United States
                  Environmental Protection
                  Agency
       Pollution Prevention
       and Toxics
       (7407)
  January 1995
  EPA 749-F-95-007a
&EPA      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 These sources include online databases, unpublished EPA information, government publications, review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.

  Common Synonyms



  Molecular Formula

  Chemical Structure



  Physical State

  Molecular Weight

  Melting Point

  Boiling Point

  Water Solubility

  Density

  Vapor Density (air =1)



  KOC

  KOW

  Vapor Pressure

  Reactivity

  Flash Point

  Henry's Law Constant

  Fish Bioconcentration Factor

  Odor Threshold

  Conversion Factors
108-90-7

monochlorobenzene; benzene chloride
MCB; chlorobenzol; Caswell No. 183A

QftCl
colorless liquid

112.56

-45.6°C

132°C

466.3 mg/L

1.1058@20°C

3.9


126

692

11.7mmHg@20°C

flammable

29.4°C

3.58x m3atm-m3/mol

45.7 (rainbow trout); 446.7 (fathead minnow)

0.05 mg/L (water); 1-8 mg/rri (air)

1 ppm = 4.7 mg/rrf; 1 mg/m3 = 0.22 ppm
ATSDR 1990
ATSDR 1990

ATSDR 1990

ATSDR 1990

ATSDR 1990

U.S. EPA 1988

ATSDR 1990

Keith and
Walters 1985

U.S. EPA 1988

U.S. EPA 1988

U.S. EPA 1988

Keith and Walters 1985

ATSDR 1990

ATSDR 1990

U.S. EPA 1988

ATSDR 1990

ATSDR 1990

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A.
PRODUCTION, USE, AND TRENDS

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

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Table 3. END USE PATTERN OF CHLOROBENZENE-1989 ESTIMATE
Derivative
(Typical Standard Industrial Classification
(SIC) Code)11
Nitrochlorobenzenes
(SIC 2865)
Solvents
(SICs 2865, 2879)
Diphenol Ether and Phenylphenols
(SIC 2865)
Sulfone Polymers
(SIC 2865)
Miscellaneous
(Various SICs)
TOTAL
Percentage of U.S. Use
40
30
15
5
10
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).
           1  The Standard Industrial Classification (SIC) code is the statistical classification
    standard for all Federal economic statistics. The code provides a convenient way to reference
    economic data on industries of interest to the researcher.  SIC codes presented here are not
    intended to be an exhaustive listing; rather, the codes listed should provide an indication of
    where a chemical may be likely to be found in commerce.

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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 2:99% 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.

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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.

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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-l,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 />-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).

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   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
                   2:3600 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 RfD2 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
        2 The RfD is an estimate (with uncertainty spanning perhaps an order of magnitude) of
the daily exposure level for the human population, including sensitive subpopulations, that is
likely to be without an appreciable risk of deleterious effects during the time period of
concern.

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                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 2:250 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 B6C3Fj mice
                (50/sex/dose) were  given chlorobenzene doses of 60 or 120 mg/kg/day by gavage, 5
                days/week for 103 weeks; male B6C3Fj 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 B6C3Fj 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,

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        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 inActinomycetes antibioticus-400 and
        Aspergillus nidulans and caused mitotic disturbances mAllium 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
                F[ generation  received the same treatment as the F0  generation.  The observed effects
                included:

                                Increased relative liver weights in F0 and Fj rats of both sexes in the mid-
                                and high-concentration groups, and in Fj 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 Fj 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 Fj 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

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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).

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        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 2:1,090 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.

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        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 ECS >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.

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TABLE 4.  EPA OFFICES AND CONTACT NUMBERS INFORMATION ON CHLOROBENZENE

EPA Office                                  Statute                            Contact Number
Pollution Prevention & Toxics                PPAa                               (202)260-1023
                                              EPCRA(§313/TRI)b               (800)535-0202
                                              TSCA (§4, §8A, §8D)C             (800)554-1404

Air                                           Clean Air Act (§111, §112B)d      (919)541-0888

Solid Waste &                               RCRA (Action levels:                 (800) 535-0202
  Emergency Response                       20 |jg/m3, air
                                               0.7 mg/L, water
                                               2000 mg/kg, soil)6
                                              CERCLA (RQ, 100 pounds)'           (800) 535-0202

Water                                        Clean Water Act (§304b,           (202) 260-7588
                                              §307a, §311)
                                              WQC  (680 ug/L [ao/do];
                                               21,000 ug/L [ao])
                                              Safe Drinking Water Act           (800) 426-4791
                                               (MCLG: 0.1 mg/L;
                                               MCL0.1  mg/L)9
                                              Health Advisories (2 mg/L
                                               [ch/1d,ch/10d, ch/lt];
                                               7 mg/L [a/It]; 0.1 mg/L
                                               [a/lifetime])11
 "PPA:  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.]
"RCRA:  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.
'CERCLA: 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).
9MCL (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 fora 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) (fora 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 7yr (10% of an individual's lifetime) of exposure, with a margin of safety .(a/It): 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.
WQC: 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.

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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, 10ppm)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).

TWA: 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).

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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 Activity Relationships, U.S.EPA, OPPT (7403), Technical Publication, 748-R-93-
002,1994.

HSDB. 1994. (Hazardous Substances Data Bank).

Howard, P.H., Ed.  1989. Chlorobenzene. In: Handbook of Environmental Fate and Exposure Data, Vol I.
Lewis Publishers, Chelsea, Ml, pp. 138-145.

John etal., 1984

Keith LH, Walters DB. 1985.  Compendium of Safety Data Sheets for Research and Industrial Chemicals, Part
III. VCH Publishers, Inc., pp. 318-319.

Mannsville Chemical  Products Corporation. Monochlorobenzene.  Chemical Products Synopsis, July 1990.

NIOSH. 1990.  National Institute for Occupational Safety and Health. 1990. NIOSH Pocket Guide to Chemical
Hazards. NIOSH, Cincinnati, OH.

NIOSH. 1992.  National Institute for Occupational Safety and Health. 1992. NIOSH Recommendations for
Occupational Safety and Health.  Compendium of Policy Documents and Statements.  NIOSH,  Cincinnati, OH.

NTP.  1985. National Toxicology Program. Toxicology and Carcinogenesis Studies of Chlorobenzene (CAS
No. 108-90-7) in F344/N  Rats and B6C3F., mice (Gavage Studies).  National Toxicology Program, Research
Triangle Park, NC.

OSHA. 1993.  Occupational Safety and Health Administration. Air Contaminants. Final rule. 29 CFR 1910.
Fed. Reg. 58:35338-35351.

Sax, N.I., and R.J. Lewis, Sr. (eds.).  Hawley's Condensed Chemical Dictionary, Eleventh edition. New York:
Van Nostrand Reinhold Company, 1987.

TRI92. 1994.  1992 Toxics Release Inventory. Public Data Release. Office of Pollution Prevention and Toxics
(7408), U.S. Environmental Protection Agency, Washington, D.C., p.88.

TSCATS. 1994. MEDLARS Online Information Retrieval System, National Library of Medicine


U.S. Air Force.  1989. Chlorobenzene. The Installation Restoration Toxicology  Guide, Vol. 2. Wright-Patterson
Air Force Base, OH, pp.24-1 - 24-35.

U.S. EPA.  1986a.  U.S. Environmental Protection Agency. Memorandum, Elaine Francis to Toxic Effects
Branch to Nancy Merrifield, Test Rules Development Branch, Review of Two-Generation Reproduction Study on
Monochlorobenzene. December 29, 1986.

U.S. EPA.  1986b.  U.S. Environmental Protection Agency. Chlorinated Benzenes;  Final Test Rule. 40 CFR
Part 799. Fed.  Reg. 51:24657-24667.

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U.S. EPA. 1988. U.S. Environmental Protection Agency. Updated Health Effects Assessment for
Chlorobenzene. Environmental Criteria and Assessment Office, U.S. EPA,
Cincinnati, OH, 34 pp. ECAO-CIN-H040a.

U.S. EPA. 1993. U.S. Environmental Protection Agency. Summary of Section 4 Activity under TSCA, Vol II,
Syracuse Research Corp.

U.S. EPA. 1994. Integrated Risk Information System (IRIS) Online. Coversheet for Chlorobenzene.  Office of
Health and Environmental Assessment, U.S. EPA, Cincinnati, OH, Retrieved 11/94.

USITC.  (United States International Trade Commission). Synthetic Organic Chemicals: United States
Production and Sales, 1992, 76th edition. USITC Publication 2720, February 1994.

Verschueren K.  1983. Handbook of Environmental Data on Organic Chemicals, 2nd ed. Van Nostrand
Reinhold Co., New York, pp. 357-359.

Windholz,  M. (ed.).  The Merck Index, Tenth edition.  Rahway, N.J.: Merck and Company, Inc., 1983.

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APPENDIX A.  SOURCES SEARCHED FOR  FACT SHEET PREPARATION

ACGIH.  Most recent. American Conference for Governmental Industrial Hygienists, Inc. TLVs®. Documentation of the Threshold Limit Values and Biological Exposure Indices, ...
ed.  ACGIH, Cincinnati, OH.

AQUIRE. 1994. Aquatic Information Retrieval online data base. Chemical Information Systems, Inc., a subsidiary of Fein-Marquart Assoc.

ATSDR. 1989-1994.  Agency for Toxic Substances and Disease Registry.  Toxicological Profiles. Chamblee, GA: ATSDR.

Budavari S, O'Neil MJ, Smith A, Heckelman PE (Eds.).  1989. The Merck Index, 11th ed. Rahway, N.J.: Merck & Co., Inc.

Clayton GD, Clayton FE.  1981-1982.  Patty's Industrial Hygiene and Toxicology, 3rd ed., Vol. 2C. NewYork: John Wiley & Sons.  (Soon to be updated)

Clean Air Act.  1990.  As amended. 42 U.S.C. 7412.

GENETOX. 1994. U.S. EPA GENETOX Program, computerized database.

Howard, P.H., Ed. 1989.  Handbook of Environmental Fate and Exposure Data.  Lewis Publishers, Chelsea, Ml.

HSDB.  1994.  Hazardous Substances Data Bank. MEDLARS Online Information Retrieval System, National Library of Medicine.

Keith LH, Walters DB.  1985. Compendium of Safety Data Sheets for Research and Industrial Chemicals, Part III. VCH Publishers, Inc.

IARC. 1979-1994. International Agency for Research on Cancer.  IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. Lyon: IARC.

IPCS. 19.... International Programme on Chemical Safety. Environmental Health Criteria.  World Health Organization, Geneva, Switzerland.

NIOSH  (National Institute for Occupational Safety and Health). 1992. NIOSH Recommendations for Occupational Safety and Health. Compendium of Policy Documents and
Statements. Cincinnati, OH:  NIOSH.

NTP. 199... National Toxicology Program.  Toxicology and Carcinogenesis Studies. Tech  Rep Ser.

NTP. 199... National Toxicology Program.  Management Status Report. Produced from NTP Chemtrack system. Aprils, 1994.  National Toxicology Program, Research Triangle
Park, NC.

OSHA.  1993.  Occupational Safety and Health Administration. Table Z-2.  Limits for Air Contaminants.

RTECS. 199...  Registry of Toxic Effects of Chemical Substances. MEDLARS Online Information Retrieval System, National Library of Medicine.

TRI92.  1994.  1992 Toxics Release Inventory.  Public Data Release. Office of Pollution Prevention and Toxics (7408), U.S. Environmental Protection Agency, Washington, D.C.

TSCATS. 1994. MEDLARS Online Information Retrieval System, National Library of Medicine.

U.S. Air Force.  1989. The Installation Restoration Toxicology Guide, Vols. 1-5. Wright-Patterson Air Force Base, OH.

U.S. EPA .  1991. U.S. Environmental Protection Agency. Table 302.4 List of Hazardous Substances and Reportable Quantities 40 CFR, part 302.4:3-271.

U.S. EPA.  U.S. Environmental Protection Agency. Appendix A. Examples of Concentrations Meeting Criteria for Action Levels.  40 CFR Part 264.521 (a)(2)(i-iv). Fed. Reg.
55:30865-30867.

U.S. EPA.  Most current.  Drinking Water Regulations and Health Advisories. Office of Drinking Water, U.S.  Environmental Protection Agency, Washington, D.C.

U.S. EPA.  Most Current.  Health Effects Assessment Summary Tables.  Cincinnati, OH:  Environmental Criteria and Assessment Office, U.S.EPA.

U.S. EPA reviews such as Health and Environmental Effects Documents, Health and Environmental Effect Profiles, and Health and Environmental Assessments, HERD Analogue
Profiles, ITC Documents.

U.S. EPA.  1994. Integrated  Risk Information System (IRIS) Online.  Cincinnati, OH: Office of Health and Environmental Assessment.

Verschueren K.  1983. Handbook of Environmental Data on Organic Chemicals, 2nd ed. Van Nostrand Reinhold Co., NewYork.
                                                                          A-1

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