Metabolism and disposition of 2-ethylhexyl-p-methoxycinnamate following oral gavage and dermal exposure in Harlan Sprague Dawley rats and B6C3F1/N mice and in hepatocytes in vitro

• Published in: Xenobiotica 2018-11, Vol.48 (11), p.1142-1156
• Main Authors: Fennell, Timothy R., Mathews, James M., Snyder, Rodney W., Hong, Yan, Watson, Scott L., Black, Sherry R., McIntyre, Barry S., Waidyanatha, Suramya
• Format: Article
• Language: English
• Subjects: 2-ethylhexyl-p-methoxycinnamate; Administration, Intravenous; Administration, Oral; Administration, Topical; Animals; Cinnamates - administration & dosage; Cinnamates - metabolism; Cinnamates - pharmacokinetics; Disposition; Feces; Female; hepatocytes; Hepatocytes - drug effects; Hexanols - metabolism; Hexanols - pharmacokinetics; Humans; Inactivation, Metabolic - drug effects; Male; metabolism; Mice, Inbred Strains; oral absorption; Rats, Sprague-Dawley; Sunscreening Agents - administration & dosage; Sunscreening Agents - metabolism; Sunscreening Agents - pharmacokinetics; Tissue Distribution
• ISSN: 0049-8254; 1366-5928
• DOI: 10.1080/00498254.2017.1400129

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 [ 14 C]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. [ 14 C]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 CO 2 (1-4%). Radioactive residues in tissues were