The potency of gamma-1,2,3,4,5,6-hexachlorocyclohexane (lindane)

Abstract

The potency of gama-1,2,3,4,5,6-hexachlorocyclohexane (lindane) as a convulsant was examined in rats by infusion into a tail vein of the unrestrained animal using a lipid emulsion as vehicle and a dose rate of 200 μg/min. The concentration of drug in brain rose linearly up to a convulsant level, the rate of rise increasing with relative organ mass. The decline from a convulsant level was biphasic with half times of, respectively, 30 min and 3 days. Convulsant concentrations (CC) in brain were within the range obtained with other modes of administration and exhibited normal distribution but there was a moderate influence of sex, the ovarian cycle, and age on the individual response. The minimally effective and the mean convulsant doses recorded in the survey were, respectively, 1.5 and 2.4 mg/kg and, thus, of the same order as doses reportedly convulsant in the American cockroach as well as, under certain circumstances, in man. In the neonate, the mean CC in brain was 2.5 as against 4.5 μg/g wet weight in the adult. An argument is put forward to support the contention that this difference might be largely accounted for by the maturational increase in the lipid content of the brain. The argument uses an approximation to the mean CC in brain water which is 70 nmol/l in both the young suckling and the adult and corresponds to concentrations in which the drug reportedly effects neuroexcitation in the cockroach nervous system or binds to the ionophore of GABA-A receptors in rat brain membranes. The findings call for convulsive states in children after dermal application of lindane to be considered in terms of individual factors favouring rapid absorption as well as in terms of individual supersensitivity of the nervous system.