© 1989 Oxford University Press
research-article |
Percutaneous Absorption and Excretion of Xenobiotics after Topical and Intravenous Administration to Pigs
Cutaneous Pharmacology and Toxicology Center, College of Veterinary Medicine and Interdepartmental Toxicology Program, North Carolina State University 4700 Hillsborough Street, Raleigh, North Carolina 27606
Received September 12, 1988; accepted June 8, 1989
Interspecies comparisons suggest that the weaning pig is a suitable surrogate for man in percutaneous absorption studies. Despite known anatomical and physiological similarities between porcine and human skin, very few investigations of percutaneous absorption phenomena have been conducted in pigs. This study examined radiolabel excretion patterns after intravenous (iv) and topical administration of six 14C-radioIabeled compounds in weanling Yorkshire sows. Radiolabel recovery from excrement collected over 6 days following iv doses in physiological saline (200 µg, 10 µCi) showed that malathion (M), parathion (P), caffeine (C), and benzoic acid (B) were primarily excreted into urine (>80%), while greater fractions of testosterone (T, 72%) and progesterone (R, 35%) were fecally eliminated. Percutaneous absorption was determined from total urine and fecal excretion of radiolabel after topical application, corrected for incomplete excretion following iv administration. Topical doses in ethanol (200 µg, 10 µCi) were applied at a surface concentration of 40 µg 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 after topical administration for four of the six compounds (B, C, P, and T, p < 0.05). Calculations based on urinary excretion alone underestimated percutaneous absorption determined from total excretion by 5–30%, although the difference between the two estimates was statistically significant only for C (p < 0.05). These results suggest that percutaneous absorption estimates based on urinary radiolabel excretion alone should be interpreted with caution whenever compounds with unknown penetration characteristics arc used. Factors known to affect human skin absorption, such as applied dose, anatomical region, sex, age, various vehicles and solvents, and differences in cutaneous metabolism, should be more closely examined in all animal species used to model percutaneous absorption phenomena in man.