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Xenobiotica
the fate of foreign compounds in biological systems
Volume 45, 2015 - Issue 9
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Animal Pharmacokinetics and Metabolism

Disposition of bisphenol AF, a bisphenol A analogue, in hepatocytes in vitro and in male and female Harlan Sprague-Dawley rats and B6C3F1/N mice following oral and intravenous administration

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Pages 811-819 | Received 23 Dec 2014, Accepted 18 Feb 2015, Published online: 29 Apr 2015
 

Abstract

1. Bisphenol AF (BPAF) is used as a crosslinking agent for polymers and is being considered as a replacement for bisphenol A (BPA).

2. In this study, comparative clearance and metabolism of BPAF and BPA in hepatocytes and the disposition and metabolism of BPAF in rodents following oral administration of 3.4, 34 or 340 mg/kg [14C]BPAF were investigated.

3. BPAF was cleared more slowly than BPA in hepatocytes with the rate: rat > mouse > human.

4. [14C]BPAF was excreted primarily in feces by 72 h after oral administration to rats (65–80%) and mice (63–72%). Females excreted more in urine (rat, 15%; mouse, 24%) than males (rat, 1–4%; mouse, 10%). Residual tissue radioactivity was <2% of the dose at 72 h. Similar results were observed following intravenous administration.

5. In male rats, 52% of a 340 mg/kg oral dose was excreted in 24 h bile and was mostly comprised of BPAF glucuronide. However, >94% of fecal radioactivity was present as BPAF, suggesting extensive deconjugation in the intestine.

6. Metabolites identified in bile were BPAF-glucuronide, -diglucuronide, -glucuronide sulfate and -sulfate.

7. In conclusion, BPAF was well absorbed following gavage administration and highly metabolized and excreted mostly in the feces as BPAF.

Acknowledgements

The authors are grateful to Drs. Vicki Sutherland and Stephen Ferguson for their review of this manuscript and to Ms. Kathy Ancheta for assistance in its preparation. 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

The authors report no conflicts of interest.

Supplementary material available online.

Supplementary Figures S1-S7.

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