United States
Environmental Protection
Agency
Office of
Toxic Substances TS-799
Washington DC 20460
January 1979
Toxic Substances
<>EPA
Third Report
of the TSCA Interagency
Testing Committee
to the Administrator,
Environmental
Protection Agency
-------
THIRD REPORT
OF THE
TSCA INTERAGENCY TESTING COMMITTEE
TO THE
ADMINISTRATOR. ENVIRONMENTAL PROTECTION AGENCY
October 1978
-------
CONTENTS
PART A. THIRD REPORT OF THE TSCA INTERAGENCY TESTING COMMITTEE TO
THE ADMINISTRATOR, ENVIRONMENTAL PROTECTION AGENCY
OCTOBER 1978
Page
COMMITTEE MEMBERSHIP 1
ACKNOWLEDGMENTS i i i
SUMMARY iv
CHAPTER 1. INTRODUCTION
1.1 Background 1
1.2 Previous Reports 1
1.3 Committee Activities During This Report Period 2
1.4 Future Committee Activities 2
CHAPTER 2. AVAILABILITY OF TESTING FACILITIES AND PERSONNEL 3
CHAPTER 3. RECOMMENDATIONS OF THE COMMITTEE
3.1 Chemical Substances and Categories Recommended for
Testing 4
3.2 Designated Substances on Which Studies are Planned
or Ongoing 4
3.3 Reasons for Recommending Testing of the Additional
Substances and Categories 6
3.3.A Chlorinated benzenes, tri-, tetra-, and
penta- 6
3.3.B 1,2-Dichloropropane 9
3.3.C Glycidol and its derivatives 10
PART B. INFORMATION DOSSIERS ON SUBSTANCES DESIGNATED
BY TSCA INTERAGENCY TESTING COMMITTEE
Section
Foreword
Chlorobenzenes I
1,2-Dichloropropane II
Glycidol and Its Derivatives III
Abstracts and Automated Data Bases Searched Appendix A
Secondary Sources Searched Appendix B
Key to Abbreviations Appendix C
Addendum
-------
Member Agencies TOXIC SUBSTANCES CONTROL ACT
Council on Environments, Quality INTERAGENCY TESTING COMMITTEE
Department of Commerce
Environmental Protection Agency 722 Jackson Place, N.W.
National Cancer Institute Washington, D.C. 20006
National Institute of Environmental
Health Sciences October 2, 1978
National Institute for Occupational
Safety and Health
National Science Foundation
Occupational Safety and Health
Administration
Liaison Agencies
Consumer Product Safety Commission
Department of Defense
Department of the Interior
Food and Drug Administration
Honorable Douglas M. Costle
Administrator
Environmental Protection Agency
Room W1200 (A-100)
401 M Street, S.W.
Washington, D.C. 20460
Dear Mr. Costle:
On behalf of the TSCA Interagency Testing Committee I am
transmitting to you our latest revisions to the Section 4(e)
Priority List. These revisions and the Committee's reasons
for recommending them are presented in the enclosed
document entitled, "Third Report of the TSCA Interagency
Testing Committee to the Administrator, Environmental
Protection Agency." The representatives of the statutory
member agencies are in consensus on these revisions.
We will be continuing our review of those chemical
substances and mixtures which have not yet been designated
to the Priority List and shall report to you on our
recommendations in accordance with the provisions of the Act.
Sincerely yours,
Marvin E. Stephenson, Ph.D.
Chairman
Enclosure
-------
TSCA INTERAGENCY TESTING COMMITTEE
Statutory Member Agencies
COUNCIL ON ENVIRONMENTAL QUALITY
Carroll Leslie Bastian
Nathan J. Karch, Alternate
DEPARTMENT OF COMMERCE
Orville E. Paynter
Bernard Greifer, Alternate
ENVIRONMENTAL PROTECTION AGENCY
Warren R. Muir
Joseph J. Merenda, Alternate
NATIONAL CANCER INSTITUTE
James M. Sontag
NATIONAL INSTITUTE OF ENVIRONMENTAL
HEALTH SCIENCES
Hans L. Falk
Warren T. Piver, Alternate
NATIONAL INSTITUTE FOR OCCUPATIONAL
SAFETY AND HEALTH
Jean G. French, Vice Chairperson
Vera W. Hudson, Alternate
NATIONAL SCIENCE FOUNDATION
Marvin E. Stephenson, Chairperson
Carter Schuth, Alternate
-------
OCCUPATIONAL SAFETY AND HEALTH
ADMINISTRATION
Joseph K. Wagoner
Fred W. Clayton, Alternate
Liaison Agencies
CONSUMER PRODUCT SAFETY COMMISSION
Joseph McLaughlin
DEPARTMENT OF DEFENSE
Seymour L. Friess
DEPARTMENT OF THE INTERIOR
Charles R. Walker
FOOD AND DRUG ADMINISTRATION
Allen H. Heim
Winston deMonsabert
COMMITTEE STAFF
Executive Secretary: Carol A. Mapes
Secretary: Madye B. Cole
-------
ACKNOWLEDGMENTS
The Committee members acknowledge the support and invaluable
contributions of the many individuals and groups who have
significantly aided us in our work. These include:
— the Federal agencies who have cooperated by providing support
through the liaison members;
-- Clement Associates, Inc., technical support contractor;
-- the U.S. Environmental Protection Agency (EPA) for funding the
technical support contract and the National Institute for
Occupational Safety and Health, the Council on Environmental
Quality, and the National Cancer Institute for assisting in
the funding;
— former liaison member Robert Hehir, Consumer Product Safety
Commission;
-- former EPA staff member Donald G. Barnes, Office of Toxic
Substances;
~ EPA staff members who assisted the Committee in a variety of
activities, in particular:
John W. Lyon, Office of General Counsel,
Ralph C. Northrop, Jr., Office of Toxic Substances, and
Amy Rispin, Office of Toxic Substances;
-- the numerous experts who prepared presentations and material
for the Committee;
— the industries that responded to the Contractor's request
for information on specific chemical substances and
categories; and
~ the many individuals and organizations who responded to the
Committee's previous reports.
iii
-------
SUMMARY
A major section (Sec. 4) of the Toxic Substances Control Act
of 1976 (TSCA, Pub. L. 94-469) provides for the testing of
chemicals in commerce which may pose an unreasonable risk to human
health or the environment. This section of the Act also provides
for establishment of a Committee, composed of representatives from
eight designated Federal agencies, to recommend chemical sub-
stances or mixtures to which the Administrator of the U.S. Environ-
mental Protection Agency (EPA) should give priority consideration
for the promulgation of testing rules. The Committee makes such
revisions in the Section 4(e) Priority List as it determines to be
necessary and transmits them to the Administrator, at least every
six months.
As a result of its deliberations during the past six months,
the Committee is revising the TSCA Section 4(e) Priority List by
the addition of one individual substance and two categories of
substances. Each of these new recommendations is being designated
by the Committee for action by EPA within twelve months. The
Committee considers these additions to be of the same priority as
the previous entries. The chemical substance and categories being
added to the Priority List are presented alphabetically, together
with the types of studies recommended, as follows:
Substance or Category Recommended Studies
Chlorinated Benzenes, Tri-, Carcinogenicity, mutagenicity,
Tetra- and Penta- teratogenicity, other toxic
effects, environmental effects,
and epidemiology
1,2-Dichloropropane Carcinogenicity, mutagenicity,
teratogenicity, other toxic
effects, environmental effects,
and epidemiology
Glycidol and Its Derivatives Carcinogenicity, mutagenicity,
teratogenicity, other toxic
effects, and epidemiology
Information dossiers on these new entries will be forwarded
to the EPA Administrator at the earliest practicable date.
IV
-------
THIRD REPORT
OF THE
TSCA INTERAGENCY TESTING COMMITTEE
TO THE
ADMINISTRATOR, ENVIRONMENTAL PROTECTION AGENCY
OCTOBER 1978
CHAPTER 1. INTRODUCTION
1.1 Background
The Interagency Testing Committee (Committee) was established
under Section 4(e) of the Toxic Substances Control Act of 1976
(TSCA, Pub. L. 94-469). The specific mandate of the
Committee is to identify and recommend to the Administrator
of the U.S. Environmental Protection Agency (EPA) chemical
substances or mixtures in commerce which should be tested to
determine their potential hazard to human health and/or the
environment. The Act specifies that the Committee's
recommendations to the Administrator will be in the form of a
list ISection 4(e) Priority Listl to be published in the
Federal Register. The Committee also is directed to make such
revisions in the list as it determines to be necessary and
transmit them to the Administrator, at least every six months
after submission of its initial list.
The Committee has eight statutory members appointed by the
Federal agencies identified for membership in Section 4(e)(2)(A)
of the Act as well as a number of alternate members as permitted
by Section 4(e)(2)(B)(i). In addition, the Committee has invited
several other Federal agencies with programs related to the
control of toxic substances to designate liaison representatives
to participate in its meetings. The current Committee members,
alternates, and liaison representatives are identified in the
front of this report.
1.2 Previous Reports
In July 1977, the Committee published a Preliminary List of 330
chemical substances and categories which it had identified
for further consideration (Reference No. 1). Using previously
described techniques (Reference No. 2), the Committee ultimately
identified approximately eighty chemical substances and categories
-------
for detailed review and requested its technical contractor to
prepare dossiers on selected chemicals and categories. The review
of these dossiers, combined with the knowledge and professional
judgment of the Committee members, formed the basis for the
Committee's initial recommendations to the EPA Administrator
(Reference No. 2) and subsequent additions to the Section 4(e)
Priority iist (Reference No. 3).
1.3 Committee Activities During This Reporting Period
During the past six months, the Committee completed a detailed
review of all chemicals and categories selected for dossier
preparation as well as the review of a number of additional
chemicals, with the following exceptions: a) those chemical
substances and categories for which dossiers are being prepared
and will be reviewed prior to the Committee's April, 1979,
report; and b) those chemicals whose further consideration has
been deferred pending receipt of additional information.
1.4 Future Committee Activities
The Committee is currently updating its Master File of chemicals;
This effort will be followed by a selection of chemicals and
scoring procedures similar to those described in previous
Committee reports (Reference Nos. 2 & 3). These procedures will
provide one method for identifying additional chemicals for
detailed review and, simultaneously, will enable a periodic
re-evaluation of those chemicals which have been reviewed, but
not selected for inclusion in the Section 4(e) Priority List.
-------
CHAPTER 2. AVAILABILITY OF TESTING FACILITIES AND PERSONNEL
The Committee again emphasizes its concerns about the National
capability for conducting long-term tests of biological effects,
as expressed in its second report to the EPA Administrator
(Reference No. 3). As previously stated, the Committee's
paramount concern is for the availability of adequately trained
personnel. The Committee, therefore, reiterates its belief that
the Civil Service Commission could do much to stimulate interest
in professions such as toxicology, pathology, epidemiology, and
related environmental and occupational health specialties by
creating series and registers for these professions.
o The Committee supports current efforts by the
Environmental Protection Agency to initiate the
establishment of a Civil Service Commission
series for toxicologists.
o The Committee again recommends a National
survey to assess the future availability of
personnel and testing facilities.
o The Committee again recommends that this survey
also determine the adequacy of the supply of
test organisms for assessing specific health
and environmental effects.
To determine whether the number of personnel and facilities are
adequate to meet the predicted needs of TSCA/EPA, there also
must be some assessment of the TSCA testing requirements in
relation to those of other Federal agencies and the private
sector.
o The predicted competition for these facilities
by users from the Federal and private sectors
might be partially alleviated if some short-term,
national-testing-priority scheme were developed
to enable the most crucial needs to be met as
additional personnel and facilities are developed.
-------
CHAPTER 3. RECOMMENDATIONS OF THE COMMITTEE
3.1 Chemical Substances and Categories Recommended for Testing
The Interagency Testing Committee is revising the TSCA Section
4(e) Priority List by the addition of one individual substance
and two categories of substances for which testing is recommended.
These chemicals were selected after consideration of the factors
identified in TSCA Section 4(e)(l)(A), other relevant factors
identified by the Committee, and the knowledge and professional
judgment of Committee members. The recommended studies deemed
appropriate for determining the potential hazard(s) of each new
entry and the reasons for such recommendations are described in
Section 3.3 of this report. As in the case of the Committee's
previous recommendations, each chemical substance and category is
being designated by the Committee for action by EPA within twelve
months.
Table 1 presents the complete Section 4(e) Priority List including
the date by which the EPA Administrator must take action on each
entry. As in previous Committee reports (Reference Nos. 2 & 3),
the entries are listed alphabetically. The Committee considers
each of its new entries to the List to be of equal importance.
Therefore, each of these new entries should be given the same
priority for purposes of initiating action as required under TSCA
Section 4(e). Unless stated otherwise, the chemical substance
recommended for testing is the product to which the population is
exposed.
3.2 Designated Substances on Which Studies are Planned or Ongoing
The Committee is aware that it has added to the Section 4(e)
Priority List certain chemical substances which are either cur-
rently under study or have been selected for study by other groups.
Such studies may concern one or more of the effects for which the
Committee has recommended testing. Set forth below is the
Committee's reasoning for its past and future designation of such
substances.
The Committee generally does not regard knowledge that studies are
planned or ongoing as a sufficient basis to defer consideration of
a substance for designation for the effect under investigation or
for any other effect. The Committee's judgment as to whether a
substance has been adequately tested for health and environmental
effects must rest with the data that are presently available.
Such data do not exist for planned studies and may be in various
stages of generation for ongoing studies. In addition, the
Committee is unable to predict if an ongoing study would be
successfully concluded (i.e., disease, toxicity, or other unfore-
seen events may cause a study to be aborted). Whenever they have
been identified, planned and ongoing studies are noted in the
dossiers on designated substances.
-------
Table 1. The TSCA Section 4(e) Priority List, Arranged
Alphabetically
Chemical Substance or Category
Designated for
Action By
Aery1 amide
Alky! epoxides
Alkyl phthalates
Aryl phosphates
Chlorinated benzenes, mono- and di-
Chlorinated benzenes, tri-, tetra- and penta-
Chlorinated naphthalenes
Chlorinated paraffins
Chloromethane
Cresols
DiChloromethane
1,2-Dichloropropane
Glycidol and its derivatives
Halogenated alkyl epoxides
Hexachloro-1,3-butadiene
Nitrobenzene
Polychlorinated terphenyls
Pyridine
Toluene
1,1,1-Trichloroethane
Xylenes
April 1979
October 1978
October 1978
April 1979
October 1978
October 1979
April 1979
October 1978
October 1978
October 1978
April 1979
October 1979
October 1979
April 1979
October 1978
October 1978
April 1979
April 1979
October 1978
April 1979
October 1978
-------
The above statement does not mean that the Committee's considera-
tion of substances will never include planned or ongoing studies.
If the details of a study are known and its conclusions imminent,
the Committee may delay considering the substance until the
results become available. When the Committee considers that
a chemical substance is under sufficient assessment by other
groups, it may defer consideration of the substance. Because
the Committee recognizes that each case must be judged indi-
vidually, it has not establish formal criteria regarding the
impact that planned or ongoing studies may have on its
recommendations.
3.3 Reasons for Recommending Testing of the Additional Substances
and Categories
Table 2 summarizes the studies recommended for each additional
entry on the Section 4(e) Priority List. As directed by TSCA
Section 4(e)(l)(B) the Committee also is presenting its reasons
for recommending specific types of studies. In addition to the
rationales presented herein, supporting dossiers of information
are being finalized and will be transmitted to the Administrator,
EPA, at the earliest practicable date.
3.3.A CHLORINATED BENZENES. TRI-. TETRA- AND PENTA-
RECOMMENDED STUDIES
Carcinogen!city
Mutagenicity
Teratogenicity
Other Toxic Effects
Environmental Effects
Epidemiology
CATEGORY IDENTIFICATION: This category consists of: 1,2,3-
trichlorobenzene (CAS No. 87-61-6); 1,2,4-trichlorobenzene (CAS
No. 120-82-1); 1,3,5-trichlorobenzene (CAS No. 108-70-3);
1,2,3,4-tetrachlorobenzene (CAS No. 634-66-2); 1,2,3,5-tetra-
chlorobenzene (CAS No. 634-90-2); 1,2,4,5-tetrachlorobenzene
(CAS No. 95-94-3); and pentachlorobenzene (CAS No. 608-93-5).
REASONS FOR RECOMMENDATIONS:
Production, Release and Exposure: Although the Committee was not
able to obtain accurate production, environmental release, and
worker exposure figures, one source suggests that over 1 million
-------
Table 2. Summary of Recommended Studies
Other* Environ-
Carcino- Muta- Terato- Toxic mental
Substance or Category genicity genicity genicity Effects Effects
Epidemiology
->.
1.
2.
3.
Chlorinated
Benzenes,
Tri-, Tetra-
and Penta- X X X Xa X
1,2-Dichloropropane X X X Xb X
Glycidol and Its
Derivatives X X X X
X
X
X
*The systems of particular concern are as follows: a) neurological and hematopoietic;
b) reproductive and neurological; and c) reproductive.
-------
workers are exposed to trichlorobenzenes. The Committee also
judges that a variety of sources are responsible for the observed
contamination of air, water, soil and food chains by chlorinated
benzenes. Possible sources of contamination include the use of
chlorobenzenes as chemical intermediates and solvents in the
manufacture of dyes, lubricants and pesticides as well as other
uses such as transformer oils. Recent decreases in the use of
polychlorinated biphenyls may result in an increased usage of
trichlorobenzenes as transformer oils. Chlorinated benzenes are
also present as contaminants in and degradation products of
pesticides and occur in chlorinated municipal, agricultural and
industrial effluents. The predicted partition coefficients of
chlorobenzenes suggest that they may accumulate in biological
systems. The high probability for exposure to the human popula-
tion and environment of these relatively persistent and toxic
substances is emphasized in the following recommendations.
Carcinogenicity: No carcinogenicity studies on tri-, tetra- and
pentachlorobenzenes were found in the searched literature,
although hexachlorobenzene is a demonstrated animal carcinogen.
The Committee, therefore, recommends that tests be conducted to
assess the carcinogenic potential of these chemicals.
Mutagenicity: Although a single mutagenicity study for 1,2,4-
trichlorobenzene was negative, additional testing is needed to
assess the mutagenic potential of the chlorobenzenes.
Teratogenicity: Pentachlorobenzene administered to pregnant rats
reduced the mean number of live fetuses per litter and increased
the incidence of sternal defects and extra ribs. Studies are
recommended to assess the teratogenic potential of the chloro-
benzenes.
Other Toxic Effects: Degeneration of liver cells and hepatic
porphyria have been observed in rodents exposed to chlorobenzenes.
Dose-related increases in liver to body weight ratios in highly
porphyric rats were accompanied by the induction of hepatic
microsomal enzymes. Monkeys given high doses of 1,2,4-trichloro-
benzene showed severe weight loss and fine tremors. Guinea pigs
given high doses of chlorobenzenes have been reported to convulse
and die. The Committee recommends testing, with emphasis on the
neurological and hematopoietic systems, to further assess the
toxic effects of the chlorobenzenes.
-------
Environmental Effects: There is a paucity of information on the
acute and chronic effects of tri-, tetra- and pentachlorobenzenes
on wild and domestic birds and mammals, fish, amphibians, reptiles,
invertebrates, plants and algae. Since residues have been
detected in aquatic situations, particular emphasis should be
placed on long-term environmental studies in freshwater and
marine environments with concern for the biological significance
of residues and effects on reproduction, behavior and survival
of fish, fish-eating birds and mammals, and food chain organisms.
Epidemiology: Since the nature of human exposure to chlorobenzenes
is extremely broad, the Committee believes that epidemiological
studies may be important in assessing the effects of long-term
exposure to chlorobenzenes.
3.3.B 1,2-DICHLOROPROPANE
RECOMMENDED STUDIES
Carcinogenicity
Mutagenicity
Teratogenicity
Other Toxic Effects
Environmental Effects
Epidemiology
SUBSTANCE IDENTIFICATION: CAS No. 78-87-5
REASONS FOR RECOMMENDATIONS:
Production, Release, and Exposure: 1,2-Dichloropropane is
produced in large quantities with a production rate in 1976 of
71 million pounds. Because of its widespread use as a solvent,
as well as a multiplicity of other uses, 1,2-dichloropropane
has a potentially high occupational exposure (over 1 million
workers). Its potential use in many consumer products also may
lead to wide general exposure. Little is known about the release
rate of 1,2-dichloropropane into the environment.
Careinogenicity: The testing carried out thus far on the
carcinogenicity of 1,2-dichloropropane is insufficient to allow
an appropriate appraisal of its carcinogenicity. The Committee,
therefore, recommends that additional carcinogenicity studies
be conducted.
-------
Mutagenicity: Although positive mutagenicity tests have been
reported in Salmonella typhimurium and in Aspergillus nedulans
for dichloropropane, the isomer was not specified. The Committee
recommends that mutagenicity testing be done specifically on
1,2-dichloropropane.
Teratogenicity: Because no information on the teratogenicity of
1,2-dichloropropane was found in the searched literature, the
Committee recommends that teratogenicity tests be conducted.
Other Toxic Effects: Fatty degeneration of the liver and kidney
and necrosis of the adrenals have been observed in experimental
animals following acute, high-level exposures to 1,2-dichloro-
propane. Although one low-level exposure study has been reported,
it is considered to be inadequate to assess the chronic effects
of 1,2-dichloropropane. Since this compound is structurally
similar to 1,2-dibromo-3-chloropropane, the Committee recommends
that particular emphasis be placed on the reproductive and
neurological effects of this chemical.
Environmental Effects: In view of its volatility and high
specific gravity, the ecological impact of 1,2-dichloropropane may
be localized to those environments receiving continuous exposure
associated with this chemical's use and disposal. The potential
for bioaccumulation suggests the need for further testing to
determine the biological significance of exposure to wild and
domestic birds, mammals, fish, and invertebrates. Specific areas
of environmental concern include: chronic toxicity to fish and
invertebrates; effects on avian and mammalian reproduction and
behavior; and effects on soil invertebrates and terrestrial insects.
Epidemiology: There is no information available on chronic
effects in humans exposed to 1,2-dichloropropane over an extended
period of time. Because of the potentially widespread exposure,
epidemiological studies may be particularly important in
assessing the human health effects of 1,2-dichloropropane.
3.3.C GLYCIDOL and ITS DERIVATIVES
RECOMMENDED STUDIES
Carcinogenicity
Mutagenicity
Teratogenicity
Other Toxic Effects
Epidemiology
10
-------
CATEGORY IDENTIFICATION: This category consists of glycidol
(CAS No. 556-52-5) and several glycidyl ethers and esters.
Example chemicals in this category are glycidyl acrylate
(CAS No. 106-90-1), glycidyl methacrylate (CAS No. 106-91-2),
ally! glycidyl ether (CAS No. 106-92-3), n-butyl glycidyl ether
(CAS No. 2426-08-6), para-cresyl glycidyl ether (CAS No.
2186-24-5), phenyl glycidyl ether (CAS No. 122-60-1), and the
diglycidyl ether of bisphenol A (CAS No. 1675-54-3).
REASONS FOR RECOMMENDATIONS:
Production, Release, and Exposure: Most of these commercially
significant chemicals have annual production volumes in excess
of 1,000 pounds (1976). Although exposure estimates are not
available for all the chemicals in this category, NIOSH estimates
that 105,000, 118,000 and 105,000 workers are exposed to glycidol,
glycidyl ethers, and glycidyl methacrylate, respectively.
Carcinogenicity: Although glycidol and glycidyl methacrylate
have been tested for carcinogenicity, neither meets current
testing standards. In view of the potential alkylating properties
of these compounds, and the demonstrated carcinogenicity of
triethylene glycol diglycidyl ether and the structurally related
glycidal, the Committee recommends carcinogenicity studies.
Mutagenicity: Since glycidol, ally! glycidyl ether, n-butyl
glycidyl ether, and phenyl glycidyl ether have been reported to
be mutagenic in several assay systems, the mutagenic potential
of other category members should be determined.
Teratogenicity: With the exception of negative test results on
phenyl glycidyl ether, the teratogenic potentials of these
compounds have not been evaluated. The Committee, therefore,
recommends studies to evaluate the teratogenic potential of other
Compounds in this category.
Other Toxic Effects: Most of these chemicals are skin and eye
irritants, while some induce sensitization and cross-sensitiza-
tion reactions in exposed workers. A diversity of toxic effects
also has been observed in experimental animals following
administration of these compounds. The most frequently observed
effects are CNS depression, incoordination and ataxia, although
some of these compounds reportedly induce testicular atrophy
and temporary sterility in rats. Adverse effects on the kidneys,
liver, pancreas, and adrenals also have been observed in
experimental animals. The Committee, therefore, recommends
studies to evaluate the toxicity of these chemicals. The
reproductive system is of particular interest.
Epidemiology: Epidemiology studies should be conducted to assess
the extent of human health effects.
11
-------
REFERENCES
1. Preliminary List of Chemical Substances for Further Evaluation,
Toxic Substances Control Act Interagency Testing Committee,
July 1977.
2. Initial Report to the Administrator, Environmental Protection
Agency, TSCA Interagency Testing Committee, October 1, 1977.
Published in the FEDERAL REGISTER, Vol. 42, No. 197, Wednesday,
October 12, 1977, pp. 55026-55080. The report and supporting
dossiers also were published by the Environmental Protection
Agency, EPA 560-10-78/001, January 1978.
3. Second Report of the TSCA Interagency Testing Committee to the
Administrator, Environmental Protection Agency, TSCA Inter-
agency Testing Committee, April 1978. Published in the
FEDERAL REGISTER Vol. 43, No. 76, Wednesday, April 19, 1978,
pp. 16684-16688. The report and supporting dossiers also
were published by the Environmental Protection Agency, EPA
560-10-78/002, July 1978.
12
-------
Member Agencies TOXIC SUBSTANCES CONTROL ACT
Counci, on Environment, QuaNty INTERAGENCY TESTING COMMITTEE
Department of Commerce
Environmental Protection Agency 722 Jackson Place, N.W.
National Cancer Institute Washington, D.C. 20006
National Institute of Environmental
Health Sciences .lamiarv ft
National Institute for Occupational January tt,
Safety and Health
National Science Foundation
Occupational Safety and Health
Administration
Liaison Agencies
Consumer Product Safety Commission
Department of Defense
Department of the Interior
Food and Drug Administration
Honorable Douglas M. Costle
Administrator
Environmental Protection Agency
Room W1200 (A-100)
401 M Street, S.W.
Washington, D.C. 20460
Dear Mr. Costle:
On behalf of the Interagency Testing Committee, I am pleased
to transmit with this letter the supporting dossiers of
information on the chemical and categories which the ITC
recommended to you for priority consideration under Section 4
of the Toxic Substances Control Act in October 1978. In a
draft version, these dossiers were used as the primary, though
not sole, source of information for the Committee's recommenda-
tions. In preparing this document in its final form, some new
information came to our attention. None of the new data would
cause the Committee to revise its recommendations at this date;
however, for the sake of completeness, an addendum of these
data has been added.
I would also like to correct an example cited in the rationale
for the category entitled "Glycidol and its Derivatives" and
clarify this category's identification. On page 11 of the
Committee's Third Report, under the heading "Carcinogenicity"
the second sentence is changed to read:
In view of the potential alkylating properties of these
compounds, and the demonstrated carcinogenicity of
triethylene glycol diglycidyl ether and the structurally
related glycidal, the Committee recommends carcinogenicity
studies.
-------
-2-
I am enclosing a copy of the October report with a corrected
page eleven. You may wish to note this correction in the
Federal Register.
The Committee staff has had considerable discussion with
representatives of industrial concerns who manufacture
glycidyl ethers concerning the name of this category. The
Committee recognizes that the glycidyl ethers and esters
are not commercially synthesized from glycidol. However,
for simplicity in naming the category, the term "derivatives"
is used to mean esters and ethers, which are, regardless of
synthetic route, considered to be derivatives of the alcohol
glycidol.
Sincerely yours,
Carter Schuth (Mrs.)
Chairperson, TSCA/ITS
-------
INFORMATION DOSSIERS ON SUBSTANCES
DESIGNATED BY
TSCA INTERAGENCY TESTING COMMITTEE
(October 1978)
Prepared by
Clement Associates, Inc.
1010 Wisconsin Avenue, NW
Washington, DC 20007
December 1978
Contract No. EQ8AC013
Prepared for
TSCA Interagency Testing Committee
Washington, DC
-------
Approved by
Jay Turim, Ph.D.
Project Director
Clement Associates,
Inc.
-------
TABLE OF CONTENTS
Section
Foreword
Chlorobenzenes I
1,2-Dichloropropane II
Glycidol and Its Derivatives III
Abstracts and Automated Data Appendix A
Bases Searched
Secondary Sources Searched Appendix B
Key to Abbreviations Appendix C
Addendum
-------
FOREWORD
This document has been prepared for the Toxic Substances
Control Act (TSCA) Interagency Testing Committee (ITC) by its
technical contractor, Clement Associates, Inc. The Committee
is charged with making recommendations to the Administrator of
the Environmental Protection Agency (EPA) with respect to which
chemicals should be tested to determine their hazards to human
health or the environment.
The dossiers in this document were originally drafted by
Clement and were reviewed in detail by the Committee, which in
certain instances added information. Conclusions made by Clement
scientists about specific studies were also reviewed by the Com-
mittee. Comments by Clement scientists are denoted in the text
with the word "comment." The information in the dossiers reflects
the collective knowledge and judgment of the Committee and its
technical contractor. These dossiers have been used by the Com-
mittee as the primary basis for recommending the chemicals for
priority testing.
The dossiers were designed to provide the Committee with
sufficient information on the chemicals' physical and chemical
properties, exposure characteristics, and biological and environ-
mental effects to support an informed judgment on whether they
should be given priority for testing.
The dossiers contain information from selected computerized
data bases (see Appendix A). Standard secondary sources (see
IV
-------
Appendix B), monographs, criteria documents, reviews, abstracts
of papers presented at scientific meetings, and reports available
from government agency files and trade association libraries
were also consulted. Material received in response to the Com-
mittee's request in the Federal Register in July 1977 for infor-
mation on certain substances was also reviewed. Relevant data
obtained from manufacturers in response to a written request
for information are included. Clement scientists and Committee
members also relied upon their own knowledge of the literature
to supplement the data derived from these sources. Except when
indicated otherwise, the information cited in these dossiers was
derived from the primary sources.
During the revision of these dossiers, some information
that had not been available to the ITC when it prepared the October
1978 report to the EPA Administrator was found. That information
is given in the Addendum.
Preparation of the dossiers was directed by Dr. Jay Turim,
Project Director, Dr. Mary R. Kornreich, Deputy Project Director
and Dr. Mukund Shah, Team Leader. Others participating in the
dossier preparation were Dr. Morton Beroza, Lorraine Cameron,
Robert Fensterheim, Nan Gray, John Guy, John Joseph, Dr. Yugal
Luthra, Fred Pinkney, Karin Rosenblatt, Dave Smith, and Barbara
Turnham. Technical editors were Lorna T. Ryan, Dr. Matthew Hale,
Jr., and Amy Turim.
-------
CHLOROBENZENES
TABLE OF CONTENTS
Page
Overview 1-1
1,2,3-Trichlorobenzene
I. Chemical and Physical Information 1-4
II. Source and Fate in the Environment 1-6
III. Biological Information 1-10
IV. Environmental Effects 1-13
V. Work in Progress 1-16
1,2,4-Trichlorobenzene
I. Chemical and Physical Information 1-17
II. Source and Fate in the Environment 1-19
III. Biological Information 1-23
IV. Environmental Effects 1-30
V. Work in Progress 1-32
1,3,5-Trichlorobenzene
I. Chemical and Physical Information 1-33
II. Source and Fate in the Environment 1-35
III. Biological Information 1-39
IV. Environmental Effects 1-42
V. Work in Progress 1-44
Trichlorobenzene 1-45
1/2,3,4-Tetrachlorobenzene
I. Chemical and Physical Information 1-46
II. Source and Fate in the Environment 1-48
III. Biological Information 1-52
IV. Environmental Effects 1-55
V. Work in Progress 1-57
1,2,4,5-Tetrachlorobenzene
I. Chemical and Physical Information 1-58
I-i
-------
II. Source and Fate in the Environment 1-60
III. Biological Information 1-63
IV. Environmental Effects 1-66
V. Work in Progress 1-68
Pentachlorobenzene
I. Chemical and Physical Information 1-69
II. Source and Fate in the Environment 1-71
III. Biological Information 1-75
IV. Environmental Effects 1-78
V. Work in Progress 1-80
Summary Table 1-81
References 1-83
I-n
-------
CHLOROBENZENES
OVERVIEW
The chlorobenzenes discussed in this dossier are 1,2,3-
•»
trichlorobenzene, 1,2,4-trichlorobenzene, 1,3,5-trichloro-
benzene, 1,2,3,4-tetrachlorobenzene, 1,2,4,5-tetrachlorobenzene,
and pentachlorobenzene. Most are white crystals or flakes, but
1,3,5-trichlorobenzene is a colorless stable liquid. They are
generally insoluble in water, slightly soluble in alcohol, and
very soluble in organic substances such as ether, benzene, and
carbon disulfide.
In 1972, 15.6 million pounds of 1,2,4-trichlorobenzene were
produced in the United States. No other production figures for
the chlorobenzenes in this dossier were found in the sources
searched. It was estimated in the National Occupational Hazard
Survey that, 5,000 workers in the United States are exposed to
1,2,4-trichlorobenzene and 3,000 workers to 1,3,5-trichloro-
benzene. It is reported in the survey that 1,081,000 workers are
exposed to "trichlorobenzene," but no indication is given of
which isomer or isomers are represented by this figure. No
production or exposure figures for the other chlorobenzenes
discussed were found in the sources searched. The chlorobenzenes
are used as chemical intermediates and solvents and in the manu-
facturing of dyes, lubricants, and insecticides. They are
present as metabolites and contaminants in such pesticides as
lindane and hexachlorobenzene.
Industrial effluents and pesticides are reported to release
1-1
-------
chlorobenzenes into the air, soil, and water, where these chem-
icals are likely to persist and accumulate in the food chain.
They have been observed in municipal, industrial, and agricul-
tural discharge and in sea and river waters. 1,2,3-Trichloro-
benzene has been found in U.S. drinking water in concentrations
of up to 0.001 mg/liter. All the chlorobenzenes have been found
in solid wastes and fish and other aquatic organisms. Penta-
chlorobenzene has been identified in wheat products, animal feed,
and chicken and pork fat. 1,2,3,4-Tetrachlorobenzene and penta-
chlorobenzene were found in human adipose tissue in Japan. The
chlorinated benzenes are likely to persist in the environment for
long periods and bioaccumulate to a great degree. 1,2,3,4-
Tetrachlorobenzene accumulated by a factor of about 100 times the
daily dose in rats fed the compound at 2 mg/kg/day for 12 weeks.
In general, the more chlorinated the benzene the more it resists
degradation.
No information on the toxicity to humans of the chloro-
benzenes in this dossier was found in the sources searched. In
animals, rates of absorption and transformation of these com-
pounds decline as the extent of chlorination increases. The less
chlorinated benzenes may be metabolized to phenolic derivatives
or dechlorinated. Pentachlorobenzene is reported to be rela-
tively inert metabolically. All the chlorobenzenes, being lipo-
philic, tend to be deposited and stored in body fat. In meta-
bolic studies with animals, the parent chlorobenzene and metab-
olites have been detected in expired air, urine, feces, gut con-
tents, and numerous tissues.
1-2
-------
Dose-related increases in liver to body weight ratios in
rats were accompanied by the induction of microsomal enzymes.
Degeneration of liver cells and hepatic porphyria have also been
observed in rats exposed to chlorinated benzenes. Highly por-
phyric rats exposed to chlorinated benzenes showed extreme
weakness, ataxia, clonic contraction, and enlarged livers.
The most highly chlorinated benzene, hexachlorobenzene,
which is not discussed in this dossier, has been found to be
carcinogenic in Syrian golden hamsters. However, no reports of
carcinogenicity studies on the incompletely chlorinated benzenes
were found in the sources searched. A single mutagenicity study
for 1,2,4-trichlorobenzene was negative but experimental details
could not be evaluated from the information given in the source.
Pentachlorobenzene administered to pregnant rats reduced the mean
number of live fetuses per litter and increased the incidence of
sternal defects and extra ribs. No other teratogenicity studies
were found.
Chlorinated benzenes have been found to retard the growth of
fungi, beetles, termites, and snails. Shrimp exposed continu-
ously to 1,3,5-trichlorobenzene at 10 ppm died within a week
without producing young.
1-3
-------
CHLOROBENZENES
1,2,3-TRICHLOROBENZENE
I. CHEMICAL AND PHYSICAL INFORMATION
A. Identification
1. CAS No.; 87-61-6
2. NIOSH No.;
3. Synonyms and Trade Names
No information was found in the sources searched.
B. Formulas and Molecular Weight
1. Structural Formula
Cl
Cl
Cl (HCP 1976)
2. Empirical Formula
C,H.,C1-, (HCP 1976)
D J J
3. Molecular Weight
181.45 (HCP 1976)
C. Physical Properties
1. Description
White crystals (CCD 1977)
1-4
-------
2. Boiling Point
218-219°C (HCP 1976)
3. Melting Point
53-54°C (HCP 1976)
4. Vapor Pressure
1 mm at 40.0°C (HCP 1976)
5. Solubility
Insoluble in water; slightly soluble in alcohol; very
soluble in ether, benzene, and carbon disulfide
(HCP 1976)
6. Octanol/Water Partition Coefficient
No information was found in the sources searched.
7. Specific Gravity
No information was found in the sources searched.
D. Composition of the Commercial Product
No information was found in the sources searched.
1-5
-------
1,2,3-TRICHLOROBENZENE
II. SOURCE AND FATE IN THE ENVIRONMENT
A. Sources
1. Production and Trends
No information was found in the sources searched.
2. Manufacturers
No information was found in the sources searched.
3. Use
As an organic intermediate, in the dyeing industry
(CCD 1977, Kites 1973)
4. Occupational Exposure
No information was found in the sources searched.
5. Release
According to Verschueren (1977), 1,2,3-trichlorobenzene is
released into water and air as a result of agricultural runoff,
termite control operations, the use of transformer oil, and its
general use in laboratories.
1,2,3-Trichlorobenzene has been identified as a metabo-
lite of the pesticide lindane in pheasant egg yolks (Saha
and Burrage 1976), in a culture of mold grown spontaneously
on grated carrots (Engst et al. 1977), and in houseflies (Reed
and Forgash 1970).
1-6
-------
B. Environmental Fate
1. Occurrence
The U.S. Environmental Protection Agency (USEPA 1977) reported
that 1,2,3-trichlorobenzene was measured at 0.021-0.046 mg/liter in
municipal discharge entering the Catawba Creek, in North Carolina.
According to Lunde (1976), the compound was found in plaice, eel,
sprat, whiting, and cod taken off Norway.
Unspecified trichlorobenzenes have been found in the
Merrimack River in New England at 0.1-0.5 ppb (Kites 1973). These
contaminants are believed to originate from local dye industries.
Unspecified trichlorobenzenes have also been identified in longnose
suckers (Catostomus catostomus) taken near a Canadian mill effluent
(Kaiser 1977) and in sprat (Clupea sprattus) (Lunde and Baumann
1976). They have been found at concentrations ranging from 0.1 to
1.6 mg/liter in water from the Coosa River in Georgia near the
cities of Dalton, Calhoun, and Rome.
The U.S. EPA (1977) has reported that unspecified trichloro-
benzenes have been measured at concentrations of up to 0.001 mg/
liter in U.S. drinking water, at 0.005 mg/liter in the Coosa
River, Georgia, and at 0.019-0.46 mg/liter in the Catawba Creek,
North Carolina. Young et al. (1976 as reported by USEPA 1977)
detected trichlorobenzenes in waste waters from several major muni-
cipal areas and in the air of Southern California. Fish from Lake
Superior and Lake Huron have been found to contain very small
amounts of trichlorobenzene (USEPA 1977).
MacKenzie (1971) reported slight residues of Polystream, which
1-7
-------
gradually disappeared, in oysters and clams. Polystream is a mix-
ture of trichlorobenzene, tetrachlorobenzene, and pentachloro-
benzene, and is used to reduce snail attack on oysters.
2. Transformation
Pseudomonas bacteria-degrade 1,2,3-trichlorobenzene at
200 mg/liter at 30°C with a ring disruption of 87% in 5 days
(Verschueren 1977). A mutant strain of the bacteria degrades the
compound under the same conditions with a ring disruption of 100% in
43 hours.
Comment: 1,2,3-Trichlorobenzene is a chemically stable solid
that is insoluble in water but soluble in fat solvents. It has a
boiling point of 218-219°C and a vapor pressure of 1 mm at 40°C. It
can react with chemical oxidizing agents (Sax 1975). The compound,
if released, could enter the water by transport with soil/sediment
and organic detritus systems. Some of the compound may also enter
the atmosphere because, like 1,2,4-trichlorobenzene, it may co-
distill with water, particularly if it is aerated. As a chlorinated
aromatic, it is susceptible to attack by hydroxyl radicals with an
estimated half-life (by extrapolation from studies of benzene and
chlorinated benzenes) of several days. In view of its chemical pro-
perties, however, the compound will probably degrade slowly in the
environment and may therefore persist if released in large amounts.
3. Bioaccumulation
According to Jondorf et al. (1955), 62% of 1,2,3-
trichlorobenzene administered to rabbits was conjugated and excreted
1-8
-------
in the urine during a period of 5 days after dosing. None of the
compound was found in the feces. For experimental details, see
1,2,3-Trichlorobenzene, Section III.B.I. De Bruin (1976) suggested
that rates of absorption and transformation of the polychlorinated
benzenes decline as halogen substitution increases.
MacKenzie (1971) found that Polystream, a mixture of trichloro-
benzene, tetrachlorobenzene, and pentachlorobenzene, accumulated in
the tissues of oysters and clams in small amounts when it was
applied to oyster beds at 1.9 hectaliters/hectare. These residues
disappeared within 119 days. See 1,2,3-Trichlorobenzene, Section
IV.A.4., for a description of experimental details.
Comment: 1,2,3-Trichlorobenzene is chemically stable, insol-
uble in water, and lipophilic, and it is somewhat volatile. These
properties as well as the data on metabolism suggest that the com-
pound is likely to bioaccumulate, but not to as great an extent as
the more highly chlorinated benzenes. The findings of low levels of
1,2,3-trichlorobenzene in fish (see 1,2,3-Trichlorobenzenes,
Section II.B.I) seem to support this judgment.
1-9
-------
1,2,3-TRICHLOROBENZENE
III. BIOLOGICAL INFORMATION
A. Effects on Humans
No information was found in the sources seached.
B. Tests on Laboratory Organisms
1. Metabolism
In a study of the metabolism of several polychlorinated
benzenes, Kohli et al. (1976) gave intraperitoneal injections
of 300 mg of 1,2,3-trichlorobenzene dissolved in 10-15 ml of
vegetable oil to an unspecified number of male rabbits, each
weighing 4-5 kg. The authors reported that in urine collected
for 10 days 11% of the dose was excreted as the metabolite
2,3,4-trichlorophenol, 2% as 3,4,5-trichlorophenyl acetate,
and 1% as 2,3,6-trichlorophenol. The authors suggested that
these metabolites may have been formed from arene oxides.
Jondorf et al. (1955) reported that 1,2,3-trichloro-
benzene was slowly metabolized by rabbits to a major
metabolite—2,3,4-trichlorophenol—and to several minor
metabolites—3,4,5-trichlorophenol, 3,4,5-tr ichlorocatechol,
and 2,3,4-trichlorophenylmercapturic acid. The authors gave
4.5 g of the compound to three rabbits by stomach tube as a 25%
(wt/vol) solution in arachis oil. In the 5 days after dosing,
62% of the dose appeared in the urine as conjugates of glu-
curonic acid (50%) and sulfuric acid (12%).
1-10
-------
Safe et al. (1976) investigated the metabolism of chlor-
inated aromatic compounds by the frog (Rana pipiens). They
dissolved 80 mg of 1,2,3-trichlorobenzene in 4-5 ml of vege-
tab^e oil and administered it intraperitoneally in equal quan-
tities to four animals. They reported that approximately 1%
of the dose was excreted in the course of 8 days as 2,3,4-tri-
chlorophenol. No other urinary metabolites were detected.
2. Toxic Effects
a. Acute Toxicity
No information was found in the sources searched.
b. Carcinogenicity
No information was found in the sources searched.
c. Mutagenicity and Cell Transformation
No information was found in the sources searched.
d. Teratogenicity, Embryotoxicity, and Fetotoxicity
No information was found in the source searched.
e. Other Toxicity
Ariyoshi et al. (1975a) investigated the effects of
1,2,3-trichlorobenzene on rats. They gave six female Wistar
rats oral doses of 250 mg/kg of the substance in 2% tragacanth
gum solution once a day for 3 days. The rats were sacrificed
24 hours after the last dose was administered and their livers
removed. The authors reported statistically significant
increases in the concentrations of cytochrome P-450, micro-
1-11
-------
somal phosphorus, and microsomal protein in the liver. They
found no effects on liver weight or on glycogen and trigly-
ceride levels.
Rimington and Ziegler (1963) administered chlorinated
benzenes to rats to induce experimental hepatic porphyria.
They gave three male albino rats 1,2,3-trichlorobenzene at
785 mg/kg by gastric intubation daily for 7 days and measured
porphyrins and porphyrin precursors in 24-hour urine samples.
The levels of coproporphyrin, uroporphyrin, porphobilinogen,
and delta-aminolevulic acid were higher in the exposed rats
than in a control group of five male albino rats. The exposed
rats lost weight and showed loss of appetite. Highly por-
phyric rats commonly showed extreme weakness, ataxia, clonic
contractions, and enlarged livers. Histologic examination
revealed degenerated liver cells but no actual necrosis.
1-12
-------
1,2,3-TRICHLOROBENZENE
IV. ENVIRONMENTAL EFFECTS
A. ECOLOGICAL EFFECTS
1. Wild and Domestic Mammals
No information was found in the sources searched.
2. Wild and Domestic Birds
No information was found in the sources searched.
3. Fishy Amphibians, and Reptiles
Safe et al. (1976) reported that approximately 1% of an
intraperitoneally administered dose of 1,2,3-trichlorobenzene
was converted to metabolites by the frog (Rana pipiens).
Comment: The experimental design and mode of exposure in this
study were not appropriate for the determination of toxic
effects. For experimental details, see 1,2,3-Trichloro-
benzene, Section III.B.I.
MacKenzie (1971) found that Polystream, a mixture of tri-
chlorobenzene, tetrachlorobenzene, and pentachlorobenzene,
was toxic to pipefish (Syngnathus fuscus) and mummichogs
(Fundulus heteroclitus) when applied to oyster beds at
1.9 hectaliters/hectare. See 1,2,3-Trichlorobenzene, Section
IV.A.4, for further details.
4. Invertebrates
Loosanoff et al. (1960a and 1960b as reported by
MacKenzie 1971) reported that trichlorinated benzenes are
1-13
-------
toxic to several species of marine gastropods, including the
thick-lipped drill (Eupleura caudata) and the Atlantic oyster
drill (Urosalpinx cinerea). MacKenzie did not provide further
details.
MacKenzie (1971) studied the efficacy of chlorinated ben-
zenes in killing-oyster drills (snails that prey on oysters).
Polystream, a mixture of polychlorinated benzenes containing a
minimum of 95% active trichlorobenzene, tetrachlorobenzene,
and pentachlorobenzene was used. Polystream was mixed with
dry sand or a granular clay that carried it to the bottom and
dispersed it. The rate of application was 1.9 hectaliters/
hectare of oyster bed. When water current velocities were
low, all oyster drills were killed. At water current veloc-
ities between 0.9 and 2.7 km/hr, 66-85% of the drills died.
When the current was strong, the Polystream was dispersed and
therefore no deaths were observed. At low water velocity,
significant numbers of small clams and other invertebrates
were killed. The growth of oysters appeared normal in the
treated beds.
Davis and Hidu (1969) studied the effect of an unspec-
ified trichlorobenzene or mixture of trichlorobenzenes on the
embryonic development of the hard clam (Mercenaria mercenaria)
and the American oyster (Crassostrea virginica) and on the
survival and growth of the hard clam at the larval stage.
Acetone was used as the solvent. According to the authors,
the percentage of eggs that developed normally in clams ex-
posed at 1 and 10 ppm was 72 and 58%, respectively, of the per-
1-14
-------
centage that developed normally in controls. The survival
rate of clam larvae exposed at the two concentrations was 108
and 69%, respectively, of the survival rate of controls.
There was no significant effect on the mean length of clam
larvae at either concentration. The percentage of eggs that
developed normally in oysters exposed at 1 and 10 ppm was 59
and 21%, respectively, of the percentage that developed
normally in controls.
According to Verschueren (1977), 1,2,3-trichlorobenzene
is used to control termites. Gibson (1957 as reported by
USEPA 1977) reported that an unspecified trichlorobenzene
mixed in a 1-5 ratio with diesel oil was 100% lethal to the
Douglas Fir beetle (Dendroctonus pseudotsugae).
5. Plants and Algae
Richardson (1968 as reported by USEPA 1977) reported that
an unspecified trichlorobenzene retarded the radial growth of
the fungi Pythium ultimum, Rhizoctonia solani, and Trichoderma
viride. No experimental details were given.
6. Bacteria and Other Microorganisms
No information was found in the sources "searched.
7. Ecological Communities and Processes
No information was found in the sources earched.
B. Other Environmental Effects
No information was found in the sources searched.
1-15
-------
1,2,3-TRICHLOROBENZENE
V. WORK IN PROGRESS
No information was found in the sources searched,
1-16
-------
1,2,4-TRICHLOROBENZENE
I. CHEMICAL AND PHYSICAL INFORMATION
A. Identification
1. CAS No.; 120-82-1
2. NIOSH No.; DC21000
3. Synonyms and Trade Names
unsym-Tr ichlorobenzene
(NIOSH 1977)
B. Formulas and Molecular Weight
1. Structural Formula
2. Empirical Formula
3. Molecular Weight
181.45
C. Physical Properties
1. Description
Colorless, stable liquid
(HCP 1976)
(HCP 1976)
(HCP 1976)
(CCD 1977)
1-17
-------
2. Boiling Point
213.5°C (HCP 1976)
3. Melting Point
16.95°C (HCP 1976)
4. Vapor Pressure
1 mm at 38.4°C (HCP 1976)
5. Solubility
Insoluble in water; slightly soluble in alcohol; very sol-
uble in ether (HCP 1976)
6. Octanol/Water Partition Coefficient
No information was found in the sources searched.
7. Specific Gravity
1.4542204 (HCP 1976)
D. Composition of the Commercial Product
No information was found in the sources searched.
1-18
-------
1,2,4,-TRICHLOROBENZENE
II. SOURCE AND FATE IN THE ENVIRONMENT
A. Sources
1. Production and Trends
15.6 million Ib (1972) (USITC 1972)
Listed by the USITC under the section "Cyclic Intermediates,"
but no production data given (USITC 1976)
2. Manufacturers
Dow Chemical Co. (USITC 1976)
3. Use
As a solvent in chemical manufacturing; in dyes and interme-
diates; as a dielectric fluid; in synthetic transformer oils; in
lubricants; as a heat-transfer medium; in insecticides
(CCD 1976)
4. Occupational Exposure
Rank: 1657
Estimated number of persons exposed: 5,000*
*rough estimate
(NOHS 1976)
5. Release
1,2,4-Trichlorobenzene has been identified as a metabolite of
the pesticide lindane in pheasant egg yolks and chicks (Saha and
Burrage 1976), in houseflies (Reed and Forgash 1970), and in a cul-
1-19
-------
ture of mold grown spontaneously on grated carrots (Engst et al.
1977) .
1,2,4-Trichlorobenzene has been identified in textile waste
effluents (see 1,2,4-Trichlorobenzene, Section II.B.I) (Erisman
and Gordon 1975 as reported by USEPA 1977).
B. Environmental Fate
1. Occurrence
Erisman and Gordon (1975 as reported by USEPA 1977) detected
1,2,4-trichlorobenzene in textile waste effluents. The compound
has also been measured in monitorings of industrial discharges
into the Catawba River, North Carolina (0.012 mg/liter) and the
Chattanooga Creek, Tennessee (0.5 mg/liter), in waste waters from
several major municipal areas (<0.01-275 yg/liter), in river
water after surface runoff (0.007 mg/liter), and in the atmos-
phere (USEPA 1977).
Traces of three trichlorobenzenes, mostly 1,2,4-
trichlorobenzene, were detected in bread and breakfast cereals
(Westoo et al. 1971). The chemicals were reported to be residues
formed from the pesticide lindane during baking.
For information on the occurrence of unspecified trichloro-
benzenes, see 1,2,3-Trichlorobenzene, Section II.B.I.
2. Transformation
Simmons et al. (1976) reported that 1,2,4-trichlorobenzene
is biodegradable in waste-water treatment plants. The extent of
biodegradation of the chlorinated benzenes, like that of many
1-20
-------
other organic compounds, is dependent on its residence time as
well as the concentration of effective microorganisms in the
system. Prior exposure to 1,2,4-trichlorobenzene led to an in-
crease in the population of effective microorganisms and thus an
increased biodegradation rate. The authors also showed that more
than 65% of 1,2,4-trichlorobenzene in the waste water of a textile
finishing plant was removed in a well-aerated basin with a 5-day
retention. Removal from another industrial waste-water treatment
plant was found to be about 75% in activated sludge with a 6-hour
retention.
Garrison and Hill (1972 as reported by USEPA 1977) reported
that 1,2,4-trichlorobenzene at 100 g/liter volatilized from
aerated water in less than 4 hours.
Pseudomonas bacteria degrade 1,2,4-trichlorobenzene at
200 mg/liter at 30°C with a ring disruption of 92% in 5 days.
A mutant strain degrades the compound under the same conditions
with a ring disruption of 100% in 46 hours (Verschueren 1977).
BOD2_ values for 1,2,4-trichlorobenzene were reported to be 78,
100, and 50% of the theoretical value, depending on the source of
the microorganisms used for biodegradation (USEPA 1977).
1,2,4-Trichlorobenzene is susceptible in air to attack by
hydroxyl radicals and its half-life in the atmosphere has been
estimated by extrapolation from studies of benzene and chloro-
benzenes to be from one to several days (Simmons et al. 1976).
Comment: Some of these data as well as the chemical and
physical properties of 1,2,4-trichlorobenzene indicate that, if
released, it may enter the atmosphere as well as water (by trans-
1-21
-------
port with soil/sediment and organic detritus systems). It is
likely to degrade slowly in the environment and therefore may
persist if released in large amounts.
3. Bioaccumulation
According to Jondorf et al. (1955), 38% of a dose of 1,2,4-
trichlorobenzene administered to rabbits was conjugated and ex-
creted in the urine during a period of 5 days after dosing. None
«--
of the compound was found in the feces. For experimental de-
tails, see 1,2,4-Trichlorobenzene, Section III.B.I. De Bruin
(1976) suggested that rates of absorption and transformation of
the polychlorinated benzenes decline as halogen substitution in-
creases.
MacKenzie (1971) found that Polystream, a mixture of
trichlorobenzene, tetrachlorobenzene, and pentachlorobenzene,
accumulated in the tissues of oysters and clams when it was ap-
plied to oyster beds at 1.9 hectaliters/hectare. The residues
disappeared within 119 days. See 1,2,3-Trichlorobenzene, Section
IV.A.4, for a description of experimental details.
Comment: 1,2,4-Trichlorobenzene is chemically stable, in-
soluble in water, and lipophilic, and it is somewhat volatile.
These properties as well as the data on metabolism given above
suggest that the compound is likely to bioaccumulate, but not to
as great an extent as the more highly chlorinated benzenes. The
findings of low levels of trichlorobenzenes in fish (see 1,2,3-
Trichlorobenzene, Section II.B.I) seem to support this judgment.
1-22
-------
1,2,4-TRICHLOROBENZENE
III. BIOLOGICAL INFORMATION
A. Effects on Humans
No information was found in the sources searched.
B. Tests on Laboratory Organisms
1. Metabolism
In a study of the metabolism of several polychlorinated ben-
zenes, Kohli et al. (1976) gave intraperitoneal injections of
300 mg of 1,2,4-trichlorobenzene dissolved in 10-15 ml of vege-
table oil to an unspecified number of male rabbits, each weighing
4-5 kg. The authors reported that in urine collected for 10 days
6% of the dose was excreted as the metabolite 2,3,5-trichloro-
phenol and 5% as 2,4,5-trichlorophenol. The authors suggested
that these metabolites may have been formed from arene oxides.
Jondorf et al. (1955) reported that 1,2,4-trichlorobenzene
was slowly metabolized by rabbits to two major metabolites—
2,4,5- and 2,3,5-trichlorophenol—and to several minor
metabolites—3,4,6-trichlorocatechol, 2,3,5-trichlorophenylmer-
capturic acid, and 2,4,5-trichlorophenylmercapturic acid. The
authors gave 6 g of the compound to three rabbits by stomach tube
as a 25% (wt/vol) solution in arachis oil. In the 5 days after
dosing, 38% of the dose appeared in the urine as oxygen conju-
gates.
Safe et al. (1976) investigated the metabolism of chlori-
nated aromatic compounds by the frog (Rana pipiens). They dis-
1-23
-------
solved 80 mg of 1,2,4-trichlorobenzene in 4-5 ml of vegetable oil
and administered it intraperitoneally in equal quantities to four
animals. The only excretory metabolite identified in the course
of 8 days was 2,4 ,5-trichlorophenol, which accounted for approxi-
mately 0.7% of the original dose.
2.
Toxic Effects
a. Acute Toxicity
The acute toxicity of 1,2,4-trichlorobenzene, as reported by
the NIOSH RTECS data base (1978) and by Brown et al. (1969), is
given in Table III-l:
TABLE III-l
ACUTE TOXICITY OF 1,2,4-TRICHLOROBENZENE
Parameter
LD501'2
LD501'2
LD502
LDLo1
Dosage
756
766
6,139
500
mg/kg
mg/kg
mg/kg
mg/kg
Animal
Rat
Mouse
Rat
Mouse
Route
Oral
Oral
Percutaneous
Intraperitoneal
,NIOSH (1978)
Brown et al. (1969)
Yang' and Peterson (1977) reported that male Holtzman rats
injected intraperitoneally with 1,2,4-trichlorobenzene
(5 mmoles/kg) exhibited greater bile duct pancreatic fluid flow
and lower pancreatic fluid protein concentration than did
control rats.
1-24
-------
b. Carcinogenicity
No information was found in the sources searched.
c. Mutagenicity and Cell Transformation
Smith et al. (1978) detected no evidence of mutagenic activ-
ity by 1,2,4-trichlorobenzene or its metabolites. The abstract
of the study did not provide any experimental details.
d. Teratogenicity, Embryotoxicity, and Fetotoxicity
No information was found in the sources searched.
e. Other Toxicity
Coate et al. (1977) exposed groups of 30 male Sprague-Dawley
albino rats, 16 male New Zealand white rabbits, and 9 male cyno-
molgus monkeys to 1,2,4-trichlorobenzene by inhalation at concen-
trations of 25, 50, and 100 ppm. The exposures were for 7 hours/
day, 5 days/week, for 26 weeks. A control group was exposed to
air. Five rats from each group were sacrificed after 13 weeks.
All surviving animals were sacrificed after 26 weeks. The
authors reported that the exposures caused no changes in hemato-
logical and serum biochemical test results or in body weights and
survival. They found no effects of exposure on pulmonary func-
tion and operant behavior tests in monkeys and in ophthalmoscopic
examinations in rabbits and monkeys. No exposure-related abnor-
malities or other effects were apparent in the tissues from
animals exposed for 26 weeks, although microscopic examination
showed changes in the livers and kidneys of rats killed after 4
1-25
-------
and 13 weeks of exposure. These included enlarged hepatocytes in
rats exposed at 50 and 100 ppm. Other changes, which were re-
ported not to be dose-related, included slightly increased vacuo-
lation* of hepatocytes, .granuloma formation, and increased biliary
hyperplasia in livers and hyaline degeneration in the inner zone
of the kidney cortex.
Carlson and Tardiff (1976) administered oral doses of 1,2,4-
trichlorobenzene, once a day, for 14 days to groups of six male
albino rats. The dosages were 0, 150, 300, and 600 mg/kg/day.
The compound was not lethal during the 14 days of dose admini-
stration, but one rat exposed at 600 mg/kg/day died during the 2
weeks of observation after the last dose. At all the dose
levels, the compound was not considered hepatotoxic, as judged by
serum isocitrate dehydrogenase activity. Liver glucose-6-
phosphatase activity was decreased in rats given 300 mg/kg/day or
higher doses. Induced metabolism of xenobiotics was indicated by
significantly decreased hexobarbital sleeping time after 14 days
of dosage at 600 mg/kg/day. 1,2,4-Trichlorobenzene was a potent
microsomal enzyme inducing agent in rats given oral doses of 10-
40 mg/kg/day for 14 days. The authors also reported dose-related
increases in glucuronyltransferase and azoreductase activities
and oxy-ethyl oxy-para-nitrophenyl phenylphosphonothioate (EPN)
detoxification. A dose-related increase in liver to body-weight
ratio substantiated these biochemical findings.
Ariyoshi et al. (1975a) also investigated the effects of
1,2,4-trichlorobenzene on rats. They gave six female Wistar rats
oral doses of 250 mg/kg of the substance in 2% tragacanth gum
1-26
-------
solution once a day for 3 days. The rats were sacrificed 24 hours
after the last dose was administered and their livers were re-
moved for biochemical analyses. The authors reported increased
activities of drug-metabolizing enzymes and statistically signi-
ficant increases in the concentrations of cytochrome P-450,
microsomal phosphorus, and microsomal protein in the liver. The
rats' liver weights increased markedly, although the concentra-
tions of glycogen and triglyceride were not affected.
Rimington and Ziegler (1963) administered chlorinated ben-
zenes to rats to induce experimental hepatic porphyria. They
gave three male albino rats 1,2,4-trichlorobenzene at 730 mg/kg
by gastric intubation daily for 15 days and measured porphyrins
and porphyrin precursors in 24-hour urine samples. The levels of
coproporphyrin, uroporphyrin, porphobilinogen, and delta-
aminolevulic acid were higher in the exposed rats than in a con-
trol group of five male albino rats. The rats lost weight and
showed loss of appetite. Highly porphyric rats commonly showed
extreme weakness, ataxia, clonic contractions, and enlarged
livers. Histologic examination revealed degenerated liver cells
but no actual necrosis.
Carlson (1977) found that porphyria did not develop in rats
administered 1,2,4-trichlorobenzene in corn oil orally at concen-
trations of 50, 100, and 200 mg/kg. Groups of five female rats
were given the substance for 30, 60, 90, or 120 days. Liver
weights increased, but there were only minor increases in liver
porphyrins. Urinary excretion of delta-aminolevulic acid and
porphobilinogen did not differ from that in control animals.
1-27
-------
Smith et al. (1978) gave rhesus monkeys single daily oral
doses of 1,2,4-trichlorobenzene at 1-173.6 mg/kg. (The abstract
did not specify the duration of the exposure period.) The
authors reported that the substance was apparently nontoxic at
25 mg/kg or lower but was toxic at 90 mg/kg or higher. When given
173.6 mg/kg, monkeys showed severe weight loss and fine tremors
and died within 20-30 days. Monkeys that received the higher
doses showed evidence of hepatic induction, including a shift in
the pattern of urinary chlorguanide metabolites and increased
clearance of labeled 1,2,4-trichlorobenzene administered intra-
venously.
Brown et al. (1969) reported that 1,2,4-trichlorobenzene was
unlikely to produce dermatitis in rabbits or guinea pigs unless
contact was repetitive or prolonged. For 3 consecutive days,
they placed 1 ml of the substance on the back of each of four male
and four female rabbits. For 5 days/week for 3 weeks, they
placed 1 ml on the back of a male rabbit, 1 ml on a female rabbit,
and 0.5 ml on each of five male and five female guinea pigs. The
authors observed fissuring, which they considered a typical re-
sult of degreasing. In histopathological examinations, the skin
from the rabbits exposed for 3 weeks showed spongiosis, acan-
thosis, parakeratosis, and inflammation of the superficial der-
mis. Some of the exposed guinea pigs had convulsions and died.
Their livers contained necrotic foci.
Powers et al. (1975) applied 0.2 ml of 1,2,4-trichloro-
benzene on the inner surfaces of rabbits' ears. Three groups of
12 rabbits received applications of 5, 25, and 100% 1,2,4-
1-28
-------
trichlorobenzene, three times a week, for 13 weeks. The authors
reported that the repeated applications caused no systemic ef-
fects or visceral lesions. Rats exposed to the substance at 25
and 100% showed no evidence of acneform dermatitis but did have
moderate to severe skin irritation characterized by erythema,
scaling, desquamation, encrustation, slight enlargement of fol-
licles, and some hair loss and scarring. Skin biopsy samples
showed dermal irritation with slight to moderate acanthosis and
hyperkeratosis.
1-29
-------
1,2,4-TRICHLOROBENZENE
IV. ENVIRONMENTAL EFFECTS
A. Ecological Effects
1. Wild and Domestic Mammals
No information was found in the sources searched.
2. Wild and Domestic Birds
No information was found in the sources searched.
3. Fish, Amphibians, and Reptiles
NIOSH (1977) reported that the Aquatic Toxicity Rating (96-
hr TLm, species unspecified) of 1,2,4-trichlorobenzene is 10-
1 ppm.
Safe et al. (1976) reported that approximately 0.7% of an
intraperitoneally administered dose of 1,2,4-trichlorobenzene
was converted to metabolites by the frog (Rana pipiens).
Comment: The experimental design and mode of exposure in this
study were not appropriate for the determination of toxic
effects. For experimental details, see Section III.B.I.
For data on unspecified trichlorobenzenes, see 1,2,3-
Trichlorobenzene, Section IV.A.3.
4. Invertebrates
For data on unspecified trichlorobenzenes, see 1,2,3-
Trichlorobenzene, Section IV.A.4.
1-30
-------
5. Plants and Algae
For data on unspecified trichlorobenzenes, see 1,2,3-
Trichlorobenzene, Section IV.A.5.
6. Bacteria and Other Microorganisms
No information was found in the sources searched.
7. Ecological Communities and Processes
No information was found in the sources searched.
B. Other Environmental Effects
No information was found in the sources searched.
1-31
-------
1,2,4-TRICHLOROBENZENE
V. WORK IN PROGRESS
N. Ito of the First Department of Pathology, Nagoya City
University Medical School, Nagoya, Japan, has completed a study
of the effects on ICR mice of exposure to 1,2,4-trichlorobenzene
by intragastric injection (WHO 1978). The results of the study
*.
have not yet been published.
1-32
-------
1,3,5-TRICHLOROBENZENE
I. CHEMICAL AND PHYSICAL INFORMATION
A. Identification
1. CAS No.; 108-70-3
2. NIOSH No.;
3. Synonyms and Trade Names
No information was found in the sources searched.
B. Formulas and Molecular Weight
1. Structural Formula
Cl
Cl
Cl
2. Empirical Formula
CCH-C1,
D J J
3. Molecular Weight
181.45
C. Physical Properties
1. Description
Crystals
(HCP 1976)
(HCP 1976)
(HCP 1976)
(Merck 1976)
1-33
-------
2. Boiling Point
208°C (HCP 1976)
3. Melting Point
63-64°C (HCP 1976)
4. Vapor Pressure
10 mm at 78°C (HCP 1976)
5. Solubility
Slightly soluble in alcohol; insoluble in water; very soluble
in ether, benzene, carbon disulfide, and ligroin
(HCP 1976)
6. Octanol/Water Partition Coefficient
No information was found in the sources searched.
7. Specific Gravity
No information was found in the sources searched.
D. Composition of the Commercial Product
No information was found in the sources searched.
1-34
-------
1,3,5-TRICHLOROBENZENE
II. SOURCE AND FATE IN THE ENVIRONMENT
A. Sources
1. Production and Trends
No information was found in the sources searched.
2. Manufacturers
i
No information was found in the sources searched.
3. Use
No information was found in the sources searched.
4. Occupational Exposure
Rate: 3713
Estimated number of persons exposed: 3,000*
*rough estimate (NOHS 1976)
5. Release
1,3,5-Trichlorobenzene has been identified as a metabolite of
the pesticide lindane in pheasant egg yolks (Saha and Burrage 1976)
and in a culture of mold grown spontaneously on grated carrots
(Engst et al. 1977) .
The compound has been identified in industrial discharge (see
1,3,5-Trichlorobenzene, Section II.B.I.)
1-35
-------
B. Environmental Fate
1. Occurrence
The U.S. EPA (1977) reported that 1,3,5-trichlorobenzene was
found at 0.026 mg/liter,in industrial waste discharged into the
Holston River, Tennessee. Trace amounts at concentrations of up to
0.9 mg/liter have been detected by Young et al. (1976 as reported
by USEPA 1977) in waste waters from several major municipal areas
and in the air of southern California. The chemical was found in
extracts of plaice, eel, sprat, whiting, and cod taken off Norway
(Lunde 1976). It has also been identified as a harmful substance
in Rhine water (Jacobs et al. 1974).
For information on the occurrence of unspecified trichloro-
benzenes, see 1,2,3-Trichlorobenzene, Section II.B.I.
2. Transformation
Pseudomonas bacteria degrade 1,3,5-trichlorobenzene at
200 mg/liter at 30°C with a ring disruption of 78% in 120 hours
(Verschueren 1977). A mutant strain of the bacteria degrades the
compound under the same conditions with a ring disruption of 100%
in 43 hours.
Comment: 1,3,5-Trichlorobenzene is a chemically stable solid
that is insoluble in water but soluble in fat solvents. It has a
boiling point of 208°C and a vapor pressure of 10 mm at 78°C. The
compound, if released, could enter the water by transport with
soil/sediment and organic detritus systems. Some of the compound
may also enter the atmosphere because, like 1,2,4-trichlorobenzene,
it may codistill with water, particularly if it is aerated. As a
1-36
-------
chlorinated aromatic, it is susceptible to attack by hydroxyl
radicals with an estimated half-life (by extrapolation from
studies of benzene and chlorinated benzenes) of several days.
In view of its chemical properties, however, the compound will
probably degrade slowly in the environment and may therefore
persist if released in large amounts.
3. Bioaccumulation
According to Jondorf et al. (1955), 23% of 1,3,5-trichloro-
4-
benzene administered to rabbits was conjugated and excreted in
the urine during a period of 5 days after dosing. For experi-
mental details, see 1,3,5-Trichlorobenzene, Section III.B.I.
De Bruin (1976) suggested that rates of absorption and transfor-
mation of the polychlorinated benzenes decline as halogen substi-
tution increases.
Jacobs et al. (1974), reported that 1,3,5-trichlorobenzene
given orally to rats at 2 mg/kg/day accumulated more in the fat
than in the liver, kidney, heart, or blood.
MacKenzie (1971) found that Polystream, a mixture of tri-
chlorobenzene, tetrachlorobenzene, and pentachlorobenzene, accu-
mulated in the tissues of oysters and clams in small amounts when
it was applied to oyster beds at 1.9 hectaliters/hectare. These
residues disappeared within 119 days. See 1,2,3-Trichloro-
benzene, Section IV.A.4, for a description of experimental
details.
Comment: 1,3,5-Trichlorobenzene is chemically stable,
insoluble in water, and lipophilic, and it is somewhat volatile.
1-37
-------
These properties as well as the data on metabolism given above
suggest that the compound is likely to bioaccumulate, but not to
as great an extent as the more highly chlorinated benzenes. The
findings of low levels of 1,3,5-trichlorobenzene in fish (see
1,3,5-Trichlorobenzene Section II.B.I) seem to support this
judgment.
1-38
-------
1,3,5-TRICHLOROBENZENE
III. BIOLOGICAL INFORMATION
A. Effects on Humans
No information was found in the sources searched.
B. Tests on Laboratory Organisms
1. Metabolism
In a study of the metabolism of several polychlorinated
benzenes, Kohli et al. (1976) gave intraperitoneal injections of
300 mg of 1,3,5-trichlorobenzene dissolved in 10-15 ml of vegetable
oil to an unspecified number of male rabbits, each weighing 4-5 kg.
The authors reported that in urine collected for 10 days 1.4% of
the dose was excreted as the metabolite 2,3,5-trichlorophenol and
3% as 2,4,6-trichlorophenol. The authors suggested that these
metabolites may have been formed from arene oxide intermediates.
In an earlier study, Parke and Williams (1960) administered
1,3,5-trichlorobenzene orally at 0.5 g/kg to female rabbits. They
reported that the compound was oxidized to a small extent to 2,4,6-
trichlorophenol and excreted in the urine. They also obtained
chromatographic evidence that 4-chlorophenol and 4-chlorocatechol
were minor urinary metabolites. They suggested that the formation
of phenols indicated that the compound was in part dechlorinated to
chlorobenzene, possible by gut bacteria. They identified mono-
chlorobenzene in exhaled air 3-4 days after treatment and they
found evidence of chlorobenzene in the tissues. In the two
animals, 13 and 1.5% of the administered dose was eliminated un-
1-39
-------
changed in the feces and 12 and 8.5% in expired air. According to
the authors, the main bulk of the 1,3,5-trichlorobenzene was found
unchanged in the gut contents (19 and 18%) and the tissues (5% in
the pelt, 5 and 4.5% in depot fat, 22 and 20% in the rest of the
body).
Jondorf et al. (1955) reported that 1,3,5-trichlorobenzene was
very slowly metabolized by rabbits to 2,4,6-trichlorophenol, a
major metabolite. The authors gave 1.5 g of the compound to six
rabbits by stomach tube as a 25% (wt/vol) solution in arachis oil.
In the 5 days after dosing, 23% of the dose appeared in the urine as
oxygen conjugates. Unchanged 1,3,5-trichlorobenzene was found in
the feces.
Jacobs et al. (1974) reported that 1,3,5-trichlorobenzene
given orally to rats at 2 mg/kg/day accumulated more in the fat
than in the liver, kidney, heart, or blood.
Safe et al. (1976) investigated the metabolism of chlorinated
aromatic compounds by the frog (Rana pipiens). They dissolved
80 mg of 1,3,5-trichlorobenzene in 4-5 ml of vegetable oil and
administered it equally by intraperitoneal injection to four
animals. They reported that approximately 0.7% of the dose was
excreted in the course of 8 days as 2,4,6-trichlorophenol. No
other metabolites were detected.
2. Toxic Effects
a. Acute Toxicity
No information was found in the sources searched.
1-40
-------
b. Carcinogenicity
No information was found in the sources searched.
c. Mutagenicity and Cell Transformation
* „
No information was found in the sources searched.
d. Teratogenicity, Embryotoxicity, and Fetotoxicity
No information was found in the sources searched.
e. Other Toxicity
Ariyoshi et al. (1975a) investigated the effects of 1,3,5-
trichlorobenzene on rats. They gave six female Wistar rats oral
doses of 250 mg/kg of the substance in 2% tragacanth gum solution
once a day for 3 days. The rats were killed 24 hours after the last
dose and their livers were removed. The authors reported statis-
tically significant increases in aminopyrine demethylase activity
and in the concentrations of microsomal phosphorus and protein in
the liver. They found no effects on liver weight or on glycogen and
triglyceride levels.
1-41
-------
1,3,5-TRICHLOROBENZENE
IV. ENVIRONMENTAL EFFECTS
A. Ecological Effects
1. Wild and Domestic Mammals
No information was found in the sources searched.
2. Wild and Domestic Birds
No information was found in the sources searched.
3. Fishy Amphibians, and Reptiles
Safe et al. (1976) reported that approximately 0.7% of an
intraperitoneally administered dose of 1,3,5-trichlorobenzene was
converted to metabolites by the frog (Rana pipiens). Comment: The
experimental design and mode of exposure in this study were not ap-
propriate for the determination of toxic effects. For experimental
details, see 1,3,5-Trichlorobenzene, Section III.B.I.
4. Invertebrates
Grosch (1973) exposed groups of 10 pairs of male and female
shrimp (Artemia salina) to 1,3,5-trichlorobenzene at 10 ppm in
water for 24 hours. He reported a statistically significant
decrease in the life span of the females, a delay of more than a
week in the appearance of the first broods, and significant
decreases in the average number of broods per pair and the average
number of zygotes produced. All shrimp in several populations of
80 each exposed continuously at 10 ppm died within a week without
producing young.
1-42
-------
Grosch and Hoffman (1973) exposed two groups of virgin female
wasps (Bracon hebetor) to 1,3,5-trichlorobenzene. The first group
received injections into the abdomen of 0.5 yl of a 10 ppm solution
of the compound in acetone. The second group was left overnight in
a shell vial whose interior walls had been coated with the com-
pound, in both groups the authors reported a marked increase in
death of embryos in eggs deposited from the 4th to the 12th day
after treatment. The average life spans of the wasps decreased
somewhat. Associated with poor hatching was an increase in the
proportion of embryos dying during cleavage. Grosch and Hoffman
suggested that 1,3,5-trichlorobenzene induced defects in the mito-
tic apparatus of the wasps.
For data on unspecified trichlorobenzenes, see 1,2,3-
Trichlorobenzene, Section IV.A.4.
5. Plants and Algae
For data on unspecified trichlorobenzenes, see 1,2,3-
Trichlorobenzene, Section IV.A.5.
6. Bacteria and Other Microorganisms
No information was found in the sources searched.
7. Ecological Communities and Processes
No information was found in the sources searched.
B. Other Environmental Effects
No information was found in the sources searched.
1-43
-------
1,3,5-TRICHLOROBENZENE
V. WORK IN PROGRESS
No information was found in the sources searched,
1-44
-------
TRICHLOROBENZENE
NIH/EPA (1978) reports a CAS No. of 12002-48-1 for an
unspecified trichlorobenzene. It lists Pyranol 1478 as a
synonym.
In the National Occupational Hazard Survey (1976), it is
estimated that 1,081,000 workers are exposed to trichlorobenzene,
which gives it a rank of 191. No indication is given of which
isomer or isomers are represented by these figures, but there are
separate entries in the survey for the 1,2,4 and the 1,3,5
isomers.
According to the USITC (1976), PPG Industries produces a
mixture of 1,2,3- and 1,2,4-trichlorobenzene.
Unspecified trichlorobenzenes have been identified in
longnose suckers (Catostomus catostomus) (Kaiser 1977) and sprat
(Clupea sprattus) (Lunde and Baumann 1976).
See 1,2,3-Trichlorobenzene, Sections II.B.3, IV.A.3, and
IV.A.4, for information on the effects of Polystream, a mixture
of trichlorobenzene, tetrachlorobenzene, and pentachlorobenzene.
1,2,3-Trichlorobenzene, Section IV.A.4, also contains informa-
tion on the effects of unspecified isomers of trichloroberizene on
invertebrates.
Information on specific isomers can be found in the respec-
tive sections of this dossier.
1-45
-------
1,2,3,4-TETRACHLOROBENZENE
I. CHEMICAL AND PHYSICAL INFORMATION
A. Identification
CAS No.; 634-66-22
NIOSH No.;
Synonyms and Trade Names
No information was found in the sources searched.
B. Formulas and Molecular Weight
Structural Formula
Cl
Empirical formula
Description
White crystals
(HCP 1976)
(HCP 1976)
Molecular Weight
215.90 (HCP 1976)
C. Physical Properties
(CCD 1977)
1-46
-------
2. Boiling Point
254°C (HCP 1976)
3. Melting Point
47.5°C (HCP 1976)
4. Vapor Pressure
1 nun at 68.5°C (HCP 1976)
5. Solubility
Insoluble in water; slightly soluble in cold alcohol; sol-
uble in hot alcohol; very soluble in ether, acetic acid, carbon
disulfide, and ligroin (HCP 1976)
6. Octanol/Water Partition Coefficient
No information was found in the sources searched.
7. Specific Gravity
No information was found in the sources searched.
D. Composition of the Commercial Product
No information was found in the sources searched.
1-47
-------
1,2,3,4-TETRACHLOROBENZENE
II. SOURCE AND FATE IN THE ENVIRONMENT
A. Sources
1. Production and Trends
No information was found in the sources searched.
2. Manufacturers
No information was found in the sources searched.
3. Use
As a component of dielectric fluids; in synthesis
(CCD 1977)
An unspecified tetrachlorobenzene used in the pesticide
Polystream (MacKenzie 1971)
4. Occupational Exposure
No information was found in the sources searched.
5. Release
1,2,3,4-Tetrachlorobenzene has been identified as a meta-
bolite of the pesticide lindane in pheasant eggs and chicks
(Saha and Burrage 1976), in flies (Reed and Forgash 1970), and
in a culture of mold grown spontaneously on grated carrots
(Engst et al. 1977). An unspecified tetrachlorobenzene may be
released as a result of its use in the pesticide Polystream
(see 1,2,3,4-Tetrachlorobenzene, Section II.B.I).
Plimmer and Klingebiel (1976) reported that photolysis of
1-48
-------
hexachlorobenzene in methanol at wavelengths greater than
260 nm or in hexane at wavelengths greater than 220 nm pro-
duced tetrachlorobenzene.
B. Environmental Fate
1. Occurrence
1,2,3,4-Tetrachlorobenzene has been found in plaice, eel,
sprat, whiting, and cod taken off Norway (Lunde 1976). Unspeci-
fied tetrachlorobenzene isomers have been identified in long-
nose suckers (Catostomus catostomus) taken near a Canadian
mill effluent (Kaiser 1977) and in sprat (Lunde and Baumann
1976) .
MacKenzie (1971) reported slight residues of Polystream,
which gradually disappeared, in oysters and clams. Polystream
is a mixture of trichlorobenzene, tetrachlorobenzene, and penta-
chlorobenzene, and is used to reduce snail attack on oysters.
2. Transformation
Pseudomonas bacteria degrade 1,2,3,4-tetrachlorobenzene
at 200 mg/liter at 30°C with a ring disruption of 33% in 5 days
(Verschueren 1977). A mutant strain of the bacteria degrades
the compound under the same conditions with a ring disruption
of 74%.
Comment: 1,2,3,4-Tetrachlorobenzene is a solid that is
insoluble in water and soluble in fat solvents. Its vapor
pressure at 68.5°C is 1 mm and, like the other chlorinated
benzenes, it can react with oxidizing agents. These properties
1-49
-------
as well as the transformation data given above indicate that
the compound, if released, could enter the water by transport
with soil/sediment and organic detritus. Degradation is likely
to be slow and the compound could become a pollutant if re-
leased in large amounts. Because it is less volatile, more
stable, and less biodegradable than the trichlorobenzenes,
it is likely to be more persistent.
3. Bioaccumulation
According to Jondorf (1958), about 43% of 1,2,3,4-tetra-
chlorobenzene administered to rabbits was oxidized to 2,3,4,5-
tetrachlorophenol and excreted in the urine. During a period
of 6 days after dosing, 10% of the dose was found in the tis-
sues, 5% in the feces, and 8% in the expired air. See also
1,2,3,4-Tetrachlorobenzene, Section IV.B.I. De Bruin (1976)
suggested that rates of absorption and transformation of the
polychlorinated benzenes decline as halogen substitution in-
creases.
Jacobs et al. (1974) reported that 1,2,3,4-tetrachloroben-
zene accumulated by a factor of about 100 times the daily dose
in the fat of rats fed the compound at 2 mg/kg body weight/day
for 12 weeks.
MacKenzie (1971) found that Polystream, a mixture of tri-
chlorobenzene, tetrachlorobenzene, and pentachlorobenzene,
accumulated in the tissues of oysters and clams in small amounts
when it was applied to oyster beds at 1.9 hectaliters/hectare.
These residues disappeared within 119 days. See 1,2,3-Trichloro-
1-50
-------
benzene, Section IV.A.4., for a description of experimental
details.
Comment: 1,2,3,4-Tetrachlorobenzene is stable, insoluble
in water, and highly lipophilic, and it has only slight vola-
tility. These properties as well as the data on metabolism
and bioaccumulation given above indicate that it has a definite
potential for bioaccumulation. In general, the tetrachloro-
benzenes bioaccumulate more than the trichlorobenzenes.
1-51
-------
1,2,3,4-TETRACHLOROBENZENE
III. BIOLOGICAL INFORMATION
A. Effects on Humans
No information was found in the sources searched.
B. Test on Laboratory Organisms
1. Metabolism
In a study of the metabolism of several polychlorinated
benzenes, Kohli et al. (1976) gave intraperitoneal injections
of 300 mg of 1,2,3,4-tetrachlorobenzene dissolved in 10-15 ml
of vegetable oil to an unspecified number of male rabbits, each
weighing 4-5 kg. The authors reported that in urine collected
for 10 days 20% of the dose was excreted as the metabolite
2,3 ,4,5-tetrachlorophenol and 2% as 2,3,4,6-tetrachlorophenol.
The authors suggested that these metabolites may have been
formed from arene oxides.
In an earlier study, Jondorf et al. (1958) administered
1,2,3,4-tetrachlorobenzene at 0.5 g/kg orally to female rab-
bits. They reported that the compound was slowly metabolized.
Approximately 43% was oxidized to 2,3,4,5-tetrachlorophenol
in 6 days and excreted in the urine, partly in free form and
partly conjugated. In the same period, 8% of the administered
dose was expired unchanged and 5% was eliminated unchanged
in the feces. Analyses of tissues after 6 days revealed 0.1%
of the dose in the liver, 2% in the skin, 5% in the depot fat,
0.5% in gut contents, and 2% in the rest of the body. The
1-52
-------
compound was not detected in the brain. The authors suggested
that some dechlorination (2%) took place in the gut.
According to Jacobs et al. (1974), 1,2,3,4-tetrachloroben-
zene administered orally to rats at 5 mg/kg/day in a mixture
of several environmental pollutants accumulated in the fat and
to a lesser extent the liver, kidney, heart, and blood.
Safe et al. (1976) investigated the metabolism of chlori-
nated aromatic compounds by the frog (Rana pipiens). They
dissolved 80 mg of 1,2,3,4-tetrachlorobenzene in 4-5 ml of
vegetable oil and administered it intraperitoneally in equal
parts to four animals. They reported that less than 1% of
the dose was excreted in the course of 8 days as 2,3,4,6-tetra-
chlorophenol. No other metabolites were detected.
2. Toxic Effects
\
a. Acute Toxicity
No information was found in the sources searched.
b. Carcinogenicity
No information was found in the sources searched.
c. Mutagenicity and Cell Transformation
No information was found in the sources searched.
d. Teratogenicity, Embryotoxicity, and Fetotoxicity
No information was found in the sources searched.
1-53
-------
e. Other Toxicity
Ariyoshi et al. (1975a) investigated the effects of 1,2,3,4-
tetrachlorobenzene on rats. They gave six female Wistar rats
oral doses of 250 mg/kg of the substance in 2% tragacanth gum
solution once a day for 3 days. The rats were sacrificed 24
hours after the last dose was administered and their livers were
removed. The authors reported statistically significant increases
in the concentrations of cytochrome P-450 and microsomal protein
in the liver. They found significantly increased delta-amino-
levulic acid synthetase activity, which they suggested was re-
lated to changes in cytochrome P-450, and increased aminopyrine
demethylase activity. Mean liver weight was significantly in-
creased, although glycogen content was decreased.
Rimington and Ziegler (1963) administered chlorinated
benzenes to rats to induce experimental hepatic porphyria. They
gave three male albino rats 1,2,3,4-tetrachlorobenzene at 660 mg/
kg by gastric intubation daily for 10 days and measured porphy-
rins and porphyrin precursors in 24-hour urine samples. The
levels of coproporphyrin, uroporphyrin, porphobilinogen, and
delta-aminolevulic acid were higher in the exposed rats than in
a control group of five male albino rats. The rats lost weight
and showed loss of appetite. Highly porphyric rats commonly
showed extreme weakness, ataxia, clonic contractions, and en-
larged livers. Histologic examination revealed degenerated
liver cells but no actual necrosis.
1-54
-------
1,2,3,4-TETRACHLOROBENZENE
IV. ENVIRONMENTAL EFFECTS
A. Ecological Effects
1. Wild and Domestic Mammals
No information was found in the sources searched.
2. Wild and Domestic Birds
No information was found in the sources searched.
3. Fish, Amphibians, and Reptiles
Safe et al. (1976) reported that less than 1% of an admin-
istered dose of 1,2,3,4-tetrachlorobenzene was converted to met-
abolites by the frog (Rana pipiens). Comment: The experimental
design and mode of exposure in this study were not appropriate
for the determination of toxic effects. For experimental details,
see 1,2,3,4-Tetrachlorobenzene, Section III.B.I.
For the effects of Polystream, which contains an unspecified
tetrachlorobenzene, see 1,2,3-Trichlorobenzene, Section IV.A.3.
4. Invertebrates
Loosanoff et al. (1960a and 1960b as reported by MacKenzie
1971) reported that tetrachlorinated benzenes are toxic to
several species of marine gastropods, including the thick-lipped
drill (Eupleura caudata) and the Atlantic oyster drill (Urosalpinx
cinerea). MacKenzie did not provide further details. .
For the effects of Polystream, which contains an unspecified
tetrachlorobenzene, see 1,2,3-Trichlorobenzene, Section IV.A.4.
1-55
-------
5. Plants and Algae
No information was found in the sources searched.
6. Bacteria and Other Microorganisms
No information was found in the sources searched.
7. Ecological Communities and Processes
No information was found in the sources searched.
B. Other Environmental Effects
No information was found in the sources searched.
1-56
-------
1,2,3,4-TETRACHLOROBENZENE
V. WORK IN PROGRESS
No information was found in the sources searched,
1-57
-------
1,2,4,5-TETRACHLOROBENZENE
I. CHEMICAL AND PHYSICAL INFORMATION
A. Identification
1. CAS No.; 95-94-3
2. NIOSH No.; DB9450
3. Synonyms and Trade Names
No information was found in the sources searched,
B. Formulas and Molecular Weight
1. Structural Formula
Cl
ci-
Cl
Cl
2. Empirical Formula
C6H2C14
3. Molecular Weight
215.90
C. Physical Properties
1. Description
White flakes
(HCP 1976)
(HCP 1976)
(HCP 1976)
(CCD 1977)
1-58
-------
2. Boiling Point
243-246°C (HCP 1976)
3. Melting Point
139.5-140.5°C (HCP 1976)
4. Vapor Pressure
40 mm at 146°C (HCP 1976)
5. Solubility
Insoluble in water, slightly soluble in hot alcohol; solu-
ble in ether, benzene, chloroform, and carbon disulfide
(HCP 1976)
6. Octanol/Water Partition Coefficient
No information was found in the sources searched.
7. Specific Gravity
1.85822 (HCP 1976)
D. Composition of the Commercial Product
No information was found in the sources searched.
1-59
-------
1,2,4,5-TETRACHLOROBENZENE
II. SOURCE AND FATE IN THE ENVIRONMENT
A. Sources
1. Production and Trends
Listed by the USITC under the section "Cyclic Intermediates,"
but no production data given (USITC 1976)
2. Manufacturers
Dow Chemical Co. (USITC 1976)
3. Use
As an intermediate for herbicides and defoliants; as an insec-
ticide; as an impregnant for moisture resistance; in electrical
insulation; as temporary protection in packing (CCD 1977)
4. Occupational Exposure
No information was found in the sources searched.
5. Release
1,2,4,5-Tetrachlorobenzene has been identified as a metab-
olite of the pesticide lindane in pheasant eggs and chicks (Saha
and Burrage 1976), in flies (Reed and Forgash 1970), and in a cul-
ture of mold grown spontaneously on grated carrots (Engst et al.
1977). An unspecified tetrachlorobenzene may be released as a
result of its use in the pesticide Polystream (see 1,2,3,4-Tetra-
chlorobenzene, Section II.B.I).
1-60
-------
B. Environmental Fate
1. Occurrence
1,2,4,5-Tetrachlorobenzene has been found in plaice, eel,
sprat,'whiting, and cod taken off Norway (Lunde 1976). On the
occurrence of unspecified tetrachlorobenzenes, see 1,2,3,4-
Tetrachlorobenzene, Section II.B.I.
2. Transformation
Pseudomonas bacteria degrade 1,2,4,5-tetrachlorobenzene at
200 ing/liter at 30°C with a ring disruption of 30% in 5 days
(Verschueren 1977). A mutant strain of the bacteria degrades the
compound under the same conditions with a ring disruption of 80%.
Comment: 1,2,4,5-Tetrachlorobenzene is a solid that is
insoluble in water and soluble in fat solvents. Its vapor pres-
sure is 1 mm at 68.5°C, and it can react vigorously with oxi-
dizing agents (Sax 1975). These properties as well as the trans-
formation data given above indicate that the compound, if
released, may enter the soil and water systems. Degradation is
likely to be slow and the compound could become a pollutant if
released in large amounts. Because it is less volatile, more
stable, and less biodegradable than the trichlorobenzenes, it is
likely to be more persistent.
3. Bioaccumulation
According to Jondorf et al. (1958), 2% of 1,2,4,5-
tetrachlorobenzene administered orally to rabbits was metab-
olized to 2,3,5,6-tetrachlorophenol and was excreted in the
1-61
-------
urine. During a period of 6 days after dosing, 48% of the dose
was found in the tissues, 16% in the feces, and 2% in the expired
air. De Bruin (1976) suggested that rates of absorption and
transformation of the polychlorinated benzenes decline as halogen
substitution increases.
According to Jacobs et al. (1974), 1,2,4,5-tetrachloro-
benzene administered orally to rats at 5 mg/kg/day in a mixture
of several environmental pollutants accumulated in the fat and to
a lesser extent the liver, kidney, heart, and blood.
An abstract of a study by Bauer (1972) reported that
1,2,4,5-tetrachlorobenzene was adsorbed by the algae Cladophera.
At 70 yg/liter of water, the bioaccumulation factor was 254. The
adsorption rate was highest in the first 24 hours.
MacKenzie (1971) found that Polystream, a mixture of
trichlorobenzene, tetrachlorobenzene, and pentachlorobenzene,
accumulated in the tissues of oysters and clams when it was
applied to oyster beds at 1.9 hectaliters/hectare. The residues
disappeared within 119 days. See 1,2,3-Trichlorobenzene, Section
IV.A.4, for a description of experimental details.
Comment: 1,2,4,5-Tetrachlorobenzene is stable, insoluble
in water, and highly lipophilic; it is only slightly volatile.
These properties as well as the data on metabolism given above
indicate that the compound has a potential for bioaccumulation.
In general, the tetrachlorobenzenes bioaccumulate more than the
trichlorobenzenes.
1-62
-------
1,2,4,5-TETRACHLOROBENZENE
III. BIOLOGICAL INFORMATION
A. Effects on Humans
No information was found in the sources searched.
B. Tests on Laboratory Organisms
1. Metabolism
In a study of the metabolism of several polychlorinated
benzenes, Kohli et al. (1976) gave intraperitoneal injections of
300 mg of 1,2,4,5-tetrachlorobenzene dissolved in 10-15 ml of
vegetable oil to an unspecified number of male rabbits, each
weighing 4-5 kg. The authors reported that in urine collected
for 10 days 2% of the dose was excreted as the metabolite
2,3,5,6-tetrachlorophenol. The authors suggested that this
metabolite may have been formed from arene oxides.
In an earlier study, Jondorf et al. (1958) administered
1,2,4,5-tetrachlorobenzene at 0.5 g/kg orally to female rabbits.
They reported that the compound was metabolized less readily than
1,2,3,4-tetrachlorobenzene. In 6 days, only about 2% was con-
verted to 2,3,5,6-tetrachlorobenzene and excreted in the urine.
Less predominant urinary metabolites were 2,5-dichlorophenol and
2,3,5-trichlorophenol. Of the original dose, 48% was found
unchanged in the tissues (25% was in depot fat), 16% in the
feces, and 2% in the expired air. The authors suggested that
somewhat more than 10-15% of the dose may have been dechlorinated
in the gut to dichlorophenols and trichlorophenols.
1-63
-------
According to Jacobs et al. (1974), 1,2,4,5-tetrachloro-
benzene administered orally at 5 mg/kg/day in a mixture of
several environmental pollutants accumulated in the fat and to a
lesser extent the liver, kidney, heart, and blood of rats.
Safe et al. (1976) investigated the metabolism of chlor-
inated aromatic compounds by the frog (Rana pipiens). They
dissolved 80 mg of 1,2,4,5-tetrachlorobenzene in 4-5 ml of vege-
table oil and administered it in equal parts by intraperitoneal
injection to four animals. They reported that less than 1% of
the dose was excreted in the course of 8 days as 2,4,5-
tetrachlorophenol. No other metabolites were detected.
2. Toxic Effects
a. Acute Toxicity
The NIOSH RTECS data base (1978) reported that the oral LD50
of 1,2,4,5-tetrachlorobenzene was 1,500 mg/kg in the rat and
1,035 mg/kg in the mouse.
b. Carcinogenicity
No information was found in the sources searched.
c. Mutagenicity in Cell Transformation
No information was found in the sources searched.
d. Teratogenicity, Embryotoxicity, Fetotoxicity
No information was found in the sources searched.
1-64
-------
e. Other Toxicity
Ariyoshi et al. (1975a) investigated the effects of 1,2,4,5-
tetrachlorobenzene on rats. They gave six female Wistar rats
oral doses of 250 mg/kg of the substance in 2% tragacanth gum
solution once a day for 3 days. The rats were sacrificed 24 hours
after the last dose was administered. The authors reported a sta-
tistically significant increase in aminopyrine demethylase
activity and in the concentrations of cytochrome P-450 and micro-
somal protein in the liver. Mean liver weight was significantly
increased, although the concentrations of glycogen and trigly-
ceride in the liver were decreased.
Rimington and Ziegler (1963) administered chlorinated
benzenes to rats to induce experimental hepatic porphyria. They
gave six male albino rats 1,2,4,5-tetrachlorobenzene at 905 mg/kg
by gastric intubation daily for 5 days and measured porphyrins
and porphyrin precursors in 24-hour urine samples. They reported
that the compound had no effect on urinary porphyrin excretion.
The rats lost weight and showed loss of appetite.
1-65
-------
1,2,4,5-TETRACHLOROBENZENE
IV. ENVIRONMENTAL EFFECTS
A. Ecological Effects
1. Wild and Domestic Mammals
No information was found in the sources searched.
2. Wild and Domestic Birds
No information was found in the sources searched.
3. Fish, Amphibians, and Reptiles
Safe et al. (1976) reported that less than 1% of an admin-
istered dose of 1,2,4,5-tetrachlorobenzene was converted to metab-
olites by the frog (Rana pipiens). Comment: The experimental
design and mode of exposure in this study were not appropriate for
the determination of toxic effects. For experimental details, see
1,2,4,5-Tetrachlorobenzene, Section III.B.I.
For the effects of Polystream, which contains an unspecified
tetrachlorobenzene, see 1,2,3-Trichlorobenzene, Section IV.A.3.
4. Invertebrates
Loosanoff et al. (1960a and 1960b as reported by MacKenzie
1971) reported that tetrachlorinated benzenes are toxic to several
species of marine gastropods, including the thick-lipped drill
(Eupleura caudata) and the Atlantic oyster drill (Urosalpinx
cinerea). MacKenzie did not provide further details.
For the effects of Polystream, which contains an unspecified
tetrachlorobenzene, see 1,2,3-Trichlorobenzene, Section IV.A.4.
1-66
-------
5. Plants and Algae
Ameen et al. (1960 as reported by USEPA 1977) reported that
1,2,4,5-tetrachlorobenzene at an unspecified concentration de-
creased the seedling vigor and germination percentage of barley,
oats, and wheat in pretreated sand, loam, clay loam, and clay
soils. In sand, where the damage was most severe, barley and
oats did not germinate when planted 1 day after treatment; 100%
germination for barley and 95% for oats occurred when they were
planted 25 days after treatment. The height of the seedlings,
according to the report, increased with the time between treat-
ment and planting.
Richardson (1968 as reported by USEPA 1977) observed that
1,2,4,5-tetrachlorobenzene retarded the radial growth of the
fungus Pythium ultimum but that its effect was less than
trichlorobenzene's. No other experimental details were given.
6. Bacteria and Other Microorganisms
No information was found in the sources searched.
7. Ecological Communities and Processes
No information was found in the sources searched.
B. Other Environmental Effects
No information was found in the sources searched.
1-67
-------
1,2,4,5-TETRACHLOROBENZENE
V. WORK IN PROGRESS
No information was found in the sources searched.
1-68
-------
PENTACHLOROBENZENE
I. CHEMICAL AND PHYSICAL INFORMATION
A. Identification
1. CAS No.; 608-93-5
2. NIOSH No.; DA66400
3. Synonyms and Trade Names
QCB
(NIOSH 1977)
B. Formulas and Molecular Weight
1. Structural Formula
Cl
Cl'
Cl
Cl
Cl
2. Empirical Formula
3. Molecular Weight
250.34
(HCP 1976)
(HCP 1976)
(HCP 1976)
C. Physical Properties
1. Description
No information was found in the sources searched.
1-69
-------
2. Boiling Point
277°C (HCP 1976)
3. Melting Point
86°C (HCP 1976)
4. Vapor Pressure
1 mm at 98.6°C (HCP 1976)
5. Solubility
Insoluble in water and alcohol; slightly soluble in ether,
benzene, carbon disulfide, and chloroform; soluble in hot alcohol
(HCP 1976)
6. Octanol/Water Partition Coefficient
No information was found in the sources searched.
7. Specific Gravity
1.834216'5 (HCP 1976)
D. Composition of the Commercial Product
No information was found in the sources searched.
1-70
-------
PENTACHLOROBENZENE
II. SOURCE AND FATE IN THE ENVIRONMENT
A. Source
1. Production and Trends
No information was found in the sources searched.
2. Manufacturers
No information was found in the sources searched.
3. Use
In pesticide used to combat oyster drills (MacKenzie 1971)
4. Occupational Exposure
No information was found in the sources searched.
5. Release
Greve (1973) suggested that pentachlorobenzene is a contam-
inant of hexachlorobenzene and that it enters the food chain as a
result of the use of hexachlorobenzene as a fungicide. Villaneuve
et al. (1974) reported that samples of hexachlorobenzene used as a
fungicide to control bunt of wheat contained 200-81,000 ppm penta-
chlorobenzene as a contaminant. Pentachlorobenzene is both a meta-
bolite of and an impurity in the soil fungicide quintozene, which
is used on lettuce, potatoes, and other crops (Dejonckheere et al.
1975, Beck and Hansen 1974), and it is an active ingredient in the
pesticide Polystream (MacKenzie 1971). Pentachlorobenzene has been
identified as a metabolite of the pesticide lindane in susceptible
and resistant strains of houseflies (Reed and Forgash 1970), in
1-71
-------
pheasant eggs and chicks (Sana and Burrage 1976), and in a culture
of mold grown spontaneously on grated carrots (Engst et al. 1977).
Plimmer and Klingebiel (1976) obtained pentachlorobenzene by
irradiating hexachlorobenzene with short-wave light.
B. Environmental Fate
1. Occurrence
Pentachlorobenzene has been found in sprat (Clupea sprattus)
(Lunde and Baumann 1976), in plaice, eel, sprat, whiting, and cod
taken off Norway (Lunde 1976), and in trout (Salmo gairdneri)
exposed to water from the Rhine River for 9 months. Koeman et al.
(1969) found pentachlorobenzene in roaches in the area of the Rhine
in the Netherlands. Pentachlorobenzene at low concentrations has
also been found in wheat products, animal feed, chicken fat, and
pork fat (Greve 1973, Stijve 1971). Beck and Hansen (1974) iden-
tified the compound in soil from a potato field treated with quint-
ozene in Denmark, and de Vos et al. (1974) identified it in green-
house soil treated with quintozene in the Netherlands. Beck and
Hansen (1974) reported that pentachlorobenzene has been found
in market samples of potatoes and carrots.
MacKenzie (1971) reported low residues of Polystream, which
gradually disappeared, in oysters and clams. Polystream is a
mixture of trichlorobenzene, tetrachlorobenzene, and pentachloro-
benzene, and is used to reduce snail attack on oysters.
Morita et al. (1975 as reported by Morita 1977) found penta-
chlorobenzene at 0.009 ppm in samples of human adipose tissue in
Japan.
1-72
-------
2. Transformation
Beck and Hansen (1975) confirmed the persistence of the fungi-
cide quintozene and several of its metabolites and impurities,
including pentachlorobenzene, in soil under controlled laboratory
conditions. They also identified these chemicals in 22 samples of
soil from potato fields that had been treated with quintozene
during the previous 11 years. They concluded that appreciable
amounts of pentachlorobenzene will enter the soil as the result of
the use of quintozene and will persist in the ground for 2-3
years.
Gab et al. (1977) reported that pentachlorobenzene is resis-
tant to photodegradation. They suggested that the compound could
be mineralized in the atmosphere only when exposed to short-wave
ultraviolet light.
Comment: These findings are consistent with pentachloro-
benzene 's chemical and physical properties. It is a chemically
stable compound that is insoluble in water and soluble in fat
solvents. Its vapor pressure (1 mm at 98.6°C) is very low.
Therefore, when present in pesticides, it enters the soil and water
systems, where it degrades very slowly. Its presence in fish,
animal fat, food, and elsewhere in the food chain supports this
judgment.
3. Bioaccumulation
De Bruin (1976) suggested that rates of absorption of the poly-
chlorinated benzenes decline as halogen substitution increases and
he reported that pentachlorobenzene is characterized by metabolic
1-73
-------
inertness. Safe et al. (1976)-reported that the halogenated aroma-
tic compounds are known to accumulate in higher trophic levels of
the food chain.
Safe et al. (1976) studied the metabolism of chlorinated arom-
atic pollutants by the frog (Rana pipiens). They found no penta-
chlorobenzene metabolites in the excretion of frogs given the
compound by intraperitoneal injection. They suggested that the
pentachlorobenzene was stored in fatty tissue and only slowly meta-
bolized after release from the tissue. Kohli et al. (1976)
obtained similar results in rabbits. For experimental details, see
Pentachlorobenzene, Section III.B.I.
MacKenzie (1971) found that Polystream, a mixture of tri-
chlorobenzene, tetrachlorobenzene, and pentachlorobenzene, accumu-
lated in the tissues of oysters and clams in small amounts when it
was applied to oyster beds at 1.9 hectaliters/hectare. These
residues disappeared within 119 days. See 1,2,3-Trichlorobenzene,
Section IV.A.4, for further details.
Comment: These findings are consistent with pentachloro-
benzene 's chemical and physical properties described in Section
II.B.2, Transformation. Its presence in fish, animal fat, food,
and elsewhere in the food chain (see Section II.B.I) confirms its
marked tendency to bioaccumulate.
1-74
-------
PENTACHLOROBENZENE
III. BIOLOGICAL INFORMATION
A. Effects on Humans
No information was found in the sources searched.
B. Tests on Laboratory Organisms
1. Metabolism
In a study of the metabolism of several polychlorinated ben-
zenes, Kohli et al. (1976) gave intraperitoneal injections of 300
mg of pentachlorobenzene dissolved in 10-15 ml of vegetable oil to
an unspecified number of male rabbits, each weighing 4-5 kg. The
authors reported that in urine collected for 10 days 1% of the dose
was excreted as the metabolite 2,3,4,5-tetrachlorophenol and 1% as
pentachlorophenol. The authors suggested that these "metabolites
may have been formed from arene oxide intermediates.
In an earlier study, Parke and Williams (1960) administered
pentachlorobenzene orally and intraperitoneally at 0.5 g/kg to two
rabbits. The authors reported that the major portion (31-45%) of
the oral dose was found unchanged in the gut contents after
3-4 days. In addition, 20% was found in the tissues generally and
about 5% in the feces. Most of the injected dose was found after
10 days in tissues near the site of injection, with 47% in the pelt
and 22% in the depot fat. About 10-20% of the oral dose was elimin-
ated in expired air, as a mixture of less chlorinated benzenes.
Not more than 1% of the dose was found as metabolites in the urine.
The main urinary metabolites were parachlorophenol and
1-75
-------
4-chlorocatechol. In two of four experiments, pentachlorophenol
was identified in the urine.
Safe et al. (1976) investigated the metabolism of chlori-
nated aromatic compounds by the frog (Rana pipiens). They dis-
solved 80 mg of pentachlorobenzene in 4-5 ml of vegetable oil
and administered it equally by intraperitoneal injection to four
animals. They reported that the compound did not yield any meta-
bolic products.
De Bruin (1976) reported that pentachlorobenzene is charac-
terized by metabolic inertness.
2. Toxic Effects
a. Acute Toxicity
No information was found in the sources searched.
b. Carcinogenicity
No information was found in the sources searched.
c. Mutagenicity and Cell Transformation
No information was found in the sources searched.
d. Teratogenicity, Embryotoxicity, and Fetotoxicity
Khera and Villeneuve (1975) administered pentachlorobenzene
at 50, 100, and 200 mg/kg to three groups of 20 pregnant Wistar
rats on days 6-15 of gestation. The mean number of live fetuses
per litter and the mean fetal weight were reduced in the dams
given 200 mg/kg but not in those receiving lower doses. The ratio
of fetal deaths to total implants for the exposed rats was not
1-76
-------
significantly different from the ratio for the control group of
20 rats. The authors reported that administration of pentachloro-
benzene at each of the doses increased the incidence of extra
ribs in fetuses. They also recorded an increased incidence of
sternal defects in fetuses from dams receiving 200 mg/kg.
e. Other Toxicity
Ariyoshi et al. (1975b) investigated the effects .of penta-
chlorobenzene on rats. They gave six female Wistar rats oral
doses of 250 mg/kg of the substance in 2% tragacanth gum solution
once a day for 3 days. The rats were sacrificed 24 hours after
the last dose. The authors reported a statistically significant
increase in the concentrations of cytochrome P-450 and triglyce-
ride in the liver and in microsomal protein, phosphorus of phospho-
lipids, and fatty acid of phospholipids. They found significantly
increased aniline hydroxylase, aminopyrine demethylase, and delta-
aminolevulinic acid synthetase activities. Liver weights were
significantly increased.
1-77
-------
PENTACHLOROBENZENE
IV. ENVIRONMENTAL EFFECTS
A. Ecological Effects
1. Wild and Domestic Mammals
No information was found in the sources searched.
2. Wild and Domestic Birds
No information was found in the sources searched.
3. Fish, Amphibiansf and Reptiles
Safe et al. (1976) measured no pentachlorobenzene metabolites
in frogs (Rana pipiens) given the compound by intraperitoneal
injection. Comment: The experimental design and mode of exposure
in this study were not appropriate for the determination of toxic
effects. For experimental details, see Pentachlorobenzene, Section
III.B.I.
For the effects on fish of Polystream, which contains an
unspecified pentachlorobenzene, see 1,2,3-Trichlorobenzene,
Section IV.A.3.
4. Invertebrates
For the effects on invertebrates of Polystream, which contains
an unspecified pentachlorobenzene, see 1,2,3-Trichlorobenzene,
Section IV.A.4.
5. Plants and Algae
Richardson (1968 as reported by USEPA 1977) reported that
pentachlorobenzene retarded the radial growth of the fungus
1-78
-------
Trichoderma viride but that its effect was less than trichloro-
benzene's. No other experimental details were given.
6. Bacteria and Other Microorganisms
No information was found in the sources searched.
7. Ecological Communities and Processes
No information was found in the sources searched.
B. Other Environmental Effects
No information was found in the sources searched.
1-79
-------
PENTACHLOROBENZENE
V. WORK IN PROGRESS
No information was found in the sources searched,
1-80
-------
SUMMARY TABLE
Name
1,2,3-
Trichlo-
robenzene
1,2,4-
H Trichlo-
' robenzene
00
1,3,5-
Trichlo-
robenzene
Trichloro-
benzene
Solubility Log P
vJC- 1
i in H20; ss in *
ale; vs in eth,
bz, and CS2
i in HO; ss in *
ale; vs in eth
ss in ale; i in *
H2O; vs in eth,
b2, Cs2, and
ligroin
* *
CHARACTERISTICS OF CHLOROBENZENES
Estimated No.
Estimated of Persons
Environmental Exposed
Release Production (Occupationally) Use
* * * As a chemical intermediate
* 15.6 million Ib 5,000 As a solvent in chemical
(1972) manufacturing; as a
dielectric fluid; in dyes,
oils, lubricants, and
insecticides; as a heat
transfer medium
* * 3,000 *
* *' 1,081,000 In pesticides
-------
SUMMARY TABLE (continued)
M
I
00
ro
Name
1,2,3,4-
Tetrachlo-
robenzene
1,2,4,5-
Tetrachlo-
robenzene
Pentachlo-
robenzene
Estimated
Environmental
Solubility Log P Release
OGt-
i in H^O; ss * *
in cola ale;
s in hot ale;
vs in eth,
acetic acid,
CS2, and
ligroin
i in HO; ss * *
in hot ale;
s in eth, bz,
chl, and CS~
Ł
i in HJD and * *
ale; ss in
eth, bz, CSor
and chl; s in
hot ale
Estimated No.
of Persons
Exposed
Production (Occupationally) Use
* * In dielectric fluids;
in organic synthesis
* * As a herbicide and
defoliant, insecti-
cide, moisture resis-
tent impregnant; in
electric insulation;
in packing materials
* * *
B
*No information was found in the sources searched
Key to abbreviations:
s—soluble
ss—slightly soluble
vs—very soluble
i—insoluble
ale—alcohol
eth—ethane
bz—benzene
chl—chloroform
-------
CHLOROBENZENES
REFERENCES
AMEEN, O.A., DAY, A.D., and HAMILTON, K.C. 1960. Effect of
1,2,4,5-tetrachlorobenzene on the germination and seedling
vigor of barley, oats and wheat. Agron. J. 52:87-89 (As
reported by USEPA 1977)
ARIYOSHI, T., IDEGUCHI, K., IWASAKI, K., and ARAKAKI, M. 1975a.
Relationship between chemical structure and activity: II.
Influences of isomers of dichlorobenzene, trichlorobenzene
and tetrachlorobenzene on the activities of drug-metabo-
lizing enzymes. Chem. Pharm. Bull. 23:824-830
ARIYOSHI, T., IDEGUCHI, K., ISHIZUKA, Y., IWASAKI, K., and
ARAKAKI, M. 1975b. Relationship between chemical structure
and activity: I. Effects of the number of chlorine atoms
in chlorinated benzenes on the components of drug-metabo-
lizing systems and the hepatic constituents. Chem. Pharm.
Bull. 23:817-823
BAUER, U. 1972. Concentration of insecticidal hydrocarbons and
PCBs by algae. Schriftenr. Ver. Wasser-Boden-Lufthyg.
Berlin-Dahlem 37:211-219 (Abstract)
BECK, J., and HANSEN, K.E. 1974. Degradation of quintozene,
pentachlorobenzene, hexachlorobenzene, and pentachloro-
aniline in soil. Pestic. Sci. 5:41-48
BROWN, V.K.H., MUIR, C., and THORPE, E. 1969. The acute tox-
icity and skin irritant properties of 1,2,4-trichloro-
benzene. Ann. Occup. Hyg. 12:209-212
CARLSON, G.P. 1977. Chlorinated benzene induction of hepatic
porphyria. Experientia 33:1627-1629
CARLSON, G.P., and TARDIFF, R.G. 1976. Effect of chlorinated
benzenes on the metabolism of foreign organic compounds.
Toxicol. Appl. Pharmacol. 36:383-394
COATE, W.B., SCHOENFISCH, W.H., LEWIS, T.R., and BUSEY, W.M.
1977. Chronic inhalation exposure of rats, rabbits, and
monkeys to 1,2,4-trichlorobenzene. Arch. Environ.
Health 32:249-255
CONDENSED CHEMICAL DICTIONARY (CCD). 1977. 9th ed. Hawley,
G.G., ed. Van Nostrand Reinhold Co., New York
DAVIS, B.C., and HIDU, H. 1969. Effects of pesticides on embry-
onic development of clams and oysters and on survival and
1-83
-------
growth of the larvae. U.S. Fish and Wildlife Service, Fish.
Bull. 67:393-404
DE BRUIN, A. 1976. Biochemical Toxicology of Environmental
Agents. Elsevier/North-Holland, New York
DEJONCKHEERE, W., STEURBAUT, W., and KIPS, R.H. 1975. Problems
posed by residues of quintozene and hexachlorobenzene in
lettuce and witloof cultures. Rev. Agric. 28:581-591
(Abstract)
DE VOS, R.H., TEN NOEVER DE BRAUW, M.C., and OLTHOF, P.O.A.
1974. Residues of pentachleronitrobenzene and related com-
pounds in greenhouse soils. Bull. Environ. Contam. Toxicol.
11:567-571
ENGST, R., MACHOLZ, R.M., and KUJAWA, M. 1977. The metaboliza-
tion of lindane in a culture of mold and the degradation
scheme of lindane. Chemosphere 6:401-418
ERISMAN, H., and GORDON, M. 1975. Identification of organic
compounds in textile plant effluents. Presented at the
First Chemical Congress of the North American Continent,
Mexico City, Mexico, November 30-December 5 (As reported
by USEPA 1977)
GAB, S., SCHMITZER, J., THAMM, H.W., PARLAR, H., and KORTE, F.
1977. Photomineralisation rate of organic compounds ab-
sorbed on particulate matter. Nature 270:331-333
GARRISON, A.W., and HILL, S.W. 1972. Organic pollutants from
mill persist in downstream waters. American Dyestuff
Reporter, 21-25, February 1972 (As reported by USEPA 1977)
GIBSON, A.L. 1957. Tests of bark-penetrating insecticides to
control the Douglas fir beetle. Econ. Entomol. 50:266-268
(As reported by USEPA 1977)
GREVE, P.A. 1973. Pentachlorobenzene as a contaminant of animal
feed. Meded. Fac. Landbouwwetensch. Rijksuniv. Gent.
38:775-784 (Abstract)
GROSCH, D.S. 1973. Reproduction tests: The toxicity for
Artemia of derivatives from non-persistent pesticides.
Biol. Bull. 145:340-351
GROSCH, D.S., and HOFFMAN, A.C. 1973. Vulnerability of specific
cells in the oogenetic sequence of Bracon hebetor Say to
some degradation products of carbamate pesticides. Environ.
Entomol. 2:1029-1032
KITES, R.A. 1973. Analysis of trace organic compounds in New
England rivers. J. Chromatogr. Sci. 11:570-574
1-84
-------
JACOBS, A., BLANGETTI, M., and HELLMUND, E. 1974. Speicherung
chlorierter Rheinwasserschadstaffe im Fettgewebe von
Ratten. Vom Wasser 43:259-274
JONDORF, W.R., PARKE, D.V., and WILLIAMS, R.T. 1955. Studies in
detoxifications: 66. The metabolism of halogenobenzenes.
1:2:3-, 1:2:4-, and 1:3:5-trichlorobenzenes. Biochem. J.
61:512-521
JONDORF, W.R., PARKE, D.V., and WILLIAMS, R.T. 1958. Studies in
detoxication: 76. The metabolism of halogenobenzenes.
1:2:3:4-, 1:2:3:5-, and 1:2:4:5-tetrachlorobenzenes.
Biochem. J. 69:181-189
KAISER, K.L.E. 1977. Organic contaminant residues in fishes
from Nipigon Bay, Lake Superior. J. Fish. Res. Board Can.
34:850-855
KHERA, K.S., and VILLENUEVA, D.C. 1975. Teratogenicity studies
on halogenated benzenes (pentachloro-, pentachloro-,
nitro-, and hexabromo-) in rats. Toxicol. 5:117-122
KOEMAN, J.H., TEN NOEVER DE BRAUW, M.C., and DE VOS, R.H. 1969.
Chlorinated biphenyls in fish, mussels and birds from the
river Rhine and the Netherlands coastal area. Nature 221:
1126-1128
KOHLI, J., JONES, D., and SAFE, S. 1976. The metabolism of
higher chlorinated benzene isomers. Can. J. Biochem.
54:203-208
LOOSANOFF, V.L., MACKENZIE, C.L. Jr., and SHEARER, L.W- 1960a.
Use of chemicals to control shellfish predators. Science
131:1522-1523 (As reported by MacKenzie 1971)
LOOSANOFF, V.L., MACKENZIE, C.L., Jr., and SHEARER, L.W. 1960b.
Use of chemical barriers to protect shellfish beds from pred-
ators. Fish., Wash. State Dept. Fish. 3:86-90 (As reported
by MacKenzie 1971)
LUNDE, G., and BAUMANN-OFSTAD, E. 1976. Determination of fat-
soluble chlorinated compounds in fish. Fresenius Z. Anal.
Chem. 282:395-399 (Abstract)
LUNDE, G. 1976. Persistent and nonpersistent fat-soluble chlor-
inated compounds in marine organisms. Nordforsk, Miljoe-
vardssekr., Publ. Issue 2 Miljoegifter Vatten, Nord. Symp.
Vattenforsk., 12:337-348 (Abstract)
MACKENZIE, C.L., Jr. 1971. Control of oyster drills Eupleura
caudata and Urosalpinx cinereus with the chemical
Polystream. Fish. Bull. 68:285-297
1-85
-------
MERCK INDEX. 9th ed. 1976. Merck & Co. Rahway, N.J.
MORITA, M. 1977. Chlorinated benzenes in the environment.
Ecotox. Environ. Saf. 1:1-6
NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH (NIOSH).
1977. Registry of Toxic Effects of Chemical Substances.
DHEW Publication No. (NIOSH) 78-104-A
NATIONAL OCCUPATIONAL HAZARD SURVEY (NOHS). 1976. National
Institute for Occupational Safety and Health, Cincinnati,
Ohio
PARKE, D.V., and WILLIAMS, R.T. 1960. Studies in detoxication:
81. The metabolism of halogenobenzenes. (a) Metadi-
chlorobenzene; (b) further observations on the metabolism of
chlorobenzene. Biochem. J. 74:5-9
PLIMMER, J.R., and KLINGEBIEL, U.T. 1976. Photolysis of hexa-
chlorobenzene. J. Agric. Food Chem. 24:721-723
POWERS, M.B., COATE, W.B., and LEWIS, T.R. 1975. Repeated topi-
cal applications of 1,2,4-trichlorobenzene. Arch. Environ.
Health 30:165-167
REED, W.T., and FORGASH, A.J. 1970. Metabolism of lindane to
organic soluble products by houseflies. J. Agric. Food
Chem. 18:475-481 (Abstract)
RICHARDSON, L.T. 1968. Selective vapor phase activity of
chloronitro- and chlorobenzene in soil. Phytopathology 58:
316-322 (As reported by USEPA 1977)
RIMINGTON, G.E., and ZIEGLER, G. 1963. Experimental porphyria
in rats induced by chlorinated benzenes. Biochem.
Pharmacol. 12:1387-1397
SAFE, S., JONES, D., KOHLI, J., RUZO, L.O. , HUTZINGER, 0., and
SUNDSTROM, G. 1976. The metabolism of chlorinated aromatic
pollutants by the frog. Can. J. Zool. 54:1818-1823
SAHA, J.G., and BURRAGE, R.H. 1976. Residues of lindane and its
metabolites in eggs, chicks, and body tissues of hen phea-
sants after ingestion of lindane- C via treated wheat seed
or gelatin capsules. J. Environ. Sci. Health Bull. 1:67-93
SAX, N.I. 1975. Dangerous Properties of Industrial Materials.
3rd ed. Reinhold Publishing Corp., New York
SIMMONS, P., BRANSON, D., and BAILEY, R. 1977. 1,2,4-Trichloro-
benzene: Biodegradable or not? Text. Chem. Color. 9:211-
213
1-86
-------
SMITH, C.C., CRAGG, S.T., and WOLFE, G.F. 1978. Subacute tox-
icity of I,2,4-trichlorobenzene (TCB) in subhuman primates.
Fed. Proc. 37:248 (Abstract)
STIJVE, T. 1971. Determination and occurrence of hexachloroben-
zene residues. Mitt. Geb. Lebensmittelunters. Hyg.
62:406-414 (Abstract)
U.S. ENVIRONMENTAL PROTECTION AGENCY (USEPA). 1977. Investiga-
tion of Selected Potential Environmental Contaminants:
Halogenated Benzenes. Office of Toxic Substances,
Washington, D.C., July 1977. EPA 560/2-77-004
U.S. INTERNATIONAL TRADE COMMISSION (USITC). 1972,1976.
Synthetic Organic Chemicals, United States Production and
Sales, 1976. Washington, D.C. USITC Publication*833
VERSCHUEREN, K. 1977. Handbook of Environmental Data on Organic
Chemicals. Van Nostrand Reinhold Co., New York
VILLANEUVE, E.G., JENNINGS, R.W., BURSE, V.W., and KIMBROUGH,
R.D. 1974. Evidence of chlorodibenzo-p-dioxin and chloro-
dibenzo-furan in hexachlorobenzene. J. Agr. Food Chem.
22:916-917
WESTOO, G., NOREN, and ANDERSON, M. 1971. Levels of organochlo-
rine pesticides and polychlorinated biphenyls in some cereal
products. Vaar. Foeda 23:341-361 (Abstract)
WORLD HEALTH ORGANIZATION (WHO). 1978. Information Bulletin on
the Survey of Chemicals Being Tested for Carcinogenicity.
No. 7. Lyon, France
YANG, K.H., and PETERSON, R.E. 1977. Differential effects of
halogenated aromatic hydrocarbons on pancreatic excretory
function in rats. Fed. Proc. 36:356 (Abstract)
YOUNG, D.R., HEESEN, T.C., and McDERMOTT-ERLICH, D.J. 1976.
Synoptic survey of chlorinated hydrocarbon inputs to the
Southern California blight. Draft Report to National
Environmental Research Center, U.S. Environmental
Protection Agency, Corvallis, Oregon (As reported by USEPA
1977)
1-87
-------
1,2-DICHLOROPROPANE
TABLE OF CONTENTS
Page
Overview II-l
I. Chemical and Physical Information II-3
II. Source and Fate in the Environment II-5
III. Biological Information II-8
IV. Environmental Effects 11-15
V. Work in Progress 11-18
References 11-19
Il-i
-------
1,2-DICHLOROPROPANE
OVERVIEW
1,2-Dichloropropane is a volatile colorless liquid that
is soluble in most organic solvents but only slightly soluble
in water. It is used primarily as a solvent and degreasing
agent, as a chemical intermediate, as a lead scavenger, and
as a soil fumigant for nematodes. In the United States, 71
million pounds of the compound were produced in 1976 and 145
million pounds in 1974. An estimated 1 million workers are
exposed to 1,2-dichloropropane.
Although no specific information on the environmental
fate or effects of 1,2-dichloropropane was found in the sources
searched, the chemical and physical properties of the compound
indicate that it is not likely to persist or bioaccumulate.
Liver appears to be a primary target organ of 1,2-dichloro-
propane toxicity. In experimental animals, exposure to 1,2-
dichloropropane has resulted in fatty degeneration, hyperplasia,
and hypertrophy of the liver and changes in the activity of
liver enzymes. In a single human case study, degeneration
of liver cells and changes in mitochondria, endoplasmic retic-
ulum, and Golgi apparatus were reported. Studies on laboratory
animals also indicated degeneration of kidney cells, hemosid-
erosis of the spleen, and necrosis of adrenals.
An unspecified isomer of dichloropropane has been shown
to cause mutations in Salmonella typhimurium and Aspergillus
II-l
-------
nidulans. No adequate tests on the carcinogenicity of 1,2-
dichloropropane were reported in the sources searched and no
information on teratogenicity was found. 1,2-Dichloropropane
has been tentatively selected for carcinogenicity testing by
the National Cancer Institute.
II-2
-------
1,2-DICHLOROPROPANE
I. CHEMICAL AND PHYSICAL INFORMATION
A. Identification
1. CAS No; 78-87-5
2. NIOSH No.; TX96250
3. Synonyms and Trade Names
ENT 15,406
Propylene dichloride
alpha,beta-Dichloropropane
Propylene chloride
alpha,beta-Propylene dichloride
(NIOSH 1977)
B. Formulas and Molecular Weight
1. Structural Formula
H
I
H_C C CH-
2| I 3
Cl Cl (HCP 1976)
2. Empirical Formula
C3H6C12 (HCP 1976)
3. Molecular Weight
112.99 (HCP 1976)
II-3
-------
C. Physical Properties
1. Description
Colorless liquid; chloroformlike odor (CCD 1977)
2. Boiling Point
96.37° (HCP 1976)
3. Melting Point
-100.44°C (HCP 1976)
4-
4. Vapor Pressure
40 mm at 19.4°C (HCP 1976)
5. Solubility
Slightly soluble in water; soluble in alcohol, ether, ben-
zene, and chloroform (HCP 1976)
6. Octanol/Water Partition Coefficient
No information was found in the sources searched.
7. Specific Gravity
?n
1.5201ZU (HCP 1976)
D. Composition of the Commercial Product
No information was found in the sources searched.
II-4
-------
1,2-DICHLOROPROPANE
II. SOURCE AND FATE IN THE ENVIRONMENT
A. Sources
1. Production and Trends
71.0 million Ib (1976) (USITC 1976)
145.1 million Ib (1974) (USITC 1974)
40.7 million Ib (1972 sales) (USITC 1972)
2. Manufacturers
BASF Wyandotte Corp.
Dow Chemical Co.
Jefferson Chemical Co.
Olin Corp.
(USITC 1976)
3. Use
As a chemical intermediate for perchloroethylene and carbon
tetrachloride; in the synthesis of amines and rubber-processing
chemicals; as an inert reaction medium in chlorination and sulfo-
nation operations; as a lead scavenger for antiknock fluids;
as a solvent for fats, oils, waxes, gums, and resins; in solvent
mixtures for cellulose esters and ethers; in scouring compounds;
in spotting agents; in metal degreasing agents; in dry-cleaning
fluids; in paint and varnish removers; as a soil fumigant for
nematodes (CCD 1977,Olin 1978)
4. Occupational Exposure
NOHS Rank: 196
Estimated number of persons exposed: 1,094,000
(NOHS 1976)
H-5
-------
ACGIH TLV-TWA: 75 ppm (350 mg/m3) (ACGIH 1978)
5. Release
1,2-Dichloropropane has been found in effluents from a
sewage treatment plant and a textile mill (Shackelford and
Keith 1976).
B. Environmental Fate
1. Occurrence
1,2-Dichloropropane has been found in river water, in
the ocean, and in drinking water (Shackelford and Keith 1976).
2. Transformation
Roberts and Stoydin (1976) reported that, because of volati-
14
lization, less than 1% of a dose of C-radiolabeled 1,2-dichloro-
propane applied to soil in an open glass container exposed
outdoors remained after 10 days. They also reported that the
compound degraded only slightly (4% or less) in 5 months when
applied to a loam soil and stored in sealed containers.
Comment: As a saturated chlorinated hydrocarbon, 1,2-
dichloropropane is chemically stable, a property that is consis-
tent with the data given above. It has a low water solubility
(2.6 g/liter at 20°C (CCD 1977)) and a high vapor pressure
(40 mm at 19.4°C (HCP 1976)), and it can react readily with
oxidizing agents (Sax 1975). 1,2-Dichloropropane is biodegrad-
able (several indigenous soil bacteria were able to use it
as an energy source (Altman 1969)). These properties indicate
II-6
-------
that, if released, most of the chemical will enter the atmos-
phere but some will enter the water systems. It will, for
the most part, be dispersed and will not persist in the envi-
ronment.
3. Bioaccumulation
No specific data on the bioaccumulation of 1,2-dichloro-
propane were found in the sources searched.
Comment: 1,2-Dichloropropane is a lipophilic solvent
and is low in water solubility and relatively stable chemically
(see Section II.B.2). These data indicate that it has a ten-
dency to bioaccumulate, but this tendency may be offset in
part by the substance's high vapor pressure (see Section II.B.2),
which allows excretion through the lungs. If released in water
for prolonged periods, however, it is likely to bioaccumulate
in fish and aquatic invertebrates, which will be exposed to
it on a continuous basis. 1,2-Dichloropropane can also be
expected to biodegrade, although the chlorine substituents
will slow this process. Its properties indicate that 1,2-
dichloropropane will not bioaccumulate in mammals, a conclusion
consistent with a recent study in rats (flutson et al. 1971,
see Section III.B.I).
II-7
-------
1,2-DICHLQROPROPANE
III. BIOLOGICAL INFORMATION
A. Effects on Humans
Chiappino and Secchi (1968) described a case in which a
59-year-old man accidentally ingested a solvent whose toxic com-
ponent was reported to be 1,2-dichloropropane (the exact dose
could not be determined). Immediate symptoms included vomiting
and a burning sensation in the esophagus and the stomach.
By the 4th day, nausea, anorexia, vomiting, and jaundice were
observed. Electron microscopy and histological studies revealed
degeneration of liver cells and ultrastructural changes in
mitochondria, endoplasmic reticulum, and Golgi apparatus.
Nater and Gooskens (1976) described three cases of derma-
titis in workers exposed to D-D, a soil fumigant containing
27.1% 1,2-dichloropropane, 53% 1,3-dichloropropene, 6.5% 3,3-
dichloropropene-1, 6.5% 2,3-dichloropropene-l, 0.4% 1,2-dichloro-
propene, 6.5% other chlorinated hydrocarbons, and 1% epichloro-
hydrin. Exposure to the fumigant at unknown concentrations
produced erythematous, itching eruptions on the face and arms.
The authors stated that, according to the Netherlands Ministry
of Social Affairs, seven other cases of skin reactions to D-D
were reported from 1966 to 1971. Almost all the cases were
reported to result from D-D dripping into the shoes of farmers
during spraying. The authors applied pure D-D and 10% D-D
in acetone to the skin of volunteers, which resulted in derma-
titis in all cases. They also performed patch tests with 1%
II-8
-------
D-D in acetone on three subjects to determine if dermatitis
occurred as a result of irritation or allergic reaction. An
allergic reaction occurred in one subject. Patch tests with
97% pure 1,2-dichloropropane did not produce an allergic reac-
tion in any of the patients.
B. Tests on Laboratory Organisms
1. Metabolism
Hutson et al. (1971) conducted two experiments on the
metabolism of 1,2-dichloropropane in rats. In one experiment,
six rats of each sex were given 0.88 mg of C-labeled dichloro-
propane as a solution in 0.5 ml arachis oil by stomach tube.
Radioactivity was measured in the urine and feces, and, after
the animals were killed on day 4, in the skin, gut, and carcass.
The authors reported that a mean of 48.5% of the radioactivity
was excreted in the urine of male rats during the first 24 hours
and a mean total of 51.1% after 4 days. In the feces, the
respective figures were 5.0 and 6.9%. After 4 days, 0.5% of
the administered dose was recovered in the gut, 1.7% in the
skin, and 4.1% in the carcass. In females, the means were
51.9% in the urine and 3.8% in the feces during the first
24 hours. After 4 days, the mean totals were 54.4% in the
urine and 4.9% in the feces; 0.5% was found in the gut, 1.4%
in the skin, and 3.2% in the carcass.
In the other experiment, five female rats were given oral
doses of 1.07 mg of C-labeled dichloropropane, and the exhaled
radioactivity was measured. Because 19.3% of the administered
II-9
-------
radioactivity was exhaled as C02, the authors concluded that
extensive metabolism of the compound occurred.
Van Dyke and Wineman (1971) studied the in vitro enzymatic
dechlorination of 1,2-dichloropropane in rat liver microsomes.
Of 1,2-dichloropropane added to an incubation medium (consisting
of the microsomal suspension, NADP, glucose 6-phosphate, glucose
6-phosphate dehydrogenase, and a cell supernatant fraction),
5.8% was enzymatically dechlorinated.
2.
Toxic Effects
a. Acute Toxicity
The acute toxicity of 1,2-dichloropropane as reported
by the NIOSH RTECS data base (1978) is given in Table III-l.
TABLE III-l
ACUTE TOXICITY OF 1,2-DICHLOROPROPANE
Parameter
LD50
LD50
LD50
LD50
LDLo
LCLo
Dosage
1,900 mg/kg
860 mg/kg
2,000 mg/kg
8,750 mg/kg
5,000 mg/kg
2,000 ppm
for 4 hr
Animal
Rat
Mouse
Guinea pig
Rabbit
Dog
Rat
Route
Oral
Oral
Oral
Skin
Oral
Inhalation
H-10
-------
b. Carcinogenicity
To determine the likelihood of 1,2-dichloropropane producing
hepatomas, Heppel et al. (1948) exposed 80 C3H mice (sex unspeci-
fied) to the compound by inhalation at 400 ppm. The mice received
37 exposures lasting from 4 to 7 hours. Only three mice survived
a 7-month observation period. Multiple hepatomas were observed
in the survivors. No controls were used in this experiment.
Comment: This study cannot be considered an adequate test
for carcinogenicity because the spontaneous incidence of hepatomas
in C3H mice is high and because no controls were used.
c. Mutagenicity and Cell Transformation
According to an abstract of a presentation by Bignami et
al. (1977), dichloropropane (isomer unspecified) induced base
substitution in the Salmonella typhimurium strains TA1538 and
TA100. The authors considered the compound to be a "definite
mutagen" in these strains. They also reported that the compound
induced point mutations in Aspergillus nidulans by significantly
increasing the frequency of mutants resistant to 8-azaguanine.
d. Teratogenicity
No information was found in the sources searched.
e. Other Toxicity
Heppel et al. (1946) exposed guinea pigs, mice, rats, and
rabbits to 1,2-dichloropropane vapor at 1,000-2,200 ppm for
7 hours/day, 5 days/week, for up to 128 exposures. Histological
studies were performed on the animals after autopsy. Guinea
11-11
-------
pigs exposed at 2,200 ppm for repeated 7-hour periods developed
conjunctival swelling to such a degree that they lost blinking
ability. By the fifth exposure, 11 of 16 guinea pigs had died.
Histological examination revealed marked fatty degeneration of
the liver and kidney and necrosis of the adrenals. Ten of eleven
mice died before the end of one 7-hour inhalation exposure at
2,200 ppm. The deaths followed the development of gross incoordi-
nation and prostration. Histological examination revealed fatty
degeneration of the liver and kidney. Five of twenty rats died
by the fifth exposure at 2,200 ppm. Histological examination
showed splenic hemosiderosis and fatty degeneration of the liver.
Two of four rabbits died after the second exposure at 2,200 ppm.
The histological findings were similar to those for the rats.
Heppel et al. (1948) exposed rats and guinea pigs (of both
sexes) and female dogs to 1,2-dichloropropane vapor at 400 ppm
for 7 hours/day, 5 days/week, for up to 140 exposures. Control
groups were exposed to air. Of 49 rats, 3 died after at least
108 exposures, but the authors stated that it was unlikely that
the deaths resulted from the exposures. They attributed the
deaths of 7 of 32 exposed guinea pigs and 12 of 42 controls to
an infectious disease characterized by enlarged lymph glands.
No deaths were reported in 5 dogs. According to the authors,
the only ill effect caused by the exposures was decreased weight
gain in rats. Histological examination showed no changes attrib-
utable to 1,2-dichloropropane. The authors also exposed' 80 mice
to 1,2-dichloropropane at 400 ppm on the same schedule for a
total of 37 exposures. Most mice died during the course of the
11-12
-------
exposures. Mice that died after 14-28 exposures showed conges-
tion, fatty degeneration, and necrosis of the liver and degener-
ation of the kidney.
Sidorenko et al. (1976) exposed an unspecified number of
white male rats to 1,2-dichloropropane by continuous inhalation
>
at 1 and 2 mg/liter for 7 days. Changes in blood catalase and
cholinesterase activity were observed 4 hours after inhalation
of dichloropropane at 2 mg/ml. Histological and histochemical
analysis of centrilobular sections of the liver showed damage
to small blood vessels, with signs of protein-fat dystrophy>
suppression of enzymic activity, and reduction in the content
of ribonucleoproteins. Changes in the peripheral sections of
liver lobules, including hyperplasia and hypertrophy, were also
reported. In the kidneys, histostructural changes were accom-
panied by suppression of oxidation enzymes and phosphomonoester-
ases.
According to an abstract of a Russian article, Kurysheva
and Ekshtat (1975) observed that daily oral administration of
14.4 and 360 mg/kg of 1,2-dichloropropane to rats raised the
concentration of serum cholesterol beta-lipoproteins and gamma-
globulin by day 10. By day 20, serum pseudocholinesterase was
inhibited and fructose 1-monophosphate aldolase, alanine trans-
aminase, and asparagine transaminase were stimulated. Alanine
transaminase was inhibited by day 30. The abstract reported
no additional experimental data.
Ekshtat et al. (1975) reported that daily oral doses of
1,2-dichloropropane at 8.8, 44, and 220 mg/kg administered to
11-13
-------
an unspecified number of rats for 20 days disturbed protein forma-
tion and enzyme and lipid metabolism by the liver. Of the four
main components of the nematocide fumigant D-D, 1,2-dichloropro-
pane was reported to have the greatest cumulative toxicity.
No other experimental details were reported in the abstract from
the Russian article.
11-14
-------
1,2-DICHLOROPROPANE
IV. ENVIRONMENTAL EFFECTS
A. Ecological Effects
Note: Because of the lack of specific information on 1,2-
dichloropropane, information on its ecological effects must be
derived from data on the nematocide D-D, a mixture of 1,2-dichloro-
propane and 1,3-dichloropropene.
1. Wild and Domestic Mammals
No information was found in the sources searched.
2. Wild and Domestic Birds
No information was found in the sources searched.
3. Fishj, Amphibians, and Reptiles
The Aquatic Toxicity Rating (96-hr TLm, species unspecified)
of 1,2-dichloropropane is 100-10 ppm, which is considered slightly
toxic (NIOSH 1977). The 96-hr TLms for bluegill sunfish and
tidewater silverside were 320 and 240 mg/liter, respectively
(Dawson et al. 1977).
4. Invertebrates
Use of D-D at an unspecified concentration completely elimi-
/
nated the springtail population in soil within 30 days (Edwards
1969). The method of treatment was not reported.
2
Five annual treatments of soil with D-D at 60 ml/m resulted
in a statistically significant increase in the numbers of earth-
11-15
-------
worms and mites and a statistically significant decrease in
the numbers of phytophagic nematodes. No significant change
was noted in populations of enchytraeids, saprophagic nematodes,
tylenchus-psilenchus, or collembola (Van den Brande and Heungens
1969) .
5. Plants and Algae
No dichloropropane or very small residues were found in
potatoes grown in D-D-treated soil (Roberts and Stoydin 1976,
Edwards 1969, Karasz and Gamengeim 1971).
Lebbink (1977) reported that soil fumigation with 1,2-
dichloropropane resulted in a 52% incidence of ear malforma-
tions in winter wheat. The author stated that yield was reduced
when the rate of ear malformations exceeded 15%. The "no effect
level" for 1,2-dichloropropane was estimated to be 5 liters/
hectare when applied in the autumn and 1 liter/hectare when
applied in the spring.
6. Bacteria and Other Microorganisms
Several soil bacteria used chlorinated hydrocarbons in
D-D as an energy source and, when the bacteria were grown on
media containing D-D at 1, 10, and 100 ppm, they produced greater
amounts of amino acids (Altman 1969).
7. Ecological Communities and Processes
No information was found in the sources searched.
11-16
-------
B. Other Environmental Effects
No information was found in the sources searched,
11-17
-------
1,2-DICHLOROPROPANE
V. WORK IN PROGRESS
1,2-Dichloropropane (NCI No. C55141) has been tentatively
selected for testing in the National Cancer Institute's carcino-
genesis bioassay program (NCI 1978).
11-18
-------
1,2-DICHLOROPROPANE
REFERENCES
ALTMAN, J. 1969. Effect of chlorinated C- hydrocarbons on
amino acid production by indigenous soil bacteria. Phyto-
pathology 59:762-766
AMERICAN CONFERENCE OF GOVERNMENTAL INDUSTRIAL HYGIENISTS (ACGIH).
1978. TLVs**: Threshold limit values for chemical sub-
stances in workroom air adopted by ACGIH. Cincinnati,
Ohio
BIGNAMI, M., CARDAMONE, G., COMBA, P., ORTALI, V.A., MORPURGO, G.,
and CARERE, A. 1977. Relationship between chemical struc-
ture and mutagenic activity in some pesticides: The use
of Salmonella typhimurium and Aspergillus nidulans. Mutat.
Res. 46:243-244 (Abstract)
CHIAPPINO, G., and SECCHI, G.C. 1968. [Description of a case
of acute intoxication from accidental ingestion of 1,2-
dichloropropane sold as trilene.] Med. Lav. 59:334-341
(Abstract, Italian)
CONDENSED CHEMICAL DICTIONARY (CCD). 1977. 9th ed. Hawley,
G.G., ed. Van Nostrand Reinhold Co., New York
DAWSON, W., JENNINGS, L., DROZDOWSKI, D., and RIDER, E. 1977.
The acute toxicity of 47 industrial chemicals to fresh
and saltwater fish. J. Hazardous Materials 1:303-318
EDWARDS, G.A. 1969. Soil pollutants and soil animals. Sci.
Am. 22:88-99
EKSHTAT, B.Y., KURYSHEVA, N.G., FEDYANINA, V.N., and PAVLENKO,
M.N. 1975. [Study of the cumulative properties of sub-
stances at different activity levels.] Uch. Zap.-Mosk.
Nauchno-Issled. Inst. Gig. 22:46-48 (Russian)
HANDBOOK OF CHEMISTRY AND PHYSICS (HCP). 1976. 57th ed.
Chemical Rubber Co., Cleveland, Ohio
HEPPEL, L.A., NEAL, P.A., HIGHMAN, B., and PORTERFIELD, V.T.
1946. Toxicology of 1,2-dichloropropane (propylene dichlo-
ride): I. Studies on effects of daily inhalations. J.
Ind. Hyg. Toxicol. 28:1-8
HEPPEL, L.A., HIGHMAN, B., and PEAKE, E.G. 1948. Toxicology
of 1,2-dichloropropane (propylene dichloride): IV. Effects
of repeated exposures to a low concentration of the vapor.
J. Ind. Hyg. Toxicol. 30:189-191
11-19
-------
HUTSON, D.H., MOSS, J.A., and PICKERING, B.A. 1971. The excre-
tion and retention of components of the soil fumigant D-D
and their metabolites in the rat. Food Cosmet. Toxicol. 9;
677-680
KARASZ, B., and GAMENGEIN, M. 1971. Gas chromatographic deter-
mination of D-D (cis- and trans-l,3-dichloro-l-propene
and 1,2-dichloropropane) in potatoes. J. Agric. Food
Chem. 19:1270-1271
KURYSHEVA, N.G., and EKSHTAT, B.Y. 1975. [Effect of 1,3-
dichloropropylene and 1,2-dichloropropane on the func-
tional state of the liver in animal experiments.] Uch.
Zap.-Mosk. Nauchno-lssled. Inst. Gig. 22:89-92 (Abstract,
Russian)
LEBBINK, G. 1977. Ear malformation in winter wheat after
soil fumigation with dichloropropene-dichloropropane mix-
tures. Down Earth 32:8-11
NATER, J.P., and GOOSKENS, V.H.J. 1976. Occupational derma-
tosis due to soil fumigant. Contact Dermatitis 2:
227-229
NATIONAL CANCER INSTITUTE (NCI). 1978. Chemicals Being Tested
for Carcinogenicity by the Bioassay Program. Division
of Cancer Cause and Prevention.
NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH (NIOSH).
1977. Registry of Toxic Effects of Chemical Substances.
DREW Publication No. (NIOSH) 78-104-A
NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH (NIOSH).
1978. Registry of Toxic Effects of Chemical Substances.
Data Base
NATIONAL OCCUPATIONAL HAZARD SURVEY (NOHS). 1976. National
Institute for Occupational Safety and Health, Cincinnati,
Ohio
OLIN. 1978. Propylene dichloride: Material safety data and
product data sheets. Enclosed in personal communication
from D.D. Palm, Director, Consumer and Product Services,
Olin Research Center, New Haven, Conn., to Clement Associ-
ates, August 16, 1978
ROBERTS, T.R., and STOYDIN, G. 1976. The degradation of (Z)-
and (E)-1,3-dichloropropanes and 1,2-dichloropropane in
soil. Pesticide Sci. 1:325-335
SAX, N.I. 1975. Dangerous Properties of Industrial Materials.
3rd ed. Reinhold Publishing Corp., New York
11-20
-------
SHACKELFORD, W.M., and KEITH, L.H. 1976. Frequency of Organic
Compounds Identified in Water. U.S. Environmental Protec-
tion Agency, Environmental Research Laboratory, Office of
Research and Development, Athens, Georgia, December 1976.
EPA-600/4-76-062
SIDORENKO, G.I., TSULAYA, V.R., KORENEVSKAYA, E.I., and
BONASHEVSKAYA, T.I. 1976. Methodological approaches
to the study of the combined effect of atmospheric pollu-
tants as illustrated by chlorinated hydrocarbons. Environ,
Health Perspect. 13:111-116
U.S. INTERNATIONAL TRADE COMMISSION (USITC). 1972, 1974, 1976.
Synthetic Organic Chemicals, United States Production
and Sales. Washington, D.C. USITC Publication 833
VAN DEN BRANDS, J., and HEUNGENS, A. 1969. Influence of re-
peated applications of nematicides on the soil fauna in
begonia culture. Neth. J. Plant Pathol. 75:40-44
VAN DYKE, R.A., and WINEMAN, C.G. 1971. Enzymatic dechlori-
nation: Dechlorination of chlorethanes and propane in
vitro. Biochem. Pharmacol. 20:436-470
11-21
-------
GLYCIDOL AND ITS DERIVATIVES
TABLE OF CONTENTS
Page
Overview III-l
Glycidol
I. Chemical and Physical Information III-3
II. Source and Fate in the Environment III-5
III. Biological Information III-7
IV. Environmental Effects 111-12
V. Work in Progress 111-13
Glycidyl Acrylate
I. Chemical and Physical Information 111-14
II. Source and Fate in the Environment 111-16
III. Biological Information 111-18
IV. Environmental Effect 111-20
V. Work in Progress 111-21
Glycidyl Methacrylate
I. Chemical and Physcial Information 111-22
II. Source and Fate in the Environment 111-24
III. Biological Information 111-26
IV. Environmental Information 111-28
V. Work in Progress 111-30
Allyl Glycidyl Ether
I. Chemical and Physical Information 111-31
II. Source and Fate in the Environment 111-33
III. Biological Information 111-35
IV. Environmental Effects 111-40
V- Work in Progress 111-41
n-Butyl Glycidyl Ether
I. Chemical and Physical Information 111-42
II. Source and Fate in the Environment 111-44
III. Biological Information 111-46
Ill-i
-------
IV. Environmental Effects 111-52
V. Work in Progress 111-53
para-Cresyl Glycidyl Ether
I. Chemical and Physical Information 111-54
II. Source and Fate in the Environment 111-56
III. Biological Information 111-57
IV. Environmental Effects 111-58
V. Work in Progress • 111-59
Phenyl Glycidyl Ether
I. Chemical and Physical Information 111-60
II. Source and Fate in the Environment 111-62
III. Biological Information 111-64
IV. Environmental Effects 111-73
V. Work in Progress 111-74
Diglycidyl Ether of Bisphenol A
I. Chemical and Physical Information 111-75
II. Source and Fate in the Environment 111-78
III. Biological Information 111-80
IV. Environmental Effects 111-84
V. Wdrk in Progress 111-85
Summary Table 111-86
References 111-88
Ill-ii
-------
GLYCIDOL AND ITS DERIVATIVES
OVERVIEW
The chemicals discussed in this dossier are glycidol,
two glycidyl esters and five glycidyl ethers. The glycidyl
ethers and esters are not commercially synthesized from glycidol
but are considered, in this report, as derivatives for simplicity
in assigning a name to the category. All of these compounds
contain at least one oxirane (epoxide) group that usually reacts
readily with nucleophilic substances. Glycidol and allyl
glycidyl ether are soluble in water and lipid solvents. Phenyl
glycidyl ether is slightly soluble in water and soluble in
lipid solvents. Glycidyl acrylate and n-butyl glycidyl ether
are insoluble and slightly soluble in water, respectively-
No production data for glycidol and its derivatives were
found in the sources searched. Glycidol is used as a
stabilizer in the production of vinyl polymers, glycidyl
acrylate in the production of thermosetting acrylic surface-
coating resins, and the glycidyl ethers in epoxy resin systems.
It was estimated in the National Occupational Hazard Survey
that 105,000 workers in the United States are exposed to
glycidol, 105,000 to glycidyl methacrylate, and 118,000 to
*
glycidyl ethers.
Skin contact is the primary route of human exposure to
the epoxides discussed in this dossier. Workers exposed to
glycidyl ethers have developed dermatitis. Symptoms observed
included tenderness, redness, itching, swelling, edema, blister
III-l
-------
formation, second-degree burns, and discharge from affected areas.
Exposure to the vapors of glycidyl ethers has been found to irri-
tate the eyes, nose, and respiratory tract of humans. These ethers
have a sensitizing effect on humans and cross-sensitization may
occur. After an initial exposure to a glycidyl ether, exposure
to the same compound or another glycidyl ether at previously non-
irritating concentrations will cause dermatitis.
In laboratory animals, glycidol and glycidyl ethers caused
central nervous system depression. Glycidol, glycidyl acrylate,
and the glycidyl ethers have caused skin and eye irritation.
Glycidol has been shown to cause temporary sterility in male rats
and necrosis of the testes has been reported in rats exposed to
the glycidyl ethers. Glycidol, glycidyl methacrylate, and digly-
cidyl ether of bisphenol A have given negative results in carcino-
genicity studies. Glycidol has been tentatively selected for
carcinogenesis bioassay by the National Cancer Institute. Glycidol
was reported to be mutagenic in Salmonella typhimurium, Drosophila,
Neurospora, barley, and yeast. Positive results in Salmonella
typhimurium have been reported for the glycidyl ethers. n-Butyl
glycidyl ether was mutagenic to mice in the dominant lethal test.
Phenyl glycidyl ether gave negative results in a teratogenicity
study. No reports on the teratogenicity of the other compounds
discussed in this dossier were found.
In goldfish, 96-hour LDSOs were reported to be 30 and 43
mg/liter for allyl glycidyl ether and phenyl glycidyl ether,
respectively.
III-2
-------
GLYCIDOL AND ITS DERIVATIVES
GLYCIDOL
I. CHEMICAL AND PHYSICAL INFORMATION
A. Identification
1. CAS No.; 556-52-5
2. NIOSH No.; UB43750
3. Synonyms and Trade Names
Oxiranemethanol
1-Propanol, 2,3-epoxy-
Allyl alcohol oxide
Glycide
Glycidyl alcohol
l-Hydroxy-2,3-epoxypropane
1,2-Epoxy-3-hydroxypropane
2-(Hydroxymethyl)oxirane
3-Hydroxy-l,2-epoxypropane
3-Hydroxypropylene oxide
(NIH/EPA 1978)
B. Formulas and Molecular Weight
1. Structural Formula
H2C CH — CH2
OH 0
(NIH/EPA 1978)
2. Empirical Formula
C,,HC00 (NIH/EPA 1978)
III-3
-------
3. Molecular Weight
74.08 (HCP 1976)
C. Physical Properties
1. Description
Colorless liquid (CCD 1977)
2. Boiling Point
56.5°C at 11 mm (HCP 1976)
3. Melting Point
No information was found in the sources searched.
4. Vapor Pressure
No information was found in the sources searched.
5. Solubility
Soluble in water, alcohol, ether, acetone, benzene,
and chloroform (HCP 1976)
6. Octanol/Water Partition Coefficient
No information was found in the sources searched.
7. Specific Gravity
1.1174° (HCP 1976)
D. Composition of the Commercial Product
No information was found .in the sources searched.
III-4
-------
GLYCIDOL
II. SOURCE AND FATE IN THE ENVIRONMENT
A. Sources
1. Production and Trends
Listed by USITC under the section "Miscellaneous Chemi-
cals," but no production data given (USITC 1976)
2. Manufacturers
Dixie Chemical Co. (USITC 1976)
3. Use
As a stabilizer for natural oils; as a demulsifier;
as a dye-leveling agent; as a stabilizer for vinyl polymers
(CCD 1977)
4. Occupational Exposure
Rank: 1118
Estimated number of/persons exposed: 105,000*
* rough estimate
(NOHS 1976)
ACGIH TLV-TWA: 50 ppm (150 mg/m3) (ACGIH 1978)
5. Release
No information was found in the sources searched.
III-5
-------
B. Environmental Fate
1. Occurrence
No information was found in the sources searched.
2. Transformation
No specific data were found in the sources searched.
Comment: Glycidol is soluble in water (HCP 1976)* and
will therefore remain in the aquatic medium when discharged
into water systems.
3. Bioaccumulation
No specific data were found in the sources searched.
Comment: Glycidol is soluble in both water and lipid
solvents (HCP 1976), which suggests a potential for bioaccu-
mulation.
III-6
-------
GLYCIDOL
III. BIOLOGICAL INFORMATION
A. Effects on Humans
No information was found in the sources searched.
B. Tests on Laboratory Organisms
1. Metabolism
Jones (1975) administered glycidol at 200 mg/kg/day by
intraperitoneal injection to five male ICI/Swiss mice for 10
days. Three male Wistar rats were given glycidol by intraper-
itoneal injection at 100 mg/kg/day for 10 days. Urine was
collected for 24 hours after dosing, and urinary metabolites
were identified as S-(2,3-dihydroxypropyl)cysteine and the
corresponding mercapturic acid.
Jones (1975) also gave two rats and three mice single
14
intraperitoneal injections of C-labeled glycidol. Rats re-
ceived 100 mg/kg and mice received 200 mg/kg. In rats 15.3%
of the dose was excreted as C02 in the first 24 hours after
administration. In mice 16.0% was excreted.
When [U-C]-glycidol was incubated for 3 hours with gluta-
thione and a rat liver supernatant, 50-60% of the radioactivity
was identified as S-(2,3-dihydroxy[U-14C]propyl) glutathione
and 30-35% was [U-14C]glycerol (Jones 1975). (The supernatant
had been obtained by spinning homogenized rat liver at 300 g
for 15 minutes and spinning the resultant supernatant at 100,000 g
for 1 hour.)
III-7
-------
2. Toxic Effects
a. Acute Toxicity
The acute toxicity of glycidol, as reported by the NIOSH
RTECS data base (1978a), is given in Table III-l.
TABLE III-l
ACUTE TOXICITY OF GLYCIDOL
Parameter
LD50
LD50
LD50
LC50
LC50
LDLo
Dosage
850
450
1,980
580
for
450
for
500
mg/kg
mg/kg
mg/kg
ppm
8 hr
ppm
4 hr
mg/kg
Animal
Rat
Mouse
Rabbit
Rat
Mouse
Mouse
Route
Oral
Oral
Skin
Inhalation
Inhalation
Intraper itoneal
Hine et al. (1956) gave mice and rats glycidol intragas-
trically at a range of doses used to determine the LD50, which
was calculated to be 450 mg/kg in mice and 850 mg/kg in rats.
CNS depression, incoordination, and ataxia were observed. Animals
were often comatose at the time of death.
Hine et al. (1956) also reported that glycidol was a moderate
irritant when 0.5 ml of undiluted compound was applied to the
skin of rabbits. Glycidol caused severe eye irritation in rabbits
III-8
-------
when 0.1 ml of undiluted compound was dropped on the cornea.
b. Carcinogenicity
Van Duuren et al. (1967) applied a 5% glycidol solution
in acetone to the skin of 20 female ICH/Ha Swiss mice three
times a week for 520 days. No tumors or lesions were observed.
c. Mutagenicity and Cell Transformation
McCann et al. (1976) reported that glycidol induced rever-
tants in Salmonella typhimurium strain TA1535. When glycidol
was applied to a plate containing S. typhimurium, 1,730 rever-
tants were observed per 223 yg of the compound.
Wade et al. (1976) reported that glycidol induced revertants
in histidine-dependent S. typhimurium strains TA98 and TA100.
Glycidol induced more revertants in TA98 (frameshift mutations)
than in TA100 (base-pair substitution mutations). Addition of
rat liver microsomal enzymes decreased the number of revertants.
Dorange et al. (1977) also studied the mutagenicity of
glycidol in S. typhimurium. They found glycidol to be mutagenic
in strains TA1535 and TA100, used to detect base-pair substi-
tution. It gave negative results in strains TA1537, TA1538,
and TA98. No activation system was used in the tests.
Kucera et al. (1975) reported that 0.3% glycidol induced
shortawned (breviaristatum) mutants in barley. No further
experimental details were given.
Kolmark and Giles (1955) reported that glycidol induced
reversions in the purple adenineless mutant 38701 of Neurospora
III-9
-------
crassa. Treatment with 0.5 M glycidol for 60 minutes induced
33.8 reverse mutations per 10 viable conidia.
Izard (1973) investigated the mutagenic activity of glycidol
in the yeast Saccharomyces cerevisiae. Eighty milliliters of
a 10%*glycidol solution was incubated at 30°C for 5 days in
a medium containing 3 x 10 cells of S. cerevisiae/petri dish.
Glycidol was mutagenic in the S211 strain of the yeast but
not in the S138 strain.
Rapoport (1948 as reported by Fishbein 1977), a Russian
investigator, found glycidol to be mutagenic in Drosophila.
No further experimental details were given.
d. Teratogenicity, Embryotoxicity, and Fetotoxicity
No information was found in the sources searched.
e. Other Toxicity
Glycidol has been shown to cause temporary sterility in
male rats. Jackson et al. (1970) and Cooper et al. (1974)
studied the effects of glycidol on the fertility of groups
of five male Wistar rats given oral doses for various periods
of time. These male rats were serially mated "with females
of proven fertility" each week. Rats given single oral doses
of 200 mg/kg showed no effect of glycidol on their fertility.
Rats given five doses of 100 mg/kg were sterile for 2 weeks.
Rats given five doses of 200 mg/kg were sterile for 4 weeks,
and two of the five rats exhibited epididymal spermatoceles.
Jones and Jackson (1974) studied the effects of glycidol
on spermatozoa of the toad Xenopug laevis and the development
111-10
-------
of eggs fertilized in vitro by the glycidol-treated spermatozoa.
Male toads were killed and the testes were macerated in
Holtfreter's solution to form a sperm suspension. Glycidol
at 0.2, lf 5, and 10 mg/ml was added to the sperm suspension,
which was used to fertilize the eggs. Normal development occurred
in the two low dose systems. About 50% of the eggs treated
for 60 minutes with sperm suspension containing glycidol at
5 or 10 mg/ml failed to cleave. At 5 mg/ml, the cleaving eggs
continued to the tadpole stage. At 10 mg/ml, no eggs'reached
the gastrula stage.
III-ll
-------
GLYCIDOL
IV. ENVIRONMENTAL EFFECTS
A. Ecological Effects
1. Wild and Domestic Mammals
No information was found in the sources searched.
2. Wild and Domestic Birds
No information was found in the sources searched.
3. Fish, Amphibians, and Reptiles
Jones and Jackson (1974) studied the effects of glycidol
on spermatozoa of the toad Xenopus laevis and the development
of eggs fertilized in vitro by the glycidol-treated spermato-
zoa. See Glycidol, III.B.2.e for experimental details.
4. Invertebrates
No information was found in the sources searched.
5. Plants and Algae
No information was found in the sources searched.
6. Bacteria and Other Microorganisms
No information was found in the sources searched.
7. Ecological Communitites and Processes
No information was found in the sources searched.
B. Other Environmental Effects
No information was found in the sources searched.
111-12
-------
GLYCIDOL
V. WORK IN PROGRESS
NCI (1978) reported that glycidol has been tentatively
selected for carcinogenesis bioassay.
111-13
-------
GLYCIDYL ACRYLATE
I. CHEMICAL AND PHYSICAL INFORMATION
A. Identification
1. CAS No.; 106-90-1
2. NIOSH No. ;. AS92750
3. Synonyms and Trade Names
2-Propenoic acid, oxiranylmethyl ester
Acrylic acid, 2,3-epoxypropyl ester
Glycidyl propenate
2,3-Epoxypropyl acrylate
(NIH/EPA 1978)
B. Formulas and Molecular Weight
1. Structural Formula
-C —0—CH.,—CH—CH
(NIH/EPA 1978)
2. Empirical Formula
C6H8°3
3. Molecular Weight
128.13
(NIH/EPA 1978)
C. Physical Properties
1. Description
Liquid
(CCD 1977)
111-14
-------
2. Boiling Point
57°C at 2 mm with polymerization (CCD 1977)
3. * Melting Point
-41.5°C (CCD 1977)
4. Vapor Pressure
No information was found in the sources searched.
5. Solubility
Insoluble in water {CCD 1977)
6. Octanol/Water Partition Coefficient
No information was found in the sources searched.
7. Specific Gravity
9D
1.10742Q (CCD 1977)
D. Composition of the Commercial Product
No information was fo-ind in the sources searched.
Ij.i-15
-------
GLYCIDYL ACRYLATE
II. SOURCE AND FATE IN THE ENVIRONMENT
A. Sources
1. Production and Trends
Listed by USITC under the section "Miscellaneous Chemicals,"
but no production data given {USITC 1975)
2. Manufacturers and Suppliers
American Aniline & Extract Co. (USITC 1975)
Thiokol Corp. (OPD 1977)
3. Use
For the manufacture of thermosetting acrylic surface coating
resins (CCD 1977)
4. Occupational Exposure
No information was found in the sources searched.
5. Release
No information was found in the sources searched.
B. Environmental Fate
1. Occurrence
No information was found in the sources searched.
2. Transformation
No information was found in the sources searched.
111-16
-------
3. Bioaccumulation
No information was found in the sources searched,
111-17
-------
GLYCIDYL ACRYLATE
III. BIOLOGICAL INFORMATION
A. Effects on Humans
No information was found in the sources searched.
B. Tests on Laboratory Animals
1. Metabolism
No information was found in the sources searched.
2. Toxic Effects
a. Acute Toxicity
The acute toxicity of glycidyl acrylate, as reported by
the NIOSH RTECS data base (1978a), is given in Table III-l.
TABLE III-l
ACUTE TOXICITY OF GLYCIDYL ACRYLATE
Parameter
LD50
LD50
LCLo
Dosage
214 mg/kg
400 mg/kg
125 ppm
for 4 hr
Animal
Rat
Rabbit
Rat
Route
Oral
Skin
Inhalation
Smyth et al. (1962) exposed two groups of six rats (sex
unspecified) to glycidyl acrylate vapor at 62.5 and 125 ppm
for 4 hours. The rats were observed for 14 days. All the
rats exposed at the higher concentration died, and those exposed
111-18
-------
at the lower concentration survived. The authors also reported
that, in rabbits, the direct application of glycidyl acrylate
caused necrosis on the clipped belly and on the cornea.
b. Carcinogenicity
No information was found in the sources searched.
c. Mutagenicity and Cell Transformation
No information was found in the sources searched.
d. Teratogenicity, Embryotoxicity, and Fetotoxicity
No information was found in the sources searched.
e. Other Toxicity
No information was found in the sources searched.
111-19
-------
GLYCIDYL ACRYLATE
IV. ENVIRONMENTAL EFFECTS
A. Ecological Effects
1. Wild and Domestic Mammals
No information was found in the sources searched.
2. Wild and Domestic Birds
No information was found in the sources searched.
3. Fish, Amphibians, and Reptiles
No information was found in the sources searched.
4. Invertebrates
No information was found in the sources searched.
5. Plants and Algae
No information was found in the sources searched.
6. Bacteria and Other Microorganisms
No information was found in the sources searched.
7. Ecological Communities and Processes
No information was found in the sources searched.
B. Other Environmental Effects
No information was found in the sources seached.
111-20
-------
GLYCIDYL ACRYLATE
V. WORK IN PROGRESS
No information was found in the sources searched.
111-21
-------
GLYCIDYL METHACRYLATE
I. CHEMICAL AND PHYSICAL INFORMATION
A. Identification
1. CAS No.; 106-91-2
2. NIOSH No.; OZ43750
3. Synonyms and Trade Names
2-Propenoic acid, 2-methyl-, oxiranylmethyl ester
Methacrylic acid, 2,3-epoxypropyl ester
Glycidol methacrylate
2,3-Epoxypropyl methacrylate
(NIH/EPA 1978)
B. Formulas and Molecular Weight
1. Structural Formula
H..C—C — C—0—CH0—CH—CH0
3 II II \ /
CH2 0 0 (NIH/EPA 1978)
2. Empirical Formula
C7H10°3 (NIH/EPA 1978)
3. Molecular Weight
142.15
C. Physical Properties
1. Description
No information was found in the sources searched.
111-22
-------
2. Boiling Point
No information was found in the sources searched,
3. Melting Point
No information was found in the sources searched.
4. Vapor Pressure
No information was found in the sources searched.
5. Solubility
No information was found in the sources searched.
6. Octanol/Water Partition Coefficient
No information was found in the sources searched.
7. Specific Gravity
No information was found in the sources searched.
D. Composition of the Commercial Product
No information was found in the sources searched.
111-23
-------
GLYCIDYL METHACRYLATE
II. SOURCE AND FATE IN THE ENVIRONMENT
A. Source
1. Production and Trends
Listed by USITC under the section "Miscellaneous Chemicals,"
but no production data given (USITC 1975)
2. Manufacturers and Suppliers
American Aniline and Extract Co. (USITC 1975)
Blemmer Chemical Corp.
Haven Chemical Div.
Thiokol Corp.
(OPD 1977)
3. Use
No information was found in the sources searched.
4. Occupational Exposure
Rank: 1113
Estimated number of persons exposed: 105,000*
* rough estimate
(NOHS 1976)
5. Release
No information was found in the sources searched.
111-24
-------
B. Environmental Fate
1. Occurrence
No information was found in the sources searched,
2. Transformation
No information was found in the sources searched.
3. Bioaccumulation
No information was found in the sources searched.
111-25
-------
GLYCIDYL METHACRYLATE
III. BIOLOGICAL INFORMATON
A. Effects on Humans
No information was found in the sources searched.
B. Tests on Laboratory Animals
1. Metabolism
No information was found in the sources searched.
2. Toxic Effects
a. Acute Toxicity
The acute toxicity of glycidyl methacrylate, as reported
by the NIOSH RTECS data base (1978a), is given in Table III-l,
TABLE III-l
ACUTE TOXICITY OF GLYCIDYL METHACRYLATE
Parameter
LD50
LD50
LD50
Dosage
770 mg/kg
1,122 mg/kg
450 mg/kg
Animal
Rat
Mouse
Rabbit
Route
Oral
Intraperitoneal
Skin
b. Carcinogenicity
Hadidian et al. (1968) evaluated the carcinogenicity of
glycidyl methacrylate in three groups of rats. The compound
111-26
-------
was administered by gavage five times a week for 1 year. The
animals were observed for an additional 6 months. The dosages
used ranged from 0.001 mg to 3 mg. No apparent difference
in the tumor incidence pattern between exposed rats and controls
was observed.
c. Mutagenicity and Cell Transformation
No information was found in the sources searched.
d. Teratogenicity, Embryotoxicity, and Fetotoxicity
No information was found in the sources searched.
e. Other Toxicity
Hadidian et al. (1968) administered glycidyl methacrylate
by gavage to groups of three weanling male rats, five times
a week, for 8 weeks. The doses were 1, 3, 10, 30, 100, and
300 mg/animal/day. The rats given the lowest dose survived,
but all rats given the other doses died. The authors did not
describe toxic effects.
111-27
-------
GLYCIDYL METHACRYLATE
IV. ENVIRONMENTAL EFFECTS
A. Ecological Effects
1. Wild and Domestic Mammals
No information was found in the sources searched.
2. Wild and Domestic Birds
No information was found in the sources searched.
3. Fish, Amphibians, and Reptiles
No information was found in the sources searched.
4. Invertebrates
Indirect evidence indicates that glycidyl methacrylate
inhibits degradation of the juvenile hormone in the blowfly
(Calliphora erythrocephala) and the southern armyworm (Prodenia
cridanin) through interference with enzymatic epoxide hydra-
tion (Slade et al. 1975). This conclusion was based on a study
with the following methods and results:
The cyclodiene insecticide HEOM (1,2,3,4,9,9-hexachloro-
6,7-epoxy 1,4,4a,5,6,7,8,8a-octahydro-l,4-methanonanaphthalene),
which is susceptible to enzymatic epoxide ring cleavage, was
used as a substrate. Insect tissues were prepared for epoxide
hydrase enzyme incubation, and glycidyl methacrylate was added
to the incubation mixture. HEOM was then added. With glycidyl
methacrylate at 5.0 x 10 M, the activity rate of epoxide hydrase
111-28
-------
was decreased by 45%. The authors interpreted this as an indi-
cation of a high degree of inhibition (Slade et al. 1975).
5. Plants and Algae
No information was found in the sources searched.
6. Bacteria and Other Microorganisms
No information was found in the sources searched.
7. Ecological Communities and Processes
No information was found in the sources searched.
B. Other Environmental Effects
No information was found in the sources searched.
111-29
-------
GLYCIDYL METHACRYLATE
V. WORK IN PROGRESS
No information was found in the sources searched.
111-30
-------
ALLYL GLYCIDYL ETHER
I. CHEMICAL AND PHYSICAL INFORMATION
A. Identification
1. CAS No.; 106-92-3
2. NIOSH No.; RR08750
3. Synonyms and Trade Names
Oxirane, [(2-propenyloxy)methyl]-
Propane, 1-(allyloxy)-2,3-epoxy
Allyl 2,3-epoxypropyl ether
l-Allyloxy-2,3-epoxypropane
1,2-Epoxy-3-allyloxypropane
(NIH/EPA 1978)
B. Formulas and Molecular Weight
1. Structural Formula
0 ,.
2 2
= CH—CHn— 0 — CH0-CH — CH2
0 (NIH/EPA 1978)
2. Empirical Formula
C6H1Q02 (dlH/EPA 1978)
3. Molecular Weight
114.14
111-31
-------
C. Physical Properties
1. Description
Colorless liquid; characteristic but not unpleasant odor
(NIOSH 1978b)
2. Boiling Point
153.9°C (NIOSH 1978b)
3. Melting Point
Forms glass at -100°C (NIOSH 1978b)
4. Vapor Pressure
4.7 nm at 25°C (NIOSH 1978b)
5. Solubility
Soluble in water, acetone, toluene, and octane
(NIOSH 1978b)
6. Octanol/Water Partition Coefficient
No information was found in the sources searched.
7. Specific Gravity
0.96984° (NIOSH 1978b)
D. Composition of the Commercial Product
No information was found in the sources searched.
111-32
-------
ALLYL GLYCIDYL ETHER
II. SOURCE AND FATE IN THE ENVIRONMENT
A. Sources
1. Production and Trends
Listed by USITC under the section "Miscellaneous Chemicals,"
but no production data given (USITC 1976)
2. Manufacturers
Alcoloc Chemical Corp. (USITC 1976)
3. Use
Glycidyl ethers are used chiefly as reactive diluents
in epoxy resin systems. (NIOSH 1978b)
4. Occupational Exposure
Glycidyl ethers
Rank: 1020
Estimated number of persons exposed: 118,000*
*rough estimate
(NOHS 1976)
ACGIH TLV-TWA: 5 ppm (22 mg/m3) (skin) (ACGIH 1978)
5. Release
No information was found in the sources searched.
B. Environmental Fate
1. Occurrence
No information was found in the sources searched.
111-33
-------
2. Transformation
No specific data were found in the sources searched.
Comment: Allyl glycidyl ether is soluble in water (NIOSH
1978b) and will therefore remain in the aquatic medium when
discharged into water systems.
3. Bioaccumulation
No specific data were found in the sources searched.
Comment: Allyl glycidyl ether is soluble in both water
and lipid solvents (NIOSH 1978b), which suggests a potential
for bioaccumulation.
111-34
-------
ALLYL GLYCIDYL ETHER
III. BIOLOGICAL INFORMATION
A. Effects on Humans
Hine et al. (1956) reviewed the medical records of workers
exposed to allyl glycidyl ether and seeking first-aid treatment
at one plant between 1947 and 1956. No worker had more than
a total of 300 hours of exposure. Ten cases of dermatitis
were reported. The symptoms and signs included tenderness,
reddening, itching, swelling, blister formation, and whitish
maculae. Exposed workers occasionally became "sensitized"
to the compound. One case of eye irritation from allyl glycidyl
ether vapor was also reported. Because immediate pain or burning
was absent, workers often delayed seeking treatment.
Fregert and Rorsman (1964 as reported by NIOSH 1978b)
tested the allergenic property of allyl glycidyl ether on 20
persons known to have contact allergies to epoxy resins of
the diglycidyl ethers of bisphenol A. Allyl glycidyl ether at
0.25% in acetone was applied in a patch test for an unspecified
exposure period. .Two of the twenty test subjects had positive
reactions.
B. Tests on Laboratory Organism
1. Metabolism
Oesch (1972 as reported by NIOSH 1978b) proposed three
111-35
-------
types of metabolic reactions for epoxides, which are shown
in Figure III-l.
FIGURE III-l
PROPOSED METABOLIC PATHWAYS FOR GLYCIDYL ETHERS*
1
*- R-0-CH2-CH-CH2
Epoxide Hydrase -I |
OH OH
0
R-0-CH-CH-CH5 Ł — *-R-0-CH2-CH-CH2
^ Glutathione S-epoxide | I
Transferase and OH SR1
Nonenzymatic
Covalent bonding
Nonenzymatic with proteins,
RNA, DMA
* Adapted from NIOSH (1978b)
Two of the proposed pathways are enzymatic. One involves the
conversion by epoxide hydrase to the corresponding diol. According
to NIOSH (1978b), Soellner and Irrgang (1965) presented evidence
that ortho-cresyl glycidyl ether was meta-bolized to the corre-
sponding diol, which was apparently more neurotoxic than the
parent compound. The second enzymatic pathway proposed by
Oesch is conjugation with glutathione. The proposed nonenzymatic
reactions of epoxides involve covalent binding to proteins,
RNA, and DNA.
Hl-36
-------
2. Toxic Effects
a. Acute Toxicity
The acute toxicity of allyl glycidyl ether, as reported
by the NIOSH RTECS data base (1978a) and Hine et al. (1956),
is given in Table III-l.
TABLE III-l
ACUTE TOXICITY OF ALLYL GLYCIDYL ETHER
Parameter
LD501
LD502
LD501'2
LD501'2
LC501'2
LCLo1
Dosage
922
1,600
390
2,550
270
for
860
for
mg/kg
mg/kg
mg/kg
mg/kg
ppm
4 hr
ppm
4 hr
Animal
Rat
Rat
Mouse
Rabbit
Mouse
Rat
Route
Oral
Oral
Oral
Skin
Inhalation
Inhalation
,NIOSH (1978a)
^Hine et al. (1956)
Hine et al. (1956) gave mice and rats allyl glycidyl ether
intragastrically at a range of doses used to determine the
LD50, which was calculated to be 390 mg/kg in mice and 1,600
mg/kg in rats. CNS depression, incoordination, and ataxia
were observed. Animals were often comatose at the time of
death.
Hine et al. (1956) observed corneal opacity in some of
111-37
-------
six rats exposed to allyl glycidyl ether vapors at an unspecified
concentration for 8 hours. They also reported that, in rabbits,
0.5 ml of undiluted allyl glycidyl ether applied to the skin
caused moderate skin irritation and 0.1 ml dropped on the cornea
caused moderate eye irritation.
b. Carcinogenicity
No information was found in the sources searched.
c. Mutagenicity and Cell Transformation
Wade et al. (1978 as reported by NIOSH 1978b) studied the
mutagenicity of allyl glycidyl ether in Salmonella typhimurium
histidine-dependent strains TA98 and TA100. Allyl glycidyl
ether was not mutagenic in TA98. Application of 10 mg of allyl
glycidyl ether to agar plates containing TA100 induced muta-
tions at 10 times the spontaneous rate. Addition of liver
microsomal extract had no effect on the mutagenic activity of
of the compound.
d. Teratogenicity, Embryotoxicity, and Fetotoxicity
No information was found in the sources searched.
e. Other Toxicity
Hine et al. (1956) exposed groups of 10 rats to allyl
glycidyl ether vapors for 7 hours/day, 5 days/week, for 10
weeks. Control groups were exposed to uncontaminated air.
Seven or eight animals from groups exposed at 600 and 900 ppm
died between the 7th and 21st exposures. The severe toxic
effects necessitated termination of the use of high doses.
111-38
-------
The authors observed a statistically significant change in the
kidney to body weight ratio in rats exposed at 400 ppm. Eye
irritation and respiratory distress were observed in rats exposed
at 260 and 400 ppm. One rat exposed at 400 ppm died after
18 exposures, and autopsy revealed emphysema, mottled liver,
and enlarged, congested adrenal glands. Bronchial dilatation,
bronchopneumonia, and emphysema were observed in rats that
survived the entire exposure period.
Kodama et al. (1961) gave five male Long-Evans rats intra-
muscular injections of allyl glycidyl ether at 400 mg/kg/day
for 4 days. Leukocyte counts were significantly reduced in
treated rats. Two rats died, and autopsies revealed pulmonary
congestion in one and a small spleen and no visible thymus
in the other. Necropsy of the three surviving rats showed
involuted thymuses. Microscopic examination revealed atrophy
of lymphoid tissue, focal necrosis of the pancreas and testes,
hemorrhage of the thymus, hemorrhage into the periphery of
the liver, and pneumonia.
111-39
-------
ALLYL GLYCIDYL ETHER
IV. ENVIRONMENTAL EFFECTS
A. Ecological Effects
1. Wild and Domestic Mammals
No information was found in the sources searched.
2. Wild and Domestic Birds
No information was found in the sources searched.
3. Fish, Amphibians, and Reptiles
Verschueren (1977) reported LD50 values for allyl glycidyl
ether in goldfish of 78 mg/liter and 30 mg/liter in 24- and
96-hour tests.
4. Invertebrates
No information was found in the sources searched.
5. Plants and Algae
No information was found in the sources searched.
6. Bacteria and Other Microorganisms
No information was found in the sources searched.
7. Ecological Communities and Processes
No information was found in the sources searched.
B. Other Environmental Effects
No information was found in the sources searched.
111-40
-------
ALLYL GLYCIDYL ETHER
V. WORK IN PROGRESS
No information was found in the sources searched,
111-41
-------
n-BUTYL GLYCIDYL ETHER
I. CHEMICAL AND PHYSICAL INFORMATION
A. Identification
1. CAS No.; 2426-08-6
2. NIOSH No.; TX42000
3. Synonyms and Trade Names
Oxirane, (butoxymethyl)-
Propane, l-butoxy-2,3-epoxy-
ERL 0810
l-Butoxy-2,3-epoxypropane
2,3-Epoxypropyl butyl ether
3-Butoxy-l,2-epoxypropane
(NIH/EPA 1978)
B. Formulas and Molecular Weight
1. Structural Formula
^CH0—0—CH —
2. 2. v /
(NIH/EPA 1978)
2. Empirical Formula
C7H14°2 (NIH/EPA 1978)
3. Molecular Weight
130.19
111-42
-------
C. Physical Properties
1. Description
Colorless liquid; slight irritating odor (NIOSH 1978b)
2. Boiling Point
164°C (NIOSH 1978b)
3. Melting Point
No information was found in the sources searched.
4. Vapor Pressure
3.2 mm at 25°C (NIOSH 1978b)
5. Solubility
Slightly soluble in water (NIOSH 1978b)
6. Octanol/Water Partition Coefficient
No information was found in the sources searched.
7. Specific Gravity
No information was found in the sources searched.
D. Composition of the Commercial Product
No information was found in the sources searched.
111-43
-------
n-BUTYL GLYCIDYL ETHER
II. SOURCE AND FATE IN THE ENVIRONMENT
A. Sources
1. Production and Trends
Listed by USITC under the section "Miscellaneous Chemicals,"
but no production data given (USITC 1974)
2. Manufacturers and Suppliers
Dow Chemical Co. (USITC 1974)
CPS Chemical Co.
Ciba-Geigy Corp.
Shell Chemical Co.
(OPD 1977)
3. Use
See Allyl Glycidyl Ether, Section II.A.3.
4. Occupational Exposure
See Allyl Glycidyl Ether, Section II.A.4.
ACGIH TLV-TWA: 50 ppm (270 mg/m3) (ACGIH 1978)
5. Release
No information was found in the sources searched.
B. Environmental Fate
1. Occurrence
No information was found in the sources searched.
111-44
-------
2. Transformation
No information was found in the sources searched,
3. Bioaccumulation
No information was found in the sources searched,
111-45
-------
n-BUTYL GLYCIDYL ETHER
III. BIOLOGICAL INFORMATION
A. Effects on Humans
Several studies on the irritating and sensitizing proper-
ties of n-butyl glycidyl ether have been reported. Kligman
(1966 as reported by NIOSH 1978b) tested the sensitization
potential of the compound in 24 healthy adults. One milliliter
of a 1% suspension in mineral oil on a cloth patch, 1.5 inches
square, was applied to the forearm or lower leg of each subject.
The patch was covered with plastic tape and left in place 24
hours. This exposure was repeated five times, with 24-hour
rest periods between patch tests. The 24 subjects were then
each exposed to a challenge dose of 0.4 ml of 10% n-butyl glycidyl
ether in mineral oil on a 1-square-inch patch left in place
for 48 hours on the lower back or forearm; 19 showed sensitization.
Lea et al. (1958 as reported by NIOSH 1978b) applied n-butyl
glycidyl ether on cotton pads to the backs of subjects. The
pads were covered with cellophane and left in place 48 hours.
Irritation was elicited in 5 of 5 subjects exposed to n-butyl
glycidyl ether at 100% and in 17, 8, 1, and 0 of 25 subjects
exposed to the substance at 10%, 5%, 2.5%, and 1.25%, respectively.
Severity of response was dose-related; reactions ranged from
mild irritation to erythema, edema, multiple vesiculation, and
superficial ulceration.
Fregert and Rorsman (1964 as reported by NIOSH 1978b)
tested the allergenic properties of n-butyl glycidyl ether
111-46
-------
on 20 persons who were allergic to epoxy resins of the diglycidyl
ethers of bisphenol A. n-Butyl glycidyl ether at 0.25% in
acetone was applied in a patch test. Three of twenty subjects
had allergic responses.
No reports on systemic effects of n-butyl glycidyl ether
in humans were found in sources searched. However, toxic side
effects have been reported in patients receiving triethylene
glycol diglycidyl ether as an antitumor agent, which according
to NIOSH (1978b) suggests that other lower-molecular-weight
glycidyl ethers may also attack rapidly dividing tissues.
B. Tests on Laboratory Organisms
1. Metabolism
See Allyl Glycidyl Ether, Section III.B.I.
2. Toxic Effects
a. Acute Toxicity
The acute toxicity of n-butyl glycidyl ether, as reported
by the NIOSH RTECS data base (1978a) and Hine et al. (1956),
is given in Table III-l.
Hine et al. (1956) gave mice and rats n-butyl glycidyl
ether intragastrically at a range of doses used to determine
the LD50, which was calculated to be 1,530 rag/kg in mice and
2,260 rag/kg in rats. CNS depression, incoordination, and ataxia
were observed. Death was preceded by agitation and excitement.
The authors also exposed six rats to vapor concentrations used
to calculate an LC50 of 1,030 ppm. Some rats developed focal
111-47
-------
inflammatory cells with moderate congestion in the liver and
hyperemia of the adrenal glands.
Hine et al. (1956) also reported that, in rabbits, 0.5 ml
of undiluted n-butyl glycidyl ether applied to the skin caused
moderate skin irritation and 0.1 ml dropped on the cornea caused
moderate eye irritation.
TABLE III-l
ACUTE TOXICITY OF n-BUTYL GLYCIDYL ETHER
Parameter
LD501
LD502
LD501
LD502
LD501'2
LD501'2
LD501
LC502
LCLo1 ' 2
Dosage
2,050
2,260
1,520
1,530
700
1,140
2,520
1,030
for 8
670
mg/kg
mg/kg
mg/kg
mg/kg
mg/kg
mg/kg
mg/kg
ppm
hr
ppm
Animal
Rat
Rat
Mouse
Mouse
Mouse
Rat
Rabbit
Rat
Rat
Route
Oral
Oral
Oral
Intragastr ic
Intraper itoneal
Intraperit^ ,al
Skin
Inhalation
Inhalation
JNIOSH (1978a)
'Hine et al. (1956)
b. Carcinogenicity
No information was found in the sources searched.
111-48
-------
c. Mutagenicity and Cell Transformation
Wade et al. (1978 as reported by NIOSH 1978b) studied the
mutagenicity of n-butyl glycidyl ether in Salmonella typhimurium
strains TA98 and TA100 with and without the addition of liver
microsomal extracts from rats pretreated with phenobarbital.
In TA100, 10 yg of n-butyl glycidyl ether caused mutations
at over 10 times the spontaneous rate. Liver microsomes had
little effect on the mutagenic activity. n-Butyl glycidyl
ether did not show mutagenic activity in strain TA98.
The mutagenicity of n-butyl glycidyl ether was examined by
Pullin and Legator (1977) in a study performed for Dow Chemical
USA and reported by NIOSH (1978b). n-Butyl glycidyl ether
was significantly mutagenic in mice in a dominant lethal assay
in which male mice were treated topically with the undiluted
compound at 1.5 g/kg body weight, three times a week, for a
minimum of 8 weeks before mating. This treatment caused a
significant increase in the number of fetal deaths. In the
Ames test, n-butyl glycidyl ether (0.5-2.0 ymoles/plate) produced
mutations in S. typhimurium strain TA1535 at 4-13 times the
spontaneous rate. Its mutagenic activity was markedly decreased
by the addition of microsomal liver extract. The compound
also caused a significant increase in unscheduled DNA synthesis
in human mononucleated white blood cells. Pullin and Legator
classified this compound as mutagenic despite a lack of demon-
strated mutagenicity in three other tests:
(1) Body fluid analysis, in which the urine of mice given
111-49
-------
oral doses (125-1,000 mg/kg/day) for 4 days was tested for
mutagenicity against S. typhimurium
(2) The host mediated assay, in which S. typhimurium
were injected into the peritoneal cavity of mice given oral
doses "(125-1,000 mg/kg/day) for 5 days
(3) The micronucleus test, in which bone marrow from
mice given unspecified oral doses for 5 days was examined for
the presence of micronuclei. The authors suggested that the
doses might have been too low to cause mutagenic activity in
these three tests. The dosage in the dominant lethal test
was much higher.
d. Teratogenicity, Embryotoxicity, and Fetotoxicity
No information was found in the sources searched.
e. Other Toxicity
Weil et al. (1963) gave 17 guinea pigs intracutaneous
injections of 0.1 ml of n-butyl glycidyl ether at an unspecified
concentration. The injections were given three times a week
for a total of eight injections during a 3-week period. An
unspecified challenge dose was given 3 weeks after the eighth
injection. Sixteen of the guinea pigs became sensitized within
48 hours of receiving the challenge dose.
Anderson et al. (1957 as reported by NIOSH 1978c) exposed
rats to n-butyl glycidyl ether by inhalation at 38, 75, 150,
and 300 ppm for 7 hours/day, 5 days/week, for a total of 50
exposures. Slight testicular atrophy was observed in 1 of
10 rats exposed at 75 ppm. Anderson et al. described the testes
111-50
-------
from 5 of 10 rats exposed at 300 ppm as "atrophic" and those
from 1 of the 10 rats as "very small."
Kodama et al. (1961) observed increased leucocyte counts
in five male rats given intramuscular injections of n-butyl
glycidyl ether at 400 mg/kg/day for 3 days.
111-51
-------
n-BUTYL GLYCIDYL ETHER
IV. ENVIRONMENTAL EFFECTS
A. Ecological Effects
1. Wild and Domestic Mammals
No information was found in the sources searched.
2. Wild and Domestic Birds
No information was found in the sources searched.
3. Fish, Amphibians, and Reptiles
No information was found in the sources searched.
4. Invertebrates
No information was found in the sources searched.
5. Plants and Algae
No information was found in the sources searched.
6. Bacteria and Other Microorganisms
No information was found in the sources searched.
7. Ecological Communities and Processes
No information was found in the sources searched.
B. Other Environmental Effects
No information was found in the sources searched.
111-52
-------
n-BUTYL GLYCIDYL ETHER
V. WORK IN PROGRESS
Tox-Tips (1978) reported that a study of the "genetic
toxicity" of butyl glycidyl ether in Swiss-Webster mice is
being conducted by Dr. Marvin Legator at the University of
Texas Medical Branch, Division of Environmental Toxicology,
in Galveston, Texas. Mice are receiving low to toxic doses
of butyl glycidyl ether topically or by intramuscular injection
five times a week for up to 3 months. Dominant lethal tests
and cytogenetic analyses will be performed. No starting or
completion time is specified.
111-53
-------
para-CRESYL GLYCIDYL ETHER
I. CHEMICAL AND PHYSICAL INFORMATION
A. Identification
1. CAS No.; 2186-24-5
2. NIOSH No.;
3. Synonyms and Trade Names
Propane, 1,2-epoxy-3-(p-tolyloxy)-
p-Tolyl glycidyl ether
Oxirane, ((4-methylphenoxy)methyl)-
Glycidyl p-tolyl ether
3-(4-Methylphenoxy)-1,2-epoxypropane
Glycidyl p-methylphenyl ether
2,3-Epoxypropyl p-tolyl ether^
p-Cresol glycidyl ether
(CHEML1NE 1978)
B. Formulas and Molecular Weight
1. Structural Formula
0—CH0—CH — CH0
2 \ / 2
0
2. Empirical Formula
C10H12°2
3. Molecular Weight
164.20
111-54
-------
C. Physical Properties
1. Description
No information was found in the sources searched.
•»
2. Boiling Point
No information was found in the sources searched.
3. Melting Point
No information was found in the sources searched.
4. Vapor Pressure
No information was found in the sources searched.
5. Solubility
No information was found in the sources searched.
6. Octanol/Water Partition Coefficient
No information was found in the sources searched.
7. Specific Gravity
No information was found in the sources searched.
D. Composition of the Commercial Product
No information was found in the sources searched.
111-55
-------
para-CRESYL GLYCIDYL ETHER
II. SOURCE AND FATE IN THE ENVIRONMENT
A. Sources
1. Production and Trends
No information was found in the sources searched.
2. Manufacturers and Suppliers
CPS Chemical Co. (OPD 1977)
3. Use
See Allyl Glycidyl Ether, Section II.A.3.
4. Occupational Exposure
See Allyl Glycidyl Ether, Section II.A.4.
5. Release
No information was found in the sources searched.
B. Environmental Fate
1. Occurrence
No information was found in the sources searched.
2. Transformation
No information was found in the sources searched.
3. Bioaccumulation
No information was found in the sources searched.
111-56
-------
para-CRESYL GLYCIDYL ETHER
III. BIOLOGICAL INFORMATION
A. Effects on Humans
No information was found in the sources searched.
B. Tests on Laboratory Organisms
1. Metabolism
See Allyl Glycidyl Ether, Section III.B.I.
2. Toxic Effects
a. Acute Toxicity
No information was found in the sources searched.
b. Carcinogenicity
No information was found in the sources searched.
c. Mutagenicity and Cell Transformation
No information was found in the sources searched.
d. Teratogenicity, Embryotoxicity, and Fetotoxicity
No information was found in the sources searched.
e. Other Toxicity
No information was found in the sources searched.
111-57
-------
para-CRESYL GLYCIDYL ETHER
IV. ENVIRONMENTAL EFFECTS
A. Ecological Effects
1. Wild and Domestic Mammals
No information was found in the sources searched.
2. Wild and Domestic Birds
No information was found dn the sources searched.
3. Fish, Amphibians, and Reptiles
No information was found in the sources searched.
4. Invertebrates
No information was found in the sources searched.
5. Plants and Algae
No information was found in the sources searched.
6. Bacteria and Other Microorganisms
No information was found in the sources searched.
7. Ecological Communities and Processes
No information was found in the sources searched.
B. Other Environmental Effects
No information was found in the sources rarched.
Hl-58
-------
para-CRESYL GLYCIDYL ETHER
V. WORK IN PROGRESS
No information was found in the sources searched,
111-59
-------
PHENYL GLYCIDYL ETHER
I. CHEMICAL AND PHYSICAL INFORMATION
A. Identification
1. CAS NO.; 122-60-1
2. NIOSH No.; TZ36750
3. Synonyms and Trade Names
gamma-Phenoxypropylene oxide
(Phenoxymethyl)oxirane
Glycidol phenyl ether
Phenol glycidyl ether
Phenyl 2,3-epoxypropyl ether
l-Phenoxy-2,3-epoxypropane
1,2-Epoxy-3-phenoxypropane
2,3-Epoxypropyl phenyl ether
3-Phenoxy-l,2-epoxypropane
3-Pheno-xy-l,2-propylene oxide
3-Phenyloxy-l,2-epoxypropane
(NIH/EPA 1978)
B. Formulas and Molecular Weight
1. Structural Formula
0 (NIH/EPA 1978)
2. Empirical Formula
C9H10°2 (NIH/EPA 1978)
111-60
-------
3. Molecular Weight
150.18
C. Physical Properties
1. Description
Colorless liquid (CCD 1977)
2. Boiling Point
245°C (CCD 1977)
3. Melting Point
3.5°C (CCD 1977)
4. Vapor Pressure
0.01 mm at 25°C (NIOSH 1978b)
5. Solubility
Slightly soluble in water; soluble in all proportions in
acetone and toluene (NIOSH 1978b)
6. Octanol/Water Partition Coefficient
No information was found in the sources searched.
7. Specific Gravity
1.11 , (CCD 1977)
D. Composition of the Commercial Product
No information was found in the sources searched.
111-61
-------
PHENYL GLYCIDYL ETHER
II. SOURCE AND FATE IN THE ENVIRONMENT
A. Sources
1. Production and Trends
Listed by USITC under the section "Miscellaneous Chemicals,"
but no production data given (USITC 1976)
2. Manufacturers
No manufacturers listed by USITC (1976)
3. Use
See Allyl Glycidyl Ether, Section II.A.3.
4. Occupational Exposure
See Allyl Glycidyl Ether, Section II.A.4.
ACGIH TLV-TWA: 10 ppm (60 mg/m3) (ACGIH 1978)
5. Release
No information was found in the sources searched.
B. Environmental Fate
1. Occurrence
No information was found in the sources searched.
2. Transformation
Lee et al. (1977) suggested that, as an acid acceptor,
IH-62
-------
phenyl glycidyl ether is very effective in stabilizing halo-
genated compounds.
3. Bioaccumulation
No specific data were found in the sources searched.
Comment: Phenyl glycidyl ether is soluble in lipid solvents
and slightly soluble in water, suggesting that significant
bioaccumulation may occur.
111-63
-------
PHENYL GLYCIDYL ETHER
III. BIOLOGICAL INFORMATION
A. Effects on Humans
Hine et al. (1956) reviewed the medical records of workers
exposed to phenyl glycidyl ether and seeking first-aid treatment
at one plant between 1947 and 1956. Exposure to phenyl glycidyl
ether was limited to about 20 workers for about 2 months a
year, with no more than 600 hours exposure per worker. Thirteen
cases of dermatitis were reported from this group. Symptoms
observed in workers included second-degree burns, blister forma-
tion, brownish lesions, diffuse or vesicular erythematous rash,
dry and defatted areas, watery discharge, macular rash and
papules, swelling of connective tissue, and edema. Because
immediate pain or burning was absent, workers often delayed
seeking treatment. Some of the workers with occupational derma-
titis developed sensitivity reactions.
Zschunke and Behrbohn (1965 as reported by NIOSH 1978b)
reported 15 cases of occupational dermatitis in workers exposed
to phenyl glycidyl ether being used as a chemical stabilizer
in two cable-manufacturing plants. Eczema in 12 of 18 workers
in one plant was reported. In the other plant, 3 persons were
referred to a physician because of suspected occupational eczema,
which had developed on the hands, lower arms, and right side
of the abdomen. These were all parts of the body that had
come in contact with cable-coating material. These areas were
reddened, itchy, and contained papules and papulo-vesicles.
111-64
-------
Ten out of the I5 cases were severe enough to result in work
loss; 8 of the 15 affected workers reacted positively to a
24-hour patch test with phenyl glycidyl ether at 0.001-1.0%.
Patch testing with pure and industrial grade phenyl glycidyl
ether also produced positive reactions. The authors concluded
>
that it was the ether itself and not its impurities that caused
the skin reactions. Patch tests on 58 persons not previously
exposed to phenyl glycidyl ether produced no positive reactions;
however, 7 persons with eczema and exposure to epoxy resins
but no known exposure to phenyl glycidyl ether had positive
sensitivity reactions. The authors concluded that either the
epoxy resins contained phenyl glycidyl ether or cross-sensitivity
had occurred.
Fregert and Rorsman (1964 as reported by NIOSH 1978b)
tested the allergenic properties of phenyl glycidyl ether on
persons known to have contact allergies to epoxy resins of
the diglycidyl .ethers of bisphenol A. When phenyl glycidyl
ether at 0.25% in acetone was applied in patch tests, 14 of
20 persons reacted positively. The details of the study were
unspecified. Ten persons not allergic to epoxy resins were
patch tested with 1.0% phenyl glycidyl ether and two became
sensitized, but the concentration used did not cause primary
irritation. The authors concluded that sensitization to phenyl
glycidyl ether may occur after exposure to epoxy resins and
that cross-sensitizations between glycidyl ethers may also
develop.
No reports describing systemic effects of phenyl glycidyl
111-65
-------
ether in humans were found in the sources searched. However,
toxic side effects have been reported in patients receiving
triethylene glycol diglycidyl ether as an antitumor agent,
which according to NIOSH (1978b) suggests that other lower-
molecular-weight glycidyl ethers may also attack rapidly
dividing tissues.
B. Tests on Laboratory Animals
1. Metabolism
See Allyl Glycidyl Ether, Section III.B.I.
2. Toxic Effects
A. Acute Toxicity
The acute toxicity of phenyl glycidyl ether, as reported
by the NIOSH RTECS data base (1978a) and Hine et al. (1956),
is given in Table III-l.
TABLE III-l
ACUTE TOXICITY OF PHENYL GLYCIDYL ETHER
Parameter
LD501'2
LD501'2
LD501
Dosage'
3,850 mg/kg
1,400 mg/kg
1,500 mg/kg
Animal
Rat
Mouse
Rabbit
Route
Oral
Oral
Skin
1NIOSH (1978a)
2Hine et al. (1956)
111-66
-------
Hine et al. (1956) gave mice and rats phenyl glycidyl
ether intragastrically at a range of doses used to determine
the LD50, which was calculated to be 1,400 mg/kg in mice and
3,850 mg/kg in rats. CNS depression, incoordination, and ataxia
were observed. Animals were often comatose at the time of
death. Animals surviving exposure showed reversal of depression
with an increase in CNS activity. The authors also reported
that, in rabbits, 0.5 ml of undiluted phenyl glycidyl ether
caused mild skin irritation and 0.1 ml caused mild eye irritation.
Terrill and Lee (1977) exposed six male Sprague-Dawley
rats during a single 4-hour session to phenyl glycidyl ether
at various unspecified concentrations. The authors observed
weight loss and severe scrotal irritation in the rats surviving
during the 14-day observation period. The approximate lethal
concentration in this experiment was 323 ppm.
Czajkowska and Stetkiewicz (1972 as reported by NIOSH
1978b) reported that oral administration of an unspecified
dose of phenyl glycidyl ether to rats resulted in death within
6-24 hours. Rats exposed dermally died in 12-48 hours. Rats
exposed by either route showed narcosis. Hyperemia of internal
organs, hemorrhaging in the submeningeal and subpleural regions,
and darkening of the epithelium in the kidney tubules and liver
tissue were seen in gross and microscopic examination of rats
that died or were sacrificed either 6-72 hours or 14 days after
exposure. The authors concluded that phenyl glycidyl ether
was extremely toxic at the site of administration, because
it caused necrosis of the mucous membranes or skin. In addition,
111-67
-------
circulatory disorders resulting in hyperemia, increased perme-
ability of the capillaries, and damage to parenchymatous organs
were observed in rats exposed by either route.
b. Carcinogenicity
No information was found in the sources searched.
c. Mutagenicity and Cell Transformation
An abstract of a paper presented at an August 1978 meeting
of the American Society for Pharmacology and Experimental Thera-
peutics by M. A. Friedman et al. (1978) reported the following
results:
1. Phenyl glycidyl ether induced concentration-dependent
reversion in S. typhimurium strains TA1535 and TA100 used to
detect base-substitution mutations but not in TA1537, TA1538,
or TA98. The compound was mutagenic with and without the presence
of rat liver microsomes.
2. Phenyl glycidyl ether at 6.2 yg/ml and higher concen-
trations transformed hamster embryo cells in a dose-dependent
manner.
3. Phenyl glycidyl ether was tested at an oral dose of
2,500 mg/kg in the host-mediated assay in C57B1/6X6C3H mice
with S. typhimurium TA1535. The mutant frequency was increased
from 0.022 to 0.298 x 10~6. According to the authors, however,
this represents a positive response in only two of five animals.
4. Phenyl glycidyl ether did not inhibit murine testicular
DNA synthesis.
111-68
-------
E. I. du Pont de Nemours & Co. (1978) reported the results
of studies performed between 1974 and 1976:
1. The effects of inhaled phenyl glycidyl ether on the
mitotic processes of somatic cells in male ChR-CD rats were
examined. Three groups of six rats each were exposed for 6 hours/
day for 19 days to heated phenyl glycidyl ether at 1.75, 5.84,
and 11.2 ppm. Another group of six rats was exposed to air.
In the treated groups, no abnormal effects were observed on
the mitotic processes of somatic (bone marrow) cells and no
chromosome breaks were evident. The authors concluded that
phenyl glycidyl ether was not mutagenic under the conditions
of this test.
2. Phenyl glycidyl ether was tested in S. typhimurium
strains TA1535, TA1537, TA1538, TA98, and TA100 in the presence
and absence of rat liver homogenate. The compound was found
to be mutagenic in strains TA1535 and TA100 in both activated
and nonactivated systems.
3. In a dominant-lethal and reproduction study, three
groups of eight male ChR-CD rats were exposed by inhalation
to heated phenyl glycidyl ether at 1.75, 5.84, and 11.2 ppm,
6 hours/day, for 19 days. Eight other rats were controls.
Each week for 6 weeks, after the last exposure, each male rat
was mated with three virgin females. One of these three females
was sacrificed on the 18th day of pregnancy, and the ovaries,
uterus, and fetuses were examined. No significant increase-
in the incidence of early or late fetal death or preimplantation
111-69
-------
loss among these females was observed. The other female rats
gave birth to pups with no genetic abnormalities.
d. Teratogenicity, Embryotoxicity, and Fetotoxicity
E. I. du Pont de Nemours & Co. (1978) reported a study
in which the teratogenic potential of phenyl glycidyl ether
was evaluated in groups of mated female ChR-CD rats. Twenty-
five rats were controls, and 3 groups of 25 rats were exposed
to heated phenyl glycidyl ether daily for 6 hours on the 4th-
15th days of gestation. The exposure concentrations were 1.7,
5.7, and 11.5 ppm. No significant differences were observed
in the maternal body weight, mortality, and gross pathology
between the control and exposed rats. There were no significant
differences in fetal malformations or survival or in implantation
efficiency between the control and exposed groups.
e. Other Toxicity
Three groups of eight male rats were exposed by inhalation
to heated phenyl glycidyl ether in the du Pont (1978) dominant-
lethal and reproduction study described in Section III.B.2.C.
The exposures were at 1.75, 5.84, and 11.2 ppm, 6 hours/day,
for 19 days. Focal degenerative changes in the seminiferous
tubules in both testes were observed in one rat in the low
dose group, one rat in the medium dose group, and three rats
in the high dose group. According to the report, one animal
in each group had marked changes in the gonads.
Terrill and Lee (1977) exposed six male Sprague-Dawley
rats to phenyl glycidyl ether at 29 ppm by inhalation for 4 hours
111-70
-------
a day, 5 days/week, for 2 weeks. The rats were observed for
an additional 2 weeks. The exposed rats showed decreased weight
gain, atrophic changes in the kidney, liver, spleen, thymus,
and testes, depletion of hepatic glycogen, and chronic catarrhal
tracheitis.
In related studies, Terrill and Lee (1977) and Lee et al.
(1977) reported the effects of phenyl glycidyl ether on groups
of 24 male and 24 female Sprague-Dawley rats and 6 male beagle
dogs. The animals were exposed to phenyl glycidyl ether at
concentrations of 1, 5, and 12 ppm for 6 hours a day, 5 days
a week, for 90 days. No toxic effects were seen in dogs exposed
at any of the concentrations or in rats at the lowest concen-
tration. Alopecia was observed in two male and seven female
rats in the 5 ppm group and in one male and five females at
12 ppm. The authors also noticed perifollicular inflammation,
keratotic follicles, and disturbances of the keratinization
of the hair follicles.
Hine et al. (1956) exposed 10 rats to phenyl glycidyl
ether at 100 ppm by inhalation 7 hours/day, 5 days/week, for
a total of 50 exposures. At necropsy, tissues appeared normal
in most rats, but the authors observed pulmonary inflammatory
cell infiltration and "cloudy swelling" in the liver in two
rats.
Kodama et al. (1961) observed increased leukocyte cpunts
in five male rats given phenyl glycidyl either by intramuscular
injection at 400 mg/kg/day for 3 days.
Stevens (1967) investigated sensitization to phenyl glycidyl
Tli-71
-------
ether in guinea pigs. On each of 3 days, 0.01 ml of phenyl
glycidyl ether was applied to the outer surface of one ear
on each of six Alderly-Park albino guinea pigs. Four days
after the last exposure, the guinea pigs received challenge
doses of 0.2 ml on a clipped flank. A group of control guinea
pigs with no previous exposure to phenyl glycidyl ether also
were given 0.2 ml on a clipped flank. No irritation was seen
in the controls, but two pretreated guinea pigs showed "light
pink" erythema. Erythema on the four others was just barely
visible. The author concluded that phenyl glycidyl ether caused
sensitization.
Tang (1971) found that phenyl glycidyl ether completely
inactivated porcine pepsin in vitro in 70 hours. The compound
also inactivated human gastricsin, human pepsin, and bovine
rennin, but it had no effect on bovine pepsinogen.
111-72
-------
PHENYL GLYCIDYL ETHER
IV. ENVIRONMENTAL EFFECTS
A. Ecological Effec -s
1. Wild and Domestic Mammals
No information was found in the sources searched.
2. Wild and Domestic Birds
No information was found in the sources searched.
3. Fishy Amphibians, and Reptiles
Twenty-four and ninety-six hour LDSOs for goldfish were
reported to be 69 and 43 mg/liter, respectively (Verschueren 1977)
4. Invertebrates
No information was found in the sources searched.
5. Plants and Algae
No information was found in the sources searched.
6. Bacteria and Other Microorganisms
The bacteriostatic concentration of alpha-phenyl glycidyl
ether for Escherichia coli was reported to be 3.2 x 10 moles/ml
(Kilpatrick and Lambooy 1967) .
7. Ecological Communities and Processes
No information was found in the sources searched.
B. Other Environmental Effects
No information was found in the sources searched.
111-73
-------
PHENYL GLYCIDYL ETHER
V. WORK IN PROGRESS
No information was found in the sources searched.
111-74
-------
DIGLYCIDYL ETHER OF BISPHENOL A
I. CHEMICAL AND PHYSICAL INFORMATION
A. Identification
1. CAS No.; 1675-54-3
2. NIOSH No.: TX38000
3. Synonyms and Trade Names
Oxirane, 2,2'-[(1-methylethylidene)bis(4,1-
phenyleneoxymethylene)]bis-
Propane, 2,2-bis[p-(2,3-epoxypropoxy)phenyl]-
Bis(4-glycidyloxyphenyl)dimethylmethane
Bis(4-hydroxyphenyl)dimethyImethane diglycidyl ether
Bisphenol A diglycidyl ether
Dian diglycidyl ether
Diglycidyl bisphenol A
Diglycidyl diphenylolpropane ether
Diomethane diglycidyl ether
2,2-Bis(p-glycidyloxyphenyl)propane
2,2-Bis(p-hydroxyphenyl)propane diglycidyl ether
2,2-Bis(4-glycidyloxyphenyl)propane
2,2-Bis(4-hydroxyphenyl)propane diglycidyl ether
2,2-Bis(4'-glycidyloxyphenyl) propane
2,2-Bis[p-(2,3-epoxypropoxy)phenyl]propane
2,2-Bis[4-(2,3-epoxypropoxy)phenyl]propane
2,2-Bis[4-(2,3-epoxypropyloxy)phenyl]propane
4,4'-Bis(2,3-epoxypropoxy)diphenyldimethylmethane
4,4'-Isopropylidenebis[l-(2,3-epoxypropoxy)benzene]
4,4'-Isopropylidenediphenol diglycidyl ether
Diphenylol propane diglycidyl ether
(NIH/EPA 1978, NIOSH 1978b)
111-75
-------
B. Formulas and Molecular Weight
1. Structural Formula
CH0—CH—CH0—0
\2 / 2
0
c
I
CH
0 — CH,.— CH— CH
2 \ /
2. Empirical Formula
C21H24°4
(NIH/EPA 1978)
(NIH/EPA 1978)
3. Molecular Weight
340.40
C. Physical.Properties
1. Description
Odorless liquid; sticky and tacky when handled
(TDB 1978)
2. Boiling Point
No information was found in the sources searched.
3. Melting Point
8-12°C
(TDB 1978)
4. Vapor Pressure
No information was found in the sources searched.
5. Solubility
No information was found in the sources searched.
111-76
-------
6. Octanol/Water Partition Coefficient
No information was found in the sources searched.
7. Specific Gravity
1.168 (TDB 1978)
D. Composition of the Commercial Product
No information was found in the sources searched.
111-77
-------
DIGLYCIDYL ETHER OF BISPHENOL A
II. SOURCE AND FATE IN THE ENVIRONMENT
A. Sources
1. Production and Trends
No information was found in the sources searched.
2. Manufacturers
No information was found in the sources searched.
3. Use
As a basic active ingredient for epoxy resins which are
used for sealing and encapsulating, for making castings and
pottings, for formulating light-weight foams, and as binders
in laminates of fiber glass, paper, wood sheets, and polyester
cloth
(Patty 1963, NIOSH 1978c)
4. Occupational Exposure
Rank: 1677
Estimated number of persons exposed: 37,000*
* rough estimate
(NOHS 1976)
5. Release
No information was found in the sources searched.
111-78
-------
B. Environmental Fate
1. Occurrence
No information was found in the sources searched.
2. Transformation
No information was found in the sources searched.
3. Bioaccumulation
No information was found in the sources searched.
111-79
-------
DIGLYCIDYL ETHER OF BISPHENOL A
III. BIOLOGICAL INFORMATION
A. Effects on Humans
Fregert and Thorgeirsson (1977) conducted patch tests
with a 1% solution of diglycidyl ether of bisphenol A in acetone
on 27 men and 7 women sensitive to epoxy resins. All 34 patients
showed positive reactions.
B. Tests on Laboratory Organisms
1. Metabolism
No information was found in the sources searched.
2. Toxic Effects
a. Acute Toxicity
The acute toxicity of diglycidyl ether of bisphenol A,
as reported by the NIOSH RTECS data base (1978a) and Hine and
Rowe (1963), is given in Table III-l.
b. Carcinogenicity
According to Hine and Rowe (1963), skin painting with
diglycidyl ether of bisphenol A for up to 2 years did not cause
any tumors in mice and rabbits. Repeated subcutaneous injections
in rats resulted in sarcomas in 25% of the animals. No further
details were given.
Weil et al. (1963) gave 30-40 mice topical applications
of diglycidyl ether of bisphenol A three times a week for the
111-80
-------
life span of the animals. Each application amounted to "one
brushful" of the undiluted compound, and the maximum period of
treatment was 23 months. One papilloma was observed at 16 months.
When the compound was retested by the same procedure, no tumors
were found. Maximum treatment time was 27 months.
TABLE III-l
ACUTE TOXICITY OF DIGLYCIDYL ETHER OF BISPHENOL A
Parameter
LD50
LD50
LD50
LD50
LD50
LD50
1
2
2
2
2
2
11
11
2
15
4
19
Dosage
,000
,400
,400
,600
,000
,800
mg/kg
mg/kg
mg/kg
mg/kg
mg/kg
mg/kg
Animal
Rat
Rat
Rat
Mouse
Mouse
Rabbit
Route
Oral
Intragast
ric
Intraperitoneal
Intragast
Intraper i
Intragast
ric
toneal
ric
RTECS (1978a)
^Hine and Rowe (1963)
c. Mutagenicity and Cell Transformation
Wade et al. (1978 as reported by NIOSH 1978b) reported that
diglycidyl ether of bisphenol A was not mutagenic in Salmonella
typhimurium TA98 and TA100. The compound was tested with and
without liver microsomal extract from rats pretreated with pheno-
barbital.
Pullin and Legator (1977 as reported by NIOSH 1978b) reported
that diglycidyl ether of bisphenol A gave weakly positive results
111-81
-------
in the Ames test with S. typhimurium TA1535 but gave negative
results in TA98. The compound was mutagenic both in the absence
and presence of rat liver microsomes.
Pullin and Legator (1977 as reported by NIOSH 1978b) reported
that diglycidyl ether of bisphenol A showed some activity in
a host-mediated assay. Mutant strains of S. typhimurium were
injected into the peritoneal cavity of mice that had been given
diglycidyl ether of bisphenol A orally at doses between 125 and
1,000 mg/kg/day for 5 days. The authors attributed the activity
of the compound to a decrease in the growth of microorganisms
in the host animals. Pullin and Legator also reported that digly-
cidyl ether of bisphenol A was negative in a dominant lethal
assay. Male mice were treated topically with the undiluted com-
pound at 3 g/kg three times a week for a minimum of 87 weeks
before mating. A control group was treated with saline. Thirteen
to fourteen days after presumptive mating with the males, female
mice were sacrificed and their uteri examined. No significant
differences in the percentage of pregnancies, the total number
of implants, and the number of fetal deaths were observed between
control and experimental groups.
d. Teratogencity, Embryotoxicity, and Fetotoxicity
No information was found in the sources searched.
e. Other Toxicity
Thorgeirsson and Fregert (1977) reported that diglycidyl
ether of bisphenol A caused sensitization in female guinea pigs.
Twenty animals received intradermal injections of 0.1 ml of
111-82
-------
5% (wt/vol) diglycidyl ether of bisphenol A in acetone and
0.1 ml of 5% (wt/vol) diglycidyl ether of bisphenol A in an
equal mixture of complete Freund's adjuvant and acetone. Skin
patch tests with 0.1 ml of the compound at 5% (wt/vol) in acetone
were performed 1 and 3 weeks later. All of the treated guinea
pigs were sensitized. No animals in a control group showed
positive reactions.
Thorgeirsson et al. (1978) in a similar study also observed
sensitization in 10 of 15 guinea pigs exposed to diglycidyl
ether of bisphenol A at one-tenth the concentration used in
the earlier study by Thorgeirsson and Fregert.
111-83
-------
DIGLYCIDYL ETHER OF BISPHENOL A
IV. ENVIRONMENTAL EFFECTS
A. Ecological Effects
1. Wild and Domestic Mammals
No information was found in the sources searched,
2. Wild and Domestic Birds
No information was found in the sources searched.
3. Fish, Amphibians, and Reptiles
No information was found in the sources searched.
4. Invertebrates
No information was found in the sources searched.
5. Plants and Algae
No information was found in the sources searched.
6. Bacteria and Other Microorganisms
No information was found in the sources searched.
7. Ecological Communities and Processes
No information was found in the sources searched.
B. Other Environmental Effects
No information was found in the sources searched.
111-84
-------
DIGLYCIDYL ETHER OF BISPHENOL A
V. Work in Progress
No information was found in the sources searched,
111-85
-------
SUMMARY TABLE
H
00
Name
Glycidol
Glycidyl
aery late
Glycidyl
methacrylate
Allyl
glycidyl
ether
Butyl
glycidyl
ether
Cresyl
glycidyl
ether
CHARACTERISTICS OF GLYCIDOL AND ITS DERIVATIVES
Estimated No.
Estimated of Persons
Environmental Exposed
Solubility Log Poct Release Production (Occupational)
s in H20, * * * ^105,000
ale, eth,
ace, bz,
and chl
i in H2O * * * *
* * * * ^105,000
s in H2O, * * * **
ace, tol,
and oct
ss in H2O * * * **
* * * * **
Use
As a stabilizer, demul-
sifier, dye-leveling
agent
In manufacture of resins
*
Diluent in resin systems
Diluent in resin systems
Diluent in resin systems
-------
SUMMARY TABLE (continued)
Name
Solubility Log
Estimated
Environmental
Release
Production
Estimated No.
of Persons
Exposed
(Occupational)
Use
H
H
H
1
00
Phenyl ss in H20; * * *
glycidyl °° in ace
ether and tol
Diglycidyl * * * *
ether of
bisphenol A
* No information was found in the sources searched.
** M.18,000 for "glycidyl ethers"
** Diluent in resin systems
^37,000 Active ingredient for
epoxy resins
Key to abbreviations:
s—soluble
ss—slightly soluble
oo—soluble in all proportions
i—insoluble
ace—acetone
ale—alcohol
bz—benzene
chl—chloroform
eth—ethane
H2O—-water
oct—octanol
tol—toluene
-------
GLYCIDOL AND ITS DERIVATIVES
REFERENCES
AMERICAN CONFERENCE OF GOVERNMENTAL INDUSTRIAL HYGIENISTS (ACGIH).
1978. TLVs^: Threshold Limit Values for Chemical Substances
in Workroom Air Adopted by ACGIH. Cincinnati, Ohio
ANDERSON, H.H., HINE, C.H., GUZMAN, R.J., and WELLINGTON, J.S.
1957. Chronic Vapor Toxicity of n-Butyl Glycidyl Ether.
Confidential Report to Shell Development Company, California.
Prepared by Department of Pharmacology and Experimental
Therapeutics, University of California School of Medicine.
U.C. Report No. 270 (As reported by NIOSH 1978c)
CHEMLINE. 1978. Data base. National Library of Medicine,
Bethesda, Md.
CONDENSED CHEMICAL DICTIONARY (CCD). 1977. 9th ed. Hawley, C.G.,
ed. Van Nostrand Reinhold Co., New York
COOPER, E.R.A., JONES, A.R., and JACKSON, H. 1974. Effects of
a-chlorohydrin and related compounds on the reproductive
organs and fertility of the male rat. J. Reprod. Fert.
38:379-386
CZAJKOWSKA, T., and STETKIEWICZ, J. 1972. [Evaluating the acute
toxicity of phenyl glycidyl ether with special regard to
percutaneous absorption.] Med. Pr. 23:363-371 (Czech, as
reported by NIOSH 1978b)
DORANGE, J.L., DELAFORGE, M., JANIAUD, P., and PADIEU, P. 1977.
Pouvoir mutagene de metabolites de la voie epoxyde-diol du
safrolet d1analogues. Etude sur Salmonella typhimurium.
Pharmacologie cellulaire 21:1041-1048
DUPONT. 1978. Haskell Laboratory Reports No. 164-75, 225-74,
133-76, and 163-75 (1974-1976). Enclosed in personal communi-
cation from Bruce W. Karrh, Corporate Medical Director,
E.I. du Pont de Nemours & Co., to Catherine Woodbury, National
Institute For Occupational Safety and Health, February 10,
1978
FISHBEIN, L. 1977. Potential Industrial Carcinogens and Mutagens.
U.S. Environmental Protection Agency, Office of Toxic Sub-
stances, Washington, D.C., May 1977, EPA 560/5-77-005
FREGERT, S., and RORSMAN, H. 1964. Allergens in epoxy resins.
Acta Allergol. 19:296-299 (As reported by NIOSH 1978b)
111-88
-------
FREGERT, S., and THORGEIRSSON, A. 1977. Patch testing with low
molecular digomers of epoxy resins in humans. Contact
Dermatitis 3:301-303
FRIEDMAN, M.A., GREENE, E.J., SHERROD, J.A., and SALERNO, J.A.
1978. Activity of phenylglycidyl ether (PGE) in genetic
in vitro screening tests. Presented to the American Society
for Ptfarmacology and Experimental Therapeutics, August
1978 (Abstract)
HADIDIAN, A., FREDRICKSON, T.N., WEISBURGER, E.K., WEISBURGER,
J.H., GLASS, R.M., and MANTEL, N. 1968. Tests for chemical
carcinogens. Report on the activity of derivatives of
aromatic amines, nitrosamines, quinolines, nitroalkanes,
amides, epoxides, aziridines, and purine antimetabolites.
J. Natl. Cancer Inst. 41:985-1025
HANDBOOK OF CHEMISTRY AND PHYSICS (HCP). 1976. 57th ed. Weast,
R.C., ed. Chemical Rubber Co., Cleveland, Ohio
HINE, C.H., and ROWE, V.K. 1963. Epoxy compounds. In Palty,
F.A., ed. Industrial Hygiene and Toxicology. 2nd ed.
Wiley Interscience, New York. 2:1593-1654
HINE, C.H., KODAMA, J.K., WELLINGTON, J.S., DUNLAP, M.K., and
ANDERSON, H.M. 1956. The toxicity of glycidol and some
glycidyl ethers. Am. Ind. Hyg. Assoc. J. 14:250-261
IZARD, C. 1973. [Mutagenic effects of acrolein and its two
epoxides, glycidol and glycidal, in Saccharomyces cerevisiae.]
C.R. Acad. Sci., Ser. D 276:3037-3040 (French)
JACKSON, H., CAMPBELL, I.S., and JONES, A.R. 1970. Is glycidol
an active intermediate in the antifertility action of alpha-
chlorohydrin in male rats? Nature 226:86-87
JONES, A.R. 1975. The metabolism of 3-chloro-, 3-bromo-and
3-iodopropan-l,2-diol in rats and mice. Xenobiotica 5:
155-165
JONES, P., and JACKSON, H. 1974. Actions of antifertility che-
micals on Xenopus laevis spermatozoa in vitro. J. Reprod.
Fert. 38:347-357
KILPATRICK, K.A., and LAMBOOY, J.P. 1967. Bacteriostatic activi-
ties of ct-glyceryl and a-glycidyl phenyl ethers for Escherichia
coli B. Proc. Soc. Exp. Biol. Med. 126:237-240
KLIGMAN, A.M. 1966. The identification of contact allergens by
human assay: III. The maximization test—a procedure for
screening and rating contact sensitizers. J. Invest.
Dermatol. 47:393-409 (As reported by NIOSH 1978b)
111-89
-------
KOLMARK, G., and GILES, N.H. 1955. Comparative studies of mono-
epoxides as inducers of reverse mutations in Neurospora.
Genetics 40:890-902
KODAMA, J.K., GUZMAN, R.J., DUNLAP, M.K., LOQUVAM, G.S., LIMA, R.,
and HINE, C.H. 1961. Some effects of epoxy compounds on
the blood. Arch. Environ. Health 2:56-67
•»
KUCERA, A., LUNDQUIST, U., and GUSTAFSSON, A. 1975. Induction
of breviaristatem mutants in barley- Hereditas 80:263-278
LEA, W.A., Jr., BLOCK, W.B., CORNISH, H.H. 1958. The irritating
and sensitizing capacity of epoxy resins. Arch. Dermatol. 78
304-308 (As reported by NIOSH 1978b)
LEE, K.P., TERRILL, J.B., and HENRY, N.W., II. 1977. Alopecia
induced by inhalation exposure to phenyl glycidyl ether.
J. Toxicol. Environ. Hlth. 3:859-869
McCANN, J., and AMES, B.N. 1976. Detection of carcinogens as
mutagens in the Salmonella/microsomic test: Assay of 300
chemicals: Discussion. Proc. Natl. Acad. Sci. 73:
950-954
NATIONAL CANCER INSTITUTE (NCI). 1978. Chemicals Being Tested
for Carcinogenicity by the Bioassay Program. Division of
Cancer Cause and Prevention.
NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH (NIOSH).
1978a. Registry of Toxic Effects of Chemical Substances.
Data Base
NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH (NIOSH).
1978b. Criteria for a Recommended Standard: Occupational
Exposure to Glycidyl Ethers
NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH (NIOSH).
1978c. NIOSH Current Intelligence Bulletin #29: Glycidyl
Ethers. Prepublication copy. October 12, 1978
NATIONAL OCCUPATIONAL HAZARD SURVEY (NOHS). 1976. National
Institute for Occupational Safety and Health, Cincinnati,
Ohio
NIH/EPA SUBSTRUCTURE SEARCH SYSTEM (NIH/EPA). 1978. Prepared
by Fein-Marquart Assoc., Baltimore, Md.
OESCH, F. 1972. Review article: Mammalian epoxide hydrases;
inducible enzymes catalysing the inactivation of carcino-
genic and cytotoxic metabolites derived from aromatic and
olefinic compounds. Xenobiotica 3:305-340 (As reported
by NIOSH 1978b)
111-90
-------
PATTY, F.A. 1963. Industrial Hygiene and Toxicology. 2nd ed.
Wiley Interscience, New York
OPD CHEMICAL BUYERS DIRECTORY. 1977. 1977-78 ed. Chemical
Marketing Reports, Schnell Publishing Co., New York
PULLIN, I., and LEGATOR, M.S. 1977. Integrated mutagenicity
testing program. Unpublished report submitted to National
Institute for Occupational Safety and Health by Dow Chemical
Co., Health and Environmental Research, Midland, Mich.
(As reported by NIOSH 1978b)
RAPOPORT, I.A. 1948. [Action of ethylene oxide glycides and
glycols on genetic mutations.] Dokl. Acad. Nauk. SSR 60:
469-472 (As reported by Fishbein 1977)
SLADE, M., BROOKS, G.T., HETNARSKI, K.H., and WILKINSON, C.F-
1975. Inhibition of the enzymatic hydration of the epoxide
HEOM in insects. Pestic. Biochem. Physiol. 5:35-46
SMYTH, H.F., CARPENTER, C.P., WEIL, C.S., and POZZANI, U.C. 1954.
Range-finding toxicity data: List V. Arch. Ind. Hlth. 10:
61-68
SMYTH, H.F., CARPENTER, C.P-, WEIL, M.A., POZZANI, U.C., and
STRIEGEL, J.A. 1962. Range-finding toxicity data: List
VI. Arch. Ind. Hlth. 23:95-107
SOELLNER, K., and IRRGANG, K. 1965. [Studies on the pharmaco-
logical action of aromatic glycidol ethers.] Arzneim.-
Forsch. 15:1355-1357 (German, as reported by NIOSH 1978b)
STEVENS, M.A. 1967. Use of the albino guinea-pig to detect the
skin-sensitizing ability of chemicals. Br. J. Ind. Med. 24:
189-202
TANG, J. 1971. Specific and irreversible inactivation of pepsin
by substrate-like epoxides. J. Biol. Chem. 246:4510-4517
TERRILL, J.B., and LEE, K.P. 1977. The inhalation toxicity of
phenylglycidyl ether: I. 90-Day inhalation study. Toxicol.
Appl. Pharmacol. 42:263-269
THORGEIRSSON, A., and FREGERT, S. 1977. Allergenicity of epoxy
resins in the guinea pig. Acta Dermatovener. 57:253-256
(As reported by Thorgeirsson et al. 1978)
THORGEIRSSON, A., FREGERT, S., and RAMNAS, 0. 1978. Sensitiza-
tion capacity of epoxy resin oligomers in the guinea pig.
Acta Dermatovener. 58:17-21
TOXICOLOGY DATA BANK (TDB). 1978. Data base. National Library
of Medicine, Toxicology Information Program, Bethesda, Md.
111-91
-------
TOX-TIPS. 1978. National Library of Medicine, Toxicology Informa-
tion Program, Bethesda, Md., September 1978
U.S. INTERNATIONAL TRADE COMMISSION (USITC). 1972, 1974, 1975,
1976. Synthetic Organic Chemicals, United States Production
and Sales. Washington, D.C. USITC Publication 833
VAN DUUREN, B.L., LANGSETH, L., GOLDSCHMIDT, B.M., and ORRIS, L.
1967. Carcinogenicity of epoxides, lactones, and peroxy
compounds: VI. Structure and carcinogenic activity. J.
Natl. Cancer Inst. 39:1217-1228
VERSCHUEREN, K. 1977. Handbook of Environmental Data on Organic
Chemicals. Van Nostrand Reinhold Co., New York
WADE, M., MOYER, J.W., and HINE, C.H. 1976. Mutagenicity of
epoxides. Fed. Proc. 35:504 (Abstract)
WADE, M.J., MOYER, J.W., and HINE, C.H. 1978. Mutagenic Action
of a Series of Epoxides. Publication No. 78-2. University
of California School of Medicine, Department of Pharmacology
(As reported by NIOSH 1978b)
WEIL, C.S., CONDRA, N., HAUN, C., and STRIEGEL, J.A. 1963.
Experimental carcinogenicity and acute toxicity of represen-
tative epoxides. Am. Indust. Hyg. Assoc. J. 24:304-325
ZSCHUNKE, E., and BEHRBOHN, P. 1965. [Eczema due to phenoxy-
propenoxide and similar glycide ethers.] Dermatol.
Wochenschr. 151:480-484 (French, as reported by NIOSH 1978b)
111-92
-------
APPENDIX A
ABSTRACTS AND AUTOMATED DATA BASES SEARCHED
Air Pollution Abstracts (APTIC)
CANCERLIT
CANCERPROJ
Chemical Abstracts (1978)
CHEMLINE
Environmental Mutagen Information Center File (EMIC)
Enviromental Teratology Information Center File (ETIC)
National Occupational Hazard Survey (NOHS)
NIH/EPA Substructure Search System
National Technical Information Service Data Base (NTIS)
Pollution Abstracts
Registry of Toxic Effects of Chemical Substances (RTECS)
Toxicology Data Bank (TDB)
Toxicology Information On-Line Backfile (TOXBACK)
Toxicology Information On-Line (TOXLINE)
-------
APPENDIX B
SECONDARY SOURCES SEARCHED
AMERICAN CONFERENCE OF GOVERNMENTAL INDUSTRIAL HYGIENISTS.
1978. TLVs®: Threshold Limit Values for Chemical Sub-
stances in Workroom Air Adopted by ACGIH. Cincinnati,
Ohio
CASARETT, L.J., and DOULL, J. 1975. Toxicity: The Basic Science
of Poisons. Macmillan Publishing Co., New York
CONDENSED CHEMICAL DICTIONARY. 1977. 9th ed. Hawley, C.G.,
ed. Van Nostrand Reinhold Co., New York
CURRENT CONTENTS. Institute for Scientific Information, Philadel-
phia
DE BRUIN, A. 1976. Biochemical Toxicology of Environmental
Agents. Elsevier/North-Holland, New York
FAITH, KEYES, & CLARK'S INDUSTRIAL CHEMICALS. 1975. 4th ed.
Lowenheim, F.A., and Moran, M.K., eds. John Wiley & Sons,
New York
FISHBEIN, L. 1977. Potential Industrial Carcinogens and Muta-
gens. U.S. Environmental Protection Agency, Office of
Toxic Substances, Washington, D.C., May 1977. EPA 560/5-
77-005
GOSSELIN, R.E., HODGE, H.C., SMITH, R.P., and GLEASON, M.N.
1976. Clinical Toxicology of Commercial Products. 4th
ed. Williams & Wilkins Co., Baltimore
HANDBOOK OF CHEMISTRY AND PHYSICS. 1976. 57th ed. Chemical
Rubber Co., Cleveland, Ohio
INTERNATIONAL AGENCY FOR RESEARCH ON CANCER, WORLD HEALTH ORGANI-
ZATION. 1972-1978. IARC Monographs on the Evaluation
of Carcinogenic Risk of Chemicals to Man. Lyon, France
KIRK-OTHMER ENCYCLOPEDIA OF CHEMICAL TECHNOLOGY. 1972. Standen,
A., ed. Interscience Publishers, New York
LEO, A., HANSCH, C., and ELKINS, D. 1971. Partition coeffi-
cients and their uses. Chem. Rev. 71:526-616
MERCK INDEX. 9th ed. 1976. Merck & Co. Rahway, N.J.
-------
MITRE. 1976. Scoring of Organic Air Pollutants: Chemistry,
Production and Toxicity of Selected Synthetic Organic Chemi-
cals. By Dorigan, J., Fuller, B., and Duffy, R. MITRE
Technical Report. MTR-7248
NATIONAL CANCER INSTITUTE. 1978. Chemicals Being Tested for
Carcinogenicity by the Bioassay Program. Division of Cancer
>Cause and Prevention
NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH. 1977.
Chemical/Industrial Profiles for NIOSH Criteria Document
Priorities
NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH. 1972-
1978. Criteria for a Recommended Standard
NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH. 1977.
Registry of Toxic Effects of Chemical Substances. DREW
Publication No. (NIOSH) 78-104-A
PATTY, F.A. 1963. Industrial Hygiene and Toxicology. 2nd
ed. Wiley Interscience, New York
PUBLIC HEALTH SERVICE. 1961-1973. Survey of Compounds Which
Have Been Tested for Carcinogenic Activity. DREW Publi-
cation No. (NIH) 73-453. Public Health Service Publication
No. 149
SAX, N.I. 1975. Dangerous Properties of Industrial Materials.
3rd ed. Reinhold Publishing Corp., New York
SEARLE, CHARLES E., ed. 1976. Chemical Carcinogens. ACS Mono-
graph 173. American Chemical Society, Washington, D.C.
SHACKELFORD, W.M., and KEITH, L.H. 1976. Frequency of Organic
Compounds Identified in Water. U.S. Environmental Protec-
tion Agency, Office of Research and Development, Athens,
Ga., December 1976. EPA-600/4-76-062
SHEPARD, T.H. 1976. Catalogue of Teratogenic Agents. 2nd
ed. Johns Hopkins University Press, Baltimore
STANFORD RESEARCH INSTITUTE. 1975. Research Program on Hazard
Priority Ranking of Manufactured Chemicals. Phase II:
Final Report. By Brown, S.L., Chan, F.Y., Jones* J.L.,
Liu, D.H., McCaleb, K.E., Mill, T., Sapios, K.N., and Schendel,
D.E. Prepared for the National Science Foundation, Menlo
Park, Calif. SRI Project ECU-3386
TOX-TIPS. 1978. National Library of Medicine, Toxicology Infor-
mation Program, Bethesda, Md.
-------
U.S. CONSUMER PRODUCT SAFETY COMMISSION. 1977. Chemical Con-
sumer Hazard Information System. Washington, D.C.
U.S. INTERNATIONAL TRADE COMMISSION. 1972, 1974, 1975, 1976.
Synthetic Organic Chemicals, United States Production and
Sales. Washington, D.C. USITC Publication 833
U.S. ENVIRONMENTAL PROTECTION AGENCY. 1976. A Study of Indus-
trial Data on Candidate Chemicals for Testing. Office
of Toxic Substances, Washington, D.C., November 1976.
EPA Contract No. 68-01-4109
U.S. ENVIRONMENTAL PROTECTION AGENCY. 1977. A Study of Indus-
trial Data on Candidate Chemcials for Testing. Office
of Toxic Substances, Washington, D.C., August 1977. EPA-560/
5-77-006
VERSCHUEREN, K. 1977. Handbook of Environmental Data on Organic
Chemicals. Van Nostrand Reinhold Co., New York
WORLD HEALTH ORGANIZATION. 1978. Information Bulletin on the
Survey of Chemicals Being Tested for Carcinogenicity, No.
7. Lyon, France
-------
APPENDIX C
KEY TO ABBREVIATIONS
LD50 Median Lethal Dose
The dose of a test material, introduced by any route
other than inhalation, that kills 50% of an experimental
animal population within a given period of time
LC50 Median Lethal Concentration
The concentration of a test material in air or water
that kills 50% of an experimental animal population
within a given period of time
LDLo Lowest Published Lethal Dose
The lowest dose of a substance, introduced by any route
other than inhalation over a given period of time, that
has been reported to have killed members of a given
species
LCLo Lowest Published Lethal Concentration
The lowest concentration of a substance in air or water
that has been reported to have killed members of a given
species over a given exposure time
TLV-TWA Threshold Limit Value-Time Weighted Average
The time-weighted average airborne concentration of a
substance for an 8-hour workday or 40-hour workweek
recommended by the American Conference of Governmental
Hygienists as safe for nearly all workers
TLm Median Tolerance Limit
The concentration of a test material at which 50% of an
experimental animal population survives for a specified
time period
BOD Biochemical Oxygen Demand
A measure of the extent of biodegradation of an organic
chemical by biota in water in a specific number of days
(x)
NOHS Occupational Exposure
Rank: A number indicating the chemical's place in a
list of approximately 7,000 occupational hazards
ranked in order of the number of workers exposed.
The lower the number, the more common the hazard.
Estimated number of persons exposed: This figure
includes full- and part-time workers. For
hazards ranked 1-200, the figure given is a
-------
ADDENDUM TO
INFORMATION DOSSIERS ON SUBSTANCES
DESIGNATED BY
TSCA INTERAGENCY TESTING COMMITTEE
(October 1978)
-------
CHLOROBENZENES
PENTACHLOROBENZENE
III.B.I. Metabolism
Villeneuve and Khera (1975) reported a study in which four
groups, each containing five pregnant Wistar rats, received
single daily oral doses of pentachlorobenzene at 25, 50, 100, and
200 mg/kg on days 6-15 of gestation. The rats were sacrificed on
day 25 of pregnancy. The accumulation of pentachlorobenzene in
the maternal and fetal viscera appeared to be dose-related. The
highest concentration in maternal tissue was in the fat. The
compound was also present in liver, brain, heart, kidney, and
spleen. The mean concentrations in tissues from females given
200 mg/kg were 3,350 ppm in fat, 91.1 ppm in liver, 62.5 ppm in
brain, 57.5 ppm in heart, 43.5 ppm in kidney, and 46.2'ppm in
spleen. In the fetuses from these females, the brain contained
pentachlorobenzene at 4.37 ppm and the liver contained 3.08 ppm.
Leber et al. (1977) examined the metabolic fate of penta-
chlorobenzene in rhesus monkeys each given an oral dose of 20 mg.
The major urinary metabolites included two isomers of tetrachlor-
ophenol, and the feces contained a substantial amount of unmetab-
olized pentachlorobenzene. The authors stated the pentachloro-
benzene might have a prolonged retention time in rhesus monkeys.
-------
REFERENCES
LEBER, A.P., FREUDENTHAL, R.I., BARON, R.L., and CURLEY, A.
1977. Pharraacokinetics and metabolism of pentachloro-
benzene in rhesus monkeys. Toxicol. Appl. Pharmacol. 41:45
(Abstract)
VILLENEUVE, D.C., and KHERA, K.S. 1975. Placental transfer of
halogenated benzenes (pentachloro-, pentachloronitro-, and
hexabromo-) in rats. Environ. Physiol. Biochem. 5:328-331
HEXACHLOROBENZENE
On page 8 of the Third Report of the TSCA Interagency
Testing Committee to the Administrator, Environmental Protection
Agency, the statement is made that "hexachlorobenzene is a
demonstrated animal carcinogen." The following articles are
relevant to the evaluation of the carcinogenicity of this com-
pound:
CABRAL, J.R.P., SHUBIK, P., MOLLNER, T., and RAITANO, F. 1977.
Carcinogenic activity of hexachlorobenzenes in hamsters.
Nature 269:510-511
CABRAL, J.R.P-, MOLLNER, T., RAITANO, F., and SHUBIK, P- 1978.
Carcinogenesis study in mice with hexachlorobenzene.
Abstracts of Papers for the Seventeenth Annual Meeting of
the Society of Toxicology, San Francisco, Calif., March
12-16
-------
1,2-DICHLOROPROPANE
II.A.I. Production and Trends
58.5 million Ib (USITC 1977)
III.B.2.C. Mutagenicity and Cell Transformation
DeLorenzo et al. (1977) reported that 1,2-dichloropropane
at 10-50 mg/plate was mutagenic in Salmonella typhimurium TA1535
and TA100 with and without microsomal activation. The compound
was reported to be nonmutagenic in S. typhimurium TA1978.
REFERENCES
DeLORENZO, F., DEGL1INNOCENTI, S., RUOCCO, A., SILENGO, L.,
and CORTESE, R. 1977. Mutagenicity of pesticides con-
taining 1,3-dichloropropene. Cancer Res. 37:1915-1917
U.S. INTERNATIONAL TRADE COMMISSION (USITC). 1977. Synthetic
Organic Chemicals, United States Production and Sales.
Washington, D.C. USITC Publication 833
-------
GLYCIDOL AND ITS DERIVATIVES
GLYCIDOL
II.A.I. Production and Trends
0.1 million Ib
(SRI 1977)
II.A.4. Occupational Exposure
Estimated number of persons exposed: 61,147 (NIOSH 1978a)
(Comment: This estimate of occupational exposure was based
on statistical extrapolation. It replaces the rougher estimate
given in the dossier.)
GLYCIDYL ETHERS
II.A.4. Occupational Exposure
Data on occupational exposure to the glycidyl ethers are
given in Table 1:
TABLE 1
OCCUPATIONAL EXPOSURE TO GLYCIDYL ETHERS*
Compound
Estimated Number of Workers
Potentially Exposed**
Glycidyl ethers***
Diglycidyl ether of bisphenol A
n-Butyl glycidyl ether
71,000
36,000
13,000
-------
TABLE 1 (continued)
nn , Estimated Number of Workers
Compound Potentially Exposed**
Phenyl glycidyl ether 8,000
Allyl glycidyl ether 2,000
*Adapted from NIOSH (1978b)
**A worker may be exposed to more than one glycidyl ether.
Thus the exposure estimates are not additive. Because of the
difficulty of obtaining data on the composition of trade name
products, these estimates may be low (NIOSH 1978b).
***Exposures were .entered into the NOHS data base either under
the specific glycidyl ether (when the information was available)
or under the general term "glycidyl ethers" (when more specific
information was not available). To the extent that an exposure
to a specific glycidyl ether was reported as exposure to "gly-
cidyl ethers," the estimates for occupational exposure to indi-
vidual glycidyl ethers may be low (NIOSH 1978b)
REFERENCES
NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH (NIOSH).
1978a. National Occupational Hazard Survey Print-Outs.
Enclosed in letter from Joseph A. Seta, Hazard Section,
Surveillance Branch, NIOSH, Cincinnati, Ohio, to Clement
Associates, August 3, 1978
NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH (NIOSH).
1978b. NIOSH Current Intelligence Bulletin No. 29: Gly-
cidyl Ethers. Prepublication copy. October 12, 1978
SRI INTERNATIONAL. 1977. Glycidol: Summary of data for chemi-
cal selection. Menlo Park, Calif. September 1977
-------
On page 11 of the Third Report of the TSCA Interagency
Testing Committee to the Administrator, Environmental Protection
Agency, reference is made to the "demonstrated carcinogenicity of
certain members" of the category of glycidol and its derivatives.
The following articles are relevant to the evaluation of the
carcinogenicity of two examples of these compounds:
Triethylene glycol diglycidyl ether (CAS No. 1954-28-5)
SHIMKIN, M.B., WEISBURGER, J.H., WEISBURGER, E.K., GUBAREFF, N.,
and SUNTZEFF, V. 1966. Bioassay of 29 alkylating chemicals
by the pulmonary-tumor response in strain A mice. J. Natl.
Cancer Inst. 36:915-935
Glycidal (CAS No. 765-34-3)
VAN DUUREN, B.L., ORRIS, L., and NELSON. 1965. Carcinogenicity
of epoxides, lactones and peroxy compounds. II. J. Natl.
Cancer Inst. 35:707-717
VAN DUUREN, B.L., LANGSETH, L., ORRIS, L., TEEBOR, G. , NELSON, N.
and KUSCHNER, M. 1966. Carcinogenicity of epoxides, lac-
tones and peroxy compounds. IV. Tumor response in epi-
thelial and connective tissue in mice and rats. J. Natl.
Cancer Inst. 37:825-834
VAN DUUREN, B.L., LANGSETH, L., GOLDSCHMIDT, B.M., and ORRIS, L.
1967a. Carcinogenicity of epoxides, lactones and peroxy
compounds. VI. Structure and carcinogenic activity. J.
Natl. Cancer Inst. 39:1217-1228
VAN DUUREN, B.L., LANGSETH, L. , ORRIS, L., BADEN, M. and
KUSCHNER, M. 1967b. Carcinogenicity of epoxides, lactones
and peroxy compounds. V. Subcutaneous injection in rats.
J. Natl. Cancer Inst. 39:1213-1216
------- |