Studies on meso-zeaxanthin for potential toxicity and mutagenicity

Abstract

The purpose of these studies was to examine the potential toxicity and genotoxicity of meso-zeaxanthin (MZ). Toxicity was assessed by administering MZ daily to rats for 13 weeks followed by a 4-week recovery period. Potential genotoxicity was assessed in separate experiments using the Ames test method. Rats were randomly assigned to four groups to receive corn oil (control) or MZ at dose levels of 2, 20 and 200 mg/kg/day by oral gavage (10/sex/group). Additional rats (five of each sex) in the control and the 200 mg/kg/day groups were retained for the recovery period. No compound-related clinical, biochemical or pathological signs or symptoms were noted and the no-observed-adverse-effect-level (NOAEL) of MZ was >200 mg/kg/day. To investigate genotoxicity, MZ was tested for its ability to induce reverse mutations (±microsomal enzymes) at 2 genomic loci; the histidine locus of 4 strains of Salmonella typhimurium and the tryptophan locus of Escherichia coli strain WP2uvrA. Six doses of MZ ranging from 10 to 5000 μg/plate were tested twice with vehicle and positive controls using 3 plates/dose. MZ did not cause any increase in the mean number of revertants/plate with any bacterial strain, with or without microsomal enzymes, and was therefore unlikely to be mutagenic.

Keywords: ARMD; Age-related macular disease; DMSO; Genotoxicity; MZ; Macular carotenoids; Meso-zeaxanthin; Meso-zeaxanthin (3R,3′S)-dihydroxy-β,β-carotene-3,3′-diol; NOAEL; S9 homogenate; TA98, TA100, TA1535 and TA1537; Toxicity; WP2uvrA; age-related macular disease; di-methyl sulphoxide; liver microsomal enzyme preparation; no-observed-adverse-effect-level; tester strain of Escherichia coli; tester strains of Salmonella typhimurium.