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.
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 [(14)C]BPAF were investigated. 3. BPAF was cleared more slowly than BPA in hepatocytes with the rate: rat > mouse > human. 4. [(14)C]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.
a Division of National Toxicology Program , National Institute of Environmental Health Sciences, Research Triangle Park , NC , USA and.
Suramya
S
Waidyanatha
James M
JM
Mathews
Purvi R
PR
Patel
Sherry R
SR
Black
Rodney W
RW
Snyder
Timothy R
TR
Fennell
D061605:Administration, Intravenous; D000284:Administration, Oral; D000818:Animals; D001559:Benzhydryl Compounds / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism*; D002250:Carbon Radioisotopes; D005260:Female; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways; D055442:Metabolome; D051379:Mice; D010636:Phenols / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D000098826:Bisphenol A Compounds; D005466:Fluorocarbons
D001559:Benzhydryl Compounds; D002250:Carbon Radioisotopes; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds; C583074:bisphenol AF; D005466:Fluorocarbons
Bisphenol AF; disposition; hepatocytes; metabolism; oral absorption