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The Tumorigenicity of Mutagenic Contact‐Sensitizing Chemicals
Author(s) -
Albert Roy E.,
Magee Philip S.
Publication year - 2000
Publication title -
risk analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.972
H-Index - 130
eISSN - 1539-6924
pISSN - 0272-4332
DOI - 10.1111/0272-4332.203031
Subject(s) - electrophile , allergic contact dermatitis , sensitization , carcinogen , chemistry , contact allergy , contact dermatitis , adduct , toxicology , genotoxicity , toxicity , biology , biochemistry , organic chemistry , allergy , immunology , catalysis
The electrophilic nature of some contact sensitizers, that is, chemicals that cause allergic contact dermatitis (ACD), is also characteristic of genotoxic tumorigens. Electrophiles can adduct protein, which is the basis for ACD, as well as DNA, which is the basis for mutagenicity and carcinogenicity. This suggests that some electrophilic contact sensitizers may be genotoxic tumorigens. To further investigate this matter, we evaluated 146 chemicals that had been bioassayed for tumorigenicity and mutagenicity in the National Toxicology Program, with an analysis of structure‐activity relationships for contact sensitization. Using the data from this analysis and from other sources, the proportion of the contact sensitizers that were both mutagenic and tumorigenic was found to range from 20% to 28%. This finding suggests that there may be in the order of 90 genotoxic tumorigens for rodents among the approximately 384 chemicals that have been validated as contact sensitizers for humans.