United States
Eovironrre -*al Protection
Agency
Office of Pesticides
and Toxic Substances
Washington, DC 20460
April 1980
EPA-560/11-80-008
Toxic Scbstances
TSCA Chemical
Assessment Series
Chemical Screening:
Initial Evaluations of
Substantial Risk
Notices, Section 8(e)
January 1, 1977 - June 30,1979
-------
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 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 560/11-80-008
March 1980
CHEMICAL SCREENING: INITIAL EVALUATIONS OF
SUBSTANTIAL RISK NOTICES, SECTION 8(e)
JANUARY 1, 1977, TO JUNE 30, 1979
Volume 1
Office of Testing and Evaluation
Office of Pesticides and Toxic Substances
Washington, DC 20460
H.Sf, Environ/.'^ r I ,O
Jki^loa :;, ,,jLV' ,, •
230 S. Dearborn i,.
, IL .60604
U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF PESTICIDES AND TOXIC SUBSTANCES
WASHINGTON, DC 20460
-------
Disclaimer
This volume has been reviewed by the Office of Pesticides and
Toxic Substances, U.S. Environmental Protection Agency, and
approved for publication. The status reports published in this
volume present the Agency's preliminary evaluations of the sub-
mitted information; they do not represent final Agency policy or
intent with respect to the submissions or the subject chemicals.
Mention of company names, trade names, or commercial products
does not constitute Agency endorsement or recommendation.
11
-------
Foreword
Evaluations of chemical substances prepared by scientists in
EPA's Office of Testing and Evaluation, Office of Pesticides and
Toxic Substances (OPTS), to implement provisions in the Toxic
Substances Control Act (TSCA), will be published periodically and
made available to the public in the TSCA Chemical Assessment
Series. Some of the volumes in the series will be reports on
single chemicals; others will be compendiums of information
received and evaluated by the Agency about many chemicals. (The
anticipated frequency of publication will vary among titles:
some will be published annually, some semiannually, and others
quarterly.)
Because the chemical assessments published in this series often
will reflect initial or intermediate steps in EPA's evaluation of
a chemical under TSCA, the Agency welcomes the submission of
additional information for or comments on its evaluations. Such
submissions will be considered either at a subsequent step in the
assessment of the subject chemical or in the decision not to pro-
ceed with further evaluation.
All information for or comments on volumes in the TSCA Chemical
Assessment Series should be submitted to:
Director, Assessment Division (TS-792)
Office of Pesticides and Toxic Substances
U.S. Environmental Protection Agency
401 "M" Street, S.W.
Washington, D.C. 20460
The TSCA Chemical Assessment Series is being distributed through
the Industry Assistance Office(IAO) in OPTS. IAO is maintaining
two mailing lists: a subscription list of persons who want to
receive all volumes in the series and a notification list of per-
sons who want to receive announcements of individual volumes as
they become available. For a place on either IAO list, telephone
IAO (toll-free 800-424-9065 or, in Washington, D.C., 554-1404) or
write to:
Industry Assistance Office (TS-799)
U.S. Environmental Protection Agency
401 "M" Street, S.W.
Washington, D.C. 20460
Toll Free: (800-424-9065)
Washington, D.C.: (554-1404)
Generally, five thousand copies of each volume will be printed.
After this supply is exhausted, copies can be purchased from the
National Technical Information Service (NTIS), whose "PB" refer-
ence number can be found in the OPTS "Comprehensive List of
Scientific and Technical Reports," also available from IAO.
iii
-------
The status reports (evaluations) prepared by OPTS on submissions
received from chemical manufacturers, processors, and distribu-
tors between January 1, 1977, and June 30, 1979, under Section
8(e) of TSCA (90 Stat. 2029, 15 U.S.C. 2607), are presented in
chronologic order in this volume. Status reports are prepared by
OPTS on all formal submissions received under Section 8(e) and on
other similar types of information received by EPA. All Section
8(e) submissions and the resulting status reports are placed in a
public file (subject to claims of confidentiality made by the
submitter) upon their receipt or completion.
EPA is publishing this volume for two reasons. First, the
collection of status reports in a single volume will make that
information more accessible to the public. Second, the volume
may, by providing specific examples of submitted information and
EPA's evaluation of it, help anyone subject to Section 8(e) to
understand better the types of information that should be
submitted to the EPA.
To date, no information submitted under Section 8(e) has resulted
in immediate regulatory action under TSCA or any other act,
although some submitted information has triggered further data
gathering and evaluation that may lead to proposal of regulations
in the future.
The original submissions, as well as all status reports, can be
viewed at EPA Headquarters (Room 447 East Tower), 401 M Street,
S.W., Washington, D.C.
Joseph J. Merenda
Director, Assessment Division
IV
-------
Contents
Foreword ill
Acknowledgment vii
Introduction 1
Status reports 8EHQ-0777-0001 to 8EHQ-0679-0291 9
Appendix A. Statement of Interpretation and Enforcement
Policy; Notification of Substantial Risk
(43 FR 11110, March 16, 1978) 538
Appendix B. List of Status Reports Alphabetized by Chem-
ical Name 546
Appendix C. List of Status Reports Arranged by CAS
Registry Number 557
Appendix D. List of Status Reports Arranged by Study
Type 567
Appendix E. List of Status Reports Arranged by Submission
Number 575
v
-------
Acknowledgment
In preparing the status reports contained in this volume, staff
of the Office of Pesticides and Toxic Substances (OPTS) have
frequently found it necessary to contact the firm submitting a
notice to request further information or clarification of the
submitted data. OPTS appreciates the effort and cooperation of
those firms that have submitted the information evaluated in this
volume:
Allied Chemical
Ameribrom, Inc.
American Petroleum Institute
Ashland Chemical Corporation
BASF Wyandotte Corporation
Biocraft Laboratories, Inc.
Celanese Corporation
Chemetron Chemical Products
Ciba-Geigy Corporation
Consolidation Coal Company
Continental Oil Co. (Conoco)
Dow Badische Company
Dow Chemical Company
E. I. Dupont de Nemours & Company
Eastman Kodak Company
Eli Lilly & Company
Emery Industries, Inc.
Ethyl Corporation
Exxon Company, USA
Exxon Corporation
Gulf Mineral Resources Co.
Hercules Incorporated
Hooker Chemicals and Plastics Corporation
ICI Americas, Inc.
International Minerals & Chemical Corporation
Kennecott Copper Corporation
Kenrich Petrochemicals, Inc.
Lonza, Inc.
M & T Chemicals, Inc.
Mallinckrodt, Inc.
Mailory & Company, Inc.
Miranol Chemical Company, Inc.
Mobay Chemical Corporation
Mobil Oil Corporation
Monsanto Company
VII
-------
Nipro, Inc.
Occidental Chemical Company
Olin Chemicals Group
PCR Incorporated
Petrolite Corporation
Phillips Petroleum Company
PPG Industries, Inc.
Reilly Tar & Chemical Corporation
Rhodia, Inc.
Rohm & Haas Company
Shell Oil Company
Shepherd Chemical Company
Sherwin-Williams Company
Smelter Environmental Research Association
Standard Oil Company (Indiana)
Standard Oil Company (Sohio)
Sun Petroleum Products Company
Tennessee Eastman Company
Texaco, Inc.
Thiokol Corporation
Thompson-Hayward Chemical Company
Toms River Chemical Corporation
Union Camp Corporation
Union Carbide Corporation
Uniroyal Chemical
Velsicol Chemical Corporation
Xerox Corporation
3M Company
Vlll
-------
Introduction
Section 8(e) of TSCA states that "any person who manufactures,
processes, or distributes in commerce a chemical substance or
mixture and who obtains information which reasonably supports the
conclusion that such substance or mixture presents a substantial
risk of injury to health or the environment shall immediately in-
form the Administrator of such information unless such person has
actual knowledge that the Administrator has been adequately in-
formed of such information." Section 8(e) was self-effectuating
and required no implementing rules; therefore, manufacturers,
processors, and distributors of chemicals became subject to
Section 8(e) as of January 1, 1977, the effective date of TSCA.
To provide further guidance to those subject to Section 8(e), on
March 16, 1978, after having received comment on a proposed
statement of policy published earlier in the Federal Register,
EPA published a "Statement of Interpretation and Enforcement
Policy; Notification of Substantial Risk" (43 PR 11110). For
easy referral when using this volume, the March 16, 1978,
statement has been reproduced as Appendix A.
The March 16, 1978, statement expresses the Agency policy that
information subject to Section 8(e) is any information that pro-
vides "reasonable support" for the conclusion that a chemical
presents a substantial risk of injury but need not necessarily
conclusively indicate such risk. A determination of "substantial
risk" does not include evaluation of economic or social benefits
of the use of the chemical and, therefore, is not synonymous with
the term "unreasonable risk" used in other sections of TSCA.
Receipt of information under Section 8(e) of TSCA does not neces-
sarily trigger immediate regulatory action; however, information
submitted under Section 8(e) is given priority for evaluation in
order to determine an Agency course of action. An action may,
for example, be further evaluation by EPA or referral to another
agency. To date, no information submitted under Section 8(e) has
resulted in immediate regulatory action under TSCA, although some
submitted information has triggered further data gathering and
evaluation that may lead to proposal of regulations in the
future.
Of the initial submissions received and evaluated by EPA as
Section 8(e) information between January 1, 1977, and June 30,
1979, approximately 100 were received before the publication of
the March 16, 1978, statement; thus, the submitters did not have
the benefit of that guidance. Approximately 25 percent of the
initial submissions received were sent to the Agency with the
caveat that the submitter was uncertain of the applicability of
the information to Section 8(e). Some submitters stated that
their reports were sent for information purposes or under other
provisions of TSCA, although EPA believes that some of those
reports are appropriate for submission under Section 8(e). A
number of submissions appear to have been sent out of an abun-
dance of caution, and, considering their content, did not in
-------
EPA's judgment warrant submission under Section 8(e). Regardless
of the nature of the submissions, EPA has evaluated and prepared
a status report for each one.
Figure 1 depicts the Agency's handling procedures for information
received under Section 8(e). Information is first received by
the OPTS Document Control Officer, who is located in the Chemical
Information Division of EPA's Office of Pesticides and Toxic Sub-
stances. The Document Control Officer checks the notice for any
information claimed by the submitter to be confidential and
assigns a Document Control Number. The Document Control Number
is used by the Agency to identify specific submissions and takes
the following form: 8EHQ-0000-0000. Starting from the left, the
first four symbols identify the information as a Section 8(e)
submission received by EPA headquarters; the next four digits
identify the month and year (e.g., -0579-) of receipt of the
information; the final four digits identify the submission's
chronological number. In addition to the basic sequence, charac-
ters may be added to the right end of the Document Control Number
to convey a special status. The characters and their meaning
follow:
C: contains confidential business information; access
is limited to persons with appropriate clearance;
S: denotes the "sanitized" version of a confidential
document; and
P: signals that the original document contains the
names or other identification of individuals, the
release of which may violate the Privacy Act (such
documents are sanitized to remove the names or
other identifiers).
The Document Control Officer next enters the information into the
appropriate file: the nonconfidential and sanitized submissions
enter the public file, while copies containing confidential bus-
iness information are placed in the confidential file. A letter
acknowledging receipt of the Section 8(e) submission is prepared
by the Document Control Officer and sent to the submitter. In
the case of submissions containing confidential data, the Docu-
ment Control Officer sends a letter asking the submitter to
support any confidentiality claims by providing the information
requested in an attachment to the letter entitled "Support
Information for Confidentiality Claims." This attachment is
reproduced as Figure 2. The submitter has 15 working days from
the date of receipt of this letter to provide EPA with the
requested information. When the Document Control Officer
receives the requested support information from the submitter, it
is forwarded to the EPA Office of General Counsel for review, in
accordance with Agency procedures. No information claimed by the
submitter as confidential will be included in any file to which
the public has access before the Agency's regulations affecting
confidential business information have been complied with
fully. This means that, before any claim for confidentiality is
-------
denied, fair and adequate notice will be given to any person who
has made a claim of confidentiality. If a claimant disagrees
with EPA'S determination on the confidentiality of a piece of
information, that person will have adequate opportunity to
challenge release of the information to the public.
Following receipt of the submission by the Chemical Information
Division, the submitted information is evaluated in OPTS to
determine its significance and to decide what action, if any, is
indicated. Submissions containing confidential data can be
handled only by persons with appropriate clearance. Most Section
8(e) submissions are evaluated by staff in the Chemical Hazard
Identification Branch of the Assessment Division in OPTS, in
consultation with appropriate scientists from that Division
and/or other units of the Office of Testing and Evaluation. The
procedures used in making such evaluations are described below.
In the case of submissions reporting "emergency incidents of
environmental contamination" (see Part V [c] of the March 16,
1978, policy statement), however, the initial evaluation is
performed by staff in the Program Integration Division in OPTS,
with scientific support as necessary from the Office of Testing
and Evaluation.
Upon receipt of a Section 8(e) submission from the OPTS Document
Control Officer, the Section 8(e) coordinator in the Chemical
Hazard Identification Branch scans the information to determine
the'type of submission (e.g., mammalian laboratory study, fish
bioaccumulation study, epidemiologic study, etc.) and its
apparent significance. The coordinator next forwards a copy of
the submission to an appropriate scientist in the Office of
Testing and Evaluation, who performs an initial evaluation of the
submission and prepares written comments on it. When the com-
ments are returned to the coordinator, a status report evaluating
the submission is prepared. The basic format of a status report
is shown in Figure 3. The Chief of the Chemical Hazard Identifi-
cation Branch reviews the prepared status report and resolves any
questions with the Section 8(e) coordinator before signing the
report. Next, the Director of the Assessment Division reviews
the status report and either approves the report or asks for
clarification. Following approval.of the status report by the
Division Director, follow-up activities on the submission are
initiated. These include delivery of a copy of the status report
to the Chemical Information Division for inclusion in the public
file, transmittal to other EPA offices or Federal agencies, and
preparation of a follow-up letter to the submitter. This letter
transmits a copy of the status report and may ask for clarifica-
tion of or additional information on the submission. Clarifica-
tion is necessary when submissions are incomplete or when the
content of the submission does not appear to "reasonably support"
a conclusion of substantial risk.
Review of notices concerning emergency incidents of environmental
contamination is handled in similar fashion by the Program
-------
Integration Division, with technical support as necessary from
the Office of Testing and Evaluation. The Program Integration
Division has lead responsibility for review of these items to
ensure full and rapid coordination with appropriate EPA regional
office personnel. The Program Integration Division has the
responsibility in OPTS for coordination of headquarters and
regional efforts related to toxic substances.
When reviewing a status report, the reader should remember that
the purpose of EPA's evaluation is to determine the significance
of the submitted information in terms of a need for possible
action by the Agency. This determination involves a critical
analysis of the notice to evaluate the extent to which the
reported hazard is supported by the submitted informationi
However, the scope of the initial evaluation generally is limited
to the submitted documents and to any closely related information
known by the reviewer. Neither a literature search to identify
other reported effects nor an in-depth analysis of possible
sources of exposure to the subject chemical is part of the
submission evaluation. Therefore, a status report should be
viewed only as an initial review of the submitted information,
not as a comprehensive assessment of the chemical for which a
Section 8(e) submission has been made.
-------
Figure 1
PROCESSING OF 8(e) NOTICES OF SUBSTANTIAL RISK
CONSULT
ERO
CHEM. ENG
REVIEW
TSCA CBI PROCEDURES
IN EFFECT ONLY AUTHORIZED
PERSONS INVOLVED IN PROCESS
AD-ASSESSMENT DIVISION
CBI-CONFIDENTIAt BUSINESS INFORMATION
CHIB-CHEMICAL HA;
CID-CHEMICAL INFORMATION DIVISION
DCO-DOCUMENT CONTROL OFFICER
E I E C -EMERGENCY INCIDENT OF ENVIRONMENTAL
CONTAMINATION
ERP-ENVIRONMENTAL REVIEW DIVISION
HRD-HEALTH REVIEW DIVISION
OE-OFFICE OF ENFORCEMENT
OGC-OFFICE OF GENERAL COUNSEL
FID-PROGRAM INTEGRATION DIVISION
-------
Figure 2
SUPPORT INFORMATION FOR CONFIDENTIALITY CLAIMS
The Environmental Protection Agency (EPA) has been receiving
many requests for access to notices submitted to EPA under
Section 8(e) of TSCA. Accordingly, EPA must make a final confi-
dentiality determination concerning the treatment of the informa-
tion in your submission. In order to make that determination,
EPA needs further information from you. Under EPA's regulations
on the treatment of information claimed as confidential in 40 CFR
Part 2 (41 FR 36902, September 1, 1976), you have an opportunity
to submit comments to substantiate your claim of confidentiality.
To comply with these requirements, you must indicate which
portions of your submission are claimed as confidential. Be
specific as to page, paragraph, or sentence as appropriate. For
those portions that you identify as confidential, you must
address the following questions. In answering the questions, be
as specific as possible, give examples if necessary, and connect
the specific answers to the specific claimed portions.
1. For how long a period do you desire confidential
treatment? May EPA disclose this information after a certain
date or after the occurrence of a specific event?
2. What measures have you taken to guard against undesired
disclosure of this information to others?
3. To what extent have you disclosed this information to
others, and what precautions have you taken in connection with
the disclosures to protect against further disclosure?
4. Have there been any confidentiality determinations made
by EPA, other federal agencies, or courts in connection with this
information? If so, please enclose copies.
5. Do you assert that disclosure of this information would
be likely to result in substantial harm to your competitive
position? If so, what are those harmful effects, and why should
they be regarded as substantial? What is the causal relationship
between the disclosure and the harmful effects?
-------
Figure 2 (cont.)
6. Do you assert that this information was voluntarily
submitted as defined in 40 CFR 2.201(i)? If so, would the
disclosure of this information tend to lessen the availability to
the Government of similar information in the future? Why?
In making your claims of confidentiality and providing
responses to the above questions, you should keep in mind that,
under Section 14(b) of TSCA, "data from health and safety
studies" are not entitled to confidential treatment, except to
the extent that disclosure of such data would reveal either the
portion of a mixture comprised of any of the chemical substances
in the mixture or the processes used in manufacturing or
processing a chemical substance or mixture. Any claim of confi-
dentiality for data from health and safety studies that goes
beyond these two types will be denied.
-------
Figure 3
STATUS REPORT FORMAT
Submission Description
The content of the submission and the chemical(s) under discus-
sion are identified in this section.
Submission Evaluation
Depending on the nature of the submission, either an environ-
mental or health scientist will perform the initial evaluation.
Comments generally include remarks on the experimental method,
the significance of the results, points of agreement or disagree-
ment with the conclusions offered, and any recommended actions.
This section can vary in length from a brief paragraph to several
paragraphs.
Current Production and Use
In this section the expected exposure to the chemical(s) is
described, as estimated by production volume and use character-
istics. The production volume information once taken from
secondary literature is now derived from the nonconfidential TSCA
Section 8(b) Chemical Inventory.
Comments/Recommendations
Additional comments that do not fit into the other sections of
the status report are presented here. Such remarks include a
listing of other submissions on the same chemical(s) and comments
on the submission in general.
Recommendations include suggested referrals to other offices or
agencies, the need for follow-up correspondence to the submitter
to clarify a point, and possible EPA actions.
8
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: August 10, 1977
SUBJECT: Status Report 8E-0777-0001
FROMs V. J. DeCarlo, Supervisor
Special Actions, OTS (WH-557)
TO: AX
AATS
Background
1. Problem Japanese chemical worker data was submitted showing that
benzoyl chloride has been identified as a carcinogen.
2. Toxicological Evaluation None required.
3. Current Production and Use Benzoyl chloride is a relatively low-
volume chemical. It is used as an intermediate in making dyes,
Pharmaceuticals, and other benzoyl compounds.
Recoinmendat ions
Based on low production volume, the highly reactive properties of benzoyl
chloride, and its use as an intermediate, no further evaluation by FPA
is necessary. This could be a NIOSH problem.
Future Actions
None.
(Signed copy of V. J. DeCarlo memo is in file; retyped for publication
Hay 10, 1979.)
8EHQ-0777-OQ01
Responsibility for Section 8(e) of TSCA was transferred from Special
Actions to the Assessment Division on February 15, 1978. The following
Comments/Recommendations were contained in a memo dated March 28, j97P,
from Frank D. Kover, Acting Director of the Assessment Division, to
Warren R. Muir, Deputy Assistant Administrator for Testing and Evaluation,
OTS.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 132O-6 (REV. 3-76)
-------
Comment s/Recommendat ions
The Japanese report cited in this submission also hinted that benzyl
chloride, benzal chloride, and benzotrichloride are suspected carcinogens.
These chemicals will undergo CHIP scrutiny in the near future.
Section 8(b) information should be checked on benzoyl chloride and these
other chemicals.
10
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
: August 15, 1977
iUiJtCT: status Report 8E-0877-0002 Approved
. ^ Revision
PROM: v. J. DeCarlo, Supervisor Needed
Special Actions, OTS (WH-557)
T0' AX
AATS
Background
1. Problem Skin tumorigenic effects to the skin of mice when a hydro-
carbon solvent is applied.
2. Toxicological Evaluation None required. Composition of the product
not identified.
3. Current Production' and Use The submission stated that 75,000
gallons were produced in 1976 and that it is not in current pro-
duction.
Recommendations
Considering that production has been halted, no further actions are
required.
Future Actions
None.
(Signed copy of V. J. DeCarlo memo is in file; retyped for publication
May 10, 1979.)
8EHQ-0877-0002
Responsibility for Section 8(e) of TSCA was transferred from Special
Actions to the Assessment Division on March 15, 1978.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
, ,
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: August 15, 1977
SUBJECT: Status Report 8E-0877-0003
FROM: V. J. DeCarlo, Supervisor
Special Actions, OTS (WH-557)
TO: AX
AATS
Background
Problem Increased incidence of aspermia and oligospermia in
employees working within the pesticides formulation area. The
company is not able to identify the specific chemical; concern is
directed at dibromochloropropane (DBCP).
Toxicological Evaluation None required.
Current Production and Use It is primarily used as a pesticide.
The two major producers manufacture about 25 million pounds
annually.
Recommendations
Transfer all coordination responsibility to OPP on this problem since
they have requested lead responsibility. Memo from'Ed Johnson is
attached.
Future Actions
Establish and maintain contact with OPP.
(Signed copy of V. J. DeCarlo memo is in file; retyped for publication
May 10, 1979.)
8EHQ-0877-0003
Responsibility for Section 8(e) of TSCA was transferred from Special
Actions to the Assessment Division on February 15, 1978.
NOTE: This status report is the result of a preliminary statt evalua-
tion of information submitted to EPA under Section 8(e) of
TSCA. Statements made herein are not to be regarded as express-
ing final Agency policy or intent with respect to this particu-
lar chemical. Any review of the status report should take
into consideration the fact that it may be based on incomplete
information.
EPA FORM 1320-6 (REV. 3-76)
12
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: January 11, 1978
SUBJECT: Status Report 8E-0977-0004
FROM: V. J. DeCarlo, Supervisor
Special Actions, OTS (WH-557)
TO: Steven Jellinek, Assistant Administrator
for Toxic Substances, OTS (WH-557)
Background
1. Problem Using a standard industrial "acute" test, PCL bottoms and
HEX PCL bottoms were shown to be highly toxic.
2. Toxicological Evaluation None performed; however, data submitted
indicate that these materials are acutely toxic at very low levels.
3. Current Production and Use PCL and HEX PCL bottoms are waste
materials. No uses have been identified.
Recommendations
Considering that these are waste materials with known toxic properties
and limited human exposure, no further evaluation by EPA is necessary.
Future Actions
None.
(Signed copy of V. J. DeCarlo memo is in file; retyped for publication
May 10, 1979.)
8EHQ-0977-0004
Responsibility for Section 8(e) of TSCA was transferred from Special
Actions to the Assessment Division on February 15, 1978. In a letter to
the submitter dated January 22, 1979, Joseph J. Merenda, Director of the
Assessment Division, questioned whether the submitted information was
appropriate for submission under Section 8(e) and asked the submitter to
provide additional information supporting his conclusion of substantial
risk.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of
TSCA. Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 1320-6 (REV. 3-76)
13
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: January 1, 1978
SUBJECT: Status Report 8E-0977-0005
FROM: V. J. DeCarlo, Supervisor
Special Actions, OTS (WH-557)
T0: Steven Jellinek, Assistant Administrator
'for Toxic Substances, OTS (WH-557)
Background
1. Problem Using a standard industrial "acute" test, dibromoethyl
acetate was shown to be highly toxic by dermal, oral, and inhalation
routes of exposure.
2. Toxicological Evaluation None performed; however, data submitted
indicate that this chemical is very acutely toxic and a strong
irritant.
3. Current Production and Use Production information on this chemical
was unavailable; expect the quantity produced is very small.
Recommendations
Considering the low production volume and high reactivity for this
compound, no further evaluation by EPA is necessary.'
Future Actions
None.
(Signed copy of V. J. DeCarlo memo is in file; retyped for publication
May 10, 1979.)
8EHQ-0977-0005
Responsibility for Section 8(e) of TSCA was transferred from Special
Action to the Assessment Division on February 15, 1978. The following
Comments/Recommendations were contained in a memo dated March 22, 1978,
from Frank D. Kover, Acting Director of the Assessment Division, to
Warren R. Muir, Deputy Assistant Administrator for Testing and Evaluation,
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be -regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 1320-6 (REV. 3-76)
14
-------
OTS. In addition, in a letter dated January 22, 1979, Joseph J. Merenda,
Director of the Assessment Division, questioned whether the submitted
information was appropriate for submission under Section 8(e) and asked
the submitter to provide additional information supporting his conclusion
of substantial risk.
Comments/Recommendations
Apparent annual production of dibromoethyl acetate is small; this point
should be confirmed when 8(b) production data become available.
15
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: March 27, 1978
SUBJECT: Status Report 8EHQ-1077-0006
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (WH-577)
TO! Warren R, Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
Three English translations of foreign articles were supplied on the
carcinogenic potential of dialkyl sulfates.
Submission Evaluation
This information is not new or surprising.
sulfates are carcinogenic in the rat.
Current Production and Use
Dimethyl and diethyl
Only dimethyl sulfate and diethyl sulfate are of commercial importance.
Exact production figures are not available; however, the U.S. ITC reports
1975 domestic production in excess of 1,000 pounds. Current uses are as
alkylating agents for phenols, amines, and thiols. Alkyl halides are
acceptable substitutes in most cases.
Recommendations
Production poundage for both diethyl and dimethyl sulfate being low
(1,000 pounds/annum, 1975), no further EPA action is warranted at this
time. Nevertheless, once the inventory production data are available,
this report should be reevaluated to confirm the estimated production
figures.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA. Statements made
herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical.
Any review of the status report should take into consideration
the fact that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
16
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: March 17, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-1077-0007
FROM: Frank D. Kover, Supervisor
Hazard Assessment Group, OTS (WH-557)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
A company interoffice memo on a reproduction study of tris(2,3-debromo-
propyl) phosphate was submitted.
Submission Evaluation
No dominant lethal postimplantation loss was observed, although there
may be effects on sperm or delayed sperm toxicity.
Part of this chemical is structurally similar to DBCP, which has been
linked to low sperm count in men.
Current Production and Use
Unconfirmed reports indicate that tris is no longer being produced in
the U.S.; 1975 production estimated at 7-12 million pounds. Only use is
as a flame retardant for plastics.
Re c ommenda t ion s
In view of (1) unconfirmed reports that tris(2,3-dibromopropyl) phosphate
is no longer manufactured, (2) NCI's (unpublished) conclusions that the
material is a proven carcinogen and (3) CPSC's announced policy that it
will prosecute suppliers of tris-treated children's sleepwear, no immediate
EPA action is required. On receipt of the NCI publication concerning the
positive identification of tris as a carcinogen, TSCA Section 8 (a) inform-
ation should be requested fron known former tris manufacturers. If any
tris is manufactured for other than textile uses, EPA should be notified
as to amount manufactured, population exposed in the manufacture, destina-
tion and use of the product, and estimated population at risk as a result
of the product's use.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 1320-6 (REV. 3-76) 17
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: March 17, 1978 (Revised May 10, 1979)
SUBJECT-, status Report 8EHQ-1077-0008
FROM: Frank D. Kover, Supervisor
Hazard Assessment Group, OTS (WH-557)
TO! Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
This submission contains three items of interoffice correspondence on
the formation of chlorinated dibenzo-p-dioxin following an explosion in
the factory.
Submission Evaluation
These dioxins have received a great deal of attention recently because
of their contamination of Agent Orange, the Seveso, Italy, accident, and
waste oil problems in the United States. These compounds are very
persistent and very toxic.
Current Production and Use
There is no intentional commercial production (in the world) of chlorinated
dibenzo-p*dioxins. They have been found as a contaminant in several
pesticides, such as trichlorophenol, pentachlorophenol, 2,4,5-T, and
others.
Recommendations
This submission should be brought to the attention of OSHA to consider
sampling the production area for the possible occurrence of the two
dioxins in the immediate vicinity of the explosion occurrence. Further,
the product obtained from the process which uses the Beaumont Banvel
equipment system should also be checked for the presence of both 2,7-
dichlorodibenzo-p-dioxin (DCDD) and 2,3,7,8-tetrachlorodibenzo-p-dioxin
(TCDD).
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
IPA PONM 1J»-« (REV. 3-76)
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
OAU: March 27, 1978
Status Report 8EHQ-1077-0010 Approved
Revision
FROM: Frank D. Kover, Acting Director Needed
Assessment Division, OTS (WH-557)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
Mutagenic evaluations on three commercial solvents were submitted along
with several articles from the literature.
Submission Evaluation
The shortcoming of this1 submission is that the toxicological and muta-
genesis data do not appear to have been obtained on any mixture o'f
chemicals now existent in commerce. According to the cover letter, the
three solvents were selected on a theoretical basis as representative
of products manufactured and available in commerce in 1969. The
submitter further states that the 1977 solvents may have a different
composition. The data submitted may, therefore, not be pertinent to
the products currently 'being produced and sold.
Current Production and Use
These solvents are apparently mixtures of hydrocarbons which are meant
to approximate solvents in use several years ago. The submitter claims
that the listed solvents may be similar to those in current use. The
amount of information provided, however, precludes any definitive
estimate of the current production of similar mixtures.
Recommendations
Petroleum-based solvents have not been addressed in any detail in OTS.
The variable formulations create a complex problem. Petroleum distillates
will be the topic of a conference by OPP later this year.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
CF-A FORM I1JO-* IMEV. »-?«> ]_g
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: March 28, 1978
SUBJECT: Status Report 8EHQ-1077-0011
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (WH-557)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
An electronic vapor soldering fluid (FC-70, composition unknown) reportedly
decomposes into highly toxic perfluoroisobutylene and an unidentified
perfluoroimine when overheated.
Submission Evaluation
These highly toxic materials react readily with tissue proteins. No
toxicity data are reported on either the starting material or the decompo-
sition products.
Some of the most powerful antileukemia drugs are imines and can destroy
cells plus being direct-acting carcinogens.
Current Production and Use
No production figures are available for FC-70, nor is it listed in the
TSCA Candidate List.
Perfluoroisobutylene is contained in the TSCA Candidate List. No informa-
tion is available on its uses, however.
Recommendations
No further evaluation is necessary.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 1320-6 (REV. 3-76) 20
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE; April 7, 1978 (Revised May 10., 1979)
SUiJfCT: status Report 8EHQ-1077-0012
FROM:
TO:
Frank D. Kover, Acting Director
Assessment Division, OTS (WH-557)
Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Approved
Revision
Needed
Submis s ion Des crip t ion
Results of lifetime skin-painting study of fire-resistant hydraulic
fluids in mice. The hydraulic fluids contained quantities of N-nitroso-
morpholine in some instances. This notice was classified at the submitter's
request on April 12, 1978.
Submission Evaluation
According to the Ames group (Proc. Nat. Acad. Sci. USA, 72:5135-5139,
1975), N-nitrosomorpholine is a carcinogen and a mutagen. The mutagenic
action required activation by the S-9 liver fraction. Therefore, unlike
the submitter, we are npt surprised that the conducting laboratory found
no tumors at the site of application on the skin. The nitrosamine could
be absorbed from the skin and not become carcinogenic until activated
by the liver and the activated product disseminated to various target
organs. The licking theory of exposure offered by the submitter is,
therefore, on weak grounds. Incidentally, workers handling the product
would probably not clean their hands before indulging in a snack.
Current Production and Use
"Fire-resistant hydraulic fluids" represent a fairly broad class of
products. The annual production of the fluids used in this experiment
is not known; however, the production volume of these fluids and similar
mixtures is likely to be fairly large. The fire-resistant character of
these products is probably due to the presence of water and not a fire
retardant as such; these products appear to be somewhat similar in
composition to synthetic cutting fluids..
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
FORM !»»-» (MCV. >-?()
21
-------
Related Past and Present Activities
These results are apparently related to those in the December 6, 1976,
edition of the Wall Street Journal which reported that certain
fire-resistant hydraulic fluids contained measurable quantities of
nitrosamines but that the products were being reformulated to eliminate
the nitrosamine problem. The submitter also commented at that time
on an ongoing skin-painting study in mice to determine the carcinogenic
potential of these products. Preliminary results indicated "possible
carcinogenic effects." (The same article claimed that 5-7 million
gallons of fire-resistant hydraulic fluids are produced annually by the
entire industry.)
At that time, these results were considered in the ongoing nitrosamine-
contaminated cutting fluids activity; however, the claimed reformulation
was thought to have solved the nitrosamine problem. (These products
apparently contain dialkylamines or dialkanolamines which can, in the
presence of nitrites, form nitrosamines. Likely the reformulation
consisted of the omission of nitrites from these products; this point
was confirmed in the present submission.) Nevertheless, the results
reported in this study indicated that the removal of nitrite from the
product was not sufficient to solve the problem as evidenced by the
"increase in the number of tumors above the level observed in untreated
animals" following nitrite removal from the product. (Note that the
submission claims that the tested formulation was similar to those
currently being marketed.)
Comments/Recommendations
These results may be of great interest to NIOSH and OSHA if they have
not received them. An unanswered question concerning N-nitrosomorpholine
and N-nitrosodiethanolamine has been their ability to be absorbed through
the skin following dermal exposure. These results appear to indicate
that N-nitrosomorpholine is absorbed through the skin and can cause
internal tumors following prolonged exposure. NIOSH is currently testing
N-nitrosodiethanolamine via the skin route (Enviro Control is conducting
the experiment) to determine its carcinogenic potential by this route.
If the results reported in this submission are any indication of what will
be seen in the NIOSH study, then the question of worker exposure to cutting
fluids becomes of crucial concern. On the basis of this submission alone,
the question of worker exposure to fire-resistant hydraulic fluids becomes
an issue that demands investigation by NIOSH and OSHA.
Of even greater significance is the observation that the tested material
retained its carcinogenic potential despite the removal of nitrites from
the formulation. This imples that another agent in the mixture is active.
There is no indication as to the identity of this other agent, but, whatever
it is, it could also be a component of the compositionally similar synthetic
cutting fluids. The further implications of this observation may also be of
interest to NIOSH and OSHA.
22
-------
This information is still confidential; however, Union Carbide received
the challenge letter on either March 21 or March 22, 1978 (registered
mail receipt is unclear). Therefore, the 15-day response period will be
over on May 10 or May 11, 1978, depending on the recognized date of
receipt. As soon as the confidentiality response period is over, and
assuming that no challenge is received from the submitter, NIOSH and
OSHA should be informed of these results and, if the information was not
previously received by these Agencies, specific referral of the
information should be made to Jane McNew of OSHA (Washington, B.C.) and
Betsy Egan or Roscoe Moore of NIOSH (Cincinnati, Ohio). In addition to
OSHA and NIOSH, the FDA Bureau of Drugs should be informed of these data
for their consideration of the hazard associated with nitrosamines in
cosmetics (Predominantly facial and hand creams and lotions).
23
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: May 4, 1978 (Revised May 10, 1979) Approved
SUBJECT: status Report 8EHQ-1177-0013
Revision
Needed
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
TO! Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Results of water, sediment, and tissue residue analyses on samples taken
from the Mississippi River. The analyses indicated the presence of
hexachlorocyclopentadiene and related compounds. This notice was declassified
on April 13, 1978.
Submission Evaluation
This report contains monitoring information on 18 HEX-related compounds,
most of which are pesticides or pesticide degradation products. Water
and sediment samples were taken above and below a sewer outfall (Wolf
Creek outfall), which was the presumed source of the contamination.
Some contamination of the sediment above the outfall was noted as represented
by HEX vinyl chloride, HEX BCH, isodrin, and endrin; however, the levels
found below the outfall were much higher. Little or no contamination
was found in water collected above the outlet. Water collected below
the outfall was contaminated with those chemicals that were found at
high concentrations in the sediments taken from the same area. For the
most part this included (sediment concentrations shown in parentheses) :
chlordene (9,372 ppb); HEX vinyl chloride (2,446 ppb) ; HEX BCH (1,409
ppb); isodrin (402 ppb); and endrin (568 ppb). These compounds pose a
potential threat for bioaccumulation taking as a model their similarity
to DDE and DDT, which are known to bioaccumulate.
Catfish (bottom feeders) caught below the same outfall showed high
concentrations (2-7 ppm) of chlordene, HEX vinyl chloride, and HEX BCH
in muscle tissue. Higher concentrations can be expected in the fat.
Two compounds ("C" and "D") were measured in fish but not identified.
Several compounds were reported in water and sediment samples (DDT, DDE,
ODD, mirex, isodrin, endrin, aldrin, and dieldrin), but no fish residue
data were presented. This is puzzling in light of the bioaccumulative
nature of these chemicals, and particularly so because all samples were
supposedly analyzed by the same group at the same time.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 1120-6 (REV. 3-76) 24
-------
Current Production and Use
All of the chemicals are pesticides or pesticide-related products, some
with sizable potential for exposure.
Current Production and Use
All of the chemicals are pesticides or pesticide-related products, some
with sizable potential for exposure.
Comment s/Recommendat ions
This submission is related to 8EHQ-0278-0054 and 8EHQ-0378-0099.
(a) All three notices should be referred to the FDA Bureau of Foods,
OPP, ERD, and pertinent EPA labs.
(b) A request for all information related to these submissions should
go out to the notifier from the DAA.
(c) All information should be referred to OE and EPA Region IV for
possible enforcement action.
25
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: March 28, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-1177-0014
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (WH-557)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
Summary of study showing triphenylphosphine in an oil solution causes
nervous system disorders in dogs, cats, and rabbits when administered
repeatedly in small doses orally or intramuscularly.
Submission Evaluation
Most phosphines have insufficient water solubility to be absorbed from
aqueous mixtures. When administered in oil solution, however, they are
absorbed from all surfaces, including intact skin. Phosphines are dis-
tributed to all lipid tissues, particularly membranes of cells in peripheral
nerves and the brain. Once inside these cells, injury can result and
produce the symptoms described. The previously assumed safety is based
on rat studies. The rat is a poor animal model for demonstrating peri-
pheral neuropathy and brain damage.
Current Production and Use
No production figures are available; however, the SRI Directory of
Chemical Producers (1975) lists four producers, implying an annual
production greater than 1,000 pounds. The submitter apparently imports
triphenylphosphine and sells approximately 75,000 pounds annually.
Reported uses include synthesis of organic compounds, phosphorous salts,
and other phosphorous compounds.
Re c ommend at ion s
Because of apparently limited U.S. production, no immediate evaluation
by EPA is necessary. Once the inventory production data are available,
however, this report should be reevaluated to confirm the estimated pro-
duction figures. The toxicological information contained in this submission
may be of interest to I-CA (or others) for product safety data sheets.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 1320-6 (REV. 3-76)
26
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
OATE. October 26, 1978
SUBJECT: Status Report 8EHQ-1177-0015C
(Supplement A - Nonconfidential)
FROM: Frank D. Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Approved
Revision
Needed
Submission Description
Information supplemental to that provided with a letter dated November
4, 1977, concerning the potential neurotoxicity of triphenylphosphine.
The present submission reports the results of additional toxicity
studies conducted on triphenylphosphine and triphenylphosphine oxide in
chickens. The study concluded that triphenylphosphine under the conditions
of the study "was not found to produce permanent locomotor impairment"
in chickens. Triphenylphosphine oxide was found to be more toxic than
triphenylphosphine; however, the locomotor impairment noted in chickens
at the highest dose of triphenylphosphine oxide was attributed to an
overall toxic response rather than a specific neurotoxic response.
Submission Evaluation
Recent publications, particularly from the Neurology Department of
Albert Einstein Medical School under the direction of Dr. Schaumberg,
have stressed the unreliability of using white Leghorn hens as an
adequately sensitive species for detecting peripheral neuropathy. Other
evidence strongly suggests that peripheral neuropathy is accompanied by
changes in the brain. The examination at necropsy did not include
microscopic sections of nerve and brain to determine whether nerve
sheaths or nerve cells were affected.
A more sensitive species, such as the cat, would have to be used to
establish that triphenylphosphine or triphenylphosphine oxide has no
neurotoxic effects.
Current Production and Use
Triphenylphosphine is used in the synthesis of organic compounds,
phosphonium salts, and other phosphorus compounds. Annual consumption
of triphenylphosphine is estimated at greater than 1,000 pounds per year.
NOTE: This status report is the result of preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 1320-6 (REV. 3-76)
27
-------
No information was located on triphenylphosphine oxide; however, the
submission identifies the material as "a by-product of some applications."
This should be clarified.
Comment s/Recommendat ions
Several other submissions have concerned this compound (8EHQ-1177-0014;
8EHQ-1177-0015C; 8EHQ-0278-0055).
(a) This submission and status report should be transmitted to N10SH
and OSHA to supplement the information received earlier on tri-
phenyIphosphine.
(b) The submitter should be asked to describe further the use or
occurrence of triphenylphosphine oxide.
28
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: January 11, 1978
SUBJECT: Status Report 8E-1177-0016
FROM: V. J. DeCarlo, Supervisor
Special Actions, OTS (WH-557)
TO: Steven Jellinek, Assistant Administrator
for Toxic Substances, OTS (WH-557)
Background
1. Problem A retrospective mortality study on 864 males exposed to
epichlorohydrin (ECH) suggests a carcinogenic risk to man.
2. Toxicological Evaluation The study submitted is considered pre-
liminary and suggestive. The types of cancer reported are lung,
colon, pancreas, and of the hematopoietic system. This first study
did not consider cigarette or alcohol usage.
3. Current Production and Use Epichlorohydrin is produced by two
companies at three locations. Production capacity is approximately
450 million pounds per year. Unrefined ECH is used to produce
synthetic glycerin and the refined material to produce epoxide
resins and elastomers.
Recommendations
This chemical is currently under evaluation by the Hazard Assessment
Group. Periodic reports will be submitted.
Future Actions
Outside of the current Hazard Assessment effort, no new actions are
required.
(Signed copy of V. J. DeCarlo memo is in file; retyped for publication
May 10, 1979.)
8EHQ-1177-0016
Responsibility for Section 8(e) of TSCA was transferred from Special
Actions to the Assessment Division on February 15, 1978.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of
TSCA. Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 1320-6 (REV. 3-76)
29
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: January 11, 1978
SUBJECT: status Report 8E-1177-0017
PROM: v. J. DeCarlo, Supervisor
Special Actions, OTS (WH-557)
TO! Steven Jellinek, Assistant Administrator
for Toxic Substances, OTS (WH-557)
Background
1. Problem This submission was limited to one piece of interoffice
correspondence on an employee with allergy problems. The employee
had worked with several chemicals, but the correspondents believe
that the material causing the reaction is dicyclopentadiene (DCPD)
acrylate vapors.
2. Toxicological Evaluation Any of the chemicals listed could be
responsible for the allergies identified.
3. Current Production and Use The submittal listed seven chemicals
which are all related to pesticide manufacturing.
Recommenda t ions
Based on the limited exposure and effects identified, no further evalua-
tion by EPA is necessary.
Future Actions
None.
(Signed copy of V. J. DeCarlo memo is in file; retyped for publication
May 10, 1979.)
8EHQ-1177-0017
Responsibility for Section 8(e) of TSCA was transferred from Special
Actions to the Assessment Division on February 15, 1978. The following
Comments/Recommendations were contained in a memo dated March 28, 1978,
from Frank D. Kover, Acting Director of the Assessment Division, to
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 1320-6 (REV. 3-76)
30
-------
Warren R. Muir, Deputy Assistant Administrator for Testing and Evaluation,
OTS. In addition, in a letter dated January 22, 1979, Joseph J. Merenda,
Director of the Assessment Division, questioned whether the submitted
information was appropriate for submission under Section 8(e) and asked
the submitter to provide additional information supporting his conclusion
of substantial risk.
Comments/Recommendations
A follow-up letter should be sent to the submitter requesting additional
information on this incident. This notice plus any follow-up information
should be referred to NIOSH and OSHA. Several dicyclopentadiene- and
dicyclopentadiene derivative-related submissions have been received;
this group of chemicals may be a candidate for 8(b) and/or CHIP presenta-
tion (preliminary assessment on dicyclopentadiene is scheduled for the
near future).
31
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATES January 16, 1978
SUBJECT: Status Report 8E-1177-0018
PROM: V. J. DeCarlo, Supervisor
Special Actions, OTS (WH-557)
TO: Steven Jellinek, Assistant Administrator
for Toxic Substances, OTS (WH-557)
Background
1. Problem This submission was limited to one piece of interoffice
correspondence on an employee who became allergic when exposed to
benzoic acid.
2. Toxicological Evaluation This allergic reaction is not surprising,
since it has been reported in the literature for years.
3. Current Production and Use Benzoic acid is produced by five com-
panies at six locations. It is used as a food preservative, in
drugs, and finds widespread usage in the drug and chemical manufacturing
industries.
Recommendations
Based on the limited health effects identified, no further evaluation by
EPA is necessary.
Future Actions
None.
(Signed copy of V. J. DeCarlo memo is in file; retyped for publication
May 10, 1979.)
8EHQ-1177-0018
Responsibility for Section 8(e) of TSCA was transferred from Special
Actions to the Assessment Division on February 15, 1978. The following
Comments/Recommendations were contained in a memo dated March 28, 1978,
from Frank D. Kover, Acting Director of the Assessment Division, to
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take .into
consideration the fact that it may be based on incomplete
information.
CPA FORM 1320-C (REV. 3-76) ->i
-------
Warren R. Muir, Deputy Assistant Administrator for Testing and Evaluation,
OTS. In addition, in a letter dated January 22, 1979, Joseph J. Merenda,
Director of the Assessment Division, questioned whether the submitted
informatipn was appropriate for submission under Section 8(e) and asked
the submitter to provide additional information supporting his conclusion
of substantial risk.
Comment s/Recommendations
Additional information should be requested from the submitter regarding
this individual's health problems. The company doctor's report and the
allergist's evaluation (if seen) should be specifically requested. This
notice and any subsequent information will be referred to NIOSH and OSHA
for appropriate follow-up.
33
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: January 12, 1978
SUBJECT: Status Report 8E-1177-0019
FROM: V. J. DeCarlo, Supervisor
Special Actions, OTS (WH-557) ,
TO: Steven Jellinek, Assistant Administrator
for Toxic Substances, OTS (WH-557)
Background
1. Problem Preliminary data from a 2-year rat inhalation study
indicate that vinyl bromide produces the same type of pathological
lesions as vinyl chloride.
2. Toxicological Evaluation The results to date are not surprising.
A limited evaluation was performed. The study in progress seems to
be excellent.
3. Current Production and Use Vinyl bromide is produced in small
quantities by five companies, with the largest producer reporting
production under 1.5 million pounds per year. It is used as a
flame retardant in acrylic, polyvinyl acetate, and polyvinyl chloride
materials.
Re co mmend a t ion s
The final report will be available in 12 months. Considering the low
level of production, no further analysis is warranted until the final
report is received.
Future Actions
None at the present time.
(Signed copy of V. J. DeCarlo memo is in file; retyped for publication
May 10, 1979.)
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 1320-6 (REV. 3-76)
34
-------
8EHQ-1177-0019
Responsibility for Section 8(e) of TSCA was transferred from Special
Actions to the Assessment Division on February 15, 1978. The following
Comments/Recommendations were contained in a memo dated March 28, 1978,
from Frank D. Kover, Acting Director of the Assessment Division, to
Warren R. Muir, Deputy Assistant Administrator for Testing and Evalua-
tion, OTS.
Comments/Recommendations
A CHIP report on vinyl bromide is available from the Assessment Division.
It is unfortunate that these results were not forwarded on a more timely
basis to the old Hazard Assessment Group for CHIP consideration; as it
was, HAG did not receive a copy until January 1978, over 2 months after
Special Actions received the report. AD is presently considering testing
vinyl bromide-based flame-resistant fabrics for residual vinyl bromide
monomer content.
35
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: March 17, 1978
SUBJECT: Status Report 8EHQ-1277-0021
FROM: Frank D. Kover, Supervisor
Hazard Assessment Group, OTS (WH-557)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
It is reported that employees at a mercuric oxide production facility
associated with battery manufacture have exhibited a variety of symptoms:
nervous system disorders, low sperm counts, and loss of weight.
Submission Evaluation
The toxicity of low-level exposure to mercury compounds has been known
since the 16th century. Mercury toxicity can involve the peripheral
nervous system, the central nervous system, the digestive system, as
well as the liver and the kidneys.
This is the first known report on low sperm count associated with exposure
to mercury compounds.
Also, they reported that the employees may be exposed to manganese,
which may have augmented the reported clinical picture.
Current Production and Use
Mercuric oxide (HgO) is available in two forms—red and yellow crystals.
Although no production figures are available, each form has six producers,
which implies a production level greater than 1,000 pounds. In all
likelihood, the actual annual production is somewhat larger than 1,000
pounds. Uses for both forms include: paint pigment, perfumery and
cosmetics; Pharmaceuticals; batteries; antifouling paints; fungicides;
etc. Batteries are reportedly the major use of mercuric oxide. Mercuric
oxide pesticide registrations were canceled In 1975.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 1320-6 (REV. 3-76) 36
-------
Recommendations
This submission should be brought to the attention of OSHA. The submitter
has already requested a NIOSH hazard evaluation. The Hazard Assessment
Group has mercury on its list of future activities.
37
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: March 28, 1978 (Revised May 10, 1979)
SUBJECT: status Report 8EHQ-1277-0022
FROM: Frank D. Kover, Acting Director
Hazard Assessment Group, OTS (WH-557)
TO! Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
Study describing in vitro malignant transformation in BALB/3T3 cells
treated with MC-984 [bis(l,3-dichloro-2-propyl)-3-chloro-2,2-dibromomethyl-
1-propyl phosphate].
Submission Evaluation
MC-984 is capable of malignant transformation in vitro; therefore, it is
suspected of being a potential carcinogen. Its phosphate ester structure
could produce delayed neurotoxicity, and the BrCl content raises questions
of potential liver toxicity.
If industry continues to utilize these types of phosphate esters, they
will ultimately have to determine where in a given series the potential
for delayed neurotoxicity becomes significant.
Current Production and Use
No production and use information was located; not on the TSCA Candidate
List.
Recommendations
Apparent low production does not support continued EPA activity. None-
theless, a number of submissions have been received on this chemical;
therefore, it may be a candidate for Section 8(a), CHIP, or NIOSH/OSHA
consideration.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of
TSCA. Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 1320-6 (REV. 3-76) 38
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: March 17, 1978
SUBJECT: Status Report 8EHQ- 1277-0023
no*. Frank D. Ko^er, Supervisor
Hazard Assessment Group, OTS (WH-557)
TO; Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Approved
Revision
Needed
Submission Description
A 28-day subacute dermal toxicity study with 2,3-dibromopropanol (DBF)
was submitted.
Submission Evaluation
This study demonstrates' absorption of DBF via the skin and storage in
liver and fat depots. The dose applied was small and below the exposure
potential. Thus, the study was inadequate and inconclusive. This com-
pound has potential for carcinogenic action and for damage to the liver,
kidneys, and nervous system.
Current Production and Use
U.S. production is estimated at more than 10 million pounds in 1976.
Major use is as an intermediate in the production of tris(2,3-dibromo-
propyl) phosphate and other flame retardants and as a reactive flame
retardant itself. It is also used in the manufacture of insecticides
and drugs. Recent actions by CPSC to regulate tris have likely depressed
the domestic production and market for 2,3-dibromopropanol.
Recommendat ions
As part of our technology assessment program on flame retardants, this
compound will receive some further attention in HAG.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
CPA rOMM 1120-4 (MCV. >-7*>
39
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: March 17, 1978
Status Report 8EHQ-1277-0024 Approved
Revision
MOM: Frank D. Kover, Supervisor Needed
Hazard Assessment Group, OTS (WH-557)
T0: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
A 28-day subacute dermal toxicity study of 2,4,6-tribromophenol (TBP)
was submitted.
Submission Evaluation
The skin lesions described are to be expected from this type of chemical.
It is surprising that the TBP was not absorbed through the skin. " The
active compound was applied as a suspension in aqueous methylcellulose
where an oil solution would have been more appropriate.
Current Production and Use
No production figures are available for this compound; however, SRI's
Directory of Chemical Producers lists three producers, which implies an
annual production in excess of 1,000 pounds. No information on uses was
located.
Recommendations
Because this compound contains approximately 73% bromine, its potential
for flame retardant use and PBB substitution should be evaluated. The
HAG will review this compound as part of its ongoing study of flame
retardant technology.
Several submissions have been received on this chemical; Section 8(a),
CHIP, and/or NIOSH and OSHA involvement may be appropriate.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
FORM i»20-« (REV. *-7*i 40
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: March 28, 1978 (Revised May 10, 1979)
SUBJECT: status Report 8EHQ-1277-0025
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (WH-557)
T0: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
Results of mutagenicity testing on three different brominated carbonates;
each was positive in the Ames test. The tested chemicals were tetrabromo-
diallyl carbonate, tetrabromo(bisphenol A) bis(2,3-dibromopropyl carbonate),
and pentabromophenyl-2,3-dibromopropyl carbonate.
Submission Evaluation
It was impossible to relate the chemicals listed in the transmitted
letter to the coded reports submitted. However, all three compounds
exhibited mutagenic activity in the Ames test.
These carbonates are probably hydrolyzed by enzymes to the brominated
propanol, which is positive in the Ames test.
Current Production and Use
No production and use information was located for any of the three
compounds identified in this submission; in addition, none were on the
TSCA Candidate List.
Recommendations
These materials will be evaluated in the ongoing Assessment Division
review of fire retardant technology.
Follow-up correspondence should request decoding of the studied compounds
A request for Section 8(a) information may be appropriate.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of
TSCA. Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 1320-6 (REV. 3-76)
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: March 17, 1978
SUBJECT: Status Report 8EHQ-1277-0027
FROM: Frank D. Kover, Supervisor
Hazard Assessment Group, OTS (WH-557)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
A summary of interim results on an inhalation study where pregnant
female rats were exposed to benzene. An increased frequency of resorptions
was observed.
Submission Evaluation
Fetal resorption usually has nothing to do with teratology, but indicates
that the developing organism was lethally poisoned. Benzene exposure
may involve immunologic phenomena within the fetus as well as the dam.
Benzene has shown that it may alter stem-blood cells and certain important
developing cells. The full study will be needed for proper evaluation.
Current Production and Use
Benzene is one of the largest volume primary organic compounds, with
approximately 10 billion pounds produced per year. Benzene is a basic
building block in the synthetic organic chemical industry. Uses include
chemical intermediates, solvents, and antiknock gasoline additive.
Recommendations
OSHA is currently in rulemaking to lower benzene exposure in the workplace.
CPSC is considering setting limits on benzene in consumer products.
OAQPS has proposed to set benzene emissions standard under Section 112
of CAA. OPP is proposing to look at benzene as one of the inactives in
pesticides.
Because of the extensive current activities, including our "15" chemicals
exercise, a follow-up to obtain the full report is in order.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of
TSCA. Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 1320-6 (REV. 3-76) 42
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE.- March 27, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0178-0028
PROM: Frank D. Kover, Acting Director
Assessment Division, OTS (WH-557)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
Interim results on a lifetime dermal application study with neopentyl
glycol diacrylate are reported indicating that tumorigenic activity is
beginning to show up in the test animals (mice).
Submission Evaluation
Some glycols, their ethers (cellosolve; carbitol), and their esters are
absorbed through the skin and can be toxic by this route. It is not
surprising that one of the esters, neopentyl glycol diacrylate, is -
carcinogenic. In part this would be determined by the rate of absorption
from the subcutaneous tissues into the blood and the rate of hydrolysis
of the ester and resultant epoxide formation. It would not be surprising
if some other acrylate esters turn out to be carcinogenic.
Current Production and Use
No production figures are available; the U.S. ITC lists one producer,
implying an annual production in excess of 1,000 pounds. No information
on uses. Company brochure implies that it is part of UV-curable coatings,
adhesives, and inks.
Recommendations
Await final results and evaluate need to test other members of the class
if positive results are obtained. This chemical should be given CHIP
consideration; a Section 8(a) information request may be in order.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of
TSCA. Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 1320-6 (REV. 3-76)
43
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
OAT*: March 28, 1978
lUBJtCT: Status Report 8EHQ-0178-0029 Approved
Revision
MO*: Frank D. Kover, Acting Director Needed
Assessment Division, OTS (WH-557)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
Preliminary report on high-boiling crude fractions and aromatic
subtractions in a mouse skin-painting study indicating carcinogenic
potential.
Submission Evaluation
It is not surprising that petroleum distillates produce cancer under the
conditions of this experiment. Final risk evaluation will require
analytical data on the nature and amounts of polynuclear aromatic hydro-
carbons and carcinogenic metals (e.g., nickel) in the various fractions.
Current Production and Ose
High-boiling petroleum crude fractions and aromatic subtractions are
derived from crude oil during fractionation procedures. Information as
to the production and use of these specific fractions is not available;
however, they are likely to represent high-volume basic petroleum feed-
stocks.
Recommendations
Await final results.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
CPA rOftM »»»-« CNCV. »-7C) .,
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE.- March 17, 1978
$u»JtCT: Status Report 8EHQ-0178-0030
MO*.- Frank D. Kover, Supervisor
Hazard Assessment Group, OTS (WH-557)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Approved
Revision
Needed
Submission Description
Preliminary report on mutagenicity studies with crude
shale oils.
Toxicological Evaluation
Almost any fossil-generated oil will probably have enough polynuclear
aromatic hydrocarbons to be potentially carcinogenic.
Current Production and Use
Recovery of oil from oil shale is a growing technology as the result of
the energy situation in' the U.S. No firm production estimates are
available at this time, and no known commercial distribution is evident
at present.
Recommendations
Submission by a trade association may be inappropriate.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM !»»-« (*CV. »-7«l
45
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE. November 6, 1978
SUBJECT: Status Report 8EHQ-0678-0030
(supplement)
MOM: Frank D. Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Approved
Revision
Needed
Submission Description
A submission dated January 4, 1978, (8EHQ-0178-0030) reported preliminary
results from a mutagenesis study of crude shale oils. This supplemental
submission represents the final report for each of the three shale oils
(designated R-01, R-03, and R-04).
Submission Evaluation
All three shale oils demonstrated mutagenic effects in in vitro bacterial
assays with microsomal activation; R-01 also showed weak activity in these
tests without activation. In the mouse lymphoma assay (in vitro), R-01 and
R-04 were weakly positive while R-03 showed no mutagenic activity. Both R-
03 and R-04 were not active in the in vitro rat bone marrow assay; R-01
increased the frequency of chromosomal aberrations in this test; however,
the results were not statistically significant.
Evaluation of these findings indicates that these shale oils are potentially
mutagenic to man and other organisms but the degree of the mutagenic hazard
is not yet adequately defined. Further in vivo testing to determine the
potential for an active form of these materials to reach the germ cells
would help to clarify the potential hazards. Mutagenic activity appears to
vary among the three shale oils; quantitative chemical analysis of each
shale oil may provide some basis for the observed differences in muta-
genic activity. For the present, it is suggested that shale oils be considered
potential mutagens and that appropriate steps be undertaken to limit exposure.
Current Production and Use
Recovery of oil from oil shale is a growing technology as the result of the
energy situation in the United States. No firm production estimates are
available at this time, and no known commercial distribution is evident
either. __
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
romtt mo-* (REV. »-?•>
46
-------
Comments/Recommendations
(a) This submission and status report should be transmitted to OSHA,
NIOSH, and U.S. DOE.
(b) The submitter should be asked to provide an analytical characterization
of each sample, if available.
47
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: March 17, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0278-0031P
FROM: Frank D. Kover, Supervisor
Hazard Assessment Group, OTS (WH-557)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submi s sion Des crip tion
A chemical company maintenance man developed a rash on the lower leg.
Submission Evaluation
None possible.
Current Production and Use
No estimates possible.
Recommendations
None possible without some estimate as to the causative agent(s) for the
rash; follow-up correspondence will request additional information. The
submitter should be asked to support his contention that the information
presented in this submission reasonably supports a conclusion of sub-
stantial risk. Any new information will be forwarded to NIOSH and OSHA.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 1320-6 (REV. 3-76)
48
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: March 17, 1978 (Revised May 10, -1979)
SUBJECT: Status Report 8EHQ-0178-0032
FROM: Frank D. Kover, Supervisor
Hazard Assessment Group, OTS (WH-557)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
Document describing results of a TL^ test and a fish accumulation study
on 2,4,6-tribromophenol.
Submis si on Evaluation
The raw data on the fish accumulation study indicate approximately 100-
fold accumulation of 2,4,6-tribromophenol (sodium salt) in carp under
conditions somewhat inadequately described; e.g., what is the pH of the
water and the pKa of the test substance? The test species used is
inappropriate and the degradation product may have greater bioaccumulation
potential than the parent compound. It is unclear whether the analysis
was for just the phenol or the Na salt.
The TLjn test also used an inappropriate test species (killifish) which
can gulp air to avoid water exposure. The TLm value may be artificially
high.
Although these test results would not trigger the about-to-be published
guidelines on substantial risk, it is likely that with a more appropriate
animal model higher accumulation would be seen. (Based on discussions
with Chuck Walker, March 7, 1979.)
Current Production and Use
No production figures are available; however, SRI's Directory of Chemical
Producers lists three producers, which implies an annual production in
excess of 1,000 pounds. No information on uses was located.
Recommendations
Potential for flame retardant use and PBB substitution should be eval-
uated. If that evaluation shows significance, more indepth review might
be in order by Gil Veith at the Duluth Labs.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into con-
sideration the fact that it may be based on incomplete information,
EPA FORM 1320-6 (REV. 3-76)
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: March 28, 1978
SUBJECT: Status Report 8EHQ-0178-0033
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (WH-557)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submiss ion De s cr ip t ion
Preliminary report on weight differential in male rats in a 90-day
subacute study on bis(l,3-dichloro-2-propyl)-3-chloro-2,2-dibromomethyl-
1-propyl phosphate. Trade name is MC-984.
Submission Evaluation
The structure of MC-984 suggests potential for liver injury and carcino-
genesis as well as delayed nerve damage. The early effect on growth
suggests that liver injury is beginning to set in. Will have to await
detailed protocol and results.
Current^ Production and Use
There is no information available on the production and use of this
chemical. It is not contained in the TSCA Candidate List.
Recommendations
Await final results. This phosphate halocarbon will be reviewed for its
possible uses in flame retardant technology as part of the Assessment
Division's activity in that field. Section 8(a) information should be
requested on this compound; several submissions have concerned this
chemical (8EHQ-1277-0022; 8EHQ-0278-0048; 8EHQ-0278-0044; 8EHQ-0278-0053;
8EHQ-378-0100).
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM I32O-6 (REV. 3-76)
50
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE.- March 17, 1978
SUBJECT: Status Report 8EHQ-0178-0034
FROM: Frank D. Kover, Supervisor
Hazard Assessment Group, OTS (WH-557)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submis s ion De s crip tion
Copies of letters issued to customers who use ammonium sulfate and/or
aluminum sulfate in the manufacture or processing of cellulosic insula-
tion materials, or resell either material for such end use application.
Letters relate to possible corrosion of metal surfaces encountered in
building structures.
Submission Evaluation
Aluminum compounds precipitate proteins but not to the extent of
destroying them; therefore, the corrosive action does not extend to
humans. Aluminum compounds, because of their mild precipitating action,
have wide use in medicine. The acid ones are used as styptic pencils,
anti-athlete foot remedies, antiperspirants, and numerous other uses on
body surfaces. The alkaline oxides are used to neutralize stomach HC1
during the treatment of peptic ulcer. There is no known health hazard
due to the use of aluminum.
Current Production and Use
Total domestic production of ammonium sulfate was over 7 billion pounds
in 1975. It is used in the manufacture of fertilizers, ammonium alum,
fireproofing compositions, and water treatment chemicals. Other uses
include tanning operations, food additives, and the production of viscose
rayon.
Aluminum sulfate production in 1975 was in excess of 1.7 billion pounds.
The chemical has a multitude of uses: leather tanning; paper sizing;
dye mordant; fireproofing and waterproofing textiles; treating sewage;
agricultural chemicals; lubricants; alums; catalyst, etc.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into con-
sideration the fact that it may be based on incomplete information,
EPA FORM 1320-6 (REV. 3*76)
51
-------
Recommendations
Copies of this submission were sent to CPSC, TC, GSA, and DOE by the
submitter. Suggest sending to HUD. No action warranted by EPA.
52
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: March 28, 1978
SUBJECT: Status Report 8EHQ-0178-0035 Approved
Revision
PROM.- Frank D. Kover, Acting Director Needed
Assessment Division, OTS (WH-557)
TO.- Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
Briefly summarizes results of subcutaneous injection of 1,2-dipiperi-
dinoethane (400 to 800 mg/kg) in rats indicating focal brain injuries
with the compound. Oral route is said not to be effective.
Submission Evaluation
i
Piperidines resemble nicotine in acting on ganglia of the autonomic
nervous system. They also act on the brain, spinal cord, and skeletal
muscles. The submitted evaluation of the environmental hazard potential
may not be appropriate since it appears that skin and vapor absorbing
potential of the compound crosses the blood-brain barrier and thus
has the potential to produce chronic effects in the central nervous
system.
A follow-up phone call revealed that the company has not done any pharma-
cology or toxicology studies with the compound.
Since this compound affects the central nervous system, it may have abuse
potential.
Current Production and Use
No information on production or use is available; compound was not on the
TSCA Candidate List.
Recommendat ions
Section 8(b) production data will be evaluated when available; further
action on this chemical will depend on annual production volume.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA rOMM U20-4 mtv. >-7CI j-o
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: March 17, 1978
SUBJECT: Status Report 8EHQ-0078-0036
FROM: Frank D. Kover, Supervisor
Hazard Assessment Group, OTS (WH-557)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
Reports employee exposure to methylaminoacetaldehyde dimethyl acetal.
Submission Evaluation
The signs described in the exposed workers suggest that more was involved
than NaOH and methylamine, although the latter is a strong irritant of the
skin and of mucous membranes in the respiratory tract and eyes. Possible
intermediates such as bromoacetaldehyde dimethyl acetal could produce
similar irritations and in addition may produce irregularities of the
heart beat and depress the central nervous system.
CH3-NH-CH2-CH.
is the formula for the product
discussed.
Br-CH -CH;
•OCR,
-OCR.
is the intermediate.
CH3-CH
OCR.
is the formula for a sleep-producing
drug used in the past.
Current Production and Use
No information was located on the production and use of methylamino-
acetaldehyde dimethyl acetal; however, the chemical is on the TSCA
Candidate List.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into con-
sideration the fact that it may be based on incomplete information.
EPA FORM «J20-« (REV. 3-76)
54
-------
Recommendat ions
Although the submitter may use the best known precautions for handling
toxicologically potent compounds, nevertheless, they should have
pharmacology and toxicology data on methylaminoacetaldehyde dimethyl
acetal and its intermediates. The submitter should supply physical-
chemical data by which to gauge solubility and volatility.
Section 8(b) information will be checked on this chemical when the data
become available; follow-up correspondence will be used to fill current
information gaps concerning this compound. This notice and any subsequent
information will be forwarded to NIOSH and OSHA for their use in any
follow-ups.
The submitter should be asked to support his contention that the infor-
mation presented in this submission reasonably supports a conclusion
of substantial risk.
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: March 27, 1978
SUBJECT: Status Report 8EHQ-0178-0037
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (WH-557)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
Report on analysis of water samples from Metro Sewer District, Louisville,
KY, for hexachlorocylopentadiene and related compounds.
Submission Evaluation
The water and the water/soil samples that were analyzed were found to contain
polychlorinated hydrocarbons which are considered to be undesirable
contaminants of water and soil. When ingested, these compounds are not
readily metabolized to water-soluble or polar compounds that can be
excreted by the kidney. It has not been established that these compounds
are significantly secreted into the feces via the enterohepatic circulation.
This probably accounts for the fact that the polychlorinated compounds
found by analysis in the samples tend to deposit in the fat depots.
Current Production and Use
Current production of hexachlorocylopentadiene is estimated at between
7 and 50 million pounds per year, with the major portion used as a chemical
intermediate in the production of insecticides (many of which are now
strictly controlled by EPA) and flame retardants.
Recommendations
HAG has prepared a profile on this chemical. An assessment document is
in preparation by ORD.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 1320-6 (REV. 3-761 _,
56
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: March 27, 1978
SUBJECT: Status Report 8EHQ-0178-0038
FROM.- Frank D. Kover, Acting Director
Assessment Division, OTS (WH-557)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
Company correspondence on Louisville, KY, sewage treatment plant incident
involving hexachlorocyclopentadiene.
Submission Evaluation
EPA should request the results of the examination of the victims flown to
Atlanta. The conditions surrounding the exposure are vague; clarification
is in order.
Current Production and Use
Current production of hexachlorocyclopentadiene is estimated at between 7
and 50 million pounds per year, with the major portion used as a chemical
intermediate in the production of flame retardants and insecticides
(many of which are now strictly controlled by EPA).
Related Past and Current Activities
Assessment Division has prepared a profile on hexachlorocyclopentadiene. A
more detailed assessment document is in preparation by ORD.
Recommendations
Assessment Division will prepare follow-up letter requesting more information.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 132O-6 (REV. 3-76)
57
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE. March 17, 1978
Status Report 8EHQ-0178-0039P Approved
Revision
FROM. Frank D. Kover, Supervisor Needed
Hazard Assessment Group, OTS (WH-557) —
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
Internal company correspondence on primary skin irritation attributed to one
or more intermediates of a trade name product.
Toxicological Evaluation
It would be necessary to see the complete skin testing data before concluding
that problems will be experienced only with MAADMA and dibromoethyl acetate.
Low-molecular-weight acetals and halogenated ethyl acetates are strong primary
irritants to the skin and are readily absorbed from it. Many of these are
also strong ocular irritants and lacrimators.
The patients referred t6 in the letter of March 12, 1977, appear to be suffer-
ing from sensitivity reactions rather than simple primary irritation. The
report of March 23, 1977, reinforces this idea. It is surprising that these
people have not experienced respiratory symptoms.
Current Production and Use
VEL-5026 intermediates:
Cyclic amine: chemical description is insufficient.
Isocyanate dimer: chemical description is insufficient.
BADMA (butylamino dimethyl acetal?): no information located.
MAADMA (methylaminoacetaldehyde dimethyl acetal): no information
located; TSCA Candidate List entry.'
Dibromoethyl acetate: no information located.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
FORM I120-* (KCV. »-7«) CO
-------
Recommendations
Personal data have been deleted. Any follow-up should be an OSHA concern.
The submitter should be asked to support his contention that the submitted
information presents reasonable support for a conclusion of substantial
risk.
59
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
D»TB: March 17, 1978 (Revised May 10, 1979)
SueJtCT-. Status Report 8EHQ-0178-0040P Approved
Revision
Frank D. Kover, Supervisor Needed
Hazard Assessment Group, OTS (WH-557)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
Internal company memos on Firemaster 680 [l,2-bis(2,4,6-tribromophenoxy)
ethane] identified as cause of skin rashes in employees.
Submission Evaluation
There appears to exist a1 current view that separating the polybrominated
benzene rings in PBB by oxygen atoms or glycol chains will decrease
toxicity. We do not have toxicity data from any manufacturer that
establish this conclusively. Therefore, the potential for producing
PBB-type lesions must be considered to be present.
In this instance, the skin rash may have been due to the volatile tri-
bromophenol products released during processing. This, however, is not
consistent with the experiences at another company. The relief
reported by showering at the end of the day and putting on freshly laundered
clothing at the start of the work day suggests that a nonvolatile substance
is in continuous contact with the skin.
Current Production and Use
Not listed in TSCA Candidate List; probably flame retardant use.
Recommendations
This compound will be addressed in the HAG technology assessment activities
on flame retardants.
Section 8(b) information should be checked on this compound. This submission
should be referred to NIOSH and OSHA for appropriate follow-up.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
C»A POMM U10-* INCV. - ,_.
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: March 17, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0178-0041)
FROM: Frank D. Kover, Supervisor
Hazard Assessment Group, OTS (WH-557)
T0: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
Documents were submitted relating to various glycols; most were copies
of published articles. One item on acute toxicity studies on benzoyl
chloride was also submitted.
Submission Evaluation
Glycols - The data submitted are contained in old (1939-41), well-established
publications. No data are presented to show that the known hazards or
toxicity of propylene glycols have been evaluated anew.
Benzoyl Chloride - The portion of the submission dealing with benzoyl
chloride presents the results of acute toxicity studies that supposedly
exonerate the chemical. We should consider calling for the experimental
data. Benzoyl chloride is considerably more toxic than the glycols and
has reportedly been linked to occupational cancers among Japanese benzoyl
chloride workers.
Current Production and Use
Glycols - Accurate production figures on polypropylene glycols are not
available due to its many captive uses. Actual production may range between
34 and 60 million pounds. Reported uses include: intermediate in urethane
foams, adhesives, coatings, elastomers, plasticizers, etc.; hydraulic
fluids; rubber lubricants; antifoam agents; paint formulations; laboratory
reagents.
In 1975, production of propylene glycol was over 390 million pounds. The
principal uses include organic synthesis, antifreeze solutions; solvents
for fats, oils, waxes, resins, etc.; plasticizers, hydraulic fluids; bac-
tericide; Pharmaceuticals; brake fluids; and deicing fluids.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into con-
sideration the fact that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
61
-------
Dipropylene glycol's 1975 production volume was 39 million pounds and
was used in polyester and alkyl resins, reinforced plastics, plasticizers,
and as a solvent.
Benzoyl Chloride - The annual production of benzoyl chloride is not known;
however, the U.S. IXC records two domestic producers, implying production
in excess of 1,000 pounds/year. Benzoyl chloride is used as an intermediate
for the introduction of the benzoyl group into alcohols, phenols, and
amines (i.e., acylation) and in production of benzoyl peroxide and various
dye intermediates.
Recommendations
HAG has a report on ethylene glycol in preparation. The toxicity of
the glycols in general appears low.
Benzoyl chloride, on the other hand, is reported to be a carcinogen.
A chemical profile will be prepared in HAG. A request for Section 8(b)
information may be in order.
The submitter should be asked to support his contention that the information
presented in this submission reasonably supports a conclusion of substantial
risk.
62
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: March 17, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0278-0042
FROM: Frank D. Kover, Supervisor
Hazard Assessment Group, OTS (WH-557)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission De s crip tion
Inhalation data on 39 fluorine compounds submitted by a manufacturer of
research chemicals.
Submission Evaluation
Practically all of these fluorine compounds could present problems if they
were in widespread use and improperly handled. Some are corrosive to the
skin, and in some instances the action can be stopped only by injecting
Ca gluconate beneath the exposed area. Some of these chemicals are highly
irritating to the respiratory tract. A few of them affect the heart and
the CNS. The latter effect can result in either anesthesia or convulsions.
Current Production and Use
A majority of the chemicals listed appear to have relatively specialized
uses. Among the listed compounds having available use information are:
(a) dichlorotetrafluoroacetone - solvent; complexing agent
(b) hydrogen fluoride - large number of uses
(c) tetrafluoroethylene - monomer for "Teflon"
(d) chlorodifluoromethane - solvent; refrigerant.
Recommendations
Apparent low volume of most of these compounds does not support further action;
however, this recommendation should be confirmed by a check of Section 8(b)
information.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 1320-6 (REV. 3-76) 63
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATt: March 17, 1978
SUBJECT: Status Report 8HEQ-0278-0043 Approved
MOM: Frank D. Kover, Supervisor
Hazard Assessment Group, OTS (WH-557)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (WH-788)
Submission Description
An internal company memo concerning a spill of leptophos (or Phosvel)
while being transported for export as a pesticide.
Submission Evaluation
This compound has the potential of causing delayed neurotoxicity in humans.
Therefore, a clearer picture of the exposure should be requested. Those who
were exposed should be medically examined at reasonable intervals for
several months.
Current Production and Use
i
Production figures are not available; however, the submitter is the only
producer. Only reported use is as an insecticide, but leptophos was
never approved for use in the United States.
Recommendations
Bring to the attention of OPP.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
romi tiao* mev. »-?•)
64
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: March 17, 1978
SUBJECT: Status Report 8EHQ-0278-0044
FROM: Frank D. Kover, Supervisor
Hazard Assessment Group, OTS (WH-557)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
jubmission Description
Interim results reported on skin-painting study with naphthenic oil
(blended petroleum product containing polynuclear aromatic hydrocarbons
[PNA]) indicating strong skin tumorigenic activity in mice.
Submission Evaluation
This formulation probably contains sufficient polynuclear aromatic hydro-
carbons to be carcinogenic under the test conditions. Production of this
formulation has been stopped. The preliminary carcinogenicity data justify
this action.
Current Production and Use
Production of these blends has been stopped.
Recommendations
The real problem here is PNA content of petroleum products. ^Significant
exposures are likely to be primarily occupational, and therefore this
submission should be referred to NIOSH and OSHA for appropriate follow-up.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 1320-6 (REV. 3-76) £5
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: March 17, 1978
SUBJECT: Status Report 8EHQ-0278-0045
FROM-. Frank D. Kover, Supervisor
Hazard Assessment Group, OTS (WH-557)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
Report on characteristics of waste effluent from ampicillin trihydrate
manufacturing process. This chemical is a drug regulated by FDA; It appears
to be a NPDES permit application.
Submission Evaluation
FDA is concerned with production of a uniform and acceptable product for
clinical use. It does not concern itself with environmental effects.
Release of penicillin may cause a variety of effects in those exposed to
it. These may be skin reactions, sensitivity, or other systemic reactions.
Skin reactions are more common during exposure to ampicillin. Bacteria
exposed via environmental release of penicillin tend to become penicillin
resistant.
Recommendations
Inappropriate for Section 8(e) review'. Solvent use of methylene chloride
and its handling and disposal are of interest to EPA. No further action
necessary.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 1320-6 (REV. 3-76) gg
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: March 17, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0178-0046
FROM: Frank D. Kover, Supervisor
Hazard Assessment Group, OTS (WH-557)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
Copy of NCI Bioassay Report on 2,4-dinitrotoluene (camera-ready, December
30, 1977).
Submission Evaluation
Although the NCI report probably exonerates 2,4-DNT from the stigma of a
carcinogen, it gives only an opinion that the two hemangiomas and prostate
adenocarcinoma in rats were not related to administration of the compound.
This compound, in common with many other aromatic nitro compounds, can
injure the bone marrow to cause anemia. It also oxidizes the hemoglobin in
red blood cells and destroys their oxygen-carrying capacity. It can also
cause liver injury.
Current Production and Use
Domestic production of 2,4-dinitrotoluene was reported by the U.S. ITC to
be over 300 million pounds per year in 1975. In addition, production of
a mixture of 2,4- and 2,6-dinitrotoluene was greater than 270 thousand
pounds in 1975. Much of the 2,4-dinitrotoluene produced is used captively
to manufacture diaminotoluene (used to make toluene-2,4-diisocyanate),
dyes, toluidines, and other products. It is also used as a gelatinizing
and waterproofing agent in explosives.
Recommendations
More information about the biotransformation of 2,4-DNT by animals and
man and its potential for skin sensitization is needed. HAG will investi-
gate to determine if such information is available and evaluate the need
for further testing. The submission of NCI and other Government reports
is not required under Section 8(e).
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into con-
sideration the fact that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
67
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: March 17, 1978
SUBJECT: Status Report 8EHQ-0278-0047
FROM: Frank D. Kover, Supervisor
Hazard Assessment Group, OTS (WH-557)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
Results of an Ames test on l,2-epoxy-3-methoxypropane (BMP).
Submission Evaluation
It is not surprising, in light of the epoxy group, that EMP is a mutagen
not requiring activation.
Current Production and Use
No information on production and use is reported in the secondary
literature; the chemical is not on the TSCA Candidate List.
Recommendations
No immediate action is necessary; a request for Section 8(b) information
may be in order.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 1320-6 (REV. 3-76> ,-g
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: May 4, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0278-0048
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
Approved_
Revision
Needed
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
A study investigating the toxicity of MC-984* on bluegill sunfish and
rainbow trout. This notice was declassified on April 13, 1978.
*MC-984: bis(l,3-dichloro-2-propyl)-3-chloro-2,2-dibromomethyl-l-propyl
phosphate.
Submission Evaluation
MC-984 is toxic to bluegills and rainbow trout at levels which should be
of environmental concern. Even at the lowest concentrations tested (1 mg/1),
bluegills demonstrated behavioral effects (labored breathing, disorientation)
and rainbow trout exhibited erratic swimming (at concentrations greater
than 0.56 mg/1). MC-984 may pose problems in an aquatic ecosystem as
trout and bluegill appear to be fairly sensitive.
Current Production and Use
There is no information available in the production and use of this
chemical; it is not contained in the TSCA Candidate List.
Recommendations
Many submissions have been received on this chemical (8EHQ-1277-0022;
8EHQ-0178-0033; 8EHQ-0278-0049; 8EHQ-0053; 8EHQ-0378-0100).
(a) Section 8(b) data should be checked for evidence of conmercial significance.
(b) MC-984 may be a candidate for CHIP and/or NIOSH/OSHA consideration.
(c) The submission should be referred to ERD for further evaluation.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into con-
sideration the fact that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
69
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: April 25, 1978 (Revised May 10, 1979) Approved
SUBJECT: Status Report 8EHQ-0278-0049
Revision
Needed
FROM: Frank D. Rover, Acting Director
Assessment Division, OTS (TS-792)
TO: warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Paper describing the results of a rat dominant lethal assay of MC-984
Ibis(1,3-dichloro-2-propyl)-3-chloro-2,2-dibromomethyl-l-propyl phophate].
Submission Evaluation
Dominant lethal tests are usually very insensitive; the fact that positive
dose-related effects are seen is very suspicious. Possible causes are
direct or hormonal effects on sperm or sperm development or hormonal
blocking effects on females through transmission of the chemical in the
seminal fluid.
Current Production and Use
There is no information available on the production and use of this chemi-
cal; it is not contained in the TSCA Candidate List.
Recommendations
Many submissions have been received on this chemical (8EHQ-1277-0022;
8EHQ-0178-0033; 8EHQ-0278-0048; 8EHQ-0278-0053; 8EHQ-0378-0100;8EHQ-0378-
0107).
MC-984 may be a candidate for CHIP and NIOSH/OSHA referral if the 8(b)
data indicate that it is a commercially significant chemical.
NOTE: This status report is the result of a preliminary staff eval-
uation of information submitted to EPA under Section 8(e) of
TSCA. Statements made herein are not to be regarded as ex-
pressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on incomplete
information.
FORM 1320-6 (REV. 3-7«) 70
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: May 11, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0278-0050
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
Approved
Revision
Needed
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Acute toxicity studies of Polyvel M-106 polymer (a mixture of petroleum-
derived hydrocarbon resins) in rabbits and rats. This notice was de-
classified on April 13, 1978.
Submission Evaluation
Polyvel M-106 appears to have no significant acute toxicity either for the
skin or ocular mucous membranes or by systemic absorption from the gas-
trointestinal tract. This lack of acute toxicity does not necessarily
mean, however, that either the polymer or the plasticizer will not have
chronic effects, particularly as sensitizing agents.
Current Production and Use
No production and use information is available; the chemical is not
contained in the TSCA Candidate List.
Recommendations
(a) Section 8(b) data should be checked to determine the annual production
of this material, and if significant, consider a CHIP investigation.
(b) The submitter should be asked to support his contention that the
information presented in this submission reasonably supports a conclusion
of substantial risk.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete information,
EPA FORM 1320-6 (REV. 3-76)
71
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
June 14, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0278-0051 Approved
Revision
PROM: Joseph J. Merenda, Acting Director Needed
Assessment Division, OTE/OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Results of Ames-type test (with and without metabolic activation) on FM-
100 (major constituent is hexabromocyclododecane) and an FM-100 (production?)
residue. This notice was declassified on April 13, 1978.
Submission Evaluation
FM-100 has limited solubility under the conditions of this test, and the
absence of mutagenic activity in this study may be related to its limited
solubility. The "FM-100 residue" (inadequately characterized), however,
did show positive results with strain TA 1535. The main difficulty with
this report is the lack of an adequate analytical characterization of the
components in the FM-100 residue. In addition, the report does not show
how the solubility problems affect the results or how they can be cir-
cumvented.
Current Production and Use
Hexabromocyclododecane (HBCD) is listed in the Directory of Chemical
Producers, thus indicating that it is produced in commercial quantities
(>1000 pounds/year). HBCD is used as a fire retardant in copolymers of
styrene with acrylonitrile, N-vinylpyrrolidinone, divinylbenzene, methyl
acrylate, poly(methyl methacrylate), or polyethylene. It is also used
as a fire retardant in molded and foamed thermoplastic styrene and in
polypropylene-based molding compositions. When incorporated into these
plastics, HBCD imparts a self-extinguishing property to the material.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 1I20-« (MCV. »-7C) 72
-------
HBCD is also used in the production of adhesives used for luting polystyrene
foam sheets. This use arises from its ability to reduce the molding time
necessary for cellular polystyrene particles to form into a compact foam
block.
Commen t s/Recommendat ions
FM-100 will be evaluated as part of the ongoing Assessment Division examina-
tion of flame retardant technology. This chemical has been the subject of
three other submissions (8EHQ-0278-0065; 8EHQ-0378-0088; 8EHQ-0478-0137).
(a) This submission, like others, was deficient in a number of areas.
The notifier should be asked to provide adequate analytical data on
the composition of both mixtures tested, but especially the FM-100
residue. Physical-chemical data on FM-100 and the residue would also
be of value.
(b) Section 8(b) data should be checked to determine the commercial
significance of this compound. FM-100 is listed in the recent "Bromine
Based Fire Retardants" report. FM-100 may be a CHIP candidate.
(c) The submitter should be asked to support his contention that the
information presented in this submission reasonably supports a con-
clusion of substantial risk.
73
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: March 17, 1978
SUBJECT: Status Report 8EHQ-0278-0052P
FROM: Frank D. Kover, Supervisor
Hazard Assessment Group, OTS (WH-557)
TO: Warren R. Mulr, Deputy Assistant Administrator
for Testing and Evaluation, OTS (WH-788)
Submission Description
Company memos and correspondence relating to exposure of personnel to
phosphonium salts.
Submission Evaluation
If the compound in question is phosphonium iodide, then a serious toxicity
problem may exist. Phosphonium iodide is readily decomposed to phosphine.
Phosphine, in addition to being a pulmonary irritant, is also capable of
hemolyzing red blood cells. This can result not only in anemia, but also
in blockage of blood vessels by the released hemoglobin, particularly in
the kidney. Milder exposure results in liver damage.
Organic phosphonium compounds simulate quaternary ammonium compounds in
their toxic effects and result in falling blood pressure, cardiac irregulari-
ties, convulsions, and finally complete paralysis of muscles of respiration.
The information submitted does not indicate what the offending agent or
agents could be. It is essential to obtain this information. The
laboratory reports indicate that liver injury, anemia, and possible
neuromuscular involvement were present.
Current Production and Use
Insufficient detail provided in submission to develop production and
use data.
Recommendations
Personal data deleted. Followup correspondence should be sent requesting
more information on the causative agent (s). The submission and any follow-
up data should be referred to NIOSH and OSHA. for appropriate action.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into con-
sideration the fact that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
74
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: May 11, 1978 (Revised May 10, 1979) Approved
SUBJECT: Status Report 8EHQ-0278-0053
Revision
Needed __________
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Des crip t ion
Study reporting the results of a mutagenicity evaluation of MC-984 [bis
(l,3-dichloro-2-propyl)-3-chloro-2-2-dibromoethyl-l-propyl phosphate])
using the mouse lymphoma assay. This notice was declassified on April
13, 1978.
Submission Evaluation
MC-984 appears to be mutagenic for mouse lymphoma cells. We do not agree
with the submitted interpretation that the results may have been an "artifact
due to the toxicity of the compound. The purity of the compound tested is
not given in the report. The clouding that occurred when the stock solvent
was added to the growth medium indicates low solubility in aqueous media,
and suggests that very little of the compound was available for reaction with
the mouse cells. In vivo conditions would most likely increase the
amount of compound available to cells.
Current Production and Use
There is no information available on the production and use of this chemical;
it is not contained in the TSCA Candidate List.
Comments/Recommendations
Many submissions have been received on this chemical (8EHQ-1277-0022;
8EHQ-0178-0033; 8EHQ-0278-0048; 8EHQ-0278-0049; 8EHQ-0378-0107).
Section 8(b) should be checked to assist in reaching a disposition decision.
If MC-984 is a commercial chemical of some significance, consideration should
be given to CHIP and/or NIOSH/OSHA evaluation of the studies.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into con-
sideration the fact that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76) 75
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: May 8, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0278-0054
PROM: Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Sheet describing residue assays of hexachlorocyclopentadiene (HEX) and
related compounds in fish taken from the Mississippi River around Memphis,
TN. This information is supplemental to 8EHQ-1177-0013 from the same
notifier. This notice was declassified on April 13, 1978.
Submission Evaluation
Monitoring information revealed that HEX and related compounds were
identified in catfish and carp (numbers tested?) taken from the Missis-
sippi River. The organs used for this residue analysis were not noted—
was this a whole fish study? Other chemicals included in this report
were: chlordene, octachlorocyclopentene, etc. The levels of HEX found
were very low (below detection limits?). Octachlorocyclopentene was
detected at 0.75 ppm in a catfish 1 mile downstream from Memphis(?).
Current
an
All compounds listed are pesticides or related chemicals used in the
manufacture of pesticides (possibly flame retardants also) .
Related Past and Current Activities
A chemical profile on hexachlorocyclopentadiene is available from the
Assessment Division; ORD is preparing an assessment report on this chemical.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular chemical.
Any review of the status report should take into consideration
the fact that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
76
-------
Recommendations
The ORD contact should forward a copy of this status report to the perti-
nent ORD people working on hexachlorocyclopentadiene (pending confiden-
tiality determination). Several other submissions have been received on
this and related chemicals (see 8EHQ-0278-0061 for a listing of related
submissions).
(a) These data and the earlier results (8EHQ-1177-0013) should be for-
warded to the FDA Bureau of Foods and OPP (pending confidentiality
determination).
(b) The submitter should be contacted about the questions raised concern-
ing the study.
77
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 22, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0278-0055
FROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
Approved_
Revision
Needed
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Information on the neurotoxic effects of triphenylphosphine supplemental
to that received in submission 8EHQ-1177-0015. The submission consists
of a (1962) published German language reference to the data referred to
in the earlier submission. This notice was declassified on April 19, 1978.
Submi s s ion Evaluat ion
Neurotoxicity of alkyl and aryl metallic organic compounds is well estab-
lished. The qualitative aspects of the toxicity vary according to the
particular compound. For instance, many low-molecular-weight aliphatic
metals have sufficient lipid solubility to distribute themselves freely
through the brain and penetrate the neuronal cells. During this phase,
they tend to act like general anesthetics and produce the signs of the
early stages of anesthesia, i.e., a mixture of excitement and depression.
This is usually a transient phase of a few minutes up to 1 hour. Some of
the alkyl metal remains within the brain cells, and usually one alkyl group
is removed to give rise to ionic forms that affect enzymes involved in
metabolism. The effect on metabolism is usually slow and may not manifest
itself for several hours or several days, when the animal begins to exhibit
signs of fear and other changes usually culminating in epileptic-form
seizures. Nonetheless, there is apparently little demonstrable permanent
peripheral nerve injury.
On the other hand, some alkyl metals, such as methyl mercury, and most
aryl metals penetrate slowly and have a longer latent period of action.
The damage to the brain cells and peripheral nerves that is produced by
these compounds is practically irreversible as in the case of methyl
mercury. Unlike some of the other aryl metals, the subject chemical in
this submission, triphenylphosphine, tends to confine its effects to the
peripheral nervous system.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular chemical.
Any review of the status report should take into consideration
the fact that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
78
-------
These alkyl metals and metalloids which are highly reactive with oxygen
and of low lipid solubility, such as some phosphines, arsines, and stibines,
react with the oxygen in red blood cells and hemolyze them. They also
produce severe irritation of the respiratory tract (refer to 8EHQ-1177-
0014 and 8EHQ-1177-0015 for additional discussion of triphenylphosphine).
Current Production and Use
No production figures are available; however, the SRI Directory of Chemi-
cal Producers (1975) lists four producers, implying an annual production
greater than 1,000 pounds. Reported uses include synthesis of organic
compounds (including homogeneous catalysts), phosphorus salts, and other
phosphorus compounds.
Recommendations
The toxicological information contained in this submission may be of
interest to MCA (or some other body) for inclusion in product safety data
sheets.
(a) Section 8(b) data should be checked to determine the production level
of triphenylphosphine.
(b) If production volume is sufficient, CHIP scrutiny may be in order.
(c) The information should be forwarded to NIOSH and OSHA.
79
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: Oune 22, 1978
SUBJECT: Status Report 8EHQ-0278-0056 Approved
Revision
FROM: Joseph J. Merenda, Acting Di rector/' Needed
Assessment Division, OTE/OTS
TO-. Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Two reports outlining the results of sterility tests conducted on
employees who were occupationally exposed to DBCP (1 ,2-dibromo-3-chlo-
ropropane) and tris (tris(2,3-dibromopropyl) phosphate). This notice
was declassified on 4/13/78.
Submission Evaluation
The significant point in this submission is that 12 workers had been
exposed to DBCP and tris for a sufficient length of time to have ob-
viously inadequate reproductive ability. The.se 12 workers had sperm
counts of less than 20 X 106/cc and 11/12 were also deficient in sperm
motility. In addition, eight of the men from this group also had inade-
quate sperm morphology. The 12 men with hypospermia or oligospermia
would still be incapable of fertilizing the ovum even though the sperm
morphology may be adequate. The deficient motility might prevent the
sperm from traveling through the cervix to reach the ovum and if they
did reach the ovum, might not be able to penetrate the cumulus or outer
covering of the ovum.
The duration and intensity of exposure are not indicated in the reports
for either group. The data, however, may contain a Deleterious Dose^
(ED(-n) relationship. Dose-response phenomena are graded rather than
all-or-none. An EDRn means that increasing the exposure will result in
more subjects being affected. Thus, the other 12 men who test out as
having normal function may not have been exposed for a sufficient length
of time and it might be expected that they could also develop reproduc-
tive incapability.
The attending physician's explanation of LH and FSH functions is partial.
LH (luteinizing hormone) and FSH (follicle stimulating hormone) are pro-
duced by the pituitary gland and are responsible for gonadal function in
men and women. They are part of an intricate feedback system that regu-
lates the formation of sex hormones and sperm. When the action of the
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
CPA rOMM IMfr* (RCV. »-7») "U
-------
gonads decreases, more gonadotrophins are released from the pituitary.
The attending physician may be intimating that the slight elevation of
LH and FSH in the ten affected men indicates that the damage to the
testis is not severe. The intimation is in error because the testis
also produces estrogens that are strong inhibitors of LH and FSH. The
regulation and feedback mechanism between pituitary and gonads is much
more intricate than the reports states. In this instance, the LH and
FSH determinations have dubious significance.
Current Production and Use
Unconfirmed reports indicate that tris is no longer being produced
domestically; 1975 production is estimated at 7-12 million Ibs. Tris
was previously used as a textile flame retardant, however, the CPSC has
moved against this use. The only reported current use is as a flame
retardant for plastics.
OPP has conditionally suspended DBCP for some uses and completely sus-
pended it for all other uses. Conditional suspension means that only
certified pesticide applicators can apply DBCP. DBCP has no known
nonpesticidal uses.
Comments/Recommendations
In view of (1) unconfirmed reports that tris is no longer manufactured,
(2) NCI's (unpublished) conclusions that the chemical is a carcinogen,
(3) CPSC's announced policy to ban the sale of tris-treated children's
sleepwear, and (4) EPA/OPP's action to restrict the only known (pesticidal)
uses of DBCP:
a) 8(b) data should be checked for evidence of continued domestic
production of tris. This follow-up should include the identi-
fication of possible tris importers. 8(a) data should also
be checked to confirm whether DBCP is being manufactured for
other than pesticidal uses.
b) Recommend to Office of Chemical Control that it consider
developing a significant new use rule for DBCP.
c) This submission should be referred to OSHA, NIOSH, CPSC,
OPP/OTS, and TS/OE.
d) The notifier should be requested to provide the fertility
history of the cohort thus supplying baseline information on
the fertility of the exposed workers. A more in-depth epidemio-
logy study may be needed at a later date.
31
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: May 2, 1978 (Revised May 10, 1979) Approved_
SUBJECT: Status Report 8EHQ-0278-0057S
Revision
Needed
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission. Description
A letter outlining the results of three in vitro tests (Ames test; mouse
lymphoma test; and mammalian cell transformation test) on AP-1155 (generi-
cally described as polyaromatic amines).
Submission Evaluation
Because this is a mixture, only qualitative statements about toxicity
are applicable. Polyaromatic amines (polycyclic aromatic amines) are a
class of well-known carcinogens. This mixture, therefore, has great poten-
tial carcinogenicity. A battery of short tests has increased the possibility
of requiring long-term carcinogenicity testing.
The material is a polymer. Although the annual production is confidential,
what is the ultimate disposition of the final product, particularly when
discarded? Does AP-1155 accumulate or is it degraded? Is there a solubility
and stability curve related to pH above 7? This is important in the context
of skin absorption of the material. (Is the material a skin sensitizer? a
light sensitizer? How leachable is the chemical, especially from the finished
product in alkaline media?)
Current Production and Use
No information on production and use is available in the secondary litera-
ture; the chemical is not entered in the TSCA Candidate List.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into con-
sideration the fact that it may be based on incomplete information.
05
EPA FORM 1320-6 (REV. 3-76) °*
-------
Recommendations
(a) This submission should be referred to NIOSH and OSHA for appropriate
follow-up, if any.
(b) The claimed production volume should be confirmed with a check of the
data.
(c) Additional information should be requested from the submitter to answer
the questions posed in the evaluation section above.
83
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
SUBJECT:
FROM:
TO:
May 5, 1978 (Revised May 10, 1979)
Status Report 8EHQ-0278-0058
Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
Approved^
Revision
Needed
Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Studies reporting the acute toxicity of chlorendic anhydride to rainbow
trout and bluegill sunfish. This notice was declassified on April 13,
1978.
Submission Evaluation
The toxicity of chlorendic anhydride to bluegills and trout was fairly
low in this test, although the experimental conditions were far from
ideal. Among the problem areas were: precipitation of chlorendic anhy-
dride from solution leading to lower water concentrations than reported;
lack of physical/chemical data on the chemical (pKa, solubility, etc.);
lack of distinction between the effects of lowered pH versus those of
the chemical.
Current Production and Use
An estimated 10 million pounds of chlorendic acid/chlorendic anhydride
were produced in 1974, with an expected growth rate of 10% per year
through 1980. Reported uses of chlorendic anhydride include: flame-
resistant polyester resins; hardening agent for epoxy resins; chemical
intermediate; source of chlorendic acid.
Related Past and Present Activities
Several other submissions have been received on this compound (8EHQ-
0278-0059; 8EHQ-0378-0094; 8EHQ-0378-0101).
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 1320-6 (REV. 3-76)
-------
Comment s/Recommendat ions
(a) The physical/chemical data should be requested in follow-up corre-
spondence to the submitter.
(b) This information should be referred to the ORD contact for distri-
bution to the people working on the hexachlorocyclopentadiene
assessment document.
(c) The submitter should be asked to support his contention that the
information presented in this submission reasonably supports a
conclusion of substantial risk.
85
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: May 11} 1978 (Revised May 10, 1979) Approved _
SUBJECT: status Report 8EHQ-0278-0059
Revision
Needed
PROM: Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
TO! Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Study reporting the acute toxicity of chlorendic anhydride to Daphnia
(water flea). This notice was declassified on April 13, 1978.
Submission Evaluation
Chlorendic anhydride was found to be toxic to Daphnia at relatively high
concentrations. The apparently low solubility of the chemical in water
appears to minimize the toxic effects on pelagic organisms but may have
implications for benthic organisms. Once again (see 8EHQ-0278-0058) the
test chemical precipitated from solution and likely lowered the actual
water concentration below the calculated value. No physical/chemical
data on chlorendic anhydride were reported.
Current Production and Use
An estimated 10 million pounds of chlorendic anhydride were produced in
1974, with an expected annual growth rate of 10% through 1980. Reported
uses of chlorendic anhydride include: flame-resistant polyester resins;
hardening agent for epoxy resins; chemical intermediate; source of
chlorendic acid.
Related Past and Present Activities
Some discussion of chlorendic anhydride can be found in the Assessment
Division report on hexachlorocyclopentadiene.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
C*»A FORM 1320-6 'REV. 3-76) 86
-------
Recommendations
Several other submissions have been received on this compound (8EHQ-
0278-0058; 8EHQ-0378-0094; 8EHQ-0378-0101).
(a) Follow-up correspondence to obtain the physical/chemical data on
chlorendic anhydride may be of value. The submitter should also be
asked to support his contention that the information presented in
this submission reasonably supports a conclusion of substantial
risk.
(b) The ORD contact should inform the ORD people working on hexachloro-
cyclopentadiene of the results of this study for possible inclusion
in their HEX report.
87
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
OATB-. May 39 1978 (Revised May 10, 1979) Approved _
SUBJECT-. status Report 8EHQ-0278-0060
Revision
Needed
PROM: Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
T0: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Study reporting the acute toxicity of MC 948* to Daphnia (water flea).
This notice was declassified on April 13, 1978.
*MC 948: primary constituent is bis(tribromoneopentyl) pentaerythritol
cyclic disphosphate; same as VC 948.
Submission Evaluation
The (acute, static) LCcQ for MC 948 in Daphnia could not be determined
as there was no significant mortality at the concentrations tested (up
to 100 mg/1). These concentrations are nominal and may be significantly
higher than the actual values because the MC 948 precipitated out of
solution at concentrations greater than 18 mg/1. The test gives no use-
ful information about the acute toxicity of MC 948 to Daphnia.
Current Production and Use
No information is available on the production and use of MC 948, nor is
it entered in the TSCA Candidate List.
Recommendations
Several other submissions have been received on this chemical (8EHQ-
0278-0071; 8EHQ-0378-0092; 8EHQ-0378-0098).
(a) Section 8(b) data should be checked for evidence of commercial
significance.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FQMM IJ2O-6 (REV. 3-76) 38
-------
(b) The chemical name provided in the submission is trivial and should
be clarified through follow-up correspondence; a. drawing of the
molecular structure should also be required,
(c) If commercially viable, MC 948 may be a candidate for CHIP and/or
NIOSH/OSHA consideration.
(d) The submitter should be asked to support his contention that the
information presented in this submission reasonably supports a
conclusion of substantial risk.
89
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
SUBJECT:
FROM:
TO:
May 8, 1978
Status Report 8EHQ-0278-0061
Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
Approved_
Revision
Needed
Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Acute toxicity study of the effects of hexachlorocyclopentadiene on
Daphnia (water flea). This notice was declassified on April 13, 1978.
Submission Evaluation
Hexachlorocyclopentadiene exhibited a high degree of toxicity to Daphnia
in acute static tests. The ~LCz,Q was 52.4 yg/1; DO and pH were kept at
acceptable levels throughout the tests. The results indicate that
hexachlorocyclopentadiene would cause serious problems if released into
the environment such that Daphnia and (potentially) other aquatic organisms
were exposed to it.
Current Production and Use
Precise production figures are not available; the U.S. ITC lists two
producers, which implies an annual production of greater than 1,000
pounds. Actual production is likely to be appreciably larger (produc-
tion of chlorendic acid/anhydride alone consumed 7-7.5 million pounds in
1974). Hexachlorocyclopentadiene is used as a chemical intermediate in
the production of insecticides (aldrin, dieldrin, endrin, Kepone ,
mirex, etc.), chlorendic acid/anhydride, fire retardants, and dyes.
Related Past and Current Activities
A chemical profile on hexachlorocyclopentadiene is available from the
Assessment Division. ORD is currently preparing an assessment document
on this chemical.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 1320-6 (REV. 3-761
90
-------
Recommendations
Several other submissions have been received on this chemical (or the
related compound chlorendic anhydride): 8EHQ-0977-0004; 8EHQ-1177-0013;
8EHQ-0178-0037; 8EHQ-0178-0038; 8EHQ-0278-0058; 8EHQ-0278-0059; 8EHQ-
0278-0062; 8EHQ-0278-0064; 8EHQ-0378-0094; 8EHQ-0378-0101; 8EHQ-0378-
0102. The OSD contact should see that the pertinent people in ORD
receive the available information for inclusion in their report.
91
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: May 8, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0278-0062
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
T°! Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Acute toxicity studies of octachlorocyclopentene in rabbits and rats.
This notice was declassified on April 13, 1978.
Submission Evaluation
The submitter acknowledges that the compound is a primary eye irritant.
The submitter further acknowledges that the compound is mildly irritating
to the skin as a primary irritant. No studies were submitted as to its
skin sensitizing properties.
The steep LD^Q curve suggests that the compound may be unusually toxic.
If the safe ceiling dose is exceeded slightly, the outcome may be
lethal. A dose-response curve study should be carried out in the range
between 500-1,000 mg/kg. This should establish some indication of the
margin of safety. Since the slope is steep, the increments of dosing
should be small.
Current Production and Use
No production and use information was located on this chemical, nor was
it contained in the TSCA Candidate List.
Comment s/Recommendat ions
The chemical may have some flame retardant applications and will be
evaluated in that context in the ongoing Assessment Division study of
flame retardant technology.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
92
EPA FORM 1320-6 (REV. 3-76)
-------
(a) Section 8(b) data on this chemical should be checked when they
become available.
(b) A copy of the status report should be sent to the notifier as a way
of suggesting the need for possible additional testing on this
compound.
93
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
SUBJECT:
FROM:
TO:
May 12, 1978 (Revised May 10, 1979)
Status Report 8EHQ-0278-0063
Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
Approved_
Revision
Needed
Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Company memo describing occupational health problems associated with
methendic anhydride/maleic anhydride. This notice was declassified on
April 13, 1978.
Submission Evaluation
The symptoms reported in the notice (irritation to eyes and respiratory
tract) correlate with those ascribed to maleic anhydride. No informa-
tion was available to judge whether or not methendic anhydride may
contribute to the observed symptoms.
Maleic anhydride is often produced from benzene feedstocks. Because
benzene is a well-known bone marrow depressant and maleic anhydride is
likely to have profound effects on other organ systems, a study should
be initiated to assess possible synergistic effects.
Some acylating agents have demonstrated carcinogenic or mutagenic activities.
Because maleic anhydride is a potent acylating agent, its mutagenic/
carcinogenic potential is perhaps an area which should be investigated.
Current Production and Use
The U.S. ITC reports that approximately 216 million pounds of maleic
anhydride were produced in 1975. The major uses are in polyester resins,
alkyd coating resins, pesticides, and permanent-press resins for textiles.
"Methendic" anhydride is a trademarked mixture of bicylic unsaturated
dibasic anhydrides. It is used as a cross-linking or curing agent in
epoxy-type resin systems. No production figures are available.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be baserl nr
incomplete information.
EPA FORM 1320-6 (REV. 3-76)
94
-------
Comments/Recommendations
(a) The submission notes that a manufacturer's safety data sheet is
available on methendic anhydride; because this is a trade name
mixture and little information is available, the data sheet should
be requested.
(b) Production volume of methendic anhydride should be determined with
a check of the 8(b) data.
(c) Follow-up correspondence should request the results of any medical
evaluation conducted on exposed workers.
(d) Maleic anhydride will undergo CHIP scrutiny in the near future.
Depending on the conclusions of the CHIP review, there may be need
for monitoring activities to measure benzene and maleic anhydride
levels at production sites. If the monitoring effort identifies a
potential problem, OTS should consider initiation of the synergistic
effects study, possibly under TSCA Section 4.
(e) This information should be referred to NIOSH and OSHA.
(f) The submitter should be asked to support his contention that the
information presented in this submission reasonably supports a
conclusion of substantial risk.
95
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
OATE: June 15, 1978 Approved_
SUBJECT: status Report 8EHQ-0278-0064
Revision
Needed
PROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
TO! Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Acute oral toxicity study of hexachlorocyclopentadiene in albino mice.
This notice was declassified on April 13, 1978.
Submission Evaluation
Hexachlorocyclopentadiene is a halogenated ring hydrocarbon Which in
larger doses produced death within 4 hours. This is indicative of
central nervous system effects on respiration and/or circulation. The
lower doses and some of the higher doses produced delayed deaths which
suggest kidney and/or liver impairment. In the absence of biotransforma-
tion and pharmacokinetic data, it is difficult to evaluate accurately
the potential toxicity of this compound. Like many halogenated compounds,
particularly polyhalogenated, it probably has carcinogenic potential
either by virtue of ring opening or dehalogenation at points which can
give rise to epoxides.
Current Production and Use
Precise production figures are not available; the U.S. ITC lists two
producers, which implies an annual production of greater than 1,000
pounds. Actual production is likely to be appreciably larger (produc-
tion of chlorendic acid/anhydride alone consumed 7-7.5 million pounds in
1974). Hexachlorocyclopentadiene is used as a chemical intermediate
in the production of insecticides (aldrin, dieldrin, endrin, Kepone ,
mirex, etc.), chlorendic acid/anhydride, fire retardants, and dyes.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 1320-6 (REV. 3-76) 96
-------
Related Past and Present Activities
A chemical profile on hexachlorocyclopentadiene is available from the
Assessment Division; ORD is currently preparing an assessment document
on this chemical.
Comment s/Recommendat ions
Several other submissions have been received on this chemical (or the
related compound chlorendic anhydride): 8EHQ-0977-0004; 8EHQ-1177-0013;
8EHQ-0178-0037; 8EHQ-0178-0038; 8EHQ-0278-0054; 8EHQ-0278-0058; 8EHQ-
0278-0059; 8EHQ-0278-0061; 8EHQ-0378-0094; 8EHQ-0378-0101; 8EHQ-0378-
0102; 8EHQ-0378-0110; 8EHQ-0478-0127; 8EHQ-0478-0134.
The ORD contact should see that the pertinent people in ORD receive the
available information on hexachlorocyclopentadiene for use in their
assessment report.
97
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
OATE! June 15, 1978 (Revised May 10, 1979) Approved_
SUBJECT: status Report 8EHO-0278-0065
Revision
Needed
FROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
TO! Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Acute toxicity studies of hexabromocyclododecane (FM 100) in rabbits and
rats. This notice was declassified on April 13, 1978.
Submission Evaluation
The magnitude of toxicity during an acute study with compounds such as
FM 100 has limited value. It is significant that an application of
FM 100 to the skin of rabbits resulted in sufficient absorption to cause
loss in body weight in one male and one female rabbit. This weight loss
will have to be accounted for. If it is real, it suggests that small
amounts of FM 100 present in the organism can produce toxic effects.
It is significant that a single oral dose of FM 100 resulted in corneal
opacity (which persisted) and drooping or closing of the eyelids in male
rats. The type of corneal opacity is not described; it is not possible
to visualize what the observer saw. If the entire cornea was clouded,
this may indicate a variety of things, including surface insensitivity so
that the animal could not respond to particles in the air, and this may
have caused the opacity. No test was made for sensitivity of the cornea.
On the other hand, if the opacity was circumscribed to the iris area,
this would suggest precipitation of lens proteins resulting in cataracts.
In any event, sufficient FM 100 was absorbed following oral administra-
tion to produce ocular changes in male rats, which will have to be
accounted for.
Although FM 100 appears to produce no serious acute effects during a
4-hour inhalation exposure and does not seem to cause fatality for 14
days thereafter, it would be desirable to observe lung tissue microscopi-
cally. The lung sections should include animals sacrificed shortly after
exposure, 7 days after exposure, and 14 days after exposure.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM J320-6 (REV. 3-76) 98
-------
Current Production and Use
Hexabromocyclododecane Is listed in the Directory of Chemical Producers,
indicating that it is produced in commercial quantities of greater than
1,000 pounds per year. Hexabromocyclododecane is used as a fire retard-
ant in copolymers of styrene with acrylonitrile, N-vinylpyrrolidine,
divinylbenzene, methyl acrylate, poly(methyl methacrylate), or polyethyl-
ene. It is also used as a fire retardant in molded and foam thermo-
plastic polystyrenes and in polypropylene-based molding composition.
When introduced into these plastics, hexabromocyclododecane imparts a
self-extinguishing property to the material. The chemical is also used
in the production of adhesives used for cementing polystyrene sheets.
This use arises from its ability to reduce the molding time necessary
for cellular polystyrene particles to form into a compact foam block.
Comments/Recommendations
FM 100 may be an environmentally persistent compound. Three other sub-
missions have been received on this compound (8EHQ-0278-0051; 8EHQ-0378-
0088; 8EHQ-0478-0137). FM 100 will be investigated as part of the on-
going Assessment Division study of flame retardant technology.
(a) This submission, like others, was deficient in a number of areas.
The notifier should be asked to provide physical-chemical data on
the test substance, gross findings on death, clinical observations,
etc. The submitter should be also asked to support his contention
that the information presented in this submission reasonably sup-
ports a conclusion of substantial risk.
(b) Section 8(b) data should be checked to determine the commercial
significance of this compound; if production is sufficient, consid-
eration should be given to CHIP and/or NIOSH/OSHA referral.
99
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
June 23, 1978 (Revised May 10, 1979) Approved^
SUBJECT: status Report 8EHQ-0278-0066
Revision
Needed
FROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
T0: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Acute oral toxicity study with poly(dibromophenylene oxide) (MC935A) in
rats. This notice was declassified on April 13, 1978.
Submission Evaluation
If this is a relatively high-molecular-weight polymer of brominated
phenylene or brominated phenylene oxides, it is not necessarily as toxic
as PBB. What is needed here is a good description of the material and
the quantitative physical data that characterize it. The situation
could be analogous to that which exists between vinyl chloride and poly-
vinyl chloride. In addition to information on the structure and molecu-
lar weight of the material, we should also be supplied with information
about its purity, particularly from the standpoint of low-molecular-
weight toxic residues that could be formed during the process of polym-
erization.
Current Production and Use
No production and use information was located; there is no entry in the
TSCA Candidate List.
Comments/Recommendations
Several other submissions have dealt with this chemical (8EHQ-0378-0090;
8EHQ-0378-0103; 8EHQ-0498-0132). MC 935A may have some potential flame
retardant uses; if so, it will be evaluated in the ongoing Assessment
Division study of flame retardant technology.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 1320-6 (REV. 3-76) 100
-------
(a) Evaluate Section 8(b) data to determine present production level.
(b) Refer this submission and the others on this chemical to the PBB
workgroup.
(c) If the chemical appears commercially viable, it should be given
CHIP and/or OSHA/NIOSH consideration.
(d) Clarify structure with follow-up letter to notifier.
(e) Quantitative analytical data on MC 935A should be requested from
the submitter; this should include a description of the compound
actually tested as well as the commercial material, if different.
Physical-chemical data would also be of value. The question of
possible dioxin contamination of this material should also be
raised with the submitter.
(f) The submitter should be asked to support his contention that the
information presented in this submission reasonably supports a
conclusion of substantial risk.
101
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 14, 1978 (Revised April 6, 1979)
SUBJECT: Status Report 8EHQ-0278-0067P Approval
Revision
FROM- Joseph J. Merenda^Acting Director Needed
Assessment DivisiWi, OTE/OTS (TS-792)
T0. Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Corporate memo describing an employee accident involving exposure to
diisopropylaminoethyl chloride hydrochloride. This notice was declas-
sified on 5/22/78.
Submission Evaluation
Beta-chloroethylamines are used in the synthesis of various drugs that
have antihistamine and beta-adrenergic receptor blocking properties. The
diisopropylamino moiety suggests that beta-blockers are being synthesized.
The hydrochloride salt was probably sufficiently irritating to produce
conjunctivitis. The free base would also be irritating. Referral to
OSHA and NIOSH is advised.
Current Production and Use
Although the chemical is not entered in the TSCA Candidate List, the
1975 Director of Chemical Producers lists one manufacturer. The chemical
is reportedly used in organic synthesis, especially for the introduction
of the beta-diisopropylaminoethyl radical.
Recommendations
Another submission referred to a similar chemical, dimethyl aminoisopropyl
chloride hydrochloride (8EHQ-0278-0073).
a) The submitter should be asked to provide a complete physician's
report on this incident. This notice and any follow-up data
should be referred to NIOSH and .OSHA.
b) The submitter should be asked to support his contention that
the information presented in this submission reasonably supports
a conclusion of substantial risk.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
Mt t»»•« mcv.
102
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: ifey 10, 1978 (Revised May 10, 1979) Approved_
SUBJECT: status Report 8EHQ-0278-0068
Revision
Needed
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
T0: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Addenda to and revisions of a previously submitted (8EHQ-1277-0023) toxi-
cology study. The report involves a subacute dermal toxicity study of
2,3-dibromopropanol (DBF). This notice was declassified on April 13,
1978.
Submission Evaluation
2,3-Dibromopropanol has several potential toxicities: irritation of the
skin and mucous membranes of the eyes and respiratory tract; liver; kid-
neys; and nervous system. In this dermal study, the tissue analyses show
that the compound is absorbed through the skin and is picked up by fat,
muscle, kidneys, and liver. The amount retained by these tissues appears
to be dose related. The kidneys and muscle tissue are expected to have
erratic levels of DBF and its metabolites as a function of the rate of
excretion and the blood supply, respectively. Fat and, to some extent,
the liver (which has much fat metabolism) tend to store compounds such
as this and so the (total) bromine content would be more regular and
constant over time. Values for blood and urine levels of the metabolites
and the unchanged compound would have been useful but were not provided.
The urine studies are not complete because almost one-half of the rabbits
had no urine samples. It is difficult to evaluate the slight increases
in pH and the presence of cells in the urine of the dosed rabbits. The
latter could be a reflection of kidney injury. Furthermore, while the
changes in urinary specific gravity might not be significant, is it
coincidental that the concentrating ability of the kidney tubules de-
creased in all of the treated animals? Or are we observing the effect
of the alcohol (2,3-dibromopropanol or a dehalogenated metabolite) on
the pituitary such that antidiuretic hormone is not being released and a
more dilute urine is being excreted? It is not clear from the study
whether we are observing this effect of the alcohol or the kidney
tubule-damaging effect of the brominated alcohol.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 1320*6 (REV. 3-76) 103
-------
Current Production and Use
U.S. production of DBF is estimated at more than 10 million pounds in
1976. The major use is as an intermediate in the production of tris
(2,3-dibromopropyl) phosphate and other flame retardants and as an active
flame retardant itself. It is also used in the manufacture of insecti-
cides and drugs. Recent actions by CFSC to regulate tris have likely
depressed the domestic production and market for DBF.
Comments/Recommendations
DBF will be considered in the ongoing AD review of flame retardant tech-
nology. Pending the ultimate disposition of tris, DBF may or may not
require additional examination. It is currently scheduled for examina-
tion in the AD's haloalkanols hazard assessment due in March 1979. One
other submission has been received on this chemical (8EHQ-1277-0023).
(a) Production estimate should be confirmed with a check of the Section
8(b) data.
(b) DBF may be a CHIP candidate if production is sufficiently great.
(c) This information should be referred to OSHA and NIOSH for appro-
priate follow-up,^il any.
(d) The submissions on DBF should be given to the contractor preparing
the haloalkanols report for possible inclusion in that document.
It may be worthwhile to ask the notifier for more complete data on
these studies (full final report, analytical data, etc.).
(e) The submitter should be asked to support his contention that the
information presented in this submission reasonably supports a
conclusion of substantial risk.
104
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
SUBJECT:
FROM:
TO:
May 10, 1978
Status Report 8EHQ-0278-0069
Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
Approved
Revision
Needed
Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Addenda to and revisions of a previously submitted (8EHQ-1277-0024) tox-
icology study on the subacute dermal toxicity of 2,4,6-tribromophenol
(TBP) in rabbits. The notice was declassifed on April 13, 1978.
Submission Evaluation
This is merely an addendum to a previous report and is confined to the
urinalysis data from rabbits which received tribromophenol by skin
application. Unfortunately, the data are very skimpy and really insuffi-
cient for an intelligent evaluation. From the data that are presented,
based on the pH changes in the urine of treated animals and the changes
in specific gravity, the suspicion arises that sufficient tribromophenol
was absorbed to produce kidney damage.
Current Production and Use
No production figures are available for TBP; however, SRI's Directory of
Chemical Producers lists three manufacturers, which implies an annual
production in excess of 1,000 pounds. No information on uses was located.
Recommenda t ion s
Because this compound contains approximately 73% bromine, its potential
for flame retardant use and PBB substitution should be evaluated. The
AD will review this compound as part of its ongoing study of flame
retardant technology.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 1320-6 (REV. 9-76)
-------
Several submissions have been received on this compound (8EHQ-1277-0024;
8EHQ-0178-0032; 8EHQ-0378-0095).
(a) EPA should be aware of the potential for dioxin contamination of
this chemical. It may be prudent to ask the submitter exactly what
steps are being taken to minimize or eliminate this problem; analyt-
ical "quality control" procedures should also be discussed.
(b) This submission and the others on TBP should be referred to the
PBB workgroup.
(c) TBP should be given CHIP scrutiny by the Assessment Division.
106
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: May 10, 1978
SUBJECT: Status Report 8EHQ-0278-0070
FROM.- Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
Approved
Revision
Needed
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Acute inhalation toxicity of 1,2-dibromoethylacetate in rats.
notice was declassified on April 13, 1978.
This
Submission Evaluation
Unhydrolyzed esters tend to be pulmonary irritants and the bromine
substituents would intensify the effect. This could account for the
extremely high toxicity of the vapors. However, it would be useful to
know how much 1,2-dibromoethylacetate, ethyldibromoacetate (and other
similar contaminants), and free bromide are in the product. The possible
bromoacetic acid metabolite of ethyldibromoacetate would be more toxic
than the bromoethanol metabolite of 1,2- (or 1,1-) dibromoethylacetate.
The product produces pulmonary edema and congestion in a dose-related
manner. High concentrations produce prompt death by direct effect on
the lungs, bronchi, and possibly the respiratory centers in the brain.
Lower concentrations produce delayed mortality probably by direct action on
the lungs. A bromoethanol metabolite would probably be a liver and
neurotoxin.
Current Production and Use
No production and use information was located; the chemical was not
entered in the TSCA Candidate List.
Conanents/Recommendations
Dibromoethylacetate may have some flame retardant applications; therefore,
it will be evaluated as part of the ongoing Assessment Division study of
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
107
EPA FOAM I320-* (REV. 3-76)
-------
flame retardant technology. Two other submissions have been received on
this chemical (8EHQ-0977-0005; 8EHQ-0478-0121).
Section 8(b) data should be checked for evidence of commercial production.
108
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 22, 1978 Approved_
SUBJECT: Status Report 8EHQ-0278-0071
Revision
Needed
FROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
T0: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE OTS (TS-792)
Submission Description
Study of VC 948 (bis(tribromoneopentyl)pentaerythritol cyclic diphosphate)
induced in vitro malignant transformation in mouse BALB/3T3 cells. The
chemical is also known as MC 948. This notice was declassified on
April 13, 1978.
Submission Evaluation
VC 948 produced significant dose-related increases in morphological
transformations of BALB/3T3 cells under the conditions of the test. It
is somewhat probable that this material may be shown carcinogenic if it
is given further testing; nevertheless, the submitted report concludes
that VC 948 has carcinogenic activity by virtue of its ability to morpho-
logically alter BALB/3T3 cells. It should be noted that VC 948 is a
phosphate ester of a sugar alcohol. Such compounds may alter intermediary
metabolism of cells.
Current Production and Use
No production and use information was located; the chemical is not
entered in the TSCA Candidate List.
Comments/Recommendations
VC 948 has been the subject of several other submissions (8EHQ-0278-
0060; 8EHQ-0378-0092; 8EHQ-0378-0098; 8EHQ-0578-0145). The nomenclature
provided is somewhat trivial; therefore, a follow-up to the notifier,
should ask for the preferred name and structure of this compound.
(a) 8(b) data should be checked to determine the comnercial significance
of this conpound.
(b) This submission should be transmitted to NIOSH and QSHA.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 1320-6 (REV. 3-76)
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
OATE! May 11, 1978 (Revised May 10, 1979) Approved
SUBJECT: Status Report 8EHQ-0278-0072
Revision
Needed
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
T0: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Acute toxicity studies of HCS-3510 [1-beta-beta-dimethoxyethyl-l-methyl-
3-(5-t-butyl-l,3,4,-thiadiazol-2-yl) urea] in rats and rabbits. This
notice was declassified on April 13, 1978.
Submission Evaluation
This compound (HCS-3510) appears to be related to the tertiary butyl
thiadiazole urethanes or carbamates. However, it does not have the
potential for significant anticholinesterase activity. Urea compounds
with substitutes on the nitrogen atoms have central nervous system
(CNS) effects. Phenylacetylurea is still used in the treatment of
epilepsy, but only as a drug of last resort because of its toxicity.
The acute toxicity studies submitted for HCS-3510 show it to be an eye
irritant. The studies do not eliminate the possibility of allergic
sensitizing reactions. It appears as though the test substance was
HCS-3510 dissolved in toluene and not the pure substance.
It is not clear what was dissolved in corn oil to determine the 1.050 •
Was it the solution in toluene or was it the pure solid compound?
In all LD5Q studies which employ solutions, it is customary to indicate
the concentration of the pure compound per ml of solution. There is no
indication of the HCS-3510 concentration in the solution that was used
for determining the H>5Q. Page 21 states that the test material was
dissolved in corn oil. Pages 23, 25, and 26 give values for HCS-3510
in toluene. This should be cleared up. Without better data, it is
impossible to tell whether the CNS depression was due to the compound
or to the possibly administered toluene.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 13ZO-6 (REV. 3-76) HO
-------
Current Production and Use
No production and use information was located; it is not entered in the
TSCA Candidate List.
Recommendations
Personal communication with the submitter indicates that this chemical
is used solely as an intermediate in the production of an (as yet)
unregistered pesticide.
(a) Section 8(b) data should be checked to determine the commercial
significance of this chemical.
(b) The submitter should be contacted regarding clarification of the
points raised in the evaluation section. It is essential for
purposes of determining toxicity to obtain precise information
on what was administered to the animals.
(c) The submitter should be asked to support his contention that the
information presented in this submission reasonably supports a
conclusion of substantial risk.
Ill
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: ^y 8, 1978 (Revised May 10, 1979) Approved_
SUBJECT: status Report 8EHQ-0278-0073
Revision
Needed
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
TO! Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Ames-type mutagenicity evaluation of dimethylaminoisopropyl chloride
hydrochloride (DMIC). This notice was declassified on April 13, 1978.
DMIC is chemically similar to diisopropylaminoethyl chloride hydrochloride,
which is the subject compound in 8EHQ-0278-0067..
Submission Evaluation
DMIC is a base pair substitution mutagen that does not require activation.
N-dialkylaminoethyl and isopropyl halides are used chiefly to introduce
side chains into drugs that affect adrenergic nerve terminals. For
instance, DMIC introduced into a simple aromatic molecule such as
catechol would produce a weak adrenalin-type drug. Introduced into a
more complicated molecule such as benzhydryl, it would probably produce
an antihistamine-like drug. Introduced into a phenothiazine molecule, it
would produce either an antihistamine or major tranquilizer. Diiso-
propylaminoethyl introduced into an appropriate molecule such as
naphthalene methyl ether would produce a compound that blocks B-adrenergic
receptors from being activated by the stimuli that normally occur in the
body.
The significance of mutagenicity of DMIC is not clear, particularly
because of the low volume of production. Most g-adrenergic blockers
that contain a diisopropylaminoethyl side chain produce tumors of the
thymus in mice and have been denied acceptance in the U.S. by FDA.
One of these, practolol, has been removed from the market in England
because prolonged usage by patients resulted in changes of the cornea
and in proliferation of the fibroblasts in the peritoneum. It is still
to be determined whether this is a cancerous type of lesion.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 1320-6 (REV. 3-76)
112
-------
In some respects, the aminochloroalkanes are derivatives of N-mustards,
which are known to produce chromosomal changes.
Current Production and Use
No production figures are available for DMIC; however, the SRI Directory
of Chemical Producers lists one manufacturer, which implies an annual
production in excess of 1,000 pounds. The chemical is apparently used
in organic synthesis for the introduction of the dimethylaminoisopropyl
radical.
Recommendations
(a) Production estimate should be confirmed with a check of the
Section 8(b) data.
(b) If production is sufficient, DMIC should be given a CHIP exami-
nation; NIOSH/OSHA referral may also be indicated.
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
OAT6! June 22, 1978 (Revised May 10, 1979) Approved
SUBJECT: status Report 8EHQ-0278-0074
Revision
Needed
FROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
T0: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Acute inhalation study of a mixture of brominated aromatic oils in
rats. This notice was declassified on April 13, 1978.
Submission Evaluation
No toxic effects were observed after a 1-hour exposure to a nominal
concentration of 2.29 mg/1. This is a calculated concentration, however,
and does not represent a value actually measured in the breathing zone
of the animals.
From the standpoint of toxicity, the test is unsatisfactory for the
following reasons: the chemical nature of the volatiles is not charac-
terized; the composition of the mixture is not specified, and therefore
it is Impossible to determine what the animals were exposed to by
inhalation.
Current Production and Use
No information was found on the production or use of this material.
The trade name, "Firemaster 680," implies that the material is used as
a fire retardant.
Comments/Recommendations
This mixture may have some flame retardant application; therefore, it
will be evaluated as part of the ongoing Assessment Division study of
flame retardant technology.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
IPA FOBM 1320-6 (REV. 3-76)
-------
(a) The submitter should be asked to support his contention that this
information reasonably supports the conclusion that FM 680 presents
a substantial risk of injury to health or the environment.
(b) Section 8(b) data should be checked to determine commercial signif-
icance.
(c) This submission should be referred to the PBB workgroup.
(d) If the chemical appears commercially viable, it should be referred
to NIOSH and OSHA for their information.
(e) Follow-up correspondence should be sent to the submitter requesting
clarification as to the composition of the mixture that was actually
tested.
115
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: March 17, 1978 (Revised May 10, 1979)
SUBJECT: status Report 8EHQ-0278-0075P
FROM:
TO:
Frank D. Kover, Supervisor
Hazard Assessment Group, OTS (WH-557)
Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
Unspecified chemicals injured an employee as the result of a ruptured
(overloaded) safety disc on process filter.
Submission Evaluation
None possible without identity of possible material of exposure.
Current Production and Use
No estimate possible.
Recommendations
Additional information on the causative agent(s) should be developed via
follow-up correspondence; referral to NIOSH and OSHA should be made for
appropriate follow-up, if any.
The submitter should be asked to support his contention that the information
presented in this submission reasonably supports a conclusion of substantial
risk.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
116
EPA FORM 1320-6 IREV. 3-76)
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: March 17, 1978 (Revised May 10% 1979)
SUBJECT: status Report 8EHQ-0278-0076P
PROM.- Frank D. Kover, Supervisor
Hazard Assessment Group, OTS (WH-557)
TO! Warren R. Mulr, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
Management prepared industrial accident report on an incident involving
accidental exposure to phosgene.
Submission Evaluation
Phosgene is highly toxic and can produce serious lung problems.
Current Production and Use
Almost 800 million pounds of phosgene were produced in 1975, princi-
pally for use in manufacture of isocyanate, polyurethane, and poly-
carbonate resins. Other uses include production of pesticides,
herbicides, dyes, organic carbonates, and chloroformates.
Recommendat ions
Personal data have been deleted. Referral should be made to NIOSH
and OSHA for appropriate follow-up, if any.
The submitter should be asked to support his contention that the infor-
mation presented in this submission reasonably supports a conclusion
of substantial risk.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section
8(e) of TSCA. Statements made herein are not to be regarded
as expressing final Agency policy or intent with respect
to this particular chemical. Any review of the status
report should take into consideration the fact that it may be
based on incomplete information.
EPA FORM 1320-6 (REV. 3-76) H7
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
MAR I 7 I9T8
SUBJECT: status Report 8EHQ-0278-0077P Approved
Revision
Frank D. Kover, Supervisor Needed
Hazard Assessment Group, OTS (wn-557)
T0: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
Internal company correspondence concerning eye irritation
and other responses to dicyclopentadiene (DCPD) and DCPD
alcohol during production of the latter.
Toxicological Evaluation
Dicyclopentadiene alcohol is an unsaturated alcohol with an
allyl configuration. Such compounds tend to irritate the
mucous membranes of the eye and respiratory tract. This
would account for the symptoms of the exposed workers. More
serious toxicity could be expected if some of the alcohol
became oxidized to the aldehyde. The resulting compounds
would be in the acrolein 'class.
Current Production and Use
Dicyclopentadiene is used, as a chemical intermediate in the
production of insecticides, ethylene/propylene/diene/monomer
(EPDM) elastomers, metallocenes, paints and varnishes, and
flame reyfc»rdants for plastics. Over 77 million Ibs. (includes
cyclopentadiene) were produced in 1975.
Recommendations
Several submissions have been received on these compounds.
Follow-up correspondence should obtain the structural formula
of DCPD alcohol ai}d further information^ on the exposure in-
cident and any medical examinations. DCPD is scheduled for
preliminary assessment treatment in the near future. DCPD
alcohol should be considered a candidate for Sec. 8(a) and
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
-------
early warning activities.. This submission and related ones
from this plant should be referred to NIOSH and OSHA for
appropriate follow-up; a note outlining the number of inci-
dents at this plant should be included.
The submitter should be asked to support his contention that the information
presented in this submission reasonably supports a conclusion of substantial
risk.
119
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: March 17, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0278-0078P
FROM: Frank D. Kover, Supervisor
Hazard Assessment Group, OTS (WH-557)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
Management prepared accident report of accidental exposure to phosphorus
oxychloride as a result of defective equipment.
Submission Evaluation
The toxic effects of phosphorus oxychloride are well known.
Current Production and Use
Over 30 million pounds of phosphorus oxychloride were produced in 1976.
Reported uses are many and include: manufacture of phosphate esters for
plasticizers, gasoline additives, hydraulic fluids, and organophosphorus
compounds; chlorinating agent and catalyst; dopant for semiconductor-
grade silicon; tricresyl phosphate and flame retardants.
Recommendations
Personal data have been deleted. Referral should be made to NIOSH and
OSHA for appropriate follow-up, if any.
The submitter should be asked to support his contention that the infor-
mation presented in this submission reasonably supports a conclusion of
substantial risk.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 1320-* (REV. J-76)
120
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: March 17, 1978 (Revised May 10, 1979)
SUBJECT.- status Report 8EHQ-0278-0079P
FROM: Frank D. Kover, Supervisor
Hazard Assessment Group, OTS (WH-557)
TO! Warren R. Mulr, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
Management prepared industrial accident reports of incidents involving
accidental exposures to phosgene/toluene vapors.
Submission Evaluation
Phosgene is highly toxic and can produce serious lung problems.
Current Production and Use
Almost 800 million pounds of phosgene were produced in 1975, with most
used captively in the manufacture of isocyanate, polyurethane, and
polycarbonate resins. Other uses include the production of carbamates,
organic carbonates and chloroformates, pesticides, herbicides, and dyes.
Over 5 billion pounds of toluene were produced in 1975 for use as a
solvent, chemical intermediate, aviation gasoline component, and high-
octane blending stock.
Recommendations
Referral should be made to NIOSH and OSHA for appropriate action, if
any. Personal data have been deleted.
The submitter should be asked to support his contention that the information
presented in this submission reasonably supports a conclusion of substantial
risk.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on incom-
plete information.
EPA FORM 1320-6 (REV. 3-76) 121
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE-. March 17, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0278-0080P
FROM: Frank D. Kover, Supervisor
Hazard Assessment Group, OTS (WH-557)
TO-. Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
Industrial accident report of incident involving release of phosphorus
oxychloride fumes causing eye irritation in an employee.
Submission Evaluation
The toxic effects of phosphorus oxychloride are well known.
Current Production and Use
Over 30 million pounds of phosphorus oxychloride were produced in 1976.
Reported uses are many and include: manufacture of phosphate esters for
plasticlzers, gasoline additives, hydraulic fluids, and organophosphorus
compounds; chlorinating agent and catalyst; dopant for semiconductor-
grade silicon; trieresyl phosphate and flame retardants.
Recommendat ions
Personal data have been deleted. Referral should be made to NIOSH and
OSHA for appropriate follow-up, if any.
The submitter should be asked to support his contention that the infor-
mation presented in this submission reasonably supports a conclusion of
substantial risk.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of
TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 1320-6 (REV. 3-76) 122
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: March 17, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0278-0081P
mot*-. Frank D. Kover, Supervisor
Hazard Assessment Group, OTS (WH-557)
T0: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
A chemical company maintenance man developed a rash on the lower leg
from an unspecified cause.
Submission Evaluat ion
None possible.
Current Production and Use
No estimates possible.
Recommendations
Personal data have been deleted. Follow-up correspondence should deter-
mine if more information on the causative agent(s) is available. Referral
should be made to NIOSH and OSHA for appropriate action, if any.
The submitter should be asked to support his contention that the information
presented in this submission reasonably supports a conclusion of substantial
risk.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular chemical.
Any review of the status report should take into consideration
the fact that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
123
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: March 17, 1978 (Revised May 10, 1979)
SUBJECT: status Report 8EHQ-0278-0082
FROM: Frank D. Kover, Supervisor
Hazard Assessment Group, OTS (WH-557)
T0: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
Preliminary report of a mutagenesis study of diesel fuel.
Submission Evaluation
This notification is acceptable if the analytical composition of the
fuel is adequately characterized in the final report (i.e., does it
contain a carcinogenic metal, such as nickel, or polynuclear aromatic
hydrocarbons, and if so, which ones and in what ratios).
While the clastogenic (broken chromosomes) effects observed in this
study are not transmissible, they could, nevertheless, be a serious
impediment to the fertility of a person whose sperm have such breaks.
Current Production and Use
Exact production figures are not available; however, over 1 billion
barrels of diesel fuel were produced in 1975. It is used as fuel for
trucks, ships, machinery, etc.; in drilling muds; and in mosquito control.
Recommendat ions
No activity necessary until final results are available for evaluation.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM !320-« (REV. 3-76) 124
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Approved
Revision
Needed
DATE; December 4, 1978
SUBJECT: Status Report 8EHQ-0678-0082
Supplement
: Frank D. Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
Final results of a mutagenesis study on diesel fuel. The preliminary
results were received in February 1978 (8EHQ-0278-0082).
Submission Evaluation
Diesel fuel was assayed for mutagenicity in the Ames test (bacteria),
mitotic gene conversion in yeast, mouse lymphoma forward mutation assay,
and in vivo rat bone marrow cytogenetic analysis.
The performing laboratory concludes that the microbial tests (yeast and
bacteria) were negative for mutagenicity. The data support this inter-
pretation. On pp. 14 and 15 of the report, diesel fuel concentrations
are referred to by a coded sequence (NA1, NA2, ...); a more desirable
approach would be to state the test concentrations as such in the tables.
The performing laboratory states that the mouse lymphoma assay was
negative; the results, however, do not suggest this interpretation. In
the nonactivation test, there is a positive dose response with increasing
concentrations that approaches a mutation frequency almost 15 times that
observed with the solvent control (see table on p. 43). The data from
the activation test are equivocal, but there appears to be some increase
over the control values at higher diesel fuel concentrations. The term
"negative control" should be defined by the submitter.
The performing laboratory concludes that diesel fuel is clastogenic
(causes chromosome breaks) in the rat bone marrow cytogenetic test; the
results support this interpretation. The submitter should, however,
offer some discussion as to the cause of the variability observed in the
number of cells with one or more chromosome aberrations within each dose
group for the rats sacrificed at 6, 24, and 48 hours postexposure (see
p. 51). Are these effects due to chromosome repair, cell death, or some
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FOMM 1l»-« (MEV. >•?•)
125
-------
other cause? The data summary given on p. 45 results from the averaging
of test values for different kill times within each dose group. Due to
the variability in the data and the different interpretations that might
be placed on the results from each sacrifice time, this is not a valid
procedure.
Production and Use
Exact production figures are not available; however, over 1 billion
barrels of diesel fuel were produced in 1975. It is used as a fuel for
trucks, ships, machinery, etc.; in drilling muds; and in mosquito control.
Comments/Recommendations
Given the large annual production of diesel fuel and the potential for
widespread exposure, the mutagenic and carcinogenic potential of diesel
fuel (and its combustion products) should be examined further.
(1) This report should be transmitted to OSHA, NIOSH, OAQPS, OWHM, OSW,
MSAPC, and OKD.
(2) The submitter should be asked to provide the following:
(a) Analytical characterization of the diesel fuel tested in this
report. Of particular interest would be the identification
and quantification of any carcinogenic metals or polynuclear
aromatic hydrocarbons.
(b) The placement of footnote "d" on p. 51 and footnotes "b" and
"c" on p. 53.
(c) A description of the submitter's planned further testing of
diesel fuel, especially with respect to mutagenicity, carcino-
genicity, and chronic effects.
(d) All other information needs contained in the evaluation sec-
tion above.
Additional Comments on the Parent Submission 8EHQ-0278-0082
The following comments deal with specific sections (as noted) of the
Preliminary Report received in February 1978.
It em 1 This paragraph states that the observed chromosomal effects are
somatic rather than germinal and thus implies that because these changes
are not viewed as heritable, there is little or no germinal risk. This
is not a supportable conclusion because the observed chromosome damage
may represent only the most obvious point mutation effects. In addition,
because these data are similar to those seen in benzene mutagenicity
battery tests, there is concern that diesel fuel may be carcinogenic.
126
-------
Item 2a While intraperitoneal injections do not represent an environ-
mentally significant route of exposure, the crucial issue in the rat
bone marrow study concerns the entry of the test material into the bone
marrow and the effects of the resultant exposure on the rapidly dividing
cells found there. If a chemical can be absorbed through the peritoneum
and affect the bone marrow, perhaps it can likewise be absorbed through
the lung following inhalation. Unless the lung can be shown to completely
detoxify diesel fuel, the results should stand. Nevertheless, the results
of a percutaneous rat bone marrow assay would be of great interest.
Item 2b The observation concerning the suppression of the mitotic index
in the rat bone marrow study is not borne out by the data.
Item 2c The applicability of cytogenetic test procedures to hydrocarbon
mixtures is not necessarily an issue. If the material breaks chromosomes,
it breaks chromosomes.
127
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE; March 17, 1978 Approved_
SUBJECT: Status Report 8EHQ-0278-0083
Revision
Needed
FROM: Frank D. Kover, Supervisor
Hazard Assessment Group, OTS (WH-557)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
Report of interim results on a skin-painting carcinogenesis study
in mice with crude shale oils indicating tumorigenic activity in the
skin.
Submission Evaluation
It is not surprising that these crude oils are carcinogenic in the skin
of mice. Probably all fossil-derived oils contain sufficient polynuclear
aromatic hydrocarbons to be carcinogenic.
Current Production and Use
No commercial distribution at present. Recovery of oil from oil shale
is a growing technology as the result of the energy situation in the U.S.
No firm production figures are available at this time.
Recommendations
These would not likely be on the inventory and may have to be addressed
eventually under Section 5.
NOTE: This status report ia the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of
TSCA. Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.•
EPA FORM 132O-6 (REV. 3-76) 128
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
: March 17, 1978
SUBJECT: Status Report 8EHQ-0378-0084 Approved
Revision
PROM: Frank D. Kover, Supervisor Needed
Hazard Assessment Group, OTS (WH-557)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
This submission was phoned in by the TSCA Regional Coordinator for
Region X to report a hazardous spill of phenol-formaldehyde resin and
diphenylmethane diisocyanate. The next day (March 8, 1978), the sub-
mitter was contacted concerning the spill in Region X and informed my
group that he considered the spill report to be under Section 311 of the
FWPCA and not Section 8(e) of TSCA. Therefore, he asked that we with-
draw the notice.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
«PA roftM »»»-« utrv. »••»«) ^29
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: May 1, 1978 (Revised May 10, 1979) Approved_
SUBJECT: Status Report 8EHQ-0378-0085
Revision
Needed
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
TO! Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Results of the analysis of an industrial production site for dioxins.
This notice was declassified on April 13, 1978.
Submission Evaluation
Measurable quantities of 2,3,7,8-tetrachlorodibenzo-p-dioxin have been
found at two sites in the plant sampled. Dioxins are extremely toxic
and persistent compounds.
Current Production and Use
There is no current production of dioxins in the world; the compounds
can occur as contaminants in (and during the production of) certain
chemicals.
Recommend at i on s
The sampling results should be forwarded to NIOSH and OSHA for appropriate
follow-up.
NOTE: This status report is the result of a preliminary staff eval-
uation of information submitted to EPA under Section 8(e) of
TSCA. Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 1320-6 (REV. 3-76)
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: March 28, 1978 (Revised May 10, 1979) Approved
SUBJECT.- Status Report 8EHQ-378-0086
Revision
Needed
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (WH-557)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
Internal company correspondence regarding employee reaction observed
following exposure to FM-680 [1,2-bis(2,4,6-tribromophenoxy)ethane].
Submission Evaluation
The dermatitis and swelling of the skin could have been due to Firemaster
680. We are not familiar with any animal and human skin testing studies
that absolve this chemical from skin sensitization possibilities.
Current Production and Use
Not listed in the TSCA Candidate List; probably used as flame retardant.
Recommendations
This chemical will be addressed in Hazard Assessment Group as part of
our technology assessment of flame retardants; a request for Section 8(a)
information may be appropriate. Referral should be made to NIOSH and
OSHA for follow-up as needed.
The submitter should be asked to support-his contention that the information
presented in this submission reasonably supports a conclusion of substantial
risk.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular chemical.
Any review of the status report should take into consideration the
fact that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
131
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE-. June 14, 1978 (Revised May 10, 1979) Approved _„_„____
SUBJECT: Status Report 8EHQ-0378-0087
Revision
Needed
FROM- Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Results of acute toxicity studies of the isocyanate dimer of 5-t-butyl-
l,3,4-thiadiazol-2-yl in rabbits and rats. This notice was declassified
on April 13, 1978.
Submission Evaluation
The structural formula suggests that there is a resemblance to physo-
stigmine by virtue of both being urethanes attached to polycyclic hetero
rings. The acute toxicity data submitted demonstrate that the compound
is a primary eye irritant and is most likely free from skin irritation.
The latter does not indicate that the compound is free from sensitizing
properties. The substance is poorly absorbed from the skin and gastroin-
testinal tract. This compound contains tertiary butyl groups which
often play the same role as quaternary ammonium groups in organic molecules.
For instance, quaternary ammonium compounds such as acetylcholine which
are highly active by subcutaneous and intravenous injection have practically
no activity when swallowed or when applied to the skin. The quaternary
ammonium residue has great difficulty in penetrating certain membranes.
The manufacturer should supply us with information about the possible
anticholinesterase activity of this compound.
Current Production and Use
No information was located on production and use; not contained in the
TSCA Candidate List. According to a personal communication with the
submitter, the chemical is an intermediate for the production of an as
yet unregistered pesticide.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 1320-6 (REV. 3-76) 132
-------
Comments/Recommendations
This chemical has abuse potential; much more information should be
required before commercial production begins.
(a) Section 8(b) data should be checked for evidence of commercial
significance.
(b) The submission will be referred to OPP with a request that they
check their files for additional data. Registration status of the
final product (identity unknown at this time) should also be checked.
(c) The notifier should be asked to provide physical-chemical data on
the chemical as well as the preferred chemical name, CAS number,
and a structural drawing; the question on anticholinesterase activity
should also be addressed.
(d) Once again, the page containing a description of the evaluation
method is missing; a request for same should be made.
(e) The submitter should be asked to support his contention that the
information presented in this submission reasonably supports a
conclusion of substantial risk.
133
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: May 10, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0278-0088
PROM: Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
Approved
Revision
Needed
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Results of acute toxicity studies of a residue of hexabromocyclododecane
(FM 100) in rats and rabbits. This notice was declassified on April 13,
1978.
Submission Eyalua,tipn
It is not clear what "FM 100 residue" is. The basic compound appears to be
a saturated ring system of 12 carbon atoms, 6 of which contain bromine. It
would be surprising if this compound is readily flammable; nonetheless, the
submission reports that the residue was a "flammable liquid." Therefore,
the residue might be a mixture containing an organic solvent that burns
readily, although this is not clear. Hexabromocyclododecane should be an
irritant with tissue storage properties similar to those of PBB's. It
would therefore be of interest to find out something about the biodegradabi-
lity of this compound and its capacity for storage in fat depots. The
important thing here is (1) what was tested, (2) did the material tested
contain significant amounts of the hexabromo compound, and (3) are there
toxicity data for the hexabromo compound.
Current Product.ion and Use
Hexabromocyclododecane is apparently used as a flame retardant. No addi-
tional information on production was located, nor is FM 100 entered in the
TSCA Candidate List. FM 100 is listed in the "Bromine Based Fire Retardants"
report, and its fire retardant applications include ABS, polymethyImethacrylate,
polypropylene, and polystyrene polymers.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
EPA FORM 1320-« (REV. 1-76)
134
-------
Comments/Recommendations
FM 100 is the subject of two earlier submissions (8EHQ-0278-0051 and 8EHQ-
0278-0065). The chemical will be evaluated as part of the ongoing Asses-
sment Division examination of flame retardant technology. FM 300 may be an
environmentally persistent compound.
(a) This submission, like others, was deficient in a number of areas.
The notifier should be asked to provide physical-chemical data on
the test substance, gross findings on death, clinical observations,
etc., as well as answers to the questions raised in the evaluation
section.
(b) Section 8(b) data should be checked to determine the commercial
significance of this compound; if production is sufficient,
consideration should be given to CHIP and/or NIOSH/OSHA referral.
(c) A specific request for p. 17 should be made (this was not included
in the submission).
(d) The submitter should be asked to support his contention that the
information presented in this submission reasonably supports a
conclusion of substantial risk.
135
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:March 21, 1978 (Revised May 10, 1979) Approved_
SUBJECT: Status Report 8EHQ-0378-0089
Revision
Needed
, Frank D. Kover, Supervisor
Hazard Assessment Group, OTS (WH-577)
TO:Warren R. Muir, Deputy Assistant Administrator
far Testing and Evaluation, OTS (TS-788)
Submission.Description
Journal article on analysis of chlorinated norbornene derivatives.
Submission Evaluation
Not needed.
Current Production and Use
Used in the production of chlorinated pesticides, e.g., endrin.
Reconmendations
This submission would not be required under proposed guidance. The
submitter should be asked to support his contention that the information
presented in this submission reasonably supports a conclusion of sub-
stantial risk.
NOTE: This status report is the result of a preliminary staff
evaluation of information to EPA under Section 8(e) of TSCA,
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
CI>A FORM U20-« (REV. 3-7«)
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
! June 20, 1978 Approved
SUBJECT.- status Report 8EHQ-0378-0090
Revision
Needed
FROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
TO! Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Acute oral toxicity study of MC-935A [poly(dibromophenylene oxide)] in
mice. (MC-935A is also known as VCC-935A). This notice was declassified
on April 13, 1978.
Submission Evaluation
The experimental protocol did not produce an 1050 value. In addition,
none of the animals were sacrificed to determine if there were any gross
effects. Information as to the blood levels, half-life, metabolism, fecal
excretion, and polymer size (MW) of this compound must be provided before
any statement as to the potential effects of MC-935A can be made.
The compound MC-935A appears to be a polymer. If the molecular weight
is high, very little acute toxicity is to be expected unless there is a
high percentage of impurities including monomers and low-molecular-
weight polymers. What should be done in this case is to administer
the compound, collect the feces, and, after killing the animals, remove
the intestinal tract and determine the amount of material present in the
feces and in the intestinal tract. This will give a pretty good indica-
tion of whether absorption has occurred. This is at the present time
not customary practice. If the LD^g exceeds 10 grams per kilo, nothing
further is usually done. Some investigators examine the visceral organs
grossly as well as microscopically, in order to determine whether any
effect has occurred.
Current Production and Use
No production and use information was located; no entry in the TSCA
Candidate List.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 1320-6 (REV. 3-76)
-------
Comment syRecommendat ions
Several other submissions have been received on MC-935A (8EHQ-0278-0066;
8EHQ-0378-0103; 8EHQ-0478-0132). The chemical may have some flame
retardant applications; if so, it will be evaluated as part of the
ongoing Assessment Division study of flame retardant technology.
(a) Section 8(b) data should be checked to determine commercial
significance.
(b) This submission and others on MC-935A should be referred to the
PBB workgroup.
(c) The submitter should be asked to support his contention that
information contained in this notice is indicative of a
substantial risk to health or the environment. The report in
its present form offers no information to indicate that MC-935A
represents a substantial risk.
138
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
June 22, 1978 (Revised May 10, 1979) Approved_
SUBJECT: status Report 8EHQ-0378-0091
Revision
Needed
FROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Results of acute toxicity studies of MC-933 [bis(2,3-dibromopropyl)ether]
in rabbits and rats. This notice was declassified on April 13, 1978.
Submission Evaluation
Although bis(2,3-dibromopropyl)ether does not appear to have high acute
toxicity, sufficient amounts were absorbed from the skin application to
cause signs of irritation as evidenced by lachrymation and discharge of
pus from the nose. The ether belongs to the same class of compounds as
dichlorodimethyl ether, although it is apparently far less noxious.
The diarrhea observed in all the rats receiving MC-933 in corn oil by
stomach tube also suggests slight irritant properties. The inhalation
studies in rats also indicate the possibility of mild irritant action.
Autopsies should have been carried out on the organs of all the rats and
rabbits receiving MC-933. This type of halogenated compound usually
does not produce marked acute pathological changes. It would be neces-
sary to know whether the kidney, liver, and other internal viscera were
at all affected by the small amounts of compound that could have been
absorbed. The respiratory tract and lungs should be examined in the rats
exposed to the dust and the rabbits to whose skin MC-933 was applied in
order to determine whether the lachrymation and nasal discharge have tox-
icological significance. If this compound is absorbed, it will probably
be stored in fat depots. Information should be supplied about the ease
with which liver enzymes and bacterial enzymes degrade this compound.
Current Production and Use
No information on the current production and use of this material was lo-
cated; it was not entered in the TSCA Candidate List.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
CPA FORM 1320-« (REV. 3-76) 139
-------
Conments/Recommendations
This material may have potential for flame retardant applications; there-
fore, it will be evaluated as part of the ongoing Assessment Division in-
vestigation of flame retardant technology.
(a) Section 8(b) data should be examined for evidence of commercial
significance.
(b) Additional information on the study should be requested from the
submitter. Of particular interest are the results of any gross
or histopathological examinations conducted on the exposed animals.
The submitter should also be asked to support his contention that
this information reasonably supports the conclusion that MC-933
presents a substantial risk of injury to health or the environment.
(c) In the event that MC-933 appears commercially viable, it should be
given CHIP and/or NIOSH/OSHA consideration.
(d) Pages 17 and 19 of the rabbit and rat acute toxicity study (February
8, 1978) are missing.
140
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: May 10, 1978 (Revised May 10, 1979)
SUBJECT.- Status Report 8EHQ-0378-0092
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
TO.- Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Approved
Revision
Needed
Submission Description
Results of an acute oral toxicity study of MC 948 [bis(tribromoneopentyl)
pentaerythritol cyclic diphosphate] in mice. This notice was declassi-
fied on April 13, 1978.
Submission Evaluation
This compound has potential for affecting nerve sheaths and inhibiting
cholinesterase. While the acute oral toxicity is low, the study fails to
consider the potential for neurologic problems. How much was really
absorbed and how much passed through into the feces? Were the animals
observed for paralysis or other neuromuscular effects?
Current Production and Use
No information is available on the production and use of MC 948, nor is
it entered in the TSCA Candidate List.
Recommendations/Comments
Request a full copy of the study from the submitter as a page is missing;
also obtain the chemical structure and available use information from the
submitter. Use information will likely dictate the extent of OTS involve-
ment with this chemical. Several submissions have been received on this
compound (8EHQ-0278-0060; 8EHQ-0278-0071; 8EHQ-0378-0098).
(a) Check Section 8(b) data for evidence of commercial significance.
(b) If use data give evidence of exposure, MC 948 should be considered
for CHIP and/or NIOSH/OSHA referral.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
141
-------
(c) Additional information on the study (especially the questions raised
in the evaluation section) should be requested from the submitter
for inclusion in OTS files.
(d) The submitter should be asked to support his contention that the in-
formation presented in this submission reasonably supports a conclu-
sion of substantial risk.
142
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: March 17, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0378-0093
FROM: Frank D. Kover, Supervisor
Hazard Assessment Group, OTS (WH-557)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
Journal article on GC determination of chlordene epoxide.
Submission Evaluation
Chlordene epoxide is a metabolite of the pesticide chlordene.
Current Production and Use
No information available.
Re commend at ions
Inappropriate submission. The submitter should be asked to support his
contention that the information presented in this submission reasonably
supports a conclusion of substantial risk.
NOTE:This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
143
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
OATE. June 23, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0378-0094
FROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Approved
Revision
Needed
Submission Description
Results of two studies on chlorendic anhydride (CA): an acute oral study
in mice and an in vitro malignant transformation study in BALB/3T3 cells.
This notice was declassified on April 13, 1978.
Submission Evaluation
The BALB/3T3 mouse lymphoma assay produced equivocal results. In order to
obtain results which can be adequately evaluated, it would be necessary to
employ doses linearly spaced around 0.1 tng/ml, which is the dose at which
significant transformation occurred. The test should be repeated using:
more sets of negative controls; another transformation system in addition
to the present one; and if activation by the S-9 liver fraction can be
utilized, it should also be included in the battery.
The reported oral LD5Q was 4,169 rag/kg in male mice and 2,884 mg/kg in
females. The study was deficient in the following ways: total volume of
material administered by gavage is close to the amount which causes physical
stress; no gross or histopathology was performed; insufficient numbers of
animals were employed in the intermediate mortality groups to obtain good
LD5Q values and dose-response curves.
The fact that chlorendic anhydride is a potent acylating agent suggests
that it may be appropriate to further define its biological activity with
other short-term tests. Consideration should also be given to its poten-
tial for irritant and sensitization effects.
Current Production and Use
An estimated 10 million pounds of chlorendic anhydride/chlorendic acid
were produced in 1974, with an expected annual growth rate of 10% through
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
5PA FORM 1320-6 (REV. 3-76)
144
-------
1980. Reported uses of the anhydride include: flame-resistant polyester
resins; hardening agent for epoxy resins; chemical intermediate; source of
chlorendic acid.
Comments/Recommendations
Several other submissions have been received on chlorendic anhydride (8EHQ-
0278-0058; 8EHQ-0278-0059; 8EHQ-0378-0101; 8EHQ-0478-0127; 8EHQ-0478-0134).
(a) A CHIP report should be prepared on CA. It may be necessary to
use Section 8(d) to generate sufficient data as the scientific
literature apparently contains little information.
(b) The comments contained in the evaluation section should be trans-
mitted to the submitter.
(c) The submitter should be asked to support his contention that the
information presented in this submission reasonably supports a con-
clusion of substantial risk.
145
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE! June 28, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0378-0095
FROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Approved
Revision
Needed
Submission Description
Results of a pilot teratology study of tribromophenol in rats.
tice was declassified on April 13, 1978.
This no-
Submission Evaluation
It would be useful to know the degree of purity of the tribromophenol
that was tested.
Since this study did not rule out teratogenic effects with certainty, a
further investigation using larger numbers of animals per group is in
order. Although the investigator does not consider the effects observed
in one animal of five receiving 10 mg/kg/day to be dose related, this is
only his surmise.
Current Production and Use
No production figures are available for this chemical; however, the Di-
rectory of Chemical Producer s lists three manufacturers, which implies an
annual production in excess of 1,000 pounds. No information on uses is
available, although the material may have some flame retardant applications.
Comments/Recommendations
Several other submissions have been received on this chemical (8EHQ-1277-
0024; 8EHQ-0178-0032; 8EHQ-0278-0069). The Assessment Division will re-
view this compound as part of its ongoing study of flame retardant tech-
nology.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of tfce status report should take into consideration the fact
that it may be based on incomplete information.
EPA FORM 1120-6 (REV. 3-76)
146
-------
(a) The submitter should be asked to clarify which tribromophenol isomer
this notice refers to.
(b) EPA should be aware of the potential for dioxln contamination of
this chemical. It may be prudent to ask the submitter exactly what
steps are being taken to minimize or eliminate this problem; analyt-
ical "quality control" procedures should also be discussed.
(c) This submission and others on tribromophenol should be referred to
the PBB workgroup for consideration in their brominated flame re-
tardants work.
(d) Section 8(b) data should be checked to determine annual production.
(e) The submitter should be asked to support his contention that the in-
formation presented in this submission reasonably supports a conclu-
sion of substantial risk.
147
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: March 30, 1978
SUBJECT: Status Report 8EHQ-0378-0096
FROM: Prank D. Kover, Supervisor
Hazard Assessment Group, OTS (WH-557)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
An industry-sponsored statistical study attempts to refute conclusions set
forth in an unavailable draft doctoral thesis on cancer in chromate pro-
duction workers.
Submis s ion Eva1uation
The submitter's attempt to demonstrate the low carcinogenic potential of
chromates (by refuting an earlier epidemiological study) does not support
consideration of the submission as an 8(e) substantial risk notice.
Current Production and Use
Chromium and chromates enjoy large-volume production and have a multitude
of uses.
Recommendations
The thesis concerns occupational exposure; therefore, referral to NIOSH and
OSHA appears appropriate.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular chemical.
Any review of the status report should take into consideration
the fact that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76) 148
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE; March 28, 1978 (Revised May 10,. 1979)
SUBJECT.- Status Report 8EHQ-03 78-0097
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (WH-557)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
Internal company correspondence concerning eye irritation and other responses
to dicyclopentadiene (DCPD) and DCPD alcohol during production of the
latter.
Submission Evaluation
This submission reports additional cases of exposure to dicyclopentadiene
(DCPD) and DCPD alcohol. An earlier submission (8EHQ-0278-0077P) reported
similar problems with these compounds. The exact chemical structure of
DCPD alcohol is uncertain; nonetheless, these compounds appear to have
irritation potential for the upper respiratory tract. If DCPD alcohol
is an unsaturated alcohol with an allyl configuration, this would account
for the observed symptoms.
Current Production and Use
Dicyclopentadiene is used as a chemical intermediate in the production
of insecticides, ethylene/propylene/dlene/monomer (EPDM) elastomers,
metallocenes, paints and varnishes, and flame retardants for plastics.
Over 77 million pounds (includes cyclopentadiene) were produced in
1975.
Recommendat ions
Personal data have been deleted. The submitter reports that they are
currently overtaxing the DCPD alcohol production facility and plan to
continue doing so for at least the next year. A follow-up by NIOSH and
OSHA appears in order. Annual production of DCPD alcohol will be checked
when Section 8(b) data become available; DCPD alcohol may be a CHIP
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
EPA FORM U20-6 (REV. 3-76)
149
-------
candidate. A preliminary assessment of DCPD is currently scheduled for
the near future.
The submitter should be asked to support his contention that the informa-
tion presented in this submission reasonably supports a conclusion of
substantial risk.
150
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: March 30, 1978 (Revised May 10,- 1979)
SUBJECT: Status Report 8EHQ-0378-0098
FROM: Frank D. Kover, Supervisor
Hazard Assessment Group, OTS (WH-557)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-788)
Submission Description
Study describing the in vitro malignant transformation effects of VC-948
[bis(tribromoneopentyl)pentaerythritol cyclic diphosphate] in BALB/3T3
cells.
Submission Evaluation
This compound appears to be a pyrophosphate which probably hydrolyzes
promptly to a phosphoric ester containing six bromine atoms. The potential
for delayed neurotoxicity, liver injury, and carcinogenicity can be
surmised. The submitted report reinforces the latter potential.
Current Production and Use
No production and use information was located; chemical is on the TSCA
Candidate List.
Recommendations
The submitter should be contacted concerning the actual structure of
VC-948 (available chemical name is trivial). Apparent low production does
not support continued EPA activity; nonetheless, a number of submissions
have concerned this chemical, and it may be a candidate for Section 8(a),
CHIP, or NIOSH/OSHA consideration.
The submitter should be asked to support his contention that the information
presented in this submission reasonably supports a conclusion of substantial
risk.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM I32O-6 (REV. 3-76) 151
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 26, 1978 Approved
SUBJECT: Status Report 8EHQ-0378-0099
Revision
Needed
FROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Report confirming the presence of various chlorinated hydrocarbons
(chlordene, octachlorocyclopentene, hex BCH, etc.) in catfish and carp
taken from the Mississippi River. This information is supplemental to
that contained in 8EHQ-1177-0013 and 8EHQ-0278-0054. This notice was
declassified on May 1, 1978.
Submission Evaluation
These three related reports have a common difficulty in that the chemical
nomenclature is inadequate and thus the identity of the compounds remains
obscure.
The report fails to note which tissues were analyzed, the number of fish
in the sample, or the type of fish used in each residue measurement.
Several of the samples had high (>1 ppm) concentrations of hex BCH and
hex vinyl chloride as reported previously in 8EHQ-1177-0013; in addition,
one of the six samples had concentrations of chlordene, isodrin, and
octachlorocyclopentene at or above 1 ppm.
The submission also offers a comparison of two analytical methods used
for residue determination, GCMS and ECGC. The techniques appear to
yield comparable results, but no indication of the variation (precision,
accuracy) of either method was given.
Current Production and Use
All of the compounds listed in the submission are pesticides or pesticide
intermediates or waste products.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 1320-6 (REV. 3-76) 152
-------
Comments/Recommendations
Octachlorocyclopentene is also discussed in 8EHQ-0278-0062.
(a) These data and the earlier related submissions should be referred
to the FDA Bureau of Foods, OFF, TS/OE, ERD, Regions IV and VI,
and appropriate EPA labs.
(b) The submitter should be contacted about the Inadequacies in the report,
and a request for the results of the chlordene epoxlde residue
determinations should be made. Chemical nomenclature should be
clarified.
153
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE-. May 8, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0378-0100
PROM: Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
Approved
Revision
Needed
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing 'and Evaluation, OTS (TS-792)
Submi s s ion D es cr ip tIon
Results of in vitro malignant transformation study of MC-984 [bis(l,3-
dichloro-2-propyl)-3-chloro-2,2-dibromomethyl-l-propyl phosphate] in mouse
BALB/3T3 cells. Several other submissions have concerned this chemical
(8EHQ-0178-0033; 8EHQ-0278-0048; 8EHQ-0278-0049; 8EHQ-0278-0053; 8EHQ-
0478-0107; 8EHQ-0478-0136). This notice was declassified on May 1, 1978.
Submission Evaluation
The tests demonstrated that MC-984 is capable of inducing malignant
transformation in BALB/3T3 cells. The correlation of this test to
potential carcinogenicity is still under active debate within the scientific
community. The phosphate ester structure could produce delayed neuro-
toxicity, and the BrCl content raises questions of potential liver
toxicity. If industry continues to utilize these types of phosphate
esters, they will ultimately have to determine where in a given series
the potential for delayed neurotoxicity becomes insignificant.
Current Production and Use
There is no information available on the production and use of this
chemical, nor is there an entry in the TSCA Candidate List.
Recommendations
(a) Section 8(b) data should be checked for evidence of commercial
significance.
(b) MC-984 may be a candidate for CHIP and/or NIOSH/OSHA consideration
if production level is significant.
(c) The submitter should be asked to support his contention that the
informatioiL.submitted reasonably supports a conclusion of substant-
ial risk.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
EPA FORM 1320-S (REV. 3-76)
154
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE.- May 11, 1978 (Revised May 10, 1979)
SUBJECT! Status Report 8EHQ-0378-0101
i Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
Approved
Revision
Needed
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Teratology study of chlorendic anhydride (CA) in rats.
declassified on May 1, 1978.
This notice was
Submission Evaluation
As a pilot study for teratogenesis, the results are perhaps inconclusive.
Had there been any indication of teratogenesis, a more elaborate study
would have been in order. Since teratogenesis is difficult to elicit in
rats, the doses that were used and the size of the groups could be open
to question. However, death did occur in two of the rats given large
doses. There are no pharmacokinetic data to indicate that absorption
occurred except at the higher doses. Since the compound appears to be
a solid, inhalation studies would be complicated. Whether dermal appli-
cation would be an advantage depends on the amount that can be dissolved
in oil. The proof that is lacking in this study is the amount that was
absorbed from the administered dose. The compound is a derivative of
phthalic anhydride. Phthalic anhydride is capable of reacting with many
compounds, particularly phenols, to form phthaleins. These substances
theoretically could react with glutathione, tyrosine, and other compounds
that occur in cells. If the compound has carcinogenic potential, it may
be on this basis rather than via the effects of its expected metabolites.
Nevertheless, epoxide formation cannot be ruled out.
Current Production and Use
An estimated 10 million pounds of chlorendic anhydrlde/chlorendic acid
were produced in 1974, with an expected annual growth rate of 10% through
1980. Reported uses of chlorendic anhydride include: flame-retardant
polyester resins; hardening agent for epoxy resins; chemical intermediate;
source of chlorendic acid.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
155
-------
Related Past and Present Activities
A CHIP report on hexachlorocylopentadiene contains some discussion of CA.
Comments/Recommendations
Several other submissions have been received on this compound (8EHQ-0278-
0058; 8EHQ-0278-0059; 8EHQ-0378-0101; 8EHQ-0478-0127; 8EHQ-0478-0134).
(a) Chlorendic anhydride may be a CHIP candidate, especially if the ORD
document does not adequately address this chemical.
(b) NIOSH and OSHA may be interested in some of the notices on chlorendlc
anhydride.
(c) The submitter should be asked to support his contention that the
information presented in this submission reasonably supports a con-
clusion of substantial risk.
156
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
28JUN 1978
SUBJECT: status Report* 8EHQ-0378-0102
FROM.- Frank D. Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Approved
Revision
Needed
Submission Description
Mutagenicity evaluation of hexachlorocyclopentadiene in the
mouse lymphoma forward mutation assay. This notice was
declassified on 5/1/78. \
Submission Evaluation
The deficiency of this test for mutagenicity of hexachloro-
cyclopentadiene is that the compound is highly toxic to
cells. This is not unique to this polyhalogenated unsat-
urated hydrocarbon. The fact that S9 liver activation
reduced the toxicity suggests that this compound is bio-
transformed in the liver to a significant degree. It is
unfortunate that there was not sufficient inactivation of
the acute toxicity by the liver system so that a dose-
response could be obtained. If this chemical is to be used
extensively and no i_n vitro mutagenesis system can be worked
out, it may be necessary to do a full blown carcinogenecity
study .in vivo. It should be possible to increase the S9
activity by graded amounts in order to obtain sufficient
detoxification of hexachlorocyclopentadiene. In this
manner, it may be possible to reveal mutagenicity. As it
is, there is insufficient evidence to prove or disprove the
mutagenicity of hexachlorocyclopentadiene in the test system
used. The only potentially positive results were in the
activation test at the .00002 and .00008 ul/ml range. It
would be good if the test could be repeated for the above
range of concentrations in order to determine whether or not
the results were repeatable. However, with the equivocal
results presented here, submission of this information under
section 8(e) is not warranted.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM U20-C (REV. »-7t)
157
-------
-2-
Current Production and Use
Current production of hexachlorocyclopentadiene is estimated
at between 7 and 50 million Ibs. per year with a major
portion used as a chemical intermediate in the production of
insecticides (many of which are now strictly controlled by
EPA) and flame retardants.
Related Past and Present Activities
An early warning report on hexachlorocyclopentadiene is
available from the Assessment Division; an assessment
document is in preparation by ORD.
Comments/Recommendations
Several submissions have been received on hexachlorocyclo-
pentadiene (8EHQ-1177-0013; 8EHQ-0178-0037; 8EHQ-0178-0038;
8EHQ-0278-0061; 8EHQ-0278-0064; 8EHQ-0378-0099; 8EHQ-0378-
0109; 8EHQ-0378-0110).
a) All submissions pertinent to hexachlorocyclo-
pentadiene (and chlorendic anhydride) should be
referred to the ORD contact for distribution to
the group preparing the HEX assessment document.
b) The submitter should be asked to support his
contention that the submitted information reason-
ably supports a conclusion of substantial risk.
158
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: May 10, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0378-0103
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
Approved_
Revision
Needed
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Results of pilot teratology and acute inhalation studies of MC-935 [poly
(dibromophenylene)oxide] in rats. This report was declassified on
May 1, 1978.
Submission Evaluat ion
MC-935A is probably a high-molecular-weight polymer derived from dibromo-
phenol or from tetrabromodiphenyloxide. Any acute toxicity or teratogenicity
would probably be due to the starting monomers or residues that were poorly
polymerized.
The inhalation technique used is inadequate because it supplies no
evidence that the material was absorbed. It does not give histological
data indicating the fate of the dust that the animals inhaled, nor does
it supply data on how much adhered to the fur. In addition, the inhalation
study did not determine the true concentration of MC-935A by measurement;
therefore, the results are of limited value.
The teratology studies suffer from the same weakness in that there is no
indication of absorption of the substance by the organism. Under these
circumstances, a teratology study would require a huge number of animals
to meet the various contingencies of exposure. In this case, the teratology
study used too few animals at the start of the experiment and then proceeded
to kill several, which further depleted the population.
Current Production and Use
No information was located on the production and use of this chemical; there
was no entry in the TSCA Candidate List.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
EPA FORM 1320-4 (REV. 3-76)
159
-------
Conmients/Recoifflnendations
Several submissions have been received on this chemical (8EHQ-0278-0066;
8EHQ-0378-0090; 8EHQ-0478-0132). MC-935A may have some flame retardant
uses; if so, it will be evaluated as part of the ongoing Assessment
Division study of flame retardant technology.
(a) Clarify structure through follow-up to notifier.
(b) Evaluate Section 8(b) data to determine present production level.
(c) Refer this submission and the others listed above to the PBB workgroup,
(d) If the chemical appears commercially viable, it should be given CHIP
and/or NIOSH/OSHA consideration.
(e) The submitter should be asked to support his contention that the
information presented in this submission reasonably supports a
conclusion of substantial risk.
160
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: April 28, 1978
SUBJECT: Status Report 8EHQ-0378-0104
FROM: Frank D« Kover, Acting Director
Assessment Division, OTS (TS-792)
Approved^
Revision
Needed
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Descript ion
Chemical analysis of a trade name product showing the presence of trace
quantities of vinyl chloride (VC).
Submission Evaluation
Vinyl chloride is an established carcinogen for animals and humans. There-
fore, intermediates that contain VC as an impurity or intermediates that
can give rise to VC during processing are of concern as possible environ-
mental pollutants. Of equal concern is the report that the finished
products contain residual VC. These, too, are possible sources of environ-
mental pollution with VC. Under these circumstances, we need information
about the degree of exposure during preparation for manufacture, the degree
of exposure during manufacture, and final dispositions of the finished pro-
ducts. Each stage of information should contain APPROPRIATE analytical
chemical data for VC.
Current Production and Use
No information on this product was located in secondary sources. Submitter
claims that production and distribution of the VC-contaminated products have
been discontinued and customers notified of the situation. Submitter
reported that sales of these products over the past 15 months reportedly
totaled less than 40,000 gallons.
Recommendations
Follow-up correspondence will be sent to the notifer confirming the
production and distribution halt. If this cannot be confirmed, the ques-
tions posed in the evaluation section above will be asked of the notifier.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 1320-6 (REV. 3-76)
161
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: April 2, 1978
SUBJECT: Status Report 8EHQ-0378-0105
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Approved
Revision
Needed
Submission Description
Account of urinary dysfunction in workers using a catalyst which contains
beta-dimethylaminopropionitrile (95% by weight) and bis(2-dimethylamino-
ethyl) ether (5% by weight). This notice was declassified on May 9, 1978.
Submission Evaluation
- i
Beta-dimethylaminopropionitrile is related to a compound known to cause
neurolathyrisms (neural toxicity associated with natural products found
in seeds produced by members of the pea family) . Such neurotoxicity
could cause the urinary dysfunction. Another possible cause is autonomic
nervous system dysfunction. Many dialkylaminoethyl compounds affect the
cholinergic and adrenergic branches of the autonomic nervous system.
These mechanisms indicate that either compound present in the catalyst could
be responsible for the observed urinary dysfunction.
Current Production and Use
The producer of this catalyst, which is used in the manufacture of poly-
urethane foams, reports 19 customers of record during 1977. Both component
chemicals are on the TSCA Candidate List. Production volume is not known.
Comments /Recommendations
OSHA, N10SH, and the Maryland Division of Labor and Industry have been
notified of the incident involving this catalyst and have initiated action.
It appears, therefore, that no further ac,tion concerning the catalyst itself
is necessary. The component compounds, however, should enter the CHIP phase
of assessment.
CPA
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
I120-4 (REV. >-7«)
-------
Supplemental Information (received May 9, 1978)
The submitter notified EPA that the following steps have been taken since
their original submission:
(1) Sales of all products containing beta-dimethylaminopropionitrile
have been suspended both in the United States and overseas.
(2) Samples of the catalyst and its components have been sent to
several laboratories for analytical and/or pharmacological or
toxicological studies.
(3) OSHA issued a Health Hazard Alert to all subject catalyst customers
on April 4.
(4) The submitter has also initiated studies to develop an analytical
method suitable for determining airborne concentrations of dimethyl-
aminopropionitrile.
163
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Approved^
Revision
Needed
DATE: December 4, 1978
SUBJECT: Status Report 8EHQ-0378-0107
FROM: Frank D. Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
The results of two mutagenicity studies conducted on MC-984 [bis (1,3-
dichloro-2-propyl)-3-chloro-2,2-dibromomethyl-l-propyl phosphate]. The
first study involved a rat dominant lethal assay, and the second study
involved a reexamination of the activity of MC 984 in the mouse lymphoma
forward mutation assay. The initial mouse lymphoma assay was reported
as 8EHQ-0278-0053. (MC 984 is also known as VC 984.) This notice was
declassified on May 22, 1978.
Submission Evaluation
A recurrent problem with these submissions is a lack of an adequate
characterization of the compound that was actually tested. In this
case, the test materials were characterized only as an "amber viscous
liquid" or a "very viscous yellow liquid." No indication as to the
purity of the material or the presence of any contaminants is given,
making the submissions extremely difficult to evaluate. Another problem
concerns the meaning of the mg/kg and nl/ml values. Do these pertain to
a measure of the amount of the viscous liquid which was used in each
case or do these, in fact, indicate the amount of active compound that
was tested? A more complete description of the composition of the
materials actually used in these experiments is needed.
In the dominant lethal assay, the submitter concluded that a "dose-
related dominant lethal effect is limited to the first mating week and
not observed thereafter." This conclusion is not entirely supportable
as the 1-week effect on sperm may indicate an inadequate dose or an
alarm reaction on part of the rats. The submitter should be asked to
support his conclusion in light of the differing views above.
The data presented in this mouse lymphoma assay are in direct conflict
with the conclusions offered earlier in 8EHQ-0278-0053 using the same test
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 1320-6 (REV. 3-76)
164
-------
system. The situation was discussed with Dr. Herbert Rosenkranz of
New York Medical College. He recommended that the study be repeated
twice to resolve the problem. Dr. Rosenkranz feels that it is good
scientific procedure to repeat these particular studies when discrepan-
cies of this nature occur. Nevertheless, in this particular test,
MC 984 exhibited considerable toxicity to test cells in a dose-related
manner. Because of this, it is difficult to evaluate the mutagenicity
of the compound using this particular test.
Current Production and Use
No information on the production and use of MC 984 is available, nor
is there a listing in the TSCA Candidate List.
Comments/Recommendations
Several other submissions have been received on MC 984 (8EHQ-1277-
0022; 8EHQ-0178-0033; 8EHQ-0278-0048; 8EHQ-0278-0049; 8EHQ-0278-0053;
8EHQ-0378-0100; 8EHQ-0478-0136). Previous status reports have recom-
mended that 8(b) data be checked and that MC 984 be considered for
possible CHIP examination.
(a) Remarks offered in the evaluation section should be transmitted
to the submitter for his consideration. Particular emphasis
should be placed on the problems associated with inadequate
analytical data.
(b) This information should be transmitted to NIOSH and OSHA.
165
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE. May 8, 1978 (Revised May 10, 1979) Approved
SUBJECT: Status Report 8EHQ-0378-0108
Revision
Needed .... -.
FROM: Frank D« Kover, Acting Director
Assessment Division, OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Acute (96 hour) toxicity study of methanol in bluegill sunfish. This
submission was declassified on May 22, 1978.
Submission Evaluation
Methanol does not appear to be toxic to bluegills. No mortality was
seen in any of the tanks despite nominal concentrations up to 1,000 mg/1.
Nonetheless, several problems with the study are apparent: (a) Static
tests were used (as opposed to continuous-flow) and the actual concentration of
methanol is unknown. The volatility of methanol may be an important factor
in the actual test concentration used. (b) The DO levels of control and
experimental tanks were very low (down to 1-2 mg/1) at the end of the
tests. Nonetheless, any DO stress on the fish was not exhibited in mortality.
Current Product ion and Use
About 5 billion pounds of methanol were produced in 1975. The major use
of methanol is in the production of formaldehyde. Methanol is also used
as an intermediate in the production of other organic compounds and has
numerous solvent applications. Potential new uses of methanol which could
have significant environmental impact are its use as a liquid chemical
fuel and its use as a carbon source for bacteria in sewage treatment
plants,
Related Past and Present Activities
An Assessment Division CHIP report on methanol was reviewed by DAA for
Testing and Evaluation with a recommendation for Section 4 consideration.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76) 166
-------
Conments/Reconnnendations
(a) Forward a copy of this submission to OTS personnel involved in
Section 4 chemical selection activities.
(b) The submitter should be asked to support his contention that the
information presented in this submission reasonably supports a
conclusion of substantial risk.
167
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
0*U: May 8, 1978
Status Report 8EHQ-0378-0109 Approved
Revision
MOM: Frank D. Kover, Acting Director Needed
Assessment Division, OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Results of an industrial hygiene survey conducted at one of the sub-
mitter's plants. The surveyed area included the hexachlorocyclopenta-
diene production unit and the quality control laboratory.
Submission Evaluation
Because of the nature of this submission, no evaluation was undertaken;
refer to recommendations below for suggested disposition.
Recommendations/Comment s
This notice should be referred to OSHA and NIOSH for evaluation in light
of the pertinence of this information to areas of NIOSH/OSHA expertise.
The submitter should be asked to support his contention that the information
presented in this submission reasonably supports a conclusion of substantial
risk.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
IMEV. »-7«) 168
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: May 8, 1978
sutJECT: Status Report 8EHQ-03 78-0110 Approved
Revision
PROM.- Frank D. Kover, Acting Director Needed
Assessment Division, OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Results of an industrial hygiene survey conducted at one of the sub-
mitter's plants. The survey was conducted to measure airborne concen-
trations of hexachlorocyclopentadiene and to determine employee exposure
to carbon tetrachloride.
Submission Evaluation
Because of the nature of this chemical, no evaluation was undertaken;
refer to recommendations below for suggested disposition.
Recommendations/Comments
_ __ (
This notice should be referred to OSHA and NIOSH for evaluation in light
of the pertinence of this information to areas of NIOSH/OSHA expertise.
The submitter should be asked to support his contention that the information
presented in this submission reasonably supports a conclusion of substantial
risk.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
roftM uao-t IMCV. »-7t> 169
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: May 2, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0378-0111
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
Approved^
Revision
Needed
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission^Description
Acute toxicity study of hydroxyacetaldehyde dimethyl acetal in bluegill
sunfish. This report was declassified on May 22, 1978.
Submission Evaluation
No mortality was seen in bluegills exposed for 96 hours to hydroxyacetalde-
hyde dimethyl acetal at concentrations up to 100 mg/1. Abnormal behavior
("irritation") was noted in fish exposed to levels above 56 mg/1. Based
on the information presented in this submission, the chemical does not
appear to be a significant problem.
Current Production and Use
No information was located on production and uses of this chemical; no
entry was found in the TSCA Candidate List.
Comments/Recommendations
Several submissions have been received on the class of chemicals related
to substituted-acetaldehyde dimethyl acetals (8EHQ-0178-0036; 8EHQ-0178-
0039P; 8EHQ-0478-0119).
(a) Section 8(b) data should be checked for evidence of commercial
significance.
(b) The submitter should be asked to support his contention that the
information presented in this submission reasonably supports a
conclusion of substantial risk.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 1320-6 (REV. 3-76)
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE. May 8, 1978
Status Report 8EHQ-0378-0112 Approved
Revision
PROM. Frank D. Kover, Acting Director Needed
Assessment Division, OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Results of an industrial hygiene survey conducted at one of the sub-
mitter's plants. The survey was a follow-up to an earlier benzene
exposure report (not received by EPA).
Submission Evaluation
Because of the nature of this chemical, no evaluation was undertaken;
refer to recommendations below for suggested disposition.
Recommendations/Comments
(a) This notice should be referred to OSHA and NIOSH for evaluation in
light of the pertinence of this-information to areas of NIOSH/OSHA
expertise.
(b) The submitter should be asked to support his contention that the
information presented in this submission reasonably supports a
conclusion of substantial risk.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
CPA FOftM I1JO-4 (N(V. »•?•) 171
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: May 8, 1978
SUBJECT: Status Report 8EHQ-0378-0113 Approved
Revision
PROM: Frank D. Kover, Acting Director Needed
Assessment Division, OTS (TS-792)
T0: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Results of an industrial hygiene survey conducted at one of the sub-
mitter's plants. The survey was conducted to determine employee expo-
sure to DBCP (1,2-dibromo-3-chloropropane) and carbon tetrachloride.
Submission Evaluation
Because of the nature of this submission, no evaluation was undertaken;
refer to recommendations below for suggested disposition.
Recommendations/Comments
This notice should be referred to OSHA and NIOSH for evaluation in light
of the pertinence of this information to areas of NIOSH/OSHA expertise.
The submitter should be asked to support his contention that the information
presented in this submission reasonably supports a conclusion of substantial
risk.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
fONM 1»»-i IMCV. »•?•) 172
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: May 1, 1978 (Revised May 10, 1979) Approved^
SUBJECT: Status Report 8EHQ-0378- 0114
Revision
Needed
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Acute aquatic toxicity study of methyl acetate in bluegill sunfish. This
notice was declassified on May 22, 1978.
Submi s sion Evaluation
The test material was not acutely toxic to bluegills exposed to nominal
concentrations up to 100 mg/1 for 96 hours in soft water. Behavioral abnor-
malities (swimming) were noted at concentrations above 56 mg/1. Because no
mortality was seen at fairly high levels, methyl acetate does not appear
particularly hazardous to bluegills (based on the information contained in
this report).
Current Production ajtid Use
Methyl acetate is used in paint remover compounds; as a solvent for lacquer,
nitrocellulose, acetylcellulose, and many resins and oils; manufacture of
artificial leather; chemical intermediate; synthetic flavoring. Methyl
acetate production in 1974 was approximately 8 million pounds.
Comments/Recommendations
No further action is indicated at this time. The submitter should be
asked to support his contention that the information presented in this
submission reasonably supports a conclusion of substantial risk.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 1320-6 (REV. 3-76) 173
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: May 8, 1978 (Revised May 10, 1979)
SUBJECT-. Status Report 8EHQ-0478-0115
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Approved
Revision
Needed
Submission Description
Results of industrial hygiene survey conducted at one of the submitter's
plants. The survey involved the FM-680 (bis-1-2 (2,4,6-tribromophenoxy)
ethane) production facilities.
Submission Evaluation
i
Because of the nature of this submission, no evaluation was undertaken;
refer to recommendations below for suggested disposition.
Comments/Recommendations
(a) This notice should be referred to OSHA and NIOSH for evaluation in
light of the pertinence of this information to areas of NIOSH/OSHA
expertise.
(b) The submitter should be asked to support his contention that the
information presented in this submission reasonably supports a con-
clusion of substantial risk.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
CPA FORM tIZO-t (REV. »-7«l
174
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: May 3, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0478-0116
FROM: Frank D. Kover, Acting Director
Assessment Division (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation (TS-792)
Submission Description
Reports that the n-octanol/water partition coefficient of tetrabromobis-
phenol A (FM BP4-A) is about 30,000. The submission notes that a fish
bioaccumulation study with this chemical is scheduled in the future.
Submission Evaluation
The partition coefficient of this compound is very high and demonstrates a
high potential for bioaccumulation if the material enters the environment
in any sizable amount.
Current Production and Use
The U.S. ITC identifies only one producer of FM BP4-A; the recent "Bromine
Based Fire Retardants" report identified three producers. Annual produc-
tion may be of significance as the chemical is used as an intermediate for
a good number of other flame retardants in addition to having fire retard-
ant applications of its own. Reported flame retardant applications include
use in paper, textiles, and many plastics and polymers (ABS, epoxy, poly-
carbonate, polyesters, polypropylene, polystyrene, etc.).
Comments/Recommendations
Several other submissions have concerned tetrabromobisphenol A or its
derivatives (8EHQ-1277-0025; 8EHQ-0478-0130).
(a) On the basis of the evidence presented here, FM BP4-A should be evaluated
by some phase of the CHIP program (fire retardant technology assessment
or CHIP treatment as such).
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular chemical.
Any review of the status report should take into consideration
the fact that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
175
-------
(b) The monitoring division should be questioned as to the existence of
any monitoring data demonstrating the environmental presence of this
compound.
(c) The submitter should be requested to furnish the fish bioaccumulation
study as soon as it is completed.
(d) This submission should be referred to the FDA Bureau of Foods as well
as appropriate EPA labs.
(e) While the reported n-octanal/water partition coefficient is greater
than the 25,000 figure specified in Part V(b)(2) of the March 16, 1978
Policy Statement (43 FR 11110), the submitter has failed to demonstrate
the "potential for widespread exposure and any non-trivial adverse
effect" associated with this chemical. The submitter should therefore
be asked to support his contention that the information presented in
this submission reasonably supports a conclusion of substantial risk.
176
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: May 11, 1978 (Revised May 10, 1979) Approved,
SUBJECT: Status Report 8EHQ-0478-0117
Revision
Needed
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Corporate memos outlining the submitter's concern that certain petroleum
refinery streams used in the production of unspecified resins may contain
polynuclear aromatic hydrocarbons (PNAs).
Submission Evaluation
The class of polynuclear (polycyclic) aromatic hydrocarbons contains
many known animal carcinogens. While the information presented in this
submission does not conclusively indicate the presence of PNAs in the
refinery stocks used for the production of the unspecified resins, the
implications are that such a finding is not totally unexpected. If PNAs
are identified in the refinery streams or in the resins, then steps must
be taken to determine the exposure potential of these materials.
Follow-up activities should be initiated to obtain the needed information.
The recent report in Nature (Feb. 2, 1978) shows that petroleum contains
a triterpane whose structure differs from the pregnane moiety present in
adrenal corticosteroids by containing an additional six-member ring. The
ring system is also closely related to the sex steroids. It is also
related to squalene, which is a precursor to cholesterol synthesis and
occurs abundantly in human skin. Steroid hormones act via a receptor
system which differs from the receptor system of ordinary pharmacological
agents. The latter triggers a transducer effect in the membrane to
release energy for tissue response. Steroid hormones, on the other
hand, have access to the nucleus of the cell and its regulating mechanisms.
This complexity of receptor-steroid movement through the cytoplasm into
the nucleus involves both RNA and DNA.
Current Production and Use
Insufficient information is provided to identify the refinery streams or
resins discussed in this submission.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 1320-6 (REV. 3-76) 177
-------
Comments/Recommendations
Several other submissions have involved PNAs (8EHQ-1277-0026C; 8EHQ-
0178-0029; 8EQ-0178-0030; 8EHQ-0278-0044; 8EHQ-0578-0140).
(a) The submitter should be requested to provide additional information
on this submission. The chemical products mentioned in the notice
should be clarified such that the refinery streams and the resins
are clearly identified or characterized. The follow-up should also
include a request that the submitter keep EPA informed of develop-
ments in this situation as well as indicating when a conclusion is
reached.
(b) NIOSH and OSHA should be kept abreast of developments.
(c) The submitter should be asked to support his contention that the
information presented in this submission reasonably supports a
conclusion of substantial risk.
178
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: May 11, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0478-0118P
Approved^
Revision
Needed
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
T0: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Internal corporate memo describing an accidental employee exposure incident
(involving an individual who was also identified in the DBCP/tris-
related sterility reports).
Submission Evaluation
The causative agent is not identified specifically, although several
chemicals are mentioned as possible candidates: ethylene dichloride
(EDC), methyl bromide (MeBr), hydrogen sulfide (^S), BADMA (bromoacetalde-
hyde dimethyl acetal?), methanol (MeOH), and DBEA (dibromoethyl acetate?).
The reported symptoms include nervousness, restlessness, insomnia, and eye
irritation. Any of the chemicals suspected as the cause of the intoxica-
tion could produce the symptoms complained of by the victim. They all have
effects on the central nervous system. Bromoacetaldehyde acetals were used
before the modern era of barbiturates and benzodiazepines to induce sleep.
Current Production and Use
All of the chemicals identified in this submission are large-volume basic
industrial products and intermediates except for BADMA and DBEA, which are
produced in unknown amounts.
Related Past and Present Activities
CHIP reports are available on EDC and MeOH; MeBr is covered in the halogenated
methanes hazard assessment. All are available from the AD.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular chemical.
Any review of the status report should take into consideration
the fact that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
179
-------
Comments/ Recommendations
Several of the chemicals have been the subject of other submissions: BADMA
(8EHQ-0178-0039P; 8EHQ-0478-0119); MeOH (8EHQ-0378-0108); and DBEA (8EHQ-
0977-0005; 8EHQ-0178-0039P; 8EHQ-0278-0070; 8EHQ-0478-0121). This incident
apparently took place in the submitter's plant where the DBCP/tris-related
sterility problems occurred.
(a) The suitability of submissions such as this should be discussed by the
8(e) staff. This may be a good example of what is not an appropriate
8(e) notice. The submitter should be asked to support his contention
that the information presented in this submission reasonably supports
a conclusion of substantial risk.
(b) The acronyms DBEA and BADMA should be clarified through a follow-up to
the submitter.
180
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE; April 24, 1978 (Revised May 10,- 1979) Approved_
SUBJECT: Status Report 8EHQ-0478-0119 Revision
Needed
Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Acute aquatic toxicity study of bromoacetaldehyde dimethyl acetal (BADMA)
in bluegill sunfish. This notice was declassified on May 22, 1978.
Submission Evaluation
BADMA is acutely toxic to bluegills. The 96-hour LC50 in static tests was
671 mg/1 (nominal concentration). Behavioral abnormalities, indicative of
stress, were noted at levels above 32 mg/1. All of the mortality occurred
within 24 hours, possibly indicating that the chemical had disappeared. pH
was held within acceptable limits; DO was low (2-5 mg/1) in test and control
tanks. This, however, was probably a minor factor in the mortality. Based
on this report, there is no great cause for concern as the reported toxicity
levels are moderate.
Current Production and Use
The SRI Directory of Chemical Producers lists two producers of BADMA,
implying an annual production in excess of 1,000 pounds. BADMA is used as
an intermediate in the production of methylamino acetaldehyde dimethyl
acetal (according to a previous submission, 8EHQ-0178-0036); other possible
uses are not known.
Comments/Recommendations
The submitter should be asked to clarify the identity of the chemicals
noted in 8EHQ-0178-0036 and 8EHQ-0178-0039 as they may be related (or
identical) to BADMA.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular chemical.
Any review of the status report should take into consideration
the fact that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 9-761
-------
(a) The class of chemicals based on acetaldehyde dimethyl acetal may be
CHIP candidates as several submissions have been received on them.
(b) The submitter should be asked to support his contention that the
information presented in this submission reasonably supports a con-
clusion of substantial risk.
182
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: May 3, 1978 (Revised May 10, 1979) Approved
SUBJECT: Status Report 8EHQ-0478-0120
Revision
Needed
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Acute toxicity study of sodium acetate in bluegill sunfish. This
notice was declassified on May 22, 1978.
Submi ss ion Evaluation
Sodium acetate is not very toxic to bluegills (96-hour L^Q = 1,000
mg/1). No mortality was seen in any of the test tanks. The chemical
might have a high oxygen demand because DO reductions were fairly severe
(1.9-1.3 mg/1 values) in the test tanks but not the control. Abnormal
behavior indicative of stress was observed at concentrations greater
than approximately 320 mg/1. The acute toxicity of sodium acetate to
bluegills appears to be of minor significance.
Current Production and Use
Sodium acetate sales were in excess of 20 million pounds in 1973. It is
used as a dye and color intermediate and in Pharmaceuticals, soaps,
photography, meat preservation, electroplating, tanning, etc.
Comments/Recommendati ons
No additional activities are recommended. The submitter should be asked
to support his contention that the information presented in this submission
reasonably supports a conclusion of substantial risk.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 1320-6 (REV. 3-76) , g-j
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: May 8, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0478-0121
Approved
Revision
Needed
PROM: Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
70s Warren R. Muir, Deputy Assistant Administrator
•for Testing and Evaluation, OTS (TS-792)
Submission Description
Acute toxicity study of dibromoethyl acetate in bluegill sunfish.
notice was declassified on May 22, 1978.
This
Submission Evaluation
Dibromoethyl acetate is toxic to bluegills exposed for short time periods
(24-hour LCt^Q = 1.43 mg/1; 96-hour LD^Q = 1.21 mg/1) . At concentrations
above approximately 1.0 mg/1, the fish exhibited signs of stress. To fully
appreciate the threat of this chemical, OTS should request additional data:
physical-chemical properties (especially solubility data); complete copy of
this study; and use information. The chemical is fairly toxic.
Current Production and Use
No production and use information was located; the chemical was not entered
in the TSCA Candidate List.
Comments/Recommendations
The flame retardant potential of dibromoethyl acetate will be evaluated in
the ongoing Assessment Division investigation of flame retardant technology.
Two other submissions have been received on this chemical (8EHQ-0977-0005
and 8EHQ-0278-0070). In all cases, dibromoethyl acetate exhibited a moder-
ate to high degree of toxicity in the test systems (rabbit and rat tested
in addition to this fish study).
(a) Check Section 8(b) data for evidence of commercial significance.
(b) Consider a CHIP investigation of this chemical on the basis of its
degree of acute toxicity in three species.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular chemical.
Any review of the status report should take into consideration
the fact that it may be based on incomplete information.
CPA FORM 1320-6 (REV. 3-76)
184
-------
(c) Request physical-chemical data from the notifier as well as additional
information on the bluegill study. Use information should also be
solicited as well.
(d) The submitter should be asked to support his contention that the
information presented in this submission reasonably supports a con-
clusion of substantial risk.
185
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 14, 1978 (Revised May 10, 1979)
SUBJECT: status Report 8EHQ-0478-0122
Approved
Revision
Needed
FROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
T0: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Pilot teratology study of PHT-4 (tetrabromophthalic anhydride) in rats.
This notice was declassified on May 22, 1978.
Submission Evaluation
The experimental design is sufficiently insensitive to preclude all but the
most severe teratogenic effects. This type of compound may be poorly
absorbed and/or have a long latent period before signs of toxicity appear
(liver and kidney toxicity, endocrine effects, fat storage, and bioaccumu-
lation are of concern).
The dosage volume of 25 ml/kg/day in the controls appears inappropriate; a
volume of 7.5 ml/300-g rat is stressful alone.
Current Production and Use
Annual production is not known; however, the U.S. ITC lists one producer,
which implies an annual production of greater than 1,000 pounds. PHT-4 is
used as a flame retardant for plastics, paper, and textiles (polyesters).
Comments/Recommendations
PHT-4 will be evaluated in the ongoing Assessment Division study of flame
retardant technology. It is listed in the recent "Bromine Based Fire
Retardants" report.
(a) Section 8(b) data should be evaluated for evidence of commercial
significance.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular chemical.
Any review of the status report should take into consideration
the fact that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
186
-------
(b) If production is sufficient, a CHIP evaluation may be advisable.
(c) The submitter should consider retesting the material using more sensi-
tive experimental procedures. The submitter should also be asked to
support his contention that the information presented in this submission
reasonably supports a conclusion of substantial risk.
187
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: April 27, 1978
SUBJECT: Status Report 8EHQ-0478-0123
Approved
Revision
Needed
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
T0: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Report outlining the results of follow-up sterility tests conducted on
employees who were occupationally exposed to DBCP (l,2-dibromo-3-chloro-
propane) and tris [tris(2,3-dibromopropyl) phosphate]. See 8EHQ-0278-0056
for the results of the initial test. This notice was declassified on May
22, 1978.
Submission Evaluation
The report covers only the effects of DBCP and not those that might result
from exposure to tris. The submission notes that the composition and work
history of the cohort apparently contain inconsistencies.
The examining physician states explicitly that the workers exposed to DBCP
are still having deficient formation of sperm, and therefore deficient
capability for reproduction. It is purely speculative on the submitter's
part that the sperm-deficient workers in the non-DBCP exposure group (with
respect to work station location) had significant exposure to DBCP despite
being assigned to other departments. Unless validated, this claim will
only serve to obscure the actual cause of the sperm deficiency in these
men, which may in fact be traceable to tris exposure, which is documented
for several of these individuals.
This is the first indication that sperm-deficient DBCP-exposed workers are
not improving despite cessation of exposure (a contention that had not
previously been advanced by the affected companies). This information
should be transmitted to NIOSH and OSHA as soon as the material has been
declassified. These authorities have already received a summary of this
information; OTS received this same summary as 8EHQ-0478-0128.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular chemical.
Any review of the status report should take into consideration
the fact that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
188
-------
Current Production and Use
OPP has conditionally suspended DBCP for some uses and completely suspended
it for all other uses. Conditional suspension means that only certified
pesticide applicators can use DBCP. Unconfirmed reports indicate that tris
is no longer being produced domestically; 1975 production is estimated at
7-12 million pounds. Tris was formerly used as a flame retardant for
textiles; however, the CPSC has moved against this use. The only current
use of tris is as a flame retardant for plastics.
Past and Present Activities
A hazard assessment report on tris is in preparation in the Assessment
Division.
Comments/Recommendations
In view of (1) unconfirmed reports that tris is no longer being manufactured,
(2) NCI's (unpublished) conclusion that the material is a carcinogen, and
(3) CPSC's announced policy to move against suppliers of tris-treated
children's sleepwear, no immediate OTS action other than referral is
required.
(a) On receipt of the NCI publication concerning the positive identifica-
tion of tris as a carcinogen, TSCA 8(a) annual notification should be
required from known tris manufacturers. If tris is manufactured for
any use, EPA should be notified as to amount manufactured, population
exposed in the manufacture, destination and use of the product, and
estimated population at risk as a result of the product's use.
(b) If DBCP is manufactured for other than pesticidal uses, TSCA 8(a)
annual notification should be required from known manufacturers.
(c) These results should be referred to OSHA, NIOSH, CPSC, OPP/OTS, and
TS/OE.
189
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: May 3, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0478-0124
Approved^
Revision
Needed
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Acute toxicity study of vinyl acetate in bluegill sunfish.
declassified on May 22, 1978.
This notice was
Submission Evaluation
Vinyl acetate is described as a clear, water-soluble, odoriferous liquid,
yet the tests were done using a solvent control. No mention of the solvent's
identity was offered nor an explanation for its necessity. The chemical
appears to exhibit moderate toxicity, the 96-hour LC5Q being 13.3 mg/1
(nominal concentration). Mortality generally occurred in the first 24
hours. Concentrations of vinyl acetate above 10 mg/1 produced evidence of
stress in the fish.
Current Production and Use
Production of vinyl acetate in 1975 exceeded 1.2 billion pounds. It is
used in the production of polyvinyl acetate, polyvinyl alcohol, polyvinyl
butyral, and polyvinyl chloride-acetate resins. These resins are used
particularly in latex paints, paper coatings, adhesives, textile finishing,
etc.
Related Past and Present Activities
A CHIP report on vinyl acetate is available from the Assessment Division.
Comments/Recommendations
Perhaps the submitter should be questioned as to the rationale for the use
of a solvent control in this experiment.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular chemical.
Any review of the status report should take into consideration
the fact that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
190
-------
(a) Due to the high annual production of vinyl acetate, this notice should
be reviewed by the EKD.
(b) The submitter should be asked to support his contention that the
information presented in this submission reasonably supports a con-
clusion of substantial risk.
191
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: May 1, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0478-0125
Approved^
Revision
Needed
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Acute toxicity study of sodium bromide in bluegill sunfish.
was declassified on May 22, 1978.
This notice
Submission Evaluation
Sodium bromide is not acutely toxic to bluegills exposed for 96 hours to
1,000 mg/1 (nominal concentration) of the chemical. Some abnormal behavior
was observed at concentrations above 320 mg/1. DO and pH were within
adequate limits. Sodium bromide is water soluble, but low concentrations
of it do not appear harmful to bluegills.
This experiment is in essence testing the acute effects of the bromide ion
on bluegills as NaBr would likely dissociate in the tanks. In mammalian
systems, bromide ion has a long tissue half-life (12 days or longer) and
can build up to toxic levels if the exposure is chronic. The effects of
elevated tissue bromide levels are lethargy, slowing of cerebration, con-
fusion, disturbed reflexes, etc. Perhaps the effects of long-term exposure
of aquatic organisms to bromine should be investigated, especially in light
of the possible use of bromine as a water purification agent in the future.
Current Production and Use
Annual production of sodium bromide is not known with any specificity;
however, inorganic bromide salts (Na, K, Nlfy) have a relatively large
annual production. Environmental loading of bromine is fairly high, with
most attributable to the combustion of EDB (ethylene dibromide) in leaded
gas. Sodium bromide is used in photography, medicines, organic chemicals,
etc. The major uses of elemental bromine are gasoline additives, flame
retardants, bleaching, etc.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular chemical.
Any review of the status report should take into consideration
the fact that it may be based on incomplete information.
CPA FORM 1320-6 (REV. 3-76)
192
-------
Related Past and Present Activities
A CHIP report on bromine and bromine compounds is available from the
Assessment Division. Current plans call for an OTS contractor evaluation
of future market trends in the bromine industry.
Comments/Recommendations
The questions surrounding the chronic effects of bromide on aquatic organ-
isms may deserve investigation before bromine is actually used as a water
purifier on a large scale.
(a) Once the confidentiality determination has been made, this study should
be referred to ERD for comment.
(b) The submitter should be asked to support his contention that the
information presented in this submission reasonably supports a con-
clusion of substantial risk.
193
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: May 8, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0478-0126
Approved
Revision
Needed
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Two acute toxicity studies on bromoacetaldehyde in bluegill sunfish.
notice was declassified on May 22, 1978.
This
Submission Evaluation
Bromoacetaldehyde is fairly toxic to bluegills exposed for 96 hours
(LCejQ = 2.5 mg/1). There is nominal concentration; a continuous-flow
test with constant renewal of the chemical might reveal a much higher
toxicity, depending on the volatility of the chemical. Behavioral abnor-
malities (indicating stress) were observed at test levels above 1.0' mg/1.
Most of the mortality occurred within the first 24 hours of the 96-hour
test, indicating possible selection or adaptation by the test organism or
removal (or degradation) of the chemical. pH levels were adequate in the
control and test tanks, but DO was curiously low in the controls while
adequate in the test tanks. In tanks where 100% mortality was observed
before the 48-hour recording time, no DO measurements were made, thus one
cannot be sure that the test chemical, as opposed to low DO, was the actual
cause of death.
The test solutions contained only 52% bromoacetaldehyde; thus it is not
possible to declare with any certainty that the observed toxicity is attrib-
utable solely to bromoacetaldehyde. No analytical data were provided on
the test solution.
This chemical appears to be fairly toxic to bluegills; therefore, if
bromoacetaldehyde has the potential to enter the aquatic environment,
further testing to determine its effects should be undertaken.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular chemical.
Any review of the status report should take into consideration
the fact that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
194
-------
Current Production and Use
No information is available on the production and use of this compound;
there is not entry in the TSCA Candidate List.
Comments/Recommendations
Chloroacetaldehyde has been suggested as an active metabolite of vinyl
chloride and possibly 1,2-dichloroethane; chloroacetaldehyde has also been
shown quite potent in the Ames test. Based on the structural similarity
between chloro- and bromoacetaldehyde, consideration should be given to
further investigation of bromoacetaldehyde.
(a) Section 8(b) data should be checked for evidence of commercial signif-
icance.
(b) Information describing the metabolism of EDB (1,2-dibromoethane)
should be checked for mention of bromoacetaldehyde.
(c) Bromoacetaldehyde should be given CHIP scrutiny in combination with
the scheduled evaluation of chloroacetaldehyde.
(d) The submitter should be asked to support his contention that the
information presented in this submission reasonably supports a con-
clusion of substantial risk.
195
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 15, 1978
SUBJECT: Status Report 8EHQ-0478-0127 Approved
Revision
FROM- Joseph J. Merenda/Actifig 'oTrector Needed
Assessment Division, OTE/OTS (TS-792)
T0. Warren R. Muir, Deputy Assistant Administrator
f&r Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
The submission consists of the results of an evaluation of chlorendic
anhydride in the mouse lymphoma forward mutation assay. This notice was
declassified on 5/22/78.
Submission Evaluation
Chlorendic anhydride was toxic to mouse lymphoma cells without affecting
cloning or mutation frequency significantly.
Current Production and Use
An estimated 10 million Ibs. of chlorendic anhydride/acid were produced
in 1974 with an expected annual growth rate of 10% through 1980.
Reported uses of the anhydride include: flame resistent polyester
resins; hardening agent for epoxy resins; chemical intermediate; source
of chlorendic acid.
Related Past and Present Activities
An early warning report on hexachlorocyclopentadiene contains some dis-
cussion of chlorendic anhydride and is available from the Assessment
Division.
Comments/Recommendations
Several other submissions have been received on chlorendic anhydride
(8EHQ-0278-0058; 8EHQ-0278-0059; 8EHQ-0378-0101; 8EHQ-0478-0134).
A question arises as to the applicability of this submission per se to
Section 8(e). Submitted in a singular fashion, the information fails to
satisfy the criteria for substantial risk established for mutagenicity
assays in the March 16 Policy Statement. In the first place, the results
are negative and secondly, no corrobative information is provided. If
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
rOMM IMb-4 (MEV. >•?«) 196
-------
the information were submitted as part of the package containing several
studies on chlorendic anhydride, perhaps then this information would be
appropriate as part of the entire presentation, despite the negative
findings. The submitter, however, persists in sending discrete bits of
information, many of which do not indicate substantial risk in and of
themselves, rather than holding the material until a coherent case
(according to the definitions and explanations offered in the Policy
Statement) for substantial risk can be made. Obviously, in certain
cases, a single piece of information is sufficient to indicate sub-
stantial risk, but with this particular submitter, the individual
bits of information are insufficient (from both the perspective of
the Policy Statement and from any reasonable definition of substantial
risk) to indicate a substantial risk to health or the environment.
The submitter should be encouraged to follow more closely the guidance
offered in the Policy Statement with respect to deciding what constitutes
substantial risk.
197
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 22, 1978 Approved
SUBJECT: Status Report 8EHQ-0478-0128
Revision
Needed
PROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
The submission consists of a copy of a letter submitted to NIOSH, OSHA,
and OPP regarding sterility retesting (refer to 8EHQ-0278-0056 for the
initial test results) of employees exposed to DBCP and/or DBCP-
contaminated tris. This is essentially identical (though lacking in
detail) to the information contained in submission 8EHQ-0478-0123.
Submission Evaluation
The ten subjects who returned for retesting were divided as follows:
four had been exposed to DBCP and six to tris. None of the four workers
exposed to DBCP had normal sperm counts on retest although the retest
showed some improvement, possibly significant in one case. Of the six
that had been exposed to tris, two who had low sperm counts on the first
examination had normal counts on the second. Two workers did not have
defective counts on the initial examination. Two subjects exposed to
DBCP who had no counts taken on the first examination had normal counts
on the second examination. (The significance of this observation is
dubious, particularly since the restoration following DBCP exposure is
much slower, if it occurs at all. This would indicate that the two
people with normal counts on the second examination may have had normal
counts previously.)
For whatever reason, whether it be duration and intensity of exposure or
inherently less toxicity to sperm by tris, the DBCP group appears to
have suffered more testicular damage and is recovering, if at all, at a
much slower rate than those exposed to tris. The deficiency in the
study is that there are no sperm counts prior to exposure and no way of
knowing if fluctuations occur in the sperm counts of these men.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 1320-6 (REV. V76) 198
-------
Current Production and Use
Unconfirmed reports indicate that tris is no longer being produced
domestically; 1975 production is estimated at 7-12 million pounds. Tris
was previously used as a flame retardant for textiles; however, CPSC has
moved to control this use. The only current use is as a flame retardant
for plastics.
OPP has conditionally suspended DBCP for some uses and completely
suspended it for all other uses. Conditional suspension means that only
certified pesticide applicators can use DBCP.
Comments
The submitter appears to be maintaining that it is the DBCP contamina-
tion in tris and not the tris itself which is causing the problem. This
contention remains to be proved at this point.
Recommendations
In view of (1) unconfirmed reports that tris (2,3-dibromopropyl) phosphate
is no longer manufactured, (2) NCI's (unpublished) conclusions that the
material is a carcinogen, (3) CPSC's announced policy to move against
suppliers of tris-treated children's sleepwear, and (4) EPA/OPP's action
to restrict the only known (pesticidal) uses of DBCP:
(a) Section 8(b) data should be checked for evidence of continued
domestic production of tris. This follow-up should include the
identification of possible tris importers. Section 8(a) data
should also be checked to confirm whether DBCP is being manufactured
for other than pesticidal uses.
(b) Recommend to Office of Chemical Control that it consider developing
a significant new use rule for DBCP.
(c) This submission should be referred to OSHA, NIOSH, CPSC, OPP/OTS,
and TS/OE.
199
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 14, 1978 Approved_
SUBJECT: Status Report 8EHQ-0478-0129
Revision
Needed
FROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Memo describing a cattleman's complaint to the notifier that three
calves were aborted recently and that the cause was contamination (by an
unknown agent) of a creek adjacent to a chemical manufacturing site.
Submission Evaluation
While insufficient information is provided for a toxicological evaluation,
nevertheless, the loss of three calves via abortion is a sign that
something untoward is happening. This situation requires investigation.
The Agency has to determine if the cause is chemically related; if so,
corrective action must be undertaken. This should be initiated as soon
as possible.
Current Product ion and Use
Insufficient information is provided to permit an evaluation.
Recommendations
(a) The submitter should be sent follow-up correspondence asking what
steps, if any, have been undertaken in response to this complaint.
(b) Notify EPA Region V of this situation and ask them to check into
the complaint.
(c) FDA should be kept abreast of developments if food contamination
potential becomes apparent.
(d) The Illinois EPA should also be alerted to this situation.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 1320-6 (REV. 3-76) 200
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 14, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0478-0130
Approved
Revision
Needed
FROM.- Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Pilot teratology study of tetrabromobisphenol A (FM BP4-A) in rats.
Submission Evaluation
This submission states that there were no teratogenic effects attributable
to tetrabromobisphenol A at doses up to 10 g/kg/day. The study, however,
was deficient in a number of ways:
(1) The number of test animals was too small.
(2) Animals were exposed only on gestation days 6-15. Potential dams
should be exposed for at least several weeks before impregnation.
(3) No pregnancies were allowed to continue to term.
togenic effects could be manifested after birth.
Significant tera-
Since only five rats received the particular dose of this compound, it is
not possible to say whether or not the post-implantation losses seen in one
rat are treatment related. The compound has definite toxicity when admin-
istered by mouth in doses above 3 g/kg/day. The green-colored stools
suggest an effect on bile pigment formation metabolism. This compound
somewhat resembles diethyl stilbestrol (DBS) in chemical structure; there-
fore, immediate teratogenic action might not occur, but delayed carcino-
genic action on the offspring and on the mother might occur. The molecular
weight and the presence of the four bromine atoms would favor liver toxicity.
Questions that need to be answered are:
(1) To what extent are the OH groups conjugated in the body, and is this
conjugation sufficient to result in excretion by the kidneys?
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular chemical.
Any review of the status report should take into consideration
the fact that it may be based on incomplete information.
EPA FORM (320-6 (REV. 3-76)
201
-------
(2) Are the bromine atoms capable of removal by bacteria and molds in the
environment?
(3) Does the compound or its conjugates accumulate in fats?
Current Production and Use
The U.S. 1TC identifies only one producer of FM BP4-A; the recent report on
"Bromine Based Fire Retardants" identifies three producers. Annual pro-
duction may be sizable as FM BP4-A is used as an intermediate for a good
number of other flame retardants in addition to having fire retardant
applications of its own. Reported flame retardant applications include use
in paper, textiles, and many plastics and polymers (ABS, epoxy, polycarbon-
ate, polyesters, polypropylene, polystyrene, etc.).
Comments/Recommendations
Several other submissions have concerned tetrabromobisphenol A or its
derivatives (8EHQ-1277-0025; 8EHQ-0478-0116; 8EHQ-0578-0142). The use
pattern and chemical properties imply potential for environmental exposure.
The compound has a moderately high octanol-water partition coefficient
(30,000; 8EHQ-0478-0116) and is likely relatively persistent.
(a) The chemical was previously recommended for CHIP examination (8EHQ-
0478-0116).
(b) The submitter should be alerted to the weaknesses evident in the
submitted study. The submitter also should be asked to support his
contention that the information presented in this submission reasonably
supports a conclusion of substantial risk.
(c) This submission and others on FM BP4-A should be referred to the PBB
workgroup for consideration in their examination of brominated flame
retardants.
202
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
OATE. June 14, 1978 (Revised May 10, 1979) Approved,
SUBJECT: Status Report 8EHQ-0478-0131
Revision
Needed
FROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Acute toxicity studies of 3-bromo-2,2-dimethylpropyl-2-chloroethyl-2-
bromoethyl phosphate in rats and rabbits. The notice was declassified on
May 22, 1978.
Submission Evaluation
The dermal toxicity study in rabbits demonstrated the following effects:
hypoactivity; decreased limb tone; ataxia; and one death (a male in the
high [20,000 mg/kg] dose group). The signs exhibited by the rabbits could
be due to (a) central nervous system effects in the spinal cord or cere-
bellum, (b) peripheral nervous system action similar to that seen with
cresyl phosphates, or (c) neuromuscular junction effects analogous to
myasthenia gravis. In any event, this chemical appears to be a neurotoxin
that is absorbed thrbugh the skin. The study itself was poorly performed
(too few animals; CNS effects not fully characterized; no controls used;
cause of death not determined; no microscopic examination of tissues; and
no determination of the blood levels or the metabolites of the compound).
The rat acute oral toxicity study was well performed as far as it went.
The LDrQ values and confidence limits were incorrectly calculated, however.
The (combined male and female rat) LD5Q should be 1,950 (1,485-2,559) mg/kg
and not the reported 1,995 (1,635-2,434) mg/kg. The slope, therefore,
changes to 1.48 and not 1.67 as reported. The lack of gross or histo-
pathology is a weakness in many of these studies, including this one.
It may be advisable to repeat these studies using multiple doses and good
pathological examination to determine possible target organs. Neuropathology
should be investigated in addition to effects on viscera. Further testing
employing chickens should also be undertaken.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular chemical.
Any review of the status report should take into consideration
the fact that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
203
-------
Current Production and Use
No information is available on the current production and use of this com-
pound; there is no entry in the TSCA Candidate List.
Comments/Re commendations
This chemical may have flame retardant uses; if so, it will be evaluated in
the ongoing Assessment Division investigation of flame retardant technology.
(a) Section 8(b) data should be checked for evidence of commercial pro-
duction.
(b) If the production level is sufficiently great, a CHIP investigation of
this material is suggested.
(c) The submitter should be asked to support his contention that the
information presented in this submission reasonably supports a con-
clusion of substantial risk.
204
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: May 3, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0478-0132
Approved
Revision
Needed
FROM.- Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Results of three tests conducted with poly(dibromophenylene oxide) (MC
935A). The first test was a mutagenicity evaluation, and the latter two
were acute toxicity studies on bluegills and trout. This notice was
declassified on May 22, 1978.
Submission Evaluation
The mutagenicity evaluation employed the BALB/3T3 mouse lymphoma cell test
system. The preliminary results provided in this notice indicated a
positive response; however, any conclusions must await receipt of the final
report.
Rainbow trout and bluegills were used in the acute (96 hour) static bio-
assay of MC 935A. The compound is reportedly only slightly soluble in
acetone, although soluble in water. The test tanks contained a precipitate
of the material, which means that the initial nominal concentration is
nowhere near the actual concentration. The true value is likely to be much
lower than the reported concentrations due to the removal of the material
from solution by precipitation. Bluegills and trout showed no mortality at
the nominal concentrations used (up to 1,000 mg/1). Both species exhibited
behavioral effects (irritability - bluegills; excitability - trout) indicating
stress at concentrations above 32 mg/1. pH was within acceptable limits
throughout the test. DO showed no decrease during the rainbow trout test
but declined in the bluegill tanks (9.0 to 5.2 mg/1 in the control tank;
9.2 to 3.4 mg/1 in the acetone control; and 9.1 to 2.7 mg/1 in the test
tanks). This observation on the surface, appears inconceivable, and no
explanation was (or is presently being) offered. No replicate tests or
tanks were used.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular chemical.
Any review of the status report should take into consideration
the fact that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
205
-------
MC 935 is not acutely toxic to rainbow trout and bluegills at the levels
actually employed in this experiment. However, the use of nominal con-
centration reporting rather than actual measured values precludes any
real evaluation of the acute toxicity of this substance. Among the other
aspects that are not adequately covered are a description of the physical-
chemical properties of MC 935 and the purity of the test material.
Current Production and Use
No information was located on the production and use of this chemical;
there was no TSCA Candidate List entry.
Comments/Recommendations
Several other submissions have been received on MC 935A (8EHQ-0278-0066;
8EHQ-0378-0090; 8EHQ-0378-0103). This chemical will be evaluated as part
of the ongoing Assessment Division examination of flame retardant tech-
nology.
(a) All submissions on MC 935A should be referred to the PBB workgroup.
(b) The questions raised in the evaluation section should be clarified
with a follow-up to the notifier; the molecular structure is also
unclear. The submitter should also be asked to support his contention
that the information presented in this submission reasonably supports
a conclusion of substantial risk.
(c) Section 8(b) data should be checked for evidence of commercial signif-
icance.
(d) This chemical may be a CHIP candidate if production is significant.
206
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: May 3, 1978
SUBJECT: Status Report 8EHQ-0478-0133
Approved^
Revision
Needed
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
T0: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Report that a commercial mixture of sodium nitrite and triethanolamine is
contaminated with 6 ppm of N-nitrosodiethanolamine. This notice was declas-
sified on May 22, 1978.
Submission Evaluation
It is not surprising that nitrosamine contamination was encountered in this
mixture as other similar formulations (cutting fluids and some cosmetics)
are also known to have a nitrosamine problem. N-nitrosodiethanolamine is,
as reported in the submission, a known rat carcinogen. It is essential
that users of this product be informed of the nitrosamine problem so that
proper caution can be exercised. Disposal of this product may also merit
inquiry.
Current Production and Use
The current production and use of this specific product are not known;
similar generic mixtures, however, are produced in the millions of pounds
per year range.
Related Past and Present Activities
A CHIP report on cutting fluids is available from the Assessment Division;
some discussion of N-nitrosodiethanolamine can be found in that report.
Comments/Recommendations
Several European countries as well as Canada have banned the use of nitrate/
nitrite salts in combination with secondary and tertiary amines in cutting
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular chemical.
Any review of the status report should take into consideration
the fact that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
207
-------
fluids because of the nitrosamine problem. NIOSH, OSHA, and FDA are
currently addressing the problem of nitrosamine-contaminated products.
OTS must be prepared to assist these other agencies wherever possible,
e.g., 8(a) information on the identification of nitrosamine-contaminated
products, 8(d) information on animal studies conducted with (a) nitros-
amine-contaminated products (hydraulic fluids, cutting fluids, etc.) or
(b) nitrosamines in general (this will bring in a lot of extraneous
information, but the first approach may miss important studies if not
carefully drafted).
(a) The notifier should be requested to inform all users and distrib-
utors of this product of the nitrosamine problem.
(b) Use information should be requested from the notifier and, if
appropriate, OSHA, NIOSH, FDA, and/or CPSC should be alerted to any
problem areas within their jurisdiction (based on the pattern of
use).
208
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 14, 1978
SUBJECT: status Report 8EHQ-0478-0134 Approved
Revision
FROM: Joseph J. Merenda, Acting Director flf' Needed
Assessment Division, OTE/OTS (TS-7
V
T0. Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Acute toxicity studies of chlorendic anhydride (CA) in rabbits and rats.
This notice was declassified on 5/22/78.
Submission Evaluation
The sample of chlorendic anhydride was 98.81% pure; the remaining 1.19%
was not characterized.
Under the conditions of the test, CA would be considered a primary eye
irritant in rabbits. In the rabbit primary skin irritation study,
erythema and edema occurred in all test animals (500 mg of CA applied
once; response was the same with intact and abraded skin).
The rabbit acute dermal toxicity study used only 8 animals, 4 per dose
group (2 of each sex), and there were no controls. The compound is
absorbed through the skin of rabbits and produced symptoms in all
those tested. CA was lethal to both male rabbits at the higher dose
(2,000 mg/kg); one must assume, therefore, until proven otherwise that
chlorendic anhydride is more toxic to males. The described effects
indicate generalized congestion in various organs, particularly the
lungs. These may have resulted either from irritation and release of
histamine or from the alarm reaction via stimulation of the adrenal
cortex. Ataxia, decreased limb tone, abnormally slowed breathing, and
hypoactivity were observed in the longer-lived (7 vs. 4 days) male rabbit
(at the high dose) and may indicate CNS effects by dermal exposure.
The toxicity (oral, acute) observed in rats may be attributed to the
consequences of an alarm reaction via the adrenal glands. The alarm
reaction can cause pathologic changes in the thymus and gastrointestinal
tract and may result in irreversible cardiovascular shock. One female
rat demonstrated alopecia, or abnormal loss of hair between days 6-11.
Alopecia occurs frequently in rats that have vitamin and nutritional
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
209
roHw im* IMCV.
-------
deficiencies. Perhaps the submitter should be asked to clarify if this
was the case. Once again, various CNS-related effects were observed
in the test animals.
Current Production and Use
An estimated 10 million Ibs. of chlorendic anhydride/acid were produced
in 1974 with an expected annual growth rate of 10% through 1980. Reported
uses of the anhydride include: flame resistant polyester resins;
hardening agent for epoxy resins; chemical intermediate; source of
chlorendic acid.
Related Past and Present Activities
An early warning report on hexachlorocyclopentadiene contains some
discussion of CA and is available from the Assessment Division.
Comments/Recommendations
Several other submissions have been received on CA (8EHQ-0278-QQ58;
8EHQ-0278-0059; 8EHQ-0378-0101; 8EHQ-0478-0127).
a) The submitter should be asked to address the alopecia comment
raised in the evaluation section. Better analytical charac-
terization of the samples should also be requested.
b) An early warning examination of CA is scheduled for the near
future. It may be necessary to use section 8(d) to collect
sufficient information for the report.
c) NIOSH and OSHA may be interested in this information.
210
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: May 1, 1978 (Revised May 10, 19.79)
SUBJECT: Status Report 8EHQ-0478-0135
Approved
Revision
Needed
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Letter describing an individual who developed a malignant bladder cancer
following occupational exposure to several suspected animal carcinogens
(especially toluene-2,4-diamine and toluene-2,6-diamine).
Submission Evaluation
Most aromatic amines are suspected carcinogens, as is well known in the dye
industry. As a class they cause liver pathology and are excreted in the
urine after transformation in the liver. Benzidine and beta-naphthylatnine
are the classical examples of such compounds producing cancer of the urinary
bladder.
Some diamines, notably p-phenylenediamine, are skin sensitizers and release
histamine. p-Phenylenediamine is used in mascara and fur dyes. The former
use was recently banned by the FDA. Toluene-2,6-diamine has some of the
properties of p-phenylenediamine.
Current Production and Use
Toluene-2,4-diamine production in 1975 exceeded 190 million pounds, accord-
ing to the U.S. ITC. The principal use is in the production of toluene
diisocyanate (TDI) foams, elastomers, and coatings; other uses include dye
intermediate and a direct oxidation black for furs and hair.
Toluene-2,6-diamine is produced as such by only one company; however, it is
present in the toluene-2,4-diamine used to make TDI foams and resins.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular chemical.
Any review of the status report should take into consideration
the fact that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
211
-------
Related Past and Present Activities
The OTE "expert evaluation" contractor has examined selected articles
pertinent to the carcinogenic and mutagenic potential of toluene-2,4-diamine.
Comments/Recommendations
It appears from the submission that the cancer is located in the urinary
bladder (as opposed to the gall bladder), although this point is not
specifically made as such.
(a) This submission should be referred to NIOSH and OSHA for appropriate
follow-up.
(b) A letter should be sent to the submitter requesting that other workers
(current and previous) be checked for reports of possible malignancies
and that the results be forwarded to EPA.
212
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: May 4, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0478-0136
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
Approved^
Revision
Needed
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submis s ion De s c r ip t ion
Corporate memo describing apparently conflicting data in two mouse lymphoma
assays with MC-984 [bis(l,3-dichloro-2-propyl)-3-chloro-2,2-dibromomethyl-l-
propyl phosphate]. These studies were previously submitted as 8EHQ-0278-0053
and 8EHQ-0478-0107. MC-984 has also been the subject of several other sub-
missions (8EHQ-1277-0022; 8EHQ-0178-0033; 8EHQ-0278-0048} 8EHQ-0278-0049;
8EHQ-0378-0100). (MC-984 is also known as VC-984).
Submission Evaluation
The discrepancy between the two mouse lymphoma studies was noted at the
time of our initial evaluation. The situation was discussed with Dr.
Herbert Rosenkranz of New York Medical College. He recommended that
the study be repeated twice to resolve the problem. Dr. Rosenkranz
feels that it is good scientific procedure to repeat these particular
studies when discrepancies of this nature occur.
Current Product ion and Use
No information on production and use is available, nor is there a
listing in the TSCA Candidate List.
Coimnents/Recommendations
(a) The remarks offered in the evaluation section should be transmitted
to the submitter for his consideration.
(b) The submitter should be asked to support his contention that the
information presented in this submission reasonably supports a
conclusion of substantial risk.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM I32O-S (REV. 3-76)
213
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 21, 1978 (Revised May 10, 1979) Approved
SUBJECT: Status Report 8EHQ-0478-0137
Revision
Needed
PROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
TO! Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Acute inhalation toxicity of FM 100 (hexabromocyclododecane) in rats.
Submission Evaluation
The weakness of this study is that it was not done on FM 100 but on a
residue which contains a flammable liquid (FM 100 presumably has low
flammability; therefore, some other material must also be present). In
this instance, the absence of controls is not of as great a concern to
as the fact that the animals showed dyspnea. This could be due either
to reflex nervous sytem effects or to direct irritant effects on the
tracheobronchial tree and/or the lungs. The squinting suggests that
there was considerable irritation. The fact that effects persisted
beyond the exposure period and that there was considerable loss in body
weight suggests that there was pulmonary damage. The dry blood seen
around the nose and in the passageway of the lungs at autopsy suggests
that irritant injury had occurred. The most important point at this
time concerns an adequate analytical characterization of the test compound.
Current Production and Use
Hexabromocyclododecane (HBCD) is listed in the Directory of Chemical Producers,
thus indicating that it is produced in commercial quantities (>1,000
Ib/yr). HBCD is used as a fire retardant in copolymers of styrene with
acrylonitrile, N-vinylpyrrolidine, divinylbenzene, methylacrylate, poly
(methyl methacrylate), or polyethylene. It is also used as a fire
retardant in molded and foamed thermoplastic polystyrenes and in polypropylene-
based molding compositions. When incorporated into these plastics, HBCD
imparts a self-extinguishing property to the material.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e\ of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 1320-6 (REV. 3-76) 214
-------
HBCD is also used in the production of adhesives used for cementing
(luting) polystyrene foam sheets. This use arises from its ability to
reduce the molding time necessary for cellular polystyrene particles to
form into a compact foam block.
Comments/Recommendations
Several other submissions have been received on FM 100 (8EHQ-0278-0051;
8EHQ-0278-0065; 8EH0^02 78-0088). The chemical will be evaluated as part
of the Assessment Division's ongoing study of flame retardant technology.
FM 100 may be an environmentally persistent compound.
(a) This submission, like others, was deficient in a number of areas.
The notifier should be asked to provide adequate analytical data on
the composition of the mixture tested, gross findings on death,
clinical observations, and physical-chemical data on the test
substance.
(b) This submission should be referred to NIOSH and OSHA.
(c) The submitter should be asked to support his contention that the
information presented in this submission reasonably supports a
conclusion of substantial risk.
215
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE-. May 5, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0478-0138P
Approved
Revision
Needed
PROM: Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Corporate memo describing a case of eye irritation in an office worker due
to dicyclopentadiene alcohol and/or benzoyl chloride. Several submissions
have noted problems with occupational exposure to dicyclopentadiene or its
alcohol (8EHQ-1177-0017P; 8EHQ-0278-0077P; 8EHQ-0378-0097).
Submission Evaluation
An office worker in a chemical plant reported moderate eye irritation
following possible exposure to benzoyl chloride and/or dicyclopentadiene.
Either compound is capable of producing this type of irritation. The
metabolites of benzoyl chloride are benzoyl glycine and hippuric acid.
Likely metabolites of dicyclopentadiene are glucuronides or ethereal
sulfates. Any of these metabolites are easily measured in urine samples.
Production line workers may be exposed to higher levels of these compounds.
Urine tests on these workers would help define the extent of exposure to
the chemicals of concern.
Current Production and Use
Annual production of dicyclopentadiene alcohol is not known; there is no
entry in the TSCA Candidate List. Dicyclopentadiene, the parent compound,
was produced in excess of 77 million pounds in 1975 (includes cyclopentadiene)
Benzoyl chloride is used in the production of Pharmaceuticals, as an inter-
mediate for the introduction of the benzoyl group, and as an intermediate
for the production of other organics. Production level is not known, but
is greater than 1,000 pounds per year.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular chemical.
Any review of the status report should take into consideration
the fact that it may be based on incomplete information.
EPA FQRM t!i»-« (REV. 3-76)
216
-------
Comments/Recommendations
(a) Notify OSHA of incident for possible follow-up. This plant site
may be a candidate for a NIOSH inspection visit as several pr blems
have been apparent there.
(b) Request full report from attending physician.
(c) Dicyclopentadiene is scheduled for CHIP treatment in the near
future.
(d) The submitter should be asked to support his contention that the
information presented in this submission reasonably supports a con-
clusion of substantial risk.
217
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE-. May 2, 1978 Approved^
SUBJECT: Status Report 8EHQ-0578-0139
Revision
Needed
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
A letter reporting that two trade name products which are sold to cosmetics
manufacturers contain 2-chloroethanol at concentrations between 1 and 3%.
The trade name mixture when formulated into the cosmetics represents 1 to
2% of the final cosmetics products (cream rinses and other hair products).
Thus the 2-chloroethanol concentration of the commercial cosmetics is be-
tween 0.01 and 0.06%.
Submission Evaluation
Ethylene chlorohydrin (2-chloroethanol) is a known highly toxic compound,
both in liquid and vapor form. The vapors affect the lungs, heart, and
brain. The liquid is irritant to skin and mucous membranes and is readily
absorbed through the skin. The absorbed compound causes kidney and liver
degeneration. The effects may be cumulative. Three percent residues of
unreacted 2-chloroethanol in the finished product is a highly significant
amount of such a toxic compound and does present a substantial risk of
injury to health. Because the finished products are used in the manufacture
of cosmetics that are applied to the scalp and have access to the rest of
the skin and because the effects of 2-chloroethanol are reported to be
cumulative, OSHA should be notified to determine effects on workers and FDA
should be notified for possible effects on consumers, even though the
finished product will have no more than 0.06% chloroethanol.
Current Production and Use
The annual production of the two trade name products is not known. 2-
Chloroethanol, as such, has many uses: solvent, organic intermediate, etc.
Annual production of the chemical is reportedly greater than 1,000 pounds;
however, the actual production is likely to be appreciably higher.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular chemical.
Any review of the status report should take into consideration
the fact that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
218
-------
Related Past and Present Activities
The Assessment Division has a Hazard Assessment on haloalkanols scheduled
for completion in March 1979.
Comments/Recommendations
(a) This information should be transmitted to the FDA Division of Cosmet-
ics Technology as rapidly as possible for appropriate follow-up.
(b) Referral to NIOSH and OSHA also appears advisable.
219
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
June 28, 1978
SUBJECT: Status Report 8EHQ-0578-0140
Approved
Revision
Needed
FROM- Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-$?)
T0 Viarren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/QTS (TS-792)
Submission Description
Results of mouse skin painting studies conducted with various petroleum
distillates.
Submission Evaluation
The significant point here is that the report shows that several of the
seven tested petroleum distillates induced squamous cell carcinomas in
the test animals (the report clearly states that 4/7 induced squamous
cell carcinomas; the 3 remaining distillates were shown to have induced
carcinomas following unspecified later studies on other materials ).
The time to first observable tumor varied from three months (four of the
seven mixtures in both sexes) to one year (one of the mixtures; in
females only, the males developed tumors at six months). Undefined
later studies determined the following tumor types: squamous cell
carcinomas (observed with all seven of the test oils); benign epithelial
papillomas; hyperkeratosis; acanthosis; and "conditions of irritation
having mononuclear cell invasion of tissue." An estimate is offered
that, in most cases, "at least 80% of (the) observable masses would be
classified as tumors (benign or malignant) with a great majority being
benign epthelial papillomas."
The applied dose was rather large (20 mg thrice weekly) and the test
materials appear to (possibly) be acting as their own initiators and/or
promoters.
A more complete review of the information generated in preparing this
notice is indicated, therefore, the following should be requested:
a) All relevant data (complete report with raw data; chemical
analysis of the tested petroleum distillates).
b) Complete description of the "later studies" (copy of final
report; raw data; slides; any analytical work) determining
the histopathology of any tumors, including those possibly
found in internal organs.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
OHM tUft-« (MCV.
-------
Current Production and Use
Six of the seven oils are apparently still available commercially; one
has been modified and is no longer sold in the form tested. Petroleum
distillates are very complex mixtures of hydrocarbons derived from crude
oil. They are generally characterized by viscosity and identity of the
refinery stream (paraffinic, naphthenic, catalytically cracked, etc.).
Related Past and Present Activities
OPP has scheduled a conference to address the question of petroleum
distillates.
Comments/Recommendations
Several other submissions have involved petroleum distillates (3EHQ-
1277-0026C; 8EHQ-0178-0029; 8EHQ-0178-0030; 8EHQ-0278-0044; 8EHQ-0478-
0117).
a) This information should be referred to NIOSH and OSHA as
much exposure to these products is occupational in nature.
CPSC and OPP should also receive the available information.
b) The information outlined in the evaluation section should
be requested.
221
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: December 5, 1978 (Revised May 10, 1979) Approved_
SUBJECT: Status Report 8EHQ-0578-0141 Revision
Needed
FROM: Frank D. Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
The results of three separate tests on VC 935A [poly(dibromophenylene)
oxide; also known as MC 935A]: (a) modified Draize multiple insult test in
humans; (b) acute toxicity in Daphnia (water flea); (c) transformation
assay in mouse BALB/3T3 cells.
Submission Evaluation
(a) It would be helpful to know how the modification of the Draize test
was used and how this modification differs from the standard Draize
test. The results suggest that about 6% of the subjects experienced
cumulative irritant reaction. The results suggest that the compound
or the plastic has cumulative irritant potential unless the reactions
experienced by the three subjects can be otherwise accounted for.
Since this polymer may be derived from dibromophenol or dibromodi-
phenol oxide, it would be desirable to know how much of these materials
and other low-molecular-weight substances are present in the plastic.
These low-molecular-weight compounds might account for the cumulative
irritation.
(b) According to this static acute bioassay, MC 935A is not lethal to 50%
of the test Daphnia at very low (£5-6 ug/1) concentrations. Higher
concentrations of the compound were not tested because of its limited
solubility; concentrations greater than 5.6 vg/1 resulted in the
formation of a precipitate which entrapped the Daphnia. DO and pH
were acceptable throughout the test. The report states that the no-
effect level was 3.2 yg/1; however, it is not clear if the "effect" is
lethality or some behavioral aberration. Five percent mortality was
seen at the next higher concentration, 5.6 ug/1 (the highest concentra-
tion tested because of the precipitation problems noted earlier). If
this mortality was not due to random effects and can in fact be attrib-
uted to the chemical, this would mean that MC 935A is very toxic to
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular chemical.
Any review of the status report should take into consideration
the fact that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
222
-------
Daphnia (LCrQ in the ppb range). Although the limited water solubility
may mediate the effects on pelagic organisms, the indication that this
chemical has any biological activity at such low levels is cause for
concern. In the end analysis, the test was not sufficiently definitive
nor did it yield sufficient information to support any strong conclu-
sions. It may be wise to retest that material to confirm its possible
extreme toxicity to Daphnia.
(c) MC 935A caused malignant transformations in BALB/3T3 cells; thus some
concern for its oncogenic potential should be recognized. The results
could be due to unreacted monomer, etc., in the plastic. If there is
significant human exposure to this material, then more intensive
studies are indicated because there is the possibility that the
plastic or entrapped chemicals are oncogenic.
Comments/Recommendations
Several submissions have been received on this chemical (8EHQ-0278-0066;
8EHQ-0378-0090; 8EHQ-0378-0103; 8EHQ-0478-0132).
(a) Section 8(b) data should be checked to determine the annual production
of VC 935A. '
(b) If the chemical is commercially viable, it should be given CHIP and/or
NIOSH/OSHA consideration.
(c) This submission should be referred to the PBB workgroup.
(d) The submitter should be asked to provide more information supporting
his contention that VC 935A presents a substantial risk of injury to
health or the environment.
223
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 15, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0578-0142
Approved_
Revision
Needed
FROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
This notice reports the results of three tests conducted on tetrabromo-
bisphenol A (FM BP4A). The first two studies investigated the acute
toxicity of FM BP4A in bluegill sunfish and rainbow trout; the third study
involved a modified Draize multiple insult test in humans.
Submission Evaluation
Bioassays of tetrabromobisphenol A were conducted using rainbow trout and
bluegill sunfish. The chemical is fairly toxic to both species, the 96-
hour LC5Q being 0.40 tng/1 for trout and 0.51 mg/1 for bluegills. Behavioral
abnormalities (irritation, erratic swimming behavior, labored respiration)
were seen in bluegills at levels below 0.32 mg/1 and in rainbow trout below
0.18 mg/1. These concentrations are nominal, i.e., no measurement of the
actual concentration was conducted; therefore, all results can be reviewed
only qualitatively. The compound is soluble in acetone, which was used as
the carrier in these experiments. No replicate tests or tanks were used.
DO and pH seemed within acceptable limits, although DO was reduced to 2-4
mg/1 during the course of the 96-hour test. No mention of the purity of
the compound was made; thus the presence of potential contaminants cannot be
ruled out. The low LC^Q and low effect levels attributed to FM BP4A are
cause for great concern if the material enters surface waters. A previous
submission (8EHQ-0478-0116) indicated that the octanol-water partition
coefficient for this compound was 30,000. If this material has a tendency
to bioaccumulate in the food chain, some EPA response will likely be required.
The description of the third study fails to indicate how the Draize test
was modified and how the method employed differs from the standard test
most commonly used. One study reported in the literature revealed a strik-
ing incidence of false negative reactions with several skin tests in current
use. The difficulty with these tests is one of adequate contact between
the test substance and the skin and adequate inclusion. Many substances,
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular chemical.
Any review of the status report should take into consideration
the fact that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
224
-------
such as lanolin and some of the antiseptics used to preserve lotions and
detergents, have been found to be sensitizers only during epidemiology
studies.
Comment on the Draize Test
The Draize test for skin irritation consists of application of the suspected
substance to the skin of rabbits to determine whether the material is an
irritant. The test correlates well with the findings in humans. Rabbit
skin develops redness and hardening which is similar to that in man and can
be easily quantitated.
Three types of irritation are now recognized. (1) Ordinary irritation is
defined as a dermatitis resulting from the contact with a chemical and
which is not mediated by an immunological mechanism. Only the severest
irritants give a reaction on the first exposure. (2) Chemicals may have a
cumulative irritancy potential rather than single-exposure potential. Such
cumulative irritancy is also nonimmunologically mediated. (3) Sensitization
dermatitis may occur in situations where cumulative irritancy is present.
Sensitization, however, requires the formation of antibodies and a subsequent
immunological reaction. At the present time, contact dermatitis in the
sense of Sensitization is not as widely diagnosed. Most so-called contact
dermatitis resulting from irritants and cosmetics does not have an immuno-
logical basis but is due to cumulative irritancy.
There is also a modified Draize test for Sensitization. This requires
repeated application of the compound to rabbits or guinea pigs with sub-
sequent challenge. The correlation with human reactions is good, and the
test has use as a predictor. The human Sensitization assays are modifica-
tions of the guinea pig assay. All of these tests have an incidence of
error, and many modifications exist which center around enhancing the test
by first damaging the skin with such things as detergents.
Current Production and Use
The U.S. ITC identifies only one producer of FM BP4A; the recent "Bromine
Based Fire Retardants" report identified three producers. Annual production
may be of significance as the chemical is used as an intermediate for a
good number of other flame retardants in addition to having fire retardant
applications of its own. Reported flame retardant applications include use
in paper, textiles, and many plastics and polymers (ABS, epoxy, polycarbonate,
polyesters, polypropylene, polystyrene, etc.).
Comments/Re commendations
Several other submissions have concerned tetrabromobisphenol A or its
derivatives (8EHQ-1277-0025; 8EHQ-0478-0130).
225
-------
(a) This chemical was previously (8EHQ-0478-0116) recommended for a CHIP
examination; the present notice supports that suggestion.
(b) In view of DHEW's policy requiring sufficient animal testing before a
drug or other material can be used for human testing, the submitter
should be asked to provide assurances that the investigating dermatolo-
gist was supplied with adequate animal data before the decision to
conduct the human tests was made. In addition, the C.V. of the
dermatologist should be supplied such that a determination of the
investigator's fitness to make the decision that a chemical should or
should not be tested on humans can be evaluated. This policy should
be followed with respect to all 8(e) submissions concerning human
studies. In addition, it may be wise to consider the inclusion of
these points in any future clarification of the 8(e) Policy Statement.
(c) While the compound is fairly toxic to fish, the submitter has failed
to provide the other information specified (for such submissions) in
Part V(b)(3) of the March 16, 1978 Policy Statement (43 FR 11110).
This states that reportable substantial risk information includes
that which demonstrates "any non-trivial adverse effect...associated
with a chemical known to have bioaccumulated to a pronounced degree
or to be widespread in environmental media" (emphasis added). The
submitter should therefore be asked to provide additional information
supporting his contention that FM BP4A presents a substantial risk of
injury to health or the environment.
226
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 15, 1978 (Revised May 10, 1979) Approved
SUBJECT: Status Report 8EHQ-0578-0143
Revision
Needed
FROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Acute rat inhalation toxicity study of the monopropanol ester of tetra-
bromophthalic anhydride.
Submission Evaluation
Several problems were evident in the experimental protocols: use of
calculated exposure concentrations rather than analytically determined
values; inadequate number of experimental animals; lack of gross or
his topathology.
Dyspnea was observed in the female rats after 10 minutes and in all rats
after 20 minutes; however, after 30 minutes a few of the animals had an
increased respiratory rate. The submitter should address the following
questions: are females more sensitive, and if so, why; is the dyspnea a
peripheral nervous system effect, a CNS effect, or is it due to secondary
or local irritation; is the increased respiratory rate a second phase of
the animals' response or is it due to anoxia caused by the dyspnea; etc.
Indications are that the compound is a histamine or other irritation
transmitter releaser which could produce all the signs described in the
toxicity report. The histamine release may be due to the esterified
molecule or to the tetrabromophthalic acid released on hydrolysis. The
toxicity of the molecule and tetrabromophthalic acid needs further
investigation.
Current Production and Use
The material is apparently used as a flame retardant, although no specific
information on production and uses is available. There is no entry in
the TSCA Candidate List.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the stacus report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 1320-6 (REV. 3-76)
-------
Comments/Recommendations
This chemical may have some flame retardant applications; if so, it will
be evaluated as part of the ongoing Assessment Division study of flame
retardant technology.
(a) Section 8(b) data should be checked to determine commercial significance.
(b) This submission should be referred to the PBB workgroup.
(c) If the chemical appears commercially viable, it should be given
CHIP and/or NIOSH/OSHA consideration.
(d) The submitter should be asked to support his contention that the
information presented in this submission reasonably supports a
conclusion of substantial risk.
228
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: May 12, 1978 (Revised May 10, 1979) Approved_
SUBJECT: Status Report 8EHQ-0578-0144
Revision
Needed
FROM: Frank D. Rover, Acting Director
Assessment Division, OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Results of an acute oral toxicity study of CN-110-356 [0-methyl-0-((2-
isopropylcarbonyl)-l-methylvinyl) thiophosphoryl benzamidine] in rats.
Submission Evaluation
CN-110-356 appears to be a malathion or parathion analog. It is also a
phosphoramide. From its potency (LD5Q =10.8 mg/kg) and from the speed
with which it is lethal, the compound appears to be an anticholinesterase
substance. If, like parathion, sulfur is removed in the organism and
replaced by oxygen, a more potent cholinesterase inhibitor will be
produced. Female rats appear to be about twice as sensitive as male
rats to the lethal action. A number of inadequacies were apparent in
this report: there was no measure of the purity of the compound; body
weight measurements should have been conducted on days 1, 2, and 3 in
addition to days 7 and 14; no gross or histopathology was performed.
Current Production and Use
No information was located on the production and uses of this chemical,
nor was there an entry in the TSCA Candidate List.
Comments/Recommendations
(a) The chemical name provided is somewhat unclear; the submitter
should be asked to clarify the nomenclature and provide a drawing
of the molecular structure. Use information would also be of
value.
(b) 8(b) data should be checked for evidence of conmercial significance
(c) This material may be a pesticide-related product; refer to OPP.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 1320-6 (REV. 3-76) 229
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: May 11, 1978 (Revised May 10, 1979)
SOBJiCT: status Report 8EHQ-0578-0145
Approved
Revision
Needed
FROM: Frank D. Kover, Acting Director
Assessment Division, OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTS (TS-792)
Submission Description
Results of a modified Draize multiple insult test in humans with MC-948
[bis(tribromoneopentyl) pentaerythritol cyclic diphosphate; also known as
VC-948].
Submission Evaluation
The tested material does not appear to be a sensitizing substance by cur-
rent definitions, nor is it a strong irritant. However, it would be useful
to know which subjects had a + reaction and which had a definite 1+ irritant
response. The current thinking among experimental dermatologists is that
cumulative irritation potential is a significant reaction even though no
sensitization occurs. Only severe irritants provoke a nonimmunological
reaction on short application. On what day did the 1+ irritant response
occur in subjects? It is becoming recognized that such short-term tests
yield a high incidence of false negative results and therefore are not
accurate predictors of irritant or sensitization reactions in a mass pop-
ulation where even an incidence of 0.25 or 0.5% becomes highly significant.
Current Production and Use
No information is available on the production and use of MC-948, neither is
it entered in the TSCA Candidate List.
Comments/Re commendations
Several other submissions have been received on this chemical (8EHQ-0278-
0060; 8EHQ-0278-0071; 8EHQ-0378-0092; 8EHQ-0378-0098).
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular chemical.
Any review of the status report should take into consideration
the fact that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
230
-------
(a) Section 8(b) data should be checked for evidence of commercial signifi-
cance .
(b) If commercially viable, MC-948 may be a candidate for CHIP and/or
NIOSH/OSHA consideration.
(c) The submitter should be asked to support his contention that the
information presented in this submission reasonably supports a con-
clusion of substantial risk.
231
-------
, UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 14, 1978 Approved
SUBJECT: Status Report 8EHQ-0578-0146
Revision
Needed
FROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
TO-. Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Report describing health complaints voiced by construction workers at a
chemical plant in Louisiana. The workers were reportedly exposed to a
variety of airborne chemicals including chlorine gas, trichloroethylene,
perchloroethylene, hydrogen chloride, and sulfur monochloride (possibly
also acrolein, diammonium phosphate, and various hydrocarbons). The
workers' complaints included loss of taste and smell, muscle weakness,
various neurological disorders, fatigue, and other health problems.
Submis s ion Ev aluation
Acrolein as well as all of the chemicals listed in the table on p. 2 of
the submission are well-established respiratory irritants. The chlori-
nated hydrocarbons are also neurotoxins. No data relating to intensity
and duration of possible exposure to these chemicals are submitted.
Therefore, it is not possible to even guess whether the complaints are
related to these compounds.
Current Production and Use
All of the chemicals listed in the submission are relatively high-volume
industrial materials. The submitter's Louisiana plant reportedly produces
chlorine, perchloroethylene, sodium chlorate, sodium hydroxide, sulfur
monochloride, 1,1,2,2-tetrachloroethane, and trichloroethylene.
Related. Past andPresent Activities
A hazard assessment on trichloroethylene and perchloroethylene is cur-
rently underway in the Assessment Division; a CHIP report on acrolein is
also available.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 1J2O-6 (REV. 3-76)
-------
C omment s/Re commendati ons
The submission notes that medical reports on the exposed workers are
available; these should be requested from the submitter.
This information as well as any developed subsequently should be referred
to NIOSH and OSHA for appropriate follow-up.
233
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 22, 1978
SUBJECT: Status Report 8EHQ-0578-0147
Approved
Revision
Needed
FROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Letter reporting chlorinated hydrocarbon contamination of ground water and
one drinking water well near a chemical plant in Michigan. Identified
ground water contaminants are: hexachlorocyclopentadiene, hexachloroben-
zene, hexachlorobutadiene, octachlorocyclopentadiene, chloroform, carbon
tetrachloride, trichloroethylene, and perchloroethylene. The last four
compounds listed, but not the others, were found in the well water.
Submission Evaluation
Contamination levels were not stated; therefore, no evaluation of the
hazard is possible. The chemicals involved in the contamination problem
are known human health hazards and some are included in EPA drinking water
standards. The submitter claims to have alerted state and EPA regional
authorities of the situation and are apparently working with them. The
notice includes an offer to provide OTS with results of the analytical work
and copies of the reports previously sent to the Michigan Department of
Natural Resources.
Current Production and Use
Several of the chemicals are high-volume industrial products (trichloro-
ethylene, perchloroethylene, carbon tetrachloride, hexachlorocyclopentadiene,
and chloroform). Others are mainly chemical waste products (hexachlorobenzene,
hexachlorobutadiene, and octachlorocyclopentadiene).
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular chemical.
Any review of the status report should take into consideration
the fact that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
234
-------
Related Past and Present Activities
All of these chemicals have been examined in the Office of Toxic Substances
at one time or another. Among those under current investigation are trichloro-
ethylene, perchloroethylene, hexachlorobenzene, and chloroform. ORD is Investi-
gating hexachlorocyclopentadiene.
Comments/Recommendations
(a) The reports noted in the evaluation section should be requested from
the submitter.
(b) A copy of this notice should be sent to EPA Region V and Michigan DNR
with a request that they confirm the situation as presented by the
submitter. Any additional actions required to resolve the matter
should be identified by DNR and Region V.
235
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 23, 1978 Approved^
SUBJECT: Status Report 8EHQ-0578-0148
Revision
Needed
PROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
A letter summarizing the results of a series of mouse skin-painting
studies conducted in the 1960's using certain hydrotreated paraffinic
distillate fractions.
Sjabmissjion Evaluation
The submission per se is inadequate because it lacks the following
information: complete copy of the final report submitted by the con-
ducting lab; adequate analytical identification of the material tested
(including boiling point, viscosity, major components, and manufacturing
process).
The submission notes that manufacture of these distillate fractions via
the hydrotreating process was halted in August 1977. Presumably, these
materials are no longer in use; therefore, these studies are of limited
relevance in the present context. It is important that toxicity studies
be conducted on the materials currently in use (i.e., solvent extraction
or a combination of solvent extraction and hydrotreating).
Current Production and Use
Insufficient information is provided to permit a determination of the
current production and use of these materials.
Comments/Recommendations
Several other submissions have reported the results of skin-painting
studies with petroleum fractions (8EHQ-1277-0026C; 8EHQ-0178-0029; 8EHQ-
0178-0030; 8EHQ-0278-0044; 8EHQ-0478-0117; 8EHQ-0578-0140).
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take Into
consideration the fact that it may be based on incomplete
information.
EPA FORM 1320-6 (REV. 3-76) 236
-------
(a) This information should be referred to NIOSH and OSHA as most
exposure to these products is occupational in nature.
(b) The inadequacies noted in the evaluation section should be rectified
via a follow-up to the submitter. The availability of toxicity
data on the currently produced fractions should also be determined.
In addition, a description of the uses of these petroleum fractions
should be requested in the follow-up letter.
(c) Section 8(b) data should be checked to determine if other producers
are currently manufacturing similar petroleum fractions (based on
the CAS numbers provided).
237
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 15, 1978
SUBJECT: Status Report 8EHQ-0578-0149
Approved_
Revision
Needed
FROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
The submission consists of the results of a medical review conducted on
employees who were accidentally exposed to methyl mercaptan, dimethyl
disulfide, and acetonitrile. The submitter notes that the health effects
which occurred in this incident can be adequately explained by the well-
known toxicity of methyl mercaptan. The submitter's particular concern in
this matter is the apparent lack of sufficient odor or irritation to serve
as an adequate warning of the presence of these toxic materials.
Submission Evaluation
Methyl mercaptan is a known poison with the ability to provoke CNS and
local respiratory stimulant and irritant actions. Acetonitrile releases
cyanide in the body. The victims had classical signs of some degree of
edema of the lungs, and their response to medical treatment tends to confirm
this. The florid color of the skin was probably due to widening of the
arteries in the skin by acetonitrile or the cyanide present in the blood.
Some of the laboratory findings concerning blood counts and electrolytes
are traceable in part to the administration of diuretics and corticosteroids.
With respect to the workers' lack of adequate sensory warning, the explana-
tion may possibly include sensory (especially olfactory) fatigue such that
the sensing organs failed to indicate the greater concentrations. This is
known to happen with hydrogen sulfide when the perceived odor of the gas is
about as strong with nearly harmless concentrations as with those that
would be very dangerous. Because of this, the use of some type of warning
device may be indicated; e.g., lead or silver paper may be sufficiently
sensitive to these agents to blacken upon exposure. OSHA and NIOSH may
want to consider looking into this.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular chemical.
Any review of the status report should take into consideration
the fact that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
238
-------
Current Production and Use
The annual production of acetonitrile is estimated to be greater than 135
million pounds. The production of dimethyl disulfide is not known, whereas
methyl mercaptan is reportedly produced in quantities greater than 1,000
pounds per year. Acetonitrile is used as a solvent in hydrocarbon extrac-
tion processes and as a starting material for acetophenone, naphthalene-
acetic acid, thiamine, acetamine, vitamin Bj, substituted pyrimidines, and
various Pharmaceuticals. Methyl mercaptan is used as an intermediate in
the production of methionine, jet fuel additives, and fungicides; it is
also used as a catalyst. While the annual production and uses of dimethyl
disulfide are not known, it is contained in the TSCA Candidate List.
Comments/Recommendations
This information should be transmitted to NIOSH and OSHA with the sugges-
tion that they initiate appropriate followups.
239
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 15, 1978
SUBJECT:.status Report 8EHQ-0578-0150 Approved
lylri Revision
FROM: Joseph J. MerendawActing Director Needed
Assessment Divis/in, OTE/OTS (TS-792)
T0. Warren R. Muir, Deputy Assistant Administrator
foY Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
The submission consists of two studies: (a) an estimation of the car-
cinogenicity and mutagenicity of some arsenic and cadmium compounds in
rats and (b) an evaluation of the impact of mining/smelting effluents on
aquatic organisms.
Submission Evaluation
(a) In this chromosomal aberration test, a number of compounds were
evaluated by injecting 1.0 rats i.p. and examining 25 bone
marrow metaphases per animal after varying periods of treatment.
The significant observation concerned the number of metaphases
with a gap or a break. The experimenter found that cacodylic
acid (dimethylarsinic acid), methyl arsenic acid, and cadmium
oxide were positive mutagens. The statistical test used,
chi square, is validly applied. However, in this case, the
power of the chi square test is low. This, type of experiment
should be performed so that one could use an analysis of
variance or a T test in order to increase the power of the
statistical test. Some indication of the variability found in
the control values would have been desirable; this could have
taken the form of either historical values or the use of a
number of different control groups.in the experiment (some rat
strains give more variable chromosomal aberration frequencies
than others). The three chemicals which gave positive results
are very likely mutagenic; however, the reported negative
values are viewed with less confidence for the reasons outlined
above. Both the 7 and 30-day studies lack positive and negative
controls. The conducting investigator should also be identified
(at least by company affiliation).
(b) The effects of calcium sulfate exposure on rainbow trout eggs
and fry were investigated. Sulfate is a major constituent of
mining/smelting effluents, ranging in concentrations from
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 1M»-« (REV. »-7«) 240
-------
540-700 mg/1. The test was adequately conducted, however,
some information is lacking. Two controls were employed:
one for hardness using calcium chloride and the other as
diluent water only. No information on fry survival was
presented for the diluent water control. This is important
information to have for comparative purposes. There appeared
to be no difference in results between the treated groups and
the hardness control groups; nonetheless, the analyses and
outcome of the statistical tests supposedly conducted should
have been presented. Sulfate does not appear to pose much of
a problem to rainbow trout eggs and fry, even at concentrations
as high as 732 mg/1.
Current Production and Use
No information on the annual production of cacodylic acid, methylarsenic
acid, and cadmium oxide was located. Cacodylic acid and methylarsenic
acid are used in the production of various pesticides. Electroplating,
manufacture of cadmium electrodes for alkaline storage batteries, and
the synthesis of other cadmium salts are the major uses of cadmium
oxide.
Related Past and Present Activities
phase I documents on arsenic and cadmium are currently in preparation.
Comments/Recommendations
a) The comments found in the evaluation section on the statistical
method should be transmitted to the submitter for possible
reconsideration of the approach used. The lack of controls
in the study should be noted as a deficiency as should the
anonymity of the investigator.
b) On the basis of this cursory review, the second study does not
appear to reasonably support the conclusion that calcium
sulfate poses a substantial risk to the environment. Perhaps
EPA should ask for additional documentation, if available, to
support the suggestion that sulfates pose a substantial risk
to rainbow trout.
241
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 14, 1978
SUBJECT: status Report 8EHQ-0578-0151
Approved
Revision
Needed
FROM- Joseph J. Me renda/Acting Director
Assessment Division, OTE/OTS (TS-792)
T0. Warren R. Muir, Deputy Assistant Administrator
fdr Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
The submission consists of several reports investigating the acute
toxicity of various chromium compounds, including sodium bichromate
crystals, sodium bichromate 69% liquid, sodium chromate crystals, and
chromic acid (chromium trioxide). The submission also included the
results of a rabbit eye irritation test conducted with a 27.5% solution
of hydrogen peroxide.
Submission Evaluation
The chromate toxicity studies do not significantly alter the descriptions
of the toxicological. effects already reported for chromates in the
literature. The studies do, however, expand the amount of information
obtained by current toxicity test methods, particularly the acute dermal
toxicity in rabbits. Preventive measures for workers exposed to chromates
have been described.
It has long been known that concentrated solutions of hydrogen peroxide
(approximately 30%) are highly corrosive and irritating to body tissues.
Such solutions can explode on contact with contaminants such as iron,
copper, other heavy metals, or organic matter.
Current Production and Use
Annual domestic production of sodium bichromate, dihydrate is estimated
at 314 million Ibs. Sodium bichromate, dihydrate is generally produced
from sodium chromate, decahydrate by the action of sulfuric acid. The
annual production of chromic acid is estimated at 60 million Ibs. Sodium
chromate is used in inks, dyeing, paint pigments, leather tanning,
production of other chromates, corrosion inhibition, and wood preserva-
tion. Sodium bichromate, dihydrate is used as a chemical reactant for
oxidation reactions, production of chromic acid, corrosion inhibitor,
pigment manufacture, leather tanning, electroplating, textile mordant,
defoliating agent, catalyst, and wood preservative. Chromic acid is
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
242
CPA POMM U»-« IMEV. »•?•)
-------
used in the production of various chemicals (chromates, oxidizing
agents, catalysts), chromium plating, intermediate, process engraving,
ceramic glazes, colored glass, metal cleaning, inks, tanning, paints,
and textile mordant.
Domestic production of hydrogen peroxide is estimated at 180 million
Ibs. yearly and its uses include: bleaching and deodorizing of textiles,
wood pulp, hair, fur, etc.; source of organic and inorganic peroxides;
pulp and paper industry; plasticizers; rocket fuel; foam rubber; dyeing;
antiseptic; chemical reagent; etc.
Related Past and Present Activities
A phase one document on chromium and its compounds is being prepared by
the Assessment Division. Many other publications on chromium or its
compounds are also available.
Comments/Recommendati ons
One other submission has been received on chromium compounds (8EHQ-0378-
0096).
a) A copy of the chromium information contained in this submission
should be entered in the Assessment Division's chromium file
for possible inclusion in future reports.
b) This submission should be forwarded to NIOSH, OSHA, CPSC, and
FDA for follow-up as needed.
243
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 14, 1978 Approved^
SUBJECT: Status Report 8EHQ-0578-0152
Revision
Needed
PROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
The submission consists of the results of several intact animal studies
conducted with CR141 [l,5,9-tris(N,N'-dibutyl-N,N'-bis(2,2,6,6-tetra-
methylpiperid-4-yl)-4,6-diamino-l,3,5-triazine-2-yl)-l,5,9-triazanonane].
Submission Evaluation
The laboratory investigations indicate that CR141 produced (a) severe
irreversible injury to the eye mucosa of rabbits; (b) slight erythema
and edema on skin application in rabbits; and (c) equivocal sensitization
in guinea pigs. It was also highly irritating to the respiratory tract
when administered by inhalation to rats.
CR141 appears to be a solid with some degree of water solubility. The
significance of the low degree of primary irritation in rabbits does not
necessarily indicate that the material will fail to produce cumulative
skin irritation in humans. The sensitization test is equivocal because
some of the guinea pigs died during the test period. The report indicates
that several of the guinea pigs were thought to have an "enteric (intestinal)
infection"; if this is true, the animals should not have been used in
this test. Nonetheless, the guinea pigs would have shown signs of
diarrhea before the tests were initiated. The observed diarrhea can
just as well be interpreted to indicate some autonomic nervous system
effects occurring during a type of allergic sensitization.
Current P r oduc t i on and Use
The submitter reports that they imported less than 100,000 pounds of
CR141 in 1977 from an Italian chemical concern. It is reportedly used
as a stabilizer in polypropylene polymers, although the submitter reportedly
no longer uses CR141.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 1320-6 (REV. 3-76)
244
-------
Comments/Recommendations
(a) Section 8(b) data should be checked to determine evidence of
the commercial significance of this material.
(b) If the importation or production of CR141 is sufficiently great,
consideration should be given to a CHIP examination of the material.
(c) This information as well as any developed in the future should
be forwarded to NIOSH and OSHA for appropriate follow-up.
245
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
15JUN1978
SUBJECT: Status Report* 8EHQ-0578-0153S Approved
Revision
PROM: Frank CBVKover Needed
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
Results of rabbit acute dermal toxicity studies on 2-amino-
2,4-dimethyl pentanenitrile.
Submission Evaluation
This compound has two potential toxicities:
1) Release of cyanide in the body following degradation by
tissue enzymes;
2) A possible lathyrogen (toxic agents associated struc-
turally with natural products found in seeds produced
by members of the pea family) which can either (a)
cause degeneration of the spinal cord and cerebellar
nerve cells to produce paralysis or (b) interfere with
the final stages of collagen synthesis, particularly in
the skin.
It would be interesting to describe the cause of death in
the rabbits who received this compound via skin application
as this may shed some light on the actual mode of toxic
action.
Current Production and Use
No information was located on the production and uses of 2-
amino-2,4-dimethyl pentanenitrile; neither was there an
entry in the TSCA Candidate List.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
246
EPA FORM !»»-« IHiv. >-7«)
-------
Comments/Recommendations
a) The submitter should be asked to amplify his
contention that this information is indicative of
substantial risk. The March 16 Policy Statement
emphasizes that previously unknown effects occur-
ring during a routine LD assay may have to be
reported if they are of possible concern to the
Agency. In this case, the submitter fails to
describe the mode of action of this compound,
therefore, the only effect reported is death. The
submitter should be asked to describe the cause of
death (in both gross and histopathological terms)
in the test rabbits.
b) This information should be transmitted to NIOSH,
OSHA and FDA.
247
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:June 20, 1978
SUBJECT:. Status Report 8EHQ-0573-0154P
Approved
FROM- Joseph J. MerendaW Acting Director
Assessment Divisitfi, OTE/OTS (TS-792)
Revision
Needed
T0. Warren R. Muir, Deputy Assistant Administrator
fOr Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
The submission reports an employee fatality attributed to dermal exposure
to molten (58 C) monochloroacetic acid.
Submission Evaluation
Monochloroacetic acid has two lethal toxic effects:
1) pulmonary edema by direct inhalation or damage to the air
sacs by delivery to them via the blood following skin
absorption;
2) interference with the aerobic oxidation of glucose by muscle
and brain tissue.
The fatality reported in this submission appears to have been due to
alveolar (lung) injury following skin absorption. However, there is a
possibility that the molten acid had sufficient hydrochloric acid and
acetic acid to have produced injury by inhalation. One question that
should be answered is: how resistant is the molten acid to decomposi-
tion during normal working conditions?
Current Production and Use
Estimated 1974 consumption of monochloroacetic acid totaled 95 million
Ibs. The consumption pattern was approximately as follows: 52 million
Ibs. used in the production of herbicides (e.g., 2,4-D and 2,4,5-T);
33 million Ibs. used to manufacture sodium carboxymethylcellulose; and
10 million Ibs. for miscellaneous uses- (production of glycine thioglycolic
acid, Pharmaceuticals, indigo dyes, ethyl chloroacetate, synthetic caffeine,
sarcosine, and EDTA).
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
IMCV.
248
-------
Comments/Recommendations
a) The comments and questions raised in the evaluation section
should be brought to the attention of the submitter. In
addition, the submitter notes that additional lab work is
being conducted to investigate the mechanism of death following
skin absorption and also to determine an antidote. EPA should
request that this information be supplied as it is developed.
b) This information should be transmitted to NIOSH and OSHA.
249
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 20, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0578-0155
Approved_
Revision
Needed
FROM: -Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Results of an acute intravenous study of tunicamycin in mice.
Submission Evaluation
The structure of tunicamycin suggests that it is a glycopeptide type of
antibiotic. Such antibiotics are highly toxic to cells and are used in the
treatment of cancer. This antibiotic does not appear to offer any greater
hazard than those already in common use for similar purposes.
Current Production and Use
No information is available.
Comments/Recommendations
This submission apparently describes the results of acute toxicity testing
on an R&D chemical which presumably has very limited environmental release.
The submitter should be asked to provide a more complete description of the
experimental protocols as well as the experimental results (particularly
pathology). The submitter should also be asked to support his contention
that the information presented in this submission reasonably supports a
conclusion of substantial risk.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular chemical.
Any review of the status report should take into consideration
the fact that it may be based on incomplete information.
EPA FORM 132O-6 (REV. 3-76)
250
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 21, 1978 (Revised May 10, 1979) Approved_
SUBJECT: Status Report 8EHQ-0578-0156
Revision
Needed
PROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Results of topical sensitization studies of benzoyl chloride, phenyl
hydrazone in guinea pigs.
Submission Evaluation
Compounds of this chemical structure (see below) could be allergenic on
two acacounts: the hydrazino structure; or the chlorine attached to the
carbon that is double bonded to nitrogen could react with sulfhydryl
groups, particularly in the skin, and thereby form a haptene which may
induce antibody formation.
ci
benzoyl chloride, phenyl hydrazone
Current Production and Use
No information is available.
Comments/Recommendat ions
This submission apparently refers to an R&D chemical which presumably
has limited environmental release.
(a) The submitter should be asked to provide a more complete description
of the experimental protocols and the method of evaluation.
(b) The submitter should be asked to support his contention that the infor-
mation presented in this submission reasonably supports a conclusion of
substantial risk.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 1320-6 (REV. 3-76) 251
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 20, 1978
SUBJECT: Status Report 8EHQ-0578-0157
Approved_
Revision
Needed
FROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Reports that intravenous doses of less than 1 mg/kg of 6,9-diamino-l-(6-
amino-9H-purin-9-yl)-l,5,6,7,8,9-hexadeoxy-D-ribo-decofuranuronic acid
caused nephrosis (degeneration of the renal tubules) in dogs.
Submission Evaluation
This compound is both a purine analog and a glycol derivative. Purine
analogs are used to treat gout and cancer. It is difficult to determine
the exact cause of the nephrosis since both glycol and purine derivatives
have been reported to have this effect. The major hazards with this fer-
mentation product are its production and disposition. This material,
however, appears to present no greater hazard than that encountered with
similar antibiotics used in the treatment of cancer.
Current Production and Use
No information is available.
Comments/Recommendations
This submission apparently refers to an R&D chemical which presumably has
limited environmental release.
The submitter should be asked to provide a more complete description of the
experimental protocols employed in this study. The submitter should also
be asked to support his contention that the information presented in this
submission reasonably supports a conclusion of substantial risk.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular chemical.
Any review of the status report should take into consideration
the fact that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
252
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 22, 1978 (Revised May 10, 1979) Approved^
SUBJECT: Status Report 8EHQ-0578-0158S
Revision
Needed
FROM: Joseph. J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
T0: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Acute toxicity studies of 3(alpha-methylstyryl)-1,2,4-thiadiazole in
rabbits.
Submission Evaluation
This thiadiazole derivative is both highly irritating and toxic by
absorption through the skin. The present state of product development
as described by the submitter does not indicate a need for further EPA
action. If additional developmental work suggests widespread usage,
acute and subchronic toxicity studies including pathological examination
of significant organs should be requested, as should carcinogenic!ty
testing.
Current Production and Use
No information was located in secondary sources; however, the submitter
notes that the material is presently undergoing laboratory-scale syn-
thesis and testing only.
C ommen t s/Recommendat ions
The submission apparently refers to an R&D chemical which presumably has
limited current environmental release.
(a) The submitter should be asked to provide a more complete description
of the experimental protocols and results.
(b) The submitter should be asked to support his contention that the
information presented in this submission reasonably supports a
conclusion of substantial risk.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 1320-6 (REV. 3-76)
253
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 19, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0578-0159S
Approved
Revision
Needed
FROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
An acute oral toxicity study of 2-N(2,2,3,3-tetrafluoropropyl-l-amide)-4-
trifluoromethyl-6-nitroaniline in rats.
Submission Evaluation
This compound is highly toxic. It is both a fluorourethane and a nitro-
aniline, both of which are potentially highly toxic. Many urethanes are
cholinesterase inhibitors. A possible metabolite of this compound, tetra-
fluoropropionic acid, could conceivably be very toxic by virtue of its in-
terfering with carboxylic acid metabolism in normal metabolic cycles. The
fluoronitroaniline moiety could be a potent hemoglobin and bone marrow poi-
son. It would therefore be useful to have more information as to the cause
of death observed with this compound. This material also has potential for
producing primary, cumulative, and sensitization skin reactions.
Current Production and Use
No information was located; however, the submitter notes that the material
is currently undergoing laboratory-scale synthesis and testing.
Comments/Recommendations
The submission apparently refers to an R&D chemical which presumably has
limited environmental release.
The submitter should be asked to provide a more complete description of experi-
mental protocols and results. Of particular interest would be the results of
any gross or histopathology conducted on the test animals. The submitter
should also be asked to support his contention that the information presented
in this submission reasonably supports a conclusion of substantial risk.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular chemical.
Any review of the status report should take into consideration
the fact that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
254
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
June 22, 1978 (Revised May 10, 1979) Approved
SUBJECT: Status Report 8EHQ-0578-0160S
Revision
Needed
FROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Results of a study which found testicular atrophy in rats, but not mice,
following 90 days of dietary administration of l(2,6-dichlorobenzoyl)-3-
(5-(4-bromophenyl)-6-methyl-2-pyrazinyl) urea.
Submissioji Evaluation
It is difficult to evaluate the significance of the testicular atrophy
which occurred in the rats. This could be a direct effect on the testis
or an effect on the neuroendocrine system, particularly the anterior
pituitary. It would be useful to have a description of the pathological
changes that were produced in various organs, especially the thymus,
adrenals, and both anterior and posterior pituitary glands. Acute toxicity
data would also be useful if such were obtained.
Current Production and Use
No information was located in the secondary sources consulted; however,
the submitter notes that the material is currently undergoing laboratory-
scale synthesis only.
Coiments/Recpiimendations
The submission apparently refers to an R&D chemical which presumably has
limited environmental release.
(a) The submitter should be asked to provide a more complete description of
experimental protocols and results, especially the areas outlined in
.. , the evaluation section above.
(b)' The submitter should Be" asked to support his contention that the
information presented in this submission reasonably supports a
conclusion of substantial risk.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76) 255
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
OATE. June 19, 1978 (Revised May 10, 1979) Approved
SUBJECT: Status Report 8EHQ-0578-0161S
Revision
Needed
FROM- Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
T0: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submiss ion Description
The study reporting severe neutropenia (bone marrow damage) in dogs after
oral dosing with 2-ethyl-7-fluoro-4-(4-methyl-l-perazinyl)10H-thieno
(2,3-b)(1,5)benzodiazepine.
Submission Evaluation
This compound belongs to the Librium and Valium class of minor tranquilizers
and sleep-producing drugs. Specifically, it most closely resembles flur-
azepam.
The test compound is a powerful bone marrow poison. It is unusual for an
organic compound to produce bone marrow injury in experimental animals,
even when such compounds are known to do so in humans.
Current Production and Use
No information was located in the secondary sources; however, the submit-
ter notes that laboratory-scale synthesis and testing of the material have
been discontinued.
Comments/Recommendations
This submission apparently refers to an R&D chemical which presumably has
limited environmental release.
(a) The submitter should be asked to provide a more complete description
of the experimental protocols and the results.
(b) The submitter should be asked to support his contention that the in-
formation presented in this submission reasonably supports
a conclusion of substantial risk.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(el of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
256
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Approved
Revision
Needed
DATE.- June 15, 1978
SUBJECT: status Report 8EHQ70578-0162S
tfttfo
FROM- Joseph J. MerendaJJ Acting Director
Assessment Divis#n, OTE/OTS (TS-792)
T0. Warren R. Muir, Deputy Assistant Administrator
frfr Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
The results of acute toxicity studies with N-(2,4-dinitro-6-(trifluoro-
methyl)phenyl)-N-methyl-2,4,6-tribromobenzenamine in rats, mice, cats,
and dogs.
Submission Evaluation
This material is a highly toxic compound for three of the four species
tested. The lesser toxicity in cats suggests that liver enzyme activa-
tion is involved in the toxic action. The human liver responds more
like the dog liver in attacking foreign compounds.
This compound is both a tribromoaniline and a dinitroaniline. The 2,4-
dinitro group tends to uncouple phosphorylation and cause rapid oxidation
of f>at thereby raising the body temperature towards the lethal point of
110 F. The trifluoromethyl group is introduced into drug molecules to
increase potency several fold.
It would be valuable to have a discussion of the effects exhibited by
the test animals just before death. Was. methemoglobinemia involved or
were there central nervous system effects?
Current Production and Use
No information was located on the current production and uses of this
compound; it is likely to be an R&D chemical.
Comments/Recommendati ons
The suitability of submissions such as this is somewhat questionable.
Acute toxicity data on R&D chemicals which presumably have very limited
exposure do not appear to be sufficient to indicate that the material
poses a substantial risk to health or the environment. A more appropriate
mechanism than section 8(e) for the dissemination of information such as
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
COnsidorat-irtn *.K
-------
this may be the publication of a yearly summary article in a scientific
publication or a letter to the editor of one of the more popular trade
journals. It would appear that the only people having an interest in
information such as is contained in submissions of this sort would be
bench R&D chemists or the academic community.
a) The submitter should be asked to provide a more complete
description of the experimental protocols as well as the
experimental results (particularly gross pathology).
258
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 28, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0578-0163
Approved
Revision
Needed
FROM: Joseph J. Merenda, Director
Assessment Division, OTE/OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Results of an acute inhalation toxicity study of N,N'-dibutyl-l,6-
hexanediamine in rats.
Submission Evaluation
The compound has been shown in the past to be corrosive to skin and to have
fairly high acute toxicity by the oral and dermal routes. The 4-hour LCco
of N,N'-dibutyl-l,6-hexanediamine (mixed with 20 mole percent of the
monobutyl form) was 23 ppm in rats under the conditions of this study.
Current Production and Use
No information was located on the production and use of this material, nor
is it entered on the TSCA Candidate List. In the submission, the notifier
indicates that his company does not make this chemical, but purchases it
for use as a polymer intermediate. It is also claimed that in the final
product the material is chemically bound in the polymer.
Related Past and Present Activities
A CHIP report on diaminohexane is available from the Assessment Division.
Comments/Recommendations
This submission is apparently an example of the situation in which the sub-
mitter is a processor who is reporting substantial risk information on a
chemical produced by another manufacturer.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular chemical.
Any review of the status report should take into consideration
the fact that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
259
-------
(a) Section 8(b) data should be checked for evidence of the chemical's
commercial significance.
(b) If the chemical is commercially viable, a CHIP investigation should
be considered; it should, however, be confined to preparation of in-
formation supplemental to that found previously for diaminohexane.
(c) This submission should be referred to NIOSH and OSHA for their in-
formation.
260
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 22, 1978
SUBJECT: Status Report 8EHQ-0578-0164
FROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
Approved
Revision
Needed
TO: Warren R. Muir, Deputy Assistant Administrator
-for Testing and Evaluation, OTE/OTS (TS-792)
SubmissionDescription
Results of toxiclty testing on N-(4,6-dichloro-s-triazin-2-yl)sulfanilic
acid, monosodium salt (Sandospace-R Paste) The submission covered a 48-
hour patch test and a mutagenicity screen on the material.
Suj>mlssign Evaluation
Delayed reactions to some skin irritants and sensitizers, while infre-
quent, are not unknown phenomena. Perhaps a more detailed description
of the technique used in applying Sandospace-R Paste to the skin might
be helpful in evaluating the reaction.
In the case of the mutagenicity testing, insufficient information was pro-
vided to permit an evaluation.
Current Production and Use
No Information on the production and uses of Sandospace-R Paste was located,
nor was there an entry in the TSCA Candidate List. The submitter reports
that Sandospace-R was used in development (product R&D), but that it is
not in current use by the notifier. An address is provided for more de-
tailed use information.
Comments/Reconnnendat ions
This submission is apparently an example of a situation in which the submit-
ter is reporting substantial risk information on a chemical produced by another
manufacturer.
(a) Section 8(b) data should be checked for evidence of commercial signif-
icance.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
261
-------
(b) Complete copies of all reports referenced in this submission should
be requested; use information should also be solicited at the ad-
dress provided.
(c) This information should be transmitted to the appropriate agencies
following receipt of the description of uses.
262
-------
UN'ITED STATES ENVIRONMENTAL PROTECTION AGENCY
DA re-.
10CJCCT:
FROM:
TO:
June 29, 1978 (revised December 10, 1979)
Status Report 8EHQ-0578-OI65 Approved
Revision
rank D. Kover, Chief . Needed
Chemical Hazard Identification Branch
Joseph J. Merenda, Director
Assessment Division, OTE
Submission Description
The submission reports positive mutagenicity findings in several
test systems with N-(2-methyl-2-nitro propyl)-4-nitrosoaniline.
A positive response was observed in each of the following
mutagencity assays: a microbial plate assay using a suspension
system with metabolic activation; a mouse lymphoma cell assay
with activation only; a DNA r.epair assay with hepatocyte
cultures; a rat liver epithelial cell assay. The submitter also
reported that in previously conducted 2-year feeding studies in
rats and dogs, no lesions indicating carcinoma were observed.
However, several of the rats developed a unique (though benign)
lesion of the urinary bladder; because *of these findings and the
mutagenicity responses, the submitter initiated a 2-year chronic
feeding study with the chemical in rats at the end of 1977. The
submitting company also indicated that it does "not feel that
this information comes within the reporting requirements in
Section 8(e)."
Submission Evaluation
It is not surprising that the test chemical is a mutagen. It is
a nitrosoaniline which can give rise to a hydroxylamine
derivative of aniline which, therefore, places the chemical in
the class of carcinogenic nitroanilines.
Current Production a»nd Use
No information on production and use was located in the secondary
literature, neither was there an entry in the TSCA Candidate
List. The submitter reports that the subject chemical is used as
a rubber additive and that it is manufactured in relatively small
quantities.
*NOTE: This status report is the result of a preliminary
staff evaluate-, o: infcrr.-ir ion sub-.ittc-d to EJ-A. f tate~.cr.-.s
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
263
-------
Comments/Recommendations
The submitter notes that purchasers of the chemical have been
informed by letter of the results of his evaluation. In these
letters, the submitter also suggests that users of the chemical
adopt a worker exposure level of 0.2 mg/m .
Following a review of this submission, the Assessment Division
has concluded that the information is of the type required for
reporting under section 8(e). The basis for this conclusion is
as follows:
The preface to Part V of the March 16, 1978, section 8(e)
policy statement (43 FR 11110) states that "a 'substantial
risk of injury to health and the environment1 is a risk of
considerable concern because of (a) the seriousness of the
effeet...and (b) the fact or probability of its
occurence." With regard to the seriousness of the effect,
Part V of the policy statement goes on to explain that the
Agency considers the 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 ...
mutation(s)." Information reporting this effect can be
obtained either directly, by observation of its occurrence,
or inferred from designed studies. According to Part VI(1)
of the policy statement, designed controlled studies include
in vitro and in vivo experiments and tests. When evaluating
in vitro tests for submission, "consideration may be given
to the existence of corroborative information, if necessary"
to reasonably support a conclusion of substantial risk.
In the present case, the submitter reports that the chemical was
positive in four mutagenicity assays and that a unique bladder
lesion was seen in rats receiving the compound in the diet for 2
years. Only limited exposure information is available to the
Agency; however, the submitter indicates that "a review of our
manufacturing experience with N-(-2-methyl-2-nitropropyl)-4-
nitrosoanilize has indicated the potential for skin sensitization
with this compound." Thus, some exposure must occur during
manufacture. In the Agency's view, when this suspected human
exposure is considered with the evidence of mutagenicity in
several in vitro tests and the reported induction of a unique
lesion in~a long-term rat feeding study, reasonable support for a
conclusion of substantial risk is evident for this chemical.
(a) Section 8(b) data should be checked for evidence of
commercial significance. If commercially viable, the
substance should be considered for a CHIP investigation.
(b) This information should be transmitted to NIOSH and OSHA.
264
-------
(c) Complete copies of all studies cited in the submission
should be requested from the notifier. EPA should also ask
to be kept abreast of the findings in the ongoing chronic
feeding study
265
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 21, 1978
SUBJECT: Status Report 8EHQ-0578-0167PS
FROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS(TS-792)
Approved
Revision
Needed
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submis s ion De scr ipt ion
The submission describes a worker who developed a skin cancer reportedly
following occupational exposure to a variety of metal salts including
those of cobalt, nickel, lead, zinc, and copper. The submission goes on
to note that the worker had previously been self-employed as a farmer.
Submission Evaluation
The individual discussed in this submission was exposed to the salts of
several heavy metals, at least one of which (nickel) has been reported to
be a carcinogen, although not by application to the skin. In most cases,
such exposure usually results in a sensitization dermatitis. It is futile
at this late date to attempt a determination as to the cause of the basal
cell carcinoma without further data. If the subject's exposure was to
micro-pulverized salts of these heavy metale, lung cancer might be expected.
Current Production and Use
Salts of the metals listed above are produced in large quantities annually
for a variety of uses, including animal feed additive, dyeing mordant, ex-
plosives, tanning, electroplating, catalysts, etc.
(^oimnents/R^econmTenda^tions
This submission should be transmitted to NIOSH and OSHA for their information.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
266
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
PATE:
Status Report* 8EHQ-0578-0168 Approved
Revision
M0«: Frank D. Kover Needed
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
The submission ostensibly consists of two epidemiologic
studies conducted among workers employed by the submitter.
The Agency, however, has received only a copy of the study
by Milby and Hine entitled "A Study of Deaths from Respira-
tory Cancer Among Employees, Former Employees, and Retirees
of the Kennecot Corporation." A second letter notes that a
two phase study entitled "A Retrospective Epidemiological
Study at Kennecott's Utah Smelter" was to be enclosed-with
the letter; however, the section 8(e) files do not include
this study. Another copy of this report will be requested.
Submission Evaluation
On page one of their report, Milby and Hine state that "this
is the third report in a series" of investigations; copies
of the first two reports are needed to permit an adequate
evaluation. The second letter refers to the two phases of
a study performed by researchers from Brigham Young Univer-
sity (one of the phases was reportedly published); these
studies, however, were not found in the section 8(e) files.
When copies of all four additional reports have been received,
a more informed judgment on the studies will be possible.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 1U»-« IMCV. K?*) 267
-------
With respect to the available Milby and Hine study, a great
deal of attention has been paid in the report to nosology
(the classification of diseases). Because the comparison
data in the study are derived from U.S. Vital Statistics,
the rules prepared by the National Center for Health Statis-
tics (NCHS) should have been used for classifying certifi-
cates of death for members of the study group. These rules,
with which every qualified nosologist is familiar, are
available from NCHS.
Another major problem with the study is its proportional
measure of risk. Because such measures involve only "numera-
tor data," they are not preferred and are usually employed
only as preliminary screens. The high proportion of respira-
tory cancer deaths among the fatalities at the Utah smelter
warrants obtaining "denominators" in the form of person-
years at risk. Expected deaths could then be generated by
life-table methods and much more valid indicators of risk
would result. The time following termination of employment
should be included in the study.
In order to interpret the possible excess of respiratory
cancers at the Utah smelter, it is essential that informa-
tion on exposure which would differentiate that facility
from the others examined in the study be included. Relevant
information would include descriptions of production process,
monitoring data, and duration of worker exposure.
Current Production and Use
The three production phases mentioned in the Milby and Hine
study are common to most copper mining operations. The
mining phase consists of blasting, loading, and hauling
the ore. Concentration includes crushing, grinding,
classification, flotation, and dewatering to increase the
proportion of copper in the ore to 15-30%. At the smelting
site, reverberatory furnaces and converters yield a copper
of high purity which can be further refined and fabricated.
Comments/Recommendations
(a) This submission and status report should be referred to
NIOSH and OSHA.
(b) The submitter should be asked to provide copies of
the studies which are not available in the literature
or in the section 8(e) files.
268
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
OATej June 28, 1978 (Revised May 10, 1979) Approved
SUBJECT: Status Report 8EHQ-0578-0169S
Revision
Needed
FROM: Frank D. Kover, Acting Chief
Chemical Hazard Identification Branch
TO: Joseph J. Merenda, Director
Assessment Division
Submission Description
Results of acute dermal toxlcity studies of N-(2-chloroethyl)-N-ethyl-
aniline in rabbits. The submission consists of essentially identical ex-
periments performed by two different laboratories.
Submission Evaluation
N-(2-chloroethyl)-N-ethylaniline is a semi-nitrogen mustard compound. The
signs observed in the dermally exposed rabbits are consistent with nitrogen
mustard activity. The autopsy findings are also consistent. The emaciation
and alopecia observed are reminiscent of the toxic effect seen in patients
receiving nitrogen mustard for the treatment of cancer. This suggests that
the compound may be an alkylating agent.
The first lab concluded that the material has a dermal LDso of less than
200 mg/kg for male albino rabbits and that it is a corrosive material (as
this term is defined by the Department of Transportation). The second lab,
however, indicated that the compound has a dermal LD5Q of 498 mg/kg for male
albino rabbits and that it is not a corrosive material (as the term is defined
by DOT). The different results obtained by the two testing facilities will
have to be resolved. Perhaps they are merely quantitative and are based on
variations in testing techniques or the expression of animal strain differences.
Current Productipn and Use
No published information is available on the production and uses of this
material; however, it is listed in the TSCA Candidate List.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
row* i3a»-« (Rev. a-7«
-------
Comments/Recommendat ions
(a) Section 8(b) data should be checked for evidence of commercial signifi-
cance.
(b) The submitter should be asked to offer an explanation for the apparent
disparity in test results evident in this submission.
(c) This information should be transmitted to N10SH and OSHA for their
information.
(d) The submitter should be asked to support his contention that the infor-
mation provided in this submission reasonably supports a conclusion
of substantial risk.
270
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 28, 1978 Approved^
SUBJECT: Status Report 8EHQ-0578-0170
Revision
Needed
FROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Results of a 6-month Industry-sponsored inhalation study of 2-nitropropane
in rats. An earlier NIOSH-sponsored study conducted by the Huntingdon Lab-
oratories found that exposure to 200 ppm of 2-nitropropane for 6 months re-
sulted in massive liver damage and neoplastic changes in rats.
Submission Evaluation
The observation by Huntingdon Laboratories that 2-nitropropane can produce
malignant changes in liver cells and that these metastasize to the lung has
been confirmed in the present study conducted by the Albany Medical College.
The experimental design used at Huntingdon is disputed by Frederick Coulston,
Ph. D., Albany Medical College, who claims to have corrected the flaws. How-
ever, neither experimental design has been submitted in detail. There may
be merit to the reasons advanced by Coulston for his view that 2-nitropropane
is not a primary carcinogen. Nonetheless, his opinion cannot be the sole
basis for classifying this compound as being a nonprimary carcinogen in humans.
The relevant slides of tissue sections and the experimental design will have
to be examined by other experts. The course of regeneration in response to
injury by liver cells may be different in humans than that observed in rats.
This difference is notable in alcoholic cirrhosis in humans who develop liver
cancer without necessarily sustaining the degree of injury postulated by
Coulston. This issue can be resolved only by liver pathologists.
The argument advanced by Coulston that no cases of hepatic failure have been
diagnosed in man during the past 30 years of 2-nitropropane's use is specious.
Vinyl chloride was used for at least this length of time before the first
vinyl chloride-related cancer was detected in humans.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76) 271
-------
Current Production and Use
Thirty million pounds of 2-nitropropane are produced annually in the United
States; 12 million pounds are sold domestically, and the remainder is used
either internally by the producer or exported. 2-Nitropropane is used as
a solvent for organic compounds, cellulose, esters, resins, gums, waxes,
fats, dyes, inks, and chlorinated rubber. 2-Nitropropane is most often used
to improve drying time, yield more complete solvent release, improve wet-
ting ability, increase pigment dispersion, etc. The material's combustion
properties have made it useful as a rocket propellant and as a gasoline and
diesel fuel additive. It is also used as a paint and varnish remover (limited
market) and as an intermediate in organic synthesis.
Related Past and Present Activities
A CHIP report on 2-nitropropane is available from the Assessment Division.
Comments/Recommendations
(a) A complete copy of the Albany Medical College study should be requested
from the submitter; this should include a description of experimental
protocols.
(b) The previously prepared CHIP report should be updated to reflect the
new information.
(c) The submitter notes that additional studies on 2-nitropropane are cur-
rently being conducted; these should also be requested from the submit-
ter when completed.
(d) NIOSH and OSHA should be informed of EPA's receipt of this information
under Section 8(e) of TSCA; the CPSC should also receive a copy of this
submission.
(e) It may be wise to consider other similar compounds (1-nitropropane, 2,2-
dinitropropane, etc.) for possible CHIP examination.
(f) The chemical class nitroalkanes should be considered for possible
Section 4 testing.
(g) It may also be advisable to initiate Section 8(d) rulemaking procedures
on 2-nitropropane.
272
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
SUBJECT:
FROM:
TO
June 21, 1978
Status Report 8EHQ-0678-0171
Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
Approved
Revision
Needed
Warren R. Mui , Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
The submission consists of two studies investigating the acute toxicity of
tetrabromophthalic anhydride (FM PHT4) in rainbow trout and Daphnia (water
flea).
Submis s ion Evaluat ion
FM PHT4, of unknown purity, was studied in bioassay determinations of a 96-
hour LC5Q in rainbow trout and a 48-hour LCso in Daphnia. The compound was
apparently not soluble in water (however, no water solubility data were pro-
vided) because a solvent (acetone) carrier was required. In trout, no
mortality was seen at concentrations up to 10 mg/1, but abnormal swimming
behavior was noted at concentrations above 1 mg/1. Higher concentrations were
not tested due to the solubility limitations of the compound in acetone.
With Daphnia, no mortality or abnormal behavior was seen at test concentra-
tions as high as 5.6 mg/1. DO and pH were within acceptable limits through-
out the test. The submission is inadequate in several respects: no
analytical determination of the purity of the test compound was provided; the
study reported nominal concentrations based on calculations rather than con-
centrations actually measured in the test tanks; no water solubility data are
provided, and therefore there is no indication as to whether FM PHT4 will
end up in the water or the sediments. FM PHT4 appears to have limited bio-
logical activity based on the information contained in this report.
Current Production and Use
Annual production is not known; however, the U.S. ITC lists one producer,
which implies an annual production of greater than 1,000 pounds. FM PHT4
is used as a flame retardant for plastics, paper, and textiles (polyesters).
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
273
-------
Comments/Recommendations
FM PHT4 will be evaluated in the ongoing Assessment Division study of flame
retardant technology. It is listed in the recent "Bromine Based Fire
Retardants" report.
(a) The submitter should be asked to support his contention that the in-
formation contained in this notice is indicative of a substantial
risk to the environment. The report in its present form offers no
information to indicate that FM PHT4 represents a substantial risk.
(b) The submitter should be requested to provide the missing information
noted in the evaluation section.
274
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 21, 1978 (Revised May 10,.1979) Approved,
SUBJECT: Status Report 8EHQ-0678-0172
Revision
Needed
PROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
TOs Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission jDescri^tlon
Acute toxicity studies of VEL 4441 [0-methyl-0-cis-(2-methoxycarbonyl-l-
methylvinyl)-thiophosphoryl-NlNl-dimethylformamidine]. VEL 4441 is the cis
form of CN-110-335, which is discussed in submission 8EHQ-0678-0175.
Submission Evaluation
The structural formula for this compound suggests that it is an insecticide
related to parathion. The high toxicity suggests that the material is a very
potent inhibitor of acetylcholinesterase. This degree of toxicity should
probably require more elaborate LD5Q determinations in a variety of species.
It would be useful to have information on the anticholinesterase activity
and the effects of atropine on the manifestations of toxicity produced by
this chemical.
Insufficient numbers of animals were tested to reach any valid conclusions
in this submission. In addition, no analytical data were provided.
Current Production and Use
No information on the production and use of this material was located, nor
was there an entry in the TSCA Candidate List.
Comments/Recommendations
(a) The submitter should be asked to provide analytical data and the results
of any gross or histopathology performed on the test animals. The sub-
mitter should also be queried as to plans for future testing as well as
the contemplated uses of this material.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76) 275
-------
(b) Section 8(b) data should be checked for evidence of commercial signifi-
cance.
(c) This submission should be transmitted to OSHA, NIOSH, and OPP.
(d) The submitter should be asked to support his contention that the in-
formation presented in this submission reasonably supports a conclu-
sion of substantial risk.
276
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
SUBJECT:
FROM:
TO:
June 21, 1978 (Revised May 10, 1979)
Status Report 8EHQ-0678-0173
Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
Approved
Revision
Needed
Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Results of a 42-day neurotoxicity study of MC 984 [bis(l,3-dichloro-2-
propyl)-3-chloro-2,2-dibromomethyl-l-propyl phosphate; also known as
VC 984] in adult chickens.
Submission Evaluation
Although MC 984 appears to be far less neurotoxic than triorthocresyl-
phosphate, some observations need explanation. How much perivascular and
interstitial lymphoid infiltration were seen in the brain, spinal cord,
and sciatic nerves of the chickens receiving only the corn oil? Are there
any data for food and water intake?
Current Production and Use
There is no information available on the production and use of this material,
It is not contained in the TSCA Candidate List.
Comments/Recommendations
Many submissions have been received on this chemical (8EHQ-1277-0022;
8EHQ-0178-0033; 8EHQ-0278-0048; 8EHQ-0278-0049; 8EHQ-0278-0053; 8EHQ-0378-
0100; 8EHQ-0378-0107; 8EHQ-0478-0136).
(a) Section 8(b) data should be checked to determine commercial significance.
(b) MC 984 may be a candidate for CHIP activities in light of the number of
submissions received to date. It may be advisable to query the submit-
ter about the possibility of additional future submissions on this
chemical before CHIP activities commence.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or Intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
277
EPA FORM 1320-6 (REV. 3-76)
-------
(c) The submitter should be asked to provide complete analytical data as
well as answers to the questions posed in the evaluation section above.
The submitter should also be asked to support his contention that the
information presented in this submission reasonably supports a conclu-
sion of substantial risk.
278
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
SUBJECT:
PROM:
TO:
June 20, 1978 (Revised May 10,. 1979)
Status Report 8EHQ-0678-0174
Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
Approved
Revision
Needed
Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Acute inhalation toxicity study of CN-010-073 [2,2-bis(bromomethyl)-3-
hydroxy-1-propyl phosphoric acid] in rats.
S ubmi s s ion Evaluat ion
The report fails to indicate whether the "gold liquid" tested in this ex-
periment was the pure compound, a mixture, or a solution of the material in
an organic solvent.
A number of unanswered questions remain with respect to this submission.
What criteria were used for determining the ratio of vapor to aerosol in the
test atmosphere? To what extent did the aerosol droplets condense on the
fur of the rats? Were the chambers appropriate for exposing animals to
aerosols? Were the nasal discharge and salivation observed in the test
animals due to irritation or to cholinergic stimulation? Did the eyes have a
bloodlike discharge? Did prior administration of atropine affect the re-
sponse?
As far as the experiment itself goes, the duration of exposure was likely
too short. In the future, the observed gross pathologic changes should be
described as such rather than attempting to relate them to the action of
the compound.
Current Prodjuction and Use
No information on the production and use of this material was located, nor
was there an entry in the TSCA Candidate List.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
279
-------
Comments/Recommendations
CN-110-523 will be evaluated in the ongoing Assessment Division study of
flame retardant technology.
(a) The submitter should be asked to provide complete analytical data as
well as the answers to the questions posed in the evaluation section.
(b) Section 8(b) data should be checked to determine commercial significance.
(c) The submitter should be asked to support his contention that the infor-
mation presented in this submission reasonably supports a conclusion of
substantial risk.
280
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
SUBJECT:
FROM:
TO:
June 21, 1978 (Revised May 10, 1979)
Status Report 8EHQ-0678-0175
Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
Approved
Revision
Needed
Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Acute oral toxicity study of CN-110-335 [0-methy1-0-trans-(2-methoxy-
carbonyl-l-methylvinyl)-thiophosphoryl-N',N'-dimethylformamidine]. This
compound is the trans form of VEL 4441, which is the subject chemical in
submission 8EHQ-0678-0172.
Submission Evaluation
The structural formula for this compound suggests that it is an insecticide
related to parathion. The high toxicity suggests that the material is a
very potent inhibitor of acetylcholinesterase.
This degree of toxicity should probably require more elaborate 1050 deter-
minations in a variety of species. It would be useful to have information
on the anticholinesterase activity and a description of the effects of
atropine on the manifestations of toxicity produced by this chemical.
Current Production and Use
No information on the production and use of this material was located in
the secondary literature, nor was there an entry in the TSCA Candidate List.
Comment s/R_ecommendations
(a) The submitter should be asked to provide analytical data on the test
material and the results of any gross or histopathology performed on
the test animals. The submitter should also be queried as to plans
for additional future testing as well as a description of the contemplated
uses of this material.
NOTE:
This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
281
-------
(b) Section 8(b) data should be checked for evidence of commercial signifi-
cance.
(c) This submission should be transmitted to OSHA, NIOSH, and OPP.
(d) The submitter should be asked to support his contention that the
information presented in this submission reasonably supports a con-
clusion of substantial risk.
282
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 21, 1978 (Revised May 10, 1979) Approved__
SUBJECT: Status Report 8EHQ-0678-0176
Revision
Needed
PROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Acute toxicity studies of VEL 4083 (0,S-dimethyl-N-tetrahydropyran-2-yl
thiophosphoramidate) in rabbits and rats.
Submission Evaluation
VEL 4083 appears to be as toxic as aspirin by oral administration; there-
fore, a more detailed investigation of the compound's LD^Q is indicated.
VEL 4083 is a thiophosphate and an amide and therefore is potentially a
neurotoxin as well as an anticholinesterase. It would be useful to have
additional information on these points.
This submission, like others, fails to provide an adequate analytical de-
scription of the test compound. In addition, no discussion of gross or histo-
pathology is provided.
Current Production and Use
No information is available on the current production and use of this material,
nor is there an entry in the TSCA Candidate List.
Comments/Recoifflnendations
(a) Section 8(b) data should be checked to determine the commercial signifi-
cance of this compound.
(b) The submitter should be asked to provide the information requested in
the evaluation section above. Use information should, also be solicited.
(c) The submitter should be asked to support his contention for the infor-
mation presented in this submission reasonably supports a conclusion
of substantial risk.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76) 283
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 21, 1978 (Revised April 9, 1979)
SUBJECT, Status Report 8EHQ-0678-0177 Approved
//Z7/7? Revision
FROM- Joseph J. Merenda/^'Ac'tirfg Director Needed _
Assessment Divis(J6n, OTE/OTS (TS-792)
T0. Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Results of an acute inhalation toxicity study of DMIC (2-chloro-N,N-l-
tr i methyl ethyl ami ne, hydrochloride) in rats.
Submission Evaluation
No quantitative determination of the purity of the test compound was
provided.
DMIC is a semi -nitrogen mustard (see below) and is therefore a potential
alkylating agent which could ultimately be either mutagenic or carcinogenic.
Compounds of this type are used in synthetic chemistry to add the dimethyl -
ami no isopropyl radical via replacement of the chlorine with the appro-
priate group.
,
3
It is not clear whether the molten DMIC remains stable or if it is
decomposed to hydrochloric acid, chloroethane, or dimethylamine. The
description on page 2 of the report suggests that DMIC is hygroscopic
(absorbs moisture from the air). The description of the exposure chambers
suggests that they were inappropriate for studies in which compounds
capable of condensing on skin surfaces were administered. Due to the
investigator's failure to determine analytically the actual concentration
of material in the chambers, the amount inhaled by the rats can only be
guessed. The duration of exposure and perhaps the intensity were also
inadequate.
The immediate response of the rats indicates exposure to a mild irritant.
Were the lungs entirely free of edema and hemorrhage?
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
CPA FORM t>2»* (NCV. >-7«) 284
-------
Current Production and Use
No production figures are available for DMIC; however, the Directory of
Chemical Producers lists one manufacturer which implies an annual production
in excess of 1,000 Ibs. The chemical is apparently used in organic
synthesis for the introduction of the dimethylanvinoisopropyl radical.
Comments/Recommendati ons
One other submission has been received on this chemical (8EHQ-0278-
0073).
a) Production estimate should be confirmed with a check of the
8(b) data.
b) The submitter should be asked to provide analytical data as
well as an answer to the question posed in the evaluation
section.
c) This information should be transmitted to NIOSH and OSHA
for their information.
d) The submitter should be asked to support his contention that the
information presented in this submission reasonably supports a
conclusion of substantial risk.
285
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 21, 1978 (Revised May 10, 1979)
SUBJECT: Status Report 8EHQ-0678-0178
Approved
Revision
Needed
FROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Preliminary results of acute and subacute studies with phenyl isocyanate in
rats.
Submission Evaluation
Aromatic isocyanates have been reported to be exceedingly toxic. They can
be easily converted chemically into aromatic urethanes and aromatic ureas .
Such compounds have the potential for affecting nerve tissue.
Diluting phenyl urethane with petroleum ether as part of the experimental
protocol was not a satisfactory solution to the problem of atmospheric con-
centration. Although the petroleum ether apparently did not affect the
control animals, it may have contributed to the intoxication of group IV by
virtue of its n-hexane content. n-Hexane is a known peripheral neurotoxin.
The rats killed after several days of exposure appeared to be in shock,
which could be related to one of several potential effects of phenyl
isocyanate. It would be useful to have the clinical chemistry and hema-
tological data as well as a description of the microscopic organ changes
observed in the liver, kidneys, and lungs.
The submitter concludes from the acute toxicity testing that phenyl isocya-
nate "must be classed as a very toxic compound, providing an extreme toxic
hazard because of its high volatility compared with its LC^Q."
Current Production and Use
No annual production figures were available on phenyl isocyanate; however,
the Directory of Chemical Producers lists three manufacturers, implying an
annual production in excess of 1,000 pounds. Phenyl isocyanate is used as
a reagent for identifying alcohols and amines and as a chemical intermediate.
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular chemical.
Any review of the status report should take into consideration
the fact that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
286
-------
Comments/Recommendations
The March 16, 1978 Policy Statement requires that all submissions include
the telephone number and signature of the person reporting the information.
Despite the fact that this submission was telecopied, the notifier failed
to provide the required signature and telephone number.
(a) Section 8(b) data should be checked to determine the annual production
volume of this chemical.
(b) Complete copies of all reports cited in this submission should be re-
quested. The notifier notes that the information presented in this
submission represents preliminary data; inquiry should be made to
determine if additional testing is contemplated.
(c) This information and any subsequently developed should be transmitted
to NIOSH and OSHA.
(d) Phenyl isocyanate should be given CHIP consideration.
287
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 26, 1978 Approved
SUBJECT: Status Report 8EHQ-0678-0179
Revision
Needed
FROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
The submission summarizes ambient and stack sampling results during the
manufacture of 2-bromo-l,l-dimethoxyethane (BADMA).
Submission Evaluation
This notice appears to be inconsistent with the minimum requirements for
submission of information indicating a substantial risk to health or the
environment as outlined in the March 16, 1978 Policy Statement. In order
to qualify for submission, a monitoring study should indicate "widespread
and previously unsuspected distribution in environmental media"; this
notice, however, merely reports ambient and stack emission values for
BADMA and DBEA (dibromoethylacetate?).
Comments/Recommendations
This submission should be noted as an example of the type of infbrmation
not required for submission under Section 8(e).
The submitter should be asked to support his contention that the information
contained in this submission reasonably supports a conclusion of substantial
risk to health or the environment.
NOTE:This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
288
EPA FORM 1320-6 (REV. 3-76)
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 28> 1978 Approved_
SUBJECT: Status Report 8EHQ-0678-0180P
Revision
Needed
FROM- Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
TO- Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Report of an employee experiencing eye irritation while working at her
desk; implicated chemicals include dicyclopentadiene and benzoyl chloride.
No other employees reported any difficulty.
Submission Evaluation
The incident reported does not appear to warrant reporting as a substan-
tial risk. As outlined in the March 16, 1978 Policy Statement, reports of
human health effects resulting from uncontrolled exposure are to be re-
ported if they refer to "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" or to less serious
effects that "may be preliminary manifestations of the more serious effects"
and are accompanied by other triggering information. There is no indica-
tion in the present submission that any effect more serious than mere eye
irritation was observed or anticipated in the affected employee.
Comments/Recommendations
The submission should be noted as an example of the type of information not
required for submission under Section 8(e).
The notifier should be asked to support his contention that the information
presented in this submission reasonably supports a conclusion of substantial
risk to health or the environment. .
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into con-
sideration the fact that it may be based on incomplete information,
OQQ
EPA FORM 1320-6 (REV. 3-76) *•
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 26, 1978 Approved
SUBJECT: Status Report 8EHQ-0678-0181
Revision
Needed
FROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
Submission Description
Report that benzoflex 9-88 (dipropylene glycol dibenzoate) causes skin sen-
sitivity in women who have used feminine pads made with this plasticizer.
Submission Evaluation
Comment 13 of the March 16, 1978 Policy Statement specifically states that
reports of dermal ailments need not be reported under Section 8(e) unless
the symptoms are precursors of more serious problems. There is no informa-
tion to demonstrate that the problems experienced by these women are of a
sufficiently serious nature to warrant reporting.
Comi^nts/RecoinmendatJ^ns
This submission should be noted as an example of the type of information not
required for notification under Section 8(e).
The submitter should be asked to support his contention that the information
presented in this submission reasonably supports a conclusion of substantial
risk to health or the environment.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
290
EPA FORM 1320-6 (REV. 3-76)
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: June 26, 1978 Approved^
SUBJECT: Status Report 8EHQ-0678-0182PS
Revision
Needed
FROM: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS (TS-792)
TO: Warren R. Muir, Deputy Assistant Administrator
for Testing and Evaluation, OTE/OTS (TS-792)
SubmissionDescription
Report of an employee who developed dermatitis following exposure to un-
specified chemicals in a laboratory situation.
Submission Evaluation
Comment 13 of the March 16, 1978 Policy Statement specifically states that
reports of dermal ailments need not be submitted under Section 8(e) unless
the symptoms are precursors of more serious problems. There is no informa-
tion presented which demonstrates that the problems experienced by this
employee are of a sufficiently serious nature to warrant reporting. In
addition, the submission fails to implicate one or a few chemicals as
specified in the Policy Statement.
Comments/Recommendations
This submission should be noted as an example of the type of information not
required for notification under Section 8(e).
The submitter should be asked to support his contention that the information
presented in this submission reasonably supports a conclusion of substantial
risk to health or the environment.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF TOXIC SUBSTANCES
DATE: $W 0 9 1979
SUBJECT: Status Report* 8EHQ-0678-0183
FROM: Walter W. Kovalick, Jr., Director
Program Integration Division (TS-793)
TO: Joseph J. Merenda, Director
Assessment Division (TS-792)
Submission Description
Naugatuck, Connecticut, release of chlorine gas.
On May 30, 1978, 20 to 25 pounds of chlorine gas were vented
to the atmosphere as a result of a mechanical failure. The
immediate area surrounding the release was evacuated. The
Connecticut State Department of Environmental Protection was
notified on May 30, and the EPA Regional office was notified
on May 31.
Submission Evaluation
Chlorine is a greenish yellow gas with a pungent, suffocat-
ing odor. It is toxic by inhalation and reacts explosively
or forms explosive compounds. It is an irritant and can
cause fetal pulmonary edema. Chlorine combines readily with
all elements except the rare gases and nitrogen.
Use
Chlorine is used largely for the manufacture of chlorinated
lime, which is used in bleaching all kinds of fabrics; for
292
-------
-2-
purifying water; disinfecting, detinning, and dezincing
iron; manufacture of synthetic rubber and plastics, chlo-
rinated hydrocarbons, and a large number of other chemicals
Comments/Recommendations
Due to the fact that a small quantity of materials was
released which was immediately dissipated into the atmo-
sphere, no further action is indicated either by the state
or by EPA.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA
under Section 8(e) of TSCA. Statements made herein
are not to be regarded as expressing final Agency
policy or intent with respect to this particular
chemical. Any review of the status report should
take into consideration the fact that it may be
based on incomplete information.
293
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
SUBJECT:
23 JAN 1979
Status Report* 8EHQ-0678-0184
FROM: Frank D. Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Approved
Revision
Needed
Submission Description
The submission consists of 28 separate pieces of information
on FM 680 (l,2-bis(2,4,6-tribromophenoxy) ethane).
Submission Evaluation
The following summary evaluations are coded to the letters
entered to the left of each entry in the cover letter
accompanying this submission. In general, the submitted
data do not appear sufficient to offer reasonable support
for a conclusion of substantial risk. The notifier will,
therefore, be asked to support its contention of substantial
risk; if the notifier can offer additional support for a
conclusion of substantial risk, the submission will accord-
ingly be evaluated further.
A) Interim results of a rat teratology study. What is
meant by the phrase "slight increase in the number of post-
implantation losses"?
B) Report of occupational problems following exposure.
The submitter should supply a copy of the "written report"
referred to in this item. The information needed to evalu-
ate the instances of occupational respiratory problems
reported include conditions and duration of exposure, air
levels, and complete physicians' reports.
C) Acute inhalation toxicity study in rats. The study
uses only nominal atmospheric concentrations of the FM 680;
actual concentrations are not reported, therefore, there is
no indication that the material remained as a uniform mist
and did not settle out on the walls of the chamber or on the
rats' fur. The analytical purity of the material is not
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
294
CPA FORM IMO-* (REV. V7t)
-------
addressed. Microscopic examination of the rats' lungs
should have been conducted.
D) 28-day rat feeding study. FM 680 displayed some
toxicity in this study and the material appears to accumu-
late in the fat and remain there for some time. The ana-
lytical purity of the test material was not recorded. Diet
concentrations of 1,000 ppm appear to interfere with organ
growth, 100 ppm interferes with the growth of the liver and
spleen. Was any effect evident on the reticuloendothelial
system? rhe "results and discussion" section of this report
is characterized by attempts to explain away observed toxic
effects as not being treatment related.
E) A Japanese testing company determined the 98-hour TL50
for orange-red killifish to be 230 mg/1. This is signif-
icantly lower than the TLSO's reported for bluegills and
rainbow trout/ although the test compound is still only
moderately toxic. Higher susceptibility of this test
species and different dissolving method (dimethyl sulfoxide
and castor oil carriers, plus sonification) may account for
the differing TL50. In a natural situation, pelagic fish
would probably not be exposed to such an insoluble chemical.
Benthic organisms would be in greater danger. As with all
static acute tests, these results do not test the chemical's
true environmental hazard potential.
The same Japanese testing company also measured the biocon-
centration of Firemaster 680 in carp exposed for 8 weeks.
The bioconcentration factors were very low (F56) indicating
a low tendency to bioconcentrate.
F) Acute toxicity studies in rabbits and rats. The
absence of primary skin irritation does not indicate the
potential for sensitization or haloacne. The dermal toxic-
ity study in the rabbits has little significance. From the
data presented in other studies in this submission, the
probability is that the observed deaths during the first
three days of the rat assay were due to substances other
than FM 680. However, once again no analytical results were
presented.
G) Acute dermal LD This would appear to represent file
emptying.
H) Acute oral toxicity study in rats. In the absence of
microscopic pathology data and evidence of absorption, FM
680 cannot be considered to be nontoxic as proposed on page
1 of this report. The 21-day inhalation study (entry "0" in
295
-------
this series) established that absorbed FM 680 does not
produce immediate effects but is stored in the body like DDT
or PBB.
I) Acute oral toxicity study in beagle dogs. No informa-
tion of value presented; this also likely represents file
emptying.
J) Acute inhalation toxicity in the rat. Problems with
this report include: no controls; inadequate necropsy; lack
of any analytical information. This study indicates only
that no immediate dramatic effects such as convulsions, odd
behavior, or death will follow exposure to FM 680 dust.
K) See (L) .
L) The 96-hour TLSO's of Firemaster 680 reported for both
species are quite high (1531 mg/1 for bluegill and 1410 mg/1
for rainbow trout) and suggest a low degree of acute toxic-
ity to fish.
Several things need to be remembered when evaluating these
data.
1. The biological loading (mass of fish per volume of
water) is higher than recommended by an EPA-Industry committee
which recommended standards for aquatic testing (EPA 660/3-
75-009). The recommended loading is not more than 0.8 g/1,
while the loading in these tests was 1 g/1 in the blue-gill
test and 1.19 g/1 in the trout test. The excess loading
would probably suggest the chemical to be more toxic than it
really is.
2. No replicate tests were conducted.
3. The test material was suspended in water by sonifi-
cation, meaning that the fish were exposed to particles of
the test material, instead of a true solution. Because of
this, it is impossible to say how much of the test material
the fish were actually exposed to. It is likely that the
fish absorbed less of the test compound because of the
larger size of the particles, meaning that the acute toxicity
may be much higher than suggested by these results.
M) No information of value to be found here.
N) 28-day dermal toxicity study in rabbits. This study
appears to represent file emptying. FM 680 is a lipid
soluble halogenated compound that stores in the fat. It is
296
-------
unfortunate that the proposed analyses for fat storage were
never carried out.
O) 21-day inhalation study in rats. No immediate and
dramatic signs, however, the compound is absorbed from the
lungs (which act as a depot). FM 680 is stored in the liver
and fat. The kidney and blood content cannot be evaluated
in the absence of urinary levels. The high bromine content
of the kidneys and the blood may be related to an active
excretion process (only summary data were submitted on this
point). The use of terms such as "few," "slight," or
"several" in lieu of actual numbers is very disconcerting.
Qualitative descriptions are not acceptable.
P) Acute inhalation toxicity in rat after pyrolysis. This
study does not appear to even involve FM 680. It is not
clear what was tested or at what concentration. The test
material appears to be an irritant of ocular and upper
respiratory mucosa. It may be a pulmonary irritant also.
This is a highly inadequate study.
Q) Acute inhalation toxicity in the rat after pyrolysis.
The test compound is inadequately characterized; no analyt-
ical data provided. The use of calculated concentrations in
lieu of actual measurements is not acceptable. How much of
the substance condensed in the chamber and on the animal's
fur is not clear. The test material appears to be an irri-
tant of the upper respiratory tract mucosa and of the eye.
Ocular porphyrin discharge (chromodaccorrhea) and diarrhea
suggests vagus nerve stimulation.
R) 14-day range finding study in rats. This is a pilot
study and not 8(e)-submittable material.
S) 28-day toxicity study in rats. This study shows that
FM 680 is absorbed and stored in fat tissue. This comple-
ments study (O) in this series insofar as fat storage is
concerned.
T) Biodegradation study with C-tagged FM 680. The test
compound was found to degrade slowly under the conditions of
this assay.
U) FM 680 was negative in both the Ames Test and in a
yeast mutagenicity assay.
V) Acute oral and dermal LD50 studies. The identity and
purity of the experimental flame retardant are not contained
297
-------
in the submission. The material is apparently non-irritat-
ing to the eye and skin. The acute dermal toxicity study is
inadequate.
14
W) Biodegradation study with C-tagged FM 680. The test
compound was found to degrade slowly over the 30 weeks of
this assay. These results, plus those presented in (T),
indicate that FM 680 is relatively nonbiodegradable in the
presence of sewage and garden soil microorganisms.
X) Primary skin irritation test. The identity of the
material tested is not revealed in the submission. The
material was found to be mildly irritating for rabbit skin.
This does not indicate the compound's potential for sensi-
tization or pseudo-sensitization due to chronic, mild
irritation.
Y) Acute vapor inhalation toxicity. The composition of
granulated FM 680 is not revealed in this submission. The
heating of the test material in the vapor study suggests
that the substance released upon heating may have possibly
been tribromophenol. The data are inadequate for an 8(e)
submission.
Z) Skin sensitization in guinea pigs. The test material
was not identified chemically. This substance is a primary
skin irritant. It was not sensitizing in guinea pigs.
However, there is no guarantee that the material will not
produce chronic irritation of the skin following persistent
exposure.
Aa) 90-day subacute oral toxicity study in rats. The
chemical identity of the FM 680 lot is not revealed in the
submission. This subacute feeding study suggests that the
material may be less toxic than PBB. However, the animals
receiving the highest dose showed liver changes histologi-
cally which were reflected by increased alkaline phosphatase
in the blood. The kidney weights of the females on the 10%
diet were significantly larger than in the control group.
The ratio of kidney weight to body weight was significantly
greater in male rats on the 1% diet. No data are presented
to show the extent of bromine retention in tissues.
Bb) 90-day subacute toxicity study in rats. Merely supple-
ments study (Aa).
Current Production and Use
Please refer to one of the below referenced submissions for
this information.
298
-------
Comments/Recommendations
Several other submissions have concerned FM 680 (8EHQ-0378-
0086; 8EHQ-0478-0115).
a) The submitter should be asked to support his con-
tention that the submitted information offers reasonable
support for the conclusion that FM 680 presents a substantial
risk of injury to human health or the environment.
299
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: JAN 25 1979
SUBJECT: Status Report* 8EHQ-0678-0185
FROM: Frank^. Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Approved
Revisi
Needed
Submission Description
This submission consists of 19 documents relating to several
different chemicals. The subject chemicals, study types,
and reported summary findings are summarized in the enclosed
table. The implication in the submitter's transmittal let-
ter that all of the submitted information concerns FM PHT4
(tetrabromo bisphenol A) is incorrect.
Submission Evaluation
Preliminary review of the submitted documents indicates that
none of them provides information of the type identified in
EPA's Statement of Interpretation and Enforcement Policy on
section 8(e) notifications (43 FR 11110, March 16, 1978).
Comments/Recommendations
a) The submitter should be asked to review the docu-
ments submitted by this notice and provide his rationale for
their submission as information offering reasonable support
for a conclusion of substantial risk of injury to health or
the environment.
b) The submitter should be requested to clearly iden-
tify the chemical substance or mixture which is the subject
of each submitted document.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM U20-6 (REV. J-761
300
-------
SUMMARY OF STUDIES SUBMITTED TO EPA
SUBMISSION No.: 8EHQ-0678-0185
Item
A
B
H
K
Test Material
FM PHT-4
Tetrabromo-
phthalic
anhydride t4
Tetrabromo-
phthalic
anhydride #4
Tetrabromo-
phthalic
anhydride
FM PHT4
(micronized)
FM PHT4
(micronized)
FM PHT4
(micronized)
FM PHT4
HIPS Resin/
Sb2o3
HIPS Resin/
PHT
HIPS Resin/
PHT4/Sb203
FM PHT4
(micronized)
Study Type
Mutagenicity Evaluation
Final Report
Acute Toxicity/Rat
Acute Toxicity/Ratobit
Acute Oral Toxicity/rat
Acute Dermal Toxicity/
Rabbit
Reported
Results
Not mutagenic
No deaths
Negative
> 10.0 gm/kg
> 10.0 gm/kg
Primary Skin Irritation/ Not a primary
Rabbit skin irritant
Eye Irritation/Rabbit
Acute Inhala'tion Toxic-
ity
Dermal Sens.itization/
guinea pig
Acute Inhalation Toxic-
ity/Rat (.after pyrol-
ysis)
Acute Inhalation Toxic-
ity/Rat (after pyrol-
ysis)
Acute Inhalation Toxic-
ity/Rat; (after pyrol-
ysis)
28-Day Dermal Toxicity/
Rabbi t
Positive for
eye irritant
Acute inhalation
toxicity>10.92
mg/L
Probable sensitiz-
ing agent
No deaths;
exposure not
quantitated
No deaths;
exposure not
quantitated
No deaths;
exposure not
quantitated
Deaths occurred
in 5000 mg/kg/day
group, some toxic
effects at lower
application levels
301
-------
SUMMARY OF STUDIES SUBMITTED TO EPA
SUBMISSION No.: 8EHQ-0678-0185
(continued)
Item Test Material
M FM PHT4
(micronized)
N FM PHT4(?)
0 FM PHT4
P FM PHT4
FM PHT4
FM PHT4
FM PHT4
Study Type
21-day Inhalation Toxic-
ity/Rat
Mutagenicity Evaluation
Final Report
Repeated insult patch
test/human
Pilot Teratology/Rat
Acute Toxicity/Bluegill
Sunf ish
Acute Toxicity/Rainbow
Trout
Acut-.e Toxicity/ .
Water Flea
Reported
Results
No deaths; some
toxic effects
were observed
Not mutagenic
No irritation
reactions or skin
sensitization
No compound-
induced effects
at dose Si 300
mg/kg/day. For
10,000 mg/kg/day
dose, death
occurred in all
but one animal.
96 hour LC,.^
10.0 mg/1 DU
96 hour LCVf^
10.0 mg/1 DU
48 hour LC
5.6 mg/1
50
302
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
PATE: July 10, 1978
SUBJECT: Status Report 8EHQ-0678-0187 Approved
Revision
MOM.- Frank D. Kover Needed
Assessment Division, OTE/OTS
T0: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS
Submission Description
Results of a mutagenicity evaluation of a mixture of 2-hydroxypropyl-2(2-
hydroxyethyl)ethylene glycol and either 2,3-dibromopropanol or 2,3-dibro-
moprophenol (?) (see evaluation section below).
Submission Evaluation
There appears to be some confusion in naming the basic compound. The letter
of June 2 to the performing laboratory states that the compound is 2,3-
dibromoprophenol. The submission cover letter dated June 9 states that the
active compound is 2,3-dibromopropanol. In any event, the compound is
directly mutagenic and does not require activation by liver enzymes.
If the material is actual'ly 2,3-dibromopropanol, the submitter should be
asked to provide information on the metabolic fate of the material. Is it
converted to one of the compounds shown below or something else? It should
be noted that 2,3-dibromopropanol is closely related to l,2-dibromo-3-chloro-
propane (DBCP).
Possible Metabolites
(1) CH -CH-CHO (2) CH -CH-CH -O-glucuronide (3) CH -CH-CH,.
I 2 I I2!2 or 2\/2
Br Br Br Br ** °
Current Production and Use
This mixture is apparently used as a flame retardant; however, the actual
application of the material is not known. No production information is
available.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
CPA rONM !»»-« INEV. »-7f>
303
-------
Coimnents/Recoiimendationa
(a) The question concerning chemical nomenclature should be cleared up
through a follow-up to the submitter. Analytical data should also
be requested.
(b) The submitter should be asked to support his contention that the
information presented in this notice reasonably supports a conclusion
of substantial risk.
(c) This mixture should be examined in the ongoing Assessment Division
evaluation of flame retardant technology.
(d) Section 8(b) data on this chemical should be included in this report
when the inventory is completed.
304
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: December 4, 1978 Approved^
SUBJECT: Status Report 8EHQ-0678-0188
Revision
Needed
PROM: Frank D. Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
Trip report cryptically describing the results of a delayed neurotoxicity
study of MC 948 [bis(tribromoneopentyl)pentaerythritol cyclic diphosphate]
in hens. This particular trip report was submitted separately as an individ-
ual submission for each of the tested compounds.
Submission Evaluation
The information presented in this submission is not sufficient to permit an
adequate evaluation.
Current Production and Use
No information was located in the secondary sources consulted.
Comments/Recommendations
The submitter should be asked to provide his rationale for the submission
of this information as offering reasonable support for the conclusion that
MC 948 presents a substantial risk of injury to health or the environment.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-7«) 305
-------
5
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
1979
MWJECT: status Report* 8EHQ-0678-0189P Approved
Revisio
MOM: FrankMD. Kover, Acting Chief Needed
Chemical Hazard Identification Branch
TO! Joseph Merenda, Director
Assessment Division
Submission Description
Report of possible well water contamination at a farm in
Hardeman County, Tennessee. This report is apparently
related to an incident that was reported in the May 24, 1978
edition of Chemical Week (122 (21) , p. 16) ; this report has
been attached.
Submission Evaluation
The submission does not offer much information except to
note that Velsicol received a request from the Tennessee
Water Quality Control Division requesting reference samples
of four chemicals that, ostensibly, were present in the
well water samples. The Chemical Week story notes that the
state identified 12 chemicals in the water and that the
presence of 11 was confirmed by EPA. Velsicol reportedly
buried more than 200,000 55-gallon drums of chemical waste
at a depth of about 15 feet in the general area of the
present contamination.
Comments/Recommendations
The information contained in this submission is not sufficient
to allow a full evaluation regarding the substantial risk of
this incident. This status report should be transmitted to
OWWM, PID, Region IV, and the Tennessee Public Health Department.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
>NM in** mew. »•?«»
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE.- July 10, 1978 Approved
SUBJECT: Status Report 8EHQ-06781-0190
Revision
Needed
FROM: Frank D. Kover
Assessment Division, OTJE/OTS
TO: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS
Submis sion De scr ip t ion
The submission reports the preliminary results of a 90-day oral toxicity
study of MC 984 [bis(l,3-dichloro-2-propyl)-3-chloro-2,2-dibromom«2thyl-
1-propyl phosphate; VC 984v] in rats. The other chemicals discussed in the
submission are handled in other notices received at the same time (see
8EHQ-0678-0188; 8EHQ-0678-0194; 8EHQ-0678-0208; 8EHQ-0678-0206).
Submis s ion Evaluation
MC 984 appears to adversely affect both growth and food consumption in white
rats. The kidneys and liver and possibly also the nervous system appear to be
affected. It will be necessary to have quantitative data to evaluate the
significance of these pathological changes.
Current Production and Use
No information is available in secondary sources on the production and use
of MC 984, nor is it entered im the TSCA Candidate List.
Comments/Recommendations
Several other submissions have been received on MC 984 (8EHQ-1277-0022;
8EHQ-0178-0033; 8EHQ-0278-0048; 8EHQ-0278-0049; 8EHQ-0278-0053; 8EHQ-0378-
0100; 8EHQ-0378-0107; 8EHQ-0478-13136; 8EHQ-0678-0173).
(a) In the event that the completed study reasonably supports a conclusion
of substantial risk, it should be submitted pursuant to Section 8(e).
With respect to the possible future submission, the submitter should be
asked to remedy the problems observed in many of his earlier submissions
(lack of any analytical dat:a, poor description of pathology, etc.) prior
to actual submission.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status repo?rt should take into consideration the fact
that it may be based on incomplete information.
3,07
EPA FORM 1320-6 (REV. 3-76)
-------
(b) The submitter should be asked to support his contention that the in-
formation presented on MC 984 reasonably supports a conclusion of
substantial risk.
(c) Section 8(b) production data on this chemical should be checked for
possible inclusion in this status report.
30>S
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: October 26, 1978 Approved_
SUBJECT: Status Report 8EHQ-0678-0191
Revision
Needed
PROM: Frank D. Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
Results of a mutagenicity evaluation of VC-935 A [poly(dibromo-phenylene
oxide)] in the unscheduled DNA synthesis assay in human cells.
Submission Evaluation
The test material, identified as only a "beige powder," was positive in this
assay, indicating some potential for mutagenic hazard. The chemical name
indicates that the compound is the polymer; therefore, it is questionable
that the polymeric material is responsible for the positive results. The
possibility exists that there is some other component in the polymer, such
as an unreacted monomer or a plasticizer, which is causing the mutagenic
activity. More extensive evaluation will be required to answer this question.
Current Production and Use
No production and use information was located in the secondary sources con-
sulted. In addition, there is no entry in the TSCA Candidate List.
Comments/Recommendations
Several other submissions have dealt with this chemical (8EHQ-0278-0066;
8EHQ-0378-0090; 8EHQ-0378-0103; 8EHQ-0478-0132; 8EHQ-0578-0141).
(a) The submitter should be asked to provide a description of the analyt-
ical purity of the test material.
(b) Information requested as part of the follow-up to earlier submissions on
this chemical should be checked for inclusion in this file.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
309
EPA FORM 1320-6 (REV. 3-76) J J
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: July 10, 1978 Approved
SUBJECT: Status Report 8EHQ-0678-0192S
Revision
Needed ____^__________
FROMI Frank D. Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS
Submission Description
The submission consists of a letter describing the results of sterility re-
testing of employees who were occupationally exposed to DBCP (2,3-dibromo-
3-chloropropane) and/or tris [tris(2,3-dibromopropyl) phosphate]. Three pre-
viously received submissions (8EHQ-0278-0056; 8EHQ-0478-0123; 8EHQ-0478-0128)
reported the results of earlier fertility studies conducted on these individuals.
Submission Evaluation
This submission indicates a continuing lack of fertility in workers who were
occupationally exposed to DBCP.
It would be desirable to have a more accurate accounting of the workers
exposed to tris and those exposed to DBCP. Even without such an accounting, it
appears that workers exposed to DBCP between January-March of 1975 and April-
June of 1976 are still sterile as judged by sperm counts. It also appears that
workers exposed to tris show recovery but to what extent is not clear from the
submitted data.
What has the submitter told these workers to this point? Has this information
been transmitted to OPP and OSHA by the submitter? It is not likely that workers
who have had continuing failure of spermatogenesis from the time of exposure in
early 1975 and early 1976 will recover reproductive capability.
Current Production and Use
Unconfirmed reports indicate that tris is no longer being produced domestically;
however, reference in this submission to an occupational group having as their
current assignment operator or warehouseman for tris raises the question of
whether the submitter is currently engaged in manufacturing or processing tris.
1975 U.S. production of tris is estimated to have been 7-12 million pounds.
Tris was previously used as a flame retardant for textiles; however, CPSC
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
CPA FORM isa»-s (REV. 3-76) 310
-------
has moved to control this use. The only current use is as a flame retardant
for plastics. OPP has conditionally suspended DBCP for some uses and com-
pletely suspended it for all other uses. Conditional suspension means that
only certified pesticide applicators can use DBCP.
Comments/Recommendations
In light of the evidence that the DBCP-exposed workers may never recover re-
productive capability, the time has come for OTS to fully pursue, this problem
with other Federal authorities and determine what actions are necessary.
(a) OTS should determine what additional information, if any, OPP has received
on DBCF under Section 6(A)2 of FIFRA.
(b) OTS should determine what information has been made available to NIOSH
and OSHA on DBCP fertility effects.
(c) OTS should convene a meeting of all involved government agencies to
facilitate and coordinate exchange of information on this situation and
also to determine the need for possible action.
(d) OTS should request a complete work history of the DBCP and tris-exposed
cohorts. In addition, OTS should determine the amount of information that
the submitter has provided to these workers. Finally, the recommendations
contained in the earlier status reports in this series should be put
into action.
(e) OTS should request that the submitter clarify its reference to current
assignments of workers as operators or warehousemen for tris by notifying
EPA whether and in what volume manufacture or processing of tris are carried
out by the submitter's firm.
(f) This information should be transmitted to NIOSH, OSHA, CPSC, TS/OE, OGC,
and OPP.
311
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: July 10, 1978
SUBJECT: status Report 8EHQ-0678-0193
FROM: Frank D. Kover
Assessment Division, OTE/OTS
TO! Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS
Approved
Revision
Needed
Submission Description
Acute toxicity studies of VEL 3838 [l-(5-t-butyl-l,3,4-thiadiazol-2-yl)-
3-methyl-5-acetoxy-2-imidazolidinone] in rats and rabbits.
Submission Evaluation
The LD5Q of VEL 3838 suggests that this compound has low acute toxicity.
However, this substance contains ring structures that are associated with
long-term toxicity following administration over time of much lower doses
than those used in the LD5Q test. The imidazolidinone ring sugggests that
the compound will have an effect on histamine release, most likely to be
manifested in the skin. However, the ring structure may also block H2
receptors. The consequences of such blockade on immune reactions, car-
cinogenicity, cardiovascular, and gastrointestinal systems are the subject
of current intense investigation. Histamine is an imidazole derivative.
All current H£ blocking agents contain the imidazole ring.
VEL 3838 also contains a cyclic ureide ring, specifically a hydantoin
structure. Compounds containing this ring are used to treat epilepsy.
Such substances have been shown to produce central nervous system
toxicity (e.g., dilantin, nirvanol), to produce teratogenesis in both
animals and humans (dilantin cleft palate), and perhaps also to affect
red blood cell maturation as well as lymphoid tumorigenesis.
Current Production and Use
No information is available in the secondary literature.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 1320-6 (REV. 3-76)
312
-------
Comments/Recommendations
(a) This submission appears to concern a chemical which is in some stage
of research and development. The submitter should be asked to provide
some use information on this material.
(b) According to the responses offered to comments 14 and 31 (q.v.) of the
March 16, 1978 Policy Statement, submission of the information contained
in this notice does not appear to be required under Section 8(e) of
TSCA. The submitter should be asked to support his contention that,
despite the guidance offered by the Policy Statement, the information
contained in this notice is in fact required for reporting and that
it reasonably supports a conclusion of substantial risk.
(c) Section 8(b) production data on this chemical should be included
in this report when the inventory becomes available.
(d) Analytical data should also be requested from the submitter.
313
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Approved
Revision
Needed
DATE: July 10, 1978
SUBJECT: Status Report 8EHQ-0678-0194
FROM: Frank D. Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS
Submission Description
Acute toxicity studies of VEL 4038 [l-(5-t-butyl-l,3,4-thiadiazol-2-yl)-
3-methyl-5-octanoylimidazolidin-2-one] in rabbits and rats.
Submission Evaluation
VEL 4038 has a structure similar to VEL 3838 (see submission 8EHQ-0678-0193).
It differs by having a longer fatty acid chain in the number 5 position of
the hydantoin (cyclic urea) ring. This may slow the rate of hydrolysis by
esterases in the tissue, increase lipid solubility, and thereby create problems
of storage in the liver and fat tissues. Acute toxicity data on such com-
pounds have little relevance for assessing chronic toxicity potential.
Current Production and Use
No information is available in the secondary literature.
Conments/Recommendations
(a) This submission appears to concern a chemical which is in some stage of
research and development. The submitter should be asked to provide some
use information on this material.
(b) According to the responses offered to comments 14 and 31 (q.v.) of the
March 16, 1978 Policy Statement, submission of the information contained
in this notice does not appear to be required under Section 8(e) of TSCA.
The submitter should be asked to support his contention that, despite the
guidance offered by the Policy Statement, the information contained in this
notice is in fact required for reporting and that it reasonably supports a
conclusion of substantial risk.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
314
-------
(c) Section 8(b) production data on this chemical should be checked for
inclusion in this report when the inventory is completed.
(d) Analytical data should also be requested from the submitter.
315
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: July 10, 1978
SUBJECT: Status Report 8EHQ-0678-0195
FROM: Frank D. Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS
Approved
Revision
Needed
Submission Description
Acute oral toxicity study of VEL 4609 [N-(2-methoxycarbonyl-l-methylvinyl-
methoxy-thiophosphoryl) benzamidine] in rats.
Submis s ion Evaluation
The structural formula of VEL 4609 closely resembles that of VEL 4578 (see
submission 8EHQ-0678-0196). Both are parathion analogs, but VEL 4609
has much greater acutely lethal toxicity for rats than does VEL 4578,
probably because the former is a more effective anticholinesterase.
Nonetheless, the exact purity of each compound tested is not specified.
In addition, no information is provided on the rate of biotransformation
of either compound or the effects of the metabolites on cholinesterase
activity.
S
II
VEL 4609
CH3
I
S
II
VEL 4578
CH3
0
CH3
CH3-0-P-0-C=CH-C-OCH 3
N=C~NH2
CH3-0-P-0-C=CH-C-0-CH
N=C-NH2
I
CH3
Current Production and Use
No information was located in the secondary sources consulted.
\
CH3
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 1320-6 (REV. 3-76)
316
-------
Comments/Recommendations
(a) This submission appears to concern a chemical which is in some stage
of research and development. The submitter should be asked to provide
some use information on this material.
(b) According to the responses offered to comments 14 and 31 (q.v.) of
the March 16, 1978 Policy Statement, submission of the information
contained in this notice does not appear to be required under
Section 8(e) of TSCA. The submitter should be asked to support his
contention that, despite the guidance offered by the Policy Statement,
the information contained in this notice is in fact required for
reporting and that it reasonably supports a conclusion of substantial
risk.
(c) Section 8(b) production data on this chemical should be checked for
inclusion in this report when the inventory becomes available.
(d) Analytical data should also be requested from the submitter. Following
receipt of the use description, additional supplemental information
may be desired.
317
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: July 10, 1978 Approved
SUBJECT: Status Report 8EHQ-0678-0196
Revision
Needed
FROM: Frank D' Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS
Submission Description
Results of acute toxicity studies of VEL 4578 [N'-(2-isopropoxycarbonyl-
1-methylvinyl-methoxy-thiophosphoramido) acetamidine] in rabbits and rats.
Submission Evaluation
VEL 4578 is acutely lethal to rats receiving it by oral administration.
The structural formula suggests that the material has some of the properties
of malathion. A more satisfactory assessment can be made if anticholinesterase
data and a description of the symptoms evoked following administration are
provided. It would also be useful to have a description of the signs of
toxicity exhibited by the animals immediately preceding death.
Current Production and Use
No information was located in the secondary sources consulted.
Comments/Recommendations
(a) This submission appears to concern a chemical which is in some stage
of research and development. The submitter should be asked to provide
some use information on this material.
(b) According to the responses offered to comments 14 and 13 (q.v.) of
the March 16, 1978 Policy Statement, submission of the information
contained in this notice does not appear to be required under Section
8(e) of TSCA. The submitter should be asked to support his contention
that, despite the guidance offered by the Policy Statement, the
information contained in this notice is in fact required for reporting
and that it reasonably supports a conclusion of substantial risk.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 1320-6 (REV. 3-76)
31G
-------
(c) Section 8(b) production data on this chemical should be checked for
inclusion in this report when the inventory becomes available.
(d) Analytical data should also be requested from the submitter. Following
receipt of the use description, additional supplemental information
may be desired.
319
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: July 10, 1978 Approved_
SUBJECT: Status Report 8EHQ-0678-0197
Revision
Needed
PROM: Frank D. Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS
Submission Description
Acute toxicity study of VEL 3510 [l-beta,beta-dimethoxyethyl-l-methyl-3-
(5-t-butyl-l,3,4-thiadiazol-2-yl) urea] in rabbits and rats.
Submis sion Evalua t ion
VEL 3510 is a noncyclic urea which resembles VEL 3838 (see 8EHQ-0678-0193)
and VEL 4038 (see 8EHQ-0678-0194) in chemical structure. The thiadiazol
ring will still be capable of exerting its effects on histamine as described
in the status reports prepared for the two previously noted submissions.
The substituted urea moiety, although open chained rather than cyclic, would
probably have chronic toxicological effects similar to those described for
the cyclic urea compounds in the two other submissions.
Current Production and Use
No information is available in the secondary literature.
Comments/Recommendations
(a) This submission appears to concern a chemical which is in some stage
of research and development. The submitter should be asked to provide
some use information on this material.
(b) According to the responses offered to comments 14 and 31 (q.v.) of the
March 16, 1978 Policy Statement, submission of the information contained
in this notice does not appear to be required under Section 8(e) of
TSCA. The submitter should be asked to support his contention that,
despite the guidance offered by the Policy Statement, the information
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 1320-6 (REV. 3-76)
320
-------
contained in this notice is in fact required for reporting and that
it reasonably supports a conclusion of substantial risk.
(c) Section 8(b) production data on this chemical should be checked for
inclusion in this status report when the inventory becomes available.
(d) Analytical data should also be requested from the submitter.
321
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
10 JUL 1978
n»JECT:Status Report* 8EHQ-0678-0198 Approved
sifl^
_ , _ (/' Re vis 10
FROM: Frank D.^Kover Needed
Assessment Division, OTE/OTS —
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
Acute oral toxicity of 2,4,6-tribromophenol in rats.
Submission Evaluation
This submission really adds nothing to what is known about
the acute toxicity of 2,4,6-tribromophenol. Compounds of
this type are of concern mainly with respect to long-term
exposure.
Current Production and Use
This information may be found in one of the earlier submis-
sions referenced below.
i
Comments/Recommendations
Several other submissions have concerned this chemical (8EHQ-1277-0024;
8EHQ-0178-0032; 8EHQ-0278-0069; 8EHQ-0378-0095).
a) Comment 14 of the March 16, 1978 Policy Statement discusses
the reporting of data developed in routine tests including
LD^n's. The response to this comment indicates that "unknown
effects occurring during such a range test may have to be
reported if they are those of concern to the Agency and if
the information meets the criteria set forth in parts V and
VI." In light of this, the submitter should be asked to
demonstrate that the information supplied fulfills the
criteria specified in Comment 14. In addition, the sub-
mitter should be asked to support his contention that the
information contained in this notice reasonably supports
a conclusion of substantial risk and that the information
is in fact required for reporting in light of the guidance
contained in Comment 14.
b) Analytical data should be requested from the submitter.
•NOTE:This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
322
CPA FORM mO-t IMEV. >-7«l
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
Approved_
Revision
Needed
DATE: August 16, 1978
SUBJECT: Status Report 8EHQ-0678-0199
FROM: Frank D. Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
Results of acute toxicity studies of VEL 3947 [l-(5-t-butyl-l,3,4-thiadiazol-
2-yi)-3-methyl-5-(m-chlorobenzoyloxy) imidazolidin-2-one] in rabbits and rats.
Submis sion Evaluat ion
The mortality data on VEL 3947 are of limited value as they only indicate
that the application of large amounts of the material to the skin or by
mouth would not have immediate dramatic consequences. The data have no value
for estimating whether exposure to these large amounts results in pathologic
changes in internal organs or if enzyme induction occurs. In addition, there
is no indication to what extent absorption occurred from either site of applica-
tion. The data have no value for estimating the effects of chronic exposure to
small amounts of VEL 3947.
Current Production and Use
No information was located in the secondary sources consulted.
Comments/RecoTmnendations
(a) The submitter should be asked to provide a description of the uses of VEL
3947.
(b) Comment 14 of the March 16, 1978 Policy Statement discusses the reporting
of data developed in routine tests including LD5Q*s. The response to this
comment indicates that "unknown effects occurring during such a range test
may have to be reported if they are those of concern to the Agency and if
the information meets the criteria set forth in parts V and VI." In light
of this, the submitter should be asked to demonstrate that the information
supplied in this submission fulfills the criteria specified in comment 14.
NOTE:This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
323
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
OATS: December 4, 1978
*U»JECT: status Report 8EHQ-0678-0200
FRO*: Frank D. Kover
Assessment Division, OTE/OTS
T8: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Approved
Revision
Needed
Submission Description
Acute inhalation toxicity study of a mixture of halobenzenes in rats. The
tested material is actually a sample collected from reactor stillbottoms
composed of l,4-dibromo-2,5-dichlorobenzene (76%), dibromodichlorobenzene
(unspecified isomer) (7%), l-bromo-2,5-dichlorobenzene (16%), and 1% unknown.
Submission Evaluation
Despite the compositional data offered by the submitter, it is essential
that EPA have good quantitative data on the composition of the test mixture
in the inhalation chamber.
The use of calculated concentrations in lieu of actual measurements inside
the test chamber is not a satisfactory procedure. It is not known how much
of the material crystallized when the vapors encountered the temperature of
the test chamber or how much settled on the surface of the chamber or on the
fur of the animals.
The study was inadequate and probably not properly interpreted. There were
no untreated controls. Although weight gain was resumed after the third day,
the gain was far less for female rats than for males. In the absence of
microscopic examination of the organs, the statement that "no compound re-
lated pathologic changes were observed" has little meaning. A better experi-
mental design is required for such a study to have significance.
Current Production and Use
This is apparently a sludge bottom resulting from an unknown production proc-
ess.
EPA
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
UJO-« tKCV. >-7«)
324
-------
Comments/Recommendations
(a) The submitter should be asked to identify the "DBDCB isomer" found on the
GC trace.
(b) The submitter should be asked to justify their submission of this infor-
mation as offering reasonable support for the conclusion that this
material presents a substantial risk of injury to health or the en-
vironment .
325
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
OATE. July 10, 1978
SUBJECT: Status Report 8EHQ-0678-0201
FROM: Frank D. Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS
Approved
Revision
Needed
Submission Description
Results of acute toxicity testing of methyl-m-chlorobenzoate in bluegill
sunfish and rainbow trout.
Submission Evaluation
The static 96-hour LC^Q for bluegill sunfish and rainbow trout was 3.0
mg/1 and 7.6 mg/1, respectively. The test was poorly conducted and prompted
the following questions:
(1) Why was dissolved oxygen decreased to such low levels (2.1-2.0 mg/1)
after 96 hours in the bluegill test tanks, but not in the rainbow trout
tanks of comparable concentration and biological loading? Was the
instrumentation adequately calibrated?
(2) What is the weight range of the test organisms used?
only provides mean values.
The submission
(3) What is the purity of the compound being tested? Any contaminants? What
are its physical-chemical properties? How water soluble is the material?
How volatile?
(4) What was the actual concentration of the test substance present in the
tanks initially and after 96 hours? The submission provides only nominal
concentrations.
Based on the information contained in this report, it is impossible to assess
the hazard of this compound. The reported 96-hour LC5Q values indicate a
moderate degree of toxicity. The low dissolved-oxygen level in the bluegill
test may have stressed the organisms such that they were more susceptible
to the effects of the material. The actual concentrations of the material
in the tanks may have been much lower than the nominal concentrations reported
(i.e., it is more toxic). Volatility and solubility data on the compound are
NOTE: This status report is the result of a preliminary staff evalua-
tion of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular chemical.
Any review of the status report should take into consideration the
fact that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
326
-------
needed to determine this. In addition, no replicate test chambers were run
to see how reproducible the results are. Behavioral abnormalities were
noticed at concentrations greater than or equal to 3.2 mg/1. In general,
static acute bioassays reveal limited information.
Current Production and Use
No information is available on the production and uses of this material; it
is contained in the TSCA Candidate List.
Comments/Recommendations
(a) The submitter should be asked to provide use information on this material.
(b) The submitter should be asked to support his contention that the infor-
mation contained in this notice reasonably supports a conclusion of
substantial risk.
(c) The submitter should be asked to respond to the questions posed in the
evaluation section.
(d) Section 8(b) production data on this chemical should be checked for
inclusion in this status report when the inventory becomes available.
327
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: August 16, 1978 Approved
SUBJECT: Status Report 8EHQ-0678-0202
Revision
Needed
FROM: Frank D« Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
Summary results of mouse skin-painting studies in which a residue product
known as polyethylbenzene tails (a by-product of the production of ethyl-
benzene by reaction of ethylene and benzene over a catalyst) was found to
induce skin carcinomas in over 90% of the painted mice.
Polyethylbenzene
^r^H
(CH2CH3)n
Submission Evaluation
Polyethylated benzene appears to be unequivocally highly carcinogenic in
mice. The submission states that "no specific chemical analysis of this
residue product has been made." The composition of the material, includ-
ing a determination of the amount of polycyclic aromatic hydrocarbons which
it may contain, should be established. No controlled studies in humans
previously exposed to polyethylbenzene tails appear to have been made, and
therefore the evidence for no harmful effects in humans is anecdotal. For
the time being, the tested compound should be considered a potent carcinogen.
Current Production and Use
The annual U.S. capacity for ethylbenzene is 11.2 x 10^ pounds; at this time,
some 96% (by pounds of capacity) involves an ethylene and benzene reaction
where polyethylbenzene by-product is produced. Approximately 7.2 x 1CP
pounds of ethylbenzene were produced in 1976; 97-99% of the material was
used in the manufacture of styrene. During the production of styrene, it is
imperative that the ethylbenzene be free of polyethylbenzenes; the polyethyl-
benzenes may comprise 10% of the reaction product and are separated from
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA.
Statements made herein are not to be regarded as expressing
final Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 1320-6 (REV. 3-76) 32G
-------
ethylbenzene by distillation. The polyethylbenzenes are further separated
into "light" polyethylbenzene (mostly diethylbenzene), which are returned
to the reactor since they can react with benzene to produce ethylbenzene,
and "heavy" polyethylbenzenes, which are components of the tails referred
to in this submission. These tails (polyethylbenzenes 'and tars) are
typically burned as fuels.
The submitter claims to have produced approximately 4 million pounds of
polyethylbenzene tails in 1977. The submitter's annual ethylbenzene
capacity is reported at 340 x 10° pounds. Therefore, if the submitter's
ratio of tails to capacity holds true industrywide, approximately 130 x
10*> pounds of tails would be produced annually. There are, however, some
differences in the processes employed by different companies, and this
may influence the ratio. Also, this estimate is based on capacity and
not actual production, and so the value may be somewhat skewed.
Related Past and Present Activities
A hazard assessment on styrene and ethylbenzene is available from the
Assessment Division.
Comments/Recommendations
(a) A full copy of the study should be requested from the submitter.
This should include any available analytical data, a description of
the pathology, statistical analyses, etc.
(b) It should be recommended to the submitter that an analytical effort
be initiated to better define the composition of "polyethylbenzene
tails."
(c) This information should be transmitted to OSW, OAQPS, NIOSH, and
OSHA.
329
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: August 16, 1978 Approved
SUBJECT: status Report 8EHQ-0678-0203
Revision
Needed
FROM: Frank D. Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
Results of acute toxicity studies of VEL 4411 [2-methyl-4-(3,4-dichloro-
phenyl) triazolidin-3-one] in rabbits.
Submission Evaluation
This report merely states that VEL 4411 is an eye irritant but is not a
primary skin irritant. In the absence of information on blood levels,
one cannot say if the material penetrates the skin. LD50 data by other
routes would be of value.
The molecular configuration of VEL 4411 raises the question of carcino-
genicity.
Current Production and Use
No information was located in the secondary sources consulted.
Comments/Recommendations
(a) The submitter should be asked to provide a description of the uses of
VEL 4411.
(b) Comment 14 of the March 16, 1978 Policy Statement discusses the report-
ing of data developed during the course of routine testing. The re-
sponse to this comment indicates that "unknown effects occurring dur-
ing such a range test may have to be reported if they are those of con-
cern to the Agency and if the information meets the criteria set forth
in parts V and VI." In light of this, the submitter should be asked
to demonstrate that the information supplied fulfills the criteria
specified in Comment 14. In addition, the submitter should be asked to
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
EPA FORM 1320-« IRSV. 3-76)
-------
support his contention that the information contained in this notice
reasonably supports a conclusion of substantial risk.
(c) The composition of the test material was not adequately characterized;
complete analytical data should be supplied by the submitter.
331
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
*: August 28, 1978
>UiJiCT: status Report 8EHQ-0678-0204 Approved
Revision
PROM: Frank D. Kover Needed
Assessment Division, OTE/OTS
T0: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
Acute toxicity studies of PCS 1375 in rabbits. The chemical identity of
PCS 1375 is in question as the molecular structure and formula supplied
by the submitter as an attachment do not agree with the name given in
their cover letter. This discrepancy must be rectified. The chemical
formula for PCS 1375 is l-(3,4-dichlorophenyl)-l-carbamyl methoxy-3-
methylurea.
Submission Evaluation
The report on PCS 1375 establishes that the compound is a primary eye ir-
ritant. It does not appear to be a primary skin irritant. There were no
studies on the material's possible skin sensitization properties. The
results of skin application to rabbits are only suggestive of the fact that
PCS 1375 is not readily absorbed through the skin. A description of the
blood levels observed following skin exposure would be most useful.
Current Production and Use
No information was located in the secondary sources consulted.
Comments/Recommendations
(a) The identity of the test material must be provided by the submitter.
(b) A description of the uses of PCS 1375 should be supplied by the sub-
mitter.
(c) Chemical analysis of the compound as well as the results of any blood
level determinations should be; provided by the submitter. The submitter
should be asked to support his contention that the information in this
submission reasonably supports a conclusion of substantial risk.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
It A FORM !»»-« (MCV. »-7«l
332
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: August 21, 1978
SUIJECT: Status Report 8EHQ-0678-0205 Approved
Revision
MOM.- Frank D. Kover Needed
Assessment Division, OTE/OTS
TO' Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
Acute toxicity studies of polyvel G 100 (trade name for a "low to medium
molecular weight petroleum hydrocarbon resin from mixtures of steam cracked
distillate with light steam cracked naphtha") in rabbits and rats.
jubmission Evaluation
The composition of polyvel G 100 is not given. The number of rats 'used to
determine the LD^,, is inadequate. However, this acute value may not be
very significant for the substance; the long-term toxicity would be of more
concern. The weight gain, particularly for the females, appears to be on
the low side, especially from days 7 to 14. In some instances, there was
actually a loss in the female weights. This suggests that a chronic intoxica-
tion is progressing and that the internal organs should be examined histolog-
ically. The observed hypoactivity could be due to CNS, cardiovascular, or
kidney toxicity.
Depending on the composition of polyvel G 100, the material may, upon long-
term testing, be found to be a carcinogen.
Current Production and Use
No information was located in the secondary literature consulted.
Comments/Recommendations
(a) Analytical data on this material should be provided by the submitter.
(b) The submitter should be asked to provide their rationale for the sub-
mission of this information as offering reasonable support for the
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
CPA FORM 1120-t (MEV. »-7() 333
-------
conclusion that polyvel G 100 presents a substantial risk of injury
to health or the environment.
(c) The submitter should be asked about their plans for further testing
of this material, especially with respect to carcinogenicity.
334
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: December 4, 1978
SUBJECT: Status Report 8EHQ-0678-0206
FROM: Frank D. Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Approved_
Revision
Needed
Submission Description
i
This submission presents the results of several studies on chlorendic
anhydride (CA).
Submission Evaluation
One of the studies involved a mutagenicity evaluation of CA in i_uo
unscheduled DNA synthesis assay. This experiment found that CA is active
both with and without activation. Because the genetic end point of this
particular test is unknown, it is difficult to make any assessment of
the risks involved. A battery of gene mutation and chromosome aberration
tests would give a more meaningful indication of the mutagenic and,
possibly, carcinogenic risk. However, since this compound has been shown
capable of damaging DNA in the unscheduled DNA synthesis tests, exposure
to CA should be kept at a minimum.
The number of rats of each sex used to determine the acute toxicity of CA
is too small to draw any meaningful conclusions. Untreated controls were
not used. The inadequacies in this study are still illustrated in the results
obtained. Under usual laboratory conditions, female rats gained weight
at approximately the same rate as males. This apparently occurred at the
highest dose level of 500 mg/kg. However, at 1/10 and 1/50 of this dose,
females gained far less than the males and one female actually lost
considerable weight. From the size of the groups tested, this can be a
random chance occurrence. On the other hand, it may reflect inadequate
recordkeeping.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 1320-6 (REV. 3-76)
335
-------
A somewhat similar phenomenon, probably a chance occurrence due to inadequate
group size, is seen in the rabbit dermal toxicity study. The one fatality
occurred in the low-dose group. This dose is 1/10 of the largest dose.
How then can the conducting laboratory conclude that the minimal lethal
dose by the dermal route of administration is greater than the largest
dose used? In addition, the weight gains and losses were more erratic
at the larger dose. This suggests the possible appearance of toxicity.
These comments assume that the recordkeeping was precise.
The conclusion of the skin sensitization study in guinea pigs suggest
that CA is probably a skin sensitization agent in humans.
Current Production and Use
Refer to one of the below-named submissions for this information.
Comment s/Recommendat ions
Chlorendic anhydride has been the subject of several other submissions
(8EHQ-0278-0050; 8EHQ-0278-0059; 8EHQ-0378-0094; 8EHQ-0378-0101; 8EHQ-0478-
0127; 8EHQ-0478-0134; 8EHQ-0878-0231).
(a) The submitter should be asked to provide its rationale for the submis-
sion of this information as offering reasonable support for the con-
clusion that chlorendic anhydride presents a substantial risk of injury
to health or the environment.
(b) The submitter should be asked to submit a more complete description
of the analytical purity of the test compound.
336
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
OAT*: August 21, 1978
SUftJCCT: Status Report 8EHQ-0678-0207 Approved
Revision
MO* Frank D. Kover Needed
Assessment Division, OTE/OTS
T0: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
Acute toxicity studies of dicyclopentadiene acrylate (DCPD acrylate) in rab-
bits and rats.
Submission Evaluation
The test for primary eye irritation was equivocal by the scoring system,
and therefore the test will be rerun. The skin test shows the substance to
be mildly irritating.
Dermal application of 20 g/kg to rabbits did not result in a dramatic re-
sponse. The weight gain was poor for two of the four male rabbits and for
two and possibly three of the four female rabbits. Two of the females
actually sustained bodyi weight losses over 14 days. The same effect on
weight gain was observed in all female rats and one male rat. Three male
rats showed excessive weight gain from the 7th to the 14th day. This may
have been the result of temporary liver enlargement due to enzyme induction
or to fat accumulation. This study has little significance for chronic
effects.
Current Production and Use
No information was located in the secondary sources consulted.
Comment s/Recommendat ions
One other submission has been received on DCPD acrylate (8EHQ-1177-0017P).
The submitter should be asked to provide their rationale for the submission of
this information as offering reasonable support for the conclusion that DCPD
acrylate presents a substantial risk of injury to health or the environment.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
CPA rOMM 1120-t (NCV. V7«l
33
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
E: December 4, 1978
SUBJECT: Status Report 8EHQ-0678-0208 Approved
, _ „ Revision
FROM: Frank D. Kover Needed
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
The submission consists of four pieces of information reporting health
or environmental information on hexachlorocyclopentadiene and, in one in-
stance, related compounds.
Submission Evaluation
The teratology studies included in this submission do not contain" sufficient
information to permit an adequate evaluation.
The summary sheet from the report on the mouse dominant lethal assay of hexa-
chlorocyclopentadiene states that there was no evidence that the chemical
caused significant dominant lethal activity. Therefore, this information
should not have been submitted under Section 8(e).
The final document, entitled "Chlorinates in Mississippi River Catfish and
Carp," reports on the levels of a number of chlorinated hydrocarbons found
in fish and water samples taken from the Mississippi near a creek (Wolf Creek)
carrying the outfall from the submitter's plant. Of particular-concern are
the high levels of several chlorinated organics identified in catfish flesh.
Fish collected above and below the creek were contaminated, although fish
from immediately below the confluence showed the highest degree of contamina-
tion, less than 1 ppm in the flesh. Carp taken 5 miles upstream showed no
contamination. Water contamination was generally quite low; however, one
would expect relatively low levels of these chemicals in the water because
of their low water solubility; the sediments would be expected to show more
contamination.
Because of the mobility of the fish sampled, one cannot prove that the sub-
mitter is the source of the contamination. However, it is clear that fish
contamination is widespread in this area of the Mississippi River and may
represent a significant threat to the environment and humans who consume
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
'OHM 1IJO-4 IMCV. »-?•)
338
-------
these fish. The chemicals of concern include chlordene and several hexa-
chlorocyclopentadiene wastes, specifically hex vinyl chloride and hex BCH
(exact chemical structure is not known). This particular report was well
written and came to generally sound scientific conclusions. The major
omission was the failure to note the upstream distance from the confluence
of Wolf Creek with the Mississippi to the point of the submitter's waste
outfall on Wolf Creek. If the outfall is located several miles upstream
of the confluence point, monitoring closer to the outfall may be more
indicative of the nature and extent of the problem. If the outfall does
contain the chlorinated hydrocarbons monitored in this report, it is
expected that more contamination would be seen closer to the outfall.
If so, chlordene, hex BCH, hex vinyl chloride, and possibly other con-
tamination could be quite significant. The introduction to the report
states that this monitoring effort was needed "to permit assessment
whether Wolf Creek contained effluents from (the submitter's) hex manu-
facturing plant...." Monitoring in the Mississippi River will not
address this question.
Current Production and Use
Refer to one of the below-named reports for this information.
Comments/Recommendations
Several other submissions have been received on hexachlorocyclopentadiene
(8EHQ-0977-0004; 8EHQ-1177-0013; 8EHQ-0178-0038; 8EHQ-0278-0054; 8EHQ-0278-
0061; 8EHQ-0278-0064; 8EHQ-0378-0099; 8EHQ-0378-0102; 8EHQ-0378-0109; 8EHQ-
0378-0110; 8EHQ-0678-0189P).
This submission and status report should be transmitted to OWWM (OWPS,
ODW, and OSW), OPP, OE, ORD, Monitoring Division (OPII), and EPA Regions
IV and VI.
339
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
08AU6 1978
SUBJECT: Status Report" 8EHQ-0778-0209
FROM: Frank D. Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Approved
Revision
Needed
Submission Description
Results of environmental monitoring studies conducted for TCDD (2,3,7,8-
tetrachlorodibenzo-p-dioxin), other polychlorinated dioxins (hexachloro-
dibenzo-p-dioxin (HxCDD) and octachlorodibenzo-p-dioxin (OCDD)), chlo-
rinated phenols, PBBs (polybrominated biphenyls), and PCBs (polychlori-
nated biphenyls) in river water, sediments, and fish generally collected
from the lower Tittabawassee River in Michigan. Please note that the
submitter's Risk Evaluation Group has "concluded that the data on TCDD
do not appear to indicate a substantial risk of injury to human health
or the environment." The submission consists of two letters plus an
attachment.
Submission Evaluation
Dioxins (The following1subheadings refer to the June 28 letter addressed
to the Document Control Officer.)
B. Plant Discharge Stream
An April, 1977 grab sample of effluent from Dow's tertiary treatment
effluent was found to contain 0.008 ppb of TCDD. Twelve other tertiary
discharge samples (composite or grab) taken from September, 1976 through
April, 1978 showed no detectable levels of TCDD although the limit of
detection was generally 0.005 ppb; the single secondary effluent sample
had no detectable TCDD. Dow suggests sample contamination as a possible
explanation of the one positive finding. Nevertheless, as described in
part D below, five of six caged trout placed in the tertiary effluent
stream were found to contain detectable quantities of TCDD.
C. Native Fish
The information presented in this section is difficult to interpret
for a number of reasons: it is not clear if the levels reported indicate
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
1IJO-4 (MCV. »-7»>
340
-------
whole fish or fish flesh values; the number of specimens collected (and
sampled) at each station is not specified; and it is not clear which
species were sampled in each case.
1. The submitter reports that analyses (apparently performed in
1977) found from 0.07 to 0.23 ppb of TCDD in four of nine catfish samples
retained from a 1976 study; no TCDD was detected in the other five.
What the cover letter fails to note is that these catfish samples were
actually collected from nine different sites, therefore, a more accurate
description of this information would indicate that four of nine sites
where catfish were sampled had evidence of TCDD contamination. Also
note that three or four of the sites where TCDD contamination was not
found are actually upstream from the Dow Chemical outfall.
2. OCDD was found in six of eight catfish samples analyzed for
that substance at concentrations ranging from 0.04 to 0.15 ppb. As noted
in number (1) above, each catfish sample had been collected from a dif-
ferent location, indicating widespread OCDD environmental contamination.
At least one of the OCDD-contaminated catfish was collected upstream
from the Dow plant in the Pine River. HxCDD was also identified in one
of these eight catfish samples.
3. Analysis (whole fish or flesh?) of a variety of fish native to
the Tittabawassee River (caught downstream of the Dow chemical plant in
May, 1977) indicated the presence of from 0.020 to 0.24 ppb of TCDD in
nine of fourteen fish samples tested (see Table IV of submission). The
fish species showing evidence of TCDD contamination included rock bass
(1/1), catfish (2/2), bullheads (3/3), and crappie (3/3). Perch and
carp samples did not show TCDD contamination. It is not clear in the
table how many carp and perch were analyzed. Dow's letter to the EPA
Document Control Officer indicates that five were analyzed; however,
from the table it appears that only one fish of each species may have
been caught.
Dow's letter to John Hesse (p.3) states that the fish represented
in Table IV were collected from the Tittabawassee River at Smith's
Crossing Road. It would appear, however, that the perch were (was)
actually collected from the Saginaw Bay, unless "Saginaw Bay Perch" is a
unique perch species.
In only three cases in Table IV were the low resolution GCMS
findings confirmed with high resolution GCMS. In all cases, EPA wants
confirmation of low resolution dioxin findings with high resolution
GCMS. Dow should be asked if the high resolution findings are available
or if the confirmatory work can still be conducted. Dow should also be
advised of EPA's desire for high resolution GCMS confirmation of all
future dioxin residue analyses. This comment applies to virtually all
341
-------
of the tables contained in this submission.
4. Perch collected from Saginaw Bay in June, 1978 showed no detectable
TCDD, from 0.3 to 0.8 ppb of PBB, and 43-140 ppb of PCBs. Catfish from
the bay, on the other hand, showed 0.024 ppb of TCDD, 21 ppb of PBBs,
and 2100 ppb of PCBs. It is not clear if the catfish results represent
analytical findings from a single specimen or if the results from
several fish have been aggregated.
Although the results presented above are somewhat sketchy, several gen-
eralizations are possible. Firstly, TCDD appears to be a fairly wide-
spread contaminant in catfish (and possibly other fish) collected from
the Tittabawassee River below the Dow plant. Although no TCDD was
identified in catfish sampled upstream from the plant, catfish collected
from Saginaw Bay which appears to lie approximately 30 or more miles
downstream from the Dow plant were contaminated with measurable levels
of TCDD. Other fish in addition to catfish (i.e., bottom feeders)
appear to be contaminated with TCDD although the significance of this,
in terms of demonstrating that mid- or upper-level feeders may be at
risk of TCDD exposure either through the presence of dissolved TCDD in
the water column or the ingestion of TCDD-contaminated organisms, is
difficult to interpret due to trivial identification of sampled fish
species. The submitter should be asked to provide proper identification
of the sampled fish as well as the location where each was collected.
D. Bioconcejitration Study
Caged rainbow trout placed in flowing water at the Freeland Monitoring
Station (approximately six miles downstream from the Dow effluent)
showed no detectable TCDD (limit of detection was 0.01 to 0.03 ppb)
following 7-, 14-, and 30-day exposure when only fish flesh (edible
portion) was analyzed. However, when the 30-day trout were subjected to
a more sensitive analysis of the whole fish, detectable quantities (0.01
and 0.02 ppb) of TCDD were found. It is not clear how many trout from
the Freeland monitoring station were analyzed.
In another study, five of six caged rainbow trout placed in a
mixture (?) of the plant's tertiary effluent under flowing conditions
showed traces of TCDD (0.02-0.05 ppb) after 7 days. The sixth fish may
have accumulated a comparable amount of TCDD, however, since the limit
of detection for that measurement was 0.06 ppb. This bioconcentration
test might have been more demonstrative if a longer exposure period had
been employed. The whole series of bioconcentration studies would
likely have profited from the use of native fish species, especially if
bottom or mid-level feeders had been employed as placement of the cages
indicated.
342
-------
The fact that TCDD was found in caged trout held near the outfall
and at some distance downstream seems to indicate that some of the
material is held in suspension (adsorbed to particulate matter) or
dissolved in the water column. (Another possibility is that the downstream
trout consumed native food organisms that were contaminated with TCDD.)
These findings indicate that downstream fish exposed to flowing water as
well as those fish residing near the Dow outfall are at risk of TCDD
exposure. Moreover, these findings appear to confirm (in a somewhat
qualitative manner) the points raised in part C above, namely that (a)
mid- and upper-level feeders as well as bottom feeders residing for some
distance downstream from the Dow plant are at risk of TCDD contamination,
and (b) TCDD contamination of the Tittabawassee River appears to be
quite widespread.
Dow should provide full details on this section of their submission.
In particular, the results of whole fish analysis are not reported for
several of the caged trout studies and the experimental protocols
(especially with regard to the number of fish tested at each site) are
inadequately presented.
Dow also reports the results of a laboratory radiotracer bioconcen-
tration study which showed that TCDD bioconcentrates on the order of
6,600 times in trout (this is corroborative of earlier findings^.
Chlorophenols
High concentrations (70 ppb) of some Chlorophenols (e.g., pentachloro-
phenol) were identified in Dow's effluent in samples taken during winter
months, with substantially lower concentrations found in spring and
summer samples. Some Chlorophenols were found in the waters below the
plant (up to 4 ppb), but much more (up to 90 ppb) was identified in
sediments below the plant. Upstream contamination was not evident.
Unidentified fish species were reported to have fairly high concentra-
tions of some Chlorophenols (levels up to 120 ppb); however, it is not
clear if this represents flesh or whole fish analysis.
PBB
Widespread PBB contamination of fish (unidentified species) above and
below the Dow plant was evident. Levels up to 2800 ppb were found
although it is unclear whether this refers to whole fish or only flesh.
PCS
Levels up to 2 ppm of PCBs were found in catfish in Saginaw Bay. This
approaches the FDA action level of 5 ppm which is currently under con-
sideration for a lowering to 2 ppm.
343
-------
Current Production and Use
Polychlorinated dioxins are impurities that may be formed as unwanted
contaminants under certain conditions during the production of chloro-
phenols. TCDD is a highly toxic contaminant which may be produced
during the manufacture of 2,4,5-trichlorophenol (2,4,5-TCP).
2,4,5-Trichlorophenoxy acetic acid (2,4,5-T) is a registered pesticide
derived from 2,4,5-TCP and therefore is potentially contaminated with
TCDD from the TCP intermediate. On April 21, 1978, the Office of
Pesticide Programs issued a Rebuttable Presumption Against Registration
(RPAR) of pesticide products containing 2,4,5-T. This notice represents
the current Agency position on the potential risks of continued regis-
tration of 2,4,5-T and its TCDD contaminant.
Overall Evaluation
DOW'S conclusion that the reported TCDD contamination presents no
substantial risk to people who might eat fish containing trace quan-
tities of TCDD has not been adequately evaluated by the Assessment
Division to this point. Nevertheless, Dow's summary of lifetime cancer
and reproductive studies in rats indicates that TCDD is a rat carcinogen
and must therefore be viewed as a potential human carcinogen. Further
discussion of the potential health risks posed by TCDD can be found in
the Rebuttable Presumption Against Registration of pesticide products
containing 2,4,5-T (43 FR 17116) and in a July 27, 1978 memo from FDA's
Bureau of Foods which have been appended.
The March 16, 1978 EPA Policy Statement on Section 8(e) specifies that
the Agency considers reportable substantial risk information to include
"widespread and previously unsuspected distribution in environmental
media, as indicated in studies." Dow does not appear to have adequately
considered this point in their evaluation of the data provided in this
notice. The information contained in this submission clearly offers
reasonable support for the conclusion that TCDD is a widespread contaminant
of the Tittabawassee River downstream from the Dow plant in Midland,
Michigan. There is some evidence that the contamination problem extends
to the Saginaw Bay, which is 30 or more miles downstream from the Dow
plant. The evidence of TCDD contamination in widely dispersed native
fish notwithstanding, perhaps the finding of most concern is that caged
trout held six miles downstream from the Dow outfall were found to have
detectable levels of TCDD (whole fish analysis) following a mere 30 days
of exposure. This is most distressing for several reasons. Firstly, it
demonstrates that TCDD is being transported downstream in flowing water.
This point offers clear refutation of any argument that the instances of
TCDD-contaminated fish resulted from movement of the fish downstream and
not the movement of the TCDD itself. In addition, this raises concern
of TCDD exposure for any persons taking their drinking water from the
Tittabawassee or Saginaw Rivers or the Saginaw Bay. Secondly, this
demonstrates that sufficient quantities of TCDD are being transported
in river waters such that exposed pelagic fish are able to bioconcen-
trate detectable amounts of TCDD despite the presumed dilution effects
344
-------
associated with six miles of river transport. It is not clear if the
TCDD identified in these caged fish results directly from exposure to
dissolved TCDD, if the TCDD in the sediments is being stirred up and
transported in conjunction with bottom particulate matter, or if TCDD
is being transported through the food chain. Another possibility is
that some of the observed TCDD is the result of historic contamination
of this waterway. Dow should provide any information in its possession
delineating the half life of TCDD in river sediments.
In response to the information reported by Dow in this submission, the
State of Michigan issued an advisory to citizens that they should not
consume any fish caught in the Tittabawassee River below Midland or in
the Saginaw River. The Bureau of Foods of the FDA has informed EPA
that they agree with this action taken by the State of Michigan.
Another aspect of Dow's submission that does not appear to have been
given adequate consideration in Dow's conclusion that the TCDD data do
not indicate a substantial risk is the possible impact of TCDD on organisms
living in or near the impacted waters. A previously published study by
Miller e_t a!L. (Env. Hlth. Perspectives, 2^, 1973, 177-186) shows that
immature fish appear to be quite sensitive to TCDD following a latency
period of 10-60 days even at exposure levels of less than 1 part per
trillion. Furthermore, the manner in which consumption of TCDD-
contaminated fish might affect fish eating birds or mammals and the
potential for such exposure to cause reproductive effects in these
animals (including fish) is not known.
In light of: (a) no detectable TCDD in fish taken upstream from Dow;
and (b) the results of the fish accumulation study conducted with caged
trout exposed to Dow's tertiary effluent; it would appear rather conclu-
sive that Dow's discharge represents the major source, if not the only
source of the TCDD contamination found in the Tittabawassee and Saginaw
Rivers and Saginaw Bay in Michigan.
The potential widespread contamination of the Tittabawassee and Saginaw
Rivers with OCDD indicated by Dow's analyses of the catfish sampled in
1976 should also be further investigated. Dow should be asked to provide
details or any follow-up investigations they have performed on OCDD
contamination.
The data showing contamination of fish by chlorophenols, PBBs and PCBs
should also be further evaluated.
Comments/Recommendations
Some of the information contained in this submission should undergo more
in-depth evaluation by appropriate experts. Therefore, it is recom-
mended that:
1) Lead responsibility for the detailed technical evaluation of
the dioxin and chlorophenol portions of this submission should be trans-
ferred to the Office of Pesticide Programs.
345
-------
2) Lead responsibility for the detailed technical evaluation of
the PCB and PBB aspects of this submission should be transferred to the
Office of Chemical Control's PBB Workgroup.
3) Dow must supply all analytical protocols including a des-
cription of the sampling methods employed. Dow should also provide
additional information on the fish sampled (date, and site of collection,
number of fish, and species) as well as a complete description of the
analytical results (especially with respect to flesh vs. whole fish
analyses and precise identification of the dioxin isomer detected in
each case). All other information needs noted in this status report
should also be provided to EPA.
4) This status report and submission should be transmitted to
OE/TS, OWHM, OGC, ODW, Region V, Michigan Dept. of Natural Resources,
FDA, and U.S. Dept. of the Interior. OE should ask Region V to check
Dow's effluent discharge permit and consider revision if indicated.
5) Any other substantial risk information in Dow's possession on
TCDD, OCDD, HxCDD, other chlorodioxins, PBB, PCB, and chlorophenols
should be forwarded to the Agency as a supplement to this initial sub-
mission. This should, if possible, include any information available in
Dow files predating January 1, 1977.
6) Table X of the letter to Hesse is not complete as no TCDD
values are reported. Dow must provide this information.
7) Dow does not provide an adequate basis for their statement
that a heavy diet of contaminated (at the levels reported) Tittabawassee
fish would have little significant impact on humans. In particular, few
of Dow's assumptions are presented and no calculation is given for Dow's
one-hundred fold safety factor for individuals relying on a fish diet
taken from the Tittabawassee River. Dow should provide this information
as well as any other factors considered by their TSCA 8(e) Risk Evaluation
Group in concluding that "the data on TCDD do not appear to indicate s
substantial risk of injury to human health or the environment."
3) Dow should describe the scope and timing of any additional
work which is planned relative to this submission. Dow should explain
in detail the program "mapped out" on page 3 of the Hesse letter.
Although the testing and monitoring data presented are not statistically
significant, the Agency (despite the preliminary nature of the present
evaluation) feels that the TCDD data in the submission "reasonably
support a conclusion of substantial risk" in and of themselves. However,
Dow should consider initiation of additional testing and monitoring
activities. The bioconcentration study which was run for periods of
only 7 to 30 days on trout does not seem long enough to provide the
shape of the bioconcentration curve to be expected in local native fish.
In addition, native fish species (such as catfish, perch, etc.) would
likely be more appropriate than the trout employed by Dow. The analyti-
cal data on TCDD and other chemical residues in native fish do not
represent a statistically valid sampling of the fish around the Dow
plant. Dow should consider additional monitoring to further define the
346
-------
limits and extent of the contamination/ including evidence of TCDD
contamination in biota other than fish.
9) Region V should bring this submission to the attention of the
chemical companies located upstream and downstream from Dow in an attempt
to pinpoint other possible sources of the observed PBB, PCB, dioxin, and
chlorophenol contamination. These companies should be asked to provide
any information in their possession which may further define the extent
or nature of this potentially hazardous situation. This request should
be made with the understanding that these companies should consider
submission of this information pursuant to section 8(e) of TSCA if
applicable.
10) Dow claims in their cover letter that it "is not a producer or
processor of PBB or PCB" and, therefore, by implication that the company
has no responsibility to report substantial risk information concerning
these chemicals. However, if PBBs or PCBs appear as an impurity in any
product Dow manufactures, processes or distributes, Dow would be con-
sidered a manufacturer, processer or distributor of the PBBs or PCBs.
The appropriate work groups should determine whether these chemicals
appear as an impurity in any Dow product.
347
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
OATE: 08FEB1979
SUBJECT: Status Report* 8EHQ-1173-0209
(Supplement)
FROM: Frank D. Kover
Assessment Division, OTE/OTS
TO.- Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Approved
Revision
Needed
Submission Description
The submission was made as a followup to Dow Chemical
Company's two earlier submissions on the detection of
chlorinated dioxins and other chlorinated organics in
various environmental samples. In a press release (attached),
Dow concluded that "its research ... has verified the follow-
ing sources for chlorinated dioxins: refuse incinerators,
fossil-fueled powerhouses, gasoline and diesel powered
automobiles and trucks, fireplaces, charcoal grills and
cigarettes." On the basis of this work, Dow concluded that
"dioxins occur everywhere as a result of normal combustion
processes." The submission consists of the press release
and related material, a report presenting Dow's data and
conclusions, and several appendices describing sampling and
analytical methodologies.
Background
The polychlorinated dibenzo-p-dioxins (PCDDs) are a series
of tricyclic aromatic compounds which exhibit similar
chemical and physical properties. The basic structure of
PCDDs (as shown below) has eight possible points of chlorine
substitution. From the monochloro to the octachloro deriva-
tives, a total of 75 different positional isomers is possible.
-0
ci
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
CPA FORM 1MB-* (REV. »-7«)
348
-------
The most extensively studied isomer of the PCDDs is 2,3,7,8-
tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD), one of the most
potent toxicants presently known. The toxic effects induced
by other TCDD isomers are less well characterized; however,
they appear to exhibit a lesser degree of toxicity (both
quantitatively and qualitatively) than 2,3,7,0-TCDD. For
these reasons, the PCDD isomer attracting the greatest
amount of Agency interest and activity is the 2,3,7,8-TCDD.
Submission Evaluation (An overall evaluation of the
submitted information will be presented in this
section of the status report; a detailed technical
evaluation of the submission can be found in the
attached appendix.)
The information contained in the present submission was
received as a followup to the Dow Chemical Company's earlier
submissions of June 28, 1978 (8EHQ-0673-0209) and October
11, 1978 (3EHQ-1078-0209 [Followup]) which concerned the
presence of chlorinated dioxins in Tittabawassee River fish
collected near Dow's Midland, MI chemical plant. A detailed
description and evaluation of the June, 1978 submission can
be found in the status report prepared for that submission.
The following listing summarizes the most important points
from that initial Dow submission.
a) Tetrachloro dibenzo-p-dioxins (TCDDs, isomers not
identified) appear to be widespread contaminants of the
Tittabawassee and Saginaw Rivers (and possibly Saginaw Bay)
downstream from Midland. Octachloro dibenzo-p-dioxin (OCDD)
also appears to be widely distributed downstream of Dow.
TCDD was not detected in 3 fish taken upstream of the Dow
Midland facility, although OCDD was apparently detected in
one of these fish.
b) Five of six caged rainbow trout held in a mixture
of Dow's tertiary waste treatment effluent under flowing
conditions for 7 days accumulated traces of TCDD (ppt).
c) Caged rainbow trout held in flowing waters appro-
ximately six miles downstream from Dow's plant accumulated
detectable amounts (ppt) of TCDD (whole fish analysis) after
30 days of exposure. This indicates downstream movement of
TCDD.
Based on the above, it appeared that Dow's discharge repre-
sented the major, if not the only, source of the chlorinated
dioxin contamination found in the Tittabawassee and Saginaw
Rivers and Saginaw Bay in Michigan.
The latest submission represents the output of a Ta,sk Force
established by Dow's Michigan Division "to identify the
349
-------
potential sources of the chlorinated dioxins" found in the
Tittabawassee River. This report advances as "strongly
supported" a number of conclusions that, on careful evalua-
tion, have no documented support in the information submitted
by Dow. A detailed evaluation of Dow's report is provided
in the attached appendix; the main points resulting from the
Agency's evaluation have been condensed as follows:
a) No information, other than purely circumstantial
evidence, has been submitted by Dow to support the premise
that polychlorinated dibenzo-p-dioxins (PCDDs) and especially
the TCDDs are typical by-products of combustion. Other
investigators have demonstrated under laboratory conditions
that PCDDs can be formed during the pyrolysis of polychloro-
phenates or polychlorophenoxy-containing materials. However,
there is no experimental evidence (either submitted by Dow
or present in the literature) indicating that combustion in
the absence of PCDD precursors normally results in PCDD
synthesis.
b) Much of the analytical work reported by Dow in this
submission used methods that have "not always been validated
and not yet corroborated by other scientists." Because of
this, little or no analytical significance can be derived
from the results reported by Dow. In order to derive signifi-
cant and valid analytical meaning and/or conclusions from
the results of part per billion (ppb) and part per trillion
(ppt) analysis for PCDDs, the results must be accompanied by
(1) appropriate quality control results and (2) a complete
description of the criteria used to identify and confirm the
presence of PCDD residues.
c) Many of the PCDD residue values relied on by Dow
when formulating its conclusions as to the "ubiquity" of
PCDDs were identical or approximately equal to the analytical
method's level of detection. Such numbers have uncertain
analytical significance especially in situations when non-
validated analytical methods are employed.
d) Dow claims (p.21 of its report) that the results of
its analysis of soil and dust samples "strongly support the
conclusion that chlorinated dioxins are produced in incinera-
tors and fossil fueled powerhouses as a consequence of
combustion." In point of fact, the results presented by Dow
offer no scientific documentation (other than weakly circum-
stantial evidence) relating its observations on PCDD contam-
ination of soil and dust to the synthesis of PCDDs as a by-
product of incineration or power generation. There is some
circumstantial evidence that the hexachloro dibenzo-p-
dioxins (HxCDDs), heptachloro dibenzo-p-dioxins (HpCDDs),
and octachloro dibenzo-p-dioxins (OCDDs) identified in the soil
samples from the urban and the metropolitan areas may be
350
-------
associated with the operation of a powerplant and an incinerator,
respectively. This, however, does not demonstrate that the
presence of these substances results from their synthesis as
a normal combustion by-product. EPA's evaluation of these
data indicates that the following conclusions, contrasting
Dow's claims, can be supported:
(1) Midland, MI, and especially the area around
the Dow plant, exhibits the greatest evidence
for gross PCDD contamination among the various
locations sampled. This is true both in
terms of the proportion of samples in which
PCDDs were detected and the degree of contamina-
tion evident in individual samples. In the
latter case, the levels of PCDDs found in
Midland are 2-4 orders of magnitude greater
than those reported at other locations. The
fact that much higher levels of PCDDs were
found in soil and dust around the Dow chemical
plant as compared to urban, metropolitan, and
rural areas suggests that polychlorophenol
production or some other activity at the Dow
plant may be the source of the observed PCDD
contamination.
(2) To the extent that TCDDs, especially 2,3,7,3-
TCDD, are the PCDDs of greatest Agency concern,
the levels of TCDDs identified in Midland soil
and dust samples indicate that this area
represents a definite TCDD "hot spot." In
comparison, there are very few instances where
TCDDs were reported at other sites.
e) In part V of its report, Dow cites several European
authors who have reported the presence of PCDDs in fly ash
from municipal incinerators and in fly ash from an industrial
heating facility. Dow notes (p.22 of its report) that one
of the authors postulates that the PCDDs are formed as a
result of the thermal condensation of chlorophenols, although
mention is made in the article that a thermal synthesis
reaction involving inorganic chloride and organic material
"was considered to be entirely possible." Dow, however,
fails to discuss several other studies which indicate that
the pattern of PCDD isomers identified in fly ash (from
incinerators and heating facilities) was almost identical to
that found when a mixture of polychlorophenates was pyrolyzed
under controlled conditions. One of these papers goes on to
state that available evidence indicates that commercial
chlorophenols cannot be excluded as the precursor to PCDDs
in fly ash. The information submitted by Dow appears to
offer some degree of support for this statement. In general,
351
-------
fly ash from Dow's chemica.1 waste incinerators show higher
levels of PCDDs than does fly ash from its fossil fueled
powerhouse. The difference may be related to the nature of
the material being burned in each operation. One possible
explanation is that the chemical wastes being burned in Dow's
incinerators already contain PCDDs or PCDD precursors (poly-
chlorophenoxy material)(i.e., wastes from Dow's chlorophenol
production processes) and that these substances are the
sources of the observed PCDDs.
f) Dow claims (on p.30 of its report) that "wipe
testing and air monitoring data are strong evidence that
(Dow) manufacturing plants do not emit levels of chlorinated
dioxins sufficient to explain the finding of these compounds
in the soil samples reported earlier." No scientific basis
for this conclusion is provided in the data presented by
Dow.
g) Dow reports (pp.33-35) trace quantities of PCDDs in
scrapings taken from the inside of car and diesel truck
mufflers. Does this necessarily mean, as Dow advances, that
PCDDs are formed during combustion in the engine? If the
car or truck was driven primarily in an industrial area or
near sources that might be considered contaminated with
PCDDs or PCDD precursors, airborne particulates containing
these substances could be drawn into the air intake of the
engine. Any PCDDs not decomposed in passage through the
engine might then be deposited in the muffler. The state-
ment (p.35) that PCDDs "are in particulate emissions from
internal combustion engines" cannot be supported because
vehicles' exhaust gases were not analyzed. The only conclu-
sions that can be supported by the observations presented in
this section are that (1) PCDDs have been identified in some
muffler scrapings, however, (2) the source of the PCDDs is
unknown.
h) Dow claims (pp.35-36) that soot collected from 2
fireplaces contains PCDDs; however, Dow offers no documenta-
tion of its claim that none of the wood burned in the fire-
place "had been treated with any wood preservatives."
Without such evidence, these results can not support Dow's
thesis concerning the synthesis of PCDDs as a normal combus-
tion by-product.
i) The geographic locations of the homes where fireplace
soot and home electrostatic precipitator particulates were
sampled may be important. This is of interest because the
dust collected in the electrostatic precipitator (electronic
air cleaner) had a higher concentration of PCDDs than the
soot samples from the fireplaces (acknowledged sources of
typical combustion by-products). A home electrostatic
precipitator functions to a certain extent as a "high volume
352
-------
air sampler." In the case cited by Pow, the electr.QSta.tic
precipitator was operated over a period of 6 spring and
summer months. Thus, the precipitator particulates analyzed
by Dow represent airborne material collected over a 6 month
period which does not coincide with the months generally
associated with heavy space heating-related combustion or
home fireplace usage. Therefore, the PCDD values for the
home electrostatic precipitator-collected particulates may,
to a certain extent, represent the results of incidental ambient
air "sampling" conducted at the site of the house.
j) Dow claims to have verified charcoal grills and
cigarettes as sources of PCDDs. No evidence is presented to
indicate that charcoal grills per se produce PCDDs, although
an attempt is made to show that steaks cooked on charcoal
grills contain newly synthesized PCDDs. The reported PCDD
residue values, however, are identical or approximately equal
to the analytical method's level of detection such that the
reported values have limited analytical significance. In
its cigarette assays, Dow reports finding picogram (10-12g)
concentrations of PCDDs per cigarette (in trapped cigarette
smoke particulates). However, several questions remain con-
cerning the significance of this assay (e.g., results of
unburned cigarette [control] analysis; geographic location
of the conducted studies, etc.).
k) Dow reports that it identified polychlorinated
dibenzofurans (PCDFs) in a number of the analyzed environ-
mental samples. This finding should be investigated in
more detail in light of the high toxicity of several PCDF
isomers.
Overview
In summary, Dow1s efforts "to identify the potential sources
of the chlorinated dioxins" found in the Tittabawassee
River indicate that it is possible that some portion, likely
quite small, of the PCDDs identified in Tittabawassee River
fish may have originally been formed and released to the
environment as a combustion by-product rather than as a
direct water effluent release as suggested by the information
in the original submission. An important consideration,
however, is that (with the exception of some OCDD) PCDDs
were not detected in fish collected upstream from Dow's
Midland, MI plant. Therefore, the available information
(especially point (d) above) continues to suggest that the Dow
Chemical Company's Midland, MI plant represents the major,
if not the only, source of the TCDD contamination found in
the Tittabawassee and Saginaw Rivers and Saginaw Bay in
Michigan.
353
-------
Current Production and Use
polychlorinated dibenzo-p-dioxins are impurities that may be
formed as unwanted contaminants under certain conditions
during the production of chlorophenols. For example,
2,3,7,8-TCDD has been identified as a contaminant produced
during the manufacture of 2,4,5,-trichlorophenol (2,4,5,-
TCP) by current production methods. Because of this, 2,4,5-
trichlorophenoxy acetic acid (2,4,5,-T), a registered
pesticide derived from 2,4,5-TCP, is also potentially
contaminated with 2,3,7,3-TCDD from the TCP intermediate.
Comments/Recommendations
a) This submission and status report should be trans-
mitted to OPP, SAD, CAD, PID, LTAT (AD), OE, OWWM, OGC,
OAQPS, ORD, OMSAPC, Region V, Michigan Department of Natural
Resources, CPSC, USDA, FDA, OSHA, NIEHS, and NIOSH.
b) The submitter should be asked to provide the
clarifications outlined in the status report and appendix.
The submitter should be asked to prepare a written response
to the questions; in addition, a meeting between Dow and EPA
is suggested to provide a full discussion of the scientific
aspects of the submission.
c) The development of a Sources/Effects Report (Phase
I document) on PCDDs is recommended. This activity should
also include consideration of the polychlorinated dibenzofurans
(PCDFs).
d) Controlled combustion studies are needed to evaluate
Dow's hypothesis that PCDD synthesis occurs in most combustion
processes as well as to indicate the scope of any future
monitoring effort.
e) SAD (OPII) should initiate consideration of an
appropriate monitoring program to determine the degree and
extent of PCDD contamination in Midland, MI, as well as
other current or historical sites of possible PCDD contami-
nation (e.g., chlorophenol manufacturing, processing, or
disposal sites). Environmental monitoring for PCDFs should
also be considered. These efforts should be closely coordi-
nated with ongoing or contemplated activities in other EPA
offices (e.g., OPP, IERL/Cinn., OWWH, OAQPS, Region V,
etc.) .
f) QTS efforts to assess the sources and extent of
PCDD and PCDF contamination as well as possible control needs
should be closely coordinated with the efforts of other EPA
offices and federal agencies by PID (OPII), possibly through
intra-agency work groups and the Regulatory Development Work
Group of IRLG, respectively. All of these efforts should be
354
-------
coordinated with the designated Headquarters Coordinator
for all dioxin-related activities.
g) An 3(d) rule to collect health and safety studies
on PCDDs and PCDFs should be considered.
355
-------
APPENDIX (8EHQ-1178-0209) (Supplement)
The polychlorinated dibenzo-p-dioxins (PCDDs) are a series
of tricyclic aromatic compounds which exhibit similar
chemical and physical properties. The basic structure of
PCDDs (as shown below) has eight possible points of chlorine
substitution. From the monochloro to the octachloro deriva-
tives, a total of 75 different positional isomers is possible.
The most extensively studied isomer of the PCDDs is 2,3,7,0-
tetrachloro dibenzo-p-dioxin (2,3,7,3-TCDD), one of the most
potent toxins presently known. The toxic effects induced by
other TCDD isomers are less well characterized; however,
they appear to exhibit a lesser degree of toxicity (both
quantitatively and qualitatively) than 2,3,7,8-TCDD. For
these reasons, the PCDD isomer attracting the greatest
amount of Agency interest and activity is 2,3,7,8-TCDD.
Submission Evaluation
(The following sections refer to
subheadings in Dow's report.)
I. Building Blocks for Chlorinated Dioxins
The report's conclusions state that "conditions in a flame
favor the occurrence of every conceivable type of chemical
reaction" (p. 5), so that PCDDs may be formed in trace
quantities wherever combustion occurs. The formation of
polycyclic organic compounds during combustion is not a new
finding. During coal combustion, the initial pyrolytic
reaction can result in fragmentation, ring closures, conden-
sation, and aromatization. The main products tend to be
polynuclear ring compounds, occasionally containing nitrogen,
oxygen, or sulfur, and simple compounds like H0, H^S, NH~,
CH4,
CO
2'
etc.
Dow opens the discussion in Part I by establishing that
inorganic chloride, gaseous products (S00, NO , CO, etc.),
metals (V, Fe, Ni, etc.), and a wide variety of aliphatic
and aromatic hydrocarbons are present during refuse- or
fossil-fueled combustion reactions. The submitter then
postulates that "at ultratrace levels, parts per billion,
the number of compounds which may possibly form on particu-
late matter approaches or exceeds that presently known to
356
-------
man." While this statement may be true, it is never linked
experimentally in Dow's submission to a demonstration that
PCDDs will typically form during combustion reactions.
Several authors (e.g., Buser et al. [Chemosphere, 7(2),
165, 1978]; Rappe et al. [Chemosphere, 7(3), 269, 1978],
Stehl and Lamparski [Science, 196, 1008, 1977]; Ahling et
al. [Chemosphere, 6(8), 461, 1977]; Buser and Rappe [Chemosphere,
7 (2) , 199, 1978]), on the other hand, have demonstrated in a
laboratory setting that PCDDs can be formed during the
pyrolysis of polychlorophenates (sodium salt) or polychloro-
phenoxy-containing materials (e.g., polychlorophenate-
impregnated leaves, wood shavings, plywood, or waste oil).
Rappe ejb al. (1973) stated that the concentration of PCDDs
in the combusted samples represented a sizeable increase
over the levels detected in the original polychlorophenate
samples.
IV. Airborne Particulate Matter
Soil samples were collected from "13 different locations
inside and outside (Dow's) Midland Plant" and analyzed for
tetrachlorodibenzo-p-dioxin (TCDD), hexachlorodibenzo-p-
dioxin (HxCDD), heptachlorodibenzo-p-dioxin (HpCDD), and
octachlorodibenzo-p-dioxin (OCDD). Dow does not further
identify the sites with respect to individual locations or
distances from the plant or specific plant operations. The
analytical results are presented in Table 1. Dow notes that
the analytical method was not validated and, therefore, the
results are qualitative only.
Table 1. PCDDs in 13 Midland Soil Samplesa
(taken from p.17 of Dow's report)
TCDD HxCDD HpCDD OCDD
4/13 9/13 13/13 13/13
a) Collected from "inside and outside the Midland
plant."
A second set of soil samples was collected in the same
manner; 5 of these, "including the ones corresponding to
those that previously gave positive TCDD results, were
analyzed by a newly developed and validated analytical
method." Dow goes on to state that this new method per-
mitted the separation of the 2,3,7,8-TCDD from "almost all
of its other 21 isomers." These results are summarized in
Table 2. The specific sample selection sites represented by
Table 2 should be clearly identified as to their placement
with respect to the Dow plant.
357
-------
Dow's claim at this juncture and at subsequent points in the
submission that its analytical method permitted separation
of TCDD isomers is not adequately supported by any of the
figures shown in the submission or the attached appendices.
Dow should be asked to provide a detailed description of the
methods of extraction and analysis as well as the criteria
utilized in the identification of TCDD isomers; e.g., (a)
GC/HRMS (gas chromatography/high resolution mass spectroscopy)
detection method, (b) elemental composition of molecular
masses m/e 320, m/e 322, and m/e 324, (c) molecular ion Cl
ratio, 0.8/1.0, (d) GC/HRMS retention time of test samples
and confirmatory samples fortified with specific TCDD
isomers, (e) m - COC1 loss, m/e 257, (f) use of and tech-
niques for GC/HRMS double ion monitoring, (g) a description
of the capillary column GC resolution measured in theoretical
and/or effective plates, and (h) a description of the degree
of GC resolution of specific TCDD isomers (Dow's tables
should be more specific and indicate identified isomers and
their contribution to the total value shown). In addition,
Dow should clarify if the quantified values of TCDD isomers
shown in its report are based on the response of specific
isomers or if the values are normalized to the response of
2,3,7,8-TCDD. Finally, there is some question that the harsh
(acid) conditions used for sample extractions may have
resulted in PCDD formation from precursors or by dechlorina-
tion of higher PCDD isomers. Dow should be asked to confirm
its findings by providing comparative results from neutral
extraction procedures, if available.
The information needs outlined in the preceding paragraph
concerning TCDD isomer values also apply in all cases to
HxCDD, HpCDD, and OCDD isomer values reported in the Dow
submission. Any available data on the presence of penta-
chloro dibenzo-p-dioxin isomers in environmental samples
should also be requested.
Dow states on p.2 of its report that the "analytical method-
ology is so very new that it has not always been validated
and not yet corroborated by other scientists." Limited
analytical significance can be derived from results generated
using nonvalidated procedures. In order to derive significant
and valid analytical meaning and/or conclusions from the
results of part per billion (ppb) and part per trillion
(ppt) analysis for PCDDs, the results must be accompanied by
(1) appropriate quality control results and (2) a complete
description of the criteria utilized to identify and confirm
the presence of PCDD residues. Furthermore, in cases where
the reported PCDD residue levels and the limit of detection
are of identical or approximately equal value, such numbers
have uncertain analytical significance especially in situations
when nonvalidated analytical methods are employed. PCDD
values which are not greater than ten times (10X) the noise
358
-------
have been identified with an asterisk (*) in this status
report. (When analyzing for trace levels of PCDDs, a
signal to noise ratio of 2.5:1 is considered to be the level
of detection; values below this ratio are reported as non-
detected [ND]. When a sufficient amount of the sample and
time are available to the analytical chemist, samples having
a signal to noise ratio between 2.5:1 and 10:1 should be
rerun a second time to verify the result. If the second
analysis falls between 2.5:1 and 10:1, the two separate
results and the average should be reported. Values result-
ing from a single analysis are not contested if the signal
to noise ratio is at least 10:1 and the ratio of peak heights
m/e 322:m/e 320 is in the proper isotopic proportion.)
Table 2. PCDDs in 5 Midland Soil Samples'
(taken from Dow's Table III)
(ppb)
Sample
1
2
3
TCDD isomers
other than ,
2,3,7,8-TCDD 2,3,7,8-TCDD
17 16
HxCDD HpCDD
230 3200
9
18
13
6
100
16
40
120
280
0.8
0.3
470
650
240
70
OCDD
20500
2500
6300
11700
490
a) Taken from "inside and outside the Midland plant."
b) Values are reportedly based on the "separation of
the 2,3,7,3-TCDD from almost all of its 21 other
isomers" (see discussion in the text).
Next, dust samples were collected at various locations in a
"Dow research building" and subsequently extracted and
analyzed using a method reportedly separating "the 2,3,7,3-
TCDD from all but about 11 of its isomers". (As discussed
earlier, this statement should be supported by documentation
indicating that eleven TCDD isomers plus the 2,3,7,8-TCDD
equals one fraction. Dow's statement to that effect is not
sufficient.) The results of this work are presented in
Table 3. Dow should be asked to clearly describe what it
means by the term "air intake." Does the PCDD contamination
of this air intake dust result from the handling of "inside"
or "outside" air?
359
-------
Table 3. Dust Samples front a Dow Research Building (ppb)
(taken from Dow's Table IV)
Sample
1st floor
1st floor
2nd floor
2nd floor
TCDD isomers
other than
2,3,7,8-TCDD
0.5
2.3
1.3
2nd floor 1.5
(2 weeks after
cleaning)
air intake 2 . 3
2,3,7,8-TCDD
1.0
2.3
2.6
0.7
1.2
2.3
HxCDD HpCDD OCDD
18* 240* 960
28
11*
9*
20*
35*
520
140
250
320
1200
3800
650
2600
2000
7500
a) Values are reportedly based on the "separation of
the 2,3,7,8-TCDD from all but about eleven of its
isomers" (see discussion in the text).
*Value is close to the detection limit for the analytical
method employed (signal is less than 10X noise).
Additional dust samples from Midland and an unspecified
"metropolitan area" were collected and analyzed for control
purposes. These samples did not satisfy this need, therefore,
dust and soil samples were collected from additional, vaguely
characterized ("rural," "urban," and "major metro") sites.
Table 4 represents a composite presentation of these results.
Dow concludes (p.21) that these data (Tables 1-4) "strongly
support the conclusion that chlorinated dioxins are produced
in incinerators and fossil fueled powerhouses as a consequence
of combustion. These results indicate that chlorinated
dioxins are more widespread than previously anticipated and
are perhaps ubiquitous". In point of fact, the results
presented offer no scientific documentation (other than
weakly circumstantial evidence) relating Dow's observations
on PCDD contamination of soil and dust to the synthesis of
PCDDs as a by-product of incineration or power generation.
There is some circumstantial evidence that the HxCDD,
HpCDD, and OCDD identified in the soil samples from the
urban and the metropolitan areas may be associated with the
operation of a powerplant and an incinerator, respectively.
This, however, does not demonstrate that the presence of
these substances results from their synthesis as a normal
combustion by-product. Table 5 presents a comparison of the
360
-------
total number of PCDD-positive samples collected from the
Midland, MI area with those collected from other locations.
From Table 5, the following observations, contrasting Dow's
claims, can be supported:
(a) Midland, MI, and especially the area around the
Dow plant, exhibits the greatest evidence for
gross PCDD contamination among the various locations
sampled. This is true both in terms of the propor-
tion of samples in which PCDDs were detected and
the degree of contamination evident in individual
samples. In the latter case, the levels of PCDDs
found in Midland are 2-4 orders of magnitude
greater than those reported at other locations.
The fact that much higher levels of PCDDs were
found in the soil and dust around the Dow chemical
plant as compared to urban, metropolitan, and rural
areas suggests that polychlorophenol production or
some other activity (spills, plant emissions,
combustion of chemical wastes, etc.) at the Dow
plant may be the source of the observed PCDD
contamination.
(b) To the extent that TCDDs, especially 2,3,7,3-TCDD,
are the PCDDs of greatest Agency concern, the levels
of TCDDs identified in Midland soil and dust samples
indicate that this area represents a definite TCDD
"hot spot." In comparison, there are very few
instances where TCDDs were reported at other sites.
V. Incineration
In its introduction to this section, Dow cites several
European authors who have reported the presence of PCDDs in
fly ash and flue gas from municipal incinerators (Olie et
al., Chemosphere, 6(8), 455, 1977), in fly ash alone from a
municipal incinerator, and in fly ash from an industrial
heating facility (Buser e_t ail. , Chemosphere, 7(2), 165,
1973). Dow notes (p.22) that Olie et al. postulate that the
PCDDs are formed as a result of the thermal condensation of
chlorophenols, although mention is made in the article that a
thermal synthesis reaction involving inorganic chloride and
organic material (especially hexachlorobenzene and other
highly chlorinated benzene) "was considered to be entirely
possible." Dow, however, fails to discuss aspects of the
Buser et al. (1973) study as well as a Rappe et al.
(Chemosphere, 7(3), 269, 1978) study which indTcate that the
pattern of PCDD isomers identified in fly ash (from incinera-
tors and heating facilities) was almost identical to that
found when a mixture of polychlorophenates was pyrolyzed
under controlled conditions. Buser et al. go on to state
361
-------
Table 4.
PCDDs in Soil and Dust Samples (ppb)
(taken from Dow's Tables III, IV, V, and VI)
Sample
Midland
TCDD
HxCDD
HpCPD
OCDD
(1) 0.03* 0.2 2.3 19
(2) 0.04* 0.4 3.9 31
(3) See Tables 2 and 3 for other Midland values.
Rural
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(3)
Urbana
(1)
(2)
(3)
(4)
(5)
Major Metro
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
(10)
(11)
(12)
(13)
(14)
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
0.03
ND
0.006*
0.005*
0.005*
ND
ND
0.04*
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
1.2
ND
0.03*
ND
ND
ND
0.03*
0.31
0.12*
0.14
0.04*
0.09*
0.02*
ND
0.34*
0.09
0.1
ND
0.3
ND
ND
ND
0.3*
0.05*
0.02*
ND
0.03*
1.6
0.23
0.30
ND
0.035*
0.14
0.24
3.3
1.4
0.85
0.36
0.96
0.10
0.64
3.2
0.3
0.3
ND
1.0
ND
0.1*
ND
0.10
0.17
0.16
ND
0.11*
2.0
0.96
2.0
0.05*
0.20
0.41
1.0*
22.0
8.5
3.2
1.4
6.0
0.35
2.6
8.2
3.5
0.4
ND
3.3
a) Samples collected from between 300-1500 feet from a
"powerhouse."
b) Samples collected from between 100-3300 feet from an
"incinerator" (except for (14) which was collected at
a "metro river shoreline").
*Value is close to the detection limit for the analytical
method employed (signal is less than 10X noise).
ND) Signal not detected at 2.5X noise.
362
-------
en
(1)
•P
CO
en
•d G
G O
rd -H
4*
rd
•H o
O O
en
0 -P
> G
0
0
en
O MH
•H
P
MH
MH
O -d
0
N
fd
G
O
en
•H
H
rd
ft
u -P
m
0
rH
X)
rd
dP
0
0
i-H
P
Q
O
O
• —
VO
CM
\
CM
O
O
rH
Q
Q
O
ft
|T]
• —
VO
CM
"K^
VO
CM
dP
CO
CO
Q
P
U
X
W
»-*
VD
CM
\.
CM
CM
Q
P
O
1
or
«.
r-
«.
n
H
CM
<#0
0
O
^
•d
rH
H
X.
rH
rH
*-*
O
O
in
o
CM
|
C^
rH
O
O
CM
CO
1
CO
•
CM
~
,— s
0
CO
CM
|
CM
•
O
~
O
o
rH
|
ro
•
o
* —
^^
OP
r-~
CO
•*-*
n
CM
x^
o
CN
dP
CO
r~
•— *
n
CM
V^
CO
rH
6P
CO
"^
~-^
n
CM
*\
o
rH
,— .
O
•
CM
rj
1
in
o
•
o
m
•
m
I
CM
O
•
o
~
CM
•
rH
|
CM
O
•
O
*~*
^x
dP
n
vc
•> —
CO
xs
LI
r-.
dP
O
m
— -*
CO
•\
^
^_x
dp
O
•— '
CO
"s^
0
^-,
dP
O
O
rH
• —
in
\
m
^.^
dp
O
CD
-—'
in
v^
^
. — .
dP
O
M1
« —
in
x.
CM
*-^
O
•
CM
l
in
c
•
o
vo
•
i— I
1
in
n
o
•
o
~
CM
•
H
1
CO
o
•
o
dP
O
o
rH
O
H
v^
O
rH
O
O
H
•— '
O
rH
^V*
O
rH
c',°
O
CO
• —
o
rH
\
. — ,
O
' t
CM
CM
|
in
ro
•
0
m
•
n
1
o
H
•
O
~
^
CO
•
o
1
CN
O
•
O
~
en
M
I
en
H
P
P
B
o
•H
•P
rd
O
O
dP
•— co
rH
rd l
in ro
CM o
^ o
dp .
CM O
CM I
^- in
o
n o
CM •
VO O
rH —• in
CO
O
in
x.
o
H
•d
•rl
&
en
§
•H
•P
rd
O —
O H
rl
0
-P
O
•P
O
4J
rd
rl
XI
rl
D
--* O
o o
in i
-' in
o
o o
in — '
O
M
•P
2
o
a
4J
d
CD
en
CD
J_|
Pl
0)
• «. if-{ (_l
P O
P >i
U CD rH
EH CD -P
1 rl G
CD di CD
- CD rl
r- -d rd
•• ft
n CD ft
^ g cd
CM O
•en c
c i
XI CD H
4J > O
CD O
M -H
CD x; en
X! O -H
-p fd x:
O -P
CD
en > c
in fd -H
CD X3
g n
O O CD
en -P -H
•H rl
*d -p •
P CD C en
P g CD H
U -H CD
EH fd rl g
rH CD O
en o A en
-P JJ -rl
C en o
CD-rl P
en H p
CD TJ rH O
in O rf3 EH
ftxi
CD -P rH
iH CD • rH
g C fd
>i O
rH rH -H U
•d fd -P o
CD U rd MH
-P -H H
>H -p rd en
O >1 ftrH
ft rH CD fd
CD rd en -P
M C 0
fd JH -P
>i CD
M CD g 0)
-p x: o -P
C -P en rd
CD -H t7>
•> CD
en . p in
•rl CD P CT>
t^H • C^) er1
EH -H EH fd
en 4-i
•H O
r]
•P >d CD
CD g
Ml tj ^
O CD en
•d
en -H M-i
CD en o
en C
O O CD
ft o o
M C
d CD fd
ft rl 0
CD -H
rl £ MH
O -H
•4H ** G
Cn
^J Tl -H
rd G en
*£ rd
4J rH
CO (^
CD O
.p en -H
O CD -P
g !— | ^)
XI H
rd rd
• EH C
-^ cd
C! g
O O CD
•P MH -P
id
0 C O
O CD -P
J lyl
im t-1**
\ fd en
en 4-> rd
CD
rH en en
ft CD C
g 3 O
fd rH -rl
en (d -P
> en
CD CD
^ • — • 13
•H * D1
Jj —
•H CD
en >d -P
ad) -H
X ft
i en en
P -rl Q) .
P >H "d en
O
{H "• -P
0 0 -rl 0
O rH en en
M XI O 0
0 rd ft,c
ft -P = -P
•
Xt
ft
ft
g
•H
en
rH
0
0
rH
*d
0
4J
0
0
-P
0
'd
MH
O
0
G
rd
PH
P
a
r)
§H
1
CO
».
f*
^
m
«.
CM
0
4J
MH
O
G
O
•H
•P
id
rl
rd
ft
(U
en
MH
O
0
0
&>
0
-d
0
g
0
en
en
-P
rj
0
en
0
ft
0 •
in en
rl
>i 0
•H g
•d 0
0 en
•P -rl
rl
0 P
ftp
0 U
H EH
J>1 M
rl 0
•P X!
C -P
0 O
en g
•H O
X! M
EH MH
(0
o -d
363
-------
that available evidence indicates that commercial chloro-
phenols cannot be excluded as the precursor to PCDDs in fly
ash. As noted briefly in the dicussion of part I, Rappe et
al. (among others) have also shown that the combustion of
Te"aves, wood shavings, plywood, or waste oil containing
chlorophenates can yield a variety of PCDD isomers in the
ash. Dow reports that it operates two major chemical waste
incinerators at Midland, MI. The first is a large stationary
tar burner and the second is a rotary kiln incinerator.
Samples of particulate matter were removed from the stacks
and analyzed for PCDDs. The resulting data are summarized
in Table 6. Particulates from the stationary tar burner and
the rotary kiln incinerator show no detectable TCDD when
operated with supplementary fuel. (The levels of the other
PCDD isomers are, nonetheless, still relatively high.)
However, when the rotary kiln incinerator is operated
without supplemental fuel, extremely high levels of TCDDs
(and other PCDDs as well) are detected. Several important
questions immediately arise. Does Dow generally operate the
rotary kiln incinerator with supplemental fuel when using it
for chemical waste incineration? Dow should specify the
types and conditions of operation of air pollution control
devices (including scrubbers) used to control particulate
emissions from these incinerators? It is also important to
know whether the particulate samples were collected from the
stacks "upstream" or "downstream" from the scrub water inlet
(i.e., before or after scrubbing) (see part VII below). In
addition, were the particulates scraped from the walls of
the stacks or were they collected from the gas phase or an
electrostatic precipitator (or some other pollution control
device).
VI. Powerhouses
Particulates from a Dow Midland powerhouse stack were col-
lected and analyzed. Fuel oil and coal are burned in the
powerhouse. The results of the PCDD analyses are presented
in Table 7.
It is not clear why the TCDD isomers (other than 2,3,7,8-
TCDD which was not detected) are so high (compared to other
PCDDs) in the powerhouse particulate. Likewise, if Dow's
thesis concerning the synthesis of PCDDs as a normal combus-
tion by-product is correct, why do the incinerators as
opposed to the powerhouse, in general, show higher levels of
PCDDs in the fly ash? The difference may be related to the
nature of the material being burned in each operation.
One possible explanation is that the chemical wastes being
burned in the incinerators already contain PCDDs or PCDD
precursors (polychlorophenoxy material); that is, the wastes
364
-------
Table 6. PCPDs in Particulate Matter from Dow Incinerators (ppb)
(taken from Dow's Tables VIII and IX)
Sample
TCDD isomers
other than
2,3,7,8-TCDD 2,3,7,8-TCDDa
HxCDD HpCDD
OCDD
(1)
(2)
(3)
(4)
(5)
Stationary tar burner (with supplemental fuel)
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
20 90 330
7 125 440
6 60 190
4 160 37.0
1 27 250
Rotary kiln incinerator (without supplemental fuel)
(1)
(2)
(3)
(4)
1,800
5,000
3,300
12,000
2,300^
8,200°
110
ND
13,000
65,000
1,300
5,600
110,000
510,000
2,000
37,000
180,000
310,000
3,000
59,000
(1)
(2)
(3)
(4)
(5)
a)
Rotary kiln incinerator (with supplemental fuel)
ND
ND
ND
ND
ND
Dow's report does not specify the number of TCDD
isomers represented by values in this column.
ND
ND
ND
ND
ND
1.4
ND
ND
5.0
4.0
13.0
4.0
6.0
27.0
110.0
30.0
9.0
15.0
170.0
950.0
b) These values may be high; see Dow's comment on p.24,
Table 7. PCDDs in Particulates from a Powerhouse Stack (ppb)
(taken from Dow's Table X)
TCDD isomers
other than
2,3,7,8-TCDD
33*
2,3,7,3-TCDD'
ND
HxCDD HpCDD OCDD
2 4 24
a) Dow's report does not specify the number of TCDD
isomers represented by this value.
*Value is close to the detection limit for the analytical
method employed (signal is less than 10X noise).
365
-------
result from Dow's chlorophenol production processes. Rappe
et al. (1978) offer several different mechanisms for the
formation of PCDDs given the presence of pre-formed PCDDs or
PCDD precursors. The 3 proposed mechanisms are:
a) by dimerization of chlorophenates,
b) by dechlorination of higher chlorinated PCDDs, and
c) by cyclization of PCDD precursors.
VII. Waterborne Particulates
Composite scrubber water samples were taken from the rotary
kiln incinerator during the same sampling reported in part V
of the report. Particulates were filtered from the scrubber
water and both the particulates and the water filtrate were
analyzed for PCDDs. (Note that Dow's analytical method ML-
AM-73-63 [Dow's Appendix B3] [specific for soil, dust, and
particulate samples] was used to analyze the scrubber water
particulates. Dow, however, does not specify the analytical
method used to examine the water filtrate. This should be
clarified.) Table 3 presents the results of these analyses
and also compares the scrubber water PCDD values with those
reported for rotary kiln fly ash (previously reported in
Table 6). When comparing the PCDD levels reported in the
different samples, it should be noted that there is no
indication whether all the samples were taken within a short
time of each other or days apart. In addition, it is not
clear if the same wastes were being burned or if similar
incineration conditions existed when the respective samples
were taken. Dow should be asked to provide a complete
description of the operating conditions (normally and during
sampling), nature of the wastes burned normally and during
sampling, and use of air pollution control devices on the
rotary kiln incinerator. Dow should also describe the
method of disposal used for scrubber water particulates and
any other solid wastes resulting from these incineration
procedures.
In addition, Dow should provide the same information for its
stationary tar burner.
VIII. Combustion of Dioxins
The U.S. EPA report entitled "At-Sea Incineration of
Herbicide Orange Onboard the M/T Vulcanus" (EPA-600/2-
78-036) was published in April, 1978. A copy of this
publication should be transmitted to Dow in any followup
to this submission.
366
-------
Table 8. PCDDs in Rotary Kiln Scrubber Water and Stack
Fly Ash (ppb)
(taken from Dow's Tables IX, XI, and XII)
Without supplemental fuel
Sample
A) scrubber water
particulates
B) scrubber water
filtrate
C) fly ash .
particulates
TCDD isomers
other than
2,3,7,3-TCDD
300
0.0013*
(1) 1,800
(2) 5,009
(3) 3,300
(4)12,000
2,3,7,3-
TCDD
2,200a
0.001'
2,300
8,200
110
ND
HxCDD HpCDD OCDD
3,400 26,000 42,000
0.005 0.24 0.026
13,000 110,000 130,000
65,000 510,000 310,000
1,300 2,000 3,000
5,600 37,000 59,000
With supplemental fuel
D) scrubber water 14
particulates
E) fly ash (1) ND
particulates (2) ND
(3) ND
(4) ND
(5) ND
32'
ND
ND
ND
ND
ND
!00
970 1,200
1.4
ND
ND
5.0
4.0
13.0
4.0
6.0
27.0
110.0
30.0
9.0
15.0
170.0
950.0
a) The analytical method reportedly did not separate
the 2,3,7,8-TCDD from 11 other isomers.
b) The high results reported for 2,3,7,3-TCDD "are
probably due to analysis by the non-specific GC-HS packed
column method" (see p.24 of Dow's report). In addition,
Dow1s report does not specify the number of TCDD isomers
represented by the values in the 2,3,7,8-TCDD column.
*Value is close to the detection limit for the analytical
method employed (signal is less than 10X noise).
367
-------
IX. Michigan Division Manufacturing Plants as Potential
Sources of Trace Levels of Chlorinated Dioxins in the
Environment
A. Wipe testing
The fact that 8 out of 230 wipe tests gave positive results
for TCDD merits consideration. The wipe test area, 100
cm , is roughly equivalent to the area of a human hand and
1 ug TCDD may be approaching a toxic level (LD5Q male guinea
pig, 0.6 ug/kg). The text indicates that the analyses were
conducted by gas chromatography with a detection limit of
1 ug/wipe; however, Appendix B4 states that analyses were
carried out by GC-MS with a level of detection of 0.1 ug/
sample. These points should be clarified. In addition,
information as to the suitability of the wipe test method-
ology to actual conditions which might be encountered in
the Michigan Division manufacturing plants should be provided
by Dow.
B. Air monitoring
The method of sample collection is not described in suffi-
cient detail in Dow's report. Are particulates sampled
during this procedure? Also, note that part of the report
appears to have been omitted at the top of page 30. This
omission should be clarified.
A statement made on p.30 could be misleading. "The few
molecules that take this path (vaporization) will be destroyed
by photodegradation within a few hours even when the day is
cloudy (23)." This statement could lead one to believe that
if PCDDs are released to the atmosphere they will be destroyed.
If these compounds are really volatilized then they could
possibly be decomposed; however, if they are adsorbed onto
fly ash or other particulate matter they would probably not
be destroyed photolytically or to only a limited extent. In
addition, the applicability of Dow's reference 23 (Nash and
Beall, 1977) to the above quotation is not clear; clarification
is required.
Dow claims on page 30 that the "wipe testing and air monitoring
data are strong evidence that (Dow) manufacturing plants do
not emit levels of chlorinated dioxins sufficient to explain
the finding of these compounds in the soil samples reported
earlier." No scientific basis for this conclusion is provided
in the data presented by Dow. In the first place, there is
no way to compare the ppb levels of TCDD found in soil and
dust with the "1 ug/wipe" values reported for the wipe
testing. To support its conclusion, Dow would either have
to "wipe test" soil samples or, preferably, analyze pesticide
plant wipes on a ng/g (ppb) basis. Handled in any other
way, one is left to compare apples with oranges. Similarly,
368
-------
there is no way to compare D'ow's plant air monitoring data
with the PCDD values reported for soil and dust samples
collected outside the plant. Furthermore, there is no
indication as to the location of each wipe test or air
sampling site in relation to the various operations involved
with polychlorophenol production or handling. Dow should
present a grid of its polychlorophenol production and
handling sites and identify the sampling points for the 230
wipe tests and 35 air monitoring assays. Any available
monitoring data (wipe tests, air sampling, etc.) regarding
Dow laboratory facilities as potential sources of PCDD
contamination should also be provided.
C. Aqueous streams
Further information on the "tests" for primary organics
reported in this section should be provided by Dow.
D. Cooling waters
The results of Dow's analyses of cooling tower "residues"
for PCDDs are shown in Table 9. It is important to know if
these towers cool steam or other effluent streams from the
polychlorophenol facilities, the power plants, or the incinera-
tors discussed earlier. Dow should provide a map of its
plant site showing the location and relationship of each
cooling tower, incinerator, powerhouse, and production
facility (especially those producing or handling polychloro-
phenols or derivatives). In addition, Dow should further
describe what it means by "cooling tower residue"; is this
a water or sediment sample? Dow should also support with
analytical results its statement on page 30 that "product
leaks to cooling towers" do not occur.
Table 9. PCDDs in Cooling Tower Residues
(taken from Dow's Table XIII)
Location
Northwest
East
Central #1
Central #2
TCDD
ND (L.O.D.
0.05)3
ND (L.O.D.
0.05)
1.6*
6.0
HxCDD
ND
ND
10
HpCDD
25
12
20
a) Level of detection was 0.05 ppb.
*Value is close to the detection limit for the analytical
method employed (signal is less than 10X noise).
369
-------
Dow states in this section (p.30) that "(it) was assumed
that cooling tower residues would be positive for chlorinated
dioxins." Dow should be asked to provide the basis for this
assumption. On page 31, Dow states that "(from) these data
(see Table 9), we conclude that the presence of chlorinated
dioxins in cooling tower residues confirms the airborne
route." Dow should b6 asked to explain the term "airborne
route" and specify the sources of the PCDDs found in cooling
tower residues.
Central to this discussion of cooling towers is the assumption
that Dow does not use 2,4,5-trichlorophenol in its cooling
tower waters as a biocide. Dow should be asked to clarify
this point. In the event that Dow does use 2,4,5-trichloro-
phenol, then the PCDDs found in the cooling tower residues
may not be from airborne particulates.
E. Various aqueous streams
For this part of the report, Dow sampled various aqueous
streams in its Midland plant. The samples were collected
from sewer lines before they entered the waste treatment
plant. The samples were selected on the basis of "the
stream source and its rate of flow." This vague description
of the samples is inadequate. Do any of the sampled aqueous
streams come directly from chlorophenol production or handling
operations? Do these samples include particulates? If
not, these analyses have limited value. Dow indicates it
employed analytical method ML-AM-73-97 (Appendix B2) for the
analyses reported in this section. The method is specified
for the analysis of fish and soil samples; its applicability
to aqueous stream analysis should be demonstrated.
On page 32, Dow states that in the case of sewer water
analyses, "the source of the chlorinated dioxins cannot be
reliably determined by the ratio of the various species."
However, in immediate juxtaposition to this statement is
Dow's remark (p.33) that "(with) the exception of sewer
water samples 2 and 4 and cooling tower central -Ll, the data
indicate that the chlorinated dioxins are from the same
source as those on soil and dust. The exceptions have
species whose ratios are similar to those found on particu-
lates from the powerhouse." Dow should clarify the meaning
and significance of these remarks. Insofar as Dow states in
the Introduction (p.2) that "(samples) were not taken by
statistical design and results are not intended to represent
anything other than the sample analyzed," how can Dow proceed
to compare the PCDD ratios from one sample with those from
another? Moreover, how can Dow draw conclusions from such a
comparison? Furthermore, how can the submitter state in one
paragraph that a comparispn of PCDD ratios will not yield a
370
-------
"reliable" determination of the source, but then in the next
paragraph draw 2 separate and distinct conclusions from
these same ratios.
Another statement on page 33 deserves comment: "The (PCDD)
ratios (found in the cooling tower or sewer waters) do not
fit those normally found in any manufactured product." The
meaning of the phrase "normally found in any manufactured
product" is not clear because no known polychlorophenol
product or derivative contains both TCDD and OCDD. In
generalf trichlorophenol contains TCDD, while pentachloro-
phenol contains HxCDD, HpCDD, and OCDD but no TCDD. If Dow
is aware that any of its products contain both TCDD and
OCDD (or for that matter, both trichlorophenol and penta-
chlorophenol), it should so inform the Agency. Dow should
describe the spatial relationship of its trichlorophenol
production facility to the location of its pentachlorophenol
production site. Are any waste water lines common to both?
What is the composition of the chlorophenol wastes incinerated
by Dow? Do these wastes represent a composite of both
trichlorophenol and pentachlorophenol wastes? Or are wastes
from the two chlorophenol production processes burned sequen-
tially in the same incinerator?
X. Chlorinated-dioxin Containing Particulate Matter from
Mufflers
DOW reports trace quantities of PCDDs in scrapings taken
from the inside of car and diesel truck mufflers. The cars
sampled were equipped with and without catalytic converters.
Does this necessarily mean, as Dow advances, that PCDDs are
formed during combustion in the engine? If the car or truck
was driven primarily in an industrial area or near sources
that might be considered contaminated with PCDDs or PCDD
precursors, airborne particulates containing these substances
could be drawn into the air intake of the engine. Any
PCDDs not decomposed in passage through the engine might
then be deposited in the muffler. The statement (p.35) that
PCDDs "are in particulate emissions from internal combustion
engines" cannot be supported because vehicles' exhaust gases
were not analyzed. The only conclusions that can be supported
by the observations presented in this section are that (1)
PCDDs have been identified in some muffler scrapings, however,
(2) the source of the PCDDs is unknown.
The analytical method (GC-EC vs. GC-MS) used to detect
TCDD isomers was not specified in Dow's Table XV; this
information should be provided.
371
-------
XI. Commonplace Sources
1. Soot from fireplaces
Dow reports that soot collected from 2 fireplaces contains
PCDDs. The results are presented in Table 10. Dow states
(pp. 35 and 36) that none of the wood burned in the fire-
places "had been treated with any wood preservatives." Dow
should be asked to document this statement.
2. Particulate matter from a home electrostatic precipitator
The results of PCDD analysis performed on this sample are
presented in Table 10.
Table 10. PCDDs in Fireplace Soot and Particulates
!E
Cl
from a Home Electrostatic Precipitator (ppb)
(taken from Dow's Table XVI)
TCDD isomers
other than
Source 2,3,7,8-TCDD
fireplace
A
fireplace
B
0.27
ND
electrostatic 0.40*
precipitator
2,3,7.3-
TCDD
0.1*
ND
0.6*
HxCDD HpCDD OCDD
3.4 16 25
0.23 0.67 0.39
34 430 1300
a) Dow1s report does not specify the number of TCDD
isomers represented by values in this column.
*Value is close to the detection limit for the analytical
method employed (signal is less than 10X noise).
The geographic location of each house sampled in Table 9
should be provided by Dow. Were these houses in the Midland,
MI area, and if so were they near Dow's plant? This is of
some interest because the particulate collected in the
electrostatic precipitator (electronic air cleaner) have
a higher concentration of PCDDs than the soot samples from
the fireplaces (acknowledged sources of typical combustion
by-products). A home electrostatic precipitator functions
to a certain extent as a "high volume air sampler." In the
case cited by Dow, the electrostatic precipitator was operated
over a period of 6 spring and summer months. Thus, the
precipitator particulates analyzed by Dow represent airborne
372
-------
material collected over a 6 month period which does not
coincide with the months generally associated with heavy
space heating-related combustion or home fireplace usage.
Therefore, the PCDD values for the home electrostatic
precipitator-collected particulates may, to a certain
extent, represent the results of incidental ambient air
"sampling" conducted at the site of the house. For this
reason, the location of this particular house may be important.
3. Charcoal broiled steaks
The results of this assay are presented in Table 11. As can
be seen, all samples were negative for TCDD and HxCDD and in
only one case (that being an "over-done" steak) did the GC-
MS (gas chromatography-mass spectrometry) method of analysis
"support" the GC-EC (gas chromatography-electron capture)
result. However, even in that case (as in all other
instances reported in the table), the reported OCDD residues
and the level of detection are of identical or approximately
equal value such that the number has limited analytical
significance. Furthermore, the blank sample (uncooked
steak?) had a concentration of 6 ppt of OCDD (determined by
GC-EC, although the value is so close to its level of
detection as to have limited analytical significance). Was
this blank (uncooked steak?) contaminated with pentachloro-
phenol, a widespread environmental contaminant?
Table 11. PCDD Content of Charcoal Grilled Steak (ppb)
(taken from Dow's Table XVII)
Sample
blank
medium-rare
well-done
over-done
TCDD isomers
other than
2,3,7,8-TCDD
ND
ND
ND
ND
2,3,7,C-
TCDD HxCDD
ND
ND
ND
ND
HpCDD OCDD
GC-MS EC GC-MS EC
ND
ND
ND
ND
ND
ND
ND
ND
0
0
0
0
.004*
.003*
.006*
.007*
ND
ND
ND
0.029*
0
0
0
.006*
.005*
.012*
0.016
*
*Value is close to the detection limit for the analytical
method employed (signal is less than 10X noise).
373
-------
XII. Cigarette Smoke
Cigarette smoke particulates were also analyzed for PCDDs;
the results are presented in Table 12,
Table 12. PCDDs in Cigarette Smoke Particulates
(10"12 g/cigarette)
(taken from Dow's Table XVIII)
Location TCDD isomers
of purchase other than 2,3,7.8-
and test 2,3,7,8-TCDD TCDD HxCDD HpCDD OCDD
urban 1 ND ND 8.0 8.5 50
urban 2 ND ND 4.2 9.0 13
a) Dow's report does not specify the number of TCDD
isomers represented by values in this column.
Several questions arise concerning this assay. Are PCDDs or
PCDD precursors present in unburned cigarettes (possibly due
to pesticide use of polychlorophenols or derivatives)? How
does 10 g/cigarette relate to 10 g/g (or ppt)? The
cigarettes were smoked in two unidentified "urban locations";
why was this method chosen over a controlled study conducted
in a lab? Were the cigarettes "smoked" near Midland, MI or
some other industrial site; in other words, how would the
results of ambient air sampling at the two locations compare
with the reported cigarette-PCDD values? Do the individual
results in Dow's Table XVIII represent GC-EC or GC-MS
analysis? Are the methods confirmatory in their results?
XIII. Other Chlorinated Compounds Identified
The polychlorinated dibenzofuran (PCDF) findings reported in
this section should be investigated further. Several investi-
gators (Buser et_ a!L., Chemosphere, 7(5), 419, 1970a; Rappe
et al., Chemosphere, 7 (5) , 431, 1978; Buser et al., Chemosphere,
7(5), 439, 1978b; Rappe e_t a!L. , Chemosphere, 6(5), 231,
1977; Buser et al., Chemosphere, 7(1), 109, 1973c; etc.)
have identified PCDFs in polychlorophenol pesticides, saw
dust from polychlorophenol-treated wood, fly ash, PCB mixtures,
and as a by-product of the combustion of PCBs. Of significance
are the Buser et al. (197°,a) findings that the major PCDF
constituents (in fly ash as well as in PCB pyrolyzates)
tended to be the most toxic PCDF isomers (2,3,7,3-tetra-CDF;
1,2 ,3,7,3-penta-CDF; and 2 , 3, 4 ,7, 'l-penta-CDF) . This contrasts
374
-------
with the Buser et al. (1978a) findings on the distribution
of PCDD isomers~Tn polychloropheriate pyrolyzates where the
less toxic isomers were in greatest concentration.
375
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
0*TE:August 16, 1978
SUftJiCT: Status Report 8EHQ-0778-0210 Approved
Revision
MOM: Frank D. Kover Needed
Assessment Division, OTE/OTS
TO'Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
Results of an acute oral toxicity study of VEL 4582 (S-methyl-n(alpha'-
methyl-N'-methylcarbamyloxymethylene) oxy-thioacetimidate) in rats. The
name and molecular structure presented by the submitter do not appear to
agree with each other. This will have to be clarified in a follow-up
letter.
Submission Evaluation
The purity of the test compound is suspect. The report speculates that
the material "may contain small amts of Hydrocarbon (?) and N-Hydroxy-
methyl deriv." The test material is characterized only as a "gold color
viscous liquid," while the formula would suggest that VEL 4582 is a solid.
The LD5Q data indicate that VEL 4582 is a significantly toxic compound
when taken by mouth. It is more toxic (in terms of lethality) than
morphine or barbiturates.
It would be useful to have microscopic sections studied for evidence of
pathological changes in the organs of animals that died 1 to 3 days after
receiving VEL 4582.
Current Production and Use
No information was located in the secondary sources consulted.
Comments/Recommendations
(a) The discrepancy between the chemical name and the molecular structure
must be clarified by the submitter.
*NOTE: This status report is the result of a preliminary
st;ff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FOU* !)»•» (ftCV. »-T«)
376
-------
(b) The submitter should be asked to provide a description of the uses
of this material.
(c) The submitter should provide histopathological findings on the test
animals, if available. In the event that this work has not been
done, the submitter should consider initiation of these studies.
(d) The submitter should be asked to support his contention that the
information presented in this submission reasonably supports a
conclusion of substantial risk.
377
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
OATC: DEC 4 1S78
*u»JECT: Status Report* 8EHQ-0778-0211
no*. Frank D. Kover
Assessment Division, OTE/OTS
T0: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Approved
Revision
Needed
Submission Description
Results of teratogenicity testing of MMT (methylcyclopenta-
dienyl manganese tricarbonyl) in rats.
Submission Evaluation
An independent laboratory conducted this study under contract
to the submitter. The data indicate to the performing labo-
ratory that the manganese compound is a teratogen for fats.
This is in addition to the well-known toxicity of the com-
pound. The identification of MMT as a teratogen raises the
suspicion of carcinogenicity.
The submission does not make it clear who is questioning the
reliability of the experiment. Is it the performing labora-
tory or the submitter's in-house TSCA committee? EPA will
need to see the final report submitted by the performing
laboratory.
Current Production and Use
MMT is used as a gasoline anti-knock agent, either alone or
admixed with tetraethyllead. Current consumption of MMT is
not known.
Comments/Recommendations
The submitter notes that additional information is expected
shortly and a follow-up report will be filed with EPA within
90 days. Therefore, pending receipt of the final report, it
is recommended that:
EPA
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
112O-* (REV. >-7()
378
-------
1) This submission and status report should be trans-
mitted to OSHA, NIOSH, and OAQPS, OMSAPC, and ORD (fuel and
fuel additive registration).
2) Request follow-up report from submitter (90 days
have passed since receipt of this submission).
379
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
SUBJECT:
FROM:
;.:•.$ GD '.379
Status Report* 8EHQ-1078-0211
Supplement
Frank Du/Kover, Acting Chief
Chemical Hazard Identification Branch
Approved
Revisio
Needed
TO: Joseph J. Merenda, Director
Assessment Division
Submission Description
The submission presents a summary of the results of a
teratology study conducted in rats with MMT (methylcyclo-
pentadienylmanganesetricarbonyl). The submitter has con-
cluded, on the basis of their audit of the results, that its
earlier preliminary conclusion that MMT presents a sub-
stantial risk of injury is not supported by the final
analysis of the study. The preliminary report (8EHQ-0778-
0211) on this study was received earlier under Section "8(e)
and a status report was prepared at that time.
Submission Evaluation
MMT produced clear tloxicity to the female rats and the
fetuses they were carrying. This toxicity appears to be
dose related. The bleeding from the nose and the difficulty
in breathing are suggestive of lung damage. The urinary
incontinence is in keeping with the known central nervous
system effects of manganese. The adrenal enlargement ob-
served in rats at 5, 10, and 20 mg/kg/day is probably a
reflection of an alarm reaction due to destruction of body
tissues.
The rats administered 20 mg/kg/day exhibited greater toxicity
than those administered 5 or 10 mg/kg/day. The cachexia
(general wasting), alopecia (hair loss), and dehydration
suggest severe nutritional disturbances.
If the investigators mean that the usual incidence of fe-
tuses with variations in ossification was increased by MMT
at a maternal dose of 20 mg/kg/day, then this is significant
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
U20-« (*EV.
380
-------
3 8EHQ-1078-0211 Supplement
effects attributed to MMT in this in_ vivo study, was sub-
mitted appropriately under Section 8(e) of the Toxic Sub-
stances Control Act (PL 94-469).
Part V of the March 16, 1978 Federal Register (Vol. 43, No.
52) "Statement of Interpretation and Enforcement Policy"
states that the Agency considers the human health effects
for which substantial-risk information must be reported to
include "Any pattern of effects or evidence which reasonably
supports the conclusion that the chemical substance or
mixture can produce cancer, mutation, birth defects or toxic
effects resulting in death, or serious or prolonged incapaci-
tation" (43 FR 11112). Additionally, the introduction to
Part V states that the "information respecting these effects
can be obtained either directly, by observation of their
occurrence, or inferred from designed studies" (43 FR 11112).
These designed, controlled studies include in vivo and in
vitro experiments and tests.
Therefore, it is the Agency's preliminary determination that
the toxicological information as submitted (8EHQ-1078-0211
Supplement) appears to reasonably support a conclusion of
substantial risk of injury to health or the environment.
a) The submitter should be requested to provide a full
copy of the final results of their teratology study, in-
cluding the test protocols.
b) The inconclusive nature of the teratology results
from this study of MMT in rats may suggest a possible need
for more definitive testing.
c) This submission and status report should be trans-
mitted to OSHA, NIOSH, OAQPS, OMSAPC, and ORD.
381
-------
8EHQ-1078-0211 Supplement
and perhaps the teratological conclusions are more than
tenuous. The reported 39% fetal incidence of either ocular
or vertebral malformations has to be accounted for.
The observation that the 20 mg/kg/day dose group had ex-
cessive maternal toxicity and embryotoxicity (thereby lim-
iting the number of litters and fetuses available for ex-
amination) , and the associated "high incidence" (39%) of
developmental malformations among the remaining fetuses,
cannot be used to justify the statement in the submitter's
cover letter that "the data does (Sic) not support a conclu-
sion that MMT is a teratogen." On the contrary, the report
strongly suggests that better studies will have to be car-
ried out before it can be said that MMT is not a teratogen.
Current Production and Use
MMT has been used as a gasoline anti-knock agent, either
alone or admixed with tetraethyl lead. Provisions of the
1977 amendments to the Clean Air Act resulted in a ban on
the use of MMT in unleaded gasoline sold in the U.S. after
September 15, 1978. However, EPA recently (May 31, 1979)
suspended enforcement of the ban on MMT in unleaded gasoline
until October 1, 1979 in order to increase the supplies of
unleaded gasoline during this summer, thus minimizing the
problem of pollution-control catalysts on automobiles being
damaged by leaded gas. The current production volume of MMT
is not known.
Comments/Recommendations
EPA disagrees with the submitter's statement that "the data
does (Sic) not support a conclusion that MMT is a teratogen".
The fact that there was a 70% maternal mortality rate in the
20 mg/kg/day dose group, which therefore limited the number
of fetuses recovered for examination, does not diminish the
significance of finding ocular and vertebral malformations
in 39% of the recovered fetuses. Also, the significance of
the "slight increase" of ocular malformations in fetuses
from some rats receiving a dose of 10 mg/kg/day should not
be minimized by the fact that the fetuses with the malforma-
tions were from rats which came from only one of the two
shipments of animals used for the study.
Also, the Agency presently believes that the reported in-
formation, regarding the serious dose-related maternal em-
bryo-toxicities and the possible, dose-related teratogenic
332
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: August 16, 1978
SUBJECT: Status Report 8EHQ-0778-0212 Approved
Revision
Frank D. Kover Needed
Assessment Division, OTE/OTS
T0: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
Preliminary results of mouse skin painting studies conducted on mid-
boiling (550-700 F) fractions and aromatic subfractions of petroleum
crude oils. This submission is related to an earlier one (8EHQ-0178-
0029) in which the same submitter reported the incidence of benign and
malignant tumors in mice subjected to higher boiling petroleum fractions
and aromatic subtractions. The present submission also notes that
systemic toxicity was observed in mice subjected to the aromatic sub-
fractions of the higher boiling petroleum crude oil fractions.
Submission Evaluation
It is generally accepted that most fossil fuels contain polynuclear
hydrocarbons that have the requisite structure for yielding carcinogenic
diol epoxides by biotransformation, especially in the liver. The pre-
liminary report states that the findings are old hat. Nonetheless,
information such of this will have more relevant meaning if the submitter
actually pursues his plan to identify the chemicals present in various
distillation and residue fractions (see the last sentence of the first
paragraph of the preliminary report).
The issue at hand is not (as the submitter seems to feel) to what extent
can carcinogenicity in experimental animals be directly translatable to
carcinogenicity in man. This is a phase of assessment that still awaits
solution. The important point is that the fractions contain carcinogens.
It is not surprising that non-tumor related toxicity was observed with
the aromatic subfractions of the higher boiling petroleum crude fractions.
Shale oil has been found to contain ring compounds that differ from
steriod compounds only in having five instead of four rings. Such
compounds could interfere with normal steroid hormone function and
affect the liver, kidneys, adrenals, pituitary, testes, ovaries and
other organs. It is probable that other fossil fuels contain such
steroid-like compounds.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
KPA FORM U20-« (MCV. »-7t)
333
-------
Current Production and Use
Mid-boiling petroleum crude fractions and aromatic subtractions are
derived from crude oil fractionation procedures. Information as to the
production and uses of these specific fractions is not available; how-
ever, they are likely to represent high-volume basic petroleum feedstocks.
Comments/ Recommendations
(a) The submitter should be asked to provide full copies of the final
studies when completed. In the meantime, the submitter should be
asked to provide a more complete description of the chemical
analyses planned to determine and define any potentially carcino-
genic, cocarcinogenic, and promoter substances found in petroleum
crude oils.
(b) This submission and status report should be transmitted to NIOSH,
OSHA, OPP, and CPSC.
384
-------
UNITED il Al£5 ENVIRONMENTAL PROTECTION AGENCY
09 ADC 197$
SUBJECT: status Report* 8EHQ-0778-0213 Approved
*-. i rv «• » ^ • ^i_ • j= Revision
FROM: Frank D. Kover, Acting Chief Needed
Chemical Hazard Identification Branch
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
This information was received from Shell Oil Company in a letter
dated February 21, 1978. The submission consisted of the results
of a battery of six mutagenicity tests conducted on butyl
glycidyl ether (BGE; 1, 2-epoxy-3-butoxy propane) and other
glycidyl ethers. Shell submitted the information pursuant to
Section 8(d) of TSCA rather than 8(e). Shell did this because,
as they claim in their letter, they do "not feel that the results
can be considered to be valid until further work... is done. It
is Shell's position, that regardless of the above questions, this
information should be made available to the Environmental Protec-
tion Agency under Section 8(d).
..."
Submission Evaluation
This study concerns a battery of six mutagenicity tests conducted
on a number of epoxides by Dr. Marvin S. Legator of the Univer-
sity of Texas Medical Branch under the sponsorship of Dow Chemi-
cal Company. In the cover letter, Shell makes reference to
several problems with the experimental design of the dominant
lethal test. These problems should be stated specifically by
Shell.
Comments on the Microbial Test Systems and the Report Itself
Ames Test. The experimenters used only two strains of
Salmonella, TA 1535 and TA 98. Ames, however, recommends that
five strains be used for increased sensitivity. The additional
strains which should have been used are: TA 1537, TA 1538, and
TA 100. Reference is made in the results section to data from
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made hetein are not to be regarded as expressing final
Agency .:•::.I icy. or intent with respect to this particular
chem, •:;•..' Any review-of the status repor- should take into
Cv>ns:/:••;.; lion, the -fact the;, it may be bas-'-i on incomplete
.• oforrr".;-'-r on .
FOR!* iiiWHi, (RE.-, j-'/i.. 385
-------
TA 98, however, these data have not been included in the submis-
sion; this information should be provided. In Table 2, the mean-
ing of "Rt/Rc _+ S.D (No. of Trials)" is not clearly stated. One
could assume that this number refers to the control value but
this is not stated. A further uncertainty concerns the genera-
tion of the standard deviation. It is not clear if this calcula-
tion was based on the raw data or a ratio. Clarification should
be provided by Shell.
Body Fluid Analysis. There are a number of problems with
this analysis. The experimenter used only strain TA 1538 to
analyze for mutations. This strain is capable of detecting base
pair mutations. However, if only one strain is to he used in the
body fluid analysis, it should be strain TA 100 which is much
more sensitive than TA 1538. In addition, the experimenter
should also have used TA 98 which would give an indication of the
presence of substances (BGE or its possible metabolites) capable
of causing frame shift mutations. The investigator used cyclo-
phosphamide as a positive control in this assay. A more suitable
positive control would have been an epoxide previously shown to
be mutagenic. Table 3 should contain information on the number
of control revertents per plate; this data should be provided by
Shell. Another problem with the study is that there was no
attempt to concentration metabolites from the urine. This
significantly decreases the sensitivity of this particular test.
Micronucleus Test. The experimenter used TEM (triethylene
melamine) as a positive control; a more appropriate control would
have been a mutagenic epoxide.
Induction of DNA Repair. In Table 14, the report does not
provide the grain count of the negative control. This assay is
otherwide known as the "unscheduled DNA synthesis test."
Host Mediated Assay. The report does not specify the Salmo-
nella strains used in this assay; this information should be pro-
vided. The statement in Table 5 that the elevated mutation
frequency observed in several of the assay was "due to decreased
growth of microorganisms in animals" should be referenced.
Dominant Lethal Assay. The dominant lethal test is dif-
ficult to analyze. The experimenter does not define the term
"Proportion Deaths/Pregnancy" used in the tables reporting the
results of this assay. In the assay itself, the experimental
group was given the chemical via (IP) injection. The positive
control should have been applied in the same way as the experi-
mental chemicals and in addition, a dermally active mutagenic
epoxide should have been used as the positive control material in
lieu of injected TEM. The "Proportion Deaths/ Pregnancy" data
seem inconsistent. In three out of seven of the epoxides tested,
this value is significantly lower than the control, however, in
one out of the seven, it is significantly higher. This raises
questions as to the adequacy of the control. It is not clear if
the control was run concurrently with the experimental groups.
3CS
-------
Failure to do this has been shown to be a factor in data varia-
bility.
Comments on Individual Chemicals
DGEBPA (diglycidyl ether of 2,2-di(p,p'-hydroxyphenyl)
propane). The experimenter states that because of the results
from body fluid analysis, host mediated assay, micronucleus test,
and dominant lethal test, the chemical is not mutagenic in animal
systems. This is not necessarily the case. The investigator did
not use the most sensitive strain possible in body fluid analysis
and no attempt was made to concentrate the urine. In addition,
the experimenter failed to utilize the total spectrum of bacteria
recommended by Ames. In the host mediated assay, the experi-
menter did not note the strain of bacteria used in the test,
therefore, it is impossible to analyze this data.
DGENPG (diglycidyl ether of neopentyl glycol). For this
compound, the statement is made that although there was some
detection of mutagenic activity in the urine, the failure to
detect mutagenicity in either the micronucleus or dominant lethal
test "could be due to the fact that the active intermediate was
not present in the animal long enough to produce activity in
these tests or that the mutagenic action was so minimal that it
was not detected in these tests." The use of the word minimal in
the preceding sentence implies that there is very little muta-
genic activity in body fluid. This is a misleading insertion,
because these tests (i.e., micronucleus and dominant lethal
assays) are so insensitive that in many cases they do not pick up
a significant effect. In addition, the micronucleus and dominant
lethal tests detect primarily chromosome-type damage. The
results from these two tests do not necessarily reflect the
potential danger due to gene mutations.
BGE (butyl glycidyl ether). The experimenter comments that
BGE is basically mutagenic and discusses why the compound was not
positive in the body fluid analysis, host mediated assay, or the
micronucleus test. He suggests that the dose used in these three
tests was too low to detect activity. However, in his earlier
discussion of DGEBPA, the experimenter indicates that because
these assays were negative, DGEBPA is, therefore, not mutagenic
in animal systems. This reasoning appears inconsistent.
Because BGE is positive in the Ames test and the unscheduled
DNA synthesis test, it is mutagenic. Indications of a positive
in the dominant lethal test suggests that the metabolically
active form of the chemical reaches the testes, and there is thus
strong concern that this chemical is mutagenic. The data for BGE
look significant because (a) the experimental is higher than the
control and (b) there is a variation with time. However, the
experimenter should submit the raw data to allow for a more
adequate analysis.
387
-------
CGE (o-cresyl glycidyl ether). The data for CGE suggest
that this chemical may be a mutagen in mammals.
Alkyl GE (alkyl glycidyl ether). The experimenter suggests
that the minimal activity observed only in the Ames test and the
negative activity seen in the remainder of the assays indicates
this chemical is not mutagenic. The preceding comments concern-
ing the insensitivity of some of the testing procedures also
pertain here.
DCPDGE (dicyclopentadiene glycidyl ether). Comments made
with regard to alkyl GE apply here.
One aspect the experimenter has not considered is that, even if
one assumes there is no danger to mammals due to mutation because
the chemical is detoxified in some manner, he still has not
eliminated the possibility that these epoxides may be carcino-
genic in some organ before the substances are detoxified.
Shell states that the doses used in the studies are much higher
than the expected worker exposure. This implies that at the
present "permissible exposure level of 50 ppm" the genetic risk
is nonexistent and thus they are advancing a threshold for muta-
genicity. However, there is no known threshold for mutagenic
effects.
Current Production and Use
Annual production figures are not available as such for BGE;
however, an estimated 6-7 million pounds of alkyl, phenyl, and
butyl glycidyl ethers were produced in 1973. BGE is reportedly
used as a reactive diluent for epoxy resins and as a stabilizer
for PVC resins, chlorinated paraffins, and other halogenated
products. It may also be used in the synthesis of certain
specialty surfactants.
The submission identified DGEBPA as a resin while the other
compounds are used as diluents (presumably in resin systems).
Producers were also identified for two of the chemicals. Dow
manufactures CGE while Procter and Gamble produces mixed alkyl
GE. No other information was located in the secondary sources
consulted.
Comments/Recommendations
The only information in this report that Shell felt any obliga-
tion to report concerned BGE. This presumably implies that Shell
does not manufacture, process, or distribute the other six chemi-
cals. This point should be confirmed by Shell.
a) This submission and status report should be transmitted to
OE, OGC, OSHA, NIOSH, and CPSC.
388
-------
b) Shell should be requested to provide the information
requested in the evaluation and comments sections of this
status report.
389
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
09 AU6 1978
SUBJECT: status Report 8EHQ-0778-0213 Approved
(supplement)
MO* Frank D. Kover, Acting Chief ^6^°"
Chemical Hazard Identification Branch -
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
Shell Chemical Company in a letter to the Assistant Administrator
for Toxic Substances dated February 21, 1978 provided the results
of an integrated mutagenicity testing program on butyl glycidyl
ether (BGE) and other glycidyl ethers. The submission was subse-
quently entered into the Section 8(e) public file and given the
document control number 8EHQ-0778-0213. A status report present-
ing the Assessment Division's evaluation of this information was
prepared and may be found (with the original submission) as
Attachment 1. On July 17, 1978, the U.S. EPA issued a subpoena
Duces Tecum (see Attachment 2) to Shell Oil Company requiring
that it "Provide the following documents: (1) Report entitled
"Chronic Vapor Toxicity of N-Butyl Glycidyl Ether," by Anderson,
Hine, Guzman, and Wellington, dated February 18, 1957. (2) All
other documents concerning substantial risk of injury to health
or the environment of Butyl Glycidyl Ether." A letter containing
the 1957 study identified in (1) above as well as some additional
mutagenicity data was mailed by Shell on July 12, 1978 and
received by the Assistant Administrator for Toxic Substances on
July 18, 1978 (see Attachment 3). In response to the adminis-
trative subpoena, Shell, in a letter dated July 26, 1978, pro-
vided seven additional pieces of information (see Attachment
4). The Shell submissions dated July 12 and July 26 were collec-
tively assigned the document control number 8EQ-0778-0213
(supplement). These two items are the subject of the present
status report.
Submission Evaluation
The discussion,in this section will initially concern itself with
the information) submitted by Shell in their letter of July 12,
CPA rOMM U20-« (KEV.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. St«'.. -.me v
made herein are not to be regarded as expressing /ire-
Agency policy or intent with respect to this par•*• 'r-...1
chemical. Any review of the status report sho1!- * '-
consideration the fact that it may be based on i..,. .
information.
390
-------
1978 (Attachment 3). The 1957 study is an adequate preliminary
investigation which suggests that butyl glycidyl ether can
produce pathologic change (e.g., liver). The fact that the
compound causes significant failure to gain body weight at 150
ppm makes it dubious that the 50 ppm workplace standard is
appropriate. The conclusion reached in this study that humans
could tolerate exposure to 50 ppm without harm is not justified
by the shallowness of the investigation. This study is suffi-
cient only as a preliminary investigation and it will likely have
to be redone.
The immediate situation presented by this submission is that:
a) By the Ames Test, BGE is routagenic
b) BGE causes failure in normal increases in body weight.
c) BGE is capable of producing liver injury.
d) BGE may be a sufficient pulmonary irritant to be of
concern in the etiology of increased lung infections (pneumonia).
e) It remains to be established whether the testicular
effect is due to direct action on the testes or if the atrophy is
secondary to some other process affecting the pituitary,
adrenals, and thymus. In the absence of evidence that the
testicular atrophy is in reality secondary to an adrenal-pitui-
tary-thymus effect, it should be assumed that the testicular
effect is the result the direct action by BGE. The assumption
offered by the authors that the testicular atrophy was probably
not a primary event but was the result of some other secondary
abnormality, especially pneumonia, is a mere guess without sup-
portive data.
f) The term "stress effect on the kidneys" (p.5 of the 1957
study) is not adequately defined and probably represents an
impression of the examiner. It is surprising that no kidney
tubule changes were observed and reported. Such changes are
characteristic of many glycols and similar compounds. An earlier
publication (Hine et al., A.M.A. Arch. Ind. Hlth., 14, 250, 1956)
reported that alpha-monochlorohydrin (l-chloro-2,3-propandiol)
(suggested as a possible metabolite of glycidol) produced kidney
changes including tubule necrosis.
The major weakness in this preliminary study is the extensive use
of circumstantial reasoning to explain an observation (i.e., this
effect occured only under certain circumstances, therefore, it
must be due to this cause). Such reasoning is neither final nor
definitive; in all such cases, the test material must be given
adequate additional testing to determine the actual causes of an
observed effect.
This submission indicates that BGE has the potential to cause
testicular atrophy as well as other adverse effects in rats. Of
391
-------
note is the surprising finding that "on repeated vapor exposure
n-butyl glicidyl ether is at least as toxic as allyl glycidyl
ether, which was the most toxic of the glycidyl ethers previously
thus tested." The author of the study attributes this finding to
"experimental variation"; nonetheless, this point should have
been examined further.
The report states that seven cases of testicular atrophy were
observed; close reading of the study reveals only six instances
(1/10 at 75 ppm; 5/10 at 300 ppm). This question should be
resolved. In addition, it is not clear from the report if the
testicular atrophy was identified following gross or histopathol-
ogy. The structure of the report appears to indicate the latter,
although this is not clear. It would also be useful to obtain
any available findings on the 4 rats in the 300 ppm group that
died early in the experiment and were not subsequently discussed.
The observation that BGE produces testicular atrophy in rats,
while never before demonstrated, is, nevertheless, not an
isolated finding for the class of glycidyl ethers. Testicular
degeneration has been noted in several animal species after
exposure to allyl glycidyl ether (rats: intramuscular injection),
diglycidyl ether (rats: dermal, inhalation; rabbits; inhalation;
dogs: intravenous injection), phenyl glucidyl ether (rats:
inhalation), and triethylene glycol diglycidyl ether (mice:
intraperitoneal).
The information transmitted by Shell in their letter of July 26,
1978 (see Attachment 4) consists of seven pieces of informa-
tion. In the cover letter, Shell notes that it (in conjunction
with Ciba-Geigy and Celanese) is sponsoring a mutagenicity study
intended to follow-up the results of the dominant lethal assay of
BGE which were forwarded to EPA in February (Attachment 1). This
study is also intended to investigate certain aspects of the 1957
study which showed the testicular changes in rats following
chronic inhalation of BGE. Unfortunately, the planned work
involves dermal exposure to BGP and is being conducted in mice
instead of rats; therefore the new work will leave unresolved
many questions concerning the 1957 study.
Data element number 3 of the July 26 letter, the University of
California report dated March 13, 1956, was subsequently pub-
lished in the A.M.A. Archives of Industrial Health (14, 250,
1956). The 1957 BGE study received with the Shell letter dated-
July 12 (Attachment 3) was originally intended as a portion of
this 1956 publication; however, for reasons not althogether
clear, the 1957 results were never published. The 1956 study is
somewhat optimistic about the toxicity of BGE when taken by mouth
or when inhaled. The data indicate that perhaps BGE will not
produce an immediate dramatic effect including fatality. Never-
theless, the data tell nothing about the other and long range
effects of a single dose or the effects of chronic exposure to
small amounts. The acutely lethal dose of BGE is in the ranges
of aspirin lethality.
392
-------
Data elements 4 through 7 of the July 26 letter report on skin
irritation aspects of BGE. This information suggests the need
for human skin testing to determine the potential for adverse
reactions in consumers or workers exposed to the material. This
is borne out in a letter (data element 4) by Dr. N. G. White of
Shell Chemical Corporation. This letter cites a reference to a
published article in A.M.A. Archives of Dermatology in which the
author reports the irritating aand sensitizing action of BGE.
Current Production and Use
Annual production figures are not available as such for BGE;
however, an estimated 6-7 million pounds of allylf phenyl, and
butyl glycidyl ethers were produced in 1973. BGE is reportedly
used as a reactive diluent for epoxy resins and as a stabilizer
for PVC resins, chlorinated paraffins, and other halogenated
products. It may also be used in the synthesis of certain
specialty surfactants.
Overall Evaluation
The Agency has received information on BGE from Shell Oil Company
that indicates the following:
a) BGE is suspected of inducing testicular atrophy in rats
exposed via inhalation.
b) BGE gave positive results in the Ames test and the
unscheduled DNA synthesis test; therefore, BGE appears mutagenic.
c) BGE is positive in the mouse dominant lethal assay by
skin absorption. The data appear significant (despite Shell's
professed lack of confidence in the results) because the experi-
mental is higher than the control and there is some variation
with time. Indications of a positive in the dominant lethal
test, expecially when combined with the finding of testicular
degeneration in rats, suggest strongly that an active form of the
chemical reaches the testes. These findings elicit heightened
concern in light of the demonstrated mutagenicity of BGE which
may indicate that germ cells are at increased risk of gene
mutation.
Additional information available to the Agency, and presumably
also to Shell, indicates that:
a) Annual production of BGE is in excess of approximately 1
million pounds; an exact figure is not available.
b) The observation that BGE produces testicular degenera-
tion in rats is not an isolated finding for the class of glycidyl
ethers. Testicular degeneration has been shown in several animal
species following exposure to four other glycidyl ethers that are
similar or related to BGF.
393
-------
Part V(a)(2) of the March 16, 1978 "Statement of Interpretation
and Enforcement Policy" states that the Agency considers Section
8(e) - reportable substantial risk information to include "Any
pattern of effects or evidence which reasonably sypports 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" (43 FR 11112).
Furthermore, the introduction to Part V states that "The human
health effects listed in Subpart (a)... are so serious that
relatively little weight is given to exposure..." (43 FR 11111)
as a factor in Section 8(e) reporting requirements. It is con-
cluded that the pattern of evidence provided by the data
contained in Shell's February 21, July 17, and July 26, 1978
submissions, together with the additional information mentioned
above, reasonably supports the conclusion that exposure to BGE
poses a substantial risk of injury to human health as defined in
the March 16, 1978 Policy Statement.
Comments/Recommendations
In addition to the uncertainties remaining with respect to the
1957 study, further information should be developed to determine
the extent of and potential for exposure to BGE.
a) The submitter should be requested to provide available
information on exposure to BGE production workers, industrial and
non-industrial users of BGE, and users of products employing
BGE. Such information is needed to better assess the need for
and proper focal point of any further follow-up actions.
b) It is recommended that NIOSH and OSHA initiate medical
surveillance of exposed workers in industries using glycidyl
ethers (expecially BGE, allyl glycidyl ether, phenyl glycidyl
ether, and other similar compounds with demonstrable annual
production).
c) This submission and status report should be transmitted
to CPSC in addition to NIOSH and OSHA.
394
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGEHCY
PATE: JAN 3 1 1979
Status Report*8EHQ-0978-0213 Approved
(Subpoena Responses)
Revision
no* Frank D. Kover Needed
Assessment Division, OTE/OTS
T0: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
On September 1, 1978, subpoenas pursuant to section 11(c) of
TSCA were issued to the following firms: Celanese Corp.;
Ciba-Geigy Corp.; Reichhold Chemicals, Inc.; Shell Oil
Company; Dow Chemical Company; and Hine, Inc. The parties
named in the subpoenas were requested to produce documents
relating to n-butyl glycidyl ether (BGE). The discussion
below offers technical comments keyed to specific sections
of each company's subpoena response.
Submission Evaluation
Shell Oil Company
(4a) Paragraph 3 of this intra-Shell note (dated April 4,
1978) presents an invalid argument. A negative dominant
lethal test is open to question; a positive result is
considered to be definitive (unless the test is mechanis-
tically deficient).
(4c) Journal article dated January, 1961; p. 57/51 (column
2, paragraph 3) - The use of rats assigned to another study
. in lieu of preinjection controls could be questioned based
on the standard error associated with such a procedure.
p. 58/52 - If the thymus, spleen, and testes were most
frequently altered histologically, what did the adrenal
cortex show? Thymic involution is usually due to discharge
of glucocorticoids from the adrenal cortex.
p. 59/53 - Table 3 does not include BGE. Is it to be assumed
that the rats receiving this compound did not show changes
in those organs listed in the table? In column 2, the rise
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
395
row* IMB* mev. »-7«i
-------
8EHQ-0978-02Z3
in leucocyte counts should be accounted for. An unexpected
rise instead of the expected fall in the count does not mean
that the compound lacks a hematopoietic effect.
(4d) Journal article dated February, 1958. This publication
does not mention BGE.
(4e) Recognition by R. E. Joyner, M.D., Shell's Medical
Director, that BGE is a potential carcinogen (December 27,
1977).
(4f) Intra-Shell note dated March 3, 1978. Offers recogni-
tion that the dominant lethal study by Legator may be valid.
(4k) Memorandum (dated April 20, 1977) by Dr. Joyner,
Shell's Medical Director, clarifying Dr. nine's role in the
toxicity studies with BGE. Table 5 shows BGE to be positive
in the Ames test. No data for the other tests are available
in the table.
(4q) Note to file by a Shell toxicologist; dated December 2,
1977. Under the conditions of the 1977 Legator study, BGE
was the most strongly mutagenic of the compounds tested in
the Ames and dominant lethal assays.
(4aa) Hine's report on the effects of epoxy compounds on
the hematopoietic system of rats, dated October 3, 1958.
BGE was not found to be radiomimetic in contrast to many
other tested glycidyl ethers; however, BGE was not extensively
tested.
(4bb) Letter dated September 4, 1956 and signed by Hine on
Shell stationery in which he states that he considers BGE to
have "slight" toxicity even though it is- much more toxic
than EPON 828, a Shell trade-named product.
(4ee) Memo from Hine on Shell stationery dated July 15,
1957. In Table 3, BGE is reported to have caused a 27.3%
increase in white blood cell counts and no change in femoral
marrow nucleated cell counts. Hine discounts the increase
and, therefore, no further examination (such as differential
counts) was conducted. The study is incomplete; white blood
cell formation, particularly in rats, is not limited to bone
marrow.
Dow Chemical U.S.A.
Letter from Tyson of Dow to Hilson of EPA dated September 20,
1978. The enclosure to the letter claims that BGE is rapidly
metabolized in the body and therefore poses limited risk to
the organism. This is not necessarily the case. The only
time that the metabolism of BGE might be rapid enough to
convert the compound to an inactive metabolite would be
396
-------
8EHQ-0978-0213
following oral ingestion. In this case, the compound would
have to first pass through the liver before reaching other
body cells. Absorption through the skin and upper respiratory
membranes would avoid potential liver detoxification and all
organs would be exposed to unmetabolized BGE.
Attachment 10 - Letter from Industrial Bio-Test to Dow dated
July 16, 1957. Industrial Bio-Test found in human studies
that BGE is a primary skin irritant and probably an allergen.
Skin depigmentation was frequently observed at the site of
application. The lab's Technical Director suspected that
BGE contained monobenzohydroquinone ether which is known to
cause leukoderma (skin depigmentation). Such depigmentation
is the result of disturbances in melanin metabolism. Note
that Industrial Bio-Test had to discontinue further testing
of the material in humans.
Attachment 29 - The first draft (December, 1977) of the
NIOSH Criteria Document on glycidyl ethers contains several
references (see pages 75-77) to observed testicular necrosis
or atrophy in lab animals (rats, rabbits, and dogs) exposed
to diglycidyl ether. Thus, anyone who reviewed this draft
Criteria Document would have available information reporting
that diglycidyl ether can cause testicular changes; this may
also indicate that the Hine-reported testicular effects of
BGE in rats are real, although diglycidyl is generally
viewed as one of the more biologically active members of the
glycidyl ethers.
Attachment 44 - Telex dated November 30, 1977. A Dow employee
expects positive mutagenicity data on BGE to lead to its
removal from the commercial market.
Attachments 66 and 68 - In these two items dated November,
1977 and January, 1978, respectively, Dow expresses concern
over BGE exposures.
Attachment 72 - Dow claims in its answers to the subpoena
questions that it does not manufacture, process, or distri-
bute BGE. However, attachment 72, dated October 24, 1975,
says that a Dow product contains BGE. What is the story
here?
Reichhold Chemicals, Inc.
Exhibit II (record of meeting held February 10, 1978) -
Point Number 8. The fact that BGE fails to show evidence of
mutagenic effects when tested in activated liver cultures
cannot be extrapolated to mean that humans will rapidly
metabolize BGE and thereby minimize cellular contact with
the chemical. There is apparently no scientific basis for
this extrapolation considering that Dow informed NIOSH it
was not familiar with any data relating to the pharmacoki-
netics and biotransformation of BGE. The response of BGE in
397
-------
8EHQ-0978-0213
the nonactivated cultures is of some concern because all
respondents acknowledge that dermal exposure to BGE is of
the greatest concern occupationally. Exposure via this
route means that BGE will not be deactivated in a first pass
through the liver but will contact many body tissues as the
active form.
Exhibit II - Point Number 22. This item recognizes a possi-
ble relationship between BGE exposure and the testicular
atrophy observed in the 1957 Hine study.
Exhibit X - W. R. Bowditch's comment (dated February 13,
1978) that all companies will withdraw BGE from the market
if the chemical is found to be a mutagen is of interest.
Exhibit XVII - Technical bulletin dated September, 1978. On
page 3, the LDso -of BGE is reported in the range of aspirin.
Does this indicate low toxicity? To put this into perspec-
tive, aspirin is a popular suicide drug in England.
Celanese Corporation
In this response, much is made of the finding that the
mutagenicity response of BGE decreases in the Ames test with
metabolic activation. This could have real significance if
BGE is swallowed. However, other routes of exposure, such
as skin and lungs, permit the unmetabolized compound to come
into contact with all tissues. These routes of exposure
bypass the liver while a substance that is swallowed has to
pass through the liver before reaching other tissues. In
addition, a substance that bypasses the liver is highly
diluted by the time it reaches the liver and less of the
total "dose" is metabolized. A classical example of this
point concerns nitroglycerin tablets used to alleviate
attacks of angina pectoris. If the tablet is placed under
the tongue, the nitroglycerin avoids the first bypass and
relieves the heart pain in a dose of 0.005 mg; however, if
the tablet is swallowed, the effective dose becomes 0.2-0.4
mg, a 40-80 fold increase.
The objection by the industry toxicologist is further
weakened by the use of deliberately elevated enzyme activity
in liver homogenates from rats administered either phenobar-
bital or PCB. The average person would not have such enzyme
induction and would, therefore, detoxify BGE at a slower
rate giving rise to greater tissue contact with BGE over a
period of time.
Response to question No. 4 posed in Section IV of the
subpoena ("What is the rationale for repeating the dominant
lethal assay portion of the 1977 (Legator) study?"). In its
answer to this question, Celanese points out the following
398
-------
8EHQ-0978-0213
problems with the experimental design employed in the 1977
study: (1) only one dose level was used and (2) the control
group was not run concurrently with the test groups. The
latter represents unacceptable scientific procedure and
seriously detracts from the significance of this study.
(Ciba-Geigy also made these points in its response to this
question.)
Ciba-Geigy Corporation
Appendix 1, Attachment 3.2 - Handwritten minutes of meeting
held March 17, 1978. This item rules out epichlorohydrin as
a significant contaminant of BGE that could account for the
positive findings in the mutagenicity tests.
Comments/Recommendations
Two significant points can be derived from evaluation of the
subpoena response. Firstly, the initial draft of the NIOSH
Criteria Document on glycidyl ethers (dated December, 1977)
contains several references to observed testicular necrosis
or atrophy in lab animals exposed to diglycidyl ether.
Later drafts of the Criteria Document, however, report that
several other glycidyl ethers have also been shown to induce
this effect. This might indicate that the identification of
other studies corroborating the evidence offered in the 1957
investigation may not have been as straight-forward as the
Assessment Division assumed previously. Secondly, two
serious flaws are apparent in the experimental design of the
Legator dominant lethal assay: (1) only one dose level was
used and (2) the controls were not run concurrently with the
experimentals. The latter flaw represents unacceptable
scientific procedure and seriously detracts from the signif-
icance of this study.
399
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: APR 4 1979
SUBJECT: Status Report* 3EHQ-0279-0213 (Updated Approved
Status Report/Summary and Conclusions) ~77
//>Vu^/ Revision/^
MOM: Frank D. Kover f U- Needed
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
This status report summarizes the information received to
date on butyl glycidyl ether (BGE) and presents the final
technical conclusions resulting from the Assessment Divi-
sions 's evaluation of the available data. During the
course of this evaluation, both confidential and noncon-
fidential data were examined, however, only nonconfidential
information is discussed in this status report. The
exclusion of confidential information from this discussion,
however, does not affect the conclusions reached.
Submission Evaluation (Summary)
The first BGE study, submitted by Shell Oil Company on
February 21, 1978, reported the results of a batter of
mutagenicity tests conducted by Dr. Marvin .Legator of the
University of Texas Medical Branch, Galveston, Texas, under
the sponsorship of Dow Chemical Company. Evaluation of the
initial submission (refer to Attachment I for a full copy of
the Status Report) showed that:
(a) BGE was positive in the Ames Test and the unsched-
uled DNA synthesis test; therefore, it should be
considered mutagenic. The current state of the art
in mutagenicity testing suggests that a consensus
is lacking on the value of some mutagenicity test
systems for indicating mutagenic potential in
humans. Nevertheless, good qualitative correlations
presently exist between positive results from
various mutagenicity test systems and positive
animal oncogenicity test results when the same
chemical is tested. Quantitative extrapolations
from these mutagenicity test systems are, however,
_ presently not valid. _
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into '
consideration the fact that it may be based on incomplete
information.
CPA FORM 1»a»-« (MEV. >-7«)
400
-------
(b) Indications of a positive in the mouse dominant
lethal assay suggest that an active form of the
chemical reaches the testes; accordingly, there
is strong concern that BGE is mutagenic. The
experimental data look significant because the
experimental values are higher than the controls
and there is a variation with time.
The second BGE submission, consisting of a 1957 study
entitled "Chronic Vapor Toxicity of n-Butyl Glycidyl Ether"
by Anderson, Hine, Guzman, and Wellington (dated February 18,
1957), was voluntarily provided to the Agency by Shell in
a letter dated July 12, 1978. On July 17, 1978, the U.S. EPA
issued a subpoena to Shell requiring that it provide a copy/
of this 1957 study and any other substantial risk informa-*'
tion in its possession on BGE. In its response (July 26,
1978) to the subpoena, Shell provided the 1957 study plus
several additional pieces of information. Evaluation of
these materials (refer to Attachment II for a full copy of
the status report) showed that:
(c) The 1957 study is an adequate preliminary investi-
gation which suggests that BGE can produce patho-
logic change (e.g., liver damage). It remains to
be established whether the testicular effect
observed in this study is due to direct action on
the testes or if the atrophy is secondary to some
other process affecting the pituitary, adrenals,
and thymus. In the absence of evidence that the
testicular atrophy is in reality secondary to an
adrenal-pituitary-thymus effect, it should be
assumed that the testicular effect is the result
of direct action by BGE (the dominant lethal study
supports this interpretation). The assumption
offered by the authors that the testicular atrophy
was probably not a primary event but was the
result of some other secondary abnormality,
especially pneumonia, is a mere guess without
supportive data. The observation that BGE pro-
duces testicular atrophy in rats, while never
before demonstrated for this chemical, is, never-
theless, not an isolated finding for the class of
glycidyl ethers. Testicular degeneration has been
observed in several animal species after exposure
to four other members of this chemical class.
401
-------
(d) No other information of significance was developed
in this series of submissions.
The final set of BGE submissions consists of the responses
from five chemical companies to a series of subpoenas issued
by the U.S. EPA on August 31, 1978. Evaluation of these
responses (refer to Attachment III for a full copy of this
status report) indicates that:
(e) One of the factors used by the Assessment Division
to bolster its conclusion that the 1957 study
offered reasonable support for the conclusion of
substantial risk was evidence that several glycidyl
ethers other than BGE had been shown to cause
testicular atrophy in test animals. An important
point to be considered, however, is precisely what
information corroborating the reported testicular
effects of BGE would be uncovered during the
course of a reasonable literature search. The
first draft of the NIOSH Criteria Document on
glycidyl ethers (dated December, 1977) contains
several references to observed testicular necrosis
or atrophy in lab animals exposed to diglycidyl
ether. Later drafts of the Criteria Document,
however, report that several other glycidyl ethers
have also been shown to induce this effect. Thus,
it should be noted that the initial NIOSH investi-
gation of the literature on glycidyl ethers did
not uncover several of the articles indicating
that other compounds in this chemical class have
been shown to cause testicular atrophy. This
might indicate that the identification of other
studies corroborating the evidence offered in the
1957 investigation may not have been as straight-
forward as the Assessment Division assumed pre-
viously.
(f) Two serious flaws in the experimental design of
the Legator dominant lethal assay are apparent:
(1) only one dose level was used and (2) the
controls were not run concurrently with the
experimentals. The latter flaw represents
unacceptable scientific procedure and seriously
detracts from the significance of this study.
402
-------
Overall Conclusions
The Assessment Division initially concluded that the results
of the Legator study when combined with the 1957 study
offered reasonable support for a conclusion of substantial
risk on the basis that: (1) BGE is mutagenic; (2) the
dominant lethal study demonstrates that an active form of
the chemical reaches the testes; (3) in the absence of data
to the contrary, it should be assumed that the testicular
atrophy observed in the 1957 study is the result of direct
action by BGE; and (4) the finding of testicular degenera-
tion following exposure to BGE is not an isolated finding
for the class of glycidyl ethers, as four other members of
the chemical class are known to cause this condition.
Further, the Assessment Division assumed that the informa-
tion represented by point (4) was reasonably available to
Shell and the other chemical companies.
Following technical evaluation of all the information avail-
able to the several chemical companies (as represented by
the subpoena responses), however, it appears that one or
more of the four supporting points outlined above may not be
valid. Specifically, the Legator dominant lethal assay has
largely been thrown open to question in light of serious
concerns about the validity of the controls (point (2)
above). In addition, the corroborative data used by the
Assessment Division to support the findings of testicular
atrophy in the 1957 study may not have been as widely avail-
able to the several companies as was suspected previously
(point (4) above). By a process of elimination, therefore,
points (1) and (3) above remain intact.
Part VI of the March 16, 1978 policy statement (43 FR 11110)
states that when considering in vitro experiments and tests
"(consideration) may be given to the existence of corrobora-
tive information, if necessary to reasonably support the
conclusion that a chemical presents a substantial risk."
BGE was found positive in two of the six mutagenicity assays
conducted (positive: Ames and unscheduled DNA synthesis;
negative: body fluid analysis, host mediated, and micro-
nucleus; uncertain: dominant lethal assay). In general,
mixed results from a battery of mutagenicity tests often
indicate the need to consider corroborative data before
403
-------
reaching a conclusion of substantial risk. (Nevertheless,
situations can arise where a single positive or even mixed
results can, when combined with the exposure picture, be
sufficient to trigger reporting [an example would be tris].)
For the most part, "corroborative data" take the form of
additional effects data and/or exposure data. The National
Occupational Hazard Survey conducted by NIOSH estimated that
13,000 workers are potentially exposed to BGE, however, actual
worker exposure is apparently controlled because of BGE's
irritating properties (for more information see the NIOSH
Criteria Document on glycidyl ethers). As far as other
effects data are concerned, without the support of the
dominant lethal assay and the structure/activity correlation
associating testicular atrophy with glycidyl ethers, the 1957
study remains "an adequate preliminary investigation" and does
not itself strongly support the conclusion that BGE can cause
serious or prolonged damage to male reproductive organs. Thus,
in conclusion, the information available to Shell and the other
companies during the first months of 1978 did not clearly offer
reasonable support for the conclusion that BGE presents a
substantial risk of injury to health or the environment, although
it does strongly suggest a need for further investigation of
BGE's genetic and male reproductive effects.
Comments/Recommendations
The final draft of the NIOSH Criteria Document on glycidyl
ethers (released in June, 1978) contains several references
to observations of testicular effects in laboratory animals
exposed to 4 different glycidyl ethers (allyl glycidyl
ether, diglycidyl ether, phenyl glycidyl ether, and trieth-
ylene glycol diglycidyl ether). When these studies are
considered in conjunction with exposure information,
reasonable support for the conclusion of substantial risk
is clearly evident for BGE. The basis for this conclusion
is that the significance of the 1957 study is greatly enhanced
when one considers the finding that four other members of the
structural class of glycidyl ethers have also been shown to
cause testicular atrophy in laboratory animals. BGE's appar-
ent mutagenicty, while not essential to this determination of
"reasonable support," nevertheless, does provide additional
support for the conclusion that BGE presents a substantial risk
of injury.
404
-------
An illustration of the significance of the 1957 study
can be found in the NIOSH decision to issue a Current
Intelligence Bulletin on glycidyl ethers (October 12,
1978) only 4 months after release of the Criteria Docu-
ment. The only new information cited in the Current
Intelligence Bulletin is the 1957 study. The expressed
purpose of this NIOSH publication is to "promptly review,
evaluate, and supplement new information received by NIOSH
on occupational hazards that are either unrecognized or are
greater than generally known."
a) The submissions and status reports on BGE should,
be transmitted to NIOSH and OSHA. Confidential
portions will have to be considered independently
for transmittal on a "need to know" basis.
405
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
SUBJECT:
JAM J
Status Report* 8EHQ-0778-0214
FROM: Frank D\ Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Approved
Revisio
Needed
Submission Description
Information reporting that Kenplast G, a proprietary mixed
aromatic hydrocarbon plasticizer, was positive in a single
strain Ames test in the presence of S-9 (microsomes).
Submission Evaluation
In all cases, the Agency prefers to see the raw data from
submitted studies. The summary provided indicates that the
chemical is a weak mutagen. The data appear a little erratic;
this may be because the mixture forms an emulsion under the
test conditions. A suspension test might give cleaner
results.
Part VI of the March 16, 1978 policy statement (43 FR 11110)
states that, with respect to in vitro experiments and tests,
11 (consideration) may be given to the existence of corrobora-
tive information, if necessary to reasonably support..." a
conclusion of substantial risk. Insofar as the present sub-
mission concerns only the results of a single Ames test in a
single bacterial tester strain, what corroborative data were
considered in reaching the conclusion of substantial risk?
The cover letter cites submission 8EHQ-0877-0002 concerning
Mobisol 44 as providing corroborative data. Mobisol 44, a
"flexibilizer (plasticizer) diluent," was found to be moder-
ately tumorigenic in a mouse skin painting test. The compo-
sition of Mobisol 44, like that of Kenplast G, was never
specified. Nevertheless, the present submitter is presumably
maintaining that the two materials are somewhat similar in
composition and that, therefore, the Mobisol 44 skin paint-
ing results tend to indicate that the Ames test data present
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 132O-6 (REV. 3-7CI
406
-------
a valid (though quite preliminary) index of the tumorigenic
potential of Kenplast G.
A single strain Ames test has uncertain value for indicating
mutagenic potential in humans. A battery of Ames tests,
using several tester strains, both with and without activa-
tion, is considered to provide a stronger indication of the
possible mutagenicity of a chemical than will a single
strain test.
Current Production and Use
No information is available in the secondary literature on
this material. As noted above, the submitter reports that
Kenplast G is used as a plasticizer.
Comments/Recommendations
Kenplast G is reportedly similar in composition to Mobisol
44, the subject of submission 8EHQ-0877-0002.
a) The submitter should be asked to provide a full copy of
the Ames test final report. The results of any other
available mutagenicity or chronic toxicity testing
should also be provided.
b) The submitter should describe any further testing of
Kenplast G that is planned.
c) The cover letter notes that information describing the
toxicology of Mobisol 44 is enclosed with the original
submission; this information was not included in the
submission and should be provided.
d) The analytical composition of Kenplast G should be pro-
vided, if available; in particular a description of the
presence of polynuclear aromatic hydrocarbons and/or
metals in the commercial product.
e) Mixed aromatic hydrocarbon plasticizers should be con-
sidered a candidate for CHIP or chemical technology
review. This submission should also enter the Assess-
ment Division carcinogens/mutagens/teratogens (CMT)
screening process.
f) This submission should be referred to NIOSH, OSHA,
CPSC, LTAT (AD), CAD, and OSW.
407
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: August 16, 1978
SUBJECT: Status Report 8EHQ-0778-0215
FROM: Frank D. Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Approved
Revision
Needed
Submissi on Des crip t ion
Results of a lifetime skin-painting study of a heating oil (No. 2 burner
fuel) in mice.
Submis si on Evaluat i on
There is a definite incidence of malignant neoplasms of the skin following
lifetime application to mice. Based on the 40 mice, the incidence of
malignant neoplasms is about 8%. The significance of this could be arrived
at only by studying a much larger group of mice. Nonetheless, the finding
must be tentatively accepted as real since the experiment was conducted
by a "well-known independent university research laboratory."
A recurrent problem with submissions such as this one is that they
generally contain very little physicochemical data on the composition of
the petroleum material. In this case, the unknown is the amount of
polynuclear hydrocarbons present in the crude and catalytically cracked
fractions. If the polynuclear content is low, then it is conceivable that
there will be batch variability in the carcinogenicity observed with
these materials. The incidence of carcinogenicity could be as low as one
in every twenty batches or so.
Current Production and Use
The submitter reports that the test material is used as a heating oil,
presumably for space heating.
Conircnts/Recomvendations
(a) Request submitter to provide a full copy of the final report,including
the results of any analytical work conducted on these sanples.
(b) Transmit submission and status report to NIOSH,OSHA, and CPSC.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 1320-6 (REV. 3-76)
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
FROM:
13/b
SUBJECT: Status Report* 8EHQ-077Q-0216
Frank D. Kover
Assessment Division, OTE/OTS
Approved
Revisio
Needed
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
Results of a battery of mutagenicity tests conducted on two
powdered oil shale ore samples ("RS-101" and "RS" (raw
shale)) and a sample of retorted (or heat-treated) shale.
Submission Description
RS-101 was found:
a) weakly mutagenic in the Ames suspension test with
metabolic activation.
b) mutagenic in the in vitro mammalian cell culture
assay both with (5X background) and without acti-
vation (3X background). A positive dose response
was found under both conditions.
c) to yield equivocal results in the in vivo rat bone
marrow cytogeneticity assay. The substance may
induce chromosome aberrations as evidenced by an
increased aberration frequency at one time point
in the high acute dose group.
RS-101 is a 'gene mutagen and may have the potential to cause
chromosome aberrations; further testing is needed.
RS (Raw Shale) was found:
a) negative in the microbial assays.
b) equivocal in the in vitro mammalian cell culture
assay. Although there was no clear dose response,
the treated values are consistently higher than
the solvent controls (3X background for nonacti-
vated and 2.5X for activated assays). The test
should be repeated to validate the results.
c) clastogenic (breaks chromosomes) in the in vivo
rat bone marrow cytogenicity assay.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 1320-6 (REV. 3-76)
409
-------
RS can cause chromosome aberrations and may have the poten-
tial to cause gene mutations; further testing is needed.
Retorted shale was found:
a) negative in the microbial assays.
b) weakly positive in an in vitro mammalian cell
culture assay (2.5X the~solvent control in the
high dose nonactivated assay). The results are
equivocal and the study should be repeated.
c) negative in the in vivo rat bone marrow cytogen-
icity study.
Retorted shale is not clastogenic; it should be retested to
further define its potential to cause gene mutations.
Current Production and Use
Oil shale ores can be retorted (destructively distilled)
above ground by two different processes: Paraho direct
pyrolysis of oil shale and the indirect Paraho process. In
both cases the product obtained is a synthetic crude oil
which is suitable for further processing using standard
petroleum refining technology. No shale oil recovery plants
are currently in commercial operation in the U.S.
Comments/Recommendations
Other submissions have concerned shale oil and have shown
this oil shale ore extraction product to be mutagenic in
various test systems (8EHQ-0178-0030) and carcinogenic in an
animal skin painting study (8EHQ-0278-0083). The present
submission indicates that oil shale solids may be mutagenic,
however, additional testing is needed to validate the results
presented. Any testing conducted on the gaseous products of
the retorting process would be of much interest to the Agency.
a) The submitter should be asked to describe any planned
future testing of shale oil or oil shale products.
b) Available data describing the analytical composition of
the oil shale solids should be requested from the submitter.
c) This submission and status report should be transmitted
to NIOSH, OSHA, DOE, OSW, and ORD.
410
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATC! August 16, 1978 Approved^
SUBJECT: status Report 8EHQ-0778-0217
Revision
Needed
FROM: prank D. Kover
Assessment Division, OTE/OTS
T0: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
The results of eye irritation tests in albino rabbits on three substances
produced in the Solvent Refined Coal (SRC) process at the SRC Pilot Plant
in Dupont, Washington. The three substances are SRC naphtha, SRC mineral
residue, and SRC wash solvent.
Submission Evaluation
OSHA should determine (1) if the eye wash procedures described in the
cover letter are adequate to protect workers and C2) if the analgesic
solution should be used without the supervision of an ophthalmologist.
Improper use of this solution, while relieving pain, may lead to more
serious complications.
The submission is admittedly incomplete; a full copy should be supplied
upon completion of the work. Of crucial concern will be the investigator's
observations of the effects seen in the rabbits' eyes. The crucial point
here is to what degree do these "extremely" or "seriously" irritating
compounds cause corneal damage producing errors of refraction, particularly
astigmatism.
Current Production and Use
The SRC Pilot Plant is capable of being operated in two modes, namely
SRC-1 with a solid product and SRC-2 with essentially liquid and gaseous
products. In each of the production modes, detailed analyses are available
as to the composition (chemical analysis) of each of the flow streams
within the plant. Therefore, the chemical composition of the three SRC
products should be available to the submitter.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 1320-6 (REV. 3-76) 4H
-------
The SRC process is being evaluated in the pilot plant to determine if it
is a commercially feasible method for the removal of undesired coal con-
taminants prior to the use of coal as a fuel.
Comments/Recommendations
(a) The submitter must provide a complete copy of the final study
when available; this should include complete chemical analysis on
all three SRC products.
(b) The submitter reports that there have been several incidents at the
pilot plant of personnel getting SRC materials in their eyes. The
submitter should be alert to the potential for subtle eye problems
(e.g., astigmatism) in addition to more severe cases of permanent
eye damage. If the attending ophthalmologist has any indication that
these subtle effects have in fact been observed, this information
should be transmitted to EPA.
(c) This submission and status report should be transmitted to NIOSH,
OSHA, and U.S. DOE.
'112
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
OATE: August 28, 1978
SUBJECT: status Report 8EHQ-0778-0218 Approved
Revision
: Frank D. Kover Needed
Assessment Division, OTE/OTS
T0rJoseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
Results of a 1-year chronic oral toxicity study with Phosvel (leptophos)
in adult chickens.
Submission Evaluation
The data presented definitely establish that 100 ppm of leptophos is
neurotoxic in chickens. This submission does not contain histopatho-
logical data as these will be provided at a later date when examination
of the slides is completed. Such an examination may reveal effects on
nerve sheaths at concentrations below those which produce clinical mani-
festations.
Current Production and Use
It is not clear if Phosvel is still in production in the United States;
the Washington Post edition of December 10, 1976, reports that the sub-
mitter stopped .producing the pesticide earlier in that year. This point
should be clarified through follow-up to the submitter. Phosvel was
apparently never approved for use as a pesticide in the United States;
however, it was approved for export. Following its use in Egypt, rural
villages reported severe health effects, including paralysis and death
of water buffalo as well as various human neurological problems. Phosvel
was produced at one of the submitter's plants apparently until nervous
disorders were recognized in exposed workers in December 1976.
Comments/Recommendations
Insofar as Phosvel is not a registered pesticide, this information was
submitted pursuant to TSCA Section 8(e) rather than FIFRA Section 6(a)(2).
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemicil. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
CPA FORM Ulfr-C (REV. »•?<>
413
-------
(a) The submitter should be asked to provide confirmation for the claim
that they are no longer manufacturing, processing, or distributing
Phosvel in commerce.
(b) This submission and status report should be transmitted to OSHA,
NIOSH, and OPP.
414
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE. August 21, 1978
SUBJECT: Status Report 8EHQ-0778-0219 Approved
Revision
. Frank D. Kover Needed
Assessment Division, OTE/OTS
T0: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
Report of an industrial hygiene survey conducted to monitor employee ex-
posure to DBCP, ethylene dichloride, and cyclohexane.
Submission Evaluation
Very little information of note was contained in this submission. For the
most part, employee exposures to ethylene dichloride, cyclohexane, and DBCP
were within current OSHA exposure limits, although the DBCP values were
above the proposed OSHA standard of 1 ppb. Previous analyses had indicated
that a TMCB (?) residue contained a substantial quantity (4-11%) of DBCP;
however, samples of the distillation fractions of crude TMCB contained no
detectable DBCP (level of detection - 2.4 ppm).
Comments/Recommendat ions
(a) The submitter should be asked to provide documentation that the find-
ings reported in this submission reasonably support a conclusion of
substantial risk of injury to health or the environment.
(b) The chemical identity of TMCB must be supplied by the submitter.
(c) This submission should be transmitted to NIOSH and OSHA for appropriate
action.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
415
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: August 21, 1978
iUiJECT: Status Report 8EHQ-0778-0220 Approved
Revision
MOM: Frank D. Kover Needed
Assessment Division, OTE/OTS ~~~
T0: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
Results of acute toxicity testing in rabbits and rats of neutral oils
from bromodichlorobenzene hydrolysis. The oils are identified as
consisting of unreacted bromodichlorobenzene (BDCB), 2,5-dichloroanisole
(DCA), p-dichlorobenzene (DCB), p-chloroanisole (CA), and chlorobromo-
anisole (CBA). Percent composition of the mixture is as follows:
Name %_
BDCB and DCA 63
DCB 22
CA 1
BCA 12
Unknown 2
Submission Evaluation
Neutral oils sample 77-1625 has primary eye irritation properties but is
not a significant primary skin irritant by the standard test. In the
acute dermal toxicity study, the material showed signs of dermal irritation.
This substance could produce pseudo-sensitization in humans as a consequence
of repeated irritation.
The acute dermal toxicity was estimated to be more than 10 g/kg and less
than 20 g/kg. The number and the types of clinical observations conducted
do not permit acceptance of these figures. In the primary skin irritation
study, one rabbit which had 0.5 ml applied to the skin died within 24 hours.
Assuming that this rabbit weighed 3 kg, the application was 0.15 ml/kg
and assuming a specific gravity of 1, the actual dose becomes less than
0.2 g/kg. This is 1/50 of their estimated toxic dose. The fact that
the 20-g/kg group required to 4 to 14 days for fatality suggests that
rabbits receiving 10 mg/kg were not observed for a long enough period.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
mcv. t-?o 416
-------
The erratic weight gain, particularly by males on the 10-g/kg dose,
suggests that histological examination of the viscera should have been
carried out. Clinical observations on the 20-g/kg rabbits suggest CNS
effects. The acute toxicity study in rats indicates an LDso °f approxi-
mately 2 g/kg. The groups of animals used in this experiment are not
large enough to determine whether one sex is more sensitive than the
other. The clinical observations in the rats are inadequate for deter-
mining the extent of CNS action. It is interesting that some rats become
hypoactive at the dose of 1 g/kg. This may be a manifestation of either
CNS depression or cardiovascular depression. Although there were no
fatalities at 1.0 and 1.5 g/kg, the weight gains were erratic at these
doses and the females gained less than the males. This suggests that
prolonged effects are occurring. The organs of the rats should have
been examined histologically.
Current Production and Use
The test material apparently represents some sort of a chemical waste
or by-product. No other information is available.
Comments/Recommendations
(a) The submitter should provide a description of the uses and/or forma-
tion of the test compound.
(b) The submitter should be asked to provide their rationale for the
submission of this information as offering reasonable support for
the, conclusion that these neutral oils present a substantial risk
of injury to health or the environment.
417 '
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE.- December 4, 1978
SUBJECT: Status Report 8EHQ-0778-0221
FROM: Frank D. Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Approved
Revision
Needed
Submission Description
Results of a mutagenicity evaluation of VC-948 (N-methoxy-4-chlorobenzamide)
in the unscheduled DNA synthesis assay in human cells.
Submission Evaluation
VC-948 was marginally positive in this test without activation. However,
when mixed with an activating liver S-9 preparation, VC-948 caused a sig-
nificant positive dose response in the unscheduled DNA synthesis test.
Because VC-948 was positive in this assay, the chemical may have oncogenic
and mutagenic potential and should, therefore, be handled with caution.
VC-948 should be tested further for its ability to cause gene mutation and
chromosome aberrations. This information would more precisely characterize
the spectrum of genetic end points that may be induced as a result of ex-
posure to the chemical. An in vitro malignant transformation assay may be
advisable to further define the oncogenic potential of VC-948.
Current Production and Use
No information was located in the secondary sources consulted.
Comments/Recommendations
(a) The submitter should be requested to provide a description of the an-
nual production and uses of this material.
(b) Part VI of the March 16, 1978 Policy Statement specifies that for
jln vitro experiments and tests "consideration may be given to the
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
418
-------
existence of corroborative information, if necessary to reasonably
support the conclusion that a chemical presents a substantial risk."
The submitter should be asked to present any additional information in
its possession that supports the conclusion that VC-948 poses a sub-
stantial risk. In most cases, a single positive response in an in vitro
assay is not sufficient to trigger reporting under Section 8(e), and the
submitter should consider the potential for exposure before submitting
such information.
419
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
OATE. August 21, 1978
SUBJECT: Status Report 8EHQ-0778-0222
FROM: Frank D. Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Approved_
Revision
Needed
Submission Description
Results of acute toxicity studies of dicyclopentadiene alcohol (DCPD
alcohol) in rabbits and rats.
Submission Evaluation
The identity of the compound tested is not revealed. Lot //C-10-3 is
described as a "pale yellow viscous liquid," while Lot #C2-7-2 is
described as a "semi-viscous yellow liquid." At any rate, this substance
is an extreme primary eye irritant. It is a mild primary skin irritant.
No studies were submitted to determine whether this alcohol is a sensitizing
agent or is capable of producing pseudo-sensitization as a result of
chronic primary skin irritation.
Female rabbits were approximately twice as sensitive as males to the
effect of skin application of DCPD alcohol. No data were submitted on
the weight gain of untreated rabbits to establish baseline laboratory
conditions. Even at 2.5 g/kg, one female had erratic weight gain; at
5 g/kg one male rabbit lost weight from day 6 to day 14 and one female
had low weight gain for the same period. The significance of these
data cannot be established in the absence of blood levels to determine
how much of the compound was absorbed from each dose administered. Female
rats also were more sensitive than males to this alcohol. Weights of
untreated rats were not included in the experiment; therefore, it is not
possible to evaluate baseline conditions of the lab. Even at 1.3 g/kg,
female rats had very little significant weight gain from day 7 to day 14.
It is a valid assumption that chronic toxicity may be developing even
following a single dose. The weight gain for the males receiving 2 g/kg
is somewhat high. This excess weight gain may be due to induction of
enzymes in the liver which may account for the lesser sensitivity of
males. Female rats receiving 2 g/kg again showed insignificant weight
gain from day 7 to day 14.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 1320-6 (REV. 3-76)
420
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: October 20, 1978
SUBJECT: Status Report 8EHQ-0778-0223
Approved
Revision
Needed
FROM: Frank D. Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submi s s ion De s cr ip t ion
Results of an acute toxicity study of methyl-m-chlorobenzoate in Daphnia
magna.
Submission Evaluation
The information contained in this report is too sketchy to indicate sub-
stantial risk. The report contains no description of the test material;
data describing its solubility in water and in the acetone carrier are
especially needed. Concentrations of the test material were not meas-
ured by the experimenter as only nominal concentrations were reported.
The observed 48-hour LC,-n (17 mg/1) indicates that methyl-m-chloroben-
zoate is probably not extremely toxic in the acute sense; however,
chronic or behavioral effects may occur at lower levels that might
coincide with expected environmental concentrations. Actual test con-
centrations may be much lower than the nominal concentration reported,
indicating that the compound may be more toxic than the figures suggest.
Current Production and Use
No information is available on the production and use of this material;
it is contained in the TSCA Candidate List.
Comments/Recommendations
This chemical was the subject of an earlier submission (8EHQ-0678-0201).
(a) The information requested in the follow-up to the earlier submis-
sion should be checked for inclusion in this report.
(b) The submitter should be asked to support his contention that the
information contained in this note reasonably supports a conclusion of sub-
stantial risk.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
421
-------
Current Production and Use
No information was located in the secondary sources consulted.
Comments/Recommendations
Several other submissions have concerned this compound (8EHQ-0478-0138P;
8EHQ-0678-0180; 8EHQ-0678-0207).
(a) Analytical data mast be provided by the submitter.
(b) The submitter should be asked to present his rationale for submis-
sion of this information as offering reasonable support for the
conclusion that DCPD alcohol presents a substantial risk of injury
to human health or the environment.
422
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: August 21, 1978
SUBJECT: Status Report 8EHQ-0778-0224
FROM: Frank D. Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Approved^
Revision
Needed
Submission Description
Acute toxicity studies of VEL 4578 [N'-(2-isopropoxycarbonyl-l-methyl-
vinylmethoxythiophosphoramido) acetamidine] in rats and rabbits.
Submission Evaluation
VEL 4578 is a thiophosphate ester and bears a class resemblance to mala-
thion; it would be expected to exhibit high toxicity. The rapid absorp-
tion from the eyes and skin caused death within 24 hours. The acute
oral toxicity data have little significance because: (a) the amount of
acetone that the rats received is not indicated, and (b) no dose less
than 50 mg/kg was administered.
Delayed death up to 24 hours in the acute oral toxicity study suggests
poor absorption or slow transformation to an anticholinesterase in the
body. However, the inhalation data suggest high toxicity for this
compound. This would indicate that either the absorption was more rapid
by this route or the lung has more effective converting enzymes (to
produce a more toxic metabolite). The deaths following inhalation of
VEL 4578 appeared to be due to asphyxiation following constriction of
the airway smooth muscle; other signs prior to death are typical of
cholinergic activation.
Current Production and Use
No information was located in the secondary sources consulted.
Comments/Recommendations
(a) The submitter should provide a description of the uses of VEL 4578.
NOTE: This status report is the result of a preliminary staff evalu-
ation of information submitted to EPA under Section 8(e) of
TSCA. Statements made herein are not to be regarded as express-
ing final Agency policy or intent with respect to this particu-
lar chemical. Any review of the status report should take
into consideration the fact that it may be based on incomplete
information.
423
EPA FORM 1320-6 (REV. 3-76)
-------
(b) The submitter should be asked to provide their rationale for the
submission of this information as offering reasonable support for
the conclusion that VEL 4578 presents a substantial risk of injury
to health or the environment.
424
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: September 20, 1978
SUBJECT: Status Report 8EHQ-0778-0225
FROM: Frank D. Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Approved_
Revision
Needed
Submission Description
Acute toxicity studies of VEL 4441 [N'-(2-methoxycarbonyl-l-methyl-
vinylmethoxythiophosphoramido)-N,N-dimethylformamidinel in rabbits and
rats.
Submission Evaluation
VEL 4441 is a malathion-type compound and therefore would be expected to
exhibit extreme toxicity, probably due to marked anticholinesterase activity.
This surmise is borne out by the lethality produced when small amounts of
the material are applied to the eye and skin of rabbits. The acute oral
toxicity in rats also places this compound in a highly toxic class, as do
the inhalation data. The symptoms following inhalation suggests that most
of the compound was inhaled as an aerosol rather than in solution. It
apparently took approximately 20 minutes for sufficient compound to be dis-
solved in biological fluids to produce cholinergic symptoms with the resul-
tant constriction of airway smooth muscle causing the gasping and death.
Current Production and Use
No information was located in the secondary sources consulted.
Comments/Recommendations
VEL 4441 was the subject of an earlier submission, 8EHQ-9678-0172.
(a) The submitter should provide a description of the uses of VEL 4441.
(b) The submitter should be asked to provide his rationale for the submitted
information as offering reasonable support for a conclusion that VEL 4441
poses a substantial risk to health or the environment.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fart
that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
425
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: December 4, 1978
$UUCCT: Status Report 8EHQ-0778-0226 Approved
Revision
FROM: Frank D. Kover Needed
Assessment Division, OTE/OTS ~~~
T0: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
Acute oral toxicity study of methyl-m-chlorobenzoate in mice.
Submission Evaluation
The purity of the test material was not stated. In the absence of control
data obtained on untreated animals and in the absence of a description of
the signs immediately preceding death, one would assume that this ester acted
like similar esters such as methyl benzoate and methyl salicylate. The
corn oil probably delayed absorption and thereby gave a more favorable LD
than is warranted. Any pathological changes observed in the lungs, liver,
and blood vessels (particularly those in the brain) would be important and
should have been reported in this study. The erratic weight gains in both
sexes could be due to the compound's effects either on the liver or on the
lungs.
Current Production and Use
No information was located in the secondary sources consulted.
Comments/Recommendations
(a) The submitter should provide a description of the uses of this compound.
(b) The submitter should be asked to provide their rationale for the submis-
sion of this information as offering reasonable support for the conclu-
sion that methyl-m-chlorobenzoate presents a substantial risk of injury
to human health or the environment.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
• PA FORM !»»-« IftCV. »-7() .«,-
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: August 21, 1978
SUBJECT: Status Report 8EHQ-0778-0227
PROM: Frank D. Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Approved
Revision
Needed
Submis sign Des cription
Acute toxicity studies of the sodium salt of tribromophenol in rabbits
and rats.
Submission Evaluation
Sodium tribromophenate was found to be a severe primary eye irritant.
No data were submitted for the concentration of the solution applied to
the eye nor for the pH of the solution. The compound was found to be a
mild skin irritant. No data were submitted for the sensitizing potential
and for chronic irritation or pseudo-sensitizing potential of the
compound.
The LD5Q values obtained by skin application of sodium tribromophenate
to rabbits have little significance. No data for untreated rabbits were
submitted to establish baseline laboratory conditions. Blood levels were
also not submitted; consequently, it is impossible to determine the amount
of test dose that was absorbed. The headings of Tables 6 through 9 are
mislabeled as representing an LD50 study in rats. The data in these tables
indicate a study of dermal irritation in rabbits. Item 4 on p. 43 reports
the body weight changes of the presumed rats. The actual starting weights
suggest that the animals used were rabbits.
Current Production and Use
Please refer to one of the below-referenced submissions for this information.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 1320-6 (REV. 3-76)
427
-------
Comments/Recommendations
Several other submissions have been received on tribromophenol (8EHQ-
1277-0024; 8EHQ-0178-0032; 8EHQ-0278-0069; 8EHQ-0378-0095; 8EHQ-0678-
0198).
(a) The submitter should be asked to address the concerns raised in the
evaluation section above.
(b) The submitter should be asked its rationale for the submission of
this information as offering reasonable support for the conclusion
that tribromophenol presents a substantial risk of injury to health
or the environment.
428
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: August 23, 1978 Approved^
SUBJECT: Status Report 8EHQ-0778-0228
Revision
Needed
FROM: Frank D. Rover
Assessment Division, OTE/OTS
TO! Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
Report of an industrial hygiene survey in which the only notable finding was
that employee exposure to ethylene dichloride (EDC) during one cleaning proc-
ess exceeded the NIOSH 15 ppm recommended peak exposure limit by 10 ppm.
Submission Evaluation
Insofar as the EDC levels did not exceed the current OSHA standard of 50 ppm,
one is hard pressed to find reasonable support for the conclusion that this
finding represents a substantial risk of injury to health or the environment.
Comment/Recommendations
(a) The submitter must provide documentation that the findings reported in
this submission reasonably support a conclusion of substantial risk of
injury to health or the environment.
(b) This submission should be transmitted to NIOSH and OSHA for appropriate
action.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
429
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
SUBJECT:
FROM:
TOi
August 21, 1978
Status Report 8EHQ-0878-0229
Frank D. Kover
Assessment Division, OTE/OTS
Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Approved
Revision
Needed
Submission Description
Acute toxicity studies of Benzoflex S-552 in rabbits and rats.
Submission Evaluation
The chemical identity of Benzoflex S-552 is not presented in the
submission. The only description offered is a CAS number which is not
contained in the TSCA Candidate List.
The test material was described as "off white chunks." Presumably these
chunks were powdered and the powder was applied to the eyes and skin of
the test animals.
The material was a primary eye irritant. This could have been due to
mild abrasion of the cornea by the powder. If the substances is highly
insoluble in body fluids or is a high-molecular-weight plastic, no absorp-
tion is to be expected by any route. Since this compound is most likely
not absorbed, the fluctuations in the individual rabbit weights suggests
that the baseline values obtained by the performing laboratory need
review.
Current Production and Use
The Condensed Chemical Dictionary identifies "Benzoflex" as a trademarked
series of plasticizers which are dibenzoesters of dipropylene glycol or
any of several polyethylene glycols. These compounds are used as primary
plasticizers for vinyl resins and in adhesive formulations. In addition,
some grades are used in food packaging adhesives.
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FORM 1320-6 (REV. 3-76)
430
-------
Comments/Recommendations
(a) The submitter must provide the chemical identity of Benzoflex
S-552.
(b) The submitter should be asked to provide their rationale for
submission of this information as offering reasonable support for
the conclusion that Benzoflex S-552 presents a substantial risk of
injury to health or the environment.
431
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: August 28, 1978
SUBJECT: Status Report 8EHQ-0878-0230
FROM: Frank D. Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Approved
Revision
Needed
Submis s ion De scription
The submission consists of an updated mortality study in workers exposed to
epichlorohydrin as well as other information on epichlorohydrin (ECH). This
submission represents a follow-up to a report forwarded to Mr. Douglas
Costle on September 26, 1977, which presented the initial results of this
epidemiology study.
Submission Evaluation
The study of Enterline and Henderson entitled "Updated Mortality in Workers
Exposed to Epichlorohydrin" reasonably supports the conclusion that epichloro-
hydrin presents a risk of human cancer. The authors' statement that the cur-
rent data are "highly suggestive of a carcinogenic risk for man" is an
accurate one.
The study is generally well reported and appears to have been adequately con-
ducted. The 98% overall follow-up rate (97% in Deer Park and 99.5% in Norco)
and the 94% overall rate for cause-of-death verification (by death certificate
review; 94% in Deer Park and 95% in Norco) are both excellent figures.
The most salient effect measures are the Standard Mortality Ratios (SMR's)
for workers from both plants (Norco and Deer-Park) combined (Table 4) who
were followed for at least 15 years from the onset of exposure. Respiratory
system cancer, leukemia, and cancer of all sites combined are in excess of
expected values.
None of the SMR's reach statistical significance at the 95% level. The authors
would have done better to report a point or closed-interval value for p to
enable a less arbitrary statistical assessment of the role of chance.
Qualitative factors tend to counter the possibility that the observed cancer
excesses were the result of random association. The same cancer types (res-
piratory system and leukemia) were elevated in workers from both plants.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
432
-------
The low SMR's for all causes combined and for most of the nonmalignant
individual causes indicate otherwise healthy populations. The SMR's for
leukemia, respiratory cancer, and all cancer rose as the length of
follow-up increased.
The importance of the separate calculations for men followed for at
least 15 years is the allowance for the induction period of cancer. The
SMR's for leukemia, respiratory cancer, and all cancer were higher in
this subset than in the total study population. All 14 cancer deaths
listed in Table 5 occurred at least 14 years after initial exposure.
The accompanying graph, based on the limited information of the nine
lung cancer deaths, does not reveal an apparent relationship among age
at first exposure, duration of exposure, and induction period. Neverthe-
less, Table 5 suggests a greater increased risk with "heavy to moderate"
exposure than with "light to nil" for total and respiratory cancer.
Such indications of dose-response are generally felt to contribute to
the certainty of a suspected etiologic relationship.
It was correctly pointed out by the authors that the relative youth of
the cohort (mean age, 48 years) may have acted to understate the actual
risk, since for many of the men it may have not been long enough since
initial exposure for the induction period to have transpired. The
preponderance of cancer deaths (especially lung cancer deaths) in the 2-
year update period supports this notion.
The risks for the Norco workers may have been underestimated by the use
of state mortality rates for calculating expected deaths. Louisiana's
white male respiratory cancer rate in 1950-69 was the highest in the
Nation (51.97 per 100,000). Texas (the location of Deer Park) ranked
17th with a rate of 38.52 (U.S. rate, 37.98).
The observation that 10 of the 14 cancer deaths in Table 5 were Deer
Park employees is not very remarkable since 10.44 of the 17.51 expected
cancer deaths were for the Deer Park group also. The concentration of
Deer Park cancer deaths among men with experience in the glycerine
department (X2 = 2.45, d.f. =1, .1 < p < .2) is intriguing but not
interpretable without exposure information for that plant area.
The letter of August 7 raises questions concerning pathological
diagnosis by cell type, the lack of quantitative exposure data, and the
likelihood that historical exposure levels were much higher than those
present today. Information on cell types would be useful but not essential
for the detection of increased risk. Monitoring data are rarely available
in occupational studies of chronic disease and cannot be considered a
mandatory requirement. The difference between past and present exposure
levels is irrelevant to the question of whether the substance should be
considered a human carcinogen.
The letter also raises the question of multiple exposure, especially by
cigarette smoking. Smoking histories would certainly be valuable and
possibly less difficult to obtain than he estimates. Nevertheless, Dr.
William Lloyd of OSHA contends that no reported excess lung cancer risk in
433
-------
any occupationally exposed cohort has yet been explained by differential
smoking patterns. Consequently, a presumption against confounding by
smoking appears to be reasonable in the absence of data to the contrary.
It would be useful to wait for further follow-up of these cohorts or to
conduct additional studies on similarly exposed workers to establish
more firmly this association with cancer. In light of the present data
and their close consistency with animal and in vitro studies, however,
it is reasonable to conclude that exposure to epichlorohydrin increases
the risk of respiratory system cancer and possibly of leukemia in humans.
Current Production and Use
Estimated U.S. consumption of epichlorohydrin in 1973 was 345 million
pounds. The major uses of ECH are in the production of synthetic glycerins,
epoxy resins, ECH elastomers, and various small-volume uses (e.g.,
manufacture of surfactants, Pharmaceuticals, textile coatings, glycidyl
ethers, paper-sizing agents and water treatment resins). A small amount
of annual ECH production apparently finds use as an "inert ingredient"
in a number of pesticides.
Comment s/Re commendations
(a) This submission and status report should be transmitted to the
Interagency Testing Committee, OSHA, NIOSH, CPSC, OAPQS, OSW, OWHM,
ODW, OPP, IAO, and ORD.
(b) It is of interest to note that the Agency recently received informa-
tion from Dr. Norton Nelson of New York State Medical University
reporting that epichlorohydrin was a positive carcinogen in a long-
term rat inhalation study.
434
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: OCT 2 0 1978
Status Report* 8EHQ-0978-0230 Approved
Supplement
Revision
Frank D. Kover Needed
Assessment Division, OTE/OTS
TO.- Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
Results of a study of testicular function among epichloro-
hydrin (ECH) workers at the submitter's Deer Park, Texas
and Norco, Louisiana plants. The study concludes that the
employees tested demonstrated no evidence of an ECH-related
impairment of testicular function. There was no observed
correlation between sperm count and either duration or
intensity of exposure to the chemical.
Submission Evaluation
The suggestion by the authors of the report that men who
suspected themselves to be subfertile or who believe them-
selves to be heavily exposed to ECH would be particularly
likely to participate in this investigation is open to
question. It might as well be argued that men who suspected
themselves to be subfertile would avoid the study in order
to avoid disclosing their inadequate virality to other
workers.
The low number of non-participant responders to the question-
naire (see page 13) may support the latter version. The sub-
mitter is making a sincere attempt to determine the reasons
for failure to participate in the study. Nevertheless, one
must question whether the non-participants will give frank
answers if the administering physicians are employees of the
submitter.
The laboratory aspects of this study were carried out very
well. The confirmatory analysis by a second lab was an
excellent step.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
CPA rout* u»-t IMCV. ».?•! 435
-------
Current Production and Use
Estimated U.S. consumption of ECH in 1973 was 345 million
pounds. The major uses of ECH are in the manufacture of
synthetic glycerins, epoxy resins, and ECH elastomers.
Small-volume uses include the production of surfactants,
Pharmaceuticals, textile coatings, glycidyl ethers, paper-
sizing agents, and water treatment resins.
Comments/Recommendations
This information was actually intended as an addendum to
an earlier notice submitted on epichlorohydrin (see 8EHQ-
0878-0230).
436
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: August 21, 1978
Status Report 8EHQ-0878-0231 Approved
Revision
MOM. Frank D. Kover Needed
Assessment' Division, OTE/OTS
TOs Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
Results of a 28-day range finding study of chlorendic anhydride in rats.
Submission Evaluation
The study suggests that chlorendic anhydride will cause a loss of body
weight in both male and female rats and that this effect is dose related.
The weight loss cannot be attributed to a reduction in food intake.' The
definitive study should include exhaustive examination of microscopic
sections of body organs.
Current Production and Use
i
Please refer to one of -the below-referenced studies for this information.
Comments/Recommendations
Several other submissions by the same submitter have involved chlorendic
anhydride (8EHQ-0278-0058; 8EHQ-0278-0059; 8EHQ-0378-0094; 8EHQ-0378-
0101; 8EHQ-0478-0127; 8EHQ-0478-0134; 8EHQ-O678-0206).'
The submitter should be asked to provide their rationale for submission
of this information as offering reasonable support for the conclusion of
substantial risk.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: August 16j 1978
SUBJECT: status Report 8EHQ-0878-0234
FROM: Frank D. Kover
Assessment Division, OTE/OTS
Approved^
Revision
Needed
TO:
Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
Preliminary results on a study investigating the oncogenic potential of
vinyl bromide during chronic inhalation exposure in rats. The present
information consists of the results of the histopathological examination
of rats sacrificed at the 18-month point in this 24-month study. This
information was actually submitted to the Agency on a "for your informa-
tion" basis.
Submission Evaluation
Vinyl bromide appears to be as potent as vinyl chloride for producing
liver angiosarcomas. Primary angiosarcomas of the liver were seen in
male and female rats exposed to vinyl bromide at 50, 250, and 1,250 ppm.
In addition, a single angiosarcoma was found in a mesenteric lymph node
from a single male rat in the 10-ppm group. The report concludes that
"enough liver angiosarcomas were observed in these sacrificed rats to
conclude that the exposure of male and female rats to vinyl bromide at
50, 250 and 1250 ppm for periods of up to 18 months has a carcinogenic
effect in the liver. The occurrence of a single angiosarcoma in the
mesenteric lymph node from a male rat exposed to 10 ppm of vinyl bromide
is suggestive of a carcinogenic effect. The spontaneous incidence of
angiosarcoma in the laboratory rat is very low and the occurrence of a
neoplasm of this type in one of ten sacrificed rats is suggestive of an
exposure related effect."
Current Production and Use
Vinyl bromide is used as an intermediate in organic synthesis and for
the preparation of plastics by polymerization and copolymerization. The
major use of vinyl bromide is in the production of flame-retardant
synthetic fibers. An example of this is a modacrylic fiber (produced by
NOTE: This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FO«M 1320-6 IREV. 3-76)
43G
-------
one of the companies co-sponsoring the vinyl bromide study) which is
composed of 79-81% acrylonitrile, 9% vinyl bromide, 8% vinylidene
chloride, and 2-4% other. The fiber is used primarily in children's
sleepwear. It is produced in a batch polymerization operation with a
suspension polymerization medium and a wet spinning process. This
method of production would probably preclude residual vinyl bromide
monomer in the final product; however, this has not been demonstrated
conclusively thus far.
Comments/Recommendations
Following review of this information, the Assessment Division's conclusion
is that the study should more properly have been submitted pursuant to
Section 8(e) of TSCA. The basis for this conclusion is as follows:
(a) The study indicates that vinyl bromide appears to be as potent a
carcinogen as vinyl chloride for producing liver angiosarcomas.
Part V(a)(2) of the March 16, 1978 Policy Statement declares that
the Agency considers reportable substantial risk information to
include "any pattern of effects or evidence which reasonably
supports the conclusion that the chemical substance or mixture can
produce cancer...." In addition, the introduction to Part V states
that "human health effects listed in Subpart (a) ... are so serious
that relatively little weight is given to exposure...." However,
in this case the annual production of vinyl bromide is (at a
minimum) somewhere between 100,000 and 1.5 million pounds per
year. The actual value is likely somewhat higher, as this
estimate accounts only for one company.
(b) Part VI(1) of the Policy Statement discusses preliminary results
of studies and declares that "not only should final results from
such studies be reported, but also preliminary results from
incomplete studies where appropriate."
Thus, on the basis of these two points, the Assessment Division has
concluded that this information offers reasonable support for the
conclusion that vinyl bromide presents a substantial risk of injury to
health and that the information is of the type required for submission
under the "Statement of Interpretation and Enforcement Policy" (43
FR 11110).
(a) A complete copy of the experimental protocol should be requested
from the sponsoring organization.
(b) The Assessment Division should immediately undertake efforts to
determine the feasibility of chemical analysis of vinyl bromide-
based fabrics to determine residual vinyl bromide content.
(c) This submission and status report should be immediately forwarded
to NIOSH, OSHA, CPSC, and OSW.
439
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: September 21, 1973 Approved
SUBJECT: Status Report 8EHQ-0878-0236
Revision
Needed
FROM: Frank D. Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
This submission reports the results of an NCI bioassay of p-cresidine which
concluded that the material is carcinogenic to rats and mice. The submit-
ter is reporting the information in light of its status as a manufacturer of
p-cresidine.
Current Production and Use
The material is used as a dye or dye intermediate.
C ommen t s/Re commendat ions
(a) The submitter should be asked to provide a description of the uses of
p-cresidine.
(b) The notifier should be informed that submission of NCI bioassay results
is not required for compliance with Section 8(e) of TSCA.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76)
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
MAY 011979
SUBJECT: Status Report 8EHQ-0878-0237
FROM: Walter W. Kovalick, Jr., Director 'J
Program Integration Division (TS-793) " "' "
TO: Joseph J. Merenda, Director
Assessment Division (TS-792)
Submission Description
Mason, Texas, Release raw natural gas to Squaw Creek
On August 3, 1978, a pipeline carrying raw natural gas
containing traces of hydrogen sulfide was damaged by
boulders carried by flash flood waters. Approximately
14,112 barrels of material was released; ninety-eight
percent to the atmosphere and two percent (282 barrels)
was released to the stream.
The incident was reported on August 3, 1978 to the Texas
Water Quality Board, Texas Railroad Commission and the
State Department of Transportation. On August 14, 1978
EPA Region VI was also notified.
Submission Evaluation
The incident does not appear to warrant reporting as a
substantial risk. As outlined in the March 16 Policy
Statement emergency incidents of environmental contamination
are to be reported if the chemical substance or mixture
involved presents adverse human health effects or environ-
mental effects which because of "the pattern, extent, and
amount of contamination 1) seriously threatens humans with
cancer, birth defects, mutation, death, or serious or
prolonged incapacitation, or 2) seriously threatens non-
human organisms with large-scale or ecologically significant
population destruction." There is no indication that any
adverse effects from the release of the gas have or will
occur due to the nature of the incident and the chemicals
involved.
Comments/Recommendations
This submission should be noted as an example of the type of
information not required for submission under Section 8(e)
emergency incidents of environmental contamination. The
notifier should be sent a copy of this status report.
cc: A. Edelman (TS-793)
F. Kover (TS-792)
EPA FORM 1320-6 (REV. 3-76)
441
-------
(2)
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA
under Section 8(e) of TSCA. Statements made herein
are not to be regarded as expressing final Agency
policy or intent with respect to this particular
chemical. Any review of the status report should
take into consideration the fact that it may be
based on incomplete information.
442
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: September 29, 1978 Approved^
SUBJECT: Status Report 8EHQ-0978-0238
Revision
Needed
FROM: Frank D. Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
Report of an employee who suffered a skin rash following exposure to a fuel
oil.
Submission Evaluation
The submission is incomplete in that it does not include a medical report of
the incident giving the physician's diagnosis, treatment, and description of
the final outcome of the situation.
Comments/Recommendations
(a) The submitter should provide the additional information noted in the
evaluation section. The submitter should also be asked to provide addi-
tional discussion of the basis for their decision that this information
offers reasonable support for the conclusion that fuel oil presents a sub-
stantial risk of injury to health. The information provided thus far is
insufficient to permit an Agency evaluation.
(b) Following receipt and evaluation of any follow-up information, considera-
tion should be given to transmittal of this submission to NIOSH and OSHA.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
EPA FORM 1320-6 (REV. 3-76) 443
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: October 23, 1978
SUBJECT: Status Report 8EHQ-0978-0239
FROM:
TO:
Frank D. Kover
Assessment Division, OTE/OTS
Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Approved
Revision
Needed
Submission Description
The results of mutagenicity teesting of chlormephos (S-chloromethy1-0,0-
diethylphosphorothiolothionate) in several Salmonella strains.
Submission Evaluation
No evaluation is possible without a full copy of the results from the complete
test.
Current Production and Use
The submitter reports that it is evaluating this material to determine its
potential for use as a pesticide.
Comments/Recommendations
(a) This submission and status report should be transmitted to OPP.
(b) The submitter should be asked to provide a full copy of the final report
upon its completion.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
c=>*
(32O-6 .REV- 3-76)
444
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: JUL '<:'•' "-•'"
SUBJECT: Status Report* 8EHQ-0978-0239 Approved
Supplement
Revisio
PROM: Franpr D. Kover, Acting Chief Needed
.
d /^^i
f
isioiv'
Chemical Hazard Identification Branch
TO: Joseph J. Merenda, Director
Assessment Division
Submission Description
The final report of mutagenicity tests of chlormephos (S-
chloromethyl-O,0-diethyl phosphorothiolothionate; CAS No.
24934-91-6) in several Salmonella strains. This new data is
supplementary to a previous submission (8EHQ-0978-0239) .
Submission Evaluation
The Ames1 Salmonella gene mutation test with microsomal
activation (Ames1 test) measures the capacity of a chemical,
and/or its metabolites, to induce gene mutations in the
bacterium Salmonella typhimur ium . This system can detect
both base pair changes and small deletions and additions in
the DNA of the bacterium. There is a good qualitative
correlation between positive Ames1 test results and positive
oncogenicity test results when the same chemical is tested.
Quantitative extrapolations from the Ames1 test are presently
not valid.
With and without metabolid activation, TA-100 was positive
(7 times the control value with activation and 3.6 times the
control value without activation) . TA-1535 was positive
only with metabolic activation (28 times the control value) .
In no instance was a positive dose response seen. The dose
response is largely negative arid toxicity was observed in
the positive response range. Some of the mutants seen at
the highest dose should be restreaked onto plates minus
histidine to check whether or not they are true revertants.
In addition, TA-100 and TA-1535 should be tested at lower
doses to establish the existence of a dose response.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
445
. »-7CI
-------
2 8EHQ-0978-0239 Supplement
Current Production and Use
As reported in a previous submission (8EHQ-0978-0239),
chlormephos is being tested for potential use as a pesticide.
No other information on the production and use of this
material was located in the secondary sources consulted.
This chemical is not listed in the TSCA Inventory.
Comments/Recommendations
In the absence of further data, the mutagenicity tests
performed should be considered positive. A positive Ames1
test indicates that the chemical and/or its metabolite is
mutagenically active in a bacterium. This raises a concern
that the chemical might be an oncogen or a mutagen in mam-
mals.
a) This submission and status report should be trans-
mitted to SPRD-OPP, NIOSH, OSHA, and FDA.
446
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF TOXIC SUBSTANCES
MEMORANDUM
SUBJECT: Status Report 8EHQ-0978-0240
FROM : Walter W. Kovalick, Jr., Director
Program Integration Division (TS-793)
TO : Joseph J. Merenda, Director
Assessment Division (TS-792)
THRU : Marilyn C. Bracken, DAA
Program Integration and Information (TS-793)
Submission Description
East Chicago, Indiana, Gas release of isobutane
On August 13, 1978, at a plant site subsidiary of the sub-
mitter, approximately 250 barrels of gas composed of 70%
isobutane and 30% isopentane were released. The release
occurred when a tank battery was overfilled, resulting in
venting to the atmosphere of the gas through a relief valve.
Local police and fire officials as well as the State Air
Pollution Control Board (Indiana Department of Health), the
local Department of Air Quality Control, and EPA Region V
were notified.
Submission Evaluation
The vapors of isobutane and isopentane are both narcotic and
asphyxiant. A single exposure on non-asphyxiant concen-
trations of either hydrocarbon would produce inebriation
from which there would be complete recovery. These vapors
are not sufficiently irritating to produce significant pul-
monary reactions. Single exposures to asphyxiant concen-
trations would usually result in rapid complete recovery.
It is possible that some individual might sustain temporary
injury to the hippocampus of the brain with resultant tem-
porary amnesia for recent events.
447
-------
In the absence of histopathology of the brain, lung, liver,
and kidney, it is not possible to evaluate the case of the
boy who died two days after the incident.
Current Production and Use
Isobutane and isopentane are large-volume hydrocarbons
derived from the fractional distillation of petroleum.
Isobutane is used in organic synthesis and as a refrigerant,
fuel, aerosol propellant, and instrument calibration fluid.
Isopentane finds use as a solvent, blowing agent for poly-
styrene, and intermediate in the manufacture of chlorinated
derivatives.
Comments/Recommendations
The incident appears to have been handled adequately; no
further action is indicated.
NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA
under Section 8(e) of TSCA. Statements made herein
are not to be regarded as expressing final Agency
policy or intent with respect to this particular
chemical. Any review of the status report should
take into consideration the fact that it may be
based on incomplete information.
448
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DAT*: 'NOV 2 4 1978
SUBJECT-. Status Report* 8EHQ-0978-0244 Approved
Revision
MOM: Frank D. Kover Needed
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
The submission consists of a variety of studies, including
two sponsored by the submitter and several references
uncovered during the course of a literature search, report-
ing the reproductive effects of benzene. The submitter
concludes, on the basis of its analysis of the information,
that in experimental animals benzene has weak toxic effects on
pregnant females and fetuses at 50 ppm. In addition, weak
teratogenic effects were observed at 500 ppm. The submitter
goes on to note that the literature search produced limited
data that may suggest a gonadal effect in male animals at a
concentration of 80 ppm; no studies dealing with effects on
females were uncovered in the literature search. A summary
table enclosed with the submission also indicates that feto-
toxic effects were observed in rats in one study at a con-
centration of 10 ppm benzene, although this finding is not
referred to in the body of the submission.
Submission Evaluation
The submission states that the purpose of these studies is
to determine the reproductive effects of benzene inhalation
in female experimental animals. The emphasis on females
appears to be due in part to the failure of the submitter's
overall literature search to identify pertinent references
detailing the reproductive effects of benzene in females.
As noted, the submitter has called attention to literature
references reporting gonadal effects of benzene in male
animals. Nevertheless, despite the submitter's discussion
of these articles only in the context of reported male
fertility effects, one of the cited studies, that by Hett
and Maak (1938; submission reference no. 5), states that
oral and inhalation administration of benzene to mice
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
fOMM «»»-« IMCV. »>7f)
449
-------
severely affected the gonads of both males and females. In
addition, a separate publication by Vera and Kinnunen (Acta
Obstet. et Gynecol. Scandanav., 26, 433-452, 1946; not cited
by the submitter) reports the results of a study in female
workers who had been chronically exposed to benzene vapors
and who subsequently developed serious gynecological problems.
Discussion of Benzene's Effects in Females
Hett and Maak (1938). The authors presented several observa-
tions on the effects of benzene vapors in female mice. The
study found degeneration of ovarian follicles, chiefly the
large ones; and ova (eggs) were multinucleate. The latter
observation is probably indicative of some abnormality in
chromosomal division or possibly, but less likely, parthe-
nogenesis (reproductive development of an ovum without its
being fertilized). In either case, embryo malformation (and
likely subsequent abortion) will result from such benzene-
induced abnormal ova.
Vera and Kinnunen (1946). The study investigated 30 female
workers who had subjective symptoms of benzene exposure
following one to ten years of chronic occupational exposure
to the substance. The benzene exposure levels experienced
by the women are not specified in the article. Of the 30
women studied, 12 had complaints related to the generative
tract. Two had excessive monthly bleeding, another had very
irregular menstruation, and six had sparse uterine bleeding
(the three remaining women apparently only had subjective
complaints). No menstrual peculiarities had been reported
by the women prior to entering their present occupations.
In some instances, the women complained of infertility and
in those cases where the cause for the infertility was not
clear, examination for the patency (condition of being open)
of the fallopian tubes was undertaken. In two such instances,
the tubes were patent such that ova could successfully
migrate; the authors surmised that benzene was responsible
for the sterility complaints. Although the objective
findings were varied, the subjective symptoms of the patients
were very much alike: most complained that the slightest
physical trauma led to bruises and that frequently the
bruises appeared spontaneously; tiredness, dizziness, and
headaches were also common. The objective findings for the
12 women were manifold. A definite leukopenia (reduction in
the number of leukocytes in the blood) was present in four
patients and in most of the women there was a decrease in
the number of neutrophilic leukocytes and thrombocytes
(blood platelets). A comparison of the gynecological
examination and the blood picture established that the
occurrences were parallel. The thrombocytopenia may relate
to the bruising and bleeding findings. Furthermore, it was
established that hypoplasia (abnormal decrease in the number
of cells) of the ovaries was the cause for the observed
450
-------
cases of sparse menstruation. On page 436 of this paper,
the authors point out that women are more sensitive than men
to benzene poisoning. This greater sensitivity is claimed
to be particularly apparent in pubescent girls and older
pregnent women. In summary, the toxic manifestations of
benzene in the female reproductive organs are expressed as
excessive monthly bleeding, irregular intermenstrual bleed-
ing, sparse bleeding, or as sterility.
For the experimental part of this study, the authors injected
five female rabbits with benzene on a daily basis until
blood .changes occurred. The blood changes were characterized
by transient leukocytosis (increase in the number of blood
leukocytes) and finally leukopenia. A similar alteration
was observed in the numbers of granulocytes, especially the
neutrophilic leukocytes. The number of thrombocytes decreased
to approximately 1/2 the normal value. In addition, the
vagina in all animals was dry and had little secretion. The
ovaries were more firm than usual and their size was reduced
to 1/4 of normal. The size reduction of the ovaries was so
severe in some cases that it was difficult to find the
organs at autopsy. Microscopic examination of the ovaries
revealed hypoplasia in addition to other findings. (Note
that the blood changes and ovarian hypoplasia seen in the
rabbits are similar to the changes seen in women workers.)
Finally, the distribution of the chromosomes in the ova
deviated from normal as the chromosomes in most cases lay
scattered and disorganized in the egg cell. Fertilization,
if possible, of such an egg would lead to an early sponta-
neous abortion. The blood dyscrasias observed in the rabbits
(and the female workers) may also contribute to the sponta-
neous abortion process because the alteration in the mother's
blood chemistry may preclude normal embryonic development.
Submitter-sponsored studies. The teratology, embryotoxicity,
and fetotoxicity studies sponsored by the submitter cannot be
used directly for determining benzene's capacity to induce
reproductive effects in humans. In particular, the expres-
sion of teratogenicity (broadly defined as "all manifesta-
tions of abnormal development, i.e., death, malformation,
growth retardation, and functional disorder," from James G.
Wilson, Environment and Birth Defects, Academic Press, 105,
1973) is more complex in humans than in rodents. The greater
complexity extends to other phases of reproduction and is
due in part to the characteristics of human placental attach-
ment which permits the intermingling of the fetus' blood
with that of the mother. This intermingling can provoke
immune reactions which may lead to the natural, spontaneous
abortion of a maldeveloping fetus. In the rat, however, the
degree of placental exchange is minimal. The experimental
design of the present studies is inadequate because it does
not take into account the duration of exposure required to
451
-------
produce the toxic effects of benzene (especially blood
decrasias, chromosome changes, and ovarian alterations) that
are relatable to human mutagenesis or teratogenesis and the
subsequent rejection of the embryo by spontaneous abortion.
As noted, the submitter-sponsored 1975 and 1977 teratology
studies are inadequate because the exposure conditions do
not coincide with the conditions required to produce the
blood and ovarian changes seen in chronically exposed females.
The 1975 study reports no bone marrow or teratogenic effects
in rats following 9-10 days of inhalation exposure during
the middle trimester of pregnancy. Although this is the
normal procedure for such studies, the relevance of these
conditions to environmental benzene exposure patterns is
somewhat suspect. Human exposure to benzene can in time
produce significant bone marrow and possibly endocrine
changes. Human pregnancies can occur during this period of
hematologic and endocrine change; thus, this animal study
does not correspond to the human exposure conditions known
to produce systemic changes and possibly teratogenesis or
mutagenesis.
The most significant aspect of the 1977 study is that feto-
toxicity was observed at a concentration of 10 ppm benzene.
The other reports provided identify the toxic benzene concen-
tration as 300 to 500 ppm. This is the lowest concentration
of benzene reported to induce fetotoxic effects and represents
an important, new finding. The current occupational standard
is a time-weighted average of 10 ppm.
The fetotoxicity (Green et al., 1977) and embryotoxicity
(Murray et al., 1978) studies suffer from the same experi-
mental inadequacies described above. On page 10, Green et
al. cite a study by Gofmekler (1968) that foudn decreased"
litter size in female rats exposed to benzene for 24 hours/
day, for 10-15 days prior to impregnation. Such a protocol
yields more significant results because the changes in
maternal hematopoiesis and ovarian effects are already in
progress when conception occurs. While such exposure condi-
tions do not, in all likelihood, reflect the human situation,
such conditions do point up the reproductive problems that
may be encountered given long-term exposure to benzene prior
to conception.
Discussion of the Other Submitted Studies
The Wolf et al. (1956) article indicates that leukopenia
and other bone marrow changes develop slowly in laboratory
animals following chronic inhalation exposure to benzene.
Diechmann et al. (1963) report that exposure to 800 ppm of
benzene required at least 14 days before evidence of bone
marrow depression was seen in rats. Exposure to 40 ppm
452
-------
required at least 5 weeks. By way of contrast, the submitter-
sponsored (1975) teratology study exposed pregnant female rats
for 9 days (days 6 through 15 of gestation) to 10, 50, or 500
ppm of benzene. The submitter-sponsored 1977 teratology
study exposed pregnent female rats to 10 or 40 ppm of benzene
for the same 9 day period used in the 1975 study. The Green
e_t al. (1977) fetotoxicity study also exposed pregnent rats
for~he same 9 day period to 100, 300, or 2,200 ppm of benzene.
The Murray et al. (1978) embryotoxicity study exposed mice and
rabbits to 500 ppm of benzene from days 6 through 15 (mice) and
6 through 18 (rabbits) of gestation. As found by Deichmann
et al., no chronic effects will develop within such limited
exposure periods.
Overall Evaluation
The experimental design of all of the submitter-sponsored
studies is inadequate because it does not take into account
the duration of exposure required to produce the toxic
effects of benzene that are relatable to human mutagenesis,
teratogenesis, and/or the process of spontaneous abortion.
Benzene-induced chromosome aberrations, blood dyscrasias,
and ovarian changes may, singly or in combination, act to
prevent or terminate a pregnancy due to mutation, gestational
difficulties, and/or hormal imbalance. Chronic exposure of
females to benzene can produce reproductive dysfunction or
malfunction leading to any of nonviable ova, spontaneous
abortions, or possibly, teratoid offspring. Finally, low
level exposure (10 ppm) to benzene at critical points during
gestation can induce fetotoxicity. Two publications, one of
which is not mentioned in the submission, report effects on
the ovary and ova that could result in nonviable or teratoid
development of the embryo. The first (Hett and Maak, 1938)
reported that benzene caused blood dyscrasias, ovarian
atresia, and the production of multinucleate ova in female
mice. The second (Vera and Kinunen, 1946) has illustrations
of chromosomal disarray and rupture in the ova of rabbits
chronically injected with benzene. In addition, the animals'
ovaries were reduced to 1/4 normal size due to ovarian
hypoplasia. This study also described various blood changes
in the rabbits; such changes could contribute to gestational
difficulties. The article describes human gynecological
conditions induced by occupational exposure to benzene vapors
at unspecified levels. These conditions are relatable to
hematopoietic, mutagenic, teratogenic, or ovarian disturb-
ances. In the female workers, benzene produced several
acquired blood dyscrasias including leukopenia, thrombocyto-
penia, and neutropenia. The chemical was implicated by the
authors (Vera and Kinnunen) as the cause of two cases of
sterility in the workers and several instances of abnormal
uterine bleeding. Blood dyscrasias are known to cause abnor-
mal menstruation in humans and such a bleeding condition
453
-------
can be life-threatening in patients with aplastic anemia,
leukemia, or thrombocytopenia (all of which can be caused by
benzene). In addition, such blood changes can adversely
impact in utero development of offspring. Vera and Kinnunen
reported that a comparison of the gynecological examination
and the blood picture established that the conditions were
parallel and that women are more sensitive than men to ben-
zene poisoning.
The submitter-sponsored 1977 teratogenicity study demonstrated
fetotoxic effects in rats exposed to 10 ppm of benzene during
the middle trimester of gestation. This is the lowest dose
reported for this effect and is a significant finding.
Thus, in summary, the available information indicates that
benzene exposure in females can lead to acquired blood
dyscrasias, abnormal uterine bleeding, and, possibly,
sterility (due to ovarian distrubances), mutagenesis,
and/or teratogenesis (due to benzene-induced malformed
embryos that are subsequently aborted spontaneously).
Current Production and Use
Approximately 9.8 billion Ibs. of benzene were produced
domestically in 1976. It is used as a chemical intermediate
for the manufacture of a number of large volume chemicals
(ethylbenzene; dodecylbenzene; cyclohexane; phenol; nitro-
benzene; maleic anhydride; chlorobenzene; diphenyl, etc.)
and as a solvent and anti-knock gasoline additive.
The current standard for occupational exposure to benzene is
a time-weighted average (TWA) of 10 ppm, with short excur-
sions as high as 50 ppm.
Comments/Recommendations
Several other submissions have concerned benzene (8EHQ-1277-
0027; 8EHQ-0378-0112; 8EHQ-0678-0106). The Assessment
Division intends to continue its evaluation of this submis-
sion and will enlist the assistance of other appropriate
offices.
a) This submission, status report, and the translation
of the EPA-identified article by Vera and Kinnunen should be
transmitted to NIOSH, OSHA, CPSC, OAQPS, ORD, OMSAPC, OWWM,
OSW, ODW, OWPS, and LTAT/AD/OTE with a request that they
provide any additional information on the effects of benzene
in females to the Assessment Division (OTS) or to OAQPS, the
lead office for preparation of the Phase I report on benzene.
b) The submitter should be asked to describe the "further
research" that is planned on the effects of benzene on male
and female reproductive organs and function.
c) An 8(4) rule to collect health and safety studies on
benzene should be considered.
454
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
PATE: December 4, 1978
SUBJECT: Status Report 8EHQ-1078-0245 Approved
Revision
MOM: Frank D. Kover Needed
Assessment" Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
The submission consists of two reports. The first presents the results of
a literature review and an in-house assessment of the estrogenic potential
of a polystyrene waste stream. The second report concerns the results of a
laboratory evaluation of the estrogenic potential of a polystyrene produc-
tion condensate in female rats.
Submission Evaluation
The three Russian articles by Zlobina reporting disturbances of the menstrua!
cycle and related effects among workers employed in Soviet polystyrene manu-
facturing plants and the submitter's laboratory findings that polystyrene
production by-products have estrogenic action in rats are the essential
health effects reported In this submission. The estrogenic substances in thi
by-product are probably low-molecular-weight condensation products of styrem
The synthetic estrogen, diethylstilbestrol (DBS; a condensation product of
stytene, see below) is a classic example -of an agent causing cancer develop-
ment in women and their children who were in uterus at the time the synthetl
estrogen was taken by the mother. The induction period was at least 15-20
years in the daughters and longer in the mothers. The effect on male off-
spring has not been established with certainty.
The low estrogenic potency of the submitter's waste material has little
relevance to the hazard. Exposure is likely to occur over long periods.
The important thing is that estrogenic action is there.
styrene monomer DES
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
roftN ttjo* IHCV. >•?•> 455
-------
Current Production and Use
Annual production of styrene monomer is on the order of 4-6 billion pounds.
Polystyrene manufacture (high impact and straight) represents approximately
55% (or 2.2-2.3 x 1CP pounds) of all styrene consumed annually in the U.S.
The submitter reports that the quantity of its polystyrene waste stream
product produced is generally less than 0.01% of the submitter's total
polystyrene production. If this value holds for the entire industry,
approximately 2.2-3.3 x 10^ pounds of this material will be generated
annually. The submitter's normal disposal practice for this waste stream
is incineration.
Related Past and Present Activities
A draft Hazard Assessment on styrene and ethylbenzene is available from the
AD.
Comments/Recommendations
This submission is somewhat related to an earlier one (8EHQ-0678-0202) which
reported carcinogenic action associated with polyethylated benzene tails, an
ethylbenzene waste stream.
This submission and status report should be transmitted to OAQPS, ORD, OWHM,
and OSW. The cover letter notes that the submission has been forwarded by
the submitter to OSHA, NIOSH, and FDA.
456
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: November 2, 1978 Approved_
SUBJECT: Status Report 8EHQ-U978-0246
Revision
Needed
PROM: Frank D. Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
Information concerning the health hazards of Raney nickel (a spongy, finely
divided form of nickel) in exposed workers.
Submission Evaluation
Raney nickel appears to be much more active than very fine nickel dust on
human tissues. It probably reacts readily with active proteins present in
the skin to produce inflammation; hence, the blisters due to accumulation
of exudate. A similar phenomenon has been described in workers who had
powdered magnesium metal driven into their skin during lathing procedures.
Magnesium reacted with tissue fluid to release hydrogen.
Many nickel compounds including the metal (which slowly reacts with tissue
proteins) have been shown to be carcinogenic and skin-sensitizing agents.
The carcinogenicity (probably) and the sensitization (definitely) involve
immune mechanisms. It is not unexpected that Raney nickel (in some re-
spects, the most active form of nickel) would be a potent skin irritant,
sensitizing agent, and carcinogen.
Current Production and Uses
No annual production figures are available; however, Raney nickel is used as
a catalyst for hydrogenation.
Comments/Recommendations
This submission and status report should be transmitted to OSHA and NIOSH.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
457
FORM 13i>€ (REV. 3-76) J
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE.- December 4, 1978
SUBJECT: Status Report* 8EHQ-1078-0247 Approved
Frank D. Kover p*»vic-ir>
FROM! Assessent Division OTE/OTS NeedZd
Joseph J. Merenda, Director
TO: Assessment Division, OTE/OTS
Submission Description
The submission reports results of a pilot teratology study with a
Solvent Refined Coal (SRC-I) process intermediate stream called
"filter feed" in albino rabbits. The test animals were exposed
dermally and exhibited some evidence of fetal toxicity in their
offspring.
Submission Evaluation
This submission establishes that "filter feed" can penetrate the
skin and thereby adversely affect the course of pregnancy. The
size of the test groups is to small to support the conslusion
offered that filter feed is nonteratogenic. The calculations
comparing rabbit to human exposure are inappropriate in the
absence of a more extensive study. There is no evidence that 1%
methylcellulose facilitated absorption through the skin. The
channels for skin absorption in rabbits differ from those in
humans. The pastelike material may have greater access to
sebaceous glands and hair follicles in human skin.
The following observations are significant in light of their
observation in such small test groups:
(1) Inadequate weight gain and actual loss of weight in mothers
(2) Unexplained spontaneous abortion in one female
(3) A possibly dose-related occurrence of resorption
(4) The unexplained occurrence of spina bifida (developmental
defect in the bony encasement of the spinal cord) in one
fetus
(5) The lower mean body weight of the progeny
(6) The decreased 24-hour survival of young rabbits.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
ei»A FORM uao-4 mev. >•?•) 458
-------
Current Production and Use
Filter feed is one of the process streams associated with the SRC-I
process which is being operated as a pilot plant by a company associated
with the submitter, under a contract with U.S. DOE. SRC-I filter feed
is made up of process solvent (either decalin or tetralin), SRC-I pro-
duct, ash (mineral residue), unreacted coal, and light oils. The con-
stituents are produced or flow at the following average hourly rates (as
determined in two equilibrium production runs at this 50-ton/day SRC
pilot plant):
Ib/hr
Wash solvent 242
Process solvent 4,357
Light oils 86.5
Ash 340
Unreacted coal 147.5
SRC-I product 2,240
Gaseous products (vent gases, fuel gas, steam, and hydrogen sulfide) are
removed from the process stream before it encounters a rotary drum filter
as the "filter feed."
Comments/Recommendations
SRC products were the subject of one other submission (8EHQ-0778-0217).
(a) The submitter should be asked to describe any additional testing
that is planned to further define the teratogenic potential of SRC-I
filter feed.
(b) This submission and status report should be transmitted to U.S. DOE,
OSHA, NIOSH, and ORD.
459
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: October 20, 1978 Approved
SUBJECT: Status Report 8EHQ-1078-0248
Revision
Needed
FROM: Frank D. Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Acting Director
Assessment Division, OTE/OTS
Submission Description
Preliminary results from a reproductive effects study of ethylene oxide in
rats. The one-generation study involved inhalation exposure to ethylene
oxide for 6 hours/day, 5 days/week at concentrations of 0, 10, 133, and
100 ppm for 12 weeks prior to mating and during the gestation period.
Submission Evaluation
The information provided is not sufficient to permit an evaluation of the
toxic effects of ethylene oxide. Histological examination of the adrenals,
thyraus, and gonads will probably establish the significance of the repro-
ductive effects seen at 100 ppm. More data will be required to assess the
depression of weight gain observed at 33 ppm.
The submitter claims that they have no evidence to indicate that their
workers have experienced such reproductive effects. It is not clear what
evidence was examined to determine the absence of reproductive effects in
workers. The submitter should clarify this point.
Production and Use
Annual production of ethylene oxide in each of 1975 and 1976 was greater
than 4 billion pounds. Ethylene oxide is used as an intermediate for the
production of ethylene glycol, acrylonitrile, ethanolamines, glycol ether,
and nonionic surfactants. It is also used as a sterilant and fumigant.
Comments/Recommendat ions
(a) The submission and status report should be transmitted to OPP, OSHA,
NIOSH, FDA, ITC, and OAQPS.
(b) Request submitter to provide additional information as noted in the
evaluation section.
NOTE: This status report is the result of a preliminary staff evaluation
of information submitted to EPA under Section 8(e) of TSCA. State-
ments made herein are not to be regarded as expressing final Agency
policy or intent with respect to this particular chemical. Any re-
view of the status report should take into consideration the fact
that it may be based on incomplete information.
460
1320-6 (REV. 1-76)
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
flCT 3 I 1979
Status Report 8EHQ-1078-0249 Approved
Revisio
PROM: Frank D. Kover, Chief Needed
Chemical Hazard Identification Branch.
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
The submission summarizes the results of a bioaccumulation study
conducted with tetraethyl (TEL) and tetramethyl lead (TML) in
eastern oysters. TEL was found to accumulate to a potentially
dangerous extent (bioconcentration factors were 17,600 and 18,138
for exposures of 0.1 and 0.8 ug TEL/1, respectively) while TML
showed little bioacummulation at similar levels. The submitter
states that "bioacbumulation could only occur in the unlikely
event of a transportation catastrophe involving bulk quantities"
and, therefore,does not believe that the data are subject to a
TSCA Section 8(e) reporting requirement.
Submission Evaluation
This submission indicates that high levels of TEL (1-14 ppm in
tissue) could be found in oyster flesh when very low levels of
TEL (0.1-0.8 ug/1) are present in water. Adult oysters, and
shellfish in general, are known metal accumulators. Previous
studies have demonstrated lead accumulation in eastern oysters.
Kopfler and Mayer (1973) found bioconcentration of total lead to
0.67-0.88 ppm (water levels at 0.5 to 3.0 ug/1). Pringle et al.
(1968) found accumulations from 17-75 ppm lead when the total
environmental lead levels ranged from 0.025-0.1 ppm. The data in
the literature indicate a bioconcentration factor of 640-1300 for
total lead, an order of magnitude below that reported by the
submitter for TEL. Evidence of the bioconcentration of TEL in
oysters is significant for several reasons. Because oysters are
a food source for humans, evidence of bioconcentration of TEL is
important from a human exposure perspective and its human health
effects should be examined. Secondly, bioconcentration of TEL
could impact the oyster population itself, although the toxic
level of TEL to oysters is not known. Shellfish are known to
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
FORM «»»-« INCV. >-7«i 461
-------
accumulate lead (and other heavy metals) even though inorganic
lead is toxic to oysters at fairly low concentrations in water*
The 12 and 18-week LC5pS for oysters are 0.5 and 0.3 mg lead/1;
lead levels in EUO as low as 0.1 to 0.2 mg/1 produced changes in
gonadal and mantle tissue (NAS, 1972). Data on other aquatic
organisms (fish; NAS, 1972) show that tetraethyl lead is 10-100
times more toxic than inorganic lead; if the extrapolation holds
true for shellfish, oyster populations could be endangered by
slight TEL levels in water. Damage to oyster populations would
have grave environmental and commercial consequences. It is
necessary to know the duration of the submitter's study and
whether any toxic effects were looked for or observed in the
oysters. It is not clear whether oyster-lead concentrations were
measured as wet or dry weight. Furthermore, it is assumed that
the submitter used adult oysters, although this was not stated.
The submitted results indicate the potential for accumulation of
lead to high levels (1.7 and 14.5 ppm) in a human food source.
Oysters should not be taken from areas contaminated with TEL.
Continuous exposure to low levels of TEL would be far more
dangerous than a spill of the material. The reasonably quick
purging mechanism in oysters would protect them from long-term
contamination resulting from a spill, but continuous exposure
could result in the accumulation of dangerous levels of lead. A
significant question is whether TEL is stable in the environ-
ment. If not, the true hazards of this material might be better
indicated by studies on its environmental by-products.
Because tetraethyl lead bioconcentrates to high levels, is toxic
to aquatic organisms at low levels, and has a widely dispersive
use (in gasoline), it is potentially quite dangerous in the
aquatic environment. Tetramethyl lead, on the other hand, bio-
concentrates to a minimal extent, and is toxic at relatively high
levels (96-hr. LCcQ is 84 ppm for bluegills and 13.5 ppm for
tidewater silversides (Dawson ^t^ ^1^ , 1977)). Based on this
information, it appears to present a much lower risk.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for tetraethyl lead (CAS No. 78-00-2) as listed in the
initial TSCA Inventory (1977) has shown that between 100 million
and 201 million pounds of this chemical were produced/imported in
1977. This production range information does not include any
production/importation data claimed as confidential by the per-
son(s) reporting for the TSCA Inventory, nor does it include any
information which would compromise Confidential Business Informa-
tion. The data submitted for the TSCA Inventory, including
production range information, are subject to the limitations con-
tained in the Inventory Reporting Regulations (40 CFR 710).
A review of the production range (includes importation volumes)
statistics for tetramethyl lead (CAS No. 75-74-1) as listed in
the initial TSCA Inventory (1977) has shown that between 1.1
462
-------
million and 11 million pounds of this chemical were produced/
imported in 1977. This production range information does not
include any production/importation data claimed as confidential
by the person(s) reporting for the TSCA Inventory, nor does it
include any information which would compromise Confidential Busi-
ness 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
710).
TEL and TML are used as commercial gasoline anti-knock com-
pounds. It is anticipated that the annual production and
consumption of lead anti-knock compounds will decrease due to the
increased use of nonleaded gasolines in many newer cars.
Comments/Recommendations
In the Agency's opinion, this information should have been
submitted under Section 8(e) of TSCA. The March 16, 1978
"Statement of Interpretation and Enforcement Policy" specifies
that information reporting bioaccumulation of a material beyond
5,000 times water concentration should be reported when coupled
with potential for widespread exposure and any non-trivial
adverse effect. The submitter reported that TEL has a biocon-
centration factor between 17,600 and 18,138, depending on the
initial concentration. Given the formidable production volumes
and the widespread use of leaded gasoline as a fuel for boats,
cars, etc., the potential for widespread exposure certainly
exists. TEL bioconcentration is of importance to organisms
(including man) that consume oysters directly or are consumers in
their food web. The effects of TEL on direct oyster predators
(flat-worms, mollusks, echinoderms, crustaceans, fishes (black
drum, toad fish, cow-nosed ray) and birds (diving ducks)
(Galtsoff, 1964)) have not been determined, however, very low
levels of TEL are acutely toxic to bluegill sunfish, a fish
bioassay model. The TEL, 96-hr. LCgQ for bluegills is 0.2 ppn
(Verschueren, 1977 and Dawson ^t^ al^., 1954). While not direct
oyster predators, they are found in low salinity rivers and bays
at the upper range of oyster fresh water tolerance. Bluegills
are not an accepted test model for estuarine or marine fishes
which may be oyster predators, but in the absence of data with
more appropriate species they are good indicators of a general
fish response to TEL. It is not unlikely that some estuarine and
marine fishes could be equally or more sensitive to TEL than
bluegills (this relationship is true for tetramethyl lead,
according to Dawson ^t_ jJL , 1977). On the basis of these points,
the Agency has determined that this submission does meet the
criteria as reportable Section 8(e) information and, therefore,
should have been submitted as such.
(a) This submission and status report should be transmitted to
FDA, U.S. Fish and Wildlife Service, ORD, OWWM, DOT, DOF,
CPSC.
463
-------
(b) The submitter should be asked to provide a full copy of the
final report of this study and to describe the test proto-
cols in detail. Any toxic effects observed in the test
oysters should be described. The submitter should also be
asked to provide any available data on the stability of TEL
in aquatic systems.
(c) The need for an assessment of TEL as an aquatic contaminant
should be further evaluated by CHIB.
References
National Academy of Sciences. 1972. Water Quality Criteria.
EPA-R3-73-033.
Galtsoff. 1964. The American Oyster. Vol. 64. Fishery
Bulletin of the Fish and Wildlife Service. Washington, DC.
Dawson ^t^ ^1^. 1977. The Acute Toxicity of 47 Industrial
Chemicals to Fresh and Saltwater Fishes. J. Hazard Mater. 1:303.
Kopfler and Mayer. 1973. Proc. Nat. Shellfish Assoc. 63:27.
Pringle et^ al_. 1968. J. Sanit. Eng. Div., Proc. Am. Soc. Civil
Eng. 94(5A3):455.
Turnbill ^t^ al_. 1954. Toxicity of Various Refinery Materials to
Fresh Water Fish. Industrial and Engineering Chemistry. 46:324.
Verschueren. 1977. Handbook of Environmental Data on Organic
Chemicals. Van Nostrand Reinhold Company. New York.
464
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
PAff: October 26, 1978
SUUICT. Status Report 8EHQ-1078-0250 Approved
Revision
MOM. Frank D. Kover Needed
Assessment Division, OTE/OTS
TOi Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
Preliminary results from a 24-month inhalation study of ethyl acrylate
in rats and mice. This report summarizes the pathology data from the
3- and 6-month sacrifices. The study is supported by the submitter and
three other companies.
Submission Evaluation
The squamous metaplasia (replacement of normal epithelial cells by cells
with greater embryonic potential) observed in both mice and rats may be
the result of chronic irritation, although it may represent a preneoplastic
change leading to tumor formation. The final results will provide the
answer. The nasal tissue hyperplasia (increase in the number of cells)
likewise may be due to either chronic irritation or to a beginning tumor;
the final report will tell.
Current Production and Use
Annual production of ethyl acrylate in 1976 was reported to be over 295
million pounds. It is used in the manufacture of polymers, acrylic
paints, and chemical intermediates.
Comments/Recommendations
(a) Consideration should be given to the preparation of a Chemical Hazard
Information Profile on ethyl acrylate.
(b) The submitter should be asked to provide the results of future
sacrifices as well as a copy of the final report.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
465
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: December 4, 1978
SUBJECT: status Report 8EHQ-1078-0251 Approved
Revision
Frank D. Kover Needed
Assessment Division, OTE/OTS
T0: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
Results of a life-time skin painting study of 2,2'-di(sec-
butoxy) acetophenone (correct molecular formula is C^gl^Os;
molecular formula in submission is incorrect) in mice. The
submitter concluded that the chemical is a weak carcinogen
in mice on the basis of this study, but that this informa-
tion does not, of itself, necessarily indicate that similar
effects will result in humans.
Submission Evaluation
The summary of the test data in the submission suggests that
this compound may be a weak carcinogen. This conclusion
cannot be evaluated with certainty in the absence of experi-
mental protocols.
Ketones of this type affect absorption of ultraviolet radia-
tion. Benzophenone derivatives are used in sunburn prepara-
tions to prevent absorption of ultraviolet light by the
skin. To determine whether this chemical initiates photo-
chemical reactions in skin, it would be necessary to expose
treated animals to ultraviolet radiation.
Current Production and Use
The tested chemical was developed as a photoinitiator in
acrylate based photo-cure coating systems begining about
1974. During its development and limited commercial use,
the submitter reports that approximately 8,000 pounds were
produced. The photoinitiator was 'used commerically by the
submitter and one other unspecified company; samples of the
£P» tOUtt II2O-* ItCV.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
466
-------
material were distributed to several other companies. In
January, 1978, the submitter reportedly decided to withdraw
from the photo-cure chemical coatings market. The submitter
notes that tests conducted with 2,2'-di(sec-butoxy) aceto-
phenone in the wet coating indicate that a significant
portion of the material is consumed in the photo-curing
process.
Comments/Recommendations
The submitter notes that a structurally similar chemical,
2,2'-diethoxyacetophenone, was used for similar purposes.
Although this compound has not been tested by skin-painting,
the submitter is advising those who have used or are using
2,2'-diaethoxyacetophone of the results of their study on
2,2'-di(sec-butoxy) acetophenone.
a) This submission and status report should be trans-
mitted to NIOSH and OSHA.
b) A Chemical Hazard Information Profile should be
prepared on these two compounds.
c) A complete copy of the mouse skin-painting study
should be requested from the submitter.
d) This submission and status report should be sent
to the ITC's lead reviewer for acetophenone.
467
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE. JAN 1 9 1979
su»JECT:Status Report* 8EHQ-1078-0252 Approved
Revision
Fuo*»:Frank D. Kover Needed
Assessment Division, OTE/OTS
T0:j0seph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
The submission consists of a preliminary report on a pilot
teratogenicity study conducted in rabbits by dermal applica-
tion with a Solvent Refined Coal (SRC-I) processed inter-
mediate stream called "wet mineral residue."
Submission Evaluation t
The term "dysmorphogenesis" is gradually replacing the term
"teratogenesis" in the sense that dysmorphogenesis refers to
any failure in the normal development of a species in con-
trast to the limited definition of a teratogen as something
causing a monstrous anatomical malformation (e.g., thalido-
mide) . Some teratolog,ists do not limit their observations
to the short period of organogenesis but also consider the
period from fertilization to sometime after delivery of the
neonate as embracing the field of teratogenesis.
It is significant that 150 mg/kg applied to the skin afforded
sufficient absorption into the doe and possibly into the
fetus or embryo to cause increased numbers of resorptions
and decreased numbers of live young, v
Current Production and Use
Wet mineral residue is one of the constituents of SRC-I
filter feed which is one of the process streams associated
with the SRC-I process that -is being operated as a pilot
plant by a company associated with the submitter under a
contract with U.S. DOE. SRC-I filter feed is made up of
process solvent (either decalin or tetralin), SRC-I product
mineral residue (ash), unreacted coal, and light oils.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
468
KPA rOMM 112O-* (REV. »-7C>
-------
Comments/Recommendations
SRC products were the subject of two other submissions
(8EHQ-0778-0217; 8EHQ-1078-0247).
a) The submitter should be asked to provide a full
copy of the final report from this study. The submitter
should also be asked to describe any additional testing that
is planned to further define the teratogenic potential of
SRC-I filter feed or its components. This is of some interest
because submission 8EHQ-1078-0247 reported fetotoxic effects
in rabbits following dermal exposure to SRC-I filter feed.
b) This submission and status report should be transmitted
to U.S. DOE, OSHA, NIOSH, and ORD.
469
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATES January 18, 1979 Approved
SUBJECT: Status Report 8EHQ-1078-0253
Revision
Needed
PROM: Frank D. Kover
Assessment Division, OTE/OTS
TOi Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
This report summarizes interim data obtained through the first 48 weeks
of a lifetime mouse skin-painting study conducted to determine the
carcinogenic activity of "intermediate clarified oil solvent extract,"
a highly aromatic petroleum oil.
Submission Evaluation
The submitted data establish that the intermediate clarified oil solvent
extract is a potent carcinogen when applied to the skin of mice. Suffi-
cient material appears to be absorbed through the skin of the mice to
result in subacute or chronic intoxication as indicated by impaired
gain in body weight and by excess mortality. Histological examination
will establish whether the chronic toxicity involves liver, kidneys,
adrenals, and/or other organs.
Current Production and Use
No information on the production and use of this material was located in the
secondary sources consulted. The submitter reports that oils of this type
are contained in catalytic cracker process streams in most refineries;
however, there is no information available as to the number of refineries
in which this type of oil is actually extracted as a unique product. The
submitter also reports that the material is used as a secondary plasticizer
for PVC resins and as a component of roof coatings.
Comments7 Recommendations
(a) This submission and status report should be transmitted to NIOSH,
OSHA, ORD, OSW, CPSC, and LTAT(AD).
(b) Chemical should be evaluated as a potential Section 4(f) candidate.
NOTE:This status report is the result of a preliminary staff
evaluation of information submitted to EPA under Section 8(e)
of TSCA. Statements made herein are not to be regarded as
expressing final Agency policy or intent with respect to this
particular chemical. Any review of the status report should
take into consideration the fact that it may be based on
incomplete information.
EPA FOAM (320-6 (REV. 3-761
470
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
SUBJECT: status Report 8EHQ-1078-0254
FROM:
TO:
Frank
Assessment Division, OTE/OTS
Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Approved
Revisio
Needed
Submission Description
This submission reports the results of an Ames assay of 1,1,2,2-
tetrabromoethane (TBE).
Submission Evaluation
The Ames Salmonella gene mutation test with microsomal activation
(Ames test) measures the capacity of a chemical and/or its
metabolite to induce gene mutations in the bacterium Salmonella
typhimurium. This system can detect both base pair changes as
well as small deletions and additions in the DNA of the
bacteria. There is a good qualitative correlation between
positive Ames test results and positive oncogenicity test results
when the same chemical is tested. Quantitative extrapolations
from the Ames test are presently not valid.
The experimental protocol employed by the testing laboratory is
not indicated; this should be requested. The positive control
with methylcholanthrene was run only with activated liver
cultures (+S-9); a positive control without activation should
have also been included in the protocol. As it was, the positive
control with S-9 activation gave positive responses only for
strains TA-98 and TA-1537; it is therefore uncertain that the
other 3 strains (TA-100, TA-1535, and TA-1538) will respond
positively under the conditions of the experiment. The meaning
of the dash (-) in the results table is unclear; this needs
clarification.
There are indications of toxicity in the assays conducted with
activated liver microsomes (+S-9). The number of revertants
(mutants) in several of the Salmonella .tester strains (TA-98,
TA-1535, and TA-1538) decrease with an increase in the concen-
tration of TBE. However, under the conditions of the test, a
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM U20-6 (REV. 9-76)
-------
positive mutagenic response was observed in strains TA-100,
TA-1535, TA-1537, and TA-1538 at the highest dose only; in
addition, the response was quite strong. However, the meaning of
such a response at only one dose is uncertain because none of the
putative revertants were restreaked to insure that reversion has
occurred, and that the change is, in fact, heritable.
Considering (1) the observed toxicity, (2) the positive response
at the high dose only, and (3) the failure to restreak the
revertants, the following is a possible explanation for the
observed results. The tester bacteria, which lack the ability to
synthesize histidine (an essential anino acid), are plated in
media containing a trace of histidine so that the bacteria can
undergo a few cell divisions (this is often necessary for the
induction and expresssion of mutations). Normally all of the
cells compete for the available histidine, deplete it rapidly,
and, if no reversion (mutation) occurs, enter a state of
equilibrium and form a milky background (as opposed to
colonies). However, if most of the bacterial cells are killed,
the survivors have few nearby competitors for the available
histidine and the surviving bacteria are able to form colonies
even though no genetic reversion has occurred (thus the need for
restreaking). Because of the points raised in this discussion,
one must question the conclusions reached by the testing facility
concerning a threshold value for the mutagenic activity of TBE.
On the basis of limited available experimental data, any discus-
sion of a "threshold" for mutagenicity is premature. At any
event, the experiment should be repeated and the putative
revertants restreaked on plates without histidine. If the
explanation advanced above is accurate, the "revertants" will be
genetically identical to the histidine-dependent tester
strains. Because the Ames plate test may provide negative or
equivocal results with TBE, the chemical should be tested with an
Ames suspension assay or a mammalian in vitro gene mutation
assay.
The analytical purity of the test material was not provided; this
information should be supplied, if available.
Current Production and Use
No production figures are available for 1,1,2,2-tetrabromo-
ethane. TBE is used for separating minerals by specific gravity,
as a solvent for fats, oils, and waxes, and as a fluid in liquid
gauges.
Comments/Recommendations
(a) The comments and questions raised in the evaluation section
above should be brought to the submitter's attention.
472
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
APR 0 9 lQ7q
'*'3 OFFICE OF TOXIC SUBSTANCES
MEMORANDUM
SUBJECT: Status Report 8EHQ-1078-0255
FROM : Walter W. Kovalick, Jr., Director
Program Integration Division (TS-793)
TO : Joseph J. Merenda, Director
Assessment Division (TS-792)
THRU : Marilyn C. Bracken, DAA
Program Integration and Information (TS-793)
Submission Description
Washington, Pennsylvania, Spill of Red Ink into Little
Chartiers Creek
On October 12, 1978, during truck-unloading operations,
approximately ten gallons of Sun-Cor Flexographic 74 red ink
was spilled into Little Chartiers Creek. The ink is for-
mulated from a mixture of water, glycol, alcohol, acrylic
binder, wetting agents, surfactants, clay pigments, and lead
molybdenate chromate pigment.
The incident was reported to EPA on October 12 and the
Commonwealth of Pennsylvania Regional Office in Pittsburgh
on October 13.
Submission Evaluation
The incident does not appear to warrant reporting as a
substantial risk. As outlined in the March 16 Policy State-
ment, emergency incidents of environmental contamination are
to be reported if the chemical substance or mixture involved
presents adverse human health effects or environmental
effects which because of "the pattern, extent, and amount of
contamination 1) seriously threatens humans with cancer,
birth defects, mutation, death, or serious or prolonged
incapacitation, or 2) seriously threatens non-human or-
ganisms with large-scale or ecologically significant pop-
ulation destruction." There is no indication that any
473
-------
adverse effects from the release of the ink have or will
occur due to the small quantity released and nature of the
chemical mixture.
Comments/Recommendations
This submission should be noted as an example of the type of
information not required for submission under Section 8(e)
emergency incidents of environmental contamination. The
notifier should be sent a copy of this status report.
NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA
under Section 8(e) of TSCA. Statements made herein
are not to be regarded as expressing final Agency
policy or intent with respect to this particular
chemical. Any review of the status report should
take into consideration the fact that it may be
based on incomplete information.
474
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
: January 18, 1979
»Ui«CT: Status Report 8EHQ-1178-0256 Approved
Revision
MO* Frank D. Kover Needed
Assessment Division, OTE/OTS
TO! Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
The submission consists of a preliminary report on the acute inhalation
toxicity of a process residue from the production of triethylene diamine
by the catalytic dehydration of 2-hydroxyethyl piperazine in a mixture
of biphenyl and biphenyl oxide in rats.
Submission Evaluation
The residue is not adequately characterized analytically and, therefore,
the significance of the inhalation study can only be guessed. The outcome
of the exposure is not surprising. The pathologist should have no difficulty
in determining to what extent the cause of death can be attributed to
precipitation of particles in the lungs vs. the alkalinity of the residue.
Current Production and Use
The submitter claims that no commercial use has been found for this residue
and notes that the material is a waste product which is currently incinerated.
Comments/Recommendations
(a) The submitter notes that additional information will be provided in
a follow-up report. The submitter should be asked to include the
analytical composition of the residue in that follow-up report.
(b) This submission and status report should be transmitted to NIOSH,
OSHA, and OSW.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
uzo-t INCV. »-7«i 475
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
SUBJECT: Status Report"8EH<3-1178-0258
FROM: Frank D. Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Approved
77
Revision^
Needed
Submission Description
The submission apparently concerns a worker's complaint that
2 materials used in his printshop caused drowsiness, dizziness,
and headaches. The specific chemical compositions of the 2
cited materials ("multilith deglazing solvent" and "ink
roller desenitizer") are not reported.
Submission Evaluation
Many "solvents" and similar materials are known to cause
dizziness, headaches, and other effects if ventilation is
not adequate. Insufficient information has been provided by
the submitter to permit an adequate evaluation.
Current Production and Use
The materials are apparently used in printing operations;
no other information is available.
Comments/Recommendations
This submission does not appear to offer reasonable support
for a conclusion of substantial risk. There is no indication
that the affected worker experienced "serious or prolonged
incapacitation" following exposure to the cited materials.
Neither is there any indication that headaches and dizziness
are newly documented effects following exposure to these
materials.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 1320-6 (REV. 3-76)
476
-------
-2-
A) The submitter should be asked to provide further
information on the reported incidents: physician's
report or some other professional evaluation (nurse,
hygienist, etc.) of the symptoms and conditions of
exposure (the vague description provided is not ade-
quate); a more complete description (chemical composi-
tion) of the implicated products and an indication that
the observed effects represent new information not
available to the Administrator (the products' manufac-
turers or distributors should be able to provide the
information needed to determine this).
477
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
SUBJECT Status Report* 8EHQ-1178-0259 Approved
i
Revision
FROM: Frank D. Kover Needed
Assessment Division, OTE/OTS
TO.- Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
The submission reports that 2,3,4,4,4-pentachloro-2-butenoic
acid, n-butyl ester is highly toxic to rabbits on dermal
application. The chemical was incorrectly listed in the
original submission.
Submission Evaluation
The extreme toxicity of this compound should have been
further investigated. It is impossible to evaluate the data
as presented because a non-lethal dose of the compound was
never tested and the number of animals used in the experiment
was not specified. In addition, the analytical purity of
the test compound and the identification of any contaminants
should be provided.
Current Production and Use
There are no data in the secondary literature on the pro-
duction or commercial uses of this compound. A search of
Chemical Abstracts titles reveals that 2,3,4,4,4-penta-
chloro-2-butenoic acid, n-butyl ester can be used as a
catalyst for the production of synthetic rubbers and other
polymers by free radical polymerization.. If it is used
commercially fo'r this purpose, the potential for residue
contamination of the final product becomes important.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 1320-6 (REV. 3-76) 478
-------
-2-
Comments/Recommendations
Although the chemical is highly toxic and the dermal LD
value reported is in the range desired for the reporting of
such studies under Section 8(e), the submitter's discussion
of the "fact or probability of occurrence" criterion (Part V
of the March 16, 1978 policy statement) as it relates to
this chemical indicates that submission does not appear to
be required for this information; however, this point should
be confirmed through a follow-up letter.
The information provided by the submitter is not sufficient
to permit an EPA evaluation of the study or its results. In
all cases, EPA desires a complete description of experi-
mental protocols and results as well as information on the
analytical purity and composition of the test material.
Without this information, it is not possible to adequately
evaluate submitted information.
a) The submitter should be asked to provide a de-
scription of the uses of this compound as well as any
available information on the presence of 2,3,4,4,4-penta-
chloro-2-butenoic acid, n-butyl ester residues in any of its
products. A full copy of the study's final report and
supporting data for points (1) "There is no exposure of the
general public..." and (2) "There is limited worker ex-
posure" in the letter should also be provided.
b) The submitter should describe any planned ad-
ditional testing of this compound.
c) Section 8(b) data should be checked for infor-
mation on annual production.
d) This submission and status report should be trans-
mitted to NIOSH and OSHA.
479
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
SUBJECT:
PROM;
TO:
NUY i 3 »y?J
Status Report 8EHQ-0379-0259
Followup Response
Frank D. Kover, Chief
Chemical Hazard Identification Branch-
Joseph J. Merenda, Director
Assessment Division, OTE
Approved
Revision-
Needed
Submission Description
Per the Agency's request in a follow-up letter to the initial
submission (8EHQ-1178-0259), the submitter has provided a copy of
the final report on the acute dermal toxicity of 2-butenoic acid,
2,3,4,4,4-pentachloro-, n-butyl ester (BPCC; n-butyl perchloro-
crotonate; CAS No. 21824-93-1). Use and exposure data on BPCC
were also requested and have been provided in this followup
submission. The acute dermal LDcn of BPCC is reported to be less
than 50 mg/kg (lowest dose tested; when applied undiluted to the
intact and abraded skin of rabbits.
Submission Evaluation
BPCC appears to be a potent escharotic (corrosive) agent that is
readily absorbed from skin following which it produces severe
systemic effects on the central nervous system and probably on
heart, blood vessels, liver, kidney and skeletal muscle. The
effects are due to depressed function of these internal organs.
The local escharotic effects on skin resemble those of trichloro-
acetic acid which has been used in medical practice, particularly
for removal of warts. Some of the BPCC would be hydrolyzed by
esterases from bacteria and fungi normally resident on skin of
animals. The resulting perchlorobutenoic acid would probably be
more potent than trichloroacetic acid as an escharotic agent.
The systemic effects are most likely due to absorption of the
ester that has escaped hydrolysis by skin bacteria. The ester
would be expected to have actions resembling those of the chloral
hydrate ("knockout drops") class of compounds but much more
potent. This class of compounds depresses function of the cen-
tral nervous system, liver, kidney, heart, blood vessels, and
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
U20-« IMEV. V7C!
430
-------
skeletal muscle. The deaths that occcurred within hours after
skin application were probably due to either medullary failure of
heart or respiration or to direct cardiac poisoning. The deaths
that occurred after 24 hours following application of a surpris-
ingly small dose may have been due to any of the above depressant
actions or a combination of them.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for BPCC (CAS No. 21824-93-1) as listed in the initial
TSCA Inventory (1977) has shown that no 1977 production/importa-
tion was reported or that all of the production range data
reported was claimed as confidential by the manufacture^s) and
importer(s) and cannot be disclosed (Section 14(a) of the TSCA,
U.S.C. 2613 (a)). The data submitted for the TSCA Inventory
including production range information, are subject to the
limitations contained in the Inventory Reporting Regulations (40
CFR 710).
The submitter states that BPCC is a catalyst extender used in the
production of ethylene propylene diene terpolymer (EPDM rubber).
EPDM rubber is then used in the production of consumer products,
mainly in the automotive industry (e.g. hoses and tire side-
walls). The submission also reports that BPCC is used in only
12-15% of the EPDM rubber produced domestically and that EPDM
rubber represents only about 6% of the total synthetic rubber
market.
Comments/Recommendations
The submitter, in response to a followup question asked by the
Agency, has reported that chemical analyses on several EPDM
rubber samples and residual solids collected after solvent
extraction of EPDM rubber indicated no traces of BPCC. This
result is reported by the submitter to have been confirmed in
similar analyses performed by a domestic customer.
(a) A copy of the original submission (8EHQ-1178-0259), the
followup submission (8EHQ-0379-0259 Followup Response), and
the respective status reports should be transmitted to
NIOSH, OSHA, and CPSC.
481
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
APR 0 9 1Q7Q OFFICE OF TOXIC SUBSTAN<-F3
MEMORANDUM
SUBJECT: Status Report 8EHQ-1178-0260
FROM : Walter W. Kovalick, Jr., Director
Program Integration Division (TS-793)
TO : Joseph J. Merenda, Director
Assessment Division (TS-792)
THRU : Marilyn C. Bracken, DAA
Program Integration and Information (TS-793)
Submission Description
Near Beggs, Oklahoma, Natural gas pipeline explosion and
fire
On October 30, 1978, a pipe carrying natural gas blew out.
The leaking gas was ignited by a passing pick-up truck that
was also destroyed, resulting in the death of two persons.
Nearby buildings and approximately 30 acres of trees and
grass were destroyed. The EPA Region VI office and DOT were
notified, and subsequently DOT and OSHA representatives were
dispatched to the site.
Submission Evaluation
The incident does not appear to warrant reporting as a
substantial risk. As outlined in the March 16 Policy
Statement, emergency incidents of environmental contamina-
tion are to be reported if the chemical substance or mixture
involved presents adverse human health effects or environ-
mental effects which because of "the pattern, extent, and
amount of contamination 1) seriously threatens humans with
cancer, birth defects, mutation, death, or serious or pro-
longed incapacitation, or 2) large-scale or ecologically
significant population destruction." Due to the nature of
the material involved and the resultant short-term effects
of the fire, there is no indication that adverse health or
environmental effects (aside from those deaths and damage
caused by the fire) will occur.
482
-------
Comments/Recommendation
This submission should be noted as an example of the type of
information not required for submission under Section 8(e)
emergency incidents of environmental contamination. The
notifier should be sent a copy of this status report.
NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA
under Section 8(e) of TSCA. Statements made herein
are not to be regarded as expressing final Agency
policy or intent with respect to this particular
chemical. Any review of the status report should
take into consideration the fact that it may be
based on incomplete information.
483
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
SUBJECT: Status Report* 8EHQ-1178-0261
FROM: Frank D. Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Approved
Revisio
Needed
Submission Description
This is a preliminary report on the acute inhalation toxicity
of tertiary-octyl mercaptan (2,4,4-trimethyl-2-pentanethiol)
in rats. It is reported that tertiary-octyl mercaptan is
significantly more toxic to female rats than to male rats.
The submission also indicates that use of an unspecified
product containing tertiary-octyl mercaptan residues may
release potentially hazardous concentrations of the material.
Submission Evaluation
It is reported that chemically uncharacterized vapors (presumably
containing tertiary-octyl mercaptan) released upon heating
and air stripping the product in question were more toxic
to female rats than1to male rats. Exposure to 0.74 mg/1 of
tertiary-octyl mercaptan (or the analytically uncharacterized
air stripped material, the submission is not clear on this
point) for one hour resulted in death of 2/5 male rats while
the same exposure resulted in 5/5 deaths in female rats. A
one-hour exposure to 0.50 mg/1 resulted in 4/5 deaths in
female rats while no fatalities were observed in male rats
at doses below 0.74 mg/1. Death in 4/5 animals at 0.5 mg/1
indicates that the material given off by the heated product
is highly toxic. However, without a full description of the
study protocols and chemical analyses of the vapors to which
the animals were exposed, it is not possible to conclude
that tertiary-octyl mercaptan was the causative agent.
There are no statistics performed on the submitted data and
it is difficult to have an intuitive feel for significance
from such a small sample size. More importantly, no mention
is made of the differences in weight and respiratory rate
between female and male rats. Without these data and
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
484
EPA FORM 1120-6 (REV. 3-76)
-------
statistical testing it is impossible to decide whether the
released vapors are more toxic to female rats than to male
rats. The submitter notes that additional information on
the study will be provided in the future.
Current Production and Use
Tertiary-octyl mercaptan is reportedly produced by two
companies in the United States.
Tertiary-octyl mercaptan is used to control the extent of
polymerization during the production of synthetic rubber and
rubber-like polymers. Annual production volume is not
known.
Comments/Recommendations
Tertiary-octyl mercaptan is relatively volatile at room
temperature. Vapor phase toxicology studies with the
source at room temperature (250°C) may detect some addi-
tional hazard.
The major deficiency in this submission concerns the uncer-
tain analytical composition of the "released vapors." The
submitter apparently assumes (or perhaps knows) that ter-
tiary-octyl mercaptan is the major toxic component in the
vapors. This point, however, is not demonstrated.
The final toxicological study may show that female rats are
more sensitive to the released vapors than male rats; how-
ever, the submitter should attempt to determine that the
females greater sensitivity is "real" and not merely
"apparent." The submitter should consider factors such as
differences in weight, respiratory rate, respiratory volume,
etc., before concluding that there are sex-related differ-
ences in the lethality of the vapors. If the conclusion is
nonetheless supported, the toxicological basis for the dif-
ference (if discernible) would be of much interest.
a) In view of the reported high toxicity of the test
vapors, this preliminary submission and status report
should be transmitted to NIOSH, OSHA, and CPSC.
b) The submitter should be requested to provide the ana-
lytical composition of the test vapors. This is essential
for determining if the toxicity is due to tertiary-octyl
mercaptan alone or some mixture of toxics characteristic of
the product treated.
485
-------
c) The submitter should be requested to provide a descrip-
tion of the types of products believed to contain tertiary-
octyl mercaptan residues and the uses of those products.
Information on the concentration of unreacted tertiary-octyl
mercaptan in the final products and the rate and potential
conditions of release should be provided to the extent
known. The submitter should be asked to describe any addi-
tional studies in progress or planned concerning the hazards
of tertiary-octyl mercaptan or products containing residues
of the substance.
d) Section 8(b) information should be checked to determine
the manufacturers and the annual production of tertiary-
octyl .mercaptan. The manufacturers should be provided a
copy of this submission and status report and requested to
provide any information in their possession relevant to
further evaluating this potential hazard.
e) A revised status report should be prepared based on the
information obtained from the above requests and the final
report from the submitter.
486
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
Status Report* 8EHQ-0579-0261 Approved
. Supplement
/>!**- Revision
PROM. Frank D.TCover, Acting Chief Needed
Chemical Hazard Identification Branch
TO: Joseph J. Merenda, Director
Assessment Division
Submission Description
The submission contains the final report of the acute
inhalation toxicities observed in rats exposed to tertiary-
octyl mercaptan (CAS No. 141-59-3) vapors evolving from
products containing that chemical, or vapors from a com-
mercial tertiary-octyl mercaptan. The submitter states that
this information describes the significant differences in
the toxicities observed for female and male rats.
The final report is supplemental to a previous submission
(8EHQ-1178-0261) in which the submitter reported, based on
preliminary information, that tertiary-octyl mercaptan was
significantly more toxic to female rats than to male rats as
measured by this short-term inhalation exposure study.
Submission Evaluation
It is reasonable to conclude that tertiary-octyl mercaptan
(t-octyl SH) and its isomer, rather than di- and tri-sulfide,
are responsible for the observed toxicities. The LCso
appears to be directly related to the amount of tertiary-
octyl mercaptan in the sample. However, this does not
account for the observation that the 100% t-octyl SH sample
was less toxic than the product containing 1.2% t-octyl SH
and not much more toxic than the product containing .37% t-
octyl SH. Female rats are approximately twice as sensitive
as the males to the toxicity of the finished products and
approximately three times as sensitive to the toxicity of
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
4C7
FORM iiao-t mev. »-7*i
-------
2 8EHQ-0579-0261 Supplement
the 100% t-octyl SH sample. Something in addition to the
mercaptans may be contributing to the toxicity. The two to
three fold greater toxicity in the female rats may have been
due to differences in biotransformation in addition to a
difference in body weight.
The type of exitus and the sharp dose/response activity
suggest a respiratory or cardiac death. The lungs had only
moderate acute injury. The color of the blood, which would
indicate changes in the hemoglobin, was not recorded. H2S
and mercaptans can affect respiration via the carotid sinus
and the medullary center resulting in respiratory paralysis.
At the cellular level, mercaptans may depress respiration
directly. Mercaptans can also stimulate the convulsive
centers in the spinal cord.
2, 4,4-trimethyl-2-pentane thiol
- C - CfJk - C - && Tertiary-Octyl Mercaptan
(CAS No. 141-59-3)
Current Production and Use
Tertiary-octyl mercaptan is used to control the extent of
polymerization during the production of synthetic rubber and
rubber-like polymers. The submitter reports that this
chemical is a component of a product used in lubricants (as
a corrosion inhibitor) and in gasoline and jet fuels to
counteract corrosiveness caused by the natural sulfur con-
tent of those fuels.
Comments/Recommendations
This submission and status report should be transmitted to
DOE, DOT, NIOSH, OSHA, CPSC, OWWM, and OAQPS.
488
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
SUBJECT:
FROM:
TO:
Status Report* 8EHQ-1278-0262
Frank D. Kover
Assessment Division, OTE/OTS
Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Approved
Revisio
Needed
Submission Description
The submission consists of preliminary results of a life-
time skin painting study of 2-ethylhexyl acrylate (CAS No.
103-11-7) in mice. The letter reports that after 21 months
of treatment, 31/40 mice have died, of which 3 were observed
to have a squamous cell papilloma in the treated area. The
submitter concludes that these results are an indication of
weak, tumorigenic activity in mice.
Submission Evaluation
The shortcoming of this study is the failure to conduct
histological examinations of the skin in all treated animals.
The sites of application may show significant cellular
changes. (This is the same deficiency that was encountered
in the study reported in submission 8EHQ-1077-0012 concern-
ing the results of life-time skin painting with N-nitroso-
morpholine-contaminated hydraulic fluids.) The submitter's
argument that 2-ethylhexyl acrylate has been in use for over
20 years and has not resulted in known chronic toxic effects
is not valid. The same argument was used for vinyl chloride
and acrylonitrile.
Current Production and Use
Annual production of 2-ethylhexyl acrylate was reported to
be greater than 44 million pounds in 1976. The chemical is
used as a monomer for plastics, protective coatings, and in
paper treatment. It is also used in water-based paints.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 1320-6 (REV. J-76)
489
-------
Comments/Recommendations
a) Consideration should be given to the preparation of a
Chemical Hazard Information Profile on 2-ethylhexyl acrylate.
b) Prior to EPA's receipt of the final report, the submit-
ter should be asked to describe in more detail the extent of
the histopathological examinations conducted on animal
tissues, especially skin sections.
490
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
OAT8: JAN 1 9 1979
Status Report* 8EHQ-1278-0263 Approved
Revision
mo*:Frank D. Kover Needed
Assessment Division, OTE/OTS
TO:Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
The acute, dermal toxicity of acetylenedicarboxylic acid,
monopotassium salt in guinea pigs is reported. The LD5Q is
between 25 and 50 mg/kg.
Submission Evaluation
The contact period for the dermal study is not described.
The dermal LD5Q in guinea pigs is similar to that previously
found for intraperitoneal administration in mice (also
reported in the submission). It is surprising that a dicar-
boxylic acid so readily penetrates the skin.
Current Production and Use
Acetylene dicarboxylic acid, monopotassium salt is manufac-
tured by two U.S. companies and is apparently sold by a
subsidiary of the submitter in only very small amounts (less
than 3 kg/year) presumably for laboratory use.
Comments/Recommendations
The March 16, 1978, "Statement of Inlysrpretatibn and Enforce-
ment Policy" (43 FR 11110) states in Part V that a "substan-
tial risk of injury to health or the environment" is a "risk
of considerable concern because of (a) the seriousness of
the effect...and (b) the fact or probability of its occur-
rence." In the present case, while the chemical exhibits a
high degree of acute lethality in a dermal study, it is
apparently produced in very limited quantities for use in
research.
•NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
roftM ujo-t mr.v. »•»•»
-------
Thus, the 2 factors to be considered when deciding if sub-
mission is required have not been met. Therefore, submission
of these data would not be required under Section 8(e).
The only other factor to be considered when evaluating
the results of routine (LD50) testing is discussed in
Comment 14 (Appendix B of the policy statement) as follows:
"many routine tests are based on knowledge of the toxicity
associated with a chemical; unknown effects occurring
during such a range test may have to be reported if they
are those of concern to the Agency and if the informa-
tion meets the criteria set forth in Parts V and VI."
Accordingly, observations of "unknown effects" may in
some cases assist the potential submitter in deciding
if notification is indicated.
a) This submission and status report should be transmitted
to NIOSH for possible inclusion in the RTECS.
492
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: &.&> ' . 1J~3
SUBJECT: Status Report* 8EHQ-1/: /8-U2b4
FROM: Frank fe^." Kover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Approved
Revision,
Needed
Submission Description
The submission reports the results of studies conducted by
the U.S.D.A. indicating that the use of dimethylamine sulfate
(DMAS) as a dehairing agent in tanneries contributed to the
formation of N-nitrosodimethylamine (NDMA; a known carcinogen)
in the tannery atmosphere.
Submission Evaluation
The U.S.D.A. report concluded that DMAS liberated dimeth-
ylamine which reacted with an unknown nitrosating agent to
form NDMA. The submitter cites a NIOSH-sponsored study
which showed that the concentrations of NDMA found in
tannery air could not be explained by .in. situ NDMA con-
tamination of DMAS; the NIOSH study couTd not, however,
identify the source of the detected nitrosamines. The
U.S.D.A. report may partially resolve this question, al-
though the details of the NDMA-formation reaction are not
yet understood. It is not clear to what extent this un-
characterized reaction might contribute to nitrosfcmine
formation in other occupational or environmental situations
Current Production and Use
DMAS is used as an accelerator for the dehairing of skins
and hides with lime, especially in the production of fine-
grained leathers. Its mild action on hair is valuable when
the tanner wants to save the hair.
*NOTE: This status report is the result o" a preliminary
staff evaluation of information submitted ; _> EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 132O-6 (REV. 3-76)
493
-------
-2-
Comments/Recommendations
a) This submission and status report should be transmitted
to NIOSH, OSHA, CPSC, NCI, and OAQPS.
b) The submitter should be asked to describe any uses of
DMAS not involving the dehairing of animal skins.
494
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: _ , . _,
J \ A. V> ' J .' J
SUBJECT: Status Report* 8EHQ-0179-0267 Approved
*
Revision
P«OM: FranKU^^ Kover Needed
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
The submission consists of the results of two dominant
lethal assays on 1,1,1-trifluoro-2-chloroethane conducted in
mice by inhalation. The first study found that the number
of successful fertilizations was reduced at exposure levels
of 10,000 and 20,000 ppm; however, the fertilizations were
unaffected at the 1,000 ppm level when compared with an
unexposed control group. The second study confirmed the
reduced fertility observed in the initial study and demon-
strated that 1,1,1-trifluoro-2-chloroethane caused a true
sperm effect in the male mice. Reduced fertility occurred
in both exposure groups (10,000 and 2500 ppm) and was also
accompanied by high cumulative mortality (34% and 27% at the
high and low dosages, respectively), reduced testicular
weight, a slight increase in the number of animals with
reduced sperm counts, and a slight increase in the percentage
of abnormal sperm. Histological examination of the testes
revealed direct toxic effects on the germinal epithelium.
The submission also includes a summary of data from a com-
munication received by the Agency dated August 31, 1977 as
information relating to EPA's investigation of chlorofluoro-
carbons. The summary states that 1,1,1-trifluoro-2-chloro-
ethane is not mutagenic to bacteria in the Ames Test, but
has been shown to be feototoxic in rats at levels of 5000
ppm but not at 500 ppm.
Submission Evaluation
Evidence is accumulating that polyhalogenated simple alkanes
can adversely affect the development of sperm.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
495
POM* U»-« IftCV. •-?•)
-------
8EHQ-0179-0267
Reducing the exposure level of the test compound by 75%
(from 10,000 to 2500 ppm) resulted in an 8% reduction in
mortality. This suggests that the dose-response curve could
be flat and that toxic effects would occur below 2500 ppm,
possibly even at 100 ppm.
The submitter reports that "normal exposure levels of 1,1,1-
trifluoro-2-chloroethane measured in our facility are less
than 2 ppm personnel exposure." Extrapolation from the data
reported in this submission suggests that exposure of workers
to 2-4 ppm is not likely to cause testicular effects.
The submitter should be requested to provide full copies of
the final reports on the dominant lethal assays.
Current Production and Use
The submitter reports that the present commercial usage of
l,l,l-trifluoro-2-chloroethane is as a chemical intermedi-
ate. No other information on production or uses was located.
Comment/Recommendations
a) This submission and status report should be trans-
mitted to CAD, OSHA, and NIOSH.
496
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
OATE: March 19, 1979
SUBJECT: Status Report* 8EHQ-0179-0269S Approved
Revision
MOM.- Frank D. Kover Needed
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
A copolymer of styrene and alpha-methylstyrene, was found to
exhibit estrogenic action in immature intact rats and dogs
when fed continuously in the diets of both species for a
period of 90 days. The ratio of styrene to alpha-methyl-
styrene is being held as confidential by the submitter.
Submission Evaluation
The important fact in this submission is that this copolymer
has estrogenic action. The "mildness" of the observed estro-
genic action could mislead one into the assumption that the
product is not likely to cause adverse effects on health.
While this assumption may be valid for those effects which
occur after short exposure to large amounts of the material,
the assumption cannot apply without further study to the
possible effects of prolonged exposure to low levels of
weakly potent estrogenic compounds. For example, the birth
control pill, even with its minimal dose of estrogen,
increases the chances for metabolic diseases, hypertension,
and diseases of blood clotting. Estrogens can also inter-
fere with function of the pituitary gland. Potent estrogens
taken for short periods (5 years) are thought to contribute
to the development of breast and uterine cancers. It remains
to be established that exposure over longer periods to com-
pounds having weaker estrogenic activity cannot cause these
effects. No one has established a no-effect exposure level
for estrogens.
The LaWall and Harrison report of October 22, 1946 does not
identify the styrene polymer that was studied. The percen-
tage of low molecular weight stilbene-type polymers in the
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
Cf»A FORM !!»-» (MEV. >-7C) 497
-------
test material is critical. The 1964 Kettering report sup-
ports this. What range of variation in styrene polymer
molecular weight did the submitter study? The failure of
the NCI study to observe gonadotrophic action by styrene is
not relevant since estrogenic and pituitary actions are
related to the stilbene structure.
CH,
Styrene monomer
alpha-methylstyrene
monomer
Stilbene structure
Current Production and Use
Information on production volumes and uses of this copolymer
was not located.
Comments/Recommendations
A previous submission reported observations of estrogenic
activity in structurally similar materials (polystyrene
waste streams, 8EHQ-1078-0245). Another submission (8EHQ-
0678-0202) reported that polyethylated benzene tails were
carcinogenic in a mouse skin painting study. A contractor-
prepared hazard assessment on styrene and ethyl benzene is
available from the Assessment Division.
aj The submitter should be asked to describe the uses
of this copolymer and to describe the disposition of any
waste streams resulting from its production.
b) This submission and status report should be trans-
mitted to OAQPS, ORD, OWWM, OSHA, NIOSH, CPSC, and FDA.
c) The finding that various styrene compounds have
estrogenic activity should be investigated in more detail by
CHIB to determine the need for a CHIP assessment.
493
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: y^/ £t "'•''•;
Status Report* 8EHQ-0179-0270 Approved
Revisio
MOM.- Frank D. Kover Needed
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
The submission presents the results of a battery of Ames
tests conducted on glycidyl acrylate (GA) and glycidyl
methacrylate (GMA).
Submission Evaluation
The Ames Salmonella gene mutation test with microsomal
activation (Ames test) measures the capacity of a chemical
and/or its metabolite to induce gene mutations in the
bacterium Salmonella typhimurium. This system can detect
both base pair changes and small deletions and additions
in the DNA of the bacterium. There is a good qualitative
correlation between positive Ames test results and posi-
tive animal oncogenicity test results when the same chemical
is studied. Quantitative extrapolations from the Ames test,
however, are presently not valid.
The study indicates that both GA and GMA are direct acting
mutagens and that they can also be metabolized to an active
mutagen in bacteria. A positive Ames test indicates that
the chemical and/or its metabolite is mutagenically active
in a bacterium. This raises concern that the chemical
might be a mutagen or an oncogen in mammals.
Current Production and Use
Acrylic acid esters are used in the manufacture of acrylic
resins which are thermoplastic polymers or copolymers of
various materials. Annual production figures are not
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
FOMM i»a»* inev. »•?•) 499
-------
available for GA and GMA. The SRI International Directory of
Chemical Producers lists several producers of these compounds;
the submtter, however, is not included in the SRI International
listing.
In his submission, the submitter reports that the materials are
used by manufacturers and processors in a variety of applica-
tions, primarily as a polymerizing agent. The submitting company
reports that, partly because of the positive Ames test results,
it has decided to discontinue the manufacture of both of these
materials, effective immediately.
Comments/Recommendations
The recent submissions have reported preliminary results from
lifetime studies of two acrylate esters: ethyl acrylate (8EHQ-
1078-0250) and 2-ethylhexyl acrylate (8EHQ-1278-0262).
GA and GMA are both members of the category "Glycidal and Its
Derivatives" recommended for section 4 test rules by the ITC.
This recommendation is under consideration by the TRDB.
(a) CHIB should request TRDB to consider the information con-
tained in this submission in the light of currently avail-
able GA and GMA effects and exposure data. TRDB should then
recommend whether section 4(f) priority assessment is
warranted.
(b) This submission and status report should be transmitted to
NIOSH, OSHA, CPSC, and NCI.
500
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
3/11/71
SUBJECT: Status Report* 8EHQ-0179-0271
FROM:
Assessment Division, OTE/OTS
Approved
Revisioj^
Needed fr
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
This submission presents the results of acute toxicity
testing of N,N-diethyl-4-(1H-1,2,4-triazol-3-ylazo)benzene-
amine in rats. The chemical was found to have an acute oral
LD50 of 13.2 mg/kg.
Submission Evaluation
I
This is a highly toxic chemical compound whose structure is
somewhat related to that of the carcinogen butter yellow.
The dose-response curve indicates little margin of safety
between toxic and lethal doses.
The serious weakness of the submission is the failure to
report the analytical purity of the material that was
tested. The submitter's response to the test results ("TRC
would like to note that this test result was obtained on
only one batch...") suggests that the purity of the material
varies from batch to batch. N,N-diethyl-para-phenylenedi-
amine and aminotriazole are potential biotransformation
products of this substance (see below). Both of these
compounds are about one tenth as acutely toxic as the parent
material. The greater toxicity is therefore due either to a
potent impurity or to the unmetabolized parent compound.
The orange colored urine following oral administration of
the orange colored parent compound suggests that the dye is
absorbed and excreted in part by the kidneys as unmetabo-
lized dye. The absorption and excretion are dose-related in
that the color appeared sooner and was more intense in the
urine of rats administered larger doses.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 1320-6 (REV. 3-76)
501
-------
The reports do not include a description of the signs that
appeared in the rats shortly before death. Most of the
descriptions of organ changes noted at necropsy are not in
terms customarily used by pathologists. The delayed appear-
ance of signs of autonomic nervous system stimulation and
coma suggests that these are not due to a primary action of
the compound but are secondary to the major effect or
effects of the material. The latent period to death indi-
cates progressive failure of either heart, blood vessels,
kidney, or liver. All of the major organs show stasis of
blood and congestion. The bloody nasal discharge (chro-
morhinorrhea) suggests early involvement of the lungs. The
yellow areas of intestine could be due to bile, unabsorbed
compound, or to that fraction excreted through the bile.
The failure of 400 times the LD5Q dose to significantly
shorten the time to death is also indicative of slow pro-
gressive failure of a vital function. It is not likely due
to histamine release because the rat is remarkably resistant
to histamine.
The submission has no data for evaluation of skin and eye
irritation studies.
N,N-diethyl-4-(lH-l,2,4-triazol-3- aminotriazole N,N-diethyl-para-
ylazo) benzeneamine phenylenediamine
Current Production and Use
No information was located in the secondary sources consulted
on the production and uses of this material. The submitter
notes that the material is used as a chemical intermediate
in the form of a wet cake. The submitter's use of the word
"internally" in his discussion of the uses of this material
can, in the context employed, give rise to misunderstanding.
Comments/Recommendations
a) The submitter should be asked to describe the uses
of this material. A description of planned further testing
would also be desirable. Copies of the skin and eye irrita-
tion studies should be requested.
b) This submission and status report should be trans-
mitted to OSHA and NIOSH.
502
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE: JUN * 6 l'J/9
sutJECT: Status Report* 8EHQ-0179-0272 Approved
, ..„ Revision
PRO* Frank glover, Acting Chief Needed
Chemical Hazard Identification Branch
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
The submission reports that isopropyl alcohol reacts slowly at
room temperature with 2O° Baume' hydrochloric acid
(concentrated HC1) to form 2-chloropropane.
room temperature
CH3-CH-CH3 + (excess) HC1 I -JS» CH3-CH-CH3 + H2O
OH slowly^ Cl
Submission Evaluation
2-Chloropropane has marked reactions on the central nervous
system (which it depresses) and on the heart (where it can
induce serious and fatal irregularities)-. It is not possible
to assess the risks of these hazards without knowing the
conditions of exposure.
Current Production and Use
Isopropyl alcohol is widely used as a chemical intermediate
and solvent in industry and is also found in many consumer
products. The submitter enclosed a reference (Keeney and
Frost, J. Petrol. Technol., 27, 552-4, 1975) which reported
that isopropyl alcohol, when used during acidic stimulation
treatment of oil and gas wells, can react with excess acid to
form 2-chloropropane. Acidic stimulation treatment is used to
enhance the recovery of gas and, to a lesser extent, oil from
*NOTE: This status report is the result of a preliminary
•taff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
503
•PA POMI ttao-4 mew. *-T«I
-------
8EHQ-0179-0272
sandstone and limestone formations. Isopropyl alcohol (or
other alcohols) is used as a component of the acid solution to
reduce the solution's surface tension and vapor pressure, mak-
ing it more easily recovered from the well after the acid
treatment.
Related Past and Present Activities
A CHIP is available on isopropyl alcohol.
Comments/Recommendations
(a) This submission and status report should be transmitted
to NIOSH, OSHA, CPSC, DOE, DOT, OWWM, and FDA.
(b) The IAO should consider transmitting this information to
all producers of isopropyl alcohol.
(c) The submitter should be asked to provide any available
data on the amount of 2-chloropropane formed during reac-
tions in a closed vessel.
504
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
SUBJECT: Status Report*8EHQ-0179-0273
FROM: Frank D.'-iCover
Assessment Division, OTE/OTS
TO: Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Approved
Revision
Needed
Submission Description
Report of an employee fatality which occurred in 1961 fol-
lowing dermal exposure to l-hexyn-3-ol. Following the
incident, the submitter conducted toxicity studies on the
compound and claimed to have found the material to be signif-
icantly more toxic when absorbed through the skin than when
swallowed.
The submitter apparently encountered this report during the
course of a recent literature review and, upon due consider-
ation, submitted the information under section 8(e).
Submission Evaluation
This belated submission reports a human fatality following
skin absorption. The report relates that death was appar-
ently due to kidney failure; this raises the possibility
that l-hexyn-3-ol is converted to a glycol in vivo with
subsequent damage to the kidney tubules.
The limited animal data provided do not establish that skin
absorption is more lethal than intestinal absorption. What
did autopsy of the rats and rabbits show on microscopic
examination?
Pharmacokinetic and biotransformation studies are in order.
Current Production and Use
l-Hexyn-3-ol is used as a corrosion inhibitor against min-
eral acids and as a high temperature oil well-acidizing
inhibitor. No production figures are available.
Recatinendations Transmit submission and status report to NIOSH and OSHA.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
505
EPA FORM 1320-6 (REV. 3-76)
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
SUBJECT: Status Beport* 8EHQ-0279-0274
FROM:
TO:
Frank D< Kover
Assessment Division, OTE/OTS
Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Approved
Revisi
Needed
Submission Description
Results of a chronic inhalation study of phenyl glycidyl
ether (PGE) in rats (100/sex/level) at exposure levels of 0,
1, and 12 ppm. After approximately 20 months of exposure
malignant nasal tumors were found in two rats exposed to 12
ppm. The submitter notes that this type of tumor is rare,
therefore, the finding is statistically significant when
compared to historical controls.
Submission Evaluation
Cancer is a hazard of exposure to epoxy compounds. It is
conceivable that substituents on the epoxy molecule are a
determinant in the reactivity of the epoxy group with macro-
molecules in tissues. On the basis of this (preliminary ?)
report, PGE presents a risk of cancer of at least 1% for
rats exposed chronically to 12 ppm (OSHA TWA equals 10 ppm).
The failure to obtain a 4-hour LC5Q in rats exposed to
saturated vapor levels has little relevance for chronic
exposure to PGE. Other duPont studies show serious subacute
and subchronic effects in rats exposed to concentrations of
5-29 ppm. Examination by our pathologist of the slides
prepared from rats exposed for 14 days to 29 ppm is in
order.
Current Production and Use
PGE is used as a reactive diluent in uncured epoxy resins to
reduce their viscosity. Annual production is reportedly
greater than 1,000 Ibs.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
EPA FORM 132O-6 (REV. 3-76)
506
-------
-2-
Comments/Recommendations
a) This submission and status report should be trans-
mitted to OWWM, OE, and OAQPS. The submitter has already
sent copies to NIOSH, OSHA, and NCI.
b) PGE should be considered for a priority assessment and as
a potential section 4(f) candidate.
c) A full copy of the final report on the lifetime
study should be requested.
d) Arrangements should be made with the submitter for
an EPA pathologist to view the slides from the 14-day
study.
507
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
$ OBJECT.
70:
, -;
Status Report* 8EHQ-0279-0275
Frank D. Kover, Acting Chief
Chemical Hazard Identification Branch
Joseph J. Merenda, Director
Assessment Division
Approved
Revisio
Needed
Submission Description
The submission reports that chronic administration of MHK Solvent
(5-methyl-2-octanone; 72% minimum) to rats by ga'vage over a
90-day period induced signs of hind-limb weakness in several of
the test animals. Histologic examination of peripheral and
central nervous system sections revealed giant axonal neuropathy
in the MHK Solvent-dosed rats.
Submission Evaluation
MHK Solvent contains several Cg-C^Q alkanes and ketones which
could be oxidized in vivo to .diketones gtructurely analogous to
the 2,5-hexanedione.metabolite (a known neurotoxin) of n-hexane.
This could account for the neurotoxicity observed in the rats
after the oral administration of MHK solvent. The oxidation to
analogous diketones might be similar to the metabolic pathway
proposed (see below) for the conversion of n-hexane to its ketone
and diketone derivatives, methyl n-butyl ketone (2-hexanone) and
2,5-hexanedione, respectively.
PROPOSED OXIDATIVE METABOLIC PATHWAY FOR n-HEXANE*(hydrogens omitted)
C-C-C-C-C-C
ft
C-C-C-C-C-C
C-C-C-C-C-C
n-Hexane (known- neurotoxin)
Methyl n-butyl ketone (known neurotoxin)
2 ,5-Hexanedione (known neurotoxin)
* adapted from the 1977 NIOSH Criteria Document C5-Cg Alkanes
DHEW (NIOSH) Publication No. 77-151
*NOTE: This status report is the result of a preliminary
r*aff evalua* :c-. 01 infer--:? icrs suh-.ittcd to F>A. f tnterr.cr.-.s
n;a-c- hers in are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
508
-------
Current Production and Use
No information on MHK Solvent was located in the secondary liter-
ature consulted. The submitter reported that 1978 sales were
approximately 1.5 million pounds, and 1979 sales are projected at
less than 900,000 pounds. The submitter noted that, based on
marketing considerations, a decision has been made that
manufacture and sale of MHK Solvent would be discontinued by the
end of 1979.
Comments/Recommendations
a) This submission and status report should be transmitted
to NIOSH, OSHA, CPSC, and OAQPS.
b) Inventory production data should be checked for this
chemical. If other producers are in evidence and if annual
production is significant, consideration should be given to the
preparation of a Chemical Hazard Information Profile on MHK
Solvent.
509
-------
3 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
SEP 2 11979
OFFICE OF TOXIC SUBSTANCES
MEMORANDUM
SUBJECT: Status Report 8EHQ-0379-0277
FROM: Walter W. Kovalick, Jr., Director
Program Integration Division (TS-793)
TO: Joseph J. Merenda, Director
Assessment Division (TS-792)
Submission Description; Sweeny Refinery, Sweeny, Texas
Release of Benzene
On February 21, 1979, a backhoe operator — hired under a
contract with Phillips Petroleum Company — punctured a
benzene pipeline on refinery property. It was estimated
that approximately 275 barrels of liquid benzene leaked from
the punctured line into a trench being dug. That same day,
approximately 195 barrels of benzene were recovered from the
trench; the benzene was covered by foam and removed by
vacuum truck. The incident was reported to the local sheriff
and the EPA Region VI office on February 22. EPA then ^
contacted the Coast Guard who did not follow up on the
incident because the leak was confined to refinery property.
Submission Evaluation
Chronic exposure to benzene can produce a variety of disease
conditions, including aplastic anemia and several different
types of cancers. Of concern in this particular incident
are possible acute or short-term effects of benzene exposure,
such as headaches, diarrhea and burning in the eyes, nose
and mouth. No such symptoms were, however, reported.
Exposure to benzene can also cause changes in the blood.
Therefore, all employees potentially exposed to benzene were
given urinary phenol and blood tests. Two persons were
found to have elevated urinary phenols; the results of
hematological studies were normal. Follow-up lab work was
initiated one month after the exposure to benzene, for the
510
-------
two people with elevated urinary phenols. The full blood
count, including platelets, was normal for both individuals.
One person, an employee of Phillips, was also given a urinary
phenol which was found to be normal. The other individual,
an employee of the contractor, was not, however, given a
urinary phenol. The results of this follow up lab work has
been summarized and sent to EPA from Phillips Petroleum,
following a request for data made to the company on August
29th. It is attached, and should be included in the record.
Comments/Recommendations
This incident appears to warrant reporting as an 8(e).
Approximately 11,000 gallons of benzene were spilled. Even
though approximately 8,000 gallons were cleaned up that same
day, the exposure to benzene required careful follow-up.
Because the spill was confined to refinery property, no
Federal agency (including the Coast Guard and EPA Region
VI), recorded or initiated follow-up on the incident.
Therefore, it was particularly important for EPA Headquarters
to follow-up and maintain a complete record of this incident.
Attachment
cc: A. Edelman (TS-793)
F. Kover (TS-792)
C. Auer/D. Williams (TS-792)
511
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
BATE:
SUBJECT:
FROM:
179
Status Report* 8EHQ-0479-0278
and 8EHQ-0479-0279
$^
Frank DV^Kover, Acting Chief
Chemical Hazard Identification Branch
Approved
Revision
Needed
TO.- Joseph J. Merenda, 'Director
Assessment Division
Submission Description
The two submissions, 8EHQ-0479-0278 and 8EHQ-0479-0279, are
identical with respect to reporting the results of acute
toxicity, mutagenicity, and carcinogenicity screening studies
using Vat Black 2BN and Vat Black DD Double Pastes/Cakes of
which C.I. (Color Index) Vat Green 9 (16-nitroviolanthrone;
CAS No. 128-60-9) represents the major portion.
Submission Evaluation
The Ames' Salmonella gene mutation test with activation
(Ames1 test), measures the capacity of a chemical, and/or
its metabolites, to induce gene mutations in the bacterium
Salmonella typhimurium. This system can detect both base
pair changes and small deletions/additions in the DNA o£ the
bacterium. There is a good qualitative correlation between
positive Ames1 test results and positive oncogenicity test
results when the same chemical is tested. Quantitative
extrapolations from the Ames1 test are presently not valid.
Tested separately, the Vat Black 2BN and DD Double Pastes
were very active in the Ames1 test both with and without
activation. Tested in combination, the DD and 2BN cake
sample was found to be mutagenically active in the Mouse
Lymphoma Forward Mutation Assay.
The results of the Cell Transformation Test were reported to
be negative with regard to a composite sample of the DD and
2BN cakes. However, the submissions did not include com-
plete copies of the protocol and experimental data. There-
fore, a full evaluation of the transformation test is not
possible at this time.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
RPA fONM !>»•« (REV. >-7(l
512
-------
2 8EHQ-0479-0278; 8EHQ-0479-0279
Current Production and Use
No current production and use information was located in the
secondary sources consulted.
Comment s/Recommendat ions
A positive Ames1 test indicates that a chemical, and/or its
metabolite, is mutagenically active in a bacterium. This
raises a concern that the chemical might be a mutagen or
oncogen in mammals. Additionally, the negative results from
an in vitro transformation assay are not conclusive that the
products (Vat Black 2BN and Vat Black DD Double Pastes/Cakes)
are not carcinogenic. The negative results do mean that
there is no evidence from this transformation test to indi-
cate that the chemical may have oncogenic potential.
a) The submitter should be requested to send complete
copies of the protocol and data from the ICI Cell Trans-
formation Test for further evaluation by the Assessment
Division.
b) The submitter should also be requested to provide in-
formation relating to the full chemical analyses and uses of
these pastes/cakes.
c) Copies of these submissions and status report should be
transmitted to NIOSH, OSHA, CPSC, and FDA.
513
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
BATE! Ju'N 1 4 1)70
.Status Report* 8EHQ-0379-0280 Approved
, ,, , ^. „, . .- Revision
PRO* Frank D. (jfover, Acting Chief Needed
Chemical Hazard Identification Branch
TO:Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Submission Description
Report of the death of an employee exposed to trimellitic
anhydride (TMA) (CAS # 552-30-7) at a plant conducting pipe-
coating operations. The chemical is normally present as a curing
agent in the pipe-coating substance. The victim exhibited
symptoms which seemed to resemble those previously reported in
the scientific literature as being TMA related, although the
submitter reports that a previously unreported syndrome of TMA
overexposure was observed in the worker.
Submission Evaluation
Trimellitic anhydride can apparently attach itself to carrier
proteins in the lungs and thereby act as a haptene to produce
antibodies. Such antibodies would react, during subsequent expo-
sures to TMA and produce an antigen/antibody reaction complex.
The syndrome described in the submission suggests an unusual
inability to dispose of this complex, with severe resultant
damage to terminal bronchioles and possibly alveoli.
It is also conceivable that the victim's conditions of exposure
to TMA permitted free access of TMA to the terminal bronchioles
and alveoli, in contrast to the more limited pulmonary access
reported in conditions 1, 2, and 3.
Current Production and Use
The estimated production capacity for TMA is 50 million pounds
per year. TMA is primarily used in the preparation of resins,
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
KPA POMM IMO-C INCV. »-7«l 514
-------
8EHQ-0379-0280
2
adhesives, polymers, dyes, pigments, printing inks, surfactants,
Pharmaceuticals.
TMA is listed in the TSCA Inventory.
Comments/Recommendations
a) Final data on the patient's blood tests should be requested
by the Assessment Division.
b) A copy of the submission and status report to be sent to
OSHA, CPSC, NIOSH, and FDA.
515
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
REJECT.
TO:
UOl I 6 i:)'y
Status Report* 8EHQ-0479-0281
FranJcD. Kover, Chief
Chemical .Hazard Identification Branch
Joseph J. Merenda, Director
Assessment Division, OTE/OTS
Approved
Revision^
Needed
Submission Description
Report of the final (24-month sacrifice) histopathological
results from a 2-year inhalation study of vinyl bromide (CAS No.
593-60-2) in rats. This study, sponsored by four companies, was
designed to investigate the oncogenic potential of vinyl
bromide. These final results show an increased incidence of
angiosarcomas at all levels of vinyl bromide tested (1235, 247,
52, and 10 parts per million).
The Agency has previously prepared status reports for two earlier
submissions (8EHQ-1177-0019 and 8EHQ-0878-0234) which reported
the pathology results from the 12-month and 18-month interim
sacrifices from this chronic inhalation study of vinyl bromide.
Submission Evaluation
Vinyl bromide appears to be more potent than vinyl chloride in
the induction of angiosarcomas. Of special significance is the
observation of angiosarcomas in rats exposed to 9.7 ppm of vinyl
bromide in air. Since angiosarcomas are not primarily tumors of
hepatocytes but of blood vessel connective tissue cells, they can
develop in many organs besides the liver. It is significant in
the present studies that angiosarcomas were found in lung,
spleen, nose, and mesentery. The incidence of true hepatocyte
tumors and proliferation of ceruminous gland tumors is also of
interest.
It is not clear whether there was an overall increase of brain
tumors and why significance was attached only to glioblastoma.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
rr.ade herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
1:20-4
. >-7t)
516
-------
8EHQ-0479-0281
Current Production and Use
A review of the production range (includes importation volumes)
statistics for vinyl bromide (CAS No. 593-60-2) as listed in the
initial TSCA Inventory (1977) has shown that no 1977 production/-
importation was reported or that all of the production range data
reported was claimed as confidential by the manufacturer(s) and
importer(s) and cannot be disclosed. (Section 14(a) of the TSCA,
U.S.C. 2613 (a)). The data submitted for the TSCA Inventory
including production range information, are subject to the
limitations contained in the Inventory Reporting Regulations (40
CFR 710). Vinyl bromide is used as an intermediate in organic
synthesis and for the preparation of plastics by polymerization
and copolymerization. The major use of vinyl bromide is in the
production of flame-retardant synthetic fibers. These fibers
(used primarily in children's sleepwear and carpets) are produced
in a batch polymerization operation with a suspension polymeri-
zation medium and a wet spinning process. This method of produc-
tion would probably preclude residual vinyl bromide monomer in
the final product.
Related Past and Present Activities
OTS has had a laboratory investigation underway to detect by
chemical analysis, the presence of residual vinyl bromide monomer
in carpet, fabric, and fiber samples submitted to EPA by two of
the sponsors of the 24 month inhalation study. The results, to
date, are negative with respect to the detection of residual
vinyl bromide monomer in these samples.
A Chemical Hazard Information Profile (CHIP) document on vinyl
bromide has been prepared by the Assessment Division.
Comments/Recommendations
The submitter indicates that levels of vinyl bromide in the
workplace are held at or below 1 ppm. The submitter also states
that attempts are being made to lower the exposure in the work-
place, and that respirators are required when vinyl bromide
levels exceed 1 ppm.
a) Vinyl bromide should be considered a candidate for further
assessment by the Chemical Review and Evaluation Branch.
b) A copy of the OTS-sponsored chemical analysis protocol and
results should be sent to the submitters when that informa-
tion is received by the Assessment Division.
c) A copy of this submission and status report should be
transmitted to NIOSH, OSHA, CPSC, FDA, OWWM, OANR, and CREB.
517
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
**T*: .;>.,j
Status Report* 8EHQ-0479-0282S
• Approved
Fit OH*
Chemical Hazard Identification Branch Needed
rank D. Kover, Chief Revision
hemical Hazard Identificat
Joseph J. Merenda, Director
TO-
Assessment Division, OTE/OTS
Submission Description
Final results of acute dermal toxicity, acute oral toxicity,
primary skin irritation, and DOT corrosivity studies of N-(2-
chloroethyl)-N-ethyl-m-toluidine (CAS No. 22564-43-8). The
results indicate that this chemical has an acute dermal LD^ of
less than 200 mg/kg (lowest dose tested) for male albino rab-
bits. The acute oral LD^Q is reported to be 655 mg/kg in rats.
Submission Evaluation
N-(2-chloroethyl)-N-ethyl-m-toluidine may be considered a half
nitrogen mustard and, therefore, very toxic because of its
alkylating properties. In addition, it is probably a hemato-
poietic poison (methemoglobin formation), a liver poison, and a
potential carcinogen. Since many aromatic amines are readily
absorbed through the skin, it is not surprising that this
compound is at least 3 times more toxic when applied to the skin
o"f rabbits than when orally administered to rats. This has been
well established in human infants who have been dressed with
aniline treated diapers.
N-(2-chloroethyl)-N-ethyl-m-toluidine also has metabolic effects
that would be reflected in changes of body temperature.
Current Production and Use
A review of the production range (includes importation volume).
statistics for N-(2-chloroethyl)-N-ethyl-m-toluidine (CAS. No.
22564-43-8) which is listed in the initial TSCA inventory (1977)
has shown that no.1977 production/importation was reported or
that all of the production range data reported were claimed as
confidential by the manufacturer(s) and importer(s) and cannot be
*NOTE: This status report is the result of a preliminary
staff evaluation of infcrir.aticn submitted to E7-A. Staterr.cr.-
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information. '
518
-------
disclosed. (Section 14(a) of the TSCA, U.S.C. 2613 (a)). The
data submitted for the TSCA Inventory including production range
information, are subject to the limitations contained in the
Inventory Reporting Regulations (40 CFR 710).
The submitter reports that N-(2-chloroethyl)-N-ethyl-m-toluidine
is currently being manufactured at one of his firm's facilities.
Use information was not located in the secondary literature
sources consulted.
Comments/Recommendations
A similar chemical, N-(2-chloroethyl)-N-ethylaniline, was the
subject of a previous submission (8EHQ-0578-0169S). The toxico-
logical findings were similar in nature.
The Agency's interest in receipt of acute toxicity studies under
section 8(e) of TSCA is, in general, fairly limited. However,
under certain circumstances the results of acute studies can
provide reasonable support for a conclusion of substantial
risk. The guidance offered on this point in the "Statement of
Interpretation and Enforcement Policy; Notification of Substan-
tial Risk" (43 FR 11110) can be summarized as follows:
- Part V of the policy statement states that a "substan-
tial risk of injury to health or the environment is a
risk of considerable concern because of (a) the serious-
ness of the effect... and (b) the fact or probability of
its occurrence."
- The response to comment 14 indicates that "unknown
effects occurring during such a range test [e.g., an
acute study] may have to be reported if they are those
of concern to the Agency and if the information meets
the criteria set forth in Parts V and VI" (emphasis
added).
Thus, when evaluating the results of acute animal studies for
submission under section 8(e), submitters are expected to consider
such factors as the lethal dose, the route of administration, the
occurrence of unexpected effects in the animals (obtained via
"cage side" observations, during necropsy, and so on), and the
extent and pattern of the chemical's exposure (insofar as known
to the submitter). In general, when evaluating such information
under section 8(e), the greater the acute toxicity of a compound,
the less heavily one weighs the exposure criterion, and vice
versa.
In the case of the present submission, the acute dermal LDj-Q in
male rabbits is less than 200 mg/kg while the acute oral LD5Q in
rats is 655 mg/kg. Furthermore, all rabbits died during the
course of primary skin irritation and D.O.T. skin corrosivity
tests; unfortunately, no doses (mg/kg) are reported for the two
519
-------
tests. The laboratory report fails to provide any "cage-side"
observations or autopsy results (despite the fact that the acute
oral and acute dermal protocols specify that the animals will be
grossly autopsied). The Agency does not have any use/exposure
data on the chemical, other than the fact that it is in
production. Given the above described information, a prudent
individual would decide to submit the studies to the EPA under
section 8(e). This decision is based on the 100% mortality
observed in the three rabbit dermal studies. The absence of
gross pathology findings does not affect this decision, although
the results of such analysis would be of interest to the Agency.
(The only factor that could possibly militate against submission
in this case is the use/exposure pattern of the chemical. If the
material is manufactured, processed, used, and stored in a
totally enclosed manner, and if disposal methods also prevented
exposure to the chemical, then one could consider not submitting
these studies. If, however, the use/exposure pattern of the
chemical is uncertain or not available, a prudent individual
would, nonetheless, decide to submit these studies under section
8(e).) Thus, in this case, because of the extreme dermal
lethality, described only as "less than 200 mg/kg", the submitter
was correct in providing these data to the Agency under TSCA
section 8(e).
(a) The submitter should be requested to provide, if available,
a description of the symptoms exhibited by the animals prior
to death as well as the autopsy reports from these acute
toxicity studies. The submitter should be asked if there
are any plans to determine with more precision the dermal
LD50'
(b) The submitter should be requested to provide any available
information on exposure to N-(2-chlorothyl)-N-ethyl-m-
toluidine, including information on the uses of the
chemical.
(c) Further EPA assessment or followup will be considered based
upon the nature of any additional information provided by
the submitter.
(d) A copy of this submission and status report should be
transmitted to OSHA and NIOSH.
520
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
ocr
SUtJECT: Status Report* 8EHQ-0579-0283 Approved
/
Revision
PROM- Frank D/y/^over, Chief Needed
Chemickl Hazard Identification Branch.
TO: Joseph J. Merenda, Director
Assessment Division
Submission Description
The submission (on behalf of a wholly owned subsidiary of
the submitter) presents a summary of the interim results
obtained from an ongoing mouse skin-painting study of a
product identified as Wellaid.PG-100. The submitter reports
that Wellaid PG-100 is a mixture of an epoxy reaction pro-
duct of polypropylene glycol, a purchased methanol, an
aromatic naptha, and a purchased product reported to be a
polymerized polyol resin in solution with isopropyl alcohol
and diluted with a high-boiling aromatic solvent.
According to this interim report, 13 of 50 mice had devel-
oped tumors at the sample application site by the 26th week
of this ongoing study. Of the 13 tumors, 11 were still
diagnosed as benign, but 2 (although previously diagnosed as
benign) had become malignant at weeks 26 and 27.
The submitter states an opinion that the carcinogenic activ-
ity of the mixture "is not directly due" to the components
manufactured by its subsidiary and reports that it will
promptly initiate investigations to insure that the components
manufactured by its subsidiary "are not the primary cause of
the carcinogenic effect reported."
Submission Evaluation
If the aromatic solvent components of Wellaid PG-100 contain
polynuclear hydrocarbons, they would be highly suspect as a
carcinogenic factor. However, until carcinogenicity test
data on the components of Wellaid PG-100 are available, a
conclusion that the observed oncogenic activity is not due
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
KPA torn* IMD-4 (NCV. *7*t
521
-------
8EHQ-0579-0283
(either directly or indirectly) to the components produced
by the subsidiary company seems inappropriate.
Current Production and Use
The submitter states that Wellaid PG-100 is intended to be
used for the separation of crude oil and water, but the
product is still in the development stage and its subsidiary
company has discontinued the manufacture, distribution, and
development work on Wellaid PG-100. According to the sub-
mission no Wellaid PG-100 has been shipped to customers in
the U.S., but 100 drums were shipped overseas for field
trial. No other current production and use information
concerning this product was located in the secondary sources
consulted.
Comments/Recommendations
a) The submitter should be requested to send full
copies of final results of this skin-painting study includ-
ing test protocols and data and to provide details of the
additional investigations being initiated on the components
of Wellaid PG-100 manufactured by its subsidiary.
b) The submission and status report should be trans-
mitted to DOE, DOT, OWWM, OSHA, and NIOSH.
522
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
OCT I 6 197;;
SUBJECT: Status Report* 8EHQ-0579-0284 Approved
MOM: Frank i^Tover, Chief w^5^
Chemical flazard Information Branch Needed
TO: Joseph J. Merenda, Director
Assessment Division
Submission Description
Preliminary results from a dermal toxicity test in rabbits with
ethoxylated C12-C15 alcohols containing a boron trifluoride
etherate catalyst (CAS No. 109-63-7). The submitter states that
the test results appear to clearly support a conclusion that the
catalyst or its derivative by reaction is responsible for the
high dermal toxicity observed. As a result of this high
toxicity, the submitter states that their use of boron tri-
fluoride etherate catalysts has been discontinued in the
manufacture of ethoxylated products.
Submission Evaluation
The conclusion that the toxicity observed by the dermal
application of the ethoxylated alcohol was due to a boron
trifluoride etherate catalyst contamination is probably
correct. The ethoxylated Ci9~c15 alcoh°ls would probably behave
pharmacologically like the carbitols and spermaceti and would
therefore be relatively non-toxic. Boron compounds, however, are
significantly toxic. Boron trifluoride is readily absorbed and
could produce damage to the lungs, heart, and central nervous
system.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
523
-------
Current Production and Uses
A review of the production range (includes importation volumes)
statistics for boron trifluoride etherate (CAS No. 109-63-7) as
listed in the initial TSCA Inventory (1977) has shown that
between 0 and 1,000 pounds of this chemical was reported
produced/imported in 1977. This production range information
does not include any production/importation data claimed as
confidential by the person(s) reporting for the TSCA inventory,
nor does it include any information which would compromise
Confidential Business Information. The data submitted for the
TSCA Inventory, including production range information, are
subject to the limitations contained in the Inventory Reporting
Regulations (40 CFR 710).
The predominant use of boron trifluoride etherate is as a
catalyst for polymerizations, alkylations and isomerizations. It
can also be used as a chemical intermediate.
Comments/Recommendations
Boron trifluoride is the subject of a NIOSH Criteria Document
(Dec. 1976).
(a) The submitter should be requested to provide full copies of
the results, including test protocols and data, from this
dermal toxicity study.
(b) Copies of this submission and status report should be
transmitted to NIOSH, OSHA, FDA, CPSC, and OWWM.
524
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
SUBJECT:
FROM:
TO:
Status Report* 8EHQ-0579-0285
FrankCF. Kover, Chief
Chemical Hazard Identification Branch
Joseph J. Merenda, Director
Assessment Division
Approved
Revisio
Needed
Submission Description
Preliminary summary report of results from several genotoxic
tests with tertiary-butyl glycidyl ether. The submission reports
that mutagenic activity was detected in several of the short-tern
assays. The submitter states that a copy of the full report,
upon completion, will be sent to the Agency.
Submission Evaluation
These summarized results do indicate a possible mutagenic
potential for t-BGE. However, without complete copies of the
test protocols and data, a full evaluation of the preliminary
results, as presented, is not possible at this time.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for tertiary-butyl glycidyl ether (CAS. No. 7665-72-7)
as listed in the initial TSCA Inventory (1977) has shown that
between 1,000 to 10,000 pounds of this chemical was reported
produced/imported in 1977. This production range information
does not include any production/importation data claimed as
confidential by the person(s) reporting for the TSCA inventory,
nor does it include any information which would compromise
Confidential Business Information. The data submitted for the
TSCA Inventory, including production range information, are
subject to the limitations contained in the Inventory Reporting
Regulations (40 CFR 710). The chief use of glycidyl ethers, in
general, is as reactive diluents in epoxy resin systems.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
FORM 1120-t (HEW. >-7«>
525
-------
Comments/Recommendations
Glycidyl ethers have been the subject of several other submis-
sions received and evaluated by the Agency under section 8(e) of
TSCA. Phenyl glycidyl ether (PGE) was found to induce nasal
tumors in rats at 12 ppn in a two-year inhalation toxicity study
(8EHQ-0279-0274); n-butyl glycidyl ether (n-BGE) was found to be
genetically active in several short-term mutagenicity assays and
to have possible effects on testicular functions in rats (8EHQ-
0279-0213); n-alkyl glycidyl ethers with alkyl groups in the C2-
Cjn range were found to be potential mutagens in a battery of
mutagenicity tests and, in additional studies, a mixture of Cg
and CIQ glycidyl ethers was found to cause testicular lesions in
certain animal species at high dose levels by atypical routes of
exposure (8EHQ-0779-0293).
The Test Rules Development Branch, in conjunction with the
Environmental and Health Review Divisions, is currently reviewing
data received by the Agency pertaining to the Interagency Testing
Committee designated category: "Glycidol and Its Derivatives."
a) A copy of this submission and status report should be
transmitted to TRDB, NIOSH, and OSHA.
526
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
OPT Q I
DATE: L'b! 31
SUBJECT: Status Report* 8EHQ-0579-0286 Approved
-7«) 527
-------
Comments/Recommendations
(a) The submitter should be requested to provide full copies of
the test protocols and data from the studies cited in this
submission.
(b) Copies of this submission and status report should be trans-
mitted to OSHA and NIOSH.
(c) The submitter should be requested to provide any available
exposure information, particularly as it relates to typical
uses of the chemical(s).
528
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
3 I 1979
SUBJECT: status Report* 8EHQ-0579-0287 Approved
^IAJ
''/w^ Revision
MOM: Frank 0,/Kover, Chief . Needed
Chemical Hazard Identification Branch '
T0: Joseph J. Merenda, Director
Assessment Division, OTE
Submission Description
The submission presents a summary of the effects of m-Xodotoluene
(CAS No. 625-95-6) in several mutagenicity and oncogenicity
assays. The submission states that the test results indicate
that this chemical is a potential mutagen and carcinogen.
Submission Evaluation
The summarized results, as presented in this submission, do indi-
cate that m-^odotoluene has both mutagenic and oncogenic poten-
tial. However, without complete copies of the test protocols and
data, a full evaluation of the submitted results is not possible
at this time.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for m-Jtodotoluene (CAS No. 625-95-6) as listed in the
initial TSCA Inventory (1977) has shown that no 1977 production/
importation was reported or that all of the production range data
reported were claimed as confidential by the manufacturer(s) and
importer(s) and cannot be disclosed. (Section 14(a) of the TSCA,
U.S.C. 2613 (a)). The data submitted for the TSCA Inventory
including production range information, are subject to the limi-
tations contained in the Inventory Reporting Regulations (40 CFR
710).
Current use information for this chemical was not located in the
secondary literature sources consulted. .
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
CPA FORM IS20-« (MEV. »-7C>
529
-------
Comments/Recommendations
(a) The submitter should be requested to provide full copies of
the test protocols and data from the studies cited in this
submission.
(b) Copies of this submission and status report should be trans-
mitted to OSHA and NIOSH.
(c) The submitter should be requested to provide any available
exposure information, particularly as it relates to typical
uses of the chemical(s).
530
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
OCT 30 !979
SUBJECT: Status Report* 8EHQ-0579-0288 Approved
/?ftjlt*> Revisio
MOM: Frank £/*Kover, Chief . Needed
Chemical Hazard Identification Branch
T0: Joseph J. Merenda, Director
Assessment Division
Submission Description
The submission presents a summary of results from a battery of in
vivo and in vitro mutagenicity tests on production grade phospho-
nitrilic "chloride (CAS No. 25034-79-1) which contains a number of
PNC12 polymeric species. The submitter states that the positive
effects obtained in a number of the in vitro tests are suggestive
that the tested material is a potential mutagen.
Submission Evaluation
The summarized in vitro results, as presented in this submission,
do indicate that .phosphonitrilic chloride has a mutagenic
potential. However, without complete copies of the test proto-
cols and data, a full evaluation of the results is not possible
at this time.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for phosphonitrilic chloride ((C12NP)X; CAS No. 25034-
79-1) as listed in the initial TSCA Inventory (1977) has shown
that no 1977 production/importation was reported or that all of
the production range data reported was claimed as confidential by
the manufacturer(s) and importer(s) and cannot be disclosed.
(Section 14(a) of the TSCA, U.S.C. 2613 (a)). The data submitted
for the TSCA Inventory including production range information,
are subject to the limitations contained in the Inventory Report-
ing Regulations (40 CFR 710).
The submitter states that this material is, at the present time,
a low volume specialty product.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
531
-------
Comments/Recommendations
a) The submitter should be requested to provide full
copies of the results, including test protocols and data, from
the studies cited in this submission.
b) A copy of this submission and status report should be
transmitted to OSHA and NIOSH.
532
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DATE:
SUBJECT:
MOM:
TO:
Status Report* 8EHQ-0579-Q289 and
8EHQ-Q579-0289 Supplement
rFrank D. Kover, Chief
Chemical Hazard Identification Branch.
Joseph J. Merenda, Director
Assessment Division, OTE
Approved
Revision
Needed
Submission Description
The initial submission presents a summary of the effects of
Epikote Resin 1002 (4,4'-isopropylidenediphenol-epichlorohydrin
resin; also known as a bisphenol A-epichlorohydriri resin) in
several in vitro mutagenicity and oncogenicity assays. The
initial submission states that the test results indicate that
Epikote 1002 Resin is a potential mutagen and potential direct-
acting carcinogent
Additional information on an essentially identical chemical
(Epon Resin 1002) was provided to EPA strictly on a "For Your
Information" basis by the manufacturer of Epon Resin 1002. This
information, which was handled as a supplement to the initial
submission, indicated the uses of Epon Resin 1002,. provided sales
figures (confidential), summarized the results of several
mutagenicity assays on a homologous series of such resins, and
included a product safety data sheet on Epon Resin 1002. It is
this, submitter's view .that, when all the data are considered, one
is "led to a conclusion that the data support a negative, rather
than positive result" with respect to the mutagenic response of
Epikote/Epon Resin 1002.
Submission Evaluation
The summarized in yitro results, as presented in the initial sub-
mission, do indicate that Epikote Resin 1002 has both mutagenic
and direct-acting carcinogenic potential. However, without com-
plete copies of the test protocols and data, a full evaluation of
the results is not possible at this time.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to tt-\. Ftat«-r.—~s
made herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
533
-------
The supplement summarizes the results from a variety of mutagen-
icity assays on several bisphenol A-epichlorohydrin based epoxy
resins ranging from liquids (MW 345) to high melting polymeric
solids (MW > 4000). In the results cited, the various Epon
resins were reportedly found positive in 5/17 studies and nega-
tive in 12/17. No further judgment can be offered, however, in
the absence of full copies of the referenced studies.
Following receipt of the requested studies, further evaluation of
this class of epoxy resins can proceed. It is of interest in
this discussion to note the results from several carcinogenicity
assays of bisphenol A-epichlorohydrin based resins (as summarized
by Andersen et_ al_.). Kotin and Falk (1963) found one skin tumor
and three malignant lymphomas in 50 mice exposed to one injection
of a bisphenol A-epichlorohydrin condensation product (MW 395).
Lifetime skin painting with undiluted resin yielded no tumors in
40 mice; however, none of the animals were alive after 24 months
(Weill^^., 1963). Hine ^t al^. (1958) reported four malignant
sarcomas at the site of injection in a study using 30 rats. In
all of these studies, the number of animals on test as well as
the duration of the observation period may be inadequate in terms
of present day protocols, although malignant tumors were demon-
strated in 2 of the studies.
Current Production and Use
A review of the production range (includes importation volumes)
statistics for bisphenol A-epichlorohydrin resins (CAS. No.
25068-38-6) which are listed in the initial TSCA Inventory (1977)
has shown that between 126 million and 669 million pounds of
these resins were produced/imported in 1977.
The supplement reported that Epikote/Epon Resin 1002 is
specifically used in molding powders (e.g., encapsulation of
electrical parts), resin-based adhesive tapes, pressure sensitive
dry inks (microencapsulation technique), and stabilizing
polypropylene by scavenging catalyst residues. Other bisphenol
A-epichlorohydrin based epoxy resins are used as protective
coatings, reinforced plastics, bondings and adhesives, flooring
and paving and other miscellaneous applications.
jVThis production range information does not include any
production/importation data claimed as confidential by the
person(s) reporting for the TSCA Inventory, nor does it include
any information which would compromise Confidential Business
Information. The data submitted for the TSCA Inventory,
including production range information, are subject to the
limitations contained in the Inventory Reporting Regulations (40
CFR 710).
534
-------
Comments/Recommendations
The presence of epichlorohydrin in these resins is presumably
responsible for the observed genetic activity, although Andersen
et_ al^. reported that the "mutagenic action of the resins is not
caused solely by the possible content of unreacted ECH {epichlo-
rohydrin)...." Quantitative support for this statement is,
however, lacking in the Andersen et al. paper.
Epichlorohydrin has been the subject of several other submissions;
8EHQ-1177-0016; 8EHQ-0878-0230; 8EHQ-0978-0230 (Supplement).
A Chemical Hazard Information Profile (CHIP) and a draft hazard
assessment are available on epichlorohydrin. Epichlorohydrin has
also been selected for TSCA section 4 testing considerations by
the ITC.
(a) The two submitters should be requested to provide full
copies of the test protocols and data from the studies cited
in their respective submissions.
(b) This submission and status report should be transmitted to
TRDB, CPSC, OSHA, and NIOSH.
(c) CHIB will review the additional data requested, revise this
Status Report as appropriate, and recommend further followup
assessment if warrented.
REFERENCES
Andersen, M., Kiel, P. Larsen, H., Maxild, J.; Nature, Volume
276, 391-392 (1978)
Hine, C.H., Guzman, R.J., Courey, M.M., Wellington, J.S.,
Anderson, H.H.; Cancer Research, Volume 18, 20-26 (1958)
Kotin, P., Falk, H.L.; Radiat. Res. Suppl., Volume _3_, 193-211
(1963)
Weil, C.S., Condra, N. Haun, C., Streigel, J.A.; Am. Ind. Hyg.
Assoc. J., Volume 24, 305-325 (1963)
535
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
NOV I IS,'*
O t « t- U S I\.G pO ITtZ \J LJ L±\S — U \J I -S~~\S£*~SJL[
8EHQ-0879-0291 Supplement AP?roved
Pto- Frank-i^TKover, Chief Revision"
Chemical Hazard Identification Branch Needed
TO: Joseph J. Merenda, Director
Assessment Division, OTE (TS-792)
Submission Description
Summarized final results from several laboratory studies on tri-
methyl phosphite (TMP; CAS No. 121-45-9). TMP was found positive
in several mutagenicity screening assays. In a 4-week inhalation
toxicity study in rats, TMP induced severe cataracts at the
highest dose tested (600 ppm). The supplemental submission
reported that TMP at the highest dose (164mg/kg) produced
teratogenic effects when administered by gavage to pregnant rats.
Submission Evaluation
Trimethyl phosphite is an alkylating agent and an anticholines-
terase. Its reaction with proteins results in a persistent
action which is finally disposed of by the regeneration of a new
protein. The cataracts observed in the rats might have been due
to an alteration in the lens proteins caused by direct alkylation
or by persistent cholinergic stimulation (anticholinesterase
activity). Cataracts can, in some cases, occur in patients
treated with anticholinesterases for glaucoma.
The teratologic effects of TMP may be due to its anticholin-
esterase activity. Imbalances in acetylcholine and cholin-
esterase appear to be involved in teratogenesis, particularly in
neural tube defects in apes and humans.
There have been several submissions in which the results of the
Ames1 test are negative while other mutagenicity test results are
positive. There is probably a significant clue here which might
merit investigation.
*NOTE: This status report is the result of a preliminary
staff evaluation of information submitted to EPA. Statements
r.ade herein are not to be regarded as expressing final
Agency policy or intent with respect to this particular
chemical. Any review of the status report should take into
consideration the fact that it may be based on incomplete
information.
536
-------
Current Production and Use
A review of the production range (includes importation volumes)
statistics for trimethyl phosphite (CAS No. 121-45-9) as listed
in the initial TSCA Inventory (1977) has shown that between 11
million to 60 million pounds of this chemical wSSF reported
^produced/imported in 1977. This production range information
does not include any production/importation data claimed as
confidential by the person(s) reporting for the TSCA inventory,
nor does it include any information which would compromise
Confidential Business Information. The data submitted for the
TSCA Inventory, including production range information, are
subject to the limitations contained in the Inventory Reporting
Regulations (40 CFR 710).
The submitter states that their only use of trimethyl phosphite
is as an intermediate. In general, TMP is used as an intermedi-
ate in the manufacture of insecticides. It is not known how
much, if any, TMP remains unreacted in final products.
Comments/Recommendations
In order to clarify the potential hazards and risk, the submitter
is planning additional toxicology testing of TMP. The submitter
states that although no evidence of cataracts has been found in
their worker population, opthalmologic examinations will be
conducted. The submitter also states that their employees and
customers are being notified of the findings reported in these
submissions and the plans to conduct further toxicological
testing.
(a) The submitter should be requested to provide full copies of
the final results, including test protocols and data from
the studies cited in their submissions. In addition, the
submitter should be requested to describe the end-uses of
TMP and to provide available information on the presence of
unreacted TMP in final products.
(b) It is recommended that TMP be considered a candidate for the
proposed Section 8(a) Level A rule.
(c) Copies of these submissions and status report should be
transmitted to NIOSH, OSHA, OPP, and OWWM.
537
-------
APPENDIX A
THURSDAY, MARCH 16, 1978
PART V
ENVIRONMENTAL
PROTECTION
AGENCY
TOXIC SUBSTANCES
CONTROL ACT
Statement of Interpretation and
Enforcement Policy; Notification
of Substantial Risk
538
-------
11110
NOTICES
[6560-01]
ENVIRONMENTAL PROTECTION
AGENCY
[FRL 849-2]
TOXIC SUBSTANCES CONTROL ACT
Notification of Substantial Ritk Und«r
Section 8(«)
AGENCY: Environmental Protection
Agency.
ACTION: Statement of interpretation
and enforcement policy.
SUMMARY: This action states EPA's
interpretation of, and enforcement
policy concerning, section 8(e) of the
Toxic Substances Control Act (TSCA)
(90 Stat. 2029, 15 U.S.C. 2607). The
provisions of that section went into
effect on January 1,1977.
Section 8(e) states that "any person
who manufactures, processes, or dis-
tributes in commerce a chemical sub-
stance or mixture and who obtains in-
formation which reasonably supports
the conclusion that such substance or
mixture presents a substantial risk of
injury to health or the environment
shall immediately inform the Adminis-
trator of such information unless such
person has actual knowledge that the
Administrator has been adequately in-
formed of such information."
DATES: The policy expressed in this
document is in effect as of the date of
publication.
FOR FURTHER INFORMATION
CONTACT:
Frank D. Kover, Assessment Divi-
sion, Office of Toxic Substances
(WH-557), Environmental Protec-
tion Agency, 401 M Street SW.,
Washington, D.C. 20460, 202-755-
2110.
SUPPLEMENTARY INFORMATION:
On September 9,1977, the Agency pro-
posed guidance (42 FR 45362) on its in-
terpretation of and policy concerning
the provisions of section 8(e). Al-
though the proposed "guidance" was
an Interpretive rule and statement of
policy exempt from the notice and
public comment provisions of the Ad-
ministrative Procedure Act (5 U.S.C.
553), the Agency solicited comments
on several issues to make more in-
formed decisions. On October 11, the
comment period was extended from
October 15 to October 31, 1977 (42 FR
54857). On November 4,1977, a supple-
mental notice to the proposed guid-
ance was published (42 FR 57744), de-
leting the November 15 date for re-
porting certain information obtained
before 1977 and stating that a new
date would be established in the final
guidance.
In developing this policy statement,
two meetings have been held (Febru-
ary 1,1977, and October 26,1977) with
selected representatives of industry
and environmental and other inter-
ested groups. Comments submitted
pursuant to the February 1 meeting
were addressed in the preamble to the
September 9 proposal. Over 100 writ-
ten comments have been submitted
pursuant to the September 9 proposal
from trade associations, businesses, en-
vironmental groups, labor unions,
State and Federal agencies, and other
interested parties. Appendix B de-
scribes significant issues raised in
these comments and the Agency's re-
sponse to them.
The major modifications to the Sep-
tember 9 proposal are summarized in
points 1 through 7 below.
(1) Pursuant to some question over
the definition and nature of "guid-
ance," this document is now described
more accurately as a "policy state-
ment." It is exempt from the notice
and public comment provisions of the
Administrative Procedure Act, as well
as provisions concerning delayed effec-
tive dates.
(2) Many commenters expressed the
view that to apply these requirements
to officers and employees of a business
organization would result in ill-consid-
ered, premature reports and would un-
fairly subject employees to conflicting
responsibilities as individual respon-
dents and as corporate agents. Other
commenters expressed support for the
view that certain employees have a re-
sponsibility to report pertinent infor-
mation, and felt that the phrase "ca-
pable of appreciating pertinent infor-
mation" appropriately described those
employees.
The September 9 proposal would
have applied section 8(e) requirements
to commercial establishments as well
as to employees capable of appreciat-
ing pertinent information, but stipu-
lated enforcement priorities intended
to encourage corporate processing and
centralized reporting of such informa-
tion (42 FR 45363). The intent was to
ensure that pertinent information ob-
tained by employees is promptly and
appropriately considered, while mini-
mizing duplicative or ill-considered
submissions.
The Agency now feels that these ob-
jectives would best be served by allow-
ing commercial establishments—under
certain conditions designed to ensure
full disclosure—to assume exclusive re-
sponsibility for reporting to EPA any
substantial-risk information obtained
by Individual officers or employees.
Accordingly, this policy statement
stipulates that individual officers and
employees will have fully discharged
their section 8(e) obligations once they
have notified the designated responsi-
ble company supervisor or official of
pertinent information, provided, that
the employing company or firm has
established, internally publicizes, and
affirmatively implements procedures
governing such notifications. These
procedures, at a minimum, must: (1)
Specify the information that must be
reported; (2) indicate how the notifica-
tions are to be prepared and submit-
ted; (3) note the Federal penalties for
failing to report; and (4) provide a
mechanism for promptly notifying of-
ficers and employees who have submit-
ted reports of the company's disposi-
tion of those reports, including wheth-
er or not they were submitted to EPA
(and if not, informing employees of
their right to report to EPA, as pro-
tected by TSCA section 23). EPA be-
lieves these four criteria will ensure
prompt and appropriate processing of
pertinent information.
Establishment of such procedures
notwithstanding, all officials responsi-
ble and having authority for the orga-
nization's execution of its section 8(e)
obligations retain personal liability for
ensuring that substantial-risk Informa-
tion is reported to EPA.
(3) The September 9 proposal stated,
in Part III, that a person obtains in-
formation when he is aware that it
"may suggest" substantial risk. Nu-
merous commenters questioned the
Administrator's authority to compel
the reporting of information which
"may suggest" substantial risk. The
Administrator agrees that section 8(e)
addresses information that "reason-
ably supports the conclusion" of sub-
stantial risk and has deleted the "may
suggest" provision, but emphasizes
that "reasonably supports the conclu-
sion" of substantial risk is not identi-
cal to a conclusive demonstration of
substantial risk. The former typically
occurs, and must be reported, at an
earlier stage. Part VI in this policy
statement provides Agency interpreta-
tion of the types of information that
"reasonably support" such a conclu-
sion.
(4) Numerous commenters requested
-clarification of different aspects of
Part V of the September 9 proposal
("Information Which Reasonably Sup-
ports a Conclusion of Substantial
Risk"), particularly concerning envi-
ronmental effects, and suggested dif-
ferent interpretations of what consti-
tutes a "substantial risk". The Agency
continues to focus in this policy state-
ment on the effects set forth in the
September 9 proposal, but clarifies
that the substantiality of a risk is a
function of both the seriousness of the
effect and the probability of its occur-
rence (see Part V).
(5) Numerous commenters main-
tained that section 8(e) only applies
prospectively to information obtained
after January 1, 1977. The Ag'ency dis-
agrees, as explained in the preamble
to the September 9 proposal. This
policy statement continues to apply
section 8(e) to information obtained
before 1977 of which a person has
FEDERAL REGISTER, VOL 43, NO. 52—THURSDAY, MARCH 16, 1978
539
-------
NOTICES
11111
been -aware since January 1, 1977. In
response to requests for clarification,
the statement defines what constitutes
such awareness. In this manner, EPA
intends to limit the need for searches
of historical records and files.
(6) This policy statement now pro-
vides that any information published
in scientific literature, in any lan-
guage, is exempt if it is referred to in
abstracts published by specified ab-
stracting services.
(7) This policy statement describes
in a new Part X how to submit claims
of confidentiality.
Accordingly, the Administrator's in-
terpretation of and policy towards sec-
tion 8(e) is set forth below.
Dated: February 24, 1978.
DOUGLAS COSTLE
Administrator.
I. DEFINITIONS
The definitions set forth in TSCA
section 3 apply to these requirements.
In addition, the following definitions
are provided for purposes of this
policy statement:
The term "manufacture or process
'for commercial purposes' " means to
manufacture or process: (1) For distri-
bution in commerce, including for test
marketing purposes, (2) for use as a
catalyst or an intermediate, (3) for the
exclusive use by the manufacturer or
processor, or (4) for product research
and development.
The term "person" includes any nat-
ural person, corporation, firm, com-
pany, joint-venture, partnership, sole
proprietorship, association, or any
other business entity, any State or po-
litical subdivision thereof, any munici-
pality, any interstate body and any de-
partment, agency, or instrumentality
of the Federal Government.
The term "substantial-risk informa-
tion" means information which rea-
sonably supports the conclusion that a
chemical substance or mixture pre-
sents a substantial risk of injury to
health or the environment.
II. PERSONS SUBJECT TO THE
REQUIREMENT
Persons subject to section 8(e) re-
quirements include both natural per-
sons and business entities engaged in
manufacturing, processing, or distrib-
uting in commerce a chemical sub-
stance or mixture. In the case of busi-
ness entities, the president, chief ex-
ecutive officer, and any other officers
responsible and having authority for
the organization's execution of its sec-
tion 8(e) obligations must ensure that
the organization reports substantial-
risk information to EPA. The business
organization is considered to have ob-
tained any information which any of-
ficer or employee capable of appreciat-
ing the significance of that informa-
tion has obtained. It is therefore in-
cumbent upon business organizations
to establish procedures for expedi-
tiously processing pertinent informa-
tion in order to comply with the
schedule set forth in Part IV.
Those officers and employees of
business organizations who are capa-
ble of appreciating the significance of
pertinent information are also subject
to these reporting requirements. An
employing organization may relieve its
individual officers and employees of
any responsibility for reporting sub-
stantial-risk information directly to
EPA by establishing, internally publi-
cizing, and affirmatively implementing
procedures for employee submission
and corporate processing of pertinent
information. These procedures, at a
minimum, must: (1) Specify the infor-
mation that officers and employees
must submit; (2) indicate how such
submissions are to be prepared and
the company official to whom they are
to be submitted; (3) note the Federal
penalties for failing to report; and (4)
provide a mechanism for promptly ad-
vising officers 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 accordance with them, shall
have discharged his section 8(e) obli-
gation. Establishment of such proce-
dures notwithstanding, all officials re-
sponsible and having authority for the
organization's execution of its section
8(e) obligations retain personal liabil-
ity for ensuring that the appropriate
substantial-risk 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 resppnsiblity 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 information to their supe-
riors for corporate processing and re-
porting, rather than to EPA directly,
they have not discharged their individ-
ual section 8(e> obligation until EPA
has received the information.
NOTE.—Irrespective of a business organiza-
tion's decision to establish and publicize the
procedures described above, it is responsible
for becoming cognizant of any substantial-
risk information obtained by its officers and
employees, and for ensuring that such infor-
mation is reported to EPA within 15 work-
ing days.
III. WHEN A PERSON WILL BE REGARDED
AS HAVING OBTAINED INFORMATION
A person obtains substantial-risk in-
formation at the time he first comes
into possession of or knows of such in-
formation.
NOTE.—This includes information of
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 sig-
nificance 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 il-
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 so
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 of disposal, or
other pertinent factors).
Note that: (i).The effects outlined
below should not be reported if the re-
FEDERAL REGISTER, VOL 43, NO. 53—THURSDAY, MARCH 16, 1978
540
-------
11112
NOTICES
spondent has actual knowledge that
the Administrator is already informed
of them.
(ii) Information respecting these ef-
fects can be obtained either directly,
by observation of their occurrence, or
inferred from designed studies as dis-
cussed in Part VI.
The Agency considers effects for
which substantial-risk information
must be reported to include the fol-
lowing:
(a) Human health effects—(I) Any
instance of cancer, birth defects, mu-
tagenicity, death, or serious or pro-
longed incapacitatlon, including the
loss of or inability to use a normal
bodily function with a consequent rel-
atively serious impairment of normal
activities, if one (or a few) chemical(s)
is strongly implicated.
(2) Any" pattern of effects or evi-
dence which reasonably supports the
conclusion that the chemical sub-
stance or mixture can produce cancer,
mutation, birth defects or toxic effects
resulting in death, or serious or pro-
longed incapacitation.
(b) Environmental effects—(1) Wide-
spread and previously unsuspected dis-
tribution in environmental media, as
indicated in studies (excluding materi-
als contained within appropriate dis-
posal facilities).
(2) Pronounced bioaccumulation.
Measurements and indicators of pro-
nounced bioaccumulation heretofore
unknown to the Administrator (includ-
ing bioaccumulation in fish beyond
5,000 times water concentration in a
30-day exposure or having an n-oc-
tanol/water partition coefficient
greater than 25,000) should be report-
ed when coupled with potential for
widespread exposure and any non-triv-
ial adverse effect.
(3) Any non-trivial adverse effect,
heretofore unknown to the Adminis-
trator, associated with a chemical
known to have bioaccumulated to a
pronouncld degree or to be wide-
spread in environmental media.
(4) Ecologically significant changes
in species' interrelationships; that is,
changes in population behavior,
growth, survival, etc. that in turn
affect other species' behavior, growth,
or survival.
Examples include: (i) Excessive stim-
ulation of primary producers (algae,
macrophytes) in aquatic ecosystems,
e.g., resulting in nutrient enrichment,
or eutrophication, of aquatic ecosys-
tems.
(ii) Interference with critical biogeo-
chetnical cycles, such as the nitrogen
cycle.
(5) Facile transformation or degra-
dation to a chemical having an unac-
ceptable risk as defined above.
(c) Emergency incidents of environ-
mental contamination—Any environ-
mental contamination by a chemical
substance or mixture to which any of
the above adverse effects has been as-
cribed and which because of the pat-
tern, extent, and amount of contami-
nation (1) seriously threatens humans
with cancer, birth defects, mutation,
death, or serious or prolonged inca-
pacitation, or (2) seriously threatens
non-human organisms with large-scale
or ecologically significant population
destruction.
VI. NATURE AND SOURCES OF INFORMA-
TION WHICH "REASONABLY SUPPORTS
THE CONCLUSION" OF SUBSTANTIAL
RISK
Information attributing any of the
effects described in Part V above to a
chemical substance or mixture is to be
reported if it is one of the types listed
below and if it is not exempt from the
reporting requirement by reason of
Part VII of this policy statement. A
person is not to delay reporting until
he obtains conclusive information that
a substantial risk exists, but is to im-
mediately report any evidence which
"reasonably supports" that conclusion.
Such evidence will generally not be
conclusive as to the substantiality of
the risk; it should, however, reliably
ascribe the effect to the chemical.
Information from the following
sources concerning the effects de-
scribed in Part V will often "reason-
ably support" a conclusion of substan-
tial risk. Consideration of corrobora-
tive information before reporting can
only occur where it is indicated below.
(1) Designed, controlled studies. In
assessing the quality of information,
the respondent is to consider whether
it contains reliable evidence ascribing
the effect to the chemical. Not only
should final results from such studies
be reported, but also preliminary re-
sults from incomplete studies where
appropriate. Designed, controlled stud-
ies include:
(i) In vivo experiments and tests.
(ii) In vitro experiments and tests.
Consideration may be given to the ex-
istence of corroborative information, if
necessary to reasonably support the
conclusion that a chemical presents a
substantial risk.
(iii) Epidemiological studies.
(iv) Environmental monitoring stud-
ies.
(2) Reports concerning and studies
of undesigned, uncontrolled circum-
stances. It is anticipated here that re-
portable effects will generally occur in
a pattern, where a significant common
feature is exposure to the chemical.
However, a single instance of cancer,
birth defects, mutation, death, or seri-
ous incapacitation in a human would
be reportable if one (or a few)
chemical(s) was strongly implicated.
In addition, it is possible that effects
less serious than those described in
Part V(a) may be preliminary manifes-
tations of the more serious effects
and, together with another triggering
piece of information, constitute repor-
table information; an example would
be a group of exposed workers experi-
encing dizziness together with prelimi-
nary experimental results demonstrat-
ing neurological dysfunctions.
Reports and studies of undesigned
circumstances include:
(i) Medical and health surveys.
(ii) Clinical studies.
(iii) Reports concerning and evi-
dence of effects in consumers, workers,
or the environment.
VII. INFORMATION WHICH NEED NOT BE
REPORTED
Information need not be reported if
it:
(a) Has been published by EPA in re-
ports;
(b) Has been submitted in writing to
EPA pursuant to mandatory reporting
requirements under TSCA or any
other authority administered by EPA
(including the Federal Insecticide,
Fungicide and Rodenticide Act, the
Clean Air Act, the Federal Water Pol-
lution Control Act, the Marine Protec-
tion, Research, and Sanctuaries Act,
the Safe Drinking Water Act, and the
Resource Conservation and Recovery
Act), provided that the information:
(1) Encompasses that required by Part
IX (c) through (f); and (2) is from now
on submitted within the time con-
straints set forth in Part IV and iden-
tified as a section 8(e) notice in accor-
dance with Part IX(b);
(c) Has been published in.the scien-
tific literature and referenced by the
following abstract services: (1) Agric-
ola, (2) Biological Abstracts, (3)
Chemical Abstracts, (4) Dissertation
Abstracts, (5) Index Medicus, (6) Na-
tional Technical Information Service.
(d) Is corroborative of well-estab-
lished adverse effects already docu-
mented in the scientific literature and
referenced as described in (c) above,
unless such information concerns
emergency incidents of environmental
contamination as described in Part
V(c), or
(e) Is contained in notification of
spills under section 311(b)(5) of the
Federal Water Pollution Control Act.
VIII. INFORMATION FIRST RECEIVED BY
A PERSON PRIOR TO THE EFFECTIVE
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
which the person participated after
January 1,1977;
FEDERAL REGISTER, VOL. 43, NO. 52—THURSDAY, MARCH 16, 1978
541
-------
NOTICES
11113
(b) Any information the contents of
which a person has been alerted to by
date received after January 1,1977, in-
cluding any information concerning a
chemical for which the person is pres-
ently assessing health and environ-
mental effects;
(c) Any other information of which
the person has actual knowledge.
IX. REPORTING REQUIREMENTS
Notices shall be delivered to the
Document Control Officer, Chemical
Information Division, Office of Toxic
Substances (WH-557), Environmental
^Protection Agency, 401 M Street SW.,
Washington, D.C. 20460.
A notice should:
(a) Be sent by certified mail, or in
any other way permitting verification
of its receipt by the Agency,
(b) State that it is being submitted
in accordance with section 8(e),
(c) Contain the job title, name, ad-
dress, telephone number, and signa-
ture of the person reporting and the
name and address of the manufactur-
ing, processing, or distributing estab-
lishment with which he is associated,
(d) Identify the chemical substance
or mixture (including, if known, the
CAS Registry Number), ,
(e) Summarize the adverse effects
being reported, describing the nature
and the extent of the risk involved,
and
(f) Contain the specific source of the
information together with a summary
and the source of any available sup-
porting technical data.
For emergency incidents of environ-
mental contamination (see Part V(O),
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, Virgin Islands), 201-548-8730.
Region III (Pennsylvania, West Virginia,
Virginia, Maryland, Delaware, District of
Columbia), 215-597-9898.
Region IV (Kentucky, Tennessee, North
Carolina, South Carolina, Georgia, Ala-
bama, Mississippi, Florida), 404-881-4062.
Region V (Wisconsin, Illinois, Indiana,
Michigan, Ohio, Minnesota), 312-353-
2318.
Region VI (New Mexico, Texas, Oklahoma,
Arkansas, Louisiana), 214-749-3840.
Region VII (Nebraska, Iowa, Missouri,
Kansas), 816-374-3778.
Region VIII (Colorado, Utah, Wyoming,
Montana, North Dakota, South Dakota),
303-837-3880.
Region IX (California, Nevada, Arizona,
Hawaii, Guam). 415-556-6254.
Region X (Washington. Oregon. Idaho,
Alaska), 206-442-1200.
X. CONFIDENTIALITY CLAIMS
(a) Any person submitting a notice
to EPA under section 8(e) of TSCA
may assert a business confidentiality
claim covering all or part of the infor-
mation contained in the notice. Any
information covered by a claim will be
disclosed by EPA only to the extent,
and by means of the procedures, set
forth in 40 CFR Part 2 (41 FR 36902,
September 1, 1976).
(b) If no claim accompanies the
notice at the time it is submitted to
EPA, the notice will be placed in an
open file to be available to the public
without further notice to the submit-
ter.
(c) To assert a claim of confidential-
ity for information contained in a
notice, the submitter must submit two
copies of the notice.
(1) One copy must be complete. In
that copy the submitter must indicate
what information, if any, is claimed as
confidential by marking the specified
information on each page with a label
such as "confidential," "proprietary,"
or "trade secret."
(2) If some information In the notice
is claimed as confidential, the submit-
ter must submitva second.copy. The
second copy must be complete except
that all information claimed as confi-
dential in the first copy must be de-
leted.
(3) The first copy of the notice will
be disclosed by EPA only to the
extent, and by means of the proce-
dures, set forth in 40 CFR Part 2. The
second copy will be placed in an open
file to be available to the public.
(d) Any person submitting a notice
containing information for which they
are asserting a confidentiality claim
should send the notice In a double
envelope.
(1) The outside envelope should bear
the same address outlined in section
IX of this policy statement.
(2) The inside envelope should be
clearly marked "To be opened only by
the OTS Document Control Officer."
XI. FAILURE To REPORT INFORMATION
Section 15(3) of TSCA makes it un-
lawful for any person to fail or refuse
to submit Information required under
section 8(e). Section 16 provides that a
violation of section 15 renders a
person liable to the United States for
a civil penalty and possible criminal
prosecution. Pursuant to section 17,
the Government may seek judicial
relief to compel submittal of section
8(e) Information and to otherwise re-
strain any violation of section 8(e).
APPENDIX A.—QUICK REFERENCE SUMMARY
FOR EMERGENCY INCIDENTS OF ENVIRONMEN-
TAL CONTAMINATION
A. WHAT SHOULD BE REPORTED AS AN
EMERGENCY INCIDENT
An emergency incident of environmental
contamination Is "any environmental con-
tamination by a chemical substance or mix-
ture . -. . which, because of the pattern,
extent and amount of contamination. (1) Se-
riously threatens humans with cancer, birth
defects, mutation, death, or serious or pro-
longed incapacitation, or (2) seriously
threatens non-human organisms with large
scale or ecologically significant population
destruction". (See Part V(c) for complete
description.)
B. WHAT NEED NOT BE REPORTED AS AN
EMERGENCY INCIDENT
Information contained in notification of
spills under section 311(b)(5) of the Federal
Water Pollution Control Act (FWPCA).
(For a complete list of exemptions to report-
ing, see Part VII.)
C. WHEN AND WHERE TO REPORT EMERGENCY
INCIDENTS
Emergency incidents of environmental
contamination are to be reported immedi-
ately by telephone to the appropriate EPA
Regional 24-hour telephone emergency line
listed below.
Region I (Maine, Rhode Island, Connecti-
cut, Vermont, Massachusetts. New Hamp-
shire), 617-223-7265.
Region II (New York, New Jersey, Puerto
Rico, Virgin Islands), 201-548-8730.
Region III (Pennsylvania, West Virginia.
Virginia,1 Maryland, Delaware, District of
Columbia), 215-597-9898.
Region IV (Kentucky, Tennessee, North
Carolina, South Carolina, Georgia, Ala-
bama, Mississippi. Florida). 404-881-4062.
Region V (Wisconsin, Illinois, Indiana,
Michigan, Ohio, Minnesota), 312-353-
2318.
Region VI (New Mexico. Texas, Oklahoma,
Arkansas, Louisiana). 214-749-3840.
Region VII (Nebraska, Iowa, Missouri.
Kansas), 816-374-3778.
Region VIII (Colorado, Utah. Wyoming,
Montana, North Dakota, South Dakota),
303-837-3880.
Region IX (California. Nevada. Arizona.
Hawaii, Guam), 415-556-6254.
Region X '(Washington, Oregon. Idaho,
Alaska), 206-442-1200.
In addition, a written report, in accord-
ance with instructions (a) through (f) of
Part IX, is to be submitted within 15 days to
the Document Control Officer, Chemical In-
formation Division, Office of Toxic Sub-
stances (WH-557), 401 M Street SW., Wash-
ington. D.C. 20460.
APPENDIX B—SIGNIFICANT COMMENTS AND
RESPONSES
A. PERSONS SUBJECT TO THESE REQUIREMENTS
Comment 1: Employees cannot be held
subject to these requirements, since: (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
542
-------
11114
NOTICES
Response: The Agency considers that dif-
ferent sections of TSCA, having different
purposes, are appropriately directed to dif-
ferent respondents. In the case of section
8(e), officers and employees who are capable
of appreciating the significance of informa-
tion have a legitimate responsibility to be
alert to and report substantial-risk informa-
tion. The guidance has been modified so
that natural persons and business entities
can fulfill their section 8(e) obligations in
different ways. Most officers and employees
can discharge their section 8(e) obligations
by submitting pertinent information to cor-
porate superiors, provided that the com-
pany has established the risk-evaluation
procedures characterized in Part II. In the
case of a business organization, its presi-
dent, chief executive officer, and other offi-
cials responsible and having authority for
the business organization's execution of its
section 8(e) obligations must ensure that
the organization reports substantial-risk in-
formation to EPA.
Comment 2: Even if employees can be held
subject to these requirements, they should
not be. To do so would force employees and
employers into conflicting positions, inviting
internal corporate dissension and over- re-
porting. Further, individuals often do not
have the overview necessary to reach con-
sidered, well-supported decisions. Corporate
reporting by designated officials will pro-
Vide EPA with more reliable data.
Response: The Agency considers that em-
ployees have a legitimate role in risk report-
ing; it is imperative that risk information
obtained by employees be appropriately
considered. Officers and employees can ful-
fill their role in the reporting of substantial-
risk information, without the disadvantages
described above, by reporting information
to superiors for corporate consideration,
and, having done so, will have discharged
their obligation to EPA. This is contingent
upon the establishment by the business or-
ganization of certain procedures for risk-
evaluation, thereby assuring the appropri-
ate consideration of such reports. Those of-
ficers responsible and having authority for
the organization's execution of its section
8(e) obligations must ensure that the orga-
nization reports substantial-risk informa-
tion to EPA.
Comment 3: Clarify which employees are
covered, and the extent of their obligation.
Are employees "capable of appreciating per-
tinent information" by virtue of rank, or
knowledge? Are rank and file employees
subject to these requirements, or just super-
visory and managerial personnel, company
lexicologists, etc.? Is an employee absolved
of further responsibility if he reports to his
supervisor?
Response: The Agency considers that the
phrase "capable of appreciating the signifi-
cance of pertinent information" appropri-
ately describes those officers and employees
who have a responsibility to be alert to and
report substantial-risk information, includ-
ing not only relatively senior corporate offi-
cers but also many corporate employees.
The policy statement modifies the Septem-
ber 9 proposal, in response to the concerns
expressed in Comments 2 and 3, to permit
most officers and employees to discharge
their obligation by submitting information
to corporate superiors, subject to the condi-
tions described in Part II.
Comment 4: Consultants and independent
labs should not be subject to these require-
ments.
Response: Contractors and independent
labs are not responsible for reporting Infor-
mation they have obtained directly to EPA;
rather, their client manufacturers, proces-
sors and distributors are responsible for
reporting such information.
B. THE "OBTAINING" OF INFORMATION
Comment 5: The "may suggest" criterion
In Part III of the proposal serves to compel
further examination of information that by
itself is not subject to section 8(e> require-
ments. The statutory language calling for
"reasonable support" does not support this.
Further, risk assessment often requires any-
where from months to several years of
study after preliminary results "suggest"
risk, far exceeding the 15-day compliance
period.
Response: The Agency does not intend to
compel under section 8(e) examination of
Information that by Itself is not subject to
section 8(e) requirements and has deleted
the "may suggest" provision, providing its
interpretation of what constitutes evidence
that "reasonably supports the conclusion"
of substantial risk in a new Part VI.
Comment 6: Section 8(e) obligations are
incurred upon obtaining conclusory substan-
tial-risk information.
Response: The Agency disagrees, and con-
siders that "reasonable support" of a con-
clusion of substantial risk is not identical to
the conclusion itself. The former typically
occurs, and must be reported, at an earlier
stage.
Comment 7: The statement, in Part III of
the proposal that a person has obtained in-
formation if he ". . . should know of the ex-
istence of such information not in his pos-
session but which would be delivered to him
on request," tends to compel an active
search for substantial-risk information
rather than the reporting of substantial-risk
information a person "obtains." This is of
particular concern to importers with limited
access to information possessed by their
suppliers.
Response: The Agency considers that sec-
tion 8(e) applies to information which a
person possesses or of which he knows. It is
not intended to compel searches for infor-
mation or extraordinary efforts to acquire
information. The Agency further considers,
however, that "known" information in-
cludes information which a prudent person
similarly situated could reasonably be ex-
pected to know. Negligence or Intentional
avoidance of information does not absolve a
person of his section 8(e) obligation. Part
III has been modified to express these in-
tentions.
Comment 8: Circumstances can exist when
coming "into possession" of risk informa-
tion does not correspond to an understand-
ing of the implications of the information;
"obtains" should be defined in terms of pos-
session of information and awareness of its
Import.
Response: The "obtaining" of information
occurs via persons who are "capable of ap-
preciating the significance of pertinent in-
formation." There will likely be circum-
stances in which the evaluation of informa-
tion clarifies its full import; the establish-
ment of corporate procedures for processing
risk-information prescribed in Part II will
expedite this.
C. TIME ALLOWED FOR COMPLIANCE
Comment 9: Fifteen calendar days is Insuf-
ficient to determine whether information
which "may suggest" substantial risk should
be reported; it is even insufficient to accom-
modate normal procedural time constraints
(corporate processing, mailing, holidays,
etc.).
Response: The Agency has changed the
compliance period to 15 business days. It is
imperative that procedures be established to
expedite the reporting of substantial-risk in-
formation, not that reporting conform to
existing procedures.
Comment 10: Allow from 30 to 00 days for
the second phase of reporting; alternatively,
do not prescribe a time limit for additional
reporting.
Response: Having deleted the "may sug-
gest" criterion, the Agency sees no need to
provide a second phase to the reporting
period. Supplemental information that is
generated after a section 8(e) notification
should, if appropriate, be immediately re-
ported.
Comment 11: Allow from 30 to 120 days to
report pre-1977 information; this period
should commence: (a) upon final publica-
tion, has
been in effect since January 1, 1977; post-
ponement in reporting substantial-risk in-
formation is not warranted.
O. EFFECTS AND INFORMATION THAT MUST BE
REPORTED
Comment 12: The reporting of "any in-
stance" of cancer, birth defects, etc., in
humans is too broad and such information
will be of little use; chemical workers, like
the general population, develop cancers and
other ailments of uncertain etiology.
Response: This policy statement clarifies
that the reporting of single occurrences of
human cancer or other serious effects will-
depend upon evidence strongly Implicating
one (or a few) chemical(s).
Comment 13: Dermal ailments and nausea
are poorly chosen examples of precursor
symptoms. Deleting these examples will
avoid unduly emphasizing them when other
symptoms may be more important, yet will
not eliminate the obligation to report them
if they are suspected precursors.
Response: The Agency agrees.
Comment 14: How are reportable data dis-
tinguished' from routine tests including
range tests such as LDH's?
Response: This policy statement directs
the reporting of specified effects when un-
known to the Administrator. Many routine
tests are based on a knowledge of toxicity
associated with a chemical; unknown effects
occurring during such a range test may have
to be reported if they are those of concern
to the Agency and if the information meets
the criteria set forth in Parts V and VI.
Comment IS: The most widespread "in
vitro" test is the Ames test, which is subject
to considerable debate. Clarify the circum-
stances under which positive results of in
vitro tests must be reported.
Response: Part VI clarifies that the re-
porting of in vitro tests will depend upon
the existence of corroborative information
if necessary to reasonably support the con-
clusion of substantial risk.
Comment 16: The description of "extreme
persistence" as a substantial risk is an exam-
ple of the need to redefine Part V(c) ("Envi-
ronmental Effects"). Persistence and bio-
accumulation should be considered risks
only when coupled with toxicity and signifi-
cant exposure.
FEDERAL REGISTER, VOL. 43, NO. 52—THURSDAY, MARCH 16, 1978
543
-------
NOTICES
11115
Response: Part V now clarifies those ef-
fects for which reporting depends upon a
significant exposure potential. Persistence
by itself is no longer itemized as a report-
able effect but rather is considered to be a
component of exposure potential; it may
also underlie the measurements described in
Part V(bXl). Laboratory indicators of pro-
nounced bioaccumulation are to be reported
when coupled with potential for widespread
exposure and any non-trivial adverse effect.
Comment 17: The n-octanol/water parti-
tion coefficient addresses a physico-chemi-
cal property, not biological effects, and is
not alone an indicator of substantial risk;
further, the values stated for the coefficient
and the bioaccumulation factor in fish do
not correspond.
Response: The Agency acknowledges the
numerical error and has amended the values
to correspond. This policy statement now
directs the reporting of an experimental
measurement of bioaccumulation when
coupled with an adverse effect and potential
for widespread exposure.
Comment 18: The requirement that infor-
mation which- "links" an effect to a chemi-
cal be reported Is too broad and contradicts
the statutory language of "reasonably
supports".
Response: The Agency has provided in a
new Part VI its interpretation of "reason-
ably supports".
Comment 19: A determination that infor-
mation "reasonably supports the conclu-
sion" of substantial risk cannot be made in-
dependently of considerations of use since
the method and manner of using a chemical
may Influence the occurrence of an effect;
in particular, the criteria should reflect a
distinction between normal and abnormal
uses of chemicals. ~^
Response: The Agency considers that the
appropriate components of a "substantial
risk" with respect to a chemical are (a) the
seriousness of the effect, and (b) total expo-
sure potential. The method and manner of
using a chemical is one of several factors de-
termining its exposure potential. As de-
scribed in Part V, the importance of expo-
sure potential as a component of "substan-
tial risk" depends upon the kind of effect of
concern. Thus, the effects described in Part
V(a) are so serious that relatively little
weight is given to exposure; the effects de-
scribed in Parts V (b) and (c) involve a sig-
nificant exposure or exposure potential.
The Agency further considers that a defi-
nition of "normal" use for a particular
chemical will often depend upon a knowl-
edge of the risks associated with the
chemical.
E. INFORMATION THAT NEED NOT BE REPORTED
Comment 20: Information published in
scientific literature in languages other than
English should be exempted if published in
summary form by abstracting services. Can
the accuracy of English language abstracts
and commercial translations of foreign lit-
erature be assumed?
Response: This policy statement now pro-
vides that information published in scien-
tific literature, whether in English or an-
other language, Is exempt from reporting if
published in summary form by certain
specified abstract services.
Comment 21: Information exchange sys-
tems with other Federal agencies should be
immediately established so that respondents
need not report to EPA information already
reported to other Agencies, and vice versa.
Such duplicative reports are unduly burden-
some.
Response: EPA is coordinating this pro-
gram with other agencies now. When this
coordination is successfully completed, the
policy statement will be amended to-exempt
from the reporting requirement Information
that has been submitted to other specified
agencies. In the meantime, substantial-risk
information must be reported directly to
EPA; such a report does not discharge any
reporting obligation to other agencies.
F. INFORMATION FIRST RECEIVED PRIOR TO THE
EFFECTIVE DATE OF TSCA
Comment 22: The tense of the verb "ob-
tains" reveals that section 8(e) was Intended
to be applied prospectively to Information
newly acquired after January 1,1977. Utilize
section 8(d) or other rules to acquire infor-
mation obtained before then.
Response: As discussed in the preamble to
the September 9 proposal, the Agency con-
siders section 8(e) to apply to risk informa-
tion possessed by or known to a person
before, on, or after January 1, 1977. Con-
cerning information first obtained before
1977, this policy statement continues to re-
quire reporting of information received if a
person has been aware of it since January 1,
1977, for the reasons discussed in the Sep-
tember 9 preamble.
Comment 23: The term "aware" is too
vague to be of any help in responding to
these requirements. Since many corporate
employees are potentially subject to these
requirements, and given uncertainty over
the extent to which they ought to be aware
of pre-1977 information, this provision tends
to compel the very file search it was intend-
ed to avoid. The term "aware" should be
further defined, possibly in terms of actual
knowledge.
Response: The Agency in Part VIII of this
policy statement now defines the pre-1977
information of which a person is considered
to be aware.
G. CONFIDENTIAL INFORMATION
Comment 24: EPA should delay guidance
until procedures are published governing
the treatment of confidential submissions.
Comment 25: EPA should treat all submis-
sions as confidential until the information is
verified.
Comment 26: EPA should automatically
publish section 8(e) notices.
Response to Comments 24 through 26:
EPA has included a new Part X which de-
scribes how to submit a claim of confiden-
tiality and states that any or all of the in-
formation submitted may be claimed as con-
fidential. Such information will be disclosed
by EPA only to the extent, and by means of
the procedures, set forth in 40 CFR Part 2.
H. MISCELLANEOUS
Comment 27: What is the statutory basis
or need for guidance? What is its exact
status under the Administrative Procedure
Act?
Response: This policy statement sets forth
EPA's interpretation of and policy concern-
ing TSCA section 8(e). As an interpretive
rule and statement of policy it is not subject
to the comment period and delayed effec-
tive date provisions of the Administrative
Procedure Act (5 U.S.C. 553). Although
TSCA does not mandate a policy statement,
the Agency of necessity must develop the
criteria which will govern enforcement ac-
tivities. Trade associations and businesses
were among those who previously expressed
interest in such a statement to guide their
compliance.
Comment 28: Clarify whether these re-
quirements apply to chemicals previously
but no longer manufactured, processed, or
distributed in commerce by a person.
Response: Information obtained before
1977 must be reported if the person has
been aware of it since January 1, 1977, as
prescribed by Part VIII. Concerning chemi-
cals which & person has discontinued manu-
facturing, processing, or distributing since
January 1, 1977, information obtained
before the time of discontinuation is subject
to these requirements. It is expected that
the acquisition of information after that
time will be minimal; however, should addi-
tional information be acquired, it may trig-
ger the reporting described in Part VIII.
Comment 29: Clarify the meaning of "sub-
stantial risk" relative to other risks ad-
dressed by TSCA.
Response: A substantial risk is defined in
Part V(a) of this policy statement as a risk
of considerable concern because of (a) the
seriousness of the effect, and (b) the fact or
probability of its occurrence. As opposed to
other risks addressed by TSCA, economic or
social benefits of use, or costs of restricting
use, are not to be considered in determining
whether a risk is "substantial".
Comment 30: To what extent are "users"
of chemicals subject to these requirements?
Response: The Agency considers that
many industrial uses of chemicals actually
fall within the scope of "processing" chemi-
cals. A manufacturer, processor, or distribu-
tor who obtains substantial-risk information
concerning chemicals he handles should be
alert to the possibility he may have to
report it.
Comment 31: Are chemicals manufac-
tured, processed and distributed in com-
merce in small quantities solely for purposes
of research and development subject to
these requirements?
Response: In general, the Agency consid-
ers that much manufacturing, processing,
and distribution in commerce of chemicals
in small quantities solely for purposes of re-
search and development is conducted for
"commercial purposes". .Such purposes
would include the sale and distribution of
such materials, as well as their use by the
manufacturer or processor in activities (for
example, product research and development
and studies assessing the feasibility and
safety of using chemicals) preceding his or a
client's commercial use of such materials or
others on a larger scale.
As described in Part V, the Agency consid-
ers that "substantial risks" depend in part
upon an exposure potential. Thus, th» 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?
Response: The Administrator considers
that raw materials, intermediates and inert
ingredients produced or used in the manu-
facture of a pesticide are substances or mix-
tures which can be regulated under TSCA.
In order to be considered a pesticide, a
substance must be intended for use as a pes-
ticide. Raw materials, intermediates, and
inert 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 pesti-
FEDERAl REGISTER, VOL. 43, NO. 52—THURSDAY, MARCH 16, 1978
544
-------
11116
NOTICES
cide 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, drug, cosmetic,
or device subject to T8CA?
Response:: The Administrator considers
that intermediates and catalysts intended
solely for use in the production of a food,
food additive, drug, cosmetic, or device are
excluded from regulation under TSCA. The
definitions of the PFDCA provide that
chemical substances which are intended for
use as a component of a food, food additive,
drug, cosmetic, or device are encompassed
within the meaning of such terms, respec-
tively. The FDA considers intermediates
and catalysts to be such components. There-
fore, they are subject to regulation under
the PPDCA. Any such substance is excluded
from regulation under TSCA insofar as it is
actually manufactured, processed, or dis-
tributed in commerce solely for use in the
production of a food, food additive, drug,
cosmetic, or device.
Comment 34: Employees should have the
option to submit reports anonymously.
Response: EPA considers that any person
may report information to EPA under
TSCA. Those who are required to do so
under section 8(e) are persons who manu-
facture, process, or distribute in commerce
chemical substances or mixtures, including
not only business entities but also such em-
ployees as described in Part II. In order to
establish that such persons have discharged
their obligations, and in order to encourage
responsible review of the quality of informa-
tion and the substantiality of risks, EPA be-
lieves that notifiers should identify them-
selves. Section 23 will adequately protect
employees from discrimination pursuant to
notifications they have made under section
8(e).
[PR Doc. 78-7064 Filed 3-15-78; 8'45 ami
FEDERAL REGISTER, VOL. 43, NO, 52—THURSDAY, MARCH 16, 1978
545
-------
o
z
z
o
t-t
to
-
pa
Ol
l—
Oi
0
a.
LU
rv
0
Z
HH
N
I-H
a:
i
o
C£
0
1
X
o
l-l
Q
* *
SO -*•
0> CM
O O
0000
r^- p~-
«o r-
o o
^•s
o
Q
z:
a:
o
X
co-
in
o
X
a.
o
I-H
X
I—
^-
X
o
X
LU
y
1
_j
^
Z
I-H
5>
_J
>-
X
K-
LU
y
1
1
>-
z
o
CO
a:
<£
O
>-
X
o
a.
o
TV
a.
0
n
1
CM
^^
1
Z
LU
Z
I-H
O
I-H
y
<£
1—
UJ
o
± «cf in CD
CD O CD CD CD *—
S-*
>—
X
0
t—
n
CQ
1
DC O
LU »— o: LU
1— _l LU IT)
to < h- ^
LU 01 U1 H
1 LU Q
o _i z: i
C* >- => -1
O X I-H >- CM
_l 1- Q Z
X LU O I-H CM
o z: to >
•*
^ LU UJ
Q Q Q Q — 1 Z
1— 1 I-H I-H I-H I-H O
O O O O Qi Z
<£ —
Q UJ X
I-H 1— UJ
O 01 X
< UJ _l
>—
O _J X
I-H >- t—
-I X LU
>- 1- 1
X LU CM
O
CQ «
a; o Q
•ft HH l-l
o o o
LU «t -—!—<
^— ^- ^_
lit ps rv
O O O
<£•<•<
*
to
*^ *j" in r^
ro to «*• m
O CD CD CD
oo oo oo co
Is-. r^- r*** t"**
»- «- CM CM
CD CD CD CD
to
LU
Z
I-H
z:
o
LU I-H
t— 1—
- a:
>- 1- X -
a. u. a: —i
— l — i H- O
3 =3 a.
(/) O1 Z
I-H 1
Z^ ^ — J
rD 3 — i in
z I-H I-H m
M Z 0 —
z: o M >-
=3 y. a. i
-J •£. •£. a.
o
CM
CD
J-N.
r^*
CM
T-
to
z
o
CQ
Di
<£
0
o
f^
Q
^_
X
o
I-H
1—
<£
E
O
o;
<3C
O
in
o
00
p^
in
CD
to
a
z
^p
o
a.
z:
o
o
o
z
I-H
1-
_J
LU
y
01
oe
o
z
I-H
Z
I-H
y
O
Z
I-H
Q
"^
1
O
z
1— 1
s^
to
o
z
"1
o
a.
z:
o
0
y
~^
i— i
z:
Q
* C~
»— CD *~ CM CM
CD CD CD CD CD
oo r~- oo oo o
r-^ r^ r^ i — r^-
•& CM IO ov to
CD *- o o CD
j
>—
fv*
o
X
a.
01
o
X
a.
0
I-H
X
h-
)
^-
X
o
X
t—
UJ
y
l
i
>-
Z
I-H
^
_J
>—
X
1—
LU
y
l
»-
1
_ j
>-
z
0
co
O£
—
X
o
X
1—
LU
z:
i
CM
^^
y
••
LU
Z
I-H
O
l-l LU
r z
-£ LU
N M
Z Z
LU LU
CQ ca
r>.
CM
O
o
[X.
«—
O
^^
O
N
<£
_j
^
1
to
1
_J
0
N
HH
OIL
h-
<*"
•«
CM
•^
^~
|
X
*—
s^
1
•&•
1
1
^.
X
1—
LU
1— 1
Q
1
Z
*.
Z
*
LU
Z
UJ
N
Z
UJ
ca
•X
CD
CD
CM
CD
00
f-*
-JD
O
1
O
Q£
0
_J
X
o
1— 1
Q
t
in
•*
CM
1
0
y~
O
a:
CQ
I-H
O
1
*J"
^
»—
•^
LU
Z
UJ
M
Z
UJ
03
•X
to
0
CD
00
fx
in
CD
CQ
1
IO
•t
CM
O
LU
I-H
X
1-
1
X
o
T-
^N
1
^.
Z
I-H
M
—
X
h-
LU
|
CM
*
LU
Z
hH
a.
LU
M
<£
l-l
o
i
in
•.
»—
i
o
N
Z
LU
CQ
•X
CM
CM
CD
00
p«*
r^
o
CM
in
in
i
to
X
LU
l
LL.
O
Nl
2£
LU
ca
•X
a.
00
o
r^
r^-
T-
*-
Q
i— i
O
^
O
1— 1
0
N
Z
UJ
CQ
546
-------
o
z
«n
.»- o- m NO
o o o o o
in
o
oo
to
o
NO
in
CM
o
oo
r».
0"- CM oo in oo
vO r— ON ON «d- 00
O O O O O O
00 oo oo 00 00 00
* * *
o o o i
r-oooooooooooooooooo
* *
* *
*• o o o o o o «- <
in
o
*—
o
00
f^
to
o
»- V-
ON to
o *•*
0 0
oooo
r^ r*-
to-d-
o o
ON
00
CSJ
0
ON
px.
m
o
Nj-
f^
o
o
CO
I-.
CM
o
NO
CM
»~
0
00
P-.
^-
o
o
CM
CM
0
00
r-^
r^
o
ON
in
CM
O
00
f^»
*—
»-
o
«J-
CSJ
o
CO
f>»
ON
O
00 ON
r-Ni^.
CSICSI
o o
ON ON
r- r--
NT Nj-
o o
o
in
w—
O
00
f*^
in
o
0 tO
•— »-
»- «—
o o
0000
r**- r^
to to
o o
to
ON
O
CO
r-.
to
o
CO
U
z:
LU
iu
z:
o
hH
LU
I
u
00
-if
O
1.
O.
o
a.
a.
o
Oi
Q.
OQ
«n
h-
Oi
O
O-
LU
-
o
N
Z
LU
CO
a.
o
Oi
QL
O
Z
LU
z:
o
X
0_
hH
O
O
_J
o
o
Oi
x
a:
LU
Z
LU
D_
Z
LU
Oi.
o
LU
Z
o
in m
hH LU
I LU t-
•a. -X. ^
t- O-
-------
o
z
z
o
CO
co
CQ
:D
co
^00 o
*- i- CM
O O O
ooco 00
i-vf- r^
m MD r~
o o o
CT"« ^D
o »-
o o
CO 00
10
o
m
CO
m
o
00
o
00
F--
in
o
CM
in
o
oo
in *-
* * * *
K> oo *~ oo *~ioioin^>o^oo*-ooo in
O O CM «- O O O O O O O •—•-»-•- CM *-
00 CO 00 00 1-^ 00 00 00 00 00 00 00 00 00 00 00 00
*~ *- »- CM CM CM IO IO IO IO «O vO in
O O O O "-OOOOOOOOOOO O
03
I
X
o
UJ
o
«t
X
O* 00
o o
CM O
o o
00 f-
LLJ
<
o
CO
x
o
DC
O
0.
UJ
o;
CO
<
I—
CO
CQ
X
M
Q
z
LU
a.
a.
UJ
E:
-
X
o
LU
-
o
a.
o
o
>-
o
m
i
^N
1
1
Z
M
Q.
1
X
1
0
z
z:
o
•>
Q
t-i
O
**
0
F-1
z
0
tt^
*^
z
-------
o
z
m
in
CO
=3
in
* * * *
0. D.
>»- p^p^coo
oo or-vCM
o oo*-
o o o o
CO P-CO CO 00 00 CO 00
* * * * -X *
* * *
oo«- >-
•- o
OCM
O O
r--oo
oo»- CM
o o o o
oooooo oo
CMtO<3- sO "~SO
O O O O »- O
CM
00
o
o
00
CM
o
p"v O1"
sO sT
O - r~ r- r~
roin •*> *- oo »-
CD "- o c»
o
HH
!E
LU
X
o
>-
O
Q.
LU
in
3
»-
<
I—
tn
oa
X
h-l
O
Q.
o.
LU
Q
a:
o
o
o
a:
a
s:
-
o
Q.
X
o
h-l
o
I
0-
o
N
z
LJJ
CQ
UJ
UJ
o
LU
o
o
CO
HH
Q
z
LU
a.
o
o
I-H
a
LU
*t
_l
>-
(£
o
•a.
LU
Z
LU
HH
If
H-
Z
LU
O.
O
_J
O
o
HH
Q
o
o
LU
Z
LJJ
Z
111
a.
o
_j
o
o
LU
«n
LU
X
o
LU
o
a.
o
cc:
a.
o
10
LU
a
in
LU
s:
H-
LL.
in
LU
>-
x
UJ
Q
n
Of
O
_l
X
o
o
a:
Q
LU
Q
1-4
OIL LU
O I-
_i «r
i x z
o o •
o _i o
tt: >- o
(- a. in
M O HH
z Q: M
i a. o
z o
in LU
LU
o
z
>->->-
X X Z
H- H- LU
LU LU X
c s: a.
HH HH HH
(~°l £^i f^i
LU
O
M
CD
I—t
Q
O
o
>- z
—I HH
O C£
a
LU >-
Z X
UJ O
-i a:
>- o
a. —i
o x
a: o
a. HH
HH a.
o LU
o
a:
o
o
i
CM
I
O
O
_J
U.
I
o
o
CO
a:
H-
LU
O
00
SO
U.
X
o
Z
LU
X
D.
O
E:
o
a:
to
s*-
CM
w
IO
-- *- CM
O
z
HH
I O
O HH
Qi Oi
O LU
—I Q.
X HH
O D-
HH HH
Q Q
CM CM
LU LU
Z Z
X X
H- H-
LU LU
LU
Z
X
H-
LU
LU
Z
LU
Z
X X
I— H-
LU LU
549
-------
* *
* *
o
z
z
o
I-)
CO
CO
t->
z:
(£1
=J
CO
o o
oooO
>a- so
o o
ro
o
oo
in
o
780256
«-
00
CM
, 0
in
13
r-
o
00
sO
o
00
0
00
sO
o
780248
o
«- rooo
OCMCM
ooo
»- 00 s3-
T- 00
o
o
00
ro
13
sO
o
00
in
o
SO
sS-
o
00
m
0
o
13
o
'80042
CM
0
00
ro
CM
o
00
OS
0
'90270
0
o
r-
CM
o
OS
0
«- inr«-
m so ro
O 0 •-
ooo
oooooo
CMCMsS-
o o o
00
00
o
o
00
ro
o
OL
O-
oo
o
00
SO
0
'90273
o
CM
O
13
0
'70002
00
13
0
0
0
O
SO
0
00
m
o
'80237
00
o
UJ
IE
•a.
Z
•a.
O
n
LU
X
O
ta
tn
t-
a:
o
a.
LU
Q ^
o
_l
X
o
o
a
o
LU
a.
a.
-
0£
O
-------
UJ
E.
O
n
UJ
X
o
CQ
in
o
a.
0£
in
in
CQ
o
z
UJ
a.
a.
o
z
z
o
r-i
in
1/3
I-H
E:
CO
=3
in
UJ
E
z
_J
^
o
E:
UJ
X
o
*
V-
o
00
ro
o
.j
-
X
UJ
E:
i
ro
1
s**
_J
s*»
1
(M
|
j
O
M
M
Q
h«4
X
1—
1
•s-
ro
•s
»—
t
1
^-
r—
^-s
CO
1
t-
1
m
s^
1
*-
*.
UJ
z
0
1
CM
1
Z
I-H
O
I-H
i
O
N
Q
t— I
y_
I-H
*
ro
«-
o
00
sD
O
1
(M
1
V
X
o
r-
UJ
O
*
m
i
5^
X
r-
UJ
z:
i
ro
1
/-s
_J
X
1
CM
1
_J
O
N
n
0
•a.
1-1
X
i—
i
*j-
•i
ro
•«
w—
1
1
s^_
1—
Z>
CQ
|
r-
1
in
s^
1
^
UJ
z
o
z
I-H
Q
H
1
o
N
Q
I-H
y
I-H
*
00
in
CM
o
00
,-
*—
rv
UJ
N
I-H
1—
l-t
to
z
UJ
in
UJ
o
O£
LU
_J
_J
O
S.X
z
ro
in
CM
0
00
0
*-
r-
0
_J
. O
in
.j
hH
O
Q
UJ
I-H
u_
hH
ft:
^
i
o
UJ
r-
^
M
Q
UJ
y
oc
UJ
i-
z
I-H
*
00
o
0
00
10
o
_J
s^.
1
CM
1
_J
O
N
O
«£
I-H
X
1-
1
sj"
•*
ro
*.
»—
1
s>-
1-
—^
CO
1
r-
1
in
u.
0
Of
UJ
E:
n
O
UJ
I-
^
Z
^
s^
o
o
in
n
«- sO
CM "
o o
00 oo
PS, in
0 0
^\
in
z
o
CQ
ft:
^
o
o
ft:
Q
s^.
X
o
l-l
r-
.
O 13 »- O O O OOO
UJ
^~
- OC
uj ft: o x o
Z Q I-H _l Z _l
UJ >- X 0 -
O UJ O X X X X
i-i — i a: r- »— i— i—
1 < UJ UJ LU LU UJ
E: E H Ji EC si E;
^-
CM
o
00
PS.
0
^ J
>-
z
o
CQ
Q^
^;
o
hH
fv/
r-
LU
in
UJ
z
^
0
z
•
_J
o
in
o
z
I-H
N
_J
s>-
0.
0
ft:
a.
o
ns
1—
Z
|
CM
1
_J
>—
X
r-
UJ
y
1
CM
s^
Z
in
CM
00
CM
O
a»
si-
o
UJ
z
n
o
I-H
— ^
1
o
1—
1
E:
i
_j
s^-
X
t—
UJ
1
z
1
^s
1
s^.
X
1—
UJ
o
fV/
o
1
X
o
1
CM
s^
1
z
*
in
CM
so
T-
o
00
in
o
UJ
Z
HH
y
»j
s^-
z
UJ
X
a.
^>
•
^.
x
i—
UJ
E:
o
ft:
o
~~t
i
LU
I-H
a:
h-
i
SO
i
o
ft:
r-
i— i
z
I-H
a
i
»^-
^
CM
O
1
Z
*
CM
CM
O
00
PS.
O
LU
Q
I-H
E:
N
Z
UJ
CQ
O
ft:
o
X
o
1
^J-
1
s*.
X
o
X
h-
UJ
y
1
Z
*
SO
ro
CD
0
00
«-
o
_J
<
1—
UJ
O
^
—I
s^-
X
r-
UJ
E:
o
UJ
o
>-
X
UJ
a
i
-------
o
z
z
0
I-H
(O
CO
E
CQ
=}
00
CM
O
O
00
.-
0
SO
si"
CM
o
00
O»
0
f*^
sO
^*
o
00
in
o
•X
CO
Os
m
*-
o
00
m
o
in
»—
CM
O
00
£;
o
•^
sO
ro
CM
o
00
00
o
CM
sO
0
o
00
CM
o
in
r^
CM
O
0>
CM
o
it
^j-
OS
»—
0
00
SO
O
•*
%J-
o
o
o
•^
Os
o
m
CM
o
0
f^
CM
*—
Q.
Os
00
o
00
SO
O
15
10
ro «-
m —
»- o
o o
oo r^
m o
o «-
•»
*—
0
o
r-
o
*-
CM
*—
CM
O
00
[^
o
Os
CM
O
o
00
_
o
000
sj" srf*
T- *-
oo
0000
in in
00
*
^j*
00
o
o
00
ro
0
* HJC
- eoooco
CM CM CM ro so
*- *- O O €3
00
*->
o
00
SO
o
* *
CLQ-
sO Os
1^. f^
00
C3 O
0000
CM CM
O O
00
00
CM
O
Os
in
o
CL
CM
in
o
o
00
CM
o
APPENDIX B. STATUS REPORTS BY CHEMICAL NAME
LATE
UJ >-
E Of
—
LU
E
in
•«
LU
Z
O
1
CM
1
Z
^
(—
o
o
in
i
x
r-
LU
E
ro
1
CM
o
N
M
O
-
X
r—
Ul
E
1-1
Q
1
sj-
(M
1
O
Z
l-l
E
X
UJ
Q
i
-
z
LU
O
I-H
Of
o
_J
X
O CO
r-
O —I
I-H «t
—I CO
o
en
o
X
a.
z
o
o
x
o.
z
o
X
o
x
a.
552
-------
* * *
I/) O.O.
1000 «»• P^^OIOOOCM
«*•«- p» OinCMCMOt
OCM »- oo>- «- •-
oo o ooooo
0000 00 p-00000000
o ^-0000
000
P*oO
o o
o o
0000
p^ p*
CM CM
00
•0
in
CM
O
CO
p-
*—
*-
o*
^
CM
O
00
p»
o
»—
0>
«*•
CM
o
00
p»
0
^*
Ov
0
CM
o
oo
r>.
p^
o
0*
o
CM
O
00
p~
p^
0
* * * * *
o 10 CM *-" (M p- in in o it
ro^o* o »- •*• o in «~
OO»-'-«-»- CM •- (SI CM O CM
oooooo o o o o o o
000000000000 00 00 00 00 00 00
CM K> fO 0 W9 <* O s9 CM
oooooo o o *• o o
10 "-
OO^- »-»-'- CM
ooooooo
I^OOOOOOOOOQOO
ooooooo
o o
o o
00 00
r-- r~
— «M
UJ
E
-
U
0.
•»
Q
n
o
**
u
l-l
o
X
h-
O
Z
o
a.
o
. a.
x
1—
UJ
E
o
f:
o
03
«n
HI
CQ
1
CM
CM
^
Q
HI
U
**
u
HI
Oi
0
a.
o
•^
UL
a.
_j
^
D-
O
ft/
O.
o
^^
£.
o
ea
HI
a
i
10
CM
,
O
HI
O
*
0
HI
Of
o
o.
o
0.
a:
o
u
X
o
en
O
X
a.
UJ
x
o
Of
o
CM
UJ
N
o
«/> —i HI
-j >- x
I >- Z O
i —i z uj
-j >- ui x ui
>- x x a. z
x H- a. HI ui
H- ui HI ca _i
uj z: aa v
HI Of O
UI UI E O Of
z z o -i ca
- -1
UJ
(O
Of
Of
Q
X
o
HI . tn
i—
•< uj
E P-
O «/>
UJ
Of.
X S
o o
a. -i
UJ X
i o
10 i
10
i
o
> X §
-I O Of
O I- (0
D_ => Hi
(0 O
vD I I
e CM CM
CM
—I -I O
a. o_ o.
o' o
o- a.
o
a.
o
a.
UJ
Of
V
O
a.
O
UJ UJ
UJ
Z
>->- O. 0.
_J -I O O
O O Of Of
a. a. o. a.
I
X
o
Of
o
CM
a.
o
Of
a.
3
t-
U
£
I
553
-------
* *
r--
(SI
o
o
790272
o
780240
o
0
o
00
in
0
CM so 00
O O «-
oo o
CM CM so
in
O
O
00
in
o
'80237
oo
o
'80239
o
o
CM
o
00
r-
o
in
o
00
in
o
in
CM
o
00
o
m
o
00
m
o
in
o
00
in
'70009C
o
CM
O
00
o .
r-CM
»- m
CM CM
O O
0000
r-o
o *-
(M
o
00
CM
o
oo
o
'90269S
'90269S
o
SO
sr
o
00
in
'70006
o
SO
0
o
o
o
SO
0
o
o
o
sO
o
0
o
Ps.
o
m
in
CM
o
00
o
UJ
APPENDIX B. STATUS REPORTS BY CHEMICAL NAME
ME
PHENOXY-
«: l
Z ro
1
-J >-
<£ X
o o
HH 0.
y~ u i
UJ 1
X CM
O «
»—
K.
UJ
z
0.
o
Oi
O_
\
o
Oi
0
_J
X
o
1
(SI
.,
UJ
z
-
X
r-
UJ
•£.
0
Qi
O
_J
X
o
1
tn
ETHYL-N'-METHYLCARBAMYLOXYMETHYLENE)OXY)1HIOACETAMIDA
y
1
m.
o
n
U
o
o
Oi
X
0
UJ
r-
y*
O
Oi
X
o
IH
to
SI
r-i
Q
0
in
UJ
o
i-i
y
0
Of
ca
r
3
t«4
O
o
tn
UJ
u-
^
y
0
X
o
E
l-l
a
o
in
YDRATE
X
Q
UJ
h-
y
O
Of
X
o
)_<
a
E
r-H
O
O
tn
in
UJ
r-
^
_j
^
K
O
i
O
tn
UJ
3
Q
I-H
(/)
UJ
0£
J
_J
o
tn
X
tn
3
U
0£
tn
_i
y.
X
r-
UJ
^
1
*
X
r-
LU
r-i
O
•k
O
t-i
U
^
o
r-i
Oi
3
U.
i
3
in
Q;
UJ
r-
tn
UJ
a.
o
Oi
a.
0
in
HH
r-i
O
•,
O
^-1
o
^
o
1— 1
Of
3
U_
_J
3
tn
K
UJ
1-
UJ
X
r-
LU
y
r-i
Q
•k
Q
^H
O
^
o
r-i
Oi
3
U.
_i
3
tn
z
r-i
a
UJ
sT
O
n
X
a.
^
fv*
O
O
X
UJ
1
u.
oc
o
o
1
z
3
m
554
-------
* *
z
o
in
in
in --
oo
CM
o
CM
o
oo
in in
CM CM
o o
o o
r- r»
-- rOX»-00
10 CM»-
o ooo
00000000
in — CM CM
o *- »- »- oooo
o
00
m
00
OOOO
o
00
sD
O
m *- »-
i-. ro o o
o «- o o
oooo
oo oo f*^ r^
r* r»- h~ r»«
CM o- r^ r-
oooo
00
t>.
CM
o
»o
o
CM
o
00
pv
CM
CM
o
00
r^
ro
ro
o
oo
r^
o
00
r»
ro
o
ON •-
CM O
O O
r»-
\o
o «-
in
in
•-in in
oo "-
oo . o
oo
•-CM in
o
UJ
o
hH
UJ
X
u
03
in
o
o.
UJ
tt
in
x
n
O
Z
UJ
0.
OL
UJ
UJ
- - o
C* OC
• z
_J UJ
-I X
< 0.
hH m
Q hH
00
o o
o o
0£ Q£
03 BQ
< <
Ott Ot^
ac
UJ
in
UJ
o
o
< uj
a. Q
O hH
ac a:
a. Q
•- x
z
UJ
X
o
X
h-
UJ
z
UJ
E
z
o
03
Ctf
X
o
>- UJ
Z E
O t
O£ CM
a. z
o
Q UJ
>- z
X hH
•a. Q
UJ
z
o
03
D£
O
X
o
X
h-
UJ
I
CM
in
z
o
I
UJ
o
UJ
z
hH Q
E hH
O
u.
UJ UJ UJ
a.
o
E
O
Oi
to
tie.
UJ
a.
o
o
03
>- X
X h-
I- UJ
UJ E
E hH
I-H O
O I
z
UJ Z
UJ
UJ
UJ
UJ
a
i
CM
UJ
UJ
CM
•i
UJ
z
o
ro
I
Z
o
N
Q
O
O
UJ
X
a.
o
o
Of
to
hH
CK
UJ
a
UJ
UJ
z
O hH hH
UJ
Z
o
z
UJ
hH
ft:
z
•4
UJ
X
a.
in
o
o.
UJ
c
x
OL
in
o
UJ
a.
hH
0£
O
O
M
Z
555
-------
I
(o
•H
6
,C 0) >U
3 (0 0)
M ,C -P
i
i
a
I
** * * *
O.O.a.0. O.
*- m*- OOO^CM
•0 f-» 00 — CM 00
O O O— «- «-
o oo oo o
000000000000
•- CM CM «
oo oo oo
, o
•H C d,
f (0 -
to
I
_) 10
>- ~
z: 10
«£ i
CO -I
UJ
£
I
UJ X
X t-
0. UJ
o >
OC X
o o
-I X
X »-
O UJ
w S
Q M
I O
•*• I
« to
ro «
^/ O3
I I
UJ UJ
Of. Of.
=> =5
in
UJ
o
UJ
o:
UJ
CJ
o
in
UJ
—I O
O O
N -
< I
to O
<* a.
UJ
>• -I O
Z -I Z
l-l UJ h-t
> 3 N
•P .
(0 *-^
,C Q)
•P ^-
00
(0
Q) C
> O
0) -H
•H +J
rH O
Q) 0)
Xi W
tX, Q)
w ID
C
0) D
•P X
(0
-P -H
n) h
5^
ro
C -H
O +J
•H C
•P ro
C -P
(I) (0
•P ^!
C D
0 n
u
«M
(0 O
4J
>O
0)
•P
W O
» +J -H C
C ^ m o
O O <0 O
-P a;
10
•-) tn-P 0
ro C -H Q)
0) CD 'U 4J
^ J3 -H ^
>i > O
^ 4J O CU
rO C Vi ft
C ro ft 3
•H ^ n
E M O
•H rO -P 0)
H ? iH
0> »O JQ
>-i 4J 0) (0
ft O -P C
C co O
fl) W
OB
c a>
o o
D (0
(0
a>
•D
•D
(0 O 0) O
(0 -rt JQ (D
556
-------
UJ
CO
E:
o
UJ O
t*. 1-H
lO
m to
<:
O
CO
>- =>
CO I/I
01
tt.
eo
eoeo
IOK)
oo
O (M
O O
CO CO
t>- f-
*- CM
oo r** CM *tf* P*- G* ^° cr* oo o CM
*- O —CMCM — — ••- CM CM CM
O OOOO O O O O O O
CO r-.oooo<7- 00 00 00 00 00 <*•
ro CMroo»ro in ro in o
D-Q-
* * * *
O. O.
r-^ r-- co o
CM
O
CO
r-
oca »- •-
OOC3OOOC5OOOOO
r^oocococooocoooeococooo
o oo
O" oooo
r^ r- r-.
•- CM CM o *- *- «- CM CM CM ro ro ro ro wa *o
o oo *- *- ooo o oo oo o o o
co oo co co
CMro^^-^D o
oooo »-
o
o.
ui
3 cy
»- uu
^ AQ
r- E
o so «o
o
z
UJ
0.
o.
»- CM
i i
NO rO
in •*
i i
f** ^
^ r^
sr co oo m
till
•- m »- oo
o o CM CM
i i i i
in in in in
•o
i
CM
m
in
«a-
<(•
m
SO
ro
i
00
l
in
557
-------
03
GISTRY NUI
UJ
0£
I/I
f^ rs> psi
^ ^ m NO
oooo
«
•e
o
00
m
o
m
CM
o
oo
f 00 CM «*•
o m «- CM CM o» «-
oo — «-'- — cv
ooooooo
1^.000000000000
o^» f^ |X fN. f*» f** f"W
'•0 W tO ^ ^ ^> C**
oooooo*a
CMCM-O
* * * *
«n o.
o> «- so
. so o m
CM O OO — — — CM O CM
O O OOOOO O O O
r* oo oo oo oo o-> r~ oo
r«. r>- i*.
. — *«• mso — r>. —
O
a.
UJ
01
3
(-
<
h-
tf)
.
0
X
0
UJ
0.
Q.
Of
LU
03
£
3
Z
(/)
fs.
i
^
0K
1
f«.
0> CM
>f m
i i
CM CM
<* Cf
r~ oo
i l
o CM
•0 -
i i
I I I I
^. 10 r*. oo
O 00 00 00
I I I I
00 00 00 «0
€*• C* 0» <*•
in r*
i i
CM sT
•a- *
i i
oo
i
558
-------
:Y NUMBER
Of.
O
UJ
Of
-
to
.in»-torxr^CMtocM
— CM — CM OCM CM CM CM »- —
OOOOOOOOOO, O
00 00 00 00 I-.00 ON ON CO 00 00
N± "CM ^*~*"00*F"*~f^lO'^>
o»-e>»-'-^oc3ooo
sor^ON^oO ^'CMCMtOstf'
l i i l i i l i i i
•- ^. ». -in
r^ ** t*v r*^ oo ON ON o o o
l i i l i l i i i i
CMtOlOtOxO s£> vO l~- I~- 00
OOOOO O O C3 C3 C3
^
e>.
o
00
CM
0
vD
1
»-
to
|
00
o
a.
r-. in un ON o CM to o to
to e> ^ es — »• «- CM CM
o oooooooo
00 00 CO oo 00 eo oo oo 00
CM CM CM IO IO •«• sS- sO 00
o oooooooo
to in
1 1
oo rv
00 CM
1 1
oo m
o --
«A ^
^ 1*
CMtOsDO^cr^ ro
CD CD CD O ^" W
OOOOO O
r^ r^ oo oo oo oo
r*"v r^ r** r*- r^ r**
CJD 00
1 1
c^ ^
r*w r>.
1 |
00 o
*- CJ
^ c^
CD CM
CD CD
oo c*
r-^ r*v
CM ^
0 0
CM C*
I |
sd- in
*~ ^
i i
CM CM
to
o
o
00
»••
0
NO
1
r»-
o
1
CM
tM
^
f^.
CM
CD
0s
r*b
»-
0
*-
t
0
S0
|
CM
CM
559
-------
LU
<0
oe.
crt
o
LU O
OC M
(O
** * *
r^-orococM o \o
omcMCM<* CM «a-
00""" " "
ooooo o o
f-00 00 00 00 00 00
r-
m
in oo
" CM
rO "00* ""CM in
CM" CM ro ro
" " O O CM
OO O O O O O O
0000 00 00 OO 00 00 G*
CM CM CM CM in in
" 00
0
D-
LU
0£
tfl
3
r-
^j
r-
•n
•
w
X
o
z
LU
O-
O.
ft/
LU
ca
y
=}
Z
rO *• m CM
CM CM CM rO
10 -c ^ »e
in o
i i
oo •*
f^* NO
1 1
VD 00
0 CM
r>. oo
w^
1
•9-
O
1
00
CM
O 0
1 1
r» CM
ro oo
i i
o ro
ro ro
_
in
i
IO
^
i
«»•
00
^
560
-------
oe.
ui
CO
z:
* * *
* *
o
HI
ft! l-l
cn
•«
o
in
in o» oo moo oo ro
o o oo rom CM —
— CM CM o— o CM
O O O OO O O
00 00 w 0000 00 00
mo«- "i
OI>.CM OCMCM
OO— CM CM CM
ooo ooo
r--oooo oooooo
CO
CO
=3
in
in —in —
O 00 O
0.
in o> so io in in »-
»*• «- r-s, •* «a- CM eo in
o— — CM — «-CM —
o oo o o o o o
00 0000 00 00 «0 o* 00
CM
in
0
m
0
in
0
Of
o
Q.
UJ
OS'
tft
V>
O
X
1-4
O
UJ
CO
in
<
o
m
CM
i
CO
K)
I
VD
CM
ro
00
I I
* CM
O 00
CM ro
ro CM
0> CM
"- CM
CM
*
CM
m
CM
sr
sr
CM
I
O
CM
I
ro
I-. ro
I i
— CM
O
I
oo
in
in
ro
oo
«*•
i^ c>
i i
ro in
CM vD
I I
oo o*
CM
I
00
i
ro
00
I
CM
in
CM
i
i
CM — in
o o — r^
I I I I
o f. r-. in
r»- »o
CM «-
i
in
o.
o_
561
-------
>~
»-
en
1-4
O
LU
ryx
-
03
co
i—
o
o.
LU
CO
t-
<
h-
co
•
o
h-4
Q
UJ
CL
a.
o
z
z
0
t-H
CO
*ft
VI
»-H
y
CO
=5
to
ft/
UJ
CO
3
Z
CO
o
*
0 sOtO
in si-oo
•»— *— *—
0 00
00 0000
in in so
o o o
ON in
i i
00 0
*- m
i i
00 CM
P* 00
p» p»
*
p»
to
CM
Q
00
00
o
«*
SO
O
1
to
00
p«.
•1C
0
SO
CM
O
00
_
*-
CM
si-
*—
1
so
O
o
00
O
ON
o
o
o
o
*-
p^
sT
o
1
10
o
o
ON
NO
x^
*-
O
00
in
o
ON
1
P-
1
in
CM
o
o
0-0-
000
o o
oca
0000
CM CM
OO
to
1
r^
00
in
CM
o
o
sf
IO
o
o
00
^
o
to
1
*»
o
1
IO
^'
o
o
*
in
m
*—
o
00
r**
in
CD
ON
|
in
>o
i
ON
00
0
*—
* * *
»- inp<-
in so to
o o *-
ooo
000000
CMCM«3-
CP O O
^f
>
00
I
si-
*-
^
*-
— •
^
CM
o
00
p^
o
to
1
to
^«
1
00
o
— -
CM
*
ON SO
in CM
CM *-
O O
00 00
— sr
^" C»
»- *—
1 1
to oo
c^ ^r
i i
^* ^x
CM in
' oo --
CM PS.
*
pv
j^
^*
o
00
sO
O
CM
1
ON
to
1
SO
m
to
p»
*
»- IOOO
00 sT^
— ' OCM
O C3O
00 0000
SO CMP*
o oo
•^ in
1 1
OS O
IO ON
1 |
ON ON
0 0
— so
O »-
i
OS
to
CM
O
00
OS
O
sD
1
V-
ON
1
s^
10
OS
sT
f\i
\Ti
ON
00
CM
O
<7>
in
o
sO
1
00
to
1
00
so
o
in
(M
*V
o.
OS
00
*—
o
00
sO
o
in
i
in
to
i
&•
CM
10
in
f\.t
*M
•X
-"
CM
CM
0
00
1^
a
00
1
si-
-------
ee
ui
to
in
W
o
UJ O
Of. l-l
m
in in
* * **
in o.
00 *O — fv f*» 00
oo m i-. •- o o
o — CM OCM o
oo oo o* f*oo r>
to
* * *
o veins? CM i*. to
i — oo r^w o
• —«- o— CM
oo o
oooo oo
in i*. —— o to in r-> . 10
CM CM C^ to sD C^ sD to in
O CM O— «- — «- CM CM
in «-
CM .«OeOeOeOoO«0«OoOeO
in «- »- \o
CM
CO
in
t-
oc
o
ft.
UJ
Of
in
in
o
x
>-»
o
•z.
eo
3
in
a:
UJ
OQ
in
<
o
<«•
i
i
r*.
ro
CM
•* •-
i i
* 00
^ in
i i
CM >o
CM
i
m
i
to oo
— *•
to
i
oo
CM
i
o
I
in in
oo oo
10 !•«.
10 to
e> «a- in CM
m in m in
i i i i i i
o« in r». oo CM r*
in »• o« <* so to
i i i i i i
o» oo — — — oo
oo CM c^ «*• •* o
* c^ r% iv fv **
in
i
oo
NO
ro
I
00
ND
563
-------
UJ
CO
3
Z
I- O
•— — — CMro^vj->3-vs-v3-vi->3-inininins£>
oooooooooooooooooo<30oeoooeeooooooooooooooooo
Of
UJ
CO
o
X
H-l
O
z
UJ
a.
o.
565
-------
z
t- o
co
I-H
O
HI O
K I-H
CO
CO CO
* * * * *
* * * *
* * *
o
>-
OQ
co
O
CL
UJ
a:
CO
CQ
r>
CO
ooooooooooooooooooooooooooooo«-~-*-*-'-ooooo
0£
UJ
OQ
u to
X O
I-H
Q
I
CO
•H
E
.Q CO >O
3 id 0>
CO ^C -P
CO >( O
•H C ft
•P ft ^
C O C
•H O O
C (7i -P
o c id
^ 1 I i ^.J
id -P o
E.-i U-J
•f~l T"t
^ E C
O £ -H
• 3
CO CD
£ •
Q) 4-> ££
di X CO
-P -H
C
•H
,C
,C CD
CO
CQ
o
0) -H
•H JJ
rH O
Q) 0)
JQ CO
DJ Cl)
W ro
cp 3
•P «O
0)
-4J
£H
C -H
O 4J
•H C
•P id
C 4J
<1) CQ
C D
O co
O
CQ O
•P
O
M -H
O co
M-J 3
CO U
•H C
CQ O
id o
-P 0)
id >-i OJ
H tn-P O
-H
c
C id
E
•H
<-t
a) id
ft 0 -P C
C « 0
id ^
«o ^
•O 10
0) C C S
(0 O Q) 0
Id -H Q) ^
OQ 09 A CO
a.
Q.
566
-------
* * * *
O
Z
UJ
D- Z
>- O
»— i-t
tn
>- en
O )-H
=3 E
I- CO
3
tn
>
CO
in
t-
£*
O
O.
UJ
O
***** *
«- CM
ooooooooooooooooooooooooooooooooooooooooooooooooooooo
Q
CO
Q
UJ
X QL
•H >-
Q
LU
CL
O.
<.
X
O
m
HH
Z
O
I-H
X
O
O
«c
567
-------
************ «** *********
Ul
0-
>- o
t-
in
>- ««
O »-i
3 £
»- eo
in =>
(\|(M(M(M(M(SI(M-
a. o
a- =>
•a. i-
m
568
-------
* * * ********
* * *
UJ
a.
to
>- «/>
Q
to
CO
to
I-
o:
o
o.
LLJ
to
O
X
a.
a.
D-Q-Q-Q-CL ft, O
r» oo>-o»-insD —csiiriooo CM so CM o cr< t\i vo co xr «o »- ro •*• oo so o co o CM CM m «*• so so *- ro CM st-«- ro so r- cr. *-i
»- *- ro >*• oo ro o ca •- *- »- CM M (M CM »*• o >*• >*• m o«- »- to 10 >j- in in o r-» oo oo oo oo oo
O C3 CJ O C3'- — •- — '-(SUM O C3 O O O O O o O O O O o O o •- — — *- CM t\l CM CO (M CM M (M CSJ (M (M CM CM . r- oo oo oo oo oo co oo oo oo oo r^ r-> r-. f^ r^ r--r>. co oo ao oo co 00 oo eo oo co oo oo eo oo oo oo oo 00 oo oo 00 o o o> crv cr> r^ oo oo oo
CO
3
in
>-
H-
>-
to
z
o
H
O
u.
z
o
n
Z
UJ
o
a:
UJ
o
t—
to
UJ
z
UJ
o
o
o
e*
-------
* *
* *
* *
Ul
o. z
> o
>- in
O h-i
=3
t- tO
«n
O— — CM — — CM
CD O CD O O O O
00 CO COO 000000
ro r~» o in o r-»
oo fo >* m ^o r~
— {M \O f)
OOOOOCDCDO*---"- — — •-•-CMCMCMCM CD O «- CM
CD CD CD ^3 C3 CO C9 O O C^ CD C3 O C3 C3 CO CD CD CD ^D CD CD CD
r^ r^ oo oo oo oo oo oo oo oO oo oo oo oo oo oo oo oo oo r^ oo oo oo
UJ
o
a.
in
Of.
to
o
LLJ
X a.
n >-
o
=3
a.
a.
>-
o
tn
o;
Q.
O
O
a.
N
O
UJ
z
o
O
X
o
O
)—i
Z
o
I
o
o
UJ
M
UJ
I
UJ
in
o
a.
x
•ef
t-
•z.
UJ
c
z
o
X
UJ
CO
UJ
LLJ
LLJ
lO
O
Q,
X
LLJ
Z
UJ
£
Z
o
Oi
Z
UJ
«3C
H-
O
z:
>-
K-
n
Q
I-H
CO
O
o
o
UJ
Q
i-l
a.
LLJ
570
-------
UJ
O- Z
>- O
h-
(A
v
en
* ********** *
Q.O. 0.0.0.0.0.0. O.
ooooo^oooooooooo^oooocaooca
f^ r^> CO 00 CO CO CO 00 CO 00 00 CO 00 00 00 00 00 CO 00 CO CO 00 CO C^ ^
0«-»-'-'-«SI(M(MinOf^'-IO
•-^-ooooooooooooooooooooooo
CO
in
h-
ec
o
0.
ai
0£
tf>
=3
Of.
o
o_
til
0£
I
(O
Q
Ul
X Q-
w >-
O I-
LJ >-
O- Q
OL =>
-------
* *
UJ
a.
o
z
z
o
00000000 — — --'-'-'-•-«-'-'-
I— CD
CO
* *
in m ro eo oo in
•- in r- oo •• f«>
o o— •- CM
Q
UJ
X 0-
f^ ^*
UJ
CL
0.
O
LU
O
O
UJ
u.
u.
UJ
o
I-I
X
o
to
t—
o
Ul
u.
u.
Ul
o
l-t
X
o
UJ
Ul
z
572
-------
o
UJ
a. z
x o
O 1-4
3
t- (0
(O =>
to
>-
CO
Of.
o
OL
UJ
to
•et
f-
O
UJ
X 0-
I-H >-
Q t-
z
UJ >-
a. o
o. =>
< >-
to
****** ****** * *
CL.
*******
IT)
sDfOOOCSJ
OOO 00— •*- f «- -- *- CM CM CM CM r--r«. i
rv
o
=>
o
o
on
o.
UJ
573
-------
I
CO
•H
E
^3 to "O
3 <0 0)
co ^; +J
LU
0. Z
>- o
I- n
O 1-4
OQ
03
o:
o
a.
LJ
a:
10
Q
H-
-
i-
^-
o
zs
i—
t-t
O
t-4
X
0
^
o
>-<
c/) ^.
O
X
o
03
(0 >, O
•H C C^
.c id tu
•P Cu ^
C 0 C
•H O O
•H
C CJi-P
o c o
CO -H
•H 4J
rH O
Q) (V
ft CC
^
^i ^ O
l-i .p 0 CX
C id ft 3
•H ^l CO
•H (d -P (0
H £ iH
CD "D ^3
OH O -P C
n)
CO 0
CU CO
CO 3 id
c CD cr-
-------
UJ
CQ
3
Z
Z
O
CO
CO
ca
co
ca
co
o
a.
UJ
co
h-
- UJ
UJUJQ. Z
0-<
OGC.
OiO
0.0.
OLV:
OO
575
-------
MC 984
PHOSPHATE
C£
UJ
CQ
E
to
01
03
01
CO
Ol
o
a.
UJ
-
aot
MO
X-J
XQ£
00
I 0-
10 ft:
I O
a.
CMro
CM « ••
r~- Ol<£
r-. M Q.
CM CQ E
«- O
•• O
z
o
M
I—
<
en.
o
a.
m
o
o
i o
OM
EE
OLU
CKX
cao
i o
roo
CM 01
-LU
z
o
M
h-
<
K
o
0_
o
o
oo
EM
OE
ttLU
CQX
MO
C£
I——I
t O
sOO
-
on_z
>±
EZ
UJ
to
z
M
E
LU
o
H-
UJ
Q_
Z
-
oMZ
CM a. E
»- o
•• o
r- xft.
CMO.E
*- o
•• o
r-.LuLULua.
CMO.H-1-E
•- o
o
• 010
• too
Z —IM
ZOI-
O MM
• too
o-^z
Z-JM
< h-
• too
•tOO
•tOO
Z-JM
•tOO
Z-JM
• 01O
o -^z
• 01
I^UJD-
CMCQE
1- O
•• o
• • s*<
• to o
O--' Z
Z-JM
to
O1LU«
Ol X ^
M O CO
«
CO
CO LU CQ
COX 13
MO tO
CQ
Ol
O M M
COLUCQ
CO X 3
M O 01
ca
co
•4 I—
ZOI- ZOI-
O M M O M M
O M M O M M
C/1LUCQ OILUCQ
COXZ) 01XZD
M O CO MO CO
E E
CQ CQ
to
to
576
cmuca
oix rs
MOOl
E
ca
co
tOUJ CQ
tOX3
MO tO
CQ
3
to
O M M
Ul LU CQ
M O Ol
E
CQ
CO
O M M
ME E
tOLUca
COX:D
MO to
E
ca
O M M
MEE
01XZ3
MO tO
E
CQ
to
-------
PHOSPHATE CMC 984
PROPY
o
z
H Z
_J LU UI O
H(- (- H
o
CO
sD
O£ Z
uj o H H a:
ea H x»- t- o
E: h- oio m a.
3 - O O UI UI <
in 0:0 H _i _i o
to o i— o o H
H -0:111 o at of !E
E: HO - oo Q < H<; o
CQ >- =?O OO LUO
_iz a: H H IOH
to oo oo: aia: *:2io
h- H UJ _l LU -3 =5<£ X-4 O. =>
a. ooi— <7»uj 001 «- z
UJ fMZ" tM-J- IO •• IO3"
OS OUI>- OO>- OUI>- OO>- OO>- O T- >- OHZ>- OZ>- OH>- OO>- OO>- OIT)>- OZ>- _
OO.Z OOSZ OQZ oZZ OZZ ov^Z o E O Z o —-ZE: »-OE: »-oz: «->E: •-UJE: '-CQQ-E:
- ZOI- ZO
H OHH O H H OHH OHH O H H O H H OH H O t-l H OHH OHH OHH OHH OHH OH
z to LU ca to LJ CQ to LJJ ta touica to UJ CQ to uj CQ inLu ra to LLJ CQ to uj tnxrs inxr> inx 3 inxz) inxs in x 3 01x13 inxr> 10x3 to x ^D
o. H o in HH o in H o to H o to noto noto HO to HOin i-ioto H o in H o to HO
-------
ON NUMBER
M
CO
CO
M
E
CO
3
CO
^-
CQ
CO
h-
cx
o
CL
UJ
ex
CO
3
1-
<£
t-
co
.
UJ
X
H
Q
Z
LU
CL
CL.
-
OOZ
00 3 <£
r^ — j o.
CM LL E
o «5
•• o
• coo
o *-' z
Z—IH
<£H-
ZOH-
O H 1— 1
HEE
COLUcQ
COX3
H OcO
E
CQ
3
co
HENYL-, 0-(4-BROMO-2,5-DICHLOROPHENYL) 0-METHYL ESTER
L CORPORATION
CL
IOO
*tf" X ••
oo_ >-
ocOZ
OOO.xo.
CMO-E
0 O
.. o
• coo
O '*-' Z
Z—IH
^ h~
Z O H-
OHH
H E E
COLUCQ
COX3
HOCO
E
CQ
—i
CO
ODUCTS COMPANY
ex
CL
LU
CX E
33
H-LU
X-i
HO
EC*
H-
-JJJJ
HO.
0
Z
O3
HCO
•a-z
sS-LU ••
OZ>-
OH-Z
00 O, <
f^ ^ Ct_
CMZE
0 O
•• o
• coo
O s-y Z
Z_IM
•^ H-
ZOH-
O HH
HEE
CO LU CO
COX3
HOCO
E
CQ
^3
CO
0
z
H
CO
LU
M
CX
0
1—
-
XI-
HLL
CX ^
K— ^V
* <->
ZO
MM
—ICQ
IO '
SJ" M ••
oO>-
OHZ
00 O- <
l^- E CL
CM - LU
tf- Z ••
OUJ>-
03Z
OO— 1 <.
I1*- O CL
CMH-E
0 O
•• O
• COO
O ^* Z
Z-JM
j- z ••
o o^ CL
CMCLE;
o o
•• O
•COO
o ^^ z
Z — J M
00 IO
«3- * ••
0-r- >-
0-w/Z
00 CO <
t~- Hft.
CMCQE
o O
•• 0
•COO
O **s Z
Z-JM
C* IO
<)• *. ••
o *- ^~
0-^Z
ooco
O
Q 1
0
\Q O
0 H
* - 01
1 -J
ELU
O — J
ITlLU ••
O > }-
o>-Z
00— K
r-^oa-
CMO-E
o O
•• o
• COO
o ^~* z
Z — 1 H
*- o
ITlCsJ ••
OCQ>-
0
CM O
CTl X ••
00_>-
o coz
00 O *C
r^XQ.
CM CLE
0 0
.. o
•COO
O "^ Z
Z ' H
•a. I—
ZOH-
O H HH
HEE
CO 1JJ CQ
01X 3
H O CO
E
CO
3
CO
YL)-3-CHLORO-2,2-DIBROMOMETHYL-1-PROPYL PHOSPHATE [MC 984
L CORPORATION
Q- •<
OO
CX H
O-E
1 LU
CMX
1 O
0
ex — j
oo
i c^_)
XH
OcO
H — 1
QLU
1 >
IOIO
in - ••
0-- >-
o -^ Z
oo co •<
r-- HH CL
CM CQE
0 0
•• O
• COO
o »^z
Z ' HH
<£ H-
ZOH-
O H H
HH E E
COUJCQ
COX 3
H O CO
E
CQ
3
co
LORO-
L CORPORATION
x-o:
oo
>d- LU
ino. ••
0 O >-
0 — 1 Z
coo<
r-> >- CL
CMOE
0 O
•• 0
• CO O
O ^Z
Z ' H
<£ 1 —
ZOH-
O HH H
HEE
COLU CQ
COX3
H O CO
E
CQ
3
co
0*
Z
H
CO
_J
^
LUO
ZH
ME
XLU
0-X
CO O
o
X H-
CL
0*
_J
>- E
inz
IALU ••
o X ^~
o O- Z
00 H <£
r- a: c_
CMH-E
0 0
•• o
•COO
O ~ Z
Z-JH
<3" H-
ZOH-
O H HH
HEE
CO LU CQ
COX3
HOcO
E
CO
3
CO
578
-------
CMC 948
Ul O Of Of Of t-C£ Of Of Of Of OOf EOS UJOf _ _
CO OflO Z O O >-O O O O O ••- O t->O OO O O
O. O. MOU 0. 0-
EOf Of OfQf Of Of
LUO O OO O O
Z OfX~ EM ~ ~ Z ~ O~ ~ ~ O ~~ Q X
O COO—i O OO LUO O OO LUO OO —IO I O OO
CO I I M MCO M M —JM -M O M EM
M tOOE I- UJE UJE >-E XE UIE E XE OfO OM QfO OfO LUO O LUO MO O OO -JO O COO MO
co ••« oft- Q Q a. * a. LUQf » o >- a M of
Ul
o
M
Of
o
_J
X
r-i O
< o
z mz Qfz z z
O IOO QO O O
M CT> M >-M M M
, . . —. , — --, — OO LUO MO IO
03 O I O _IQ ZO ZO ZO UJO OO OfXO UJO _JO XO EO K)O
< CM I-H OM - M O Z M M M OM O_ M 3- IO O Q> O> CQ> Z5> O> «tM=> Z> E> Df3> O> _l> >
a. voouu r^in ooz tr«z OM «- LU CM—i 10 o ^r LU ino ^ca r^of coo CN •>
uj irtxz** ioirj«» IT»LU«» irtui** %^of** ^o.*- NDX»» sooz** ^CL.** «j^of*> S^>M»» >oo.** %oz»' so —j ••
oca>- oo>- oo>- o-o- oo>-
OCOO.Z C3«-Z OOZ OOZ owz o_IZ 0-Z o CO Z o O-Z OZZ
co eooo< ooco< ooo< 001— <£ oo_ii—^nA o*XiX !>>XO. h*MO- f^->-DL i>-OO_ r^--0- f^-LUCL, t^-OO. r^MCL r**0£Ct. I^-XCX-
a. i^o-O- r^xa. i>.xo. h>MQ. I^>-Q. r>.oa_ r~«rujo- r^j-o. r~.uja. 1^.00. r~MO_ r--oiQ- r--xo_
E CM- ZO \- ZOH- ZOt- ZO>- ZOH- ZOI- ZOI-
M OM M OMM OMM OMM OMM O M M OMM O M M O M (-1 OMM OMM OMM O M M OMM
C3 ^*H *" J^ ^-H ^ - £^ H4 f*. 2» HH £• «t* I*H £• £. HH ^*, f^, t-H j^ g^ rH £^ 2^ I-H ji. 2_ hH ^k. «^ ^*H £_ ^ I*H > _ 7^_ I^H j . 2Z I^H ^ ^_
z coui ca coLUca coLUca coLUca coLUca COLUCQ COLUCO COLU ca couica COLUCQ coLUca COLUCQ COLUCQ couJca
UJ cox 3 cox=> cox=> cox=2 cox=> co x z> coxr> cox => cox=5 cox^ coxr) coxrs cox3 coxr>
CL. M O CO I—I OCO I-H O CO MOtO MOCO M O CO M O CO HH O CO M O CO HH O CO M O CO I-H O CO I-H O CO M O CO
0-E EEEEEEE EEEEEE
-------
ft/
UJ
CO
E
Z
z
o
M
to
CO
M
E
CQ
•^
CO
}_
CO
CO
1-
of
o
0-
LU
ft/
to
^
t—
-co
X-l
>-UJ
OO
r-E ••
oo>-
o Of Z
eoca<
I^-MQ.
CMQE
0 0
.. o
• co O
O s-/ Z
Z ' M
<£ H-
ZOh-
OMM
MICE
COLU ca
COX3
MOtO
E
CO
— ^
CO
L CYCLIC DIPHOSPHATE CMC 948]
oz
1-0
MM
Of 1—
x<
t-Qf
Of O.
UJOf
o
— JM
}_ y
K-UJ
zx
UJO
o.
O — -1
UJO
zo
OM
E co
O— 1
Of LU
CO >
«- M
r^ of ••
O H— >-
O s^ Z
oOcO-oC
r^ M o.
IMCQE
o O
•• 0
• coo
O s— ' Z
Z-IM
.
X-l
t-
CM *~
r*-» ••
0 ->-
C3 ^C IZ
00 ILU <£
r**- fx tx.
^i ""3 j^
o O
•• O
•CO O
O wZ
Z-JM
*f. l~"
ZOI-
OMM
MEE
COLU en
cO X "^
MOtO
ca
-~^
CO
OCHLORIDE
Of Z
QO
>-M
Xt-
4{
UJ Of
QO
MO_
Of Of
oo
-JO
X
O —i
<£
-JO
^- h-4
Q-E
OUJ
Of X
O.O
o
CO-1
MO
oo
ZM
MtO
y ^
K> ^~
P^ X ••
O H~ ^~
OUJZ
00 E -^
r^ M O-
CM Q E
0 O
•• o
•COO
0 — Z
Z-IM
•^ t—
zo»-
OMM
t— i j^ y
coujca
CO X ~^
MO tO
E
ca
•^
CO
n
0
— Z
1 O
OM
»- t—
*- ^
1 Of
zo
oo.
0
o
to *
i ^
MO
OM
E
OUJ
MX
t-o
E-i
oo
Of O
^ HH
* 10
UJLU
!-=>
s^ -
o ^ *y
ooo
MOtO
E
ca
=3
CO
z
o
M
1—
^
ft/
O
0.
Qf
O
O
— 1
^
O
M
E
UJ
X
o
^J
o
UJO
COM
•fc ID CO
^ —1
OUJ
Q. >
inz
j** 3 ••
oo V
OZZ
r^zo_
CM=5E
0 O
.. o
• coo
O s^ Z
Z— IM
sDZ
r^ UJ ••
oO>-
ocoz
ooo<
j^v X 0.
CMO.E
0 O
•• o
• too
O s^ Z
Z-IM
^X h—
ZOI-
OMM
MEE
coLUca
CO X Z3
MOCO
E
CQ
=J
to
z
o
M
h-
- ^J
xo
oo
M
•x to to
3-1
OUJ
ft ft/ >
000
f^w X ••
00. >-
OCO Z
COCK
r^ X o.
CMQ.E
0 O
•• o
•COO
O s^ Z
Z-IM
MOCO
E
ca
-^
to
z
o
M
1-
4^
Of
0
a.
Of
o
0
— 1
^
0
M
E
UJ
X
o
— 1
0
o
M
* co
UJ
O.UJ >
Osz UJ
MUZ ••
oOUJ>-
OCOZJZ
OOO-J<
r--xoo.
CMO-I-E
0 O
o
•CO O
Os^ Z
Z-J M
< h-
zo »-
OM M
ME E
CO LU CO
COX =>
MO tO
E
CQ
*— s.
to
z
o
M
h-
^
Of
o
a.
Of
o
o
— 1
II 1 ^
QO
»-HM
Of E
OUJ
—IX
xo
o
>- _ J
xo
oo
M
•K to tO
3 '
OLD
ft ft/ >
OO
00 X ••
00. >-
OCOZ
ooo-a:
i^xo.
CMO-E
0 0
•• o
•coo
o •*/ z
Z — 1 M
MOtO
E
CQ
— s.
co
z
o
M
»-
Of
o
a.
Of
o
o
1
CO
^ '
OUJ
0- >•
<- z
003 ••
OO>-
OZZ
r^zo-
CMZJE
o o
•• o
•COO
O •*- ' Z
Z-IM
^ 1—
zo»-
O M M
i— i E E
CO LUcQ
cox rs
MOtO
E
ca
— ^
to
LU
h-
— ^
t-
1-1
1-
co
z
M
E
LU
—1
o
t-
LU
0.
z
o
l-l
-JOf
LULU
•—i y
U-<
CM
00 -» ••
OLU>-
otOZ
OOLU<£
f^- M O.
fMQE
0 0
.. o
• too
O s-/ Z
Z— IM
»-
M
»-
CO
z
l-l
E
UJ
_J
o
Of
f-
LU
a.
to
-IZ
M -
OQZ
f-Of O_
CMOE
0 O
.. o
• too
O w Z
Z—IH-I
<£»-
z o >—
O M M
MEE
COLU CQ
coxrs
MO CO
E
ca
3
co
580
-------
MC 948
UJ
CO
z
o
CO
CO
CO
CO
CO
CO
I—
ta
o
a.
ui
co
co
ui
X
n
Q
Z
Ul
o.
O_
UJ
Z
o
COM
Ull-
IflZ r-iZ
too too
CM-I IO M
MO£
I—O
XO
oo
0.1-H
« UJtO
UIUJ
xo
zo
-XQ.
o
o
oQ>-
0>-Z
00—K
r^OQ-
100-E
o o
•• o
OCM >-
00 CO <
I^M a.
toco E
O O
•• o
OOJ>-
OOZ
00-K
r--xa.
K)OE
O O
•• o
Ofti>-
OOZ
rOOE
o O
•• o
e>O>-
OZZ
00 UK
I--.XCL.
(OO.E
O O
•• o
OOZ
ooa:<
OOO>-
K)O
o
o
•COO
•COO
• coo
Ov/Z
•COO
Z -JM
•COO
o ^/ z
Z-IM
•COO
•COO
•COO
Z—IM Z—IM Z—IM
ZOI-
O M I-H
MEE
CO UJCQ
cox=>
MO CO
CO
CO
zot- zoi-
O I-H M O M I-H
zo>-
O M M
CO UJCQ CO UJ CQ
COX=3 COX=)
MOCO MOCO
E E
CO CQ
CO
CO
CO UJCQ
COXI3
MOCO
CQ
co
ZOh-
OMM
MEE
couica
MOCO
CQ
CO
ZOH-
O M M
MEE
couica
COXZ3
MOCO
E
CQ
CO
ZOh-
OM M
MEE
CO LU CQ
COXI3
MOCO
E
CQ
CO
ZOh-
O M M
MEE
CO UJ CQ
coxn
MOCO
E
CQ
CO
581
-------
It- <*•
eo eo
o* c»
O O
E E
i~i i—i
to
E
O
w
to
to
M
E
CO
3
to
CO
to
o
a.
ui
to
3
I-
I-
tO
UJ
X zoi- zoi- zoi- zo>- zoi- zoi- zoi- zo i- zoi- zoi- zoi- zo i- zdi- zoi-
W OHHW OWhH O I-H M OWW OHM O W W O W W O l-l M OMM O M M OWW OW M O W M Own
0 MEE MEE WEE MEE MEE 1-1E E WEE wE E WEE wEE wEE wE E WEE wEE
Z to UJ« m UJ CQ co uj« co UJ CQ co lu (a en UJ CQ co UJ CQ co UJ ca co UJ CQ co UJ ra co UJ M eo UJ ca touJca co LU ca
Ul IOX3 tOX3 (0X3 tOX3 CO X 3 tO X 3 tO X 3 tO X 3 lO X 3 CO X 3 tO X 3 tO X 3 CO X 3 IO X 3
a. woto MOto woto woto woto woco woto wo to woto MOIO MOIO MO co MOCO MOCO
Q.EEEEEEEE EEEE EE
^pocacocQcocococo cacacaca caco
33333333 3333 33
tOtOlOtOlOlOtOtO CO CO CO CO CO CO
582
-------
LU
M
z:
z
o
M
£
CQ
CO
ca
to
OC.
O
0-
LU
oc.
CO
CO
LU
X
M
a
z
LU
a.
D_
•a.
583
-------
PHOSPHATE CMC 984
-PROPY
UJ
CQ
E
Z
o
M
CO
CO
M
E
CO
3
CO
to
I-
o
a.
UJ
co
Z
o
o
a.
Qf
o
o
o
M
E
LU
X
o
o
UJO
COM
OUJ
OZZ
o O
•• o
o
LUZ
Z M
_JZ
oo
Z-J
OLUZ
OOM-
O < Z
eOX<
Is- uj a.
XZZ-I
OLUUJUJ
0- 0-Q.>
00-100
ro >-_i_i ••
»- ooo>-
o N >- >- Z
OOZOO<
i-» LUM M a.
0
o
o
X
M
Q
Z
LU
a.
a.
•coo
zoi-
O MM
MEE
CO LU CQ
COX3
MO CO
E
CO
•CO O
Z-JM
• coo
• too
Z —IM
• too
Z —I M
ZOr-
O M 1-1
O M M
ZOr-
O M M
CO LU CO
toxrs
MOcO
E
CO
to
CO LUCQ
COX3
M O tO
E
ro
co
tO LU CQ
OMM
MEE
tOLUCQ
• too
Z-JM
•ft. (—
ZOI—
OMM
MEE
tO LU CQ
• too
O—-Z
• too
• too
coo
MOCO
E
CQ
3
to
MO to
E
CQ
CO
M O tO
E
CQ
OMM
MEE
CO LUCQ
CO X3
MOCO
E
CQ
CO
O M M
MEE
lOLUcQ
COX3
MO CO
E
CQ
to
O
O
o
Z
M
E
CQ
584
-------
00 (ft
•j- a
ff« Z
3
o o
£ OL
•-• E
o
LU O
- r* oc z 10
H- O 00 Hi <
to o o £
LU _J ~ Z
z oz z oz in in < o o
o zo o i-o o o z z oc
M OH M HIHI HI HI •« M <
H- EH- H- OtSH- H- H- HI Q LU
oc o o< <
a: _>c^ o: t-oc < < z _i ui
03 <-iO O OO O >-O _l _l M O Of O
E co a. o. za. a. oia. a. a. ^ z M
3 H- CkJ QJ - ^ < < LU •
O OO -< a-< ~co zco z: z E E Q
CO D. OO O *~ O OO ^>O I CM—I O_J O —l 3 Z O >- •
co co n -z: a: i NO 0:0 ui o a. of z HILU
-lUJ LULU MUJ H-LU OO _J HI < HI H-—I HI E HI O Q HI
W Of
5 —I-I —IO ZO -4O QO LUO XOLUv^UJ OLU -IO O LU O Z LU LUH-
CO -JO >- LU —l Q_ O—1Q X KX _J HI X LU H- H- CO
t->Ot Z_i X-l - H-H- LUO O.O XO ZO LUO - H- OC -I 3 H- CK E H- £ Q
« COLU 3:0 coo H-O «ro zo H-noi-ta: x<* to E HI X HI Q.
o =DCO a;> o> o> -J> ca> LULULUZOX - inn MIZZZLU r~.z OOLU O-HI>-LU ooz: »•
LU xr—i" -i" - —Q>- "-O- —<>- -LU>- *-H->- •r-OC-i->0=3>- '-OO- —0>- '-OH-- — Z HI >-
OttZ 0>-Z OQfZ OO£Z OXZ O^Z OO>->-Q:LLZ OOZ OttZ OH-LUXZ OLUOZ OHIHIHIZ
co —-Lua. t^MQ. r^na. r-> x H-H->-:s a. r^xo. r^iua. F-^OMLUQ. r^ac^a. r^oooa.
i- ina.5: IOCL£: irii-z: mi-iE inaz: mcoz: m o LU LU x co j-: inoz: ma-E ITI O
• o^z o •^ z o ^ z ov->z o-^z o ^ z o^ z o^z o-^z o*^ z o^^ z o^ z
LU Z—li-l Z—li-l Z-JM Z-Jl-l Z-JM Z-IM Z-l HI Z-IHI Z-JHI Z-l HI Z-J HI Z_l Hi
COX3 CO X =) CO X 3 CO X 3 CO X 3 COX O COX 3 IO X 3
D- HI O CO I-H O CO H) O CO HI O CO Ht O CO HI O CO Hi O CO HI O CO HI O CO HI O CO HI O CO HI O «/>
Q-EEEEEEE EEE E E
•
-------
ON NUMBER
hH
CO
CO
hH
z:
03
3
to
s>-
CQ
to
(—
a:
o
Q.
LU
fy
to
3
f-
^
K-
CO
•
UJ
X
hH
O
Z
LU
Q.
D_
^
RATED
o
0-
O£
O
0
z
hH
to
UJ
_J
3
0
at
LU
X
CM
m*- ••
-•*>-
o-- Z
oo 1 <
r^ o£ o~
moz:
0 O
.. o
• to o
O **-" Z
Z _JM
: z:
to ui ro
COX 3
M OCO
x:
CQ
—}
CO
0-2,4-DIMETHYL
MISSION
ZCQ
M3
ZItO
-
of-Z
ooz<
r*^ LU o_
ina.y.
0 O
.. o
•coo
O xv Z
Z ' M
< h-
zot-
O hH hH
hn y y
CO LU CQ
CO X 3
M O CO
z:
ca
3
CO
RATED
o
a.
o£
1 O
oo
0£Z
OM
_J
X CO
OUJ
_J
* 3
QO
M fV
OLU
ft -tr ~r
%3"
ino ••
^" M >-
OKZ
00 UJ<
r^oo-
m-stz:
o O
., o
•CO O
O xv Z
Z -J i-i
<£ h-
z 01-
O »-H 1— 1
i-H y y
to UJ ca
CO X 3
M OCO
z:
CQ
3
co
Z
-LU
in y
m -
O-l
hH —1
CUM
O '
* -1
X M
O-J
LU
sO — J
in x ••
*"" O >-
orsiz
ooz >-H
O otf
"4
^-
O-J
M —1
ZM
O— 1
•1C C£
3M
Z— 1
Z
Z-JM
«£ ^_
ZOI-
O 1— 1 hH
hH y_ y
CO LUCQ
COX3
MO CO
CQ
3
CO
,3TETRAFLUOROPROPYL-1-AMIDE)-4-TRIFLUOROMETHYL-
MISSION
fOCQ
-3
CM CO
•*
CM-I
ZM
1 1-
CMZ
LU
-Q
LJJt-H
4C ZU.
MZ
-JO
COMO
&\ Z
in ^ ••
»- Q ^.
<=>a:z
oot—<
r^- *— < Q-
inzz:
o O
•• O
• coo
O s-i* Z
Z ' hH
- O
OZ
sD I-H ••
^~ f\J J*-
0 <[ Z
00 Q£ <
r^ x Q-
in c. ^
0 0
•• o
• COO
O x-» Z
Z ' hH
-
o- Z
ooz-a:
t-^ »o_
inzs:
o O
•• 0
•COO
O s-* Z
Z ' hH
^ 1 —
ZOh-
OI-H M
hn y 3^
CO LU CQ
COX 3
MO fl,.
inzz:
o O
•• o
•COO
Ox-'Z
Z-IM
•dh-
ZOH-
OMhH
HH y y.
COLUCQ
COX3
MOtO
s:
CQ
3
CO
586
-------
X «* E
o eo i
z c* —
i- i
111 O —I
E E >-
>- •-• 'x.
•z. o
M UJ CQ
•> t- of
_l < - x o
x n- >-
i- X
ui o o
EX Z
I O. I—
«- UJ
i >; ?
>- O. CM
Z O f
O Of I
CQ Q- tO
Of I -J Z
- - —I O I-
X >- Of I
O O X O. O Ul
M X t- I I Q
»- h- UJ •- _J _l l-l
- >- Of
Of E O >- Z Z O
O I E X t- O —I
O. CM O O Ul Of Z
Of I Of Of E >- O
O Z CQ Q I O. O
O M >- O O Of
ox of a
_l Ul I I •> Q >-
•a. z co 10 ui >- z
O M - I Z X
M Q CM ^ M «S «
E Z MZ I Z -IZ OZ OfZ I Z Z
z ui o EO oo >-o MO i-o _io o
O X M -M M
M OH- OfH- Ot- t-l- - h- -Q. i a. ED- -jo. —10. MO. < >-CL
3 E a. _io -J uiof zof roof oof >-of >-of ofQf of Xof
Z O Of MZ < OO 1-0 I O OfO XO XO I-O O OO
o o ZM of MO uio «o coo i-o i-o i o a. zo
z z a-i M_I >-_j to _i E-I E-I i _i o ui_i
M < ZOf >-«n M >-< Q< O-< ME IE - CO CO-I to _l Of ZO >-M K--o - ZOf ZM OfM ZM ->- OfM
in tn> I > of > cO> to> IH> ME >
0- r-v Ul Ul eo o» —i oUI »- of CM o toro .X" r^x«- r»-X" r^<" rN._i" P^UI«
o-Z OZZ 0-MQ. r>.xflL r-»xo. i^xo. r%i—a. r^zo.
i- inoo—izNE IOOE ITIZE ina.E «oi—E voi— E NOCOE oa.E
< o ooooooooooooooooooooooooo
f_ .. o •• O •• O » O •• O •• O •• O •• O •• O •• O •• O •• O •• O
tO •• ^ •• ^^ •• '"* •• ^ •• *"* •• ''^ •• ^% •• ^^ •• '^ •• *"* •• ^^ •• <^N " ^^
• to o • tn o • to o •
-------
«0
OS
o
L_I i
(SI
LU I
I- >-
< X
X O
a. i-
IO UJ
o o
i-i x - ~1
OO. >-
E o x
1-J Of H-
Q_ UJ
UJ ^ E
< I 10
X -1 I
o. >- ^
CO X -I
~ O I- >-
_J X UJ I
r-i >- O- E CM
O X W O I
«0 H- O E -J
«o UJ o o
>- O Of Of N
E X w CO LU <
U- O -I i-l I- w
>-> of o Q too
Q >- I Ul <
>- O (M IH w
« X r-i Of X
>- I -I CM < H- I-
Z Z Z XZ Z CM Z OZ Z I Z ITtZ Z I Z
O O O OO O *-• O I— O O OO IOO » O sl-O
M I-l IH ZW I-l CM W WW W OfW CT» W _J M « H
t- »- i- mi- i— i i- ofi- t- 01— i- >- i- tot—
Of < - of i-of of xof Eof o eg «- of
CO O O O OO O OL O >-O O OO t_iO Of I O I O
JT o. mo. Q_ J;Q_ Q_ o a. ofa. a. ID. a. 0.00. — IQ_
3 of i-of of oaf ot: a: a: UIK i o: toot: a: 00:0; >-Q£
z o - O h-O Of UJO ~ O LUO O — I O => O
Z N i-l XZOZ-IQ O£X CO
O — ' Z — I —I —1 Of— I —I O — I LU — 1 —I LU_J >-_! M_l OQO—I I _J
M •< UI«S < IH I-HH IH IH \OIH -OIH _l I-H «t UJ - E XMH-Z: O, E UJ E rOOE ^E
E UJ UJ UJ UJ -3-LU _)LU I OLD I- UJ LU Q Z LU I LU Z UJ -lETLU I UJ
(O x -ix x x -T: ox CMofx zx X|H OL -OfO O >- -03 -
OLU—I >-_l _l _i cO_l X— I -JO— I O— I LULUO— I— I Of— 1 Z —I Q IH _ I LU — I
>- IHIHO -JO O - BOO lOO OlOO ZO UJUJOfVO — 1O XO O I O OO
O- -.IH OIH IH IH O O IH X IH O- IH < CM IH Z IH
«n *_ii-io * iuin DC * CM en * totn * -itMtn -KHio aazocn * om am -m -K t-nto
i- xz_i z_i <_i >H »_i o— i o —i o_j -"Koof-i IH-I z:_i o«-_ i Q-J
Of OLULU LUtU OLU Z ^- LU K LU -LU Of UJ I- 1- Of O LU O LU O LU IH LU IH LU
O Q-> _l> O. > LU=> > 0> LU_I> OQ> Q.ZZO-I> I > Of> COOf - >• — I >
a. o_io *- >- >UJUJ_IX OKI «- co CM OLU 100
LU CO >-—"" COOL- 003" «0>H" COLU" OOM" » LU Z •• COOf" OOO.O.XO" ON-- CMH» O^XZ" tMSJ ••
Of »-OO>- »-OV «-O>- »-Of>- "-Z>- •-<>• «-_i-<>- «-!->- '-OOOO- •"-•*->- »-Q>- >- O- -
ON>-Z OOfZ OZZ OOZ oQ_Z C3<^Z o— I— IO-Z ox^Z 0>-Z otOO-Z OCIZ
tn eozo< goa-«c «ov-xuJLUo_ r-.no. r~oo_ r^xoitt-
H- sDCQClZ: sCOE vOZ)E sCOE «C LU E «O t— E so LU Q- E >O M E so O O X 0. E so CO E SOCLE SOO.O.E
#• ^^ »* ^N •• ^% •• r\ •* ^^
• «/> o -»no 'CD - z o^z os^z o^ z o^z
UJ Z — ' IH Z — I IH Z — I M Z — I M Z — I IH Z — IH Z— I IH Z — 1 IH Z— I IH Z — J IH Z — I IH Z— I IH
X ZO I- ZO^ ZOI- ZOI- ZOH- ZOI— ZO I- ZOH- ZO t- Z O I- ZOI- ZO I-
IH OIH IH OWIH OIHIH OMIH O IH IH O IH IH OIH IH O IH IH OIH IH O IH IH O >-< H OIH M O MIH
Q HE E IHES: wEE WEE wEE wEE wE E WEE WE E wEE wEE wE E wEE
Z tox=) «nx=) toxr> tox=> tnxs cox 3 toxu «nx 3 tox=j 10x3 cox 3 coxr>
O. wO CO woco no CO wOcn woco wOcO wo (O wOtO wo CO wOcO woco wo co no CO
O.E EEEEEE EE EEE E
=>3 3=3 =J=J=> 3
«n totoiocotoco coco cococo co
588
-------
o
N
Z
LU
CQ
I ~ O
in o of
I Q O
-I M -I
>- E x
X ~ O
K- _I Of. _l I
LU >- O >- E
z: of x i ^
i o a. CM in
10 x to i i
i a. o _i -i
~ CO X O >-
_i o a. N x
>- x o «t i-
i a. M M LU
CM o x o E
I M I- «C I
_i x >- M 10 i
O I- X X I -J
N I O H- ^ >-
«n >- x i —i x
M x (- * >- H-
Q O LU - I LU
«C X E K> CM E
M h- I «. I <-\ I
X LU _l »- -J —I IO
I- E >- I O >- I
I I Z -J N Z >-
•S- -I M >- •« LU X
« >. > I— M X O
ro Z -I 3 O O. X
- M >- CQ x i M as UJ
I _l r~ Ir- X O E
-I >- LU I I— _J
>- x E »n p x _i
i- i- i ~ •* o >-
3 UJ «~ IO « ME
CQZ EZ I Z I Z Z IOZ Z Z QZ -M >- M M 1- M I M M ^ l-l Of M M
II- I r- Zl- Xh- I- I H- Oh- I- -t- - Of CQ Of LU Of - Of OOf Of O w Of I Of Of
CQ I O ZO OfO EO O »—O —IO O M I O *- O O
E «- O. OO. Of Of
Z -O OfO >-O I O O I O MO O tOOf -JO —IO O
LUO - O >-O O
Z Z O O >• II MO. X Z
M I < «< LU«I K- O LU < X - M EM "" M I M - NO ZO I O MO I O CMO QO OfO O I O QO O
CQ OO I O I O OO Q 10 O I O oO
Q M -M -M I M -M Z M "d" M _l M LU Z I M ^M O M
tO *McO *LUtO -X LUin #CQtO -K»d-lO *MtO -K-tO .fcXtO t-O -KZcO -to -K--10
h- E —J Z —I Z —I -—i --J Q—J •-—J O-J Q>- Q> I > => —1> -> E> >-=3 Ml
D_ «J- >- in M >D M t>-»- CO - O> O O LU »- I CMX IO _J
LU O^ O •• CJ^ E •• ^ E •• *^ •' <^ ' •• ON N •• CD Z •• O —J •• CD H- •• O O
Of *-Z>- — - *-•«>- «- ->- *-0>- »-- CMLU>- CM>-V CMLU>- CM N >-
o-Z
CO 001— H M OMM O I-H I-H O M M O M l-l O M M O M M O M M O I-H M OMM O M I-H O M I-H OMM OMI
Z in UJ rQ tOLUcQ tOLUCQ COLUCQ tOLUcq tOLUcQ tOLUcQ tOLUCQ
LU COX3 tOX3 tOX3 tO X 3 tO X 3 tO X 3 tO X 3
D. MOtO MOtO MOcO MOcO MOtO MOtO MOtO
O.EEEEEEE
3333333
COcOtOCOtOtOtOtOcOcO
589
-------
Ul QX
£ U
5 *-
S IS
2 >f
UJ i
O H
< UJ
P E
OXY
£ 3=
z O.
ui 5
d <*
>: o
X _l ^
fr. x m
UJ O M
E M m
b Q >-
X I -J
o in o
—j •> of
> -J CM Q
5 > i >
< z ox
BO O ^ E
of « in o E
i < of z of o
o o < o at of
z of _iz o ta i z z LUZ
o o >-o M ui of • ui 4-0 o o
M _» XM Of h- - >-io in in i o. oo. _in_
3 I Of UJ ZOf Z Z X X-J Z UJ -JOf OfOf •oCOf
Z OO H- >- I O < MO < M O >-O OO OfO
OfO I Z _IO O O. OO Of ZO -JO H-O
z o oo in< >- z inE UJ MM E 3 ui x 3
o _j_i -in_jo. x_i - H-E z 3 o x-i o_i LU_J
M x< r-.-J>-E H-< EO oui 10z -acai o LU to o_-ZO UIO —IM M—I «< EX M _l UJ O IOO
-H- H-O (MO. oo H-O of -M i M M
M XE -LUX I E Z< OOf I E OfO -J< Of OE OE UJ E
E UIUI CMXO I >• Ul UlOf -O < Of Ul Of H- UJ _l M Ul E Ul Z LU
BO xx z O.M< o ui => - ZO M XOUJUI E OO I O OO
MM —IMH-- oof -~—i of z>o uiof —KOLL xin * >in 41 oin
H- <_j uiz i ZMS z_i _ix ui "-ui oz oax -jui -LU 3< -m y-^ CMUI x
o. oo LU ozo-oo—i o>- --o CMLU »o LU - CMOfOfZoaO>- (MH-X- CM >->- CM O >- CM <( >- CM -I >- CM LU >- CM Ul >- CM E Z 3 >- CM O. >- CM - (MOV
o_iz oooui>->-z outz oxz oofz OQ.Z oo.z ooaz ooz o z oinz oa.z OEZ
in OOO< CO—I—ItO—I—imo -too >ino *mo -mo • o ino
UJ Z-IM Z-l M Z—IM Z-JM Z-JM Z—IM Z—IM Z—I M Z -I M Z-I M Z-I M Z -J M Z —IM
X ZOH- ZO H- ZOH- ZOH- ZOh- ZOH- ZOH- ZOH- ZOH- ZO H- ZOH- ZOH- ZOH-
M OMM OM M OMM O l-l HI OMM OMM OMM OMM OMM OM M OMM OMM OMM
z couica inui oa tnuioa inutca totuoa inuioa inuica inuico inuico inui oa inujea inixioa inuieo
LU in x 3 inx 3 in x 3 inx3
-------
OPHOSPHORAMIDO
OXY
VINYMETHOX
ME
HOXYCARBONY
YLV
N-2
or
UJ
CQ
z:
i.
o
M
CO
co
I—I
z:
CQ
co
ca
CO
o
Q.
LU
c*
CO
UJ
X
o
•z
0.
a.
•COO
•a.\-
z o t—
OMM
co LU en
coxrs
MOCO
o
z
z:
CO
591
-------
LU
t-
<
O
M
X
h-
O (-
-I O
o a >• - I >- I- • ^ . ZM
Of Z 0. Z -10 Z o« >-Z O LUX
UJ < tO O
ca a. o BL u. M (O on _i- O tt O Z eOOi O >- I
-i z 'x* o E o i o QJ _iz o
z -i >- E in«: 03 a. uj <*M oo. =j M< E
o < x 3 z £0. 0:0 a: - z LUI- uio: o on. o
I-H oh- LU o £ LUO - O. QLU M DC. Z
E O I • t- O£ «n_i <_J Q >-ZH- —IDS I Q LU_J U-_i H- n
BQ l-l OO I LU O < • O-O > M =>< MM LU
3 I— -Z I -JO. Q- LUO O OQ£ M I— LU O XO (M OQ Q Oi Of O \~ -
- a: I-M z LU a: uino. t- -oe: MLU < i JE:
o i >-xtn o _ >-< _i * xi—a. o -< I-LUM 3X * ZE Q h-l- -LU « oiZ: < Cd to
O XM LUjr-J z O O M MZ LULU • QZ LUZ LUQ -M
in * in i-a £: i -i o LU a: LULL xo I-H-M M< zo -JLL t-z »-0!:
t- z uio i MM x Z3 a. LU_J OM o—i OM z . » . - '-E
o —JO oa: -Q. LU txa z o uo LULUUI o ui=> uio din - >o i>-(- ooz c^zz oo •- x (MZ IOLU >s- -
LU roo- loo- -« sr_i- vrz- >*-LU» ^a-•GC- «M-J>- - CMLU>- CM in >- (M LU >- (M LU >- CM -I >- - CM _1 >- (M O >- (M E >- (M OS >- (M Z >-
o_IZ OXZ CXD-Z ONZ 0>-Z o ^ Z o 3> Z o>-Z OEEZ o >- Z o I-Z o Z o LU Z
in OOLU«C OOO< 00»-O=>< 000r!< OOLU«
3 r-*=>a. r>. i a. r-.r3QiCL r^uia. r^oo. I*.MO_ r^oo. r^»-o. r—i—10. r^oo. r-.oo_ r-*tea_ r-^zo.
l- o>U_E tMnE ooQU-E o»«OE OQ.E o*ZE oinE oLUE OO.O.E o<«E o < z: oinE o M z:
< OOOOO OOO'-OOO'-O'-O'- O'-O'-O'-O'-O'-O
h- .. o •• O O •• O •• O •• O « O •• O O •• O » O •• O •• O •• O
\f) •• ^% •• ^% •• ^^ •• ^^ •• ^% •• ^% •• ^^ •• ^N •* ^^ •• ^^ •• ^^ •* ^\ •• ^% •• ^N
• ^Z O^Z O~ Z O^Z OwZ O^-Z Ov^Z O^Z O'-' Z O^Z O^Z OwZ O^-Z O^Z
LU Z-JM Z-JHH Z-J M Z-IM Z-JM Z-IM Z-I M Z-I M Z-I M Z-I M Z-I M Z —I M Z -J M Z-I M
X ZOI- ZOI- ZO I- ZOf- ZOI- ZOh- ZOI- ZOI- ZO h- ZOI- ZOI- ZOI- ZO»- ZOI-
M OMM OMM OM M OMM OMM OMM OMM OMM OM M OMM OMM OMM OMM OMM
O MHZ: MEE ME E MEE MEE MEE MEE MEE ME E MEE ME*: MEE MEE MEE
z muJcQ mujtfi inui ca tnuica muica muica inuica muica inui ca coiua tnuica muJca inuica IOLUCQ
a. Mo«n MOW) MO MOOI MOin MOin MOin MOUI MO in MOin Mom MOcn MOin MOin
O-EEE EEEEEE EEEEE
< to a CQ to co ca ca co co ca co co ca ca
333 333333 33333
inmm intninininin tn
-------
DC
UJ
I-
01
UJ *"N
o
-I M
>- <
H- ->
3 H- >-
CO -J I
I < IO
z 01 i
—I
O 3
o£ <•>(-<
o < to
_j z 01
o < <
>- < >- M h- I
Oi Z I- Z O OdZ O O
UJ ^ - X
Z QM I ZO «if O >- Of. EZ O
UJt- —I UJ - Z —IO - I
z oi- >-i M -I - IM CM O ^—O —I -UJ *t >-»-O 3
E MO O • I—ZO CMI— I— <—I XQ O< >O Q. O£O UJcQ -JO —I I -M Z-*£ 3Z< Of. M
Oi< —IX UJ-JQ i-l V OI EO CM< X 01 X \-Ot
>- OO V I - O1OM OO Q- —tot O OZ •» I UJ
CO O ZCMO UJUJ—I --O1 3 ZUJ —I—IQi M OI »X
0- inoi vo>- f\l eo_jM CAUJ o—i »- oi CMO iouj ^>->- r^ » ozz*>
Qi CMO>- C\JUJDJOi>- MOiMX - CMOiX CMM>- CM —I >- t\l>->- C\ll-t->- CMZ>- - CMMM>- CMUJV
o I Z OILUUJZ o h-Z o I Z 03Z Oh-Z o >-Z o I-Z o UJ UJ Z O< Z o Oi Qi Z OOOZ oNZ
OI 00 Z ^ CO 0- X 0. *t CO *^ * ^ cO l~* "*t CO ^ <£ CO Oi ^C 00 Q£ •'t 00 UJ ^ 00 E E ^ ^* "i* ^ CN X- >- —I OMM OMM OMM O M I—I OM M O M I—* OM I—I OI—* M OMM
O MEE ME E ME E MEE MEE MEE MEE MEE ME E MEE ME E ME E MEE
Z O1LUCQ O1UJ CO O1UJ CO 01 UJ CO OI UJ CO 01 UJ CO OI UJ CO OIUJCQ 01 UJ CO OI UJ CO O1UJ CO O1UJ CO tOUJca
UJ 01X3 01X 3 01X 3 01X3 OI X 3 01X3 OI X 3 OI X 3 OI X 3 OI X 3 OI X 3 OI X 3 O5 X 3
O- MOOI MO OI MO OI MOOI MOOI MOtO MOOI MOOI MO OI MOOI MO OI MO O1 MOOI
0-EE E EEEEEE EE E E
<£COCO CO CQCOCO(£CQCO CQcQ CO CO
33 3 333333 33 3 3
O1O1 OI O1O1O1O1O1O1 O1O1 OI OI
593
-------
LU
CO
z:
•x.
o
to
to
z:
CO
CQ
to
O
CL
LU
c*
to
Q
LU
ex.
o
0_
C£
o
O
I 'Z.
On
Oi
o to
—ILU
X -I
CL
z:
o
o
•<
o
I O
-
OCL Z
OO
I O
IOIO
CMZ>-
-LU
(M-
OCLZ
COMPANY
LU
_J
O
LU
Q.
tO
CL
CL
I-^LU
r-z ••
CMLU>-
ONZ
z
o
as
o
CL
O
O
CONOCO
O
o
LUn
OO
OLUIDINE
ANA
ND
Q<
ZLU
LUO
LU I
XZ
ZLU
O cQ
eo<
Ol-
nz
H-O
LUO
CM
O
>-
•Z
oo-i ••
CMLU>-
OZIZ
- o_z:
o o
•• O
l~- LUCL
"- xz;
o o
r^LUCL
roeoz:
o o
•• O
o
o
•a-oz:
O O
•• o
o
o
LU
I-Z
LU-
VOO
eo
r~ LU CL
o o
•• O
O
o
X
z
LU
CL
CL
<
• too
Z in
• too
Z_Jn
CO
CO
O 1-1 n
to LU cQ
co xra
n o to
CQ
•=>
CO
• COO
o n n o i—i n
to LU co
COXZJ
no to
z:
CO
13
to
tO LUCQ
COX=3
noto
z:
CQ
CO
594
-------
CO
Oi
UJ
ta
z
o
tO
CO
=>
oa
O
O.
UJ
Oi
1UZ
do
Mt-l
UJ
a:
az
>-o
xn
o<
O
a.
te
O
O
UJ
zx
UJO
xo
oa.
00
HO
_IUJ
ox
oo o »
CMO>-
OOZ
i-x
(HI—
ZLU
COO
COX "
CJQ->-
OCOZ
xn.
oaf
1-1 O
0.0
UJ
i X
<0
0£
_JUJ
OX
z
o
o
Q.
ex
UJO
I-O
O.M
too
o
X_l
D.M
oa
00 UJ ••
CMX>-
OO.Z
-
o
o
UJ
Q
UJ
a.
a.
Z-IM
•«Cr-
zot-
OwZ
Z-JHI
zoi-
OH1H
inuJco cOUJeo
MOCO
E
to
HOtO
CO
OI-HHH
(/>LU(£)
COX3
tOLJCQ
BO
3
(O
E
03
3
CO
e •
JQ CO "O
3 id fl)
co f 4)
to >, o
•H c a
rC id fl)
-P Q* b
E
C 0 C
•HOC
•H
C Oi-P
o c id
4J 4J p
0 fl> CO
fl) -H 4J X!
•H .p C 3
rH U O CO
0) 0) U
.fl CC «M
CO 0
< rl -P
CU H fl)
3 rC M
H Oi -P O
fO C ^^
> -H CU
fl) fl) 'O -P
^5 -H ^
>i > Q
tl +J O ft
Id fi rl Ol
fi id a 3
•H M CO
E ^ O
•H Id -P 0)
H^ ^1
f rH
fl) *O .Q
rl 4J 0) Id
a, o -P c
fi CO 0
id a) co
co 3 id
C O O* W
0 0 fl) rl
•O rl
•O CO
0) fi fi ^
co O fl) 0 ••
id *H (u >fi fTi
CQ CO .Q CO EH
0
* £
CO
4-) !*4
>-i 0) O
C ^ >
•H id
"O O4 CO
C fl) -H
fl) rl rC
cu a-p
U
CO
VO
CM
O
ffv
O
O
w
CO
u
VO
VO
CM
o
I
I
CO
CO
o
fl)
id
o
•H
fl)
rH
O
fl)
3
•O
0)
O
4J
•O CO
fl) -p
V-i C
0) 0)
•C E
•H 3
CO O
c o
0 "C
o
0) fl)
CM en r-- in
^* ^J* If) VO
CM CM CM CM
O O O O
I
o o oo
53 E BG EC
W W W W
00 CO CO 00
CM CO ID rH
CO CO CO *J*
CM CM CM CM
O O O O
? -,- T
oooo
E ffi E S3
EE] U CL) W
00 00 CO 00
,C id
SH E
595
-------
TECHNICAL REPORT DATA
(Please read Instructions on the reverse before completing)
1. REPORT NO.
2.
3. RECIPIENT'S ACCESSION>NO.
4. TITLE AND SUBTITLE
CHEMICAL SCREENING: INITIAL EVALUATIONS OF
SUBSTANTIAL RISK NOTICES, SECTION 8(e), JANUARY 1,
1977 to JUNE 30, 1979
5. REPORT DATE
6. PERFORMING ORGANIZATION CODE
7. AUTHOR(S)
Chemical Hazard Identification Branch/Assessment
Division/OTE/OPTS/EPA
8. PERFORMING ORGANIZATION REPORT NO.
9. PERFORMING ORGANIZATION NAME AND ADDRESS
10. PROGRAM ELEMENT NO.
11. CONTRACT/GRANT NO.
12. SPONSORING AGENCY NAME AND ADDRESS
Office of Pesticides and Toxic Substances
U.S. Environmental Protection Agency
401 M. Street, S.W.
Washington, D.C. 20460
TS-792
13. TYPE OF REPORT AND PERIOD COVERED
1-1-77 to 6-30-79
14. SPONSORING AGENCY CODE
15. SUPPLEMENTARY NOTES
16. ABSTRACT
This collection of Status Reports (initial evaluations) was prepared by scientists
in the EPA Office of Pesticides and Toxic Substances (OPTS) on submissions received
between January 1, 1977 and June 30, 1979 from chemical manufacturers, processors,
and distributors under Section 8(e) of the Toxic Substances Control Act (TSCA).
The volume is being published for two reasons. First, the collection of status
reports in a single volume will make that information more accessible to the public
Second, the volume may, by providing specific examples of submitted information
and EPA's evaluation of it, h^lp anyone subject to Section 8(e) to understand
better the types of information that should be submitted to the Agency.
To date, no information submitted under Section 8(e) has resulted in immediate
regulatory action under TSCA or any other act, although some submitted information
has triggered further data gathering and evaluation that may lead to proposal of
regulations in the future.
17.
KEY WORDS AND DOCUMENT ANALYSIS
DESCRIPTORS
b.lDENTIFIERS/OPEN ENDED TERMS
c. COS AT I Field/Group
Section 8(e)
Substantial Risk
Toxic Substances Control Act
TSCA
18. DISTRIBUTION STATEMENT
19. SECURITY CLASS (ThisReport)
21. NO. OF PAGES
20. SECURITY CLASS (Thispage)
22. PRICE
EPA Form 2220-1 (9-73)
*U.S GOVERNMENT PRINTING OFFICE. 1980 311-132/32 1-3
-------
|