Consideration of Variables in Evaluation of Toxicity to Skin

Abstract

Certain systems for estimation of toxicity to skin are discussed, in which fuller consideration of variables led to improved study design and better prediction of human hazard. Three areas are considered: skin irritation; dermal carcinogenesis; prediction of carcinogenic potential (in vitro). (1) Variation in the guidelines of various U.S. and foreign agencies for evaluation of skin irritation and corrosiveness of chemicals was addressed by use of multiple-site patching in the rabbit. Data obtained from this “composite assay,” as well as from other published studies, indicated that no single set of guidelines was adequate for proper human hazard assessment. (2) Practical questions are raised about latency time and incidence of skin tumors from limited exposure to chemical carcinogens. In benzo[a]pyrene (BaP) carcinogenesis in mice, the duration of treatment is a key factor in tumor onset and frequency, with a “saturation level” resulting from interplay of duration and dose level. Age at inception of treatment can also be a factor in susceptibility to BaP-induced skin cancer, depending on conditions of exposure. (3) The question of carcinogenic potential of oil industry raw materials requires short-term answers, such as might be provided by an in vitro mutagenicity test. However, such tests are not appropriate for these water-immiscible mixtures. Studies on bioavailability of oil-related materials enabled modification of the Ames bacterial test, vastly improving sensitivity. With this modified Ames test, high correlation is seen among mutagenicity, content of polycyclic aromatics, and dermal carcinogenicity.