Metabolism and kinetics of endosulfan in rats.

Mustafa Ali Mohd¹, Abdul Rani Abdullah² and Melissa Chan Pui Ling¹

Department of Pharmacology, Faculty of Medicine, University of Malaya,

²Alam Sekitar Malaysia (ASMA) Sdn. Bhd., Malaysia

The LD₅₀ of endosulfan (isomeric mixture) varies widely depending on the mode of administration, species, dosing vehicle and sex of the animal. It was apparent from the studies on oral LD₅₀ of endosulfan (Gupta and Gupta, 1977) that female rats (8 - 49 mg/kg) were more susceptible than male rats (47 – 89 mg/kg) to its acute lethal action, often by one order of magnitude or more. Stimulation of the Central Nervous System (CNS) is the major characteristic of endosulfan poisoning (Farm Chemicals Handbook, 1992). The clinical signs of intoxication include piloerection, salivation, hyperactivity, respiratory distress, diarrhea, tremors, hunching and convulsions.

In this study, technical grade endosulfan was administered to male Sprague-Dawley rats orally at a dose level of 10 mg/kg body weight, blood was sampled at selected intervals and analysed for a-endosulfan, b-endosulfan, endosulfan sulfate and endosulfan diol. The concentrations of the parent compound and metabolites were determined in the kidneys and livers seven days following administration.

The plasma concentration of a-endosulfan as a function of time was found to best fit a one-compartment model, with estimated biological half-life of 55 minutes and not detected after four hours following administration.

a-endosulfan and b-endosulfan were detected in the kidneys averaging 0.38 ± 0.17 mg/g and 0.35 ± 0.19 mg/g respectively. Endosulfan sulfate and the diol were undetected in the kidneys and liver.

The body weight and the weights of the liver, kidneys, testes and epididymis in treated animals were statistically insignificant compared to control rats (p > 0.05). However, the sera testosterone levels in treated animals were significantly lower than control animals (p < 0.05).