Smith, 1991). Appearance of tremors has not been reported. Lindane caused hypothermia and anorexia in rats (Aldegunde Villar et al., 1981; Camon et al., 1988; Woolley et al., 1985).
Repeated exposure of rats to subconvulsant doses of lindane led to persistent alterations in the CNS as evidenced by increased susceptibility to experimentally induced seizures (Gilbert, 1995). Repeated exposure to lindane also increased the number of errors in a food-reinforced maze; this suggested lindane interference with learning (Dési, 1974). Nonconvulsant doses of lindane were reported to interfere with the ability to acquire and use new information (Tilson et al., 1987).
Rivera and colleagues (1998) investigated the persistent effects of lindane (single or repeated dose) on motor activity. Rat pups were treated with lindane in a single dose (20 mg/kg) or for 7 days (10 mg/kg per day). Motor activity was tested on postnatal day 15. Acute lindane administration decreased motor activity, whereas repeated lindane administration increased motor activity. The authors suggested that the effect was due to an imbalance of the central monoaminergic and GABAA neurotransmitter system (Rivera et al., 1998).
There is not complete agreement on the carcinogenicity of the chlorinated hydrocarbon insecticides, including lindane (Smith, 1991). A number of studies have been conducted on the carcinogenicity of lindane and technical-grade HCH, which contained lindane. Liver tumors and lung tumors were detected in mice fed diets that contained lindane at 12.5–600 ppm for 24–110 weeks (Hanada et al., 1973; Herbst et al., 1975; Ito et al., 1973a; Thorpe and Walker, 1973; Weisse and Herbst, 1977). Other researchers, however, reported no liver tumors in mice fed diets that contained lindane (100–500 ppm) for shorter periods (24–32 weeks) (Ito et al., 1973a,b; Nagasaki et al., 1972). Studies in rats fed lindane-containing diets did not detect an increase in tumors of any type, including liver tumors (Fitzhugh et al., 1950; Ito et al., 1975; NCI, 1977).
Data generally indicate that lindane and HCH are not mutagenic (Buselmaier et al., 1973; Lawlor et al., 1979; Probst al., 1981; Shahin and Von Borstel, 1977; Shirasu et al., 1976; Tsushimoto et al., 1983; Wildemauwe et al., 1983).
Reproductive studies of lindane have had mixed results. Although a low dose (5 mg/kg/day) of lindane had no effect on reproduction in rats, long-term administration of low doses (10 mg/kg/day for 138 days) of lindane reduced fecundity and litter size in one study (Trifonova et al., 1970). Dzierzawski (1977) reported an increase by a factor of 2–20 in the number of resorbed fetuses in hamsters, rabbits, and rats. In another study, a very low dose (0.5 mg/kg/day) of lindane increased the duration of diestrus, shortened the duration of estrus, lengthened the gestation period, decreased the number of fetuses, increased the number of dead fetuses, and decreased the growth of the young (Nayshteyn and Leybovich, 1971). Lindane given to rats by gavage on days 6–15 of gestation had no effect on the numbers of pregnancies, abortions, and dead or resorbed fetuses (Khera et al., 1979).