Induction of trimethyltin neurotoxicity by dietary administration

Groups of 12 male and 12 female rats were fed diets containing 0 or 8ppm trimethyltin chloride for up to 25 days. All the animals were observed prior to the study start and daily throughout the study for any changes in clinical condition. In addition, detailed clinical observations, including quantitative assessments of landing foot splay, sensory perception, muscle weakness and locomotor activity were monitored during the study. At the end of the study, the rats were killed and subjected to a full Post-mortem. Selected nervous system tissues were removed, processed and examined microscopically. Clinical signs typical of trimethyltin neurotoxicity (e.g. aggression, shaking and convulsions) were seen in rats receiving diets containing 8ppm trimethyltin chloride for as little as 22 days. Neuropathological lesions consisting of extensive neuronal cell necrosis in the limbic region of the brain, vacuolar degeneration of ventral horn cells of the spinal cord and a marginal increase in Wallerian-type degeneration were seen. The study demonstrates that trimethyltin neurotoxicity can be induced by dietary administration and that both male and female rats are equally sensitive.