43 research outputs found

    Enhanced drug-metabolizing capacity within liver adjacent to human and rat liver tumors.

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    Semen quality in Peruvian pesticide applicators: association between urinary organophosphate metabolites and semen parameters

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    <p>Abstract</p> <p>Background</p> <p>Organophosphates are broad class of chemicals widely used as pesticides throughout the world. We performed a cross-sectional study of associations between dialkylphosphate metabolites of organophosphates and semen quality among pesticide applicators in Majes (Arequipa), Peru.</p> <p>Methods</p> <p>Thirty-one men exposed to organophosphate (OP) pesticides and 31 non-exposed were recruited (age, 20–60 years). In exposed subjects, semen and a blood sample were obtained one day after the last pesticide application. Subjects were grouped according to levels of OP metabolites in urine. Semen samples were analyzed for sperm concentration, percentage of sperm motility, percentage of normal morphology, semen leucocytes and concentrations of fructose and zinc. Exposure to OP was assessed by measuring six urinary OP metabolites (dimethyl and diethyl phosphates and thiophosphates) by gas chromatography using a single flame photometric detector.</p> <p>Results</p> <p>Diethyldithiophosphate (p = 0.04) and diethylthiophosphate (p = 0.02) better reflected occupational pesticide exposure than other OP metabolites. Semen analysis revealed a significant reduction of semen volume and an increase in semen pH in men with OP metabolites. Multiple regression analysis showed that both occupational exposure to pesticides and the time of exposure to pesticides were more closely related to alterations in semen quality parameters than the single measurement of OP metabolites in urine.</p> <p>Conclusion</p> <p>The study demonstrated that occupational exposure to OP pesticides was more closely related to alterations in semen quality than a single measurement of urine OP metabolites. Current measurement of OP metabolites in urine may not reflect the full risk.</p

    Factors involved in the differential acute toxicity of the insecticides chlorpyrifos and methyl chlopyrifos in mice

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    The ip LD50s of the insecticides chlorpyrifos [O,O-diethyl O-(3,5,6-trichloro-2-pyridyl) phosphorothioate] and methyl chlorpyrifos [O,O-dimethyl O-(3,5,6-trichloro-2-pyridyl) phosphorothioate] were determined to be 192 and 2325 mg/kg, respectively, in male mice. In an attempt to explain this 12-fold difference in toxicity, the extent of glutathione (GSH)-dependent detoxification of chlorpyrifos, methyl chlorpyrifos, and their oxygen analogs was examined. Incubation of 1000 nmol of insecticides with GSH-fortified mouse liver cytosol resulted in the disappearance of 458 and 819 nmol of chlorpyrifos oxon and methyl chlorpyrifos, respectively. However, chlorpyrifos and methyl chlorpyrifos oxon were not substrates for GSH-dependent biotransformation in vitro. Pretreatment of mice with diethyl maleate resulted in a 2.0- and 8.5-fold increase in the acute toxicities of chlorpyrifos and methyl chlorpyrifos, respectively. Administration of methyl chlorpyrifos (1000 mg/kg) to mice produced a marked, prolonged depletion of hepatic GSH, while administration of chlorpyrifos (70 mg/kg) resulted in a moderate, transient decrease in hepatic GSH content. Both doses inhibited brain and plasma cholinesterase, and brain and liver nonspecific esterase activities to a similar degree. HPLC analyses of brain concentrations of methyl chlorpyrifos and chlorpyrifos revealed that brain levels of methyl chlorpyrifos 46 times greater than those of chlorpyrifos were required to achieve the same degree of brain cholinesterase inhibition. Furthermore, the concentration of methyl chlorpyrifos oxon needed to produce 50% inhibition of bovine red blood cell or mouse brain cholinesterase was 480 times greater than that required for chlorpyrifos oxon. These data suggest that differences in the extent of GSH-mediated detoxification can account for only a portion of the observed differences in acute toxicity between chlorpyrifos and methyl chlorpyrifos. © 1982

    Determination of organophosphorus insecticides, their oxygen analogs and metabolites by high pressure liquid chromatography

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    A convenient procedure for the extraction and determination of three organophosphate insecticides, their active oxygen analogs, and their inactive metabolites in biological tissues is described. The utility of this technique is demonstrated by measurement of the in vitro biotransformation of both parathion and chlorpyrifos by mouse hepatic microsomes. © 1982 Friedr. Vieweg &amp; Sohn Verlagsgesellschaft mbH
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