Relationship between lindane concentration in blood and brain and convulsant response in rats after oral or intraperitoneal administration

Abstract

The relationships between brain and blood concentrations of lindane and its convulsant effects have been studied in rats after different po and ip doses. A good correlation was observed between dose and the frequency and time to onset of tonic seizures, the intensity of the response and lethality. An oral ED50 (84 mg/kg) and an ip ED50 (131 mg/kg) for the half-maximal incidence rate of lindane-induced tonic seizures was determined. The incidence of response was directly proportional to the log of lindane concentration in brain and blood, with an EC50 of 5.3 micrograms/g and 1.5 micrograms/ml, respectively. The threshold concentration of lindane eliciting tonic seizures was estimated to be approximately 5 micrograms/g in brain and approximately 1.5 micrograms/ml in blood. The kinetics of lindane in brain and blood were examined after a single 60 mg/kg po or ip dose over a period from 5 min to 1 week. Concentrations of lindane in brain and blood were found to be highly correlated.