Alterations in hepatic detoxifying enzymes induced by new organophosphorus insecticides following subchronic exposure in rats.

The present study examined the structure-toxicity relationship of two novel phosphorothionates, a methyl ester (RPR-II) and an ethyl ester (RPR-V), with regard to their interaction with certain biochemical indices in rat. Male rats were treated orally with 10% (low), 20% (medium) and 30% (high) doses of the two compounds (14, 28 and 42 microg kg(-1) day (-1) of RPR-II and 33, 66 and 99 microg kg(-1) day(-1) of RPR-V) daily for 90 days. The activity of hepatic glutathione S-transferase (GST) and UDP-glucuronyl transferase (UDPGT) and the level of glutathione (GSH) were estimated at 0, 45 and 90 days of treatment as well as 28 days after cessation of treatment. RPR-II caused statistically significant depletion of GSH after 45 and 90 days of treatment at the high dose, whereas RPR-V depleted GSH only after 90 days at the high dose. RPR-II inhibited GST after 45 and 90 days at medium and high doses, whereas RPR-V caused inhibition of GST after 45 and 90 days only at the high dose. Significantly, UDPGT activity was increased only by the high dose of RPR-II after 90 days. However, a dose and time-dependent increase in UDPGT activity was observed at all three doses of RPR-V after 45 and 90 days. There was no modulation in any of the three indices at low doses of the two organophosphorus insecticides. The withdrawal study revealed that induced changes in hepatic parameters were reversible 28 days after cessation of treatment. The results indicated that the two insecticides had different potential to modulate hepatic GST, UDPGT and GSH due to subchronic exposure and that these metabolic alterations are quite reversible after withdrawal of treatment. Copyright 2001 John Wiley & Sons, Ltd.