-------
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
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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
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(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
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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
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(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
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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
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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
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(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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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(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
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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
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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
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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
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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
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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)
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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) *•
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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)
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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
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-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
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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
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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
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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
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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
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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
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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
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(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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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.
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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
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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.
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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"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
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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
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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
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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
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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
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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
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(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
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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
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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
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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
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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
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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
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b) Shell should be requested to provide the information
requested in the evaluation and comments sections of this
status report.
389
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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
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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
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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
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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
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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
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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
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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
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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
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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
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(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
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(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
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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
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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
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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
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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
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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)
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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)
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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
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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
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(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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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