PERCUTANEOUS-ABSORPTION OF PARATHION AND ITS METABOLITES, PARAOXON AND P-NITROPHENOL, ADMINISTERED ALONE OR IN COMBINATION - IN-VITRO FLOW-THROUGH DIFFUSION CELL STUDIES

The percutaneous absorption of individual pesticides has been well studied. However, the absorption of a mixture of pesticides and decomposition products or metabolites has not received attention. The percutaneous absorption of parathion (PA) relative to its two metabolites, paraoxon (PO) and p-nitrophenol (PNP), was studied in vitro using weanling pig skin in a flow-through diffusion cell system. Concentrations of 4, 40, or 400 ·g/cm2 of PA, PO, PNP, PA + PO (1:1), PA + PNP (1:1), and PO + PNP (1:1) in ethanol were applied topically. Environmental conditions such as air and perfusate temperature (37°C), relative humidity (60%), and flow rate (4 ml/hr) were controlled, and Kreb's-Ringer bicarbonate buffer with 4.5% bovine serum albumin media was used. The total absorption of PA, PO, and the mixed compounds increased as the dose increased, whereas the absorption efficiency (percentage of applied dose absorbed) decreased as the doses increased. For the most water-soluble metabolite, PNP, both total absorption and absorption efficiency increased as the dose increased. Except for the 4 ·g/cm2 dose, the individual compounds followed the absorption order of PNP > PO > PA. For the mixed compounds, the rate of absorption followed the order PO + PNP > PA + PNP > PA + PO for all three dose combinations. However, after HPLC analysis of the perfusate, the amount of absorption of each component (PA, PO, and PNP) in mixed compounds was significantly different (p < 0.05). PNP dramatically enhanced PA absorption, while PA slightly decreased both PO and PNP absorption. This study demonstrated that the absorption data from a single-parent compound or metabolite alone were not adequate to determine the rate of PA absorption from a mixture. Chemical impurities in PA may significantly affect the interpretation of transdermal absorption, metabolism, and risk estimation studies. © 1994 by Academic Press, Inc.