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Abstract
1. 2-Ethylhexyl-p-methoxycinnamate (EHMC) is commonly used as an ingredient in sunscreens, resulting in potential oral and dermal exposure in humans.
2. Clearance and metabolism of EHMC in hepatocytes and disposition and metabolism of EHMC in rodents following oral (8–800 mg/kg) intravenous (IV) (8 mg/kg) or dermal (0.8–80 mg/kg representing 0.1–10% formulation concentration) exposure to [14C]EHMC were investigated in rats and mice.
3. EHMC was rapidly cleared from rat and mouse hepatocytes (half-life ≤3.16 min) and less rapidly (half-life ≤48 min) from human hepatocytes.
4. [14C]EHMC was extensively absorbed and excreted primarily in urine by 72 h after oral administration to rats (65–80%) and mice (63–72%). Oral doses to rats were excreted to a lesser extent (3–8%) in feces and as CO2 (1–4%). Radioactive residues in tissues were <1% of the dose. There were no sex or species differences in disposition in rats.
5. Following dermal application, 34–42% of an 8–mg/kg dose was absorbed in rats, and 54–62% in mice in 72–h.
6. Among numerous urinary metabolites associated with hydrolysis of the ester, two potential reproductive and developmental toxicants, 2-ethylhexanol and 2-ethylhexanoic acid were produced by metabolism of EHMC.
Acknowledgments
The authors are grateful to Drs. Anika Dzierlenga and Stephen Ferguson for their review of this manuscript, and Ms. Kathy Ancheta for her assistance in preparation of the manuscript.
This work was performed for the National Toxicology program, National Institute of Environmental Health Sciences, National Institutes of Health, U.S. Department of Health and Human Services, under contract No. N01-ES-75563 (HHSN29120077563).
Declaration of interest
No potential conflict of interest was reported by the authors.