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OCR for page 29
LINDANE
BACKGROUND INFOR - T ION
Lindane is the gas- isomer of hexachlorocyclohexane and is commonly
referred to by the misnomer hexachlorobenzene. Technical-grade
1 indane contains 99 percent ga~-hexachlorocyclohexane, but also
contains 1 percent of other isomers. Lindane in Stable in the
presence of 1 ight, heat, air, carbon dioxide, and strong acids;
however, it is dehalogenated in the presence of alkali. Physical and
chemical properties of 1 indane are shown in Table 1.
About 1 mil 1 ion pounds of 1 indane are used yearly in the United
States. It is used primarily for seed treatment and to control
various wood-inhabiting beetles. Very little lindane is used for
termite control; for this purpose, application is primarily to soil as
a surface spray, rather than by injection or trenching. Lindane
is also used in the treatment of scabies and 1 ice infestation.
Lindane was the subject of an EPA rebuttable presumption against
registration proceedings. Booker Chemical Corporation terminated
production as a resul t of the proceedings, and there has been no
reported production in the United States ~ ince 1976.
SUMMARY OF TOXICITY INFO~T ION
,
Several comprehensive reviews of 1 indane are available (NRC, 1977b;
IARC, 1974, 1979; EPA, 197 9d) .
EFFECTS IN HUMANS
l
Several reports have 1 inked exposure to 1 indane with development of
aplas tic anemia, ant these nave been reviewed elsewhere (NRC, 197 7b;
IARC, 1979; Morgan et al., 1980) . However, this result has not been
replicated in a seeiefactory denial model, and no fir causal
relationabip has been established between lindane exposure and anemia.
Nantel et al . ( 1977) investigated the health effects in 50 people
who ate foot contaminated with lindane. Within hours, all experienced
one or more of the following: nausea, vomiting, diarrhea, headache,
dizziness, and paresthesia. Twenty suffered grand mat seizures and
were hospitalized for 1 d.
A series of reports (Brassow et al., 1981; Baumann et al., 1980,
1981; To~zal' et at., 1981) described the health status of 60 men
(mean age, 40 yr) involved in lindane production for 1-30 yr (mean,
7.2 ye); 20 cleave ant 20 fairy workers were used as controls. The
authors found no increase in mortality, no impairment of the central
nervous syeeemor peripheral motor nerves, and co effects onECGe,
liver enzymes, red and white blood cells, platelet counts, or
hemoglobin. Neurologic effects were measured through electromyograms,
e 1 ec troencephal ograme, ma tor~nerve c onduc tion ve ~ oc i ty, f oref inger
tremors, and dexterity tracking tests. The authors noted an increas e
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in polymorponuclear leukocytes and prothrombin time. In 54 of the
workers and in controls, blood concentrations of follicle-stimulating
hormone (FSH), luteinizing hormone (LH), and testosterone were
measured. There was no difference in FSIl, and testosterone
concentrations were slightly, but not significantly, lower than those
in controls. Lindane workers had significantly higher LIl
concentrations. Further research is needed to determine whether these
changes represent an adverse health risk.
EFFECTS IN ANIMALS
Ac ute Exposure
The oral LDsos of lindane for mice, rats, guinea pigs, ant rabbits
are 86, 125-230, 100-127, ant 60-200 mg/kg of body weight,
respectively (Gaines, 1969). The dermal LDs`' in rats is 1,000 mg/kg
f o r mal e ~ and 90 0 mg/kg f or f emal e ~ . S igns o f intoxicat ion inc lude
diarrhea, hypothermia, hyperirritability, incoordination, and
consul ~ ions .
Chronic Exposure and Care Erogenic ity
Lindane was administered daily by stomach tube to male and female rats
for 6 ma at 32 mg/~g or for 17 ma at 10 mg/kg (Klimmer, 1955~.
Observed effects in rats given 32 mg/kg included fatty degeneration of
the liver and renal tubular epithelium, vacuolization of cerebral
cells, and an increase in mortality. Effects were not observed at the
lower dosage. Rats were also given lindane in the diet at 2, 3. 4, 5,
or 10 ppm for 12 ma, and no adverse effects were obeer~red (Melis,
1 9 55) .
In a 2-yr feeding study (WHO/FAD, 1967), lindane was given to rats
in the diet at 25, 50, or 100 ppm. At 50 and 100 ppm, there was
hypertrophy of the liver, and at 100 ppm also fatty degenerative
changes. No effects were observed at 25 ppm.
Several authors have investigated the care ~nogenic potential of
lindane. These studies have been thoroughly reviewed (NRC, 1977b;
Reuber, 1979; IARC, 1979~. Nagasaki et al. (1972a) fed male mice
lintane in the diet at 100, 250, or 500 ppm for 24 ok; no rumors were
observed at any dose. Thorpe and Walker (1973) administered lindane
to CF1 mice in the diet at 400 ppm; both sexes had increase. in liver
t''~rs, compared with controls. In an NCI (1977c) bioassay, groups of
50 B6C3F} mice of each sex were given lindens in the tier at 80 or 160
ppe for 80 wk. Me incidence of hepatocellular carcinoma was
significantly greater in the low~dose group, but not the high-dose
group, compared with controls. The investigatore concluded that
lindens was not carcinogenic under the condition. of the test. Groups
of 50 mice of each sex were given lindane in the diet at 12.5, 25, or
50 ppm for 80 wk (Weisee and Herbet, 1977~; there was no significant
increase in tumors, compared wi th c ontro 1~.
The carcinogenicity of lindane has also been investigated in
rate. Nagasaki et al . ( 1972b) administered 1 indane to groups of seven
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Wistar rats in the diet at 250, 5()0, ant 1,000 ppm. At 48 Wk. one rat
at the highest dose had a hepatoma and three others had hypertrophic
nodules without signs of malignant tumors. In another study (NCI,
1977c), groups of 50 Osborne~ende} rats of each sex were given
lindane in the diet--at 236 or 472 ppm for males and 135 or 270 ppm
for females--for 80 wk. There was no statistically significant
increase in tumors in any of the test groups.
Teratogenicity and Reproductive Effects
No effects on reproductive function were observed and there was no
increase in malformations in a three-generation rat study in which
1 indane was given in the diet at 25, SO, or 100 ppm (Palmer et al .,
1978b). Teratogenic effects were not observed when lindane was given
orally at 5, 10, or 15 mg/kg of body weight to rabbits on days 6-18 of
gestation and to rats on days 6-16 of gestation (Palmer et al., 1978a)
When 1 indane was given orally for 4 ma at ().5 mg/kg to female
rats, disturbances in the estrus cycle and diminished reproductive
capacity were observed (Nai~htein and Leibovich, 1911~. There was an
increase in the incidence of stillborn pups when beagles were given
lindane at 7.5 or 15 mg/kg from day 5 through the end of gestation.
Khera _ al . ( 1979) administered Benesan (50 percent lindane) to
rats oral ly at 0 ~ 6.25, 12.5 ~ or 25 mg/kg on days 6-15 or pregnancy
There were no observed effects on fetal body weight or survival and no
increase in Intrauterine deaths or anomal ies in the groups exposed to
1 indane.
Mu tagenic i ey
In a dominant-lethal assay, no mutations or reproductive effects were
observed (NRC, 1977b). Lintane was not mutagenic in the host~ediated
assay with Salmonella typhimurium or Serratia marcescens.
Toxicokinet ic ~
In animals, 1 indane is biotransfonned to chlorophenole
~ trichlorophenol , tetrachlorophenol , and pentachlorophenol), which are
excreted free or as sulfuric acid or glucuronic acid conjugates (Engat
et al., 1976; Freal and Chadwick, 1973~. Chadwick et al. (1975)
reported that 1 indane is f irat converted to a hexachlorocyclohexane
intermediate and then to two tetrachlorophenol ~ and three
trichlorophenol a.
Lindane accumulates primarily in body fat ~ Davidow and Frawley,
1951; Oshibe, 1972~. In rats given lindane in the diet at 800 mg/kg
of diet for 20 month, adipose tissue was the primary store (l)avidow
and Frawley, 1951~. Concentration. in other tissues were lower by at
reset 80 percent. Lindane was eliminated from tissue within 3 wk
af ter exposure ended . Concentrations of 1 indane in the general
populations of many countries have ranged from 0.02 to 1.43 ppm in
adipose tissue and from 0.0031 to 0.0042 ppm in blood (Durham, 1969~.
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EXISTING GUIDELINES AND STANDARDS
The EPA (1979d) nas estimated that exposure of lindane in the drinking
water at a concentration of 5.4 ag/L would result in a lifetime cancer
rise of 10~6.
The ACGIH (1981) has recommended a TEV-TWA of 0.5 mg/m3 and a
TLV-STEL of 1.5 mg/m3. The OSHA (1981) permissible workplace
exposure ~ imit is 0. S mg/m3. Both agencies noted that 1 Mundane is
absorbed through the skin and that dermal exposure should therefore be
avoided.
— 32 —
Representative terms from entire chapter:
reproductive effects
