{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:43:49Z","timestamp":1785426229848,"version":"3.56.0"},"reference-count":23,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T00:00:00Z","timestamp":1761350400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003569","name":"Ministry of Food and Drug Safety, Republic of Korea","doi-asserted-by":"publisher","award":["18181MFDS362"],"award-info":[{"award-number":["18181MFDS362"]}],"id":[{"id":"10.13039\/501100003569","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Gyeongsangbuk-do RISE(Regional Innovation System & Education) project"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>MDM hydantoin (MDMH), a formaldehyde-releasing preservative widely used in cosmetics, poses potential health risks due to its conversion to formaldehyde and systemically absorbed metabolites. Current safety assessments lack quantitative exposure data due to rapid degradation of MDMH in biological matrices. In the present study, we developed a validated LC-MS\/MS assay for simultaneous determination of MDMH and its stable metabolite DMH in rat plasma, and characterized their toxicokinetics using population modeling following intravenous and transdermal administration. MDMH exhibited extremely rapid elimination (t1\/2 = 0.4 \u00b1 0.1 min) with near-complete conversion to DMH (97.6 \u00b1 9.6%), while DMH demonstrated prolonged retention (t1\/2 = 174.2 \u00b1 12.2 min) and complete bioavailability (100.9 \u00b1 18.0%) after transdermal application. Population modeling estimated that 84% (relative standard error: 42.8%) of applied MDMH undergoes cutaneous absorption and metabolism to DMH and formaldehyde within skin tissues. This study demonstrates that stable metabolite monitoring combined with population modeling enables toxicokinetic characterization of rapidly degrading compounds following dermal exposure.<\/jats:p>","DOI":"10.3390\/toxics13110917","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T03:44:39Z","timestamp":1761795879000},"page":"917","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Toxicokinetic Characterization of MDM Hydantoin via Stable Metabolite DMH: Population Modeling for Predicting Dermal Formaldehyde Formation"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-5745-6962","authenticated-orcid":false,"given":"Woohyung","family":"Jung","sequence":"first","affiliation":[{"name":"College of Pharmacy, Daegu Catholic University, Gyeongsan 38430, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaewoong","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Daegu Catholic University, Gyeongsan 38430, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woojin","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Daegu Catholic University, Gyeongsan 38430, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seongwon","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Daegu Catholic University, Gyeongsan 38430, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woojin","family":"Nam","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Daegu Catholic University, Gyeongsan 38430, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In-Soo","family":"Myeong","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Daegu Catholic University, Gyeongsan 38430, Republic of Korea"},{"name":"Convergence Research Institute for Biomedical Sciences, Daegu Catholic University, Gyeongsan 38430, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwang Ho","family":"Kim","sequence":"additional","affiliation":[{"name":"Gyeongbuk Technopark Medical Convergence Materials Commercialization Center, Gyeongsan 38430, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soyoung","family":"Shin","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Hwan","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Daegu Catholic University, Gyeongsan 38430, Republic of Korea"},{"name":"Convergence Research Institute for Biomedical Sciences, Daegu Catholic University, Gyeongsan 38430, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1111\/ics.12212","article-title":"Investigation on formaldehyde release from preservatives in cosmetics","volume":"37","author":"Lv","year":"2015","journal-title":"Int. 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