https://bura.brunel.ac.uk/bitstream/2438/18351/1/FullText.pdf

An overview of chemical additives present in plastics: Migration, release, fate and environmental impact during their use, disposal and recycling.

In 1991, a group of 21 scientists gathered at the Wingspread Conference Center to discuss evidence of developmental alterations observed in wildlife populations after chemical exposures. There, the term "endocrine disruptor" was agreed upon to describe a class of chemicals including those that act as agonists and antagonists of the estrogen receptors (ERs), androgen receptor, thyroid hormone receptor, and others. This definition has since evolved, and the field has grown to encompass hundreds of chemicals. Despite significant advances in the study of endocrine disruptors, several controversies have sprung up and continue, including the debate over the existence of nonmonotonic dose response curves, the mechanisms of low-dose effects, and the importance of considering critical periods of exposure in experimental design. One chemical found ubiquitously in our environment, bisphenol-A (BPA), has received a tremendous amount of attention from research scientists, government panels, and the popular press. In this review, we have covered the above-mentioned controversies plus six additional issues that have divided scientists in the field of BPA research, namely: 1) mechanisms of BPA action; 2) levels of human exposure; 3) routes of human exposure; 4) pharmacokinetic models of BPA metabolism; 5) effects of BPA on exposed animals; and 6) links between BPA and cancer. Understanding these topics is essential for educating the public and medical professionals about potential risks associated with developmental exposure to BPA and other endocrine disruptors, the design of rigorously researched programs using both epidemiological and animal studies, and ultimately the development of a sound public health policy.

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Bisphenol-A and the Great Divide: A Review of Controversies in the Field of Endocrine Disruption

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.

http://jmclachlan.tulane.edu/PDFs/wetherilletal2007.pdf

In vitro molecular mechanisms of bisphenol A action.

Comparative study of the endocrine-disrupting activity of bisphenol A and 19 related compounds.

Estrogenic activity of an antioxidant, nordihydroguaiaretic acid (NDGA).

Substances that mimic the actions of causative gene products of familial Parkinson's disease (PD) are candidate as causative agents of idiopathic PD. 1-Benzyl-1,2,3,4-tetrahydroisoquinoline (1BnTIQ), an endogenous neurotoxin, is present at three times higher levels in CSF of PD patients than in CSF of control subjects. However, the mechanism of 1BnTIQ's neurotoxicity is unclear. In this study, we tried to identify 1BnTIQ-binding proteins by using a diazido-functionalized 1BnTIQ analog, 1-(3-azido-5-azidomethylbenzyl)-1,2,3,4-tetrahydroisoquinoline, designed and synthesized as a probe for radioisotope-free photoaffinity labeling. One major photolabeled protein identified using this probe was tubulin beta, which has been reported to be a substrate of parkin, a ubiquitin E3 ligase and a causative gene product of familial PD. Loss of function mutation of parkin is reported to result in loss of tubulin beta ubiquitination. Therefore, we examined the effect of 1BnTIQ on ubiquitination of tubulin beta. The polyubiquitinated tubulin beta level in human neuroblastoma SH-SY5Y cells was reduced in the presence of 1BnTIQ, even at concentrations as low as those detected in parkinsonian CSF. In vitro ubiquitination assay gave similar results. It is suggested that 1BnTIQ has the same effect on tubulin ubiquitination as does mutant parkin in familial PD. Taken together, substances which reduce polyubiquitination of tubulin such as 1BnTIQ are supposed to be candidates of etiological factors of PD.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1471-4159.2010.06576.x

1-Benzyl-1,2,3,4-tetrahydroisoquinoline binds with tubulin β, a substrate of parkin, and reduces its polyubiquitination

trans-Stilbene exhibits estrogenic activity in an estrogen reporter assay after metabolic activation. In this study, uterotrophic assay was conducted using ovariectomized B6C3F1/Crj female mice treated with trans-stilbene, trans-4-hydroxystilbene, trans-4,4'-dihydroxystilbene and diethylstilbestrol. Administration of trans-4-hydroxystilbene, trans-4,4'-dihydroxystilbene and diethylstilbestrol elicited increases in absolute and relative uterus weight. Furthermore, the uterine response caused by the hydroxylated stilbenes was accompanied with an increase in the thickness of epithelial cell layers. trans-Stilbene itself also showed estrogenic activity, affecting uterine weight and causing histological changes of the uterus. This suggests that trans-stilbene is activated to hydroxylated metabolites to exhibit its estrogenic activity. Indeed, trans-hydroxystilbenes were detected in the urine and feces of mice dosed with trans-stilbene. The effect of stilbene derivatives on testis in newborn B6C3F1/Crj mouse was examined. Administration of diethylstilbestrol slightly decreased the testis weight and atrophy of seminiferous tubules. However, trans-stilbene and trans-4-hydroxystilbene affected neither testis weight nor the histological appearance of the testis.

/pdf/effects-of-stilbene-and-related-compounds-on-reproductive-1p2qttywm3.pdf

Effects of Stilbene and Related Compounds on Reproductive Organs in B6C3F1/Crj Mouse

In this study, liver microsome-mediated activation of diphenyl (DP), diphenylmethane (DPM) and 2,2-diphenylpropane (DPP) to estrogens was demonstrated. These three compounds were negative in estrogen reporter assay using estrogen-responsive human breast cancer cell line MCF-7. However, they exhibited estrogenic activity after incubation with liver microsomes of 3-methylcholanthrene-treated rats in the cases of DP and DPM, or of phenobarbital-treated rats in the cases of DP and DPP, in the presence of NADPH. When these compounds were incubated with liver microsomes in the presence of NADPH, monohydroxyl and dihydroxyl derivatives were formed. These hydroxylated metabolites, 4-hydroxydiphenyl, 3-hydroxydiphenyl, 2-hydroxydiphenyl, 4-hydroxydiphenylmethane, 2-(4-hydroxyphenyl)-2-phenylpropane (4-OH-DPP), 4,4′-dihydroxydiphenyl, 4,4′-dihydroxydiphenylmethane and 2,2-bis(4-hydroxyphenyl)propane (bisphenol A), all exhibited estrogenic activity in MCF-7 cells. Binding assay of these hydroxylated compounds with rat uterus estrogen receptor was also positive. These results suggest that the estrogenic activities of DP, DPM and DPP were due to the formation of hydroxylated metabolites by the liver cytochrome P450 system.

/pdf/metabolic-activation-of-proestrogenic-diphenyl-and-related-2gzspe1zea.pdf

Ryuki Kohta

Papers

Comparative study of the endocrine-disrupting activity of bisphenol A and 19 related compounds.

Estrogenic activity of an antioxidant, nordihydroguaiaretic acid (NDGA).

1-Benzyl-1,2,3,4-tetrahydroisoquinoline binds with tubulin β, a substrate of parkin, and reduces its polyubiquitination

Effects of Stilbene and Related Compounds on Reproductive Organs in B6C3F1/Crj Mouse

Metabolic Activation of Proestrogenic Diphenyl and Related Compounds by Rat Liver Microsomes