A review of the genotoxicity of food, drug and cosmetic colours and other azo, triphenylmethane and xanthene dyes.

The genetic toxicology of the major dyestuffs used in foods, drugs and cosmetics has been reviewed. Published data for azo, triphenylmethane and xanthene dyes from short-term assays for muta-carcinogenicity have been summarized and discussed according to usage, current and previous worldwide legislative status. Certain other synthetic food dyes, commercial mixtures, natural and polymeric colourants as well as a section on aminoazobenzene and its derivatives have been included. Genotoxicity has been discussed with reference to structural chemistry, levels of exposure, absorption and metabolism and to epidemiological information. The extent of agreement between data from different tests and correlations with animal cancer assays have been considered. Synthetic dyes from the 3 major structural classes exhibit genotoxicity, whilst only 2 natural colours have proved active. Activity may be due to the presence of certain functional groups, notably nitro- and amino-substituents which are metabolized to ultimate electrophiles that may be stabilized by electronic interaction with aryl rings. Metabolic processes such as azo-reduction may be activating or detoxifying. the low but significant correlation between animal carcinogenicity and short-term test data may be increased with further screening, especially involving chromosome assays. It is suggested that a human cancer hazard may exist where significant quantities of finished benzidine dye samples are handled. Such risks from exposures to other colours and the possibility of human germ-line mutation induction by dyestuffs cannot be meaningfully assessed.

Evaluation of the genotoxicity of some natural food colours using bacterial assays.

The genotoxicity of 5 natural food colours currently permitted within the European Economic Community has been studied. Ability to induce DNA damage was investigated by the use of a recently-developed E. coli rec assay. The induction of reverse mutations in E.coli WP2 trp uvrA and S.typhimurium TA1538 his rfa uvrB was detected in fluctuation assays. Both types of assays were conducted with and without metabolic activation using caecal extracts and liver microsomes from rats. Results obtained in these systems suggest that none of the colourings screened induced detectable genotoxicity.

Studies on the genotoxicity of some fluorescein dyes.

The activities of 2,4,5,7-tetraiodofluorescein, disodium salt (erythrosine) and 2 phloxine dyes (2,4,5,7-tetrabromo-12,15-dichlorofluorescein, dipotassium salt and the disodium salt of 2,4,5,7-tetraiodo-12,15-dichlorofluorescein) have been determined using DNA-repair, fluctuation and treat-and-plate assays. Tests were conducted with and without illumination from a daylight fluorescent lamp. Both phloxine dyes were active in a rec assay but only in the absence of a rat-liver microsomal metabolising system. Erythrosine was inactive under all conditions. Although the results agreed with some of the published data for these foods and cosmetic colours, previous reports of photodynamic activation and mutagenicity were not confirmed. In the light of recent concern over the efficacy of bacterial DNA-repair tests, it is considered that the results obtained are not at present conclusive evidence for genotoxic hazard of any of the dyes studied.

Methodology for the testing of food dyes for genotoxic activity: experiments with red 2G (C.I. 18050).

A methodology for investigating genotoxicity of food colours using the fluctuation and DNA-repair assays with bacteria is described. In addition, a liquid repair test, developed to permit incorporation of microsomes and the quantitative estimation of cell viability, has been characterised with a number of positive control agents. Results obtained in these systems suggest that the food colour Red 2G induces repairable DNA damage and base-substitution mutation, but only in the presence of a rat-liver microsomal preparation. The significance of the data in the light of other toxicological information is discussed.