The study of interactive effects of pollutants: a biomarker approach

Biochemical biomarkers, such as inhibition of serum butyryl cholinesterase (BuChE) and brain acetyl cholinesterase (AChE), have been useful in studies of interactive effects of pesticides in birds. Examples of interactions due to increased activation or decreased detoxication are reviewed. Studies have shown that hybrid red-legged partridges (Alectoris rufa cross) pretreated with the inducing ergosterol biosynthesis inhibiting (EBI) fungicide, prochloraz, were more sensitive to the toxic effects of the organophosphorous (OP) insecticide, malathion, than controls. A dose of 90 mg/kg prochloraz produced greater inhibition at 1, 4 and 24 h following oral administration of 50 mg/kg malathion, compared to corn oil controls. Pigeons (Columba livia) given 180 or 90 mg/kg prochloraz showed greater inhibition of BuChE activity following malathion administration than did control birds. Starlings (Sturnus vulgaris), however, appeared not to be induced by 180 or 300 mg/kg prochloraz, and no difference in BuChE activity following dosing with malathion was apparent in comparison with controls. Other EBIs and OP combinations have been investigated in the partridge. Birds pretreated with prochloraz showed a trend towards greater inhibition of serum BuChE activity at most time points following dosing with the OPs dimethoate and chlorpyriphos. Birds pretreated with the EBI penconazole showed significantly greater inhibition of serum BuChE activity at 1, 4 and 24 h after malathion administration than did controls. The mechanism of increased activation of malathion due to induction of cytochrome P-450 by prochloraz is reviewed. In the case of interactions due to inhibition of detoxication, inhibition of brain AChE activity was a useful biochemical biomarker. An increased sensitivity of partridges to the carbamate pesticide, carbaryl, following pretreatment with malathion was attributed mainly to suicide inhibition (by malathion) of cytochrome P-450, resulting in an inhibition of carbaryl metabolism. The enhancement (or potentiation) of toxicity found in these studies was the consequence of modulations of cytochrome P-450-induction (by EBIs) or inhibition (by malathion). More generally, interactions of this kind may also occur between other environmental chemicals, for example, as the consequence of inductions caused by persistent compounds such as PCBs. The biomarker assays for monooxygenases based upon cytochrome P-450 employed in the present study (measurement of enzyme activies and Western blotting) can be used to measure these changes in vertebrates in the field.