title: Interactions of chlorpyrifos and methyl mercury: a mechanistic approach to assess chemical mixtures.
abstract: The mechanism of interaction between chlorpyrifos, an organophosphate insecticide, and methyl mercury was assessed utilizing the amphipod, Hyalella azteca. Previous studies have demonstrated that chlorpyrifos and methyl mercury interact additively with survival as the endpoint. In addition, exposure to chlorpyrifos and methyl mercury increased the accumulation and decreased the elimination of methyl mercury. To further examine the mechanism responsible for these interactions, the in vivo and in vitro inhibition of acetylcholinesterase enzyme activity was assessed following exposure to methyl mercury and chlorpyrifos. In vivo, methyl mercury antagonized the effects of chlorpyrifos on acetylcholinesterase inhibition. Additional studies demonstrated that methyl mercury did not affect the in vitro bioactivation of chlorpyrifos or the subsequent inhibition of acetylcholinesterase enzyme activity. Chemical-chemical interactions were examined utilizing chromatographic techniques and suggested the formation of a chlorpyrifos-methyl mercury complex. The formation of this complex may result in increased accumulation of methyl mercury, apparent additive toxicity, and protection against chlorpyrifos-mediated acetylcholinesterase inhibition.
authors.affiliation: Environmental and Community Health Research and Department of Pharmacology, School of Pharmacy, University of Mississippi, University, MS 38677, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Steevens
authors.forename: W H
authors.initials: WH
authors.lastname: Benson
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D004390:Chlorpyrifos / Q000008:administration & dosage / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000633:toxicity; D002855:Chromatography, Thin Layer / Q000662:veterinary; D003445:Crustacea / Q000187:drug effects*; D004347:Drug Interactions; D007306:Insecticides / Q000633:toxicity*; D008767:Methylmercury Compounds / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D002800:Cholinesterase Inhibitors; D007306:Insecticides; D008767:Methylmercury Compounds; D000110:Acetylcholinesterase; D004390:Chlorpyrifos