Metabolism and disposition of 2-hydroxy-4-methoxybenzophenone, a sunscreen ingredient, in Harlan Sprague Dawley rats and B6C3F1/N mice; a species and route comparison

Xenobiotica. 2020 Jun;50(6):689-704. doi: 10.1080/00498254.2019.1680906. Epub 2019 Oct 31.

Abstract

2-Hydroxy-4-methoxybenzophenone (HMB) is a common ingredient in personal care products and used as an UV stabilizer. In these studies, disposition and metabolism of [14C]HMB in rats and mice was assessed following single gavage administration (10, 100, or 500 mg/kg), single IV administration (10 mg/kg), or dermal application (0.1, 1, 10, or 15 mg/kg).Following gavage administration, [14C]HMB was well absorbed and excreted mainly in urine (39-57%) and feces (24-42%) with no apparent difference between doses, species or sexes. Distribution of HMB in tissues was minimal in rats (0.36%) and mice (<0.55%).Distribution of HMB following dermal application was comparable to that following gavage administration; no differences between doses, sexes, or species were observed but absorption varied between dose vehicles. Light paraffin oil had the highest absorption and excretion (98% of the HMB dose absorbed).In rats, HMB slowly appeared in the systemic circulation (Tmax ∼2-6 h) and had poor bioavailability (F%<1).Urine metabolites for both species and all routes included HMB, HMB-glucuronide, 2,4-dihydroxybenzophenone (DHB), DHB-glucuronide, and DHB-sulfates, and novel minor dihydroxy metabolites including 2,5-dihydroxy-4-methoxybenzophenone.In vitro hepatic metabolism in mice differed from human and in vivo metabolism especially for phase II conjugates.

Keywords: 2-hydroxy-4-methoxybenzophenone; Sunscreen; UV stabilizers; absorption; benzophenone-3; distribution; excretion; metabolism; oxybenzone.

MeSH terms

  • Animals
  • Benzophenones / metabolism*
  • Humans
  • Mice
  • Mice, Inbred Strains
  • Rats
  • Rats, Sprague-Dawley
  • Sunscreening Agents / metabolism*

Substances

  • Benzophenones
  • Sunscreening Agents
  • oxybenzone