BackgroundIncreasing concern over bisphenol A (BPA) as an endocrine-disrupting chemical and its possible effects on human health have prompted the removal of BPA from consumer products, often label...

Bisphenol S and F: A Systematic Review and Comparison of the Hormonal Activity of Bisphenol A Substitutes.

Numerous studies have investigated the environmental occurrence, human exposure, and toxicity of bisphenol A (BPA). Following stringent regulations on the production and usage of BPA, several bisphenol analogues have been produced as a replacement for BPA in various applications. The present review outlines the current state of knowledge on the occurrence of bisphenol analogues (other than BPA) in the environment, consumer products and foodstuffs, human exposure and biomonitoring, and toxicity. Whereas BPA was still the major bisphenol analogue found in most environmental monitoring studies, BPF and BPS were also frequently detected. Elevated concentrations of BPAF, BPF, and BPS (i.e., similar to or greater than that of BPA) have been reported in the abiotic environment and human urine from some regions. Many analogues exhibit endocrine disrupting effects, cytotoxicity, genotoxicity, reproductive toxicity, dioxin-like effects, and neurotoxicity in laboratory studies. BPAF, BPB, BPF, and BPS have been show...

Bisphenol Analogues Other Than BPA: Environmental Occurrence, Human Exposure, and Toxicity-A Review.

A review of dietary and non-dietary exposure to bisphenol-A.

This review provides a critical analysis of the biological effects of the most widely used plasticizers, including dibutyl phthalate, diethylhexyl phthalate, dimethyl phthalate, butyl benzyl phthalate and bisphenol A (BPA), on wildlife, with a focus on annelids (both aquatic and terrestrial), molluscs, crustaceans, insects, fish and amphibians. Moreover, the paper provides novel data on the biological effects of some of these plasticizers in invertebrates, fish and amphibians. Phthalates and BPA have been shown to affect reproduction in all studied animal groups, to impair development in crustaceans and amphibians and to induce genetic aberrations. Molluscs, crustaceans and amphibians appear to be especially sensitive to these compounds, and biological effects are observed at environmentally relevant exposures in the low ng l−1 to µg l−1 range. In contrast, most effects in fish (except for disturbance in spermatogenesis) occur at higher concentrations. Most plasticizers appear to act by interfering with the functioning of various hormone systems, but some phthalates have wider pathways of disruption. Effect concentrations of plasticizers in laboratory experiments coincide with measured environmental concentrations, and thus there is a very real potential for effects of these chemicals on some wildlife populations. The most striking gaps in our current knowledge on the impacts of plasticizers on wildlife are the lack of data for long-term exposures to environmentally relevant concentrations and their ecotoxicity when part of complex mixtures. Furthermore, the hazard of plasticizers has been investigated in annelids, molluscs and arthropods only, and given the sensitivity of some invertebrates, effects assessments are warranted in other invertebrate phyla.

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A critical analysis of the biological impacts of plasticizers on wildlife.

The use constructed wetlands with horizontal sub-surface flow for various types of wastewater

Although abundant data are available on the toxicity of bisphenol-A (2,2-bis (4-hydroxydiphenyl)propane; BPA), little is known about the toxicities of the structurally similar compounds, namely bisphenols (BPs). A variety of BPs were examined for their acute toxicity against Daphnia magna, mutagenicity, and estrogenic activity using the Daphtoxkit (Creasel Ltd.), the umu test system, and the yeast two-hybrid system, respectively, in comparison with BPA. BPA was moderately toxic to D. magna (48-h EC50 was 10 mg/l) according to the current U.S. EPA acute toxicity evaluation standard, and it was weakly estrogenic with 5 orders of magnitude lower activity than that of the natural estrogen 17 beta-estradiol in the yeast screen, while no mutagenicity was observed. All seven BPs tested here showed moderate to slight acute toxicity, no mutagenicity, and weak estrogenic activity as well as BPA. Some of the BPs showed considerably higher estrogenic activity than BPA, and others exhibited much lower activity. Among the tested BPs, two compounds, i.e., bisphenol-S (bis(4-hydroxydiphenyl)sulfone) and bis(4-hydroxyphenyl)sulfide, have never been reported for their estrogenic activity previously.

Acute toxicity, mutagenicity, and estrogenicity of bisphenol-A and other bisphenols

Biodegradation of bisphenol-A (BPA), which is known as an estrogenic chemical, proceeds via complicated metabolic routes and leads to formation of several kinds of biodegradation products. Through the major route BPA can be completely mineralized; however, p-hydroxyacetophenone (p-HAP), p-hydroxybenzaldehyde (p-HBAL), and p-hydroxybenzoic acid (p-HBA) are transiently accumulated at relatively high concentrations. On the other hand, degradation of BPA through the minor route tends to cause the accumulation of 2,3-bis(4-hydroxyphenyl)-1,2-propanediol and p-hydroxyphenacyl alcohol as the dead-end products. To fully assess the impact of BPA discharge into the environment, the considerable BPA degradation products p-HAP, p-HBAL, and p-HBA and the mixture of the dead-end products were examined for their acute toxicity, mutagenicity, and estrogenicity using the Daphtoxkit (Creasel Ltd.), umu test system, and yeast two-hybrid system, respectively. BPA was moderately toxic to Daphnia magna (48-h EC(50) was 10 mg/L) and weakly estrogenic, with activity that was 5 orders of magnitude lower than that of 17beta-estradiol in the yeast screen, though no mutagenicity was observed. All the tested BPA biodegradation products showed very low acute toxicity compared with BPA, and none was mutagenic. A slight estrogenic activity was detected only for p-HAP among the tested degradation products. It was concluded that biodegradation can remarkably reduce the toxic effects of BPA.

Acute toxicity, mutagenicity, and estrogenicity of biodegradation products of bisphenol-A.

Simple Summary Ovarian clear-cell carcinoma is a unique subtype of epithelial ovarian cancer. This collaborative study aimed to provide important information regarding patient demographics and treatment-associated prognostic factors in ovarian clear-cell carcinoma in Asia. Given the difference in prognoses between early- and advanced-stage cohorts, varying predictors between these two cohorts were clarified in separate analyses. Efforts should be made to promote early diagnosis and the inclusion of advanced-stage patients in clinical trials. Additionally, early recognition of poor responders to platinum-based chemotherapy and those with cancer progression occurring within seven months after completing primary chemotherapy should be emphasized in research and clinical settings. Our findings suggest that treatment selection for patients with platinum-resistant/refractory features (e.g., novel biomarkers) or relapsed disease should be based on the results of ongoing clinical trials for ovarian clear-cell carcinoma. Our results (if confirmed) will guide and inform treatment recommendations for patients at risk for poor prognosis. Abstract This large-scale study aimed to determine the long-term influences of potential prognostic predictors and progression-free interval (PFI) criteria for grading platinum-sensitivity in ovarian clear cell carcinoma (OCCC). We retrospectively reviewed the medical records of OCCC patients presenting at nine tertiary centres (1995–2015), and evaluated patient characteristics, therapeutic factors, clinical outcomes, and hazard ratios for disease progression and death. We enrolled 536 patients (median follow-up, 36.6 months) and developed newly defined distributions of PFIs (seven and 14 months) for grading platinum sensitivity. In the multivariate model, preoperative CA125 levels and chemo-response independently predicted early-stage progression-free survival (PFS) risk. Post-progression cytoreduction correlated with reduced mortality risk. No unfavourable outcomes were observed with respect to coexisting endometriosis, fertility-sparing strategies, or platinum-based regimens. A PFI of <7 months, the strongest predictor of both post-progression mortality and second relapse risks, correlated with chemo-resistance, advanced tumour stage, and shortened post-progression survival. Chemotherapy regimens commonly used in front-line or relapse settings were limited in improving prognoses, especially in the advanced-stage cohort. Clinical trials of novel targeted agents and/or innovative biomarkers for chemoresistance should be comprehensively investigated and offered early to advanced-stage patients or those with OCCC progression occurring within seven months after receiving chemotherapy.

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Predicting Long-Term Prognoses and Grading Platinum Sensitivity Using a Novel Progression-Free Interval Criterion in Ovarian Clear Cell Carcinoma: A Multi-Institutional Cohort Study

Min-Yu Chen

Papers

Acute toxicity, mutagenicity, and estrogenicity of bisphenol-A and other bisphenols

Acute toxicity, mutagenicity, and estrogenicity of biodegradation products of bisphenol-A.

Predicting Long-Term Prognoses and Grading Platinum Sensitivity Using a Novel Progression-Free Interval Criterion in Ovarian Clear Cell Carcinoma: A Multi-Institutional Cohort Study