Will experts prove a cover-up of the toxicity and dangers of the herbicide glyphosate ?

Of mice, Monsanto and a mysterious tumor

By Carey Gillam, for Environmental Health News, June 8, 2017.
Glyphosate spraying image via Chafer Machinery.

Call it the case of the mysterious mouse tumor.

It’s been 34 years since Monsanto Co. presented U.S. regulators with a seemingly routine study analyzing the effects the company’s best-selling herbicide might have on rodents. Now, that study is once again under the microscope, emerging as a potentially pivotal piece of evidence in litigation brought by hundreds of people who claim Monsanto’s weed killer gave them cancer.

This week tissue slides from long-dead mice in that long-ago research study are being scrutinized by fresh eyes as an expert pathologist employed by lawyers for cancer victims looks for evidence the lawyers hope will help prove a cover-up of the dangers of the weed killer called glyphosate.

Glyphosate, which is the active ingredient in Monsanto’s branded Roundup products, is the most widely used herbicide in the world, and is applied broadly in the production of more than 100 food crops, including wheat, corn and soy, as well as on residential lawns, golf courses and school yards.

Residues have been detected in food and human urine, and many scientists around the world have warned that exposure through diet as well as through application can potentially lead to health problems. The World Health Organization’s International Agency for Research on Cancer (IARC) declared glyphosate a probable human carcinogen in 2015 based on a review of scientific literature, triggering the wave of lawsuits against Monsanto, and pushing California regulators to announce they would add glyphosate to a list of known carcinogens.

What the expert finds, or doesn’t find, is expected to be key evidence in hearings slated for the week of Dec. 11 in dozens of consolidated cases being overseen by a federal judge in San Francisco.

Rewind to 1983

Monsanto, as well as many other scientists and regulatory bodies, have defended glyphosate’s safety. They say research showing a cancer connection is flawed and hundreds of studies support its safety.

And yet—rewind to July 1983 and a study titled “A Chronic Feeding Study of Glyphosate (Roundup Technical) in Mice.” Following the document trail that surrounds the study offers an illuminating look into how science is not always clear-cut, and the lengths Monsanto has had to go to in order to convince regulators to accept scientific interpretations that support the company’s products.

The two-year study ran from 1980-1982 and involved 400 mice divided into groups of 50 males and 50 females that were administered three different doses of the weed killer or received no glyphosate at all for observation as a control group. The study was conducted for Monsanto to submit to regulators. But unfortunately for Monsanto, some mice exposed to glyphosate developed tumors at statistically significant rates, with no tumors at all in non-dosed mice.

February 1984 memo from Environmental Protection Agency toxicologist William Dykstra stated the findings definitively: “Review of the mouse oncogenicity study indicates that glyphosate is oncogenic, producing renal tubule adenomas, a rare tumor, in a dose-related manner.” Researchers found these increased incidences of the kidney tumors in mice exposed to glyphosate worrisome because while adenomas are generally benign, they have the potential to become malignant, and even in noncancerous stages they have the potential to be harmful to other organs. Monsanto discounted the findings, arguing that the tumors were “unrelated to treatment” and showing false positives, and the company provided additional data to try to convince the EPA to discount the tumors.

“Glyphosate is suspect. Monsanto’s argument is unacceptable.”

Herbert Lacayo, EPA, wrote in response to Monsanto’s 1985 defense of the weedkiller

But EPA toxicology experts were unconvinced. EPA statistician and toxicology branch member Herbert Lacayo authored a February 1985 memo outlining disagreement with Monsanto’s position. A “prudent person would reject the Monsanto assumption that Glyphosate dosing has no effect on kidney tumor production,” Lacayo wrote. ”Glyphosate is suspect. Monsanto’s argument is unacceptable.”

Eight members of the EPA’s toxicology branch, including Lacayo and Dykstra, were worried enough by the kidney tumors in mice that they signed a consensus review of glyphosate in March 1985 stating they were classifying glyphosate as a Category C oncogen, a substance “possibly carcinogenic to humans.

Research rebuttal

That finding did not sit well with Monsanto, and the company worked to reverse the kidney tumor concerns. On April 3, 1985, George Levinskas, Monsanto’s manager for environmental assessment and toxicology, noted in an internal memorandum to another company scientist that the company had arranged for Dr. Marvin Kuschner, a noted pathologist and founding dean of the medical school at the State University of New York at Stony Brook, to review the kidney tissue slides.

Kushner had not yet even accessed the slides but Levinskas implied in his memo that a favorable outcome was assured:

“Kuschner will review kidney sections and present his evaluation of them to EPA in an effort to persuade the agency that the observed tumors are not related to glyphosate,”

Levinskas wrote. Notably, Levinskas, who died in 2005, was also involved in efforts in the 1970s to downplay damaging findings from a study that found rats exposed to Monsanto’s PCBs developed tumors, documents filed in PCB litigation revealed.

Kuschner’s subsequent re-examination did —as Monsanto stated it would—determine the tumors were not due to glyphosate. Looking over slides of the mouse tissue from the 1983 study, Kuschner identified a small kidney tumor in the control group of the mice – those that had not received glyphosate. No one had noted such a tumor in the original report. The finding was highly significant because it provided a scientific basis for a conclusion that the tumors seen in the mice exposed to glyphosate were not noteworthy after all.

Additionally, Monsanto provided the EPA with an October 1985 report from a “pathology working group” that also rebutted the finding of the connection between glyphosate and the kidney tumors seen in the 1983 study. The pathology working group said “spontaneous chronic renal disease” was “commonly seen in aged mice.” Monsanto provided the report to the EPA stamped as a “trade secret” to be kept from the prying eyes of the public.

The EPA’s own scientists still did not agree, however. An EPA pathologist wrote in a December 1985 memo that additional examination of the tissue slides did not “definitively” reveal a tumor in the control group. Still, the reports by the outside pathologists brought into the debate by Monsanto helped push the EPA to launch a reexamination of the research.

And by February 1986 an EPA scientific advisory panel had dubbed the tumor findings equivocal; saying that given the tumor identified in the control group by some pathologists, the overall incidences of tumors in the animals given glyphosate were not statistically significant enough to warrant the cancer linkage.

The panel did say there may be reason for concern and noted that the tumor incidences seen in the mice given glyphosate were “unusual.”

The advisory panel told the EPA the studies should be repeated in hopes of more definitive findings, and that glyphosate be classified into what the agency at that time called Group D—“not classifiable as to human carcinogenicity.” The EPA asked Monsanto for a repeat of the mouse oncogenicity study but Monsanto refused to do so.

The company argued “there is no relevant scientific or regulatory justification for repeating the glyphosate mouse oncogenicity study.” Instead, the company provided EPA officials with historical control data that it argued supported its attempt to further downplay the tumor incidences seen in the worrisome 1983 study.

“There is no relevant scientific or regulatory justification for repeating the glyphosate mouse oncogenicity study.”

– Monsanto, in response to EPA requests to replicate the mouse study

The company said the tumors in mice appear “with some regularity” and were probably attributable to “genetic or environmental” factors. “It is the judgement of Monsanto scientists that the weight-of-evidence strongly supports a conclusion that glyphosate is not oncogenic in the mouse.” Monsanto said repeating the mouse study would “require the expenditure of significant resources… and tie-up valuable laboratory space.”

Feds fold

The discussions between Monsanto and the EPA dragged on until the two sides met in November 1988 to discuss the agency’s request for a second mouse study and Monsanto’s reluctance to do so. Members of the EPA’s toxicology branch continued to express doubts about the validity of Monsanto’s data, but by June of 1989, EPA officials conceded, stating that they would drop the requirement for a repeated mouse study.

By the time an EPA review committee met on June 26, 1991, to again discuss and evaluate glyphosate research, the mouse study was so discounted that the group decided that there was a lack of convincing carcinogenicity evidence in relevant animal studies. The group concluded that the herbicide should be classified far more lightly than the initial 1985 classification or even the 1986 classification proposed by the advisory panel. This time, the EPA scientists dubbed the herbicide a Group E chemical, a classification that meant “evidence of non-carcinogenicity for humans.” At least two members of the EPA committee refused to sign the report, stating that they did not concur with the findings. In a memo explaining the decision, agency officials offered a caveat. They wrote that the classification “should not be interpreted as a definitive conclusion that the agent will not be a carcinogen under any circumstances.”

Despite the EPA’s ultimate conclusion, the mouse study was among those cited by IARC for classifying glyphosate as a probable human carcinogen. Indeed, many other animal studies have similarly had questionable results, including a 1981 rat study that showed an increase in incidences of tumors in the testes of male rats and possible thyroid carcinomas in female rats exposed to glyphosate and a 1990 study that showed pancreatic tumors in exposed rats. But none have swayed the EPA from its backing of glyphosate safety.

Christopher Portier, who was an invited specialist to the IARC review of glyphosate and is former director of the National Center for Environmental Health and Agency for Toxic Substances and Disease Registry at the U.S. Centers for Disease Control and Prevention, believes the evaluations applied to glyphosate data by regulators are scientifically flawedand putting public health at risk.

“The data in these studies strongly supports the ability of glyphosate to cause cancer in humans and animals; there is no reason to believe that all of these positive studies arose simply by chance,”

Portier said.

Monsanto fought the plaintiffs’ request to view the mouse tissue slides, calling it a “fishing expedition,” but was overruled by U.S. District Judge Vince Chhabria who is overseeing the roughly 60 combined lawsuits under his purvey. Monsanto has confirmed that roughly 900 additional plaintiffs have cases pending in other jurisdictions. All make similar claims – that Monsanto manipulated the science, regulators and the public in ways that hid or minimized the danger posed by its herbicide.

“The importance of the original kidney slides and the re-cut kidney slides is immense to the question of general causation and played a critical role in the EPA’s decision to re-categorize glyphosate…”

the plaintiffs’ attorneys stated in a court filing.

Plaintiffs’ attorney Aimee Wagstaff reiterated that in a recent court hearing, telling Judge Chhabria that the events surrounding the 1983 mouse study “sort of dominoed,” and potentially are “extremely relevant” to the cancer litigation.

Carey Gillam,
Research Director at U.S. Right to Know and veteran journalist who specializes in coverage of food, agriculture and environmental issues.

Are junior doctors reluctant to speak up about unprofessional behaviour ?

Speaking up about traditional and professionalism-related patient safety threats: a national survey of interns and residents

New doctors are less likely to speak up about a colleague’s unprofessional behaviour than they are about traditional threats to patients’ safety, even when they perceive high potential for harm to patients, a US study has found.

The study found that junior doctors reported “fear of conflict” as a barrier to speaking up about unprofessional behaviour. The authors said that their findings, published in BMJ Quality and Safety, showed “important safety deficits” and the need to provide more supportive clinical environments to foster open communication.

…continue reading Junior doctors hesitate to speak up over unprofessional behaviour, study finds, on The BMJ Careers, 05 Jun 2017.

2017 Study Abstract

Open communication between healthcare professionals about care concerns, also known as ‘speaking up’, is essential to patient safety.

Compare interns’ and residents’ experiences, attitudes and factors associated with speaking up about traditional versus professionalism-related safety threats.

Anonymous, cross-sectional survey.

Six US academic medical centres, 2013–2014.

1800 medical and surgical interns and residents (47% responded).

Attitudes about, barriers and facilitators for, and self-reported experience with speaking up. Likelihood of speaking up and the potential for patient harm in two vignettes. Safety Attitude Questionnaire (SAQ) teamwork and safety scales; and Speaking Up Climate for Patient Safety (SUC-Safe) and Speaking Up Climate for Professionalism (SUC-Prof) scales.

Respondents more commonly observed unprofessional behaviour (75%, 628/837) than traditional safety threats (49%, 410/837); p<0.001, but reported speaking up about unprofessional behaviour less commonly (46%, 287/628 vs 71%, 291/410; p<0.001). Respondents more commonly reported fear of conflict as a barrier to speaking up about unprofessional behaviour compared with traditional safety threats (58%, 482/837 vs 42%, 348/837; p<0.001). Respondents were also less likely to speak up to an attending physician in the professionalism vignette than the traditional safety vignette, even when they perceived high potential patient harm (20%, 49/251 vs 71%, 179/251; p<0.001). Positive perceptions of SAQ teamwork climate and SUC-Safe were independently associated with speaking up in the traditional safety vignette (OR 1.90, 99% CI 1.36 to 2.66 and 1.46, 1.02 to 2.09, respectively), while only a positive perception of SUC-Prof was associated with speaking up in the professionalism vignette (1.76, 1.23 to 2.50).

Interns and residents commonly observed unprofessional behaviour yet were less likely to speak up about it compared with traditional safety threats even when they perceived high potential patient harm. Measuring SUC-Safe, and particularly SUC-Prof, may fill an existing gap in safety culture assessment.

Sources and Press Releases

Phthalates and Thyroid Function in Preschool Age Children: Sex Specific Associations

Household Chemicals May Impair Thyroid in Young Girls

Early childhood exposures to specific phthalates are associated with depressed thyroid function in girls at age 3, according to a May 2017 study conducted by scientists at Columbia University’s Mailman School of Public Health. Image credit columbia.edu.


  • 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.

More evidence about Duogynon dramatic side effects

A Scottish biologist examines the damaging effects of the Duogynon pregnancy drug

They were born with an open back, with heart defects and brain damage, shortened or missing limbs, deformed intestines, bladders or genitals. The cause for the malformations, among which hundreds of Germans and Britons born between the beginning of the 1950s and the middle of the 1970s, still today as adults, is given to a former drug of the Berlin pharmacy company Schering.

Mothers had received a drug from their doctors at the beginning of their pregnancy to determine if they really expected a child : named Duogynon in Germany, Primodos in the UK. Their content, a combination based on the female sex hormones gestagen and estrogen, was the same ; it could be swallowed or injected and was able to cause a menstrual bleeding.

If menstruation did not take place despite the hormone shock, the woman was considered pregnant. Urine test strips had not yet prevailed.

For the first time, the serious suspicions that are on the preparations of the past could be systematically examined by independent experts and at the present state of science. Neil Vargesson, professor of biology at the Scottish University of Aberdeen, researched on embryonic malformations for many years. He has worked with a team of his faculty to reproduce the Duogynon, Primodos, active ingredient and has already been tested in the laboratory for zebrafish embryos for its fruit-damaging effects.

“We were able to demonstrate that Primodos actually damages fish embryos, depending on both the stage of embryonic development and its dosage.”

Vargesson told the taz.

The Missing Proof

So far there have been indications, but no evidence for a causal link between the intake of Duogynon and the malformations. On the one reason being that clinical studies from the 1950s – when Schering brought the drug on the market – were not carried out in a way from which evidence could be derived. Another reason being that Duogynon has not been produced anymore for almost 40 years. Schering was taken over by Bayer AG in 2006, and they categorically excludes Duogynonas the cause of embryonic malformations“.

“The exact mechanism of action of Primodos / Duogynon on zebrafish is not yet known, but there are indications that the developmental stage of the blood vessels and the nerves play a key role in the nature and extent of embryonic damage”

said Vargesson.

“We could see enlarged hearts, open backs, damaged blood cells and damage to the nervous system. It is not just premature, but dubious, from these first results, to draw conclusions about possible damage to human embryos, I estimate that we will have to research at least three to five years in the lab and in very different animals”

said the scientist.

“Zebrafish, whose embryonic development is similar to those of higher vertebrate animals, and which develop completely and very quickly outside the mother’s body, are an important model organism for biologists. However, further experiments on rodents, fish and also sheep are essential in order to make assured statements. Research on pregnant women is prohibited for ethical reasons”

Vargesson said.

“You have to emphasize again and again that there is no such a thing as a natural malformation rate. Three per cent of all newborns are born with malformations, without apparent causes.”

added Vargesson.

New Hopes

The research approach of Neil Vargesson brings nevertheless new, great hope for the alleged Duogynon victims who have so far vainly struggled in the United Kingdom and in Germany as self-help groups for the recognition of their suffering by governments and parliaments and for a compensation fund based on the model of the foundation for contergan victims. Whether and how fast reliable results will be available, however, is also a matter of financing. The British parliament, which has been examining medical and scientific findings on Duogynon for one and a half years, has recently invited the Scottish biologists to a meeting. There were no concrete financial commitments so far.

“It’s also unusual to want to research a drug that is not there. My attention for Duogynon, came about by chance, almost as a by-product of my actual research interest.”

admited Vargesson.

Contergan was recommended to pregnant women in the 1960s against morning sickness and triggered one of the biggest drug scandal of the past century. The question of how the drug, can be used without harming unborns in the mother’s womb has been the focus for many years. Contergan is still of great therapeutic interest and use, said Vargesson, for the treatment of leprosy as well as certain types of cancer of the plasmatic cells.

Contergan Open Questions

​​Despite years of intensive research, it is still unclear as what exact building blocks of Contergan drug cause the malformations.

Vargesson does research on this, since he wants to know which molecules he has to forego completely, which he could change as well as which he should exchange, in order to make the medium safe and yet medically usable. Vargesson has recently patented several promising varieties of a slightly modified conteric.

Vargesson is optimistic:

“When I heard that another drug might also cause malformations in unborn babies, I had to look at the matter more closely.
Certain substances that were present in Duogynon are still found today in modified form in antibabies. There should be an interest in exploring possible undesirable side effects.
Whether it goes, and how, will depend above all on financial decisions.”

  • Original press release : FEHLBILDUNGEN DURCH DUOGYNON, on taz, 2.6.2017.
  • Translation via Google.
  • Image credit taz.

Every child deserves the opportunity to thrive, in safe and healthy settings

Inheriting a sustainable world: Atlas on children’s health and the environment


WHO ‘s publication outlines the impact of the environment on children’s health and recommends solutions for preventing diseases and deaths in the future.

More than a decade after WHO published Inheriting the world: The atlas of children’s health and the environment in 2004, this new publication presents the continuing and emerging challenges to children’s environmental health.

This 2015 edition – download here – is not simply an update but a more detailed review; we take into account changes in the major environmental hazards to children’s health over the last 13 years, due to increasing urbanization, industrialization, globalization and climate change, as well as efforts in the health sector to reduce children’s environmental exposures. Inheriting a sustainable world? Atlas on children’s health and the environment aligns with the Global Strategy for Women’s, Children’s and Adolescents’ Health, launched in 2015, in stressing that every child deserves the opportunity to thrive, in safe and healthy settings.

This book seeks to promote the importance of creating sustainable environments and reducing the exposure of children to modifiable environmental hazards. The wide scope of the SDGs offers a framework within which to work and improve the lives of all children. To this end, we encourage further data collection and tracking of progress on the SDGs, to show the current range of global environmental hazards to children’s health and identify necessary action to ensure that no one is left behind.

The impact of chemicals on children’s brain development

A cause for concern and a need for action

No Brainer

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

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.

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

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.
  • Phthalates
    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.
  • Perchlorate
    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.

Policy recommendations

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.

Post-marketing studies are not transparent enough and do not improve drug safety surveillance

Contribution of industry funded post-marketing studies to drug safety: survey of notifications submitted to regulatory agencies

BMJ 2017;356:j337 Study (Published 07 February 2017)

Our findings do not support the aspiration of the German Medicinal Products Act that post-marketing studies serve to improve long term drug safety surveillance.

In contrast, we found evidence that drug safety could be jeopardised by the current practice, as post-marketing studies are expected to contribute to pharmacovigilance, but in reality their data and results are treated as business secrets.

Our data support the view that the high remunerations paid by the sponsor to the participating physician could be serving commercial purposes rather than transparent and effective pharmacovigilance.

In our opinion the major problem with post-marketing studies is the confidentiality clauses in the contracts between physicians and sponsors. These contracts impose a major obstacle to scientific evaluation and discussion of post-marketing studies. In the interest of drug safety and public health, post-marketing surveillance should become more transparent. Data about and from such studies should no longer be considered confidential business information but should be made available to independent scientific evaluation and public scrutiny. Such increased transparency would allow future researchers to evaluate whether the changes in 2012 to EU pharmacovigilance legislation have been associated with any material improvements in the situation.

The importance of advising GPs and clinicians on their indispensable role in detecting, diagnosing, and reporting adverse drug reactions cannot be overestimated.

What is already known on this topic

  • Systematic evaluations of post-marketing industry funded trials are sparse
  • The few studies available have criticised post-marketing studies for their low scientific value and lack of scientific integrity and for being seeding trials masking marketing interests of the sponsors as research
  • Current legislation relies on post-marketing studies for drug safety surveillance

What this study adds

  • Post-marketing studies are not serving as a key tool for drug safety surveillance, at least among those registered in Germany
  • Sample sizes are generally too small to allow for the detection of rare adverse drug reactions, and many participating physicians are strictly obliged to maintain confidentiality towards the sponsor about all data, including adverse drug reactions
  • The post-marketing studies analysed are doing no measurable good to patients and could be taking resources away from more effective pharmacovigilance systems

Contribution of industry funded post-marketing studies to drug safety: survey of notifications submitted to regulatory agencies, BMJ 2017;356:j337, 07 February 2017.

To investigate the practice of post-marketing studies in Germany during a three year period and to evaluate whether these trials meet the aims specified in the German Medicinal Products Act.

Survey of notifications submitted to German regulatory agencies before post-marketing studies were carried out, 2008-10.

Notifications obtained through freedom of information requests to the three authorities responsible for registering post-marketing studies in Germany.

Main outcome measures
Descriptive statistics of post-marketing studies, including the products under study, intended number of patients, intended number of participating physicians, proposed remunerations, study plan and protocol, and availability of associated scientific publications and reports on adverse drug reactions.


Image credit The BMJ Fig 3 : Example of confidentiality agreement for post-marketing study (source: notification sent by Merck Serono on 18 March 2010 regarding post-marketing study of cladribine)

Information was obtained from 558 studies, with a median of 600 (mean 2331, range 2-75 000) patients and 63 (270, 0-7000) participating physicians per study. The median remuneration to physicians per patient was €200 (€441, €0-€7280) (£170, £0-£6200; $215, $0-$7820), with a total remuneration cost of more than €217m for 558 studies registered over the three year period. The median remuneration per participating physician per study was €2000 (mean €19 424), ranging from €0 to €2 080 000. There was a broad range of drugs and non-drug products, of which only a third represented recently approved drugs. In many notifications, data, information, and results were, by contract, strictly confidential and the sole property of the respective sponsor. No single adverse drug reaction report could be identified from any of the 558 post-marketing studies. Less than 1% of studies could be verified as published in scientific journals.

Post-marketing studies are not improving drug safety surveillance. Sample sizes are generally too small to allow the detection of rare adverse drug reactions, and many participating physicians are strictly obliged to maintain confidentiality towards the sponsor. High remuneration and strict confidentiality clauses in these studies could influence the physicians’ reporting behaviours of adverse drug reactions.

The cause of birth defects is known in less than a quarter of cases

Etiology and clinical presentation of birth defects: population based study

Understanding the etiology of birth defects should be both a public health and research priority. Our findings underscore the large gaps in current knowledge of the causes of birth defects. These gaps in turn represent opportunities for both basic and translational researchers. Such research can be particularly powerful and efficient if done in collaboration with population based birth defect surveillance programs enhanced with clinical expertise and meaningful case classification. Advances in the knowledge of the causal pathway leading to birth defects can be the basis for better primary prevention interventions, resulting in longer and better lives. For clinicians and parents, it is important to understand what can be done today to prevent birth defects, in particular the role of preconception care focusing on optimal women’s health (including screening/treating chronic illnesses, attaining folic acid sufficiency, etc). In addition, investigation of potential causes of a birth defect at the time of diagnosis (such as whether a genetic condition is present) can help to better plan management and appropriately counsel families, including the relief of anxiety related to unfounded information and guilt.

Approximately 3-10% have been attributed to exogenous and environmental agents. Those environmental agents known to cause birth defects include lead; polychlorinated biphenyls; ethanol; organic mercury; and drugs such as thalidomide, diethylstilbestrol, valproic acid, and 13-cis-retinoic acid.

What is already known on this topic

  • Birth defects are common, costly, and critical
  • Two hospital based studies have tried to directly assess the proportion of birth defects with or without a known etiology

What this May 2017 study adds

  • In this population based birth defect case cohort, the cause was established in only one in every five infants
  • The inability to understand etiology in four of five cases highlights the urgent need for better basic and translational research as a basis for primary prevention and care
  • In addition, many birth defects are associated with fetal loss: estimates of the global burden of birth defects that consider only liveborn infants with isolated conditions will underestimate this burden by at least 25%, and even more for selected conditions


Etiology and clinical presentation of birth defects: population based study, BMJ 2017;357:j2249, 30 May 2017.

To assess causation and clinical presentation of major birth defects.

Population based case cohort.

Cases of birth defects in children born 2005-09 to resident women, ascertained through Utah’s population based surveillance system. All records underwent clinical re-review.

5504 cases among 270 878 births (prevalence 2.03%), excluding mild isolated conditions (such as muscular ventricular septal defects, distal hypospadias).

Main outcome measures
The primary outcomes were the proportion of birth defects with a known etiology (chromosomal, genetic, human teratogen, twinning) or unknown etiology, by morphology (isolated, multiple, minors only), and by pathogenesis (sequence, developmental field defect, or known pattern of birth defects).


Known and unknown etiology of birth defects – image credit BMJ Fig 1.

Definite cause was assigned in 20.2% (n=1114) of cases: chromosomal or genetic conditions accounted for 94.4% (n=1052), teratogens for 4.1% (n=46, mostly poorly controlled pregestational diabetes), and twinning for 1.4% (n=16, conjoined or acardiac). The 79.8% (n=4390) remaining were classified as unknown etiology; of these 88.2% (n=3874) were isolated birth defects. Family history (similarly affected first degree relative) was documented in 4.8% (n=266). In this cohort, 92.1% (5067/5504) were live born infants (isolated and non-isolated birth defects): 75.3% (4147/5504) were classified as having an isolated birth defect (unknown or known etiology).


Cause could not be identified in almost 80% of children with major birth defects.
Shouldn’t we be doing better?

These findings underscore the gaps in our knowledge regarding the causes of birth defects. For the causes that are known, such as smoking or diabetes, assigning causation in individual cases remains challenging. Nevertheless, the ongoing impact of these exposures on fetal development highlights the urgency and benefits of population based preventive interventions. For the causes that are still unknown, better strategies are needed. These can include greater integration of the key elements of etiology, morphology, and pathogenesis into epidemiologic studies; greater collaboration between researchers (such as developmental biologists), clinicians (such as medical geneticists), and epidemiologists; and better ways to objectively measure fetal exposures (beyond maternal self reports) and closer (prenatally) to the critical period of organogenesis.

Pharmaceutical industry payments and oncologist drug selection

Payments linked to higher odds of doctors prescribing certain cancer drugs

In preliminary findings that will be presented at the American Society of Clinical Oncology Annual Meeting 2017 in Chicago on Saturday, June 3, researchers show that when physicians had to choose between multiple, on-patent drugs for metastatic kidney cancer and chronic myeloid leukemia, they were more likely to prescribe drugs from companies they had received general payments – for meals, talks, travel, etc. – from.

2017 Study Abstract

Financial relationships between physicians and the pharmaceutical industry are common, and have the potential to influence clinical practice in potentially inappropriate ways. Oncology may be an ideal setting to study the influence of industry payments on physician drug choice given the high levels of competition for market share and high prices commanded by orally administered oncologic drugs.

We linked the Open Payments database of industry-physician financial transactions with the Medicare Part D Prescriber file by physician name and practice location. We used McFadden’s conditional logit model to determine whether receipt of industry payments was associated with higher odds of using a drug manufactured by the same company. We applied this model to clinical scenarios in which oncologists may choose between multiple, on-patent drugs: metastatic renal cell cancer (mRCC) (sunitinib, sorafenib, and pazopanib) and chronic myeloid leukemia (CML) (imatinib, dasatinib, and nilotinib). The primary, binary independent variable was receipt of payments from a manufacturer of one of these drugs in 2013; the primary dependent variable was choosing that manufacturer’s drug in 2014. We divided industry payments into two categories, research payments and non-research “general” payments (including meals, travel, lodging, and speaking/consulting fees), and analyzed each payment type separately.


More evidence that drug companies are able to influence prescribing practices through gifts to physicians.

Physicians who received general payments from a manufacturer had increased odds of prescribing that manufacturer’s drug for both mRCC (OR: 1.78, 95%CI 1.23-2.57, mean payments $566) and CML (OR: 1.29, 95%CI 1.13-1.48, mean payments $166). Research payments were associated with an increased odds of manufacturer drug use for mRCC (OR: 2.13, 95%CI 1.13-4.00, mean payments $33,391) but not CML (OR: 1.10, 95%CI 0.83-1.45, mean payments $185,763).

Receipt of general payments from pharmaceutical companies is associated with increased prescribing of those companies’ drugs. An association between research payments and prescribing was less consistent. This study suggests that conflicts of interest with the pharmaceutical industry may influence oncologists in high-stakes treatment decisions for patients with cancer.

Sources and Press Release

The BMJ Research looks at prenatal antidepressant use and risk of ADHD in children

Prenatal antidepressant use and risk of attention-deficit/hyperactivity disorder in offspring: population based cohort study

Previous reports might have overestimated the association between gestational use of antidepressants and ADHD in offspring because they have failed to control for shared family factors. Although we cannot completely discount the possibility that gestational use of antidepressants is a causal factor, our findings raise the possibility that confounding by indication might at least partially explain the observed association. We propose that if a causal association exists, then the size of the effect is probably smaller than that previously reported. However, decision making about antidepressant use in pregnancy remains important and requires an assessment of the risks and benefits in the context of the individual woman and family.

What is already known on this topic

  • Whether to prescribe drugs for depression during pregnancy is a complex decision
  • Prenatal use of antidepressants is considered a risk factor for attention-deficit/hyperactivity disorder (ADHD) in children, but evidence is inconclusive
  • The negative consequences of untreated maternal depression might also affect childhood development

What this study adds

  • The risk of ADHD was similar between the offspring of mothers who used antidepressants during pregnancy and those who used before pregnancy only, whereas the risk was higher for offspring of mothers with psychiatric disorders irrespective of whether antidepressants were used
  • Evidence suggests that the association between prenatal antidepressant use and risk of ADHD may at least partially be explained by confounding by indication of antidepressants
  • If there was a causal association; then the size of the effect is probably smaller than what has been reported previously

2017 Study Abstract

To assess the potential association between prenatal use of antidepressants and the risk of attention-deficit/hyperactivity disorder (ADHD) in offspring.

Population based cohort study.

Data from the Hong Kong population based electronic medical records on the Clinical Data Analysis and Reporting System.

190 618 children born in Hong Kong public hospitals between January 2001 and December 2009 and followed-up to December 2015.

Main outcome measure
Hazard ratio of maternal antidepressant use during pregnancy and ADHD in children aged 6 to 14 years, with an average follow-up time of 9.3 years (range 7.4-11.0 years).

Among 190 618 children, 1252 had a mother who used prenatal antidepressants. 5659 children (3.0%) were given a diagnosis of ADHD or received treatment for ADHD. The crude hazard ratio of maternal antidepressant use during pregnancy was 2.26 (P<0.01) compared with non-use. After adjustment for potential confounding factors, including maternal psychiatric disorders and use of other psychiatric drugs, the adjusted hazard ratio was reduced to 1.39 (95% confidence interval 1.07 to 1.82, P=0.01). Likewise, similar results were observed when comparing children of mothers who had used antidepressants before pregnancy with those who were never users (1.76, 1.36 to 2.30, P<0.01). The risk of ADHD in the children of mothers with psychiatric disorders was higher compared with the children of mothers without psychiatric disorders even if the mothers had never used antidepressants (1.84, 1.54 to 2.18, P<0.01). All sensitivity analyses yielded similar results. Sibling matched analysis identified no significant difference in risk of ADHD in siblings exposed to antidepressants during gestation and those not exposed during gestation (0.54, 0.17 to 1.74, P=0.30).

The findings suggest that the association between prenatal use of antidepressants and risk of ADHD in offspring can be partially explained by confounding by indication of antidepressants. If there is a causal association, the size of the effect is probably smaller than that reported previously.