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Xenobiotica
the fate of foreign compounds in biological systems
Volume 50, 2020 - Issue 6
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Animal Pharmacokinetics and Metabolism

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

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Pages 689-704 | Received 19 Aug 2019, Accepted 12 Oct 2019, Published online: 31 Oct 2019
 

Abstract

  1. 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).

  2. 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%).

  3. 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).

  4. In rats, HMB slowly appeared in the systemic circulation (Tmax ∼2–6 h) and had poor bioavailability (F%<1).

  5. 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.

  6. In vitro hepatic metabolism in mice differed from human and in vivo metabolism especially for phase II conjugates.

Acknowledgements

Authors would like to thank Mr. Bradley J. Collins and Dr. Madelyn C. Huang for their review of this manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

Please see below for raw data link for the reviewers; https://doi.org/10.22427/NTP-DATA-002-01338-0023-0000-2

Additional information

Funding

This work was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences, Intramural Research project ZIA ES103316-04 and was conducted for the National Toxicology Program by Lovelace Biomedical and Environmental Research Institute under the contract HHSN291200775562C.

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