Lindane also has been reported to cause the testes of rats to become atrophied. Seminiferous tubules and Leydig cells degenerated completely over a 10-day treatment period (8 mg/kg/day) (Chowdhury et al., 1987). The decreases in sperm production in mice treated with lindane for 8 months were reversible (Smith, 1991). Lindane also reduced “reproductive behavior” in young rams (Beard et al., 1999).

A number of studies indicate that lindane is not teratogenic. No birth defects were noted in the pups of beagles given lindane (7.5 or 15 mg/kg per day) from gestation day 5 through the end of gestation (US National Library of Medicine, 1995). A three-generation study of rats (Palmer et al., 1978) and experiments with mice (Chernoff and Kavlock, 1983; Gray and Kavlock, 1984) also did not demonstrate any teratogenic effects. Rat offspring exposed to lindane via lactation were reported to have deficiencies that appeared in adulthood; the deficiencies included decreases in testicular weight, lowered number of sperm, and reduced testosterone production (Dalsenter et al., 1997). In utero exposure of rats to lindane reduced [35S]t-butyl bicylcophosphorothionate (TBPS) binding in the brainstem, indicating a decrease in expression of GABAA receptors, but the clinical significance is unknown (Brannen et al., 1998).

Immunotoxic Effects

Weanling rats fed high doses of HCH for 90 days showed hypertrophy of the adrenals, reduction of steroidogenic enzymes, and accumulation of lipids that contain cholesterol (Shivanandappa et al., 1982). Immunosuppression was also reported (Descotes, 1986). Lindane given to weanling rats at low doses suppressed the humoral immune response to typhoid-paratyphoid vaccine (Dewan et al., 1980). Lindane in rats also suppressed the formation of an antibody against human serum albumin and at higher doses inhibited the uptake and lysis of bacteria by phagocytes (Rosival et al., 1974). Reduction of titers in an agglutination test was reported in cats that inhaled lindane and in rabbits that received it in their food (Burkatzkaya, 1963).

N,N-DIETHYL-3-METHYLBENZAMIDE (DEET)

N,N-Diethyl-3-methylbenzamide (N,N-diethyl-m-toluamide; DEET) has been on the worldwide market since the 1950s, and has proved to be an effective, broad-spectrum insect repellent. The compound was developed and patented by the US Army in 1946 for use by military personnel and was registered by US EPA in 1957 (US EPA, 1998). DEET can be applied directly to human skin and to clothing and other materials. It is also used on pets and livestock. It has been estimated that more than 30% of the US population uses DEET during insect-biting seasons. Its use reduces the incidence of vectorborne disease transmission, especially in tropical regions, and of insect bites.

Chemistry

The chemical structure of DEET is shown in Figure 3.5. The DEET in registered formulations must be at least 95% meta-isomer (Figure 3.5), but small amounts of the more toxic ortho-isomer and the less toxic para-isomer are permitted (Robbins and Cherniack, 1986). Formulations vary widely, but most products contain 10–25% DEET in alcohol.



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