Final report of the amended safety assessment of Dioscorea Villosa (Wild Yam) root extract.

Dioscorea Villosa (Wild Yam) Root Extract is an extract of the rhizomes of the wild yam, D. villosa. A manufacturing process was described in which cut up and ground rhizomes are combined with an eluant (e.g., oleyl alcohol), the plant material precipitated with addition of a miscible solvent, washed, and redissolved in the original eluant. The extract contains glycoside and steroidal saponins (< or =0.4%), diosgenin (< or =3.5%), alkaloids, tannins, phytosterols, and starch. Levels of heavy metals, 1,4-dioxane, chloroform, methylene chloride, trichloroethylene, and benzene are reported to be below limits of detection. Although only one use was reported to the U.S. Food and Drug Administration (in a body and hand preparation), industry reported uses in body and hand creams, lotions, powders, and sprays at a concentration of 0.00001% (equivalent to 0.000002% plant solids), and in moisturizing creams, lotions, powders, and sprays at concentrations up to 15% (equivalent to 0.5% plant solids). Preparations fromD. villosaare used in herbal medicine for treatment of a variety of ailments and by the pharmaceutical industry in the preparation of steroids. Using Dioscorea Villosa (Wild Yam) Root Extract prepared via a specified process, it is possible to produce a stable extract with a narrow range of diosgenin content. The extract produced using this methodology was tested in acute and short-term toxicity tests, dermal irritation tests, a sensitization test, an ocular irritation test, a rat uterotropic assay, and genotoxicity tests. An acute oral toxicity test produced hypoactivity, piloerection, and dyspnea and a death in 1 of 10 rats at 2 g/kg using the specified extract, but no toxicity in rats given 0.5 g/kg. A dermal toxicity test using the specified extract demonstrated no acute toxicity in rats. Both a 7-day local tolerance test and a 28-day dermal toxicity test in rats produced no significant adverse effects at the maximum tested concentration of 10%. A single application of undiluted extract to the intact and abraded skin of rabbits produced sufficient irritation for the test material to be rated"irritant,"but a 10% dilution was not irritating. Undiluted extract was only mildly irritating to the conjuctiva of the rabbit eye; irritation in the iris and cornea was mild and transient. Undiluted extract was not irritating during the induction phase of a guinea pig sensitization study, nor did challenge with a 25% dilution elicit any sensitization. The specified extract at concentrations up to 500 mg/kg/day did not have any estrogenic activity in the juvenile rat uterotrophic assay. Genotoxicity assays in bacterial and mammalian systems were negative, except that Ames test strain TA 1537 was positive at one dose level using the plate incorporation method, but not using a preincubation method. Although the concentration at which the actual plant extract is used in cosmetic products is low, one of the primary safety concerns with this plant extract is the possible metabolic/endocrine activity, e.g., estrogen-like or progesterone-like activity as a result of the presence of small amounts of plant phytosterols such as diosgenin. Extracts prepared as described in this safety assessment, with an upper limit of 3.5% diosgenin, did not have any estrogenic activity, demonstrating that it is possible to produce material that does not present this specific safety concern. Although extracts from pesticide-free plants were not considered genotoxic and it was the view of the Cosmetic Ingredient Review (CIR) Expert Panel that there do not appear to be any components that could be carcinogenic, pesticide residues could raise this issue. It was urged that manufacturers limit pesticide residues to the limit previously used for lanolin of not more than 40 ppm (with not more than 10 ppm for any one residue). Based on these data, it was concluded that Dioscorea Villosa (Wild Yam) Root Extract is safe as used in cosmetic formulations. This conclusion regarding safety, however, is valid only for extracts prepared in a manner that produces a similar chemical profile as that described in this report, particularly as regards diosgenin. Extracts not prepared in a manner that produces a similar chemical profile would be considered safe if they have a similar safety test profile.