Environmental Science › Health, Toxicology and Mutagenesis

Effects and risks of endocrine disrupting chemicals

Works Count: 48874

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Description

This cluster of papers focuses on the impact of endocrine-disrupting chemicals, such as Bisphenol A and Phthalates, on human health. It covers a wide range of topics including hormonal activity, environmental exposure, reproductive disorders, toxicity testing, and metabolic disorders.

Keywords

Endocrine-Disrupting Chemicals; Bisphenol A; Phthalates; Hormonal Activity; Environmental Exposure; Health Effects; Reproductive Disorders; Toxicity Testing; Metabolic Disorders; Human Biomonitoring

Activation of the Aryl Hydrocarbon Receptor by Structurally Diverse Exogenous and Endogenous Chemicals

2003-01-22

Michael S. Denison , Scott R. Nagy

The induction of expression of genes for xenobiotic metabolizing enzymes in response to chemical insult is an adaptive response found in most organisms. In vertebrates, the AhR is one of … The induction of expression of genes for xenobiotic metabolizing enzymes in response to chemical insult is an adaptive response found in most organisms. In vertebrates, the AhR is one of several chemical/ligand-dependent intracellular receptors that can stimulate gene transcription in response to xenobiotics. The ability of the AhR to bind and be activated by a range of structurally divergent chemicals suggests that the AhR contains a rather promiscuous ligand binding site. In addition to synthetic and environmental chemicals, numerous naturally occurring dietary and endogenous AhR ligands have also been identified. In this review, we describe evidence for the structural promiscuity of AhR ligand binding and discuss the current state of knowledge with regards to the activation of the AhR signaling pathway by naturally occurring exogenous and endogenous ligands.

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

2009-02-01

Laura N. Vandenberg , Maricel V. Maffini , Carlos Sonnenschein +2 more

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 … 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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Human exposure to bisphenol A (BPA)

2007-08-01

Laura N. Vandenberg , Russ Hauser , Michele Marcus +2 more

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

2011-05-20

Beverly S. Rubin

Research needs for the risk assessment of health and environmental effects of endocrine disruptors: a report of the U.S. EPA-sponsored workshop.

1996-08-01

Robert J. Kavlock , G. P. Daston , Claudio De Rosa +7 more

The hypothesis has been put forward that humans and wildlife species adverse suffered adverse health effects after exposure to endocrine-disrupting chemicals. Reported adverse effects include declines in populations, increases in … The hypothesis has been put forward that humans and wildlife species adverse suffered adverse health effects after exposure to endocrine-disrupting chemicals. Reported adverse effects include declines in populations, increases in cancers, and reduced reproductive function. The U.S. Environmental Protection Agency sponsored a workshop in April 1995 to bring together interested parties in an effort to identify research gaps related to this hypothesis and to establish priorities for future research activities. Approximately 90 invited participants were organized into work groups developed around the principal reported health effects-carcinogenesis, reproductive toxicity, neurotoxicity, and immunotoxicity-as well as along the risk assessment paradigm-hazard identification, dose-response assessment, exposure assessment, and risk characterization. Attention focused on both ecological and human health effects. In general, group felt that the hypothesis warranted a concerted research effort to evaluate its validity and that research should focus primarily on effects on development of reproductive capability, on improved exposure assessment, and on the effects of mixtures. This report summarizes the discussions of the work groups and details the recommendations for additional research.

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The environmental fate of phthalate esters: A literature review

1997-08-01

Charles A. Staples , Dennis R. Peterson , Thomas F. Parkerton +1 more

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

2015-03-16

Johanna R. Rochester , Ashley L. Bolden

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

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Developmental effects of endocrine-disrupting chemicals in wildlife and humans.

1993-10-01

Theo Colborn , F. S. vom Saal , Ana M. Soto

Large numbers and large quantities of endocrine-disrupting chemicals have been released into the environment since World War II. Many of these chemicals can disturb development of the endocrine system and … Large numbers and large quantities of endocrine-disrupting chemicals have been released into the environment since World War II. Many of these chemicals can disturb development of the endocrine system and of the organs that respond to endocrine signals in organisms indirectly exposed during prenatal and/or early postnatal life; effects of exposure during development are permanent and irreversible. The risk to the developing organism can also stem from direct exposure of the offspring after birth or hatching. In addition, transgenerational exposure can result from the exposure of the mother to a chemical at any time throughout her life before producing offspring due to persistence of endocrine-disrupting chemicals in body fat, which is mobilized during egg laying or pregnancy and lactation. Mechanisms underlying the disruption of the development of vital systems, such as the endocrine, reproductive, and immune systems, are discussed with reference to wildlife, laboratory animals, and humans.

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Endocrine Disruption in Wildlife: A Critical Review of the Evidence

1998-01-01

Charles R. Tyler , Susan Jobling , John P. Sumpter

In recent years, a number of man-made chemicals have been shown to be able to mimic endogenous hormones, and it has been hypothesized that alterations in the normal pattern of … In recent years, a number of man-made chemicals have been shown to be able to mimic endogenous hormones, and it has been hypothesized that alterations in the normal pattern of reproductive development seen in some populations of wildlife are linked with exposure to these chemicals. Of particular importance are those compounds that mimic estrogens and androgens (and their antagonists), because of their central role in reproductive function. In fact, the evidence showing that such chemicals actually do mimic (or antagonize) the action of hormones in the intact animal is limited. In only a few cases have laboratory studies shown that chemicals that mimic hormones at the molecular level (in vitro) also cause reproductive dysfunction in vivo at environmentally relevant concentrations. In addition, the reported studies on wild populations of animals are limited to a very few animal species and they have often centered on localized 'hot-spots' of chemical discharges. Nevertheless, many of these xenobiotics are persistent and accumulate in the environment, and therefore a more widespread phenomenon of endocrine disruption in wildlife is possible. This article reviews the evidence, from both laboratory and field studies, that exposure to steroid hormone mimics may impair reproductive function and critically assesses the weight of evidence for endocrine disruption in wildlife.

Vitellogenesis as a biomarker for estrogenic contamination of the aquatic environment.

1995-10-01

John P. Sumpter , Susan Jobling

A rapidly increasing number of chemicals, or their degradation products, are being recognized as possessing estrogenic activity, albeit usually weak. We have found that effluent from sewage treatment works contains … A rapidly increasing number of chemicals, or their degradation products, are being recognized as possessing estrogenic activity, albeit usually weak. We have found that effluent from sewage treatment works contains a chemical, or mixture of chemicals, that induces vitellogenin synthesis in male fish maintained in the effluent, thus indicating that the effluent is estrogenic. The effect was extremely pronounced and occurred at all sewage treatment works tested. The nature of the chemical or chemicals causing the effect is presently not known. However, we have tested a number of chemicals known to be estrogenic to mammals and have shown that they are also estrogenic to fish; that is, no species specificity was apparent. Many of these weakly estrogenic chemicals are known to be present in effluents. Further, a mixture of different estrogenic chemicals was considerably more potent than each of the chemicals when tested individually, suggesting that enhanced effects could occur when fish are exposed simultaneously to various estrogenic chemicals (as is likely to occur in rivers receiving effluent). Subsequent work should determine whether exposure to these chemicals at the concentrations present in the environment leads to any deleterious physiological effects.

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Urinary Concentrations of Bisphenol A and 4-Nonylphenol in a Human Reference Population

2004-12-20

Antonia M. Calafat , Zsuzsanna Kuklenyik , John A. Reidy +3 more

Bisphenol A (BPA) is used to manufacture polycarbonate plastic and epoxy resins, which are used in baby bottles, as protective coatings on food containers, and for composites and sealants in … Bisphenol A (BPA) is used to manufacture polycarbonate plastic and epoxy resins, which are used in baby bottles, as protective coatings on food containers, and for composites and sealants in dentistry. 4-Nonylphenol (NP) is used to make nonylphenol ethoxylates, nonionic surfactants applied as emulsifying, wetting, dispersing, or stabilizing agents in industrial, agricultural, and domestic consumer products. The potential for human exposure to BPA and NP is high because of their widespread use. We measured BPA and NP in archived urine samples from a reference population of 394 adults in the United States using isotope-dilution gas chromatography/mass spectrometry. The concentration ranges of BPA and NP were similar to those observed in other human populations. BPA was detected in 95% of the samples examined at concentrations > or = 0.1 microg/L urine; the geometric mean and median concentrations were 1.33 microg/L (1.36 microg/g creatinine) and 1.28 microg/L (1.32 microg/g creatinine), respectively; the 95th percentile concentration was 5.18 microg/L (7.95 microg/g creatinine). NP was detected in 51% of the samples examined > or = 0.1 microg/L. The median and 95th percentile concentrations were < 0.1 microg/L and 1.57 microg/L (1.39 microg/g creatinine), respectively. The frequent detection of BPA suggests widespread exposure to this compound in residents of the United States. The lower frequency of detection of NP than of BPA could be explained by a lower exposure of humans to NP, by different pharmacokinetic factors (i.e., absorption, distribution, metabolism, elimination), by the fact that 4-n-nonylphenol--the measured NP isomer--represents a small percentage of the NP used in commercial mixtures, or a combination of all of the above. Additional research is needed to determine the best urinary biomarker(s) to assess exposure to NP. Despite the sample population's nonrepresentativeness of the U.S. population (although sample weights were used to improve the extent to which the results represent the U.S. population) and relatively small size, this study provides the first reference range of human internal dose levels of BPA and NP in a demographically diverse human population.

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Phthalates: Toxicology and exposure

2007-09-22

U Heudorf , Volker Mersch‐Sundermann , J. Angerer

Toxicity Testing in the 21st Century: A Vision and a Strategy

2010-06-17

Daniel Krewski , Daniel Acosta , Melvin E. Andersen +7 more

With the release of the landmark report Toxicity Testing in the 21st Century: A Vision and a Strategy, the U.S. National Academy of Sciences, in 2007, precipitated a major change … With the release of the landmark report Toxicity Testing in the 21st Century: A Vision and a Strategy, the U.S. National Academy of Sciences, in 2007, precipitated a major change in the way toxicity testing is conducted. It envisions increased efficiency in toxicity testing and decreased animal usage by transitioning from current expensive and lengthy in vivo testing with qualitative endpoints to in vitro toxicity pathway assays on human cells or cell lines using robotic high-throughput screening with mechanistic quantitative parameters. Risk assessment in the exposed human population would focus on avoiding significant perturbations in these toxicity pathways. Computational systems biology models would be implemented to determine the dose-response models of perturbations of pathway function. Extrapolation of in vitro results to in vivo human blood and tissue concentrations would be based on pharmacokinetic models for the given exposure condition. This practice would enhance human relevance of test results, and would cover several test agents, compared to traditional toxicological testing strategies. As all the tools that are necessary to implement the vision are currently available or in an advanced stage of development, the key prerequisites to achieving this paradigm shift are a commitment to change in the scientific community, which could be facilitated by a broad discussion of the vision, and obtaining necessary resources to enhance current knowledge of pathway perturbations and pathway assays in humans and to implement computational systems biology models. Implementation of these strategies would result in a new toxicity testing paradigm firmly based on human biology.

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A variety of environmentally persistent chemicals, including some phthalate plasticizers, are weakly estrogenic.

1995-06-01

Susan Jobling , Thomas Reynolds , R White +2 more

Sewage, a complex mixture of organic and inorganic chemicals, is considered to be a major source of environmental pollution. A random screen of 20 organic man-made chemicals present in liquid … Sewage, a complex mixture of organic and inorganic chemicals, is considered to be a major source of environmental pollution. A random screen of 20 organic man-made chemicals present in liquid effluents revealed that half appeared able to interact with the estradiol receptor. This was demonstrated by their ability to inhibit binding of 17 beta-estradiol to the fish estrogen receptor. Further studies, using mammalian estrogen screens in vitro, revealed that the two phthalate esters butylbenzyl phthalate (BBP) and di-n-butylphthalate (DBP) and a food antioxidant, butylated hydroxyanisole (BHA) were estrogenic; however, they were all less estrogenic than the environmental estrogen octylphenol. Phthalate esters, used in the production of various plastics (including PVC), are among the most common industrial chemicals. Their ubiquity in the environment and tendency to bioconcentrate in animal fat are well known. Neither BBP nor DBP were able to act as antagonists, indicating that, in the presence of endogenous estrogens, their overall effect would be cumulative. Recently, it has been suggested that environmental estrogens may be etiological agents in several human diseases, including disorders of the male reproductive tract and breast and testicular cancers. The current finding that some phthalate compounds and some food additives are weakly estrogenic in vitro, needs to be supported by further studies on their effects in vivo before any conclusions can be made regarding their possible role in the development of these conditions.

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Maternal nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development

2007-08-02

Dana C. Dolinoy , Dale Huang , Randy L. Jirtle

The hypothesis of fetal origins of adult disease posits that early developmental exposures involve epigenetic modifications, such as DNA methylation, that influence adult disease susceptibility. In utero or neonatal exposure … The hypothesis of fetal origins of adult disease posits that early developmental exposures involve epigenetic modifications, such as DNA methylation, that influence adult disease susceptibility. In utero or neonatal exposure to bisphenol A (BPA), a high-production-volume chemical used in the manufacture of polycarbonate plastic, is associated with higher body weight, increased breast and prostate cancer, and altered reproductive function. This study shows that maternal exposure to this endocrine-active compound shifted the coat color distribution of viable yellow agouti (Avy) mouse offspring toward yellow by decreasing CpG (cytosine-guanine dinucleotide) methylation in an intracisternal A particle retrotransposon upstream of the Agouti gene. CpG methylation also was decreased at another metastable locus, the CDK5 activator-binding protein (CabpIAP). DNA methylation at the Avy locus was similar in tissues from the three germ layers, providing evidence that epigenetic patterning during early stem cell development is sensitive to BPA exposure. Moreover, maternal dietary supplementation, with either methyl donors like folic acid or the phytoestrogen genistein, negated the DNA hypomethylating effect of BPA. Thus, we present compelling evidence that early developmental exposure to BPA can change offspring phenotype by stably altering the epigenome, an effect that can be counteracted by maternal dietary supplements.

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Endocrine disrupting chemicals and disease susceptibility

2011-08-29

Thaddeus T. Schug , Amanda Janesick , Bruce Blumberg +1 more

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Inhibition of testicular growth in rainbow trout <i>(Oncorhynchus mykiss)</i> exposed to estrogenic alkylphenolic chemicals

1996-02-01

Susan Jobling , John P. Sumpter , David A. Sheahan +2 more

Abstract It is becoming evident that an increasing number of widely used industrial and agricultural chemicals are estrogenic. The biodegradation products of a major group of nonionic surfactants, the alkylphenol … Abstract It is becoming evident that an increasing number of widely used industrial and agricultural chemicals are estrogenic. The biodegradation products of a major group of nonionic surfactants, the alkylphenol polyethoxylates, are one such group. Some of these chemicals are widespread aquatic pollutants, and bioconcentrate in aquatic biota. Exposure of male rainbow trout (Oncorhynchus mykiss) to four different alkylphenolic chemicals caused synthesis of vitellogenin, a process normally dependent on endogenous estrogens, and a concomitant inhibition of testicular growth. The magnitude of these estrogenic effects was dependent on the estrogenic potency of the chemical, the stage of reproductive development of the fish, and the concentration of the chemical in the water. These results support the contention that exposure of wildlife to environmentally persistent estrogenic chemicals can result in deleterious reproductive consequences.

Transplacental Carcinogenesis by Stilbestrol

1971-08-12

Judah Folkman

This editorial argues the cause-and-effect relationship between in utero exposure to diethylstilbestrol (DES) and incidence of vaginal adenocarcinoma among young women. It is conjectured that the mechanism by which DES … This editorial argues the cause-and-effect relationship between in utero exposure to diethylstilbestrol (DES) and incidence of vaginal adenocarcinoma among young women. It is conjectured that the mechanism by which DES induces tumors is a result of transplacental carcinogenesis; i.e., DES causes a malignant change in any fetal cell of future vaginal tissue, resulting in a genetic defect which may not be realized until puberty, when endogenous hormone production acts as a promoter of the malignancy initiated by DES exposure during gestation. If this theory is correct, local progestational therapy may arrest future adenocarcinoma cases. Though it is obvious that DES therapy must be avoided in the future in the population of pregnant women, of more concern is the presence of residual DES in foodstuffs, particularly livestock meat. A ban of such diet supplementation of human foodstuffs is called for.

Decrease in Anogenital Distance among Male Infants with Prenatal Phthalate Exposure

2005-05-23

Shanna H. Swan , Katharina M. Main , Liu Fan +7 more

Prenatal phthalate exposure impairs testicular function and shortens anogenital distance (AGD) in male rodents. We present data from the first study to examine AGD and other genital measurements in relation … Prenatal phthalate exposure impairs testicular function and shortens anogenital distance (AGD) in male rodents. We present data from the first study to examine AGD and other genital measurements in relation to prenatal phthalate exposure in humans. A standardized measure of AGD was obtained in 134 boys 2-36 months of age. AGD was significantly correlated with penile volume (R = 0.27, p = 0.001) and the proportion of boys with incomplete testicular descent (R = 0.20, p = 0.02). We defined the anogenital index (AGI) as AGD divided by weight at examination [AGI = AGD/weight (mm/kg)] and calculated the age-adjusted AGI by regression analysis. We examined nine phthalate monoester metabolites, measured in prenatal urine samples, as predictors of age-adjusted AGI in regression and categorical analyses that included all participants with prenatal urine samples (n = 85). Urinary concentrations of four phthalate metabolites [monoethyl phthalate (MEP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), and monoisobutyl phthalate (MiBP)] were inversely related to AGI. After adjusting for age at examination, p-values for regression coefficients ranged from 0.007 to 0.097. Comparing boys with prenatal MBP concentration in the highest quartile with those in the lowest quartile, the odds ratio for a shorter than expected AGI was 10.2 (95% confidence interval, 2.5 to 42.2). The corresponding odds ratios for MEP, MBzP, and MiBP were 4.7, 3.8, and 9.1, respectively (all p-values < 0.05). We defined a summary phthalate score to quantify joint exposure to these four phthalate metabolites. The age-adjusted AGI decreased significantly with increasing phthalate score (p-value for slope = 0.009). The associations between male genital development and phthalate exposure seen here are consistent with the phthalate-related syndrome of incomplete virilization that has been reported in prenatally exposed rodents. The median concentrations of phthalate metabolites that are associated with short AGI and incomplete testicular descent are below those found in one-quarter of the female population of the United States, based on a nationwide sample. These data support the hypothesis that prenatal phthalate exposure at environmental levels can adversely affect male reproductive development in humans.

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Application of the threshold of toxicological concern (TTC) to the safety evaluation of cosmetic ingredients

2007-06-27

R. Kroes , A. G. Renwick , V.J. Feron +6 more

Environmentally persistent alkylphenolic compounds are estrogenic.

1994-07-01

R White , Susan Jobling , Susan Hoare +2 more

We show that a number of alkylphenolic compounds, used in a variety of commercial products and found in river water, are estrogenic in fish, birds, and mammals. 4-Octylphenol (OP), 4-nonylphenol, … We show that a number of alkylphenolic compounds, used in a variety of commercial products and found in river water, are estrogenic in fish, birds, and mammals. 4-Octylphenol (OP), 4-nonylphenol, 4-nonylphenoxycarboxylic acid, and 4-nonylphenoldiethoxylate were each capable of stimulating vitellogenin gene expression in trout hepatocytes, gene transcription in transfected cells, and the growth of breast cancer cell lines. The most potent of the chemicals is OP, which was able to stimulate these biological responses to a similar extent as 17 beta-estradiol itself, albeit at a 1000-fold greater concentration. The action of alkylphenols is mediated by the estrogen receptor, as their effects depended on its presence and was blocked by estrogen antagonists. OP, 4-nonylphenol, and 4-nonylphenoxycarboxylic acid appear to possess intrinsic estrogenic activity, because they compete for binding to the estrogen receptor. Moreover, it is likely that they interact with a similar region of the hormone-binding domain as 17 beta-estradiol, because the mutant receptor G-525R, which is defective in estrogen binding, is also insensitive to OP. Like 17 beta-estradiol, OP is capable of stimulating the activity of both transcriptional activation functions, TAF-1 and TAF-2, in the receptor, as judged by analyzing the activity of the wild-type and mutant receptors in transiently transfected cells. The significance of our results will depend to a large extent on the degree of exposure of wildlife and humans to these estrogenic alkylphenolic compounds.

Exposure of the U.S. Population to Bisphenol A and 4- <i>tertiary</i> -Octylphenol: 2003–2004

2007-10-23

Antonia M. Calafat , Xiaoyun Ye , Lee‐Yang Wong +2 more

BackgroundBisphenol A (BPA) and 4-tertiary-octylphenol (tOP) are industrial chemicals used in the manufacture of polycarbonate plastics and epoxy resins (BPA) and nonionic surfactants (tOP). These products are in widespread use … BackgroundBisphenol A (BPA) and 4-tertiary-octylphenol (tOP) are industrial chemicals used in the manufacture of polycarbonate plastics and epoxy resins (BPA) and nonionic surfactants (tOP). These products are in widespread use in the United States.ObjectivesWe aimed to assess exposure to BPA and tOP in the U.S. general population.MethodsWe measured the total (free plus conjugated) urinary concentrations of BPA and tOP in 2,517 participants ≥ 6 years of age in the 2003–2004 National Health and Nutrition Examination Survey using automated solid-phase extraction coupled to isotope dilution–high-performance liquid chromatography–tandem mass spectrometry.ResultsBPA and tOP were detected in 92.6% and 57.4% of the persons, respectively. Least square geometric mean (LSGM) concentrations of BPA were significantly lower in Mexican Americans than in non-Hispanic blacks (p = 0.006) and non-Hispanic whites (p = 0.007); LSGM concentrations for non-Hispanic blacks and non-Hispanic whites were not statistically different (p = 0.21). Females had statistically higher BPA LSGM concentrations than males (p = 0.043). Children had higher concentrations than adolescents (p < 0.001), who in turn had higher concentrations than adults (p = 0.003). LSGM concentrations were lowest for participants in the high household income category (> $45,000/year).ConclusionsUrine concentrations of total BPA differed by race/ethnicity, age, sex, and household income. These first U.S. population representative concentration data for urinary BPA and tOP should help guide public health research priorities, including studies of exposure pathways, potential health effects, and risk assessment.

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

2011-05-24

Yujing Huang , Chris K.C. Wong , Jinming Zheng +5 more

A review of the environmental fate, effects, and exposures of bisphenol A

1998-04-01

Charles A. Staples , Philip B. Dome , Gary M. Kleĉka +2 more

Occurrence, Fate, Behavior and Ecotoxicological State of Phthalates in Different Environmental Matrices

2015-03-02

Sopheak Net , Richard Sempéré , Anne Delmont +2 more

Because of their large and widespread application, phthalates or phthalic acid esters (PAEs) are ubiquitous in all the environmental compartements. They have been widely detected throughout the worldwide environment. Indoor … Because of their large and widespread application, phthalates or phthalic acid esters (PAEs) are ubiquitous in all the environmental compartements. They have been widely detected throughout the worldwide environment. Indoor air where people spend 65–90% of their time is also highly contaminated by various PAEs released from plastics, consumer products as well as ambient suspended particulate matter. Because of their widespread application, PAEs are the most common chemicals that humans are in contact with daily. Based on various exposure mechanisms, including the ingestion of food, drinking water, dust/soil, air inhalation and dermal exposure the daily intake of PAEs may reach values as high as 70 μg/kg/day. PAEs are involved in endocrine disrupting effects, namely, upon reproductive physiology in different species of fish and mammals. They also present a variety of additional toxic effects for many other species including terrestrial and aquatic fauna and flora. Therefore, their presence in the environment has attracted considerable attention due to their potential impacts on ecosystem functioning and on public health. This paper is a synthesis of the extensive literature data on behavior, transport, fate and ecotoxicological state of PAEs in environmental matrices: air, water, sediment, sludge, wastewater, soil, and biota. First, the origins and physicochemical properties of PAEs that control the behavior, transport and fate in the environment are reviewed. Second, the compilation of data on transport and fate, adverse environmental and human health effects, legislation, restrictions, and ecotoxicological state of the environment based on PAEs is presented.

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Phthalates, Alkylphenols, Pesticides, Polybrominated Diphenyl Ethers, and Other Endocrine-Disrupting Compounds in Indoor Air and Dust

2003-09-13

Ruthann A. Rudel , David Camann , John D. Spengler +2 more

Chemicals identified as endocrine-disrupting compounds (EDCs) have widespread consumer uses, yet little is known about indoor exposure. We sampled indoor air and dust in 120 homes, analyzing for 89 organic … Chemicals identified as endocrine-disrupting compounds (EDCs) have widespread consumer uses, yet little is known about indoor exposure. We sampled indoor air and dust in 120 homes, analyzing for 89 organic chemicals identified as EDCs. Fifty-two compounds were detected in air and 66 were detected in dust. These are the first reported measures in residential environments for over 30 of the compounds, including several detected at the highest concentrations. The number of compounds detected per home ranged from 13 to 28 in air and from 6 to 42 in dust. The most abundant compounds in air included phthalates (plasticizers, emulsifiers), o-phenylphenol (disinfectant), 4-nonylphenol (detergent metabolite), and 4-tert-butylphenol (adhesive) with typical concentrations in the range of 50−1500 ng/m3. The penta- and tetrabrominated diphenyl ethers (flame retardants) were frequently detected in dust, and 2,3-dibromo-1-propanol, the carcinogenic intermediate of a flame retardant banned in 1977, was detected in air and dust. Twenty-three pesticides were detected in air and 27 were detected in dust, the most abundant being permethrins and the synergist piperonyl butoxide. The banned pesticides heptachlor, chlordane, methoxychlor, and DDT were also frequently detected, suggesting limited indoor degradation. Detected concentrations exceeded government health-based guidelines for 15 compounds, but no guidelines are available for 28 compounds, and existing guidelines do not consider endocrine effects. This study provides a basis for prioritizing toxicology and exposure research for individual EDCs and mixtures and provides new tools for exposure assessment in health studies.

Are oestrogens involved in falling sperm counts and disorders of the male reproductive tract?

1993-05-01

Richard M. Sharpe , Niels E. Skakkebæk

An updated review of environmental estrogen and androgen mimics and antagonists

1998-04-01

Carlos Sonnenschein , Ana M. Soto

Male reproductive health and environmental xenoestrogens.

1996-08-01

Jorma Toppari , J. C. Larsen , P. Christiansen +7 more

Male reproductive health has deteriorated in many countries during the last few decades. In the 1990s, declining semen quality has been reported from Belgium, Denmark, France, and Great Britain. The … Male reproductive health has deteriorated in many countries during the last few decades. In the 1990s, declining semen quality has been reported from Belgium, Denmark, France, and Great Britain. The incidence of testicular cancer has increased during the same time incidences of hypospadias and cryptorchidism also appear to be increasing. Similar reproductive problems occur in many wildlife species. There are marked geographic differences in the prevalence of male reproductive disorders. While the reasons for these differences are currently unknown, both clinical and laboratory research suggest that the adverse changes may be inter-related and have a common origin in fetal life or childhood. Exposure of the male fetus to supranormal levels of estrogens, such as diethlylstilbestrol, can result in the above-mentioned reproductive defects. The growing number of reports demonstrating that common environmental contaminants and natural factors possess estrogenic activity presents the working hypothesis that the adverse trends in male reproductive health may be, at least in part, associated with exposure to estrogenic or other hormonally active (e.g., antiandrogenic) environmental chemicals during fetal and childhood development. An extensive research program is needed to understand the extent of the problem, its underlying etiology, and the development of a strategy for prevention and intervention.

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A framework for prioritizing fragrance materials for aquatic risk assessment

2002-06-01

Daniel Salvito , Ronald J. Senna , Thomas W. Federle

More than 2,100 chemically defined organic chemicals are listed in the Research Institute of Fragrance Materials/Flavor and Extract Manufacturers' Association (RIFM/FEMA) Database that are used as ingredients of fragrances for … More than 2,100 chemically defined organic chemicals are listed in the Research Institute of Fragrance Materials/Flavor and Extract Manufacturers' Association (RIFM/FEMA) Database that are used as ingredients of fragrances for consumer products. An approach was developed for prioritizing these fragrance materials for aquatic risk assessment by first estimating the predicted environmental concentration (PEC) of these fragrance materials in the aquatic environment based upon their physicochemical properties and annual volume of use. Subsequently, an effect level was predicted with a general quantitative structure-activity relationship (QSAR) for aquatic toxicity, and a predicted no-effect concentration (PNEC) was calculated from this effect level by using an assessment factor (AF) that accounts for uncertainty in the toxicity QSAR prediction. A conservative AF of 10(6) was applied to the endpoint predicted by the QSAR to provide an adequate margin of safety in the calculation of the PNEC. The PEC was compared to the PNEC to characterize the risk to freshwater aquatic organisms (e.g., Daphnia magna and Pimephales promelas). If the ratio of PEC to PNEC was below one, the material was considered to have negligible environmental risk and to be acceptable for the aquatic environment at current use levels. If this ratio exceeded one, the PNEC was refined by using more specific QSAR models (Ecological Structure-Activity Relationships [ECOSAR]). If the ratio continued to exceed one, the material became a candidate for further aquatic risk assessment procedures, which involve iterative steps to refine the PEC, the PNEC, or both by using measured ecotoxicological endpoints. Prioritization for this latter process can be based upon the magnitudes of the estimated PEC:PNEC ratios. When using the first tier of this approach, only 568 of 2,141 fragrance materials (26.5%) in the RIFM/FEMA Database had PEC:PNEC ratios greater than one. This percentage decreased to only 164 materials (7.7%) when PNECs were derived with ECOSAR. Comparison of predicted PECs and PNECs with those based upon measured data confirmed the conservatism and low risk for type I errors associated with the framework. These combined exercises demonstrated the ability of this highly precautionary risk-based screening approach to quickly prioritize a large number of materials without benefit of experimental ecotoxicological or fate data.

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

2010-03-25

Laura N. Vandenberg , Ibrahim Chahoud , Jerrold J. Heindel +3 more

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

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Correlation of chemical structure with reproductive and developmental toxicity as it relates to the use of the threshold of toxicological concern

2011-10-16

Michael C. Laufersweiler , Bernard Gadagbui , Irene Abraham +7 more

Human exposure to phthalates via consumer products

2005-09-11

Ted Schettler

Phthalate exposures in the general population and in subpopulations are ubiquitous and widely variable. Many consumer products contain specific members of this family of chemicals, including building materials, household furnishings, … Phthalate exposures in the general population and in subpopulations are ubiquitous and widely variable. Many consumer products contain specific members of this family of chemicals, including building materials, household furnishings, clothing, cosmetics, pharmaceuticals, nutritional supplements, medical devices, dentures, children's toys, glow sticks, modelling clay, food packaging, automobiles, lubricants, waxes, cleaning materials and insecticides. Consumer products containing phthalates can result in human exposures through direct contact and use, indirectly through leaching into other products, or general environmental contamination. Historically, the diet has been considered the major source of phthalate exposure in the general population, but all sources, pathways, and their relative contributions to human exposures are not well understood. Medical devices containing di-(2-ethylhexyl) phthalate are a source of significant exposure in a susceptible subpopulation of individuals. Cosmetics, personal care products, pharmaceuticals, nutritional supplements, herbal remedies and insecticides, may result in significant but poorly quantified human exposures to dibutyl phthalate, diethyl phthalate, or dimethyl phthalate. Oven baking of polymer clays may cause short-term, high-level inhalation exposures to higher molecular weight phthalates.

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State-of-the-science of endocrine disrupting chemicals, 2012

2012-05-11

Åke Bergman , Jerrold J. Heindel , Susan Jobling +2 more

Exposure based waiving: The application of the toxicological threshold of concern (TTC) to inhalation exposure for aerosol ingredients in consumer products

2009-03-10

P. Carthew , Catherine J. Clapp , Steve Gutsell

Estrogenic activity of surfactants and some of their degradation products assessed using a recombinant yeast screen

1996-03-01

Edwin J. Routledge , John P. Sumpter

Abstract An estrogen‐inducible screen was developed in yeast ( Saccharomyces cerevisiae ) in order to assess whether surfactants and their major degradation products are estrogenic. The DNA sequence of the … Abstract An estrogen‐inducible screen was developed in yeast ( Saccharomyces cerevisiae ) in order to assess whether surfactants and their major degradation products are estrogenic. The DNA sequence of the human estrogen receptor (hER) was integrated into the yeast genome, which also contained expression plasmids carrying estrogen‐responsive sequences (ERE) controlling the expression of the reporter gene lac‐Z (encoding the enzyme β‐galactosidase). Thus, in the presence of estrogens, β‐galactosidase is synthesized and secreted into the medium, where it causes a color change from yellow to red. This recombinant strain was used to determine whether representatives of major surfactant classes and some of their principal degradation products possess estrogenic activity. The results were compared to the effects of the main natural estrogen 17β‐estradiol. None of the parent surfactants tested possessed estrogenic activity. However, one class of surfactants, the alkylphenol polyethoxylates, degrade to persistent metabolites that were weakly estrogenic. Another group of degradation products, the sulfophenyl carboxylates, which are derived from the biodegradation of linear alkylbenzene sulfonates, do not appear to possess estrogenic activity.

Perinatal Exposure to the Phthalates DEHP, BBP, and DINP, but Not DEP, DMP, or DOTP, Alters Sexual Differentiation of the Male Rat

2000-12-01

L. Earl Gray

In mammals, exposure to antiandrogenic chemicals during sexual differentiation can produce malformations of the reproductive tract. Perinatal administration of AR antagonists like vinclozolin and procymidone or chemicals like di(2-ethylhexyl) phthalate … In mammals, exposure to antiandrogenic chemicals during sexual differentiation can produce malformations of the reproductive tract. Perinatal administration of AR antagonists like vinclozolin and procymidone or chemicals like di(2-ethylhexyl) phthalate (DEHP) that inhibit fetal testicular testosterone production demasculinize the males such that they display reduced anogenital distance (AGD), retained nipples, cleft phallus with hypospadias, undescended testes, a vaginal pouch, epididymal agenesis, and small to absent sex accessory glands as adults. In addition to DEHP, di-n-butyl (DBP) also has been shown to display antiandrogenic activity and induce malformations in male rats. In the current investigation, we examined several phthalate esters to determine if they altered sexual differentiation in an antiandrogenic manner. We hypothesized that the phthalate esters that altered testis function in the pubertal male rat would also alter testis function in the fetal male and produce malformations of androgen-dependent tissues. In this regard, we expected that benzyl butyl (BBP) and diethylhexyl (DEHP) phthalate would alter sexual differentiation, while dioctyl tere- (DOTP or DEHT), diethyl (DEP), and dimethyl (DMP) phthalate would not. We expected that the phthalate mixture diisononyl phthalate (DINP) would be weakly active due to the presence of some phthalates with a 6-7 ester group. DEHP, BBP, DINP, DEP, DMP, or DOTP were administered orally to the dam at 0.75 g/kg from gestational day (GD) 14 to postnatal day (PND) 3. None of the treatments induced overt maternal toxicity or reduced litter sizes. While only DEHP treatment reduced maternal weight gain during the entire dosing period by about 15 g, both DEHP and DINP reduced pregnancy weight gain to GD 21 by 24 g and 14 g, respectively. DEHP and BBP treatments reduced pup weight at birth (15%). Male (but not female) pups from the DEHP and BBP groups displayed shortened AGDs (about 30%) and reduced testis weights (about 35%). As infants, males in the DEHP, BBP, and DINP groups displayed femalelike areolas/nipples (87, 70, and 22% (p < 0.01), respectively, versus 0% in other groups). All three of the phthalate treatments that induced areolas also induced a significant incidence of reproductive malformations. The percentages of males with malformations were 82% (p < 0.0001) for DEHP, 84% (p < 0.0001) for BBP, and 7.7% (p < 0.04) in the DINP group. In summary, DEHP, BBP, and DINP all altered sexual differentiation, whereas DOTP, DEP, and DMP were ineffective at this dose. Whereas DEHP and BBP were of equivalent potency, DINP was about an order of magnitude less active.

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

2012-03-14

Laura N. Vandenberg , Theo Colborn , Tyrone B. Hayes +7 more

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

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Bisphenol-A: an estrogenic substance is released from polycarbonate flasks during autoclaving.

1993-06-01

Arunkumar Krishnan , P Stathis , Steve Permuth +2 more

In studies to determine whether Saccharomyces cerevisiae produced estrogens, the organism was grown in culture media prepared using distilled water autoclaved in polycarbonate flasks. The yeast-conditioned media showed the presence … In studies to determine whether Saccharomyces cerevisiae produced estrogens, the organism was grown in culture media prepared using distilled water autoclaved in polycarbonate flasks. The yeast-conditioned media showed the presence of a substance that competed with [3H]estradiol for binding to estrogen receptors (ER) from rat uterus. However, it soon became clear that the estrogenic substance in the conditioned media was not a product of the yeast grown in culture, but was leached out of the polycarbonate flasks during the autoclaving procedure. [3H]Estradiol displacement activity was monitored by ER RRA, and the active substance was purified from autoclaved medium using a series of HPLC steps. The final purified product was identified as bisphenol-A (BPA) by nuclear magnetic resonance spectroscopy and mass spectrometry. BPA could also be identified in distilled water autoclaved in polycarbonate flasks without the requirement of either the organism or the constituents of the culture medium. Authentic BPA was active in competitive RRAs, demonstrating an affinity approximately 1:2000 that of estradiol for ER. In functional assays, BPA (10-25 nM) induced progesterone receptors in cultured human mammary cancer cells (MCF-7) at a potency of approximately 1:5000 compared to that of estradiol. The BPA effect on PR induction was blocked by tamoxifen. In addition, BPA (25 nM) increased the rate of proliferation of MCF-7 cells assessed by [3H]thymidine incorporation. Thus, BPA exhibited estrogenic activity by both RRA and two functional bioresponse assays. Finally, MCF-7 cells grown in media prepared with water autoclaved in polycarbonate exhibited higher progesterone receptor levels than cells.grown in media prepared with water autoclaved in glass, suggesting an estrogenic effect of the water autoclaved in polycarbonate. Our findings raise the possibility that unsuspected estrogenic activity in the form of BPA may have an impact on experiments employing media autoclaved in polycarbonate flasks. It remains to be determined whether BPA derived from consumer products manufactured from polycarbonate could significantly contribute to the pool of estrogenic substances in the environment.

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

2008-09-16

Iain Lang

<h3>Context</h3>Bisphenol A (BPA) is widely used in epoxy resins lining food and beverage containers. Evidence of effects in animals has generated concern over low-level chronic exposures in humans.<h3>Objective</h3>To examine associations … <h3>Context</h3>Bisphenol A (BPA) is widely used in epoxy resins lining food and beverage containers. Evidence of effects in animals has generated concern over low-level chronic exposures in humans.<h3>Objective</h3>To examine associations between urinary BPA concentrations and adult health status.<h3>Design, Setting, and Participants</h3>Cross-sectional analysis of BPA concentrations and health status in the general adult population of the United States, using data from the National Health and Nutrition Examination Survey 2003-2004. Participants were 1455 adults aged 18 through 74 years with measured urinary BPA and urine creatinine concentrations. Regression models were adjusted for age, sex, race/ethnicity, education, income, smoking, body mass index, waist circumference, and urinary creatinine concentration. The sample provided 80% power to detect unadjusted odds ratios (ORs) of 1.4 for diagnoses of 5% prevalence per 1-SD change in BPA concentration, or standardized regression coefficients of 0.075 for liver enzyme concentrations, at a significance level of P < .05.<h3>Main Outcome Measures</h3>Chronic disease diagnoses plus blood markers of liver function, glucose homeostasis, inflammation, and lipid changes.<h3>Results</h3>Higher urinary BPA concentrations were associated with cardiovascular diagnoses in age-, sex-, and fully adjusted models (OR per 1-SD increase in BPA concentration, 1.39; 95% confidence interval [CI], 1.18-1.63; P = .001 with full adjustment). Higher BPA concentrations were also associated with diabetes (OR per 1-SD increase in BPA concentration, 1.39; 95% confidence interval [CI], 1.21-1.60; P < .001) but not with other studied common diseases. In addition, higher BPA concentrations were associated with clinically abnormal concentrations of the liver enzymes γ-glutamyltransferase (OR per 1-SD increase in BPA concentration, 1.29; 95% CI, 1.14-1.46; P < .001) and alkaline phosphatase (OR per 1-SD increase in BPA concentration, 1.48; 95% CI, 1.18-1.85; P = .002).<h3>Conclusion</h3>Higher BPA exposure, reflected in higher urinary concentrations of BPA, may be associated with avoidable morbidity in the community-dwelling adult population.Published online September 16, 2008 (doi:10.1001/jama.300.11.1303).

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In vivo effects of bisphenol A in laboratory rodent studies

2007-06-27

Catherine A. Richter , Linda S. Birnbaum , Francesca Farabollini +6 more

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The E-SCREEN assay as a tool to identify estrogens: an update on estrogenic environmental pollutants.

1995-10-01

Ana M. Soto , Carlos Sonnenschein , KunMo Chung +3 more

Estrogens are defined by their ability to induce the proliferation of cells of the female genital tract. The wide chemical diversity of estrogenic compounds precludes an accurate prediction of estrogenic … Estrogens are defined by their ability to induce the proliferation of cells of the female genital tract. The wide chemical diversity of estrogenic compounds precludes an accurate prediction of estrogenic activity on the basis of chemical structure. Rodent bioassays are not suited for the large-scale screening of chemicals before their release into the environment because of their cost, complexity, and ethical concerns. The E-SCREEN assay was developed to assess the estrogenicity of environmental chemicals using the proliferative effect of estrogens on their target cells as an end point. This quantitative assay compares the cell number achieved by similar inocula of MCF-7 cells in the absence of estrogens (negative control) and in the presence of 17 beta-estradiol (positive control) and a range of concentrations of chemicals suspected to be estrogenic. Among the compounds tested, several

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Mechanism-Based Concepts of Size and Maturity in Pharmacokinetics

2007-10-03

Brian J. Anderson , Nicholas H. G. Holford

Growth and development can be investigated using readily observable demographic factors such as weight and age. Size is the primary covariate and can be referenced to a 70-kg person with … Growth and development can be investigated using readily observable demographic factors such as weight and age. Size is the primary covariate and can be referenced to a 70-kg person with allometry using a coefficient of 0.75 for clearance and 1 for volume. The use of these coefficients is supported by fractal geometric concepts and observations from diverse areas in biology. Fat free mass (FFM) might be expected to do better than total body weight when there are wide variations in fat affecting body composition. Clearance pathways develop in the fetus before birth. The use of postnatal age as a descriptor of maturation is unsatisfactory because birth may occur prematurely; therefore postmenstrual age is a superior predictor of elimination function. A sigmoid E max model (Hill equation) describes gradual maturation of clearance in early life leading to a mature adult clearance achieved at a later age.

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

2005-04-12

Frederick S. vom Saal , Claude L. Hughes

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

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

2012-06-27

R. Thomas Zoeller , T. R. Brown , Loretta L. Doan +5 more

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

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EDC-2: The Endocrine Society's Second Scientific Statement on Endocrine-Disrupting Chemicals

2015-11-06

Andrea C. Gore , Vesna A. Chappell , Suzanne E. Fenton +5 more

The Endocrine Society's first Scientific Statement in 2009 provided a wake-up call to the scientific community about how environmental endocrine-disrupting chemicals (EDCs) affect health and disease. Five years later, a … The Endocrine Society's first Scientific Statement in 2009 provided a wake-up call to the scientific community about how environmental endocrine-disrupting chemicals (EDCs) affect health and disease. Five years later, a substantially larger body of literature has solidified our understanding of plausible mechanisms underlying EDC actions and how exposures in animals and humans—especially during development—may lay the foundations for disease later in life. At this point in history, we have much stronger knowledge about how EDCs alter gene-environment interactions via physiological, cellular, molecular, and epigenetic changes, thereby producing effects in exposed individuals as well as their descendants. Causal links between exposure and manifestation of disease are substantiated by experimental animal models and are consistent with correlative epidemiological data in humans. There are several caveats because differences in how experimental animal work is conducted can lead to difficulties in drawing broad conclusions, and we must continue to be cautious about inferring causality in humans. In this second Scientific Statement, we reviewed the literature on a subset of topics for which the translational evidence is strongest: 1) obesity and diabetes; 2) female reproduction; 3) male reproduction; 4) hormone-sensitive cancers in females; 5) prostate; 6) thyroid; and 7) neurodevelopment and neuroendocrine systems. Our inclusion criteria for studies were those conducted predominantly in the past 5 years deemed to be of high quality based on appropriate negative and positive control groups or populations, adequate sample size and experimental design, and mammalian animal studies with exposure levels in a range that was relevant to humans. We also focused on studies using the developmental origins of health and disease model. No report was excluded based on a positive or negative effect of the EDC exposure. The bulk of the results across the board strengthen the evidence for endocrine health-related actions of EDCs. Based on this much more complete understanding of the endocrine principles by which EDCs act, including nonmonotonic dose-responses, low-dose effects, and developmental vulnerability, these findings can be much better translated to human health. Armed with this information, researchers, physicians, and other healthcare providers can guide regulators and policymakers as they make responsible decisions.

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Bisphenol A and human health: A review of the literature

2013-08-30

Johanna R. Rochester

Endocrine-Disrupting Chemicals: An Endocrine Society Scientific Statement

2009-06-01

Evanthia Diamanti‐Kandarakis , Jean‐Pierre Bourguignon , Linda C. Giudice +5 more

Abstract There is growing interest in the possible health threat posed by endocrine-disrupting chemicals (EDCs), which are substances in our environment, food, and consumer products that interfere with hormone biosynthesis, … Abstract There is growing interest in the possible health threat posed by endocrine-disrupting chemicals (EDCs), which are substances in our environment, food, and consumer products that interfere with hormone biosynthesis, metabolism, or action resulting in a deviation from normal homeostatic control or reproduction. In this first Scientific Statement of The Endocrine Society, we present the evidence that endocrine disruptors have effects on male and female reproduction, breast development and cancer, prostate cancer, neuroendocrinology, thyroid, metabolism and obesity, and cardiovascular endocrinology. Results from animal models, human clinical observations, and epidemiological studies converge to implicate EDCs as a significant concern to public health. The mechanisms of EDCs involve divergent pathways including (but not limited to) estrogenic, antiandrogenic, thyroid, peroxisome proliferator-activated receptor γ, retinoid, and actions through other nuclear receptors; steroidogenic enzymes; neurotransmitter receptors and systems; and many other pathways that are highly conserved in wildlife and humans, and which can be modeled in laboratory in vitro and in vivo models. Furthermore, EDCs represent a broad class of molecules such as organochlorinated pesticides and industrial chemicals, plastics and plasticizers, fuels, and many other chemicals that are present in the environment or are in widespread use. We make a number of recommendations to increase understanding of effects of EDCs, including enhancing increased basic and clinical research, invoking the precautionary principle, and advocating involvement of individual and scientific society stakeholders in communicating and implementing changes in public policy and awareness.

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

2016-05-04

Da Chen , Kurunthachalam Kannan , Hongli Tan +4 more

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 … 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 shown to exhibit estrogenic and/or antiandrogenic activities similar to or even greater than that of BPA. Knowledge gaps and research needs have been identified, which include the elucidation of environmental occurrences, persistence, and fate of bisphenol analogues (other than BPA), sources and pathways for human exposure, effects on reproductive systems and the mammary gland, mechanisms of toxicity from coexposure to multiple analogues, metabolic pathways and products, and the impact of metabolic modification on toxicity.

Biodegradation of phthalates DIBP, DMP, and DEP by Paenarthrobacter sp. strain PH1 - analysis of degradation, pathway, and its bioremediation potentiality in soil microcosm

2025-06-25

Ping Ren , Sirshendu Gayen , Subhankar Chatterjee | World Journal of Microbiology and Biotechnology

Endocrine disrupting chemicals exposure and health: An umbrella review

2025-06-24

Junhao Chen , Song Pan , Chao Li +5 more | Ecotoxicology and Environmental Safety

Extensive exposure to di-n-hexyl phthalate with significant seasonal variation across infants, children and adults including pregnant women in Denmark

2025-06-24

Hanne Frederiksen , Holger M. Koch , Stine Müller +6 more | International Journal of Hygiene and Environmental Health

Di-n-hexyl phthalate (DnHxP) is one of the most potent phthalates with adverse effects on the male reproductive system. Despite a European ban on DnHxP since 2020, high urinary excretion of … Di-n-hexyl phthalate (DnHxP) is one of the most potent phthalates with adverse effects on the male reproductive system. Despite a European ban on DnHxP since 2020, high urinary excretion of mono-n-hexyl phthalate (MnHxP), the major metabolite of DnHxP, has been observed in recent European human biomonitoring (HBM) studies. Sunscreen products containing the UV-filter diethylamino hydroxybenzyl hexyl benzoate (DHHB), which can be contaminated with DnHxP, were pointed out as a relevant source of exposure to DnHxP. To study possible seasonal variation in urinary excretion of MnHxP in different Danish study populations. MnHxP was measured by LC-MS/MS in 1591 urine samples collected in 2016-2022 from pregnant women, 7-year-old children, and infants and their parents participating in three different cohort studies. Urinary MnHxP was above the limit of detection (0.04 μg/L) in 84 % and above 1 μg/L in 33 % of samples. The 7-year-old children was the study population with the highest excretion rate (97 %). The highest urinary MnHxP concentration (72.5 μg/L) exceeded the health-based guidance value (HBM-I value) of 60 μg/L. A significantly higher urinary excretion of MnHxP was observed in the summer compared to the winter season in all study populations. 80 % of the urine samples with MnHxP concentrations > 1 μg/L were from the summer season. 40 % of Danish sunscreen products contain DHHB. The marked seasonal variation with higher MnHxP excretions in the summer season supports the hypothesis that the recently unveiled DnHxP contamination of the UV-filter DHHB in sunscreen products could be driving these exposures.

Prophylactic role of omega 3 fatty acids in bisphenol F-induced sexual and erectile dysfunction is associated with penile redox homeostasis

2025-06-23

Adeyemi Fatai Odetayo , Moses Agbomhere Hamed , Grace Edet Bassey +4 more | Biochemistry and Biophysics Reports

Relación de los contaminantes ambientales con trastornos autoinmunes: una revisión sistemática y análisis comparativo

2025-06-23

Oscar Rodrigo Coronel-Sigcho , A. Orozco , J. Montero +1 more | Esprint Investigación

Los trastornos autoinmunes han experimentado un notable incremento en las últimas décadas. Diversos factores ambientales, en particular los contaminantes químicos, han sido identificados como posibles desencadenantes. El objetivo de esta … Los trastornos autoinmunes han experimentado un notable incremento en las últimas décadas. Diversos factores ambientales, en particular los contaminantes químicos, han sido identificados como posibles desencadenantes. El objetivo de esta investigación es analizar la relación entre los contaminantes ambientales y la incidencia de trastornos autoinmunes. El estudio, de enfoque cualitativo, incluyó investigaciones publicadas entre 2010 y 2023, e identificó mecanismos moleculares involucrados, como la alteración de la tolerancia inmunológica, el estrés oxidativo y las modificaciones epigenéticas. Los hallazgos revelan que existe una relación clara entre la exposición a contaminantes ambientales y los trastornos autoinmunes. Diversos agentes tóxicos alteran el sistema inmunológico mediante mecanismos como el estrés oxidativo, la inflamación crónica y las modificaciones epigenéticas, especialmente en personas genéticamente predispuestas o expuestas en etapas vulnerables. Esta evidencia resalta la importancia de reducir la exposición ambiental como medida clave de prevención.

Phthalate Exposure During Pregnancy and Lactation Transgenerationally Impairs the Epididymis in the Offspring of Rats

2025-06-23

Ana Paula Franco Punhagui‐Umbelino , Giovanna Fachetti Frigoli , Ariana Musa de Aquino +6 more | Journal of Biochemical and Molecular Toxicology

Phthalates are chemical compounds used as plasticizers in plastic products, for guaranteeing their flexibility. These compounds damage the epididymal morphophysiology. This study aimed to verify the changes in the epididymis … Phthalates are chemical compounds used as plasticizers in plastic products, for guaranteeing their flexibility. These compounds damage the epididymal morphophysiology. This study aimed to verify the changes in the epididymis of neonatal and adult rats over two generations. Pregnant Sprague-Dawley females were divided into four groups and gavaged daily from GD10 to PND21 with corn oil (Control:C) or the phthalate mixture at three doses (20, 200, and 200 mg/Kg). F1 animals were euthanized at 22PND and 120PND; unexposed females were mated with 90PND males to obtain the F2 generation. Male rats were euthanized at 22PND. Tissue remodeling of the compartments was observed at all doses in the 22PND animals of both generations. Treatment at 200 mg/Kg resulted in alterations, a decrease in the epithelium and a consequent increase in the lumen in the cauda in F1 PND22. The lumen in the caput and cauda increased, with a reduction in the interstitium at 200 mg/Kg in F2 PND22. The lumen diameter was reduced in the caput and increased in the interstitium at the two highest doses in adult animals. The expression of GPR30, GPX3, GSR, IL10, and TNFa was reduced in adult animals at the highest dose. GPR30 expression increased at 200 mg/Kg dose in PND22. TNFa expression was reduced at all doses in F1 PND22 animals and significantly increased in F2 PND22 animals at 200 µg/Kg and 200 mg/Kg doses. In conclusion, phthalates modify the epididymal structure and impair gene expression, mainly in the late phase.

Therapeutic Effects of Naringin on Bisphenol A‐Induced Oxidative Stress Damage in Nervous and Reproductive Systems of Cockerel Chickens

2025-06-23

Leah Oluwaseyanu Esuola , Oluwaseun Olanrewaju Esan , Adamu Shafiu Maikifi +7 more | Veterinary Medicine and Science

Bisphenol A (BPA) is an endocrine-disrupting chemical, and it is mostly used in plastic industries. Naringin is a potent flavonoid that has been reported to possess several beneficial pharmacological properties … Bisphenol A (BPA) is an endocrine-disrupting chemical, and it is mostly used in plastic industries. Naringin is a potent flavonoid that has been reported to possess several beneficial pharmacological properties such as antioxidant, anti-inflammatory, and antiapoptotic properties. The aim of this study was to determine the protective effect of naringin against the damage induced by BPA in the brain and testes of commercial chicken. Thirty-day-old cockerel chickens were purchased and reared for 6 weeks and subsequently divided into six groups: group A (control), group B (100 ppm BPA-treated), group C (BPA and 100 mg/kg naringin-treated), Group D (BPA and 200 mg/kg naringin-treated), group E (100 mg/kg naringin-treated), and group F (200 mg/kg naringin-treated). BPA was administered via drinking water, while naringin was administered via oral gavage. Analyses such as biochemical assays, hormonal assays, histopathology, and immunohistochemistry were done. The results showed a decrease in the level of LH, FSH, and testosterone, an increase in the level of oxidative stress markers (MDA and H2O2), and alteration in the levels of enzymatic and non-enzymatic antioxidants (GSH, GST, SOD, GPx) in the brain and testes of the BPA-intoxicated group. Histologically, neuronal necrosis and degeneration were observed in the brain, and degeneration of testicular cells was seen in the testes of BPA-intoxicated chickens. Immunohistochemical evaluation revealed low expression of myelin basic protein in the brain and increased expression of caspase 3 in the testes of the BPA-intoxicated group. Naringin reversed the neurotoxicity and reproductive toxicity of BPA by normalizing the values of the altered parameters. Hence, naringin ameliorated the deleterious effects caused by BPA in both the brain and testes by enhancing the antioxidant defence mechanism.

Associations Between Endocrine-Disrupting Chemical Exposure and Fertility Outcomes: A Decade of Human Epidemiological Evidence

2025-06-21

Zoe Tzouma , Panagiota Dourou , Athina Diamanti +6 more | Life

Endocrine-disrupting chemicals (EDCs) are exogenous compounds that interfere with the endocrine system by mimicking or blocking the action of endogenous hormones such as estrogens, androgens, and thyroid hormones. This systematic … Endocrine-disrupting chemicals (EDCs) are exogenous compounds that interfere with the endocrine system by mimicking or blocking the action of endogenous hormones such as estrogens, androgens, and thyroid hormones. This systematic review aims to evaluate the current epidemiological evidence linking EDC exposure with adverse reproductive outcomes in males and females of reproductive age. A total of 14 observational studies published between 2014 and 2024 were included following structured searches in PubMed, Scopus, and Google Scholar. The most commonly studied EDCs included bisphenol A (BPA), its analogs (such as bisphenol S, BPS), phthalates, parabens, per- and polyfluoroalkyl substances (PFAS), and persistent organic pollutants (POPs). The review found consistent associations between EDC exposure and multiple reproductive endpoints, such as impaired semen quality, decreased ovarian reserve, infertility, polycystic ovary syndrome (PCOS), altered hormone levels—specifically estradiol (E2), luteinizing hormone (LH), and follicle-stimulating hormone (FSH)—and adverse outcomes in assisted reproductive technologies (ART), including in vitro fertilization (IVF). Despite methodological heterogeneity, the findings support the biological plausibility of EDCs in disrupting reproductive function. The review highlights the urgent need for regulatory measures, increased public awareness, and longitudinal studies to assess the cumulative effects of chronic EDC exposure on human fertility.

A population-based study to understand the association between Bisphenol-A (BPA) and Polycystic Ovarian Syndrome (PCOS): correlating with anthropometric parameters and clinical features

2025-06-21

Shrinjana Dhar , Ankita Das , Pritha Bhattacharjee | Environmental Geochemistry and Health

Optimization of Targeted Water Sample Extraction Methods for Different Toxicity End Points of <i>In Vitro</i> Bioassays

2025-06-20

Shanglin Yang , Kai Zhu , Y. L. Han +3 more | ACS ES&T Water

Occurrence, Migration Behavior, and Environmental Burden of Phthalate Esters in Flooring Materials Used in Newly Renovated Chinese Homes

2025-06-20

Ying Zhang , Libo Chen , Haoyang Shen +4 more | Toxics

Phthalic acid esters (PAEs), a class of synthetic semi-volatile organic compounds, are extensively incorporated into decorative materials. However, their specific occurrence, migration behaviors, and environmental impact on these materials—which comprise … Phthalic acid esters (PAEs), a class of synthetic semi-volatile organic compounds, are extensively incorporated into decorative materials. However, their specific occurrence, migration behaviors, and environmental impact on these materials—which comprise the largest surface areas in residential settings—remain insufficiently understood. This study investigated the distribution, emission dynamics, and environmental burdens of PAEs in flooring commonly used in Chinese households. The results showed that PAEs are widespread in flooring, with total concentrations ranging from 1220 to 166,000 ng/g (14,100 ng/g, median value). Solid wood flooring (55,900 ng/g) exhibited significantly higher PAE levels compared to engineered flooring (22,600 ng/g) and laminate flooring (4000 ng/g) (p < 0.05). Migration experiments revealed that solid wood flooring tended to continuously release PAEs, laminate flooring showed a pronounced capacity for PAE absorption, and engineered flooring exhibited both release and absorption behaviors. The initial PAE concentration is the dominant factor influencing migration rates, while the flooring type and substrate density also contribute to varying degrees. The estimated environmental burdens of PAEs resulting from flooring in newly renovated Chinese households ranged from 3.63 × 109 ng to 3.45 × 1011 ng, with a median value of 1.23 × 1010 ng. Households in the eastern and southwestern regions exhibited the highest PAE burdens, while the southern region showed the lowest. Socioeconomic factors such as residential floor area, number of rooms, household income, and renovation budget significantly influenced the environmental burden of PAEs derived from flooring.

Microplastic pollutant exposures and Cancer: a pooled analysis

2025-06-20

X.Q. Liu , Lijuan Wang , Xiaoyu Liu +7 more | International Journal of Surgery

Comprehensive Profiling of Phthalic Acid Esters (PAEs) in Air-Conditioning Filters from Diverse Indoor Environments Across 12 Major Cities in China

2025-06-20

Jiaqian Yan , Bailiang Liu , Boyue Jia +6 more | Environmental Pollution

Preventive antioxidant strategies to reduce the effects of phthalate exposure on reproductive health

2025-06-19

Mega Obukohwo Oyovwi , Joy Oluwasemilore Oyelami , Kehinde Henrietta Babawale +1 more | Discover Environment

Divergent effects of EDCs on bone maturation: Role of body mass index and puberty

2025-06-19

Shurong Huang , Zhuoguang Li , Chushan Wu +7 more | Ecotoxicology and Environmental Safety

Exposure Levels and Health Risks of Phthalate Alternatives: A Urinary Metabolite Study

2025-06-19

Jing Ren , Qingqing Zhu , Chunyang Liao +1 more | Environment & Health

Evaluation of Reproductive Toxicity Potential of Bisphenol A in Sprague Dawley Rats

2025-06-19

A. Adak , Saktipada Pradhan , Sandeep K. Chaudhuri +5 more | Deleted Journal

High-throughput transcriptomics analysis of equipotent and human relevant mixtures of BPA alternatives reveal additive effects in vitro

2025-06-18

Geronimo Matteo , Eunnara Cho , Marc Rigden +7 more | Archives of Toxicology

Measurement of vinyl acetate monomer in consumer products and modeled estimates of consumer exposure

2025-06-18

Alison Gauthier , William Behymer , Jennifer L. Bare +5 more | Journal of Exposure Science & Environmental Epidemiology

Natural Organic Matter Aggregates Modulate Dibutyl Phthalate Desorption Hysteresis: Insights from Coarse-Grained Molecular Dynamics Simulations

2025-06-18

Quan Chen , Wenjun Wang , Yi Peng +5 more | Environmental Science & Technology Letters

Cytotoxicity and Endocrine Disruption in Materials Used for Removable Orthodontic Retainers: A Comprehensive Review

2025-06-17

Katarzyna Chojnacka , Marcin Mikulewicz | Dentistry Journal

Objective: To evaluate the cytotoxicity and endocrine-disrupting potential of materials used in removable orthodontic retainers. Methods: A literature search (2015-2025) covered in vitro cytotoxicity, estrogenicity, in vivo tissue responses, and … Objective: To evaluate the cytotoxicity and endocrine-disrupting potential of materials used in removable orthodontic retainers. Methods: A literature search (2015-2025) covered in vitro cytotoxicity, estrogenicity, in vivo tissue responses, and clinical biomarkers in PMMA plates, thermoplastic foils, 3D-printed resins, PEEK, and fiber-reinforced composites. Results: Thirty-eight in vitro and ten clinical studies met inclusion criteria, identified via a structured literature search of electronic databases (2015-2025). Photopolymer resins demonstrated the highest cytotoxicity, whereas thermoplastics and PMMA exhibited predominantly mild effects, which diminished further following 24 h water storage. Bisphenol-type compound release was reported, but systemic exposure remained below regulatory limits. No statistically significant mucosal alterations or endocrine-related effects were reported in clinical studies. Conclusions: Retainer materials are generally biocompatible, though data on long-term endocrine effects are limited. Standardized biocompatibility assessment protocols are necessary to enable comparative evaluation across diverse orthodontic materials. Single-use thermoplastics contribute to microplastic release and pose end-of-life management challenges, raising concerns regarding environmental sustainability.

Children's Exposure To Persistent Organic Pollutants in Playground Dust: A Comparative Study of Artificial and Natural Playground

2025-06-17

Pikakhanım Ahlimanova , Mihriban Civan | Water Air & Soil Pollution

Associations between environmental chemical mixtures and anthropometric measures in Korean girls: a cross-sectional study

2025-06-16

Erdenetuya Bolormaa , Ki‐Jeong Kim , Hoyol Jhang +3 more | European Journal of Pediatrics

Phthalic acid esters (PAEs) in surface water from five tropical estuaries: Spatial distribution, seasonal variations, and mass loads

2025-06-16

Thao Thi Nguyen , Chi Linh Thi Pham , Xuyen Nguyen Thi +7 more | Marine Pollution Bulletin

Parabens and Their Metabolites in Surface Sediment from Estuaries to the Sea: Occurrence, Spatial Distribution, and Potential Sources

2025-06-16

Feng‐Jiao Peng , Rong-Gui Zhu , Chang‐Gui Pan +5 more | ACS ES&T Water

Release of Bisphenol A from Dental Materials: Risks and Future Perspectives

2025-06-16

Antonín Tichý , Tereza Šrolerová , Falk Schwendicke | Journal of Dental Research

The gradual phaseout of dental amalgam has contributed to a significant increase in the use of resin-based materials. While these materials offer several desirable properties, concerns persist regarding their biocompatibility, … The gradual phaseout of dental amalgam has contributed to a significant increase in the use of resin-based materials. While these materials offer several desirable properties, concerns persist regarding their biocompatibility, particularly the release of bisphenol A (BPA). BPA is an endocrine-disrupting chemical linked to adverse effects on human health, including reproductive, developmental, and metabolic disorders. Although food contact materials are the primary source of human BPA exposure and the contribution of dental materials is minor, the associated risks cannot be dismissed due to BPA’s nonmonotonic dose-response relationship. In 2023, the European Food Safety Authority proposed a 20,000-fold reduction in the tolerable daily intake of BPA to 0.2 ng/kg body weight, citing immune system effects at extremely low doses. This proposal has sparked regulatory and scientific debate, as adopting such a stringent limit would effectively ban the use of BPA in food contact materials and many other products. Given this context, it is essential to assess the release of BPA from dental materials both in vitro and in vivo. However, data interpretation is complicated by methodological inconsistencies, including variations in material composition, specimen preparation, choice of extraction media, experimental duration, and analytical methods. In addition, pivotal differences in reporting results make it difficult to synthesize findings and draw reliable conclusions. This review examines the controversy surrounding BPA, critically evaluates evidence on its release from dental materials, and explores mitigation strategies. By highlighting gaps in knowledge and proposing future research directions, this review aims to provide clinicians, researchers, and policymakers with a clearer understanding of BPA-related complexities, ultimately contributing to patient safety and material innovation.

Bisphenol A caused abnormal spermatogenesis of Eriocheir sinensis through es-ERR/es-KIF4A pathway with discussion of BPA substitutes

2025-06-14

Yang Yu , Di Wu , Lei Tian +7 more | Journal of Hazardous Materials

Bisphenol AF Induced Neurodevelopmental Toxicity of Human Neural Progenitor Cells via Nrf2/HO-1 Pathway

2025-06-13

Huan Luo , Mengchao Ying , Yun Yang +4 more | International Journal of Molecular Sciences

Bisphenol AF (BPAF) is widely utilized as an analog of bisphenol A (BPA) in the plastics industry. However, there is limited evidence on its neurodevelopmental toxicity. Existing studies suggest that … Bisphenol AF (BPAF) is widely utilized as an analog of bisphenol A (BPA) in the plastics industry. However, there is limited evidence on its neurodevelopmental toxicity. Existing studies suggest that BPAF has greater accumulation in vivo than other bisphenol analogs, and could pass through the placental barrier and the blood–brain barrier. In this study, we used the human neural progenitor cells line ReNcell CX, which was derived from 14-week human cortical brain tissue, as an in vitro model to investigate the neurodevelopmental toxicity effects of BPAF and BPA on ReNcell CX cells, and explored the possible mechanism by which BPAF induced neurodevelopmental toxicity on ReNcell CX cells. The results showed that BPAF reduced the proliferation of neural progenitor cells and changed the differentiation towards neurons after exposure for 24 h. Compared with BPA, ReNcell CX cells are more susceptible to BPAF exposure. In a 3D neurospheres model, BPAF affected the distance that neurons migrated outwards at the concentration of 2 μM. Furthermore, BPAF increased ROS levels in cells and reduced the expression of key proteins in the Nrf2/HO-1 pathway and its downstream molecules, such as SOD, GSH, and CAT. In conclusion, BPAF induces damage to critical nodes in neural progenitor cell development through the Nrf2/HO-1 pathway. Therefore, clarifying its neurodevelopmental toxicity and elaborating on the neurodevelopmental toxicity effects and mechanisms of bisphenol AF will help identify intervention targets for neurodevelopmental toxicity, and will have important public health significance for the safety assessment and risk prediction of bisphenol-related chemicals.

Di (2-ethylhexyl) Phthalate decrease pregnancy rate via disrupting the microbe-gut-hypothalamic-pituitary-ovarian axis in mice

2025-06-13

Linjie Xu , Jun Yan , Tingting Yin +5 more | npj Biofilms and Microbiomes

Di (2-ethylhexyl) Phthalate (DEHP), a widely used plasticizer and endocrine disruptor, poses risks to human health, particularly reproductive function. Using a mouse model, we investigated how DEHP exposure impacts the … Di (2-ethylhexyl) Phthalate (DEHP), a widely used plasticizer and endocrine disruptor, poses risks to human health, particularly reproductive function. Using a mouse model, we investigated how DEHP exposure impacts the hypothalamic-pituitary-ovarian (HPO) axis through gut microbiome disruption. DEHP decreased pregnancy rates by impairing ovarian function, activating hypothalamic astrocytes, and increasing neuregulin 1 (NRG1) expression. NRG1 binding to astrocyte ErbB2 receptors elevated prostaglandin E2 (PGE2) and gonadotropin-releasing hormone (GnRH), disrupting HPO axis homeostasis. Additionally, DEHP altered gut microbiota, destabilized microbial networks, and impacted β-glucuronidase-related taxa, leading to hormone fluctuations and reduced fertility. This study highlights gut microbiome perturbations as a novel mechanism linking DEHP exposure to reproductive dysfunction. Our study provides novel insights concerning perturbations of the gut microbiome and HPO axis and their functions as a potential new mechanism by which DEHP exposes interferes with the reproductive function-related human health.

Common phthalate plasticizers pose health risks, EPA finds

2025-06-13

Britt Erickson | C&EN Global Enterprise

Examining the association between gestational phenol exposure and infant non-nutritive suck in two Environmental influences on Child Health Outcomes cohorts

2025-06-13

Megan Woodbury , Andréa Aguiar , Sarah Dee Geiger +7 more | Environmental Epidemiology

Background: Non-nutritive suck (NNS) is a measure of neurofunction sensitive to environmental exposures in utero. This study aimed to evaluate the relationship between gestational phenol exposure and NNS patterning. Methods: … Background: Non-nutritive suck (NNS) is a measure of neurofunction sensitive to environmental exposures in utero. This study aimed to evaluate the relationship between gestational phenol exposure and NNS patterning. Methods: Mother-infant pairs from two diverse prospective cohorts were enrolled in the Environmental influences on Child Health Outcomes Program. Phenols were measured in prenatal maternal urine samples and adjusted for specific gravity. NNS was sampled in 1–8-week-old infants using a custom pacifier for ~5 minutes. Associations of 11 phenols and triclocarban with 5 NNS outcomes were assessed individually and as a mixture using generalized linear models adjusted for cohort, child sex and assessment age, and maternal age and education. Results: Altogether, 215 mother-infant pairs were included. Bisphenol-F was related to a lower NNS frequency. Triclosan was associated with a higher NNS frequency. Propylparaben, 2,4-dichlorophenol, and 2,5-dichlorophenol were associated with lower NNS amplitude. Benzophenone-3, 2,4-dichlorophenol, and 2,5-dichlorophenol were related to more NNS bursts/minute. Propylparaben was associated with more NNS cycles/bursts. Seven phenols were included in mixture analyses: 2,4-dichlorophenol, 2,5-dichlorophenol, benzophenone-3, bisphenol-A, bisphenol-S, methylparaben, and propylparaben. Both Bayesian kernel machine regression and quantile g-computation showed that higher concentrations of the mixture were associated with lower amplitude but more bursts/minute and cycles/burst. Propylparaben was important in the overall mixture effect on amplitude, whereas benzophenone-3 was important in the relationship with bursts/minute. Conclusions: Gestational phenol exposure is linked to altered NNS patterning in neonates. Future work should further investigate phenol mixture effects, potential mechanisms, and the association of altered NNS with neurodevelopment.

Ecotoxicological effects of phthalate esters: A review

2025-06-13

Ying Xu , Mengyuan Pei , Zhuofan Li +7 more | Environmental Pollution

Determination of Phthalates in Purified Drinking Water in Italy

2025-06-13

Claudia Lino , Serena Indelicato , David Bongiorno +3 more | Beverages

This study investigated the presence and concentration of selected phthalates in municipal tap waters and purified waters sourced from domestic water purifiers and municipal reverse osmosis-based supplies. Five target compounds: … This study investigated the presence and concentration of selected phthalates in municipal tap waters and purified waters sourced from domestic water purifiers and municipal reverse osmosis-based supplies. Five target compounds: Diethyl phthalate (DEP), Diisobutyl phthalate (DiBP), Butyl octyl phthalate (BOP), Dibutyl phthalate (DBP), and bis(2-ethylhexyl) phthalate (DEHP) were identified and quantified in the samples using the solid-phase microextraction gas chromatography-mass spectrometry (SPME-GC/MS) method. The analytical protocol demonstrated good sensitivity, precision, and accuracy, with low limits of detection and quantification, making it suitable for routine monitoring applications. Phthalates were detected in all samples, including both inlet and treated water, highlighting their widespread occurrence. The results show a significant percentage of reduction in total phthalate concentrations (from 4% to 53%; 30% on average) in purified water samples compared to untreated inlet water, thereby indicating the potential efficacy of such systems in reducing organic pollutants. Risk assessment based on the EFSA guidelines showed that the estimated daily intakes for all detected phthalates remained well below tolerable daily intake limits for both adults and toddlers. The findings underscore the importance of monitoring phthalates in drinking water and support the implementation of regular maintenance strategies for filtration devices. The analytical approach developed may be adopted as a cost-effective tool for water quality assessment and offers promising potential for broader application in public health and commercial water treatment systems.

D-Limonene Alleviates Bisphenol-A Hepatotoxicity in Male Albino Rats via Suppression of Oxidative Stress and Inflammation

2025-06-12

Mohamed Mahgoub , Elie K. Mehanna , Samah Oda +2 more | Egyptian Journal of Veterinary Science

Renin–Angiotensin System Role in Cardiovascular Effects of Plasticizers: A Systematic Review

2025-06-12

Guilherme dos Santos Reis , L. Ferraz , Milena Campos da Silva +6 more | Cardiovascular Toxicology

Sex-specific neurotoxicity induced by long-term bisphenol A exposure: Single-cell sequencing reveals dual mechanisms involving hippocampal gliosis and neuronal apoptosis

2025-06-11

Ziwen Wang , Chenghao Li , Hongjuan He +7 more | The Science of The Total Environment

Bioaccumulation of Metals in Hairs of Breast Cancer Patients: Current Work and Future Prospects

2025-06-11

Rimsha , Kamarul Ariffin Khalid , Fouzia Tanvir +7 more | Current Signal Transduction Therapy

Background: Breast cancer, a complex disease characterized by aberrant cellular physiology, poses a significant health threat to women globally. Its prevalence and mortality rates emphasize the need to understand its … Background: Breast cancer, a complex disease characterized by aberrant cellular physiology, poses a significant health threat to women globally. Its prevalence and mortality rates emphasize the need to understand its etiology and risk factors. Recent studies recommend a possible association between heavy metal revelation and the development of breast cancer. Objective: The work aimed to study heavy metal exposure in the hair of breast cancer patients across different stages of the disease according to previous work. Methods: The data from already reported studies was collected, including Google Scholar, PubMed, Web of Science, and many more. Results: Previous research has shown elevated levels of cadmium in hair samples from breast cancer patients compared to controls. Other metals like zinc, lead, Hg, mercury, cobalt, nickel, selenium, tin, antimony, scandium, silver, gold, boron, barium, beryllium, calcium, cerium, cesium, gadolinium, manganese, and arsenic play an important role in spreading of breast cancer to people. Additionally, a comparison of metal concentrations in hair samples revealed significant differences between cancer patients and healthy individuals. Correlations between certain metals within each group were also found, suggesting distinct patterns in metal distribution among breast cancer patients. Conclusion: The elevated level of certain metals in hairs from breast cancer patients needs further investigation into the processes underlying their association with disease development and progression. Cadmium and other metals play an important role in breast cancer development either by oral, skin, or food ingestion. Understanding the part of metals in breast cancer may offer insights into preventive strategies and therapeutic interventions.

Plasticizers Analysis in Extractables and Leachables by Gas Chromatography–Mass Spectrometry with Parallel Polyarc®/Flame Ionization Detector

2025-06-10

Jianxin Yu , Scott Citrowske , John Strange +2 more | PubMed

Abstract Plasticizers such as phthalate acid esters including di-(2-ethylhexyl) phthalate (DEHP) and its alternatives are commonly found in extractables and leachables (E&Ls) from plastic-based medical devices. Regulatory agencies require manufacturers … Abstract Plasticizers such as phthalate acid esters including di-(2-ethylhexyl) phthalate (DEHP) and its alternatives are commonly found in extractables and leachables (E&Ls) from plastic-based medical devices. Regulatory agencies require manufacturers to monitor, qualify and quantify the E&Ls from medical devices to ensure the safety. Analyzing E&Ls from medical devices is difficult due to the unpredictability and complexity of matrices. The advent of the novel Polyarc/Flame Ionization Detector (FID), which features compound-independent response, provides the opportunity of quantitation of unknowns-to-be-identified E&Ls without using pure substances for establishing calibration. The present work evaluated firstly the feasibility and efficacy of full scan GC–MS with parallel Polyarc/FID system through analysis of plasticizers in E&Ls. In the same injection, E&Ls were identified by full scan GC–MS, then quantified through Polyarc/FID response factor of internal standards. The results showed that quantitation via response factor from internal standards are more accurate so the need for standards of the identified E&Ls is eliminated. The method can combine screening process and target analysis into a one-step execution, which makes it desirable for E&L analysis. The method was applied to a polyvinyl chloride medical device, yielding 1.183 g/device of acetyl tri-n-butyl citrate, 370.2 mg/device of trioctyltrimellitate, and 3.068 mg/device of DEHP.