Acute toxicity of methyl isocyanate, administered subcutaneously in rabbits: changes in physiological,...

Subcutaneous administration of methyl isocyanate (MIC) in 0.5 LD50 and 1 LD50 doses in female rabbits resulted in significant changes in physiological, clinico-chemical and histological parameters. There was a fall in arterial blood pressure and cardioacceleration in both the 0.5 LD50 and 1 LD50 groups, while the respiration showed a differential response in these groups with the former showing hyperpnoea and the latter showing respiratory inhibition. A significant increase in the arterial blood lactic acid, lactate/pyruvate ratio and 2,3-diphosphoglycerate levels, and the significant changes in acid-base status of both arterial and venous blood indicated tissue hypoxia of a stagnant type. Histopathological observations revealed a mild to moderate degree of congestion, focal lymphocytic infiltrations and necrosis in all visceral organs examined. These findings suggest that acute toxicity of MIC in vivo may be mediated by its effects on vascular beds.