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Fenitrothion: Toxicokinetics and Toxicologic Evaluation in Human Volunteers

Jean Meaklim, Jinming Yang, Olaf H. Drummer, Sheila Killalea, Voula Staikos, Soumela Horomidis, David Rutherford, Lisa L. Ioannides-Demos, Stephen Lim, Allan J. McLean and John J. McNeil
Environmental Health Perspectives
Vol. 111, No. 3 (Mar., 2003), pp. 305-308
Stable URL: http://www.jstor.org/stable/3455597
Page Count: 4
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Fenitrothion: Toxicokinetics and Toxicologic Evaluation in Human Volunteers
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Abstract

An unblinded crossover study of fenitrothion 0.18 mg/kg/day [36 times the acceptable daily intake (ADI)] and 0.36 mg/kg/day (72 × ADI) administered as two daily divided doses for 4 days in 12 human volunteers was designed and undertaken after results from a pilot study. On days 1 and 4, blood and urine samples were collected for analysis of fenitrothion and its major metabolites, as well as plasma and red blood cell cholinesterase activities, and biochemistry and hematology examination. Pharmacokinetic parameters could only be determined at the higher dosage, as there were insufficient measurable fenitrothion blood levels at the lower dosage and the fenitrooxone metabolite could not be measured. There was a wide range of interindividual variability in blood levels, with peak levels achieved between 1 and 4 hr and a half-life for fenitrothion of 0.8-4.5 hr. Although based on the half-life, steady-state levels should have been achieved; the area under the curve ( AUC)0-12 hr to AUC0-∞ ratio of 1:3 suggested accumulation of fenitrothion. There was no significant change in plasma or red blood cell cholinesterase activity with repeated dosing at either dosage level of fenitrothion, and there were no significant abnormalities detected on biochemical or hematologic monitoring.

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