Genetic toxicity of some important epoxides

In various biological systems, 1,2-epoxides are able to cause biological effects with genetic mechanisms: point mutations, deletions, chromosomal aberrations, gene conversion, crossing-over, cancer and virus (prophage) induction. Dose—response curves are linear, or should be interpreted to have a linear component that predominates at low doses or concentrations. In forward mutation systems the effectiveness is related to the dose in the target cells and to the chemical reactivity. By applying experimentally determined correction factors for difunctionality (in the case of diepoxides or monoepoxides with a reactive substituent such as a carbonyl group), genetic risks may be estimated by a unitary approach, valid for epoxides in general, if not for all alkylating agents. The use of this approach, to calculate type-II errors in negative carcinogenicity tests, indicates that no data presently available support a conclusion that certain epoxides are non-mutagenic or non-carcinogenic, i.e. are less effective than expected from reactivity data. Determination of the rad-equivalence of genetic risks, i.e. the use of corresponding risks from a unit dose of ionizing radiation as a standard, indicates that the risks associated with Threshold Limit Values for epoxides in work environments in Western countries are 1–2 orders of magnitude higher than permissible risks for radiological workers.