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

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

Endocrine Reviews, Journal Year: 2009, Volume and Issue: 30(1), P. 75 - 95

Published: Feb. 1, 2009

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

Language: Английский

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An Extensive New Literature Concerning Low-Dose Effects of Bisphenol A Shows the Need for a New Risk Assessment

Environmental Health Perspectives, Journal Year: 2005, Volume and Issue: 113(8), P. 926 - 933

Published: April 12, 2005

Bisphenol A (BPA) is the monomer used to manufacture polycarbonate plastic, resin lining of cans, and other products, with global capacity in excess 6.4 billion lb/year. Because ester bonds these BPA-based polymers are subject hydrolysis, leaching BPA has led widespread human exposure. recent report prepared by Harvard Center for Risk Analysis funded American Plastics Council concluded that evidence low-dose effects weak on basis a review only 19 studies; was issued after delay 2.5 years. current comprehensive literature reveals opposite true. As December 2004, there were 115 published vivo studies concerning BPA, 94 significant effects. In 31 publications vertebrate invertebrate animals, occurred below predicted "safe" or reference dose 50 microg/kg/day BPA. An estrogenic mode action confirmed vitro experiments, which describe disruption cell function at 10(-12) M 0.23 ppt. Nonetheless, chemical manufacturers continue discount findings because no industry-funded have reported low doses although > 90% government-funded Some ignored results positive controls, many reporting strain rat inappropriate study responses. We propose new risk assessment needed based a) extensive adverse animals dose; b) high rate from food beverage containers, leading exposure; c) reports median level blood tissues, including fetal blood, higher than causes mice; d) epidemiologic related disease women.

Language: Английский

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Bisphenol A (BPA) in China: A review of sources, environmental levels, and potential human health impacts

Environment International, Journal Year: 2011, Volume and Issue: 42, P. 91 - 99

Published: May 24, 2011

Language: Английский

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Large Effects from Small Exposures. III. Endocrine Mechanisms Mediating Effects of Bisphenol A at Levels of Human Exposure

Endocrinology, Journal Year: 2006, Volume and Issue: 147(6), P. s56 - s69

Published: May 12, 2006

Over 6 billion pounds per year of the estrogenic monomer bisphenol A (BPA) are used to manufacture polycarbonate plastic products, in resins lining metal cans, dental sealants, and blends with other types products. The ester bond linking BPA molecules undergoes hydrolysis, resulting release free into food, beverages, environment, numerous monitoring studies now show almost ubiquitous human exposure biologically active levels this chemical. exerts effects through classical nuclear estrogen receptors, acts as a selective receptor modulator. However, also initiates rapid responses via receptors presumably associated plasma membrane. Similar estradiol, causes changes some cell functions at concentrations between 1 pm nm, mean median range unconjugated measured by multiple techniques pregnant maternal, fetal, adult blood tissues exceeds these levels. In contrast published findings, manufacturers persist describing weak insist there is little concern Our derives from 1) identification molecular mechanisms mediating animal very low doses, 2) vivo experimental animals caused doses within exposure, 3) widespread that cause adverse animals.

Language: Английский

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In vitro molecular mechanisms of bisphenol A action

Reproductive Toxicology, Journal Year: 2007, Volume and Issue: 24(2), P. 178 - 198

Published: May 30, 2007

Language: Английский

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Human exposure to bisphenol A

Toxicology, Journal Year: 2006, Volume and Issue: 226(2-3), P. 79 - 89

Published: June 19, 2006

Language: Английский

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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

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Early-life exposure to EDCs: role in childhood obesity and neurodevelopment

Nature Reviews Endocrinology, Journal Year: 2016, Volume and Issue: 13(3), P. 161 - 173

Published: Nov. 18, 2016

Language: Английский

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Chapel Hill bisphenol A expert panel consensus statement: Integration of mechanisms, effects in animals and potential to impact human health at current levels of exposure

Reproductive Toxicology, Journal Year: 2007, Volume and Issue: 24(2), P. 131 - 138

Published: July 31, 2007

Language: Английский

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