The Botanical Safety Consortium: A public-private partnership to enhance the botanical safety toolkit.

Botanical dietary supplement use is widespread and growing, therefore, ensuring the safety of botanical products is a public health priority. This commentary describes the mission and objectives of the Botanical Safety Consortium (BSC) - a public-private partnership aimed at enhancing the toolkit for conducting the safety evaluation of botanicals. This partnership is the result of a Memorandum of Understanding between the US FDA, the National Institute of Environmental Health Sciences, and the Health and Environmental Sciences Institute. The BSC serves as a global forum for scientists from government, academia, consumer health groups, industry, and non-profit organizations to work collaboratively on adapting and integrating new approach methodologies (NAMs) into routine botanical safety assessments. The objectives of the BSC are to: 1) engage with a group of global stakeholders to leverage scientific safety approaches; 2) establish appropriate levels of chemical characterization for botanicals as complex mixtures; 3) identify pragmatic, fit-for-purpose NAMs to evaluate botanical safety; 4) evaluate the application of these tools via comparison to the currently available safety information on selected botanicals; 5) and integrate these tools into a framework that can facilitate the evaluation of botanicals. Initially, the BSC is focused on oral exposure from dietary supplements, but this scope could be expanded in future phases of work. This commentary provides an overview of the structure, goals, and strategies of this initiative and insights regarding our first objectives, namely the selection and prioritization of botanicals based on putative toxicological properties.

α-Retinol and 3,4-didehydroretinol support growth in rats when fed at equimolar amounts and α-retinol is not toxic after repeated administration of large doses.

Dietary α-carotene is present in oranges and purple-orange carrots. Upon the central cleavage of α-carotene in the intestine, α-retinal and retinal are formed and reduced to α-retinol (αR) and retinol. Previous reports have suggested that αR has 2% biopotency of all-trans-retinyl acetate due in part to its inability to bind to the retinol-binding protein. In the present work, we carried out three studies. Study 1 re-determined αR's biopotency compared with retinol and 3,4-didehydroretinol in a growth assay. Weanling rats (n 40) were fed a vitamin A-deficient diet for 8 weeks, divided into four treatment groups (n 10/group) and orally dosed with 50 nmol/d retinyl acetate (14.3 µg retinol), α-retinyl acetate (143 µg αR), 3,4-didehydroretinyl acetate (14.2 µg DR) or cottonseed oil (negative control). Supplementation was continued until the control rats exhibited deficiency signs 5 weeks after the start of supplementation. Body weights and AUC values for growth response revealed that αR and DR had 40-50 and 120-130% bioactivity, respectively, compared with retinol. In study 2, the influence of αR on liver ROH storage was investigated. The rats (n 40) received 70 nmol retinyl acetate and 0, 17.5, 35 or 70 nmol α-retinyl acetate daily for 3 weeks. Although liver retinol concentrations differed among the groups, αR did not appreciably interfere with retinol storage. In study 3, the accumulation and disappearance of αR over time and potential liver pathology were determined. The rats (n 15) were fed 3.5 µmol/d α-retinyl acetate for 21 d and the groups were killed at 1-, 2- and 3-week intervals. No liver toxicity was observed. In conclusion, αR and didehydroretinol are more biopotent than previously reported at sustained equimolar dosing of 50 nmol/d, which is an amount of retinol known to keep rats in vitamin A balance.