Significant effects of application vehicle, skin occlusion, cutaneous CYP450 induction, and ambient temperature on dermal absorption and cutaneous disposition of pentachlorophenol (PCP).
To assess the impacts of skin exposure variables on dermal absorption and cutaneous disposition of PCP, one of the most highly detected environmental contaminants, 14C-PCp was dosed in ethanol, acetone, a water-ethanol mixture, or a soilbased mixture in a porcine skin flap model (40 ug/cm2, n=3-4/treatment). Effects of vehicle composition, skin occlusion, skin pre-exposure to a CYP 450 inducer (benzo [a] pyrene, B[a]P), and ambient temperature change were examined. Significant exposure-dependency in PCP dermal absorption and tissue disposition were determined: The ex vivo 8-hr dermal absorption varied from 0.2 to 26% under different exposure scenarios. Ethanol and acetone vehicles yielded identical total absorption of 1.1%, but very different absorption profiles. Water addition to the ethanol vehicle dramatically enhanced PCP dermal uptake from 1.1 to 14.1 % (14fold, P<0.05). Mixing soil dust into the liquid water-ethanol vehicle significantly decreased dermal absorption (14.1 -> 3.4%, P<0.05). Occlusion of the dosed skin markedly enhanced dermal absorption (3.4 -> 26%) and cutaneous tissue penetration from the soil matrix. An air temperature drop from 37 to 25 c decreased PCP absorption by 6-fold (ethanol, 1.1 % -> 0.2%, P<0.05). Cutaneous CYP 450 induction by B[a]P pre-exposure tripled the dermal absorption (1.1 -> 3.2%, P<0.05) and decreased the absorption/penetration ratio. In conclusion, organic vehicle selection, water-organic solvent mixing, soil dust mixing, skin occlusion, cutaneous CYP 450 status, and ambient temperature variation can dramatically change dermal absorption and cutaneous disposition, and thus alter local vs systemic risk from occupational and environmental exposures to toxicants similar to PCP.
The Toxicologist. Society of Toxicology 40th Annual Meeting, March 25-29, 2001, San Francisco, California