Metabolism of fluroxypyr, fluroxypyr methyl ester, and the herbicide fluroxypyr methylheptyl ester. I: During percutaneous absorption through fresh rat and human skin in vitro

Percutaneous absorption of pesticides is a major determinant for risk asses sment. Furthermore, cutaneous metabolism plays a role in penetration of cer tain chemicals. Therefore, the aim of these studies was to determine the tr ansdermal metabolism of three related compounds [the herbicide, fluroxypyr methylheptyl ester (FPMH), fluroxypyr methyl ester (FPM), and fluroxypyr (F P)] during penetration through human and rat skin in vitro. The data presen ted in this article show that both FPM and FPMH were completely metabolized during their passage through human and rat skin in vitro. The only metabol ite produced was that of the hydrolysis product, FP, with no parent ester p enetrating through the skin. The extent of FP formation within the skin was directly correlated to the degree of stratum corneum reservoir formation. The larger the stratum corneum reservoir, the lower the levels of FP recove red from within the skin. This suggests that as the ester partitioned out o f the SC it was immediately hydrolyzed to FP, which could then pass freely through the remainder of the epidermis and dermis. Similar metabolic profil es were observed for the transdermal metabolism of FPM and FPMH in previous ly frozen rat skin, indicating the robust nature of the esterase enzymes in volved. In conclusion, systemic exposure after skin contact with FPM or FPM H is likely to be to the acid metabolite, FP, only and not to the parent es ter. In addition, the rate and extent of percutaneous absorption will be a major determinant of cutaneous metabolism.