Histopathology of acute toxic response in rats and mice exposed to methyl chloride by inhalation

Abstract

Histopathology of Acute Toxic Response in Rats and Mice Exposed to Methyl Chloride by Inhalation. Morgan, K.T., Swenberg, J.A., Hamm, T.E., Jr., Wolkowski-Tyl, R. and Phelps, M. (1982). Fundam. Appl. Toxicol. 2:293–299. Both sexes of one strain of rat (F344), two strains of mice (C3H and C57BL/6) and the cross (B6C3F1) of these 2 strains of mice were exposed by inhalation to methyl chloride for 6 hours per day for up to 12 days. Methyl chloride concentrations in air were 0, 500, 1000, or 2000 ppm for mice, and 0, 2000, 3500 or 5000 ppm for rats. All male B6C3F1 mice exposed to 2000 ppm were dead or moribund by day 2, and all male and female mice in the remaining 2000 ppm groups were moribund by day 5. Prior to death many of these mice exhibited ataxia, and hematuria with the latter occurring mainly in females. Treatment associated lesions in mice included hepatocellular degeneration and necrosis, degeneration and necrosis of proximal convoluted tubules and/or basophilic tubules in the renal cortex, and focal areas of necrosis of the internal granular layer of the cerebellum. Brain lesions were most severe in female C57BL/6 mice, while hepatocellular degeneration was most severe in male C57BL/6 and B6C3F1 strains. Approximately 50% of the male and female rats exposed to 5000 ppm were killed in extremis on day 5. The principal clinical signs, which were confined to the 5000 and 3500 ppm groups, included severe diarrhea, incoordination of the fore-limbs, and in a small number of animals, hind limb paralysis and convulsions. In rats, lesions were observed in the liver, kidney and brain which resembled those seen in mice but were generally less severe. Lesions observed in tissues examined only in rats included vacuolar degeneration of the zona fasciculata of the adrenal glands and degenerative changes in the seminiferous tubules and epididymis. Rats appeared to respond in a similar manner to mice but were more resistant to methyl chloride toxicity. These findings demonstrate species, strain and sex differences in susceptibility to methyl chloride.