820K87101
                                                               March  31.  1987
                                 CHLOROBEN2ENE

                                Health Advisory
                            Office  of Drinking Water
                      U.S.  Environmental  Protection Agency
I. INTRODUCTION
        The Health Advisory  (HA)  Program,  sponsored by  the Office of Drinking
   Water (ODW),  provides  information on the health effects,  analytical  method-
   ology and treatment technology that  would be useful  in dealing with  the
   contamination of drinking water.   Health Advisories  describe nonregulatory
   concentrations  of drinking water  contaminants at which adverse health effects
   would not be  anticipated  to  occur over  specific exposure  durations.  Health
   Advisories contain a margin  of safety to protect sensitive members of the
   population.

        Health Advisories  serve as informal technical guidance to assist Federal,
   State and local officials responsible for protecting public health when
   emergency spills or contamination situations occur.  They are not to be
   construed as  legally enforceable  Federal standards.  The  HAs are subject to
   change as new information becomes available.

        Health Advisories  are developed for One-day, Ten-day, Longer-term
   (approximately  7 years, or 10% of an individual's lifetime) and Lifetime
   exposures based on data describing noncarcinogenic end points of toxicity.
   Health Advisories do not  quantitatively incorporate  any potential carcinogenic
   risk  from such  exposure.   For  those  substances that  are known or probable
   human carcinogens,  according to the  Agency classification scheme (Group A or
   B), Lifetime  HAs are not  recommended.   The chemical  concentration values for
   Group A or B  carcinogens  are correlated with carcinogenic risk estimates by
   employing a cancer potency (unit  risk)  value together with assumptions for
   lifetime exposure and the consumption of  drinking water.  The cancer unit
   risk  is usually derived from the  linear multistage model  with 95% upper
   confidence limits.   This  provides a  low-dose estimate of  cancer risk to
   humans that is  considered unlikely to pose a carcinogenic risk in excess
   of  the stated values.   Excess  cancer risk estimates  may also be calculated
   using the One-hit,  Weibull,  Logit or Probit models.  There is no current
   understanding of the biological mechanisms involved  in cancer to suggest that
   any one of these models is able to predict risk more accurately than another.
   Because each  model  is based  on differing  assumptions, the estimates that are
   derived can differ  by several  orders of magnitude.

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                                                              March  31, 1987
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         This Health Advisory  (HA)  is  based  on  information presented  in  the Office
    of Drinking Water's  draft  Health Effects Criteria  Document  (CD) for  Chloroben-
    zene (U.S. EPA,  1985a).  The  HA and  CD formats  are similar  for easy  reference.
    Individuals desiring further  information on the toxicological data base or
    rationale for risk characterization  should  consult the CD.  The CD is available
    for review at each EPA Regional Office of Drinking Water  counterpart (e.g.,
    Water Supply Branch  or Drinking Water Branch),  or  for a fee from  the National
    Technical Information Service,  U.S.  Department  of  Commerce, 5285  Port Royal
    Rd., Springfield, VA 22161, PB  #86-117769/AS. The  toll-free number is (800)
    336-4700; in the Washington,  D.C.  area:  (703) 487-4650.
II. GENERAL INFORMATION AND PROPOERTIES
    CAS No.   108-90-7
    Structural Formula
    Synonyms
         0  Monochlorobenzene,  benzene chloride,  chlorobenzol,  phenyl  chloride.
    Uses
            Production of chloronitrobenzene and diphenyl  ether;  rubber inter-
            mediates;  solvent in adhesives,  paints,  waxes,  polishes;  and inert
            solvent.
    Properties;   (Irish,  1963)

            Chemical Formula
            Molecular Weight
            Physical State (room temp.)
            Boiling Point
            Melting Point
            Density
            Vapor Pressure
            Specific Gravity
            Water Solubility
            Oil/Water Coefficient
            Log  Octanol/Water Partition
              Coefficient
            Odor/Taste Threshold (water)

            Odor Threshold (water)
            Odor Threshold (medium unknown)
            Conversion Factor (air)
C6H5C1
112.6
Colorless,
132°C
-45°C
neutral liquid
11.8 mm Hg (at 25°C)
1.106 (at 25°C)
500 mg/L (at 20°C)
918 (Sato and Nakajima, 1979)
2.84 (Leo et al., 1971)

0.41-1.5 ug/L (Tarkhova, 1965)
10-20 ug/L (Varshavskaya, 1968)
50 ug/L (Amoore and Hautala, 1983)
0.21 mg/L (A.D. Little, 1968)
1 ppm = 4.7 mg/m3

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     Chlorobenzene                                                March 31, 1987

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     Occurrence

          0  There are no natural sources of Chlorobenzene.

          0  Chlorobenzene production in 1984 was 256 million Ibs (USITC, 1985).
             The majority of releases result from Chlorobenzene's use as a solvent.
             Due to Chlorobenzene's volatility, most of its environmental releases
             occur to air.  Chlorobenzene is released to water and the ground
             during the disposal of waste solvent.  Because Chlorobenzene is used
             in metal cleaning operations,  releases occur in industrial areas
             nationwide (U.S. EPA,  1987).

          0  Chlorobenzene released to the atmosphere is expected to degrade slowly
             by free radical oxidation.  Chlorobenzene released to surface water
             is expected to partition rapidly to air where it also is expected to
             degrade.  Chlorobenzene has been shown to be relatively resistant to
             biodegradation.  Based on limited studies,  EPA estimates the half-life
             of Chlorobenzene in soil to be several months.  When released to the
             ground,  Chlorobenzene  is expected to bind to soil and to migrate slowly
             to ground water.  Chlorobenzene has been reported to bioaccumulate in
             fish,  aquatic invertebrates and algae.  In higher organisms,  Chloro-
             benzene has been shown to be metabolized to other compounds (U.S. EPA,
             1979).

          0  Chlorobenzene rarely occurs as an environmental contaminant.   Federal
             surveys of drinking waters derived from surface water have not reported
             the presence of Chlorobenzene. (A few groundwater systems have been
             found with Chlorobenzene levels in the low ppb range.  No information
             of the occurrence of Chlorobenzene in food has been identified.
             Chlorobenzene has been identified as a contaminant of air at very low
             levels (less than 1 ppb) in urban and suburban areas.  Even with the
             low levels of Chlorobenzene in air, inhalation is probably the major
             route of environmental exposure (U.S. EPA,  1983).

III. PHARMACOKINETICS

     Absorption

          0   No data are available  which demonstrate the percentage  of the dose
             absorbed following oral exposure.  Based upon what is known about the
             high lipid solubility  of Chlorobenzene along with absorption  charac-
             teristics of benzene and the smaller chlorinated ethanes and  ethylenes
             which  are also highly  lipid soluble, it will be assumed, for  the
             purpose of the development of Health Advisories, that 100% of any
             orally administered dose is absorbed, while 60% of a dose inhaled
             over a period of one to several hours is absorbed and retained
             (Astrand,  1975; Dallas et al.,  1983).

     Distribution

          0   Sullivan et al. (1983) studied the distribution of 14C-Chlorobenzene
             in male Sprague-Dawley rats following single or multiple 8-hour
             inhalation exposures at 100,  400 or 700 ppm (460,  1,880 or 3,290

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     Chlorobenzene                                                March 31,  1987
             mg/m3).  The highest concentrations were found in the fat (epididymal
             and perirenal).  The kidneys and liver also showed significant amounts.
             The amounts found in these tissues were proportional to dose except
             for adipose tissue which showed greatly exaggerated accumulation with
             dose when compared to the other tissues.  The 14c burden of adipose
             tissue increased with increasing exposure concentrations.  In addition,
             there also was a tendency for multiply-exposed rats to exhibit higher
             tissue burdens than rats exposed only once.

     Metabolism

          0  The metabolic transformation of Chlorobenzene has been studied in
             several mammalian species, including the human (Williams et al.,
             1975).  While absolute quantities and ratios differ between species,
             the principal metabolites for each species are p-chlorophenol/
             p-chlorocatechol and p-chlorophenyl-mercapturic acid.

         0   Because of its lipophilicity (log P =2.96), Chlorobenzene tends to
             bioaccumulate in adipose tissue as exposure continues (Sullivan,
             et al., 1983).  Upon termination of exposure, the chemical would
             be expected to be released from the fat stores and become available
             for metabolic activation and potential continuation of induction
             of toxicity.
     Excretion
             The chlorophenol metabolite is excreted as the ethereal sulfate or
             the glucuronide (Spencer and Williams,  1950;  Azouz,  et al,  1953).
             Other excretion products include the chlorophenyl mercapturic acid,
             4-chlorocatechol,  and to a lesser degree in some species, phenol and
             hydroquinone (Williams et al., 1975; Sullivan et al., 1983).

             When the metabolic pathways for Chlorobenzene biotransformation
             become saturated,  increasing amounts of the chemical are exhaled
             unchanged (Sullivan et al., 1983).  In  rats exposed  to 100  ppm
             (470 mg/m3)  (a dose which did not saturate metabolic pathways) in  air
             for 8 hours, 5% was excreted via inhalation and 95%  in the  urine.
             Repeated dosing (8 hr/day for 4 or 5 days) at 700 ppm (a dose that
             does saturate metabolic pathways) results in 32% being exhaled and
             68% excreted in the urine.
IV.  HEALTH EFFECTS
     Humans
             The only information available on the effects of  Chlorobenzene in the
             human comes  from case reports  of poisonings  or occupational exposures.
             No data on actual exposure concentrations  are presented in any of
             these reports.

             Inhalation exposure to Chlorobenzene  has been observed to result in
             signs of central nervous  depression (sedation and narcosis) as well

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Chlorobenzene                                                   March 31,  1987

                                       -5-
            as irritation of the eye and respiratory tract (Rozenbaum et al.,
            1947; Girard et al., 1969; Smirnova and Granik,  1970).

            Rozenbaum et al. (1947)  also noted thrombocytopenia and leukopenia
            in some of the workers described in their study.  The question arises
            as to whether this effect was induced by the chlorobenzene or some
            contaminant.

            Cardiac effects such as  chest pain,  bradycardia  and ECG irregularities
            and toxemia of pregnancy have been noted in individuals exposed to
            chemicals used in the production of chlorobenzene (Ounaeveskii,  1972;
            Petrova and Vishnevskii, 1972).  Chlorobenzene cannot be identified
            as the causative agent since these workers were  exposed to mixtures
            of substances over varying periods of time.
    Animals
    Short-term Exposure
            Reported oral LD$Q'S  in adult animals  range from 2.8 to 3.4
            (Irish,  1963; Vecerek et al.,  1976).   Reported inhalation
            range from 0.05 (guinea pig)  to 20 mg/1  (mouse-2 hour exposure)
            {Rozenbaum et al.,  1947; Lecca-Radu,  1959).

            In rats, single subcutaneous  doses greater than 5 g/kg produced  hyper-
            excitability and muscle spasms,  followed by CNS depression and death
            (Rozenbaum,  et al,  1947; von  Oettingen,  1955).

            Chlorobenzene causes  necrosis of the  liver and interferes with
            porphyrin metabolism  (Rimington and Ziegler,  1963;  Khanin,  1969;
            Knapp et al., 1971).   Oral doses of 1140 mg/kg/day  administered  to
            rats  for 5 days resulted in increases  in urinary excretion of copro-
            porphyrin III,  uroporphyrin and porphobilinogen (Rimington and Ziegler,
            1963).  Delta-aminolevulinic  acid levels also were  increased as  were
            liver protoporphyrin  and uroporphyrin.

            Kidneys  of rabbits  receiving  2 to 20 doses of chlorobenzene at 0.9 mg/kg
            by injection over a two-week  period showed swelling of the tubular and
            glomerular epithelia  (Rozenbaum et al.,  1947).

            Chlorobenzene has been shown  to produce  alterations in bile duct-
            pancreatic flow (a  phenomenon of unexplained significance)(Yang  et al.,
            1979), and blood dyscrasias such as leukopenia and  lymphocytosis
            (Cameron et al. 1937;  Rozenbaum et al.,  1947;  Zub,  1979).  As noted
            for the  human,  there  is a question as  to whether these hematopoietic
            effects  resulted from chlorobenzene or a contaminant.

            Administration  of chlorobenzene  in corn  oil by gavage  for 14 consecutive
            days  to  male and female F344/N rats and  B6C3F1  mice was ineffective
            in rats  and  mice at doses of  500 mgAg/day.  Rats were also given
            1,000 and 2,000 mg/kg/day doses,  which were fatal.   Survival, body
            weights  and  necropsies data were obtained.  Histopathology was not
            performed.

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Chlorobenzene                                                March 31, 1987

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Long-term Exposure

     0  Adolescent dogs (6/sex/group) were exposed to Chlorobenzene vapors
        at target levels of 0, 0.78, 1.57 or 2.08 mg/1 air for 6 hr/day,  5
        days/week for 6 months (Monsanto, 1980).  Significant changes included
        a decrease in absolute adrenal weights in males at the mid- and high-
        dose levels, an increase in liver: body weight ratio in females at the
        mid- and high -doses, a sex-independent, dose-related increased inci-
        dence in emesis and an increase in the frequency of abnormal stools
        in treated females.  The NOAEL is 0.78 mg/L.

     0  Oral administration of Chlorobenzene by capsule at doses of 0, 27.25,
        54.5 or 272.5 mg/kg/day to male and female beagle dogs daily, 5 days/
        week, until sacrifice at 93 days resulted in observable effects
        (mortality, lesions, various toxic effects) only at the high dose
        (Knapp et al.,  1971; Hazelton,  1967a).  The NOAEL is 54.5 mg/kg/day.

     0  Oral dosing of  rats at levels of 14.4, 144 or 288 mg/kg/day, 5 days/
        week for 6 months yielded significant increases in liver and kidney
        weights and histopathological changes in the livers of mid- and
        high-dose animals (Irish, 1963).  No changes were observed at the
        low dose.  The NOAEL is 14.4 mg/kg/day.

     0  Male and female rats were fed Chlorobenzene in their diets at levels
        equal to 12.5,  50, 100 or 150 mg/kg/day for 90 to 99 days (Knapp, et
        al., 1971; Hazelton, 1967b).  Males showed retarded growth at the
        highest dose.  At the mid- and high dose levels, significant increases
        in liver and kidney weights were noted.  The two lowest dose produced
        no adverse effects.  The NOAEL is 50 mg/kg/day.

     0  In subchronic (90 or 91 day) studies in which both sexes of rats  and
        mice received Chlorobenzene in corn oil by gavage five times weekly
        with 0, 60, 125, 250, 500 or 750 mg/kg/day (NTP, 1985; Battelle,
        1978a,b).  Rats and mice showed depressed body weight gain at the
        highest three doses.  In rats,  polyuria and porphyria were noted  at
        the two highest doses.  Histopathology was noted in the liver, kidney
        and lymphoid tissue in both species at the three highest doses.
        Liver and liver/body weights were increased in male mice and female
        rats at doses above 60 mg/kg.  The NOAEL is 60 mg/kg/day.

     0  The only chronic exposure study available on Chlorobenzene is the NTP
        gavage bioassay in rats and mice (NTP, 1985).  On five days/week, both
        sexes of rats and female mice received 60 or 120 mg chlorobenzene/kg
        day in corn oil; male mice received 30 or 60 mg/kg/day.  Significant
        changes included equivocal mild to minimal liver necrosis in the  rats
        and a decrease  in the survival rate for low dose male mice,  but not
        high dose male  mice.  The NOAEL is 60
Reproductive Effects

     8  There are no available data on reproductive effects of Chlorobenzene.

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Chlorobenzene                                                  March 31, 1987

                                     -7-


Developmental Effects

     0  John et al. (1984) and Hayes et al. (1982) have reported the results
        of a two-phase teratology study in which pregnant rats and rabbits
        were exposed via inhalation to 0, 75,  210 or 590 ppm Chlorobenzene,
        6 hr/day, during the period of major organogenesis (days 6 through
        15 for rats;days 6 through 18 for rabbits).  In the rats, maternal
        toxicity (decreased body weight gain)  was observed at the highest
        dose.  No teratological changes were observed in fetuses from rats
        exposed at any dose.  Rabbits showed maternal toxicity (statistically
        significant increase in relative and absolute liver weights) at the
        mid and high doses.  Again, no structural malformations were noted
        in the fetuses.  However, since the control group exhibited malforma-
        tions at levels higher than historically noted, the rabbit study was
        repeated, using doses of 0, 10, 30, 75 or 590 ppm.  In this study, no
        significant changes in rates and types of malformations were observed.

Mutagenicity

     0  Chlorobenzene has been shown to cause  mitotic disturbances in Allium
        cepa (Ostergen and Levan, 1943) and reverse mutations in Streptococcus
        antibioticus (Koshkinova, 1968) and Aspergillus nidulans (Prasad and
        Pramer, 1968;Prasad, 1970).

     0  Chlorobenzene was not mutagenic in the Ames Salmonella assay or in
        E. coli, either with or without metabolic activation (Monsanto, 1976a;
        Dup"on€, 1977,-Merck, 1978; Simmon et al., 1979).

     0  Chlorobenzene did not induce specific  locus forward mutations in mouse
        lymphoma L5178Y cells,  either with or  without activation (Monsanto,
        1976b).

     0  Chlorobenzene did induce reciprocal recombination in the yeast
        Saccharomyces cerevisiae strain D3 in  the presence of the metabolic
        activation system (Simmon et al. 1979).

Carcinogenicity

     0  Chlorobenzene has been tested for carcinogenic potential in rats and
        mice in the NTP Bioassay Program (NTP, 1985).  The report of these
        studies states that the chemical produced a statistically significant
        increase in the incidence of neoplastic nodules of the liver in high
        dose (120 mgAg/day) male rats.  Incidences of neoplastic nodules in
        male rats were 2/50 in untreated controls, 2/50 in vehicle controls,
        4/49 in low dose and 8/49 in high dose.  However,  there were also
        hepatocellular carcinomas in two vehicle control male rats, and
        combining these with the neoplastic nodule data results in an increase
        in high dose males of borderline significance (P = 0.048) by one
        statistical test (life table) of the three used (also incidental tumor
        test and Fischer's exact test) by the  NTP.  No increased incidence
        was observed in numbers of hepatocellular carcinomas in male rats or
        of neoplastic nodules or hepatocellular carcinomas in female rats or
        mice of either sex.

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    Chlorobenzene                                                 March 31,  1987

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V.  QUANTIFICATION OF TOXICOLOGICAL EFFECTS

         Health Advisories (HAs) are generally determined for One-day, Ten-day,
    Longer-term (approximately 7 years) and Lifetime exposures if adequate data
    are available that identify a sensitive noncarcinogenic end point of toxicity.
    The HAs for noncarcinogenic toxicants are derived using the following formula:
    where:
                  HA = (NOAEL or LOAEL) x (BW) = _ m/L ( _ ug/L)
                         (UF) x ( _ L/day)
            NOAEL or LOAEL = No- or Lowest-Observed-Adverse-Effect-Level
                             in mg/kg bw/day.

                        BW = assumed body weight of a child (10 kg) or
                             an adult (70 kg).

                        UF = uncertainty factor (10, 100 or 1,000), in
                             accordance with NAS/ODW guidelines.

                 _ L/day = assumed daily water consumption of a child
                             (1 L/day) or an adult (2 L/day).

    One-day and Ten-day Health Advisories

         No satisfactory data are available from which to calculate One-day and
    Ten-day HAs for the 10 kg child.  The 14-day studies in rats and mice by the
    NTP (1985) are not selected because of inadequate assessment of toxicity in
    these studies.  It is recommended that, for this duration of exposure, the
    Longer-term HA for a 10-kg child be applied.  Therefore, the One-day and
    Ten-day Health Advisories are 4.3 mgA (4,300 ugAK

    Longer-term Health Advisory

         Subchronic studies were conducted in which both rats and mice were dosed
    by gavage five times weekly with chlorobenzene at 0, 60, 125, 250, 500 or 750
    mg/kg in corn oil (10 animals/species/sex/dose level) (NTP, 1985; Battelle,
    1978a,b).  Deaths were found with the three highest doses in mice and the two
    highest doses in rats.  Food consumption did not vary among the groups in
    mice, but it was lower in the two highest dose rat groups.  Body weight gain
    was affected in both species, with significant changes observed in mice and
    rats at the three highest doses.  No clinically significant chlorobenzene-
    related changes were observed in any of the hematological parameters measured
    in either species.  None of the clinical chemistry parameters measured in mice
    were changed.  However, in the rats, alkaline phosphatase and GGPT levels
    were slightly elevated at 500 and 750 mg/kg.  Urinalyses of the controls and
    two highest dose groups revealed a dose-dependent polyuria with concomitant
    decreases in specific gravity and creatinine concentration.  At the two highest
    doses, urinary coproporphyrin excretion was increased in rats.  In mice, this
    increase was observed only in females at 250 and 500 mgAg-  Liver and liver:
    body weights were increased significantly in female mice at 250 and 500 mgAg
    and in male mice at 125 and 250 mgAg.  Both male and female rats at 250 and

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Chlorobenzene                                                  March 31,  1987

                                     -9-
500 mgAg and females at 125 mg/kg showed these increases.  Absolute and
organ/body weights for spleen were decreased in all treated groups of male
rats but with no clear dose response.  Mice and rats at the three highest
doses (250, 500 and 750 mgAg) all exhibited significant histopathological
changes including hepatic necrosis, nephrosis,  myeloid depletion, lymphoid
depletion and lymphoid necrosis.  The 60 mgAg/day NOAEL with 5 days/week
treatment of rats and mice in the NTP (1985) study is equivalent to the 54.5
mgAg/day, 5 days/week NOAEL in dogs and the 50 mg/kg/day, 7 days/week NOAEL
in the Hazelton (1967a,b) studies.

     From the NTP (1985) data, a NOAEL of 60 mgAg/day was identified.

     A Longer-term Health Advisory is calculated as follows:

     For the 10-kg child:
     Longer-term HA = (60 mgAg/day) (10 kg) (5) = 4>3   /L {4f300   /L)
        y                  (100) (1 L/day)   (7)
where:
        60 mgAg/day = NOAEL, based Upon absence of various effects at
                       higher doses in rats and mice.

               10 kg = assumed body weight of a child.

                 5/7 = conversion of 5 day/week exposure to 7 day/week
                       exposure.

                 100 = uncertainty factor, chosen in accordance with NAS/ODW
                       guidelines for use with a NOAEL from an animal study.

             1 L/day = assumed daily water consumption of a child.

     For the 70-kg adult:

    Longer-term HA = (60 mg/kg/day) (70 kg) (5) = 15.0 mg/L (15,000 ug/L)
                         (100) (2 L/day)     (7)
where:
        60 mgAg/day = NOAEL, based upon absence of various effects at
                       higher doses in rats and mice.

               70 kg = assumed body weight of an adult.

                 5/7 = conversion of 5 day/week exposure to 7 day/week
                       exposure.

                 100 = uncertainty factor, chosen in accordance with NAS/ODW
                       guidelines for use with a NOAEL from an animal study.

             2 L/day = assumed daily water consumption of an adult.

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Chlorobenzene                                                   March 31, 1987

                                     -10-


Lifetime Health Advisory

     The Lifetime HA represents that portion of an individual's total exposure
that is attributed to drinking water and is considered protective of noncar-
cinogenic adverse health effects over a lifetime exposure.  The Lifetime HA
is derived in a three step process.  Step 1 determines the Reference Dose
(RfD), formerly called the Acceptable Daily Intake (ADI).  The RfD is an esti-
mate of a daily exposure to the human population that is likely to be without
appreciable risk of deleterious effects over a lifetime, and is derived from
the NOAEL (or LOAEL), identified from a chronic (or subchronic) study, divided
by an uncertainty factor(s).  From the RfD, a Drinking Water Equivalent Level
(DWEL) can be determined (Step 2).  A DWEL is a medium-specific (i.e., drinking
water) lifetime exposure level, assuming 100% exposure from that medium, at
which adverse, noncarcinogenic health effects would not be expected to occur.
The DWEL is derived from the multiplication of the RfD by the assumed body
weight of an adult and divided by the assumed daily water consumption of an
adult.  The Lifetime HA is determined in Step 3 by factoring in other sources
of exposure, the relative source contribution (RSC).  The RSC from drinking
water is based on actual exposure data or,  if data are not available, a
value of 20% is assumed for synthetic organic chemicals and a value of 10%
is assumed for inorganic chemicals.  If the contaminant is classified as a
Group A or B carcinogen, according to the Agency's classification scheme of
carcinogenic potential (U.S. EPA, 1986), then caution should be exercised in
assessing the risks associated with lifetime exposure to this chemical.

     The data base used for the derivation of the Longer-term Health Advisories
also is selected for deriving the Lifetime Health Advisory in that more toxico-
logic endpoints and species were assessed in the subchronic studies compared
to the NTP (1985) carcinogenicity bioassay.

     The Lifetime Health Advisory is calculated as follows:

Step 1:  Determination of the Reference Dose (RfD)

                  RfD = (60 mg/kg/day)(5) = 0<043   /kg/day
                            1,000)    (7)

where:

        60 mg/kg/day = NOAEL based upon absence of various effects at higher
                       doses.

                 5/7 - conversion of 5 day/week exposure to 7 day/week exposure.

               1,000 = uncertainty factor,  chosen in accordance with NAS/ODW
                       guidelines for use with a NOAEL from an animal study
                       of less-than-lifetime duration.

Step 2:  Determination of the Drinking Water Equivalent Level (DWEL)

          DWEL = ..(0.043 mg/kg/day) (70 kg)  = K51  mg/L (1/510   /L)
                         (2 L/day)

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    Chlorobenzene                                                   March 31,  1987

                                         -11-


    where:

            0.043 mg/kg/day = RfD.

                      70 kg = assumed body weight of an adult.

                    2 L/day = assumed daily water consumption of an adult.

    Step 3:   Determination of the Lifetime Health Advisory

                  Lifetime HA = 1.5 mg/L x 20% = 0.3 mg/L (300 ug/L)

         It  is important to note that the taste and odor threshold in water  has
    been identified at levels ranging from 0.41 to 1.5 ug/L (Tarkhova,  1965) to
    10 to 20 ug/L (Varshavskaya, 1967).   All of the Health Advisories derived  in
    this document have been developed on the basis of toxicity, not on the aesthetic
    characteristics of the water quality.  Any guidance developed on a site-specific
    basis may, however, require one to consider the aesthetic, in addition to  the
    toxic, consequences following exposure to chlorobenzene in the drinking  water.

    Evaluation of Carcinogenic Potential

         0  The EPA Carcinogenic Assessment Group (CAG) did not derive  a  carcino-
            genic potency factor or range of risk estimates for chlorobenzene
            (U.S. EPA, 1985b).

         0  EPA has classified chlorobenzene as to its carcinogenic potential,
            using the weight of evidence classification scheme in its risk assess-
            ment guidelines for carcinogens (U.S. EPA,  1986). The Agency  has
            placed the chemical in Group D:  Inadequate evidence.  EPA's  Carcinogen
            Assessment Group has not derived a carcinogenicity potency  factor
            (qi*) or a range of excess lifetime cancer risk estimates.


VI. OTHER CRITERIA, GUIDANCE AND STANDARDS

        "°  EPA (1980) proposed ambient water quality criteria for chlorobenzene,
            one based upon available toxicity data (488 ug/L) and one based  upon
            organoleptic effects (20 ug/L).  These criteria were derived  for the
            70 kg adult, assumed to drink 2 liters of water per day and eat
            6.5 g of contaminated  fish and seafood per day.  The toxicity-based
            criteria were calculated using the 14.4 mg/kg/day NOAEL from  the
            study by Irish et al.  (1963) and an uncertainty factor of 1,000.

         0  ACGIH (1982) has adopted a TLV of 75 ppm (350 mg/m3) for chloro-
            benzene in the workplace.

         0  On the basis of a 1983 draft of the NTP report (NTP,  1985), the
            National Academy of Sciences performed a quantitative risk  assessment
            to estimate excess lifetime  cancer risk (NAS,  1983).  The upper  95%
            confidence limit estimate of that risk was  2.13 x 10-7 per  ug/L  of
            drinking water.  This  corresponds to a drinking water concentration
            of 2.35 ug/L being equivalent to a 1  in a million excess risk.

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      Chlorobenzene                                                  March 31,  1987

                                           -12-
              Assumptions were defined for a 70-kg adult,  drinking 2 liters  of
              water per day.

           0  WHO (1984) recommended a guideline for chlorobenzene of 3 ug/L
              based upon avoidance of taste and odor problems.

           0  The U.S. EPA Office of Drinking Water proposed an RMCL of 0.06 mg/L
              (U.S. EPA, 1985c).


VII.  ANALYTICAL METHODS

           0  Analysis of chlorobenzene is by the purge-and-trap gas chromatographic
              procedure used for the determination of volatile organohalides in
              drinking water (U.S. EPA, 1984a).  This method calls for the bubblir/g
              of an inert gas through the sample and trapping chlorobenzene  on  an
              adsorbant material.  The adsorbant material  is heated to drive off
              the chlorobenzene onto a gas chromatographic column.  This method is
              applicable to the measurement of chlorobenzene over a concentration
              range of 0.05 to 1500 ug/L.  Confirmatory analysis for chlorobenzene
              is by mass spectrometry (U.S. EPA, 1985d).  The detection limit for
              confirmation by mass spectometry is 0.3 ug/L.


VIII. TREATMENT TECHNOLOGIES

           0  Treatment techniques which are effective in  removing chlorobenzene
              from drinking water include adsorption on granular activated carbon
              (GAC) or powdered activated carbon (PAC). Aeration, reverse osmosis
              and boiling also are capable of removing chlorobenzene.

           0  Dobbs and Cohen (1980)  developed adsorption  isotherms for a number
              of organic chemicals,  including chlorobenzene.  They found that
              Filtrasorb * 300 carbon had a capacity of 91  mg of chlorobenzene
              per gram of carbon at an equilibrium concentration of 1.0 mg/L and
              9.3 mg/g at a concentration of 100 ug/L.

           0  PAC gave inconsistent removal rates when it  was added to well  water
              containing several contaminants including chlorobenzene (U.S.  EPA,
              1985b).

           0  Conventional coagulation filtration treatment does not appear  to  be
              effective in chlorobenzene removal.  Limited data collected at Water
              Factory  21  indicated that there was an 18.2% removal of chlorobenzene
              when only filtration was used (U.S. EPA, 1985b).  Another study of
              conventional treatment practices found them  to be completely ineffectiv
              in chlorobenzene removal (Love et al., 1983).

           0  The Henry's Law Constant for chlorobenzene is 145 atm at 20°C  (U.S.
              EPA,  1985b).  This indicates that the chemical might be amenable  to
              removal  by aeration.  In a bench-scale study, a diffused air aerator
              reduced  the chlorobenzene in a 97 ug/L solution by 90% using a 15:1
              air-to-water ratio (Love et al., 1983).

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                                     -13-
        Air stripping is an effective,  simple and relatively inexpensive
        process for removing chlorobenzene and other volatile organics from
        water.  However, the use of this process then transfers the contaminant
        directly into the air stream.  When considering use of air stripping
        as a treatment process,  it is suggested that careful consideration be
        given to the overall environmental occurrence,  fate, route of exposure
        and various hazards associated with the chemical.

        Degradation with ozone is ineffective as a method for removing
        chlorobenzene (U.S. EPA,  1985d).

        Reverse osmosis appears  to have the potential for use in chlorobenzene
        removal.  A laboratory study reviewed by EPA reported successful
        decontamination with 97  to 100% of the chlorobenzene removed.

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    Chlorobenzene                                                 March  31,  1987

                                         -14-


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                                     -16-
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                                     -17-
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