No. 42
Chlorobenzene
Health and Environmental Effects
U.S. ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
APRIL 30, 1980
EPA 950-F-80-001
-------
DISCLAIMER
This report represents a survey of the potential health
and environmental hazards from exposure to the subject chemi-
cal. The information contained in the report is drawn chiefly
from secondary sources and available reference documents.
Because of the limitations of such sources, this short profile
may not reflect all available information including all the
adverse health and environmental impacts presented by the
subject chemical. This document has undergone scrutiny to
ensure its technical accuracy.
-------
CHLOPOBENZENE
Summary
There is little data on the quantities of chlorobenzene in air, water
and food, although this compound has been identified in these media. Chron-
ic exposure to chlorobenzene appears to cause a variety of pathologies under
different experimental regimens; however, the liver and kidney appear to be
affected in a number of species. There have been no studies conducted to
evaluate the mutagenic, teratogenic, or carcinogenic potential of chloro-
benzene.
Four species of freshwater fish have 96-hour LCjg values ranging from
24,000 to 51,620 jug/1. Hardness does not significantly affect the values.
In saltwater, a fish and shrimp had reported 96-hour LCjg values of 10,500
ug/1 and 6,600 ug/1, respectively. NO chronic data involving chlorobenzene
are available. Algae, both fresh and saltwater, are considerably less sen-
sitive to chlorobenzene toxicity than fish and invertebrates.
-------
I. INTRODUCTION
This profile is based on the Ambient Water Quality Criteria Document
for Chlorinated Benzenes (U.S. EPA, 1979).
Chlorobenzene, most often referred to as monochlorobenzene (MCB;
C6H5C1; molecular weight 112.56), is a colorless liquid with a pleasant
aroma. Monochlorobenzene has a melting point of -45.6°c, a boiling point
of 131-132°C, a water solubility of 488 mg/1 at 25°C, and a density of
1.107 g/ml. Monochlorobenzene has been used as a synthetic intermediate in
the production of phenol, DDT, and aniline. It is also used as a solvent in
the manufacture of adhesives, paints, polishes, waxes, diisocyanates,
Pharmaceuticals and natural rubber (U.S. EPA, 1979).
Data on current production derived from U.S. International Trade Com-
mission reports show that between 1969 and 1975, the U.S. annual production
of mcnochlorobenzene decreased by 50 percent, from approximately 600 million
pounds to approximately 300 million pounds (U.S. EPA, 1977).
II. EXPOSURE
A. water
Based on the vapor pressure, water solubility, and molecular weight
of Chlorobenzene, Mackay and Leinonen (1975) estimated the half-life of
evaporation from water to be 5.8 hours. Monochlorobenzene has been detected
in ground water, "uncontaminated" upland water, and in waters contaminated
either by industrial, municipal or agricultural waste. The concentrations
ranged from 0.1 to 27 pg/1, with raw waters having the lowest concentration
and municipal waste the highest (U.S. EPA, 1975, 1977). These estimates
should be considered as gross estimates of exposure, due to the volatile
nature of monochlorobenzene.
-------
B. Food
The U.S. EPA (1979) has estimated the weighted average bioconcen-
tration factor of monochlorobenzene to be 13 for the edible portions of fish
and shellfish consumed by Americans. This estimate was based on-octancl/-
water partition coefficients.
C. Inhalation
Data have not been found in the available literature which deal
with exposure to chlorobenzene outside of the industrial working environment.
III. PHARMACOKINETICS
A. Absorption
There Is little question, based on human effects and mammalian
toxicity studies, that chlorobenzene is absorbed through the lungs and from
the gastrointestinal tract (U.S. EPA, 1977).
B. Distribution
Because chlorobenzene is highly lipophilic and hydrophobic, it
would be expected that it would be distributed throughout total body water
space, with body lipid providing a deposition site (U.S. EPA, 1979).
C. Metabolism
Chlorobenzene is metabolised via an NAOPH-cytochrome P-4A8 depen-
dent microsomal enzyme system. The first product, and rate limiting step,
is a epoxidation; this is followed by formation of diphenolic and mcnophe-
nolic compounds (U.S. EPA, 1979). Various conjugates of these phenolic
derivatives are the primary excretory products (Lu, et al. 1974). Evidence
indicates that the metabolism of monochlorobenzene results in the formation
of toxic intermediates (Kohli, et al. 1976). Brodie, et al. (1971) induced
microsomal enzymes with phenobarbital and showed a potentiationin in 'the
toxicity of monochlorobenzene. However, the use of 3-methylcho-
-------
lanthrene to induce microsomal enzymes provided protection for rats (Oesch,
et al. 1973). The metabolism of chlorobenzene may also lead to the forma-
tion of carcinogenic active intermediates (Kohli, et al. 1976).
D. Excretion
The predominant route of elimination is through the formation of
conjugates of the metabolites of monochlorobenzene and elimination of these
conjugates by the urine (U.S. EPA, 1979). The types of conjugates formed
vary with species (Williams, et al. 1975). In the rabbit, 27 percent of an
administered dose appeared unchanged in the expired air (Williams, 1959).
IV. EFFECTS
Pertinent data could not be located in the available literature on the
carcinogenicity, mutagenicity, teratogenicity, or other reproductive effects
of chlorobenzene.
A. Chronic Toxicity
Data on the chronic toxicity of chlorobenzene is sparse and some-
what contradictory. "Histopathological changes" have been noted in lungs,
liver and kidneys following inhalation of monochlorobenzene (200, 475, and
1,000 ppm) in rats, rabbits and guinea pigs (Irish, 1963). Oral administra-
tion of doses of 12.5, 50 and 250 mg/kg/day to rats produced little patholo-
gical change, except for growth retardation in males (Knapp, et al. 1971).
B. Other Relevant Information
Chlorobenzene appears to increase the activity of microsomal NADPH-
cytochrome P-450 dependent enzyme systems. Induction of microsomal enzyme
activity has been shown to enhance the metabolism of a wide variety of
drugs, pesticides and other xenobiotics (U.S. EPA, 1979).
-------
V. AQUATIC TQXICITY
A. Acute Toxicity
Pickering and Henderson (1966) reported observed 96-hour LCeg
values for goldfish, Carassius auratus, guppy, Poecilia retieulatus. and
bluegill, Lepomis macrochirus. to be 51,620, 45,530, and 24,000 jug/1,, re-
spectively, for chlorobenzene. Two 96-hour LCjg values for chlorobenzene
and fathead minnows, Pimephales promelas, are 33,930 pg/1 in soft water (20
mg/1) and 29,120 jug/1 in hard water (360 mg/1), indicating that hardness
does not significantly affect the acute toxicity -of chlorobenzene (U.S. EPA,
"•
1978). With Daphnia maqna. an observed 48-hour EC-, value of 86,000 pg/1
was reported.' In saltwater studies, sheepshead minnow had a reported un-
adjusted LCX (96-hour) value of 10,500 pg/1, with a 96-hour ECjQ of
16,400 jjg/1 for mysid shrimp (U.S. EPA, 1978).
8. Chronic Toxicity
NO chronic toxicity studies have been reported on the chronic
toxicity of chlorobenzene and any salt or freshwater species.
C. Plant Effects
The freshwater alga Selenastrum caoricomutum is considerably less
sensitive than fish and Daphnia maqna. Based on cell numbers, the species
i
has a reported 96-hour ECcg value of 224,000 pg/1. The saltwater alga,
Skeletonema costatum, had a 96-hour EC--, based on cell numbers of 341,000
0. Residues
A bioconcentration factor of 44 was obtained assuming an 8 percent
lipid content of fish.
£-7
-------
VI. EXISTING GUIDELINES AND STANDARDS
Neither the human health nor the aquatic criteria derived by U.S. EPA
(1979), which are summarized below, have gone through the process of public
review; therefore, there is a possibility that these criteria will be
changed.
A. Human
The American Conference of Governmental Industrial Hygienists
(ACGIH, 1971) threshold limit value for chlorobenzene is 350 mg/m3. The
acceptable daily intake (ADI) was calculated to be-.1.008 mg/day. The U.S.
EPA (1979) draft water criterion for chlorobenzene is 20 jjg/1, based on
threshold concentration for odor and taste.
8. Aquatic
For chlorobenzene, the drafted criterion to protect freshwater
aquatic life is 1,500 jjg/1 as a 24-hour average; the concentration should
not exceed 3,500 jjg/1 at any time. To protect saltwater aquatic life, a
draft criterion of 120 ^ig/1 as a 24-hour average with a concentration not
exceeding 280 pg/1 at any time has been recommended (U.S. EPA, 1979).
-------
CHLOROBENZENE
REFERENCES
American Conference of Governmental Industrial Hygienists.
1971. Documentation of the threshold limit values for sub-
stances in workroom air. 3rd. Ed.
Brodie, B.B., et al. 1971. Possible mechanism of liver ne-
crosis caused by aromatic organic compounds. Proc. Natl.
Acad. Sci. 68: 160.
Irish, 0.0. 1963. Salogenated hydrocarbons: II. Cyclic.
jCnjIndustrial Hygiene and Toxicology, Vol. II, 2nd Ed., ed.
F.A. Patty , Interscience, New York. p. 1333.
Rnapp, W.K., Jr., et al. 1971. Subacute oral tcaeicity of
monochlorobenzene in dogs and rats. Topxicol. Appl. Pharma-
col. 19: 393.
Rohli, I., et al. 1976. The metabolism of higher chlori-
nated benzene isomers. Can. Jour. Biochem. 54: 203.
Lu, A.Y.H., et al. 1974. Liver microsomal electron trans-
port systems. III. Involvement of cytochrome b$ in the
NADH-supported cytochrome p*-450 dependent hydroxylation of
chlorobenzene. Biochem. Biphys. Res. Contra. 61: 1348.
Mackay, 0., and P.J. Leinonen. 1975. Rate of evaporation of
•low-solubility contaminants from water bodies to atmosphere.
Environ. Sci. Technol. 9: 1178.
Oesch, P., et al. 1973. Induction activation and inhibition
of epoxide hydrase. Anomalous prevention of chlorobenzene-
induced hepafcotoxicity by an inhibitor of epoxide hydrase.
Chem. Biol. Interact. 6: 189.
Pickering, Q.H., and C. Henderson. 1966. Acute toxicity of
some important petrochemicals to fish. Jour. Water Pollut.
Control Fed. 38: 1419.
U.S. EPA. 1975. Preliminary assessment of suspected carcin-
ogens in drinking water. Report to Congress. Environ.
Prot. Agency, Washington, D.C.
O.S. EPA. 1977. Investigation of selected potential envi-
ronmental contaminants: Halogenated benzenes. EPA 560/2-77-
004.
U.S. EPA. 1978. In-depth studies on health and environmen-
tal impacts of selected water pollutants. U.S. Environ.'
Prot. Agency, Contract No. 68-01-4646.
-------
U.S. EPA. 1979. Chlorinated Benzenes: Ambient Water Quality
Criteria (Draft).
Williams, R.T. 1959. The metabolism of halogenated aromatic
hydrocarbons. Page 237 in Detoxication mechanisms. 2nd ed.
John Wiley and Sons, New York.
Williams, R.T., et al. 1975. Species variation in the meta-
bolism of some organic halogen compounds. Page 91 Tn'A.D.
Mclntyre and C.F. Mills, eds. Ecological and tox icoTogical
research. Plenum Press, New York.
------- |