Cholinesterase inhibition by organophosphorus and carbamate pesticides in aggregate cultures of neural cells from the foetal rat brain: The effects of metabolic activation and pesticide mixtures

Abstract

The effects of pesticide mixtures on cholinesterase activity in aggregate cultures of neural cells were investigated; we also determined whether exogenous rat-liver microsomal fraction (S-9) might be used in conjunction with the cultures to mimic the in vivo activation of pesticides such as malathion. Studies of the effects of pesticide mixtures on the cholinesterase activity of cultures demonstrated that a hepatic microsomal fraction (S-9) played a major role in the nature of the interaction between combinations of malathion and fenitrothion or carbofuran. In the absence of S-9, malathion potentiated the anti-cholinesterase effect of fenitrothion, while neither synergistic nor antagonistic interactions occurred with mixtures of carbofuran and malathion. When S-9 was added to cultures with the pesticide mixtures, malathion's interaction with fenitrothion was antagonistic, and a synergistic response was observed for the mixtures of malathion and carbofuran. The antagonistic interaction of mixtures of fenitrothion and carbofuran was demonstrated to be independent of exogenously added S-9. Neither antagonistic nor synergistic interactions were observed for mixtures of triallate and fenitrothion or carbofuran. The data indicate that the addition of exogenous S-9 may be used to mimic certain aspects of the in vivo biotransformation of pesticides in aggregate cultures of neural cells from rat brain. Furthermore, the effects on cholinesterase activity of several of the pesticide mixtures tested were dependent upon the presence of exogenous S-9.