Percutaneous absorption of an insect repellent p-menthane-3,8-DIOL: a model for human dermal absorption

p-Menthane-3,8-diol(38DIOL) was recently introduced as a natural topical insect repellent in the commercial product "OFF! Botanicals" lotion. The objective of this study was to provide an estimate of the potential for 38DIOL systemic absorption in humans. Carbon-14-labeled 38DIOL formulated in the lotion and in an ethanol solution was applied to excised pig skin in an in vitro flow-through test system predictive of skin absorption in humans. Twenty-four hours after application, radiolabel recovered from the dermis and receptor fluid was summed to determine percent absorption. At a dose of approximately 80 microg/cm(2) of 38DIOL in the lotion, a value of 3.5 +/- 0.8% of applied dose was obtained with pig skin. The corresponding value for 38DIOL in ethanol (90 microg/cm(2)) was not significantly different (3.0 +/- 1.2%). Most of the applied dose of 38DIOL was found to evaporate from pig skin (77 +/- 8% for the lotion and 87 +/- 1% for ethanol solution), thus limiting percutaneous absorption values. For reference purposes, the pig skin absorptions of piperonyl butoxide (PBO) at 100 microg/cm(2) in isopropanol, N,N-diethyl-m-toluamide (DEET) at 500 microg/cm(2) in ethanol, and neat isododecane at 650 microg/cm(2) (in order of increasing volatility) were 15 +/- 6%, 23 +/- 3%, and 0.09 +/- 0.05% of applied dose respectively. Isododecane was lost almost exclusively from the skin surface by evaporation. For additional reference, absorptions of PBO, DEET, and 38DIOL were found to be higher with excised rat skin.