{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T04:32:13Z","timestamp":1762144333959,"version":"3.38.0"},"reference-count":32,"publisher":"SAGE Publications","issue":"2_suppl","license":[{"start":{"date-parts":[[2004,3,1]],"date-time":"2004-03-01T00:00:00Z","timestamp":1078099200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int J Toxicol"],"published-print":{"date-parts":[[2004,3]]},"abstract":"<jats:p> 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 (\u22640.4%), diosgenin (\u22643.5%), 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 from\u03b2. villosa are 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 \u201c;irritant,\u201d 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., estrogenlike 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. <\/jats:p>","DOI":"10.1080\/10915810490499055","type":"journal-article","created":{"date-parts":[[2004,10,12]],"date-time":"2004-10-12T16:53:17Z","timestamp":1097599997000},"page":"49-54","source":"Crossref","is-referenced-by-count":25,"title":["Final Report of the Amended Safety Assessment of Dioscorea Villosa (Wild Yam) Root Extract1"],"prefix":"10.1177","volume":"23","member":"179","published-online":{"date-parts":[[2004,3,1]]},"reference":[{"key":"atypb1","unstructured":"Active Organics. 2000a. Preparation of Wild Yam Extract and analysis of diosgenin (HPLC method). Unpublished data submitted by CTFA. 8 pages."},{"key":"atypb2","unstructured":"Active Organics. 2000b. Product specification, composition statement, certificate of analysis, and material safety data sheet for hexyldecanol extract. Unpublished data submitted by CTFA. 10 pages."},{"key":"atypb3","unstructured":"Active Organics. 2000c. Product specification, composition statement, certificate of analysis on material used in safety tests and material safety data sheet. Unpublished data submitted by CTFA. 9 pages."},{"key":"atypb4","unstructured":"Active Organics. 2000d. Characterization of Actiphyte Mexican Wild Yam Concentrate Special in hexyldecanol. Unpublished data submitted by CTFA. 15 pages."},{"key":"atypb5","unstructured":"Active Organics. 2000e. Characterization of Actiphyte Mexican Wild Yam Concentrate Special in oleyl alcohol. Unpublished data submitted by CTFA. 24 pages."},{"key":"atypb6","unstructured":"Centre Internationale de Toxicologie (CIT). 2000a. Ultraviolet spectrum. Unpublished data submitted by CTFA. 16 pages."},{"key":"atypb7","unstructured":"CIT. 2000b. Acute Oral toxicity in rats - fixed dose method. Unpublished data submitted by CTFA. 25 pages."},{"key":"atypb8","unstructured":"CIT. 2000c. Acute dermal toxicity in rats. Unpublished data submitted by CTFA. 22 pages."},{"key":"atypb9","unstructured":"CIT. 2000d. Local tolerance after cutaneous applications for seven days in rats. Unpublished data submitted by CTFA. 88 pages."},{"key":"atypb10","unstructured":"CIT. 2000e. Four-week toxicity study by cutaneous route in rats. Unpublished data submitted by CTFA. 225 pages."},{"key":"atypb11","unstructured":"CIT. 2000f. Acute dermal irritation in rabbits. Unpublished data submitted by CTFA. 15 pages."},{"key":"atypb12","unstructured":"CIT. 2000g. Skin sensitization test in guinea pigs. Unpublished data submitted by CTFA. 28 pages."},{"key":"atypb13","unstructured":"CIT. 2000h. Study for estrogenic activity by oral route (gavage) in juvenile female rats (uterotrophic assay). Unpublished data submitted by CTFA. 132 pages."},{"key":"atypb14","unstructured":"CIT. 2000i. Bone marrow micronucleus test by oral route in rats. Unpublished data submitted by CTFA. 35 pages."},{"key":"atypb15","unstructured":"Cosmetic Ingredient Review (CIR). 1999. Final report on the safety assessment of Wild Yam (Dioscorea Villosa) Extract. Washington, DC: CIR."},{"key":"atypb16","unstructured":"Cosmetic, Toiletry, and Fragrance Association (CTFA). 1999a. Botanical Cosmetic Ingredient Description for Dioscorea Villosa (Wild Yam) Root Extract. Dated June 28. Unpublished data submitted by CTFA. 2 pages."},{"key":"atypb17","unstructured":"CTFA. 1999b. Product type and concentration of use for Dioscorea Villosa (Wild Yam) Root Extract. Dated July 19. Unpublished data submitted by CTFA. 1 page."},{"key":"atypb18","unstructured":"CTFA. 2000. Letter to CTFA from Active Organics. Unpublished data submitted by CTFA. 1 page."},{"key":"atypb19","unstructured":"Eagon, P. K. 2000. Personal communication to Alan Andersen."},{"key":"atypb20","first-page":"161","volume":"40","year":"1999","journal-title":"Proceedings of the American Association for Cancer Research Annual Meeting"},{"key":"atypb21","unstructured":"European Economic Community. 2000. Cosmetics Directive of the European Union. Updated version-Incorporating all amendments until August 1,1995. Dir. 76\/768\/EEC."},{"key":"atypb22","unstructured":"Food and Drug Administration (FDA). 1998. Frequency of use of cosmetic ingredients. FDA database. Washington, DC: FDA."},{"key":"atypb23","unstructured":"Laboratorie de Recherche et D'Exp\u00e9rimentation. 1998. Determination of primary skin irritation index and eye irritation index in the rabbit. Unpublished data submitted by CTFA. 16 pages."},{"key":"atypb24","unstructured":"Mowrey, D. B.1986.The scientific validation of herbal medicine, 111\u2013112. New Canaan, CT: Keats Publishing, Inc."},{"key":"atypb25","unstructured":"Murad, H. 1998. U.S. Patent (5,804,168) for pharmaceuticals, compositions, and methods for protecting and treating sun damaged skin. http:\/\/www. uspto.gov\/patft\/index.html"},{"key":"atypb26","unstructured":"Ody, P.1993.The complete medicinal herbal, 52. New York, NY: DK Publishing, Inc."},{"key":"atypb27","unstructured":"Pepe, R. C., J. A. Wenninger, and G. N. McEwen, Jr, eds, 2000.International cosmetic ingredient dictionary and handbook, 8th ed., vol. 1, 462. Washington, DC: CTFA."},{"key":"atypb28","unstructured":"Phoenix International. 2000. Bacterial reverse mutation test. Unpublished data submitted by CTFA. 104 pages."},{"key":"atypb29","unstructured":"Polunin, M., and C. Robbins1992.The natural pharmacy. An illustrated guide to natural medicine, 48, 99. New York: Macmillan Publishing Co."},{"volume-title":"CTFA List of Japanese Cosmetic Ingredients","year":"1997","key":"atypb30"},{"key":"atypb31","unstructured":"Ritchason, J.1995.The little herb encyclopedia, 3rd ed., 248\u2013249. Utah: Woodland Health Books."},{"key":"atypb32","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-217-44247"}],"container-title":["International Journal of Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1080\/10915810490499055","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1080\/10915810490499055","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T21:47:41Z","timestamp":1741643261000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1080\/10915810490499055"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,3]]},"references-count":32,"journal-issue":{"issue":"2_suppl","published-print":{"date-parts":[[2004,3]]}},"alternative-id":["10.1080\/10915810490499055"],"URL":"https:\/\/doi.org\/10.1080\/10915810490499055","relation":{},"ISSN":["1091-5818","1092-874X"],"issn-type":[{"type":"print","value":"1091-5818"},{"type":"electronic","value":"1092-874X"}],"subject":[],"published":{"date-parts":[[2004,3]]}}}