March 31, 1987
LINDANE
Health Advisory
Office of Drinking Water
U.S. Environmental Protection Agency
INTRODUCTION
The Health Advisory iHA) 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. Healtn 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 understand!
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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Lindane
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This Health Advisory (HA) is based upon information presented in the
Office of Drinking Water's Draft Health Effects Criteria Document (CD) for
Lindane (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 # 86-1 17819/AS.
The toll free number is (800) 336-4700; in the Washington, D.C. area:
(703) 487-4650.
GENERAL INFORMATION AND PROPERTIES
CAS No. 58-89-9
Structural Formula
° Lindane has been used in the control of various wood-inhabiting
beetles, seed treatment, and pharmaceutical preparations (1% lotion,
cream or shampoo) as a scabicide and pediculocide
Properties (U.S. EPA, 1985a)
ci
a
Synonyms
0 Gamma-hexachlorocyclohexane
Gamma-benzene hexachloride
Kwell
Uses
Chemical Formula
Molecular Weight
Physical State
Boiling Point
Melting Point
Density
Vapor Pressure
Water Solubility
Log Octanol/Water Partition
C6H6Cl6
290.85
white crystals
323.4°C
112.5°C
1 .85
(0.094-3.3) x 10-4 mm Hg (20°C)
7.3-7.9 mg/L (25°C)
3.61-3.72
Coef ficient
Taste Threshold
Odor Threshold
Conversion Factor
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Occurrence
° Lindane is imported into the U.S. Import levels are confidential,
bat in the late 1970s, less than one million lbs were imported.
° Lindane is degraded poorly in the environment. Lindane is hydrolyzed
poorly and undergoes biodegradation slowly. Soil half lives are
reported to be on the order of 100 days. Lindane is relatively immobile
in soil and migrates slowly. However, lindane has a slight vapor
pressure and does volatilize from soil. Once in air, lindane photo-
degrades. Lindane has been reported to bioaccumulate, however, its
potential is limited since it can be metabolized by plants and animals.
° Lindane has not been found in large amounts in drinking water. Only
1 ground water sample out of 71 in the Rural Water Survey reported a
measurable level of lindane: 0.006 ug/L. No water system has
reported exceeding the interim drinking water standard of 4 ug/L.
Lindane has been found in a few non-drinking water surface and ground
waters in areas near its agricultural use. Level up to 0.5 ug/L have
been reported. Lindane has been found in low levels in food and air.
The current information is insufficient to indicate which is the major
route of exposure for lindane.
III. PHARMACOKINETICS
Absorption
0 Fasted IRC rats absorbed 70.7 percent of an mtragastrically admini-
stered dose of 1 mg/kg lindane 60 minutes after treatment (Ahdaya
et al., 1981).
° Albro and Thomas (1974) estimated 95-99 percent absorption of technical
grade lindane within 4 days following single oral doses. Variations
of dosage rates from 30-120 mg/kg had no influence on the proportion
absorbed.
0 Human studies of topically applied pharmaceutical preparations con-
taining 0.3-1.0 percent lindane (Ginsburg et al., 1977; Hosier et al.,
1979; Lange et al., 1981) showed ready absorption. Peak blood levels
were obtained within 6 hours.
Distribution
° Technical grade lindane preferentially accumulated in the fatty
tissue of albino rats when fed at 2.5 mg/kg bw in the diet (Chand and
Ramachandran, 1980). Accumulation in the brain also has been reported
(Lakshmanan et al., 1979).
° Extensive accumulation of lindane occurs in the milk of exposed women
(Siddigui et al., 1981). Lindane also has been shown to enter -.n.e
fetus through the placenta (Poradovsky et al., 1977).
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Metabolism
° Metabolism of lindane in humans entails dehydrocnlorination to form
cyclohexene derivatives and various chlorinated phenols by way of
either oxicative or nonoxidative pathways (U.S. EPA, 1985a).
0 Fitzloff et al. (1982) reported that haman liver microsomes converted
lindane to hexachlorocyclohexene, 1,3,4,5,6-pentachlorocyclohexene,
2, 4, 6-trlchlorophenol, 2, 3, 4, 6-tetrachlorophenol and pentachlorobenzer.e.
Engst et al. (1979} observed that lindane was metabolized to tri- and
pentachlorophenols when inhaled by humans.
0 The half-life of radioactive lindane in rats was 3 to 5 days (Engst,
et al., 1979). Kujawa et al. (1977) administered lindane orally to
rats (8 mg/kg bw) after which they studied the nature of the metabo-
lites in urine, liver and blood. The major products found m urine
were pentachlorophenol, 2,3,4,6- and 2,3,5,6-tetrachlorophenol ana
2,4,6-trichlorophenol. Metabolites in the blood were the same as
those found in urine. In the liver, 2, 3,4,5, 6-pentachlorobenzene and
pentachlorcyclohexene were found in addition to the tetrachloro-
phenols. The kidneys contained considerably higher levels of the
pentachlorocyclohexene than did the liver. Pentachlorocyclohexene
also was detectable in the spleen, heart and brain. No metabolites
were found in the adrenals.
° Lindane has been shown to induce increases in levels of xenobiot^c
metabolizing enzymes m the liver in several stJdies (Lowy et al.,
1977; Plass et al. , 1981, RCC, 1983).
Excretion
0 Even after prolonged administration, lindane is eliminated completely
from the body soon after application is terminated. Frawley ari
Fitzhugh (1949) demonstrated that, in rat fatty tissue, a lindane
concentration of 102 mg/kg (102 ppm) dropped to zero 1 week after
administration of lindane was discontinued. Lehman (1952a,b) cerc •-
strated that a concentration of 281 mg/kg (281 ppm) in the fatty
tissue was eliminated completely within 2 weeks. Kitamura et al.
(1970) fed rats a diet containing 10 mg/kg of gamma lindane over a
20-day period. One day after return to a normal diet, no resicije
could be detected in the body.
0 Very little lindane is excreted unaltered. Laug (1948) detected :
about 4% gamma lindane in the urine of rats fed lindane in the ?.r-
(dosage unspecified). No reports of unaltered gamma lindane e
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Lindane
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IV. HEALTH EFFECTS
Humans
° Case reports indicate that the acute effects of lindane resulting
from either excessive dermal or oral intake include functional
alterations in the nervous system in the form of seizures and uncon-
trollable eye movements. The effects appear to be reversible, with
full recovery within 1 year of exposure.
° Lindane appears to have a definite inhibitory effect on white blood
cells (lymphocytes) in vitro. In a study conducted by Roux et al.
(1979), 10~4 M lindane sharply inhibited protein, DNA and RNA synthesis
in cultured lymphocytes, either in the unstimulated, phytohemagglutinin
(PHA)-stimulated or in the lymphoblast state. Lindane treatment
resulted in sharply inhibited PHA-mduced mitogenesis in the exposed
lymphocytes.
0 The only reported effects of lindane on the blood cells have been
equivocal (including possible anemia) (U.S. EPA, 1985a).
Animals
Short-term Exposure
° Lindane has higher acute toxicity than other chlorinated hydrocarbons
because it is absorbed rapidly. Clinical symptoms are apparent soon
after exposure (Lehman, 1951). Its high water solubility and rapid
rate of absorption explain the narrow range between its NOAEL and
lethal doses as compared with wider ranges in similar compounds, sjch
as DDT (Gunther et al., 1968; Martin, 1971).
0 The single dose oral LD50 has been shown to vary from a high of 1000
mg/kg bw in mice (Wolfe and Esher, 1980) to 840 mg/kg in adult
(Engst et al., 1979), 400 mg/kg in pigeons (Blakley, 1982), 180
in children (Engst et al., 1979), 125 mg/kg in rats (Farkas et al.,
1976) and 60 mg/kg in rabbits (Desi et al., 1978).
0 Muller et al. (1981) reported a decrease in motor conduction ve.cc.:/
in the tail nerve of Wistar rats fed gamma lindane in the diet ::r
30 days at doses of 25.4, but not at 12.3 or 1.3 mg/kg bw.
0 Desi (1974) measured behavioral endpoints in Wistar rats (8 aniT.a.s
per group) exposed to lindane up to 40 days at daily intakes c: 2.r,
5, 10 and 50 mg/kg bw. After approximately 2 weeks of exposure,
running times and numbers of errors were increased significant..'
at dosages > 5 mg/kg. The number of lever presses in an opera: t
conditioning test (Skinner Box) was increased significantly eve- j*
the 2.5 mg/kg dose level, indicating an effect upon irritabii."
0 Muller et al. (1981) studied the electroneurophysiological e::
of lindane when fed in the diet to groups of IS-Wistar rats f:r
days. A delay in conduction velocity was observed in animals • ¦
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Li ndar.e
March 31, 1987
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daily dose of 25 mg/kg but not 12 or 1.3 mg/kg bw. The lindane
metabolite gamma-pentachlorocyclohexene caused a conduction delay when
administered at concentrations of 38-782 mg/kg bw.
° Desi et al. (1978) studied the response of rabbits to Salmonella typhi
vaccine following treatment with lindane at 1.5-12 mg/kg bw given
orally 5 times/week for 5-6 weeks and compared the immunologic behavior
with normal, untreated animals. Six animals were used in each group.
The treated rabbits displayed a dose-related decrease in immunologic
titers, indicating immunosuppressive effects. Similar results were
reported by Dewan et al. (1980) who found that male and female
albino rats fed lindane (6.25 or 25 mg/kg in olive oil on alternate
days for 35 days) displayed immunosuppressive behavior when challenged
with £. typhi and £. paratyphi antigens. Again, the effects were
dose-dependent.
Long-term Exposure
0 In the RCC (1983) study, both male and female rats of the KFM-HAN
(outbred) SPF strain were fed 99.85% pure lindane in the diet at
levels of 0, 0.2, 0.8, 4, 20 and 100 ppm for 84 consecutive days.
Liver hypertrophy, kidney tubular degeneration, hyaline droplets,
tubular casts, tubular distension, interstitial nephritis and
basophilic tubules were seen at the 20 and 100 ppm levels. Effects
were rare and very mild when noted at 4 ppm.
0 Fitzhugh et al. (1950) exposed 10 Wistar rats of each sex per dosage
group to gamma lindane at levels of 5, 10, 50, 100, 400, 800 or 1600
mg/kg in the diet for 2 years or longer. An increase in liver weight
and a the slight degree of kidney and liver damage were noted at 100
mg/kg in the diet but not at 50 mg/kg.
0 Wolfe and Esher (1980) exposed two strains of wild mice to 200 ppm
lindane in the diet for 8 months with no reported effects on food
consumption, growth rate, mortality, reproduction or behavior. Weisse
and Herbst (1977) exposed SPF mice to 12.5, 25 or 50 mg/kg lindane m
the diet for 80 weeks and reported no fine structural hepatocellular
alterations.
0 In a study conducted by Fitzhugh et al. and reported by Lehman (1965)
dogs were fed (2 animals/sex/group) 0 or 15 mg/kg lindane in the diet
for 63 weeks. No differences were noted for food consumption, hemato-
logical or histopathological parameters. Rivett et al. (1978), fed
beagles (4 dogs/sex/group) 0, 25, 50 or 100 mg/kg lindane in the diet
for 2 years. The daily intake of lindane based on measured food
consumption was 0.83, 1.60 or 2.92 mg/kg bw, respectively. No effects
were reported for the 25 and 50 ppm groups. At 100 ppm, serum alkali re
phosphatase was increased significantly and the livers were dark,
friable and greatly enlarged.
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Reproductive Effects
° Palmer et al. (1978b) reported no effects of lindane on reproductive
function or on the incidence of malformation following dietary admini-
stration of 0, 25, 50 or 100 ppm (1.25, 2.5 or 5 mg/kg bw) lindane.
° No effects were observed in pregnant rabbits fed lindane on days
6 through 18 of gestation at levels equivalent to 5, 10 and 15 mg/kg
bw and to pregnant CFY rats fed the same doses of lindane on gestation
days 6 through 16 (Palmer et al., 1978a).
Developmental Effects
° Contrary to the results of the above studies, Dzierzawski (1977)
reported a 2- to 20-fold increase in resorbed fetuses in hamsters
treated with 20 or 40 mg/kg lindane on day 8 of pregnancy. Similar
results were obtained in rats treated with 50 or 100 mg/kg on day 9
of pregnancy and 40 mg/kg doses on days 6, 8 and 10, and in rabbits
treated with 40 or 60 mg/kg on day 9. While the three reports
presented above indicate that there is no evidence of reproductive
or teratogenic effects on mammals at lower doses, the report by
Dzierzawski (1977) suggests that further studies may be necessary
before a final conclusion is reached.
0 In a study in which female Wistar rats were dosed orally with lindane
at levels ranging from 6.25-25 mg/kg bw from days 6 through 15 of
gestation, Khera et al. (1979) observed no statistically significant
changes in numbers of dead or resorbed fetuses, nor did they observe
any type of birth defects in the offspring.
Mutagenicity
° The evidence of the mutagenic activity of lindane is equivocal. Only
one study indicated a weak mutagenic effect of lindane at a dose of
50 mg/kg in mice (Rohrborn, 1977). Another study indicated a positive
dominant lethal mutation in male Swiss mice fed approximately 65 mg/kg
bw technical grade lindane for 4 to 8 months (Lakked et al., 1982).
These cases, however, appear to be an exception as the majority of
similar studies indicate negative results (Benes and Sram, 1969,
Ahmed et al., 1977; Rohrborn, 1977; Probst et al., 1981).
Carcinogenicity
° NCI (1977) reported no significant increases in the incidence of liver
cancer in male or female B6C3F1 rats fed up to 472 ppm (74 mg/kg bw)
in the diet for 80 weeks. Reuber (1979), however, reevaluated the
results and reexamined tissue sections from the same study and
concluded that the incidence of tumors was increased in the treated
animals. Since he gave no indication as to why he considered the
original NCI interpretation of the tissues questionable or how tne
tissues were reexamined, it is difficult to draw conclusions from ^.5
review.
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Lindane
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0 In the study by NCI (1977), both male and female B6C3F1 mice were
exposed to lindane in the diet at either 80 or 160 ppm (10.4 or
20.8 mg/kg bw). A significant increase in liver tamor incidence was
reported only for low-dose males. Because of the high spontaneous
incidence (20.8%) of hepatocellular carcinoma in B6C3Fi male mice and
because the incidence among high-dose males was not increased signifi-
cantly, NCI (1977) concluded that the occurrence of these tumors m
these mice could not be related conclusively to the administration of
lindane under the conditions of this bioassay. On the other hand,
the incidence of hepatocellular carcinomas in low-dose males, while
not showing a significant increase compared with matched controls,
did exhibit a highly statistically significant increase compared with
pooled controls. As was the case with the data resulting from the
rat study, Reuber (1979) reported a different interpretation of the
results of the same experiment.
0 Thorpe and Walker (1973) exposed 30/sex/group CF1 mice to gamma
lindane at 400 ppm in the diet (52 mg/kg bw) for up to 110 weeks.
Liver tumors developed in exposed males and females (P <0.001). This
study was compromised by the low percentage of exposed mice surviving
110 weeks (3% of females and 17% of males).
0 Goto et al. (1972) reported liver tumors in 5 of 10 IRC-JCL male mice
fed gamma lindane at 600 mg/kg/day in diet.
0 Hanada et al. (1973) reported that 1 of 3 surviving female mice and
3 of 4 surviving male mice developed liver tumors after 37 to 38 weeks
or exposure to 600 mg/kg/day in diet lindane compared with none in
controls.
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 noncarcmogenic end point of toxicity.
The HAs for noncarcmogenic toxicants are derived using the following formula:
HA = (NOAEL or LOAEL) y BW) = mg/L ( ug/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).
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One-day Health Advisory
There are insufficient toxicological data in the scientific literature
to derive a One-day HA. The Ten-day HA of 1.2 mg/L is recommended as a
conservative estimate for a One-day exposure.
Ten-day Health Advisory
The electroneurophysiological effects of lindane on Wistar rats were
studied by Muller et al. (1981). Fifteen rats were fed daily doses of 1.3,
12.3 or 25.4 mg/kg bw in the diet for 30 days. Nerve conduction delay was
observed in the animals fed a daily dose of 25.4 mg/kg but not 12.3 or
1.3 mg/kg. A NOAEL of 12.3 mg/kg/day was identified. The Ten-day HA for
a 10 kg child is calculated as follows:
Ten-day HA = <12.3 mg/kg/day) (10 kg) _ 1>2 mg/L or 1200 ug/L
(100) (1 L/day)
where:
12.3 mg/kg/day = NOAEL based on absence of nerve conductance delay
in rats.
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.
Longer-term Health Advisory
Male and female rats of the KFM-HAN (outbred) SPF strain were fed pure
lindane at dietary levels of 0, 0.2, 0.8, 4, 20 or 100 mg/kg/day for 84
consecutive days (RCC, 1983). Liver hypertrophy, kidney tubular degeneration,
hyaline droplets, tubular casts, tubular distension, interstitial nephritis and
basophilic tubules were observed in the 20 and 100 ppm groups. Effects were
rare and very mild when noted at 4 ppm. The NOAEL was considered to be 4 ppm
in this study. Based upon measured food consumption, the daily intake of
lindane at 4 ppm in the diet was 0.29 mg/kg in males and 0.33 mg/kg in females.
Using 0.33 mg/kg as the NOAEL, the Longer-term HA is calculated as follows:
For a child:
Longer-term HA = mg/kg/day) (10 kg) _ o.033 mg/L or 33 ug/L
(100) (1 L/day)
where:
0.33 mg/kg/day = NOAEL based on absence of liver hypertrophy m rats.
10 kg = assumed body weight of a child.
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Lindane
March 31, i 98 7
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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 an adult:
Longer-term HA =
(0.33 mg/kg/day) (70 kg)
(100) (2 L/day)
= 0.12 mg/L or 120 ug/L
where:
0.33 mg/kg/day = NOAEL based on absence of liver hypertrophy in rats
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%
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 ir
assessing the risks associated with lifetime exposure to this chemical.
The study by RCC (1983) has been selected as the basis for calculating
a Lifetime HA. Four longer-term studies were identified as potential card.-
dates for the determination of the RfD. Collectively, they describe doses
spanning the toxic threshold, thus allowing a maximum NOAEL to be defined.
They include the chronic study of Fitzhugh et al. (1950), the chronic st-rj.
in rats for 80 weeks (NCI, 1977), the chronic dog study by Rivett et al.
(1978) and the 12-week feeding study using rats by RCC (1983). The st^d/ c
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RCC (1983) is the most appropriate from which to derive the Lifetime HA. The
reasons for selecting the study by RCC (1983) for the Lifetime HA have been
delineated in the Drinking Water Criteria Document for Lindane (U.S. EPA,
1985a). Male and female rats were fed pure lindane at dietary levels of 0,
0.2, 0.8, 4, 20 or 100 ppn for 84 consecutive days. Various adverse effects
as noted earlier were observed in the 20 and 100 ppn groups. Effects were
rare and mild at 4 ppn. From these results a NOAEL of 0. 3 3 mg/kg/day was
identifled.
Using this NOAEL, the Lifetime HA is calculated as follows:
Step 1: Determination of the Reference Dose (RfD)
RfD = (0.33 mg/kg/day) = 0.0003 mg/kg/day
(1,000)
where:
0.33 mg/kg/day = NOAEL based on absence of liver hypertrophy in rats.
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 = (0.0003 mg/kg/day) (70 kg) = -|0 Ug/L
(2 L/day)
where:
0.0003 mg/kg/day = RfD.
7 0 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 = 10 U9/L x 20% = 0.0002 mg/L (0.2 ug/L)
1 0
where:
10 mg/L = DWEL.
20% = assumed relative source contribution.
10 = additional uncertainty factor per ODW policy to
account for possible carcinogenicity.
Evaluation of Carcinogenic Potential
° Applying the criteria described in EPA's guidelines for assessment
carcinogen risk (U.S. EPA, 1986), lindane appears to fall somewhere
between Group B2: Probable Human Carcinogen and Group C: Poss i s .e
Human Carcinogen. The Group B category is for agents for which t-ero
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March 31, 1987
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is inadequate evidence from human studies and sufficient evidence
from animal studies, while Group C is for agents with limited evidence
of carcinogenicity in animals in the absence of human data. However,
the Office of Pesticide Programs recently has decided to treat lindane
as a Group C carcinogen (U.S. EPA, 1985b).
Risk estimates were calculated by EPA's Carcinogen Assessment Group
(U.S. EPA, 1980) and the National Academy of Sciences (NAS, 1977)
based on the oncogenic effects observed in the liver of CF1 mice fed
lindane in the diet (Thorpe and Walker, 1973). The estimated levels
that would result in increased lifetime risks of 10-4, 10-5 and 10-6
are given below:
Excess Lifetime Cancer Risk (ug/L)
10-4 10-5 10-6
CAG 2.65 0.265 0.0265
NAS 5.5 0.55 0.055
An overall IARC (1982) classification for lindane is group 3, indi-
cating that carcinogenicity cannot be determined.
VI. OTHER CRITERIA, GUIDANCE AND STANDARDS
° An MCL of 0.004 mg/L or 4 ug/L for lindane in drinking water was
promulgated in 1975 as an interim primary standard by EPA (Federal
Register, 1975).
° The World Health Organization (WHO, 1984) has recommended a drinking
water criterion of 3 ug/L for lindane.
0 It should be noted that an estimated concentration for detection by
taste and odor in water was 12.0 mg/L (Sigworth, 1965).
VII. ANALYSIS
0 Determination of lindane is by a liquid-liquid extraction gas chromato-
graphic procedure (U.S. EPA, 1978; Standard Methods, 1985). Specific-
ally, 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, micro-coulometric 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 captjre
detector.
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VIII. TREATMENT TECHNOLOGIES
0 Treatment technologies which are capable of removing lindane from
drinking water are adsorption or granular activated carbon (GAC),
reverse osmosis (RO) and oxidation. Granular activated carbon columns
(GAC) have been tested for their effectiveness in removing lindane.
A pilot-scale column was tested on lake water which was spiked with
50 ug/L of lindane. Three different carbons were tested and reportedly
produced lindane removal efficiencies of 99.9, 94.8 and 99.8%.
° A treatment plant in Mount Clemens, Michigan has used GAC to remove
pesticides including lindane from the source water. The columns
proved to be 100% effective in reducing lindane from an initial
concentration of 5 ng/L (U.S. EPA, 1978).
° One bench-scale study evaluated the performance of RO cellulose
acetate membrane in the removal of insecticides, including lindane.
Water containing different concentrations of lindane (0.683 mg/L,
50 mg/L and 500 mg/L) was fed to the RO membranes. Removal
efficiencies of 52, 84 and 73%, respectively, were reported (U.S.
EPA, 1978). A pilot-scale plant was field tested in Miami, Florida,
for the removal of SOC, including lindane. The RO process removed
40 percent of the lindane at initial concentrations of 40 ug/L (U.S.
EPA, 1978).
0 Oxidation by ozone (O3) has been tested primarily at bench-scale for
the removal of SOC from drinking water. A number of researchers
presented on the ability of ozone to remove several SOCs from water,
including lindane. Lindane initial concentration varied from 0.05 to
0.1 mg/L. Lindane was not removed appreciably (0 to 10%) at low
levels of ozone does, i.e., 0.4 to 11 mg/L. However, when the ozone
dose was increased to 149 mg/L, lindane was completely removed from the
source water. The high ozone dose might make this treatment technique
economically unfeasible for the removal of lindane.
0 Other treatment technologies, such as reverse osmosis and oxidation
have not been extensively evaluated (except on an experimental level).
An evaluation of some of the physical and/or chemical properties of
lindane indicates that these methods would be candidates for further
investigation.
0 Selection of individual or combinations of technologies for lindane
reduction must be based on a case-by-case technical evaluation, and
an assessment of the economics involved.
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March 31
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