Absorption and Metabolism of Dermally Applied Phenothrin in Rats

Abstract

In dermal treatment of male rats with dust and emulsifiable concentrate (E. C.) of both ¹⁴C-[(+)-trans]- and ¹⁴C-[(+)-cis]-phenothrin at the rates of 0.2 and 2mg/rat, the ¹⁴C absorption into the body was estimated to be 3-7% of the initial dose with dust and 8-17% with E. C. The absorption rate of ¹⁴C was 4-5 times faster with E. C. than with dust, whereas the half-life of ¹⁴C in the blood was 2-3 times longer with E. C. than with dust. The radiocarbon absorbed through the skin was almost completely eliminated into urine and feces 6 days after treatment. The ¹⁴C tissue residues were very low, except on the treated portion of skin. With single oral administration of both isomers of ¹⁴C-phenothrin, roughly 96% of the dose was recovered into the excreta during the following 6 days; a larger amount of ¹⁴C was excreted into the feces with the [(+)-cis]-isomer and into the urine with the [(+)-trans]-isomer. Nearly the same metabolites were obtained in oral and dermal treatments with either the [(+)-trans] or the [(+)-cis]-isomer, although the nature and amount of metabolites differed. The major metabolites from the [(+)-trans]-isomer were 3-phenoxybenzoic acid (free and glycine conjugate) and 3-(4′-hydroxyphenoxy) benzoic acid (free and sulfate), although small amounts of ester metabolites were also obtained. The cis-isomer afforded larger amounts of ester metabolites which resulted from oxidation at the 4′-position of the alcohol moiety, at the trans and cis methyl of the isobutenyl group, at the trans methyl of the gem-dimethyl group of the acid moiety and at combinations of these oxidations; the amount of the ester-cleaved metabolites was about one-fifth of those from the trans-isomer. It is likely that in dermal treatment, once entering the blood stream through the skin, the phenothrin isomers are metabolized in a manner similar to oral administration.