Dose-additive design, mixture studies

A recent study of Moser eoworkers (2005) Mo,ser et uL (2005), using a do.se-additive design with mixtures of five commonly used OP pesticides (chlorpyrifos, diazinon, dimeihoate, acephaic, and malathion), showed a more-than-additive interaction on multiple end points blood and brain cholinesterase inhibition, motor activity, and gait score (tail-pinch response did not. show a more-than-additive interaction). This study is noteworthy because (i) relatively sensitive end points were used to test the toxic interaction of the OP pesticides, such as cholinesterase inhibition or depression of motor activity (ii) more than two OP compounds were used in the mixture and (iii) comprehensive statistical analyses of the data were performed. The pharmacokinetic interaction of two of the aimpounds in the mixture, chlorpyrifos and diazinon, has been studied in rats (Timchalk et a ., 2004). The authors found that one compound did not affect the pharmacokinetics of the other unless high doses were given, concluding that a more-than-additive interaction is unlikely at environmentally relevant concentrations. 

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