ALTERATIONS IN HEPATIC BIOCHEMISTRY OF MICE INTOXICATED WITH MIC, CARBARYL AND THIRAM

The effect of different doses of methyl isocyanate (MIC), carbaryl and thiram on liver microsomal mixed-function oxygenases (MFO) was studied in adult Swiss Portan mice by intraperitoneal (i.p.) injection for different durations. The LD50 dose of all three toxicants after 0.75 h of administration could increase cytochrome P-450 and cytochrome b5 contents (82-143%), and the 1/4LD50 of these compounds could elicit the same effect after 168 h (168-393%). The 1/4LD50 dose of thiram decreased the cytochrome P-450 content below the control level (69.62%) in 0.75 h and the same dose of MIC could decrease the cytochrome P-450 level by 40% compared to the control after 3 days of consecutive injection. The activities of drug-metabolizing enzymes (aminopyrine demethylase-NADH and NADPH-linked-and aniline hydroxylase) were found to increase with all three compounds in general. Marked changes in the activity of the marker enzyme glucose-6-phosphatase were also seen after i.p. injection if MIC, carbaryl and thiram. These findings suggested that these compounds were hepatotoxic, which could be due to their carbamylating nature.