Safety and uptake of fully oxidized ß-carotene.

ABSTRACT

Spontaneous oxidation of ß-carotene yields a polymer-rich product (OxBC) together with minor amounts of many apocarotenoids. OxBC's activity extends ß-carotene's benefits beyond vitamin A, finding utility in supporting health in livestock, pets, and humans. Although the naturally occurring form of OxBC is consumed in foods and feeds, a direct demonstration of synthetic OxBC's safety provides additional support for its usage. A toxicological study in rats showed a maximum tolerated single oral dose of 5000 mg/kg, an LD50 of more than 10,000 mg/kg, and a NOAEL of 1875 mg/kg body weight. A repeat-dose 90-day oral toxicity study showed no adverse physiological or pathological effects. A study of OxBC uptake by mice over 2-5 days showed OxBC already was naturally present. The highest levels were in liver, lung, and hamstring. Dosing did not increase levels in liver, kidney, lung, and muscle. Increases occurred in urine, intestinal content, plasma, feces, spleen, and cecum with preferential elimination of polymer, consistent with processing of OxBC. Compared to the 41 polymer apocarotenoid ratio of OxBC, polymer was enriched in liver and spleen and depleted in lung, kidney, hamstring, and abdominal muscle. The apparent control of OxBC in major tissues further supports its safety.