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|Title||Organophosphorus pesticide degradation product in vitro metabolic stability and time-course uptake and elimination in rats following oral and intravenous dosing.|
|Publication Type||Journal Article|
|Year of Publication||2011|
|Authors||Forsberg ND, Rodriguez-Proteau R, Ma L, Morré J, Christensen JM, Maier CS, Jenkins JJ, Anderson KA|
|Administration, Oral, Animals, Environmental Monitoring, Humans, Injections, Intravenous, Male, Mass Spectrometry, Organophosphorus Compounds, Pesticides, Rats, Rats, Sprague-Dawley, Time Factors|
Levels of urinary dialkylphosphates (DAPs) are currently used as a biomarker of human exposure to organophosphorus insecticides (OPs). It is known that OPs degrade on food commodities to DAPs at levels that approach or exceed those of the parent OP. However, little has been reported on the extent of DAP absorption, distribution, metabolism and excretion. The metabolic stability of O,O-dimethylphosphate (DMP) was assessed using pooled human and rat hepatic microsomes. Time-course samples were collected over 2 h and analyzed by LC-MS/MS. It was found that DMP was not metabolized by rat or pooled human hepatic microsomes. Male Sprague-Dawley rats were administered DMP at 20 mg kg(-1) via oral gavage and i.v. injection. Time-course plasma and urine samples were collected and analyzed by LC-MS/MS. DMP oral bioavailability was found to be 107 ± 39% and the amount of orally administered dose recovered in the urine was 30 ± 9.9% by 48 h. The in vitro metabolic stability, high bioavailability and extent of DMP urinary excretion following oral exposure in a rat model suggests that measurement of DMP as a biomarker of OP exposure may lead to overestimation of human exposure.
|PubMed Central ID||PMC3148839|
|Grant List||P30 ES000210 / ES / NIEHS NIH HHS / United States |
P30 ES000210 / ES / NIEHS NIH HHS / United States
P30 ES000210-38 / ES / NIEHS NIH HHS / United States