Office parlementaire d’évaluation des choix scientifiques et technologiques, Rapport 2011
En 2011, à l’occasion d’une proposition de loi visant à interdire le Bisphénol A dans les plastiques alimentaires, l’Office parlementaire d’évaluation des choix scientifiques et technologiques a été saisi pour réaliser une étude portant sur la question des perturbateurs endocriniens et l’état des recherches.
Les substances anthropiques représentent des milliers de produits et comprennent des produits de l’industrie chimique (phtalates, bisphénol A, métaux lourds, etc.) et les produits phytosanitaires utilisés en agriculture (herbicides, fongicides, insecticides, etc.).
PRINCIPALES SOURCES DES PERTURBATEURS ENDOCRINIENS CONFIRMÉS OU POTENTIELS
DES (Distilbène), éthynil-oestradiol (contraceptif), kétokonazole (traitement du pityriasis, pommade)…
DES, trenbolones (augmentent la masse musculaire)…
UCSF Program on Reproductive Health and the Environment, 2017
The University of California San Francisco (UCSF) Program on Reproductive Health and the Environment (PRHE)’s mission is to create a healthier environment for human reproduction and development through advancing scientific inquiry, clinical care and health policies that prevent exposures to harmful chemicals in our environment.
PRHE is housed within the Department of Obstetrics, Gynecology and Reproductive Sciences, in the UCSF School of Medicine, one of the nation’s most prestigious medical schools. The Department is renowned for promoting cutting-edge reproductive science research, extending the frontiers of multidisciplinary women’s health care and professional education, advocating for women’s health at local, state and national levels, and engaging community involvement.
In a study of inner-city mothers and their children, we measured metabolites of several phthalates in maternal prenatal urine and child urine collected at age 3.
We also measured serum free thyroxine and thyroid stimulating hormone in the children at age 3.
We found inverse and sex specific associations between specific phthalate metabolites measured in children at age 3 and free thyroxine.
The associations were limited to girls.
Maternal prenatal urine concentrations of MEHP, a metabolite of DEHP, were associated with increases in free thyroxine in children at age 3.
No associations were found between phthalate metabolites and thyroid stimulating hormone.
Research relating either prenatal or concurrent measures of phthalate exposure to thyroid function in preschool children is inconclusive.
In a study of inner-city mothers and their children, metabolites of di-n-butyl phthalate, butylbenzyl phthalate, di-isobutyl phthalate, di(2-ethylhexyl) phthalate, and diethyl phthalate were measured in a spot urine sample collected from women in late pregnancy and from their children at age 3 years. We measured children’s serum free thyroxine (FT4) and thyroid stimulating hormone (TSH) at age 3. Linear regression models were used to investigate the associations between phthalate metabolites, measured in maternal urine during late pregnancy and measured in child urine at age 3 and thyroid function measured at age 3.
Mean concentrations (ranges) were 1.42 ng/dL (1.02–2.24) for FT4, and 2.62 uIU/mL (0.61–11.67) for TSH. In the children at age 3, among girls, FT4 decreased with increasing loge mono-n-butyl phthalate [estimated b = − 0.06; 95% CI: (− 0.09, − 0.02)], loge mono-isobutyl phthalate [b = − 0.05; 95% CI: (− 0.09, − 0.01)], loge monoethyl phthalate [b = − 0.04; 95% CI: (− 0.07, − 0.01)], and loge mono(2-ethyl-5-hydroxyhexyl) phthalate [b = − 0.04; 95% CI: (− 0.07, − 0.003)] and loge mono(2-ethyl-5-oxy-hexyl) phthalate [b = − 0.04; 95% CI: (− 0.07, − 0.004)]. In contrast, among boys, we observed no associations between FT4 and child phthalate metabolites at age 3. On the other hand, in late gestation, FT4 increased with increasing loge mono-(2-ethylhexyl) phthalate [estimated b = 0.04; 95% CI: (0.02, 0.06)] and no sex difference was observed. We found no associations between phthalate biomarkers measured in either the child or prenatal samples and TSH at age 3.
The data show inverse and sex specific associations between specific phthalate metabolites measured in children at age 3 and thyroid function in preschool children. These results may provide evidence for the hypothesis that reductions in thyroid hormones mediate associations between early life phthalate exposure and child cognitive outcomes.
Science has shown that many thousands of people have been exposed to now mostly banned chemicals such as lead and PCBs at high enough levels to have had their brain development negatively affected. This report finds that there are other chemicals which are still in routine use in our homes where there is evidence of similar developmental neurotoxic (DNT) properties, and also identifies huge gaps in our knowledge of the impacts of other chemicals on brain development. It also points out the unpleasant reality that we are constantly exposed to a cocktail of chemicals, something which is still largely ignored by chemical safety laws.
In spite of the lessons of the past, regulators are continuing to only regulate after harm is caused, instead of acting to effectively protect the most precious of things; children’s developing brains.
In June 2007 CHEM Trust wrote the briefing Chemicals Compromising Our Children, which highlighted growing concerns about the impacts of chemicals on brain development in children. Almost 10 years later, CHEM Trust has revisited the issue with this report, which includes contributions from two of the most eminent scientists in this area, Professor Barbara Demeneix (Laboratory of Evolution of Endocrine Regulations, CNRS, Paris) and Professor Philippe Grandjean (Department of Environmental Medicine, University of Southern Denmark, Denmark & Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, USA), who also peer reviewed the report.
Our brain and its development
Our brains are astoundingly complex, made up of over 85 billion neurons, which have grown, developed and interconnected during our lives. The brain is the organ that takes the longest to develop, with initial stages of cell division, creation of neurons and their migration taking place from the first hours after fertilisation and throughout the foetus’ time in the womb. However, brain development does not stop at birth – it’s not until our twenties that neurons are fully developed with their myelin coats.
Throughout this complex developmental process a range of signalling chemicals and other processes operate in order to control what happens. The thyroid hormone system is intimately involved in brain development and function, yet it is well established that this system can be disrupted – for example by a lack of iodine (essential to make thyroid hormone) or by certain chemicals. If developmental processes are disrupted, this most often creates permanent problems.
The complexity of brain development and function means that deficits can be very subtle – small reductions in IQ, disabilities that exist with a broad spectrum of seriousness such as autism, or in some cases conditions which do not have fully agreed diagnostic criteria.
Disruption of brain development by chemicals
We are all exposed to hundreds of man-made chemicals in our daily life, coming from everyday products including food, furniture, packaging and clothes. Many of these chemicals will have no negative effects on us, but it is now well established that some are able to disrupt normal development of the brain. Chemicals with long established DNT properties such as lead, PCBs and methylmercury, have been joined by others where DNT effects have been identified more recently, and which are being used in everyday products. There are also rising concerns about chemicals that are very similar to chemicals that have had their use restricted, but which we continue to use as there isn’t sufficient information about their toxic effects. We know even less about thousands of other chemicals in routine use, which have had no testing for DNT properties.
Chemical exposures are so ubiquitous that experts have recognized that babies are born “pre-polluted”. Scientific paediatric and gynaecology & obstetrics societies have consistently warned about chronic health implications from both acute and chronic exposure to chemicals such as pesticides and endocrine disruptors.
The report identifies evidence of DNT properties for the following chemicals:
Bisphenol A (BPA)
a chemical that was used to make baby bottles, is currently being phased out of till receipts (in the EU), but is still used in the making of food can linings and many polycarbonate plastics. There are also concerns about closely related chemicals that are not restricted, including Bisphenol S.
Brominated Flame Retardants (BFRs)
a group of chemicals added to furniture, electronics and building materials. The evidence for neurodevelopmental effects is strongest for the PBDE (polybrominated diphenyl ether) group of BFRs, which are already banned or nearly banned in the EU, though they are still in furniture in our homes, and in dust. However, other BFRs are now being found in dust and human blood serum, with concerns that these BFRs might have similar effects.
a group of chemicals used as plasticisers in PVC and in other products. Some chemicals in this group are now banned in the EU, but many others are still in use.
Per- and poly-fluorocarbons (PFCs)
used as non-stick coatings or breathable coatings, are a large group of chemicals, a few of which are in the process of being restricted by the EU. There is evidence that some PFCs can disrupt the action of the thyroid hormone. PFCs are very persistent in the environment, and many of them can accumulate in our bodies – they are routinely found in blood.
a contaminant of food, related to the use of certain fertilisers and hypochlorite bleach, and is known to disrupt the thyroid hormone system.
Are we protected?
The EU has the most sophisticated regulations in the world for controlling chemical use. However, there are a number of key flaws in this system:
There is often inadequate safety information about individual chemicals, including a lack of information about neurodevelopmental effects.
The processes to ban chemicals are too slow, and the restrictions created often have big loopholes as a result of industry lobbying.
Chemicals are addressed one at a time, so one chemical may have its use restricted, but closely related chemicals remain in use.
We are always exposed to multiple chemicals, but regulations almost always assume we are only exposed to one at a time, even though numerous scientists have shown that chemical effects can add together in our bodies.
It is clear that our children are not currently being protected from chemicals that can disrupt brain development. We have identified a range of policy measures that could improve the situation, including:
Acting faster to ban chemicals of concern, including addressing groups of similar substances, not just those where we have the most information.
Ensuring that any safety testing of chemicals includes evaluation of DNT effects.
Ensuring better identification and regulation of neurodevelopmental toxic chemicals.
Ensuring that all uses of chemicals are properly regulated; for example there is a lack of effective regulation of chemicals in food packaging including paper, card, inks, glues and coatings.
The UK and Ireland should remove the requirement for an open flame test for furniture. This test is not required in the rest of the EU, and leads to increased use of flame retardant chemicals.
Finally, it is important to note that EU regulations have already controlled a number of chemicals of concern, and that EU laws provide a tool to address these problems. We therefore think it is vital for the UK Government to work to stay aligned with EU chemicals laws, whatever the eventual outcome of the UK’s Brexit process.
Though full protection will only come from proper regulation of chemicals, the report also includes a chapter with tips for reducing your and your family’s exposures in daily life.
Sources and More Information
Download the full report “No Brainer The impact of chemicals on children’s brain development: a cause for concern and a need for action”, chemtrust, 2017.
IT’S A NO BRAINER! Action needed to stop children being exposed to chemicals that harm their brain development!, chemtrust, MARCH 7, 2017.
Human amniotic fluid contaminants alter thyroid hormone signalling and early brain development in Xenopus embryos
In a recent experiment conducted on tadpoles, researchers tested the hypothesis that common chemicals in the environment, singly and as a mixture, can interfere with human brain development.
2017 Study Abstract
Thyroid hormones are essential for normal brain development in vertebrates. In humans, abnormal maternal thyroid hormone levels during early pregnancy are associated with decreased offspring IQ and modified brain structure.
As numerous environmental chemicals disrupt thyroid hormone signalling, we questioned whether exposure to ubiquitous chemicals affects thyroid hormone responses during early neurogenesis.
We established a mixture of 15 common chemicals at concentrations reported in human amniotic fluid. An in vivo larval reporter (GFP) assay served to determine integrated thyroid hormone transcriptional responses.
Dose-dependent effects of short-term (72 h) exposure to single chemicals and the mixture were found. qPCR on dissected brains showed significant changes in thyroid hormone-related genes including receptors, deiodinases and neural differentiation markers.
Further, exposure to mixture also modified neural proliferation as well as neuron and oligodendrocyte size.
Finally, exposed tadpoles showed behavioural responses with dose-dependent reductions in mobility.
In conclusion, exposure to a mixture of ubiquitous chemicals at concentrations found in human amniotic fluid affect thyroid hormone-dependent transcription, gene expression, brain development and behaviour in early embryogenesis. As thyroid hormone signalling is strongly conserved across vertebrates the results suggest that ubiquitous chemical mixtures could be exerting adverse effects on foetal human brain development.
Sources and Press Releases
Human amniotic fluid contaminants alter thyroid hormone signalling and early brain development in Xenopus embryos, Nature, doi:10.1038/srep43786, 07 March 2017.
Everyday chemicals may affect brain development, including foetal IQ, the conversation, May 11, 2017.
Phthalates increase the risk of allergies among children
Phthalates, which are used as plasticizers in plastics, can considerably increase the risk of allergies among children. According to a new study, an increased risk of children developing allergic asthma exists if the mother has been particularly heavily exposed to phthalates during pregnancy and breastfeeding.
2017 Study Abstract
Prenatal and early postnatal exposures to environmental factors are considered responsible for the increasing prevalence of allergic diseases. Although there is some evidence for allergy-promoting effects in children due to exposure to plasticizers like phthalates, findings of previous studies are inconsistent and lack mechanistic information.
We investigated the effect of maternal phthalate exposure on asthma development in the subsequent generations and their underlying mechanisms including epigenetic alterations.
Phthalate metabolites were measured within the prospective mother-child cohort LINA and correlated with asthma development in the children. A murine trans-generational asthma model was used to identify involved pathways.
In LINA maternal urinary concentrations of mono-n-butyl phthalate, a metabolite of butyl benzyl phthalate (BBP), were associated with an increased asthma risk in the children. Using a murine trans-generational asthma model, we demonstrate a direct effect of BBP on asthma severity in the offspring with a persistently increased airway inflammation up to the F2 generation. This disease-promoting effect was mediated by a BBP-induced global DNA hypermethylation in CD4 T cells of the offspring as treatment with a DNA demethylating agent alleviated exacerbation of allergic airway inflammation. 13 transcriptionally down-regulated genes linked to promoter or enhancer hypermethylation were identified. Among these, the GATA-3 repressor Zfpm1 emerged as a potential mediator of the enhanced susceptibility for Th2-driven allergic asthma.
These data provide strong evidence that maternal BBP exposure increases the risk for allergic airway inflammation in the offspring by modulating the expression of genes involved in Th2 differentiation via epigenetic alterations.
Sources and Press Releases
Maternal Phthalate Exposure Promotes Allergic Airway Inflammation over Two Generations Via Epigenetic Modifications, jacionline, DOI: 10.1016/j.jaci.2017.03.017, 1 March 2017.
Phthalates increase the risk of allergies among children, medicalxpress, May 3, 2017.
Image credit: UFZ/André Künzelmann – In the course of the LINA mother-child cohort study, UFZ scientists investigated the lifestyle and environmental factors of pregnant women and their influence on the allergy risk of infants.
Millions of persons are exposed to substances toxic for reproduction in many work-related activities
Putting more than 10 years of paralysis behind it, the European Commission finally launched a revision of the directive on the prevention of occupational cancers in May 2016. Lawmakers can now address reprotoxic substances in the workplace, writes Laurent Vogel, a researcher at the European Trade Union Institute (ETUI).
“The rules are insufficient as far as workplace protection is concerned. Whereas carcinogenic and mutagenic substances are the subject of more stringent prevention requirements by employers, reprotoxic substances have the “advantage” of a more lenient framework. A lot is at stake: out of 235 substances identified as proven or suspected reprotoxic substances, over 160 evade the most stringent regulation because they are not also classified as carcinogenic or mutagenic. If we confine ourselves to production volumes, the inadequately controlled risks are considerable. They concern lead, bisphenol A (a massively produced endocrine disruptor) and several phthalates.
A directive concerning the protection of pregnant or breastfeeding workers does certainly exist. But reprotoxic disorders concern men as much as women. Limiting specific measures to pregnant women may lead to various forms of discrimination. Furthermore, reprotoxic substances usually act on sex cells (eggs and spermatozoids) or on the first stages of embryo development. Rules concerning pregnant or breastfeeding workers obviously do not make it possible to prevent harmful effects on fertility. European legislation triggers a specific preventive action only from the time when a woman worker has informed her employer that she is pregnant. Such information is seldom communicated before the tenth week of pregnancy. Now, the risks for foetal development arising from chemical substances are at their highest during the first three months. Legislative provisions are therefore fairly ineffective and are likely to have stigmatising effects on pregnant women.”
Read Workplace cancer prevention must be extended to reprotoxic substances, euractiv, Mar 30, 2017.
100% of the personalities have traces of Bisphenols, PCBs, pesticides and phthalates
Générations Futures EXPPERT survey number 9 provides the results of tests for the presence of suspected or known endocrine disruptors in hair samples of some leading environmentalists in France. The worrying and conclusive results are the basis for a further call to the European Commission to improve its proposal on criteria for identifying endocrine disrupting chemicals ahead of a possible vote by EU Member States on 28 February 2017.
Paris, Brussels, 24 February 2017 – Seven environmentalists in France have their hair analysed for traces of endocrine disrupting chemicals. Generations Futures, with the support of HEAL and other members of the EDC-Free Europe coalition, published a new report yesterday, the 9th survey of the EXPPERT series on population exposure to chemicals that are suspected or known to disrupt the endocrine system. The results are unchallengeable!
In this new survey, Générations Futures asked personalities from the environmental movement to entrust to us a lock of their hair, which we had analysed by a competent laboratory. The participants were Yann Arthus-Bertrand, Isabelle Autissier, Delphine Batho, José Bové, Nicolas Hulot, Yannick Jadot and Marie-Monique Robin.
Approximately 200 pesticides (products used in agriculture and in the home to get rid of “harmful” or “undesirable” flora and fauna) and pesticide metabolites (resulting from metabolism), three bisphenols (plasticiser used in the composition of the polycarbonate – hard plastic), 13 phthalates and metabolites of phthalates (plasticisers used to soften plastics) and 32 PCB congeners (PCBs have been banned since 1987 but were used massively in electric transformers and as heat transfer fluid.).
Results? 100% of the personalities has traces of each of the families of compounds analysed in their bodies!
– We discover between 36 (D. Batho) and 68 (I. Autissier) endocrine disrupters per personality. The quantities varied from 9 031 μg/mg of endocrine disrupting chemical (D. Batho) to 158 643 μg/mg (I. Autism) – a discrepancy factor of 17.5 times between the least contaminated person (D. Batho) and the most contaminated person (I. Autissier). This clearly shows that individual’s exposure is not uniform but rather varies considerably according to the environment in which they circulate and/or in which they have developed and lived.
All the personalities tested had at least one of the three bisphenols in their hair. Three out of the seven people tested had the renowned Bisphenol A in their hair: M-M. Robin, Y. Arthus-Bertrand and I. Autissier. All 7 had Bisphenol S but none had signs of Bisphenol F.
11 of the 13 phthalates or metabolites of phthalates tested for were found at least in one person. Neither MMP or DPP were found in any sample. The number of phthalates and metabolites of phthalates found ranged from eight to 11 depending on the individual. Between six and 10 of these molecules could be quantified in each person.
All samples that could be analysed contained PCBs: between 14 and 30 PCBs were found in participants’ samples.
32 molecules suspected of being endocrine disruptors or endocrine disrupting metabolites were found in at least one person. Between nine and 25 of these pesticides were found in each hair sample tested.
“The hair of the personalities tested all contain an important cocktail of many endocrine disruptors (between 36 and 68 per person) although tests were only carried out on four families of chemicals. And these cocktails pose a problem – what is the health impact of this mixture?”
“This report points out more than ever the need to remove endocrine disrupting substances from our environment. Only a truly protective definition within the European framework will ensure that endocrine disruptors are excluded from the market and protect populations from these hazardous compounds. That is why the vote on the Standing Committee on Plants, Animals, Food and Feed (SCOPAFF) on 28 February is so important! We urge all national governments to reject the European Commission’s proposal on the criteria for endocrine disrupting chemicals in its current form and insist on major changes to ensure that proven, probable or suspected endocrine disruptors to which we are exposed are identified as such. Only in this way will these chemicals be prohibited from use as required in the European legislation voted in 2009, to protect our health.”