title: Fluorene-9-bisphenol is anti-oestrogenic and may cause adverse pregnancy outcomes in mice.
abstract: Bisphenol A (BPA) is used in the production of plastic but has oestrogenic activity. Therefore, BPA substitutes, such as fluorene-9-bisphenol (BHPF), have been introduced for the production of so-called 'BPA-free' plastics. Here we show that BHPF is released from commercial 'BPA-free' plastic bottles into drinking water and has anti-oestrogenic effects in mice. We demonstrate that BHPF has anti-oestrogenic activity in vitro and, in an uterotrophic assay in mice, induces low uterine weight, atrophic endometria and causes adverse pregnancy outcomes, even at doses lower than those of BPA for which no observed adverse effect have been reported. Female mice given water containing BHPF released from plastic bottles, have detectable levels of BHPF in serum, low uterine weights and show decreased expressions of oestrogen-responsive genes. We also detect BHPF in the plasma of 7/100 individuals, who regularly drink water from plastic bottles. Our data suggest that BPA substitutes should be tested for anti-oestrogenic activity and call for further study of the toxicological effects of BHPF on human health.
authors.affiliation: College of Urban and Environmental Sciences, MOE Laboratory for Earth Surface Process, Peking University, Beijing 100871, China.
authors.forename: Zhaobin
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: College of Urban and Environmental Sciences, MOE Laboratory for Earth Surface Process, Peking University, Beijing 100871, China.|College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen, Guangdong 518060, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.affiliation: College of Urban and Environmental Sciences, MOE Laboratory for Earth Surface Process, Peking University, Beijing 100871, China.
authors.forename: Jilong
authors.initials: J
authors.lastname: Guo
authors.affiliation: College of Urban and Environmental Sciences, MOE Laboratory for Earth Surface Process, Peking University, Beijing 100871, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Yu
authors.affiliation: College of Urban and Environmental Sciences, MOE Laboratory for Earth Surface Process, Peking University, Beijing 100871, China.
authors.forename: Libei
authors.initials: L
authors.lastname: Sun
authors.affiliation: College of Urban and Environmental Sciences, MOE Laboratory for Earth Surface Process, Peking University, Beijing 100871, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Laboratory Animal Centre, Peking University, Beijing 100871, China.
authors.forename: Desheng
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Laboratory of Hygienic Chemistry and Molecular Toxicology, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, Gifu 501-1196, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Nakanishi
authors.affiliation: Laboratory of Hygienic Chemistry and Molecular Toxicology, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, Gifu 501-1196, Japan.|Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3, Minamitamagaki, Suzuka, Mie 513-8670, Japan.
authors.forename: Youhei
authors.initials: Y
authors.lastname: Hiromori
authors.affiliation: College of Urban and Environmental Sciences, MOE Laboratory for Earth Surface Process, Peking University, Beijing 100871, China.
authors.forename: Junyu
authors.initials: J
authors.lastname: Li
authors.affiliation: College of Urban and Environmental Sciences, MOE Laboratory for Earth Surface Process, Peking University, Beijing 100871, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Fan
authors.affiliation: College of Urban and Environmental Sciences, MOE Laboratory for Earth Surface Process, Peking University, Beijing 100871, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wan
authors.affiliation: College of Urban and Environmental Sciences, MOE Laboratory for Earth Surface Process, Peking University, Beijing 100871, China.
authors.forename: Siyu
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Laboratory Animal Centre, Peking University, Beijing 100871, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: College of Urban and Environmental Sciences, MOE Laboratory for Earth Surface Process, Peking University, Beijing 100871, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Guo
authors.affiliation: College of Urban and Environmental Sciences, MOE Laboratory for Earth Surface Process, Peking University, Beijing 100871, China.
authors.forename: Jianying
authors.initials: J
authors.lastname: Hu
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000097:blood / Q000737:chemistry / Q000633:toxicity*; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D020134:Catalytic Domain; D004781:Environmental Exposure / Q000032:analysis; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000097:blood / Q000737:chemistry / Q000633:toxicity*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D005449:Fluorenes / Q000097:blood / Q000737:chemistry / Q000633:toxicity*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D064368:Healthy Volunteers; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D062105:Molecular Docking Simulation; D010636:Phenols / Q000097:blood / Q000737:chemistry / Q000633:toxicity*; D010969:Plastics; D011247:Pregnancy; D011256:Pregnancy Outcome; D066244:Proton Magnetic Resonance Spectroscopy; D012098:Reproduction / Q000187:drug effects; D013334:Students; D036401:Toxicity Tests, Chronic; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D004958:Estradiol; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D005449:Fluorenes; D010636:Phenols; D010969:Plastics; C041509:fluorene; C006780:bisphenol A; D000098826:Bisphenol A Compounds