{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:16:04Z","timestamp":1783570564445,"version":"3.55.0"},"reference-count":26,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Paraphenylenediamine (PPD) is a primary component of permanent hair dyes and is known for its dermal toxicity; however, systematic dose\u2013response data for chronic exposure are lacking. This study investigated the hepatotoxic and hematotoxic effects of commercial PPD\u2010based dyes using a rabbit model to establish safety thresholds and inform regulatory limits. Seventy\u2010two male rabbits received dermal applications of natural henna (control) or PPD\u2010containing dyes at concentrations of 0.098, 0.187, or 2.375\u2009mg\/g every 10\u2009days for 6\u2009months. PPD exposure induced dose\u2010dependent mortality (0% to 22.2%), elevated hepatic enzyme levels (4\u2010 to 5\u2010fold increase at the highest dose), and macrocytic anemia (hemoglobin decreased by 28%, red blood cells by 39%). Histopathological analysis revealed progressive hepatocyte damage ranging from mild inflammation to severe necrosis. These findings demonstrate that PPD concentration, rather than the carrier matrix, determines systemic toxicity, and suggest that the current 2% regulatory limit may be insufficiently protective under chronic exposure conditions. This research provides quantitative hazard data for PPD risk assessment and supports the implementation of stricter concentration limits in cosmetic formulations.<\/jats:p>","DOI":"10.1002\/jat.70335","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T03:52:36Z","timestamp":1783569156000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Toxicological Evaluation of Natural and Synthetic Hair Dyes Containing Paraphenylenediamine (PPD) on Biochemical Parameters in Rabbits"],"prefix":"10.1002","author":[{"given":"Umsalama B.","family":"Eissa","sequence":"first","affiliation":[{"name":"Faculty of Productional Technology and Agricultural Processing International University of Africa  Khartoum Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6085-2780","authenticated-orcid":false,"given":"Khalid A.","family":"Gadein","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Technology, Faculty of Science and Technology Omdurman Islamic University  Omdurman Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somia","family":"A. Agab","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Technology, Faculty of Science and Technology Omdurman Islamic University  Omdurman Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohaned Abadallh","family":"Sahl","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Technology, Faculty of Science and Technology Omdurman Islamic University  Omdurman Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma H.","family":"Hamed","sequence":"additional","affiliation":[{"name":"Faculty of Productional Technology and Agricultural Processing International University of Africa  Khartoum Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emtithal Alamen","family":"Mahadi","sequence":"additional","affiliation":[{"name":"Faculty of Productional Technology and Agricultural Processing International University of Africa  Khartoum Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sulayman al\u2010Said Qasm","family":"Nasir","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science and Technology Omdurman Islamic University  Omdurman Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajr A.","family":"Ismail","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences, Faculty of Animal and Veterinary Sciences University of Nyala  Nyala Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima Abdelhameed","family":"Hussein","sequence":"additional","affiliation":[{"name":"Department of Dairy Production, Faculty of Animal Production University of Khartoum  Khartoum Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejfs.2012.06.003"},{"issue":"2","key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.33899\/ijvs.2011.5640","article-title":"Effect of Nitrate Poisoning on Some Biochemical Parameters in Rats","volume":"25","author":"Azeez O. 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D.","year":"2008"},{"key":"e_1_2_10_5_1","first-page":"629","volume-title":"Contact Dermatitis","author":"Basketter D.","year":"2010"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(83)90539\u20101"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jece.2018.04.041"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3923\/jpt.2009.221.228"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/pai.12043"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840070623"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.4103\/0378\u20106323.100547"},{"issue":"1","key":"e_1_2_10_12_1","first-page":"13","article-title":"The Effect of Potash on Liver Function of Wistar Rats","volume":"5","author":"Iweka F. 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S.","year":"2017","journal-title":"Journal of Asthma and Allergy"},{"key":"e_1_2_10_17_1","unstructured":"NTP.1992. \u201cNational Toxicology Program.\u201d Toxicology and Carcinogenesis Studies of Resorcinol in F344\/N Rats and B6C3F1 Mice. Technical Report Series no. 403. 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