Distribution and fate of diethyl malonate and dilsopropyl fluorophosphate on pig skin in vitro

The in vitro distribution and fate of [14C]diethyl malonate and [14C]diisopropyl fluorophosphate were evaluated on normal and heat‐treated pig skin. The extent of hydrolysis from the skin surface, skin, and receptor fluid was determined. A significant skin‐mediated hydrolysis (15–35% of applied dose) was observed for diethyl malonate in normal skin, but not in heat‐treated skin. These results indicated that a heat labile process (e.g., enzymatic hydrolysis) was in part responsible for the degradation of diethyl malonate after topical application to normal skin. Heat treatment tripled the skin penetration of diisopropyl fluorophosphate and reduced the amount of recovered hydrolysis product, diisopropyl phosphoric acid. Enzymatic and spontaneous hydrolysis, as well as impurity, accounted for the presence of degradation product.