Percutaneous absorption can be determined by applying a known amount of js chemical to a specified surface area and then measuring levels of the chemical -a in the urine and/or feces. Because the analytical techniques to measure the chemi- <
cal are not always available and because some chemicals may be metabolized, 4
radiolabeled chemicals, 14C or 3H, are often used. |
In vivo studies have been conducted in humans and other species (12). Comparison of absorption rates of a number of compounds showed that absorption rates in the rat and rabbit tend to be higher than humans and that the skin permeability of monkeys and swine more closely resembles that of humans. No significant mouse-human skin comparisons exist. Guinea pig-human comparisons offer some promise for refinement of guinea pig-human irritation and sensitization extrapolations (13). Although these differences are not predicted by any single factor, they are not unexpected in light of differences in metabolism and in routes of excretion. Therefore, the metabolic capabilities of the species should be considered when selecting an animal model and designing the experiment. Although there is no question that pharmacokinetic studies of this type in humans or animals provide the best estimate of percutaneous absorption, the cost and difficulty in conducting well-controlled studies have led to the use of other in vivo assays that are poorer predictive tools and to the development of in vitro models.
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