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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Human exposure to bisphenol A (BPA)

Reproductive Toxicology, Journal Year: 2007, Volume and Issue: 24(2), P. 139 - 177

Published: Aug. 1, 2007

Language: Английский

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Association of Urinary Bisphenol A Concentration With Medical Disorders and Laboratory Abnormalities in Adults

JAMA, Journal Year: 2008, Volume and Issue: 300(11), P. 1303 - 1303

Published: Sept. 16, 2008

Context

Bisphenol A (BPA) is widely used in epoxy resins lining food and beverage containers. Evidence of effects animals has generated concern over low-level chronic exposures humans.

Objective

To examine associations between urinary BPA concentrations adult health status.

Design, Setting, Participants

Cross-sectional analysis status the general population United States, using data from National Health Nutrition Examination Survey 2003-2004. Participants were 1455 adults aged 18 through 74 years with measured urine creatinine concentrations. Regression models adjusted for age, sex, race/ethnicity, education, income, smoking, body mass index, waist circumference, concentration. The sample provided 80% power to detect unadjusted odds ratios (ORs) 1.4 diagnoses 5% prevalence per 1-SD change concentration, or standardized regression coefficients 0.075 liver enzyme concentrations, at a significance level P < .05.

Main Outcome Measures

Chronic disease plus blood markers function, glucose homeostasis, inflammation, lipid changes.

Results

Higher associated cardiovascular age-, sex-, fully (OR increase 1.39; 95% confidence interval [CI], 1.18-1.63; = .001 full adjustment). Higher also diabetes 1.21-1.60; .001) but not other studied common diseases. In addition, higher clinically abnormal enzymes γ-glutamyltransferase 1.29; CI, 1.14-1.46; alkaline phosphatase 1.48; 1.18-1.85; .002).

Conclusion

Higher exposure, reflected BPA, may be avoidable morbidity community-dwelling population.Published online September 16, 2008 (doi:10.1001/jama.300.11.1303).

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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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

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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

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In vivo effects of bisphenol A in laboratory rodent studies

Reproductive Toxicology, Journal Year: 2007, Volume and Issue: 24(2), P. 199 - 224

Published: June 27, 2007

Language: Английский

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Endocrine-Disrupting Chemicals and Public Health Protection: A Statement of Principles from The Endocrine Society

Endocrinology, Journal Year: 2012, Volume and Issue: 153(9), P. 4097 - 4110

Published: June 27, 2012

An endocrine-disrupting chemical (EDC) is an exogenous chemical, or mixture of chemicals, that can interfere with any aspect hormone action. The potential for deleterious effects EDC must be considered relative to the regulation synthesis, secretion, and actions variability in these events across life cycle. developmental age at which exposures occur a critical consideration understanding their effects. Because endocrine systems exhibit tissue-, cell-, receptor-specific during cycle, produce complex, mosaic This complexity causes difficulty when static approach toxicity through mechanisms driven by rigid guidelines used identify manage risk human wildlife populations. We propose principles taken from fundamental endocrinology employed exposed emphasize importance stage and, particular, realization exposure presumptive "safe" dose may impact there normally no endogenous exposure, thereby underscoring very low-dose have potent irreversible Finally, regard current program designed detect putative EDC, namely, Endocrine Disruptor Screening Program, we offer recommendations strengthening this incorporation basic promote further complex effects, especially due exposures.

Language: Английский

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

Food and Chemical Toxicology, Journal Year: 2012, Volume and Issue: 50(10), P. 3725 - 3740

Published: Aug. 4, 2012

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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