EDCs : evidence that co-exposures should be considered when evaluating the risk of a single chemical

Endocrine Disruption in Human Fetal Testis Explants by Individual and Combined Exposures to Selected Pharmaceuticals, Pesticides, and Environmental Pollutants

2017 Study Abstract

Numerous chemicals are capable of disrupting androgen production, but the possibility that they might act together to produce effects greater than those of the most effective component in the mixture has not been studied directly in human tissues. Suppression of androgen synthesis in fetal life has been associated with testis maldescent, malformations of the genitalia at birth, and poor semen quality later in life.

Our aim was to investigate whether chemicals can act together to disrupt androgen production in human fetal testis explants and to evaluate the importance of mixture effects when characterizing the hazard of individual chemicals.

We used an organotypic culture system of human fetal testes explants called FEtal Gonad Assay (FEGA) with tissue obtained at 10 and 12 gestational wk (GW 10–12), to screen 27 chemicals individually for their possible anti-androgenic effect. Based on the results of the screen, we selected 11 compounds and tested them as mixtures.

We evaluated mixtures composed of four and eight antiandrogens that contained the pharmaceuticals ketoconazole and theophylline and several previously untested chemicals, such as the pesticides imazalil and propiconazole. Mixtures of antiandrogens can suppress testosterone synthesis in human fetal testicular explants to an extent greater than that seen with individual chemicals. This revealed itself as a shift towards lower doses in the dose–response curves of individual antiandrogens that became more pronounced as the number of components increased from four to eight.

Our results with the FEGA provide the foundations of a predictive human mixture risk assessment approach for anti-androgenic exposures in fetal life.


Concerns that the traditional focus of chemical risk assessment on single chemical exposures might underestimate the risks associated with adverse effects of multiple chemicals have been expressed earlier (Kortenkamp 2014), but the impact on risk estimates has been proven difficult to define. This is partly due to incomplete information about the complexity of combined human exposures and to a lack of clarity about the approaches and methods that should be used for mixture risk assessment. Our study provides important advances in improving the scientific basis for human mixture risk assessment. To our knowledge, we demonstrate for the first time that the mixture assessment concept of dose addition is applicable to human tissues. This not only enabled us to avoid certain uncertainties associated with animal-to-human extrapolations, but also enabled us to use a predictive approach. Rather than studying every conceivable combination of chemicals within a mixture, the joint effects of anti-androgenic chemicals in the FEGA can now be approximated on the basis of the effects of each single component by using dose addition as the default assumption.

To utilize the FEGA in multi-component mixture studies required making a leap from qualitative studies to quantitative dose–response analyses. Due to the inhomogeneity of the material and the variations inevitably introduced through the age differences of the fetal testes, the assay outcome (fetal testosterone production) shows high variability, which we had to deal with by rigorously controlling experimental conditions. We achieved good reproducibility, which was essential for realizing our goal of analyzing whether the combined effects of multiple chemicals can be predicted accurately on the basis of the effects of individual mixture components and of assessing the impact of co-exposures on the dose–response curves of single chemicals.

A difficulty in using the FEGA as a screening method for the identification of chemicals with endocrine disruptive properties is the limited availability of human fetal tissue. An additional challenge is in the requirement of collecting tissues of comparable age.

Our study provides direct evidence that co-exposures should be considered when evaluating the risk of a single chemical. We show that effects of a single chemical are underestimated when co-exposure to related chemicals are not considered, and that this underestimation is driven by the number, type, and potency of co-occurring chemicals. In this study, overlooking co-exposures to only seven chemicals led to an underestimation of the potency of BPA by a factor of 10. A corollary of the principles of dose addition is that co-exposure to a larger number of chemicals will drive up the extent of such underestimations if these chemicals are present at levels equipotent with the components we used in our experiments. Alternatively, replacement of some components with larger numbers of other chemicals, but at lower levels, may lead to similar underestimations. More studies using the FEGA are needed to establish these assumptions.

Based on our findings, we suggest that the impact of mixture effects on male sexual differentiation during the first trimester of pregnancy may be considerable. However, although in this study the selection of chemicals was empirically based on the results obtained in our dose–response study, analysis of individual chemicals, assessment of the extent of adverse effects in human fetuses will require more knowledge about the spectrum of chemicals capable of suppressing testosterone synthesis. Future FEGA studies will help close this knowledge gap, especially if based on companion studies that identify all of the exogenous chemicals found in maternal and fetal tissues.

Full Study
  • Featured image : predicted and observed testosterone secretion in human fetal testis by four chemical mixtures. Experimental data are shown as mean ± SEM (blue) of at least four independent experiments. Testosterone production is represented as relative to the first day of culture (D0) production and the control level, see text for more details. The mixture effects were predicted according to dose addition (DA) (thick red curve), with dashed curves the respective 95% confidence intervals (CIs) (dotted orange lines) credit ehp.
  • Endocrine Disruption in Human Fetal Testis Explants by Individual and Combined Exposures to Selected Pharmaceuticals, Pesticides, and Environmental Pollutants, Environmental Health Perspectives, DOI:10.1289/EHP1014, AUGUST 2017 | VOLUME 125 | ISSUE 8. Full PDF.
Endocrine Disruptors

Toward Consistent Methodology to Quantify Populations in Proximity to Oil and Gas Development

Seventeen Million in U.S. Live Near Active Oil or Gas Wells

A number of studies indicate that there may be negative health outcomes associated with living in close proximity to oil and gas development. Degraded air quality; surface water, groundwater and soil contamination; and elevated noise and light pollution are exposure pathways that contribute to potential human health impacts.

Studies have identified multiple symptoms reported by residents living with oil and gas infrastructure in their communities, including respiratory symptoms, such as nose, eye, and throat irritation; headaches; and fatigue, among others.

One study has pointed to increased hospitalization rates for multiple medical categories, including cardiology, neurology, and oncology. Increased asthma incidence and severity has also been reported in Pennsylvania.

Preliminary epidemiological studies that use distance of oil and gas development as the exposure metric have found positive associations with adverse birth outcomes, including preterm birth, lower birth weight, and small for gestational age, as well as neural tube defects and congenital heart defects.

Studies also identified increased incidence of childhood hematologic cancer among children that live in close proximity to oil and gas development compared to those that live farther away.

While many findings in the public health literature on oil and gas development are sometimes inconsistent and studies often lack the designs to arrive at causal claims, the body of literature serves as an indication that proximity to oil and gas development is associated with adverse health risks and impacts.

Previous Population Proximity Studies

Public concern and the public health scientific literature to date has spurred interest in quantitative assessments of populations potentially at increased risk of health impacts from living in close proximity to oil and gas development. Four peer-reviewed studies were published in the last 2 y: two reporting population counts, and three reporting demographic subgroups. Three additional studies were identified in the gray literature. The earliest study we could identify was published in The Wall Street Journal. This early study has substantial methodological flaws, but is included in our review because it was the first published attempt to quantify populations near oil and gas wells.

2017 Study Abstract

Higher risk of exposure to environmental health hazards near oil and gas wells has spurred interest in quantifying populations that live in proximity to oil and gas development. The available studies on this topic lack consistent methodology and ignore aspects of oil and gas development of value to public health–relevant assessment and decision-making.

We aim to present a methodological framework for oil and gas development proximity studies grounded in an understanding of hydrocarbon geology and development techniques.

We geospatially overlay locations of active oil and gas wells in the conterminous United States and Census data to estimate the population living in proximity to hydrocarbon development at the national and state levels. We compare our methods and findings with existing proximity studies.

Nationally, we estimate that 17.6 million people live within 1,600 m (∼1 mi) of at least one active oil and/or gas well. Three of the eight studies overestimate populations at risk from actively producing oil and gas wells by including wells without evidence of production or drilling completion and/or using inappropriate population allocation methods. The remaining five studies, by omitting conventional wells in regions dominated by historical conventional development, significantly underestimate populations at risk.

The well inventory guidelines we present provide an improved methodology for hydrocarbon proximity studies by acknowledging the importance of both conventional and unconventional well counts as well as the relative exposure risks associated with different primary production categories (e.g., oil, wet gas, dry gas) and developmental stages of wells.

More Information

  • Toward Consistent Methodology to Quantify Populations in Proximity to Oil and Gas Development: A National Spatial Analysis and Review, Environmental Health Perspectives, DOI:10.1289/EHP1535, AUGUST 2017 | VOLUME 125 | ISSUE 8.
  • Seventeen Million in US Live Near Active Oil or Gas Wells, Truthout, September 06, 2017.
  • Featured image credit EHP : confirmed active well counts by U.S. county. Well data are from DrillingInfo. Administrative boundaries are from the U.S. Census Bureau.

The Florence Statement on Triclosan and Triclocarban

More than 200 scientists outline a broad range of concerns for triclosan and triclocarban and call for reduced use worldwide

Two ingredients used in thousands of products to kill bacteria, fungi and viruses linger in the environment and pose a risk to human health, according to a statement released today by more than 200 scientists and health professionals.

The scientists say the possible benefits in most uses of triclosan and triclocarban – used in some soaps, toothpastes, detergents, paints, carpets – are not worth the risk.


“Triclosan and triclocarban have been permitted for years without definitive proof they’re providing benefits.”

Avery Lindeman, Green Policy Institute

The Florence Statement on Triclosan and Triclocarban documents a consensus of more than 200 scientists and medical professionals on the hazards of and lack of demonstrated benefit from common uses of triclosan and triclocarban.

These chemicals may be used in thousands of personal care and consumer products as well as in building materials. Based on extensive peer-reviewed research, this statement concludes that triclosan and triclocarban are environmentally persistent endocrine disruptors that bioaccumulate in and are toxic to aquatic and other organisms. Evidence of other hazards to humans and ecosystems from triclosan and triclocarban is presented along with recommendations intended to prevent future harm from triclosan, triclocarban, and antimicrobial substances with similar properties and effects.

Because antimicrobials can have unintended adverse health and environmental impacts, they should only be used when they provide an evidence-based health benefit. Greater transparency is needed in product formulations, and before an antimicrobial is incorporated into a product, the long-term health and ecological impacts should be evaluated.

Sources, Studies, Press Releases

  • The Florence Statement on Triclosan and Triclocarban, Environ Health Perspect; DOI:10.1289/EHP1788, JUNE 2017.
  • Patterns, Variability, and Predictors of Urinary Triclosan Concentrations during Pregnancy and Childhood, Environ. Sci. Technol., DOI: 10.1021/acs.est.7b00325, May 18, 2017
  • Hundreds of scientists call for caution on anti-microbial chemical use, EHN, June 20, 2017.
  • Hygiene leaves kids with loads of triclosan, EHN, June 1, 2017.
  • Image credit Mike Mozart.

The Evidence of the EDCs Effect on Gender: the DES Situation

Are EDCs blurring issues of gender?


Although scientists have postulated a wide range of adverse human health effects of exposure to endocrine-disrupting chemicals (EDCs), the nexus of the debate is the concern that prenatal and childhood exposure to EDCs may be responsible for a variety of abnormalities in human sexuality, gender development and behaviors, reproductive capabilities, and sex ratios. Scientists today are asking hard questions about potential human effects: Do EDC exposures impair fertility in men or women? Can they cause sexual organ malformations, stunted reproductive development, or testicular or breast cancer? Do fetal exposures to EDCs alter sex phenotypes? Do they change later gender-related neurobiological characteristics and behaviors such as play activity and spatial ability? Could such exposures even be involved in the etiology of children born with ambiguous gender?

Are EDCs Blurring Issues of Gender?, Environnement Health Perspectives, NCBI PubMed PMC1281309, 2005 Oct.

EDCs include a spectrum of substances that can be loosely classified according to their known or suspected activity in relation to sex hormone receptors and pathways. The most-studied and best known are the environmental estrogens, which mimic estradiol and bind to estrogen receptors (ERs). ER agonists include the pesticide methoxychlor, certain polychlorinated biphenyls (PCBs), bisphenol A (BPA; a high production volume chemical used to make polycarbonate plastic), pharmaceutical estrogens such as diethylstilbestrol (DES) and ethinyl estradiol, and phytoestrogens, which occur naturally in many plants, most notably in soybeans in the form of genistein and related substances. There are a few known ER antagonists, or antiestrogens. Antiandrogens, or androgen receptor (AR) antagonists, include the fungicide vinclozolin, the DDT metabolite p,p′-DDE, certain phthalates (a group of chemicals used to soften polyvinyl chloride plastics), and certain other PCBs. And there are other types of EDCs that affect particular endocrine targets. The various EDCs differ greatly in their potencies relative to natural hormones, and in their affinity for target receptors. Some have been shown to act via non–receptor-mediated mechanisms, for example by interfering with hormone synthesis.

In many well-documented cases of high-level fetal exposures to known EDCs such as DES, certain PCBs, and DDT, the answer to the question of whether exposure is associated with gender-related effects is clearly yes. But high-level exposures such as these are relatively rare and isolated. The debate today centers on low-dose exposures—generally defined as doses that approximate environmentally relevant levels—and the idea that low-dose intrauterine exposure to some EDCs during certain critical windows of development can have profound, permanent impacts on subsequent fetal development and adult outcomes.

Critics of this idea maintain that thus far there is no credible evidence to suggest that low-dose exposures cause any adverse human health effects. But if low-dose exposures were confirmed to be the threat that proponents of the concept insist they are, public health would clearly be at risk, regulatory agencies’ risk assessment approach would need to be revised, and certain common chemicals—including some that are massively produced and economically important—would likely disappear from the marketplace.

In a June 2000 EHP review article on human health problems associated with EDCs, Stephen Safe, director of the Center for Environmental and Genetic Medicine at Texas A&M University, concluded that

“the role of endocrine disruptors in human disease has not been fully resolved; however, at present the evidence is not compelling.”

Frederick vom Saal, a developmental biologist at the University of Missouri–Columbia, disagrees, particularly in light of the research that’s been presented in the years since that review. He says

“The jury is not out on human effects. In terms of the amount of information we have in animals and the amount of information we have in humans, clearly there is a huge difference, but that’s a lot different than saying the jury is out on whether EDCs influence humans.”

One thing both scientists might agree on, though, is that right now there are still more questions than answers.

Evidence of Effects: the DES situation

The Global Assessment further states that the only evidence showing that humans are susceptible to EDCs is currently provided by studies of high exposure levels. There is, in fact, clear evidence that intrauterine EDC exposures can alter human reproductive tract development and physiology. The most thoroughly characterized example is DES, the synthetic estrogen prescribed to millions of pregnant women in the United States and elsewhere from the 1940s to the 1970s to prevent miscarriage. The drug is known to have caused a rare form of vaginal cancer in thousands of daughters of women who took DES, as well as a variety of adverse reproductive tract effects in both the daughters and sons of those women.

The DES situation could be seen as a worst-case scenario for prenatal EDC exposure—the deliberate delivery of a potent estrogenic chemical in high doses. Viewed another way, it has provided researchers a rare opportunity to study the effects of prenatal EDC exposure in a relatively controlled fashion, with a well-defined population and well-characterized exposure to a single potent agent.

Over the course of her research, Newbold has developed a mouse model of DES exposure that has proven extremely useful in studying the effects of DES and other environmental estrogens, particularly those outcomes that may be manifested only later in life. She says

“With the experimental model, there are a lot of questions we can ask with DES that will tell us about the weaker environmental estrogens. We can change the timing of exposure and the amount of exposure, and we can look at different target tissues.”

The animal model has replicated numerous abnormalities reported in DES-exposed humans, and has also predicted some human outcomes.

“We have published documentation [see, for example, the October 1985 issue of Cancer Research and volume 5, issue 6 (1985) of Teratogenesis, Carcinogenesis, and Mutagenesis] that a number of the reproductive anomalies seen in DES-exposed mice, such as retained testes and abnormalities in the oviduct in females, were also later reported in DES-exposed humans,”

says Newbold.

More DES DiEthylStilbestrol resources

Prenatal exposure to flame retardants linked to poorer behavioral function in children

Children’s mental development could be stunted by chemicals found in couches and upholstery, carpet pads, electronics, some textiles and sofas…

New research from the University of Cincinnati (UC) College of Medicine suggests that prenatal exposure to flame retardants and perfluoroalkyl substances (PFASs) commonly found in the environment may have a lasting effect on a child’s cognitive and behavioral development, known as executive function.


Maternal Polybrominated Diphenyl Ether (PBDE) Exposure and Thyroid Hormones in Maternal and Cord Sera: The HOME Study, Cincinnati, USA, Environ Health Perspect; DOI:10.1289/ehp.1408996, January 2016.

Polybrominated diphenyl ethers (PBDEs) reduce blood concentrations of thyroid hormones in laboratory animals, but it is unclear whether PBDEs disrupt thyroid hormones in pregnant women or newborn infants.

We investigated the relationship between maternal PBDE levels and thyroid hormone concentrations in maternal and cord sera.

We used data from the Health Outcomes and Measures of the Environment (HOME) Study, a prospective birth cohort of 389 pregnant women in Cincinnati, Ohio, who were enrolled from 2003 through 2006 and delivered singleton infants. Maternal serum PBDE concentrations were measured at enrollment (16 ± 3 weeks of gestation). Thyroid hormone concentrations were measured in maternal serum at enrollment (n = 187) and in cord serum samples (n = 256).

Median maternal serum concentrations of BDEs 28 and 47 were 1.0 and 19.1 ng/g lipid, respectively. A 10-fold increase in BDEs 28 and 47 concentrations was associated with a 0.85-μg/dL [95% confidence interval (CI): 0.05, 1.64] and 0.82-μg/dL (95% CI: 0.12, 1.51) increase in maternal total thyroxine concentrations (TT4), respectively. Both congeners were also positively associated with maternal free thyroxine (FT4). We also observed positive associations between BDE-47 and maternal total and free triiodothyronine (TT3 and FT3). A 10-fold increase in BDE-28 was associated with elevated FT3 concentrations (β = 0.14 pg/mL; 95% CI: 0.02, 0.26). In contrast, maternal PBDE levels were not associated with thyroid hormone concentrations in cord serum.

These findings suggest that maternal PBDE exposure, particularly BDEs 28 and 47, are associated with maternal concentrations of T4 and T3 during pregnancy.

Prenatal exposure to flame retardants linked to poorer behavioral function in children, sciencedaily, January 27, 2016.

BPS Chemical Product linked to irregular Heartbeats at low-Dose

New ingredient in plastic bottles, receipts has same effect on lab animals as the old chemical does

BPS ingredient has same effect on lab animals hearts as the BPA chemical does… BP Girls image via David Merrett.

Exposure to bisphenol-S (BPS), an ingredient that has replaced BPA in many items, caused irregular heartbeats in female lab rats, according to the study by Hong-Sheng Wang and colleagues published this 26 February 2015. The findings were “remarkably similar—if not identical to—what we find in BPA” Wang said.

Bisphenol S (BPS) is increasingly been used as a substitute for BPA in some “bisphenol A (BPA)-free” consumer goods and in thermal papers. Wide human exposure to BPS has been reported; however, the biological and potential toxic effects of BPS are poorly understood.
Objective: To elucidate the sex-specific rapid impact of BPS in rat hearts and its underlying mechanism.

Rapid effects of BPS in rat hearts were examined using electrophysiology, confocal and conventional fluorescence imaging, and immunoblot.

In female rat hearts, acute exposure to 10-9 M BPS increased heart rate and in the presence of catecholamine-induced stress condition, markedly increased the frequency of ventricular arrhythmia events. BPS increased the incidence of arrhythmogenic triggered activities in female ventricular myocytes, and altered myocyte Ca2+ handling, particularly spontaneous Ca2+ release from the sarcoplasmic reticulum. The dose responses of BPS’ actions were inverted-U shaped. The impact of BPS on myocyte Ca2+ handling was mediated by estrogen receptor β signaling and rapid increases in the phosphorylation of key Ca2+ handling proteins including ryanodine receptor and phospholamban. The pro-arrhythmic effects of BPS were female-specific; male rat hearts were not affected by BPS at the organ, myocyte and protein levels.

Rapid exposure to low-dose BPS has pro-arrhythmic impact on female rat hearts; these effects at the organ, cellular and molecular levels are remarkably similar to those reported for BPA. Evaluation of the bioactivity and safety of BPS and other BPA analogs is necessary before they are used as BPA alternatives in consumer products.

Sources and more information
  • Chemical in BPA-Free Products Linked to Irregular Heartbeats, nationalgeographic news, FEBRUARY 25, 2015.
  • Rapid Responses and Mechanism of Action for Low-Dose Bisphenol S on ex Vivo Rat Hearts and Isolated Myocytes: Evidence of Female-Specific Proarrhythmic Effects, Environ Health Perspect; DOI:10.1289/ehp.1408679, 26 February 2015, full study PDF.

Agricultural Pesticides during Pregnancy linked to Autism Spectrum Disorders

Autism risk is higher near pesticide-treated fields

Neurodevelopmental Disorders and Prenatal Residential Proximity to Agricultural Pesticides: The CHARGE Study

Pesticide Exposure during Pregnancy linked to Autism.

Gestational exposure to several common agricultural pesticides can induce developmental neurotoxicity in humans, and has been associated with developmental delay and autism.

To evaluate whether residential proximity to agricultural pesticides during pregnancy is associated with autism spectrum disorders (ASD) or developmental delay (DD) in the Childhood Autism Risks from Genetics and Environment (CHARGE) Study.

The CHARGE study is a population-based case-control study of ASD, developmental delay (DD), and typical development. For 970 participants, commercial pesticide application data from the California Pesticide Use Report (1997-2008) were linked to the addresses during pregnancy. Pounds of active ingredient applied for organophophates, organochlorines, pyrethroids, and carbamates were aggregated within 1.25km, 1.5km, and 1.75km buffer distances from the home. Multinomial logistic regression was used to estimate the odds ratio (OR) of exposure comparing confirmed cases of ASD (n = 486) or DD (n = 168) with typically developing referents (n = 316).

Approximately one-third of CHARGE Study mothers lived, during pregnancy, within 1.5 km (just under one mile) of an agricultural pesticide application. Proximity to organophosphates at some point during gestation was associated with a 60% increased risk for ASD, higher for 3rd trimester exposures [OR = 2.0, 95% confidence interval (CI) = (1.1, 3.6)], and 2nd trimester chlorpyrifos applications: OR = 3.3 [95% CI = (1.5, 7.4)]. Children of mothers residing near pyrethroid insecticide applications just prior to conception or during 3rd trimester were at greater risk for both ASD and DD, with OR’s ranging from 1.7 to 2.3. Risk for DD was increased in those near carbamate applications, but no specific vulnerable period was identified.

This study of ASD strengthens the evidence linking neurodevelopmental disorders with gestational pesticide exposures, and particularly, organophosphates and provides novel results of ASD and DD associations with, respectively, pyrethroids and carbamates. Children of mothers who live near agricultural areas, or who are otherwise exposed to organophosphate, pyrethroid, or carbamate pesticides during gestation may be at increased risk for neurodevelopmental disorders.
Further research on gene-by-environment interactions may reveal vulnerable sub-populations.

  • Neurodevelopmental Disorders and Prenatal Residential Proximity to Agricultural Pesticides: The CHARGE Study, Environ Health Perspect; DOI:10.1289/ehp.1307044, 23 June 2014 – PDF
  • Supplemental Material, Aerial image showing further descriptions of the study population and exposure model, ehp.1307044.s001.
  • Autism risk higher near pesticide-treated fields, study says, Environmental Health News, autism-and-pesticides, June 23, 2014

Bisphenol A Long-Term Adverse Reproductive and Carcinogenic Effects

Prenatal exposure to bisphenol a at environmentally relevant doses adversely affects the murine female reproductive tract later in life


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BPA causes long-term adverse reproductive and carcinogenic effects if exposure occurs during critical periods of differentiation.

Exposure to endocrine-disrupting chemicals during critical developmental periods causes adverse consequences later in life; an example is prenatal exposure to the pharmaceutical diethylstilbestrol (DES). Bisphenol-A (BPA), an environmental estrogen used in the synthesis of plastics, is of concern because its chemical structure resembles that of DES, and it is a “high-volume production” chemical with widespread human exposure.

In this study we investigated whether prenatal Bisphenol-A causes long-term adverse effects in female reproductive tissues in an experimental animal model previously shown useful in studying effects of prenatal DES.

Timed pregnant CD-1 mice were treated on days 9-16 of gestation with BPA (0.1, 1, 10, 100, or 1,000 mug/kg/day). After delivery, pups were held for 18 months; reproductive tissues were then evaluated.

Ovarian cysts were significantly increased in the 1-mug/kg BPA group; ovarian cyst-adenomas were seen in the other three BPA-treated groups but not in corn-oil controls. We observed increased progressive proliferative lesions of the oviduct after BPA treatment, similar to those described in response to DES. Further, although not statistically different from the controls, prominent mesonephric (Wolffian) remnants and squamous metaplasia of the uterus, as well as vaginal adenosis, were present in BPA-treated mice, similar to lesions reported following DES treatment. More severe pathologies observed in some BPA-treated animals included atypical hyperplasia and stromal polyps of the uterus; sarcoma of the uterine cervix; and mammary adenocarcinoma. We did not observe these lesions in controls.

These data suggest that BPA causes long-term adverse reproductive and carcinogenic effects if exposure occurs during critical periods of differentiation.

  • Prenatal exposure to bisphenol a at environmentally relevant doses adversely affects the murine female reproductive tract later in life., Environ Health Perspect ; 117(6):879-85. doi: 10.1289/ehp.0800045, 19590677, 2009 Jun.
  • Full text : NCBI, PMC2702400, Jan 15, 2009.

Bisphenol A BPA is a Reproductive Toxicant and has the Potential to affect Male Reproductive System

BPA is a reproductive toxicant because it impacts female reproduction, and has the potential to affect male reproductive systems in humans and animals


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EHP Report: BPA is a female reproductive toxicant.

In 2007, an expert panel reviewed associations between bisphenol A (BPA) exposure and reproductive health outcomes. Since then, new studies have been conducted on the impact of BPA on reproduction.

This review summarizes the data obtained since 2007, focusing on:

  1. findings from human and animal studies,
  2. the effects of BPA on a variety of reproductive endpoints,
  3. and mechanisms of BPA action.

We reviewed the literature using a PubMed search from 2007-2013 based on keywords related to BPA and male and female reproduction.

BPA is an ovarian toxicant because it affects the onset of meiosis in both animal and in vitro models, interferes with germ cell nest breakdown in animal models, accelerates follicle transition in several animal species, alters steroidogenesis in multiple animal models and women, and reduces oocyte quality in animal models and women undergoing IVF. BPA is a uterine toxicant because it impairs uterine endometrial proliferation, decreases uterine receptivity, and increases implantation failure in animal models. BPA exposure may be associated with adverse birth outcomes, hyperandrogenism, sexual dysfunction, and impaired implantation in humans, but additional studies are required to confirm whether this is the case. BPA is a testicular toxicant in animal models, but the data in humans are equivocal. Finally, insufficient evidence exists regarding effects of BPA on the oviduct, placenta, and pubertal development.

BPA is a reproductive toxicant because it impacts female reproduction, and has the potential to affect male reproductive systems in humans and animals.

  • Bisphenol A and Reproductive Health: Update of Experimental and Human Evidence, 2007–2013, Environ Health Perspect ; DOI:10.1289/ehp.1307728, 4 June 2014
  • Full text PDF
  • Supplemental Material PDF