Table 2.

List of genotoxicity, repeat dose, and reproductive safety studies conducted with DSM-manufactured synthetic zeaxanthin based on international regulatory study designs.

Safety studies	Formulation nominal %	Concentration or dosage	Result
		Concentration
Genotoxicity in vitro
Ames, S. typhimurium mutation assay	Crystalline	0, 2.4–1500 μg/plate	Negative
Gene mutation in V79 cells	Crystalline	0, 1–16 μg/mL	Negative
Unscheduled DNA Synthesis (UDS) in rat hepatocytes	Crystalline	0.1–16 μg/mL	Negative
Human lymphocytes	Crystalline	0, 60, and 120 μg/mL	Negative
		Dose (mg/kg bw/day)
Genotoxicity assays in vivo
Mouse micronucleus	10% beadlet	0, 44.5, 89, and 178	Negative
Subchronic and chronic
13-week oral (admix) in mice	10% beadlet	0, 0, 250, 500, and 1000	NOAEL, high dose
13-week oral (admix) in rats	10% beadlet	0, 0, 250, 500, and 1000	NOAEL, high dose
13-week oral (feed cubes) in dogs	10% beadlet	0, 123, 204, and 422 males : 0, 104, 238, and 442 females	NOAEL, high dose
1-year oral (gavage) in monkeys zeaxanthin or lutein	10% beadlet	0, 0.2, and 20 for zeaxanthin or lutein	NOAEL, high dose
Reproductive studies
Teratology oral (admix) in rats	10% beadlet	0, 250, 500, and 1000	NOAEL, high dose
Teratology oral (gavage) in rabbits	Crystalline in oil	0, 100, 200, and 400	NOAEL, high dose
Two-generation (admix) in rats	10% beadlet	0, 0, 50, 150, and 500	NOAEL, inter. dose