title: The estrogenic potential of salicylate esters and their possible risks in foods and cosmetics.
abstract: Salicylate esters (SEs), a class of chemicals extensively used as flavor and fragrance additives in foods, beverages and a wide variety of consumer products, are suspected to have estrogenic activity based on chemical analysis of in silica molecular docking. We evaluated the estrogenic potentials of phenyl salicylate (PhS), benzyl salicylate (BzS), phenethyl salicylate (PES), ethyl salicylate (ES) and methyl salicylate (MS) using an in vitro human estrogen receptor α (hERα)-coactivator recruiting assay and in vivo immature rodent uterotrophic bioassays. We found that PhS, BzS and PES showed obvious in vitro hERα agonistic activities; BzS in particular exhibited a higher estrogenic activity compared to bisphenol A (BPA). The uterine weights were significantly increased in mice treated with 11.1, 33.3, 100 and 300 mg/kg/day BzS and 33.3mg/kg/day PES and rats treated with 3.7, 11.1, 33.3 and 100mg/kg/day BzS for 3 days (P<0.05). Finally, we transformed the daily intakes and the dermal exposures of SEs in the real world into estradiol equivalent concentrations (EEQs). We found that the EEQ of BzS daily intake in consumers in the U.S. and the EEQs of dermal BzS and PES exposure among high-volume users worldwide were higher than the maximum secure daily estradiol intake recommended by the U.S. Food and Drug Administration (FDA). In particular, the EEQ for dermal BzS exposure was up to 162 ng EEQ/kg, which is 3.3 times higher than the maximal acceptable daily E(2) intake recommended by the Joint FAO/WHO Expert Committee on Food Additives (JECFA).
authors.affiliation: College of Urban and Environmental Sciences, MOE Laboratory for Earth Surface Processes, Peking University, Beijing 100871, China. maurizio.gualtieri@unimib.it
authors.forename: Zhaobin
authors.initials: Z
authors.lastname: Zhang
authors.forename: Chengxia
authors.initials: C
authors.lastname: Jia
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.forename: Libei
authors.initials: L
authors.lastname: Sun
authors.forename: Jian
authors.initials: J
authors.lastname: Jiao
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.forename: Desheng
authors.initials: D
authors.lastname: Zhu
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Yonglu
authors.initials: Y
authors.lastname: Tian
authors.forename: Huicheng
authors.initials: H
authors.lastname: Bai
authors.forename: Ruobao
authors.initials: R
authors.lastname: Li
authors.forename: Jianying
authors.initials: J
authors.lastname: Hu
mesh_terms: D000818:Animals; D001681:Biological Assay; D003358:Cosmetics / Q000737:chemistry; D052244:Endocrine Disruptors / Q000633:toxicity*; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000378:metabolism*; D005260:Female; D005502:Food; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012459:Salicylates / Q000633:toxicity*; D013329:Structure-Activity Relationship
chemical_list: D003358:Cosmetics; D052244:Endocrine Disruptors; D047628:Estrogen Receptor alpha; D012459:Salicylates