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.
Full Text
The Full Text of this article is available as a PDF (145.3 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Nosál M., Hladká A. Determination of the exposure to fenitrothion (0,0-dimethyl-0-3-methyl-4-nitrophenyl-thiophosphate) on the basis of the excretion of p-nitro-m-cresol by the urine of the persons tested. Int Arch Arbeitsmed. 1968;25(1):28–38. doi: 10.1007/BF00404665. [DOI] [PubMed] [Google Scholar]
- Tamura H., Maness S. C., Reischmann K., Dorman D. C., Gray L. E., Gaido K. W. Androgen receptor antagonism by the organophosphate insecticide fenitrothion. Toxicol Sci. 2001 Mar;60(1):56–62. doi: 10.1093/toxsci/60.1.56. [DOI] [PubMed] [Google Scholar]