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

Abstract

1.?Bisphenol AF (BPAF) is used as a crosslinking agent for polymers and is being considered as a replacement for bisphenol A (BPA).<br><br>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.<br><br>3.?BPAF was cleared more slowly than BPA in hepatocytes with the rate: rat?>?mouse?>?human.<br><br>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.<br><br>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.<br><br>6.?Metabolites identified in bile were BPAF-glucuronide, -diglucuronide, -glucuronide sulfate and -sulfate.<br><br>7.?In conclusion, BPAF was well absorbed following gavage administration and highly metabolized and excreted mostly in the feces as BPAF.