{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T15:39:57Z","timestamp":1790177997185,"version":"4.1.0"},"reference-count":47,"publisher":"SAGE Publications","issue":"1_suppl","license":[{"start":{"date-parts":[[2008,1,1]],"date-time":"2008-01-01T00:00:00Z","timestamp":1199145600000},"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":[[2008,1]]},"abstract":"<jats:p>HC Red No. 7 functions as a semipermanent (direct) hair colorant in one cosmetic product at 1%. Analytical studies found the relative purity of HC Red No. 7 to be &gt;98.5%. Impurities may include 2-nitro-benzene-1,4-diamine; 3-(4-amino-3-nitro-phenyl)oxazolin-2-one; 2-chloroethyl 4-amino-3-nitrophenylcarbamate; residual solvents ethanol, DMF, or isopropyl acetate; chloride ions; and heavy metals. Around 0.10% of the applied HC Red No. 7 was absorbed in human dermatomed skin samples. In an acute oral toxicity study in rats, the maximum nonlethal dose was 300 mg\/kg. The no observed effect level (NOEL) in a subchronic oral toxicity study in rats was 50 mg\/kg day-1 . HC Red No. 7 was not a dermal or ocular irritant in rabbits, but lymphoproliferative responses in mice indicated that HC Red No. 7 should be considered a moderate sensitizer. The NOEL for maternal toxicity was 50 mg\/kg\/day and the no observed adverse effect level (NOAEL) for embryonic development was 200 mg\/kg\/day in a prenatal toxicity study of HC Red No. 7 using rats. HC Red No. 7 was nonmutagenic at the hprt locus but mutagenic at the TK locus in mouse lymphoma cells, was mutagenic in several Salmonella typhimurium strains, was not active in an unscheduled DNA synthesis assay, and was unclear in a micronucleus assay in human lymphocyte cultures. No carcinogenicity studies were available, nor were any clinical tests reported. Available hair dye epidemiology studies are insufficient to conclude a causal relationship between hair dye use and cancer or other diseases, but more relevant is that direct hair dyes, although not the focus in all investigations, appear to have little evidence of an association with adverse events as reported in epidemiology studies. As reviewed by the Cosmetic Ingredient Review (CIR) Expert Panel, HC Red No. 7 appears to be a moderate sensitizer in animals. No human sensitivity data concerning this ingredient have been reported. However, hair dyes containing HC Red No. 7, as coal tar hair dye products, are exempt from the principal adulteration provision and from the color additive provisions in sections 601 and 706 of the Federal Food, Drug, and Cosmetic Act, when the label bears a caution statement and patch test instructions for determining whether the product causes contact dermatitis. The Expert Panel expects that following this procedure will identify prospective individuals who would have an irritation\/sensitization reaction and allow them to avoid significant exposures. The CIR Expert Panel also noted that mutagenicity studies available for HC Red No. 7 gave both positive and negative results. Based on the available data, it was concluded that, at most, this ingredient is a weak mutagen. Due to its low dermal absorption potential and its use as a semipermanent hair dye, the CIR Expert Panel believes there is low risk of genotoxicity and that HC Red No. 7 is safe as a hair dye ingredient in the practices of use and concentrations as described in this safety assessment.<\/jats:p>","DOI":"10.1080\/10915810802032438","type":"journal-article","created":{"date-parts":[[2008,6,21]],"date-time":"2008-06-21T08:29:33Z","timestamp":1214036973000},"page":"45-54","source":"Crossref","is-referenced-by-count":3,"title":["Final Report on the Safety Assessment of HC Red No. 71"],"prefix":"10.1177","volume":"27","member":"179","published-online":{"date-parts":[[2008,1,1]]},"reference":[{"key":"atypb1","doi-asserted-by":"publisher","DOI":"10.1016\/S0190-9622(85)70258-7"},{"key":"atypb2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.11729"},{"key":"atypb3","first-page":"305","volume":"7","year":"1994","journal-title":"In Vitro Toxicol."},{"key":"atypb4","first-page":"5","year":"2005","journal-title":"Int. J. Epidemiol."},{"key":"atypb5","unstructured":"CIT Safety and Health Research Laboratories. 2005b. Evaluation of skin sensi-tization potential in mice using the local lymph node assay (LLNA). Unpublished data submitted by CTFA. 28 pages."},{"key":"atypb6","unstructured":"CIT Safety and Health Research Laboratories. 2005a. Acute oral toxicity in rats \u201cfixed dose method\u201d. Unpublished data submitted by CTFA. 25 pages."},{"key":"atypb7","unstructured":"Colipa. 2005. Analytical file on HC Red No. 7: 1-amino-2-nitro-4-(\n                      \u03b2\n                      -hydroxyethyl)aminobenzene (Colipa B036). Unpublished data submitted by CTFA. 75 pages."},{"key":"atypb8","unstructured":"Cosmetic, Toiletry, and Fragrance Association (CTFA). 2005. Current use concentration of HC Red No. 7. Unpublished data provided by CTFA. 1 page."},{"key":"atypb9","unstructured":"CTFA. 2001.\n                      In vitro\n                      percutaneous absorption of Imexine FZ (Colipa B036). Unpublished data submitted by CTFA. 69 pages."},{"key":"atypb10","unstructured":"Covance Laboratories, Ltd. 2005a. HC Red No. 7 (B036): Mutation at the\n                      hrpt\n                      locus of L5178Y mouse lymphoma cells using the Microtitre fluctuation technique. Unpublished data submitted by CTFA. 49 pages."},{"key":"atypb11","unstructured":"Covance Laboratories, Ltd. 2005b. HC Red No. 7 (B036): Reverse mutation in five histidine-requiring strains of\n                      Salmonella typhimurium.\n                      Unpublished data submitted by CTFA. 63 pages."},{"key":"atypb12","unstructured":"Covance Laboratories, Ltd. 2005c. HC Red No. 7 (B036): Induction of mi-cronuclei in cultured human peripheral blood lymphocytes. Unpublished data submitted by CTFA. 54 pages."},{"key":"atypb13","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwj187"},{"key":"atypb14","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-004-3121-0"},{"key":"atypb15","doi-asserted-by":"publisher","DOI":"10.1016\/S0190-9622(82)70080-5"},{"key":"atypb16","doi-asserted-by":"crossref","unstructured":"Elder, R. L., ed. 1985. Final report on the safety assessment of\n                      p\n                      -phenylenediamine.\n                      J. Am. Coll. Toxicol.\n                      4:203-266.","DOI":"10.3109\/10915818509078673"},{"key":"atypb17","unstructured":"European Commission. 2005. Commission Directive 2005\/80\/EC of 21 November 2005 amending Council Directive 76\/768\/EEC, concerning cosmetics products, for the purposes of adapting Annexes II and III thereto to technical progress.\n                      Official J. European Union\n                      22.11. 2005. http:\/\/ec.europa.eu\/enterprise\/cosmetics\/doc\/2005 80\/dir 2005 80 en.pdf. accessed June 13, 2006."},{"key":"atypb18","unstructured":"EViC-CEBA. 1996a. Acute eye irritation\/corrosion of the substance Imexine FZ-Batch T 81. Unpublished data submitted by CTFA. 9 pages."},{"key":"atypb19","unstructured":"EViC-CEBA. 1996b. Acute dermal irritation\/corrosion of the substance Imexine FZ-Batch T 81. Unpublished data submitted by CTFA. 8 pages."},{"key":"atypb20","unstructured":"Food and Drug Administration (FDA). 2005. Frequency of use of cosmetic ingredients.\n                      FDA database.\n                      Washington, DC: FDA."},{"key":"atypb21","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0215(200002)9999:9999<::AID-IJC1092>3.0.CO;2-S"},{"key":"atypb22","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/24.3.483"},{"key":"atypb23","volume-title":"International cosmetic ingredient dictionary and handbook","year":"2006"},{"key":"atypb24","doi-asserted-by":"publisher","DOI":"10.1007\/s10552-005-3204-z"},{"key":"atypb25","doi-asserted-by":"publisher","DOI":"10.1177\/003335490512000107"},{"key":"atypb26","unstructured":"International Agency for Research on Cancer (IARC). 1993. IARC monographs on the evaluation of carcinogenic risks to humans. Vol 57. Occupational exposures of hairdressers and barbers and personal use of hair colourants; some hair dyes, cosmetic colourants, industrial dyestuffs and aromatic amines, 43-118. Lyon, France: IARC."},{"key":"atypb27","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6602473"},{"key":"atypb28","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.21195"},{"key":"atypb29","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2006.02.009"},{"key":"atypb30","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-06-0156"},{"key":"atypb31","doi-asserted-by":"publisher","DOI":"10.1007\/s10552-005-1229-y"},{"key":"atypb32","first-page":"117","volume":"55","year":"2005","journal-title":"Zbl Ar-beitsmed."},{"key":"atypb33","unstructured":"Ministry of Health, Labor and Welfare (MHLW). September 2000. MHW Ordinance No. 332, Ingredients of quasi-drugs. Products to be used directly on the body. Ministry of Health, Labor and Welfare, Pharmaceutical and Medical Safety Bureau, Inspection and Guidance Division, 2-2, 1-chome, Kasumi-gaseki, Chiyoda-ku, Tokyo 100-8045, Japan."},{"key":"atypb34","unstructured":"North American Contact Dermatitis Group. 1980.\n                      Patch testing in allergic contact dermatitis.\n                      Evanston: IL: American Academy of Dermatology."},{"key":"atypb35","doi-asserted-by":"publisher","DOI":"10.1002\/ajim.20178"},{"key":"atypb36","first-page":"9","volume":"160","year":"2004","journal-title":"Am. J. Epidemiol."},{"key":"atypb37","unstructured":"RCC Group. 1995.\n                      In vivo\/in vitro\n                      unscheduled DNA synthesis in rat hepato-cytes. Unpublished data submitted by CTFA. 27 pages."},{"key":"atypb38","doi-asserted-by":"publisher","DOI":"10.1080\/10937400600681455"},{"key":"atypb39","unstructured":"Sequani Ltd. 2005. Histopathology examination of tissue from study LRL\/25\/93. 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Unpublished data submitted by CTFA. 20 pages."},{"key":"atypb46","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwh033"},{"key":"atypb47","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwh067"}],"container-title":["International Journal of Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1080\/10915810802032438","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1080\/10915810802032438","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T10:22:49Z","timestamp":1777458169000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1080\/10915810802032438"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,1]]},"references-count":47,"journal-issue":{"issue":"1_suppl","published-print":{"date-parts":[[2008,1]]}},"alternative-id":["10.1080\/10915810802032438"],"URL":"https:\/\/doi.org\/10.1080\/10915810802032438","relation":{},"ISSN":["1091-5818","1092-874X"],"issn-type":[{"value":"1091-5818","type":"print"},{"value":"1092-874X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,1]]}}}