Relationship between the results of in vitro receptor binding assay to human estrogen receptor alpha and in vivo uterotrophic assay: comparative study with 65 selected chemicals.
ABSTRACT For screening chemicals possessing endocrine disrupting potencies, the uterotrophic assay has been placed in a higher level in the OECD testing framework than the ER binding assay to detect ER-mediated activities. However, there are no studies that can demonstrate a clear relationship between these assays. In order to clarify the relationship between the in vitro ER binding and in vivo uterotrophic assays and to determine meaningful binding potency from the ER binding assay, we compared the results from these assays for 65 chemicals spanning a variety of chemicals classes. Under the quantitative comparison between logRBAs (relative binding affinities) and logLEDs (lowest effective doses), the log RBA was well correlated with both logLEDs of estrogenic and anti-estrogenic compounds at r(2)=0.67 (n=28) and 0.79 (n=23), respectively. The RBA of 0.00233% was found to be the lowest ER binding potency to elicit estrogenic or anti-estrogenic activities in the uterotrophic assay, accordingly this value is considered as the detection limit of estrogenic or anti-estrogenic activities in the uterotrophic assay. The usage of this value as cutoff provided the best concordance rate (82%). These findings are useful in a tiered approach for identifying chemicals that have potential to induce ER-mediated effects in vivo.
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ABSTRACT: Halogenated bisphenol A (H-BPAs), widely used in industrial production, have been identified in various environmental matrices and detected in human serum and breast milk. The persistence and prevalence of H-BPAs in the environment underscore the need to in-depth understand their adverse effects to humans and other organisms. In the present study, zebrafish embryos/larvae were used as models to investigate the developmental toxicities of three H-BPAs, namely tetrabromobisphenol A (TBBPA), tetrachlorobisphenol A (TCBPA), and bisphenol AF (BPAF). The half lethal concentration (LC50) values indicated that the rank order of toxicities of the chemicals were TCBPA>TBBPA>BPAF. Three H-BPAs exposure resulted in a variety of developmental lesions in the embryos/larvae, such as a delay in time to hatch, edema, and hemorrhage. The estrogenic activities of H-BPAs were determined by means of in vivo vitellogenin (vtg) assay and in vitro MVLN assay. Here only BPAF specifically shows a stronger estrogenic activity than BPA both in in vivo and in vitro. These data suggest that TCBPA, TBBPA, and BPAF are more potent toxicants than BPA, and indicate that further research of the mechanisms on their toxicities is required.Chemosphere 10/2014; 112C:275-281. · 3.14 Impact Factor
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ABSTRACT: Bisphenol AF (BPAF) is an environmental pollutant to disrupt endocrine system or cause cancer, thus the detection of trace BPAF is very important. In this study, a simple and highly sensitive electroanalytical method for the determination of BPAF was developed. In pH 6.0 phosphate buffer solutions, carboxyl functionalized multi-walled carbon nanotubes (MWCNT-COOH) modified glassy carbon electrode exhibits an enhanced effectiveness for the oxidation of BPAF. This electrode exhibited two linear relationships with BPAF concentration range of 0.02μmolL(-1) to 8.0μmolL(-1) and a detection limit of 0.0077μmolL(-1) (S/N=3). The proposed method was successfully applied to determine BPAF in real samples and the results were satisfactory. The MWCNT-COOH/GCE electrode showed good reproducibility, stability and anti-interference. The electrochemistry and spectroscopy methods are also described for the evaluation of BPAF-HSA interaction. In the presence of HSA, the peak currents of BPAF decreased linearly due to the formation of a super-molecular complex. The binding constant between BPAF and HSA, obtained by differential pulse voltammetry (DPV), was consistent with the fluorescence analysis. The molecular modeling studies were carried out to clearly describe the interaction between BPAF and HSA.Journal of Hazardous Materials 05/2014; 276C:105-111. · 4.33 Impact Factor
- Separation and Purification Technology 09/2013; 116:145–153. · 3.07 Impact Factor