Neurotoxicity of 1-methoxycycloheptatriene--a Purkinje cell toxicant

The toxicity of 1-methoxycycloheptatriene (1-MCHT), a sensory irritant, has been investigated in beagles. It was found to produce gross inco-ordination of the limbs at intravenous doses greater than 10 mg kg-1. The main histological abnormalities were in the cerebellum and consisted of Purkinje cell death and subsequent reactive gliosis. A few necrotic neurons were seen in the diencephalon, pons and medulla. Haematological abnormalities, e.g. leucocytosis with relative lymphopenia, were seen, while biochemical changes included hyperglycaemia and a rise in plasma aminotransferases. The no-effect dose for the histological and biochemical changes was the same. These abnormalities are compared with cerebellar changes observed in acrylamide and other toxic states.