
ees is considered minimal, and no consumer exposure occurs
since the material has not been introduced into commerce."
Comments/Recommendations
In the cover letter to its submission, the Gulf Oil Chemicals
Company stated that although the company's "long-standing work
practices, and current safety, health, and hygiene procedures
114
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8EHQ-I083-0498
Page 4 of 4
provide adequate protection for the approximately 20 persons per
shift who work in the process area," the company is revising the
Gulf Aromatic Pyrolysis Oil Material Safety Data Sheet (MSDS),
reviewing appropriate company industrial hygiene data, and noti-
fying Gulf employees and potential customers about the results of
the reported studies. The submitter also stated that the final
report of the BALB/3T3 Mouse Cell Transformation Test will be
provided to EPA when the report is received from the laboratory.
EPA's Office of Toxic Substances (OTS) has received and evaluated
a number of TSCA Section 8(e) and "For Your Informationh submis-
sions containing toxicologic and/or exposure data on a variety of
coal, shale, and petroleum oils, process streams, and/or wastes.
a)
In view of EPA's general interest in corporate actions
that are taken on a voluntary basis in response to chem-
ical toxicity and/or exposure information, the Chemical
Screening Branch (CSB/ECAD/OTS) will ask the Gulf Oil
Chemicals Company if it is conducting, or has plans to
conduct, additional laboratory studies designed to
further define the toxicity of Aromatic Pyrolysis Oil.
b)
The Chemical Screening Branch will screen the reported
information to determine if further OTS assessment of
this petroleum stream is warranted.
c)
The Chemical Screening Branch will send a copy of this
status report to NIOSH, OSHA, DOE, OW/EPA, OSWER/EPA,
ORD/EPA, and OANR/EPA. A copy of this report will also
be sent to the TSCA Assistance Office (TAO/OTS/OPTS/EPA)
for further distribution.
115
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
~ 29 933
8EHQ-I083-0499
Page 1 of 3
Approved ~ II/~
SUlutC:T.
Status Report* 8EHQ-I083-0499
Justine L. we~Aclction Chief
Chemical RiSk~lJf:n~fication Section/CSB
Revision
Needed
'10M.
TO Frank D. Kover, Branch Chief
I Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
Vulcan Chemicals submitted copies ot abstracts from two male rat
reproduction studies of chloromethane (methyl chloride; CAS No.
74-87-3) that were conducted at the Chemical Industry Institute
of Toxicology (CIIT). According to Vulcan, the results of the
.performed studies show that chloromethane produced "a strong but
reversible dominant lethal effect in the male F-344 rat, as well
as a lowered sperm number and motility in exposed animals." The
submitted abstracts follow:
"A DOMINANT LETHAL STUDY OF INHALED METHYL CHLORIDE IN MALE F-344
RATS. P.K. Working, J.S. Bus, R.M. Norton and T.E. Hamm, Jr.,
Chern. Indus. Inst. Toxicol., Research Triangle Park, NC 27709.
"The genotoxic effect of inhaled methyl chloride (MeCl), a known
testicular toxicant, was assessed in a dominant lethal test (DLT)
using male F-344 rats. Four groups of 40 males were exposed to
0, 1000 or 3000 ppm MeCl 6 hr/day for 5 days or received an ip
injection of triethylenemelamine (TEM, 0.2 mg/kg) on the after-
noon of day 5 as a positive control. After a 2 day recovery
period, an F-344 female was caged with each male weekly for 8
weeks. Necropsy of females was 17 days after the first day of
cohabitation. Exposure to 0 6r 1000 ppm caused no change in any
DLT parameter measured. Exposure to 3000 ppm resulted in sperm
granulomas in one or both of the epididymides of 39% of the
males. TEM caused increases in both dead implants/total implants
(D/T, up to 0.98) and preimplantation loss (PI loss, up to 7.3/-
female) only at weeks 1 to 5 post-exposure (PE), indicative of a
strong dominant lethal effect and subsequent recovery. 3000 ppm
MeCl caused slight increases in D/T only at weeks 1 and 2 PE
(0.17 and 0.33 respectively), and increases in PI loss (up to
9.1/female) during all 8 weeks. Pregnancy rate was decreased at
every week PE, ranging from 28-78% (control range = 83-95%).
[The authors] conclude that MeCl is an inducer of dominant lethal
mutations in .mature sperm exposed in the vas deferens and [the]
epididymis."
-NOTE: T~is status reDo=t is the result of a prelirnina=v
. ...
staff evaluation of i~for.mation subrnitt~d to EPA. Stateme~ts
mace herein are no~ to be regarded as e~?ressing final
Ase~cy ?olicy or intent with respect to t~is particular
chemical. .~y review of the status report should take into
consideration the iact that it may be based on incomDlete
infonna tion. .. .
116
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8EHQ-I083-0499
Page 2 of 3
"EFFECTS OF INHALED METHYL CHLORIDE ON SPERM OF F-344 RATS. P.K.
Working, J.S. Bus, L.L. Earle and T.E. Hamm, Jr., Chem. Indus.
Inst. of Toxicol., Research Triangle Park, NC 27709.
"In a dominant lethal test using male F-344 rats, 3000 ppm of
inhaled methyl chloride (MeCl) increased post-implantation loss
in weeks 1 and 2 post-exposure (PE), and increased pre-implanta-
tion (PI) loss and decreased pregnancy rate up to 8 weeks PEe
[The authors] examined the cause of these changes in male F-344
rats exposed to 0, 1000 or 3000 ppm MeCl 6 hr/day for 5 days or
after a single ip injection of 0.2 mg/kg triethylenemelamine
(TEM). Five males per treatment were examined each week for 8
weeks PEe In the 3000 ppm-exposed males the testis/body weight
ratio was decreased to 88% of control by week 3 PE and declined
to 50% of control at week 8. In sperm isolated from the vas
deferens, motility was decreased to 70% of control at 1 week PE
and cell number was decreased to 52% of control by week 2. Both
parameters continued to decline throughout the 8 wk observation
period. Testicular spermatid count at week 8 (a measure of sper-
matogonial survival) was 22% of control levels and was depressed
as early as 2 weeks PE, suggesting destruction of more mature
spermatogenic stages. No effect of exposure to 1000 ppm MeCl or
TEM was seen on any parameter measured. Thus, the increased PI
loss and decreased pregnancy rate in females bred to 3000 ppm ex-
posed males is due primarily to failure of fertilization because
of lowered sperm number and motility."
Submission Evaluation
The evaluation of the reported and other toxic effects of chloro-
methane is being conducted by the Test Rules Development and Risk
Management Branches within the Existing Chemical Assessment
Division/OTS in conjunction with 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
published (45 FR 48524) a proposed "test rule" for chloromethane
carcinogenicity and teratogenicity testing. In addition, OTS is
currently gathering additional exposure and toxicity information
on chloromethane under TSCA Sections 8(a) and 8(d).
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 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 those 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,
117
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8EHQ-I083-0499
Page 3 of 3
are subject to the limitations contained in the TSCA Inventory
Reporting Regulations (40 CFR 710). According to information
contained in the July 14, 1982 issue of Chemical & Engineering
News, U.S. chloromethane production in 1981 was estimated to be
362 millions pounds.
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 chloromethane threshold limit value
(TLV) of 50 ppm in air.
In addition to the TSCA-related chloromethane actions/activities
described in the Submission Evaluation section of this status
report, Volume II of the June 1982 EPA Chemical Activities Status
Report (EPACASRi EPA 560/TIIS-82-002b) indicates that there are a
number of chloromethane actions/activities in other EPA Program
Offices under such authorities as the Clean Water Act (CWA)i the
Comprehensive Environmental Response, Compensation, and Liability
Act (CERCLAi"Superfund") i and the Resource Conservation and Re-
covery Act (RCRA). EPA's Office of Toxic Substances has also
received and evaluated several other TSCA Section 8(e) and "For
Your Information (FYI)" submissions containing toxicity and/or
exposure data on chloromethane.
a)
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure information, the Chemical Screening
Branch (CSB/ECAD/OTS) will request Vulcan Chemicals to
describe the actions the company has taken in light of
the reported toxicity information on chloromethane to
warn workers and others and to reduce and/or eliminate
exposure to the chemical.
b)
The Chemical Screening Branch will transmit a copy of
this status report to NIOSH, OSHA, CPSC, FDA, OW/EPA,
OSWER/ EPA, OANR/EPA, ORD/EPA, OPP/OPTS, TRDB/ECAD/OTS
and RMB/ECAD/OTS. In addition, a copy of this status
report will be transmitted to the TSCA Assistance Office
(TAO/OTS/OPTS/EPA) for further distribution.
118
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UNITED STA TESEHYIROHMENTAL.PROTECTTOH AGENCY
8EHC-1283-0500 S
Page I of 2
DAn:
DEe 22 m3
SUlJEC:TI Status Report*
8EHQ-1283-0500 S
bff-
App:oved' '-"
Revision
Needed
fJI.?bj15
.
,.01&1 Justine Welch SChaefOw.JCgection Head
Chemical Risk Identi~~tion Section/CSB
TO. Fran~ D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTb
Note
The submitting company has claimed its identity and the exact
identity of the subject chemical substance to be TSCA Confiden-
tial Business Information (TSCA CBI) The OTS Document Control
Office has requested the submitter ,to substantiate all of the
company's confidentiality claims
Submission Description
The submitting company provided summarized final results from a
battery of in vitro genotoxicity tests of a "substituted poly-
g lyc idyl benzenamine." A ccording to the submi tted information,
the chemical was positive both in the presence 'and aqsence of
exogenous metabolic activation in an Ames Salmonella typhimurium
(bacteria) Mutagenicity Assay, an L5178Y Mouse Lymphoma Cell
Forward MutatIon Assay, and a Chinese Hamster Ovary (CHO) Cell
Sister Chromatid Exchange (SCE) Assay. The chemical was also
reported to be mutagenic in yeast (Saccharomyces cerevisiae
strain D7) but only in the presence of metabolic activation.
Submission Evaluation
Although the submission did not contain any of the actual data
from the performed genotoxicity studies, the experimental design
reports and summary statements of results which were submitted do
indicate that the substituted polyglycidyl benzenamine was posi-
tive in all of the cited assays. Considering that many compounds
of this type have been shown to be genotoxic, there is no reason
to assume that the submitted reports do not accurately reflect
the obtained experimental findings. In order to ensure that this
is the case, however, a complete copy of the final report, in-
cluding the actual test protocol(s) and data, from each of the
genotoxicity studies that were cited in the submission should be
obtained for r.eview.
-NOTE: This status reoo:t is the result of a Drelirnina:v
staff evaluation of i~fo~ation submitted to EPA. State;ents
made herein are no~ to be reaarded as ex~ressinc final
Agency policy or intent with-res?ec~ to t~is particular
chemical. .~y review of the ~tatus repor~ should take into
consideration the tact that it mav be based on incomolete
information .
119
.C,.. '0". ..~ CIilEV. """
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8EHQ-1283-0500 S
Page 2 of 2
Current Production and Use
Although the submitting company did not provide any information
concerning the proposed use(s) of the substituted polyglycidyl
benzenarnine, it was reported that the chemical is currently in
the research and development (R&O) stage and that the number of
people potentially exposed to the chemical is very small. The
submitter also reported that current exposures to the substituted
polyglycidyl benzenamine are being controlled by good laboratory
practices.
Comments/Recommendations
Although a positive genotoxicity test result, when considered
alone, may not be sufficient to offer reasonable support for a
conclusion of substantial risk, the Agency believes that such
results are of value in assessing possible risks posed by chem-
icals to health and/or the environment. EPA also believes that
positive genotoxicity test results in combination with additional
information (e.g., knowledge of potential exposure to, or high
production of, the chemical substance or mixture), would suggest,
in many cases, the need to conduct additional toxicologic studies
with the results of such studies considered for possible submis-
sion to the Agency pursuant to Section 8(e) of TSCA.
a)
The Chemical Screening Branch (CSB/ECAO/OTS/OPTS) will
request the submitter to provide a complete copy of the
final report (including the actual test protocol(s) and
data) from each of the in vitro substituted polyglycidyl
benzenamine genotoxicitY-assays that were cited in the
submission. In addition, the submitting company will be
requested to submit a structural diagram of the subject
chemical. In view of the Agency's general interest in
corporate actions that are taken on a voluntary basis in
response to chemical toxicity/exposure information, the
Chemical Screening Branch will also ask the submitting
company if it is conducting or plans to conduct addi-
tional studies designed to further define the toxicity
of the substituted polyglycidyl benzenamine.
b)
The Chemical Screening Branch will screen the reported
information to determine if further OTS assessment of
the substituted polyglycidyl benzenamine is warranted
at the present time.
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, F~, NTP, OW/EPA,
OSWER/EPA, ~NR/EPA, and ORO/EPA. A copy of this status
report will also be sent to the TSCA hssistance Office
(TAO/OTS/OPTS) for further distribution.
120
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UNITED STATES EHY.IRONMENTAL PROTECTION AGENCY
DATE;
JAM
9-
8EHQ-1283-0501 S
Page I of 3
SUaJ£CT, Status Report*
8EHQ-1283-0501 S
Approved
fl-- t/?f
J (
nOli, Justine Welch SChaef~Ahction Head
Chemical Risk Identi~ti;n Section/CSB
TO, Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Revision
Needed
Not~
The submitting company claimed its name and the exact identity
and use category of the subject chemical substance to be TSCA
Confidential Business Information (TSCA CBI). The OTS Document
Control Officer has requested the submitter to substa~tiate all
of the company's confidentiality claims.
(See note on Page 3 of this report.)
Submission Description
The submitting company provided summarized findings from two (2)
acute rat toxicity studies of a chemical substance that was iden-
tified generically by the submitter as an acylcyclohexyldione.
The following synopsis of the obtained results was presented in
the submission:
"In a preliminary evaluation of the acute oral toxicity of
this material, graded doses ranging from 100 to 500 mg/kg
were given to adult Sprague-Dawley rats of both sexes. At all
levels, including 100 mg/kg (which dose was nonlethal to the
animals), severe paralysis of the hind limbs was observed. In
a dermal toxicity screen, rats were given doses of 2000 or
500 mg/kg. At 2000 mg/kg, 4/4 females and 3/4 males died. The
survivor displayed signs of hindlimb weakness and decr~ased
motor activity. At 500 mg/kg, no animals died, but 3/4 fe-
males and 1/4 males showed hindlimb weakness and decreased
motor activity. In the case of those animals which did not
die, the condition persisted until it became necessary to
sacrifice the animals because of the nature of their con-
ditions. A preliminary pathological examination of material
from these animals indicates a direct effect upon the nervous
s y stem. "
-NOTE: This status recort is the result of a creliminarv
staff evaluation of i~fo~ation submitt~d to EPA. Sta~e;ents
mace herein are no~ to be regarded as expressing final
Agency policy or intent with res?ec~ to this ?articular
chemical. .~y review of the stat~s report should take into
consideration the iact that it may be based on incomplete
information. 121 .
E~A rcr;t. II~ IIII~Y. ~!'I
-------
8EHQ-1283-050l S
)?age 2 ot 3
Submission Evaluation
The submitted summarized information indicates that the observed
development of severe and persistent paralysis following acute
exposure to non-lethal doses of acylcyclohexyldione is the result
of a direct neurotoxic effect rather than a behavioral phenomenon
secondary to other systemic toxicity or general depression of the
central nervous system. A complete copy of the final report from
each of the acute toxicity studies cited in the submission should
be requested in order to evaluate better the reported findings.
Current production and Use
Although the submitting company has claimed the exact identity
and use category of the subject chemical to be TS~ Confidential
Business Information, the company did report non-confidentially
that the chemical is .Ia research compound which is the fifth in-
termediate in a chain of seven, including the final product.... II
(See note on Page 3 of this report)
Comments/Recommendations
a)
The Chemical Screening Branch (CSB/E~D/OTS/OPTS) will
request the submitting company to submit complete copies
of the final reports (including test protocols and data)
from the acute oral and dermal toxicity studies of the
acylcyclohexyldione in rats. Considering EPA's general
interest in company actions which are taken on a volun-
tary basis in response to chemical toxicity/exposure in-
formation, the Chemical Screening Branch will request
the submitting company to describe the actions that it
has taken which are designed to reduce and/or eliminate
worker and other exposure to the subject chemical. The
Chemical Screening Branch will also ask the submitting
company to descibe the studies that the company has con-
ducted, is presently conducting, or is planning to con-
duct that are designed to define better the toxicity of
and/or exposure to acylcyclohexyldione.
b)
The Chemical Screening Branch will screen the reported
information to determine if further OTS assessment of
the subject chemical is warranted at the present time.
c)
The Chemical Screeing Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FD\, NTP, OW/EPA.
OSWER/EPA, OANR/EPA, and ORD/EPA. In addition, a copy
of this- status report will be transmi tted to the TSCA
Assistance Office (TAO/OTS) for further distribution.
122
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8EHQ-1283-0501 S
Page 3 of 3
NOTE:
In a non-confidential letter (dated January 24, 1984), the
Chevron Chemical Company stated that the company had decided
to withdraw its confidentiality claims for the information
contained in the company's initial Section 8(e) submission.
The declassified initial submission reported that the subject
chemical is 2-(2-oxobutyl)-5-(2-ethylthio)-propyl-3-hydroxy-
2-cyclohexen-l-one and that the CAS Registry No. was 79419-
43-5. In addition, the initial 8(e) submission reported that
"this research compound, which is the fifth intermediate in a
chain of seven, including the final product, in the manufac-
ture of a chemical that, if developed succcessfully, would be
registered as a pesticide." The Section 8(e) submission also
reported that although 2-(2-oxobutyl)-5-(2-ethylthio)-propyl-
3-hydroxy-2-cyclohexen-I-one is produced in batches at the
present time, "it is not known whether, in the final process,
this material will be manufactured in batch mode, thereby
isolating it, or whether it will be subject to a continuous
manufacturing process." According to Chevron, "it is not
known whether this intermediate will appear in the final
product."
In its initial 8(e) submission, the Chevron Chemical Company
also included a preliminary draft Material Safety Data Sheet
(MSDS) which contains summarized findings from the company's
acute toxicity studies of and recommended safe handling pro-
cedures for 2-(2-oxobutyl)-5-(2-ethylthio)-propyl-3-hydroxy-
2-cyclohexen-l-one. According to Chevron, the MSDS has been
distributed to Chevron employees who handle the chemical and
"will be sent to potential toll manufacturers."
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will send a
copy of this updated status report to each office listed
in item c) on page 2 of this report and to EPA's Office
of pesticide Programs.
123
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-1283-0502 P
Page 1 of 4
DAU:
JAM 21 ~
SUIJ£CT. Status Report *
8EHQ-1283-0502 P
APp=oved~
Revision
Needed
'(31 /~'f
~
nOli. Justine Welch Schaeff' ection Head
Chemical Risk Identi 'cation Section/CSB
T~ Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The General Motors Corporation submitted information concerning a
report from an employee of the Packard Electric Division (General
Motors) that the fumes generated during the heating/molding of
Hypalon Molding Compound are "very irritating" and "cause a bur-
ning sensation in the lungs, throat and nasal passages." In its
submission, the General Motors Corporation provided 1) a copy of
the employee's report; 2) summaries of internal General Motors
and Packard Electric Division investigations, conclusions, and
recommendations; 3) a list of the ingredients used to formulate
the Hypalon Molding Compound; 4) copies of Material Safety Data
Sheets (MSDSs) for each ingredient; and 5) the process specifi-
cations for the Hypalon molding operation. In the cover let~er
to its submission, the General Motors Corporation stated that the
company believes that the irritation experienced by the employee
may have been caused by aldehydes, hydrogen chloride, and/or
sulfur oxides that originate from the thermal decomposition of
Hypalon Molding Compound during the molding operation. General
Motors also stated that the affected employee may be more sensi-
tive to such irritants due to the fact tha~ other workers exposed
in a similar manner have complained only about the odors.
Submission Evaluation
General Motors' hypothesis that the reported irritation was due
to aldehydes, hydrogen chloride (hydrochloric acid) and/or sulfur
oxides is plausible but does not appear to be supported by data
from actual monitoring of the workplace air, particularly the
breathing-zone air around the molding operation. Considering the
large number of ingredients used in the formulation of Hypalon
Molding Compound and the high temperature (i.e., 40bOF) required
during part of the molding operation, it is not suprising that a
wide variety of irritating substances (including those cited by
the submitter) could be released. Although the General Motors
Corporation contends that the affected worker (i.e., the Packard
Electric Division employee who made the formal complaint) is un-
usually sensitive to thermal decomposition products of Hypalon
-NOTE: This status recort is the result of a crelirnina=v
staff evaluation of i~formation submittec to EPA. State;e~ts
mace herein are no~ to be regarded as expressing final
Ase~cy policy or intent with respect to t~is ?articular
chemical. .;ny review of the status report should take into,
consideration the tact that it may be based on incornolete
informa tion. - .. .
124
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8EHQ-1283-0502 P
Page 2 of 4
Holding Compound (because other workers who are exposed in a
similar manner have complained only about the odors), the General
Motors Corporation's contention is not supported by a submitted
Packard Electric Division investigative report which states that
other workers involved in the Hypalon molding operation have made
complaints similar to those issued by the affected worker. Al-
though it is possible that the affected worker has a natural (or
possibly acquired?) low tolerance to the thermal decomposition
products of Hypalon Molding Compound, the fact remains that other
employees are being exposed in a similar manner and have com-
plained, even if only about the odors. It should be noted that
chemical substances can, and in many cases, do elicit serious
toxic effects (e.g., liver damage) at levels well below those
which can be detected by smell or which cause overt irritation to
skin, eyes, lungs, nasal passages, etc.
A submitted internal General Motors memorandum recommends that
the company's Industrial Hygiene Department be consulted for an
evaluation of the molding process environment. This recommended
action appears to be prudent in view of the workers' complaints
and the large number of chemicals to which the employees are po-
tentially exposed during the molding operation. If the submitter
is correct that hydrochloric acid and sulfur oxides are among the
thermal decomposition products of Hypalon Molding Compound, the
corrosive effects of these chemicals on the workplace ventilation
system should be taken into account by the company. With regard
to the existing ventilation system, the submission did not indi-
cate whether air from the molding operation is directed through
an air quality control system prior to release to the outside.
Current Production and Use
According to an engineering specification sheet contained in the
submissiocl, Hypalon Molding Compound, once formulated, is used to
manufacture spark plug boots. Considering the nature of the sub-
mission, no information concerning the production and use of the
individual ingredients used to formulate Hypalon Molding Compound
or the reported (and other) thermal decomposition products of the
Hypalon Molding Compound will be included in this status report.
Comments/Recommendations
It is EPA's initial position that the acute human toxicity
informacion, as presented in this submission, did not warrant
reporting under Section 8(e), the substantial risk information
reporting provision of the Toxic Substances Control Act (TSCA).
It should also be noted that a submitted report prepared by the
General Motors Corporation's "Toxic Materials Control Activity"
stated that a Section 8(e) notification was not necessary. The
"Toxic Materials Control Activity" position was based on a review
of the Hypalon molding process and the materials involved and a
finding that no new or undocumented effects had been observed.
The basis for EPA's position with regard to the Section 8(e)-
applicability of the submitted information is as follows:
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8EHQ-1283-0502 P
Page 3 of 4
According the Part V of EPA's !'1arch 16, 1978, TSCA Section
8(e) policy statement ("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, EPA considers
the human health effects for which substantial risk informa-
tion 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 if one (or a few) chemical(s)
is strongly implicated. In addition, Part VI(2) of the 8(e)
policy document states that it is possible that effects less
serious than those described above may be preliminary mani-
festations of those more serious effects and together with
another triggering piece of information, constitute Section
8(e)-reportable information.
In view of the above discussion and considering that the acute
human health effects reported in this submission do not appear to
have been serious or to have resulted in prolonged incapacitation
or serious impairment of normal bodily functions/activities, EPA
does not believe that the information warranted submission under
Section 8(e) of TSCA. It must be emphasized, however, that the
Agency's position with regard to the 8(e)-reportability of the
subject information is based solely on the information submitted
to EPA and not on other pertinent information that may have been
available to and/or considered by the General Motors Corporation
in the company's ultimate decision to submit the information to
EPA under Section 8(e) of TSCA.
It is also important to note that although the Agency does not
believe that the human health effects information, as presented
in the General Motors submission, warranted reporting under TSCA
Section 8(e), the Agency does believe that the employee's report
could possibly constitute an "allegation of a significant adverse
reactionh as defined under Section 8(c) of TSCA. Section 8(c) of
TSCA requires that "any person who manufactures, processes, or
distributes in commerce any chemical substance or mixture" must
keep "records of significant adverse reactions to health or the
environment, as determined by the Administrator by rule, alleged
to have been caused by the substance or mixture." Section 8(c)
of TSCA also requires that allegations of adverse reactions to
the health of employees be kept for thirty (30) years, and all
other allegations be kept for five (5) years. In addition, the
Agency is empowered to inspect and/or require submission of the
Section 8(c) records. On August 22, 1983, EPA published (48 FR
38178) the final rule implementing Section 8(c) of TSCA. Full
compliance with the Section 8(c) rule has been required since
November 21, 1983.
126
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8EHQ-1283-0502 P
Page 4 of 4
a)
The Chemical Screening Branch (CSB/ECAD/OTS/OPTS) will
transmit a copy of the August 22, 1983, Federal Register
(48 FR 38178) notice pertaining to TSCA Section 8(c) to
General Motors. In addition, the Chemical Screening
Branch will request the General Motors Corporation to
provide its rationale as to why the company ultimately
decided to report the acute human health effects infor-
mation to EPA under Section 8(e) of TSCA.
In view of the Agency's general interest in corporate
actions that are taken on a voluntary basis in response
to chemical toxicity/exposure information, the Chemical
Screening Branch will request General Motors to describe
the actions it has taken to determine the identities and
concentrations of the thermal decomposition products of
Hypalon Molding Compound in work (and other) areas and
to provide the results of such studies to the Agency.
In addition, the General Motors Corporation will be re-
quested to describe the actions it has taken, or plans
to take, that are designed to reduce and/or eliminate
worker and other exposure to the ingredients and thermal
decomposition products of Hypalon Molding Compound, and
to Hypalon Molding Compound itself.
b)
The Chemical Screening Branch will review the reported
information to determine if further OTS assessment is
warranted at the present time.
c)
The Chemical Screening Branch will transmit copies of
this status report to NIOSH, OSHA, OW/EPA. OSWER/EPA,
OANR/EPA and ORD/EPA. A copy of this report will also
be sent to the TSCA Assistance Office (TAO/OTS/OPTS/EPA)
for further distribution.
127
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UNITED STATES ENVIRONMENTAL. PROTECTION A.GENCY
8EHQ-1283-0503
Page 1 of 6
OAT!:
JAN 30 ~
SUIJ£C:T,
Stat us Report *
8EHQ-1283-0503
1\pp:oved
~
nOM,
Justine Welch sChaefiJJ~ection Head
Chemical Risk Identi~~t~on Section/CSB
Revision
Needed
T~ Fran~ D. Kover, Branch Chief
ChemIcal Screening Branch/ECAD/OTS/OPTS
Submission Description
The Dow Chemical Company provided summarized results from several
short-term in vitro genotoxicity tests on 3-chloro-2-hydroxypro-
pyltrimethylammonium chloride (CAS No. 3327-22-8.). According to
the submitter, the chemical produced positive responses in an
Ames Salmonella tymphimurium (bacteria) Mutagenicity Assay, in an
Unscheduled DNA Synthesis Assay in cultured rat hepatocytes, and
in an Hypoxanthine Guanine Phosphoribosyl Transferase Mutageni-
city Assay using cultured Chinese hamster ovary (CHO) cells. Dow
reported that 3-chloro-2-hydroxypropyltrimethylammonium chloride
is a chemical intermediate having the following two major uses:
"In the first [use], 3-chloro-2-hydroxypropyltrimethylammonium
chloride is reacted with either starch or guar gum to form a
wet and dry strength additive in paper. In the second [use],
3-chloro-2-hydroxypropyltrimethylammonium chloride is reacted
with hydroxyethyl cellulose to form a component used in sham-
poos and cosmetics. In both processes, 3-chloro-2-hydroxypro-
pyltrimethylammonium chloride is first converted to the more
reactive 2,3-epoxypropyltrimethylammonium chloride [CAS No.
3033-77-0] by raising the pH. The amount of 2,3-epoxypropyl-
trimethylammonium chloride present in an aqueous solution of
3-chloro-2-hydroxypropyltrimethylammonium chloride is a func-
tion of pH. A small amount of 2,3-epoxypropyltrimethylammonium
chloride is present in the 3-chloro-2-hydroxypropyltrimethyl-
ammonium chloride which Dow manufactures and was present in
the compound used in the tests."
According to the submitted information, Dow tested both technical
and purified grades of 3-chloro-2-hydroxypropyltrimethylammonium
chloride. The technical grade was reported to contain 50.9% 3-
chloro-2-hydroxypropyltrimethylammonium chloride and 1.3% to 2.6%
2,3-epoxypropyltrimethylammonium chloride, whereas the purified
grade was reported to contain 99% 3-chloro-2-hydroxypropyltri-
methylammoni urn chloride and <0.1% 2.,3-epoxypropyltrimethylam-
monium chloride.
-NOTE: T~is status recort is the result of a creliminarv
staff evaluation of-information subrnitt~c to EPA. State;'e~ts
mace herein are. no~ to be recrarded as ex:;)ressino final
~se~cy ?olicy or intent with'res?ec~ to t~is ?articula~
chemical. .;ny review 6f the status re?ort should take into
consideration the tact that it may be based on incomplete
in forma tion.
128
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8EHQ-1283-0503
Page 2 of 6
In its submission, the Dow Chemical Company also provided copies
of two product information letters (dated January 26, 1978 and
December 6, 1982) from the Shell International Chemical Company
Limited (England) in which Shell International notified its cus-
tomers (and possibly others) about the results of toxicologic
studies that Shell International had conducted or was about to
conduct on 2,3-epoxypropyltrimethylammonium chloride. In the
1978 letter, Shell International recounted that previous letters
(dated October 30, 1975 and December 1, 1976) had presented in-
formation on the primary toxicity of and recommended handling
precautions for 2,3-epoxypropyltrimethylammonium chloride. In
addition, the 1978 letter reported that 2,3-epoxypropyltrimethyl-
ammonium chloride had been found to display mutagenic activity
in bacteria and in mammalian cells and reaffirmed the need to
follow recommended handling procedures when using the compound.
The 1978 letter also reported that chronic mammalian studies of
2,3-epoxypropyltrimethylammonium chloride would be conducted to
determine the nature of any long-term effects of exposure to the
compound. In its 1982 letter, Shell International reported that
the exposure portion of a life-time mouse skin application study
of various doses of 2,3-epoxypropyltrimethylammonium chloride had
ended and that only the skin had been examined as of the date of
the letter. Although the 1982 Shell International letter did not
specify what doses were tested, the number of animals tested or
whether appropriate controls were used in the chronic mouse skin
application study, the letter did present the following prelimi-
nary findings from that study:
"At the top dose, [2,3-epoxypropyltrimethylammonium chloride]
produced skin tumors. This dose was set at a level close to
the maximum consistent with the long term survival of the ani-
mals and the absence of obvious signs of irritation. At the
lowest dose there were no skin tumors, while at the intermedi-
ate dose the incidence was extremely low."
Considering the nature of the preliminary findings in the life-
time mouse skin application study, the 1982 Shell International
letter re-emphasized Shell's earlier recommendations to avoid all
contact with 2,3-epoxypropyltrimethylammonium chloride. The 1982
Shell International letter also recommended that other companies
who had purchased or had received samples of 2,3-epoxypropyltri-
methylammonium chloride be contacted to ensure that appropriate
handling procedures were being followed. At the end of its 1982
letter, Shell International reported that an evaluation of the
final results of the chronic mouse skin application study along
with any necessary changes to safe-handling procedures would be
communicated in mid-1983.
Dow Chemical Company's Section 8(e) submission did not contain
any further correspondence from the Shell International Chemical
Company Limited nor did the Dow Chemical Company's submission
indicate that Dow had ever received any further correspondence
concerning Shell International's life-time mouse skin application
study of 2,3-epoxypropyltrimethylammonium chloride.
129
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8ERQ-1283-0503
Page 3 of 6
Submission Evaluation
Dow tested 3-chloro-2-hydroxypropyltrimethylammonium chloride for
its ability to induce gene mutation in bacteria (Ames Assay) and
in cultured Chinese hamster ovary (CRO) cells. Dow also tested
the compound for its ability to induce unscheduled DNA synsthesis
(UDS) in cultured rat hepatocytes. Although experimental details
were not presented in the submission, the submitted data do show
that the technical grade of 3-chloro-2-hydroxypropyltrimethyl-
ammonium chloride does induce unscheduled DNA synthesis in rat
hepatocytes and does induce mutations in Salmonella typhimurium
(bacteria) strain TA 1535 (Ames Assay) and cultured CRO cells.
The Ames Assay data indicate that the test was performed in the
presence and absence of exogenous metabolic activation and that
the compound was positive under both conditions. Although the
only data that were presented for cultured CRO cells were for an
assay that was conducted without metabolic activation, the data
were also clearly positive. The provided data also show that a
purified sample of 3-chloro-2-hydroxypropyltrimethylammonium
chloride induced mutations in Salmonella typhimurium strain TA
1535 when tested both in the presence and absence of exogenous
metabolic activation. Although Dow did not submit data on the
activity of the purified material in either the cultured CRO or
rat hepatocyte assays, there is no reason to believe that the
purified material would behave in a different manner in these
assays than it does in the Ames Assay.
The submitted Shell International letters contain evidence that
2,3-epoxypropyltrimethylammonium chloride possesses a mutagenic
activity both in bacteria and cultured mammalian cells and a
dose-dependent oncogenic activity toward mouse skin following
chronic skin application; such activities are not necessarily
suprising considering that the chemical has a highly reactive
epoxide moiety. An initial review of several standard secondary
scientific literature sources {e.g., the NIOSH Registry of Toxic
Effects of Chemical Substances (RTECS» and several on-line com-
puterized scientific literature data bases (e.g., TOXLINE) did
not, however, reveal any citations indicating that 2,3-epoxy-
propyltrimethylammonium chloride has been actually shown to
display oncogenic activity toward mouse skin following chronic
dermal application.
Current Production and Use
A review of the production volume (includes importation volumes)
statistics for 3-chloro-2-hydroxypropyltrimethylammonium chloride
(CAS No. 3327-22-8), which is listed in the initial TSCA Inven-
tory, has shown that between 1.1 million and 11 million pounds
were reported as produced/imported in 1977. A review of the
production volume (includes importation volumes) statistics for
2,3-epoxypropyltrimethylammonium chloride (CAS No. 3033-77-0),
which is also listed in the TSCA Inventory, has shown that be-
tween 210 thousand and 2.1 million pounds of this chemical were
reported as produced/imported in 1977. {NOTE: This production
130
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8EHQ-1283-0503
Page 4 of 6
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 TSCA Confidential Business Information (CBI). The
data submitted for the TSCA Inventory, including the production
range information, are subject to the limitations contained in
the TSCA Inventory Regulations (40 CFR 710)).
Information submitted by Dow concerning
chloro-2-hydroxypropyltrimethylammonium
porated into the Submission Description
report.
the two major uses of 3-
chloride has been incor-
section of this status
Comments/Recommendations
In the cover letter to its submission, Dow stated that it was
immediately notifying Dow employees, Dow customers, and other
known domestic producers of 3-chloro-2-hydroxypropyltrimethyl-
ammonium chloride about the data contained in the company's
submission. Dow reported that the company's notification will
include a recommendation that "work practices be reviewed in
those areas-where employees are occupationally exposed to 3-
chloro-2-hydroxypropyltrimethylammonium chloride to be sure
adequate measures are taken with respect to skin contact and
opportunity for ingestion."
EPA believes that the preliminary findings that 2,3-epoxypropyl-
trimethylammonium chloride produced skin tumors in mice is of the
type required for sumbmission under Section 8(e), the substantial
risk information reporting provision of the Toxic Substances Con-
trol Act (TSCA; 90 Stat. 2029, 15 V.S.C. 2607). It also appears
that these preliminary oncogencicity findings should have been
submitted to the Agency under Section 8(e) at an earlier date.
The basis for the EPA's position is as follows:
Section 8(e) of TSCA states that "any person who manufactures,
processess, 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 sub-
stantial risk of injury to health or the environment shall im-
mediately inform the [EPA] Administrator of such information
unless such person has actual knowledge that the Administrator
has been adequately informed of such information."
The preface to Part V of EPA's March 16, 1978 Section 8(e)
policy statement ("Statement of Interpretation and Enforcement
Policy; Notification of Substantial Risk" 43 FR 11110) states
that "a substantial risk of injury to health...is a risk of
considerable concern because of (a) the seriousness of the
effect...and (b) the fact or probability of its occurrence."
With regard to the seriousness of the effect, Part V explains
further that that EPA considers the health effects for which
substantial risk information must be reported to include "any
pattern of effects or evidence which reasonably supports the
131
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8EHQ-1283-0503
Page 5 of 6
conclusion that the chemical substance or mixture can produce
cancer...." The information concerning this effect can be ob-
tained directly or inferred from designed studies (e.g., in
vivo studies as described in Part VI of the 8(e) policy state-
ment). In addition, Part VI explains that "a person is not to
delay reporting until he obtains conclusive information that a
substantial risk exists, but is to immediately report any evi-
dence which reasonably supports that conclusion." Part VI of
the policy document also states that "not only should final
results from such studies be reported, but also preliminary
results from incomplete studies where appropriate."
With regard to the "fact or probability of its [i.e., the
serious effects'] occurrence" criterion, Part V of the policy
document explains that certain types of health effects (e.g.,
cancer, birth defects) are so serious that relatively little
weight should be given to a chemical's exposure in determining
whether a risk is substantial; the mere fact that an implica-
ted chemical is in commerce would constitute sufficient evi-
dence of exposure.
With regard to the requirement that the EPA Administrator be
immediately informed of substantial risk information, Part IV
of the 8(e) policy document states that the EPA Administrator
is immediately informed "if [substantial risk] information is
received by EPA [according to the reporting procedures out-
lined in Part IX of the policy statement] not later than the
15th working day after the date the [subject] person obtained
such information. Part III of the 8(e) policy statement ex-
plains that the Agency considers an establishment as having
obtained substantial risk information at the time any officer
or employee capable of appreciating the significance of such
information obtains (i.e., possesses or knows of) such infor-
mation.
Part VII of EPA's Section 8(e) policy statement explains that
the the Agency considers the information about which the EPA
Adminstrator has been adequately informed (i.e., information
which need not be reported under Section 8(e» to be that in-
formation that has been, for example, published in the scien-
tific literature and abstracted by certain abstract services,
or submitted to EPA pursuant to a mandatory reporting require-
ment under TSCA or other authority administered by EPA.
Based on the preceeding discussion and considering that 1) the
preliminary information contained in the December 6, 1982 Shell
International Chemical Company letter provides laboratory animal
evidence offering reasonable support for the conclusion that 2,3-
epoxypropyltrimethylammonium chloride can produce cancer; and 2)
the chemical is in commerce thereby indicating the potential for
exposure, the Agency believes that the preliminary oncogenicity
information contained in the December 6, 1982 letter, when com-
bined with knowledge that the implicated chemical is in commerce,
does present reasonable support for a conclusion of a substantial
132
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8EHQ-1283-0S03
Page 6 of 6
risk of injury to health as defined in EPA's March 16, 1978
Section 8(e) policy statement. Considering that EPA's initial
scientific literature review did not reveal any information
indicating that 2,3-epoxypropyltrimethylammonium chloride has
been shown to produce cancer in mice via skin application, it
appears that the preliminary oncogenicity information contained
in the December 6, 1982 Shell International Chemical Company's
letter submitted by the Dow Chemical Company on December 15, 1983
and received by EPA on December 27, 1983, should have been re-
ceived by EPA at an earlier date under Section 8(e) of TSCA. In
other words, any manufacturer, processor, or distributor of 2,3-
epoxypropyltrimethylammonium chloride who obtained preliminary
evidence that 2,3-epoxypropyltrimethylammonium chloride can pro-
duce cancer in mice following chronic skin application, should
have reported such information to EPA under Section 8(e) within
15 working days after obtaining such information.
a) The Chemical Screening Branch (CSB/~~AD/OTS) will request
the Dow Chemical Company to submit complete copies of all
documents including, but not limited to, preliminary re-
ports, final reports, protocols, data, letters, memoranda,
etc. in the possession of the Dow Chemical Company that
pertain to the life-time mouse skin application study of
2,3-epoxypropyltrimethylammonium chloride that was cited
in the Shell International Chemical Company's December 6,
1982 letter. In addition, the Dow Chemical Company will
be requested to provide complete copies of the final re-
ports (including the protocols and data) from all of the
in vitro genotoxicity studies on 3-chloro-2-hydroxypropyl-
trimethylammonium chloride cited in Dow's submission.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure information, the Chemical Screening
Branch will request the Dow Chemical Company to describe
the actions that the company has taken, or plans to take,
that are designed to reduce/eliminate worker and/or other
exposures to 2,3-epoxypropyltrimethylammonium chloride.
The Chemical Screening Branch will also request the Dow
Chemical Company to describe the nature of all studies
that the company has conducted, is currently conducting,
and/or plans to conduct which are designed to determine
the toxicity of 3-chloro-2-hydroxypropyltrimethylammonium
chloride and/or 2,3-epoxypropyltrimethylammonium chloride.
b) The Chemical Screening Branch will review the reported
information to determine if further OTS assessment of the
subject chemicals is warranted at the present time.
c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, OANR/EPA, ORD/EPA and the Compliance Monitoring
Staff (CMS/OPTS/EPA). A copy will also be sent to the
TSCA Assistance Office (TAO/OTS) for further distribution.
133
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0184-0504
Page I of 4
01.1£; FEB 2 I 1984
SuaJ£CT. Status Report*
8EHQ-0184-0504
d~
Approved
,7--' ( ,:2- ,
no.. Justine Welch SChaef0Mection Head
'Chemical Risk Identification Section/CSB
\.
Revision
Needed
TO Frank D. Kover, Branch Chief
'Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Rio Blanco Oil Shale Company (a general partnership of the
Gulf Oil Corporation and the Standard Oil Company (Indiana)) sub-
mitted the following summarized findings from a study of a Lurgi
light/middle shale oil administered to rats via inhalation at
doses of 0, 56, 120, or 490 mg/m3 for 6 hours per day, 5 days per
week for 90 days:
"In addition to the test animal mortality ~57 percent mortali-
ty at an aeroso~ concentration of 490 mg/m , with no mortality
at 56, 120 mg/m or in the ~ontrol animal group], a variety of
toxicological effects were attributed to test material expo-
sures. These included: dose-related decreases in body weight
gain~ changes in various organ weights; a variety of clinical
observations including ocular and nasal discharges and peri-
anal soiling~ decreases in total erythrocytes, leukocytes and
platelet counts at the high dose level~ elevations in BUN,
.creatinine, alkaline phosphatase, SGOT and SGPT in the high
dose males. The following findings were reported upon histo-
pathological examination and generally increased in frequency
and severity as the dose level increased. They included:
hyperplasia of the alveolar macrophag~s~ congestion, edema,
and atrophy of the bone marrow~ severe atrophy of the thymus~
atrophy of the lymph nodes~ atrophy of the white splenic pulp.
Other possibly treatment-related effects included: epithelial
necrosis of the proximal convoluted tubules in the kidney~
atrophy of the thyroid follicles~ acanthosis, hyperkeratosis
and focal. dermatitis of the skin~ atrophy of the testicular
epithelium~ necrosis of the liver parenchyma. Several neo-
plasms were observed~ none were attributed to test material
exposures."
In explaining the rationale for high doses used in the 90-day
study, Rio Blanco stated that the study was designed originally
as a 30-day pilot study to determine doses which elicit animal
toxicity. Rio Blanco also stated that the animal exposures were
"excessive relative to observed or anticipated worker exposures."
-NOTE: T~is status recort is the result of a crelirninarv
staff evaluation of i~fo~ation subrnitt~c t~ EPA. State;e~ts
mace herein are nOt to be re~arded as ex~ressir.a final
Ase~cy policy or intent with-respect to t~is particular
chemical. .;nv review of the status recort should take into
consideration-the tact that it may be based on incompletG
informa tion. 134
r:,..& , 0...1:1 1J:a:>-& 1111 ev. ~'"
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8EIIQ-0184-0504
Page 2 of 4
Submission Evaluation
According to the submitted information, the liver and kidney
damage observed in the male rats was found to increase in both
frequency and severity with increasing dose. With regard to the
kidney damage, EPA's Office of Toxic Substances has received and
evalua ted several TSCA Section 8 (e) and "For Your I nforma tion"
submissions in which kidney damage was reported only in male rats
exposed to a variety of petroleum fractions. In addition, the
liver damage (as evidenced by the observed necrosis and an eleva-
tion of serum enzymes) which was reported in this submisssion is
not entirely unexpected. It should also be noted that the dermal
toxicity (i.e., acanthosis, hyperkeratosis and focal dermatitis)
which was observed would not be considered unusual findings if
the study involved whole-body exposure to the Lurgi oil.
Although the observed atrophy of the thyroid gland and testicular
epithelium are unexpected findings and of biological importance,
the submitting company reported that these adverse effects were
only "possibly treatment-related."
One of the more striking and potentially life-threatening effects
reported in this submission is the apparent dose-dependent damage
to hematopoietic/immune functions as evidenced by decreases in
total erythrocytes, leukocytes, and platelets; congestion, edema,
and atrophy of the bone marrow; severe atrophy of the thymus; and
atrophy of the lymph nodes and white splenic pulp. The observed
hyperplasia of the pulmonary alveolar macrophages may be a com-
pensatory response to rid the body of the inhaled foreign matter.
On balance, however, the provided results indicate that the rats'
resistance to infection is profoundly compromised following in-
halation of Lurgi light/middle shale oil.
Finally, the Rio Blanco oil Shale company reported that several
neoplasms had been observed but not attributed to exposure to the
test material. In order for the Agency to evaluate better the
neoplastic and other toxicologic findings reported in this sub-
mission, a full copy of the final report, including experimental
protocols and data, should be requested from the Rio Blanco Oil
Shale Company.
Current Production and Use
In general, crude shale oils are obtained from oil shale via a
destructive distillation process followed by hydrotreating. The
Lurgi-Ruhrgas process involves indirect heating whereby heat is
transferred by mixing hot retorted shale with oil shale resulting
in high oil yields and high quality product gas. Although the
Rio Blanco oil Shale Company did not provide any information con-
cerning the current or planned production volumes of the Lurgi
light/middle shale oil, the company did report that its Lurgi
process development operations are located in a pilot plant at a
Gulf Oil Corporation facility.
135
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8EHQ-Ol84-0504
Page 3 of 4
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. This production range information does not include any
production/importation data claimed as confidential by person(s)
reporting for the TSCA Inventory, nor does it include any infor-
mation that 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).
Comments/Recommendations
In its submission, Rio Blanco stated that the company "has been
conducting a toxicity testing program in conjunction with the de-
velopment of methods for shale oil extraction" and that the tox-
icity testing program included studies of oils derived from shale
via the Lurgi retorting technology- Rio Blanco also stated that
"industrial hygiene monitoring at the pilot plant has shown mini-
mal organic aerosol exposure to workers, below OS~ standards and
usually below detection limits" and that "the industrial hygiene
monitoring and work practices being employed at the pilot plant
are adequate to prevent health risk to workers."
EPA's Office of Toxic Substances has received and evaluated many
TSCA Section 8(e) and/or "For Your Information" (FYI) submissions
containing toxicologic and/or exposure information on a variety
of coal-, shale- (including Lurgi). and petroleum-derived oil
products, process intermediates, and/or waste materials.
a)
The Chemical Screening Branch (CSB/ECAO/OTS/OPTS) will
request the Rio Blanco oil Shale Company to provide a
complete copy of the final report, including protocol(s)
and data, from the 90-day rat inhalation study of Lurgi
light/middle shale oil which was cited in the company's
submission. Rio Blanco will also be requested to submit
the actual results of the industrial hygiene monitoring
study conducted at the Lurgi process pilot plant.
In view of the Agency's general interest in corporate
actions that are taken on a voluntary basis in response
to chemical toxicity/exposure information, Rio Blanco
will also be requested to describe the nature of studies
that the company has conducted, is conducting, or plans
to conduct, that are designed to define the toxicity of
and/or exposure to Lurgi light/middle shale oil and/or
other oil shale~derived materials.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of Lurgi light/middle shale oil at the
present time.
136
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c)
8EHQ-Ol84-0504
Page 4 of 4
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, NTP, DOE, OWjEPA,
OSWERjEPA, OANRjEPA, ORDjEPA and to the OTS "Synfuels
Workgroup." A copy of this status report will also be
provided to the TSCA Assistance Office (TAOjOTSjOPTS)
for further distribution.
137
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UNITED STATES EHYIRONMENTAL PROTECTION AGENCY
DAU:
M~R '5 934
8EHQ-0284-05c15
Page 1 of 3
Approved dIU-
Revision n~~ ~~. ~
~-
~ lIP /'i'f
.
suaJtC:T. Status Report* 8EHQ-0284-0505
~/t-
Justine Welch Schaef ., Section Head
'I~ Chemical Risk Identi . at ion Section
T Frank D. Kover, Branch Chief
01 Chemical Screening Branch/ECAD/OTS
Submission Description
[See NarE on Page 3 of this 'Status Report]
On behalf of the Amoco Oil Company, the Standard Oil Company
(Indiana) submitted the following summarized preliminary findings
from a three week rat dermal toxicity study of a solvent-refined
heavy paraffinic distillate (CAS No. 64741-88-4) that had been
processed further by dewaxing:
"The test animals [(rats)] were divided into two groups, each
consisting of 10 males and 10 females. One group was treated
with 2.0 ml/kg of base oil by application on the skin for 15
consecutive weekdays. The rats in the sham control group did
not receive. the test material but were otherwise handled e~-
actly like the treated rats. There were no treatment related
lesions observed in the treated or sham control group upon
gross observation. However, microscopic examination did in-
dicate testicular lesions of all male rats at the 2.0 ml/kg
dose level. The testicular lesions were characterized by
diffuse hypoplasia and degeneration of germinal cells in the
seminiferous tubules."
The submitter stated that the single dose level used in the study
did not permit establishment of a dose-response relationship and
that the study was not designed to examine the reversibility of
the observed effects.
Submission Evaluation
[See NOl'E on Page 3 of this Status R~port]
According to the provided summarized information, the testicular
lesions (characterized by "diffuse hypoplasia and degeneration of
the germinal c~lls in the seminiferous tubules") were observed
microscopically in all (10/10) male rats following exposure to a
dewaxed solvent-refined heavy paraffinic petroleum distillate
applied to the skin at a dose of 2.0 ml/kg for 15 consecutive
weekdays. Although the 100% incidence of testicular lesions in
the treated male rats indicates that the observed adverse effects
-NOTE: T~is status reDort is the result of a prelirnina=v
staff evaluation of i~formation submitt~c to EPA. Sta~e;e~~s
mace herein are no~ to be re~arded as ex~ressir.o final
Agency policy or intent wi~~~res?ec~ to t~is particular
chemical. .~y review 6f the status repor~ should tak~ into
consideration the iact that it mav be based on incomolete
information 8 138 . .
£~. '0111. ..~ 1111£..... ~,.,
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8EHQ-0284-0505
Page 2 of 3
on the testes are real,
other?) fi ndi ngs shoul d
pi ete copy of the fi nal
protocol and dat a .
further evaluation of the reported (and
be possible upon EPA's receipt of a com-
report which should include the study
Current Production and Use
The test material was described by the submi tter as a "sol vent-
refined heavy paraffinic distillate (CAS No. 64741-88-4) which is
further processed by dewaxi ng. " The submi tter stated al so that
al though there are other sol vents that can be used in sol vent-
refining, the solvent used in this case was N-methylpyrrolidone.
According to Volume I of the T8CA Chemical Substances Inventory,
sol vent-refi ned heavy paraffi nic di still ates are defi ned as "a
complex combination of hydrocarbons obtained as the raffinate
from a solvent extraction process [and] consists predominantly of
saturated hydrocarbons having carbon numbers predominantly in the
range of C20 through C50 and produces a finished oil with a vis-
cosity of at least 100 8US at 100°F (19cSt at 40°C)."
A review of the production range (includes importation volumes)
statistics for solvent-refined heavy paraffinic distillate (CAS
No. 64741-88-4), which is listed in the initial TSCA Inventory,
has shown that in excess of 9.5 billion pounds were reported as
produced/imported in 1977. 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 that would compromise TSCA Con-
fidential Business Information. The data submitted for the TSCA
Inventory, including the production range information, are sub-
ject to the limitations contained in the TSCA Inventory Reporting
Regulations (40 CFR 710).
Comments/Recommendations
The Standard Oil Company (Indiana) stated that when the subject
3-week dermal toxicity study has been completed, a copy of the
final report will be forwarded to EPA.
EPA's Office of Toxic Substances has received and evaluated many
TSCA Section 8(e) and "For Your Information" (FYI) submissions
containing toxicologic and/or exposure information on a variety
of petroleum oils, process streams and/or wastes.
a)
The Chemical Screening Branch (CSB/ECAD/OTS/OPTS) will
request the Standard Oil Company (Indiana) to ensure that
the Agency recieves, upon completion, a full copy of the
final report including protocol(s) and data from the 3-
week rat dermal toxi ci ty st udy of the dewaxed sol vent-
refined heavy paraffinic distillate. In view of EPA's
general interest in corporate actions that are taken on a
voluntary basis in response to chemical toxicity and/or
exposure information, the submitter will also be
139
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NOTE:
8EHQ-0284-0505
Page 3 of 3
requested to describe the nature of all studies that the
Standard Oil Company (Indiana) and the Amoco Oil Company
have conducted, are conducting, or plan to conduct to
define the toxicity of and/or exposure to dewaxed
solvent-refined heavy paraffinic distillate.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of dewaxed solvent-refined heavy paraf-
finic distillate at the present time.
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, NTP, DOE, OW/EPA,
OSWER/EPA, OANR/EPA, and ORD/EPA. A copy of this status
report will also be transmitted to the TSCA Assistance
Office (TAO/OTS/OPTS) for further distribution.
In follow-up submissions dated October 10, 1984 and
November 9, 1984, the Standard Oil Company (Indiana)
provided complete copies Qf the final reports from the
subject 3-week dermal application study as well as from
a repeated study. In summary, the submitted information
shows that the adverse testicular effects reported in the
initial TSCA Section 8(e) notice were actually artifacts
that resulted from improper tissue sectioning of testes
from the treated animals. In addition, data from the
repeated 3-week study show that there were no adverse
morphological effects in the testes of rats exposed
dermally to dewaxed solvent-refined heavy paraffinic
distill ate.
The Chemical Screening Branch will transmit copies of
this updated status report to the submitting company and
to all EPA Offices and Federal Agencies that are listed
in c) ab ove .
{f/ti-- /2/S/8~
140
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UNITED STATES EHYIROHMEHTAL PROTECTION AGENCY
8EHG-0384-0506 S
Page 1 of 3
DATE:
~ 211E4
SUaJiCT. Status Report *
8EHQ-0384-0506 S
Approved
rft-- 1~/e,y
,.01&. Justine Welch SChaeffrkh~tion Head
Chemical Risk Identif~~ion Section/CSB
Revision
Needed
T~Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The submitting company (company name claimed as TSCA Confidential
Business Information (TSCA CBI» provided summarized results from
a battery of in vitro and- in vivo genotoxicity studies of 1,3,5-
triacryloylhexahydro-s-triazine-(CAS No. 959-52-4). According to
the submitter, the results of the performed studies showed that:
"1,3,5-triacryloylhexahydro-s-triazine did not produce
activity, in vitro, consistent with that of a chemical
mutagen in-a forward point mutation assay in CHO [Chinese
Hamster Ovary] cells, in a sister chromatid exchange test
in CHO cells, or in a test for the unscheduled synthesis
of DNA. The presence of chromosomal aberrations in the CHO
cells used in the sister chromatid exhcange test was con-
firmed, in a concentration related manner, as an in vitro
clastogenic effect by the conduct of a definitive-Cytogene-
tic test in cultured CHO cells. Additional confirmation of
the clastogenic potential of the triazine chemical was demon-
strated, in vivo, by a micronucleus test in mice. These find-
ings indicate that 1,3,5-triacryloylhexahydro-s-triazine is
a clastogenic material, but devoid of mutagenic activity."
Submission Evaluation
According to the submitted information, 1,3,5-triacryloylhexa-
hydro-s-triazine was tested in a battery of assays which'included
tests for gene mutation (HPRT locus) in cultured Chinese Hamster
Ovary (CHO) cells, Sister Chromatid Exchange (SCE) formation in
cultured CHO cells, Unscheduled DNA Synthesis (UDS) in isolated
rat hepatocytes, chromosomal aberrations in cultured CHO cells,
and micronucleus formation in peripheral blood of Swiss-Webster
mice. These assays were conducted in three stages with the in
vitro CHO cell gene mutation, SCE, and UDS assays being conducted
first. Although the reported findings from the first stage as-
says did not provide any evidence that the chemical caused gene
mutation, SCE formation, or UDS, the cultured CHO cells used
.-NOTE: T~is status reDort is the result of a preliminarv
staff evaluation of i~formation submitt~c to ,EPA. State;'e~ts
mace herein are n6~ 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 fact that it may be based on incomoletG
information. 141 .. .
£~.. '0.. U:I)o4 uu:v. ~,.,
-------
8EHQ-0384-0506 S
~~2cl3
in the SCE assay were reported to have shown an abnormally high
frequency of chromosomal aberrations. In order to confirm this
finding, a chromosomal aberration assay in cultured CHO cells was
performed. According to the submitted information, the results
of this assay showed that chromosomal aberrations were induced in
a dose-related manner (beginning with the lowest dose) both with
and without exogenous metabolic activation. Finally, the subject
chemical was tested for its ability to induce micronuclei in the
peripheral blood of male and female Swiss-Webster mice following
intraperitoneal injection. The provided results indicate that
micronuclei were induced in a dose-related manner in both sexes.
Although the submitted findings do not provide any evidence that
1,3,5-triacryloylhexahydro-s-triazine is a mutagen, the chemical
does appear to possess clastogenic activity as evidenced by the
induction of chromosomal aberrations in vitro and micronuclei in
the peripheral blood of treated animals. Complete copies of the
final reports (including test protocols and data) from all of the
tests cited in this submission would be needed to evaluate better
the findings reported for this chemical.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for 1,3,5-triacryloylhexahydro-s-triazine (CAS No. 959-
52-4). which is listed in the initial TSCA Inventory, has shown
that no 1977 pro~uction/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 TSCA, U.S.C. 2613 (a». The data submitted for
the Inventory, including production range information, are sub-
ject to the limitations contained in the TSCA Inventory Reporting
Regulations (40 CFR 710).
The submitting company did not provide any information concerning
the use(s) of 1,3,5-triacryloylhexahydro-s-triazine nor was any
information on the use(s) of this chemical located in the secon-
dary literature sources consulted by EPA.
Comments/Recommendations
The submitter stated that because the company has "recognized
from the outset that the material had the potential of biological
activity, [the company] initiated and continues to take measures
to protect employees working in research and development from the
cytotoxic effects of 1,3,5-triacryloylhexahydro-s-triazine by
various safety handling procedures [including] avoidance of skin
contact by the use of protective body and hand clothing, and the
[use] of respiratory protective equipment. The submitter also
stated that "the only U.S. supplier and the only foreign manu-
facturer known to the submitter" were being notified about the
reported information. Finally, the submitter stated that the
final reports of the studies cited in the submission would be
transmitted to EPA when the reports are completed.
142
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8ffi1Q-0384-0506 S
Page 3 of 3
a)
The Chemical Screening Branch (CSB/ECAD/OTS/OPTS) will
request the submitting company to ensure that the Agency
receives complete copies of the final reports (including
protocols and data) from all of the genotoxicity studies
cited in the company's submission on 1,3,5-triacryloyl-
hexahydro-s-triazine.
In view of the Agency's general interest in corporate
actions which are taken on a voluntary basis in response
to chemical toxicity and/or exposure information, the
Chemical Screening Branch will request the submitting
company to describe all other studies that the company
has conducted, is now conducting, or is planning to con-
duct that define the toxicity of and/or exposure to
1,3,S-triacryloylhexahydro-s-triazine.
b)
The Chemical Screening Branch will review the reported
information to determine if further OTS assessment of
1,3,S-triacryloylhexahydro-s-triazine is warranted at
the present time.
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OW/EPA,
OSWER/EPA, OANR/EPA and ORD/EPA. A copy of this status
report will also be sent to the TSCA Assistance Office
(TAO/OTS/OPTS) for further distribution.
143
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UNITED STATES EHV IRONMENTAL PROTECTION AGENCY
SUIJ£CT.
Status Report *
8EHQ-0384-0507
8EHQ-0384-0507
Page 1 of 3
App=oved tJlr 'I/,/tt
Revision
Needed
DATE:
APR - 5 rJJ4
'10M.
Justine Welch Schaeffe(}~ction Head
Chemi~al Risk Identifi~tion Section/CSB
TO.
Frank D. Kover, Branch Chief
Chemi~al Screening Branch/ECAD/OTS/OPTS
Submission Description
The Gulf Oil Products Company submitted summarized findings from
a I3-week dermal toxicity study of Gulf Process 65 Oil (CAS No.
64742-11-6), Gulf 100 Texas Distillate (Cas No. 64741-53-3) and
Gulf 100 Texas Oil (CAS No. 64742-52-5). According to the sub-
mitted information,
"Gulf Process 65 Oil and Gulf 100 Texas Distillate were each
painted on the backs of C3H mice, 50 males and 50 females per
dose level, at two dose levels (50 AIl undi luted and 50.All
diluted 50% w/v mineral oil), 3 times/week for 13 weeks. ~t
the end of that time, all treated and control animals were
necropsied and subjected to gross and micr~scopic patho-
logical examination. The application of Process 65 Oil
resulted in the appearance of one squamous cell carcinoma and
one benign papilloma. The application of 100 Texas
Distillate produced one squamous cell carcinoma and two
benign papillomas.... The application [same protocol] of 100
Texas Oil did not result in the appearance of any
neoplasms. However, it did produce histological changes in
the skin, including mild to moderate levels of epidermal
acanthosis and hyperkeratosis in both sexes."
Submission Evaluation
The submitted results from the 13 week dermal toxicity study
indicate that Gulf Process 65 Oil and Gulf 100 Texas Distillate
possess oncogenic activity toward mouse skin. A more complete
evaluation of the reported findings should be possible upon EPA's
receipt of the final report which should include all protocols
and test data..
-NOTE: T~is status reDo~t is the result of a orelirninarv
staff evaluation of i~formation subrnittec to EPA. State;'e~ts
mace herefn are no~ to be regarded as e~?ressir.g final
Age~cy policy or intent wi~h respect to t~is particular
chemical. .;nv review of the status reoort should take into
consideration-the iact that it mav be bas~d on incornolet~
informa tion. .. ..
144
E~' ,~". 11=>-4 1111£.".. ~"I
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8EHQ-0384-0507
Page 2 of 3
Current Production and Use
Volume I of the TSCA Chemical Substances Inventory, defines the
test materials by CAS Number as follows:
CAS No. 64741-53-3 (Gulf 100 Texas Distillate): "...a complex
combination of hydrocarbons produced by vacuum distillation
of the residuum from atmospheric distillation of crude oil.
It consists of hydrocarbons having carbon numbers predomi-
nantly in the range of C20-C50 and produces a finished oil
with a viscosity of at least 100 SUS at 1000P (19cSt at
40°C). It contains relatively few normal paraffins. II
CAS No. 64742-11-6 (Gulf Process 65 Oil): "...a complex
combination of hydrocarbons obtained as the extract from a
solvent extraction process. It consists predominantly of
aromatic hydrocarbons having carbon numbers predominantly in
the range of C20-C50. This stream is likely to contain 5 wt%
or more of 4- to 6- membered condensed ring aromatic
hydrocarbons. II
CAS No. 64742-52-5 (Gulf 100 Texas Oil): "...a complex
combination of hydrocarbons obtained by treating a petroleum
fraction with hydrogen in the presence of a catalyst. It
consists of hydrocarbons having carbon numbers predominantly
in the range of C20-C50 and produces a finished oil of at
least 100 SUS at 1000p (19cSt at 40°C). It contains
relatively few normal paraffins."
A review of the production range (includes importation volumes)
statistics for the subject test materials, which are listed in
the Initial TSCA Inventory, shows that in excess of 6.6 billion
pounds, between 1.2-2.9 billion pounds, and in excess of 2.1
billion pounds for CAS No's 64741-53-3, 64742-11-6 and 64742-52-
5, respectively, 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 that would compromise TSCA Confidential Business
Information. The data submitted for the TSCA Inventory,
including the production range information, are subject to the
limitations contained in the TSCA Inventory Reporting Regulations
(40 CPR 710).
Comments/Recommendations
The Gulf Oil Products Company stated that when the final report
from the subject 13-week dermal toxicity study is available, a
copy will be forwarded to EPA. The company also stated that it
is reviewing the current "handling procedures, labeling practices
and Material Safety Data Sheets to determine if any changes are
needed to assure safe handling for Gulf's employees, contractors
or customers. II
145
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8EHQ-0384-0507
P~3oc3
EPA's Office of Toxic Substances (OTS) has reviewed and evaluated
previously submitted toxicologic information on Gulf Process 65
Oil and Gulf 100 Texas Oil (8EHQ-0281-0385 et seq.) as well as
many other TSCA Section 8(e) and "For Your Information" (FYI)
submissions containing toxicologic and/or exposure information on
a variety of petroleum oils, process streams and/or wastes.
a)
The Chemical Screening Branch (CSB/ECAD/OTS/OPTS) will
request the Gulf Oil Products Company to ensure that the
Agency receives, when available, a full copy of the final
report (including protocol(s) and data) from the 13-week
mouse dermal toxicity study on Gulf Process 65 Oil, Gulf
100 Texas Distillate and Gulf 100 Texas Oil.
In view of EPA's general interest in corporate actions
that are taken on a voluntary basis in response to
chemical toxicity and/or exposure information, the 'Gulf
Oil Products Company will also be requested to describe
the nature of all studies that it has conducted
(exclusive of the previously submitted toxicologic
information), is conducting or plans to conduct to
further define the toxicity of and/or exposure to the
test materials.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of Gulf Process 65 Oil, Gulf 100 Texas
Distillate and/or Gulf 100 Texas Oil at the present time.
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, NTP, DOE, OW/EPA,
OSWER/EPA, OANR/EPA and ORD/EPA. A copy of this status
report will also be transmitted to the TSCA Assistance
Office (TAO/OTS/OPTS) for further distribution.
146
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UNITED STATES EI'IVIROHMEHTAL PROTECTION AGENCY
suaJ&CT.
Status Report*
8EHQ-0384-0508 P
8EHQ-0384-0S08 P
Page 1 of 3
App"ovec! ~
Revision
Needed
?I
DATE:
APR 2 3 It&1
flOM.
Justine Welch Schaef~tion Head
Chemical Risk IdentitfCation Section/CSB
TOt
Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
Racon Inc. reported that on January 24, 1984, five Racon workers
were exposed accidentally to a number of chemicals released due
to an overpressurization in a shutdown reactor. According to the
submitted information, hydrochloric acid, hydrofluoric acid, re-
frigerants (unspecified), and antimony pentachloride were in the
reactor at the time of the incident. Racon stated that the five
exposed workers experienced acute reactions (i.e., headache; eye,
nose and throat irritation; and some chest and arm pains) common-
ly known to occur after exposure to such chemicals. Racon also
stated that although the five employees did not require hospi-
t"ali iation and all symptoms have si nce di sappeared, four of the
exposed wQrkers did go to physicians and four of the exposed
workers prepared complaint reports. Racon reported that it had
decided to place the four reports in the company's TSCA Section
8(c) file and to submit two of those reports under Section 8(e)
.
Submission Evaluation
Racon's decision to submit the two Section 8(c) reports under
8(e) appears to have been based mainly on conflicting medical
opinions as to the cause(s) of "internal nose blisters" noted in
one report and a "sharp pain in the abdomen followed by swelling"
noted in the other report. Although it is not possible to deter-
mine if the abdominal pain and subsequent swelling experienced by
one of the workers was chemical-related, a~l of the other signs
and symptoms are of the type that can occur following exposure to
potent irritants such as hydrochloric and hydrofluoric acid. In
general, all of the exposed workers appear to have recovered in a
relatively short period of time.
Current Production and Use
Due to the nature of this submission, production/use information
on the subject chemicals will not appear in this status report.
-NOTE: This status reco~t is the result of a crelirnina=v
staff evaluation of i~formatio~ submitt~c to EPA. State;ents
mace herein are not to be re~arded as e~~ressino final
Agen~y poli~y or in~ent with~res?e~t to t~is ?arti~ular
chemical. .~y review of the status report should take into
consideration the fact that it may be based on in~omplete
information. 147
E~' "-0". u».. U'CY."~"I
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8EHQ-0384...0S08 P
Page 2 of 3
Comments/Recommendations
It is the Agency's position that the acute human toxic effects
information, as presented in Racon's notice, did not need to be
submitted under Section 8(e), the substantial risk information
reporting provision of the Toxic Substances Control Act (TSCA).
The basis for EPA's position with regard to the Section 8(e)-
applicability of the reported information is as follows:
According the 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), 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 occur-
rence." With regard to the seriousness of the effect, EPA
considers the human health effects for which substantial risk
information must be reported to include "any instance of can-
cer, birth defects, mutagenicity, death or serious or pro-
longed incapacitation, including the loss of or inability to
use a normal bodily function with a consequent relatively
serious impairment of normal activities if one (or a few)
chemical(s) is strongly implicated." In addition, Part VI(2)
of the 8(e) policy document states that it is possible that
effects less serious than those described above may be pre-
liminary manifestations of those more serious effects and
together with another triggering piece of information, con-
stitute Section 8(e)-reportable information.
In view of the above discussion and considering that the acute
human health effects reported in Racon's submission do not appear
to be serious or to have resulted in prolonged incapacitation or
serious impairment or loss of normal bodily functions, the Agency
believes that the information did not need to be reported under
Section 8(e). It must be emphasized, however, that the Agency's
position with regard to 8(e)-reportability is based solely on the
submitted information and not on other pertinent information that
may have been available to and considered by Racon in deciding to
report the information under Section 8(e).
It is also important to note that although EPA does not believe
that the human health effects information, as presented in the
Racon submission, warranted reporting under TSCA Section 8(e),
the Agency does believe that the employees' reports may be of the
type required to be maintained by the company under Section 8(c),
a major recordkeeping provision of TSCA. On August 22, 1983, EPA
published (48 FR 38178) a final Section 8(c) rule that required
full compliance with 8(c) of November 21, 1983. In general, the
Section 8(c) rule requires chemical manufacturers and certain
processors to maintain records of significant adverse reactions
to health or the environment alleged to have been caused by chem-
ical substances or mixtures. The Section 8(c) rule also requires
that allegations involving significant adverse reactions in em-
ployees be kept for 30 years and that all other allegations be
148
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8EHQ-0384-0508 P
Page 3 of 3
kept for 5 years. The Agency is empowered to both inspect and
require submission of TSCA Section 8(c) records. It should be
noted, however, that there are no automatic Section 8(c) record
reporting requirements in place at the present time.
a)
The Chemical Screening Branch (CSB/ECAD/OTS/OPTS) will
ask Racon Inc. to provide the company's rationale as to
why the acute human health effects information was re-
ported to EPA under Section 8(e), the substantial risk
information reporting provision of TSCA.
b)
The Chemical Screening Branch will review the reported
information to determine if further OTS assessment is
warranted at the present time.
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, OW/EPA, OSWER/EPA, OANR/EPA
and ORD/EPA. A copy of this report will also be sent to
the TSCA Assistance Office (TAO/OTS/OPTS/EPA) for further
distribution.
149
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UNITED STATES ENVIRONMENTAL PROTECT.ION AGENCY
:rage 1 of 7
DATE:
MM I 3 1984
Status Report* 8EHQ-I083-0509 and
SUIJ£.CTI 8EHQ-0184-0509 Followup
,.-~f ~BranCh Chief
Chemical Screening BranchiECAD/OTS
Approved ~~)'
Revisio/
Needed
T~ Joseph J. Merenda, Director
Existing Chemical Assessment Division/OTS
Submission Description
In response to an informal EPA request for information on diethyl
sulfate (CAS No. 64-67-5), the Union Carbide Corporation provided
a final report from each of the following Union Carbide-sponsored
studies: 1) "Evaluation of the Dermal Carcinogenic Potential of
Diethyl Sulfate" (report dated July 26, 1979) and 2) "Diethyl
Sulfate - In Vitro Mutagenesis Studies: 3-Test Battery" (report
dated September 17, 1980). (In vi ew of the fact that the Union
Carbide Corporation sent these reports to the Agency on a "For
Your Information" (or FYI) basis, the following Document Control
Number was assigned to the information: FYI-OTS-I083-0271).
The following findings were presented in the July 26, 1979 report
of the Union Carbide Corporation IS dermal carcinogenicity study
of diethyl sulfate:
"A group of 40 C3H/HeJ male mice was painted 3 times per week
for their lifespan on the skin of the back, clipped free of
fur, with undiluted diethyl sulfate at an average dose of
0.0074 grams diethyl sulfate/mouse/application. A negative
control group of 40 C3H/HeJ male mice received skin paintings
of acetofle three times per week at an average dose of 0.0126
grams acetone/mouse/application and a positive control group
of 40 C3H/HeJ male mice received skin paintings of methyl-
cholanthrene as a 0.2% dilution in benzene three times per
week at an average dose of 0.033 milligrams/mouse/applica-
tion. Both diethyl sulfate and methyl cholanthrene showed
dermal carcinogenic activity in mice. The median latent per-
iods, which are measures of relative potency, were approx-
imately 16 months for diethyl sulfate as compared to 4 to 5
months for methylcholanthrene. The tumor and cancer indices
for the diethyl sulfate group were both 87.5 as compared to
100 and 94.4, respective~y, for the group painted with
methylcholanthrene. No skin. tumors were observed in the mice
painted with acetone."
-NOTE: T~is status report is the result of a preliminarv
staff evaluation of i~formation submitted to EPA. State;e~ts
made herein are no~ to be "regarded as expressing final
Ase~~y policy or intent with respec~ to t~~s particular
che~~cal. .~y review of the status repor~ should take into
~onslder~tion the iact that i~ may be based on incomplet~
.lnforma t.lon. 150
t~.. "0111111 IJ~ '1111:'11. ..",
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8TI:-IQ-1083-050Q
8EHQ-0184-0509 Fol1awup
Page 2 of 7
According to Union Carbide, the company selected diethyl sulfate
for genotoxicity testing because the chemical was positive in the
mouse dermal carcinogenesis assay. The following information was
contained in the September 27, 1980 report of the Union Carbide
Corporation's genotoxicity studies of diethyl sulfate:
"Diethyl sulfate was evaluated for potential mutagenic acti-
vity with a battery of three in vitro tests, which were: the
Chinese Hamster Ovary (CHO) Mutation test, the Sister Chroma-
tid Exchange (SCE) test and an assay for [the] induction of
Unscheduled DNA Synthesis (UDS) in rat liver cells. The pat-
tern of positive responses obtained in the 3-test battery of
mutagenicity assays indicated that diethyl sulfate produced a
significant mutagenic effect typical of identified chemical
mutagens and appeared to possess significant mutagenic poten-
tial in all three of the in vitro tests performed."
In the performed Chinese Hamster Ovary Mutation assay, all test
concentrations of diethyl sulfate were reported to have produced
a statistically significant and dose-related increase in mutation
frequency both with and without S9 metabolic activation. In the
Sister Chromatid Exchange assay, diethyl sulfate was reported to
have produced a highly statistically significant and dose-related
increase in SCE frequency at the low and mid-dose levels without
S9 activation and the high dose was reported to be cytotoxic.
The SCE report further stated that "the sample of diethyl sulfate
was classified as a positive mutagenic agent by direct action and
testing with an S9 activation system was not performed." In the
performed Unscheduled DNA Synthesis assay, diethyl sulfate was
reported to have induced statistically significant increases in
UDS detected both with nuclei and DNA. According to the UDS
report, "diethyl sulfate was classified as an active mutagenic
agent in the induction of UDS in the present test with the
hepatocyte test system."
In addition to the previously described toxicologic reports, the
Union Carbide Corporation provided to EPA a copy of the company's
product literature sheet and a May 1, 1981 Material Safety Data
Sheet (MSDS) on diethyl sulfate. The MSDS states that "diethyl
sulfate has been shown to be...carcinogenic in chronic laboratory
animal experiments."
Following EPA's initial review of the provided genotoxicity and
carcinogenicity data (see the Submission Evaluation section of
this status report), the Union Carbide Corporation was informed
(EPA letter dated December 12, 1983) that the Agency believed
that Union Carbide's observation that diethyl sulfate produced
benign/malignant skin tumors in mice following repeated dermal
application was new "substantial risk" information which should
have been submitted at an earlier date to EPA under Section 8(e),
the substantial risk information reporting provision of the Toxic
Substances Control Act (TSCA). Union Carbide was requested to
provide its rationale as to why the subject oncogenicity findings
had not been submitted in a timely manner under Section 8(e).
151
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8EHQ-I083-0509
8m1Q-0184-0509 Followup
Page 3 of 7
In a letter dated January 25, 1984 (FYI-OTS-0284-0271 Followup),
the Union Carbide Corporation responded to EPA's question about
the Section 8(e)-reportability of a positive carcinogenic effect
in a species (mouse) and via a route of exposure (skin painting)
for which such an effect has not been previously reported. In
addition to citing a number of scientific publications relating
to the oncogenic activity (and other toxic effects) of diethyl
sulfate (and dimethyl sulfate), Union Carbide provided a descrip-
tion of the company's activities (beginning in 1975) that were
designed to further define the toxicity of diethyl sulfate and to
reduce and/or eliminate worker exposure to the chemical.
According to Union Carbide, the chronic mouse skin application
study of diethyl sulfate was started in 1976 and was part of a
Union Carbide product safety initiative for the chemical. Union
Carbide stated that on September 16, 1977, the director of the
study reported to the company's toxicology advisory group that
"some mice had developed skin tumors and cancers." Union Carbide
also stated that the study director's September 16, 1977 report
was made via an established "system for early notification to the
toxicology group of any adverse effects as they developed during
the course of such studies."
With regard to Union Carbide's rationale for not
company's findings that diethyl sulfate produced
mice following chronic dermal application, Union
the following information:
reporting the
skin cancer in
Carbide provided
"The informal group who reviewed the preliminary data from
the mouse study concluded that the information was not sub-
ject to reporting since it corroborated the fact that diethyl
sulfate was established as an animal carcinogen in rat stu-
dies as stated in [the 1977 NIOSH Registry of Toxic Effects
of Chemical Substances (RTECS)]. [The group's] judgment was
reinforced by the fact that diethyl sulfate was a known muta-
gen and a structural analogue of dimethyl sulfate, a known
carcinogen."
With regard to EPA's belief that Union Carbide's finding of skin
cancer in mice following chronic dermal application had not been
previously reported for diethyl sulfate, Union Carbide stated
that the Agency was correct. Union Carbide also stated, however,
that the Agency's March 16, 1978 Section 8(e) policy statement
("Statement of Interpretation and Enforcement Policy; Notifica-
tion of Substantial Risk" 43 FR 11110) "does not indicate that a
carcinogenic effect in an animal study will not be considered by
EPA to be corroborative of a previously reported carcinogenic ef-
fect if it occurs in a different species and by a different route
of exposure."
The Union Carbide Corporation's rationale for not reporting the
subject oncogenicity findings will be addressed by the Agency in
the Comments/Recommendations section of this status report.
152
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8EHQ-l083-0509
8EH(}-0184-0509 Followup
Page 4 of 7
Submission Evaluation
--
Like other alkylsulfates, diethyl sulfate appears to be a typical
alkylating agent. The carcinogenicity (and mutagenicity) of its
homolog, dimethyl sulfate, is well known. Dimethyl sulfate has
been shown to be carcinogenic in rats following inhalation or
subcutaneous administration, but negative in mice following der-
mal application or intravenous administration. Diethyl sulfate
has been shown to be carcinogenic in rats following subcutaneous
injection or via transplacental exposure. The test results pro-
vided by Union Carbide clearly demonstrate that diethyl sulfate
is also a moderate/potent carcinogen toward the skin of C3H/HeJ
male mice following dermal application (when evaluated against 3-
methyl cholanthrene as a positive control). The positive results
from the performed 3-test genotoxicity battery are consistent
with the diethyl sulfate carcinogenicity bioassay findings and
previously reported genotoxicity test results for this chemical
substance.
Although Union Carbide's bioassay does demonstrate the dermal
carcinogenicity of diethyl sulfate in mice, the inbred mouse
strain used in the study may not have been the best choice to
assess the full carcinogenic potential of diethyl sulfate in
terms of multiplicity of tissue targets affected. Inbred mouse
strains may possess an unusual sensitivity or resistance to the
development of any given tumor type. Indeed, the C3H/HeJ mice in
the acetone (negative control) group displayed a high spontaneous
incidence of hepatic tumors. It may have been a better choice to
use random-bred Swiss mice which are known to have a generally
low incidence of spontaneous neoplasms.
Production and Use
A review of the production range (including importation volumes)
statistics for diethyl sulfate (CAS No. 64-67-5). which is listed
in the initial TSCA Inventory, has shown that between 1.25 mil-
lion and 12.5 million pounds were reported as produced/imported
in 1977. This production range information does not include any
production/importation data claimed to be confidential by those
person(s) reporting for the TSCA Inventory, nor does it include
any information that would compromise TSCA Confidential Business
Information. All of the data submitted for the TSCA Inventory,
including the production range information, are subject to the
limitations contained in the TSCA Inventory Reporting Regulations
(40 CFR 710).
According to secondary literature sources and product information
provided by the Union Carbide Corporation, diethyl sulfate can be
used as an ethylating agent in the manufacture of aliphatic and
aromatic ethers, amines, amides, and esters for dyestuff and
pharmaceutical synthesis, in the manufacture of quaternary tex-
tile finishing compounds, as an accelerator in the sulfation of
ethylene and in some sulfonations. It can be produced by absor-
bing ethylene in concentrated sulfuric acid or by the action of
153
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8EHQ-1083-0509
GEHQ-0184-0509 Follawup
Page 5 of 7
fuming sulfuric acid on ethyl ether or ethyl alcohol. Diethyl
sulfate is also produced as an intermediate in one method for the
production of ethyl alcohol from ethylene.
Comments/Recommendations
EPA's position is unchanged with regard to the TSCA Section 8(e)-
applicability/reportability of the Union Carbide Corporation's
oncogenicity findings in mouse skin following chronic dermal ap-
plication of diethyl sulfate. EPA believes that Union Carbide's
findings do not corroborate those already documented for diethyl
sulfate and therefore should have been submitted to EPA in a
timely manner pursuant to Section 8(e) of TSCA.
It is EPA's experience that chemical companies subject to Section
8(e) consider a number of factors (including those listed below)
in determining whether obtained information may warrant reporting
to EPA under Section 8(e) of TSCA:
1)
2 )
3)
4 )
5)
6 )
species (and strain of species) tested;
nature (including severity) of the observed
time to onset of the observed effect(s);
target organ(s)i
route of exposure/administration; and
dose(s) administered
effect(s);
It should be noted that new information relating to such factors
does play an extremely vital role in 1) assessing, and in some
cases, re-assessing the degree of risk of injury to health or en-
vironment posed by exposure to a chemical substance or mixture,
and 2) determining the most appropriate course(s) of action for
reducing or eliminating such risk. For example, a risk assess-
ment which is based on a reported finding that chemical X can
produce injection-site sarcomas in rats could be changed in a
significant way by new information which indicates that chemical
X can produce lung or other tumors via inhalation in rats. Such
a change in the risk assessment could lead in many cases to a
change in the course of the action(s) needed to reduce risk. It
should be evident, therefore, that an observation that chemical X
produces lung or other tumors via inhalation should not be viewed
as simply corroborating a previously reported and/or well known
observation that the chemical produces injection-site sarcomas
following subcutaneous injection.
Many chemical manufacturers, processors, and distributors have
correctly recognized that in order for new health effects infor-
mation to be corroborative, the information must verify or con-
firm previously reported and/or published information that the
subject chemical substance or mixture when administered at a
specific dose by a specific route produced a specific toxic ef-
fect (e.g., squamous cell carcinoma) in a specific target organ
(e.g., skin) in a specific species or strain of species. This
interpretation is supported by the fact that many companies who
have submitted information under Section 8(e) have reported that
154
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8EH0-1083-0509
8RQQ-0184-0509 Followup
Page 6 of 7
their decision to submit was based on the fact that a difference
observed in as few as one of the previously listed factors had
caused the obtained information to become sufficiently different
from that which was previously known for the tested chemical sub-
stance or mixture. EPA continues to believe that the interpreta-
tion is correct and consistent with the legislative intent of
TSCA and the legislative intent and language of the Section 8(e)
provision itself. EPA also continues to believe that the prepon-
derant industry interpretation is consistent with the Agency's
well publicized concern about cancer (as well as other serious
health effects) and with the intent and language of the Agency's
Section 8(e) policy statement with regard to the timely reporting
of such serious health effects information.
The preface to Part V of EPA's March 16, 1978, TSCA Section
8(e) policy statement (i.e., "Statement of Intrepretation and
Enforcement Policy; Notification of Substantial Risk" 43 FR
11110) states the Agency's belief that a "substantial risk of
injury to health or the environment is a risk of considerable
concern because of (a) the seriousness of the effect...and
(b) the fact or probability of its occurrence." With regard
to the seriousness of the effect, Part V explains that EPA
considers the health effects for which substantial risk in-
formation 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. Information concerning 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 explains
that certain types of health effects (e.g., cancer) are so
serious that relatively little weight should be given to the
chemical's exposure in determining whether a risk is substan-
tial; the mere fact that an implicated chemical or mixture is
in commerce would constitute sufficient evidence of exposure.
In the case of the information provided in FYI-OTS-I083-0271, the
Union Carbide Corporation found that diethyl sulfate can produce
skin cancers in mice after repeated dermal application, a finding
which the company has acknowledged was not previously known for
diethyl sulfate. For the purposes of Section 8(e)-reporting, EPA
does not believe that this finding corroborates information that
had been previously reported to EPA or published in the available
scientific literature. Therefore, EPA has determined that Union
Carbide should have reported its mouse skin cancer findings for
diethyl sulfate to EPA in a timely manner under Section 8(e) of
the Toxic Substances Control Act.
155
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8~IQ-1083-0509
8&QQ-0184-0509 Followup
Ba~e 7 of 7
The Risk Management Branch (RMB/ECAD/OTS/OPTS) has been assessing
available toxicity and exposure information on diethyl sulfate in
order to determine the need for and scope of a formal (or other)
EPA response designed to reduce potential risks posed by exposure
to this chemical. In addition, it should be noted that diethyl
sulfate was listed in EPA's June 22, 1982 TSCA final Section 8(a)
chemical exposure information-reporting rule (47 FR 26992).
a)
The Chemical Screening Branch (CSB/ECAD/OTS/OPTS) will
inform the Union Carbide Corporation of EPA's determina-
tion concerning the Section 8(e)-reportability of the
company's observation that diethyl sulfate can produce
skin cancers in mice following repeated dermal applica-
tion. In light of this EPA determination, the Chemical
Screening Branch will deliver FYI-OTS-I083-0271 and FYI-
OTS-0284-0271 Followup Response to the Document Control
Office (DCO/IMD/OTS/OPTS) for appropriate handling/filing
under Section 8(e) of the Toxic Substances Control Act.
b)
The Chemical Screening Branch will send a copy of this
status report to OSHA, NIOSH, CPSC, FDA, NTP, OANR/EPA,
ORD/EPA, OW/EPA, OSWER/EPA, RMB/ECAD/OTS/OPTS, and the
Compliance Monitoring Staff (CMS/OPTS). A copy of this
report will also be sent to the TSCA Assistance Office
(TAO/OTS/OPTS) for further distribution.
156
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0484-05l0
Page 1 of 3
DA Tt: APR I 6 1'&1
SUIJ£C:T. Stat us Report *
8EHQ-0484-05l0
Approved
?fJ- 1'1-Y
nOli. Justine Welch SChae~ction Head
Chemical Risk IdentitVcation Section/CSB
TO. Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Revision
Needed
Submission Description
The IBM Corporation provided summarized results from several in
vitro genotoxicity and in vivo acute toxicity studies of 2,3,4-
trihydroxybenzophenone (THBPi CAS No. 1143-72-2). According to
IBM, THBP was found to induce Sister Chromatid -Exchanges (SCEs)
in cultured Chinese Hamster Ovary (CHO) cells in the presence and
absence of exogenous metabolic activation and found to produce
chromosomal aberrations in cultured CHO cells in the presence but
not in the absence of exogenous metabolic activation. IBM also
reported that THBP had been found to be non-mutagenic in the pre-
sence and absence of metabolic activation in a previously conduc-
ted Ames/Salmonella typhimurium (bacteria) assay. With regard to
the negative results of the chromosomal aberration assay that was
conducted in the absence of metabolic activation, the submitter
stated that the validity of these results was in question and
exp~essed the company's opinion that positive results migh~ be
obtained using higher doses of THBP.
. I~.I ,
In addition to the submitted in vitro genotoxicity informati~n,
IBM reported that THBP is strongly irritating to rabbit eyes and
mildly irritating to rabbit skin. The company also reported that
the LD50 for THBP is in excess of 5 g/kg in male rats.
Submission Evaluation
Although the 'submitted information indicates that THBP does
possess some degree of in vitro clastogenic activity, complete
copies of the final reports (including test protocols and data)
from all of the studies cited in this submission should be ob-
tained from IBM in order for EPA to evaluate more properly the
reported findings.
-NOTE: This status recort is the result of a oreliminarv
staff evaluation of i~formation submitted to.EPA. State;e~ts
mace herein are no~ to be regarded as expressing final
Agency policy or intent w~th res?ec~ to t~is particular
chemical. .~y review of the status report should take into
consideration the fact that it may be based on incomplete
information. 157 r
E~4. 1'0". 11»4 '''EY. ~,'I
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BEHQ-04B4-0510
Page 2 of 3
Current Production and Use
A review of the production range (includes importation volumes)
statistics for THBP (CAS No. 1143-72-2), 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. This production range information does not include any
production/importation data claimed as confidential by the per-
sones) reporting for the TSCA Inventory, nor does it include any
information that would compromise TSCA Confidential Business
Information (TSCA CBI). All of 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).
With regard to IBM's THBP production, IBM stated that THBP "is
manufactured at one IBM location approximately once every three
years and used in small quantities approximately twice a year
with no more than 10 employees working with the material for more
than two hours on each occasion for the manufacture of a photo-
active substance." IBM also stated that the company "uses THBP
exclusively for internal manufacturing of [the] photo-active
compound." Although IBM did not report the identity of this
photo-active chemical, IBM did ~eport that THBP is reacted com-
pletely and "does not become a part of any IBM product." No
information concerning any other users) of THBP was located by
EPA in the secondary literature sources consulted.
Comments/Recommendations
In its submission, the IBM Corporation stated that the company
believes that "under the actual conditions of manufacture and
use, THBP represents a minimal health risk to IBM employees who
handle this compound." The company also stated that employee
exposure to THBP "is controlled by full protective clothing when
this substance is not in a fully enclosed process."
Although a positive in vitro genotoxicity test result, when con-
sidered alone, may not be sufficient to offer reasonable support
for a conclusion of substantial risk, the Agency believes that
such results are of value in assessing possible risks posed by
chemicals to health and/or the environment. EPA also believes
that positive genotoxicity test results in combination with ad-
ditional information (e.g., knowledge of potential exposure to,
or high production of, the chemical substance or mixture), would
suggest, in many cases, the need to conduct additional toxicity
studies. The results of such studies should be considered also
for possible ?ub~ission to EPA pursuant to Section B(e) of TSCA.
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will
request the IBM Corporation to provide to EPA complete
copies of the final reports (including test protocols
and data) from all of the in vitro and in vivo THBP
toxicity studies that were-Cited in IBM'S submission.
158
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8EHQ-0484-0510
Page 3 of 3
In view of the Agency's general interest in corporate
actions that are taken on a voluntary basis in response
to chemical toxicity/exposure information, the Chemical
Screening Branch will also request IBM to describe the
actions IBM has taken to notify workers and others and
to describe the nature of all other studies that IBM has
conducted, is now conducting, or is planning to conduct
to define the toxicity of and/or exposure to THBP.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of THBP at the present time.
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OW/EPA,
OSWER/EPA, OANR/EPA and ORD/EPA. A copy of this status
report will also be sent to the TSCA Assistance Office
(TAO/OTS/OPTS/EPA) for further distribution.
159
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OA1£;
.118
UNITED STATES E!'IY1RO~ENTAl PROTECTION AGENCY
8EHQ-0484-0511
Page 1 of 2
SUIJ£CTI St at us Report *
8EHQ-0484-0511
Approved ~/k- ~/~3
L.-7
Revision
Needed
'IOMI Justine Welch SChaeff~ction Head
Chemical Risk Identi~~t~on Section/CSB
TOI Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Gulf Oil Products Company provided summarized results from a
battery of in vitro and in vivo genotoxicity studies of Gulf's
butadiene feedstock whic~is reported to contain 1,3-butadiene
(40-69%), I-butene (11-19%), isobutene (5-20%), and mixed butenes
and butane (7-24%). According to the submitter, the butadiene
feedstock was found to be weakly positive in an in vitro primary
rat hepatocyte DNA repair test, weakly positive in an in vivo
mouse micronucleus test, negative in an in vitro Chinese Hamster
Ovary (CHO) cell mutagenicity test, and negative in an in vitro
BALB/c mouse cell transformation test.
Submission Evaluation
Although the submitted information does indicate that the tested
butadiene feedstock possesses some degree of in vitro and in vivo
genotoxic activity, full copies of the final reports (includi~
protocols and data) from all of the cited studies are needed in
order to evaluate the reported findings.
Current Production and Use
The Gulf Oil Products Company did not provide any information
concerning the current production/importation volumes of its
butadiene feedstock nor was such information located in the
secondary literature sources consulted. 1,3-Butadiene is a
short-chain unsaturated hydrocarbon used primarily in the
manufacture of various types of synthetic rubber, plastic, and
latex. According to secondary literature, the current yearly
U.S. production of 1,3-butadiene is around 3 billion pounds.
Comments/Recommendations
The Gulf Oil Products Company reported that it was reviewing
"handling procedures, labeling practices and Material Safety
Sheets to determine if any changes are needed to assure safe
handling for Gulf employees, contractors, and customers."
the
Data
-NOTE: This status recort is the result of a creliminarv
staff evaluation of i~fo=mation submitt~c to EPA. State;ents
mace here~n are not to be regarded as ex?ressing final
Ase~cy policy or intent with respect to t~is ?articular
chemical. .~y review 6f the status report should tak~ into
consideration the iact that it may be bas~d on incomplete
informa tion. 160
t~" 0"'. 1J:z:>-6 .'" 1:.... ..",
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8EHQ-0484-0511
Page 2 of 2
On January 5, 1984, EPA announced in the Federal Register (49 FR
845) that EPA had started a 180-day review of 1,3-butadiene under
Section 4(f) of TSCA. This 180-day review was undertaken by EPA
in order to determine "whether to initiate appropriate action to
prevent or reduce risk from the chemical or to find that the risk
is not unreasonable." EPA is under a statutory obligation to
decide in a 180-day period whether to initiate regulatory action
if EPA makes a threshold determination under Section 4(f) of TSCA
that there "may be a reasonable basis to conclude that a chemical
substance or mixture presents or will present a significant risk
of serious or widespread harm to human beings from cancer, gene
mutations, or birth defects..." On May 15, 1984, EPA published
in the Federal Register (49 FR 25024) an Advanced Notice of Pro-
posed Rulemaking (ANPR) concerning 1,3-butadiene. The following
information is presented in the summary section of that ANPR:
"This notice announces the initiation of regulatory action by
EPA to determine and implement the most effective means of
controlling exposures to the chemical 1,3-butadiene under the
Toxic Substances Control Act (TSCA). Recent bioassays have
established that 1,3-butadiene causes cancer in experimental
animals. EPA, concerned about potential unreasonable risks
posed mainly by occupational exposures to 1,3-butadiene, will
explore regulatory options to reduce or eliminate such risks.
The Occupational Safety and Health Administration (OSHA) has
decided to cooperatively collect and evaluate information re-
garding 1,3-butadiene with EPA...."
In addition, it should be noted that the National Institute for
Occupational Safety and Health (NIOSH) published (March 9, 1984)
a "Current Intelligence Bulletin" in which NIOSH recommended that
the current Occupational Safety and Health Administration (OSHA)
workplace exposure standard of 1,000 ppm (TWA) for 1,3-butadiene
be re-examined. It should also be noted that EPA's Office of
Toxic Substances has received and evaluated several TSCA Section
8(e) and "For Your Information" submissions on 1,3-butadiene and
has prepared a Chemical Hazard Information Profile (CHIP) on 1,3-
butadiene.
a)
The Chemical Screening Branch (CSBjECADjOTS) will request
the Gulf Oil Products Company to provide to EPA complete
copies of the final reports (including test protocols and
data) from all of the butadiene feedstock genotoxicity
studies that were cited in the company's submission.
b)
The Chemical Screening Branch will provide copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWERjEPA,
OWjEPA, OANRjEPA, ORDjEPA, CCDjOTS, and RMBjECADjOTS. A
copy of this status report will also be sent to the TSCA
Assistance Office (TAOjOTSjOPTS) for further distribution.
161
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UNITED STATES EHYtRONMENTAL PROTECTION AGENCY
SUIJ£CTI St at us Report *
8EHQ-0484-0512
8EHQ-0484-05l2
Page 1 of 2
App:-oved ~7/.?5
Revision
Needed
DAn;
MAY 2 \ ~
f£~
'ICMIJustine Welch Schaeff Section Head
Chemical Risk Identif- ation Section/CSB
TOIFrank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Gulf Oil Products Company submitted summarized findings from
a battery of genotoxicity studies of Gulfcrown Grease E.P. No.2.
According to the company, the grease was found to be positive in
an in vitro primary rat hepatocyte DNA repair test, negative in
an in vitro Chinese Hamster Ovary (CHO) cell mutagenicity test,
negative in an in vivo mouse micronucleus test, and equivocal in
an in vitro BALB/c mouse cell transformation assay.
Submission Evaluation
Although the submitted information does indicate that Gulfcrown
Grease E.P. No.2 possesses some degree of in vitro genotoxic
activity, full copies of the final reports (including protocols
and data) from all of the studies cited in the submission are
needed in order to evaluate the reported findings
Current Production and Use
The Gulf Oil Products Company did not provide any information
concerning the actual production or use(s) of Gulfcrown Grease
E.P. No.2 nor was such information located by the Agency in the
secondary literature sources consulted.
Comments/Recommendations
In its submission, the Gulf Oil Products Company reported that it
is reviewing the company's Gulfcrown Grease E.P. No.2 "handling
procedures, labeling practices and Material Safety Data Sheets to
determine if any changes are needed to assure safe handling for
Gulf's employees, contractors and customers."
-NOTE: T~is status reDo~t is the resu2t of a Drelirnina~v
staff evaluation of i~fo~ation submitted to EFA. Sta~e;ents
mace herein are no~ to be reaarded as ex~ressir.a final
Asency policy or intent wi~h-res?ec~ ~o t~is particular
chemical. .~Y. review 6f the status repor~ should take into
consideration the fact that it may be based on incomplete
informa tion. 162
~~, '0"'''' U~ I'll:"'. ..'I'
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BEHQ-04B4-0512
Page 2 of 2
Although a positive in vitro genotoxicity test result, when con-
sidered alone, may not be sufficient to offer reasonable support
for a conclusion of substantial risk, the Agency believes that
such results are of value in assessing possible risks posed by
chemicals to health and/or the environment. EPA also believes
that positive genotoxicity test results in combination with ad-
ditional information (e.g., knowledge of potential exposure to,
or high production of, the chemical substance or mixture), would
suggest, in many cases, the need to conduct additional toxicity
studies. The results of such studies should be considered also
for possible submission to EPA pursuant to Section B(e) of TSCA.
a)
The Chemical Screening Branch (CSB/ECAD/OTS/OPTS) will
request the Gulf Oil Products Company to submit complete
copies of the final reports (including protocols and
data) from all of the genotoxicity studies cited in the
company's submission. In addition, the submitter will be
requested to report the exact chemical name, CAS Registry
Number (if known), and amount of each constituent in
Gulfcrown Grease E.P. No.2.
In view of the Agency's general interest in corporate
actions that are taken on a voluntary basis in response
to chemical toxicity/exposure information, the Gulf Oil
Products Company will be requested to describe the nature
of all other studies that the company has conducted, is
conducting, or plans to conduct that are designed to de-
fine the toxicity of and/or exposure to Gulfcrown Grease
E . P. No.2.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of Gulfcrown Grease E.P. No.2 and/or its
constituent(s).
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, OW/EPA, OSWER/EPA,
ORD/EPA, and OANR/EPA. Copies of this report will also
be sent to the TSCA Assistance Office (TAO/OTS/OPTS/EPA)
for further distribution.
163
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UNITED STATES ENY IROHMENT AL PROTECTION AGENCY
SUaJECTI Status Report *
8EHQ-0484-0513
8EHQ-0484-0513
Page 1 of 4
App:oved t#- !~IJt
DATE;
MAY 2 9 ~
nCIMI Justine Welch Schaef
Chemical Risk Identif
ection Head
ation Section/CSB
Revision
Needed
TOI Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
Mallinckrodt, Inc. submitted a complete copy of the final report
of an acute rabbit dermal toxicity study of a mixture (M278) con-
taining approximately 500 mg phenylhydroxylamine (PHA; CAS No.
100-65-2) per liter of methanol. Mallinckrodt also submitted a
description of "skin effects presumed to have resulted from [wor-
ker] exposure to [a] PHA/methanol solution." In addition, the
company submitted an English translation of a paper by L. Lewin
entitled "The Effects of Phenylhydroxylamine. A Further Contri-
bution to the Knowledge of Blood Poisons" (Archiv. f. Experiment.
Pathol. y. Pharmakol. 35:401-414, 1895) that was cited in NIOSH1s
Registry of Toxic Effects of Chemical Substances (RTECS».
The following information was contained in the Summary/Conclusion
section of the submitted final report from Mallinckrodt1s acute
rabbit dermal toxicity study of M278 (500 mg/l PHA/methanol):
"Undiluted M278 was applied for twenty-four hours to the
intact skin of New Zealand White rabbits, weighing 2.32 to
2.98 kilograms, at dosage levels of 50, 200, 500 and 2,000
mg per kilogram of body weight (2 animals of each sex/level).
Based on the limited number of animals used for the study,
the acute dermal LD50 appears to be between 200 and 500 mil-
ligrams per kilogram of body weight. Complete blood counts
performed on the animals at the 50 and 500 milligram per ki-
logram of body weight dosage levels at 1, 2, 3 and 24 hQurs
post-application, showed at both levels, mild to moderate
le~kocytosis, a shift between the segmented neutrophil and
lymphocyte counts and crenation and ghosting of red blood
cells. Paleness and/or cyanosis of the eyes and/or mucous
membranes, signs apparently related to the observed hemato-
logical abnormalities, were observed in fourteen of the six-
teen animals and persisted in one survivor throughout the
fourteeD- day observation period." (Mallinckrodt also pointed
out that adverse skin, kidney, and liver effects had been
observed grossly in the exposed animals).
-NOTE: T~is status recort is the result of a crelirninarv
staff e~aluation of i~formation submitt~c to EPA. Sta~e;'ents
mace herein are not to be re~arded as ex~ressino final
Agency poli~y 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 incomplete
informa tion.
164
E~" ~C)... U:D-6 '!liE"'. """
-------
8EHQ-0484-0513
Page 2 of 4
With regard to the adverse skin effects noted in workers exposed
to a PHA/methanol solution, Mallinckrodt provided the following
information:
"During new facility start-up, Mallinckrodt workers accident-
ly had contact with an intermediate solution containing about
500 gm/l PHA in methanol. The workers subsequently developed
skin rashes/blisters/irritations of varying degrees. In some
cases, the skin effects did not develop immediately but were
delayed for up to 24 hours after initial contact. Healing
time varied from one to several weeks."
In addition to detailing the adverse hematologic and other toxic
effects observed in humans whose skin was exposed to a phenylhy-
droxylamine/alcohol solution, the submitted paper by Lewin con-
tains summarized results from a number of acute toxicity studies
of phenylhydroxylamine alone or mixed with alcohol administered
via dermal, oral, or subcutaneous routes to rabbits, pigeons,
snakes and frogs. According to Mallinckrodt, Lewin's studies
showed that:
"dermal contact of a human with PHA resulted in development
of methemoglobinemia;
application of PHA moistened with alcohol to the skin of a
human also caused inflammation and development of nodules
that finally began to subside after some 10 days;
alcoholic solutions of PHA are readily absorbed;
application of PHA to freshly drawn blood caused destruction
of erythrocytes; and
development of methemoglobinemia in experimental
exposed to PHA was observed; subsequent reversal
condition was attributed to decomposition of PHA
uptake of oxygen."
animals
of the
following
It should be noted that Lewin's paper also included summarized
results from acute animal studies of nitrobenzene, hydroxylamine,
aniline, aminophenol, p-aminophenol hydrochloride, azoxybenzene,
and azobenzene.
Submission Evaluation
The submitted animal studies and human clinical case reports
demonstrate that phenylhydroxylamine (PHA) in solution in alcohol
penetrates the skin readily and can cause serious local and sys-
temic toxic effects.
In addition to adverse skin effects (e.g., irritation, edema,
erythema), Mallinckrodt's acute dermal toxicity study of PHA in
rabbits showed that the lungs, liver, and kidneys of the exposed
animals manifested systemic intoxication. The severity of the
165
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8EHQ-0484-0513
Page 3 of 4
lung congestion appears to be dose-related. Methemoglobinemia
and hemolysis were also observed. However, the rare cases of
profound hemolysis occurred only in the low-dose group. The
reported paleness and/or cyanosis of mucous membranes suggests
appreciable anemia and/or interference with oxygenation of the
blood. The observed cyanosis is most likely due to pulmonary
congestion, rather than due to hemolysis or methemoglobinemia
which did not appear to have been very severe. It should be
noted that the development of methemoglobinemia will promote
hemolysis by increasing erythrocyte rigidity and osmotic fra-
gility (Lux and Glader in Beck 1977, Hematology, Page 286).
Mallinckrodt's acute rabbit dermal toxicity study of PHA appears
to present the following new information with regard to toxicity:
(1) a demonstration of a dose-response relationship, (b) a semi-
quantitative appreciation of the extent of dermal absorption
(i.e., estimated 90% absorption in 24 hours) , and (c) congestion
of the lungs. Lewin's paper does not mention lung congestion in
animals and only implies that such an effect occurs in humans
("...rattle-like noise following respiration....") following der-
mal exposure to phenylhydroxylamine.
The submitted information raises a question with regard to the
sensitizing potential of phenylhydroxylamine. Lewin's findings
suggest that PHA is a dermal sensitizer (delayed recurring red-
ness after recovery from PHA exposure which Lewin attributed to
participation of the lymphatic system). This would tend to lower
the effective dose for adverse dermal effects. There is also the
possibility that PHA can cause respiratory sensitization, because
PHA (like phenylethanolamine) is vasoactive. Although it has not
been shown that PHA can cause constriction of bronchiolar smooth
muscle, it should be noted that dyspnea (difficulty in breathing)
was a common finding in the PHA-exposed animals in the Lewin and
Mallinckrodt studies.
Scientifically, it would be interesting to know 1) whether PHA
alone or in alcohol is a dermal sensitizer, 2) whether PHA alone
or in alcohol administered by the dermal route is a respiratory
sensitizer, 3) the extent of methemoglobinemia induced by PHA,
and 4) the extent of PHA-induced impairment of oxygen transport
in order to help sort out the relative contribution(s) of bron-
chiolar constriction, pulmonary congestion, hemolysis, and/or
methemoglobinemia to the observed cyanosis.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for phenylhydroxylamine (CAS No. 100-65-2), which is
listed in the initial TSCA Inventory, has shown that between 10
thousand and 101 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 con-
fidential by the person(s) reporting for the TSCA Inventory, nor
does it include any information that would compromise Confidential
166
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8EHQ-0484-0513
Page 4 of 4
Business Information (TSCA CBI). 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).
Although Mallinckrodt did not submit any information concerning
the use(s) of phenylhydroxylamine, the company did report that
the chemical is a site-limited intermediate that is produced in
batches via a totally enclosed process. According to secondary
literature sources, phenylhydroxylamine is used to manufacture
cupferron (ammonium nitroso-beta-phenylhydroxylamine), which is
an analytical reagent for separating/precipitating metals such as
copper and iron. Secondary literature sources also report that
phenylhydroxylamine can be used in the preparation of p-amino-
phenol, which is a dye intermediate and a photographic developer.
Comments/Recommendations
Mallinckrodt, Inc. stated that the company has informed its
workers about the toxicity of the PHA/methanol mixture and has
"implemented appropriate operating procedures." In addition,
Mallinckrodt reported that the "start-up conditions causing [the
workers'] contact with the intermediate PHA solution have been
resolved" and that "no further exposure contact is anticipated."
The Chemical Screening Branch (CSB/ECAD/OTS/OPTS) has prepared
Chemical Hazard Information Profiles (CHIPs) on nitrobenzene,
aniline, p-aminophenol, p-aminophenol hydrochloride, and azo-
benzene. A CHIP on hydroxylamine, hydroxylamine hydrochloride,
and hydroxylamine sulfate is currently in preparation. In ad-
dition, the Test Rules Development Branch (TRDB/ECAD/OTS) is
evaluating toxicity and exposure information on aniline and
nitrobenzene under Section 4 of TSCA as recommended by the
Interagency Testing Committee (ITC).
a)
In light of the the Agency's general interest in company
actions that are taken on a voluntary basis in response
to chemical toxicity/exposure information, the Chemical
Screening Branch will request Mallinckrodt to describe
the nature of all other studies that the company has
conducted, is conducting, or plans to conduct that are
designed to define the toxicity of and/or exposure to
phenylhydroxylamine alone or mixed with alcohol.
b)
The Chemical Screening Branch will review the reported
information to determine whether further OTS assessment
of phenylhydroxylamine is needed at the present time.
c)
The Chemical Screening Branch will send a copy of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OW/EPA,
OSWER/EPA, OANR/EPA, ORD/EPA, and TRDB/ECAD/OTS/OPTS.
Copies of this status report will also be sent to the
TSCA Assistance Office (TAO/OTS/OPTS/EPA) for further
distribution.
167
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UNITED 5T A TES ENVIRONMENTAL PROTECT"ION AGENCY
8EHQ-0584-05l4
Page 1 of 3
Cu.T£;
~
8~
SUIJ£CT. Status Report *
8EHQ-0584-0514
Approved
~
0/11
.
nOMI Justine Welch SChaef~ction ~ead
Chemical Risk Identi~~ti~n Sectlon/CSB
Revision
Needed
TOI Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Celanese Corporation provided summarized results from a
chronic dermal application study of n-pentanoic acid (CAS No.
109-52-4), heptanoic acid (CAS No. 111-14-8), and nonanoic acid
(CAS No. 112-05-0) in C3H/HeJ mice. According to Celanese, the
results indicate that there was "a significant increase in [skin]
tumor incidence rate in the [n-pentanoic acid] exposed mice as
compared to the control group." Celanese also reported that the
results "do not show an increase in [skin] tumor incidence rate"
for mice exposed dermally to heptanoic acid or nonanoic acid.
Submission Evaluation
In view of the inferences that can be drawn from knowledge about
the structure-activity relationships of chemical carcinogens, the
~eported oncogenicity findings for n-pentanoic acid are very sur-
prising. It should be noted that there may be at least two other
plausible reasons for the observed oncogenic activity. Firstly
the synthesized valeric acid used in the chronic study may have
been contaminated. Although the submitted contract laboratory's
protocol (standard operating procedure?) for the study indicates
that the purity and stability of the test substances was to be
determined by Celanese, no purity/stability information was pre-
sented in the submission. Secondly, it appears that the overall
health" of the mice may have been poor. The submitted information
shows that the untreated C3H/HeJ mice maintained in the animal
quarters had experienced a 48% mortality by the 78th week of the
study. Considering that the average life-span of most mouse
strains (including random-bred strains) is slightly over 2 years,
the short life span of the control animals suggests that there
was something toxic (oncQgenic?) in the animal room environment
(e.g., bedding, air, drinking-water, feed). In view of the fact
that straight chain fatty acids of intermediate chain length are
polar-nonpolar molecules that can act as weak promoters, it is
possible that n-pentanoic acid may have acted as a promoter for
some other substance to which the mice were exposed. It should
also be noted that, in general, mouse skin is a very sensitive
-NOTE: T~is status reDort is the result of a crelirninarv
staff evaluation 0: i~forma~ion submitted to EPA. State;ents
m9ce herein are nOt to be re~arded as ex~ressir.a final
Ase~cy policy or intent with-respect to t~is ?articular
chemical .~y review of the status report should tak~ into
consid~ration the iact that it may be based on incomplete
information. 168
[~. '0"''' IJ~ II"';V. ~,..
-------
8EHQ-0584-0514
Page 2 of 3
indicator of even traces of chemical substances for which this
tissue is a possible target organ. Moreover, there are known
initiator/promoter combinations in which the promoter, when
applied to the skin, re-directs the target orientation of the
initiating carcinogen to the skin (not otherwise acting on this
tissue).
Further evaluation of the reported oncogenicity findings must
await EPA's receipt of a complete copy of the final report (in-
cluding the actual experimental protocol, data, purity/stability
information, etc.) from the chronic mouse skin application study.
In addition, information about the process by which the tested n-
pentanoic acid was synthesized would be of great value.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for n-pentanoic acid (CAS No. 109-52-4), 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 and/or 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 that would compromise TSCA
Confidential Business Information. The data submitted for the
TSCA Inventory, including production range information, are sub-
ject to the limitations contained in the TSCA Inventory Reporting
Regulations (40 CFR 710).
The Celanese Corporation reported that n-pentanoic acid "is not
manufactured or processed commercially by Celanese, so there is
no potential for employee exposure to the material other than in
occasional laboratory use." In addition, Celanese reported that
it synthesized the n-pentanoic acid "on a small scale for poten-
tial end use evaulation" but did not report the nature of the end
use. According to secondary literature sources, n-pentanoic acid
is used as an intermediate in the manufacture of drugs, flavoring
agents, perfumes, plasticizers, lubricants, and stabilizers.
Comments/Recommendations
The Celanese Corporation stated that the reported oncogenicity
findings for n-pentanoic acid were being brought to the attention
of the Occupational Safety and Health Administration (OSHA), the
National Institute for Occupational Safety and Health (NIOSH).
and the National Cancer Institute (NCI).
a)
The Chemical Screening Branch (CSB/ECAD/OTS/OPTS) will
request Celanese to provide to EPA a complete copy of
the final report (including the actual experimental pro-
tocol, data, purity/stability information, etc.) of the
chronic mouse skin application study. The submitting
company will also be requested to describe the process
by which the tested n-pentanoic acid was synthesized.
169
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8EHQ-OS84-0Sl4
Page 3 of 3
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of n-pentanoic acid at the present time.
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OW/EPA,
OSWER/EPA, ORD/EPA, and OANR/EPA. Copies of this status
report will also be sent to the TSCA Assistance Office
(TAO/OTS/OPTS) for further distribution.
170
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DA1£:
MAY 3 0 \984
8EHQ-0584-0515 S
Page I of 2
SUIJ£CTI Stat us Report *
8EHQ-0584-0515 S
Approved
~ ~/'I
nOMI Justine Welch SChaef~ection Head
Chemical Risk IdentifTJation Section/CSB
TOI Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Revision
Needed
Note: The submitting company has claimed that its identity, the
identities of the tested "epoxy finish" components, and the iden-
tity of the industrial fiber to which the finish is applied are
considered to be TSCA Confidential Business Information. The
Information Management Division (IMD/OTS/OPTS) has requested the
submitter to substantiate all of these confidentiality claims.
Submission Description
The submitting company provided summarized results from several
in vitro genotoxicity tests, conducted with an epoxy finish that
is described non-confidentially by the submitter as a proprietary
mixture of 2 epoxy resins. According to tbe submitting company,
"the epoxy finish gave positive results with and without activa-
tion in an Ames test, a Mouse Lymphoma test ana a Sister Chroma-
tid Exchange test."
Submission Evaluation
Although the submitted information indicates that the proprietary
epoxy resin finish does possess some degree of in vitro genotoxic
activity, complete copies of the final reports (including test
protocols and data) are needed to evaluate the reported findings
Current Production and Use
In light of the fact that the submitting company has claimed the
identities of the epoxy resin finish components to be TSCA Confi-
dential Business Information, no production information will ap-
pear in this status report. The submitting company'did report
non-confidentially that the epoxy finish "is added topically to
the industrial fiber at a very low concentration."
Comments/Recommendations
The submitter stated that the company is in the process of re-
viewing its "manufacturing process and industrial hygiene program
to insure that employee protection is adequate." In addition,
-NOTE: T~is status report is the result of a preliminary
staff evaluation of i~formation submitt~c to EPA. Stateme~~s
mace herein are not to be re~arded as e~~ressir.o final
Ase~cy po~icy or intent with~res?ec~ to t~is particular
chemical. .~y review of the status repor~ should take into
consideration the fact that it mav be based on incomolete
information. 171 .. .
r;~. "0"'1:1 i.~ I8IE.... ""I
-------
8EHQ-OS84-0SlS S
Page 2 of 2
the submitter stated that the Occupational Safety and Health
Administration (OSHA), the National Institute for Occupational
Safety and Health (NIOSH), the National Cancer Institute (NCI)
and the supplier of the proprietary epoxy resin mixture are being
notified about the results of the genotoxicity studies. The sub-
mitter also stated that, upon receipt, the final reports of the
genotoxicity studies would be transmitted to EPA.
Although a positive in vitro genotoxicity test result, when con-
sidered alone, may not be sufficient to offer reasonable support
for a conclusion of substantial risk, the Agency believes that
such results are of value in assessing possible risks posed by
chemicals to health and/or the environment. EPA also believes
that positive genotoxicity test results in combination with addi-
tional information (e.g., knowledge of potential exposure to or
high production of the chemical substance or mixture), would sug-
gest, in many cases, the need for additional toxicity studies.
The results of such studies should be considered also for pos-
sible submission to EPA under Section 8(e) of TSCA.
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will request
the submitter to ensure that EPA receives complete copies
of the final reports (including protocols and data) from
all genotoxicity studies cited in the submission. In ad-
dition, the submitter will be asked to report the exact
chemical identity, CAS Registry Number (if known), and
amount of each constituent of the tested epoxy resin fi-
nish. The submitting company will also be requested to
report the exact identity of the "industrial fiber" to
which the epoxy finish is applied.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity or exposure information, the Chemical Screening
Branch will request the submitting company to describe
the nature of all other studies that the company has con-
ducted, is conducting, and plans to conduct that are de-
signed to define the toxicity of and/or the exposure to
the proprietary epoxy finish or its components. In addi-
tion, the submitter will be requested to describe the
actions the company has taken to notify its own workers
about the reported genotoxicity findings.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of the proprietary epoxy resin mixture
and/or its components at the present time.
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OW/EPA,
OSWER/EPA, OANR/EPA, and ORD/EPA. Copies of this status
report will also be sent to the TSCA Assistance Office
(TAO/OTS/OPTS/EPA) for further distribution.
172
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UNITED STATES EHV IRONMENTAL PROTECTION AGENCY
8EHQ-0584-05l6 S
Page 1 of 3
DAn:
..uN
8004
SUaJECT. S_tatus "Repor't*
8EHQ-0584-0516 S
App=oved
:J~ b/PJ!o/
,.01& Justine Welch sChaeC.AM.4tion Head
'Chemical Risk Ident~~~~~ Section/CSB
Revision
Needed
TO Frank D. Kover, Branch Chief
'Chemical Screening Branch/ECAD/OTS/OPTS
Note: The submitting company has claimed its name and certain
information pertaining to the intended use of the tested material
as TSCA Confidential Business Information (CBI). The Information
Management Division (IMD/OTS) has requested the submitting com-
pany-to substantiate all of its confidentiality claims.
Submission Description
The submitting company provided a final report from an Ames test
and summarized results from several other genotoxicity tests of
an oxirane/methyloxirane polymer (CAS No. 9003-11-6). According
to the submitter, the tested material ~is the polymerization pro-
duct of 26 moles oxirane and 67 moles methyloxirane" and has an
average molecular weight of 5000. With regard to the results of
the performed genotoxicity tests, the submitter reported that:
"a water emulsion of the test material gave a positive re-
sponse in the Ames/Salmonella Microsome plate Test with meta-
bolic activation. The tests were negative in the absence of
the metabolic activation. In addition, preliminary reports
from the same test laboratory have reported positive respon-
ses in a Mouse Lymphoma test and a Sister Chromatid Exchange
test. A Cell Transformation test was negative.... A test of
the article coated with the appropriate amount of the finish
gave a negative response in the Ames test."
Submission Evaluation
Although the laboratory that performed the Ames/Salmonella
typhimurium (bacteria) assay considered the oxirane/methyloxirane
polymer to be mutagenic only for strain TA 98, EPA believes that
a positive response was observed also with strain TA 1538. In
evaluating data from Ames assays, the performing laboratory has
established an arbitrary value of 3X the spontaneous reversion
rate as being indicative of a positive resPQnse with strain TA
1538. Rather than rely on an arbitrary maximum response rate, it
is more appropriate to look for a concentration-related response
-
-NOTE: T~is status reco=t is the result of a crelirnina=y
staff evaluation of i~formation submittec to EPA. Stace~e~ts
mace herein are no~ to be regarded as expressing final
Agency policy' or intent with res?ec~ to t~is ?artic~lar
chemical. .~'i review 6f the status repor~ should take into
consideration the fact" that it may be based on incomolete
information. 173 . .
r,.& '0"'. U~ ....... ......
-------
8EHQ-0584-05l6 S
Pqge 2 of 3
and/or a significant, reproducible response at a single concen-
tration. In the case of the present submission, there was a
reproducible, concentration-related response that in both in-
stances reached a maximum of 2.6X the spontaneous mutation rate
for strain TA 1538. This should be considered as a positive re-
sponse for the tested polymer. Further, the performing labora-
tory conducted the Ames assay with one plate per concentration
point for all strains except TA 98 which was tested with three
plates per concentration point. The current Office of Toxic
Substances (OTS) testing guidelines for the Ames assay recommend
the use of three plates per point for all strains. The submitted
final report does not offer any explanation for the unequal dis-
tribution of plates per point in this assay. In addition, the
final report states that a preliminary toxicity assay showed that
the polymer was toxic for the indicator organism, strain TA 100.
A review of the data, however, shows that the tested polymer was
virtually non-toxic at concentrations up to a maximum of 10,000
pg/plate. Overall, these particular discrepancies do not affect
the Agency's evaluation and interpretation of the submitted Ames
test data.
Complete copies of the final reports, including protocols and
data, are needed in order to evaluate the results from the other
genotoxicity assays that were cited in the submission.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for the oxirane/methyloxirane polymer (CAS No. 9003-
11-6), which is listed in the initial TSCA Inventory, has shown
that between 13.4 million and 84.3 million pounds were reported
as produced and/or imported in 1977. This production range in-
formation does not include any production or importation data
claimed as confidential by the person(s) reporting for the TSCA
Inventory, nor does it 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 TSCA Inventory
Reporting Regulations (40 CFR 710).
According to the submitting company, the oxirane/methyloxirane
polymer "is being reviewed by [the submitting company in its]
research and test market programs" and "is being considered for
use as a finish at low levels on articles manufactured by the
submitter." The submitter did not provide any information per-
taining to the types of articles to which the oxirane/methyl-
oxirane finish would be applied.
Comments/Recommendations
The submitting company stated that the manufacturer of the
polymer (who was informed by the submitter about the reported
genotoxicity findings) "is attempting to determine if the ma-
terial itself caused the response or if the response was due to
174
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8EHQ-0584-0516 S
Page 3 ot 3
impurities, breakdown products or contaminants." In addition,
the submitter stated that the reported information was sent to
the Occupational Safety and Health Administration (OSHA), the
National Institute for Occupational Safety and Health (NIOSH),
and the National Cancer Institute (NCI). The submitter also
stated that, upon receipt, copies of the final reports from the
other genotoxicity assays would be transmitted to EPA and that
EPA would be notified about any new significant information that
the submitter receives.
Although a positive in vitro genotoxicity test result, when con-
sidered alone, may not be sufficient to offer reasonable support
for a conclusion of substantial risk, the Agency believes that
such results are of value in assessing possible risks posed by
chemicals to health and/or the environment. EPA also believes
that positive genotoxicity test results in combination with addi-
tional information (e.g., knowledge of potential exposure to or
high production of the chemical substance or mixture), would sug-
gest, in many cases, the need to conduct additional toxicologic
studies. The results of such studies should be considered also
for possible submission to EPA pursuant to Section 8(e) of TSCA.
a)
The Chemical Screening Branch (CSB/ECAD/OTS/OPTS) will
request the submitting company to ensure that the Agency
receives complete copies of the final reports (including
protocols and data) from all of the genotoxicity studies
cited in the submission. The submitting company will be
requested also to describe the articles to which the
company plans to apply the oxirane/methyloxirane finish.
In view of the Agency's general interest in corporate
actions that are taken on a voluntary basis in response
to chemical toxicity and/or exposure information, the
submitting company will be requested to describe the
nature of all other studies that it has conducted, is
conducting, or plans to conduct that are designed to
define the toxicity of and/or the exposure to the sub-
ject polymer. In addition, the submitting company will
be asked to describe the actions it has taken to notify
its workers about the reported genotoxicity information
on the oxirane/methyloxirane polymer.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of the oxirane/methyloxirane polymer.
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OW/EPA,
OSWER/EPA, ORD/EPA, and OAR/EPA. Copies of this status
report will be sent also to the TSCA Assistance Office
(TAO/OTS/OPTS/EPA) for further distribution.
175
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UNITED STATES EHY1RaNMENTAL PROTECTION AGENCY
suaJ£CT. Status Report*
8EHQ-0584-0517
8EHQ-0584-0517
Page 1 of 3
App=oved tJXr bfy
Revision
Needed
CAn;
.138
flOMIJustine Welch SChaef~~ection Head
Chemical Risk Identi~~tion Section/CSB
TOtFrank D. Kover,. Branch Chief
Chemical ScreenIng Branch/ECAD/OTS/OPTS
Submission Description
Exxon Company, U.S.A. submitted summarized results from a chronic
skin-painting study of a "solvent-cutback type rust-preventive"
product in C3H/HeJ male mice. According to Exxon, the tested
product contained Stoddard solvent (CAS No. 8052-41-3) (90.9% by
volume), 2-butoxyethanol (CAS No. 111-76-2) (2.5% by volume), and
a "calcium soap of oxidized wax acids blended with a minor amount
of calcium petroleum sulfonate" (6.6% by volume) (the submitter
stated that the supplier of these last components considers the
CAS Numbers to be "trade sec.ret"). .Exxon 'provided the following
information with regard to the results of the chronic study:
"The lifetime mouse skin-painting study began on September
26, 1979 and ended after 864 days, which was the day of death
of the last surviving animal. ["All tests were performed
utilizing C3H/HeJ male mice painted with 25 microliters of
material three times weekly."] At termination, 3 animals out
of the original 50 (6%) had grossly diagnosed squamous cell
carcinomas in or adjacent to the treatment area. During the
final histopathologic examination, these tumors were con-
firmed by microscopic examination, and 3 additional animals
were determined to have squamous cell carcinomas for a total
of 6 tumor-bearing animals (12%). Also, one tumor-bearing
animal had a papilloma in addition to the malignancy. Two
concurrent controls, positive and negative, were also uti-
lized in the study. The positive control, a 10% catalytic-
cracked clarified oil [CAS No. 64741-62-4] in white mineral
oil, U.S.P. [CAS No. 8042-47-5], elicited tumors in 48 of 50
animals (96%) by the 431st day of the test. The negative
control consisted of white mineral oil, U.S.P. only, which
caused no tumors during the test duration of 878 days."
-NOTE: T~is status reDo~t is the result of a Drelimina~v
staff evaluation of i~£ormation submitt~c to EPA State;ents
mace herein are no~ to be regarded as ex?re~sing final
Ase~cy policy or intent with res?ec~ to thi~ particular
chemical. .;nv review of the status repor~ should take into
consideration-the fact that it may be ~ased on incomolete
information. 176 .. .
r~. ~OA" 1I:D-4 'IIItV. ~"I
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8EHQ-0584-0517
Page 2 of 3
Submission Evaluation
The submitted information indicates that the tested solvent-
cutback type rust-preventive product was carcinogenic to the skin
of male C3H/HeJ mice. In general, it is not necessarily sur-
prising that a product containing approximately 90% Stoddard
solvent (a refined petroleum distillate with a typical boiling
range of approximately 300-400°F) is carcinogenic considering the
increasing body of evidence which indicates that most (if not
all) petroleum derivatives may possess some degree of oncogenic
or co-oncogenic potential. A complete copy of the final report,
including experimental protocol and data, is needed in order to
evaluate the reported oncogenicity findings properly.
Current Production and Use
Although Exxon Company, U.S.A. did not provide any information on
the production volume or specific use(s) of the tested product,
the company did provide the following information with regard to
one component of the tested mixture:
"As a result of Exxon's ongoing program of quality and per-
formance evaluation of its products, one of the components
[2-butoxy-ethanol] in the product tested has been eliminated
from the formulation. This action was taken independently of
the mouse skin painting study. Accordingly, since early in
1984, the specific product tested by skin painting is no
longer being manufactured by Exxon."
Comments/Recommendations
Exxon Company, U.S.A. reported that it would "advise customers of
record for this product of the results of the skin painting study
and will send them a revised Material Safety Data Sheet with re-
commended precautions."
EPA's Office of Toxic Substances (OTS) has received and evaluated
other TSCA Section 8(e) and "For Your Information" (FYI) submis-
sions on 2-butoxyethanol, Stoddard solvent, and catalytic-cracked
clarified oil. The Risk Management Branch (RMB/ECAD/OTS) has
been evaluating available toxicologic and exposure information on
2-butoxyethanol and catalytic-cracked clarified oil.
a)
The Chemical Screening Branch (CSB/ECAD/OTS/OPTS) will
request Exxon Company, U.S.A. to provide to the Agency a
complete copy of the final report (including the experi-
mental protocol and data) from the chronic mouse skin-
painting study cited in the submission. Exxon will be
asked also to provide the actual product names of the
tested and new formulations.
177
-------
8EHQ-0584-05l7
Page 3 of 3
In view of the Agency's general interest in corporate
actions that are taken on a voluntary basis in response
to chemical toxicity and/or exposure information, the
Chemical Screening Branch will request Exxon Company,
U.S.A. to describe the nature of all other studies that
the company has conducted, is conducting, or plans to
conduct that are designed to define the toxicity of or
the exposure to the tested formulation, the new formula-
tion (i.e., the one without 2-butoxyethanol) and/or the
individual components of those products. In addition,
Exxon will be asked to describe the actions it has taken
to notify Exxon workers and customers of the new formula-
tion about the reported oncogenicity findings.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment.
c)
The Chemical Screening Branch will send copies of this
status report to OSHA, NIOSH, CPSC, NTP, OW/EPA, OAR/EPA,
OSWER/EPA, ORO/EPA, and RMB/ECAO/OTS. Copies of this
status report will also be sent to the TSCA Assistance
Office (TAO/OTS/OPTS) for further distribution.
178
-------
UNITED 5T A TES ENV IRONMENTAL PROTECTION AGENCY
DATE;
~ 181984
8EHQ-0584-0518 S
Page I of 3
IUIJEC:T, Sta tus Report *
8EHQ-0584-0518 S
App=oved
vk- 1tqjt1
flOM,Justine Welch SChaefV~~ction Head
Chemical Risk Ident~~jf~tion Section/CSB
T~Fran~ D. Kover, Branch Chief
Chemlcal Screening Branch/ECAD/OTS/OPTS
Revision
Needed
Note: The submitting company has claimed its name and the use(s)
of the tested material as TSCA Confidential Business Informati.on.
The Information Management Division (IMD/OTS/OPTS) has requested
the submitting company to substantiate all of its confidentiality
claims.
Submission Description
The submitting company provided summarized preliminary results
from several in vitro genotoxicity studies of a product that is
identified by the submitter as "a proprietary mixture of epoxy
resins marketed under the trade name of EPON 815 (CAS No. 29407-
84-9)." According to the submitteF, EPON 815 produced "a posi-
tive response with and without [metabol}c] activation in the Ames
test, the Mouse Lymphoma test and the Sister Chromatid Exchange
tes t. " [See NOIE on Page 3 of this status report]
Submission Evaluation
Although the submitted information indicates that EPON 815 does
possess some degree of in vitro genotoxic activity, complete
copies of the final reports (including the actual experimental
protocols and data) from all of the cited studies are needed in
order for EPA to evaluate the reported findings.
Current production and Use
Although the submi"tting company reported that its use of EPON 815
was confidential, the submission did not contain any information
concerning the submitter's intended or actual use(s) of EPON 815.
It should be noted that neither EPON 815 nor CAS No. 29407-84-9
were located during a review of the non-confidential portion of
the TSCA Inventory. According to a publicly available on-line
computerized data base (Chemical Abstacts), EPON 815 (CAS No.
29407-84-9.) is a polymer comprised of bisphenol A (CAS No. 80-05-
7), epichlorohydrin (CAS No. 106-89-8), and butoxymethyloxirane
(CAS No. 2426-08-6). [See NOTE on Page 3 of this status report]
*NOTE: This status reco=t is the result of a prelirnina:y
staff evaluation of i~forIT.ation subrnittec to EPA. Sta~e~en~s
mace herein are no~ to be regarded as e~?ressir.g final
A~ency policy or intent wi~h r~s?ect to t~is .?articular
chemical. .~v review of the status report should take into
consideration-the fact that it may be based on incomolete
information. 179 - ..
E~' ~O". 11:1>006 1..1:". ~"I
-------
8EI-IQ-0584-05l8 S
Page 2 of 3
Comments/Recommendations
The submitting company stated that it had notified the supplier
of EPON 815, the Occupational Safety and Health Administration
(OSHA), the National Institute for Occupational Safety and Health
(NIOSH), and the National Cancer Institute (NCI) about the repor-
ted genotoxicity findings. The submitting company also stated
that, upon receipt, copies of the final reports from the cited
genotoxicity studies and "any significant new information" will
be sent to EPA.
Although a positive in vitro genotoxicity test result, when con-
sidered alone, may not be sufficient to offer reasonable support
for a conclusion of substantial risk, the Agency believes that
such results are of value in assessing possible risks posed by
chemicals to health and/or the environment. EPA also believes
that positive genotoxicity test results in combination with ad-
ditional information (e.g., knowledge of potential exposure to
or high production of the chemical substance or mixture), would
suggest, in many cases, the need to conduct additional studies.
The results of such studies should be considered also for possi-
ble submission to the Agency under Section 8(e) of TSCA.
It should be noted that EPA's Office of Toxic Substances (OTS)
has received and evaluated TSCA Section 8(e) and/or "For Your
Information" submissions containing information on bisphenol A,
epichlorohydrin, butoxymethyloxirane and other EPON resins. The
Chemical Screening Branch (CSB/ECAD/OTS) has prepared a Chemical
Hazard Information Profile (CHIP) on bisphenol Ai the Test Rules
Development Branch (TRDB/ECAD/OTS) is reviewing toxicity and ex-
posure information on bisphenol A, epichlorohydrin, and butoxy-
methyloxiranei and the Risk Management Branch (RMB/ECAD/OTS) is
reviewing toxicity and exposure information on epichlorohydrin
and butoxymethyloxirane.
a)
The Chemical Screening Branch will ask the submitter to
ensure that EPA receives complete copies of the final
reports (including the actual test protocols and data)
from all studies cited in the submission. In addition,
the submitting company will be requested to describe its
actual or intended use(s) of EPON 815.
In view of the Agency's general interest in corporate
actions that are taken on a voluntary basis in response
to chemical toxicity and/or exposure information, the
Chemical Screening Branch will request the submitting
company to describe all other studies that it has con-
ducted, is conducting, or plans to conduct that are
designed to further define the toxicity of and/or the
exposure to EPON 815 and any of its components. In ad-
dition, the submitting company will be requested to de-
scribe the actions that it has taken to 1) notify its
workers about the genotoxic activity reported for EPON
815 and 2) reduce and/or eliminate exposure to EPON 815
or its constituents.
180
-------
8EHQ-0584-0518 S
Page 3 of 3
b)
The Chemical Screening Branch will review the submitted
information in order to determine the need for further
OTS assessment of EPON 815.
c)
The Chemical Screening Branch will send copies of this
status report to OSHA, NIOSH, CPSC, FDA, NTP, OW/EPA,
OSWER/EPA, OAR/EPA, ORD/EPA, IMD/OTS, TRDB/ECAD and
RMB/ECAD. Copies of this status report will also be
sent to the TSCA Assistance Office (TAO/OTS/OPTS/EPA)
for further distribution.
NOTE:
In a supplemental submission (8EHQ-0684-0518 S Supplement),
the Shell Oil Company provided the following information:
"EPON Resin 815 is a mixture of about 86.5% wt. of epoxy
resin (CAS No. 25068-38-6) and about 13% wt. of n-butyl
glycidyl ether (n-BGE) (CAS No. 2426-08-6) [**]. Since
it is a mixture, the CAS No. 29407-84-9 provided by [the
submitting company] is incorrect; that CAS No. refers to
a polymer of the resin and n-BGE. Shell does not manu-
facture, process, or sell the product corresponding to
that CAS No. In EPON Resin 815, the resin and n-BGE
have not reacted. EPON Resin 815 has been a commercial
Shell-resin for about 30 years. It is used in many ap-
plications which require a lower viscosity than that of
the base epoxy resin; n-BGE is a reactive diluent used
to reduce the viscosity of the base resin. EPON Resin
815 is used directly by some [Shell] customers and is
formulated into proprietary products by others. In all
cases, it is used in conjunction with other products
such as amines, anhydrides, Lewis acids, fillers, and/or
reinforcements."
In addition, the Shell Oil Company stated that in light of
the known in vitro genotoxic activity of n-BGE, it is not
surprising-nthat epoxy resins diluted with n-BGE produce an
effect similar to n-BGE itself."
[**] butoxymethyloxirane
181
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0584-05l9
Page 1 of 4
DATt:
JLl2
9J4
SuaJ£tTI
Status Report *
8EHQ-0584-0519
App=oved tJX-
Revision
Needed
7/}/~
I
'IOMI
Justine Welch SChaef~'~ction Head
Chemical Risk Identi~ation SectionjCSB
TOI
Frank D. Kover, Branch Chief
Chemical Screening BranchjECADjOTSjOPTS
Submission Description
The 3M Company provided summarized results from several toxicity
studies conducted with a 3M research chemical and a commercial
chemical that 3M processes. According to 3M, the commercial
chemical, which is "purchased from American Hoechst under the
trade name Pina Sensitizer KF 501 #28296", is 2,21-[(2-carboxy-p-
phenylene)bis(iminovinylene)]bis[3-ethyl]-2-thiazolium diiodide
(CAS No. 20328-87-4). 3M reported that the research chemical,
which is the triethylamine salt of the commercially available
chemical, is the subject of ? TSCA Section 5 Premanufacture
Notification (PMN No. P84-688) currently under EPA review.
With regard to the toxicity of the PMN chemical, 3M provided the
following information:
"Eye Irritation Test - albino rabbits. Forty milligrams of
PMN substance were applied to one eye of each of six rabbits.
When the investigator returned to check the I-hour response,
all six rabbits were dead. Assuming a two to three kg body
weight, the delivered dose was approximately 13-20 mgjkg.
Dosing two males and two females at 5 mgjkg resulted in one
male and one female death within fifteen minutes. Death was
preceded by respiratory depression, prostration and mild
tremors. Survivors had miosis. Dosing at 1 mgjkg did not
result in death.
"Acute Oral Toxicity Test - rats. Five female and five male
rats were dosed with 2.5 gjkg of PMN substance. Three per
sex died. Symptoms included fasiculations and tremors.
"Skin Irritation Test - albino rabbits, Draize method. PMN
substance was minimally irritating after placement of 0.5 g
on the skin under semi-occlusion.
-NOTE: T~is status reDort is the result of a Drelirnina=v
staff evaluation of i~formation submitt~c to EPA. State;'e~ts
mace herein are no~ to be re~arded as ex~ressir.o final
Agency policy or i~tent with.r~s?e~t~o ~~is ?a~ticular
chemical. .~y review of the status report should tak~ into
~onsideration the iact that it may be based on incomplete
inforrna ticn. 182
E~' '0"'18 U:::I)ooC I"C:Y. ..,..
-------
8EHQ-0584-0519
Page 2 of 4
"r-licrobial Mutagenicity Assay - Salmonella typhimurium (Ames
Test). No toxicity or mutagenicity was noted with and with-
out metabolic activation."
3M provided the following information with regard to the toxicity
of Pina Sensitizer KF 501:
"Eye Irritation/Toxicity Test - albino rabbits. Three male
and three female albino rabbits were dosed with 27 mg of KF
501 placed in one eye each. All three males and two females
died within 15 minutes. Death was preceded by respiratory
depression, prostration and mild tremors."
Submission Evaluation
It is not necessarily surprising that Pina Sensitizer KF 501 and
its triethylamine salt (PMN chemical) can act qualitatively the
same in terms of toxicity. The rapid lethal toxicity in albino
rabbits that occurred following ocular/conjunctival administration
of either chemical appears to be real, especially considering the
fact that 1) the rapid lethality of the Pr-IN chemical was found to
be reproducible and dose-related and 2) the deaths of the animals
exposed to either chemical were "preceded by respiratory depres-
sion, prostration, and mild tremors." It should be noted that it
is unusual to see such a large disparity between the lethal dose
administered by the oral (gavage) and ocular routes (the oral
LD50 for the PMN chemical appears to be approximately 2 g/kg; in
the eye the LD50 for the pr1N chemi cal is about 5 mg/kg). The
LDIOO via the ocular route is estimated to be 13-20 mg/kg for the
PMN chemical and approximately 27 mg/kg for the commercial
chemical.
While the negative irritancy and mutagenicity findings reported
for the PMN chemical are of interest in their own right, they
shed little light on the lethality observed in rabbits. The lack
of difference in the Ames test with and without activation does
not rule out the possibility of a first-pass detoxification by
the liver in rats following oral administration.
The possibility exists that absorption could occur also via the
oral or nasal mucous membranes. In addition, it is possible that
enhanced dermal absorption could occur through the action of sol-
vents or other agents that may damage skin.
Current Production and Use
The commercial chemical substance (Pina Sensitizer KF 501) was
not located during a review of the non-confidential portion of
the TSCA Inventory. In its submission, 3M stated that 3M uses
Pina Sensitizer KF 501 "in very small quantities as a dye com-
ponent for a specialized graphic arts film." In addition, 3M
provided the following worker exposure information:
183
-------
8EHQ-0584-0519
Page 3 of 4
"At present no more than 153M workers are involved in pro-
cessing the subject chemical in both powder and solution form
and handling dried coated film. To date less than 1.0 kg of
[KF 501] has been handled in the plant. Hygienic handling
procedures and precautions have been reviewed and augmented
as follows:
a.
In addition to disposable impervious gloves and cover-
alls, powdered form handlers who make up the solution
for coating will wear air-line continous flow helmet
respirators rather than half-mask dust respirators,
safety goggles rather than safety glasses and will
continue to use filtered local exhaust ventilation.
b.
Solution handlers, who handle the 0.33% dye solution in
methanol, will wear safety goggles instead of safety
glasses, and continue to wear gloves (to be disposed
immediately after use) and use filtered local exhaust.
c.
Coater operators who may come into contact with the
coating solution which contains 0.18 mg/g of emulsion
will wear safety glasses and gloves.
"[3M does] not believe persons handling [the] dry coated film
product are at risk. The coating on the film is composed of
only 0.01% of the ~ubstance which is equivalent to a coating
weight of 8.0 mg/m. The dye is not expected to leach during
normal contact. [3M] has done extracti on tests to veri fy
this. When extracted in 0.9% saline buffered at pH 7.3, no
dye was detected at a delection limit of 1.0 ~g/ml. The
amount which could have been extracted was 13 .ug/ml. II
Although the 3r1 Company I s Section 8 (e) s ubmissi on did not contain
any information concerning 3M's planned production volumes or use
of the PMN chemical, PMN No. P84-688 stated that the PMN chemical
would be produced in quantities of 4-8 kg Fer year and used "as a
sensitizing dye in lithographic plates."
Comments/Recommendations
In addition to the previously mentioned safe handling changes, 3M
reported that the company plans to conduct addi~ional toxicologic
studies on the commercial and PMN chemicals. Specifically, 3M
stated that the planned studies would involve 1) "lower dosing in
the acute oral toxicity test depending on the availability of the
test [Pr-W] compound", 2) "acute dermal toxicity evaluation of the
0.33% dye solution in methanol with both the [PMN compound and KF
501]", and 3) "ocular toxicity of film developer containing dye."
In addition, 3M stated that the toxicity findings for the PMN
compound were reported previously to EPA's Chemical Control
Division (CCD/OTS/OPTS). 3M also stated that American Hoechst
was notified about the toxicity of Pina Sensitizer KF 501 and
would communicate further the need for safe handling.
184
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8EHQ-0584-0519
Page 4 of 4
a)
The Chemical Screening Branch (CSB/ECAD/OTS/OPTS) will
request the 3M Company to provide complete copies of the
final reports (including the experimental protocols and
data) from all of the performed and planned studies on
Pina Sensitizer KF 501 that were cited in the company's
Section 8(e) submission. (The Chemical Control Division
will be requesting the 3M Company to provide additjonal
information concerning the PMN substance).
In light of EPA's general interest in company actions
that are taken on a voluntary basis in response to chem-
ical toxicity and/or exposure information, the Chemical
Screening Branch will ask American Hoechst to describe
the actions that it has taken to 1) warn workers and
others, and 2) reduce and/or eliminate exposure to Pina
Sensitizer KF 501. American Hoechst will also be asked
to describe the nature of all other studies that it has
conducted, is conducting, or plans to conduct that are
designed to define the toxicity of and/or the exposure
to Pina Sensitizer KF 501.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of Pina Sensitizer KF 501.
c)
The Chemical Screening Branch will send copies of this
status report to OSHA, NIOSH, CPSC, NTP, FDA, OSWER/EPA,
OW/EPA, OAR/EPA, ORD/EPA, CCD/OTS and IMD/EPA. Copies
of this report will also be sent to the TSCA Assistance
Office (TAO/OTS/OPTS) for further distribution.
185
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UNITED STATES ENY IRONMEN1AL PROTECTION AGENCY
DA1£:
JJ. I I 004
8EHQ-0684-0520
Page 1 of 3
IUaJttT, Stat us Report *
8EHQ-0684-0520
Approved ~
Revision
Needed
'7/1 t--'
,
'IOM, James F. Darr, Acting Section Head8t/J/
Chemical Risk Identification Section/CSB
T~ Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The CIBA-GEIGY Corporation provided a copy of the final report
from a 28-day rat oral toxicity study of 2-methyl-l-[(4-methyl-
thio}phenyl]-2-(4-morpholinyl}-1-propanone (Irgacure@ 907; CAS
No. 71868-10-5). CIBA-GEIGY presented the following information
with regard to the results of the performed study:
"The test material, Irgacure@ 907. was administered daily by
gavage [to groups of 5 male/5 female rats] at dose levels of
0, .30, 100, and 300 .mg/kg of body-weight for 28 days. The ob-
servations of greatest concern toxicologically were seen at
the high dose level only (300 mg/kg/day) and consisted of
pale/opaque eyes (6 of 10 animals) and lameness of hind legs
(8 to 10 animals). As clarified in oral dicussions with the
investigators, the notation of "opaque eyes" indicates likely
corneal opacity and "lameness of hind legs" is indicative of
transient paralysis of the hrnd legs. As noted. above, these
effects were observed only at the highest dose (a level that
caused the death of 3 of 10 rats) when administered by a
route which has little relevance to the human experience."
Submission Evaluation
Although the reported' "hind limb lameness" suggests a neurotoxic
action, the final report does not note the intensity, time of
onset, or duration (other than the use of the term "transient")
of the' observed paralysis. It is apparent that the study did not
include any histopathologic examination of the nervous system.
Although the lack of such an examination is quite common in clas-
sical sub-acute toxicity studies, a thorough examination of the
nervous system in the case of the 28-day study of Irgacure@ 907
could have yielded information important for understanding the
apparent neurotoxic activity of the chemical.
-NOTE: T~is status reDo~t is the resu2t of a Drelimina~v
staff evaluation of i~formation-subrnitted to EPA. State;'e~ts
mace herein are nOt to be recrarded as ex~ressir.o final
Ase~cy policy or int~nt with~res?ect to t~is particular
chemical. .~y review of the status report should take into
consideration ~he iact tha~ it may be based on incomplete
in forma ti on .
186
'E~" "QR.. 1J:t)o1 "":". ~,..
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8EHQ-0684-0520
Page 2 of 3
Although it is known that certain chemicals when administered via
non-ocular routes can produce corneal opacities and/or other de-
leterious effects in the eyes, such findings are not common.
In addition to the transient hind limb paralysis in 8/10 rats,
corneal opacity in 6/10 rats, and death of 3/10 rats, the animals
in the 300 mg/kg group exhibited salivation, diarrhea, ruffled
fur, hair loss, and emaciation; these signs were not observed in
the animals in the lower dose groups. In addition, there was a
significant and dose-dependent mean body weight loss in both male
and female rats in the 100 and 300 mg/kg dose groups, and a dose-
dependent decrease in mean food consumption for males in the 100
and 300 mg/kg dose groups and for females in the 30, 100, and 300
mg/kg dose groups. Metabolic and hematologic disturbances were
also observed in males and females in the 300 mg/kg dose group.
With regard to the submitter's statement that the oral route of
exposure used in the 28-day study of Irgacure@ 907 "has little
relevance to the human experience," it should be noted that the
normal body clearance mechanisms for inhaled materials such as
dusts or mists can and in many cases do involve swallowing.
Current Production and Use
The CIBA-GEIGY Corporation reported that Irgacure@ 907 "was the
subject of a [TSCA Section 5] Premanufacture Notification, PMN
No. 84-35, for which a Notice of Commencement (of importation)
was submitted to EPA on February 22, 1984." CIBA-GEIGYalso
reported that Irgacure@ 907 "is in a very early stage of com-
mercialization" and "only limited quantities have thus far been
distributed." With regard to the uses of and potential exposure
to Irgacure@ 907, CIBA-GEIGY presented the following information:
"Irgacure@ 907 is used as a high extinction photoinitiator in
UV curable inks and coatings. It is added to pigment concen-
trates or to monomer/oligomers in such quantitites that the
use level is between 0.5 to 5.0% based on finished ink or
coating. In view of the nature of some of the other coating
ingredients, workers are likely to be wearing gloves and res-
pirators or dust masks, limiting actual exposure. Once incor-
porated into the cured ink or coating, exposure to Irgacure@
907 is essentially precluded."
Comments/Recommendations
CIBA-GEIGY reported that in response to the observed toxicity it
had 1) revised the Irgacure@ 907 label and Material Safety Data
Sheet (MSDS) and 2) noti fi ed workers and customers. (Copies of
the customer notification letters and revised Irgacure@ 907 MSDS
and product label were provided in the submission.)
187
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8EHQ-0684-0520
Page 3 of 3
a)
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity or exposure information, the Chemical Screening
Branch (CSB/ECAD/OTS/OPTS) will request the CIBA-GEIGY
Corporation to describe the nature of all other studies
that the company is conducting or plans to conduct that
are designed to define the toxicity of and/or exposure to
Irgacure@ 907.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of Irgacure@ 907.
c)
The Chemical Screening Branch will send copies of this
status report to OSHA, NIOSH, FDA, CPSC, NTP, OSWER/EPA,
OW/EPA, OAR/EPA, ORD/EPA, CCD/OTS and IMD/OTS. Copies of
the report will also be provided to the TSCA Assistance
Office (TAO/OTS/OPTS) for further distribution.
188
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DATE:
8218
UNiTED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0784-0S21 S
Page 1 of 6
*
SUIJEC:TI Status Report 8EHQ-0784-0S2l S
App:oved
1»- sf»ftf
James F. Darr, Acting Section Hea~ 1'. [i;,
-------
8EHQ-0784-0521 S
Page 2 of 6
"...PCBs have been found to be present in the pump oil used
at the facility and in trichloroethylene solvent still bot-
toms generated by the facility's solvent distillation unit.
In investigating this situation, the company has discovered
that waste pump oil has been sold to oil companies and others
for recycling or burning as fuel, and that the solvent still
bottoms have been shipped to Chemical Waste Management in
EmelIe, Alabama for land disposal. In addition, the pumps at
the facility are vented to the atmosphere, and preliminary
test results have shown PCBs to be present in the exhaust.
Preliminary results have also indicated that PCBs are present
on the roof and in soi1 outside the facility."
According to the submitted information, PCBs were also detected
in a number of drums located in Hebron, Ohio.
Production and Use of PCBs
Polychlorinated biphenyls (PCBs; CAS No. 1336-36-3) are members
of a broad family of organic chemicals known as chlorinated hy-
drocarbons. PCBs have heavy oil-like consistencies and weigh
approximately 10-12 pounds per gallon. PCBs are characterized by
a high degree of chemical stability, low solubility in water,
high solubility in fat, low flammability. low electrical conduc-
tivity, and high boiling points. These physical/chemical proper-
ties have made PCBs commercially attractive.
Although PCBs can be produced naturally in the environment,
almost all PCBs in existence today have been manufactured syn-
thetically. The primary uses of PCBs were, and continue to be,
electical transformer cooling liquids and capacitor dielectric
fluids. Most of the PCBs marketed in the U.S. 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 carbon less copy paper;
plastizers in paints, adhesives, and caulking compounds; fillers
in investment casting wax; and as dust control agents, sealants,
and coatings on roads.
Submission Evaluation
The very characteristics of PCBs that make them commercially
attractive also make their environmental and health effects of
significant concern. Once released into the environment, the
more highly chlorinated PCBs decompose very slowly over a period
of several decades. Due to this chemical stability, PCBs remain
in the environment and can be taken up by organisms and accumu-
lated in fatty tissues. In man, PCBs can enter the body via the
lungs, gastrointestinal tract and skin; circulate throughout the
body; and be stored in adipose tissue.
190
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8EHQ-0784-0521 S
Page 3 of 6
PCBs can be hazardous to health at extremely low levels; animal
studies have shown that PCBs can cause toxic effects in many spe-
cies at doses in the low parts per million (ppm) range. In well
documented tests with laboratory animals, PCBs have been shown to
cause reproductive failures, gastric disorders, skin lesions,
tumors, and developmental toxicity. The limited epidemiological
data which are available indicate that the animal studies are
predictive of potential adverse effects of PCBs on human health.
Legislative and Regulatory Actions on PCBs
A report by the President's Council on Environmental Quality
(CEQ) in May of 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 pas-
sage of TSCA, EPA could only regulate facilities that discharged
PCBs into navigable waterways. On February 2, 1977, the Agency
promulgated a final rule (42 FR 6532) under Section 307(a) of the
Federal Water Pollution Control Act (FWPCA) banning the discharge
of PCBs into waterways by electrical transformer and capacitor
manufacturers.
When the Toxic Substances Control Act was passed in 1976, there
was widespread concern about the potential adverse effects of
PCBs on the environment and human health. Congress responded to
this problem by designating PCBs for regulation in Section 6(e)
of TSCA. Specifically, the provisions of Section 6(e):
o prohibit the use of PCBs after January 1, 1978;
o prohibit the manufacture of PCBs after January 1, 1979;
o prohibit PCB processing and commercial distribution after
July 1, 1979;
o create two exceptions under which EPA may, by rule, allow
the use of PCBs to continue by finding that:
1) the use of PCBs is in a "totally enclosed" manner, and
2) the activity "will not result in an unreasonble risk of
injury to health or the environment" (for uses of PCBs
in other than a "totally enclosed" manner); and
o provide for the adequate marking and disposal of PCBs still
in use.
TSCA Section 6(e)(3)(B) provides further that the Administrator
may, by rule, grant an exemption from the general ban on the man-
ufacture, processing and distribution in commerce of PCBs upon
finding that an unreasonable risk of exposure is not present and
that good faith efforts have been made to develop substitutes for
the PCBs.
191
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8EHQ-0784-0521 S
Page 4 of 6
Since the passage of TSCA, EPA has implemented the Section 6(e)
provisions by phased rule making:
On February 17, 1978, EPA promulgated the PCB Marking and
Disposal Rule (43 FR 7150) that 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, the Agency promulgated the PCBs Manufacturing,
Processing, Distribution in Commerce, and Use Prohibitions (PCB
Ban Rule; 44 FR 31514). In addition to implementing the major
provisions of Section 6(e) of TSCA, this rule:
o established a regulatory cutoff of 50 ppm for PCBs;
o authorized the use of PCB-containing electrical equipment by
finding such uses to be "totally enclosed;"
o authorized eleven other miscellaneous uses which EPA found
would not present an unreasonable risk of injury to health or
the environment; and
o amended the PCB Marking and Disposal Rule.
In 1980, the Environmental Defense Fund, Inc. (EDF) sucessfully
challenged EPA's 50 ppm regulatory cutoff and the finding that
the use of PCBs in electrical equipment was "totally enclosed."
Since then, EPA has promulgated court ordered rulemaking in order
to adress the aspects of the PCB Ban Rule overturned in EDF vs.
EPA.
On August 25, 1982, EPA promulgated the final PCB Electrical
Use Rule (47 FR 37342) amending the portions of the original
PCB Ban Rule dealing with electrical equipment. This rule
authorized the use of PCBs in eight categories of electrical
equipment in accordance with use and servicing restrictions
specified for each category. The use authority for the eight
categories is not based upon a finding that the activities are
"totally enclosed." Rather, EPA found that these uses would
not present an unreasonable risk. The PCB Electrical Use Rule
did stipulate that electrical equipment containing PCBs which
may pose an unreasonable risk of exposure to food or animal
feed are not allowed after 1988.
The EDF vs. EPA court decision invalidated the 50 ppm cutoff for
regulation of PCBs. Therefore, EPA promulgated two rules to deal
with PCBs at concentrations of less than 50 ppm (primarily PCBs
that are produced as undesired byproducts of other chemical pro-
cesses).
On October 21, 1982, EPA promulgated the Closed and Controlled
Waste Manufacturing Rule (47 FR 46980). Under this rule, a
manufacturing process may be excluded from regulation under
Section 6(e) of TSCA if the process meets the criteria for:
192
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8EHQ-0784-0521 S
Page 5 of 6
o "closed manufacturing processes" (i.e., those processes
that produce PCBs in concentrations below limits of quanti-
tat ion (LOQ) for specified media, such as waste streams,
ambient air, effluent water and products); or
o "controlled waste manufacturing processes" (i.e., those
that produce PCBs in the waste stream above the LOQ but
concentrations below the LOQ in all other media).
On July 10, 1984, EPA promulgated the Uncontrolled PCBs Rule
(49 FR 28173) which excluded from the general ban those manu-
facturing processes that inadvertantly produce PCBs below an
annual average of 25 ppm, not exceeding a maximum of 50 ppm at
any time. These manufacturing processes are subject to other
criteria and disposal requirements specified in the rule.
On July 10, 1984, EPA also issued a Final Exemptions Rule (49 FR
28154) acting on 109 petitions for exemption from the prohibition
against the manufacture, processing and distribution in commerce
of PCBs. EPA granted 58 of these petitions and granted one other
petition in part after making the determination that the proposed
activities do not pose an unreasonable risk of injury to health
or the environment and that good faith efforts were made by the
petitioners to develop a PCB substitute. Of the 109 petitions,
49 were denied and one was dismissed. Action on an additional 49
petitions was deferred pending further EPA evaluation based on
the Uncontrolled PCBs Rule.
The July 10, 1984 rulemakings (49 FR 28183-28202) also authorized
the use of PCBs:
o in small quantities for research and development (R&D) (small
quantities for R&D is defined as PCBs that are 1) originally
packaged in hermetically sealed containers of a volume of no
more than 5 milliliters, and 2) used only for purposes of ex-
perimentation on or analysis of PCBs but not for research or
analysis for the purpose of developing a PCB product);
o in hydraulic and heat transfer fluids at concentrations below
50 ppm;
o in compressors and condensates of natural gas pipelines at
concentrations below 50 ppm;
o as a mounting medium;
o as a low fluorescence immersion oil; and
o as
an optical fluid.
The use authorizations listed above are based upon the Agency's
determination that such uses do not pose unreasonable risks to
human health or the environment.
193
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8EHQ-0784-052l S
Page 6 of 6
Comments/Recommendations
In its Section 8(e) notice, the Emhart Corporation stated that
"further investigations are being conducted to determine the
amount of wastes sent off site and their disposition so that
appropriate action can be taken to assure proper handling of
these wastes." The Emhart Corporation also reported that the
company "has contracted with outside environmental consultants
and assigned its environmental personnel to deal in a proper
manner with this situation."
The Office of Toxic Substances has received a number of TSCA
Section 8(e) and "For Your Information" (FYI) submissions that
have contained information on PCBs (8EHQ-0778-0209, 8EHQ-1079-
03r9, 8EHQ-0180-0330, 8EHQ-0780-0352, 8EHQ-098l-04l3, 8EHQ-0982-
0457, FYI-AX-0878-0006 and FYI-OTS-l08l-0l40).
a)
Immediately upon receipt of Emhart Corporation's Section
8(e) notice, the Chemical Screening Branch (CSB/ECAD/OTS)
sent copies of the 8(e) notice to EPA Region IV and V, the
Chemical Regulation Branch (CRB/EED/OTS/OPTS), the Office
of Water (OW/EPA) and to the Compliance Monitoring Staff
(CMS/OPTS) for appropriate followup action. The Chemical
Screening Branch will send copies of this status report to
NIOSH, OSHA, OW/EPA, OSWER/EPA, ORD/EPA, OAR/EPA, Region
IV and V, CRB/EED/OTS/OPTS, and CMS/OPTS. Copies of this
status report will also be sent to the TSCA Assistance
Office (TAO/OTS/OPTS) for further distribution.
194
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DA1£:
U218
UNITED STATES EHY IROHMENTAL PROTECTION AGENCY
8EHQ-0784-0522
Page 1 of 3
nOM, James F.
~hemical
App:oved ~
t:~ ~Revision
D~rr, Acti~g.Sec~ion Hea~ . Needed
R1Sk Ident1flcatlon Sectl n/CSB
8EHQ-0784-0522
e/~l/ff
, ,
SUIJEC:T, St at us Report *
TO,Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Witco Chemical Corporation provided the final reports from a
battery of in vitro genotoxicity studies that had been conducted
with a mixture of the following two chemical substances:
7-0xabicyclo[4.1.0Jheptane-3-carboxylic acid
7-oxabicyclo[4.1.0.]hept-3-ylmethyl ester
(CAS No. 2386-87-0); and
Phosphorous acid, isodecyl diphenyl ester
(CAS No. 26544-23-0).
According to the submitter, the tested mixture exhibited in vitro
genotoxic activity in the Ames Salmonella typhimurium (bacteria)
Assay, the Mouse Lymphoma Cell Forward Mutation Assay, and the
Chinese Hamster Ovary (CHO) Cell Sister Chromatid Exchange (SCE)
Assay.
Submission Evaluation
Although the s~bmitted final reports did not include the actual
experimental protocols for the performed studies, it does appear
that the tested mixture induced an increased revertant frequency
in Salmonella typhimurium strain TA 1535 in the presence of exo-
genous metabolic activation, induced an increased mutation fre-
quency in cultured mouse lymphoma cells both with and without
activation, and induced an increased number of Sister Chromatid
Exchanges (SCEs) in cultured CHO cells both with and without
activation.
-NOTE: T~is status reco:t is the result of a crelirnina:v
. ...
staff evaluation of i~fo~ation submitted to EPA. Sta~e~ents
made herein are no~ to be reoarded as ex~ressir.o final
Agency policy or i~tent with'res?ec~ to t~is particular
chemical. .~y review of the status repor~ should take into
consideration the fact tha~ it may be based on incomclet~
in forma tion. 195 .
E"A "0"'11 U:%)04 11111:"'. ,,'''I
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8EHQ-0784-0522
Page 2 of 3
Current Production and Use
A review of the production range (includes importation volumes)
statistics for CAS No. 2386-87-0, 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 TSCA Confidential Business Information (TSCA CBI) by
the manufacturer(s) and/or importer(s) and cannot be disclosed
(Section 14(a) of TSCA, U.S.C. 2613(a». The data submitted for
the TSCA Inventory, including the production range information,
are subject to the limitations contained in the TSCA Inventory
Reporting Regulations (40 CFR 710).
A review of the production range (includes importation volumes)
statistics for CAS No. 26544-23-0, which is also listed in the
initial TSCA Inventory, has shown that between 1.2 and 12 million
pounds were reported as produced/imported in 1977. This produc-
tion range information does not include any production/importa-
tion data claimed as TSCA CBI by the person(s) reporting for the
initial TSCA Inventory nor does it include any information that
would compromise TSCA CBI. All of the data submitted for the
TSCA Inventory, including production range information, are sub-
ject to the limitations contained in the TSCA Inventory Reporting
Regulations (40 CFR 710).
According to the submitter, the mixture is a "non-volatile, non-
distillable liquid" which is used at a concentration of "0.1 to
0.15% in polycarbonates as a color stabilizer." With regard to
possible exposure to the mixture, the submitter stated that:
"The only situation where exposure to the undiluted mixture
may occur is through accidental skin contact during manufac-
ture or during handling while being incorporated into poly-
carbonate resin. [The company believes] that any potential
health hazards would be well protected against by observing
commonly used industrial hygiene practices. This includes
wearing protective clothing, safety goggles and impervious
gloves. Any potential exposure to the general public from
the tested mixture is likely to be extremely small [because
the mixture] is used at low levels and is bound up in a non-
volatile, insoluble polycarbonate resin."
No further information concerning the use(s) of the individual
chemicals or the mixture itself was located by the Agency in any
of the secondary literature sources consulted.
Comments/Recommendations
In its submission, the Witco Chemical Corporation stated that it
was notifying its employees and customers about the reported in
vitro genotoxicity findings.
196
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8EHQ-0784-0522
Page 3 of 3
a)
The Chemical Screening Branch (CSB/ECAD/OTS/OPTS) will
request the Wit co Chemical Corporation to provide a com-
plete copy of the actual experimental protocol used for
each in vitro genotoxicity study that was cited in the
company's submission. In addition, Witco will be asked
to report the exact amount of each of the chemicals in
the tested mixture.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of the subject mixture or its components.
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, FDA, CPSC, NTP, OW/EPA,
OSWER/EPA, ORD/EPA and OAR/EPA. Copies of this status
report will also be sent to the TSCA Assistance Office
(TAO/OTS/OPTS) for further distribution.
197
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UNITED STATES EHYIRONMENTAL PROTECTION AGENCY
Page 1 of 4
DA1£:
u; 27 RW
App=oved ~ rPrllI
*
SUaJEC:T, Status Report 8EHQ-0884-0523 and
8EHQ-0884-0523 Supplement
'IOM, James F. Darr, Acting Section Head,~ 7: D.Vvv
Chemical Risk Identification Secti~n/CSB
Revision
Needed
TOI Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Velsicol Chemical Corporation provided complete copies of a
preliminary draft report (8EHQ-0884-0523) and final report (8EHQ-
0884-0523 Supplement) of a cohort mortality study of workers em-
ployed at Velsicol's Chattanooga, Tennessee facility between 1943
and 1982. The "Summary" section of the final report presented
the following information concerning the results of the study:
"The cohort of this historical prospective mortality study con-
sisted of 697 male employees at Velsicol Chemical Corporation's
chlorination plant in Chattanooga. A majority of the cohort
was potentially exposed to benzotrichloride [CAS No. 98-07-7],
benzyl chloride [~AS No. 100-44-7], benzoyl chloride [CAS No.
98-88-4], and other related chemicals. The mortality experience
of the cohort was observed from 1943 through 1982. Vital sta-
tus follow-up showed that 622 (89.24%) were alive, 47 (6.74%)
were deceased, and 28 (4.02%) were of unknown status as of 31
December 1982. Among those identified as deceased, death cer-
tificates were obtained for 44 (93.62%). Underlying causes of
death were coded according to the International Classification
of Diseases. Cause-specific mortality analyses were based on
the U.S. male population as comparison.
"For the cohort as a whole, no ~tatistically significant mor-
tality excess was d~tected. The overall Standardized Mortality
Ratio (SMR) was 100.3 and the SMR for all cancers combined was
121.6; neither was significa~tly different from the expected
value of 100, based on the U.S. male mortality experience.
Contrary to the finding reported by Sorahan et al (1983), no
death from cancer of the digestive system occurred among the
cohort. The respiratory cancer SMR for the Chattanooga cohort
as a whole was 246.3 (7 observed vs. 2.84 expected). The ex-
cess was of borderline statistical significance, the lower 95%
confidence limit being 98.9. Analysis by race showed that all
7 respiratory cancer deaths came from the white male employees,
with an SMR of 264.5, statistically signficant at the 0.05 le-
vel. The respiratory cancer mortality excess was higher among
-NOTE: T~is status repo~t is the result of a prelimina~v
st~ff evaluation of i~forIT.ation submitt~c to EPA. State;'ents
mace herein are no~ to be regarded as expressing final
Ase~cy policy or intent with respect to t~is particular
chemical. .;ny review of the status report should take into
consideration the iact that it mav be based on incomplete
informa tion. . .
198
£~~ 'O~"" IJ~ 'l1li1:\1. ..,tI
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8EHQ-0884-0523
8EHQ-0884-0523 Supplement
Page 2 of 4
employees in maintenance (SMR = 228.7) than among those in
operations or production (SMR = 178.2). The lung cancer mor-
tality excess among the laboratory employees was statistically
significant (SMR = 1292.5). However, this obseration should be
viewed with caution, since it was based on only two deaths.
Further analysis indicated that the respiratory cancer mortali-
ty excess was limited to white male employees with 15 or more
years of employment (SMR = 388.8, statistically significant).
Analysis by major chemical exposure showed that employees po-
tentially exposed to benzotrichloride, benzyl chloride and/or
benzoyl chloride experienced significantly increased risk of
respiratory cancer. However, it should be pointed out that the
majority of cohort was potentially exposed to all these three,
as well as to other chemicals present at the plant. The fin-
ding on respiratory cancer was consistent with those reported
by Sakaba et al (1976), Sakaba and Fukuda (1977), Sorahan et al
(1983), and Rockette and Arena (1983). For other causes of
death, the study did not suggest an increased risk for the
Chattanooga cohort.
"Major limitations of the study included the small study size
and the lack of smoking history, as well as other occupational
and environmental exposure information. Without smoking his-
tory information for the entire cohort, the contribution of
cigarette smoking to the observed respiratory cancer excess
could not be quantitatively evaluated. However, based on ani-
mal data as well as other epidemiological studies, together
with the internal consistency of analysis by length of employ-
ment, the data suggested an association between the chlorina-
tion process of toluene at the Chattanooga plant and an in-
creased risk of respiratory cancer...."
The following references were cited in the above summary:
Rockette and Arena (1983), Mortality Patterns of Workers in the
Niagra Plant. Report Submitted to Hooker Chemical Company
Sakabe et al (1976), Cancer Among Benzoyl Chloride Workers.
Ann NY Acad Sci 271, 67-70.
Sakabe and Fukuda (1977), An Updating Report on Cancer Among
Benzoyl Chloride Manufacturing Workers (letter). Ind. Health
15, 173-174
Sorahan et al (1983), A Mortality Study of Workers in a Factory
Manufacturing Chlorinated Toluenes. Ann Occup Hyg 27, 173-182
Submission Evaluation
The preliminary draft report and the final report of the cohort
mortality study have been transmitted to the Risk Management
Branch (RMB/ECAD/OTS) for inclusion into its ongoing review of
available toxicity/exposure data on chlorinated toluenes.
199
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8EHQ-0884-0523
8EHQ-0884-0523 Supplement
Page 3 of 4
Production and Use
A review of the production range (includes importation volumes)
statistics for the subject substances, which are listed in the
TSCA Inventory, has shown that the following amounts were re-
ported as produced/imported in 1977:
Chemical Name CAS Number Approximate Prod./lmport. Range
Benzoyl Chloride 98-88-4 10 million to 52 million pounds
Benzyl Chloride 100-44-7 52 million to 110 mi llion pounds
Benzotrichloride 98-07-7 10 million to 50 mi llion 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 TSCA Confidential Business Information (TSCA CBI). The
data submitted for the TSCA Inventory, including the production
range information, are subject to the limitations contained in
the TSCA Inventory Reporting Regulations (40 FR 710).
Benzoyl chloride is used as a chemic91 intermediate in the acyla-
tion of alcohols, phenols and amines, and in the manufacture of
benzoyl peroxide and certain 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 manu-
facture of synthetic dyes and other organic chemicals, including
some types of pesticides.
According to Velsicol, "the subject chemicals are produced and,
where used by Velsicol, used in a completely closed system except
during sampling, loading and unloading." In addition, Velsicol
reported that the results of an industrial hygiene survey had
shown that "during routine operations the levels of worker ex-
posure were below 1 ppm." Velsicol also reported, however, that
"in one case where a worker was repairing a leak in the benzoyl
chloride process, exposures reached 1 ppm."
Comments/Recommendations
Velsicol reported that the company has notified its own workers
and the National Institute for Occupational Safety and Health
(NIOSH) about the findings of the submitted cohort mortality
study. In addition, Velsicol reported that the company had "re-
commended that [the subject] chemicals "be handled as suspect
carcinogens and recommended the use of protective clothing and
respirators." Velsicol also reported that "in order to remove a
major source of potential exposure," the company had "renovated
the Quality Control Laboratory at the Chattanooga Plant" and that
the "renovation included upgrading of the air handling system,
ventilation and laboratory hoods." Finally, Velsicol reported
200
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8EHQ-0884-0523
8EHQ-0884-0523 Supplement
Page 4 of 4
that the company plans to notify its customers about the submit-
ted findings and plans to conduct further investigations in order
to obtain "a more definitive answer to the specific question of
whether long term exposure to the subject chemicals did result in
an increase of lung cancer."
The Office of Toxic Substances (OTS/OPTS/EPA) has received and
evaluated several TSCA Section 8(e) and "For Your Information"
(FYI) submissions that have presented toxicity/exposure data on
benzoyl chloride, benzyl chloride, and benzotrichloride, as well
as other chlorinated toluenes. In addition, Chemical Screening
Branch (CSB/ECAD/OTS) has prepared Chemical Hazard Information
Profiles (CHIPs) on benzoyl chloride, benzyl chloride, and
benzotrichloride.
a)
The Chemical Screening Branch will request the Velsicol
Chemical Corporation to keep EPA abreast of the results
of Velsicol's further investigations into the possible
relationship between long term human exposure to the
subject chemicals and lung cancer.
b)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, OAR/EPA, ORD/EPA, OPP/OPTS, and RMB/ECAD/OTS.
Copies of this status report will also be sent to the
TSCA Assistance Office (TAO/OTS/OPTS/EPA) for further
distribution.
201
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OA T£:
SEP
5- 1984
UNITED STATES ~HY IRONMENTAL PROTECTION AGENCY
8EHQ-0884-0524
Page 1 of 4
App:ovec! ~
8EHQ-0884-0524
r ~ /tit
SUaJ£C:T. Stat 11S Report *
'IOIi.Jame~ F. Darr, Acting Section Headr:: r. ~
ChemIcal Risk Identification Section/CSB
Revision
Needed
T Frank D. Kover, Branch Chief
~Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Union Carbide Cor~oration provided summarized results from a
sub-chronic rat inhalation study of gamma-methacryloxypropyltri-
methoxysilane (Silane A-174; CAS No. 2530-85-0). According to
Union Carbide, "the results of this study in rats indicate that
repeated exposure to moderately high concentrations of a respi-
rable aerosol of hydrolysis and condensation products derived
from an aqueous solution of Silane A-174 caused a chronic in-
flammatory reaction whi ch was locali zed to the larynx...." In
addition, Union Carbide provided the following information with
regard to the performed study:
"Fischer 344 ra~s were used in groups containing 18 males _and
18 females. Groups were exposed to the aerosol for 6 hours a
day, 5 days a week, for 14 weeks. The mean concentrations of
aerosol solids 10 which three groups were exposed were 244,
100 and 50 mg/m. The aerosol was generated-from a 15% aque-
ous solution of hydrolysis and condensation products of Silane
A-174, and the average mass median aerodynamic diameter was
1.6 microns and therefore the droplets were respirable. A
control group of animals, for comparative purposes, was ex-
posed to chamber air alone. Shortly after the final exposure
period, 10 male and 10 female rats from all aerosol-exposed
groups and the control group were sacrificed. The remaining
animals were kept for a 14-week post-exposure observation
period. Animals were obse~ved daily for signs of toxicity,
and weighed weekly during the exposure period. During the
post-exposure period, the rats were weighed weekly for the
first four weeks, and thereafter on alternate weeks. Addi-
tionally, food and water consumption were measured, analyses
performed, and various clinical chemistry and hematological
analyses performed. Immediately following sacrifice at the
ends of both the exposure periods and the post-exposure peri-
ods, animals were subjected to autopsy and a large variety of
tissues removed for examination by light microscopy."
-NOTE: T~is sta~us reco=t is the result of a creli~ina=v
staff evaluation of i~fo=mation subrnitt~d to EPA. State;ents
mace herein are no~ to be recrarded as ex~ressir.a final
Ase~~y policy or intent with-respect to t~is particular
chem~cal. .~y review of the status report should tak~ into
~~nslderation the iact that it may be based on incomplete
J.nf0rma tion.
202
I:~. "Olln. U~ IJlCV. ..",
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8EHQ-0884-0524
Page 2 of 4
"No deaths occurred during the study and, apart from a de-
crease in the rate of gain in bOdj weight during exposure of
the male rats exposed to 250 mgjm , there were no signs of
toxicity- No significant differences between controls and
aerosol-exposed animals were seen with respect to urinalysis,
hematology and clinical chemistry. The only histopathological
findings were treatment-related upper respiratory tract le-
sions in all three exposure groups. There was hyalinization
of the epithelial cells of the olfactory mucosa and, of most
biological significance, the presence of a granulomatous reac-
tion in the larynx. The granulomatous reaction was focal, of-
ten associated with formation of polyps projecting into the
lumen of the larynx, and was present with a similar incidence
and severity at all three exposure concentrations. Also, the
chronic inflammatory lesion was still present following a 14-
week post-exposure recovery period."
Union Carbide reported that "the scientists responsible for the
conduct of the study and for the interpretation of the test re-
sults believe that the production of the granulomatous reaction
was positively related to exposure to a respirable aerosol de-
rived from Silane A-174." In addition, Union Carbide stated that
"although certain aspects of the conduct of the study do not re-
flect in-use practices with Silane A-174, for example the use of
a more concentrated aqueous solution favoring polymerization and
therefore a foreign body reaction," Union Carbide considered it
appropriate to report the findings under Section 8(e) of TSCA
"because of the chronic inflammatory nature of the lesion and its
anatomical localization."
With regard to the interpretation of the practical significance
of the submitted findings, Union Carbide reported that "it is
relevant to note that there was an indication of a laryngeal
granulomatous reaction in a pilot study involving a 9-day ex-
posure to the aerosol, but no such laryngeaJ, pathology was ap-
parent following a 9-day exposure to the vapor from Silane A-
174." Union Carbide aiso stated that the findings from the pilot
study suggest that the hazard indicated by exposure to Silane A-
174 "is specific to a respirable aerosol and not a factor in
vapor exposure."
Finally, Union Carbide stated that the company "has no evidence
or knowledge of any untoward health effects associated with over
20 years of manufacture and marketing of Silane A-174, either of
a kind implied by the testing results or of any other kind."
Submission Evaluation
Although it is not necessarily suprising that Silane A-174 and
its hydrolysis products would be highly irritating to respiratory
tract tissue, it is important to note that 1) the granulomatous
lesions of the larynx, which were found in many cases to be as-
sociated with polyps, were observed in the animals exposed to all
Silane A-174 concentrations tested, and 2) the granulomatous
203
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8EHQ-0884-0524
Page 3 of 4
lesions were still present at the end of a 14-week post-exposure
observation period. It should also be noted that granulomatous
lesions of the larynx have been observed in humans as the result
of trauma associated with intratracheal intubation.
Further evaluation of the sub-chronic inhalation study findings
should be possible upon EPA's receipt of a complete copy of the
final report which should include a full copy of the experimental
protocols and data. In addition, the submitter should be asked
to provide a complete copy of the final report, including test
protocols and data, from the 9-day pilot inhalation study that
was cited in the submission. It would also be of interest to
know the pH of the test samples.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for CAS No. 2530-85-0, which is listed in the initial
TSCA Inventory, has shown that between 0 and 1000 pounds were re-
ported as produced/imported in 1977. This 1977 production range
information does not include any production/importation data that
was claimed as TSCA Confidential Business Information (TSCA CBI)
by the person(s) reporting for the TSCA Inventory, nor does it
include any information that would compromise TSCA CBI. All of
the data submitted for the TSCA Inventory, including production
range information, are subject to the limitations contained in
the TSCA Inventory Reporting Regulations (40 CFR 710).
Although Union Carbide did not provide any information concerning
its current production of Silane A-174, the company did provide
the following information with regard to the use of and potential
exposure to the chemical:
"Silane A-174 is used in industrial applications as a coupling
agent, principally in the manufacture of coated glass fiber
materials and objects, in which use the chemical loses its
identity and is converted into a matrix material. In a pilot
industrial hygiene st~dy at an actual use location, concentra-
tions up to 0.68 mg/m of total material (only part of which
was derived from Silane A-174) were found, which are seen. to
be an order of magnitude lower than the lowest level used in
the animal studies."
No further information concerning the production or use of the
subject chemical was located in the secondary literature sources
consulted by EPA.
Comments/Recommendations
In the cover letter to its submission, Union Carbide stated that
the company "intends to undertake further studies to define the
conditions necessary for development of the granulomatous lesion,
and, if necessary, to develop measures to protect employees from
potential respiratory tract injury resulting from exposure to
204
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8EHQ-0884-0524
Page 4 of 4
respirable aerosols derived from Silane A-l74." In addition,
Union Carbide stated that the company is "advising its employees
who are involved in the manufacture and handling of Silane A-l74,
its customers, and other producers" of the chemical about the re-
ported findings. Union Carbide also stated that upon completion
of the final report from the sub-chronic inhalation study, a copy
of that report will be sent to the Agency.
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will request
the Union Carbide Corporation to ensure that EPA receives
a complete copy of the final report (including the actual
experimental protocol(s) and data) from the sub-chronic
Silane A-l74 inhalation study that was cited in the sub-
mission. In addition, Union Carbide will be requested to
submit a complete copy of the final report (including the
actual experimental protcol(s) and data) from the 9-day
inhalation study with Silane A-l74 that was cited in the
initial submission.
b)
The Chemical Screening Branch will review the reported
information to determine the need for further OTS assess-
ment of the subject chemical substance.
c)
The Chemical Screening Branch will transmit copies of this
status report to NIOSH, OSHA, CPSC, NTP, OW/EPA, OAR/EPA,
OSWER/EPA, and ORD/EPA. Copies of this report will also
be sent to the TSCA Assistance Office (TAO/OTS/OPTS) for
further distribution.
205
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'UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
0101£:
SEP
5 1004
8EHQ-0884-0525
Page 1 of 2
SuaJ£CT. Stat us Report *
8EHQ-0884-0525
App:OVI""
~ :/tlif
'ICM. James F. Darr, Acting Section Head~~~
Chemical Risk Identification Section/CSB
Revision
Needed
TOI Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
On behalf of the U.S. producers of methylene chloride (CAS No.
75-09-2), the Halogenated Solvents Industry Alliance (HSIA) sub-
mitted summarized "preliminary, and as yet unverified" results
from a National Toxicology Program (NTP) bioassay of methylene
chloride which was administered via inhalation to male and female
F344 rats at doses of 0, 1000, 2000, or 4000 ppm and to male and
female B6C3Fl mice at doses of 0, 2000, or 4000 ppm. According
to the submitted information, the preliminary results of the bio-
assay (which is currently in the histopathology phase) "indicate
that methylene chloride induces 'a very high incidence of lung and
liver tumors in both sexes of mice."
Submission Evaluation
The submitted information has been transmitted to the Test Rules
Development Branch (TRDB/ECAD/OTS) and the Risk Management Branch
(RMB/ECAD/OTS) for inclusion in their ongoing review of available
toxicologic and exposure data on methylene chloride.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for methylene chloride (CAS No. 75-09-2), which is
listed in the initial TSCA Inventory, has shown that between 350
million and 1.4 billion pounds were reported as produced/imported
in 1977. This production range information does not include any
information claimed by the manufacturer(s) "and/or importer(s) as
TSCA Confidential Business Information (TSCA CBI) nor does it in-
clude any information that would compromise TSCA CBI. All data
submitted for the TSCA Inventory, including the production range
information, are subject to the limitations contained in the TSCA
Inventory Reporting Regulations (40 CFR 710).
According to secondary literature sources, the U.S. production of
methylene chloride was approximately 530 million pounds in 1983.
-NOTE: T~is status reDort is the result of a orelirnina:v
staff evaluation of i~fo~ation submitt~c to EPA. Sta~e;ents
mace herein are no~ to be regarded as expressing final
As~ncy policy or intent with res?ec~ to t~ii particular
chemical. .;nv review of the status reoort should take into
consideration-the iact that it may be based on incompleta
information -
206
~~.. '0""" 1J;!)-6 I"C"'. ~,.,
-------
8EHQ-0884-0525
Page 2 of 2
Methylene chloride has uses in paint removers; propellants for
aerosol sprays; blowing agents in foam; plastics processing; and
solvent degreasing and extraction procedures.
Comments/Recommendations
The Office of Toxic Substances (OTS) has received and evaluated
other TSCA Section 8(e) and "For Your Information" submissions
that have contained toxicologic and/or exposure information on
methylene chloride.
a)
The Chemical Screening Branch (CSB/ECAD/OTS/OPTS) will
receive (directly from NTP) a complete copy of the draft
technical report from the methylene chloride inhalation
study as soon as the report is formally released by NTP
for peer review by the Technical Report Peer Review Sub-
committee of NTP's Board of Scientific Counselors. Ac-
cording to NTP staff, the draft technical report will be
available in the spring of 1985.
b)
The Chemical Screening Branch will transmit a copy of
this status report to NIOSH, OSHA, CPSC, FDA, OW/EPA,
OSWER/EPA, OAR/EPA, ORD/EPA, TRDB/ECAD and RMB/ECAD.
A copy of this status report will also be sent to the
TSCA Assistance Office (TAO/OTS/OPTS/EPA) for further
distribution.
2Q7
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DAn;
SEPIO.
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-0384-0526
Page 1 of 3
5UaJ£CT, Status Report *
8EHQ-0884-0526
1\pp:oved
eM-
qi'''/itf -
~]1 Di/i Revision
nOM,James F. Darr, Acti ng Section Head . ~ Needed
Chemical Risk Identification Secti n/CSB
Tolran~ D. Kover, Branch Chief
Chemlcal Screening Branch/ECAD/OTS/OPTS
Submission Description
The Union Carbide Corporation provided summa~ized results from a
chronic mouse Skin application study of a mixture of unsaturated
aliphatic oils (C16-32). According to the submitter, there were
"a small number of [late developing] neoplasms at the site of
[recurrent] application of the test material...." Union Carbide
presented the following details concerning the performed study:
"Three groups, each containing 50 mice of the C3H/HeJ strain
were used. One group of mice had a 50% (v/v) solution of Ali-.
phatic Oils in acetone applied to the skin, the second received
acetone alone (negative control), and the third received 0.1%
methylcholanthrene in acetone (positive control). Each mouse
received 25~1 of solution on each treatment day. Applications
were made to the hair-clipped dorsal skin, three times a week
until death. Necropsy was performed on all animals dying and
on sacrificed moribund survivors. All animals have now died,
and histological confirmation of tumor types has been under-
taken. "
"In the group of 50 animals receiving Aliphatic Oils, three
animals each developed a squamous cell carcinoma at the site of
application of the test material. One of these animals also
had systemic lymphosarcoma. Additionally, a fourth animal with
lymphosarcoma had a metastatic deposit at the site of applica-
~ion of the test material. The relationship of the latter ef-
fect to treatment is uncertain. The first squamous cell car-
cinoma was diagnosed at 526 days (i.e., 75 weeks) from the
first application of Aliphatic Oils. With the acetone control
group, one mouse developed a subcutaneous fibrosarcoma in the
area of acetone application. A high incidence of squamous cell
carcinomas developed early in the group of mice treated with
methylcholanthrene."
-NOTE: T~is status reoort is the result of a prelirninarv
staff evaluation of i~fo~ation submitted to EPA. State;e~ts
made herein are nOt to be reaarded ~s ex~ressinc final
Ase~cy policy ~r intent with.respect to t~is ?articular
chemical. .~v review of the status reoor~ should take into
consideration-the tact that it mav be based on incom~'ete
informa tion. - . -
208
£~. 'OR. 1):1)0-4 '"1:"'. ..,..
-------
8EHQ-0884-0526
pag'e 2 of 3
"The incidence of malignant neoplasms was low, and their laten-
cy to detection long, following recurrent application of Ali-
phatic Oils to mouse skin.... Comparison of the incidence and
latency of these neoplasms with those developing in the methyl-
cholanthrene-treated animals would suggest that Aliphatic Oils
are of low potency with respect to dermal carcinogenic poten-
tial."
Submission Evaluation
The submitted information does indicate that the tested material
displays a weak carcinogenic activity toward the skin of C3H/HeJ
mice. The provided spectral analysis information shows that 3
types of double bonds are present in the mixture (i.e., pendant
methylene, terminal vinyl, and internal trans-vinylidene). It
should be noted that double bonds may react with certain func-
tional groups in key cellular macromolecules by Michael addition
and/or can undergo epoxidation through metabolism. Therefore,
the reported findings are consistent with the concept that double
bonds are "soft" electrophiles that can confer oncogenic activity
on an otherwise non-oncogenic molecule.
Current Production and Use
The Union Carbide Corporation provided the following information
concerning the use of and the potential for exposure to the test
material:
"The test substance is an oil that is intermediate in the
process of polymerizing ethylene by the low-pressure process.
Except for interrupting the continuous process by which poly-
ethylene is manufactured, the intermediates are not isolated
and hence did not qualify for reporting to the TSCA Inventory.
The stimulus for testing the material was from a concern to
understand any potential biological properties in the event
[the material was] to be isolated or released by either de-
liberately or inadvertently interrupting the process. Spectral
data indicate [that the aliphatic oils] are aliphatic hydro-
carbons, unsaturated with pendant methylene groups, terminal
vinyl groups, and (principally) internal trans-vinylidene un-
saturation - spectra consistent with being telomers of ethyl-
ene. They are predominantly in the C16-C32 range. The chem-
icals are neither isolated or used for any particular purpose.
...Union Carbide licenses the process for manufacturing poly-
ethylene...."
Comments/Recommendations
In its submission, Union Carbide reported that its licensees are
being notified about the submitted findings. In addition, Union
Carbide reported that "full details of the study will be made
available upon completion of the report and conclusion of the
Quality Assurance process." It was also reported that "no fur-
ther toxicological studies are anticipated with this material."
209
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8EHQ-0834-0526
Page 3 of 3
a) The Chemical Screening Branch (CSB/ECAD/OTS/OPTS) will ask
the Union Carbide Corporation to ensure that EPA receives,
immediately upon completion, a full copy of the final re-
port (including the actual experimental protocol(s) and
data) from the company's chronic mouse skin application
study of unsaturated aliphatic oil (C16-C32).
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further OTS
assessment of C16-C32 unsaturated aliphatic oil.
c) The Chemical Screening Branch will transmit copies of this
status report to NIOSH, OSHA, NTP, OW/EPA, OSWER, OAR/EPA,
and ORD/EPA. Copies of this status report will also be
provided to the TSCA Assistance Office (TAO/OTS/OPTS) for
further distribution.
210
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UNITED STATES ENYIRONMENTALPROTECTION AGENCY
DATE:
SEP
7 1004
8EHQ-0884-0527
Page 1 of 2
SUIJECT. Status Report *
App:-oved
Ci: 7\ Revision
flOI&. James F. Darr, Acting Section Head / ~Needed
Chemical Risk Identification Secti n/CSB
8EHQ-0884-0527
;7t<-
rfo/rtf
I I I
TO Frank D. Kover, Branch Chief
I Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
On behalf of its American members, the International Chlorinated
Paraffin Producers Testing Consortium submitted summarized pre-
liminary findings from a study of "C-l4/l7, 52% chlorinated,
chlorinated paraffin (CAS No. 63449-39-8)" administered in the
feed to pregnant rats "prior to and during gestation and during
lactation." According to the submitter, at the highest dose
tested (6250 ppm), "there was subcutaneous bleeding and death in
rat pups, but the darns apparently were not affected." .
The submitter reported that "exposure to humans under similar
circumstances is not foreseeable, and based on use and handling
experience, similar human health hazards are highly unlikely."
The submitter also stated that "chlorinated paraffins have been
produced commercially for several decades" during which time
"there has never been an indicati6n of any adverse health effects
Submission Evaluation
The submitted information has been transmitted to the Test Rules
Development Branch (TRDB/ECAD/OTS) and the Risk Management Branch
(RMB/ECAD/OTS) for inclusion in their ongoing review of available
toxicologic and exposure information on chlorinated paraffins.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for CAS No. 63449-39-8, which is listed in the initial
TSCA Inventory, has shown that between 27 million and 170 million
pounds were produced/imported in 1977. This production range in-
formation does n9t include any data claimed as TSCA Confidential
Business Information (CBI) by the person(s) reporting for the
Inventory, nor does it include any data that would compromise
TSCA CBI. The data submitted for the TSCA Inventory, including
the production range information, are subject to the limitations
contained in the Inventory Reporting Regulations (40 CFR 710).
-NOTE: This status repo:-t is the result of a prelimina:-y
staff evaluation of i~forma~ion submitt~c to EPA. Sta~e~ents
mace herein are no~ to be re~arded as ex~ressino final
~gency policy or intent wi~h-res?ec~ to t~is ?articular
chemical. .~y review 6f the status repor~ should take into
consideration the tact tha~ it may be based on incomplete
information.
211
~'-"Ollt. i.::D004 Cio. _Yo ..,.,
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8EHQ-0884-0527
Page 2 of 2
The chlorinated paraffins are a family of chlorinated compounds
that are derived from primarily saturated, straight-chain hydro-
carbons. The maximum amount of chlorination that is achievable
is 70% by weight. In general, the chloroparaffins are viscous
liquids with the viscosity increasing as the percent chlorine
increases. These compounds are considered to be soluble in oils
and oil solvents, insoluble in water, readily emulsifiable and
nonflammable. Chlorinated paraffins are used as fire retardants,
as plasticizers and as additives in extreme pressure lubricants.
It should be noted that chlorinated paraffins are used in some
applications as substitutes for polychlorinated biphenyls (PCBs),
a class of compounds that are strictly regulated by EPA.
Comments/Recommendations
The submitter stated that the final report from the ongoing rat
study will be forwarded to EPA upon completion of the statistical
analysis and data audit. In addition, the submitter stated that
other studies will be conducted in accordance with a Negotiated
Testing Agreement under Section 4 of TSCA.
EPA has received and evaluated several TSCA Section 8(e) notices
that have contained toxicity and/or exposure information on the
chlorinated paraffins.
a) The Chemical Screening Branch will request the submitter
to ensure that EPA receives, immediately upon completion,
a full copy of the final report including the actual test
protocol, statistical analyses, and data from the feeding
study that was cited in the submission.
b) The Chemical Screening Branch will transmit a copy of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, OAR/EPA, ORD/EPA, TRDB/ECAD/OTS and RMB/ECAD/OTS.
A copy of this status report will also be sent to the TSCA
Assistance Office (TAO/OTS/OPTS) for further distribution.
212
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DA U: SEP I I 84
8EHQ-0884-0528
Page 1 of 3
SUIJ£CT. St at us Report *
8EHQ-0884-0528
App=oved
tJlk- r;/"jgy
"'" rr-'"- Revision
'10M. James F. Darr, Acting Section.Hea~V.~ Needed
Chemical Risk Identification Secti~n/CSB
TOt Fran~ D. Kover, Branch Chief
ChemIcal ScreeningBranch/E~AD/OTS/OPTS
Submission Description
The Dow Chemical Company submitted summary results from a number
of toxicologic studies of 2-phenoxyethanol (CAS No. 122-99-6) in
rabbits. The submitter provided the following information with
regard to the results of the performed tests:
"A dermal probe teratology study in pregnant New Zealand white
rabbits was conducted at [2-phenoxyethanol] dose levels of 0,
300, 600 and 1000 mg/kg/day with 10 rabbits per group. The
animals were treated on days 6 through 19 of gestation. Ne-
cropsy was conducted on day 19 of gestation. No unexpected
results were observed."
"In the full dermal teratology study using the same test spe-
cies [New Zealand white rabbits] and dose levels, but with 20
rabbits per group, a total of 9 high dose (1000 mg/kg/day) and
4 middle dose (600 mg/kg/day) rabbits died or were killed in
moribund condition following 5 to 13 applications of 2-phen-
oxyethanol. Many of these rabbits died showing signs of hema-
tologic changes indicative of the breakdown of red blood cells
characterized by hemoglobinuria, pale livers, dark red-black
kidneys and dark red-black urine in the bladder. As a result
of this excessive mortality. the 1000 mg/kg dosing was discon-
tinued and all remaining high dose animals were sacrificed.
The remaining animals in the 300 mg/kg and 600 mg/kg groups
continued treatment and will be examined for teratologic ef-
fects. Hematologic parameters were monitored in these animals
on day 19 of gestation (the day after dosing was completed).
The survivors did not exhibit any hematologic changes, and no
deaths or signs of toxicity were observed in the low dose (300
mg/kg/day) animals. Teratologic data have not been tabulated
or evaluated to date."
"To confirm the hematologic effects observed in the maternal
animals in the teratology study, a seperate 2-week toxicity
study was initiated wherein 10 female (non-pregnant) rabbits
were given 2-phenoxyethanol via the dermal route at a dose
-NOTE: T~is status reco=t is the result of a crelirninarv
staff evaluation of ir:fo=mation submittec to EPA. State;ents
mace herein are nOt to be re~arded as ex~ressino final
~gency policy or intent with-res?ec~ to t~is ?articular
chem~cal. .'~Y review of the status repo~t should take into
cons~derat~on the tact that it mav be based on incornolete
information. 213 .. ..
E~. ,"0". II'" IJIII::V. ~"I
-------
8EHQ-0884-0528
Page 2 of 3
level of 1000 mg/kg/day for a planned 14 days. Concurrently,
five control rabbits received distilled water daily via the
dermal route. In this study, 7 of the 2-phenoxyethanol treated
rabbits either died or were killed in moribund condition be-
tween 5 - 8 days of treatment, indicating that non-pregnant
animals are also sensitive to the hemolytic effects of 2-
phenoxy ethanol. Each of these rabbits exhibited signs which
were similar to those of the affected animals in the tera-
tology study, the prominent sign being hematologic changes
indicative of red blood cell breakdown. The three surviving
rabbits treated with 2-phenoxyethanol did not exhibit hema-
tologic changes."
Submission Evaluation
The submitted information has been transmitted to the Test Rules
Development Branch (TRDB/ECAD/OTS/OPTS) for inclusion in their
ongoing evaluation of toxicologic and exposure information on 2-
phenoxyethanol, a chemical recommended by the Interagency Testing
Committee (ITC) for testing consideration by EPA under Section 4
of TSCA.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for 2-phenoxyethanol (CAS No. 122-99-6), 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 to be
TSCA Confidential Business Information (TSCA CBI), nor does it
include any information that would compromise TSCA CBI. All of
the data submitted for the TSCA Inventory, including production
range information, are subject to the limitations contained in
the TSCA Inventory Reporting Regulations (40 CFR 710).
In its submission, Dow stated that "the major use of 2-phenoxy-
ethanol is as a paint coalescing agent in latex paints." Dow
also stated that the minor applications of 2-phenoxyethanol in-
clude "cleaners, polishes, photographic developers, and cosme-
tics."
Comments/Recommendations
Dow reported in its submission that its employees, customers, and
the co-sponsors of the teratology study were being notified about
the submitted toxicologic findings. In addition, Dow stated that
although its "current work practices are not expected to result
in exposures at the levels where toxicity was first noted in
these studies," the company plans to review its work practices to
ensure that workers exposed occupationally to 2-phenoxyethanol
are taking appropriate precautions with regard to skin contact.
214
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8EHQ-0884-0528
Page 3 of 3
EPA's Office of Toxic Substances (OTS) has received and evaluated
several TSCA Section 8(e) and/or "For Your Information" (FYI)
submissions containing toxicologic and/or exposure information on
a number of glycol ethers, including 2-ethoxyethanol (and its
acetate), 2-methoxyethanol (and its acetate), and 2-butoxyethanol
(and its acetate). The Chemical Screening Branch (CSB/ECAD/OTS)
has prepared Chemical Hazard Information Profiles (CHIPs) on 2-
methoxyethanol and its acetate, and 2-ethoxyethanol and its ace-
tate. The Risk Management Branch (RMB/ECAD/OTS) is currently
evaluating the available toxicologic and exposure data on a num-
ber of glycol ethers.
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will request
the Dow Chemical Company to provide a complete copy of the
final report, including the actual experimental protocol
and data, from each toxicity study that was cited in the
submission.
b)
The Chemical Screening Branch will transmit a copy of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, OAR/EPA, ORD/EPA, TRDB/ECAD/OTS, and RMB/ECAD/OTS.
Copies of the status report will also be sent to the TSCA
Assistance Office (TAO/OTS/OPTS) for further distribution.
215
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£)A 1£;
SEP21~
UNITED STArES ENVIRONMENTAL PROTECTION AGENCY
8EEQ-0984-0529
Page 1 of 5
SUaJECT. Stat us Report *
8EHQ-0984-0529
1I.pp=oved
~ q !lK
A/I tr' Revision
'101&. James F. Darr, Acting Section Head~ " J)UV1/ Needed
Chemical Risk Identification Sectl~n/CSB
T~Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Eastman Kodak Company submitted summarized results from a
subchronic feeding study of I-phenyl-3-pyrazolidinone(phenidone;
CAS No. 92-43-3) in rats. The company provided the following in-
formation with regard to the performed study:
"Male and female rats were exposed to phenidone in the diet
for either 42 (hereafter referred to as the interim group) or
90 days. The interim groups consisted of 10 rats of each sex
while those fed for 90 days contained 20 rats of each sex.
Target doses were 0.02, 0.08, and 0.32 percent in the diet.
Estimated doses for the interim group males were 12, 59, and
244 mg/kg/day; for the females estimated doses were 13, 61,
and 270 mg/kg/day. Estimated doses for males in the 90-day
study were 9, 46, and 214 mg/kg/day; for females, estimated
doses were 10, 51, and 239 mg/kg/day."
"Males and females in the 0.08% and 0.32% groups showed re-
tarded weight gains and lower final body weights; 0.02% in the
diet had no effect on weight gains or final body weights. Feed
consumption was reduced in both males and females at 0.08% and
0.32% although not for every time period; changes in feed con-
sumption were minor and transient at 0.02%."
"Hematologic effects were observed in males and females from
both the interim and 90 day groups in a dose-related manner.
Two types of effects were observed: 1) a mild anemia with
Heinz bodies, macrocytosis and increased hemoglobin in red
cells, and 2) an increase in platelet counts and white cells.
Animals ingesting the diet with 0.02% phenidone showed very
slight hematologic effects. Serum clinical chemistries were
variable; the changes were of no toxico16gical significance."
-NOTE: T~is status reco~t is the result of a crelimina:v
staff evaluation of i~formation subrnitt~c to EPA. State;'ents
mace herein are no~ to be re~arded as ex~ressina final
Ase~cy policy or intent with~res?ec~ to t~is ?a;ticular
chemical. .~v review of the status recor~ should take into
consideration-the iact that it may be based on-incomoietB~
informatiori. - .
216
f~& '0"'" ..~ '''EV. ~,.,
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8ERQ-0984-0529
Page 2 of 5
"Changes in organ weights were observed, but were mainly at-
tributed to decreased body weights. Target organ effects based
on organ weight changes were enlargement of spleens at 0.08%
and 0.32% (both interim and 90 day groups) in males and fe-
males and testicular atrophy in males at 0.32% (both interim
and 90 day groups). No toxicologically significant effects on
organ weights were observed at 0.02%."
"Gross and/or histopathological changes were observed in a
dose-related manner in the spleen, liver, kidneys, testes, and
epididymides, as follows:
Liver
0.32%
0.08%
0.02%
Kidneys
0.32%
0.08%
0.02%
Spleen
0.32%
0.08%
0.02%
Testes
0.32%
0.08%
0.02%
Epididymides 0.32%
0.08%
0.02%
Kupffer cell hemosiderosis; extramedullary
hematopoiesis (except interim males).
Kupffer cell hemosiderosis (except interim
males); extramedullary hematopoiesis (90
day females only).
No effects.
Proximal tubule cell pigmentation; tubular
casts (interim females only); increased
severity of hyalin droplet degeneration
(interim males only).
Proximal tubule cell pigmentation (interim
female and 90 day male only).
No effects.
Increased congestion, hemosiderosis, ex-
tramedullary hematopoiesis, and red pulp
atrophy.
Increased congestion, hemosiderosis, ex-
tramedullary hematopoiesis, and red pulp
atrophy only in female interim and 90 day
groups.
Increased congestion and
(equivocal in all groups
males where there was no
hemosiderosis
except interim
hemosiderosis).
Atrophy and degeneration of seminiferous
tubules.
Atrophy of seminiferous tubules (only in 1
of 10 males of the interim group).
No effects.
Contains degenerating
creased or absence of
No effects.
No effects."
spermatozoa and de-
mature spermatozoa.
Eastman Kodak also stated that "with the exception of dermatitis,
[the company is] "not aware of any advserse health problems asso-
ciated with the use of [phenidone] or solutions containing this
chemical."
217
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8ERQ-0984-0529
Page 3 of 5
Submission Evaluation
The reported adverse effects are most probably real (treatment-
related) in that they were dose-related. Although the lower food
consumption observed in the two highest dosage groups (0.08% and
0.32%) may mean that the chemically treated food was less pala-
table, these groups apparently did receive higher doses judging
from the more severe effects that were found. The observed hemo-
siderosis (i.e., the excess storage of iron/hemosiderin) in the
spleen and in the Kupffer cells (macrophages) of the liver and
the observed but unspecified pigmentation of the proximal con-
voluted tubules of the kidney suggests the development of a hemo-
lytic disorder. This is supported by the finding of mild anemia
and macrocytosis. Although an increase in white blood cells and
platelets was also reported, it is not clear that this increase
was absolute or due to a decrease in circulating blood volume.
It would be of interest to know the results of a differential
white-cell count as well as the specific gravity of the urine.
The finding of Heinz bodies in the red cells suggests that some
of the hemoglobin was changed to methemoglobin. It is not clear
whether the observed atrophy of the red splenic pulp was a direct
toxic effect or was secondary to an attempted compensation for
the loss of oxygen-carrying capacity caused by hemolysis which
resulted in exhaustion of the red pulp of the spleen.
Dose-related degenerative changes were noted in the seminiferous
tubules of the testes, as well as in the spermatozoa in the epi-
didymides. It is not clear that these changes were direct toxic
effects or resulted from impaired nutrition (either general mal-
nutrition from decreased food consumption or local impairment of
nutrition of stored spermatozoa as the result of damage to the
epididymides). Although it is possible that phenidone produces
its diverse toxic effects via several different mechanisms, it
could be speculated that there may be a common factor involved
between the observed hemolytic effects and the observed testi-
cular atrophy. In addition, it should be noted that phenidone
can inhibit the metabolism of arachidonic acid to prostaglandins,
and hydroperoxy fatty acids (Fischer et aI, Carcinogenesis, 1982,
3:1243-1245). It is not clear whether or how the inhibition of
arachidonic acid metabolism plays a role in toxic action(s) of
phenidone.
It should be noted that the submitting company's statement with
regard to dermatitis differs from the information contained in
the Merck Index (9th Edition, 1976, page 951) which indicates
that dermatitis has not been experienced following exposure to
phenidone. One might infer from this disparity that if phenidone
is irritating to the skin, it may be only weakly irritating.
Further evaluation of the reported toxicologic findings for
phenidone should be possible upon the Agency's receipt of a
complete copy of the final report (including the experimental
protocol and data).
218
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8EHQ-0984-0529
Page 4 of 5
Current Production and Use
A review of the production range (includes importation volumes)
statistics for phenidone (CAS No. 92-43-3), which is listed in
the initial TSCA Inventory, has shown that between 131 thousand
and 1.31 million pounds were reported as produced/imported in
1977. This production range information does not include any
production/importation data claimed as TSCA Confidential Business
Information (TSCA CBI) by the person(s) reporting for the TSCA
Inventory, nor does it include any information that would com-
promise TSCA CBI. All data reported for the TSCA Inventory, in-
cluding production range information, are subject to the limita-
tions contained in the TSCA Inventory Reporting Regulations (40
CFR 710).
In its submission, the Eastman Kodak Company reported that it
does not manufacture phenidone. The company stated that lithe
major use of the purchased material is as a minor component in
the formulation of x-ray developer solutions." In addition, the
company stated that small amounts of phenidone "are also used as
minor components in the formulation of a few commercial photo-
graphic developer products." According to secondary literature
sources, phenidone is used also as a labcratory reagent.
Comments/Recommendations
Eastman Kodak stated that its supplier has been informed about
the reported toxicologic findings on phenidone. In addition,
Eastman Kodak stated that, upon completion, EPA will receive a
copy of the final report from the company's subchronic phenidone
study.
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will request
the Eastman Kodak Company to ensure that, upon completion,
EPA receives a full copy of the final report (including
the actual experimental protocol and data) from the sub-
chronic phenidone feeding study that was cited in the
submission.
Considering the Agency's general interest in corporate
actions that are taken on a voluntary basis in response to
chemical toxicity/exposure data, the Chemical Screening
Branch will ask Eastman Kodak to describe the actions the
company has taken to .reduce and/or eliminate exposure to
phenidone. In addition, the Eastman Kodak Company will be
asked to describe the nature of all other studies that the
company has conducted, is conducting, or plans to conduct
that are designed to determine the toxicity of and/or the
exposure to phenidone.
b)
The Chemical Screening Branch will review the submitted
information in order to determine the need for further OTS
assessment of phenidone.
219
-------
8EHQ-0984-0529
rage 5 of 5
c)
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, OAR/EPA, and ORD/EPA. In addition, copies of the
status report will be sent to the TSCA Assistance Office
(TAO/OTS/OPTS) for further distribution.
220
-------
DA T!~
SEP 179M
UH1T~D STATES ENY IRONMENTAL PROTECTION AGENCY
8EHQ-0984-0530
. Page 1 of 3 .
SUIJ£CTI Status Report *
8EHQ-0984.,.0530
App:-oved
01>'
.'/," "1>.
"/"1 "~,,!
~~~ Revision
'IOMIJames F. Darr, Acting Section Head v.~ Needed
Chemical Risk Identification Secti njCSB
TO Frank D. Kover, Branch Chief
'Chemical Screening BranchjECADjOTSjOPTS
Submission Description
E. I. Du Pont de Nemours & Company, Inc. submitted summarized
preliminary results from a 2-year inhalation study of titanium
tetrachloride (CAS No. 7550-45-0) in rats. The submitter pro-
vided the following information with regard to the study:
"Under the conditions of the test, 100 male and 100 female
Charles River-CD rats were exposed to titaniumtetrachlor~de
(TiC14) vapors at exposure levels of 0, 0.1, 1 or 10 mgjm ,
for 6 hours a day, 5 days a week. Exposure atmospheres were
gener~ted by passing a stream of nitrogen through liquid ti-
tanium tetrachloride at ambient temperature. This saturated
vapor was diluted with humidified air and fed into the expo-
sure chamber. Since titanium chloride reacts with the moisture
in the air, this generation procedure resulted in an atmos-
phere containing primarily particulate and gaseous titanium
tetrachloride hydrolysis products. These particulates were
100% respirable with a mass median diameter of approximately
0.4 microns."
"A total of 20 rats per group were sacrificed at 3, 6, and 12
months to evaluate chronic toxicity. No unusual effects were
observed in these rats. The surviving rats were sacrificed at
the end of the 104 week exposure period. -All major tissues and
organs were evaluated and, except for the respiratory tract,
were normal. In the lungs, h~stopathological examination re-
vealed tumors at the 10 mgjm exposure level. These tumors
were keratinized, cystic squamous cell carcinoma (one male and
one female) and squamous cell carcinoma, differentiated (one
male and two female). No compound-related tumors were seen ?t
lower exposure levels. In addition, inflammation typical of
nuisance dust exposure, predominantly at the higher exposure
levels, was observed." [The submitter provided draft tables of
the reported respiratory tract findings.]
-NOTE: This sta~us reoo:-t is the resul: of a orelirnina:-v
staff evaluation of informa~ion submittec to EPA. State;e~ts
mace herein are no~ to be re~arded as'ex~ressino final
Agency policy or intent with-r~s?ect to t~is particular
chemical. .~y review 6£ the status repor~ should take into
consideration the fact' that ii may be based on incomolete
information. 221 .
E~a ro- "" CIilCY. ~'"
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8EHQ-0984-0530
Page 2 of 3
In its submission, Du Pont stated that titanium tetrachloride,
which is a liquid at room temperature, is known to be highly ir-
ritating to skin and eyes. In addition, Du Pont stated that tqe
chemical is highly toxic via inhalation (4-HR LC50 of 460 mg/m
in rats). Du Pont also stated that titanium tetrachloride was
non-mutagenic in a Chinese Hamster Ovary (CHO) cell/HGPRT assay
and in a Bacillus subtillis rec-assay.
Finally, Du Pont stated that "...preliminary indications from a
brief review of medical records indicate that the employees in
[Du Pont's] manufacturing operations in which titanium tetra-
chloride is made, experienced no statistically significant in-
crease in incidence of mortality from lung cancer."
Submission Evaluation
The submitted information suggests that titanium tetrachloride,
at the highest tested dose only, displays marginal oncogenic ac-
tivity toward the lung tissue of Charles River-CD rats. Further
evaluation of the findings should be possible upon the Agency's
receipt of a full copy of the final report which should include
the actual experimental protocol and data.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for titanium tetrachloride (CAS No. 7550-45-0), which
is listed in the initial TSCA Inventory, has shown that between
250 million and 1.1 billion pounds of this che;ilical were reported
as produced/imported in 1977. This production range information
does not include any production/importation data that was claimed
as TSCA Confidential Business Information (TSCA CBI) by the per-
son(s) reporting for the TSCA Inventory, nor does it include any
information that would compromise TSCA CBI. The data submitted
for the TSCA Inventory, including production range data, are sub-
ject to the limitations contained in the TSCA Inventory Reporting
Regulations (40 CFR 710).
According to secondary literature sources, titanium tetrachloride
is used as a mordant, as a catalyst in polymerization reactions,
and as a raw material for titanium metal. In addition, titanium
tetrachloride is used in the manufacture of iridescent glass, ar-
tificial pearls, and titanium pigments.
Comments/Recommendations
In its submission, Du Pont stated that in light of the reported
findings the comp~ny has 1) "established a workplace exposure
level of 0.5 mg/m (8- and 12-hour Time Weighted Average)," and
2) "communicated the test results and [Du Pont's] assessment of
their meaning to [Du Pont] employees and to other agencies (OSHA,
222
-------
8EHQ-0984-0530
Page 3 of 3
NIOSH)." In addition, Du Pont stated that the company plans to
notify Du Pont's customers and competitors about the reported
bioassay results and Du Pont's assessment of the meaning of the
findings. Du Pont also stated that the company plans "to deter-
mine the feasibility of conducting an epidemiology study of those
employees in [Du Pont's] manufacturing plants who have the poten-
tial for exposure to titanium tetrachloride during their normal
plant duties...." Finally. Du Pont stated that copies of the
final report of the 2-year titanium tetrachloride rat inhalation
bioassay would be provided to EPA and other government agencies.
a)
The Chemical Screening Branch (CSB/ECAD/OTS) will request
Du Pont to ensure that EPA receives, immediately upon com-
pletion, a full copy of the final report (including the
actual experimental protocol and data) from Du Pont's 2-
year inhalation study of titanium tetrachloride. Du Pont
will also be requested to provide a complete copy of the
final report (including the actual experimental protocol
and data) from each in vitro mutagenicity assay that was
cited in the submisslOn.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of titanium tetrachloride.
c)
The Chemical Screening Branch will transmit copies of this
status report to NIOSH, OSHA, CPSC, NTP, OW/EPA, OAR/EPA,
OSWER/EPA, and ORD/EPA. Copies of this status report will
be sent also to the TSCA Assistance Office (TAO/OTS/OPTS)
for further distribution.
223
-------
UNITED STATES EHYIRONM"ENTAL PROTECT!OH" A~ENCY
8EEQ-0984-0531 S
Page 1 of 4
OAT!:
ocr
2 934
SUaJEC:TI
Status Report*
8EHQ-0984-0S31 S
Approved {;$t-- JO/:J-/o/
t:q..,~ReVision
'IOMI James F. Darr, Acting Section Head V. Needed
Chemical Risk Identification Secti n/CSB
TO Frank D. Kover, Branch Chief
I Chemical Screening Branch/ECAD/OTS/O~fS
NOTE:
The submitting company has claimed its name and the exact
identity of the subject chemical to be TSCA Confidential
Business Information (TSCA CBI). The submitter reported
non-confidentially that the subject chemical is a fatty
acid imidazoline listed in the TSCA Inventory under the
following CAS No.: 68442-97-7. According to Volume I of
the TSCA Inventory, CAS No. 68442-97-7 pertains to 2-nor-
tall-oil alkyl derivatives of 4,S-dihydro-IH-imidazole-l-
ethanamine. Staff of the Information Management Division
(IMD/OTS/OPTS/EPA) will request the submitting company to
substantiate all of its claims of confidentiality.
Submission Description
The submitting company provided summarized results -..Jm several
acute in vivo toxicity studies of the fatty acid imidazoline.
According~the submitter,. the chemical was found to be severely
irritating to skin (species not specified) and corrosive (site
and species not specified), and to have an oral LDSO of approxi-
mately 5 g/kg in rats (6 of 10 rats died during days 2 through 6
following oral administration).
Submission Evaluation
On the basis of the reported LD50 of approximately S g/kg, the
tested chemical would be classified as being only slightly to
moderately toxic via the oral route of administration. The pH of
the subject chemical (which is expected to be high (i.e., basic»
may be responsible for the observed irritation/corrosion. The
submitter should be asked to report the pH (if known) for the
tested chemical substance. In addition, a complete copy of the
final report (including experimental protocol and data) from each
acute toxicity study that was cited in the submission should be
requested.
-NOTE: This status reoo~t is the result of a orelimina:v
staff evaluation of i~fo~.ation submitt~c to EPA. Sta~e;'e~ts
mace herein are no~ to be re~arded as ex~ressino final
Ase~cy policy or intent with~res?ect to t~is ?articular
chemical. .~v review of the status reoort should take into
consideration-the tact that it may be based on incom?let~
inforrna tion.. ;'224
E~. 'Ollila IJ;!)04 Cillev. ~"I
-------
8EHQ-0984-053l S
Page 2 of 4
Current Production and Use
A review of the production range (includes importation volumes)
statistics for CAS No. 68442-97-7, 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 TSCA Confidential Business Information (TSCA CBI) by
the manufacturer(s) and/or importer(s) and cannot be disclosed
(Section 14(a) of TSCAi U.S.C. 2613(a)). The data submitted for
the TSCA Inventory, including the production range information,
are subject to the limitations contained in the TSCA Inventory
Reporting Regulations (40 CFR 710).
In its submission, the company reported that the "fatty acid
imidazoline is being developed as a competitive product for use
as a corrosion inhibitor in the petroleum industry" and "expo-
sures to the substance are minimal as use is in closed systems."
The submitter also stated that "similar products with similar
ingredients have been in commercial use for approximately 25
years without reports, known to [the submitting company], of
adverse effects."
Comments/Recommendations
It should be noted that it has been EPA's longstanding position
that certain types of acute animal toxicity information may not
warrant submission to EPA under Section 8(e), the "substantial
risk" information reporting provision of the Toxic Substances
Control Act (TSCA). The basis for EPA'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 PolicYi 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 [adverse] effect...and (b) the
fact or probabi Ii ty of its occurrence." Wi th regard to the
seriousness of the effect, Part V explains that the Agency
considers the health effects for which substantial risk in-
formation 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 seri-
ous or prolonged incapacitation." Information with respect
to these effects can be obtained directly or inferred from
designed studies (i.e.. in vivo experiments as described in
Part VI of the Section 8Te) policy statement). With regard
to the criterion concerning the "fact or probability" of the
occurrence of such effects, Part V of the Section 8(e) policy
statement explains that certain types of health effects are
so serious that relatively little weight should be given to
the chemical's exposure in determining whether a risk is sub-
stantial.
225
-------
8EHQ-0984-0531 S
Page 3 of 4
EPA's response to Comment 14 in Appendix B of the Section
8(e) policy statement provides guidance concerning the 8(e)-
applicability of results obtained from routine acute in vivo
range finding studies (e.g.. LD50 determinations, skinJe~
irritation tests, etc.). In its response, the Agency stated
that "many routine tests are based on knowledge of toxicity
associated with a chemical...." EPA's response also directed
that unknown effects that occur and are observed/determined
during such routine studies may have to be reported to EPA
under Section 8(e) if such effects are serious and meet the
reporting requirements set forth in the Section 8(e) policy
statement. Thus, when evaluating the results of acute animal
toxicity studies for possible submission to EPA under Section
8(e) of TSCA, EPA believes that subject companies should con-
sider such factors as the lethal dose, the pH of the tested
chemical or mixture, the route of administration, the occur-
rence of unexpected effects (which could be determined via
"cage-side" observation or during necropsy), and the extent
and pattern of the actual or potential exposure to the tested
chemical or mixture. In general, when evaluating such infor-
mation for TSCA Section 8(e) reporting, the greater the acute
toxicity, the less heavily a subject company should weigh the
exposure to the tested chemical or mixture, and vice versa.
In light of the preceeding discussion, it does not appear that
the acute toxicity information, as presented in this sUbmission,
warranted reporting to EPA under Section 8(e) of TSCA. In making
this initial determination, however, it should be understood that
the Agency may not be aware of additional pertinent information
that may have been available to and/or considered by the submit-
ting company in deciding to report under Section 8(e).
a) The Chemical Screening Branch will request the submitter
to provide to EPA a complete copy of the final report (in-
cluding experimental protocol and data) from each toxicity
study that was cited in the submission. In addition, the
submitter will be asked to report the exact structure (if
known) and pH (if known) of the tested material. Finally,
the submitting company will be requested to provide its
rationale (in light of the discussion presented in the
Comments/Recommendations section of this report) as to why
the acute in vivo toxicity information is believed to have
warranted submission to EPA under Section 8(e) of TSCA.
Considering EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure information, the submitting company will
be asked to describe the actions it has taken or plans to
take to (1) warn workers and others, and (2) reduce and/or
eliminate exposure to the tested chemical. The submitting
company will be asked also to describe the nature of all
other tests that it has conducted, is conducting, or plans
to conduct that are designed to determine the toxicity of
and/or the exposure to the chemical.
226
-------
8EHQ-0984-0531 S
rage 4 of 4
b) The Chemical Screening Branch will review the reported in-
formation in order to determine the need for further OTS
assessment of the subject chemical substance.
c) The Chemical Screening Branch will send a copy of this
status report to NIOSH, OSHA, CPSC, OW/EPA, OSWER/EPA,
OAR/EPA, and ORD/EPA. Copies of this status report will
be sent also to the TSCA Assistance Office (TAO/OTS/OPTS)
for further distribution.
227
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UNITED STATES ENVIRONMENTAL PROTECTION. AGENCY
DAn:
(£1'25 ~
8EEQ-I084-0532
Page 1 of 3
Approved z;IJI-- ",;..,h
SUIJECTI Status Report * 8EHQ-I084-0532
David R. WilliamS~ing Section Head
nOMI Chemi cal Ri sk Identi fication Section/CSB
Revision
Needed
Frank D. Kover Branch Chief
TOI Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Allied Corporation provided the following summarized results
from several toxicologic studies of 5,7,11-dodecatriyn-l-ol:
"Dermal Irritation - moderately irri tatin9.
Sensi ti zation (maximi zation test) - extreme sensi ti zer. [A
Section] 8(c) notification was also recorded which indicated
a possible dermal irritation and sensitization 'in a labora-
tory technician.
Photosensitization (guinea pig) - negative. NOTE: Histopath-
ological examination showed a brain lesion in each o~ two
animals observed to have neuromuscular effects.
Cross-sensitization ~ may induce the potential
sitization by other compounds or will react as
ate sensitizer where animals have been induced
sensitizing substances.
for cross-sen-
an intermedi-
wi th other
Mutagenicity - negative [in vitro] Ames [bacteria] test.
Acute Oral Toxicity (rats) - LD50
Pathological examination suggests
lesions similar to those observed
photosensitization).
appears to be <0.3 ml/kg.
the development of brain
in guinea pigs (noted for
Subacute Probe Oral Toxicity (rats) - non-pregnant rats were
dosed for 21 days. Neurobehavioral screens indicated balance
problems and weakness of fore and hind legs.
Feiotoxicity Study - no maternal toxicity after dosing for 5
days premating and 15 days into gestation. However,-there
may be a statistically significant difference in litter size
and weight when comparing the high dose and controls. Other
aspects of this study (just now being completed) are still
under evaluation."
-NOTE: T~is status reoo~t is the result of a orelimina~v
staff evaluation of i~forrnation submittec to EPA. State;ents
mace herein are no~ to be re~arded as ex~ressino final
Ase~~y policy or intent with.res?ec~ to t~is ?articular
chenucal. .~y review 6f the status report should take into
~onsideration the iact that it may be based on incomplete
l.nformation.
228
r~' ,.O"."IJ~ 1.8ICY. ..",
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8EHQ-I084-0532
Page 2 of 3
Submission Evaluation
The submitted information indicates that 5,7,11-dodecatriyn-l-ol
and/or its metabolite(s) can be absorbed following either dermal
application or oral administration. The information also indi-
cates that the chemical and/or its metabolite(s) possess neuro-
toxic, sensitizing, and potential fetotoxic activities. Further
evaluation of the reported findings should be possible upon the
Agency's receipt of a full copy of the final report (including
the actual experimental protocol and data) from each study that
was cited in the submission.
It should be noted also that there is some degree of structural
analogy between 5,7,11-dodecatriyn-l-ol and l-hexyn-3-01. The
latter chemical was the subject of a previous TSCA Section 8(e)
notice (8EHQ-0179-0273) which was submitted by the Dow Chemical
Company). In its Section 8(e) notice, Dew reported that l-hexyn-
3-01 had been shown to be toxic to laboratory animals via dermal,
oral, and inhalation routes of exposure and caused the death of
an employee (of a former Dow subsidiary) following an accidental
single dermal exposure to "a large amount" of the chemical.
Current Production and Use
According to Allied, all of its work to date with 5,7,11-dodeca-
triyn-l-ol has been research and development (R&D) related. The
company stated in its submission that the projected commercial
use of the subject chemical "is as an intermediate which though
it would be isolated would also be in a closed system, a fact
limiting exposure potential." Allied also reported, however,
that the company is "not sure at this time that this material
will be commercialized." Finally. the Allied Corporation stated
that approximately 1 kg of the chemical has been synthesized to
date and that "exposure has been limited to laboratory personnel
at Allied and two other contract laboratories."
Comments/Recommendations
In its submission, Allied reported that all personnel working
with 5,7,ll-dodecatriyn-l-ol have been notified about the sub-
mitted toxicologic findings.
On August 22, 1983, the Agency published (48 FR 38178) a final
rule that required full compliance with Section 8(c) of TSCA as
of November 21, 1983. In general, the final 8(c) rule requires
chemical manufacturers/importers and certain processors to main-
tain records of significant adverse reactions to health or the
environment alleged to have been caused by chemical substances or
mixtures. The final Section 8(c) rule also requires that allega-
tions involving significant adverse reactions in employees be
maintained for 30 years and that all other allegations be main-
tained for 5 years. It should be noted that although there is no
automatic Section 8(c) record-reporting requirement in place at
the present time, EPA can inspect and/or require the submission
of TSCA Section 8(c) records to the Agency.
229
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8ECIQ-1084-0532
Page 3 of 3
a) The Chemical Screening Branch (CSB/ECAD/OTS) will ask the
Allied Corporation to provide to EPA a complete copy of the
TSCA Section 8(c) allegation/report and the final report
(including the actual experimental protocol and data) from
each toxicity study that was cited in Allied's submission.
In view of the Agency's general interest in company actions
that are taken on a voluntary basis in response to chemical
toxicity/exposure information, the Chemical Screening Branch
will also request Allied to describe the nature of all other
studies that the company has conducted, is conducting, or is
planning to conduct that are designed to define the toxicity
of and/or the exposure to S,7,II-dodecatriyn-I-ol.
b) In light of the structural analogy between l-hexyn-3-01 and
S,7,ll-dodecatriyn-l-ol, the Chemical Screening Branch will
request the Dow Chemical Company to describe the nature of
all studies (with the exception of those reported by the
company in 8EHQ-Ol79-0273) that Dow has conducted, is con-
ducting, or plans to conduct that are designed to determine
the toxicity of and/or the exposure to l-hexyn-3-01. In ad-
dition, Dew will be asked if the company has recorded any
TSCA Section 8(c) allegations, concerning l-hexyn-3-ol, and
if so, how many.
The Chemical Screening Branch will review the reported in-
formation to determine the need for further OTS assessment
of S,7,II-dodecatriyn-I-ol and/or l-hexyn-3-01.
d) The Chemical Screening Branch will transmit copies of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, OAR/EPA and ORD/EPA. In addition, copies of this
status report will be sent to the TSCA Assistance Office
(TAO/OTS/OPTS) for further distribution.
230
-------
01.1£:
ocr 2 5 1984
UNITED STATES EHYIROHMENTAL PROTECTION AGENCY
8EC:Q-I084-0533 S
Page 1 of 3
ILlIJEt,. Status Report* 8EHQ-I084-0533 S
,..... David R. WilliamS~ting Section Head
Chemical Risk Identification SectionjCSB
App:oved
#
kJ/JD!etf
~ I
Revision
Needed
TO Frank D. Kover, Branch Chief
I Chemical Screening.BranchjECADjOTSjOPTS
Not e :
The submitting company has claimed its name as TSCA
Confidential Business Information (TSCA CBI). The
Information Management Division (IMDjOTSjOPTS) has
requested the submitting company to substantiate its
confidentiality claim.
Submission Description
The submitting company provided summarized results from.several
genotoxicity studies of 2-chloro-5-trichloromethyl pyridine (CAS
No. 69045-78-9). According to the submitter:
"A preliminary Ames test in Salmonella strain TA 98 with a
metabolic activation system (S9), gave a negative result.
Recently further tests were conducted with five Salmonella
strains, with and without S9, and a positive result was ob-
tained in TA 98 without activation. Subsequently positive
results were obtained in a mouse lymphoma assay and an in
vitro human lymphocyte cytogenetic assay.
"Our [the submitter's] laboratory concludes that 2-chloro-
5-trichloromethyl pyridine is mutagenic to bacteria under
certain conditions and should be considered potentially
mutagenic to higher animals and man."
Submission Evaluation
Although the submitted information does indicate that 2-chloro-
5-trichloromethyl pyridine possesses some degree of genotoxic
activity, complete copies of the final reports (including the
actual experimental protocols and data) from all of the cited
studies are needed in order for the Agency to evaluate the
reported findings. -
-NOTE: T~is status reDo~t is the resu2t of a Drelimina:v
. ."
staff evaluation of i~forma~ion submitted to EPA. State~en~s
mace herein are noi to be regarded as expressing final
Agency policy or intent with res?ec~ to t~is particular
chemical. .~v review 6f the status reDort should take into
consideration"the fact that it may be based on incom~lete
information. 231 " -
E~' , ° ilia 1J:D-4 IIU:V. .~'"
-------
8EHQ-I084-0533 S
Page 2 of 3
Current Production and Use
The subject chemical was not located during a review of the non-
confidential portion of the TSCA Inventory. The submitting com-
pany reported that it "does not currently manufacture, distribute
or process ... [2-chloro-5-trichloromethyl pyridine]...." and
"that to our [the company's] knowledge, this material has been
used only as an industrial intermediate under conditions that
ensure minimal exposure, whether by inhalation or skin contact."
According to a publicly available on-line computerized data base
(Toxline), 2-chloro-5-trichloromethyl pyridine is associated with
a patent (Eur. Pat. Appl. (Patent No. 4414) 10/03/79) concerning
the synthesis and uses of herbicides.
Comments/Recommendations
Although a positive genotoxicity test result, when considered
alone, may not be sufficient to offer reasonable support for a
conclusion of substantial risk, the Agency believes that such
results are of value in assessing the possible risks posed by
chemicals to health and/or the environment. EPA also believes
that positive genotoxicity test results in combination with
additional information (e.g., knowledge of potential exposure to
or high production of the chemical substance or mixture), would
suggest, in many cases, the need to conduct additional studies
designed to define better the toxicity of and/or exposure to the
chemical substance or mixture. The results of such studies
should be considered also for possible submission to the Agency
under Section 8(e) of TSCA.
It should be noted that EPA's Office of Toxic Substances (OTS)
has received and evaluated several TSCA Section 8(e) notices con-
taining toxicologic and/or exposure information on a number of
substituted pyridines. In addition, the Chemical Screening
Branch (CSB/ECAD/OTS) has prepared Chemical Hazard Information
Profiles (CHIPs) on 2-, 3-, and 4-methyl pyridine and staff of
the Risk Management Branch (RMB/ECAD/OTS) is currently evaluating
the available toxicity/exposure information on these chemicals.
It should be noted also that EPA has received and evaluated a
number of TSCA Section 5 Premanufacturing Notifications (PMNs)
for substituted pyridines.
a)
The Chemical Screening Branch will ask the submitter to
ensure that EPA receives a complete copy of the final
report (including the actual test protocol and data) from
each genotoxicity study that was cited in the submission.
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure information, the Chemical Screening
Branch will request the submitting company to describe
all other studies that it has conducted, is conducting,
or plans to conduct to define the toxicity of and/or the
exposure to 2-chloro-5-trichloromethyl pyridine.
232
-------
8EHQ-1084-0533 S
Page 3 of 3
b}
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of 2-chloro-5-trichloromethyl pyridine.
c)
The Chemical Screening Branch will send a copy of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORO/EPA, OAR/EPA, OPP/OPTS, and CCO/OTS/EPA. In
addition, copies of this status report will be provided
to the TSCA Assistance Office (TAO/OTS/OPTS) for further
distribution.
233
-------
UNITED STA TES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-I084-0534
Page 1 of 3
DAn:
tOI
7~
App=oved (;J- 1/ /!)?/ r,
SUlutC:T. Status Report* 8EHQ-I084-0534
,""... David R. Wil1iamS'&~ing Section Head
Chemical Risk Identification Section/CSB
Revision
Needed
TO Frank D. Kover, Branch Chief
I Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Tennessee Eastman Company provided the following summarized
results from a sub-acute oral toxicity study of 2-methoxyethyl
palmitate (2-MEP; CAS No. 111-07-9) in rats:
"Groups of 5 male rats were treated with either 100 or 1000
mg/kg of 2-methoxyethyl palmitate by gavage 11 times over 15
days. The primary effect was observed on the testes. All high
dose animals showed small, soft testes with severe bilateral
atrophy of testicular epithelium and degenerations of sperma-
tidsi multinucleated spermatid formation was observed in 2 of
5 animals, while 3 of 5 animals showed reduced amounts of se-
minal fluid in the seminal vesicles. In low dose animals, 2
of 5 showed minimal bilateral atrophy of testicular epitheli-
um with degeneration of spermatids and minor to moderate re-
duction of spermatozoa in.the epididymal lumena."
Submission Evaluation
The submitted information indicates that 2-methoxyethyl palmitate
(2-MEP) causes dose-related adverse testicular effects in rats
after 11 oral exposures (over ~5 days) at levels of 100 mg/kg/day
and .1000 mg/kg/day. The observed testicular effects were most
likely caused by 2-methoxyethanol (2-ME), a suspected in vivo
metabolite of 2-MEP. Other esters of 2-ME, such as 2-HE acetate
and 2-ME phthalate, produce the same toxicity profile as 2-ME, a
chemical that has been shown to cause adverse testicular and
developmental effects in several species via oral, dermal and
inhalatio~ exposure.
-NOTE: T~is status reco=t is the result of a crelimina=v
staff evaluation of i~fo=ma~ion subm~tted to EPA. State;'e~ts
mace herein are no~ to be re~arded as ex~ressino final
Ase~cy policy or intent with-res?ec~ to t~is ?articular
chemical. .~y review 6f the status repor~ should take into
consideration the fact that it may be based on incomolete
informa tion. 234 . .
...
E~. '.01181:1 II~ 1111£"". ..".
-------
8EHQ-1084-0534
rage 2 of 3
Current Production and Use
A review of the production range (includes importation volumes)
statistics for 2-methoxyethyl palmitate (CAS No. 111-07-9), which
is listed in the initial TSCA InventorYt 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 TSCA
Confidential Business Information (TSCA CBI) by the person(s)
reporting for the TSCA Inventory, nor does it include any infor-
mation which would compromise TSCA CBI. The data submitted for
the TSCA Inventory, including the production range information,
are subject to the limitations contained in the TSCA Inventory
Reporting Regulations (40 CFR 710).
The submitter provided the following information with regard to
the current production and uses of and the potential for exposure
to 2-MEP:
112-MEP is manufactured and used by Tennessee Eastman Company.
Total annual production is less than 1 million kg. The pri-
mary use is as a plasticizer for cellulosic plastics. A se-
condary use is as a minor component in a fiber lubricant. The
majority of manufacturing and processing operatons for 2-MEP
are enclosed or are controlled release processes. Employee
exposure is limited by the use of personal protective equip-
ment, local or building ventilation, and by the very low
volatility (boiling point of 310°C) of the chemical."
Comments/Recommendations
In its submission, the Tennessee Eastman Company reported that
the current handling procedures and precautionary information for
2-methoxyethyl palmitate will be updated to reflect the reported
toxicologic findings. The company also reported that, upon com-
pletion, a final report of the IS-day toxicity study will be sent
to the Agency.
EPA's Office of Toxic Substances (OTS) has received and evaluated
a number of TSCA Section 8(e) and "For Your Information" (FYI)
submissions containing toxicologic and/or exposure information on
glycol ethers including: 2-methoxyethanol (and its acetate), 2-
ethoxyethanol (and its acetate). and 2-butoxyethanol. In addi-
tion, the Chemical Screening Branch (CSB/ECAD/OTS) has prepared
Chemical Hazard Information Profiles (CHIPs) on 2-methoxyethanol
and its acetate and 2-ethoxyethanol and its acetate. It should
be noted also that the Risk Management Branch (RMB/ECAD/OTS) is
currently evaluating available toxicologic and exposure data on
a number of glycol ethers. Finally, the Test Rule Development
Branch (TRDB/ECAD/OTS) is currently evaluating available toxi-
cologic and exposure data on 2-phenoxyethanol, a chemical that
was recommended by the Interagency Testing Committee (ITC) for
testing consideration by EPA under Section 4 of TSCA.
235
-------
a)
8EHQ-I084-0534
Page 3 of 3
The Chemical Screening Branch (CSB/ECAD/OTS/OPTS) will
request the Tennessee Eastman Company to ensure that EPA
receives a complete copy of the final report (including
the actual experimental protocol and data) from the 15-
day rat toxicity study of 2-MEP that was cited in the
company's submission.
In light of the Agency's general interest in corporate
actions that are taken on a voluntary basis in response
to chemical toxicity and/or exposure information, the
Chemical Screening Branch will ask the Tennessee Eastman
Company to describe the nature of all other studies that
the company has conducted, is conducting, or is planning
to conduct to define the toxicity of and/or the exposure
to 2-methoxyethyl palmitate.
b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of 2-methoxyethyl palmitate.
c)
The Chemical Screening Branch will send copies of this
status report to OSHA, NIOSH, CPSC, FDA, NTP, OSWER/EPA,
OW/EPA, ORD/EPA, OAR/EPA, and RMB and TRDB/ECAD/OTS. In
addition, copies of this report will be sent to the TSCA
Assistance Office (TAO/OTS) for further distribution.
236
-------
DAn:
to' 20 ~
UNITED STATES ENVIRONMENTAL PROTECTIONAGENCY
8EHQ-I084-0535
Page 1 of 6
SUIJ£CT.Status Report* 8EHQ-I084-0535
nOl&.David R. William~ting Section Head
Chemical Risk Identification Section/CSB
APp=oved~ 'j.:zt
Revision
Needed
TOIFran~ D. Kover, Branch Chief
Chem1cal Screening Branch/ECAD/OTS/OPTS
Submission Description
The 3M Company reported that the results of several recently
conducted acute inhalation toxicity studies in rats and quail
indicate that mixtures of l,l,l-trichloroethane (TCE) and
perfluoroalkyl resins are more toxic than l,l,l-trichloroethane
a19ne. The submitter also reported that the provided information
is considered new in that "it was previously believed, based on
past studies, that the acute toxicity and hazard of the mixture
was the same as the acute toxicity and hazard of the [TCE]
solvent." The 3M Company provided the following compositional
information for the tested mixtures:
T-3500
0.5% perfluoroalkyl Resin (CAS No. 68298-78-2)
.03% Stearamide Solid (CAS No. 10212-58-5)
0.3% Freon 113 (CAS No. 76-13-1)
0.3% Methyl Isobutyl Ketone (CAS No. 108-10-1)
\
99% l,l,l-Trichloroethane (CAS No. 71-55-6)
.'
T-3499
10% perfluoroalkyl Resin (CAS No. 68555-92-0)
90% l,l,l-Trichloroethane (CAS No. 71-55-6)
The 3M Company provided the following information regarding the
conduct and results of the performed acute toxicity studies as
well as two studies designed to define human exposure to products
containing T-3500.
-NOTE: This sta~us reDort is the resul: of a creliminarv
staff evaluation of i~forma~ion submitt~c to EPA. State;'ents
mace herein are no~ to be recrarded as ex~ressir.a final
Agency policy or intent with-respect to t~is particular
chemical. .~y review of the status report should take into
consideration the iac~ that it may be based on incornplet~
inforrna tion. 237
I:~' "0". 11::1)04_1111£'\1. ""'.
-------
8EHQ-I084-0535
Page 2 of 6
"Protocol: The inhalation exposures were for 4 hours in a
one cubic meter chamber. Animals were suspended in individual
cages in the middle of the chamber. Ten rats and ten quail
(five males, five females per species) were exposed. Airflow
was approximately 180 l/minute with a temperature of [appro x.]
72°F and relative humidity [of approx.] 50%. The solutions
were injected into the air stream by a syringe pump through a
1/4' J-nozzle nebulizer at the top of the chamber. TCE levels
were measured using a MIRAN analyzer. Resin levels were meas-
ured by chemical analysis of glass fiber filters. Particle
size was measured using a TSI particle size analyzer.
"Results: The LCSOs for TCE [alone] were determined to be
about 14,000 ppm for both rats and quail. The TCE LCSO (rat)
is comparable to that in the literature. T-3S00 was initially
run at the LCSO for the solvent and then at progressively
lower levels. The LCSO (rat1 was determined to be 170 ppm TCE
(with [approx.] 2 mg resin/m). Particle size data indicate
approximately 95% of the particles to be in the respirable
range. Preliminary gross pathology indicates death to be the
result of pulmonary effects rather than CNS depression or
cardiac sensitization which are known causes of toxicity in
TCE exposures. jn quail, the LCSO is less than 14 ppm TCE
(0.25 mg resin/m). Further runs to determine the LCSO for
quail were abandoned due to problems in delivering so little
material over a four hour period. A trial run of T-3499
showed the resin content (10%) to cause delivery problems by
clogging the nebulizer. A 10-fold dil~tion of T-3499 with TCE
was run at 1910 ppm TCE (66 mg resin/m ) resulting in the
death of all rats and quail.
"Additional Animal Study Results: LC50s for rats of 1:30 and
1:60 dilutions of T-3S00 to TCE were determined. The 1:30
dilution had 0.0167% solids and the 1:60 dilution had 0.OO~3%
solids. The LC50s are about 1500 ppm TCE (0.34 mg resin/m )
and 1450 ppm TCE (Resin levels have not yet been determined.),
respectively.
"The toxicity data indicate that under the condition of the
experiments:
1. The TCE/perfluoroalkyl resin solutions are extremely
toxic to quail.
2. The mixtures are more toxic to rats than the solvent
alone.
3. T-3500 dilutions are less toxic than T-3500 but are more
toxic than the solvent alone."
238
,-
-------
8EHQ-I084-0535
Page 3 of 6
"Human Exposure Study: Since T-3500, when sprayed directly
into the chamber, was more toxic than expected, simulated
applications were run to determine if users of spray products
containing T-3500 could be at risk. During use, the product
is sprayed away from the user's breathing zone on to a sub-
strate. Most of the resin is deposited onto the cloth.
Therefore, the actual resin level that the user is exposed to
is less than that sprayed directly into the chamber.
"As an exaggerated use condition, four 16 oz. containers of
T-3500 were sprayed sequentially onto 10 square yards of cloth
in an unventilated room. Operator breathing zone levels of
TCE ranged from 563 ppm after spraying one container to 1650
ppm after four [containers]. The analysis of resin levels
vari3d inconsistently. Levels ranged from 0.008 to 0.130
mg/m. (This may indicate an analytical or contamination
problem.) Particle size was not determined. There appears to
be an estimated 30 to 60 fold reduction in resin levels in the
applicator's breathing zone as compared to the measured resin
values in the animal inhalation studies.
"Additional Human Exposure Study: Air sampling was conducted
during the spraying of a sofa in a room following the instruc-
tions on the 16 oz. product. Three cans were used. Maximum
TCE levels in the operator breathing zone were achieved after
spraying one can (136 ppm). TCE levels averaged 34 ppm over
the time period for spraying 3 cans. Again, resin values
varied inconsistently (nondetectab1e to 0.095 mg/m3). Resin
particle size was not determined.
"The air sampling data indicate that in simulated use:
1. TCE levels vary widely depending on the amount of
aerosol sprayed and the degree of ventilation in the
room.
2. Perfluoroalkyl resin levels are not yet reliably
known."
Current Production and Use
The 3M Company provided the following information concerning the
uses of commercial products containing TCE and perfluoroalkyl
resins.
"Perfluoroalkyl resins are constituents of some stain
repellent products. Numerous stain repellent products are
sold by 3M and other manufacturers. Most are sold as water
emulsions for application by fabric mills and would not be
included in the consideration of this [TSCA Section] 8(e)
submittal. 3M does sell five products that contain 1,1,1-
trichloroethane solutions of perfluoroa1kyl resins: two of
these products are sold as high solids industrial products
for use by textile finishers~ and one is a ready-to-use
239
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8EHQ-I084-0535
Page 4 of 6
formulation applied by the retailer as an airless spray, under
controlled conditions, to upholstered furniture. A fourth
product is sold as an industrial product used by leather
finishers and to a smaller extent as a concentrate for
formulation in an aerosol stain repellent sold by retail
outlets. ...[3M] believe[s] the manufacture of these pro-
ducts, and their use by industrial customers or licensed
retailers, does not present a risk to workers because the
recommended industrial hygiene procedures and precautions
preclude significant exposure to the mixtures.
"The fifth product is an aerosol stain repellent sold by
retail outlets. During the past two decades tens of millions
of units have been sold. Given this broad consumer experience
with the product, the numbers of adverse health complaints
have been low. Pulmonary complaints have numbered about 25
since 1965. There have been no known deaths from the use of
the product under normal or misuse conditions. There have
been 7 known deaths in the u.s. due to intentional abuse,
i.e., deliberately inhaling spray from a bag, (4 teenage
males, 1 male and 1 female in their 20's, and 1 unknown).
"The toxicity and simulated use air sampling data indicate
aerosol usage of a TCE/perfluoroalkyl resin mixture may pre-
sent a greater hazard than was previously thought. However,
the 20 years of customer history would indicate the risk (the
probability of the hazard occurring) is quite low. The
reasons for this may be attributable to:
1. Time of exposure. It takes about 6 minutes to spray a
16 oz. container which is enough to cover 20-50 square
feet of cloth. The toxicity studies are based on
exposures where the material is being continuously
sprayed into the test chamber for 4 hours.
2. Ratio of the Mixture. The aerosol product is intended
to deposit the resin directly onto the material. The
actual amount of resin available for inhalation with
solvent is extremely low.
3. Labelling. The current aerosol product label instructs
the user to provide adequate ventilation, including fans
and open windows or to use outdoors if possible. [The
label] warns against using in small rooms, bathrooms, or
closets, that intentional misuse or use in a poorly ven-
tilated or closed area may be harmful or fatal and that
small children and pets should be kept out of the area
until treated substrate is dry."
Submission Evaluation
The submitting company compared the LC50 for l,l,l-trichloro-
ethane (TCE) aerosol propellant (which was determined to be
approximately 14,000 ppm for both rats and quail) with the LC50
240
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8EHQ-I084-0535
Page 5 of 6
for a mixture containing 99% l,l,l-trichloroethane and 0.5%
perfluoroalkyl resin, plus additional organic compounds including
0.3% methyl isobutyl ketone. The LC50 was dramatically reduced
in the 4-hour inhalation tests on the mixture: 170 ppm TCE (with
approximately 2 mg of resin per cubic meter of air) in the rat
and 14 ppm TCE (with approximately 2 mg of resin per cubic meter
of air) in the quail. Death was attributed by the testing
laboratory to unspecified "pulmonary effects rather than CNS
depression or cardiac sensitization," based on preliminary gross
pathology findings. Approximately 95% of the resin particles
were of respirable size. It may be misleading to speak of the
LC50 in terms of units (ppm) of TCE. The experiment does not
establish (nor rule out) that a synergistic reduction in the LC50
for TCE has occurred~ TCE may have been no more than an inert
carrier that was measured for convenience, assuming a reasonably
homogenous mixture, with toxicity being attributable to the
resin. If the toxicity is in fact due chiefly or exclusively to
the resin, then this submission is an instructive exception to
general expectations that polymers are inherently non-toxic.
The final reports (including protocols and experimental data)
from all of the cited studies should be requested by EPA in order
to evaluate more fully the reported toxicologic findings. In
particular, it would be useful to know the nature of the observed
"pulmonary effects." It would also be useful to know whether the
perfluoroalkyl resins decompose to yield toxic products, and
under what conditions such decomposition can occur.
The submission does not make clear whether the tested substances
have been used in marketed products for either professional or
consumer use. Although it is inviting to reason that the poten-
tial human hazard is probably minimal (because great numbers of
aerosol cans have been used without serious harm), this conclu-
sion may be untenable if the experience with human exposures has
involved different resins, or if cases of toxicity have occurred
but have gone unrecognized or unreported.
Comments/Recommendations
According to 3M, additional inhalation studies are underway and
aerosol product labels are being revised in order to place
greater emphasis upon the precautions to be observed during
use. In addition, 3M reported that the Consumer Product Safety
Commission (CPSC) and foreign governments were being notified
about the findings presented in the company's TSCA Section 8(e)
submission.
EPA's Office of Toxic Substances (OTS) has received and evaluated
a number of TSCA Section 8(e) and "For Your Information" (FYI)
submissions containing toxicologic and/or exposure information on
methyl isobutyl ketone, l,l,l-trichloroethane and perfluoroalkyl
compounds. It should also be noted that the Risk Management
Branch (RMB/ECAO/OTS) is currently evaluating available toxico-
logic and exposure data on a number of perfluoroalkyl compounds.
241
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8EHQ-I084-0535
Page 6 of 6
Finally, the Test Rule Development Branch (TRDB/ECAD/OTS) is
currently evaluating available toxicologic and exposure data on
l.l.l-trichlorethane and methyl isobutyl ketone, chemicals that
were recommended by the Interagency Testing Committee (ITC) for
testing consideration by EPA under Section 4 of TSCA.
a) The Chemical Screening Branch (CSB/ECAD/OTS/OPTS) will request
the 3M Company to ensure that EPA receives a complete copy of
the final report (including the actual experimental protocol
and data) from each of the toxicity and human exposure studies
that were cited in the company's submission.
In light of the Agency's general interest in corporate actions
that are taken on a voluntary basis in response to chemical
toxicity and/or exposure information, the Chemical Screening
Branch will ask the 3M Company to describe the nature of all
other studies that the company has conducted, is conducting,
or is planning to conduct to define the toxicity of and/or the
exposure to TCE/perfluoroalkyl resin mixtures. In addition,
3M will be asked to describe the actions the company has taken
to notify 3M workers about the reported findings. Finally, 3M
will be asked if the company's revised product label will in-
clude further more explicit wording with regard to potential
serious health effects.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further OTS
assessment of the subject chemicals.
c) The Chemical Screening Branch will send copies of this status
report to OSHA, NIOSH, CPSC, FDA, NTP, OSWER/EPA, OW/EPA,
ORD/EPA, OAR!EPA, and RMB and TRDB/ECAD/OTS. In addition,
copies of this report will be sent to the TSCA Assistance
Office (TAO/OTS) for further distribution.
242
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UNITED STATES ENVIRONMEHTAL PROTECTJO~AGENCY
DATE:
DEC I 7 1984
8EE(}-1l84-0536
Page I of 3
APp:oved~ /~/17}f~
5UaJEtTI status Report* 8EHQ-1184-0536
'10161 David R. Williams~~cting Section Head
Chemical Risk Identification Section/CSB
Revision
Needed
TOI Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Gulf Oil products Company provided the following summarized
information concerning the results of two genotoxicity tests
conducted with cumene «l~methylethyl)benzene; CAS NO. 98-82-8):
"In the Cell Transformation Test, BALB/3T3 mouse embryo cells
were exposed to cumene while growing in tissue culture. posi-
tive and vehicle controls were run simultaneously. Transfor-
mation was observed at 60 mcg/ml. The test was considered
positive.
"In the second test, the Hepatocyte primary Culture/DNA
Repair Test, primary hepatocytes from Fisher 344 rats were
exposed to cumene while growing in tissue culture. The abili-
ty of the cells to take up radioactive thymidine during the
exposure period was measured. positive and vehicle controls
were run simultaneously. Unscheduled DNA synthesis was ob-
served at 16 mcg/ml. This test was considered positive for
cumene."
In its submission, the Gulf Oil Products Company reported also
that a "Mammalian Cell Point Mutation Test (CHO) and a Chromosome
Aberration (Micronucleus) Test are in progress at the Gulf Life
Sciences Laboratory," but "no information on the outcome-of these
tests [is available] at this time."
Submission Evaluation
Although the submitted information indicates that cumene does
possess some degree of genotoxic activity, a full copy of the
final report (including the actual experimental protocol and
data) from each study that was cited in the submission is needed
~NOTE: This status repo:t is the result of a preliminary
staff evaluation of i~forma~ion subrnitt~c to BPA. State~e~ts
mace herein are no~ to be recrarded as ex~ressir.c final
Agency policy or intent with-res?ec~ to t~is ?articular
chemical. .~y review of the status repo=~ should tak~ into
consideration the fact that it may be based on incomplete
informa tion.
243
E~. '0". IJ~ IIilCY. ~,.,
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8EHQ-1184-0536
Page 2 of 3
in order for EPA to evaluate the significance of the reported
findings. Immediately upon receipt of this submission, a copy
was provided to the Test Rules Development Branch (TRDB/ECAD/OTS)
for inclusion in their review of available toxicologic/exposure
information on cumene, a chemical recently recommended by the
Interagency Testing Committee (ITC) for testing under Section 4
of TSCA.
Current Production and use
A review of the production range (includes importation volumes)
statistics for cumene (CAS No. 98-82-8), which is listed in the
initial TSCA Inventory, has shown that over 2.5 billion pounds of
this chemical were reported as produced/imported in 1977. This
production range information does not include any production/im-
portation data claimed as TSCA Confidential Business Information
(TSCA CBI) by the person(s) reporting for the TSCA Inventory, nor
does it include any information that would compromise TSCA CBI.
The data submitted for the TSCA Inventory, including production
range information, are subject to the limitations contained in
the TSCA Inventory Reporting Regulations (40 CFR 710).
The May 7, 1984 issue of Chemical & Engineering News estimates
that the annual cumene production was 2.74 and 3.30 billion
pounds in 1982 and 1983, respectively.
According to secondary literature sources, cumene is used 1) in
the production of phenol and acetone (major uses), acetophenone,
alpha-methylstyrene, oxidation catalysts, and peroxides; 2) as an
aviation fuel additive; and 3) as a solvent.
Comments/Recommendations
In its submission, the Gulf Oil Products Company stated that the
company plans to conduct a thorough review of its cumene handling
procedures and "intends to review the Material Safety Data Sheet
(MSDS) and the label for ...[cumene] to be sure they delineate
the toxic properties of this material and adequately warn workers
and customers about procedures for safe handling...." The sub-
mitter also stated that "if there is any change in the MSDS, Gulf
will mail the revised form along with an explanatory letter to
all customers of record." Finally, the submitter stated that,
upon completion, copies of the final genotoxicity study reports
would be transmitted to the Agency-
Although a positive genotoxicity test result, when considered
alone, may not be sufficient to offer reasonable support for a
conclusion of substantial risk, the Agency believes that such
results are of value in assessing the possible risks posed by
chemicals to health and/or the environment. EPA also believes
that positive genotoxicity test results in combination with addi-
tional information (e.g., knowledge of potential exposure to or
244
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8EHQ-1184-0536
Page 3 of 3
high production of the chemical substance or mixture), would
suggest, in many cases, the need to conduct additional studies
designed to define better the toxicity of and/or exposure to the
subject chemical substance or mixture. The results of such
studies should be considered also for possible submission to the
Agency under Section 8(e) of TSCA.
On November 28, 1984, EPA published TSCA Section 8(a) and 8(d)
reporting rules (49 FR 46739 and 49 FR 46741, respectively) for
cumene. It should be noted also that the 'Chemical Screening
Branch (CSB/ECAD/OTS) has prepared a Chemical Hazard Information
profile (CHIP) on cumene hydroperoxide, a chemical intermediate
in the cumene-phenol/acetone production process.
(a) The Chemical Screening Branch (CSB/ECAD/OTS) will request the
Gulf Oil Products Company to ensure that EPA receives, when
completed, a full copy of the final report (including the
actual experimental protocol and data) from each genotoxicity
study cited in the submission. Immediately upon receipt of
the requested reports, the Chemical Screening Branch will
provide copies to the Test Rules Development Branch/ECAD for
inclusion in their review of cumene under Section 4 of TSCA.
(b) The Chemical Screening Branch will send a copy of this status
report to NIOSH, OSHA, CPSC, NTP, OW/EPA, OSWER/EPA, ORD/EPA,
OAR/EPA, ORD/EPA, and TRDB/ECAD/OTS. In addition, copies of
this status report will be sent to the TSCA Assistance Office
(TAO/OTS/OPTS) for further distribution.
245
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UNITED STATES EHV1RONMENTAL PROTECTION AGENCY
8EHQ-1l84-0537
Page I of 3
CAn;
DEC I 1 1984
APp=oved~ 'i/1/8y
Revision
Needed
SUIJ£CT, Status Report* 8EHQ-1184-0537
,"00. David R. Wi1liamS~Cting section Head
Chemical Risk Identification Section/CSB
TOI Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
The Gulf Oil Products Company provided the following summarized
information with regard to the results of several genotoxicity
studies conducted with Gulf's Light pyrolysis Fuel Oil:
"Light pyrolysis Fuel Oil was tested for the ability to
damage DNA in the primary rat hepatocytes growing in tissue
culture by using autoradiography to measure the ability of
the cells to incorporate radioactive thymidine. vehicle and
positive control groups were run simultaneously. unscheduled
DNA Synthesis was observed at 8 mcg/ml. The Study Director
concluded that the test was positive for genetic damage.
"Three other genetics tests have been performed on this
product. A Mammalian Cell point Mutation Test was negative
for point mutations. The material had no effect on the fre-
quency of micronucleated erythrocytes in the bone marrow,
i.e., the Micronucleus Test was negative. In a Cell Trans-
formation Test in BALB/3T3 Mouse Embryo Cells, transforma-
tion was not observed at any level of Light pyrolysis Fuel
Oil dosing."
Submission Evaluation
Although the submitted information indicates that Gulf's
pyrolysis Fuel Oil does possess some degree of genotoxic
vity, a complete copy of the final report (including the
experimental protocol and data) from each study cited in
submission is needed in order for the Agency to-evaluate
significance of. the reported findings.
Light
acti-
actual
the
the
-NOTE: T~is status reco=t is the resu2t of a crelirninarv
staff evaluation of i~fo~.ation subrnitt~c to EPA. State;e~ts
mace herein are no~ to be re~arded as ex~ressinc final
Agency policy or intent with-IesDect to ~his ?a~ticular
chemical. .;ny review of the status report should take into
consideration the tact that it may be based on incompletG
information.
246
I:~. '0"'. U~ UII:V. ~,.,
-------
8EHQ-1l84-0537
Page 2 of 3
Current Production and use
Although no Chemical Abstract Service (CAS) Number was located
for Light pyrolysis Fuel Oil, the TSCA Inventory (Appendix A)
defines pyrolysis fuel oil as follows:
"The complex combination of hydrocarbons obtained from the
initial water quenching of the effluent gases from a thermal
cracking of ethane, propane or light naphtha. This stream is
likely to contain 5 wt. % or more of 4- to 6- membered con-
densed ring aromatic hydrocarbons."
A review of the production range (includes importation volumes)
statistics for pyrolysis fuel oil (CAS No. 69013-21-4), which is
listed in the initial TSCA Inventory, has shown that no 1977 pro-
duction/importation was reported or that all of the production
range data reported were claimed as TSCA Confidential Business
Information (TSCA CBI) by the manufacturer(s) and/or importer(s)
and cannot be disclosed (Section 14(a) of 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 TSCA Inventory Reporting Regulations (40 CFR 710).
The Gulf Oil Products Company did not provide any
with regard to the current production or specific
Light pyrolysis Fuel Oil nor was such information
secondary literature sources consulted.
information
use(s) of its
located in the
Comments/Recommendations
In its submission, the Gulf Oil Products Company reported that it
"intends to review the Material Safety Data Sheet and the label
for ...[Gulf's Light pyrolysis Fuel Oil] product to be sure they
adequately reflect the toxi~ity data available and that the pro-
tective practices recommended are adequate to protect both Gulf
workers and customers." The submitter also reported that "if
there is any change in the MSDS, Gulf will mail the revised form
with an explanatory letter to all customers of record." Finally,
the Gulf Oil Products Company stated that copies of the final
genoxicity study reports (upon completion) would be sent to EPA.
Although a positive genotoxicity test result, when considered
alone, may not be sufficient to offer reasonable support for a
conclusion of substantial risk, the Agency believes that such
results are of value in assessing the possible risks posed by
chemicals to health and/or the environment. EPA also believes
that positive genotoxicity test results in combination with addi-
tional information (e.g., knowledge of potential exposure to or
high production of the chemical substance or mixture), would sug-
gest, in many cases, the need to conduct further studies designed
to define better the toxicity of and/or exposure to the chemical
substance or mixture. The results of such further studies should
be considered also for possible submission to the Agency under
Section 8(e) of TSCA.
247
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8EHQ-1l84...0537
Page 3 of 3
EPA's Office of Toxic Substances (OTS) has received and evaluated
a number of TSCA Section 8(e) and "For Your Information" submis-
sions containing toxicologic and/or exposure data on a variety of
coal, shale, and petroleum oils, process streams, and/or wastes.
(a)
The Chemical Screening Branch (CSB/ECAD/OTS) will
request the Gulf Oil Products Company to ensure that
EPA receives, when completed, a full copy of the final
report (including the actual experimental protocol and
data) from each genotoxicity study that was cited in
the company's submission.
In view of EPA's general interest in company actions
that are taken on a voluntary basis in response to
chemical toxicity/exposure information, the Chemical
Screening Branch will request the submitting company
to describe all other studies that it has conducted,
is conducting, or plans to conduct to define the toxi-
city of and/or the exposure to Gulf's Light pyrolysis
Fuel Oil.
(b)
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of Light pyrolysis Fuel Oil.
( c)
The Chemical Screening Branch will send a copy of this
status report to NIOSH, OSHA, DOE, CPSC, NTP, OW/EPA,
OSWER/EPA, OAR/EPA and ORD/EPA. Copies of the status
report will also be provided to the TSCA Assistance
Office (TAO/OTS/OPTS) for further distribution.
248
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UNITED STATES EHY1RONMENTAL PROTECTION AGENCY
DATE:
DEC 2 0 1984
8SIIQ-~284-0538
Page 1 of 2
suaJ&CT, status Report* 8EHQ-1284-0538
nOM, David R. Williams4t1fcting Section Head
Chemical Risk Identification Section/CSB
App=oved
d&: Ir~llf#/
Revision
Needed
TO, Frank D. Kover, Branch Chief
Chemical Screening Branch/ECAD/OTS/OPTS
Submission Description
Air products and Chemicals, Inc. provided the following summary
with regard to the interim results of an ongoing 2-year inhala-
tion study of Solvent-Refined Coal (SRC) Solid "dust" in rats.
According to the company,
"An intermediate (12 months) sacrifice has been performed, and
the preliminary results obtained indicate occurrence of tumors
in only the females of the highest exposure group (50 mg/m3).
They have been initially described as keratinizing squamous
epithelioma (a potentially malignant tumor). pathological
evaluation of tissues from the lower exposure groups is being
undertaken. This inhalation study will continue for another
year after which time more complete data will be available."
In its submission, Air products and Chemicals, Inc. reported that
this study is being conducted by the company under contract for
the U.S. Department of Energy (DOE). In addition, the company
noted that "two [Section] 8(e) Notices previously submitted ...by
the International Coal Refining Company [8EHQ-0683-0482 and 8EHQ-
1283-0482 Followup] reported positive results in an Ames Test and
Mouse Lymphoma Test using [a] DMSO extract of the SRC Solid and
on other portions of SRC-I solids. Those previous [Section] 8(e)
notices are related to the present one."
Submission Evaluation
Although the reported interim findings do indicate that SRC Solid
dust possesses some degree of oncogenic activity in female rats,
complete copies of future interim reports and the final report
(including the experimental protocol and data) from the 2-year
inhalation study are needed in order for the Agency to evaluate
the significance of the findings.
-NOTE: This status reoort is the result of a orelirnina=v
staff evaluation of i~£o=mation ~ubrnlttec to EPA. Sta~e;e~ts
mace herein are no~ to be re~arded as ex~ressir.a final
Agency policy or int~nt with~res?ec~ to t~is particular
chemical. .~y review of the status report should take into
consideration the tact that it may be based on incomplete
information.
249
r~A '0"" u:o"'. I~£"'. ~"I
-------
8EHQ-1284-0538
Page 2 of 2
Current production and Use
Although Air Products and Chemicals, Inc. did not provide any
information concerning current production or use(s) of the sub-
ject SRC material, the International Coal Refining Company did
report (in the previously cited Section 8(e) submissions) that
the "current use of SRC-I materials, in addition to being care-
fully controlled, is limited to research and testing purposes at
a limited number of research and testing facilities." It should
be noted also that a number of SRC materials are listed in the
initial TSCA Chemical Substances Inventory.
Comments/Recommendations
EPA's Office of Toxic Substances (OTS) has received and evaluated
a number of TSCA Section 8(e) and "For your Information" (FYI)
submissions containing toxicity/exposure information on a variety
of coal, shale, and petroleum oil refinery products, streams,
and/or waste materials.
(a) The Chemical Screening Branch (CSB/ECAD/OTS) will request
Air Products and Chemicals, Inc. to provide complete copies
of the experimental protocol, future interim reports, and
final report (including all data) from the 2-year SRC Solid
dust inhalation study that was cited in the submission.
In view of the Agency's general interest in company actions
that are taken in response to chemical toxicity/exposure
information, the Chemical Screening Branch will ask Air
Products and Chemicals, Inc. to describe the actions it has
taken to 1) warn workers and others, and 2) reduce and/or
eliminate exposure to SRC Solid dust. In addition, the
submitting company will be asked to describe the nature of
all other studies that the company has conducted, is con-
ducting, or plans to conduct to define the toxicity of
and/or the exposure to SRC Solid dust.
(b) The Chemical Screening Branch will review the reported
information to determine the need for further OTS assess-
ment of SRC Solid dust.
(c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, DOE, OW/EPA, OSWER/EPA,
OAR/EPA and ORD/EPA. Copies will be provided also to
the TSCA Assistance Office (TAO/OTS/OPTS) for further
distribution.
250
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DAT£:
DEC 2 1 1984
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
8EHQ-l284-0539
Page 1 of 3
SUlaJ£C:T. Status Report* 8EHQ-l284-0539
'10M. David R. Williams~ting Section Head
Chemical Risk Identification Section/CSB
App:,oved
{JA- a/21/t;tf
Revision
Needed
TO,Fran~ D. Kover, Branch Chief
ChemIcal Screening Branch/ECAD/OTS/OPTS
Submission Description
The NOR-AM Chemical Company .provided summarized resul ts from a
battery of in vitro genotoxicity assays of pyrogallol (1,2,3-
benzenetriol; CAS No. 87-66-1). According to the submitter,
pyrogallol was found to be positive in' the presence and absence
of exogenous metabolic activation in 1) an Ames Test (Salmonella
typhimurium bacteria strains TA 100 and TA 1537); 2) a cultured
Mouse Lymphoma Cell Assay; and 3) a Metaphase Chromosome Analysis
of cultured human lymphocytes. The submitter reported that the
posi tives obtained in the performed studies "w,ere produced by
concentrations which were at or close to toxic levels in each
test system." The submitter also stated that these results are
not com~letely unexpected in that "pyrogallol is structurally
similar to the catechols which are mutagenic in in vitro test
systems."
Submission Evaluation
Considering that the 1981-82 National Institute for Occupational
Safety and Health (NIOSH) Registry of Toxic Effects of Chemical
Substances (RTECS) cites a variety of in vitro and in vivo geno-
toxicity studies in which pyrogallol was found to bepositive,
the submitted information appears to provide additional evidence
that pyrogallol is genotoxic. A full copy of the final report
(including the actual experimental protocol and data) from each
study cited in the submission is needed in order for the Agency
to evaluate the significance of the reported findings.
-NOTE: T~is status reco=t is the result of a crelirnina:y
staff evaluation of i~£orrnation submittec to EPA. Sta~eme~~s
mace herein are no~ to be regarded as ex?ressing final"
Agen~y poli~y or intent with res?e~~ to t~is particular
chemical. .~y review of the status report should tak~ into
consideration the fact that it may be based on incomolete
information. .. ..
251
r~A '0'-" II~ IRii:V. ~,..
-------
8EHQ-1284-0539
Page 2 of 3
Current production and Use
A review of the production range (includes importation volumes)
statistics for pyrogallol (CAS NO. 87-66-1), which is listed in
the initial TSCA Inventory, has shown that between 10 thousand
and 101 thousand pounds were reported as produced/imported in
1977. This production range information does not include any
production/importation data claimed as TSCA Confidential Business
Information (CBI) by the person(s) reporting for the Inventory,
nor does it include any information that would compromise TSCA
CBI. All data submitted for the Inventory, including production
range information, are subject to the limitations contained in
the TSCA Inventory Reporting Regulations (40 CFR 710).
According to secondary literature sources, pyrogallol is used as
an intermediate in the manufacture of a variety of substances
(e.g., dyes, inks), as an antioxidant in lubricant oils; as an
analytical reagent; as a reducing agent; as an antibacterial in
medicine; as an intermediate in drug synthesis; as a photographic
process chemical; and as a component in cosmetics and hair dyes.
Comments/Recommendations
Although a positive in vitro genotoxicity test result, when con-
sidered alone, may not be sufficient to offer reasonable support
for a conclusion of substantial risk, the Agency believes that
such results are of value in assessing the possible risks posed
by chemicals to health and/or the environment. EPA also believes
that positive genotoxicity test results in combination with addi-
tional information (e.g., knowledge of potential exposure to or
high production of the chemical substance or mixture), would sug-
gest, in many cases, the need to conduct further studies designed
to define better the toxicity of and/or exposure to the chemical
substance or mixture. The results of such further studies should
be considered also for possible submission under Section 8(e).
(a) The Chemical Screening Branch (CSB/ECAD/OTS) will request
the NOR-AM Chemical Company to submit a full copy of the
final report (including the actual experimental protocol
and data) from each genotoxicity study that was cited in
the company's submission.
In light of the Agency's general interest in corporate
actions that are taken on a voluntary basis in response
to chemical toxicity/exposure information, the Chemical
Screening Branch will ask the NOR-AM Chemical Company to
describe the actions the company has taken to 1) warn
workers and others, and 2) reduce or eliminate exposure
to pyrogallol. In addition, the NOR-AM Chemical Company
will be asked to describe all other studies that the com-
pany has conducted, is conducting, or plans to conduct to
define the toxicity of and/or the exposure to pyrogallol.
252
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8EHQ~1284-0539
Page 3 of 3
(b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of pyrogallol.
(c) The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, FDA, CPSC, NTP, OSWERjEPA,
OWjEPA, OARjEPA, ORDjEPA, and OPPjOPTS. In addition,
copies of this report will sent to the TSCA Assistance
Office (TAOjOTSjOPTS) for further distribution.
253
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DAU:
.2311&
UNITED STATES EHYIROHMENTAL PROTECTION AGENCY
8EHQ-1284-0540 S
Page 1 of 4
SUaJECT. Stat-llS Report* 8EHQ-1284-0540 S
'10M. David R. Williams~ction 8(e) 'Coordinator
Chemical Risk Identification Section/CSB
~pp:oved
rJIIr f1N
Revision
Needed
TOI Fran~ D. Kover, Branch Chief
Chem~cal Screening Branch/ECAD/OTS/OPTS
Note
The submitting company has claimed its company name and the
amount of each constituent in the tested mixture to be TSCA
Confidential Business Information. The Information Management
Division (IMD/OTS) has requested the submitter to substantiate
these confidentiaLity claims.
Submission Description
The submitting company provided the following summarized findings
from three acute rabbit dermal application studies of a mixture
comprised of imidazole and 2-ethyl-4-methylimidazole:
"A mixture of ...imidazole (CAS [NO.] 288-32-4) ... [and]
2-ethyl-4-methylimidazole (CAS [~o.] 931-36-2) applied at
2 Gm/Kg of body weight to the shaved skin of albino rabbits
produced death in 10 of 10 animals between 4 and 24 hours
after dosing. In another experiment, this effect was con-
firmed in the death of 3/3 animals with the same formulation
but using other chemical lot numbers. In a third study, two
of three animals also died using the same formulation but
with ingredients supplied by another manufacturer."
In its submission, the company noted that 1) "no toxicological
information exists on 2-ethyl-4-methylimidizole" and 2) "there
...[are] no dermal toxicity data on imidazole."
Submission Evaluation
In order to evaluate the significanc~ of the reported findings,
the submitter should be asked to provide a full copy of the final
report (including the actual experimental protocol and data) from
each of the cited acute dermal application studies. Without such
information, one can only speculate about the possible cause(s)
of the observed lethality: 1) the 2-ethyl-3-methylimidazole may
be the more potent toxicant in the.mixture; 2) there could be
synergism or some type of dose-addition or response-addition
-NOTE: T~is status recort is the resul~ of a prelimina:v
staff evaluation of i~forma~ion submitted to EPA. State;ents
mace herein are no~ to be re~arded as ex~ressfr.o final
Agency policy or intent with~r~s?ec~ tot~is particular
chemical. .~y review of the status repor~ should take into
consideration the iact that it may be based on-incomplete
informa tion. 254
t~. '0". U:D-t ."1:.... ~,.,
-------
8EHQ-1284-0540 S
Page 2 of 4
between the constitutents of the mixture; 3) an unidentified
toxic contaminant may be present in the mixture; and/or 4) the
dermal ~oute of exposure to the mixture could make a real dif-
ference in terms of the observed toxicity.
Current Production and use
A review of the production range (includes importation volumes)
statistics for imidazole (CAS No. 288-32-4), which is listed in
the initial TSCA Inventory, has shown that between 101 thousand
and 1 million pounds were reported as produced/imported during
1977. **/
A review of the production range (includes importation volumes)
statistics for 2-ethyl-4-methylimidazole (CAS No. 931-36-2),
which is listed in the initial TSCA Inventory, has shown that
between 1 thousand and 13 thousand pounds were reported as
produced/imported during 1977. **/
The submitting company
the current production
components. According
is used (in many cases
the biological control
reportedly used in the
did not provide any information concerning
or use(s) of the tested mixture or its
to secondary literature sources, imidazole
in combination with other chemicals) for
of insects; 2-ethyl-4-methylimidazole is
curing of epoxy resins.
Comments/Recommendations
It should be noted that it has been EPA's longstanding position
that certain types of acute animal toxicity information may not
warrant submission to EPA under Section 8(e), the "substantial
risk" information reporting provision of the Toxic Substances
Control Act (TSCA). The basis for EPA'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 [adverse] 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 effects for which substantial
[[[
**/
This production range information does not include any
production/importation data claimed as TSCA Confidential
Business Information (TSCA CBI) by the persons reporting
for the TSCA Inventory, nor does it include any informa-
tion that would compromise TSCA CBI. The data submitted
for the TSCA Inventory, including production range data,
-------
8EHQ-l284-0540 S
Page 3 of 4
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." Information with
respect to these effects can be obtained directly or inferred
from designed studies (e.g., in vivo experiments as described
in Part VI of the TSCA Section-8~policy statement). With
regard to the criterion concerning the "fact or probability"
of the occurrence of such effects, part V of the TSCA Section
8(e) policy statement explains that certain types of health
effects are so serious that relatively little weight should
be given to the chemical's exposure in determining whether a
risk is substantial.
EPA's response to Comment 14 in Appendix B of the Section
8(e) policy statement provides guidance concerning the 8(e)-
applicability of results obtained from routine acute in vivo
range finding studies (e.g., LD50 determinations, skinve~
irritation tests, etc.). In its response, the Agency stated
that "many routine tests are based on knowledge of toxicity
associated with a chemical...." EPA's response also directed
that unknown effects that occur and are observed/determined
during such routine studies may have to be reported to EPA
under Section 8(e) if such effects are serious and meet the
reporting requirements set forth in the Section 8(e) policy
statement. Thus, when evaluating the results of acute animal
toxicity studies for possible submission to EPA under Section
8(e), the Agency believes that subject companies should con-
sider such factors as the lethal dose, the pH of the tested
chemical or mixture, the route of administration, the occur-
rence of unexpected effects (which could be determined via
"cage-side" observation or during necropsy), and the extent
and pattern of the actual or potential exposure to the tested
chemical or mixture. In general, when evaluating such infor-
mation for TSCA Section 8(e) reporting, the greater the acute
toxicity, the less heavily a subject company should weigh the
exposure to the tested chemical or mixture, and vice versa.
In light of the preceeding discussion, it does not appear that
the acute toxicity information, as presented in this submission,
warranted reporting at this stage under Section 8(e) of TSCA. In
making this initial determination, however, it should be under-
stood that the Agency may not be aware of additional pertinent
information that may have been available to and/or considered by
the submitting company in deciding to report the findings to EPA
under Section 8(e) of TSCA.
a) The Chemical Screening Branch will request the submitting
company to provide a full copy of the final report (in-
cluding the actual experimental protocol and data) from
each toxicity study that was cited in the submission. In
addition, the submitting company will be asked to provide
its rationale (in light of the discussion presented in the
256
-------
8EHQ-1284-0540 S
Page 4 of 4
Comments/Recommendations section of this report) as
the acute in vivo toxicity information as presented
submission-WaSiEelieved to have warranted reporting
under Section 8(e) of TSCA.
to why
in the
to EPA
In view of EPA's general interest in company actions that
are taken on a voluntary basis in response to chemical
toxicity/exposure information, the submitting company will
be asked to describe the actions it has taken or plans to
take to (1) warn workers and others, and (2) reduce or
eliminate exposure to the tested chemicals. In addition,
the submitting company will be requested to describe the
nature of all other studies that it has conducted, is con-
ducting, or plans to conduct that are designed to further
define the toxicity of and/or the exposure to the tested
mixture or its components.
b) The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of the subject chemicals.
c) The Chemical Screening Branch will send a copy of this
status report to NIOSH, OSHA, CPSC, FDA, NTP, OW/EPA,
OSWERjEPA, OAR/EPA, ORD/EPA, and OPP/OPTS. Copies of
this report will be sent also to the TSCA Assistance
Office (TAO/OTS/OPTS) for further distribution.
257
-------
UNITED STATES EHYIRONMENlAl. PROTECTION AGENCY
8EHQ-1284-0541 S
Page I of 2
DAn:
JAN - 9 1985
SUlu£CTI Status Report* 8EHQ-1284-0 541 S
"OM, Dav id R. Will i ams ~ct ion 8 ( e ) Coord i na tor
Chemlcal Risk Identification Section/CSB
App:-oved
~
/ jll hS
I '
Revision
Needed
TO Frank D. Kover, Branch Chie f
I Chemical Screening Branch/ECAD/OTS/OPTS
Note
The sUQmitting company has claimed its company name as TSCA
Confidential Business Information (CBI). The Information
Management Division (IMD/OTS) has requested the submitting
company to substantiate this confidentiality claim.
Submission Description
The submitting company provided summarized findings from two. in
vitro genotoxicity studies of benzofurazan-I-oxide (CAS NO. 480-
96-6). Accord ing to the company, the chemical" tested pos i tive
for mutagenicity in both the Ames Salmonella/Microsome plate Test
(with activation) and the Mouse Lymphoma Cell Forward Mutation
Assay (with and without activation)."
Submission Evaluatibn
It should be noted that there are several published scientific
papers which present information on the genotoxic activity of
benzofurazan-l-oxide in bacteria. Although the summarized in-
formation contained in this submission indicates also that the
chemical possesses some degree of genotoxic activity in bacteria
(as well as in cultured mouse cells), a complete copy of the
final report (including the actual experimental protocol and
data) from each study cited in th~ submission is needed in order
for EPA to evaluate the significa~ce of the reported findings.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for benzofurazan-l-oxide (CAS No. 480-96-6), 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 TSCA Confidential Business
Information (TSCA CBI) by the manufacturer(s) and/or importer(s)
and cannot be disclosed (TSCA Section l4(a), U.S.C. 26l3(a)).
The data submitted for the TSCA Inventory, including production
range information, are subject to the limitations contained in
the TSCA Inventory Reporting Regulations (40 CFR 710).
-NOTE: T~is status reco:-t is the result of a prelirnina:-v
staff evaluation of i~formation submittec to EPA. State;ents
mace" herein are no~ to be regarded as expressing final
Ase~cy policy or intent with respect to t~is ?articular
chemical. .;ny review 6f the status report should take into
consideration the iact that it mav be based on incornolete
informa ticn. 258 .. ..
E,.r '0"11 IJ~ 11111:\01. ...".
-------
8EHQ-1284-0541 S
Page 2 of 2
The submitting company did not provide any information regarding
the current production or specific use(s) of benzofurazan-l-
oxide. The submitter did report, however, that the chemical is
being used "on an experimental basis" by the company. According
to secondary literature sources, benzofurazan-I-oxide is used as
a laboratory reagent.
Comments/Recommendations
Although a positive in vitro genotoxicity test result, when
considered alone, maY-not be sufficient to offer reasonable
support for a conclusion of substantial risk, EPA believes that
such results are of value in assessing the possible risks posed
by chemicals to health and/or the environment. In addition, EPA
believes that positive genotoxicity test results in combination
with additional information (e.g., knowledge of potential expo-
sure to or high production of the chemical substance or mixture)
would suggest, in many cases, the need to conduct other studies
designed to better define the toxicity of and/or exposure to the
chemical substance or mixture. The results of such additional
studies should be considered also for possible submission under
Section 8(e) of TSCA.
( a)
The Chemical Screening Branch (CSB/ECAD/OTS) will ask
the submitting company to provide a full copy of the
final report (including the actual experimental proto-
col and data) from each genotoxicity study cited in the
company's submission.
(b)
In light of the Agency's general interest in corporate
actions that are taken on a voluntary basis in response
to chemical toxicity/exposure information, the Chemical
Screening Branch will ask the submitting company to de-
scribe the actions it has taken or plans to take to 1)
warn workers and others, and 2) reduce or eliminate ex-
posure to benzofurazan-I-oxide. In addition, the sub-
mitter will be asked to describe all other studies that
the company has conducted, is conducting, or plans to
conduct to better define the toxicity of and/or the
exposure to benzofu,azan-I-oxide.
The Chemical Screening Branch will review the reported
information in order to determine the need for further
OTS assessment of benzofurazan-I-oxide.
( c )
The Chemical Screening Branch will send copies of this
status report to NIOSH, OSHA, FDA, CPSC, NTP, OW/EPA,
OSWER/EPA, OAR/EPA, ORD/EPA, and OPP/OPTS. Copies of
this report will be sent also to the TSCA Assistance
Office (TAO/OTS/OPTS) for further distribution.
259
-------
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AP£ENDlX A
THURSDAY, MARCH 16, 1978
PART V
ENVIRONMENTAL
PROTECTION
AGENCY
.
TOXIC SUBSTANCES
CONTROL ACT
Statement of Interpretation and
Enforcement Policy; Notification
of Substantial Risk
260
-------
11110
[6560-01]
ENVIRONMENTAL PROTECTION
AGENCY
[FRL 849-2]
TOXIC SUIST AHCES CONTROL ACT
Notification of s..bltantlol 1111e Unde.
Sedlon I(e)
AGENCY: Environmental Protection
Agency.
ACTION: Statement of interpretation
and enforcement policy.
SUMM.ARY: This action states EPA's
interpretation of, and enforcement
policy concerning. section 8(e) of the
Toxic Substances Conlrol Act (TSCA)
(90 Stat. 2029, 15 U.S.C. 2607). The
provisions of that section went into
effect on January 1, 1977.
Section 8(e) states that "any person
who manufactures, processes. or dis-
tributes in commerce a chemiclI.I 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 Admlnis.
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
publ1cation.
FOR FURTHER INFORMATION
CONTACT:
Frank D. Kover, Assessment Dlvi.
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.
mlnistrative 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, f977 (42 FR
54857). On November 4, 1977, a supple-
mental notice to the proposed guld.
ance was publ1shed (42 FR 57744), de.
leting the November 15 date for reo
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 (F~bru-
NOTICES
ary 1. 1977. and October 26. 197'/) 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 th.;'! September 9 proposal
from trade associations, businesses. en-
vironmental groups. labor unions,
State and Federal agencies, and other
interested parties. Appendix B de-
scribes slgnlfJcant issues raised In
these comments and the Agency's reo
sponse to them.
The major modifications to the Sep-
tember II 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 frorn 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 conflictJng
responsibilities as individual respon-
dents and as corporate agents. Other
commenters expressed support for the
view that certain employees have a r~-
sponsibllity to report pertinent InfoI"
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 ill-considered
submissions.
The Agency now feels that these ob.
jectlves would best be served by allow-
ing commercial establishments-under
certain conditions designed to en.sure
full disclosure-to assume exclusive re-
sponsibility for reporting to EPA any
substantial-risk information obtained
by Individual officers or employees,
Accordingly, this polky statement
stipulates that individual officers and
employees will have fully discharged
their section 8(e) obligations once they
have notified the designated responsi-
ble l'ompany 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: 0)
Specify the information that must be
reported; (2) indicate how the notifica-
tions are to be prepared and submit-
ted: (3) note the Fcderal 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 wh€'th-
er or not they were submitted to EPA
(and If not. Informing employees of
their right to report to EPA, as pro-
tected by TSCA sectIon 23). EPA be-
lieves these four criteria wiJ! ensure
prompt and appropriate processing of
pertinent Information.
Establishment of such procI?dures
notwithstanding, all officials responsi-
ble and having authority for the orga-
nization's execution of Its section 8(e)
obligations retain personal liability for
ensuring that substantial-risk informa-
tion Is reported to EP A.
(3) The September 9 proposal stated.
in Part III. that a person obtains in-
formation when he Is aware that it
"may suggest" substantial risk. Nu-
merous cornmenters 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 substantiai 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 polley
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 1, 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 ha.s
FEDERAllEGISTER, VOL. 43, NO. 52-THURSDAV, MARCH 16, 1~?8
261
-------
been aware since January 1. 1977. In
response to requests for clarification,
the statement defines what constitutes
such awareness. In this manner. EPA
Intends to limit the need for searches
of historical records and flies.
(6) This policy statement now pro-
vides that any Information pubJJshed
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(1') 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-
ura! person, corporation, firm, com-
pany, joint-venture, partnership. sole
proprietorship, association, or any
other business entity, any Sta.te 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(1') 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 bus!-
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(1') 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 01 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 and 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 EPA, 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 accord:mce with them, shall
have discharged his section 8(1') obli-
gation. Establishment of such proce-
dures notwithstanding, all officials re-
sponsible and having liuthorlty for the
organization's execution of its section
8(1') obligations retain personal liabil-
ity for ensuring that the appropriate
substantial.rlsk information Is report-
ed to EPA.
Business organizations that do not
establish such procedures cannot re-
lieve their individual officers and em-
ployees of the responslbllty for ensur.
Ing that substantial-risk Information
they obtain is reported to EPA. While
officers and employees of such organi-
zations may also elect to submit sub-
stantial-risk Informlitlon to their supe-
riors for corporate processing and re-
porting, rather than to EPA directly,
they have not discharged their Individ-
ual section 8<1') obligation until EPA
has received the information.
NOTE.-IrrespecUve of a business organiza-
tion's decision to establish and publicize the
procedures descrlbt.ct above. It 18 responsible
for becoming cogntz.a.nt of any substantial-
risk information obtained by Its officers and
employees, and for ensuring that such Infor-
mation 18 reported to EPA wtthln 15 work-
Ing days.
III. WHEN A PERSON WILL Bi!: REGARDED
AS HAVING OBTAINED IN1'ORMATION
A person obtains substantial-risk in-
formation at the time he first comes
11111
into possession of or knows of such in-
formation.
Non:.-Thls Includes Information 01
which a prudent person similarly situated
could reasonably be expected to possess or
have knowledge.
An establishment obtains informa-
tion at the time any officer or em-
ployee capable of appreciating the slg-
nlilcance of such Information obtains
It.
IV. REQUIREMENT THAT A PERsoN "IM-
MEDIATELY INFORM" THE ADMINISTRA-
TOR
With the exception of Information
on emergency Incidents of environ-
mental contamination [see Part V(C»)
a person has "Immediately informed"
the Administrator if information is re-
ceived by EPA not later than the 15th
working day after the date the person
obtained such information. Supple-
mentary Information generated after a
section 8(e) notification should, if ap-
propriate, be immediately reported.
For emergency Incidents of environ-
mental contamination. a person shall
report the incident to the Administra-
tor by telephone as soon as he has
knowledge of the incident (see Part IX
for appropriate telephone contacts).
The report should contain as much of
the information required by Part IX
as possible. A written report In accor.
dance with Part IX (a) through (f) is
to be submitted within 15 days.
Information currently in the posses-
sion of a person who is subject to re-
porting must be reported within 60
days of pUblication of this policy state-
ment.
V. WHAT CONSTITUTES SUBSTANTIAL
RISKS
A "substantial risk of injury to
health or the environment" is a risk of
considerable concern because of (a)
the seriousness of the effect [see Sub-
parts (a), (b). and (c) below for an n-
lustrative list of effects of concern),
and (b) the fact or probability of its
occurrence. (Economic or social bene-
fits of use, or costs of restricting use,
are not to be considered In determin-
ing whether a risk Is "substantial",)
These two criteria are differentially
weighted for different types of effects.
The human health effects listed In
Subpart (a) below, for example, are 80
serious that relatively little weight is
given to exposure; the mere fact the
Implicated chemical is In commerce
constitutes sufficient evidence of expo-
sure. In contrast, the remaining ef-
fects listed in Subparts (b) and (c)
below must Involve, or be accompanied
by the potential for, significant levels
of exposure (because of general pro-
duction levels, persistence. typical
uses, common means 01 dl.sposal, or
other pertinent factors).
Note that: (i) The effects outlined
below should not be reported if the re-
ftDERAL UGISiU. VOL 43, NO. 52-THURSDAY, MARCH 16, 1978
262
-------
11112
spondent has actual knowledge that
the Administrator is already Informed
of t.hem.
; 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,
uniess such information concerns
emergency incidents of environmental
contamination as described in Part
VCc), or
(e) Is contained in notification of
spills under section 31l(b)(5) of the
Federal Water Pollution Control Act.
VIII. INFORMATION FIRST RECEIVED BY
A PERsON PRIOR TO THE EFn:cTm
DATE OF TSCA
Any substantial risk information
possessed by a person prior to January
1, 1977, of which he is aware after that
date shall be reported within 60 dayS
of publication of this policy statement.
The Agency considers that a person is
"aware" of:
(a) Any information reviewed after
January 1, 1977, including not only
written reports, memoranda and other
documents examined after January 1,
1977, but also information referred to
in discussionS and conferences in
wqich the person participated after
January I, 1977;
fEDERAL IROISTEIT. VOL 43. NO. 52-THURSDAY, MAICH 16. 1971
263
-------
(b) Any information the contents of
which a person has been alerted to by
date received after January 1. 1977, In-
cluding any Information concerning a
chemical for which the person Is pres-
ently assessing health and environ-
mental effects;
(c) Any other information of which
the persoi£ has actual knowledge.
IX. REPORTING REQUlREKDTS
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 mall, or in
any other way permitting verification
of Its receipt by the Agency.
(b) State that It Is being submitted
In accordance with section See).
(c) Contain the job title. name, ad-
dress, telephone number. and signa-
ture of the person reporting and the
name and address of the manufactur-
ing, processing. or distributing estab-
lishment with which he Is associated.
(d) IdentlfY.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 written 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, VIrg1n I81ands), 201-548-8730.
Region III (Pennsylvania, West Virginia,
VIrg1nIa, 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, IDinols, Indiana,
Michigan, Ohio, Minnesota), 312-353-
2318.
Region VI (New Mexico, Texas, Oklahoma,
Arkansas, Louisiana>, 214-749-3840.
Region VII (Nebraska, Iowa, Missouri,
Kansu), 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 EPA under section See) of TSCA
may assert a business confidentiality
claim covering all or part of the infor-
mation contained In the notice. Any
Information covered by a claim will be
disclosed by EPA only to the extent.
and by means of the procedures. set
forth In 40 CFR Part 2 (41 FR 36902,
September 1. 1976).
(b) If no claim accompanies the
notice at the time It Is submitted to
EP A, 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 Inf-ormatlon. 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 INFORKATION
Section 15(3) of TSCA makes it un.
lawful for any person to fall or refuse
to submit information required under
section See). Section 16 provides that a
violation of section 15 rendell' a
person liable to the Uulted States for
a clvU penalty and possible criminal
p~ecutlon. 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 See).
1J1J3
APPENDIX A.-QU(CK REFEREIfCE SUIDIAIIY
raa ElaRGENCY INCIDENTS OF ENvIRONKD-
TAL CONTAMINATIOlf
A. WHAT SHOULD BE REPORTED AS AN
IUU:JIGENCY 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 sllDlflcant population
destruction". (See Part V(c) for complete
description,)
B. WHAT !fEED NOT BE REPORTED AS .ur
_GENCY INCIDENT
Information contained in notification of
spills under section 311, 214-749-3840.
Region VII (Nebra.~ka, Iowa, MIssouri,
~),816-374-3778.
Region VIII (Colorado, Utah, Wyoming,
Montana, North Dakota, South Dakota).
303-837-3880.
Region IX (California, Nevada, Arizona,
HawaII, Guam), 415-558-8254.
Region X (Wasj}jneton. OretJ'm. Idaho,
-AI........), 2U6="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 COKIIENTS AND
RESPONSES
A. Pl:RSONS SUBJECT TO TIlES!!: REQUIRDIEIn'S
Camaml 1: Employees cannot be held
subJect to these requirements, since: (a)
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-
sistently defined, and (c) the application of
criminal penalties mandates a strict inter-
pretation of this word,
FEDERAL REGISTER, VOL 43, NO. 52-THURSDAY, MARCH 16, 1978
264
-------
11 11
-------
&3JK1me: Part V now clarifies those ef-
fects for which reporting depends upon a
lla'nIflcant exposure potential. Persistence
by Itself Is no longer Itemized as a report-
able effect but rather Is considered to be a
component of exposure - potential; It mlli'
&Iao underlie the measurements described In
Part V(b)(l). Laboratory indicators of pro-
nounced bloaccumulatlon are to be reported
when coupled with potential for widespread
exposure and any non-trivial adverse effect.
Comment 11: The n-octanol/water parti-
tion coefficient addresses a physlco-cheml-
cal property, not biological effects, and Is
not alone an indicator of substantial risk;
further, the values stated for the coefficient
and the bloaccumulatlon factor In fish do
not correspond.
RUpome: The Agency acknowledges the
numerical error and has amended the valueR
to correspond. This polley statement now
directs the reporting of an experimental
meuurement of bloaccumulatlon when
coupled with an adverse effect and potential
for widespread exposure.
Comment 11: The requlrement that Infor.
matlon which "links" an effect to a cheml.
cal be reported Is too broad and contradicts
the statutory language of "reasonably
8UPporta".
Rupome: The Agency has provided In a
new Part VI Its interpretation of "reason-
ably IUPPOrts".
Comment 11: A determination that infor-
mation "reasonably supports the conclu.
alon" of substantial risk cannot be made In.
dependently of considerations of use since
the method and manner of using a chemical
may tnnuence the occurrence of an effect;
In particular, the criteria should reflect a
dI8tlnction between normal and abnormal
U8e8 of chemlcal8.
Rupome: The Agency considers that the
appropriate components of a "substantial
risk" with respect to a chemical are (a) the
aerioURleu of the effect, and (b) total expo-
sure potential. The method and manner of
using a chemical Is one of several factors de-
tennlnlna Its exposure potential. As de-
acrlbed In Part V, the Importance of expo.
lure potential as a component of "substan-
tial risk" depends upon the kind of effect of
concern. Thus, the effects described In Part
V(a) are so serious that relatively little
weight Ia given to exposure; the effects de-
acribed 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.
Eo IlfPORJIATIOK THAT NEED KOT 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?
Rupon3e: 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: EPA Is coordinating this pro-
gram with other agencies now. When this
coordination is successfullY completed, the
policy statement will be amended to exempt
from the reporting requirement information
that has been submitted to other specified
agencies. In the meantime, substantial-risk
Information must be reported directly to
EPA; such a report does not discharge any
reporting obligation to other agencies.
r. INFORMATIOK FIRST RECEIVED PRIOR TO THE
un:criVl: DATI: or 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.
matlon obtained before then.
Respome: As discussed In the preamble to
the September 9 proposal, the Agency con.
siders section 8(e) to apply to risk Informa.
tlon possessed by or known to a person
before, on, or after January I, 1977. Con.
cernlng information first obtained before
1977, this policy statement continues to re-
quire reporting of information received If a
person has been aware of It since January 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.
Re!pome: 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 INI'ORJoU.TIOIf
Comment 24: EPA should delay guidance
until procedures are published governing
the treatment of confidential submillslons.
Comment 25: EPA should treat all submla.
slons as confidential until the information Is
verified.
Comment 26: EPA should automatically
publish section 8(e) notices.
Respon!i! to Comments 24 through 26:
EPA has Included a new Part X which de-
scribes how to submit a claim of conflden.
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. MISCELLANl:OUS
Comment 21: 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 reo
qulrements apply to chemicals p"evlously
but no longer manufactured, processed, or
distributed In commerce by a person.
Rupome: 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 cheml.
cals which a person has discontinued manu-
facturing, processing, or distributing since
January I, 1877, 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.
tlonal 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 rlaks ad.
dressed by TSCA.
Respome: A substantial risk Is defined In
Part V(a) of this polley statement as a risk
of considerable concern because of (a) the
seriOURleu 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 ",I;ubstantlal".
Comment 30: To what extent are "users"
of chemlcala subject to these requirements?
Rupome: The Agency considers that
many industrial uses of chemlcal8 actually
fall within the scope of "processing" cheml.
caIs. A manufacturer, processor, or dlstrlbu.
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 'dlstrlbuted 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 chemlcal8
In small quantities solely for purposes of re-
search and development Is conducte~ for
"commercial purposes". Such purposes
would Include the sale and distribution of
such materials, 88 well as their use by the
manufacturer or processor In activities (for
example, product research and development
and studies assessing the feasibility and
safety of using chemicals) preceding his or a
client's commercial use of such materials or
others on a larger scale.
As described In Part V, the Agency consld.
ers that "substantial risks" depend In part
upon an exposure potential. Thus, the oc-
currence of the effects described In Part
V(a) presuppose exposure to the chemical
and must be reported; reporting of the
other effects will depend upon a potential
for significant levels of exposure.
Comment 32: Are raw materials, Interme-
diates, and Inert ingredients produced or
used In the manufacture of a pesticide sub-
Ject to TSCA?
Re3Pome: 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 ingredients produced or used In the
manufacture of a pesticide are not them-
selves regulated under FIFRA (unless they
happen to be pesticides themselves) and,
therefore, are subject to TSCA. The pestl-
FEDERAL REGISTER, VOL. 43, NO. 52-THURSDAY, MARCH 16. 197.
266
-------
11116
clde regulations at 40 CFR 162.4 are consis-
tent with this view.
Comment 33: Are Intermediates and cata-
lysts Intended solely for use In the produc-
tion of a food. food additive. drua. cosmetic.
or device subject to TSCA?
Re!POn3e: The Administrator considers
that 'lntermedlates and catalysts Intended
solely for use In the production of a food.
food additive. drua. cosmetic... or device are
excluded from regulation under TSCA. The
definitions of the FFDCA provide that
chemical substances which are Intended for
use u a component of a food. food additive.
drul. cosmetic. or device are encompassed
within the meanlnl 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 lIS It Is
actually manufactured, processed. or dis-
tributed In commerce solely for use In the
NOTICES
production of a food. food additive. druI.
cosmetic. or device.
Comment 34: Employees should have the
option to submit reports anonymously.
Resporue: EPA considers that any person
may report information to EPA under
TSCA. Those who are required to do so
under section 8
-------
APPENDIX B:
STATUS REPORTS BY CAS NUMBER
CAS NUMBER: 50-00-0 CHEMICAL NAME: FORMALDEHYDE
SUBMISSION #: 8EHQ-0383-0474
CAS NUMBER: 51-78-5 CHEMICAL NAME: PHENOL, 4-AMINO-, HYDROCHLORIDE
SUBMISSION #: 8EHQ-0484-0513
CAS NUMBER: 62-53-3 CHEMICAL NAME: BENZENAMINE
SUBMISSION 11:: 8EHQ-0484-0513
CAS NUMBER: 64-67-5 CHEMICAL NAME: SULFURIC ACID, DIETHYl ESTER
IV SUBMISSION #: 8EHQ-1083-0509
0'\
co
CAS NUMBER: 67-56-1 CHEMICAL NAME: METHANOL
SUBMISSION #: BEHQ-0484-0513
CAS NUMBER: 71-55-6 CHEMICAL NAME: ETHANE, 1,1,1-TRICHLORO-
SUBMISSION #: 8EHQ-1084-0535
CAS NUMBER: 74-87-3 CHEMICAL NAME: METHANE, CHLORO-
SUBMISSION #: BEHQ-1083-0499
CAS NUMBER: 75-07-0 CHEMICAL NAME: ACETALDEHYDE
SUBMISSION #: BEHQ-0383-0474
-------
APPENDIX B: STATUS REPORTS BY CAS NUMBER (CONT.)
CAS NUMBER: 75-09-2 CHEMICAL NAME: METHANE, DICHLORO-
SUBMISSION i: 8EHQ-0884-0525
CAS NUMBER: 75-09-2 CHEMICAL NAME: METHYLENE CHLORIDE
SUBMISSION #: 8EHQ-0884-0525
CAS NUMBER: 75-28-5 CHEMICAL NAME: PROPANE, 2-METHYL -
SUBMISSION #: 8EHQ-0484-0511
CAS NUMBER: 76-13-1 CHEMICAL NAME: ETHANE, 1,1,2-TRICHLORO-1,2,2-TRIFLUORO-
SUBMISSION #: 8EHQ-1084-0535
IV
0"\ CAS NUMBER: 76-13-1 CHEMICAL NAME: FREON 113
\.D
SUBMISSION I: 8EHQ-1084-0535
CAS NUMBER: 79-06-1 CHEMICAL NAME: ACRYLAMIDE
SUBMISSION I: 8EHQ-0783-0488
CAS NUMBER: 79-06-1 CHEMICAL NAME: 2-PROPENAMIDE
SUBMISSION I: 8EHQ-0783-0488
CAS NUMBER: 87-66-1 CHEMICAL NAME: 1,2,3-BENZENETRIOL
SUBMISSION jt: 8EHQ-1284-0539
CAS NUMBER: 87-66-1 CHEMICAL NAME: PYROGAllOL
SUBMISSION I: 8EHQ-1284-0539
-------
APPENDIX B: STATUS REPORTS BY CAS NUMBER (CONT.)
CAS NUMBER: 89-62-3 CHEMICAL NAME: BENZENAMINE, 4-METHYL-2-NITRO-
SUBMISSION II: 8EHQ-1083-0496
CAS NUMBER: 92-43-3 CHEMICAL NAME: PHENIDONE
SUBMISSION II: 8EHQ-0984-0529
CAS NUMBER: 92-43-3 CHEMICAL NAME: 3-PYRAZOLIDINOHE, 1-PHENYL-
SUBMISSION II: 8EHQ-0984-0529
CAS NUMBER: 98-07-7 CHEMICAL NAME: BENZENE, (TRICHLOROMETHYL)-
SUBMISSION #: 8EHQ-0884-0523
N CAS NUMBER: 98-82-8 CHEMICAL NAME: BENZENE, (l-METHYLETHYL)-
-.J
0
SUBMISSION ;: 8EHQ-1184-0536
CAS NUMBER: 98-82-8 CHEMICAL NAME: CUMENE
SUBMISSION II: 8EHQ-1l84-0536
CAS NUMBER: 98-88-4 CHEMICAL NAME: BENZOYL CHLORIDE
SUBMISSION II: 8EHQ-0884-0523
CAS NUMBER: 98-95-3 CHEMICAL NAME: BENZENE, NITRO-
SUBMISSION II: 8EHQ-0484-0513
CAS NUMBER: 100-44-7 CHEMICAL NAME: BENZENE, (CHlOROMETHYl)-
SUBMISSION II: 8EHQ-0884-0523
-------
APPENDIX B: STATUS REPORTS BY CAS HUMBER (CONT.)
CAS NUMBER: 100-65-2 CHEMICAL NAME: BENZENAMINE. H-HYDROXY-
SUBMISSION It: 8EHQ-0484-0513
CAS HUMBER: 103-33-3 CHEMICAL NAME: DIAZENE, DIPHENYL-
SUBMISSION It: 8EHQ-0484-0S13
CAS NUMBER: 106-89-8 CHEMICAL NAME: EPICHlOROHYDRHf
SUBMISSION It: 8EHQ-0584-0518 S
CAS NUMBER: 106-89-8 CHEMICAL NAME: OXIRANE, (CHlOROMETHYL)-
SUBMISSION It: 8EHQ-0584-0S18 5
!\J
-...J CAS NUMBER: 106-97-8 CHEMICAL NAME: BUTANE
f-'
SUBMISSION I: 8EHQ-0484-0S11
CAS NUMBER: 106-98-9 CHEMICAL NAME: I-BUTENE
SUBMISSION It: 8EHQ-0484-0511
CAS NUMBER: 106-99-0 CHEMICAL NAME: 1,3-BUTADIENE
SUBMISSION I: 8EHQ-0484-0511
CAS NUMBER: 108-10-1 CHEMICAL NAME: 2-PENTANONE, 4-METHYL-
SUBMISSION It: 8EHQ-I084-0535
CAS HUMBER: 109-52-4 CHEMICAL NAME; PENTANOIC ACID
SUBMISSION It: 8EHQ-0584-0514
-------
APPENDIX B:
CAS NUMBER: 111-07-9
SUBMI~SION #: BEHQ-I084-0534
CAS NUMBER: 11 b14-8
SUBMISSION #: 8EHQ-0584-0514
CAS NUMBER: 111-76-2
SUBMISSION #: 3EHQ-0483-0475
STATUS REPORTS BY CAS NUMBER (CONT.)
CHEMICAL NAME: HEXADECANOIC ACID, 2-METHOXYETH(L ESTER
CHEMICAL NAME: HEPTANOIC ACID
CHEMICAL NAME: ETHANOL, 2-BUTOXY-
8EHQ-0584-0517
CAS NUMBER: 112-05-0 CHEMICAL NAME: NONANOIC ACID
SUBMISSION #: 8EHQ-0584-0514
tv
~
tv CAS NUMBER: 115-11-7 CHEMICAL NAME: I-PROPENE, 2-METHYL-
SUBMISSION #: 8EHQ-0484-0S11
CAS NUMBER: 122-99-6 CHEMICAL NAME: ETHANOL, 2-PHENOXY-
SUBMISSION It: 8EHQ-0884-0528
CAS NUMBER: 123-30-8 CHEMICAL NAME: PHENOL, 4-AMINO-
SUBMISSION #: 8EHQ-0484-0S13
CAS NUMBER: 288-32-4 CHEMICAL NAME: IH-IMIDAZOLE
SUBmSSION #: BEHQ-1284-0540 S *
CAS NUMBER:
382-10-5
SUBMISSION #: 8EHQ-0483-0476 S
CHEMICAL NAME: I-PROPENE, 3,3,3-TRIFlUORO-2-(TRIFlUOROMETHYl)-
-------
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
tV
-...J
W
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
APPENDIX B:
480-96-6
SUBMISSION #: 8EHQ-1284-0541 S
495-48-7
SUBMISSION #: 8EHQ-0484-0513
540-63-6
SUBMISSION #: 8EHQ-0683-0481
931-36-2
SUBMISSION #: 8EHQ-1284-0540 S
959-52-4
SUBMISSION #: 8EHQ-0384-0506 S
1116-54-7
SUBMISSION #: 8EHQ-0283-0469 S
1116-54-7
SUBMISSION #: 8EHQ-0283-0469 S
1134-36-7
SUBMISSION #: 8EHQ-I083-0495
1143-72-2
SUBMISSION #: 8EHQ-0484-0510
STATUS REPORTS BY CAS NUMBER (CaNT.)
CHEMICAL NAME: BENZOFURAZAN, I-OXIDE
CHEMICAL NAME: DIAZENE, DIPHENYL-, I-OXIDE
CHEMICAL NAME: 1,2-ETHANEDITHIOl
CHEMICAL NAME: IH-IMIDAZOlE, 2-ETHYl-4-METHYl-
*
CHEMICAL NAME: 1,3,5-TRIAZINE, HEXAHYDRO-l,3,5-TRIS(I-0XO-2-PROPENYl)-
CHEMICAL NAME: ETHANOL, 2,2'-(NITROSOIMINO)BIS-
CHEMICAL NAME: N-NITROSODIETHANOlAMINE
CHEMICAL NAME: 11,1'-BIPHENYl]-4-0l, 3-AMINO-
CHEMICAL NAME: METHANONE, PHENYl(2,3,4-TRIHYDROXYPHENYl)-
-------
APPENDIX B:
STATUS REPORTS BY CAS NUMBER (CONT.)
CAS NUMBER: 1318-00-9 CHEMICAL NAME: VERMICULITE
SUBMISSION It: 8EHQ-0383-0473
CAS NUMBER: 1336-36-3 CHEMICAL NAME: 1,1'-BIPHENYL. CHlORO DERIVS.
SUBMISSION It: 8EHQ-0784-0521 S
CAS NUMBER: 1336-36-3 CHEMICAL NAME: POLYCHLORINATED BIPHENYLS (PCB)
SUBMISSION i: 8EHQ-0784-0521 S
CAS NUMBER: 1429-50-1 CHEMICAL NAME: PHOSPHONIC ACID. [1,2-ETHAHEDIYLBISINITRllOBIS(METHYlENE)IIT
ETRAKIS-
SUBMISSION I: 8EHQ-0683-0483 S
f',J
-..J
,j:::.
CAS NUMBER: 2386-87-0 CHE.MICAL ~.AME: 7-0XABICYClO[4.1.0IHEPTANE-3-CARBOXYlIC ACID, 7-0XABICYCLO[4
.1.01~EPT-3-YlMETHYL ESTER
SUBMISSION I: 8EHQ-0784-0522
CAS NUMBER: 2426-08-6 CHEMICAL NAME: BUTYL GLYCIDYL ETHER
SUBMISSION #: 8EHQ-0584-0518 S
CAS NUMBER: 2426-08-6 CHEMICAL NAME: OXIRANE, (BUTOXYMETHYl) -
SUBMISSION #: 8EHQ-0584-0518 S
CAS NUMBER: 2451-62-9 CHEMICAL NAME: ARALDITE PT-SIO
SUBMISSION I: 8EHQ-0883-0490
-------
APPENDIX B:
CAS NUMBER:
2451-62-9
SUBMISSION #: 8EHQ-0883-0490
CAS NUMBER:
2530-85-0
SUBMISSION #: 8EHQ-0884-0524
STATUS REPORTS BY CAS NUMBER (CONT.)
CHEMICAL NAME: 1.3.5-TRIAZINE-2.4,6CIH,3H.5H)-TRIONE, 1,3.5-TRISCOXIRANYLME
THYl) -
CHEMICAL NAME: 2-PROPENOIC ACID, 2-METHYL-. 3-CTRIMETHOXYSILYL)PROPYL ESTER
CAS NUMBER: 2530-85-0 CHEMICAL NAME: SILANE A-174
SUBMISSION I: 8EHQ-0884-0524
CAS NUMBER: 3033-77-0 CHEMICAL NAME: G-MAC
SUBMISSION It: 8EHQ-1283-0503
IV
-....J
U1 CAS NUMBER: 3033-77-0
SUBMISSION I: 8EHQ-1283-0503
CAS NUMBER: 3327-22-8
SUBMISSION I: 8EHQ-1283-0503
CAS NUMBER:
5915-41-3
SUBMISSION I: 8EHQ-0783-0485 S
CAS NUMBER:
5915-41-3
SUBMISSION #: 8EHQ-0783-0485 S
CHEMICAL NAME: OXIRANEMETHANAMINIUM, N.N,N-TRIMETHYL-, CHLORIDE
CHEMICAL NAME: I-PROPANAMIHIUM, 3-CHLORO-2-HYDROXY-N,N,N-TRIMETHYL-, CHLORI
DE
CHEMICAL NAME: TERBUTHYLAZINE
*
CHEMICAL NAME: 1.3,5-TRIAZINE-2,4-DIAMINE, 6-CHLORO-N-Cl.1-DIMETHYLETHYL)-N
, -ETHYl-
*
-------
APPENDIX B: STATUS REPORTS BY CAS NUMBER (CONT.)
CAS NUMBER: 7550-45-0 CHEMICAL NAME: TITANIUM CHLORIDE (TICL4), (T-4)-
SUBMISSION #: 8EHQ-0984-0530
CAS NUMBER: 7647-01-0 CHEMICAL NAME: HYDROCHLORIC ACID
SUBMISSION #: 8EHQ-0384-0508 P *
CAS NUMBER: 7647-18-9 CHEMICAL NAME: ANTIMONY CHLORIDE (SBCL5)
SUBMISSION #: 8EHQ-0384-0508 P *
CAS NUMBER: 7664-39-3 CHEMICAL NAME: HYDROFLUORIC ACID
SUBMISSION #: 8EHQ-0384-0508 P *
N
-.J CAS NUMBER: 7803-49-8 CHEMICAL NAME: HYDROXYLAMINE
0'\
SUBMISSION #: 8EHQ-0484-0513
CAS NUMBER: 8008-20-6 CHEMICAL NAME: KEROSINE
SUBMISSION #: 8EHQ-0283-0471 S 8EHQ-0283-0472 S
CAS NUMBER: 8052-41-3 CHEMICAL NAME: SOLVENT, STODDARD
SUBMISSION #: 8EHQ-0584-0517
CA~ NUMBER: 8052-41-3 CHEMICAL NAME: STODDARD SOLVENT
SUBMISSION #: 8EHQ-0584-0517
CAS NUMBER: 9003-07-0 CHEMICAL NAME: POLYPROPYLENE
SUBMISSION #: 8EHQ-0583-0479 S
-------
APPENDIX B:
STATUS REPORTS BY CAS NUMBER CCONT.>
CAS NUMBER:
9003-07-0
CHEMICAL NAME: I-PROPENE, HOMOPOLYMER
SUBMISSION #: 8EHQ-0583-0479 S
CAS NUMBER: 9003-11-6 CHEMICAL NAME: OXIRANE, METHYL-, POLYMER WITH OXIRANE
SUBMISSION ,: 8EHQ-0584-0516 S
CAS NUMBER: 10039-54-0 CHEMICAL NAME: HYDROXYLAMINE, SULFATE C2: 1) C SAL T>
SUBMISSION 1P 8EHQ-0783-0486
CAS NUMBER: 10212-58-5 CHEMICAL NAME: l-AZIRIDINECARBOXAMIDE, 2-METHYL-N-OCTADECYL-
SUBMISSION I: 8EHQ-I084-0535
IV
--.J CAS NUMBER: 13463-67-7 CHEMICAL NAME: TITANIUM OXIDE CTI02>
--.J
SUBMISSION #: 8EHQ-I083-0497
CAS NUMBER: 14567--73-8 CHEMICAL NAME: TREMOLITE
SUBMISSION 1P 8EHQ-0383-0473
CAS NUMBER: 20328-87-4 CHEMICAL NAME: PINA SENSITIZER KF 501
SUBMISSION ,: 8EHQ-0584-0519
CAS NUMBER:
20328-87-4
CHEMICAL NAME: 2-THIAZOLIUM, 2,2'-[C2-CARBOXY-P-PHENYLENE)BISCIMINOVINYLENE
)]BISC3-ETHYL)DIIODIDE
SUBMISSION ,: 8EHQ-0584-0519
-------
APPENDIX B:
STATUS REPORTS BY CAS NUMBER (CONT.)
CAS NUMBER:
20762-60-1
CHEMICAL NAME: POTASSIUM AZIDE (K(N3»
SUBMISSION #: 8EHQ-1083-0494
*
CAS NUMBER:
25068-38-6
CHEMICAL NAME: PHENOL, 4,4'-C1-METHYlETHYlIDENE)BIS-, POLYMER WITH CCHlOROM
ETHYl )OXIRANE
SUBMISSION #: 8EHQ-0584-0518 S
CAS NUMBER:
25167-67-3
CHEMICAL NAME: BUTENE
SUBMISSION #: 8EHQ-0484-0511
CAS NUMBER:
26544-23-0
CHEMICAL NAME: PHOSPHOROUS ACID, ISODECYL DIPHENYl ESTER
SUBMISSION #: 8EHQ-0784-0522
N
'.J
00
CAS NUMBER: 26628-22-8 CHEMICAL NAME: SODIUM AZIDE (NACN3»
SUBMISSION #: 8EHQ-1083-0494 *
CAS NUMBER: 51200-87-4 CHEMICAL NAME: OXAZOLIDINE, 4, 4-DIMETHYl-
SUBMISSION ij: 8EHQ-0283-0470
CAS NUMBER:
51365-70-9
CHEMICAL NAME: EPON CURING AGENT D
SUBMISSION #: 8EHQ-0583-0478 S
CAS NUMBER:
51365-70-9
CHEMICAL NAME: HEXANOIC ACID, 2-ETHYl-, COMPO. WITH 2,4,6-TRIS[(DIMETHYlAMI
NO)METHYl]PHENOl
SUBMISSION #: 8EHQ-0583-0478 5
-------
APPENDIX B:
CAS NUMBER:
61791-44-4
SUBMISSION #: 8EHQ-0583-0479 S
STATUS REPORTS BY CAS NUMBER (CONT.)
CHEMICAL NAME: ETHANOL, 2,2'-IMINOBIS-, N-TALLOW ALKYL DERIVS.
CAS NUMBER: 63449-39-8 CHEMICAL NAME: CHLORINATED PARAFFINS
SUBMISSION #: 8EHQ-0983-0491 S 8EHQ-0484-0S12 8EHQ-0884-0527
CAS NUMBER: 63449-39-8 CHEMICAL NAME: PARAFFIN WAXES AND HYDROCARBON WAXES, CHLORINATED
SUBMI.5SION #: 8EHQ-0983-0491 S 8EHQ-0484-0512 8EHQ-0884-0527
CAS NUMBER: 64741-53-3 CHEMICAL NAME: DISTILLATES (PETROLEUM), HEAVY NAPHTHENIC
SUBMISSION #: 8EHQ-0384-0507
N
~ CAS NUMBER: 64741-53-3 CHEMICAL NAME: GULF 100 TEXAS DISTILLATE
1..0
SUBMISSION #: 8EHQ-0384-0507
CAS NUMBER: 64741-59-9
SUBMISSION #: 8EHQ-0183-0468
CAS NUMBER: 64741-60-2
SUBMISSION #: 8EHQ-0183-0468
CAS NUMBER: 64741-61-3
SUBMISSION #: 8EHQ-0183-0468
CAS NUMBER: 64741-62-4
SUBMISSION #: 8EHQ-0584-0517
CHEMICAL NAME: DISTILLATES (PETROLEUM), LIGHT CATALYTIC CRACKED
CHEMICAL NAME: DISTILLATES (PETROLEUM), INTERMEDIATE CATALYTIC CRACKED
CHEMICAL NAME: DISTILLATES (PETROLEUM), HEAVY CATALYTIC CRACKED
CHEMICAL NAME: CLARIFIED OILS (PETROLEUM), CATALYTIC CRACKED
-------
APPENDIX B:
CAS NUMBER: 64742-11-6 CHEMICAL NAME: GULF N.E. 61 (PROCESS 65)
SUBMISSION 3: 8EHQ-0384-0507
IV CAS NUMBER: 64742-30-9
00
0
SUBMISSION 3: 8EHQ-0683-0480
CAS NUMBER: 64742-30-9
SUBMISSION #: 8EHQ-0683-0480
CAS NU\1BEr - 64742-30-9
SUBMISSION #: 8EHQ-0683-0480
CAS NUMBER: 64742-52-5
SUBMISSION #: 8EHQ-0384-0507
CAS NUMBER:
64741-68-0
SUBMISSION #: 8EHQ-0283-0472 S
CAS NUMBER:
64741-88-4
SUBMISSION #: 8EHQ-0284-0505
CAS NUMBER:
64742-11-6
SUBMISSION #: 8EHQ-0384-0507
CAS NUMBER:
64742-52-5
SUBMISSION #: 8EHQ-0384-0507
STATUS REPORTS BY CAS NUMBER (CONT.)
CHEMICAL NAME: NAPHTHA (PETROLEUM), HEAVY CATALYTIC REFORMED
CHEMICAL NAME: DISTILLATES (PETROLEUM), SOLVENT-REFINED HEAVY PARAFFINIC
CHEMICAL NAME: EXTRACTS (PETROLEUM), HEAVY NAPHTHENIC DISTILLATE SOLVENT
CHEMICAL NAME: DISTILLATES (PETROLEUM), CHEMICALLY NEUTRALIZED MIDDLE
CHEMICAL NAME: MENTOR 28
CHEMICAL NAME: SOMENTOR 43
CHEMICAL NAME: DISTILLATES (PETROLEUM), HYDROTREATED HEAVY NAPHTHENIC
CHEMICAL NAME: GULF 100 TEXAS OIL
-------
APPENDIX B:
CAS NUMBER:
64742-54-7
SUBMISSION #: 8EHQ-0484-0512
CAS NUMBER: 64742-57-0
SUBMISSION #: 8EHQ-0484-0512
CAS NUMBER: 64742-65-0
SUBMISSION #: 8EHQ-0284-0505
CAS NUMBER: 64742-90-1
SUBMISSION #: 8EHQ-1083-0498
N
00
I-'
CAS NUMBER:
68131-74-8
SUBMISSION #: 8EHQ-0683-0482
CAS NUMBER:
68298-78-2
SUBMISSION #: 8EHQ-1084-0535
CAS NUMBER:
68298-78-2
SUBMISSION #: 8EHQ-I084-0535
CAS NUMBER:
68308-34-9
SUBMISSION #: 8EHQ-0184-0504
STATUS REPORTS BY CAS NUMBER (CONT.)
CHEMICAL NAME: DISTILLATES (PETROLEUM), HYDROTREATED HEAVY PARAFFINIC
CHEMICAL NAME: RESIDUAL OILS (PETROLEUM), HYDROTREATED
CHEMICAL NAME: DISTILLATES (PETROLEUM), SOLVENT-DEWAXED HEAVY PARAFFINIC
CHEMICAL NAME: RESIDUES (PETROLEUM), STEAM-CRACKED
CHEMICAL NAME: ASHES (RESIDUES)
CHEMICAL NAME: PERFLUOROALKYL RESIN
CHEMICAL NAME:
2-PROPENOIC ACID, 2-METHYL-, 2-!!!!5-!!!2-!ETHYL!(HEPTADECAF
LUOROOCTYL)SUlFONYlJAMINOJETHOXYJCARBONYlJAMINOJ-2-METHYlPHE
NYlJAMINOJCARBONYlJOXYJPROPYL ESTER, TELOMER WITH BUTYL 2-PR
OPENOATE, 2-[[![5-![[2-[ETHYl[CNONAFLUOROBUTYl)SULFONYlJAMIN
OJETHOXYJCARBONYLIAMINOI-2-METHYLPHENYLJAMINOJCARBONYL10XY1P
CHEMICAL NAME: SHALE OILS
-------
APPENDIX B:
CAS NUMBER:
68409-94-9
SUBMISSION #: 8EHQ-0683-0482
CAS NUMBER: 68409-94-9
SUBMISSION #: 8EHQ-0683-0482
CAS NUMBER: 68442-97-7
SUBMISSION #: 8EHQ-0984-0531 S
CAS NUMBER: 68476-79-9
SUBMISSION #: 8EHQ-0683-0482
tV CAS NUMBER: 68477-31-6 (See Below ***)
co
tV CAS NUMBER: 68479-98-1
SUBMISSION #: 8EHQ-0883-0489
CAS NUMBER: 68555-92-0
SUBMISSION #: 8EHQ-1084-0535
CAS NUMBER: 68555-92-0
SUBMISSION #: 8EHQ-1084-0535
CAS NUMBER: 68911-57-9
SUBMISSION #: 8EHQ-0683-0482
*** CAS NUMBER: 68477-31-6
SUBMISSION t: 8EIJ;r0283-0472 S
STATUS REPORTS BY CAS NUMBER (CONT.)
CHEMICAL NAME: FUEL. SRC SOLID
CHEMICAL NAME: RESIDUES (COAL). SOLVENT-REFINING (SRC), VACUUM-DISTN.
CHEMICAL NAME: 1H-IMIDAZOlE-1-ETHANAMINE, 4.5-DIHYDRO-, 2-NORTAll-OIl ALKYL
DERIVS.
*
CHEMICAL NAME: NAPHTHA (COAL). SOLVENT-REFINING
CHEMICAL NAME: BENZENEDIAMINE. AR.AR-DIETHYl-AR-METHYl-
CHEMICAL NAME: PERFlUOROAlKYl RESIN
CHEMICAL NAME:
2-PROPENOIC ACID. 2-METHYl-. 2-[[(HEPTADECAFlUOROOCTYl)SUlFO
NYlIMETHYlAMINOIETHYl ESTER, POLYMER WITH 2-[METHYl[CNONAFlU
OROBUTYl)SUlFONYlIAMINOIETHYl 2-METHYl-2-PROPENOATE, 2-£METH
Yl[CPENTADECAFlUOROHEPTYl)SUlFONYlIAMINOIETHYL 2-~'ETHYl-2-PR
OPENOATE. 2-£METHYl[(TRIDECAFlUOROHEXYl)SULFONYLIAf1INOIETHYL
CHEMICAL NAME: DISTILLATES (COAL). SOLVENT-REFINING (SRC), MIDDLE
CHEMICM, NAME:
DISTILIATES (PETROlEUM), CATALYTIC REFOR-IER
FRAcrIONA'lm RESIDUE, LOi-OOILING
-------
CAS NUMBER: 69013-21-4 CHEMICAL NAME: FUEL OILS, PYROLYSIS
SUBMISSION #: 8EHQ-1l84-0537
CAS NUMBER: 69045-78-9
SUBMISSION #: 8EHQ-1084-0533 S
CAS NUMBER: 70776-26-0
SUBMISSION #: 8EHQ-0283-0471 S
CAS NUMBER: 71868-10-5
SUBMISSION #: 8EHQ-0684-0520
N
00 CAS NUMBER: 71868-10-5
w
APPENDIX B:
SUBMISSION #: 8EHQ-0684-0520
CAS NUMBER:
76379-66-3
SUBMISSION #: BEHQ-1084-0532
CAS NUMBER:
77536-68-6
SUBMISSION #: 8EHQ-0383-0473
CAS NUMBER:
79419-43-5
SUBMISSION #: 8EHQ-1283-0501
STATUS REPORTS BY CAS NUMBER (CONT.)
CHEMICAL NAME: PYRIDINE, 2-CHLORO-5-TRICHLOROMETHYL-
CHEMICAL NAME: DISULFIDE, BIS(2-CHLOROOCTYL)
CHEMICAL NAME: IRGACURE 907
CHEMICAL NAME: 1-PROPANONE, 2-METHYL-1-[(4-METHYlTHIO)PHENYl]-2-(4-MORPHOlI
NYl)-
CHEMICAL NAME: 5,7,11-DODECATRIYN-1-0l
CHEMICAL NAME: TREMOLITE ASBESTOS
CHEMICAL NAME: 2-CYClOHEXEN-1-0NE, 2-(2-0XOBUTYl)-5-(2-ETHYlTHIO)-PROPYl-3-
HYDROXY-
-------
~
00
~
APPENDIX B:
STATUS REPORTS BY CAS NUMBER
-------
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME
CAS NUMBER: 75-07-0 CHEMICAL NAME: ACETALDEHYDE
SUBMISSION It: 8EHQ-0383-0474
CAS NUMBER: 79-06-1 CHEMICAL NAME: ACRYLAMIDE
SUBMISSION It: 8EHQ-0783-0488
CAS NUMBER: CONFIDENT CHEMICAL NAME: ACRYLIC POLYMER
SUBMISSION It: 8EHQ-0683-0484 S
CAS NUMBER: 7647-18-9 CHEMICAL NAME: ANTIMONY CHLORIDE (SBCL5)
~ SUBMISSION I: 8EHQ-0384-0508 P *
U1
CAS NUMBER: 2451-62-9 CHEMICAL NAME: ARALDITE PT-810
SUBMISSION It: 8EHQ-0883-0490
CAS NUMBER: CONFIDENT CHEMICAL NAME: AROMATICS, SUBSTITUTED
SUBMISSION I: 8EHQ-0583-0477 S
CAS NUMBER: 68131-74-8 CHEMICAL NAME: ASHES (RESIDUES)
SUBMISSION #: 8EHQ-0683-0482
CAS NUMBER: 10212-58-5 CHEMICAL NAME: l-AZIRIDINECARBOXAMIDE, 2-METHYL-N-OCTADECYL-
SUBMISSION I: 8EHQ-I084-0535
-------
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
tv
co
0'\
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
APPENDIX C:
62-53-3
SUBMISSION #: 8EHQ-0484-0513
100-65-2
SUBMISSION #: 8EHQ-0484-0513
CONFIDENT
SUBMISSION #: 8EHQ-1283-0500 S
89-62-3
SUBMISSION ft: 8EHQ-1083-0496
100-44-7
SUBMISSION #: 8EHQ-0884-0523
68479-98-1
SUBMISSION #: 8EHQ-0883-0489
98-95-3
SUBMISSION #: 8EHQ-0484-0513
98-07-7
SUBMISSION #: 8EHQ-0884-0523
87-66-1
SUBMISSION #: 8EHQ-1284-0539
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CHEMICAL NAME: BENZENAMINE
CHEMICAL NAME: BENZENAMINE, N-HYDROXY-
CHEMICAL NAME: BENZENAMINE, SUBSTITUTED POLYGLYCIDYL
CHEMICAL NAME: BENZENAMINE, 4-METHYL-2-NITRO-
CHEMICAL NAME: BENZENE, (CHLOROMETHYL)-
CHEMICAL NAME: BENZENEDIAMINE, AR,AR-DIETHYL-AR-METHYL-
CHEMICAL NAME: BENZENE, NITRO-
CHEMICAL NAME: BENZENE, (TRICHLOROMETHYL)-
CHEMICAL NAME: 1,2,3-BENZENETRIOL
-------
APPENDIX C:
CAS NUMBER:
98-82-8
SUBMISSION i: 8EHQ-1184-0536
CAS HUMBER:
480-96-6
SUBMISSION i: 8EHQ-1284-0541 S
CAS NUMBER:
98-88-4
SUBMISSION #: 8EHQ-0884-0523
CAS NUMBER: 1336-36-3
SUBMISSION #: 8EHQ-0784-0521 S
IV
00 CAS NUMBER: 1134-36-7
-..J
SUBMISSION i: 8EHQ-I083-0495
CAS NUMBER: 106-99-0
SUBMISSION i: 8EHQ-0484-0511
CAS NUMBER: NONE
SUBMISSION i: 8EHQ-0484-0511
CAS NUMBER:
106-97-8
SUBMISSION #: 8EHQ-0484-0511
CAS NUMBER:
106-98-9
SUBMISSION i: 8EHQ-0484-0511
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CHEMICAL NAME: BENZENE, (l-METHYlETHYl)-
CHEMICAL NAME: BENZOFURAZAN, I-OXIDE
CHEMICAL NAME: BENZOYL CHLORIDE
CHEMICAL NAME: 1,1'-BIPHENYl, CHlORO DERIVS.
CHEMICAL NAME: [l,1'-BIPHENYlJ-4-0l, 3-AMINO-
CHEMICAL NAME: 1,3-BUTADIENE
CHEMICAL NAME: 1,3-BUTADIENE FEEDSTOCK
CHEMICAL NAME: BUTANE
CHEMICAL NAME: I-BUTENE
-------
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME (CONT.)
N
0")
00
CAS NUMBER: 25167-67-3 CHEMICAL NAME: BUTENE
SUBMISSION fI: 8EHQ-0484-0511
CAS NUMBER: 2426-08-6 CHEMICAL NAME: BUTYL GL YCIDYL ETHER
SUBMISSION fI: BEHQ-0584-0518 S
CAS NUMBER: CONFIDENT CHEMICAL NAME: CARBAMATE, ALIPHATIC
SUBMISSION 1P 8EHQ-0983-0492 S
CAS NUMBER: NONE CHEMICAL NAME: CARBON BLACK FEEDSTOCK
SUBMISSION #: 8EHQ-0183-0468
CAS NUMBER: 63449-39-8 CHEMICAL NAME: CHLORINATED PARAFFINS
SUBMISSION 11= 8EHQ-0983-0491 S 8EHQ-0484-0512
8EHQ-0884-0527
CAS NUMBER:
64741-62-4
CHEMICAL NAME: CLARIFIED OILS (PETROLEUM), CATALYTIC CRACKED
SUBMISSION #: 8EHQ-0584-0517
CAS NUMBER:
NONE
CHEMICAL NAME: COAL, SOLVENT-REFINING (SRC) PROCESS/PRODUCTS
8EHQ-1284-0538
SUBMISSION fI: 8EHQ-0683-0482
CAS NUMBER:
NONE
CHEMICAL NAME: CONFIDENTIAL
SUBMISSION #: 8EHQ-0583-0479 S
CAS NUMBER:
CONFIDENT
CHEMICAL NAME: CONFIDENTIAL
SUBMISSION #: 8EHQ-0683-0483 S
-------
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
N
co
\D
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
APPENDIX C:
98-82-8
SUBMISSION #: 8EHQ-1184-0536
NONE
SUBMISSION #: 8EHQ-0283-0469 S
79419-43-5
SUBMISSION #: 8EHQ-1283-0501
103-33-3
SUBMISSION #: 8EHQ-0484-0513
495-48-7
SUBMISSION #: 8EHQ-0484-0513
68911-57-9
SUBMISSION #: 8EHQ-0683-0482
UNKNOWN
SUBMISSION #: 8EHQ-0683-0482
64742-30-9
SUBMISSION #: 8EHQ-0683-0480
CAS NUMBER: 68477-31-6
SUBMISSION ~:
8ElfJ-0283-0472 S
STATUS REPORTS BY CHEMICAL NAME !CONT.)
CHEMICAL NAME: CUMENE
CHEMICAL NAME: CUTTING FLUID
8EHQ-0283-0471 S
CHEMICAL NAME: 2-CYCLOHEXEN-1-0NE, 2-(2-0XOBUTYL)-5-(2-ETHYLTHIO)-PROPYL-3-
HYDROXY-
CHEMICAL NAME: DIAZENE, DIPHENYL-
CHEMICAL NAME: DIAZENE, DIPHENYL-, 1-0XIDE
CHEMICAL NAME: DISTIllATES (COAL), SOLVENT-REFINING (SRC), MIDDLE
CHEMICAL NAME: DISTILLATES (COAL), SOLVENT-REFINING (SRC), MIDDLE, TWO STAG
E LIQUEFACTION (TSl)
CHEMICAL NAME: DISTILLATES (PETROLEUM), CHEMICALLY NEUTRALIZED MIDDLE
OfEJ.lICAL toW1E:
DISTlUATES (PE'l'R)Lf1JII), CATALYTIC ~R
FAACl'IONATCR RESIDUE, ~OOILING
-------
CAS NUMBER: 64741-61-3 CHEMICAL NAME: DISTILLATES (PETROLEUM), HEAVY
SUBMISSION #: 8EHQ-0183-0468
CAS NUMBER: .64741-53-3
S[JBMISSION #: 8EHQ-0384-0507
CAS NUMBER: 64742-52-5
SUBMISSION #: 8EHQ-0384-0507
CAS NUMBER: 64742-54-7
SUBMISSION #: 8EHQ-0484-0512
[\J
1.0 CAS NUMBER: 64741-60-2
0
SUBMISSION i: 8EHQ-0183-0468
CAS NUMBER: 64741-59-9
SUBMISSION #: 8EHQ-0183-0468
CAS NUMBER: 64742-65-0
SUBMISSION #: 8EHQ-0284-0505
CAS NUMBER: 64741-88-4
SUBMISSION #: 8EHQ-0284-0505
CAS NUMBER: 70776-26-0
SUBMISSION #: 8EHQ-0283-0471 S
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME (CONT.>
CATALYTIC CRACKED
CHEMICAL NAME: DISTILLATES (PETROLEUM), HEAVY NAPHTHENIC
CHEMICAL NAME: DISTILLATES (PETROLEUM), HYDROTREATED HEAVY NAPHTHENIC
CHEMICAL NAME: DISTILLATES (PETROLEUM), HYDROTREATED HEAVY PARAFFINIC
CHEMICAL NAME: DISTILLATES (PETROLEUM), INTERMEDIATE CATALYTIC CRACKED
CHEMICAL NAME: DISTILLATES (PETROLEUM), LIGHT CATALYTIC CRACKED
CHEMICAL NAME: DISTILLATES (PETROLEUM), SOLVENT-DEWAXED HEAVY PARAFFINIC
CHEMICAL NAME: DISTILLATES (PETROLEUM), SOLVENT-REFINED HEAVY PARAFFINIC
CHEMICAL NAME: DISULFIDE, BIS(2-CHLOROOCTYL)
-------
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
I'V
~
\-'
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
APPENDIX C:
76379-66-3
SUBMISSION #: 8EHQ-I084-0532
UNKNOWN
SUBMISSION #: 8EHQ-1284-0538
106-89-8
SUBMISSION I: 8EHQ-0584-0518 S
51365-70-9
SUBMI~SION I: 8EHQ-0583-0478 S
NONE
SUBMISSION I: 8EHQ-0584-0518 S
NONE
SUBMISSION I: 8EHQ-0883-0490
8EHQ-0584-0518 S
540-63-6
SUBMISSION I: 8EHQ-0683-0481
71-55-6
SUBMISSION I: 8EHQ-I084-0535
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CHEMICAL NAME: 5,7,II-DODECATRIYN-I-0L
CHEMICAL NAME: DUST. SRC SOLID
CHEMICAL NAME: EPICHLOROHYDRIN
CHEMICAL NAME: EPON CURING AGENT D
CHEMICAL NAME: EPON 815
CHEMICAL NAME: EPOXY RESINS
8EHQ-0584-0515 S
CHEMICAL NAME: 1,2-ETHANEDITHIOL
CHEMICAL NAME: ETHANE. 1.1.1-TRICHLORO-
8EHQ-0584-0516 S
-------
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CAS NUMBER:
76-13-1
CHEMICAL NAME: ETHANE, 1,1,2-TRICHLORO-1,2,2-TRIFLUORO-
SUBMISSION I: 8EHQ-1084-0535
CAS NUMBER:
111-76-2
CHEMICAL NAME: ETHANOL, 2-BUTOXY-
8EHQ-0584-0517
SUBMISSION I: 8EHQ-0483-0475
CAS NUMBER:
122-99-6
CHEMICAL NAME: ETHANOL, 2-PHENOXY-
SUBMISSION I: 8EHQ-0884-0528
CAS NUMBER: 61791-44-4
SUBMISSION I: 8EHQ-0583-0479 S
N
\.0 CAS NUMBER: 1116-54-7
N
SUBMISSION I: 8EHQ-0283-0469 S
CAS NUMBER: 64742--11-6
SUBMISSION I: 8EHQ-0384-0507
CHEMICAL NAME: ETHANOL, 2,2'-IMINOBIS-, N-TALLOW ALKYL DERIVS.
CHEMICAL NAME: ETHANOL, 2,2'-(NITROSOIMINO)BIS-
CHEMICAL NAME: EXTRACTS (PETROLEUM), HEAVY NAPHTHENIC DISTILLATE SOLVENT
CAS NUMBER: 50-00-0 CHEMICAL NAME: FORMALDEHYDE
SUBMISSION I: 8EHQ-0383-0474
CAS NUMBER: 76-13-1 CHEMICAL NAME: FREON 113
SUBMISSION I: 8EHQ-1084-0535
CAS NUMBER: UNKNOWN CHEMICAL NAME: FUEL OIL, LIGHT PYROLYSIS
SUBMISSION I: 8EHQ-1184-0537
-------
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME (CONT.>
CAS NUMBER:
69013-21-4
CHEMICAL NAME: FUEL OILS, PYROLYSIS
SUBMISSION I: 8EHQ-1184-0537
CAS NUMBER:
68409-94-9
CHEMICAL NAME: FUEL, SRC SOLID
SUBMISSION #: 8EHQ-0683-0482
CAS NUMBER: UNKNOWN CHEMICAL NAME: FUEL, TSl SOLID
SUBMISSION #: 8EHQ-0683-0482
CAS NUMBER: NONE CHEMICAL NAME: GREASE, GULFCROWN E.P. NO. 2
SUBMISSION I: 8EHQ-0484-0512
N
I.D CAS NUMBER: NONE CHEMICAL NAME: GULFCROWN GREASE E.P. NO. 2
w
SUBMISSION #: 8EHQ-0484-0512
CAS NUMBER: 64742-11-6 CHEMICAL NAME: GULF N.E. 61 (PROCESS 65>
SUBMISSION I: 8EHQ-0384-0507
CAS NUMBER: 64741-53-3 CHEMICAL NAME: GULF 100 TEXAS DISTILLATE
SUBMISSION II: 8EHQ-0384-0507
CAS NUMBER: 64742-52-5 CHEMICAL NAME: GULF 100 TEXAS OIL
SUBMISSION I: 8EHQ-0384-0507
CAS NUMBER: 111-14-8 CHEMICAL NAME: HEPTANOIC ACID
SUBMISSION i: 8EHQ-0584-0514
-------
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CAS NUMBER:
111-07-9
CHEMICAL NAME: HEXADECANOIC ACID, 2-METHOXYETHYL ESTER
SUBMISSION #: 8EHQ-1084-0534
CAS NUMBER:
51365-70-9
CHEMICAL NAME: HEXANOIC ACID, 2-ETHYL-, COMPD. WITH 2,4,6-TRIS[(DIMETHYLAMI
NO)METHYLJPHENOL
SUBMISSION #: 8EHQ-0583-0478 S
CAS NUMBER: 7647-01-0 CHEMICAL NAME: HYDROCHLORIC ACID
SUBMISSION #: 8EHQ-0384-0508 P *
CAS NUMBER: 7664-39-3 CHEMICAL NAME: HYDROFLUORIC ACID
SUBMISSION #: 8EHQ-0384-0508 P *
IV
'.0
~
CAS NUMBER: 7803-49-8 CHEMICAL NAME: HYDROXYLAMINE
SUBMISSION #: 8EHQ-0484-0513
CAS NUMBER:
10039-54-0
CHEMICAL NAME: HYDROXYLAMINE, SULFATE (2:1) (SALT)
SUBMISSION #: 8EHQ-0783-0486
CAS NUMBER:
NONE
CHEMICAL NAME: HYPALON MOLDING COMPOUND (THERMAL-DECOMPOSITION PRODUCTS)
SUBMISSION #: 8EHQ-1283-0502 P
*
CAS NUMBER:
288-32-4
CHEMICAL NAME: 1H-IMIDAZOLE
SUBMISSION #: 8EHQ-1284-0540 S
*
-------
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CAS NUMBER:
68442-97-7
CHEMICAL NAME: 1H-IMIDAZOLE-1-ETHANAMINE, 4,5-DIHYDRO-, 2-NORTAll-OIl ALKYL
DERIVS.
SUBMISSION #: 8EHQ-0984-0531 S
*
CAS NUMBER:
931-36-2
CHEMICAL NAME: 1H-IMIDAZOlE, 2-ETHYl-4-METHYL-
SUBMISSION #: 8EHQ-1284-0540 S
*
CAS NUMBER:
71868-10-5
CHEMICAL NAME: IRGACURE 907
SUBMISSION #: 8EHQ-0684-0520
N
'-0
lJ1
CAS NUMBER: NONE CHEMICAL NAr>'" JP-8
SUBMISSION #: 8EHQ-0283-0471 S
CAS NUMBER: 8008-20-6 CHEMICAL NAME: KEROSINE
SUBMISSION #: 8EHQ-0283-0471 S 8EHQ-0283-0472 S
CAS NUMBER: NONE CHEMICAL NAME: KlARUS 1717
SUBMISSION #: 8EHQ-0283-0471 S
CAS NUMBER:
3033-77-0
CHEMICAL NAME: G-MAC
SUBMISSION #: 8EHQ-1283-0503
CAS NUMBER:
64742-30-9
CHEMICAL NAME: MENTOR 28
SUBMISSION #: 8EHQ-0683-0480
-------
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
APPENDIX C:
74-87-3
SUBMISSION #: 8EHQ-1083-0499
75-09-2
SUBMISSION #: 8EHQ-0884-0525
67-56-1
SUBMISSION #: 8EHQ-0484-0513
CAS NUMBER: 1143-72-2
SUBMISSION #: 8EHQ-0484-0510
IV
1.0 CAS NUMBER: 75-09-2
m
SUBMISSION #: 8EHQ-0884-0525
CAS NUMBER: NONE
SUBMISSION #: 8EHQ-1283-0502 P
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
68476-79-9
SUBMISSION #: 8EHQ-0683-0482
64741-68-0
SUBMISSION i: 8EHQ-0283-0472 S
UNKNOWN
SUBMISSION i: 8EHQ-0783-0487 S
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CHEMICAL NAME: METHANE, CHlORO-
CHEMICAL NAME: METHANE, DICHlORO-
CHEMICAL NAME: METHANOL
CHEMICAL NAME: METHANONE, PHENYl(2,3,4-TRIHYDROXYPHENYl)-
CHEMICAL NAME: METHYLENE CHLORIDE
CHEMICAL NAME: MISC. CHEMICALS
*
8EHQ-0384-0508 P
*
CHEMICAL NAME: NAPHTHA (COAL), SOLVENT-REFINING
CHEMICAL NAME: NAPHTHA (PETROLEUM), HEAVY CATALYTIC REFORMED
CHEMICAL NAME: NICOTINIC ACID DERIVATIVE
*
-------
CAS NUMBER:
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME (CONT.)
NONE
SUBMISSION #: 8EHQ-0283-0469 S
CAS NUMBER:
1116-54-7
SUBMISSION #: 8EHQ-0283-0469 S
CAS NUMBER: 112-05-0
SUBMISSION #: 8EHQ-0584-0514
CAS HUMBER: UNKNOWN
SUBMISSION #: 8EHQ-0184-05G4
1\J
~ CAS NUMBER: UNKNOWN
--...J
SUBMISSION #: 8EHQ-0884-0526
CAS NUMBER: 79419-43-5
SUBMISSION #: 8EHQ-1283-0501
CAS NUMBER: 2386-87-0
SUBMISSION #: 8EHQ-0784-0522
CAS NUMBER: 51200-87-4
SUBMISSION #: 8EHQ-0283-0470
CHEMICAL NAME: NITROSAMINES
CHEMICAL NAME: N-NITROSODIETHANOlAMINE
CHEMICAL NAME: NONANOIC ACID
CHEMICAL NAME: OIL (SHALE), lURGI lIGHT/MIDDLE
CHEMICAL NAME: OIL, UNSATURATED ALIPHATIC (C16-C32)
CHEMICAL NAME: ORTHO 36015
CHEMICAL NAME: 7-0XABICYCLO[4.1.0JHEPTANE-3-CARBOXYlIC ACID, 7-0XABICYCLO[4
.1.0JHEPT-3-YlMETHYL ESTER
CHEMICAL NAME: OXAZOLIDINE, 4,4-DIMETHYL-
-------
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
APPENDIX C:
CONFIDENT
SUBMISSION #: 8EHQ-0983-0493 S
CONFIDENT
SUBMISSION #: 8EHQ-OS84-0S17
2426-08-6
SUBMISSION #: 8EHQ-OS84-0S18 S
106-89-8
SUBMISSION #: 8EHQ-0584-0518 S
N
\.D CAS NUMBER: 3033-77-0
00
SUBMISSION #: 8E:HQ-1283-0503
CAS NUMBER: 9003-11-6
SUBMISSION #: 8EHQ-0584-0516 S
CAS NUMBER: 63449-39-8
SUBMISSION #: 8EHQ-0983-0491 S
CAS NUMBER:
CAS NUMBER:
109-52-4
SUBMISSION #: 8EHQ-0584-0514
108-10-1
SUBMISSION #: 8EHQ-1084-0535
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CHEMICAL NAME: OXIDES, METALLIC (MIXTURE)
*
CHEMICAL NAME: OXIDIZED WAX ACIDS, CALCIUM SOAP
CHEMICAL NAME: OXIRANE, (BUTOXYMETHYL)-
CHEMICAL NAME: OXIRANE, (CHLOROMETHYL)-
CHEMICAL NAME: OXIRANEMETHANAMINIUM, N,N,N-TRIMETHYL-, CHLORIDE
CHEMICAL NAME: OXIRANE, METHYL-, POLYMER WITH OXIRANE
CHEMICAL NAME: PARAFFIN WAXES AND HYDROCARBON WAXES, CHLORINATED
8EHQ-0484-0512
8EHQ-0884-0527
CHEMICAL NAME: PENTANOIC ACID
CHEMICAL NAME: 2-PENTANOHE, 4-METHYL-
-------
APPENDIX C:
CAS NUMBER: NONE
,I I
~UBMISSION I: 8EHQ-I084-0535
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
t\J
\0
\0
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
68298-78-2(
SUBMISSION .: 8EHQ-I084-0535
68555-92-0
SUBMISSION #: 8EHQ-I084-0535
CONFIDENT
SUBMISSION #: 8EHQ-0584-0517
92-43-3
SUBMISSION I: 8EHQ-0984-0529
123-30-8
SUBMISSION #: 8EHQ-0484-0513
51-78-5
SUBMISSION #: 8EHQ-0484-0513
25068-38-6
SUBMISSION #: 8EHQ-0584-0518 S
STA!US REPORTS BY CHEMICAL NAME (CONT.>
CHEMICA~ NAME: PERFLUOROALKYL COMPOUNDS
CHEMICAL NAME: PERFLUOROALKYL RESIN
CHEMICAL NAME: PERFLUOROALKYl RESIN
CHEMICAL NAME: PETROLEUM SULFONATE, CALCIUM
CHEMICAL NAME: PHENIDONE
CHEMICAL NAME: PHENOL, 4-AMINO-
CHEMICAL NAME: PHENOL, 4-AMINO-, HYDROCHLORIDE
CHEMICAL NAME: PHENOL, 4,4'-(1-METHYLETHYLIDENE)BI5-, POLYMER WITH (CHLOROM
ETHYL )OXIRANE
-------
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CAS NUMBER: 1429-50-1
SUBMISSION #: 8EHQ-0683-0483 S
CAS NUMBER: 26544-23-0
SUBMISSION #: 8EHQ-0784-0522
CAS NUMBER: 20328-87-4
SUBMISSION #: 8EHQ-0584-0519
CAS NUMBER: 1336-36-3
SUBMISSION #: 8EHQ-0784-0521 S
w
0
0
CAS NUMBER: 9003-07-0 CHEMICAL NAME: POLYPROPYlENE
SUBMISSION #: 8EHQ-0583-0479 S
CAS NUMBER: 20762-60-1 CHEMICAL NAME: POTASSIUM AZIDE (K(N3))
SUBMISSIGN #: 8EHQ-I083-0494 *
CHEMICAL NAME: PHOSPHONIC ACID, £1,2-ETHANEDIYlBIS£NITRIlOBIS(METHYlENE)JJT
ETRAKIS-
CHEMICAL NAME: PHOSPHOROUS ACID, ISODECYl DIPHENYl ESTER
CHEMICAL NAME: PINA SENSITIZER KF 501
CHEMICAL NAME: POLYCHLORINATED BIPHENYLS (PCB)
CAS NUMBER:
3327-22-8
CHEMICAL NAME: 1-PROPANAMINIUM, 3-CHlORO-2-HYDROXY-N,N,N-TRIMETHYl-, CHlORI
DE
SUBMISSION #: 8EHQ-1283-0503
CAS NUMBER:
75-28-5
CHEMICAL NAME: PROPANE, 2-METHYl-
SUBMISSION #: 8EHQ-0484-0511
-------
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
w
o
I-'
CAS NUMBER:
.CAS NUMBER:
CAS NUMBER:
APPENDIX C:
71868-10-5
SUBMISSION #: 8EHQ-0684-0520
79-06-1
SUBMISSION #: 8EHQ-0783-0488
9003-07-0
SUBMISSION #: 8EHQ-0583-0479 S
115-11-7
SUBMISSION #: 8EHQ-0484-0511
382-10-5
SUBMISSION #: 8EHQ-0483-0476 S
68555-92-0
SUBMISSION #: 8EHQ-I084-0535
68298-78-2
SUBMISSION #: 8EHQ-I084-0535
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CHEMICAL NAME: I-PROPANONE, 2-METHYL-l-[(4-METHYLTHIO)PHENYLJ-2-(4-MORPHOLI
NYL) -
CHEMICAL NAME: 2-PROPENAMIDE
CHEMICAL NAME: I-PROPENE, HOMOPOLYMER
CHEMICAL NAME: I-PROPENE, 2-METHYL-
CHEMICAL NAME: I-PROPENE, 3,3,3-TRIFLUORO-2-CTRIFLUOROMETHYL)-
CHEMICAL NAME:
2-PROPENOIC ACID, 2-METHYL-, 2-[[CHEPTADECAFLUOROOCTYL)SULFO
NYLJMETHYLAMINOJETHYL ESTER, POLYMER WITH 2-[METHYL[CNONAFLU
OROBUTYL)SULFONYLJAMINOJETHYL 2-METHYL-2-PROPENOATE, 2-[METH
YL[CPENTADECAFLUOROHEPTYL)SULFONYLJAMINOJETHYL 2-METHYL-2-PR
OPENOATE, 2-[METHYL[CTRIDECAFLUOROHEXYL)SULFONYLJAMINOJETHYL
CHEMICAL NAME:
2-PROPENOIC ACID, 2-METHYL-, 2-[[[[5-[[[2-[ETHYL[CHEPTADECAF
LUOROOCTYL)SULFONYLJAMINOJETHOXYJCARBONYLJAMINOJ-2-METHYLPHE
NYLJAMINOJCARBOHYLJOXYJPROPYL ESTER, TELOMER WITH BUTYL 2-PR
OPENOATE, 2-[[[[5-[[[2-[ETHYL[CNONAFlUOROBUTYL)SULFONYlJAMIH
OJETHOXYJCARBONYlJAMINOJ-2-METHYLPHENYLJAMINOJCARBONYlJOXYJP
-------
APPENDIX C:
CAS NUMBER:
2530-85-0
SUBMISSION 3: 8EHQ-0884-0524
CAS NUMBER:
9'2-43-3
SUBMISSION #: 8EHQ-0984-0529
CAS NUMBER:
6'9045-78-9
SUBMISSION #: 8EHQ-1084-0533 S
CAS NUMBER:
87-66-1
SUBMISSION #: 8EHQ-1284-0539
w CAS NUMBER: 64742-57-0
0
N
SUBMISSION It: 8EHQ-0484-0512
CAS NUMBER: 68409-94-9
SUBMISSION #: 8EHQ-0683-0482
CAS NUMBER: UNKNOWN
SUBMISSION #: 8EHQ-0683-0482
CAS NUMBER: 64742-90-1
SUBMISSION #: 8EHQ-I083-0498
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CHEMICAL NAME: 2-PROPENOIC ACID. 2-METHYl-. 3-(TRIMETHOXYSILYL)PROPYL ESTER
CHEMICAL NAME: 3-PYRAZOLIDINONE. 1-PHENYL-
CHEMICAL NAME: PYRIDINE. 2-CHlORO-5-TRICHLOROMETHYL-
CHEMICAL NAME: PYROGALLOL
CHEMICAL NAME: RESIDUAL OILS (PETROLEUM). HYDROTREATED
CHEMICAL NAME: RESIDUES (COAL>. SOLVENT-REFINING (SRC). VACUUM-DISTN.
CHEMICAL NAME: RESIDUES (COAL>. SOLVENT-REFINING (SRC), VACUUM-DISTN., TWO
STAGE LIQUEFACTION (TSL>
CHEMICAL NAME: RESIDUES (PETROLEUM). STEAM-CRACKED
-------
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
w
o
w
CAS HUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
APPENDIX C:
NONE
SUBMISSION #: 8EHQ-0584-0517
68308-34-9
SUBMISSION #: 8EHQ-0184-0504
2530-85-0
SUBMISSION #: 8EHQ-0884-0524
26628-22-8
SUBMISSION #: 8EHQ-1083-0494
8052-41-3
SUBMISSION #: 8EHQ-0584-0517
64742-30-9
SUBMISSION #: 8EHQ-0683-0480
NONE
SUBMISSION #: 8EHQ-0683-0482
8052-41-3
SUBMISSION #: 8EHQ-0584-0517
64-67-5
SUBMISSION #: 8EHQ-1083-0509
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CHEMICAL NAME: RUST-BAN 392
CHEMICAL NAME: SHALE OILS
CHEMICAL NAME: SILANE A-174
CHEMICAL NAME: SODIUM AZIDE (NA(N3»
*
CHEMICAL NAME: SOLVENT, STODDARD
CHEMICAL NAME: SOMENTOR 43
CHEMICAL NAME: SRC PROCESS/PRODUCTS
8EHQ-1284-0538
CHEMICAL NAME: STODDARD SOLVENT
CHEMICAL NAME: SULFURIC ACID, DIETHYL ESTER
-------
CAS NUMBER:
APPENDIX C:
STATUS REPORTS BY CHEMICAL NAME (CONT.)
5915-41-3
SUBMISSION #: 8EHQ-0783-0485 S
CAS NUMBER:
20328-87-4
SUBMISSION #: 8EHQ-0584-0519
CAS NUMBER:
UNKNOWN
SUBMISSION #: 8EHQ-0584-0519
CAS NUMBER: 7550-45-0
w SUBMISSION #: 8EHQ-0984-0530
o
*'"
CAS NUMBER: 13463-67-7
SUBMISSION #: 8EHQ-1083-0497
CAS NUMBER:
14567-73-8
SUBMISSION #: 8EHQ-0383-0473
CAS NUMBER:
77536-68-6
SUBMISSION #: 8EHQ-0383-0473
CAS NUMBER:
959-52-4
SUBMISSION #: 8EHQ-0384-0506 S
CHEMICAL NAME: TERBUTHYLAZINE
*
CHEMICAL NAME: 2-THIAZOLIUM, 2,2'-[(2-CARBOXY-P-PHENYLENE)BIS(IMINOVINYLENE
)]BIS(3-ETHYL)DIIODIDE
CHEMICAL NAME: 2-THIAZOLIUM, 2,2'-[(2-CARBOXY-P-PHENYLENE)BIS(IMINOVINYLENE
)]BIS(3-ETHYL)DIIODIDE, TRIETHYLAMINE SALT
CHEMICAL NAME: TITANIUM CHLORIDE (TICL4), (T-4)-
CHEMICAL NAME: TITANIUM OXIDE (TI02)
CHEMICAL NAME: TREMOLITE
CHEMICAL NAME: TREMOLITE ASBESTOS
CHEMICAL NAME: 1,3,5-TRIAZINE, HEXAHYDRO-l,3,5-TRI3(1-0XO-2-PROPENYL)-
-------
APPEHDIX C:
STATUS REPORTS BY CHEMICAL NAME (CONT.)
CAS HUMBER:
5915-41-3
CHEMICAL NAME: 1,3,S-TRIAZINE-2,4-DIAMINE, 6-CHLORO-N-(I,I-DIMETHYLETHYL)-N
, -ETHYL-
SUBMISSION #: 8EHQ-0783-0485 S
*
CAS NUMBER:
2451-62-9
CHEMICAL NAME: 1,3,S-TRIAZINE-2,4.6(IH.3H.5H)-TRIONE. 1.3.S-TRIS(OXIRANYLME
THYl)-
SUBMISSION #: 8EHQ-0883-0490
CAS NUMBER:
1318-00-9
CHEMICAL NAME: VERMICULITE
SUBMISSION #: 8EHQ-0383-0473
CAS NUMBER: NONE
w SUBMISSION #: 8EHQ-0484-0512
o
lJ1
CAS NUMBER: UNKNOWN
SUBMISSION #: 8EHQ-0484-0512
CHEMICAL NAME: ZINC DIALKYL DITHIOPHOSPHATES (ZDDP)
CHEMICAL NAME: ZINC DIAMYL DITHIOCARBAMATES
.
Based on a preliminary evaluation, EPA believes that the submitted information did not warrant reporting pursuant to
Section 8(e) of TSCA. In most cases, the submitter was requested to provide the basis for the company's contention
that the information offered reasonable support for the conclusion that the subject chemical(s) posed a substantial
risk of injury to health or the environment as defined in the Agency's March 16, 1978 Section 8(e) policy statement
(see Appendix A of this volume).
-------
APPENDIX D: STATUS REPORTS BY INFORMATION TYPE
ACUTE TOXICITY (ANIMAL)
SUBMISSION #: 8EHQ-0183-0468 8EHQ-0283-0471 S 8EHQ-0483-0476 S
8EHQ-0583-0478 S 8EHQ-0583-0479 S 8EHQ-0683-0482
8EHQ-0783-0485 S * 8EHQ-0783-0486 8EHQ-0783-0487 S *
8EHQ-0883-0490 8EHQ-0983-0492 S 8EHQ-I083-0494 *
8EHQ-I083-0495 8EHQ-I083-0496 8EHQ-I083-0497
8EHQ-1283-0501 8EHQ-0484-0510 8EHQ-0484-0513
8EHQ-0584-0519 8EHQ-0884-0528 8EHQ-0984-0530
8EHQ-0984-0531 S * 8EHQ-I084-0532 8EHQ-I084-0535
8EHQ-1284-0540 S *
w
0
0'\ ACUTE TOXICITY (HUMAN)
SUBMISSION #: 8EHQ-0283-0471 S 8EHQ-0783-0486 8EHQ-0983-0493 S *
8EHQ-1283-0502 P * 8EHQ-0384-0508 P * 8EHQ-0484-0513
8EHQ-0984-0529 8EHQ-1084-0532 8EHQ-I084-0535
ALLERGENICITY (ANIMAL)
SUBMISSION #: 8EHQ-0283-0471 S 8EHQ-0683-0482 8EHQ-0783-0486
8EHQ-0883-0490 8EHQ-I083-0495 8EHQ-1084-0532
ALLERGENICITY (HUMAN)
SUBMISSION #: 8EHQ-0283-0471 S 8EHQ-I084-0532
CELL TRANSFORMATION (IN VITRO)
SUBMISSION #: 8EHQ-0583-0477 S 8EHQ-0883-0490 8EHQ-I083-0495
-------
APPENDIX D: STATUS REPORTS BY INFORMATION TYPE
(CONT.)
CEll TRANSFORMATION (IN VITRO) (CONT.)
SUBMISSION j:
8EHQ-I083-0496
8EHQ-0484-0512
8EHQ-I083-0498
8EHQ-0584-0516 S
8EHQ-0484-0511
8EHQ-1184-0536
8EHQ-1184-0537
CHEMICAL/PHYSICAL PROPERTIES
w
o
-.J
8EHQ-I083-0496
8EHQ-1283-0502 P
*
8EHQ-0583-0478 S 8EHQ-0583-0479 S
8EHQ-0683-0481 8EHQ-0683-0482
8EHQ-0783-0486 8EHQ-0883-0490
8EHQ-0983-0492 S 8EHQ-I083-0495
8EHQ-I083-0498 8EHQ-1283-0501
8EHQ-1283-0503 8EHQ-I083-0509
8EHQ-0584-0519 8EHQ-0684-0520
8EHQ-0984-0530 8EHQ-I084-0534
SUBMISSION j:
8EHQ-0483-0475
8EHQ-0683-0480
8EHQ-0683-0484 S
8EHQ-0983-0491 S
8EHQ-0484-0513
8EHQ-0784-0522
CHRONIC TOXICITY (ANIMAL>
SUBMISSION j: 8EHQ-0283-0469 S
8EHQ-0683-0480
8EHQ-I083-0497
8EHQ-0584-0514
8EHQ-0884-0526
CHRONIC TOXICITY (HUMAN)
SUBMISSION j: 8EHQ-0383-0473
8EHQ-0283-0472 S
8EHQ-0683-0483 S
8EHQ-0383-0474
8EHQ-0783-0488
8EHQ-1283-0503
8EHQ-0584-0517
8EHQ-I083-0509
8EHQ-0884-0525
8EHQ-0984-0530
8EHQ-1284-0538
8EHQ-0884-0523
-------
CLASTOGENICITY (ANIMAL)
SUBMISSION #:
CLASTOGENICITY (IN VITRO)
SUBMISSION II:
w
o
00
DNA DAMAGE/REPAIR
SUBMISSION #:
ECOTOXICITY/AQUATIC TOXICITY
SUBMISSION It:
ENV. OCCURRENCE/RELEASE/FATE
SUBMISSION #:
EPIDEMIOLOGY/CLINICAL
SUBMISSION It:
APPENDIX D: STATUS REPORTS BY INFORMATION TYPE
8EHQ-0483-0476 5
8EHQ-0384-0506 5
8EHQ-0583-0477 S
8EHQ-0484-0511
8EHQ-1184-0537
8EHQ-0683-0481
8EHQ-I083-0509
8EHQ-1283-0500 5
8EHQ-0484-0510
8EHQ-0584-0516 5
8EHQ-I084-0533 S
8EHQ-0584-0518 S
8EHQ-1284-0539
8EHQ-0583-0477 5
8EHQ-0384-0506 5
8EHQ-0683-0481
8EHQ-I083-0509
8EHQ-0484-0512
8EHQ-1184-0536
8EHQ-0783-0486
8EHQ-0983-0491 5
8EHQ-0983-0491 S
8EHQ-0784-0521 5
8EHQ-IC83-0495
8EHQ-0383-0473
8EHQ-I083-0497
(CONT.)
8EHQ-0883-0490
8EHQ-0484-0512
8EHQ-0384-0506 5
8EHQ-0584-0515 5
8EHQ-0784-0522
8EHQ-1283-0503
8EHQ-0484-0511
8EHQ-1184-0537
8EHQ-I083-0495
8EHQ-0384-0508 P
*
8EHQ-0884-0523
-------
HUMAN EXPOSURE (ACCIDENTAL)
SUBMISSION II:
HUMAN EXPOSURE (MONITORING)
SUBMISSION II:
APPENDIX D: STATUS REPORTS BY INFORMATION TYPE
(CONT.)
8EHQ-0384-0508 P
*
8EHQ-0484-0513
8EHQ-0383-0473
8EHQ-0184-0504
BEHQ-1083-0495
BEHQ-07B4-0521 S
8EHQ-I083-0497
8EHQ-I084-0535
SUBMISSION II:
HUMAN EXPOSURE (PRODUCT CONTAMINATION)
8EHQ-0784-0521 S
8EHQ-0283-0469 S
8EHQ-0383-0473
w
o
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SUBMISSION II:
METABOLISM/PHARMACOKINETICS (ANIMAL)
8EHQ-0983-0491 S
SUBMISSION II:
METABOLISM/PHARMACOKINETICS (HUMAN)
8EHQ-0484-0513
MUTAGENICITY (IN VITRO)
SUBMISSION II:
8EHQ-0183-0468
8EHQ-0483-0476 S
8EHQ-0283-0470 8EHQ-0283-0471 S
8EHQ-0583-0477 S 8EHQ-0683-0481
8EHQ-0783-0486 8EHQ-0883-0489
8EHQ-I083-0495 8EHQ-I083-0496
8EHQ-1283-0503 8EHQ-0384-0506 S
8EHQ-0484-0510 8EHQ-0484-0511
BEHQ-0584-0515 S 8EHQ-0584-0516 S
8EHQ-0584-0519 8EHQ-0784-0522
8EHQ-I084-0532 8EHQ-I084-0533 S
8EHQ-0683-0482
BEHQ-OB83-0490
8EHQ-12B3-0500 S
BEHQ-I083-0509
8EHQ-0484-0S12
8EHQ-OSB4-0S18 S
BEHQ-09B4-0530
-------
APPENDIX D: STATUS REPORTS BY INFORMATION TYPE (CONT.)
MUTAGENICITY (IN VITRO) (CONT.)
SUBMISSION II: 8EHQ-1184-0537 8EHQ-1284-0539 8EHQ-1284-0541 S
MUTAGENICITY (IN VIVO)
SUBMISSION II: 8EHQ-0483-0476 S 8EHQ-I083-0499
NEUROTOXICITY (ANIMAL)
SUBMISSION II: 8EHQ-0583-0478 S 8EHQ-I083-0494 * 8EHQ-1283-0501
8EHQ-0684-0520 8EHQ-I084-0532
ONCOGENICITY (ANIMAL)
w SUBMISSION II: 8EHQ-0283-0469 S 8EHQ-0283-0472 S 8EHQ-0383-0474
f-'
0
8EHQ-0683-0480 8EHQ-0683-0483 S 8EHQ-0783-0486
8EHQ-0783-0488 8EHQ-I083-0497 8EHQ-1283-0503
8EHQ-0384-0507 8EHQ-1083-0509 8EHQ-0584-0514
8EHQ-0584-0517 8EHQ-0884-0525 8EHQ-0884-0526
8EHQ-0984-0530 8EHQ-1284-0538
ONCOGENICITY (HUMAN)
SUBMISSION #: 8EHQ-0383-0473 8EHQ-0884-0523
PRODUCT COMPOSITION/CHEMICAL IDENTITY
SUBMISSION II: 8EHQ-0283-0469 S 8EHQ-0283-0471 S 8EHQ-0583-0477 S
8EHQ-0583-0479 S 8EHQ-0683-0480 8EHQ-0683-0483 S
8EHQ-0683-0484 S 8EHQ-0783-0485 S * 8EHQ-0783-0487 S *
8EHQ-0983-0491 S 8EHQ-0983-0493 S * 8EHQ-1283-0500 S
-------
APPENDIX D: STATUS REPORTS BY INFORMATION TYPE
SUBMISSION #:
PRODUCT COMPOSITION/CHEMICAL IDENTITY
PRODUCTION/USE/PROCESS
SUBMISSION #:
W
f-'
f-'
8EHQ-1283-0501
8EHQ-0384-0508 P
8EHQ-0484-0513
8EHQ-0584-0517
8EHQ-0884-0526
8EHQ-0583-0477 S
8EHQ-0683-0481
8EHQ-0783-0487 S
8EHQ-0983-0493 S
8EHQ-I083-0496
8EHQ-1283-0500 S
8EHQ-1283-0503
8EHQ-0384-0506 S
8EHQ-0484-0513
8EHQ-0584-0516 S
8EHQ-0684-0520
8EHQ-0884-0523
8EHQ-0884-0528
8EHQ-I084-0532
8EHQ-I084-0535
(CONT.>
(CONT.>
8EHQ-1283-0502 P * 8EHQ-1283-0503
* 8EHQ-0484-0510 8EHQ-0484-0511
8EHQ-0584-0515 S 8EHQ-0584-0516 S
8EHQ-0584-0519 8EHQ-0784-0521 S
8EHQ-1284-0540 S *
8EHQ-0583-0479 S 8EHQ-0683-0480
8EHQ-0683-0483 S 8EHQ-0783-0485 S
* 8EHQ-0883-0490 8EHQ-0983-0492 S
* 8EHQ-1083-0494 * 8EHQ-I083-0495
8EHQ-I083-0497 8EHQ-1083-0498
8EHQ-1283-0501 8EHQ-1283-0S02 P
8EHQ-0184-0504 8EHQ-0284-0S05
8EHQ-I083-0S09 8EHQ-0484-0S10
8EHQ-0584-0S14 8EHQ-0584-0515 S
8EHQ-0584-0517 8EHQ-0584-0519
8EHQ-0784-0S21 S 8EHQ-0784-0522
8EHQ-0884-0S24 8EHQ-0884-0S26
8EHQ-0984-0S29 8EHQ-0984-0S31 S
8EHQ-I084-0S33 S 8EHQ-1084-0S34
*
*
*
-------
APPENDIX D: STATUS REPORTS BY INFORMATION TYPE
(CONT.)
REPORTING RATIONALE
SUBMISSION I:
8EHQ-0783-0485 S
*
8EHQ-1083-0494
*
8EHQ-0384-0508 P
*
REPRODUCTIVE TOXICITY/TERATO. (ANIMAL)
SUBMISSION It:
8EHQ-0483-0475
8EHQ-0284-0505
8EHQ-0783-0485 S
8EHQ-0884-0527
*
8EHQ-1083-0499
8EHQ-0884-0528
8EHQ-I084-0532
8EHQ-I084-0534
SUBACUTE TOXICITY (ANIMAL)
SUBMISSION It:
8EHQ-0483-0476 S
8EHQ-0683-0484 5
8EHQ-0583-0478 5
8EHQ-0783-0485 5
*
8EHQ-0683-0483 5
8EHQ-I083-0495
W
f-'
tV
8EHQ-I083-0498
8EHQ-I084-0532
8EHQ-0284-0505
8EHQ-I084-0534
8EHQ-0684-0520
SUB CHRONIC TOXICITY (ANIMAL)
SUBMISSION #:
8EHQ-0683-0483 S
8EHQ-0384-0507
8EHQ-I083-0494
8EHQ-0884-0524
*
8EHQ-0184-0504
8EHQ-0984-0529
*
Based on a preliminary evaluation, EPA believes that the submitted information did not warrant reporting pursuant to
Section 8(e) of TSCA. In most cases, the submitter was requested to provide the basis for the company's contention
that the information offered reasonable support for the conclusion that the subject chemical(s) posed a substantial
risk of injury to health or the environment as defined in the Agency's March 16, 1978 Section 8(e) policy statement
(see Appendix A of this volume).
-------
8EHQ-0183-0468
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS HUMBER:
8EHQ-0283-0469 S
CAS NUMBER:
CAS HUMBER:
CAS NUMBER:
W
i'-'
W
CAS NUMBER:
8EHQ-0283-0470
CAS NUMBER:
8EHQ-0283-0471 S
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
APPENDIX E:
STATUS REPORTS BY SUBMISSION HUMBER
NONE
SUBMITTER: PHILLIPS PETROLEUM COMPANY
CHEMICAL NAME: CARBON BLACK FEEDSTOCK
64741-59-9
64741-60-2
CHEMICAL NAME: DISTILLATES (PETROLEUM), LIGHT CATALYTIC CRACKED
CHEMICAL NAME: DISTILLATES (PETROLEUM), INTERMEDIATE CATALYTIC CRACKED
64741-61-3
CHEMICAL NAME: DISTILLATES (PETROLEUM), HEAVY CATALYTIC CRACKED
SUBMITTER: CONFIDENTIAL
NONE CHEMICAL NAME: CUTTING FLUID
NONE CHEMICAL NAME: NITROSAMINES
1116-54-7 CHEMICAL NAME: ETHANOL, 2,2'-(NITROSOIMINO)BIS-
1116-54-7 CHEMICAL NAME: N-NITROSODIETHANOLAMINE
SUBMITTER: ANGUS CHEMICAL COMPANY
51200-87-4
CHEMICAL NAME: OXAZOLIDINE, 4,4-DIMETHYL-
NONE
NONE
SUBMITTER: FERRO CORPORATION
CHEMICAL NAME: CUTTING FLUID
CHEMICAL NAME: JP-8
CHEMICAL NAME: KLARUS 1111
NONE
8008-20-6
CHEMICAL NAME: KEROSINE
CHEMICAL NAME: DISULFIDE, BIS(2-CHLOROOCTYL)
10716-26-0
-------
8EHQ-0283-0472 S
CAS NUMBER:
CAS HUMBER:
CPS NUMBER:
8EHQ-0383-0473
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
8EHQ-0383-0474
CAS NUMBER:
w
,......
.~
CAS NUMBER:
8EHQ-0483-0475
CAS NUMBER:
8EHQ-0483-0476 S
CAS NUMBER:
8EHQ-0583-0477 S
CAS NUMBER:
8EHQ-0583-0478 S
CAS NUI'1BER:
CAS NUMBER:
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CONT.)
SUBMITTER: CONFIDENTIAL
CHEMICAL NAME: KEROSINE
CHEMICAL NAME: NAPHTHA (PETROLEUM), HEAVY CATALYTIC REFORMED
CHEMICAL NN'fE: DISTIUATES (PETIDLflJM), CATALYTIC REFDR1ER
FRAcrr~ RESIDUE, IaJ-OOILING
SUBMITTER: W. R. GRACE & CO.
8008-20-6
64741-68-0
68477-31-6
1318-00-9
14567-73-8
CHEMICAL NAME: VERMICULITE
CHEMICAL NAME: TREMOLITE
77536-68-6
CHEMICAL NAME: TREMOlITE ASBESTOS
SUBMITTER: CElANESE CORPORATION
50-00-0 CHEMICAL NAME: FORMALDEHYDE
75-07-0 CHEMICAL NAME: ACETALDEHYDE
SUBMITTER: EASTMAN KODAK COMPANY
111-76-2
CHEMICAL NAME: ETHANOL, 2-BUTOXY-
SUBMITTER: CONFIDENTIAL
382-10-5
CHEMICAL NAME: I-PROPENE, 3,3,3-TRIFlUORO-2-(TRIFlUOROMETHYL)-
SUBMITTER: CONFIDENTIAL
CONFIDENT
CHEMICAL NAME: AROMATICS, SUBSTITUTED
SUBMITTER: SHELL OIL COMPANY
51365-70-9
51365-70-9
CHEMICAL NAME: EPON CURING AGENT D
CHEMICAL NAME: HEXANOIC ACID, 2-ETHYL-, COMPD. WITH 2,4,6-TRIS[(DIMETHYLAMI
NO)METHYlJPHENOL
-------
8EHQ-0583-0479 S
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
8EHQ-0683-0480
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
W
f-'
U1
8EHQ-0683-0481
CAS NUMBER:
8EHQ-0683-0482
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CONT.)
SUBMITTER: CONFIDENTIAL
NONE CHEMICAL NAME: CONFIDENTIAL
9003-07-0 CHEMICAL NAME: POLYPROPYLENE
9003-07-0 CHEMICAL NAME: I-PROPENE. HOMOPOLYMER
61791-44-4 CHEMICAL NAME: ETHANOL, 2.2'-IMINOBIS-, N-TALLOW ALKYL DERIVS.
SUBMITTER: EXXON COMPANY, U.S.A.
64742-30-9 CHEMICAL NAME: DISTILLATES (PETROLEUM), CHEMICALLY NEUTRALIZED MIDDLE
64742-30-9 CHEmCAL NAME: MENTOR 28
64742-30-9 CHEMICAL NAME: SOMEt/TOR 43
SUBMITTER: PHILLIPS PETROLEUM COMPANY
540-63-6
CHEMICAL NAME: 1.2-ETHANEDITHIOL
NONE
NONE
SUBMITTER: INTERNATIONAL COAL REFINING COMPANY
CHEMICAL NAME: COAL. SOLVENT-REFINING (SRC) PROCESS/PRODUCTS
UNKNOWN
CHEMICAL NAME: SRC PROCESS/PRODUCTS
CHEMICAL NAME: DISTILLATES (COAL). SOLVENT-REFINING (SRC). MIDDLE. TWO STAG
E LIQUEFACTION (TSL)
UNKNOWN
UNKNOWN
CHEMICAL NAME: FUEL, TSL SOLID
CHEMICAL NAME: RESIDUES (COAL). SOLVENT-REFINING (SRC), VACUUM-DISTN., TWO
STAGE LIQUEFACTION (TSL)
68131-74-8
68409-94-9
CHEMICAL NAME: ASHES (RESIDUES)
CHEMICAL NAME: FUEL. SRC SOLID
-------
8EHQ-0683-0482
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
8EHQ-0683-0483 S
CAS NUMBER:
CAS NUMBER:
W
f--'
0"\
8EHQ-0683-0484 S
CAS NUMBER:
8EHQ-0783-0485 S
CAS NUMBER:
CAS NUMBER:
8EHQ-0783-0486
CAS NUMBER:
8EHQ-0783-0487 S
CAS NUMBER:
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CONT.)
CCONT.)
SUBMITTER: INTERNATIONAL COAL REFINING COMPANY
68409-94-9
68476-79-9
CHEMICAL NAME: RESIDUES (COAL), SOLVENT-REFINING CSRC), VACUUM-DISTN.
CHEMICAL NAME: NAPHTHA (COAL), SOLVENT-REFINING
68911-57-9
CHEMICAL NAME: DISTILLATES (COAL), SOLVENT-REFINING (SRC), MIDDLE
SUBMITTER: CONFIDENTIAL
CONFIDENT
1429-50-1
CHEMICAL NAME: CONFIDENTIAL
CHEMICAL NAME: PHOSPHONIC ACID, 11,2-ETHANEDIYLBISINITRIlOBIS(METHYLENE»)IT
ETRAKIS-
SUBMITTER: ROHM AND HAAS COMPANY
CONFIDENT
CHEMICAL NAME: ACRYLIC POLYMER
*
SUBMITTER: CIBA-GEIGY CORPORATION
5915-41-3
5915-41-3
CHEMICAL NAME: TERBUTHYLAZINE
CHEMICAL NAME: 1,3,5-TRIAZINE-2,4-DIAMINE, 6-CHLORO-N-(1,1-DIMETHYlETHYL)-N
'-ETHYl-
SUBMITTER: ALLIED CORPORATION
10039-54-0
CHEMICAL NAME: HYDROXYLAMINE, SULFATE (2:1) (SALT)
*
SUBMITTER: AMERICAN CYANAMID COMPANY
UNKNOWN
CHEMICAL NAME: NICOTINIC ACID DERIVATIVE
-------
8EHQ-0783-0488
CAS NUMFR.:
CAS NUMBER:
,
I
8EHQ-0883'1-0489
CAS NUMBER:
8EHQ-0883-0490
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
W
f-'
-..J
8EHQ-0983-0491 S
CAS NUMBER:
CAS NUMBER:
8EHQ-0983-0492 S
CAS NUMBER:
8EHQ-0983-0493 S
CAS NUMBER:
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CONT.)
SUBMITTER: DOW CHEMICAL COMPANY
79-06-1
79-06-1
CHEMICAL NAME: ACRYlAMIDE
CHEMICAL NAME: 2-PROPENAMIDE
SUBMITTER: lONZA INC.
68479-98-1
CHEMICAL NAME: BENZENEDIAMINE, AR,AR-DIETHYl-AR-METHYl-
NONE
SUBMITTER: CIBA-GEIGY CORPORATION
CHEMICAL NAME: EPOXY RESINS
2451-62-9
2451-62-9
CHEMICAL NAME: ARAlDITE PT-810
CHEMICAL NAME: 1,3,5-TRIAZINE-2,4,6(IH,3H,5H)-TRIONE, 1,3,5-TRIS(OXIRANYlME
THYl) -
SUBMITTER: CHLORINATED PARAFFIN PRODUCERS TESTING CONSORTIUM
63449-39-8
63449-39-8
CHEMICAL NAME: CHLORINATED PARAFFINS
CHEMICAL NAME: PARAFFIN WAXES AND HYDROCARBON WAXES, CHLORINATED
SUBMITTER: CONFIDENTIAL
CONFIDENT
CHEMICAL NAME: CARBAMATE, ALIPHATIC
*
SUBMITTER: CONFIDENTIAL
CONFIDENT
CHEMICAL NAME: OXIDES, METAllIC (MIXTURE)
-------
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CONT.)
8EHQ-1083-0494
*
SUBMITTER: PPG INDUSTRIES, INC.
CAS NUMBER:
CAS NUMBER:
20762-60-1
26628-22-8
CHEMICAL NAME: POTASSIUM AZIDE (K(N3»
CHEMICAL NAME: SODIUM AZIDE (NA(N3»
8EHQ-1083-0495
CAS NUMBER:
SUBMITTER: EASTMAN KODAK COMPANY
1134-36-7
CHEMICAL NAME: [1,1'-BIPHENYl]-4-0L, 3-AMINO-
8EHQ-1083-0496
CAS NUMBER:
SUBMITTER: EASTMAN KODAK COMPANY
89-62-3
CHEMICAL NAME: BENZENAMINE, 4-METHYL-2-NITRO-
8EHQ-I083-0497 SUBMITTER: E. 1. DUPONT DE NEMOURS & COMPANY, INC.
Lv CAS NUMBER: 13463-67-7 CHEMICAL NAME: TITANIUM OXIDE (TIOZ)
f--'
0:>
8EHQ-1083-0498 SUBMITTER: GUl F OIL CHEMICALS COMPANY
CAS NUMBER: 64742-90-1 CHEMICAL NAME: RESIDUES (PETROLEUM), STEAM-CRACKED
8EHQ-1083-0499
CAS NUMBER:
SUBMITTER: VULCAN CHEMICALS
74-87-3
CHEMICAL NAME: METHANE, CHlORO-
8EHQ-1Z83-0500 S
CAS NUMBER:
SUBMITTER: CONFIDENTIAL
CONFIDENT
CHEMICAL NAME: BENZENAMINE, SUBSTITUTED POLYGlYCIDYL
8EHQ-1283-0501
CAS NUMBER:
SUBMITTER: CHEVRON CHEMICAL COMPANY
79419-43-5
CHEMICAL NAME: 2-CYClOHEXEH-1-0HE, 2-(2-0XOBUTYl)-5-(2-ETHYlTHIO)-PROPYL-3-
HYDROXY-
CHEMICAL NAME: ORTHO 36015
CAS NUMBER:
79419-43-5
-------
8EHQ-1283-0502 P
CAS NUMBER:
CAS NUMBER:
8EHQ-1283-0503
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
W
I-'
~
8EHQ-0184-0504
CAS NUMBER:
CAS NUMBER:
8EHQ-0284-0505
CAS NUMBER:
CAS NUMBER:
8EHQ-0384-0506 S
CAS NUMBER:
8EHQ-0384-0507
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CONT.)
*
SUBMITTER: GENERAL MOTORS CORPORATION
CHEMICAL NAME: HYPALON MOLDING COMPOUND (THERMAL-DECOMPOSITION PRODUCTS)
NONE
NOHE
CHEMICAL NAME: MISC. CHEMICALS
SUBMITTER: DOW CHEMICAL COMPANY
3033-77-0
3033-77-0
CHEMICAL NAME: G-MAC
CHEMICAL NAME: OXIRANEMETHANAMINIUM, N,N,N-TRIMETHYl-, CHLORIDE
3327-22-8
CHEMICAL NAME: 1-PROPANAMIHIUM, 3-CHLORO-2-HYDROXY-H,N,H-TRIMETHYL-, CHLORI
DE
SUBMITTER: RIO BLANCO OIL SHALE COMPAHY
UNKNOWN
68308-34-9
CHEMICAL NAME: OIL (SHALE), LURGI LIGHT/MIDDLE
CHEMICAL NAME: SHALE OILS
SUBMITTER: STANDARD OIL COMPANY (INDIANA)
64741-88-4
64742-65-0
CHEMICAL NAME: DISTILLATES (PETROLEUM), SOLVENT-REFINED HEAVY PARAFFINIC
CHEMICAL NAME: DISTILLATES (PETROLEUM), SOLVENT-DEWAXED HEAVY PARAFFINIC
SUBMITTER: CONFIDENTIAL
959-52-4
CHEMICAL NAME: 1,3,5-TRIAZINE, HEXAHYDRO-1,3,5-TRIS(1-0XO-2-PROPENYL)-
SUBMITTER: GULF OIL PRODUCTS COMPANY
64741-53-3 CHEMICAL NAME: DISTILLATES (PETROLEUM), HEAVY NAPHTHENIC
64741-53-3 CHEMICAL NAME: GULF 100 TEXAS DISTILLATE
64742-11-6 CHEMICAL NAME: EXTRACTS (PETROLEUM), HEAVY NAPHTHENIC DISTILLATE SOLVENT
-------
8EHQ-0384-0507
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
8EHQ-0384-0508 P
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
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8EHQ-I083-0509
CAS NUMBER:
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CONT.)
(CONT.)
SUBMITTER: GULF OIL PRODUCTS COMPANY
64742-11-6
64742-52-5
CHEMICAL NAME: GULF N.E. 61 (PROCESS 65)
CHEMICAL NAME: DISTIllATES (PETROLEUM), HYDROTREATED HEAVY NAPHTHENIC
64742-52-5
CHEMICAL NAME: GULF 100 TEXAS OIL
*
SUBMITTER: RACON INC.
CHEMICAL NAME: MISC. CHEMICALS
NONE
7647-01-0
7647-18-9
CHEMICAL NAME: HYDROCHLORIC ACID
CHEMICAL NAME: ANTIMONY CHLORIDE (SBCL5)
7664-39-3
CHEMICAL NAME: HYDROFLUORIC ACID
SUBMITTER: UNION CARBIDE CORPORATION
64-67-5
CHEMICAL NAME: SULFURIC ACID. DIETHYL ESTER
8EHQ-0484-0510 SUBMITTER: IBM CORPORATION
CAS NUMBER: 1143-72-2 CHEMICAL NAME: METHANONE. PHENYl(2.3.4-TRIHYDROXYPHENYl)-
8EHQ-0484-0S11 SUBMITTER: GULF OIL PRODUCTS COMPANY
CAS NUMBER: NONE CHEMICAL NAME: 1, 3-BUT ADI ENE FEEDSTOCK
CAS NUMBER: 75-28-5 CHEMICAL NAME: PROPANE. 2-METHYL-
CAS NUMBER: 106-97-8 CHEMICAL NAME: BUTANE
CAS NUMBER: 106-98-9 CHEMICAL NAME: I-BUTENE
CAS NUMBER: 106-99-0 CHEMICAL NAME: 1, 3-BUT ADI ENE
CAS NUMBER: 115-11-7 CHEMICAL NAME: I-PROPENE. 2-METHYL-
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8EHQ-0484-0511
CAS NUMBER:
8EHQ-0484-0512
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CA S NUf1B ER :
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CAS NUf1BER:
CAS NUMBER:
8EHQ-0484-0513
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CONT.)
(CONT.)
SUBMITTER: GULF OIL PRODUCTS COMPANY
25167-67-3
CHEMICAL NAME: BUTENE
SUBMITTER: GULF OIL PRODUCTS COMPANY
NONE CHEMICAL NAME: GREASE, GULFCROWN E.P. NO. 2
NONE CHEMICAL NAME: GULFCROWN GREASE E.P. NO. 2
NONE CHEMICAL NAME: ZINC DIALKYL DITHIOPHOSPHATES (ZDDP)
UNKNOWN CHEMICAL NAME: ZINC DIAMYL DITHIOCARBAMATES
63449-39-8 CHEMICAL NAME: CHLORINATED PARAFFINS
63449-39-8 CHEMICAL NAME: PARAFFIN WAXES AND HYDROCARBON WAXES, CHLORINATED
64742-54-7 CHEMICAL NAME: DISTILLATES (PETROLEUM), HYDROTREATED HEAVY PARAFFINIC
64742-57-0 CHEMICAL NAME: RESIDUAL OILS (PETROLEUM), HYDROTREATED
SUBMITTER: MALLINCKRODT, INC.
51-78-5
CHEMICAL NAME: PHENOL, 4-AMINO-, HYDROCHLORIDE
62-53-3 CHEMICAL NAME: BENZENAMINE
67-56-1 CHEMICAL NAME: METHANOL
98-95-3 CHEMICAL NAME: BENZENE, NITRO-
100-65-2 CHEMICAL NAME: BEHZENAMINE, N-HYDROXY-
103-33-3 CHEMICAL NAME: DIAZENE, DIPHENYL-
123-30-8 CHEMICAL NAME: PHENOL, 4-AMINO-
495-48-7 CHEMICAL NAME: DIAZENE, DIPHENYL-, I-OXIDE
7803-49-8 CHEMICAL NAME: HYDROXYLAMINE
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APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CONT.)
8EHQ-0584-0514
CAS NUMBER:
SUBMITTER: CELANESE CORPORATION
CAS NUMBER:
CAS NUMBER:
109-52-4
111-14-8
CHEMICAL NAME: PENTANOIC ACID
CHEMICAL NAME: HEPTANOIC ACID
112-05-0
CHEMICAL NAME: NONANOIC ACID
8EHQ-0584-0515 S SUBMITTER: CONFIDENTIAL
CAS NUMBER: NONE CHEMICAL NAME: EPOXY RESINS
8EHQ-0584-0516 S SUBMITTER: CONFIDENTIAL
CAS NUMBER: NONE CHEMICAL NAME: EPOXY RESINS
CAS NUMBER: 9003-11-6 CHEMICAL NAME: OXIRANE, METHYl-, POLYMER WITH OXIRANE
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8EHQ-0584-0517 SUBMITTER: EXXON COMPANY, U.S.A.
CAS NUMBER: CONFIDENT CHEMICAL NAME: OXIDIZED WAX ACIDS, CALCIUM SOAP
CAS NUMBER: CONFIDENT CHEMICAL NAME: PETROLEUM SULFONATE, CALCIUM
CAS NUMBER: NONE CHEMICAL NAME: RUST-BAN 392
CAS NUMBER: 111-76-2 CHEMICAL NAME: ETHANOl, 2-BUTOXY-
CAS NUMBER: 8052-41-3 CHEMICAL NAME: SOLVENT, STODDARD
CAS NUMBER: 8052-41-3 CHEMICAL NAME: STODDARD SOLVENT
CAS NUMBER: 64741-62-4 CHEMICAL NAME: CLARIFIED OILS (PETROLEUM), CATALYTIC CRACKED
8EHQ-0584-0518 S SUBMITTER: CONFIDENTIAL
CAS NUMBER: NONE CHEMICAL NAME: EPON 815
CAS NUMBER: NONE CHEMICAL NAME: EPOXY RESINS
-------
8EHQ-0584-0518 S
CAS NUMBER:
I
CAS NUMBER:
CAS NUMBER:
CtjS NUMB!;R:
CAS NUMBE~:
8EHQ-0584-0519
CAS NUMBER:
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CAS NUMBER:
CAS HUMBER:
8EHQ-0684-0520
CAS NUMBER:
CAS NUMBER:
8EHQ-0784-0521 S
CAS NUMBER:
CAS NUMBER:
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CONT.)
(CONT.)
SUBMITTER: CONFIDENTIAL
106-89-8 CHEMICAL NAME: EPICHlOROHYDRIN
106-89-8 CHEMICAL NAME: OXIRANE, (CHLOROMETHYU-
2426-08-6 CHEMICAL NAME: BUTYL GLYCIDYl ETHER
2426-08-6 CHEMICAL NAME: OXIRANE, (BUTOXYMETHYL) -
25068-38-6 CHEMICAL NAME: PHENOL, 4,4'-(1-METHYlETHYlIDENE)BIS-, POLYMER WITH CCHlOROM
ETHYUOXIRAHE
SUBMITTER: 3M COMPANY
UNKNOWN
CHEMICAL NAME: 2-THIAZOLIUM, 2,2'-[(2-CARBOXY-P-PHENYLEHE)BISCIMINOVINYLENE
)]BIS(3-ETHYl)DIIODIDE, TRIETHYLAMINE SALT
CHEMICAL NAME: PINA SENSITIZER KF 501
20328-87-4
20328-87-4
CHEMICAL NAME: 2-THIAZOlIUM, 2,2'-[(2-CARBOXY-P-PHENYlEHE)BISCIMINOVINYlENE
)]BIS(3-ETHYL)DIIODIDE
SUBMITTER: CIBA-GEIGY CORPORATION
71868-10-5
71868-10-5
CHEMICAL NAME: IRGACURE 907
CHEMICAL NAME: I-PROPANONE, 2-METHYl~1-[(4-METHYLTHIO)PHENYL]-2-(4-MORPHOLI
NYl)-
SUBMITTER: EMHART CORPORATION
1336-36-3
1336-36-3
CHEMICAL NAME: 1,1'-BIPHENYL, CHLORO DERIVS.
CHEMICAL NAME: POLYCHLORINATED BIPHENYLS (PCB)
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8EHQ-0784-0522
CAS NUMBER:
CAS NUMBER:
8EHQ-0884-0523
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
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8EHQ-0884-0524
CAS NUMBER:
CAS NUMBER:
8EHQ-0884-0525
CAS NUMBER:
CAS NUMBER:
8EHQ-0884-0526
CAS NUMBER:
8EHQ-0884-0527
CAS NUMBER:
CAS NUMBER:
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CONT.)
SUBMITTER: WITCO CHEMICAL CORPORATION
2386-87-0
CHEMICAL NAME: 7-0XABICYCLO£4.1.0IHEPTANE-3-CARBOXYLIC ACID, 7-0XABICYCLO[4
.1.OIHEPT-3-YLMETHYL ESTER
CHEMICAL NAME: PHOSPHOROUS ACID, ISODECYL DIPHENYL ESTER
26544-23-0
SUBMITTER: VELSICOL CHEMICAL CORPORATION
98-07-7 CHEMICAL NAME: BENZENE, (TRICHLOROMETHYL)-
98-88-4 CHEMICAL NAME: BENZOYL CHLORIDE
100-44-7 CHEMICAL NAME: BENZENE, (CHLOROMETHYU-
SUBMITTER: UNION CARBIDE CORPORATION
2530-85-0
2530-85-0
CHEMICAL NAME: 2-PROPENOIC ACID, 2-METHYL-, 3-(TRIMETHOXYSILYL)PROPYL ESTER
CHEMICAL NAME: SILANE A-174
SUBMITTER: HALOGENATED SOLVENTS INDUSTRY ALLIANCE
75-09-2
75-09-2
CHEMICAL NAME: METHANE, DICHLORO-
CHEMICAL NAME: METHYLENE CHLORIDE
SUBMITTER: UNION CARBIDE CORPORATION
UNKNOWN
CHEMICAL NAME: OIL, UNSATURATED ALIPHATIC (C16-C32)
SUBMITTER: CHLORINATED PARAFFIN PRODUCERS TESTING CONSORTIUM
63449-39-8
63449-39-8
CHEMICAL NAME: CHLORINATED PARAFFINS
CHEMICAL NAME: PARAFFIN WAXES AND HYDROCARBON WAXES, CHLOPINATED
-------
8EHQ-0884-0528
CAS NUMBER:
8EHQ-0984-0529
CAS NUMBER:
CAS NUMBER:
8EHQ-0984-0530
CAS NUMBER:
8EHQ-0984-0531 S
W
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CAS NUMBER:
8EHQ-1084-0532
CAS NUMBER:
8EHQ-1084-0533 S
CAS NUMBER:
8EHQ-1084-0534
CAS NUMBER:
8EHQ-1084-0535
CAS NUMBER:
CAS NUMBER:
122-99-6
92-43-3
92-43-3
7550-45-0
*
68442-97-7
76379-66-3
69045-78-9
111-07-9
NONE
71-55-6
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CONT.)
SUBMITTER: DOW CHEMICAL COMPANY
CHEMICAL NAME: ETHANOL, 2-PHENOXY-
SUBMITTER: EASTMAN KODAK COMPANY
CHEMICAL NAME: PHENIDONE
CHEMICAL NAME: 3-PYRAlOLIDINONE, 1-PHENYL-
SUBMITTER: E. I. DUPONT DE NEMOURS & COMPANY, INC.
CHEMICAL NAME: TITANIUM CHLORIDE (TICL4), (T-4)-
SUBMITTER: CONFIDENTIAL
CHEMICAL NAME: 1H-IMIDAlOLE-1-ETHANAMINE, 4,5-DIHYDRO-, 2-NORTALL-OIL ALKYL
DERIVS.
SUBMITTER: ALLIED CORPORATION
CHEMICAL NAME: 5,7,11-DODECATRIYN-1-0L
SUBMITTER: CONFIDENTIAL
CHEMICAL NAME: PYRIDINE, 2-CHLORO-5-TRICHLOROMETHYL-
SUBMITTER: TENNESSEE EASTMAN COMPANY
CHEMICAL NAME: HEXADECANOIC ACID, 2-METHOXYETHYL ESTER
SUBMITTER: 3M COMPANY
CHEMICAL NAME: PERFLUOROALKYL COMPOUNDS
CHEMICAL NAME: ETHANE, 1,1,1-TRICHLORO-
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8EHQ-1084-0535
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
W
N
0'\
CAS NUMBER:
CAS NUMBER:
APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CONT.)
(CONT.)
SUBMITTER: 3M COMPANY
76-13-1
76-13-1
CHEMICAL NAME: ETHANE, 1,1,2-TRICHLORO-l,2,2-TRIFLUORO-
CHEMICAL NAME: FREON 113
108-10-1
10212-58-5
CHEMICAL NAME: 2-PENTANONE, 4-METHYL-
CHEMICAL NAME: 1-AZIRIDINECARBOXAMIDE, 2-METHYL-N-OCTADECYL-
68298-78-2
68298-78-2
CHEMICAL NAME: PERFLUOROALKYL RESIN
CHEMICAL NAME:
2-PROPEHOIC ACID, 2-METHYL-, 2-[[[[5-[[[2-[ETHYL[(HEPTADECAF
LUOROOCTYL)SULFONYLIAMINOIETHOXYICARBONYLIA~1INOI-2-METHYLPHE
NYLIAMIHOICARBONYLJOXYIPROPYL ESTER, TELOMER WITH BUTYL 2-PR
OPENOATE, 2-[[[[5-[[[2-[ETHYl[(NONAFlUOROBUTYl)SUlFONYlIAMIN
OIETHOXYJCARBONYlJAMINOI-2-METHYlPHENYlJAMINOICARBOIIYlJOXYIP
CHEMICAL NAME: PERFlUOROAlKYl RESIN
68555-92-0
68555-92-0
CHEMICAL NAME:
2-PROPENOIC ACID, 2-METHYl-, 2-[[(HEPTADECAFlUOROOCTYl)SUlFO
NYlJt1ETHYlAMINOJETHYl ESTER, POLYMER WITH 2-[METHYl[(NONAFlU
OROBUTYl)SUlFONYlJAMINOJETHYl 2-METHYl-2-PROPENOATE, 2-[METH
Yl[(PENTADECAFLUOROHEPTYl)SUlFONYlJAMINOIETHYl 2-METHYL-2-PR
OPENOATE, 2-[METHYl[(TRIDECAFlUOROHEXYl)SUlFONYlJAMINOJETHYl
8EHQ-1184-0536 SUBMITTER: GULF OIL PRODUCTS COMPANY
CAS NUMBER: 98-82-8 CHEMICAL NAME: BENZENE, (I-METHYl ETHYl)-
CAS NUMBER: 98-82-8 CHEMICAL NAME: CUMENE
8EHQ-1184-0537 SUBMITTER: GULF OIL PRODUCTS COl1PANY
CAS NUMBER: UNKNOWN CHEMICAL NAME: FUEL OIL, LIGHT PYROLYSIS
CAS NUMBER: 69013-21-4 CHEMICAL NAME: FUEL OILS, PYROLYSIS
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APPENDIX E:
STATUS REPORTS BY SUBMISSION NUMBER (CONT.)
8EHQ-1284-0538
CAS NUMBER:
CAS NUMBER:
CAS NUMBER:
NONE
NONE
SUBMITTER: AIR PRODUCTS AND CHEMICALS, INC.
CHEMICAL NAME: COAL, SOLVENT-REFINING (SRC) PROCESS/PRODUCTS
UNKNOWN
CHEMICAL NAME: SRC PROCESS/PRODUCTS
CHEMICAL NAME: DUST, SRC SOLID
8EHQ-1284-0539
CAS NUMBER:
SUBMITTER: NOR-AM CHEMICAL COMPANY
CAS NUMBER:
87-66-1
87-66-1
CHEMICAL NAME: 1,2,3-BENZENETRIOL
CHEMICAL NAME: PYROGALLOL
8EHQ-1284-0540 S
*
SUBMITTER: CONFIDENTIAL
CAS NUMBER: 288-32-4 CHEMICAL NAME: IH-IMIDAZOLE
w
tV CAS NUMBER: 931-36-2 CHEMICAL NAME: 1H-IMIDAZOLE, 2-ETHYL-4-METHYL-
-..J
8EHQ-1284-054I S SUBMITTER: CONFIDENTIAL
CAS NUMBER: 480-96-6 CHEMICAL NAME: B ENZO FURAZM1, I-OXIDE
*
Based on a preliminary evaluation, EPA believes that the submitted information did not warrant reporting pursuant to
Section 8(e) of TSCA. In most cases, the submitter was requested to provide the basis for the company's contention
that the information offered reasonable support for the conclusion that the subject chemical(s) posed a substantial
risk of injury to health or the environment as defined in the Agency's March 16, 1978 Section 8(e) policy statement
(see Appendix A of this volume).
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TECHNICAL REPORT DATA
(Please read Instructions on the reverse before completing)
1. REPORT NO. 12. 3. RECIPIENT'S ACCESSION NO.
EPA 560/2-85-001
4. TITLE AND SUBTITLE 5. REPORT DATE
"Preliminary Evaluations of Initial TSCA MARCH 1985
Section 8(e) Substantial Risk Notices" 6. PERFORMING ORGANIZATION CODE
January 1, 1983 to December 31, 1984
7. AUTHOR(S) 8. PERFORMING ORGANIZATION REPDRT NO.
Office of Toxic Substances/OPTS
U.S. Environmental Protection Agency (EPA)
9. PERFORMING ORGANIZATION NAME AND ADDRESS 10. PROGRAM ELEMENT NO.
Office of Pesticides and Toxic Substances (TS-788)
U.S. Environmental Protection Agency (EPA) 11. CONTRACT/GRANT NO.
401 "M" Street, S.W.
Washington, D.C. 20460
12. SPONSORING AGENCY NAME AND ADDRESS 13. TYPE OF REPORT AND PERIOD COVERED
Office of Pesticides and Toxic Substances (TS-788) 01/01/83 to 12/31/84
U.S. Environmental Protection Agency (EPA) 14. SPONSORING AGENCY CODE
401 "M" Street, S.W.
Washington, D.C. 20460
15. SUPPLEMENTARY NOTES
16. ABSTRACT
This volume contains, in ascending submission number order, "status report" (Le.,
preliminary evaluations) prepared by staff of the Office of Toxic Substances in
EPA's Office of Pesticides and Toxic Substances for initial submissions received
by EPA from chemical manufacturers, importers, processors, and distributors from
January 1, 1983 to December 31, 1984 under Section 8 (e), the "substantial risk"
information reporting provision of the Toxic Substances Control Act (TSCA). The
status reports contained in this compendium reflect only the initial phases of
EPA's evaluation process for the submitted information.
This TSCA Section 8(e) status report volume has been published by the Agency for
two reasons. First, a volume of Section 8(e) status reports with appropriate in-
dices 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) under-
stand better the types of information that should be submitted to EPA pursuant
to this mandatory reporting provision of TSCA.
-
17. KEY WORDS AND DOCUMENT ANALYSIS
a. DESCRIPTORS b.IDENTIFIERS/OPEN ENDED TERMS c. COSATI Field/Group
Toxic Substances Control Act
TSCA
Section 8(e)
Substantial Risk
18. DISTRIBUTION STATEMENT 19. SECuRiTY CLASS (Tllis Repoytl 21. NO. OF PAGES
340
Unlimited Distribution 20 SECURITY CLASS (This page) 22. PRICE
.-
EPA Form 2220-1 (Rev. 4-77)
PREVIOUS EDITION IS OBSOLETE
*u . 5 ~ GOVERNMENT PRINTING OFFICE:
1985-461-22./24046
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