title: Fenitrothion: toxicokinetics and toxicologic evaluation in human volunteers.
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 X 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 AUC(0-(infinity) )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.
authors.affiliation: Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
authors.forename: Jean
authors.initials: J
authors.lastname: Meaklim
authors.forename: Jinming
authors.initials: J
authors.lastname: Yang
authors.forename: Olaf H
authors.initials: OH
authors.lastname: Drummer
authors.forename: Sheila
authors.initials: S
authors.lastname: Killalea
authors.forename: Voula
authors.initials: V
authors.lastname: Staikos
authors.forename: Soumela
authors.initials: S
authors.lastname: Horomidis
authors.forename: David
authors.initials: D
authors.lastname: Rutherford
authors.forename: Lisa L
authors.initials: LL
authors.lastname: Ioannides-Demos
authors.forename: Stephen
authors.initials: S
authors.lastname: Lim
authors.forename: Allan J
authors.initials: AJ
authors.lastname: McLean
authors.forename: John J
authors.initials: JJ
authors.lastname: McNeil
mesh_terms: D000284:Administration, Oral; D000328:Adult; D002802:Cholinesterases / Q000494:pharmacology; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005278:Fenitrothion / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D006207:Half-Life; D006801:Humans; D007306:Insecticides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D008297:Male; D008875:Middle Aged; D014018:Tissue Distribution
chemical_list: D007306:Insecticides; D002802:Cholinesterases; D005278:Fenitrothion