Mechanistic aspects of organophosphorothionate toxicity in fish and humans

Metabolic transformation plays a major role in the mechanism of toxicity of organophosphorous (OP) pesticides. The modulation of their toxicity by oxonases and monooxygenases, alone or in combination, has been shown in mammals and fish. Very limited information exists for the identification of the metabolic factors relevant in the human toxicology of such chemicals. In this paper, we develop a simple algorithm, based on in vitro data, for the identification of fish species more susceptible to diazinon (D). Similar algorithms are likely to be applicable to other organophosphothionate (OPT) pesticides. We also report on preliminary studies on the OPT substrate specificity of human liver cytochromes P450 (CYPs): such information may be useful to understand the role of sulphoxidation in OPT toxicity to humans and to identify individuals with increased susceptibility to OPT toxicity. Studies of the mechanism of OPT toxicity may provide useful tools for a more detailed characterisation of these chemicals, with reference to the risk for the human population and to the impact on the fish species present in specific environments.