ABSTRACT
There are numerous methods that have been employed to assess the percutaneous absorption of toxic chemicals using both in vitro and in vivo animal models. There is little debate that in vivo human studies are optimal for predicting the absorption of topically applied chemicals in man. However, for highly toxic or carcinogenic chemicals, ethics preclude conducting such studies when a risk analysis is to be conducted. Similar considerations apply to the humane use of animal surrogates. For chemicals that pose little direct adverse risk to man or animals, experimental design and sampling limitations often apply to any in vivo study. An important limitation is the inability to noninvasively sample the venous drainage of a topical application site to determine the true cutaneous fl ux for use as an input into systemic risk assessment models. Although microdialysis provides one approach to this dilemma, it does not allow recovery of all absorbed compound since the dermal vasculature is still intact. Similarly, extensive biopsies may not be taken to quantitate subtle, preclinical morphological or biochemical manifestations of dermatotoxicity.
