TY - JOUR
T1 - Evidence of increased estrogenicity upon metabolism of Bisphenol F - Elucidation of the key metabolites
AU - Shao, Ying
AU - Zhu, Linyan
AU - Chen, Zhongli
AU - Thalmann, Beat
AU - Zhou, Shangbo
AU - Hollert, Henner
AU - Seiler, Thomas Benjamin
N1 - Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/9/15
Y1 - 2021/9/15
N2 - The increasing concern over bisphenol A (BPA) has directed much attention toward bisphenol F (BPF) and bisphenol S (BPS) as BPA alternatives for the development of “BPA-free” products. Consequently, BPS and BPF were frequently detected in surface water, sediment, sewage effluent, indoor dust, and even in food and biological fluids in humans. Thus, environmental researches start to focus on the potential environmental risks of BPA alternatives. While the estrogenically active metabolites and the specific estrogenically active structure are still unknown. In this study, the MTT assay on acute cytotoxicity and the recombinant transactivation assay were carried out to determine whether BPF and BPS are suitable alternatives to BPA. Our results show that the cytotoxic and estrogenic activities of BPS and BPF are lower than those of BPA. However, after the addition of a rat liver homogenate to simulate mammal metabolism, BPF exhibited higher estrogenic activity than BPA. To identify the chemical structures and estrogen receptor binding affinities of active estrogenic metabolites, LC-MS, MetaPrint2D(-React), and VirtualToxLab were integrated. The observed results indicated that the para-hydroxylated BPF and BPF-OCH3 might have strong ER binding affinities. These results demonstrate that metabolization is important to consider upon investigating endocrine disruption of chemicals getting into contact with humans, such as in dental sealing or food packaging. Alternatives to potentially hazardous substances should be thoroughly tested prior to use.
AB - The increasing concern over bisphenol A (BPA) has directed much attention toward bisphenol F (BPF) and bisphenol S (BPS) as BPA alternatives for the development of “BPA-free” products. Consequently, BPS and BPF were frequently detected in surface water, sediment, sewage effluent, indoor dust, and even in food and biological fluids in humans. Thus, environmental researches start to focus on the potential environmental risks of BPA alternatives. While the estrogenically active metabolites and the specific estrogenically active structure are still unknown. In this study, the MTT assay on acute cytotoxicity and the recombinant transactivation assay were carried out to determine whether BPF and BPS are suitable alternatives to BPA. Our results show that the cytotoxic and estrogenic activities of BPS and BPF are lower than those of BPA. However, after the addition of a rat liver homogenate to simulate mammal metabolism, BPF exhibited higher estrogenic activity than BPA. To identify the chemical structures and estrogen receptor binding affinities of active estrogenic metabolites, LC-MS, MetaPrint2D(-React), and VirtualToxLab were integrated. The observed results indicated that the para-hydroxylated BPF and BPF-OCH3 might have strong ER binding affinities. These results demonstrate that metabolization is important to consider upon investigating endocrine disruption of chemicals getting into contact with humans, such as in dental sealing or food packaging. Alternatives to potentially hazardous substances should be thoroughly tested prior to use.
KW - Bisphenol-OCH
KW - Dental fissure sealants
KW - ER binding affinities
KW - Para-hydroxylated BPF
KW - Benzhydryl Compounds/toxicity
KW - Chromatography, Liquid
KW - Phenols
KW - Biological Assay
KW - Estrone
UR - http://www.scopus.com/inward/record.url?scp=85105746265&partnerID=8YFLogxK
U2 - 10.1016/j.scitotenv.2021.147669
DO - 10.1016/j.scitotenv.2021.147669
M3 - Journal article
C2 - 34000551
AN - SCOPUS:85105746265
SN - 0048-9697
VL - 787
JO - Science of the Total Environment
JF - Science of the Total Environment
M1 - 147669
ER -