Comparative developmental toxicity and oxidative stress of synthetic and natural yellow food colorants in zebrafish (Danio rerio) embryos.

Food colorants are widely used in the food industry; however, information regarding the comparative developmental toxicity of natural and synthetic yellow colorants remains limited. This study evaluated the embryotoxic, teratogenic, and oxidative stress effects of saffron (Crocus sativus L.), safflower (Carthamus tinctorius L.), and the synthetic azo dye tartrazine using zebrafish (Danio rerio) embryos. Embryos were exposed to serial concentrations (0.0001-1%, w/v) of each colorant from 2 to 96 h post-fertilization (hpf). Survival, hatchability, morphological abnormalities, median lethal concentration (LC₅₀), median effective concentration (EC₅₀), teratogenic index (TI), and malondialdehyde (MDA) levels were assessed. Safflower extract exhibited the greatest embryotoxicity, characterized by reduced survival, delayed hatching, elevated mortality, and the lowest LC₅₀ value among the tested colorants. Tartrazine produced pronounced, concentration-dependent developmental abnormalities, including cardiac edema, yolk sac edema, spinal deformities, and pigmentation abnormalities, and showed a comparatively higher teratogenic index than safflower, although both values remained below the classical TI > 1 threshold for teratogenicity. In contrast, saffron extract showed comparatively low toxicity, with minimal developmental abnormalities and higher survival rates at sublethal concentrations. Oxidative stress analysis revealed significant increases in MDA levels following exposure to safflower and tartrazine, indicating enhanced lipid peroxidation and oxidative damage. Principal component analysis further distinguished the toxicological profiles of the tested colorants, separating safflower-associated embryotoxicity from tartrazine-associated comparatively higher TI than safflower. These findings demonstrate that both natural and synthetic yellow food colorants can adversely affect embryonic development in a concentration-dependent manner and suggest that natural origin alone does not necessarily predict biological safety. The zebrafish embryo model provides a useful platform for comparative food colorant safety assessment and developmental toxicity screening.