820K87110
March 31, 1987
HEXACHLOROBENZENE
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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This Health Advisory (HA) is based on information presented in the Office
of Drinking Water's Health Effects Criteria Document (CD) for hexachlorobenzene
(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 # 86-117777/AS. The toll-free number is (300)
336-4700; in the Washington, D.C. area: (703) 487-4650.
II. GENERAL INFORMATION AND PROPERTIES
CAS No. 118-74-1
Structural formula
Synonyms
HCB, HEXA C.B., Perchlorobenzene
Uses
Hexachlorobenzene is not manufactured as a commercial product in the
United States, but an estimated 2-5 million pounds were produced each
year during the synthesis of several chlorinated chemicals as of 1979
(Mumma and Lawless, 1,975). Hexachlorobenzene also is an ingredient of
a fungicide of which 200,000 pounds were imported each year as of 1979
(IARC, 1979).
Properties (U.S. EPA, 1985a)
Chemical Formula
Molecular Weight
Boiling Point
Melting Point
Density
Vapor Pressure (mm Hg)
Water Solubility
Henry's Law Constant
Odor Threshold
Taste Threshold
Conversion Factor
C6C16
284.79
322.9°C
230°C
1.57 g/mL at 23°C
1 at 144.4°C
1.68 x 10-5 at 25°C
1.089 x 10-5 at 20°C
0.005 mg/L at 25aC
0.12 atm m3 raol-1
Not available
Not available
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Occurrence
Hexachlorobenzene (HCB) is a synthetic organic compound with no
natural sources. HCB is no longer directly produced but occurs as a
byproduct during the manufacture of other chlorinated compounds. HCB
has been used as a fungicide, but this use has been discontinued.
HCB can occur as a contaminant in a number of chemically similar
compounds, which are used as pesticides (U.S. EPA, 1984a).
Because HCB has an extremely low solublity in water, releases to the
environment rapidly partition to soil. HCB is resistant to hydrolysis
and biodegradation and has a reported half life in soil of approxi-
mately 3-6 years. HCB has been demonstrated to bioaccumulate in
fresh water fish (Lu and Metcalf, 1975).
HCB has been included in one Federal Survey of drinking water supplies
HCB was analyzed for in 104 surface water and 12 ground water supplies,
No supply contained HCB above the detection limit of 0.1 ug/L. HCB
has been detected at levels of 0.005 ug/L in two drinking water
supplies in the midwest. HCB has been reported to occur in some
surface water samples at less than ug/L levels (U.S. EPA, 1984a).
HCB has been reported to occur in some foods at the ppb level. Due
to HCB's physical properties, diet is probably the major route of
exposure (U.S. EPA, 1984a).
III. PHARMACOKINETICS
Absorption
Absorption of HCB from the gut has been studied in detail; however,
no information has been found in the available literature on HCB
absorption through the lungs or skin (U.S. EPA, 1985a).
Absorption of HCB from the intestinal tract appears to depend on the
solvent vehicle used during test material administration. When HCB
is administered in olive oil, approximately 80% of the dose is absorbed;
when it is administered in an aqueous suspension, in 1% methyl cellulose,
or in a solid crystalline form, relatively little (<20%) is absorbed
(U.S. EPA, 1985a).
Intestinal absorption of HCB occurs primarily through lymphatic
channels with only a minor portion being absorbed into the portal
circulation (U.S. EPA, 1985a).
Distribution
Following intestinal absorption, HCB, which is lipophilic, distributes
to tissues that are rich in lipid content (U.S. EPA, 1985a). The
adipose tissue accumulates the greatest concentrations of HCB in all
species studied, although bone marrow and skin, which contain large
amounts of lipids, also accumulate HCB. The adrenal cortex accumulates
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HCB at concentrations approaching those of fat. Other tissues (e.g.,
liver, kidneys, lungs, heart, spleen and blood) generally contain
lower amounts of HCB.
0 Intravenous injection of HCB results in a tissue distribution similar
to the following oral administration (U.S. EPA, 1985a).
0 Hexachlorobenzene is transported via the placenta and is distributed
in fetal tissue (U.S. EPA, 1985a).
Metabolism
The metabolism of HCB has been studied in male and female rats following
oral administration, in Rhesus monkeys and beagles following intravenous
injection and in rabbits following intraperitoneal injection (Renner,
1981).
Hexachlorobenzene is metabolized slowly into other lower chlorinated
benzenes, chlorinated phenols and other minor metabolites, and forms
glucuronide and glutathione conjugates (Renner, 1981).
Tissues were found to contain mainly unchanged HCB together with
small amounts of metabolites (Renner, 1981).
Only small amounts of HCB metabolites were detected in feces. Most
of the HCB metabolites were excreted in the urine together with small
amounts of unchanged HCB (U.S. EPA, 1985a).
Excretion
The excretion of HCB from treated animals is slow and occurs mainly
as the parent compound through the feces, with relatively little
being excreted in the urine. It is characterized by an initial rapid
phase followed by a very slow phase. This slow phase of excretion
can be enhanced by the administration of mineral oil, paraffin and
n-hexadecane (U.S. EPA, 1985a).
Both biliary and intestinal excretion contribute to fecal excretion (U.S.
EPA, 1985a).
A three-compartment mammalian model has been reported for the behavior
of HCB in beagles and Rhesus monkeys following intravenous injection
of a single dose. Radioactivity was not detected in exhaled air
following intraperitoneal injection of 14C-HCB. Hexachlorobenzene has
been detected in the milk of nursing mammals (U.S. EPA, 1985a).
IV. HEALTH EFFECTS
Humans
The exposure of humans to seed wheat contaminated with HCB in Turkey
from 1955-1959 caused an epidemic of HCB-induced PCT, also known as
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porphyria turcica, which is manifested by disturbed porphyrin metabolism,
cutaneous lesions and hyperpigmentation. Two investigators (Cam and
Nigogosyan, 1963) estimated that 0.05 to 0.2 g/day were ingested. In
children under 1 year of age, pink sores were observed as well as 95%
mortality (U.S. EPA, 1985a).
0 Follow-up studies conducted with patients 20 to 25 years after the
onset of porphyria showed that a few patients (10%) still had active
porphyria, whereas >50% exhibited hyperpigmentation (78%;) and scarring
(83%) as well as other dermatologic, neurologic and skeletal features
of HCB toxicity. Enlarged thyroids were diagnosed in 60% of the
female patients. Hexachlorobenzene residues also were found in the
blood, fat or breast milk of some patients (U.S. EPA, 1985a).
Animals
Short-term Exposure
0 Information on the acute toxicity of HCB is limited to oral LD^Q
values determined with a few mammalian species. The following 1^50
values were reported in the available literature: rats, 3,500-10,000
mg/kg; rabbits, 2,600 mg/kg; cats, 1,700 mg/kg; and mice, 4,000 mg/kg
(NAS, 1977; IARC, 1979; Sax, 1979).
Long-term Exposure
0 Subchronic oral toxicity studies with a number of mammalian species
indicated statistically significant increases in liver and kidney
(rats only) weights in hexachlorobenzene-treated animals. Some
studies have shown increases in the weights of other organs as well.
Chronic oral toxicity studies revealed similar effects to those seen
in the subchronic studies plus HCB-associated mortality and various
hepatic and renal lesions. These subchronic and chronic effects wera
usually dose-related with effect levels as low as 2 mg/kg/day in
subchronic studies and 0.29 to 0.4 mg/kg/day in chronic studies.
Other effects included multiple alopecia and scabbing, together vith
neurologic effects in rats, mice and dogs (U.S. EPA, 1985a).
0 Dose-related histopathologic changes in the ovaries of monkeys given
8 to 128 mg/kg/day by gavage for 60 days also have been reported
(U.S. EPA, 1985a).
0 The livers of HCB-exposed animals have shown histologic changes such
as irregular shaped and moderately enlarged liver .mitochondria and
increases in the size of the centrilobular hepatocytes (U.S. EPA,
1985a).
0 Increased porphyrin levels in the liver and in urine have been reported
for all species studied except the dog. Hexachlorobenzene was found
to cause the accumulation of p-H-steroids which induce porphyrin bio-
synthesis and to inhibit uroporphyrinogen decarboxylases (U.S. EPA,
1985a) .
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0 The inhibition of uroporphyrinogen. decarboxylases appears to be due
to pentachlorophenol, a HCB metabolite (U.S. EPA, 1985a).
0 Indications are that females are more susceptible to HCB-induced
porphyria than are males, which may be related to higher estrogen
levels and greater HCB metabolism in females (U.S. EPA, 1985a).
0 Hexachlorobenzene was reported to produce a rai'xed-type induction of
cytochromes resembling that produced by a combination of phenobarbital
(P-450) and 3,4-benzpyrene (P-448). In addition, the activities of
several hepatic microsomal enzymes were found to be induced by HCB
(U.S. EPA, 1985a).
Reproductive Effects
0 Hexachlorobenzene has been shown to cross the placenta into fetal
tissues and to be present in the milk of nursing dams (U.S. EPA, 1985a).
0 The NOAEL in a four-generation reproduction study with rats was
reported to be 20 ppm of HCB in the diet (Grant et al., 1977). Pups
from treated dams receiving diets containing 80 ppm HCB recovered
from elevated liver weights when nursed by untested foster dams
(Mendoza et al., 1978).
0 Hepatomegaly and reduced survival were reported in kittens from cats
receiving 263 ppm of HCB in their diets (8.7 mg/day/cat (Hansen
et al., 1979).
0 Three infant Rhesus monkeys nursed by mothers given HCB by gavage at
64 mg/kg/day for 60 days developed clinical signs of toxicity, and
2 infants which died while nursing had severely congested lungs or
bilateral hemorrhagic pneumonia (Bailey et al., 1980).
0 Feeding female minks with dietary HCB at doses as low as 1 ppm during
gestation and lactation resulted in increased mortality of kits (Rush
et al., 1983).
Developmental Effects
0 Fetal mice from dams treated with 100 mg HCB/kg/day by gavage during
days 7 through 16 of gestation exhibited teratogenic responses, e.g.,
cleft palate, and decreased fetal weight. Maternal liver:body weights
were also increased (Courtney et al., 1976).
0 Hexachlorobenzene was not teratogenic in Wistar rats with gavage
doses of 10, 20, 40, 60, 80 or 120 mg HCB/kg/day in corn oil or 0.25%
aqueous gum tragacanth given during gestation days 6-21. Maternal
toxicity (body weight loss, central nervous system effects) and reduced
fetal body weight occurred at the two highest doses (Khera, 1974).
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Hexachlorobenzene March 31, 1987
Mutagenicity
0 Hexachlorobenzene was not found to be mutagenic in 5 strains of
- S. typhimurium, with or without metabolic activation (Lawlor et al.,
1979).
0 Hexachlorobenzene was mutagenic in the yeast, _S_. cerevisiae, at a
minimum concentration of 100 ppm (Guerzoni et al., 1976).
0 Hexachlorobenzene was negative in dominant lethal mutation studies
with rats (Khera, 1974; Simon et al., 1979).
Carcinogenicity
0 In a lifetime study with HCB administration to hamsters, hepatoma was
induced in both males and females (Cabral et al., 1977). The response
at a dose of 4 to 5 mg/kg/day dissolved in corn oil and mixed in the
feed was 47%| for both sexes; controls had no hepatomas. In addition
to hepatomas, hamsters responded to HCB treatment with malignant
liver haemangioendotheliomas and thyroid adenomas. The incidence of
haemangioendotheliomas was 20% in males (versus 0% in controls) at
8 mg/kg/day and 12% in females (versus 0% in controls) at 16 mg/kg/day.
Thyroid adenomas occurred at 14% incidence in males treated with
16 mg/kg HCB (versus 0% in controls).
0 Liver cell tumors, described as hepatomas, also were produced in both
sexes of Swiss mice (Cabral et al., 1979). At 24 mg/kg/day, the
incidence was 34% for females and 16% for males, and the response
showed a dose-dependency not only in the number of tumor-bearing
animals but also in the latent period, and multiplicity and size of
tumors. In ICR mice, HCB administered concurrently with polychlorinated
terphenyl induced hepatocellular carcinomas (Shirai et al., 1973).
0 In rats, the target organs for HCB-induced tumors in various studies
included the liver, kidney, adrenal gland and parathyroid gland.
Liver tumors were found in three studies which included three different
strains of rat: Agus, Wistar and Sprague-Dawley. These tumors were
induced with doses between 1.5 and 8 mg/kg/day. The incidence was as
high as 100% in Agus rats but lower for the other strains. Renal
cell tumors were found in one study on Sprague-Dawley rats. In two
studies with Sprague-Dawley rats, significant increases in adrenal
pheochromocytoma in females were found. In one of these studies the
incidence of parathyroid tumors in males .was increased significantly
as well (Smith and Cabral, 1980; Lambrecht, et al., 1983a, 1983b;
Arnold, 1983, 1984; Arnold et al., 1985).
0 Lambrecht et al. (1983a, 1983b) fed male and female Sprague-Dawley
rats HCB in the diet for up to two years at estimated doses of
4-5 mg/kg/day and 8-9.5 mg/kg/day. By 48 weeks, females had gross
liver tumors. Significant increases in tumor incidence included
hepatoma in both sexes at both doses, hepatocellular carcinomas in
females at both doses, renal cell adenomas in females at both doses,
and adrenal pheochromocytoma in females at both doses. Hepatocellular
carcinoma was slightly higher in males at both doses.
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Hexachlorobenzene March 31, 1987
The data on HCB provide sufficient evidence of the carcinogenicity of
HCB since there were increased incidences of malignant tumors of the
liver in two species (haemangioendothelioma in hamsters and hepato-
cellular carcinoma in rats) as well as reports of hepatoma in mice,
rats and hamsters.
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;
HA = (NOAEL or LOAEL) x (BW) , „ ( /L }
(UF) x ( L/day)
where:
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).
The following Health Advisories, which are based on toxicological effects,
are above the solubility of hexachlorobenzene in water (0.005 mg/L at 25°C).
One-day and Ten-day Health Advisories
Available evidence for the acute toxicity of hexachlorobenzene is con-
sidered to be insufficient for calculation of One-day and Ten-day Health
Advisory (HAs). Therefore, the Longer-term HA (0.05 mg/L) for a 10-kg child
is proposed as a conservative estimate for One-day and Ten-day HAs for the
10-kg child.
Longer-term Health Advisory
In the Kuiper-Goodman et al. (1977) study, groups of 70 male and 70
female Charles River (COBS) rats were fed diets with hexachlorobenzene at
0.5, 2.0, 8.0 or 32.0 mg/kg bw/day dissolved in corn oil for as long as 15
weeks. Female rats were found to be more susceptible to hexachlorobenzene,
as indicated by all parameters studied, and an "apparent" NOAEL of 0.5 mg/kg/
day was concluded by the authors. Increased liver porphyrin levels in females
and increases in the size of centrilobular hepatocytes along with the depletion
of hepatocellular marker enzymes were noted with higher doses.
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Using the NOAEL of 0.5 mg/kg bw/day reported by Kuiper-Goodman et al.
(1977), the Longer-term HA for a 10-kg child is calculated as follows:
Longer-term HA = (0>5 mg/kg/day) (10 kg) = 0.050 rag/L (50 ug/L)
(100) (1 L/day)
where:
0.5 mg/kg/day = NOAEL based on absence of liver effects.
10 kg = assumed body weight of a child.
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 a 70 kg-adult:
Longer-term HA = (0.5 mg/kg/day) (70 kg) = 0.175 m /L (1 75 u /L)
(100) (2 L/day)
where:
0.5 mgAg/day = NOAEL based on absence of liver effects.
70 kg = assumed body weight of an adult.
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.
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%
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Hexachlorobenzene March 31, 1987
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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 derivation of the DWEL is based on a 130-week study by Arnold et al.
(1985). This study involved feeding male and female Sprague-Dawley rats (the
Fg generation) diets containing 0, 0.32, 1.6, 8.0 or 40 ppm of hexachlorobenzene
(analytical grade) for 90 days before mating and until 32 days after parturition
(at weaning).
The number of offspring (F-j generation) from these matings was reduced
to 50 males and 50 females per dose group at 28 days of age and fed their
respective parents' diets. Thus, the FI animals were exposed to hexachloro-
benzene and metabolites in utero, from maternal nursing and from their diets
for the remainder of their lifetime (130 weeks). No hexachlorobenzene-induced
effects were reported in the 0.32 ppm hexachlorobenzene FI group, indicating
this level is a NOAEL. Although a. significant (p<0.05) increase in the inci-
dence of periportal glycogen depletion was found in FI male rats fed 1.6 ppm
hexachlorobenzene, the 1.6 ppm level of hexachlorobenzene also is concluded
to be a NOAEL in that this result was not evident in other treated groups of
male rats. The 8.0 ppm hexachlorobenzene F-] groups were reported to have
an increase (p<0.05) in the incidence of hepatic centrilobular basophilic
chromogenesis. The 40 ppm hexachlorobenzene F-| groups were reported to have
increases (p<0.05) in pup mortality, hepatic centrilobular basophilic chromo-
genesis, peribiliary lymphocytosis and fibrosis, severe chronic nephrosis in
males, adrenal pheochromocytomas in females and parathyroid tumors in males.
It is difficult to estimate lifetime doses on a mg/kg bw basis in this study
because of the initial exposure of the animals to hexachlorobenzene and its
metabolites in utero and during lactation. However, in an attempt to estimate
the lifetime hexachlorobenzene doses on a mg/kg bw basis, the 1.6 mg/kg
hexachlorobenzene dietary level, interpreted from this study as the highest
NOAEL level, was converted to a daily intake dose of 0.08 mg/kg bw/day by
averaging the dosage data provided by Arnold (1984).
Using this NOAEL, the DWEL is derived as follows:
Step 1: Determination of the Reference Dose (RfD)
RfD = (0.08 mg/kg/day) (1,000 ug/mg) = 0.8 ug/kg/day
(100)
where:
0.08 mg/kg/day = NOAEL.
1,000 ug/mg = Conversion of NOAEL in mg to ug.
100 = uncertainty factor, chosen in accordance with NAS/ODW
guidelines for use with a NOAEL from an animal study.
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Step 2: Determination of the Drinking Water Equivalent Level (DWEL)
DWEL = (0.8 ug/kg/day) (70 kg) = 2Q u /L
(2 L/day)
where:
0.8 ug/k9/day = RfD.
70 kg = assumed body weight of an adult.
2 L/day = assumed daily water consumption of an adult.
Hexachlorobenzene may be classified as Group 3: probable human carcinogan.
The estimated excess cancer risk associated with lifetime exposure to drinking
water containing hexachlorobenzene at 28 ug/L is approximately 1 x 10~3.
This estimate represents the upper 95% confidence limit from extrapolations
prepared by EPA's Carcinogen Assessment Group using the linearized, multistage
model. The actual risk is unlikely to exceed this value, but there is considerable
uncertainty as to the accuracy of risks calculated by this methodology.
Evaluation of Carcinogenic Potential
0 Data on hepatocellular carcinomas in female rats after oral ingestion
from the study by Lambrecht et al. (1983) have been used by the U.S.
EPA Carcinogenic Assessment Group to estimate the carcinogenic potency
of hexachlorobenzene and the risks associated with one unit of the
compound in drinking water (U.S. EPA, 1984b). This particular data
set was selected because it is a malignant tumor in the primary target
organ and results in the highest potency estimate. The 95% upper bound
cancer risks associated with 1 ug/L of hexachlorobenzene in drinking
water is estimated to be 4.9 x 10~5. Accordingly, upper bound cancer
risks of 10-6, 1Q-5 and 10~4 would be associated with 0.02, 0.2 and
2 ug/L, respectively, of hexachlorobenzene in drinking water.
0 Maximum likelihood estimates as well as 95% upper limits of cancer
risks by the multistage model have been calculated (U.S. EPA, 1984b,
1985a). For example, at 0.01 mg/kg/day or 0.35 mg/L cancer risk
estimates are 1.4 x 10~2 (MLE) and 1.7 x 1 0~2 (UL) and at 0.1 mg/kg/day
cancer risk estimates are 1.3 x 10~1 (MLE) and 1.7 x 1O'1 (UL).
0 The EPA's Carcinogen Assessment Group has estimated cancer risks vith
other models besides the multistage (U.S. EPA, 1984b, 1985a). As an
example, 0.1 mg/kg/day lifetime exposure was associated with additional
risks (95% upper confidence limit) of 1.7 x 1O'1 by the multistage and
one-hit, 1.3 x 10~1 by the probit, and 2.9 x 10~1 by the Weibull.
While recognized as statistically alternative approaches, the range of
risks described by using any of these modeling approaches has little
biological significance unless data can be used to support the
selection of one model over another. In the interest of consistency
of approach and in providing an upper bound on the potential cancer
risk, the EPA has recommended use of the linearized multistage approach.
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In the absence of evidence of human carcinogenicity, hexachlorobenzene
would be classed in IARC category 2B, meaning that it has been demon-
strated to be carcinogenic in animals and is probably carcinogenic in
humans.
Applying the criteria described in EPA's guidelines for assessment of
carcinogenic risk (U.S. EPA, 1986), hexachlorobenzene may be classified
in Group B2: Probable human carcinogen. This category is for agents for
which there is inadequate evidence from human studies and sufficient
evidence from animal studies.
VI. OTHER CRITERIA, GUIDANCE AND STANDARDS
0 The U.S. EPA (1980) has set ambient water quality criteria for hexa-
chlorobenzene of 7.2, 0.72, and 0.072 ug/L corresponding to cancer
risks of 10-5, 10~6, and 10-7, respectively, assuming 70 kg humans
daily consume 2 L of water and 6.5 g of fish and shellfish.
0 The National Academy of Sciences (1983) estimated a cancer risk of
1.85 x 10~6, with lifetime consumption of 1 L of water containing
1 ug of hexachlorobenzene, based on the carcinogenicity study in mice
by Cabral et al. (1979). In 1980, the NAS also calculated a 7-day
SNARL (suggested-no-adverse-response-level) of 0.03 mg/L.
0 The WHO (1984) guideline value for hexachlorobenzene is 0.01 ug/L.
VII. ANALYTICAL METHODS
0 Determination of hexachlorobenzene is by a liquid-liquid extraction
gas chromatographic procedure (U.S. EPA, 1978; Standard Methods, 1985),
Specifically, the procedure involves the use of 15% methylene chloride
in hexane for sample extraction, followed by drying with anhydrous
sodium sulfate, concentration of the extract and identification by gas
chromatography. Detection and measurement is accomplished by electron
capture, microcoulometric or electrolytic conductivity gas chromato-
graphy. Identification may be corroborated through the use of two
unlike columns or by gas chromatography-mass spectroscopy (GC-MS).
The method sensitivity is 0.001 to 0.010 ug/L for single component
pesticides and 0.050 to 1.0 ug/L for multiple component pesticides
when analyzing a 1-liter sample with the electron capture detector.
VIII. TREATMENT TECHNOLOGIES
Treatment technologies for the removal of hexachlorobenzene (HCB)
from water have not been evaluated extensively. An evaluation of
some of the physical and/or chemical properties of hexachlorobenzene
indicates that carbon adsorption is a candidate for further investi-
gation. Individual or combinations of technologies selected to
attempt hexachlorobenzene removal must be based on a case-by-case
technical evaluation, and an assessment of the economics involved.
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Sased on its Freundlich constants (X = 450; 1/n = 0.6) hexachloro-
benzene is a viable candidate for removal from water by activated
carbon adsorption (U.S. EPA, 1985b). There are, however, limited
available data to substantiate this. Home water treatment units of
the line bypass faucet and pour-through type were tested by Gulf
South Research Institute to determine their effectiveness in removing
hexachlorobenzene from water. Six of ten units tested had initial
efficiencies of 99%; however, by the end of the test the effectiveness
of some units had fallen to as low as 45% (U.S. EPA, 1985b).
Hexachlorobenzene has a Henry's Law Constant of 2.06 atm at 20°C (U.S.
EPA, 1985b). This indicates that air stripping would not be effective
in removing HCB from solution.
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IX. REFERENCES
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