{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:55:47Z","timestamp":1787507747955,"version":"build-2736575974"},"reference-count":18,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2003,9,1]],"date-time":"2003-09-01T00:00:00Z","timestamp":1062374400000},"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":[[2003,9]]},"abstract":"<jats:p>Excipients are essential components of drug products. They are also potential toxicants. Examples of known excipient-induced toxicities include renal failure and death from diethylene glycol, osmotic diarrhea caused byingested mannitol, hypersensitivity reactions from lanolin, and cardiotoxicity induced by propylene glycol. Proposals to test or market new drug products in the United States should adequately address the safety of the proposed exposure to the excipients in those products. The specific safety data that may be needed will vary depending upon the clinical situation, including such factors as the duration, level, and route of exposure, but may include acute, repeat-dose, reproductive, and genetic toxicity data, carcinogenicity data, and specialized toxicology information, such as sensitization or local irritation data. Many guidances exist to aid in the development of pharmaceuticals, including the International Conference on Harmonization (ICH) documents and various Food and Drug Administration\/Center for Drug Evaluation and Research (FDA\/CDER) pharmacology and toxicology guidances. The FDA\/CDER has recently adopted a new guidance for industry, \u201cNonclinical Studies for Development of Pharmaceutical Excipients,\u201d which focuses on issues associated with development of safety databases that will support clinical use of excipients in drug products. The new guidance document is introduced and discussed in this article.<\/jats:p>","DOI":"10.1177\/109158180302200507","type":"journal-article","created":{"date-parts":[[2009,6,17]],"date-time":"2009-06-17T00:33:30Z","timestamp":1245198810000},"page":"377-380","source":"Crossref","is-referenced-by-count":66,"title":["Toxicity of Excipients\u2014A Food and Drug Administration Perspective"],"prefix":"10.1177","volume":"22","author":[{"given":"Robert E.","family":"Osterberg","sequence":"first","affiliation":[{"name":"Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norman A.","family":"See","sequence":"additional","affiliation":[{"name":"Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2003,9,1]]},"reference":[{"key":"atypb1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.10154"},{"key":"atypb2","first-page":"48","author":"de Jong, H.","year":"2001","journal-title":"Curr. 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Detection of toxicity to reproduction for medicinal products."},{"key":"atypb12","unstructured":"ICH-S5B. 1996, 2000. Detection of toxicity to reproduction for medicinal products: Addendum on toxicity to male fertility."},{"key":"atypb13","unstructured":"ICH-S7A. 2001. Safety pharmacology studies for human pharmaceuticals."},{"key":"atypb14","unstructured":"Rossoff, I. S. 2002. Encyclopedia of toxicology, 363. New York: The Parthenon Publishing Group."},{"key":"atypb15","first-page":"1537","volume":"109","author":"Ruprecht, H. A.","year":"1937","journal-title":"J.A.M.A."},{"key":"atypb16","doi-asserted-by":"publisher","DOI":"10.1006\/rtph.1996.0120"},{"key":"atypb17","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM196904102801520"},{"key":"atypb18","first-page":"59","volume-title":"Excipient toxicity and safety","author":"Winek, C. L.","year":"2000"}],"container-title":["International Journal of Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/109158180302200507","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/109158180302200507","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,2]],"date-time":"2025-03-02T06:52:40Z","timestamp":1740898360000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/109158180302200507"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,9]]},"references-count":18,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2003,9]]}},"alternative-id":["10.1177\/109158180302200507"],"URL":"https:\/\/doi.org\/10.1177\/109158180302200507","relation":{},"ISSN":["1091-5818","1092-874X"],"issn-type":[{"value":"1091-5818","type":"print"},{"value":"1092-874X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,9]]}}}