title: A hairless mouse model for assessing the chronic toxicity of topically applied chemicals.
abstract: An enormous number of synthetic chemicals are incorporated in topical drugs, cosmetics and toiletries. These have the potential to cause irritant reactions when chronically applied to human skin. In predictive tests for assessing the irritancy potential of these chemicals, haired species, especially rabbits, guinea pigs and mice, have figured prominently. Customarily these tests, including the renowned Draize rabbit test, have entailed a single acute exposure or at most daily exposures over a few weeks. Estimation of inflammation and tissue injury in these models have relied on visual assessment. We submit that this approach is no longer acceptable. Visual assessments are unreliable. Reactions which are scored equivalently by the naked eye may differ strikingly when examined histologically. Moreover, tissue injury may be present in clinically normal skin. Short-term results. even when abetted by routine histological evaluations, cannot predict the degree of injury from long-term exposures. Cosmetics and toiletries, for example, are used daily for decades, often over most of the lifespan of persons who are well groomed. We present the hairless mouse as a convenient, reliable model for assessing the chronic toxicity of diverse chemicals. Histological examination enables a detailed description of the different tissue components which participate in the complex cascade of changes that comprise the inflammatory response.
authors.affiliation: Department of Dermatology, University of Pennsylvania, School of Medicine, Philadelphia 19104, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Kligman
authors.forename: L H
authors.initials: LH
authors.lastname: Kligman
mesh_terms: D000287:Administration, Topical; D000818:Animals; D001585:Benzoyl Peroxide / Q000008:administration & dosage / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity; D005260:Female; D006880:Hydroxy Acids / Q000008:administration & dosage / Q000633:toxicity; D007150:Immunohistochemistry; D007509:Irritants / Q000008:administration & dosage / Q000633:toxicity*; D007641:Keratolytic Agents / Q000008:administration & dosage / Q000633:toxicity; D051379:Mice; D008812:Mice, Hairless; D009226:Myristates / Q000008:administration & dosage / Q000633:toxicity; D019384:Nucleic Acid Synthesis Inhibitors / Q000008:administration & dosage / Q000633:toxicity; D012867:Skin / Q000187:drug effects* / Q000473:pathology; D012997:Solvents / Q000008:administration & dosage / Q000633:toxicity; D013194:Staining and Labeling; D013501:Surface-Active Agents / Q000008:administration & dosage / Q000633:toxicity; D018675:Toxicity Tests / Q000379:methods*; D014212:Tretinoin / Q000008:administration & dosage / Q000633:toxicity
chemical_list: D002273:Carcinogens; D006880:Hydroxy Acids; D007509:Irritants; D007641:Keratolytic Agents; D009226:Myristates; D019384:Nucleic Acid Synthesis Inhibitors; D012997:Solvents; D013501:Surface-Active Agents; C008205:isopropyl myristate; D014212:Tretinoin; D001585:Benzoyl Peroxide