Hormones and Endocrine-Disrupting Chemicals: Low-Dose Effects and Nonmonotonic Dose Responses

Endocrine Reviews, Journal Year: 2012, Volume and Issue: 33(3), P. 378 - 455

Published: March 14, 2012

For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged traditional concepts in toxicology, particular the dogma “the dose makes poison,” because EDCs can effects at low doses that are not predicted by higher doses. Here, we review two major EDC studies: and nonmonotonicity. Low-dose were defined National Toxicology Program as those occur range human exposures or observed below used for toxicological studies. We mechanistic data low-dose use a weight-of-evidence approach to analyze five examples from literature. Additionally, explore nonmonotonic dose-response curves, nonlinear relationship between effect where slope curve changes sign somewhere within examined. provide detailed discussion mechanisms responsible generating these phenomena, plus hundreds cell culture, animal, epidemiology illustrate responses remarkably common natural hormones EDCs. Whether influence certain disorders is no longer conjecture, epidemiological show environmental associated with diseases disabilities. conclude when curves occur, cannot be high Thus, fundamental chemical testing safety determination needed protect health.

Language: Английский

---

Polycystic ovary syndrome: etiology, pathogenesis and diagnosis

Nature Reviews Endocrinology, Journal Year: 2011, Volume and Issue: 7(4), P. 219 - 231

Published: Jan. 25, 2011

Language: Английский

---

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

Environmental Health Perspectives, Journal Year: 2015, Volume and Issue: 123(7), P. 643 - 650

Published: March 16, 2015

Increasing 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 labeled "BPA-free." Some replacements, however, are also bisphenols may similar physiological in organisms. Bisphenol S (BPS) F (BPF) two such substitutes.This review was carried out to evaluate endocrine activities substitutes BPS BPF. Further, we compared hormonal potency BPF that BPA.We conducted a systematic based Office Health Assessment Translation (OHAT) protocol.We identified body literature date, consisting 32 studies (25 vitro only, 7 vivo). The majority these examined found their be same order magnitude action (estrogenic, antiestrogenic, androgenic, antiandrogenic) vivo. has potencies estradiol membrane-mediated pathways, which important for cellular actions proliferation, differentiation, death. showed other vivo, altered organ weights, reproductive end points, enzyme expression.Based current literature, hormonally active BPA, they effects.Rochester JR, Bolden AL. 2015. F: comparison activity substitutes.

Language: Английский

---

Bisphenol A: An endocrine disruptor with widespread exposure and multiple effects

The Journal of Steroid Biochemistry and Molecular Biology, Journal Year: 2011, Volume and Issue: 127(1-2), P. 27 - 34

Published: May 20, 2011

Language: Английский

---

Urinary, Circulating, and Tissue Biomonitoring Studies Indicate Widespread Exposure to Bisphenol A

Environmental Health Perspectives, Journal Year: 2010, Volume and Issue: 118(8), P. 1055 - 1070

Published: March 25, 2010

Bisphenol A (BPA) is one of the highest-volume chemicals produced worldwide, and human exposure to BPA thought be ubiquitous. Thus, there are concerns that amount which humans exposed may cause adverse health effects. Importantly, results from a large number biomonitoring studies at odds with two toxicokinetic studies.We examined several possibilities for why could come seemingly conflicting conclusions.We > 80 published measured concentrations in tissues, urine, blood, other fluids, along metabolism.The included measurements thousands individuals different countries, these overwhelmingly detected individual adults, adolescents, children. Unconjugated was routinely blood (in nanograms per milliliter range), conjugated vast majority urine samples (also range). In stark contrast, proposed not internally BPA. Some regulatory agencies have relied solely on models their risk assessments.Available data clearly indicate general population internal unconjugated The suggested negligible significant deficiencies, directly contradicted by hypothesis-driven studies, therefore reliable assessment purposes.

Language: Английский

---

Endocrine disrupting chemicals and disease susceptibility

The Journal of Steroid Biochemistry and Molecular Biology, Journal Year: 2011, Volume and Issue: 127(3-5), P. 204 - 215

Published: Aug. 29, 2011

Language: Английский

---

Plastics Derived Endocrine Disruptors (BPA, DEHP and DBP) Induce Epigenetic Transgenerational Inheritance of Obesity, Reproductive Disease and Sperm Epimutations

PLoS ONE, Journal Year: 2013, Volume and Issue: 8(1), P. e55387 - e55387

Published: Jan. 24, 2013

Environmental compounds are known to promote epigenetic transgenerational inheritance of adult onset disease in subsequent generations (F1–F3) following ancestral exposure during fetal gonadal sex determination. The current study was designed determine if a mixture plastic derived endocrine disruptor bisphenol-A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and dibutyl phthalate (DBP) at two different doses promoted associated DNA methylation epimutations sperm. Gestating F0 generation females were exposed either the "plastics" or "lower dose plastics" embryonic days 8 14 determination incidence evaluated F1 F3 rats. There significant increases total disease/abnormalities male female animals from plastics lineages. Pubertal abnormalities, testis disease, obesity, ovarian (primary insufficiency polycystic ovaries) increased animals. Kidney prostate only observed direct fetally lineage Analysis sperm epigenome previously identified 197 differential regions (DMR) gene promoters, termed epimutations. A number these DMR form unique connection network have been shown correlate with pathologies identified. Observations demonstrate that compounds, BPA phthalates, can disease. provide potential biomarkers for and/or environmental exposures.

Language: Английский

---

The Blood-Testis Barrier and Its Implications for Male Contraception

Pharmacological Reviews, Journal Year: 2011, Volume and Issue: 64(1), P. 16 - 64

Published: Oct. 28, 2011

The blood-testis barrier (BTB) is one of the tightest blood-tissue barriers in mammalian body. It divides seminiferous epithelium into basal and apical (adluminal) compartments. Meiosis I II, spermiogenesis, spermiation all take place a specialized microenvironment behind BTB compartment, but spermatogonial renewal differentiation cell cycle progression up to preleptotene spermatocyte stage outside compartment epithelium. However, not static ultrastructure. Instead, it undergoes extensive restructuring during epithelial spermatogenesis at VIII allow transit spermatocytes BTB. Yet immunological conferred by cannot be compromised, even transiently, avoid production antibodies against meiotic postmeiotic germ cells. Studies have demonstrated that some unlikely partners, namely adhesion protein complexes (e.g., occludin-ZO-1, N-cadherin-β-catenin, claudin-5-ZO-1), steroids testosterone, estradiol-17β), nonreceptor kinases focal kinase, c-Src, c-Yes), polarity proteins PAR6, Cdc42, 14-3-3), endocytic vesicle clathrin, caveolin, dynamin 2), actin regulatory Eps8, Arp2/3 complex), are working together, apparently under overall influence cytokines transforming growth factor-β3, tumor necrosis factor-α, interleukin-1α). In short, "new" created while "old" above transiting cells timely degeneration, so can maintained traversing We also discuss recent findings regarding molecular mechanisms which environmental toxicants cadmium, bisphenol A) induce testicular injury via their initial actions elicit subsequent damage germ-cell adhesion, thereby leading loss, reduced sperm count, male infertility or subfertility. Moreover, we critically evaluate field studies on drug transporters testis how these influx efflux pumps regulate entry potential nonhormonal contraceptives exert effects. Collectively, illustrate multiple targets present for innovative contraceptive development better delivery drugs alleviate toxicant-induced reproductive dysfunction men.

Language: Английский

---

Bisphenol A exposure, effects, and policy: A wildlife perspective

Journal of Environmental Management, Journal Year: 2012, Volume and Issue: 104, P. 19 - 34

Published: April 4, 2012

Language: Английский

---

Plastics and Health Risks

Annual Review of Public Health, Journal Year: 2010, Volume and Issue: 31(1), P. 179 - 194

Published: March 1, 2010

By 2010, the worldwide annual production of plastics will surpass 300 million tons. Plastics are indispensable materials in modern society, and many products manufactured from a boon to public health (e.g., disposable syringes, intravenous bags). However, also pose risks. Of principal concern endocrine-disrupting properties, as triggered for example by bisphenol A di-(2-ethylhexyl) phthalate (DEHP). Opinions on safety vary widely, despite more than five decades research, scientific consensus product is still elusive. This literature review summarizes information 120 peer-reviewed publications effects plasticizers lab animals humans. It examines problematic exposures susceptible populations briefly adverse environmental impacts plastic pollution. Ongoing efforts steer human society toward resource conservation sustainable consumption discussed, including concept 5 Rs—i.e., reduce, reuse, recycle, rethink, restrain—for minimizing pre- postnatal potentially harmful components plastics.

Language: Английский

---