Allergic contact sensitizing chemicals as environmental carcinogens.

Chemicals that were bioassayed by the National Toxicology Program (NTP) and that also produce allergic dermatitis (ACD) in humans were evaluated for their tumorigenic characteristics. The impetus for the study was that most contact sensitizers, i.e., those that produce ACD, and genotoxic carcinogens are chemically similar in that they are electrophilic, thereby producing adducts on macromolecules including protein and DNA. This similarity in chemical behavior suggests that many contact sensitizers might be environmental carcinogens. All of the published NTP bioassays by early 1996 that had both genotoxicity and carcinogenicity studies were included in this analysis. The NTP chemicals had been chosen for bioassay without regard to their ability to produce ACD. Of the 209 chemicals that were bioassayed, there were 36 (17%) that were known to be human contact sensitizers; about half of these were positive on tumor bioassays. The contact sensitizers differed from the NTP sample as a whole by having a proportionately larger number of nongenotoxic chemicals by the Ames Salmonella assay, presumably because more of them were selected on the basis of widespread usage rather than structural resemblance to known carcinogens. Compared to the nongenotoxic chemicals, the genotoxics were stronger carcinogens in that they had a higher incidence of positive tumor bioassays, with twice the number of organs in which tumors were induced. The nongenotoxic chemicals had a preference for tumor induction in parenchymal tissues in contrast to epithelial tissues. The contact sensitizers showed essentially the same characteristics as the whole NTP sample when stratified according to genotoxicity. Judging by the chemicals that were chosen primarily for their widespread use rather than for their structural resemblance to carcinogens, the addition of a test for contact sensitization to the Ames test as a screening tool would increase the tumorigenic detection efficiency by about 40% because of the nongenotoxic tumorigens. A ballpark estimate suggests that there could be several thousand contact sensitizers for humans in commercial use that are rodent tumorigens.