Hiromichi Hasegawa

Neurotoxicity and metabolism of methyl bromide in rats

Changes in locomotor activity, body temperature, and body weight gain, and the enhancement of thiopental-induced sleep were investigated in rats as indices of the functional changes in the CNS caused by methyl bromide (CH3Br) exposure. The correlations of these behavioral changes with CH3Br metabolism are discussed. The LC50 value and its 95% confidence limits for an 8-hr exposure of CH3Br was 302 ppm (267-340) ppm. Effects were examined following exposure to 63, 125, 188, or 250 ppm CH3Br for 8 hr. CH3Br concentrations as low as 63 ppm remarkably enhanced the sleep-inducing potency of thiopental, but CH3Br exerted no effect on thiopental metabolism. The body temperature and body weight gain were decreased at exposure to concentrations of 125 ppm or higher, and locomotor activity was reduced at 188 ppm or higher. These effects were reversible and, at 24 hr after the exposure, locomotor activity and body temperature were almost the same as in control rats. In a time-course study of CH3Br, bromine, and methyl alcohol, CH3Br was rapidly eliminated from rat tissues following the cessation of exposure, with a half-life of about 30 min in the early post-exposure period. In contrast, the elimination rate of bromine was very slow, with a half-life about 5 days. The methanol amount was below that reported to induce the changes in CNS functions. These results suggest that the CNS depression caused by CH3Br exposure may be due to the CH3Br molecule or the methyl moiety incorporated into tissues and may not be attributable to bromine or methanol. A linear relationship was obtained between bromine amounts in blood and the exposure concentration or duration. This result suggests the possibility that the extent of CH3Br exposure may be estimated from the bromine quantities in blood.

EFFECT OF PHENYLHYDRAZINE ON THE OXIDATION OF OXYHAEMOGLOBIN BY SODIUM NITRITE

In the previous papers, the oxidation mechanism of oxyhaemoglobin by sodium nitrite and the effects of various substances on the oxidizing reaction were investiga-ted. In the present paper, the effect of phenylhydrazine on the oxidation of oxy-haemoglobin was studied parallel with the haematological change. In the poisoned rabbits, the decrease of the red blood cells and the formation of Heinz-bodies were observed. At the same time, the oxidation rate of oxyhaemoglobin prepared from the poisoned rabbits was found to be notably reduced with increasing dose of the poison. The change of the oxidation rate was further ascertained by the experiments in vitro, although there were some differences between the results in vivo and in vitro.The measurement of the oxidation rate of oxyhaemoglobin prepared from the blood of animals exposed to poisonous substances, which cause the blood changes, seems to be useful for the early detection of the poisoning.