Assessing Delayed Neurotoxicity in Rodents after Nerve Gas Exposure

Abstract

Delayed neurotoxicity of an organophosphorus nerve gas Sarin (a chemical warfare agent) following repeated inhalation exposure in rats and mice, was studied by behavioural, biochemical and histopathological analyses. Rats exposed to Sarin aerosols (12.5 mg/m/sup 3/ for 20 min) daily for ten days did not exhibit any clinical sign of delayed neurotoxicity. Neurotoxic esterase (NTE) activity in the brain, spinal cord and platelets was significantly inhibited, but the inhibition was below the threshold. Histopathological examination of spinal cord did not show any axonal degeneration. Mice exposed to Sarin aerosols (5 mg/m/sup 3/ for 20 min) daily for ten days developed mild ataxia and muscular weakness of the hind limb on 14th day after the start of exposure. NTE activity was significantly inhibited in brain, spinal cord and platelets. Histopathology of spinal cord showed focal axonal degeneration. Acetyl-choline esterase activity in the platelets of both the animals was significantly inhibited. We conclude that mice are sensitive to delayed neurotoxicity induced by repeated exposure to sarin whereas rats are insensitive.