Direct Comparison of the Impacts of Bisphenol A, Bisphenol F, and Bisphenol S in a Male Rat 28-Day Oral Exposure Study

Although Bisphenol A (BPA) is still used in consumer products, concerns about its toxicity led to the adoption of structurally related replacement products such as Bisphenol F (BPF) and Bisphenol S (BPS). Unfortunately, comparing the biological responses to BPA and BPA substitutes <i>in vivo</i> can be challenging, as the available information is often derived from different studies using various animal strains and experimental protocols. To address this issue, we directly compared the impacts of BPA, BPF, and BPS in the same <i>in vivo</i> exposure study. Briefly, 8-week-old male Fischer rats were exposed to BPA, BPF, or BPS (at five different doses) and to 17α-ethinylestradiol (positive control for estrogenicity) by gavage for 28 consecutive days. Rat health, dietary intakes, and weight gains were monitored, 24-hour urine samples were collected, and blood and tissues were harvested at the terminal necropsy. The impacts of BPA, BPF, and BPS on rat weight gains, organ weights and histology, liver enzymatic activities, hematology, clinical chemistry, and serum hormone levels were relatively modest and mostly limited to the highest doses administered. However, bisphenol cross-contamination observed in urine samples from the vehicle control group may have interfered with the evaluation of their effects at lower doses. Although BPA, BPF, and BPS exposures all shared similarities with the 17α-ethinylestradiol positive control group, their impacts on serum hormone levels and endocrine-responsive tissues also presented noticeable differences. This suggests that BPA, BPF, and BPS may interfere with endocrine functions through slightly different molecular mechanisms.