NTP Developmental and Reproductive Toxicity Technical Report on the Modified One-Generation Study of Bisphenol AF (CASRN 1478-61-1) Administered in Feed to Sprague Dawley (Hsd:Sprague Dawley® SD®) Rats with Prenatal, Reproductive Performance, and Subchronic Assessments in F1 Offspring

Abstract

Bisphenol AF (BPAF) is used as a curing or crosslinking agent in the processing of fluorocarbon elastomers, rubber processing, and specialty polymers due to its material characteristics, including thermal stability, chemical resistance, and compression set resistance, which are useful in plastics manufacturing and other fabrication processes. BPAF was selected for evaluation based on a review of compounds that are potentially endocrine-active after concerns were raised about possible effects of bisphenol A (BPA) on the brain, behavior, and prostate gland of fetuses, infants, and children at current human exposure levels. The review assessed a number of agents that could have endocrine activity and are either persistent in the environment or have high human exposures, including chemicals that are structurally related to BPA. BPAF was selected because of its potential for endocrine activity, lack of adequate toxicity data, and potential environmental persistence due to the presence of fluorine atoms. The objective of the present study was to characterize the potential for BPAF to adversely affect any phase of rat development, maturation, and ability to reproduce. The potential for BPAF to induce subchronic toxicity in the F1 generation, adversely affect the ability of the F1 generation to reproduce viable F2 offspring, and adversely affect F2 embryo-fetal development was assessed in Sprague Dawley (Hsd:Sprague Dawley® SD®) rats administered BPAF in 5K96 feed, a diet low in phytoestrogens, using the National Toxicology Program (NTP) modified one-generation (MOG) study design. NTP conducted a dose range-finding study with exposure concentrations of 0, 937.5, 1,875, 3,750, 7,500, and 15,000 ppm and based on findings of maternal and pup toxicity (significantly decreased body weights) observed at ≥7,500 ppm, exposure concentrations of 338, 1,125, and 3,750 ppm were selected for the MOG study.