{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T12:44:49Z","timestamp":1792586689022,"version":"4.5.0"},"reference-count":0,"publisher":"The Journal of Food and Drug Analysis (JFDA), Food and Drug Administration, Taiwan (TFDA)","issue":"2","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Food and Drug Analysis"],"abstract":"<jats:p>Tyrosinase is an enzyme involved in the early stages of melanin synthesis. Melanin, which gives skin its pigment, is the most targeted molecule in the development of skin-whitening cosmetic products. Consequential risks of chemically induced skin diseases are associated with the usage of skin-whitening products that contain tyrosinase-inhibiting compounds. Currently, products containing tyrosinase inhibitors on the market lack collective analysis of their toxicity on melanocytes. Moreover, national regulatory agencies (e.g., FDA) place the burden of ensuring the safety of whitening products on manufacturers, risking bias and selective reporting. In fact, the ASEAN Cosmetic Directive does not include more than half of the 'novel' whitening agents currently on the market. This review describes the relationship of lipophilicity of cosmetic whitening ingredients (CWI) with melanocyte cytotoxicity. A systematic search of databases using the phrase (((Skin Whitening) OR (Skin Brightening) OR (Skin Lightening) OR (Skin Bleaching)) AND ((Melanocyte Cytotoxicity) OR (Cytotoxicity) OR (Cytotoxic Effect)) AND Mechanism)) was carried out. Data such as the assay and medium used, mechanism of action, cLogP, and cell viability were extracted from the 11 articles in the study. The cell viability data and respective concentration used for the MTT assays were used to calculate the IC50 values of each CWI using the drc-R package in R. The identified CWIs were categorized by their respective lipophilicity; subsequently, linear regression analysis was conducted. It was revealed that the cLogP of the CWIs was able to exhibit a moderate positive correlation between IC50 values (R2 = 0.3263; m = 57.85). Lipophilic CWIs also exhibit moderate direct relationships between the variables (R2 = 0.3535; m = 83.36). However, for hydrophilic CWIs (R2 = 0.00021; m = -3.263), only a weak negative correlation exists, but the effect is negligible and not significant (p-value &gt; 0.05; 0.8537). Out of the 18 identified CWIs, 7 were found to be potentially toxic (IC50 value &lt; 50 ug\/mL); however, only hydroquinone is officially classified under the ASEAN Cosmetics Ingredient List (ACIL) to be banned in skin cosmetic products. The results of this study suggest that cytotoxicity is potentially influenced by cLogP and may also be attributed to other characteristics such as molecular structure, solubility, and cell line interaction. In addition, this study emphasizes the necessity for current safety regulations and guidelines and further investigation of in vitro safety data pertinent to human applications.<\/jats:p>","DOI":"10.38212\/2224-6614.3577","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T08:16:36Z","timestamp":1783584996000},"source":"Crossref","is-referenced-by-count":0,"title":["Effect of Cosmetic Whitening Ingredients\u2019 Lipophilicity on Melanocyte Cytotoxicity: A Systematic Review"],"prefix":"10.38212","volume":"34","author":[{"given":"Lord Sam B.","family":"Liston","sequence":"first","affiliation":[{"name":"Department of Pharmacy, School of Health Care Professions, University of San Carlos, Nasipit, Talamban, Cebu, 6000, The Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zach Uriel","family":"Cabije","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Health Care Professions, University of San Carlos, Nasipit, Talamban, Cebu, 6000, The Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico John","family":"Belleza","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Health Care Professions, University of San Carlos, Nasipit, Talamban, Cebu, 6000, The Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Ortega","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Health Care Professions, University of San Carlos, Nasipit, Talamban, Cebu, 6000, The Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark Ni\u00f1o","family":"Melgo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Health Care Professions, University of San Carlos, Nasipit, Talamban, Cebu, 6000, The Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanbeth","family":"Camson","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Health Care Professions, University of San Carlos, Nasipit, Talamban, Cebu, 6000, The Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Dahlizar","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Health Science, Syarif Hidayatullah State Islamic University Jakarta, Banten 15419, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pajaree","family":"Sakdiset","sequence":"additional","affiliation":[{"name":"Drug and Cosmetics Excellence Center, Walailak University, Thasala, Nakhon Si Thammarat, 80161, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gea Abigail","family":"Ecoy","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Health Care Professions, University of San Carlos, Nasipit, Talamban, Cebu, 6000, The Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard Lee","family":"See","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Health Care Professions, University of San Carlos, Nasipit, Talamban, Cebu, 6000, The Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florencio Jr.","family":"Arce","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Health Care Professions, University of San Carlos, Nasipit, Talamban, Cebu, 6000, The Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"25385","published-online":{"date-parts":[[2026,7,6]]},"container-title":["Journal of Food and Drug Analysis"],"original-title":[],"language":"en","deposited":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T12:14:38Z","timestamp":1792584878000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jfda-online.com\/journal\/vol34\/iss2\/2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,6]]},"references-count":0,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,7,6]]}},"URL":"https:\/\/doi.org\/10.38212\/2224-6614.3577","relation":{},"ISSN":["2224-6614"],"issn-type":[{"value":"2224-6614","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,6]]}}}