Binary combinations of organophosphorus pesticides exhibit differential toxicity under oxidised and un-oxidised conditions

Abstract

Acetylcholinesterase (AChE) inhibition has been demonstrated to be useful as a biomarker for exposure to organophosphorus (OP) insecticides in many environments. The objective of this study was to investigate the response of housefly (Musca domestica) head AChE (HF-AChE) exposed to five OPs as individual compounds and their binary mixtures under in vitro conditions. To examine the effects of oxidation on OP potency in the HF-AChE system, bromine water was used as an oxidisng agent. With oxidation, the sensitivity of HF-AChE to chlorpyrifos (CPF), malathion (MLT) and triazophos (TRZ) increased significantly. Monocrotophos (MCP) and profenofos (PRF) did not exhibit any significant differences in toxicity under oxidised and un-oxidised conditions. The toxicological interaction of five organophosphorus pesticides was evaluated using the concentration addition model, the combination index–isobologram equation and the toxic unit approach. All three models provided similar predictions for the 10 binary combinations of OPs under oxidised and un-oxidised conditions. In the present study, the antagonistic effects of the binary combination of OPs (CPF+PRF, CPF+MLT, MCP+MLT, PRF+MLT, MLT+TRZ and PRF+TRZ) were observed under oxidised conditions. This may be due to dispositional and/or receptor antagonism. Most of the binary combinations assayed under un-oxidised conditions exhibited synergistic responses. Triazophos showed very strong synergism in binary combinations with CPF, MCP and PRF un-oxidised conditions. In contrast, under oxidised conditions, only CPF+TRZ exhibited synergism. The results obtained indicate differential toxicity of binary combinations of OPs under oxidised and un-oxidised conditions. This information could be a valuable tool in understanding the mechanisms of OPs interactions and the interpretation of future in vivo studies with mixtures of OP insecticides.