Assessment of five typical environmental endocrine disruptors and thyroid cancer risk: a meta-analysis.

Introduction: There are conflicting reports on the association between environmental endocrine disruptors (EEDs) and thyroid cancer. This meta-analysis aimed to elucidate the relationship between EEDs and thyroid cancer. Methods: We searched for epidemiological studies on EEDs and thyroid cancer published in PubMed and Web of Science up to December 2022. We then screened the articles that could extract data on EEDs concentration levels in both thyroid cancer patients and healthy controls. We excluded articles that could not calculate effect sizes, focused on other thyroid diseases, or lacked controls. Standardized mean difference (SMD) was calculated to analyze the association between EEDs and thyroid cancer. We measured the heterogeneity among the included studies using I2, assessed publication bias by Egger's and Begg's test, and evaluated article quality using the Newcastle-Ottawa Quality Score (NOS). In the end, fifteen eligible case-control studies were included. Results: Our comprehensive analysis revealed that polychlorinated biphenyls (PCBs) were negatively associated with thyroid cancer{ SMD = -0.03, 95% confidence interval (CI) = (-0.05, -0.00), P = 0.03}, while polybrominated diphenyl ethers (PBDEs), phthalates (PAEs), and heavy metals were positively associated with thyroid cancer{PBDEs: SMD = 0.14, 95%CI = (0.04, 0.23), P = 0.007; PAEs: SMD = 0.30, 95%CI = (0.02, 0.58), P = 0.04; heavy metals: SMD = 0.21, 95%CI = (0.11, 0.32), P < 0.001}. We did not find a statistically significant relationship between bisphenol A (BPA) and thyroid cancer. Most of the included studies did not show publication bias, except for those on PCBs. Discussion: Our results indicate that exposure to certain EEDs, such as PBDEs, PAEs, and heavy metals, increases the risk of thyroid cancer. However, further large-scale epidemiological studies and mechanism studies are needed to verify these potential relationships and understand the underlying biological mechanisms.

From old pollutants to the regulation of bisphenol A: Lessons learned for health promotion and disease prevention.

Citizens deserve regulatory changes and policies more sensitive to the current needs of humans, the climate, and nature. In this work we draw on prior experiences of preventable human suffering and economic losses caused by delayed regulation of legacy and emerging pollutants. Heightened awareness of environmental health problems is necessary among health professionals, the media, and citizens' organizations. Improved translation from research to the clinical world and to policy is critical to reduce the population burden of diseases caused by exposure to endocrine disruptors and other environmental chemicals. Numerous lessons can be learned from science-to-policy processes built for "old pollutants" (as persistent organic pollutants, heavy metals, tributyltin), as well as from current trends regarding the regulation of non-persistent chemicals, such as the prototypical endocrine disruptor bisphenol A. We end discussing relevant pieces of the puzzle to tackle the environmental and regulatory challenges faced by our societies.

Acculturation and endocrine disrupting chemical-associated personal care product use among US-based foreign-born Chinese women of reproductive age.

BACKGROUND: Personal care products (PCPs) are an important source of endocrine disrupting chemicals (EDCs) linked to adverse reproductive health outcomes. OBJECTIVE: We evaluated EDC-associated PCP use and acculturation among Asian women. METHODS: Our study included 227 foreign-born Chinese women ages 18-45 seeking obstetrics-gynecology care at community health centers (Boston, MA). Acculturation was measured by English-language use, length of US residence, and age at US entry. Self-reported use of PCPs (crème rinse/conditioner, shampoo, perfume/cologne, bar soap/body wash, liquid hand soap, moisturizer/lotion, colored cosmetics, sunscreen, and nail polish) in the last 48 h was collected. Latent class analysis was used to identify usage patterns. We also conducted multivariable logistic to determine the cross-sectional associations of acculturation measures and the use of individual PCP types. RESULTS: Those who used more PCP types, overall and by each type, tended to be more acculturated. Women who could speak English had 2.77 (95% CI: 1.10-7.76) times the odds of being high PCP users compared to their non-English speaking counterparts. English-language use was associated with higher odds of using perfume/cologne and nail polish. SIGNIFICANCE: Our findings give insight about EDC-associated PCP use based on acculturation status, which can contribute to changes in immigrant health and health disparities.

Endocrine-disrupting chemicals: economic, regulatory, and policy implications.

Endocrine-disrupting chemicals (EDCs) substantially cost society as a result of increases in disease and disability but-unlike other toxicant classes such as carcinogens-have yet to be codified into regulations as a hazard category. This Series paper examines economic, regulatory, and policy approaches to limit human EDC exposures and describes potential improvements. In the EU, general principles for EDCs call for minimisation of human exposure, identification as substances of very high concern, and ban on use in pesticides. In the USA, screening and testing programmes are focused on oestrogenic EDCs exclusively, and regulation is strictly risk-based. Minimisation of human exposure is unlikely without a clear overarching definition for EDCs and relevant pre-marketing test requirements. We call for a multifaceted international programme (eg, modelled on the International Agency for Research in Cancer) to address the effects of EDCs on human health-an approach that would proactively identify hazards for subsequent regulation.

Significance of and Challenges in Regulating Endocrine Disruptors - How Regulators and Industry Can Conquer?

Endocrine disruptors (EDs) disrupt the standard operation of the endocrine systems, resulting in untoward effects. EDs have gained extensive consideration due to their severe adverse impacts on public and wildlife health. A variety of compounds from both natural and synthetic origin may cause endocrine disruptions. These may be found in industrial chemicals, persistent organic pollutants, and products of regular use including pharmaceuticals, medical equipment, implants, medical/surgical and dental devices, cosmetics, food products, other consumer goods, their packaging and processing materials. Apart from direct consumption or use, these chemicals may impact by entering our food chain or ecosystem. These chemicals act by mimicking the hormones or blocking their receptors or interfering in their normal production, absorption, distribution, metabolism and excretion. The implementation of a regulatory framework on the complex multidisciplinary field of EDs brings enormous challenges, which pose barriers to the regulatory process. This study aims to focus on the key public and ecological health concerns presented by EDs, challenges faced by regulators to achieve successful regulatory proposition and the importance of collaboration endeavours to potentially conquer such challenges. Endocrine-disrupting chemicals (EDCs) or EDs can impact at low exposure levels, bringing about a broad range of health issues including disorders related to reproductive, fetal development, neurological, immunological, metabolic and cancer, etc. They may cause health effects across generations. The regulatory frameworks available across major regulators are tackling the identification of EDs and their mechanisms to provide necessary guidance on the safety and disposal of such substances. However, the challenges faced outweigh the regulatory mechanisms in place. The major challenges are related to structural ranges at times leading to no representative structures, active metabolites, substantiate quantum, delayed effects, epigenetic changes, widespread existence, concentration correlation for different biological species, availability of appropriate methods, exposure to a mixture of chemicals, complex endocrinology principles, unknown sources, routes and mechanisms, impacts at early stages of life, geographical movement of EDs, hazard-based vs. risk-based approaches. Regulators of healthcare and environmentalists needs to collaborate amongst them and with wider stakeholders including industry sponsors to find ways of dealing with such challenges and capitalize on the research-based knowledge grid available across institutions. Existence of EDs, their impact on living beings and mechanism of influence are like a tangled web, which induces difficulties in regulating them with conventional mindset. Conquering these challenges necessitates that regulators should join forces amongst themselves, with other institutions operating for environment, with industry sponsors and researchers to achieve success in public health safety.

The GOLIATH Project: Towards an Internationally Harmonised Approach for Testing Metabolism Disrupting Compounds.

The purpose of this project report is to introduce the European "GOLIATH" project, a new research project which addresses one of the most urgent regulatory needs in the testing of endocrine-disrupting chemicals (EDCs), namely the lack of methods for testing EDCs that disrupt metabolism and metabolic functions. These chemicals collectively referred to as "metabolism disrupting compounds" (MDCs) are natural and anthropogenic chemicals that can promote metabolic changes that can ultimately result in obesity, diabetes, and/or fatty liver in humans. This project report introduces the main approaches of the project and provides a focused review of the evidence of metabolic disruption for selected EDCs. GOLIATH will generate the world's first integrated approach to testing and assessment (IATA) specifically tailored to MDCs. GOLIATH will focus on the main cellular targets of metabolic disruption-hepatocytes, pancreatic endocrine cells, myocytes and adipocytes-and using an adverse outcome pathway (AOP) framework will provide key information on MDC-related mode of action by incorporating multi-omic analyses and translating results from in silico, in vitro, and in vivo models and assays to adverse metabolic health outcomes in humans at real-life exposures. Given the importance of international acceptance of the developed test methods for regulatory use, GOLIATH will link with ongoing initiatives of the Organisation for Economic Development (OECD) for test method (pre-)validation, IATA, and AOP development.

The Undervalued Effects of Polychlorinated Biphenyl Exposure on Breast Cancer.

The incidence of breast cancer across the world has been on the rise in recent decades. Because identified risk factors can only explain a relatively small portion of the cases, environmental exposure to organic pollutants is suspected to play a role in breast cancer etiology. Polychlorinated biphenyls (PCBs) are among the most abundant pollutants, and the impact of their exposure on breast cancer risk has been extensively studied in recent decades. However, the results of most epidemiologic studies do not support an association between PCB exposure and breast cancer risk. We hypothesized that the effects of PCBs on breast cancer might have been undervalued for reasons such as insufficient recognition of the confounding effects of several factors and lack of attention on the innate heterogeneity of PCB mixtures or breast cancer. After reviewing the evidence in the existing literature, we concluded that early life exposure, known risk factors of breast cancer, and impact of exposure to other pollutants are the main sources of confounding effects and have potentially masked the associations between PCBs and breast cancer. Because PCBs are mixtures of congeners with varied properties, and because breast cancers of different subtypes are etiologically distinct diseases, the absence of stratified subgroup analysis on individual PCBs and patients with specific biological subtypes and insufficient attention paid to the results of these subgroup analyses may result in an underestimation of the correlations between PCBs and breast cancer. In future studies, these factors must be taken into consideration when exploring the effect of PCB exposure on breast cancer risk.

Guidelines on the benefit-risk assessment of the presence of phthalates in certain medical devices covering phthalates which are carcinogenic, mutagenic, toxic to reproduction (CMR) or have endocrine-disrupting (ED) properties.

By the new Medical Device Regulation (MDR, EU 2017/745) the use of certain phthalates which are carcinogenic, mutagenic, toxic to reproduction (CMR) or have endocrine-disrupting (ED) properties, above 0.1% by weight (w/w) is only allowed after a proper justification. The SCHEER provide Guidelines on the benefit-risk assessment (BRA) of the presence of such phthalates in certain medical devices. The Guidelines describe the methodology on how to perform a BRA for the justification of the presence of CMR/ED phthalates in medical devices and/or or parts or materials used therein at percentages above 0.1% w/w. They also describe the evaluation of possible alternatives for these phthalates used in medical devices, including alternative materials, designs or medical treatments. Relevant stakeholders e.g. manufacturers, notified bodies and regulatory bodies, can use the guidelines. The approach of these guidelines may also be used for a BRA of other CMR/ED substances present in medical devices. SCHEER noticed that a number of BRA methodologies are theoretically available. However, there is a considerable lack of data needed for the BRA for potential relevant alternatives to be used in medical devices. Therefore, SCHEER encourages manufacturers to generate data of high quality on such alternatives for CMR/ED phthalates in medical devices.

Disease burden attributable to endocrine-disrupting chemicals exposure in China: A case study of phthalates.

While it has been acknowledged that exposure to endocrine-disrupting chemicals (EDCs) is associated with human diseases, the overall disease burden attributable to the exposure to a specific EDC has rarely been evaluated. Based on existing models for assessing probabilities of causation and a comprehensive review of available data, we analyzed the burden of three diseases, i.e., male infertility, adult obesity, and diabetes, among the general Chinese population resulting from exposure to phthalates. Our estimation indicates that exposure to phthalates is associated with ~2.50 million cases of the three diseases across China in 2010, causing ~57.2 billion Chinese Yuan (equivalent to ~9 billion US dollars) of health care costs in a year. Male infertility has the largest number of cases, followed by adult obesity and diabetes. Based on these phthalate-specific estimates, we further estimated that the total disease cost due to exposure to the overall EDCs amounted to ~429.43 billion Chinese Yuan in China in 2010, accounting for 1.07% of nationwide gross domestic product (GDP). When comparing our results with an earlier estimate for the European Union (EU) member countries, we find that exposure to phthalates leads to quite a similar disease burden per unit of GDP in both regions. Our study illustrates the considerable socio-economic impact of EDC exposure on human society, implying the imperative need for global risk reduction actions on EDCs, especially in view of the 2030 Sustainable Development Goals.

[Environmental Chemical Exposure and Its Effects on Infants' Reproductive Hormones].

In recent years, the birthrate has been continuously declining in Japan. The main causes of the decline are social factors. On the other hand, there is increasing evidence that many environmental chemicals show endocrine disrupting properties. Thus, we hypothesized that exposure to these chemicals would also be a causal for the fertility crisis. In this review, we examined current evidence that focused on environmental chemical exposure in utero and its association with reproductive hormones in children. We have included the findings from a prospective birth cohorts, the Hokkaido Study on Environment and Children's Health Sapporo cohort. According to the literature, environmental chemical levels in utero, such as polychlorinated biphenyl, dioxins, perfluorinated chemical substances, phthalates, and bisphenol A were somewhat associated with the levels of reproductive hormones, such as testosterone, estradiol, progesterone, inhibin B, and insulin-like factor-3 in cord blood, in early childhood and adolescence. The literature also suggests the association between exposure to these chemicals and brain-sexual differentiation or the anogenital distance, which suggests the disruption of androgen shower during the developmental stage in the fetal period. There are still knowledge gaps on whether these hormones at an early stage affect the pubertal development and reproductive functions in later life. In addition, alternative chemicals are produced after banning one type. The health effects of alternative chemicals should be evaluated. Effects of exposure to a mixture of the chemicals should also be examined in future studies. In conclusion, the prevention of environmental chemical hazards in relation to human reproductive function is important. It would be one of the countermeasures to the falling birthrate caused by fertility issues.

Assessment of endocrine disruption potential of essential oils of culinary herbs and spices involving glucocorticoid, androgen and vitamin D receptors.

Essential oils (EOs) of culinary herbs and spices are consumed on a daily basis. They are multicomponent mixtures of compounds with already demonstrated biological activities. Taking into account regular dietary intake and the chemical composition of EOs, they may be considered as candidates for endocrine-disrupting entities. Therefore, we examined the effects of 31 EOs of culinary herbs and spices on transcriptional activities of glucocorticoid receptor (GR), androgen receptor (AR) and vitamin D receptor (VDR). Using reporter gene assays in stably transfected cell lines, weak anti-androgen and anti-glucocorticoid activity was observed for EO of vanilla and nutmeg, respectively. Moderate augmentation of calcitriol-dependent VDR activity was caused by EOs of ginger, thyme, coriander and lemongrass. Mixed anti-glucocorticoid and VDR-stimulatory activities were displayed by EOs of turmeric, oregano, dill, caraway, verveine and spearmint. The remaining 19 EOs were inactive against all receptors under investigation. Analyses of GR, AR and VDR target genes by means of RT-PCR confirmed the VDR-stimulatory effects, but could not confirm the anti-glucocorticoid and anti-androgen effects of EOs. In conclusion, although we observed minor effects of several EOs on transcriptional activities of GR, AR and VDR, the toxicological significance of these effects is very low. Hence, 31 EOs of culinary herbs and spices may be considered safe, in terms of endocrine disruption involving receptors GR, AR and VDR.

Assessment and monitoring of water quality of the gulf of Morbihan, a littoral ecosystem under high anthropic pressure.

This field study is intended to propose a global methodology to assess and monitor the water quality of the gulf of Morbihan, a littoral ecosystem under increasing anthropic pressure. To this end, the Locmariaquer site, where Crassostrea gigas is extensively cultivated, was selected to perform a one-year follow-up of tissular glutathione S-transferase and acetylcholinesterase specific activities in this filter feeder organism. Calculation of an integrated index, corresponding to the ratio of the two enzymes activities, allowed to discriminate from the environmental noise, several clusters which could be representative environmental stress, potentially latent pollution. Moreover, the estrogenic activity was assessed in water samples collected at Locmariaquer and other strategic sites of the gulf. The results evidenced a low estrogenic-disrupting compound contamination of waters. Overall, this methodology produced an accurate outlook of a basal state for the gulf and could be developed in the context of a chronic monitoring of this site.

Environmental influences on reproductive health: the importance of chemical exposures.

Chemical exposures during pregnancy can have a profound and life-long impact on human health. Because of the omnipresence of chemicals in our daily life, there is continuous contact with chemicals in food, water, air, and consumer products. Consequently, human biomonitoring studies show that pregnant women around the globe are exposed to a variety of chemicals. In this review we provide a summary of current data on maternal and fetal exposure, as well as health consequences from these exposures. We review several chemical classes, including polychlorinated biphenyls, perfluoroalkyl substances, polybrominated diphenyl ethers, phenols, phthalates, pesticides, and metals. Additionally, we discuss environmental disparities and vulnerable populations, and future research directions. We conclude by providing some recommendations for prevention of chemical exposure and its adverse reproductive health consequences.

Female Reproductive Disorders, Diseases, and Costs of Exposure to Endocrine Disrupting Chemicals in the European Union.

CONTEXT: A growing body of evidence suggests that endocrine-disrupting chemicals (EDCs) contribute to female reproductive disorders. OBJECTIVE: To calculate the associated combined health care and economic costs attributable to specific EDC exposures within the European Union (EU). DESIGN: An expert panel evaluated evidence for probability of causation using the Intergovernmental Panel on Climate Change weight-of-evidence characterization. Exposure-response relationships and reference levels were evaluated, and biomarker data were organized from carefully identified studies from the peer-reviewed literature to represent European exposure and approximate burden of disease as it occurred in 2010. Cost-of-illness estimation used multiple peer-reviewed sources. SETTING, PATIENTS AND PARTICIPANTS AND INTERVENTION: Cost estimation was carried out from a societal perspective, ie, including direct costs (eg, treatment costs) and indirect costs such as productivity loss. RESULTS: The most robust EDC-related data for female reproductive disorders exist for 1) diphenyldichloroethene-attributable fibroids and 2) phthalate-attributable endometriosis in Europe. In both cases, the strength of epidemiological evidence was rated as low and the toxicological evidence as moderate, with an assigned probability of causation of 20%­39%. Across the EU, attributable cases were estimated to be 56 700 and 145 000 women, respectively, with total combined economic and health care costs potentially reaching €163 million and €1.25 billion. CONCLUSIONS: EDCs (diphenyldichloroethene and phthalates) may contribute substantially to the most common reproductive disorders in women, endometriosis and fibroids, costing nearly €1.5 billion annually. These estimates represent only EDCs for which there were sufficient epidemiologic studies and those with the highest probability of causation. These public health costs should be considered as the EU contemplates regulatory action on EDCs.