Mutagens and Sensitizers—An Unequal Relationship?

Abstract

For some years, those involved with the safety assessment of chemicals have in one way or another considered the degree to which data on either skin sensitization potential or on carcinogenicity may inform them on the other endpoint for a particular substance. In this work, we have taken a pragmatic perspective on the question and assessed mutagens, rather than carcinogens, and sensitizers as this better reflects the potential for biological macromolecule interaction. A dataset of 100 substances, the majority of which have come under scrutiny for one reason or another during our own toxicology investigations, was interrogated. We focused on the extent to which results from the primary screen for skin sensitization correlated with the results from the two in vitro tests used as a screen for mutagenicity, namely the bacterial mutation assay and the in vitro chromosome aberration assay. Although there was some concordance between the two endpoints, as standalone methods, neither predicted the other particularly accurately, with 32% showing disagreement. It is probable that there are several critical elements missing from this top level assessment, not least an appreciation of which substances are positive in mutagenicity tests via non‐genotoxic mechanisms which could seriously impair such a correlation between results from the two different endpoints.

Keywords :

• Mutagenicity
• Carcinogenicity
• Sensitization
• Bacterial mutation assay
• In vitro chromosome aberration assay
• Local lymph node assay