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Toxicokinetic Characterization of MDM Hydantoin via Stable Metabolite DMH: Population Modeling for Predicting Dermal

Woohyung Jung1, Jaewoong Lee1, Woojin Kim1

  • 1College of Pharmacy, Daegu Catholic University, Gyeongsan 38430, Republic of Korea.

Toxics
|November 27, 2025
PubMed

Insights

Methyl DMDM hydantoin (MDMH) is rapidly converted to DMH in the body. Monitoring DMH levels helps assess toxicokinetics of MDMH exposure, especially after skin contact.

Area of Science:

  • Toxicology
  • Pharmacokinetics
  • Analytical Chemistry

Background:

  • Methyl DMDM hydantoin (MDMH) is a cosmetic preservative that releases formaldehyde.
  • MDMH degrades rapidly in biological samples, hindering toxicokinetic studies.
  • Quantitative exposure data is lacking for MDMH safety assessments.

Purpose of the Study:

  • To develop and validate an LC-MS/MS assay for MDMH and its metabolite DMH.
  • To characterize the toxicokinetics of MDMH and DMH after intravenous and transdermal administration in rats.
  • To assess MDMH absorption, distribution, metabolism, and excretion (ADME) following dermal exposure.

Main Methods:

  • Validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for simultaneous determination of MDMH and DMH in rat plasma.
  • Administered MDMH intravenously and transdermally to rats.
  • Utilized population modeling to characterize toxicokinetics and estimate dermal absorption.

Main Results:

  • MDMH showed extremely rapid elimination (t½ = 0.4 min) with >97% conversion to DMH.
  • DMH exhibited prolonged retention (t½ = 174.2 min) and 100% bioavailability after transdermal application.
  • Population modeling indicated 84% of applied MDMH was absorbed and metabolized in skin.

Conclusions:

  • Stable metabolite monitoring (DMH) combined with population modeling is effective for characterizing toxicokinetics of rapidly degrading compounds like MDMH.
  • This approach provides crucial quantitative exposure data for dermal exposure assessments of MDMH.
  • Findings support improved risk assessment for formaldehyde-releasing preservatives in cosmetics.
Keywords:
DMHMDMHformaldehyde releaserpopulation toxicokinetic modelingtoxicokinetics

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