Percutaneous absorption of [¹⁴C]methacrylamide in animals

Abstract

Percutaneous absorption of [^l4C]methacrylamide was determined in rabbits, rats and mice. Radioactivity in blood of rabbits increased rapidly after IV injection, after topical application with a cloth and after direct topical application of a 15 or 5% test solution, suggesting high permeability of the skin for methacrylamide. Radioactivity then began to decrease exponentially within 1 h. Tissue radioactivity 24 h after IV dosing was high in blood, liver and serum, and low in brain, nerve and muscle. The radioactivity was more uniformly distributed with the exception of liver, after application with a cloth and after direct contact than after IV dosing. When the application site was washed with water after direct application, decline of radioactivity in blood was accelerated slightly and a decrease in radioactivity in some tissues was found, although the difference between non-wash and wash groups was not significant in either the declining curve or the tissue radioactivity, with the exception of serum for the latter. Between 25 and 60% of the radioactivity found in tissues was protein-bound after 24 h. Recovery of radioactivity in urine was highest after IV administration, intermediate after direct contact, and lowest after cloth application. Radioactivity in expired air and bile was small. Both radioactivity in tissues and its recovery in urine in rats, and tissue radioactivity in mice, were lower than in rabbits, when adjusted for dose per unit body weight, suggesting lower skin permeability for methacrylamide in the former species. In rats, radioactivity in some tissues was significantly decreased after washing. An autoradiographic study on rabbit skin indicated that the test material penetrated the skin largely through hair follicles.