Bisphenol AF (BPAF) is a fluorinated analog of bisphenol A (BPA), and it is a more potent estrogen receptor (ER) agonist. BPAF is mainly metabolized to BPAF-glucuronide (BPAF-G), which has been reported to lack ER agonist activity and is believed to be biologically inactive. The main goal of the current study was to examine the influence of the metabolism of BPAF via glucuronidation on its ER activity and adipogenesis. Also, as metabolites can have different biological activities, the effects of BPAF-G on other nuclear receptors were evaluated. First, in-vitro BPAF glucuronidation was investigated using recombinant human enzymes. Specific reporter-gene assays were used to determine BPAF and BPAF-G effects on estrogen, androgen, glucocorticoid, and thyroid receptor pathways, and on PXR, FXR, and PPAR gamma pathways. Their effects on lipid accumulation and differentiation were determined in murine 3T3L1 preadipocytes using Nile Red, with mRNA expression analysis of the adipogenic markers adiponectin, Fabp4, Cebp alpha, and PPAR gamma. BPAF showed strong agonistic activity for hER alpha and moderate antagonistic activities for androgen and thyroid receptors, and for PXR. BPAF-G was antagonistic for PXR and PPAR gamma. BPAF (0.1 mu M) and BPAF-G (1.0 mu M) induced lipid accumulation and increased expression of key adipogenic markers in murine preadipocytes. BPAF-G is therefore not an inactive metabolite of BPAF. Further toxicological and epidemiological investigations of BPAF effects on human health are warranted, to provide better understanding of the metabolic end-elimination of BPAF. (C) 2018 Elsevier Ltd. All rights reserved.

HHCB [1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta(g)-2-benzopyran] and 4-tert-octylphenol [4-(1,1,3,3-tetramethylbutyl)phenol] are widely used emerging contaminants that have the potential to cause adverse effects in the environment. The purpose of this study was to observe if and how environmentally realistic concentrations of these contaminants alter growth in plant populations. It was hypothesized that within an exposed Gypsophila elegans Bieb (annual baby's breath) population especially fast-growing seedlings are impaired even when the population mean is unaffected, and small doses can cause hormesis and, thus, an increase in shoot or root length. In a dose-response experiment, an experimental population of G. elegans was established (total 15.600 seeds, 50 seeds per replicate, 24 replicates per concentration, 5.2 seedlings/cm(2)) and exposed to 12 doses of HHCB or 4-tert-octylphenol. After five days, shoot and root length values were measured and population averages, as well as slow- and fast-growing subpopulations, were compared with unexposed controls. Growth responses were predominantly monophasic. HHCB seemed to selectively inhibit both root and shoot elongation among slow- and fast-growing individuals, while 4-tert-octylphenol selectively inhibited both root and shoot elongation of mainly fast-growing seedlings. The ED50 values (dose causing 50% inhibition) revealed that the slow-growing seedlings were more sensitive and fast-growing seedlings less sensitive than the average of all individuals. Although there was toxicant specific variation between the effects, selective toxicity was consistently found among both slow- and fast-growing plants starting already at concentrations of 0.0067 mu M, that are usually considered to be harmless. This study indicates that these contaminants can change size distribution of a plant population at low concentrations in the nM/mu M range.