Percutaneous Absorption and Excretion of Xenobiotics after Topical and Intravenous Administration to Pigs

Interspecies comparisons suggest that the weaning pig is a suitablesurrogate for man in percutaneous absorption studies. Despiteknown anatomical and physiological similarities between porcineand human skin, very few investigations of percutaneous absorptionphenomena have been conducted in pigs. This study examined radiolabelexcretion patterns after intravenous (iv) and topical administrationof six ¹⁴C-radioIabeled compounds in weanling Yorkshire sows.Radiolabel recovery from excrement collected over 6 days followingiv doses in physiological saline (200 µg, 10 µCi)showed that malathion (M), parathion (P), caffeine (C), andbenzoic acid (B) were primarily excreted into urine (>80%),while greater fractions of testosterone (T, 72%) and progesterone(R, 35%) were fecally eliminated. Percutaneous absorption wasdetermined from total urine and fecal excretion of radiolabelafter topical application, corrected for incomplete excretionfollowing iv administration. Topical doses in ethanol (200 µg,10 µCi) were applied at a surface concentration of 40µg cm^–2 and penetrated in the following rank order(percentage dose): B (25.7%) > R (16.2%) > C (11.8%) >T (8.8%) > P (6.7%) > M (5.2%). Fecal clearances of radiolabel,expressed as a percentage of total excretion, were greater aftertopical administration for four of the six compounds (B, C,P, and T, p < 0.05). Calculations based on urinary excretionalone underestimated percutaneous absorption determined fromtotal excretion by 5–30%, although the difference betweenthe two estimates was statistically significant only for C (p< 0.05). These results suggest that percutaneous absorptionestimates based on urinary radiolabel excretion alone shouldbe interpreted with caution whenever compounds with unknownpenetration characteristics arc used. Factors known to affecthuman skin absorption, such as applied dose, anatomical region,sex, age, various vehicles and solvents, and differences incutaneous metabolism, should be more closely examined in allanimal species used to model percutaneous absorption phenomenain man.