© 1983 Oxford University Press
research-article |
Unidirectional Cross-Tolerance Between the Carbamate Insecticide Propoxur and the Organophosphate Disulfoton in Mice*
Division of Toxicology, Department of Pharmacology, University of Texas, Medical School at Houston P.O. Box 20708, Houston, TX 77025
Unidirectional Cross-tolerance Between the Carbamate Insecticide Propoxur and the Organophosphate Disulfoton in Mice. Costa, L.G. and Murphy, S.D. (1983). Fundam. Appl. Toxicol. 3:483–488. Previous studies have shown that subchronic treatment of mice with the organophosphate insecticide, disulfoton, or the carbamate insecticide, propoxur, leads to the development of tolerance to their toxicity. Tolerance to disulfoton was due to a decrease in the number of muscarinic cholinergic receptors, while tolerance to propoxur appeared to be due to an induction of hepatic microsomal enzymes. In the present study we investigated if cross-tolerance between disulfoton and propoxur would occur. Cross-tolerance was evaluated by measuring acute toxicities, cholinesterase and carboxylesterase inhibition and hypothermic and antinociceptive effects. Mice tolerant to propoxur were cross-tolerant to the hypothermic and anticholinesterase effects of disulfoton. Similarly, when mice were pretreated with the microsomal enzyme inducer, phenobarbital, the toxicity of disulfoton was decreased. Mice made tolerant to disulfoton were cross-tolerant to the organophosphate chlorpyrifos, but were more sensitive than controls to the toxicity of propoxur. The acute toxicity of the organophosphate malathion was also increased in disulfoton-tolerant mice. Propoxur is metabolized by mixed function oxidases and possibly by a carboxylesterase. While hepatic microsomal enzymes appeared to be unchanged in disulfoton-tolerant mice, brain and liver carboxylesterase activities were significantly inhibited. Pretreatment of mice with the specific carboxylesterase inhibitor triorthotolyl phosphate is known to greatly potentiate the toxicity of malathion and also potentiated, to a lesser extent, the toxicity of propoxur. The results indicate that chronic exposure to an anticholinesterase insecticide may lead to tolerance to the toxicity of the inducing compound by more than one mechanism and that the of other insecticides may be either increased or decreased.