Tag: endocrine disruptors

Categories : Environmental Effects PaediatricsTags :

Girls may Start Puberty Early Due to Chemical Exposure

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Girls exposed to certain endocrine-disrupting chemicals (EDCs) may be more likely to start puberty early, according to new research published in Endocrinology, the flagship basic science journal of the Endocrine Society. EDCs mimic, block or interfere with hormones in the body’s endocrine system.

There has been an alarming trend toward early puberty in girls, suggesting the influence of chemicals in our environment. Early puberty is associated with an increased risk of psychosocial problems, obesity, diabetes, cardiovascular disease, and breast cancer.

“We conducted a comprehensive screen of 10 000 environmental compounds with extensive follow-up studies using human brain cells that control the reproductive axis, and our team identified several substances that may contribute to early puberty in girls,” said study author Natalie Shaw, MD, MMSc, of the National Institute of Environmental Health Sciences (NIEHS).

Those substances include musk ambrette, which is a fragrance used in some detergents, perfumes, and personal care products, and a group of medications called cholinergic agonists.

“More research is needed to confirm our findings,” noted Shaw. “But the ability of these compounds to stimulate key receptors in the hypothalamus – the gonadotropin-releasing hormone receptor [GnRHR] and the kisspeptin receptor [KISS1R] – raises the possibility that exposure may prematurely activate the reproductive axis in children.”

According to the research team, musk ambrette is potentially concerning because it can be found in personal care products, and some rat studies have suggested it can cross the blood-brain barrier. Children are less likely to encounter cholinergic agonists in their daily lives.

Canadian and European regulations restrict musk ambrette use because of its potential toxicity, and the U.S. Food and Drug Administration removed the fragrance from its “generally recognized as safe” list. Yet it is still available on the market in some personal care products.

“This study suggests that, out of an abundance of caution, it is important for parents to only use personal care products for their children that are federally regulated,” Shaw said.

As part of the study, the research team screened a Tox21 10 000-compound library of licensed pharmaceuticals, environmental chemicals and dietary supplements against a human cell line overexpressing GnRHR or KISS1R. They conducted follow-up analysis using human hypothalamic neurons and zebrafish, finding that musk ambrette increased the number of GnRH neurons and GnRH expression.

“Using human hypothalamic neurons and zebrafish provides an effective model for identifying environmental substances that stimulate the KISS1R and GnRHR,” said co-author Menghang Xia, PhD, from the National Center for Advancing Translational Sciences (NCATS) “This study was a multidisciplinary team effort, and it showed that we can efficiently reduce the time and cost of assessing environmental chemicals for their potential effects on human health.”

Source: Endocrine Society

Categories : Environmental EffectsTags :

UN Report Reveals Extent of Endocrine Disruptors in Many Products

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A report from the world’s leading scientific and medical experts on hormone-related health conditions raises new concerns about the profound threats to human health from endocrine disrupting chemicals (EDCs) that are ubiquitous in our surroundings and everyday lives.

The report, “Endocrine Disrupting Chemicals: Threats to Human Health” provides a comprehensive update on the state of the science around EDCs, with increasing evidence that this large group of toxic substances may be implicated in rising global health concerns.

The report from the Endocrine Society, co-produced with the International Pollutants Elimination Network (IPEN), includes detailed analyses on exposure to EDCs from four sources: plastics, pesticides, consumer products (including children’s products), and per-and polyfluoroalkyl substances (PFAS), a class of thousands of chemicals known or suspected to be EDCs.

The Endocrine Society-IPEN report is being released during the U.N. Environment Assembly (UNEA-6) meeting in Nairobi.

At UNEA key agenda items include welcoming the newly adopted Global Framework on Chemicals, advancing global action on highly hazardous pesticides, and threats to the circular economy from plastics and toxic chemicals.

The groups’ report anticipates an update from UNEP and the WHO expected later this year on their 2012 Report on State of the Science of Endocrine Disrupting Chemicals.

“A well-established body of scientific research indicates that endocrine-disrupting chemicals that are part of our daily lives are making us more susceptible to reproductive disorders, cancer, diabetes, obesity, heart disease, and other serious health conditions,” said the report’s lead author, Andrea C. Gore, PhD, of the University of Texas at Austin, and a member of the Endocrine Society’s Board of Directors.

“These chemicals pose particularly serious risks to pregnant women and children. Now is the time for the UN Environment Assembly and other global policymakers to take action to address this threat to public health.”

By interfering with hormones and their actions, EDC exposure can impact many health-related functions, with consequences for increased risks of many serious conditions.

Evidence suggests that EDCs in the environment contribute to disorders such as diabetes, neurological disorders, reproductive disorders, inflammation, and compromised immune functioning.

Two of the four analyses in the report look at EDCs used in plastics and as pesticides.

Global production of plastics and pesticides is increasing even as scientists warn that chemical and plastic pollution is an escalating crisis. Glyphosate is the world’s most widely used herbicide, and a recent study found that glyphosate has eight of ten key characteristics of an EDC. Other studies have found links between glyphosate and adverse reproductive health outcomes.

Plastics are made with thousands of known toxic substances, some of which are known or suspected EDCs. The report examines bisphenols and phthalates, two toxic chemical groups found in many plastics. Exposures to EDCs from plastics occur at all phases of plastics production, use, disposal, and even from recycled plastics.

The Endocrine Society-IPEN report notes that, while evidence of health threats from EDCs is mounting, current regulations have not kept pace.

“EDCs are different than other toxic chemicals, but most regulations fail to address these differences,” said IPEN Science Advisor Sara Brosché, PhD. “For example, we know that even very low doses of endocrine disrupting chemicals can cause health problems and there may be no safe dose for exposure to EDCs. However, regulations typically do not protect against low-dose effects. We need a global approach to controlling EDCs based on the latest science with a goal of protecting the human right to a healthy environment.”

At the UNEA-6 meeting, IPEN is also releasing a new report on “The Global Threat from Highly Hazardous Pesticides,” highlighting ongoing health and environmental risks from HHPs, especially in low- and middle-income countries.

DDT, glyphosate, and chorpyrifos, three HHPs reviewed in the Endocrine Society report, are also highlighted in the new IPEN report as they continue to pose health threats especially in the Global South.

In addition to plastics and pesticides, the report looks at EDC exposures from arsenic and lead, and from widely used per- and polyfluoroalkyl substances (PFAS), humanmade “forever chemicals” used as oil and water repellents and coatings. Lead remains in use in paint in many countries, as documented in recent IPEN reports. Endocrine-related conditions from lead exposure may include delayed onset of puberty and early menopause. Arsenic is a common metal that has long been linked to cancer and other health conditions, and more recent evidence shows that arsenic can disrupt multiple endocrine systems. PFAS are used in hundreds of products including clothing and food packaging, but recent studies show that some PFAS can disrupt hormones such as oestrogen and testosterone and impair thyroid hormone functions.

Source: The Endocrine Society

Categories : Environmental Effects Obstetrics & GynaecologyTags :

Cadmium Detected in Urine of Women with Endometriosis

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Women with a history of endometriosis had higher concentrations of cadmium in their urine compared to those without that diagnosis, according to a study with a large representative study that suggests the toxic metal, which is also an endocrine disruptor, could be linked to the development of endometriosis. The researchers, from Michigan State University, published these findings in the journal Human Reproduction.

Affecting one in 10 reproductive-age women, endometriosis is when tissue that looks like the lining of the uterus, appears outside of it. Those with endometriosis can experience chronic, painful and debilitating symptoms, which can interfere with all aspects of life, including daily activity, work productivity, school performance and personal relationships.

“Despite the adverse impact of endometriosis on quality of life, it remains an understudied condition,” said Kristen Upson, assistant professor in the Department of Epidemiology and Biostatistics at the MSU College of Human Medicine and senior author of the study.

“By looking at environmental risk factors such as metal cadmium, we are moving the needle closer to understanding risk factors for this condition,” added the study’s first author, Mandy Hall, a data analyst in the MSU Department of Epidemiology and Biostatistics.

Cadmium is a toxic metal and a “metalloestrogen,” meaning it can act like oestrogen. In the US, people are commonly exposed to cadmium by breathing in cigarette smoke and eating contaminated food like spinach and lettuce.

While this is not the first study exploring a potential link between cadmium and endometriosis, the researchers said it’s the largest study to look at cadmium measured in urine, which reflects long-term exposure between 10 and 30 years.

For their study, researchers used data from NHANES, a national US population study between 1999 and 2006. Out of the survey’s more than 41 000 participants, the researchers limited their study population to those 20 to 54 years of age with information on endometriosis diagnosis.

The researchers then analysed the data, dividing the cadmium levels into four classes, or quartiles, with the first quartile being the lowest exposure and the fourth being the largest exposure.

They found that participants in the second and third quartiles were twice as likely to have been diagnosed with endometriosis than those in the first quartile. The data also suggests a 60% increased prevalence of endometriosis based on urinary cadmium concentrations in the fourth quartile.

“The findings are interesting given that cadmium can act like the hormone estrogen, and this hormone is central to the development of endometriosis,” Hall said.

The researchers say further studies are needed to confirm their findings. Upson said this work is part of her larger research looking at everyday factors that may increase toxic metal exposure in women as well as the impact of toxic metals on gynaecologic health. Hall plans to incorporate environmental factors in their ongoing research on endometriosis and other gynaecologic conditions.

Source: Michigan State University

Categories : Environmental Effects NeurologyTags :

Endocrine-disrupting Chemicals may Raise Risk of Cognitive Disorders in Future Generations

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Adverse cognitive effects linked to polychlorinated biphenyls (PCBs) exposure, a type of endocrine-disrupting chemical (EDC), have the potential to be passed down through generations, according to an animal study being presented Thursday at ENDO 2023, the Endocrine Society’s annual meeting in Chicago, USA.

PCBs can mimic the effect of oestrogen on the body, contributing to a variety of neuroendocrine, metabolic and reproductive problems.

“Endocrine-disrupting chemicals present in our food, air, water and personal products may cause cognitive-behavioural disorders like attention-deficit/hyperactivity disorder or overeating in future generations,” said Emily N. Hilz, PhD, a postdoctoral fellow at the University of Texas at Austin.

To explore this further, Hilz and colleagues administered a common PCB mixture called Aroclor 1221 to pregnant female rats. The adults (n=40), their offspring (n=80), and their future grandchildren (n=80) were all tested on behavioural tasks to assess pleasure-seeking, ability to pay attention, and cognitive flexibility.

“The grandchildren of rats exposed to EDCs while pregnant performed significantly worse on these tasks, showing impaired cognitive function and increased pleasure-seeking,” Hilz said. “This suggests EDCs program potential cognitive disorders or behavioural problems that only emerge in later generations.”

Grandchildren of rats that were exposed to the PCB mixture were more interested in eating for pleasure, according to the results of the sucrose preference test. While all of the tested animals preferred the sucrose solution to water, the grandchildren of mothers exposed to the PCB mixture consumed more of the sucrose solution.

The same rats had an impaired ability to switch between tasks or learn new rules. However, only the male grandchildren were more likely to become fixated with a visual cue, which is common in disorders such as ADHD.

The PCB mixture impaired different aspects of cognitive behavior between male and female rats, depending on the life stage when they were exposed. It’s not yet clear which biological systems might be driving this.

“Our findings suggest regulating EDCs in industrial and consumer products could reduce the prevalence of certain cognitive or behavioural disorders in the future,” Hilz said.

Source: The Endocrine Society

Categories : Obstetrics & GynaecologyTags :

Endocrine-disrupting Chemicals Present in Many Pregnancies

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Researchers in Europe have shown that up to 54% of pregnant women in Sweden were exposed to complex mixtures of endocrine-disrupting chemicals disruptive to brain development.

While current risk assessment tackles chemicals and their allowable exposures on an individual basis, these findings show the need to take mixtures into account for future risk assessment approaches. The study was published in Science.

A growing body of evidence has shown that industrially produced chemicals have endocrine disrupting properties and can thus be dangerous to human and animal health and development. A huge number of new compounds is released every year into the environment during the production of plastic derivatives and other goods.

While exposures for individual chemicals falls below thresholds, exposure to the same chemicals in complex mixtures can still impact human health. However, all current exposure thresholds, are based on chemicals being examined individually. Therefore, an alternative strategy needed to be tested, in which the actual mixtures measured in real life exposures could be tested as such in both the epidemiological and experimental setting. The EDC-MixRisk project set out to tackle this unmet need.

“The uniqueness of this comprehensive project is that we have linked population data with experimental studies, and then used this information to develop new methods for risk assessment of chemical mixtures,” said Carl-Gustaf Bornehag, professor at Karlstad University, Project Manager of the SELMA study.

The study was conducted in three steps:

  1. A mixture of chemicals in the blood and urine of pregnant women was identified in the Swedish pregnancy cohort SELMA, associated with delayed language development in children at 30 months. This critical mixture included a number of phthalates, bisphenol A, and perfluorinated chemicals.
  2. Experimental studies uncovered the molecular targets through which human-relevant levels of this mixture disrupted the regulation of endocrine circuits and of genes involved in autism and intellectual disability.
  3. The findings from the experimental studies were used to develop new principles for risk assessment of this mixture.

“It is striking that the findings in the experimental systems well reflected what we found in the epidemiological part, and that the effects could be demonstrated at normal exposure levels for humans,” said Joëlle Rüegg, professor of environmental toxicology at Uppsala University.

“Human brain organoids (advanced in vitro cultures that reproduce salient aspects of human brain development) afforded, for the first time, the opportunity to directly probe the molecular effects of this mixture on human brain tissue at stages matching those measured during pregnancy. Alongside other experimental systems and computational methods, we found that the mixture disrupts the regulation of genes linked to autism (one of whose hallmarks is language impairment), hinders the differentiation of neurons and alters thyroid hormone function in neural tissue,” said Giuseppe Testa, principal investigator of the EDC-MixRisk responsible for the human experimental modelling.

“One of the key hormonal pathways affected was thyroid hormone. Optimal levels of maternal thyroid hormone are needed in early pregnancy for brain growth and development, so it’s not surprising that there is an association with language delay as a function of prenatal exposure,” said Barbara Demeneix, professor of physiology and endocrinology at the Natural History Museum in Paris.

By combining these techniques, the researchers were able to show that 54% of children included in the SELMA study were at risk of delayed language development (at age 30 months) as they were prenatally exposed to a mixture of chemicals at levels that were above the levels predicted to impact neurodevelopment. Yet this risk fell below the exposure limits for individual chemicals.

Source: EURION Cluster

Categories : Cancer Environmental EffectsTags :

Brominated Flame Retardants May Raise Breast Cancer Risk

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Brominated flame retardants (BFRs) are present in a wide variety of household fixtures and furniture, and particles of this may increase the risk of breast cancer through prolonged exposure at critical times in a woman’s life.

BFRs are endocrine disruptors, and since they are not tightly bound to the substances they are included into, they are able to escape into the household environment. Endocrine disruptors can be problematic to protect against since they can exert harmful effects even at low doses. Exposure to endocrine disruptors is most disruptive in the foetal stage and during infancy; these compounds also easily cross the placental boundary and are found in breast milk. At high exposures, cells have a toxic response, but at a low dose, similar to the levels of naturally occurring hormones, endocrine dysregulation is the outcome.

Exposure to these compounds can cause problems for organs such as mammary glands, which are sensitive to hormones, which BFRs can mimic. “BFRs pose a significant risk, particularly during sensitive periods, from intrauterine life to puberty and during pregnancy,” said Professor Plante, co-director of the Intersectoral Centre for Endocrine Disruptor Analysis and environmental toxicologist.

The researchers exposed female rodents to a mixture of BFRs, similar to that found in house dust, prior to mating, during gestation and during lactation. Biologists were able to observe the effects on the offspring at two stages of development and on the mothers.

Early development of mammary glands was seen in prepubertal rats. For pubescent rats, the results, published in 2019, showed a deregulation of intercellular communication. Similar effects were observed in female genitors in a 2017 study. All of these effects are associated with an increased risk of breast cancer.

In the early 2000s, observation showed that human exposure to BFRs peaked, Professor Isabelle Plante pointed out. “Young women exposed to BFRs in utero and through breastfeeding are now in the early stages of fertility. Their mothers are in their fifties, a period of increased risk for breast cancer,” said Prof Plante. This is why the team is currently studying endocrine disruptors related to a predisposition to breast cancer, funded by the Breast Cancer Foundation and the Cancer Research Society.

In all three studies, most of the effects were observed at a low dose, raising questions about the current legislation for endocrine disruptors. “To evaluate the ‘safe’ dose, experts give an increasing dose and then, when they observe an effect, identify it as the maximum dose. With endocrine disruptors, the long-term consequences would be caused by lower doses,” reported Prof Plante.

Source: Medical Xpress

Journal information: Rita-Josiane Gouesse et al, In Utero and Lactational Exposure to an Environmentally Relevant Mixture of Brominated Flame Retardants Induces a Premature Development of the Mammary Glands, Toxicological Sciences (2020). DOI: 10.1093/toxsci/kfaa176