PT  - JOURNAL ARTICLE
AU  - Graham W. Burton
AU  - Trevor J. Mogg
AU  - Jacek Stupak
AU  - Felicity C. Stark
AU  - Susan M. Twine
AU  - Jianjun Li
TI  - Safety and uptake of fully oxidized β-carotene
AID  - 10.1101/2022.06.27.497750
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.06.27.497750
4099  - http://biorxiv.org/content/early/2022/06/29/2022.06.27.497750.short
4100  - http://biorxiv.org/content/early/2022/06/29/2022.06.27.497750.full
AB  - Spontaneous oxidation of β-carotene yields a polymer-rich product (OxBC) also containing small amounts of many apocarotenoids. OxBC extends β-carotene’s benefits beyond vitamin A, finding utility in supporting health in livestock, pets, and humans. Although naturally occurring OxBC is consumed in foods and feeds, a direct demonstration here of safety of synthetic OxBC supports its increasing usage. A toxicological study in rats showed a maximum tolerated single oral dose, an LD50, and a NOAEL of 5,000, 30,079 and 1875 mg/kg body weight, respectively. The repeat-dose 90-day oral toxicity study showed no adverse physiological or pathological effects. A first study of OxBC uptake by mice over 2-5 days into a select set of tissues showed OxBC already was naturally present. The highest levels were in liver, lung, and hamstring. Despite dosing, no net increases occurred in liver, kidney, lung, and muscle. Net increases occurred in urine, intestinal content, plasma, feces, spleen, and cecum, consistent with processing of OxBC and preferential elimination of polymer. Compared to the 4:1 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.Competing Interest StatementGWB and TJM are employees of Avivagen Inc. GWB owns shares in Avivagen Inc.OxBCfully oxidized β-caroteneapoCapocarotenoidDHAdihydroactinidiolideMTDmaximum tolerated doseMRMmultiple reaction monitoringNOAELno observed adverse effect levelNRCNational Research Council of CanadaPEGpolyethylene glycol