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DEVELOPMENT OF AN IN VITRO ASSAY THAT MAY IDENTIFY WHICH ORGANOPHOSPHORUS PESTICIDES ARE MORE TOXIC TO THE YOUNG.
Citation:
Padilla, S., V C. Moser, P. Phillips, H. Sung, AND L. Jackson. DEVELOPMENT OF AN IN VITRO ASSAY THAT MAY IDENTIFY WHICH ORGANOPHOSPHORUS PESTICIDES ARE MORE TOXIC TO THE YOUNG. Presented at Society of Toxicology, Nashville, TN, March 17-21, 2002.
Description:
Some, but not all, organophosphorus pesticides are more acutely toxic to the young as compared to adults. We have developed an in vitro assay which measures the detoxification potential (via carboxylesterase and A-esterases) of tissues. Previous results using this in vitro assay correlated with the marked in vivo sensitivity of the young to chlorpyrifos and also correlated with the equal sensitivity of the young and adult to methamidophos (Padilla et al., Neurotoxicology, 2000). We have now extended these observations to two other pesticides which have already been shown in the literature to be more toxic to the young: paraoxon and malathion. In our in vitro assay, liver and plasma from 7-day old rats were much less effacacious than adult tissues at detoxification of the active metabolites of these two pesticides. Using our in vitro assay we also tested the active metabolite of diazinon, diazoxon, and again found that young liver or plasma possessed much less detoxification capability than adult tissues. From these results, we predicted that young animals would be more sensitive to diazinon, which, in fact, was the case: when postnatal day (PND)17 or adult rats were given a dosage of 75 mg/kgdiazinon, adult brain cholinesterase (ChE) was only inhibited 38% while the brain ChE in the PND 17 animals showed much more inhibiton (75%). Furthermore, higher doses (200-500 mg/kg) were lethal to PND17 rats but adults only showed signs of toxicity. We conclude that our in vitro test may prove to be a useful, quick convenient test for predicting age-related sensitivity to organphosphorus pesticides.
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