Metabolic Studies on the Mechanisms of Increased Susceptibility of Weanling Rats to Parathion

Abstract

Equitoxic doses of 32P-parathion (1.5 mg/kg in weanlings of both sexes, 2.0 mg/kg in adult females, and 3.1 mg/kg in adult males) were given by the intravenous route to immature and adult rats in order to investigate the respective contribution of biotransformation, distribution, and excretion phenomena to the increased susceptibility of weanling rats to the acute toxic effects of parathion. At various intervals, the animals were sacrified and the amounts of parathion, paraoxon, diethylphosphorothioic acid, and diethylphosphoric acid in the liver, kidneys, tibial muscle, plasma, brain, adipose tissue, and urine were determined. In vitro metabolism of 32P-parathion by liver homogenates was also investigated. The results obtained suggest that weanlings are more susceptible to parathion than adults mainly because of deficient hepatic mechanisms for degradation of parathion and its toxic metabolite, paraoxon. In addition, the brain tissue of weanlings appears to be more sensitive to the toxic effects of paraoxon than the brain of male adults. On the other hand, the passage of parathion and paraoxon across the blood–brain barrier does not seem to be facilitated in weanlings by comparison with adults. Finally, there is no evidence that the renal handling of parathion and its metabolites might influence the acute toxicity of parathion in weanling and adult rats.