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 concentration	Result
Genotoxicity in vitro
Ames, S. typhimurium mutation assay	Crystalline	0, 2.4–1500 g/plate	Negative
Gene mutation in V79 cells	Crystalline	0, 1–16 g/mL	Negative
Unscheduled DNA synthesis (UDS) in rat hepatocytes	Crystalline	0.1–16 g/mL	Negative
Human lymphocytes	Crystalline	0, 60, and 120 g/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 generations (admix) in rats	10% beadlet	0, 0, 50, 150, and 500	NOAEL, high dose