Abstract
Gardenia blue is widely used in Eastern Asia as a natural food colorant. The genotoxic potential of gardenia blue, and genipin, the natural starting material for its production, was evaluated in a GLP- and OECD-compliant test battery. No evidence of mutagenicity of gardenia blue was measured in a 5-strain Ames assay, with or without metabolic activation; an equivocal response for genipin occurred in Salmonella strain TA97a without metabolic activation. In in vitro micronucleus and chromosome aberration assays, with and without metabolic activation, genipin tested positive under some test conditions; however, gardenia blue tested negative in both assays. To assess the ability of these compounds to induce DNA damage in a rodent model, combined micronucleus/comet assays were conducted in male and female B6C3F1 mice. Micronucleated reticulocyte frequencies in blood were determined by flow cytometry and induction of DNA damage in liver, stomach and/or duodenum was assessed using the comet assay. No reproducible effects occurred at genipin doses reaching toxicity or gardenia blue up to the limit dose. Thus, although our studies showed some in vitro evidence of genotoxic potential of genipin, there was no evidence of DNA or chromosome structural damage in mice exposed to either genipin or gardenia blue. Furthermore, use of a modified comet assay in mouse liver did not provide evidence of DNA crosslinking induced by genipin, known to form crosslinks with other macromolecules, or gardenia blue. Our results indicate that consumption of gardenia blue or genipin in food does not pose a significant genotoxic concern for humans.
