Inhibition of methyl isocyanate toxicity in mice by starvation and dexamethasone but not by sodium thiosulfate, atropine, and ethanol.
Effects of starvation (24 and 48 h), dexamethasone, sodium thiosulfate, atropine, and ethanol on the toxicity of methyl isocyanate (MIC) vapor, which escaped during the Bhopal accident of December 3, 1984, were studied in male Swiss-Webster mice. Toxicity to MIC appeared to be biphasic; majority of animals died between 1 and 2 d or between 7 and 21 d after exposure to 40 ppm MIC. Starvation (24 or 48 h) or an injection of 2 mg dexamethasone/kg prior to exposure inhibited the toxicity of MIC, especially during the first 6-7 d; administrations of sodium thiosulfate, alcohol, and atropine before or of dexamethasone after the exposure to MIC were ineffective. Starvation increased serum corticosterone levels. The antidotal effects of both starvation and dexamethasone might be due to suppression of the inflammatory response to MIC.
Varma
D R
DR
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
Ferguson
J S
JS
Alarie
Y
Y
D000818:Animals; D001273:Atmosphere Exposure Chambers; D001285:Atropine / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D003485:Cyanates / Q000037:antagonists & inhibitors* / Q000633:toxicity; D003907:Dexamethasone / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D017953:Isocyanates; D008297:Male; D051379:Mice; D013217:Starvation / Q000503:physiopathology*; D013885:Thiosulfates / Q000494:pharmacology*
D003485:Cyanates; D017953:Isocyanates; D013885:Thiosulfates; D000431:Ethanol; D001285:Atropine; D003907:Dexamethasone; C008461:methyl isocyanate; C017717:sodium thiosulfate; D003345:Corticosterone