March 31, 1967
HEPTACHLOR AND HEPTACHLOR EPOXIDE
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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Heptachlor and Heptachlor Epoxide
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March 31, 1987
This Health Advisory (HA) is based on information presented in the Office
of Drinking Water's Health Effects Criteria Document (CD) for Heptachlor,
Heptachlor Epoxide and Chlordane (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 #
86-117991 /AS. 13ie toll free number is (800) 336-4700; in the Washington, D.C.
areat (703) 487-4650.
II. GENERAL INFORMATION AND PROPERTIES
CAS No. 76-44-8
Structural Formula
a
A. Heptachlor
Synonyms
3-Chlorochlordenef 3,4,5,6,7,8,8a-heptachlorodicyclopentadiene;
1,4,5,6,7,8,8-heptachloro-3a,4,1,7a-tetrahydro-4,7-endomethanoindene
Use
Insecticide
Properties
Chemical Formula
Molecular Weight
Physical State (room temp.)
Boiling Point
Melting Point
Density
Vapor Pressure
Water Solubility
Log Octanol/Water Partition
C10H5Cl7
373.32
white, crystalline solid
135-1 45*C (at 1-1.5 mm Hg)
93*C
3 x 10~* mm Hg (at 25°C)
0.056 mg/L (at 25°C)
3.87
Coefficient
T&ste Threshold
Odor Threshold
Conversion Factor

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Heptaehlor and Heptachlor Epoxide
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March 31, 1987
B. Heptachlor Epoxide
CAS No. 1024-57-3
Structural Formula
Synonyms
° 1,4,5,6,7,8,8,
Use
0 Insecticide
Properties
Chemical Formula
Molecular Weight
Physical State (room temp.)
Boiling Point
Melting Point
Density
Vapor Pressure
Water Solubility
Log Octanol/Water Partition
Coefficient
Taste Threshold
Odor Threshold
Conversion Factor
Occurrence
° Heptachlor is an insecticide which in the past has been used on corn,
alfalfa, hay and vegetables, and as a termiticide. During the mid-
708, use of heptachlor on food crops was phased out due to the per-
sistence of the chemical and its epoxide. Currently, heptachlor is
used only as a termiticide and on a very limited number of crops.
° Heptachlor is considered to be a moderately persistent compound, with
a half life in soil of 6 months. However, heptachlor is biotransformed
to an epoxide which is very resistant to further biological or chemical
change. The half lives of heptachlor epoxide in various soils have
been reported to be as long as several years. Heptachlor and its
epoxide bind to aoil and migrate slowly.
° Heptachior has been analyzed for in a number of national and regional
surveys of drinking water supplies. However, heptachlor has not been
detected in any of the surveys. Heptachlor and its epoxide have been
detected in private drinking water wells at levels of less than 0.02
ug/L. Heptachlor has been found at similar levels in a few surface
water samples (not drinking water).
CI
CC1
CI
CI
-Heptachloro-2,3-epoxy-3a,4,7,7a-tetrahydro-4,7-methanoindan
Ci0HSC170
389.32
solid
160-161.5®C (99.5% pure)
3 x 10~4 mm Hg (at 25°C)
0.35 mg/L (at 25°C)
2.65, 4.43, 5.40 (by 3 methods)

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° Heptachlor epoxide, but not heptachlor itself, is a common low level
contaminant in food. Heptacnlor has been detected in air at very lo^
levels, approximately 1 ppt. However, the availaole data are insuf-
ficient to evaluate exposures from these areas or to determine if
drinking water is a significant route of exposure.
III. PHARMACOKINETICS
Absorption
° Heptachlor was absorbed rapidly from the gastrointestinal tract of rats
following intragastric administration as evidenced by its detection in
blood within one hour after dosing (Mizyukova and Kurchatov, 1970).
Distribution
° In female rats, intragastrically administered heptachlor was detected
in blood, liver, kidney and adipose tissue'within one hour. After
four hours, heptachlor epoxide was detected in blood, liver and fat,
persisting in adipose tissue for 3 to 6 months (Mizyukova and Kurchatov,
1970). With dietary -administration of heptachlor to rats for two
months or to dogs by capsule for 12 to 18 months, Radomski and Davidow
(1953) reported similar tissue distribution. Heptachlor epoxide
levels in the fat of female rats, however, were about 5 to 10 times
higher than those in male rats. Retention in adipose tissue was 6
and 8 weeks for male and female rats respectively.
° Heptachlor epoxide has been detected in tissue samples from 77 autopsies
performed from 1966 to 1968 at 1 to 32 ppb per whole tissue, with
highest concentrations in bone marrow and liver (Klemmer et al., 1977).
° Heptachlor epoxide has been detected in human adipose tissue in surveys
conducted in Great Britain (Abbott et al., 1972; 1981), Brazil (Wasser-
mann et al., 1972), Japan (Curley et al., 1973), Israel (Wassermann
et al., 1974), Texas (Burns, 1974), Louisiana (Greer et al., 1980)
and the United States (Kutz et al., 1979; Sovocool and Lewis, 1975).
° Evidence of transplacental transfer of heptachlor or heptachlor
epoxide in humans (levels of 0.01-0.3 mg/kg in fat; 0.001 mg/L in
blood) comes from a study by Curley et al. (1969), who detected
heptachlor epoxide in adipose tissue, brain, adrenals, lungs, heart,
liver, kidney and spleen of ten stillborn babies and two babies who
died soon after birth and in 27 of 30 samples of cord blood from
healthy neonates.
Metabolism
° Metabolism of heptachlor to heptachlor epoxide ^ri vitro was similar
using rat and human liver microsomal preparations. A major species
difference was that four times more heptachlor epoxide was formed in
the rat system than in the human system (Tashiro and Matsumura, 1978).

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° The major fecal metabolites
include heptachlor epoxide,
epoxychlordene (Tashiro and
Excretion
of orally administered heptachlor in rats
1-hydroxycnlordene, and 1-n/dru.
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° A single, acute oral dose of 60 mg/kg heptachlor in rats was associ-
ated with increased levels of serum GPT and serum aldolase, and
moderate to severe histological liver damage (Krampl, 1971).
° Evidence of significant liver damage and altered liver function was
reported in rats maintained on diets containing heptachlor at 7 to 12
mg/kg bw/day for up to 14 days (Krampl, 1971) and 10 mg/kg diet for
5 to 7 days (Enan et al., 1982).
° A dose-related significant induction of liver microsomal enzymes, at
dietary levels of heptachlor of 2 to 50 mg/kg diet for 14 days, was
observed in rats (Den Tonkelaar and Van Esch, 1974).
Long-term Exposure
° At dietary levels of 10 mg/kg of heptachlor or heptachlor epoxide in
mice for 2 years, Reuber (1977a) diagnosed hepatic vein thrombosis
and cirrhosis of the liver from slides of the Davis (1965) study.
0 In the IRDC (1973) study, reviewed by Epstein (1976), a 75% heptachlor
epoxide and 25% heptachlor mixture was fed to mice for 18 months;
females and males had dose-related significantly increased mean liver
weights and hepatocytomegaly at 1, 5 and 10 mg/kg diet.
° Jolley et al. (1966) found dose-related increased mortality in rats
fed 5 to 12.5 mg/kg diet levels of a 75% heptachlor and 25% heptachlor
epoxide mixture for 2 years.
° Witherup et al. (1955) found non-neoplastic lesions in rats at
dietary levels *7.0 mg/kg diet of heptachlor for 110 weeks. Treated
males had dose-related increased liver weights at levels of 3 to 10
mg/kg diet.
0 Dose-related liver weight increases, hepatocytomegaly and hepatic
cell vacuolization were observed in rats jnaintained for 108 weeks on
diets containing heptachlor epoxide at 0.5-10 mg/kg diet (Witherup
et al., 1959).
° Dose-related changes in clinical measurements related to liver
function and microscopic changes in liver were noted in dogs admini-
stered heptachlor epoxide in the diet at dose levels of 3, 5, 7 and
10 mg/kg/day for 2 years (U.S. EPA, 1971; IRDC, 1973).
° Beagle dogs from 23 to 27 weeks of age were given diets containing
0, 0.5, 2.5, 5 or 7.5 mg/kg/day of heptachlor epoxide for 60 weeks.
Results included liver weight to body weight ratios which were
significantly increased in a treatment-related fashion. Effects were
noted for both males and females at the dose of 0.5 ppm. No NOEL was
determined from this study (U.S. EPA, 1958, Kettering Laboratory).
Reproductive Effects
° No information was found in the available literature on the reproductive
effects of heptachlor or heptachlor epoxide.
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Developmental Effects
° No information was Eound in the available literature on tne develop-
mental effects of heptachlor or heptachlor epoxide.
Mutagenicity
0 Heptachlor has been tested for mutagenicity in a number of systems.
Negative results have been obtained in bacterial systems (Monya
et al., 1983; Probst et al., 1981; Gentile et al., 1982; Shirasu
et al., 1976), in mitotic gene conversion (Gentile et al., 1982),
in the recessive lethal assay in fruit flies (Benes and Sram, 1969),
in assays for unscheduled ONA synthesis in rat, mouse and hamster
primary hepatocyte cultures (Probst et al., 1981; Maslansky and
Williams, 1981), and for the dominant lethal assay in mice (Arnold
et al., 1977).
° Positive results were reported for unscheduled ONA synthesis in
transformed human fibroblasts with S-9 activation (Ahmed et al.,
1977) and in the dominant lethal assay in rats (Cerey et al., 1973).
0 Heptachlor epoxide was negative in bacterial systems (Moriya et al.,
1983; Marshall et al.<, 1976), in the recessive lethal assay in fruit
flies (Benes and Sram, 1969) and in the dominant lethal assay in mice
(Arnold et al., 1977).
0 Heptachlor epoxide was positive for unscheduled DNA synthesis in
human fibroblasts in the presence o-f S-9 (Ahmed et al., 1977).
Carcinogenicity
° In a National Cancer Institute bioassay (NCI, 1977), heptachlor was
tested for possible carcinogenicity in male and female mice and rats.
Male B6C3F] mice received heptachlor at dietary concentrations of 0,
6.1 and 13.8 mg/kg diet and female B6C3Fj mice received diets contain-
ing 0, 9.0 and 18.0 mg/kg diet, both for 80 weeks. The incidence of
hepatocellular carcinomas was statistically significant in the high-
dose males, while a highly significant dose-related trend also was
observed between high- and low-dose females. Heptachlor was not
carcinogenic in male and female Osborne-Mendel rats similarly treated
with concentrations of 25.7 to 77.9 mg/kg diet.
° Re-analysis of the study results reported by Witherup et al. (1955),
indicate that administration of heptachlor to male and female CF rats
at dietary levels of 1.5 to 10.0 ppm (mg/kg diet) for 110 weeks
resulted in a statistically significant increase in malignant and any
tumors in multiple sites in some female test groups (Epstein, 1976).
0 Significantly increased incidences of hepatic carcinoma were determined
by Reuber and Williams (Epstein, 1976) upon re-analysis of histologic
slides from the Witherup et al. (1959) study. Witherup administered
heptachlor epoxide to male and female CFN rats at doses of 0, 0.5,
2.5, 5.0, 7.5 and 10.0 mg/kg diet for 108 weeks. , The incidences were
significantly different from controls for female rats at the 5 and
10 mg/kg dietary concentrations (Epstein, 1976).
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0 Histological re-examination of the slides from the Davis (1965) study
resulted in a conclusion of significantly increased incidence of
hepatocellular carcinoma in C3H mice receiving 10 mg/kg diet of
heptachlor epoxide for 728 days (Reuber, 1977b).
° Histological re-examination of the slides of the IRDC (1973) study
resulted in a conclusion of significantly increased incidence of
hepatocellular carcinoma in CD-1 mice administered a 75:25 mixture of
heptachlor epoxide:heptachlor in the diet at concentrations of 1.0,
5.0 or 10.0 ppm (mg/kg diet) for 18 months (Reuber, 1977b).
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 (	 /L)
(UF) x (	 L/day)
where:
NOAEL or LOAEL = No- or Lowest-Observed-Adverse-Effect-Level
in mg/kg bw/day.
BW a 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 a assumed daily water consumption of a child
(1 L/day) or an adult (2 L/day).
One-day Health Advisory
There are insufficient toxicological data available to derive a One-day
HA for heptachlor or heptachlor epoxide. The Ten-day HA, however, would be
protective for a One-day exposure period for heptachlor of 0.01 mg/L.
Ten-day Health Advisory
A Ten-day HA for heptachlor can be derived from a study conducted by
Enan et al. (1982) in which rats were administered heptachlor at 1.0 mg/kg/day
(10 ppm) in the feed for 14 days. Exposure resulted in evidence of liver
damage and altered liver function: increased blood urea, increased blood
glucose, decreased liver glycogen content, and increased acid and alkaline
phosphatase levels when compared with controls. Using 1.0 mg/kg/day as the
LOAEL, the Ten-day HA for the 10 kg child is calculated as follows:
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Heptachlor ana Heptachlor Epoxide
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Ten-day HA = I1'° mg/kg/day)(10 kg) = q.010 ng/L (10 ug/L)
(1,000) (1 L/day)
where:
1.0 ng/kg/day = LOAEL based on liver effects in rats.
10 kg = Assumed body weight of a child.
100 = Uncertainty factor, chosen in accordance with NAS/ODW
guidelines for use with a LOAEL from an animal study.
1 L/day = Assumed daily water consumption of a child.
No data are available from which to derive a Ten-day HA for heptachlor
epoxide.
Longer-term Health Advisory
There are insufficient toxicological data available to derive a Longer-
term HA for heptachlor or heptachlor epoxide. The DWEL of 0.0015 mg/L adjusted
for a 10-kg child is recommended as a conservative estimate for a longer-term
exposure.
Lifetime Health Advisory for Heptachlor
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 classifed 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 study by Witherup et al. (1955) is the most appropriate from which
to derive the DWEL. Investigators studied the effects of heptachlor on
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Heptachlor and Heptachlor Epoxide
Marcn 31, 1987
-10-
groups of 20 male and 20 female CF rats. The compound was administered at
dietary concentrations of 0, 1.5, 3, 5, 7 or 10 ppm (10 mg/kg/dose) of
heptacilor. Mortality among test groups was not dose-related. Lois of body
weight, decreased food consumption and increased liver weights vera seen
among treated males. Lesions in the liver were Limited to 7 ppm and above
and were characteristic of chlorinated hydrocarbons, i.e., hepatocellular
swelling, homogeneity of the cytoplasm and peripheral arrangements of the
cytoplasmic granuled of cells of the central zone of the liver lobules.
The NOEL for increased liver to body weight for males only was 3 ppm and LEL
was 5 ppm. [Note: A re-analysis of the Witherup et al. (1955) dietary study
on the toxicity of heptachlor to rats (by the OPP, RfD Work Group, 1987)
indicated that the NOEL of 3 ppm (0.15 mg/kg/day) for increased liver to body
weight for male rats was the most appropriate for a Lifetime Health Advisory
for heptachlor.] Using this NOEL, the DWEL is derived as-follows:
Step 1: Determination of the Reference Dose (RfD)
RfD = (0.15 mg/kg/day) = 0.0005 mg/kg/day
(300)
where:
0.15 mg/kg/day (3 ppm) = NOEL based on absence of increased liver
to body weight for male rats.
300 = uncertainty factor, chosen in accordance with
NAS/ODW guidelines for use with a NOAEL from
an animal study (also RfD meeting, April 16,
1987).
Step 2: Determination of the Drinking Water Equivalent Level (DWEL)
DWEL = 10*0005 mg/kg/day) (70 kg) a 0.0175 mg/L (17.5 ug/L)
(2 L/day)
where:
0.0005 mg/kg/day = RfD.
70 kg =» assumed weight of an adult.
2 L/day = assumed daily water consumption of an adult.
Heptachlor is classified as Group B: Probable human carcinogen. The
estimated excess cancer risk associated with lifetime exposure to drinking
water containing heptachlor at 17.5 ug/L is approximately 3 x 10~4. 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.
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Heptachlor and Heptachlor Epoxide	March 31, 1987
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Lifetime Health Advisory for Heptachlor Epoxide
Two studies in dogs are the most appropriate from which to derive the
DWEL. In the 60-week dog feeding study (U.S. EPA, 1958) beagle dogs from 23
to 27 weeks of age were divided into five groups (three females and tvo nales)
and were given diets containing 0, 0.5, 2.5, 5 or 7.5 ppm of heptachlor
epoxide. Results included liver weight to body weight ratios which were
significantly increased in a treatment-related fashion. Effects were noted
for both males and females at the 0.5 ppm (0.0125 mg/kg/day) dose level of
heptachlor epoxide. No NOEL was determined for the study. In another two-
generation reproduction study in dogs (U.S. EPA, 1971) animals were administered
diets containing various dose levels of heptachlor epoxide. The dose levels
were 0, 1, 3, 5, 7 or 10 ppm of heptachlor epoxide in the diet. This study
was designed to investigate reproduction parameters associated with heptacnlor
epoxide administration. The OPP and the RfD Work"Group considered that the
former study in dogs, 60-week dog feeding study providing the LEL of 0.5 ppm
(0.0125 mg/kg/day) is the most appropriate for the derivation of the DWEL.
Using this LEL, the DWEL is derived as follows:
Step 1: Determination of the Reference Dose (RfD)
RfD = (0.0125 mg/kg/day) = 0.000013 mg/kg/day
(1,000)
Where:
0.0125 mg/kg/day = Low Effect Level (LEL).
1,000 = uncertainty factor, chosen m accordance with NAS/ODW
guidelines for use with a LOAEL from an animal study.
Step 2: Determination of the Drinking Water Equivalent Level (DWEL)
DWEL = (0.000013 mg/kg/day) (70 kg) = 0.00044 mg/L (0.4 ug/L)
(2 L/day)
Where:
0.000013 mg/kg/day = RfD.
70 kg = assumed weight of an adult.
2 L/day = assumed daily water consuption of an adult.
Heptachlor epoxide is classified in Group B: Probable human carcinogen.
The estimated excess cancer risk associated with lifetime exposure to drinking
water containing heptachlor epoxide at 0.4 ug/L is approximately 2 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 consid-
erable uncertainty as to the accuracy of risks calculated by this methodology.
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Evaluation of Carcinogenic Potential
° The U.S. EPA (1987) derived a human carcinogenic potency factor, qi*,
of 4.5 (mg/kg/day)-1 for heptachlor. This derivation wao based on
the geometric mean of four potency estimates which were based on tne
incidence of hepatocellular carcinoma in male and female CH3 mice
(Davis, 1965, as diagnosed by Reuber, 1977b) and male and female
B6C3Fi mice (NCI, 1977). this estimate supersedes the potency of
3.37 (mg/kg/day)-1 previously calculated by the U.S. EPA (1980). The
concentrations in drinking water corresponding to increased lifetime
risk levels of 10-4, 10-5 and 10-6 for a 70 kg human consuming 2 L/day
are 7.6, 0.76 and 0.076 ug/L, respectively (U.S. EPA, 1987).
° Cancer risk estimates (95% upper limit) with other models are presented
for comparison with that derived with the multistage. For example,
one excess cancer per 1,000,000 (10-6) is associated with exposure to
heptachlor epoxide at levels pf <0.0001 ug/L (probit), <0.00001 ug/L
(logit) and <0.0001 ug/L (Weibull) .
0 The U.S. EPA (1987) derived a human carcinogenic potency factor, q-|*,
of 9.1 (mg/kg/day) "I for heptachlor epoxide. This derivation was
based on the geometric mean of four potency estimates which were
based on the incidence of hepatocellular carcinoma in male and female
CH3 mice (Davis, 1965, as diagnosed by Reuber, 1977b) and male and
female CD-1 mice (IRDC, 1973). this estimate supersedes the potency
of 5.786 (mg/kg/day)"1 previously calculated by the U.S. EPA. The
concentrations in water corresponding to increased lifetime risk
levels of 10"4, 10"5 and 10"® for a 70 kg human consuming 2 L/day
are 3.8, 0.38 and 0.038 ug/L, respectively (U.S. EPA, 1987).
° The NAS (1977) determined 0.119 ug/L for heptachlor as the water
concentration corresponding to an increased lifetime risk of cancer
of 10-5. NAS (1977) categorizes heptachlor epoxide as a suspect animal
carcinogen, but noted that there are insufficient data to permit a
statistical extrapolation of risk.
° IARC (1979) classified heptachlor as Group 3s inadequate evidence
of carcinogenicity in humans and limited evidence of carcinogenicity
in animals. The IARC (1979) position on heptachlor epoxide is that
there is limited evidence that heptachlor epoxide is carcinogenic in
experimental animals.
0 Applying the criteria described in EPA's guidelines for assessment of
carcinogenic risk (U.S. EPA, 1986), heptachlor and heptachlor epoxide
is 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.
OTHER CRITERIA, GUIDANCE AND STANDARDS
° In 1980, EPA estimated a range of excess cancer risks for lifetime
exposure to heptachlor when developing ambient water quality criteria
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(U.S. EPA, 1986). This range was 2.78
respectively, for risks of 10-5, 10-6
of 2 liters of water and 6.5 grams of
a 70 kg adult.
ng/L, 0.28 ng/L and 0.028 ng/L,
and 10-7, assuming consumption
contaminated fish per day by
° FAO/WHO recommended an ADI value of 0.5 ug/kg bw for heptachlor or
heptachlor epoxide. This recommendation was established by tne Joint
FAO/WHO Expert Committee on Food Additives (FAO/WHO, 1978).
° A guideline value of 0.1 ug/L in drinking water also was recommended
by the WHO (1984), based upon this level as one percent of the ADI.
0 The American Conference of Governmental Industrial Hygienists (ACGIH,
1983) has adopted" -TWA-TLVs of 0.5 mg/m^ for heptachlor in workroom
air.
° It should be noted that an estimated concentration for detection by
taste and odor in water for heptachlor was 0.02 mg/L (Sigworth, 1965).
VII. ANALYTICAL METHODS
0 Determination of heptachlor 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
chromatography. 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
0 Treatment technologies which are capable of removing heptachlor from
drinking water include adsorption by granular activated carbon (GAC)
and ozone (O3) or ozone/ultraviolet oxidation (O3/UV).
0 Dobbs and Cohen (1980) developed adsorption isotherms for a number of
organic chemicals in drinking water, including heptachlor. Based on
the isotherm data, they reported that the activated carbon Filtrasorb®
300 exhibited adsorptive capacities of 45 mg, 18 mg and 8 mg of
heptachlor per gm of carbon at equilibrium concentrations of 100
ug/L, 10 ug/L, and 1 ug/L, respectively.
0 The GAC system in U.S. EPA's Hazardous Materials Spills Treatment
Trailer was used to treat 104,000 gal of pesticide-contaminated water
containing heptachlor. Water analysis showed 6.1 ug/L of heptachlor
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Heptachlor and Heptachlor Epoxide
March 31, 1987
-14-
ln the contaminated water. Ninety-nine percent heptachlor removal
was achieved at a contact time of 17 minutes (U.S. EPA, i'^<35d).
° Hansen (1 977) reported on the efficiency of GAC used in -lount Clements
water treatment plant to remove synthetic organic chemicals from the
raw water source. Heptachlor epoxide was detected in the raw vatar
at concentrations of 220 ng/L. The GAC column reportedly was capable
of removing 99.9+ percent (below its detectable limit) of the heptachlor
epoxide.
° Gilbert (as referenced in U.S. EPA, 1985b) summarized the results pre-
sented by a number of different researchers on the ability of ozone
to remove several SOCs from drinking water, including heptachlor.
The results indicate that greater than 99% of the heptachlor was
removed by ozone oxidation, while heptachlor epoxide was only partially
removed (i.e., 26%) at an applied ozone dose of 17 mg/L.
° Treatment technologies for the removal of heptachlor from drinking
water have not been extensively evaluated (except on an experimental
level). An evaluation of some of the physical and/or chemical
properties of heptachlor indicates that the following techniques
would be candidates for further investigation: adsorption by granular
activated carbon and ozone oxidation. Whichever individual or combi-
nations of technologies for heptachlor reduction are used, it must be
based on a case-by-case technical evaluation, and an assessment of
the economics involved.
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Heptachlor and Heptachlor Epoxiie
March 31, 1987
-15-
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