United States Pollution Prevention January 1995
Environmental and Toxics EPA 749-F-95-007a
Protection
Agency (7407)

		 OPPT Chemical Fact Sheets

		 Chlorobenzene Fact Sheet:
		Support Document (CAS No. 108-90-7)

This summary is based on information retrieved from a systematic search
limited to secondary sources (see Appendix A). These sources include
online databases, unpublished EPA information, government publications,
review documents, and standard reference materials. The literature
search was done in January of 1995. No attempt has been made to verify
information in these databases and secondary sources.

I. CHEMICAL IDENTITY AND PHYSICAL/CHEMICAL PROPERTIES

 The chemical identity and physical/chemical properties of
chlorobenzene are summarized in Table 1.

 TABLE 1. CHEMICAL IDENTITY AND CHEMICAL/PHYSICAL PROPERTIES OF
CHLOROBENZENE
_______________________________________________________________________
Characteristic/Property Data Reference
_______________________________________________________________________

CAS No. 108-90-7

Common Synonyms monochlorobenzene; ATSDR 1990
			 benzene chloride
			 MCB; chlorobenzol;
			 Caswell No. 183A

Molecular Formula C6H5Cl

Chemical Structure

Physical State colorless liquid ATSDR 1990

Molecular Weight 112.56 ATSDR 1990

Melting Point 45.6C ATSDR 1990

Boiling Point 132C ATSDR 1990

Water Solubility 466.3 mg/L U.S. EPA 1988

Density 1.1058 @ 20C ATSDR 1990

Vapor Density (air = 1) 3.9 Keith and
 Walters 1985

KOC 126 U.S. EPA 1988

KOW 692 U.S. EPA 1988

Vapor Pressure 11.7 mm Hg @ 20C U.S. EPA 1988

Reactivity flammable Keith and Walters
1985

Flash Point 29.4C ATSDR 1990

Henry's Law Constant 3.58 x 10-3 atm m3/mol ATSDR 1990

Fish Bioconcentration Factor 45.7 (rainbow
trout); 446.7 (fathead minnow) U.S. EPA 1988

Odor Threshold 0.05 mg/L (water); 1-8 mg/m3 (air) ATSDR
1990

Conversion Factors 1 ppm = 4.7 mg/m3; 1 mg/m3 = 0.22 ppm
ATSDR 1990
___________________________________________________________________________

II. PRODUCTION, USE, AND TRENDS

A. PRODUCTION

 In 1992, the United States production volume of chlorobenzene
was 231 million pounds (USITC 1994). In 1984, the U.S. exported 41
million pounds of chlorobenzene (HSDB 1994). USITC (1994) and
Mannsville (1990) have identified three U.S. producers of
chlorobenzene, listed in Table 2 along with plant locations and
production capacities.

Table 2. U.S. PRODUCERS OF CHLOROBENZENE AND THEIR CAPACITIES

______________________________________________________________________
Producer Plant Location 1990 Capacity
						 (Millions of Pounds)
______________________________________________________________________
Monsanto Company Sauget, IL 176
PPG Industries, Inc. Natrium, WV 44
Standard Chlorine Delaware City, DE 150
Chemical Company of
Delaware, Inc.

TOTAL 370
______________________________________________________________________
Source: Mannsville 1990.

B. USES

 Chlorobenzene is used as a chemical intermediate in the production
of ortho- and para-nitrochlorobenzenes. These chemicals are used as
intermediates in the manufacture of rubber chemicals, agricultural
chemicals, antioxidants, and dyes and pigments (Mannsville 1990).
Chlorobenzene has also been used in the production of phenol; the
insecticide DDT; and aniline (HSDB 1994) (see Table 3 for applicable
SIC Codes). Chlorobenzene is also used as a solvent in the manufacture
of adhesives, paints, polishes, waxes, diisocyanates, pharmaceuticals,
and natural rubber (HSDB 1994; Sax and Lewis 1987; Windholz 1983).
Other applications include use as a fiber swelling agent and dye
carrier in textile processing; as a tar and grease remover in cleaning
and degreasing operations; as a solvent in surface coating and surface
coating removers; and as a heat-transfer medium (HSDB 1994).

Table 3. END USE PATTERN OF CHLOROBENZENE--1989 ESTIMATE
_______________________________________________________________
Derivative Percentage of U.S. Use
(Typical Standard Industrial
Classification(SIC) Code)1
_______________________________________________________________
Nitrochlorobenzenes
(SIC 2865) 40
Solvents
(SICs 2865, 2879) 30
Diphenol Ether and Phenylphenols
(SIC 2865) 15
Sulfone Polymers
(SIC 2865) 5
Miscellaneous
(Various SICs) 10
______________________________________________________________
TOTAL 100

Source: Mannsville 1990.

C. TRENDS

 Over the past two decades, chlorobenzene has lost several of its
U.S. markets, including the manufacture of phenol and aniline due to
other, more efficient processes, and the manufacture of DDT, due to the
ban on its domestic use. Over the next few years, overall demand for
chlorobenzene is expected to remain flat (Mannsille 1990).

III. ENVIRONMENTAL FATE

 A. Environmental Release

 There was no information in the secondary sources searched to
 indicate that chlorobenzene occurs naturally. Chlorobenzene
 enters the atmosphere as fugitive emissions from the
 pesticide industry and from other industries that use it as a
 solvent (Howard 1989). Release of the chemical also occurs
 during the disposal of industrial wastes (Howard 1989).
 Concentrations of chlorobenzene in the atmosphere have
 typically ranged from <0.02 ppb for remote areas to 0.8 ppb
 in cities; the maximum reported value measured was 12 ppb
 (Howard 1989).

 Chlorobenzene was detected in the drinking water of several
 U.S. cities at concentrations of 5.6 ppb (micrograms/L). It
 was reported in ground water in 0.1% of 945 wells tested [at
 two sites, concentrations were 2.7 ppb and 14 ppt
 (nanograms/L)] and in surface water in 9.6% of the
 unspecified "large number" of samples tested (only 0.01% of
 the samples were >1 ppb; the maximum reported concentration
 was >10 ppb) (Howard 1989).

 In 1992, environmental releases of chlorobenzene, as reported
 to the Toxic Release Inventory by certain types of U.S.
 industries, totaled about 2.3 million pounds, including 2.2
 million pounds to the atmosphere, 72 thousand pounds to
 underground injection sites, 21 thousand pounds to surface
 water, and 817 pounds to land, (TRI92 1994).

 B. Transport

 Chlorobenzene is volatile (vapor pressure, 11.7 mm Hg) and
 slightly soluble in water (466.3 mg/L) (ATSDR 1990; U.S. EPA
 1988). Evaporation is an important transport process for the
 chemical from water and soil. Chlorobenzene evaporated from
 an unaerated aqueous solution at the rate of 99% in 72 hours
 (ATSDR 1990). The chemical may also adsorb moderately onto
 organic sediments (KOC of 126) (Howard 1989).

 If released to moist soil, most of the chlorobenzene should
 volatilize to the atmosphere; if released to sandy soil, the
 chemical is mobile and is expected to leach into groundwater;
 it will biodegrade very slowly or not at all (Howard 1989).
 Under experimental conditions, chlorobenzene (1.04 mg/L) was
 added to a 140 cm deep soil column packed with sandy soil
 (Howard 1989). The fate of the chemical in the column was as
 follows: 27% volatilized, 23-33% percolated through the
 column, and 40-50% degraded or was not accounted for. At a
 chlorobenzene concentration of 0.18 mg/L, 54% volatilized,
 26-34% percolated through the soil column, and 12-20%
 degraded or was not accounted for (Howard 1989). The time-span of
 this experiment was not reported.

 C. Transformation/Persistence

 1. Air One source estimated the half-life of
	 chlorobenzene in air to be about 9 days (U.S. EPA 1988);
	 another source estimated the half-life to be 20 to 40
	 hours under simulated atmospheric conditions (ATSDR
	 1990). The predominant removal mechanism for
	 chlorobenzene in the atmosphere is the reaction with
	 photochemically generated hydroxyl radicals (U.S. EPA
	 1988). Chlorobenzene absorbs light in the 290-310 nm
	 region, suggesting photolysis as an additional, but
	 slow, mechanism of degradation, resulting in the
	 production of monochlorobiphenyl (Howard 1989). In the
	 atmosphere, photolysis would occur over the course of a
	 month (Howard 1989).

 2. Water The main fate processes for chlorobenzene in
	 water are vaporization and biodegradation (U.S. EPA
	 1988; Howard 1989). Reported half-lives of
	 chlorobenzene in water are 0.3 days in a river (U.S. EPA
	 1988); about 1 to 12 hours in a rapidly flowing stream
	 (Howard 1989); and 75 days in sediment in an estuarine
	 river under near natural conditions (Howard 1989).
	 Biodegradation will occur in warm weather, particularly
	 with acclimated microorganisms, proceeding more rapidly
	 in fresh water than in estuarine and marine systems
	 (Howard 1989). The biodegradation half-life of
	 chlorobenzene was 150 days in river water and 75 days in
	 sediment (Howard 1989). Direct photolysis is not a
	 significant process for the removal of chlorobenzene
	 from surface water (half-life, ~170 years in summer at
	 40 latitude) (Howard 1989).

 3. Soil Evaporation is expected to be the main removal
	 process for chlorobenzene at the soil surface (U.S. EPA
	 1988). Over the course of one day, chlorobenzene
	 applied to soil at the concentration of 1 kg/ha at
	 depths of 1 cm and 10 cm disappeared at the rate of 86.5
	 and 23.4%, respectively (Howard 1989). Based on these
	 data, the volatilization half-lives were estimated to be
	 0.3 and 12.6 days, respectively (Howard 1989).
	 Chlorobenzene may adsorb to organics in soil and, if
	 retained long enough, may undergo biodegradation.
	 Acclimation of the microorganisms is important in the
	 biodegradation of chlorobenzene (Howard 1989). Twenty
	 percent mineralization in a week was reported in one
	 study; the main products of biodegradation are 2- and
	 4-chlorophenol (Howard 1989).

 4. Biota The bioconcentration factors for chlorobenzene
	 (45.7, rainbow trout; 446.7, fathead minnow) and the
	 chemical's octanol/water partition coefficient (692)
	 (U.S. EPA 1988), suggest a some potential for
	 bioconcentration. Howard (1989) predicts little or no
	 bioconcentration for chlorobenzene.

IV. HEALTH EFFECTS

 A. Pharmacokinetics

 1. Absorption Reports of toxic effects in humans
	 following ingestion or inhalation of chlorobenzene
	 indicate that the chemical is absorbed by these routes
	 (U.S. EPA 1988). In one study, a human volunteer
	 absorbed about 31% of orally administered chlorobenzene
	 (ATSDR 1990). Rats given chlorobenzene orally absorbed
	 18% to 22% of the dose. Absorption of chlorobenzene
	 from the gastrointestinal tract is facilitated by the
	 ingestion of fats and oils (U.S. EPA 1988).

	 Two workers exposed to 0.84 and 0.5 ppm of chlorobenzene
	 by inhalation absorbed 38 and 45%, respectively, of the
	 administered dose (ATSDR 1990). Rats inhaling 14C-labeled
	 chlorobenzene readily absorbed concentrations up
	 to 700 ppm (ATSDR 1990).

	 No information was found regarding the dermal absorption
	 of chlorobenzene. However, a report of "signs of
	 toxicity" in rats following skin application of high
	 doses of chlorobenzene (ACGIH 1991) suggests dermal
	 absorption of the chemical.

 2. Distribution In rats exposed by inhalation to 14C-labeled
	 chlorobenzene in single or multiple 8-hour
	 exposures, the chemical was distributed preferentially
	 to the epididymal and perirenal adipose tissue (ATSDR
	 1990). The amount of the label in fat tissue increased
	 8 to 10 times when the concentration of chlorobenzene
	 was increased from 100 to 400 ppm and 3 to 5 times when
	 the concentration was increased from 400 to 700 ppm. In
	 the remainder of the tissues (which were not
	 identified), the radioactivity increased in proportion
	 to the exposure concentration.

 3. Metabolism Chlorobenzene is oxidized to the
	 intermediate, 4-chlorobenzene-1,2-epoxide (ATSDR 1990).
	 The epoxide undergoes glutathione conjugation,
	 hydrolysis, or transition to form p-chlorophenylmercapturic
	 acid, 4-chlorocatechol, or 4-chlorophenol, respectively.
	 p-Chlorophenylmercapturic acid and 4-chlorocatechol, the main
	 metabolites, were detected in the urine of humans exposed to
	 chlorobenzene orally or by inhalation, and in the urine of rats
	 following oral administration of the chemical (ATSDR 1990).

 4. Excretion The major routes for the excretion of
	 chlorobenzene are in the urine as metabolites (see
	 section IV.A.3) and in expired air, mainly unchanged
	 (ATSDR 1990). For two workers exposed to 0.84 and 0.5
	 ppm of chlorobenzene in air, the excretion of
	 p-chlorophenylmercapturic acid was significantly lower
	 than that of 4-chlorocatechol; however, the ratios of
	 p-chlorophenylmercapturic acid to 4-chlorocatechol were
	 similar for subjects exposed either orally or by
	 inhalation (ATSDR 1990). The respiratory elimination of
	 radiolabel by rats exposed for 8 hours to 14C-chlorobenzene
	 vapor concentrations ranging from 100 to
	 700 ppm indicated a two compartment elimination (ATSDR
	 1990). Rabbits given oral doses of 14C-labeled
	 chlorobenzene excreted 22% of the label in the urine and
	 the remainder in expired air (ATSDR 1990).

B. Acute Effects

 Chlorobenzene can be irritating to the eyes and respiratory
 tract of humans. In animals, the chemical is moderately
 irritating to the eyes and skin. Chlorobenzene has low to
 moderate systemic toxicity in animals, causing death at
 moderate to high oral doses and at high inhalation
 concentrations.

 1. Humans A 70-year-old woman, exposed over a period of 6
	 years (frequency of exposure not specified) to a glue
	 containing 70% chlorobenzene, experienced headaches and
	 irritation of the upper respiratory tract and eyes from
	 the onset of exposure (U.S. EPA 1988).

 2. Animals Oral LD50 values of chlorobenzene are 400 to
	 1600 mg/kg for rats and 2830 mg/kg for rabbits
	 (ACGIH 1991). Inhalation LC50 values for chlorobenzene
	 are 12,000 ppm (30 minutes) in the rat and 8,000 ppm (30
	 minutes) in the cat (Verschueren 1983). Exposure of
	 rats by inhalation to 22,000 ppm killed two of three
	 animals in 2.3 hours; at 9000 ppm two of three animals
	 died within 3 hours (ACGIH 1991). Doses of 10 mL/kg
	 applied to the skin of guinea pigs were nonlethal (ACGIH
	 1991). Rats given single dermal applications of 3600
	 mg/kg of chlorobenzene exhibited unspecified signs of
	 toxicity (ACGIH 1991).

	 Chlorobenzene is a moderate skin irritant in the guinea
	 pig and a moderate eye irritant in the rabbit (ACGIH
	 1991).

 C. Subchronic/Chronic Effects

 EPA has derived a chronic oral reference dose RfD of 0.02
 mg/kg/day for chlorobenzene, based on histopathologic changes
 in the liver of dogs. High doses of chlorobenzene
 administered to animals orally or by inhalation produced
 adverse effects on body weight, liver, kidney, bone marrow,
 and nervous system (see section IV.G.). A single case study
 reported aplastic bone marrow resulting from exposure of a
 worker to chlorobenzene.

 1. Humans A 70-year-old woman, exposed over a period of 6
	 years (frequency of exposure not specified) to a glue
	 containing 70% chlorobenzene developed aplastic bone
	 marrow (U.S. EPA 1988).

 2. Animals EPA has derived a chronic oral RfD for
	 chlorobenzene of 0.02 mg/kg/day, based on
	 histopathologic changes in the liver of dogs treated
	 with the chemical for 13 weeks (U.S. EPA 1994). Male
	 and female beagle dogs received chlorobenzene doses of
	 27.25, 54.5, or 272.5 mg/kg/day in capsules, 5 days/week
	 for 13 weeks. The animals given 54.5 mg/kg/day [the
	 LOAEL (lowest-observed-adverse-effect level)] exhibited
	 liver changes that included slight bile duct
	 proliferation, cytologic alterations, and leukocytic
	 infiltration of the stroma. At the highest dose, the
	 effects were more severe and included death; body weight
	 loss; changes in hematology, clinical chemistry, and
	 urine composition; and pathologic changes in the liver,
	 kidney, gastrointestinal mucosa, and hematopoietic
	 tissue (U.S. EPA 1994). The NOAEL (no-observed-adverse-effect
	 level) for the study was 27.25 mg/kg/day.

	 In other studies, subchronic or chronic administration
	 of chlorobenzene produced the following adverse effects
	 in animals: (1) increased liver and kidney weights in
	 rats given 100 mg/kg/day in a 90-day feeding study
	 (NOAEL, 50 mg/kg/day); (2) liver histopathology in rats
	 given 144 mg/kg/day in a 6-month gavage study (NOAEL,
	 14.4 mg/kg/day); (3) increased liver weights in rats and
	 mice given 125 mg/kg/day in 90-day gavage studies (NOAEL
	 for both species, 60 mg/kg/day); and (4) liver
	 histopathology in rats and mice given 120 mg/kg/day in
	 2-year gavage studies (NOAEL for both species, 60
	 mg/kg/day) (U.S. EPA 1994).

	 Higher oral doses of chlorobenzene, 500 and 750
	 mg/kg/day administered to rats for 13 weeks, caused
	 decreased body weight gain, increased enzyme levels,
	 increased excretion of porphyrins, liver necrosis,
	 nephropathy, and myeloid depletion of bone marrow.
	 Animals given 750 mg/kg/day also exhibited higher
	 mortality and lymphoid depletion in the thymus and
	 spleen (U.S. EPA 1988). Mice given doses of 250 mg/kg
	 for 13 weeks had decreased body weight gain, decreased
	 survival, dose-dependent hepatocellular necrosis,
	 nephropathy, thymic necrosis and lymphoid or myeloid
	 depletion of the thymus, spleen and bone marrow.

	 Inhalation exposure of animals to chlorobenzene produced
	 the following effects: hepatomegaly and
	 histopathological changes (rats, 475 ppm 7 hours/day, 5
	 days/week for 44 days); liver necrosis and regeneration;
	 kidney hyperplasia and pneumonia (0.021 or 0.21 ppm,
	 continuously for 72-80 days); focal lesions in adrenal
	 cortex and kidney tubules, congestion of liver and
	 kidney, decreased SGOT (rats, 75 ppm, 7 hours/day, 5
	 days/week for 120 days) (U.S. EPA 1988). Other studies
	 reported no effects in rats exposed to 425 ppm, 6
	 hours/day, 5 days/week for 87 days and in rabbits and
	 guinea pigs exposed to 200 ppm, 7 hours/day, 5 days/week
	 for 44 days (U.S. EPA 1988). The concentrations of
	 0.021 ppm (the lowest effective concentration with
	 continuous exposure) and 475 ppm (the highest
	 concentration producing no effect with intermittent
	 exposure) convert to doses of 0.06 and 228 mg/kg/day,
	 respectively (U.S. EPA 1988).

 D. Carcinogenicity

 Based on cancer information in humans, equivocal animal data,
 and predominantly negative genetic toxicity information (see
 Section IV.E), the EPA has classified chlorobenzene as a
 Group D; it is not classifiable as to human carcinogenicity
 potential.

 1. Humans No information was found in the secondary
	 sources searched regarding the carcinogenicity of
	 chlorobenzene in humans.

 2. Animals In an NTP bioassay, male and female F344/N
	 rats and female B6C3F1 mice (50/sex/dose) were given
	 chlorobenzene doses of 60 or 120 mg/kg/day by gavage, 5
	 days/week for 103 weeks; male B6C3F1 mice received 30 or
	 60 mg/kg/day (NTP 1985; U.S. EPA 1994). Increased
	 mortality was statistically significant for male rats
	 (P=0.033, high dose), but not for female rats and mice
	 and male mice (NTP 1985; U.S. EPA 1994). A
	 statistically significant positive trend in the
	 incidence of hepatocellular neoplastic nodules was
	 observed in male rats (4/50, 2/50, 4/49, and 8/49 for
	 untreated controls, vehicle controls, low-dose, and high
	 dose groups, respectively). There were no increases in
	 hepatocellular neoplastic nodules for female rats and
	 male and female mice, and there were no increases in
	 hepatocellular or other site-specific tumors for male
	 and female rats and mice. The NTP concluded that "under
	 the conditions of these studies, chlorobenzene
	 administration increased the occurrence of neoplastic
	 nodules of the liver in high-dose male F344/N rats,
	 providing some, but not clear evidence of
	 carcinogenicity of chlorobenzene in male rats.
	 Carcinogenic effects of chlorobenzene were not observed
	 in female F344/N rats or in male or female B6C3F1 mice"
	 (NTP 1985). Based on no human data, inadequate animal
	 data and predominantly negative genetic toxicity data,
	 the EPA has classified chlorobenzene as D, not
	 classifiable as to human carcinogenicity (U.S. EPA
	 1994). Note that this bioassay meets earlier NCI
	 guidelines but not current NTP or TSCA guidelines.

 E. Genotoxicity

 The genotoxicity information for chlorobenzene is mostly
 negative. It is not adequate to support a concern for
 mutagenicity or for carcinogenicity for MCB.

 Results of unscheduled DNA synthesis testing on
 monochlorobenzene have been voluntarily submitted to EPA.
 Rat cells were exposed in vitro to the following percent
 volume to volume concentrations of MCB: 10-1, 10-2, 10-3, 10-4.
 Cytotoxicity was observed at all concentrations.
 Chlorobenzene did not induce DNA repair at any concentration.

 Chlorobenzene was negative for genotoxicity in Salmonella
 typhimurium strains TA98, TA100, TA1535, TA1537 or TA1538
 with or without metabolic activation; did not induce DNA
 damage in Escherichia coli strains WP2 uvr A+ rec A+ or WP100
 uvr A- rec A- or S. typhimurium strains TA1978 uvr B+ or
 TA1538 uvr B- (U.S. EPA 1994). The chemical was also
 negative for the induction of specific locus forward
 mutations in mouse lymphoma L5178Y cells, both with and
 without metabolic activation.

 Chlorobenzene treatment increased the number of revertants in
 Actinomycetes antibioticus-400 and Aspergillus nidulans and
 caused mitotic disturbances in Allium cepa (U.S. EPA 1994).
 The chemical induced reciprocal recombination in
 Saccharomyces cerevasiae strain D3 with metabolic activation
 (U.S. EPA 1994).

 F. Developmental/Reproductive Toxicity

 The chlorinated benzene industry has submitted to EPA results
 of a 2-generation reproductive effects study on MCB. Results
 show that testicular damage occurred in rats exposed by
 inhalation to MCB concentrations as low as 150 ppm. The
 no-observed-effect level in the study was 50 ppm.

 1. Humans No information was found in the secondary
	 sources searched regarding the developmental/reproductive
	 toxicity of chlorobenzene in humans.

 2. Animals Pregnant Fischer 344/N rats and New Zealand
	 rabbits (30-33 animals/group) were exposed by inhalation
	 to 0, 75, 210, or 590 ppm of chlorobenzene for 6
	 hours/day on days 6-15 of gestation (rats) or days 6-18
	 of gestation (rabbits). Maternal toxicity was evident
	 in the rats exposed to 590 ppm. The fetuses of the
	 animals of this group had delayed ossification of the
	 vertebral centra and bilobed thoracic centra, indicative
	 of a slight delay in skeletal development that was
	 possibly related to the maternal toxicity. No other
	 signs of developmental toxicity were observed (John et
	 al., 1984). The rabbits exposed to 210 and 590 ppm also
	 displayed signs of maternal toxicity. External and
	 visceral malformations occurred among the exposed
	 fetuses, but these effects were neither dose-related nor
	 consistent in type. A repeat study using concentrations
	 of chlorobenzene up to 590 ppm did not reveal any
	 significant increase or trend for clustering of
	 malformations in the exposed groups, although there were
	 signs of maternal toxicity at the higher concentrations.

	 EPA issued a final rule under Section 4 of the Toxic
	 Substances Control Act requiring manufacturers and
	 processors of monochlorobenzene to conduct testing for
	 reproductive and fertility effects of MCB in rats
	 exposed by inhalation. The study appears to have been
	 well conducted (U.S. EPA 1986a). Male and female
	 Sprague-Dawley rats (30/sex/group) were exposed to
	 chlorobenzene concentrations of 0, 50, 150, or 450 ppm 6
	 hours/day, 7 days/week for 10 weeks prior to mating, and
	 during mating, gestation, and lactation (females were
	 not exposed during days 1-5 of lactation). Beginning 1
	 week after weaning, both sexes from the F1 generation
	 received the same treatment as the F0 generation. The
	 observed effects included:

	 Increased relative liver weights in F0 and F1
	 rats of both sexes in the mid- and high-concentration groups,
	 and in F1 males exposed to 50 ppm;

	 Decreased survival index for the pups in the
	 high-concentration, F2 litters;

	 Increased incidences of dilated renal pelvis
	 and small flaccid testes in high-concentration
	 F0 and F1 adults; and

	 Increased incidences of hepatocellular
	 hypertrophy, renal degeneration and
	 inflammation, and bilateral degeneration of
	 the germinal epithelium of the testes in male
	 F0 and F1 rats exposed to the mid and high
	 concentrations.

	 The lowest-observed-effect level for adverse
	 reproductive effects of MCB in this study was 150 ppm.
	 The no-observed-effect level in this study was 50 ppm.
	 Results of these studies provide sufficient information
	 to conclude that MCB has potential to produce adverse
	 reproductive effects in human males (U.S. EPA 1986a).

	 In an inhalation study, 2 of 4 dogs exposed to 434 ppm,
	 6 hours/day, 5 days/week for 62 exposures had bilateral
	 atrophy of the germinal epithelium of the seminiferous
	 tubules. This effect was not observed in dogs exposed
	 to 319 ppm (U.S. Air Force 1989).

	 Three of four male dogs given 272.5 mg/kg/day of
	 chlorobenzene orally for 13 weeks exhibited decreased
	 spermatogenesis and tubular atrophy; this dose also
	 caused an unspecified number of deaths or moribundity
	 (U.S. Air Force 1989).

 G. Neurotoxicity

 Chlorobenzene can cause neurotoxic effects in humans in cases
 where exposure occurs either orally or by inhalation.
 Symptoms of acute exposure to large amounts of chlorobenzene
 include unconsciousness and cyanosis. Chronic exposure can
 cause headaches, drowsiness, numbness of the extremities, and
 spastic contractions of the muscles. Animals exhibited
 narcosis and muscle spasms following acute exposure to high
 concentrations, and neuromuscular disorders following
 continuous exposure to low concentrations.

 1. Humans A two-year-old male who swallowed 5 to 10 cc
	 (0.53-1.06 g/kg for a 10 kg child) of a stain remover
	 consisting almost entirely of chlorobenzene became
	 unconscious, did not respond to skin stimuli, had muscle
	 spasms, and was cyanotic; the odor of chlorobenzene was
	 apparent in his urine and exhaled air. The child
	 recovered uneventfully (ATSDR 1990).

	 Factory workers (n=28) reportedly exposed to
	 chlorobenzene via inhalation for 1-2 years (details of
	 exposure not specified) experienced headaches;
	 somnolence; dyspepsia; tingling, numbness, and stiffness
	 of the extremities (8 workers); hyperesthesia of the
	 hands (4 workers); and spastic contractions of the
	 finger muscles (9 workers) or of the gastrocnemius (2
	 workers) (U.S. EPA 1988). In another survey, workers
	 (n=26) exposed to chlorobenzene alone or to a
	 combination of benzene and chlorobenzene for <1 year
	 (study details not provided) showed no signs of
	 neurotoxicity (U.S. EPA 1988).

 2. Animals Rats and mice exposed to chlorobenzene
	 concentrations of 5,850 ppm for 30 minutes by inhalation
	 exhibited central nervous system depression, whereas
	 animals exposed to 2,990 ppm were not sedated (ACGIH
	 1991). Narcosis was observed in animals inhaling 1,200
	 ppm chlorobenzene for 2 hours, but narcosis was not
	 observed in animals inhaling 220-660 ppm (ACGIH 1991).
	 Rabbits exposed by inhalation to 1,090 ppm
	 chlorobenzene for 2 hours exhibited muscle spasms
	 followed by narcosis (ATSDR 1990).

	 Subchronic or chronic inhalation exposure of rats to
	 chlorobenzene produced the following effects:
	 encephalopathy (0.021 or 0.21 ppm, continuously for 72-80 days);
	 inhibition of chronaxia of antagonistic
	 muscles and increased blood cholinesterase (rats, 0.21
	 ppm continuously for 60 days); and chronaximetric
	 inhibition (21 ppm for 49-98 days). Information was
	 identified in a table presented in U.S.EPA 1988. The
	 subject studies were not addressed in the text and no
	 additional information is available. No conclusions
	 were drawn as regards the reversibility of the effects
	 seen or the overall significance of these studies. In
	 addition, due to the absence of corroborating evidence
	 from domestic literature, the information is not
	 considered reliable for use in risk assessment (U.S. EPA
	 1988).

V. ENVIRONMENTAL EFFECTS

 Chlorobenzene is moderately toxic to aquatic organisms with
 toxicity values in the range between >1 mg/L to 100 mg/L.
 Chlorobenzene is not expected to be toxic to aquatic or
 terrestrial animals at levels normally found in the U.S.
 environment.

 A. Toxicity to Aquatic Organisms

 Threshold limit values for chlorobenzene in fish exposed for
 24 to 96 hours are as follows: 29-39 mg/L for the fathead
 minnow (Pimephales promelas); 24 mg/L for the bluegill
 (Lepomis macrochirus); 51-73 mg/L for the goldfish (Carassius
 auratus); and 45 mg/L for the guppy (Poecilia reticulata)
 (Verschueren 1983). The 24-hour LD50 is 1.8 mL/L for the
 rainbow trout and the 14-day LC50 is 19 mg/L for the guppy
 (Verschueren 1983). Toxicity threshold values for the cell
 multiplication inhibition test are as follows: 17 mg/L for
 bacteria (Pseudomonas putida); 120 mg/L for algae
 (Microcystis aeruginosa); and an EC3 >390
 mg/L for green algae (Scenedesmus quadricauda); and >390 mg/L
 for protozoa (Entosiphon sulcatum) (Verschueren 1983). An
 algal 96-h EC50 of 8.9 mg/L is predicted for chlorobenzene
 using the neutral organic quantitative structure activity
 relationship (QSAR) (Clements et al.,1986). In the absence
 of daphnid data, a 48-h EC50 daphnid value of 13.6 mg/L is
 predicted for chlorobenzene using the neutral organic QSAR
 (Clements et al., 1986).

 B. Toxicity to Terrestrial Organisms

 No information was found in the secondary sources searched
 regarding the toxicity of chlorobenzene to terrestrial
 organisms. However, the acute toxicity values for laboratory
 rats [oral LD50, 400 to 1600 mg/kg (ACGIH 1991); inhalation
 LC50, 12,000 ppm for 30 minutes (Verschueren 1983)] indicate
 that the chemical would not be toxic to terrestrial animals
 at levels expected to be present in the U.S. environment.

 C. Abiotic Effects

 No information was found in the secondary sources searched
 regarding the abiotic effects of chlorobenzene.

VI. EPA/OTHER FEDERAL/OTHER GROUP ACTIVITY

 The Clean Air Act Amendments of 1990 list chlorobenzene as a
 hazardous air pollutant. Chlorobenzene has been included in the
 first Toxic Substance Control Act ( TSCA) section 4 proposed test
 rule for hazardous air pollutants for the following tests: acute
 effects, subchronic inhalation toxicity, neurotoxicity, and
 immunotoxicity. Occupational exposure to chlorobenzene is
 regulated by the Occupational Safety and Health Administration
 (OSHA). The OSHA permissible exposure limit (PEL) is 75 parts per
 million of air (ppm) as an 8-hour time-weighted average (TWA) (29
 CFR 1910.000). In addition to OSHA, other federal agencies and
 groups may develop recommendations to assist in controlling
 workplace exposure. These agencies and groups (listed in Tables 4
 and 5) should be contacted regarding workplace exposures and for
 additional information on chlorobenzene.

TABLE 4. EPA OFFICES AND CONTACT NUMBERS INFORMATION ON CHLOROBENZENE

____________________________________________________________________
EPA Office Statute Contact Number
____________________________________________________________________

Pollution Prevention PPAa (202) 260-1023
 & Toxics EPCRA (313/TRI)b (800) 424-9346
			 TSCA (4, 8A, 8D)c (800) 554-1404
Air Clean Air Act (111, (919) 541-0888
			 112B)d
Solid Waste & RCRA (Action levels: (800) 424-9346
 Emergency Response 20 g/m3, air
				0.7 mg/L, water
				2000 mg/kg, soil)e
			 CERCLA (RQ, 100 pounds)f (800) 424-9346

Water Clean Water Act (202) 260-7588
				(304b, 307a, 311)
				WQC (680 g/L [ao/do];
				21,000 g/L [ao])
			 Safe Drinking Water Act (800) 426-4791
				(MCLG: 0.1 mg/L;
				MCL: 0.1 mg/L)g
			 Health Advisories (2 mg/L
				[ch/1d, ch/10d, ch/lt];
				7 mg/L [a/lt]; 0.1 mg/L
				[a/lifetime])h

______________________________________________________________________

aPPA: Pollution Prevention Act
bEPCRA: Emergency Planning and Community Right to Know Act of 1986
cTSCA: Toxic Substances Control Act
dListed as hazardous air pollutant under  112 of Clean Air Act [42
U.S.C. 7401 et seq.]
eRCRA: Resource Conservation and Recovery Act (40 CFR 264.94). Action
Level: Health and environmental-based levels used by the EPA as
indicators for the protection of human health and the environment and
as triggers for a Corrective Measure Study.
fCERCLA: Comprehensive Environmental Response, Compensation, and
Liability Act of 1980, as amended. RQ: level of hazardous substance,
which, if equaled or exceeded in a spill or release, necessitates the
immediate reporting of that release to the National Response Center (40
CFR Part 302).
gMCL (Maximum Contaminant Level): promulgated pursuant to the Safe
Drinking Water Act [40 CFR Part 141 (1994)]. MCLG (Maximum Contaminant
Level Goal): a non-enforceable concentration of a drinking water
contaminant that is protective of adverse human health effects and
allows an adequate margin of safety.
hDrinking Water Health Advisories: estimated for a 10-kg child
consuming 1 L of water per day or a 70-kg adult consuming 2 L of water
per day. (ch/1d) (one-day health advisory for a child): the
concentration of a chemical in drinking water that is not expected to
cause any adverse noncarcinogenic effects for up to 5 consecutive days
of exposure, with a margin of safety. (ch/10d) (for a child): the
concentration of a chemical in drinking water that is not expected to
cause any adverse noncarcinogenic effects up to 14 consecutive days of
exposure, with a margin of safety. (ch/lt) (child, long-term health
advisory): the concentration of a chemical in drinking water that is
not expected to cause any adverse noncarcinogenic effects up to
approximately 7 yr (10% of an individual's lifetime) of exposure, with
a margin of safety. (a/lt): adult, long-term health advisory; may
cover several months to several years. lifetime (lifetime health
advisory): the concentration of a chemical in drinking water that is
not expected to cause any adverse noncarcinogenic effects over a
lifetime of exposure, with a margin of safety.
iWQC: Federal ambient water quality criteria for the protection of
human health (56 FR 58420). Ambient Water Quality Criteria standards:
established pursuant to the Clean Water Act, 57 FR 60848, December 22,
1992. (ao/dw): protection for consuming aquatic organisms and drinking
water; (ao): protection for consuming aquatic organisms.

TABLE 5. OTHER FEDERAL OFFICES/CONTACT NUMBERS FOR INFORMATION ON
CHLOROBENZENE
_____________________________________________________________________
Other Agency/Department/Group Contact Number
_____________________________________________________________________
Agency of Toxic Substances & Disease Registry (404) 639-6000
American Conference of Governmental
Industrial Hygienists (513) 742-2020
 (TLV-TWA, 10 ppm)a
Consumer Product Safety Commission (301) 504-0994
Food & Drug Administration (301) 443-3170
National Institute for Occupational Safety & Health (800) 356-4674
 (TWA, not established; IDLH, 2400 ppm)b
Occupational Safety & Health Administration
 (TWA, 75 ppm)c
 Check local phone book for phone number under Department of Labor
_____________________________________________________________________

aTLV-TWA: Time-weighted-average concentration for a normal 8-hour
workday and a 40-hour workweek to which nearly all workers may be
repeatedly exposed without adverse effects (ACGIH 1993-1994).

bIDLH: Immediately dangerous to life or health (NIOSH 1990; 1992).

cTWA: Time-weighted-average that must not be exceeded during any 8-hour
work shift of a 40-hour workweek. Standard promulgated pursuant
to the Occupational Safety and Health Act, 29 CFR 1910 (OSHA 1993).

VII. CITED REFERENCES

ACGIH. 1991. American Conference of Governmental Industrial
Hygienists. Chlorobenzene. Documentation of Threshold Limit Values
and Biological Exposure Indices, 6th ed. ACGIH, Cincinnati, OH, pp.
271-274.

ACGIH. 1993-1994. American Conference of Governmental Industrial
Hygienists. Threshold Limit Values for Chemical Substances and
Physical Agents and Biological Exposure Indices. ACGIH, Cincinnati,
OH.

ATSDR. 1990. Agency for Toxic Substances and Disease Registry.
Toxicological Profile for Chlorobenzene. ATSDR, Chamblee, GA, 87 pp.
TP-90-06.

Clements, R.G.; Nabholtz, J.V. ECOSAR: A Computer Program for
Estimating the Ecotoxicity of Industrial Chemicals Based on Structure
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748-R-93-002, 1994.

HSDB. 1994. (Hazardous Substances Data Bank).

Howard, P.H., Ed. 1989. Chlorobenzene. In: Handbook of
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John et al., 1984

Keith LH, Walters DB. 1985. Compendium of Safety Data Sheets for
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Mannsville Chemical Products Corporation. Monochlorobenzene. Chemical
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NIOSH. 1990. National Institute for Occupational Safety and Health.
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NIOSH. 1992. National Institute for Occupational Safety and Health.
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NTP. 1985. National Toxicology Program. Toxicology and
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Research Triangle Park, NC.

OSHA. 1993. Occupational Safety and Health Administration. Air
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U.S. EPA. 1993. U.S. Environmental Protection Agency. Summary of
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