Journal
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES
Volume 74, Issue 5, Pages 325-335Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15287394.2011.534423
Keywords
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Funding
- Consumer Specialty Products Association
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The objectives of this study were to (1) determine the percutaneous absorption of radiolabeled permethrin and piperonyl butoxide (PBO) in vivo in rats and in vitro to permit a calculation of the ratio of in vitro to in vivo values, and (2) test a method of estimating in vivo human absorption. Carbon-14 labeled permethrin in ethanol solution was applied to the clipped skin of rats in vivo at doses of 2.25, 20, or 200 mu g/cm(2). As a reference compound, (14)C-labeled PBO in isopropanol solution was applied to rat skin in vivo at a dose of 100 mu g/cm(2). All applications were washed at 24 h postapplication, and rats were sacrificed either at 24 h for permethrin or 5 d for both compounds. The radiolabel recovered from carcass, urine including cage wash, and feces was summed to determine percent absorption. For the 24-h time point, at doses of 2.25, 20, and 200 mu g/cm(2) of permethrin, values of 22, 22, and 28%, respectively, were obtained for in vivo rat percutaneous absorption (n = 6 per dose). For the 5-d time point, at doses of 2.25, 20, and 200 mu g/cm(2) of permethrin, values of 38, 38, and 30%, respectively, were obtained for in vivo rat percutaneous absorption (n = 6 per dose). The 5-d percutaneous absorption of (14)C-PBO at 100 mu g/cm(2) was determined to be 42% (n = 6). Dose and test duration did not exert a statistically significant effect on percutaneous absorption of permethrin in the rat in vivo. For in vitro absorption determination, (14)C-permethrin in ethanol solution was applied to freshly excised human skin in an in vitro test system predictive of skin absorption in humans. Twenty-four hours after application, the radiolabel recovered from dermis and receptor fluid was summed to determine percent absorption. At doses of approximately 2.25, 20, and 200 mu g/cm(2) permethrin, values of 1, 3, and 2%, respectively, were obtained for percutaneous absorption (n = 9 per dose). Excised human skin absorption of (14)C-PBO at 100 mu g/cm(2) was determined to be 7% (n = 9). Excised rat skin absorptions of permethrin at 2.25, 20, and 200 mu g/cm(2) were found to be 20, 18, and 24%, respectively (n = 6 per dose), approximately 10-fold higher than human skin absorption. Excised rat skin absorption of PBO was also higher (35%) than the value obtained for human skin by a factor of about 5.
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