Kinetics and thresholds of several indices of lindane-induced toxicity

The effects of lindane, administered either IP (4, 6 or 8 mg/kg in dimethylsulfoxide, 0.5 ml/kg) or PO (30, 40 or 50 mg/kg in oil, 1 ml/kg), were compared in male rats. Effects appeared later and lasted longer after PO administration. After either route, convulsant effects occurred first and were over before hypothermic effects were maximal. Also, hypothermia subsided before hypophagia ended. After IP administration, hypothermia had the lowest threshold and convulsions the next lowest; reduced food intake was produced only by the highest dose, which also produced 43% deaths. By contrast, after PO administration, all doses reduced food intake and produced hypothermia, but deaths did not occur after even the highest dose. The different time courses and thresholds for the different indices of toxicity suggest that different target sites or mechanisms may be involved. Thus, effects on the gut, in addition to effects on the brain, may account for the longer duration and greater sensitivity of reduced food intake, compared to lethal and hypothermic effects, after PO administration of lindane. After administration of lindane IP, peripheral vasodilation (as demonstrated by an increase in tail temperature) preceded colonic hypothermia. This could be explained if lindane inappropriately activated heat-loss mechanisms.