title: Further assessment of an in vitro screen that may help identify organophosphorus pesticides that are more acutely toxic to the young.
abstract: Some, but not all, organophosphorus pesticides are more acutely toxic to the young as compared to adults. We have developed an in vitro assay that measures the detoxification potential (via carboxylesterase and A-esterases) of tissues. Previous results using this in vitro screen 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., 2000). We have now extended these observations to two other pesticides that have already been shown in the literature to be more toxic to the young: parathion (paraoxon) and malathion (malaoxon). In our in vitro assay, liver or plasma from 7-d-old rats were much less efficacious 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/kg diazinon, adult brain cholinesterase (ChE) was only inhibited 38%, while the brain ChE in the PND 17 animals showed much more inhibition (75%). We conclude that our in vitro screen may prove to be a useful, quick, convenient test for identifying which organophosphorus pesticides may be more acutely toxic to the young as compared to adults.
authors.affiliation: Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, North Carolina 27711, USA. padilla.stephanie@epa.gov
authors.forename: S
authors.initials: S
authors.lastname: Padilla
authors.forename: H-J
authors.initials: HJ
authors.lastname: Sung
authors.forename: V C
authors.initials: VC
authors.lastname: Moser
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001681:Biological Assay / Q000379:methods* / Q000592:standards; D005260:Female; D066298:In Vitro Techniques; D008658:Inactivation, Metabolic; D007306:Insecticides / Q000378:metabolism / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008294:Malathion / Q000031:analogs & derivatives* / Q000633:toxicity; D008297:Male; D008403:Mass Screening / Q000379:methods* / Q000592:standards; D023421:Models, Animal; D009943:Organophosphorus Compounds / Q000633:toxicity; D010261:Paraoxon / Q000633:toxicity; D010949:Plasma / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011874:Radiometry / Q000379:methods / Q000592:standards; D051381:Rats; D020318:Rats, Long-Evans; D013053:Spectrophotometry / Q000379:methods / Q000592:standards; D018675:Toxicity Tests / Q000379:methods* / Q000592:standards
chemical_list: D007306:Insecticides; D009943:Organophosphorus Compounds; C100082:malaoxon; C000912:diazoxon; D010261:Paraoxon; D008294:Malathion