On November 29, an op-ed article, co-signed by 94 scientists, and entitled “Let’s Stop the Manipulation of Science” was published in Le Monde. It makes numerous allegations, most prominent among them that industry is “manufacturing doubt” about the science on endocrine disrupting chemicals (EDCs). But as anyone who has followed the issue of endocrine disruptors knows, it is highly controversial and polarized with serious questions raised on both sides about exactly who is, in fact, manipulating the science. In the following paragraphs, I tackle this allegation and others made by the co-signers of the Le Monde op-ed and ask that you the reader arrive at your own conclusions.
Allegation #1 — The petrochemical and agro-chemical industries, much like the tobacco industry before them, intentionally distort the science to manufacture doubt about purported EDCs.
Response to Allegation #1
This is a very serious allegation, and you would think the authors would cite at least one example to support it. But in fact they don’t. Not one scintilla of evidence is provided, which makes defense against it either very easy or difficult, depending on your perspective.
From the mid-1990’s until 2012, I was director of product safety for one of the largest, global chemical chemical companies, with responsibility for world class toxicology and environmental fate laboratories, product stewardship, regulatory compliance and product sustainability. I can tell you firsthand that since it was first raised we have always taken with the utmost seriousness the allegation that low levels of chemicals in the environment might alter the functioning of endocrine systems of humans and wildlife and tried to contribute constructively to address it. To do otherwise, would have been irresponsible and reckless, especially with activist management teams, board of directors, an external sustainability advisory council, insurers, customers and shareholders constantly demanding answers from me and my team to their tough questions about it.
I’m proud of the actions that the global chemical industry has taken in response to the endocrine issue. To highlight just a few:
- sponsoring fundamental research through the International Council of Chemical Associations (ICCA) Long-Range Research Initiative in the US, EU and Japan;
- organizing and participating in scientific conferences on the topic;
- participating in the development and validation of endocrine screening assays both at the OECD level and via the US EPA Endocrine Disruptor Screening Program, including development of High Throughput (HTP) Assays which will accelerate the pace of chemical screening;
- and employing such assays to determine whether selected chemicals are capable of interacting or interfering with the endocrine system to determine if additional risk management steps are warranted.
It is also inaccurate and highly irresponsible to equate the actions of the chemical industry to those of the tobacco industry when discussing product safety. The chemical industry has always readily acknowledged the hazards of its products, and has taken steps to manage them through risk reduction strategies.
A bit of history -- long before there were any government regulations that required it, the chemical industry was conducting toxicology and environmental fate testing of its raw materials, products and by-products and was placing hazard warnings via labels on its products to protect those who handled them. Material Safety Data Sheets for this purpose were voluntarily created in the 1940’s.
Industry leaders such as Dow, Dupont, BASF, Bayer and others established toxicology laboratories in the 1930’s (note US EPA wasn’t created until the early 1970’s and TSCA wasn’t law until 1976) for this purpose and early industry scientists were pioneers in the fields of mammalian- and eco-toxicology, environmental chemistry, industrial hygiene, occupational medicine and related disciplines. They readily shared their scientific expertise and knowledge by publishing in the peer-reviewed literature, and presenting at scientific conferences. Results of toxicology testing on specific chemicals were published in journals, but also in books such as Patty’s Toxicology, and WHO monographs.
The science of toxicology has continued to develop and advance and in recent decades has included the use of computer modeling and HTP assays which has increased speed and reduced use of laboratory animals.
Have some mistakes been made along the way? Certainly, and hindsight is always 20:20. Regrettable discoveries were made along the journey, but nothing that closely reached the scale of wholesale denial and obfuscation practiced over decades by the tobacco industry.
Allegation #2 — The petrochemical and agro-chemical industries deny the science on climate change and oppose international efforts to address it.
Responses to Allegation #2
This allegation is completely false, and is easily refutable. ICCA has well-developed policies on energy and climate change that are publicly accessible. In brief, ICCA believes governments should undertake actions that will intensify the deployment of products and technologies to address global climate change challenges. Addressing global climate issues, particularly through improved energy efficiency, is very important to the chemical industry, which enables greater carbon efficiency throughout the economy with the use of its products.
Chemical products have two effects on greenhouse gases (GHGs):
1 GHGs are emitted in the manufacture of chemical products;
2 Use of many of these products enables significant emission reductions in other sectors, often greater than the amount of GHGs emitted during their production.
ICCA says it further believes successful implementation of the landmark Paris Agreement hinges in large part on the private sector transforming international policy directives on climate into action by investing, developing and deploying innovations to address global sustainability challenges, including reducing GHG emissions. The global chemical industry will be instrumental to the development, production, and delivery of these products and technologies.
Allegation #3 — “The European Commission is about to implement the first regulation for endocrine disruptors in the world. While many other governments have also expressed concern about endocrine disruptors, regulations for these chemicals are missing altogether.”
Response to Allegation #3
The co-signatories to the Le Monde article continue to perpetuate a myth that the EU is the only government body that is regulating chemicals that are endocrine active. The truth is that these chemicals have been and continue to be regulated by a variety of means by government agencies around the world. Even the EU Commission acknowledges this.
Endocrine disruption is a mechanism of action for causing adverse health effects. Government agencies have never required knowledge of a chemicals’ mechanism of action before taking action to regulate it.
Instead, they base their regulatory decisions on the most sensitive adverse effect produced by a chemical and the lowest dose that causes that adverse effect and apply safety factors to deal with uncertainties. Many of the chemicals that the proponents of the issue allege are endocrine disruptors such as DDT and its metabolites, PCBs, dioxins, organophosphates, brominated flame retardants, etc. have already been either phased out or voluntarily withdrawn from consumer markets and a lack of knowledge of their precise mechanism of action was never a barrier to taking necessary risk management.
Such an allegation also ignores the tremendous efforts that have been undertaken by the Japanese and US regulators to develop and apply validated screening tests to detect chemicals that have the ability to interact or interfere with the normal functioning of endocrine systems. Japan, the US, Canada, Australia and other countries all consider endocrine disruption in applying their respective regulatory schemes that are science and risk-based.
This allegation also ignores the multi-national efforts at the OECD to develop validated screens and tests to detect endocrine activity. It also fails to acknowledge the importance of early screening of chemicals to detect not only chemicals that are potential EDCs but those that are not EDCs which is critical to being able to introduce safe chemicals to the market and avoiding regrettable substitution.
The EU is unique in its decision to take a hazard-only rather than a risk-based approach to regulating crop protection chemicals and biocides that are identified as endocrine disruptors. This was a political decision made by the EU Parliament rather than a scientific decision made by the European Commission which must now implement it.
A large number of stakeholders have been highly critical of the EU approach because it ignores real life exposures and will likely lead to unnecessary bans and restrictions on products that are safe to use, thereby reducing consumer choice and raising costs for consumers with no concomitant increased public health or environmental benefits.
Allegation #4 — “Never before have we faced a higher burden of hormonal diseases, such as cancers of the breast, testes, ovaries and prostate, compromised brain development, diabetes, obesity, non-descending testes, malformations of the penis, and poor semen quality. The overwhelming majority of scientists actively engaged in researching the causes of these worrying health trends agree that several factors are involved, among them chemicals capable of interfering with our hormone systems.”
Response to Allegation #4
There are actually two allegations here: (1) that the trends for all of the diseases listed are actually increasing everywhere globally; and (2) there is consensus among an overwhelming majority of scientists that chemicals of unspecified identity have been conclusively shown to be playing a causal role. Both are wrong.
As demonstrated below, the evidence that the incidence of these diseases is increasing is weak or non-existent. As is also demonstrated, the evidence that low levels of chemicals in the environment actually cause these diseases is inconsistent and insufficient. Several of the signatories to the Le Monde article have authored papers which attempt to make a case for causation; however, they have been accused of failing to use systematic review methods, cherry picking studies, over weighting single un-replicated results, ignoring the role of dose of exposure, failing to acknowledge small sample sizes, and misusing and mis-interpreting statistics.
Perhaps most disturbingly, attached to both allegations is the implication that if you disagree with this group of scientists then you are denying the science, in industry’s pockets and are among the “manufacturers of doubt”.
This amounts to a none too subtle threat to either get in line with their particular view of the science or face being labeled with a pejorative and publicly harassed. No doubt their intent is to silence anyone who disagrees with them which is, of course, antithetical to the scientific process itself. Such behavior is repulsive and should not be tolerated.
Let’s first tackle the allegation that trends for the listed diseases are increasing, and focus first on cancers of the breast, testes, prostate and ovary. First of all, reliable cancer trend data for Europe as a whole is difficult to find as there are significant variations in incidence and mortality rates across the individual countries. These reflect differences in the national health system policies (e.g. organized screening), the completeness of recording cancer incidence and death, the varying prevalence – of risk factors between countries and regions, and disparities in human development and the effective delivery of cancer control measures.
With the exception of lung cancer among women and pancreatic cancer among both sexes, overall cancer mortality has been steadily declining in Europe since its peak in 1988, translating to an overall 26% fall in men and 21% in women, and the avoidance of over 325 000 deaths in 2015 compared with the peak rate. Since 2009, breast cancer rates in women fell 10.2% and prostate cancer rates among men fell 12.2%.
In the U.S., during the last decade, breast cancer incidence has been level, prostate cancer has been falling on average 5.1% each year, and ovarian cancer has been declining 1.9% each year. Although testicular cancer incidence has been rising 0.8% per year, this appears completely attributable to earlier detection as mortality rates have been stable and five year survival rates have been increasing. Contrary to the assertion in the Le Monde article, rates for the four types of cancer are not increasing. Nor is there an overwhelming scientific consensus that EDCs play a causal role in the etiology of cancers of the breast, testis, prostate, and ovaries.
Also, contrary to the assertion of compromised brain development, IQ scores continue to increase globally with the most significant gains occurring in the lower half of the distribution. This is known as the Flynn effect, named after the scientist who discovered it and the causes for it are unknown but competing theories for it abound.
A recent systematic review of the literature on intellectual disability found it was impossible to make any conclusions about time trends owing to substantial differences in study settings, methodologies, age groups, and case definitions contributed to a range of prevalence estimates (0.05 to 1.55 %). According to the authors, future research should include reproducible and consistent definitions of intellectual disabilities, provide age-specific estimates, and monitor changes in prevalence over time. Whether chemicals are playing a role in causing a decline in IQ and an increase in intellectual disability remains in some dispute.
The allegation that rates for male reproductive diseases and disorders are increasing is highly controversial. According to Skakkebaek — a signatory to the Le Monde op-ed, they are, but according to Sengupta the picture is much more complicated. He concluded the evidence for secular changes is “indecisive”. Sengupta also concluded that “Although the ‘environmental oestrogen’ hypothesis has attracted much attention, and there exist some biological data to confirm its plausibility, evidence that it is causally related to changes in human male reproductive health remains circumstantial. “… association does not imply causality, and several other possible explanations require to be considered.”
Although it is clear that the prevalence of obesity and adult onset diabetes have both increased substantially worldwide over the past several generations, and some chemicals are alleged to be playing a role, recent review articles (see for example Wang and Starling) have concluded their is insufficient evidence for a causal role and have recommended additional research, especially for prospective epidemiology studies that include serial measurements for chemical biomarkers.
Lakind et al have reviewed some general problems with the environmental epidemiology literature that often precludes an ability to draw robust conclusions regarding the presence or absence of causal links between specific exposures and human health effects. They note that to develop policies that are protective of public health and can withstand scrutiny, the investigations need to be of sufficiently high quality in terms of exposure assessment, health outcome ascertainment, data analysis and reporting of results. They propose a three part approach addressing methods for improving the quality and accessibility of systematic reviews, access to information on ongoing and completed studies, and principles for reporting study results. If followed this approach could certainly improve our ability to gain scientific consensus on a causal role for chemicals for the diseases mentioned in the Le Monde article as well as other health conditions.
Allegation #5 — “It would indeed be worrying if any of our political opinions clouded our scientific judgment. But it is those who deny the science who are allowing their politics to cloud their judgment.”
Response to Allegation #5
This is another serious allegation, and one could more easily argue that it is the co-signatories to the Le Monde article who have allowed their politics to interfere with their scientific judgment. Indeed, many of their arguments, which are cloaked in the precautionary principle — have no or little basis in science and instead solely reflect political choices. Of course, the precautionary principle is not science, it is a policy choice, invoked when there is a lack of scientific certainty. But when and how it is applied is subject to considerable legitimate debate and must take into account a myriad of competing factors.
Allegation #6 — “However, we are concerned that the regulatory options proposed by the European Commission fall well short of what is needed to protect us and future generations. They set a level of proof for the identification of endocrine disruptors much higher than for other hazardous substances, such as cancer-causing substances – in practice, this will make it very difficult for any substance to be recognized as an endocrine disruptor in the EU.”
Response to Allegation #6
The allegation that the EC has set too high a level of proof to identify EDCs is simply not true. The proponents have falsely claimed that the EC criteria to identify EDCs requires a show of harm in humans or wildlife. The EC has provided a rebuttal that proves that application of their criteria could lead to the identification of a chemical as an EDC based solely on animal data or even on in vitro data, without the availability of any evidence of harm from human studies.
At the time the EC published its proposed criteria it also outlined how they would apply them. (They have subsequently asked the European Food Safety Authority (EFSA) and the European Chemicals Agency to develop implementation advice.) They rightfully pointed out that the most difficult determination to make in identifying EDCs is assessing whether the interaction or interference with the components of the endocrine system actually is the cause of any adverse effects that are observed. They relied on precedent set by the EFSA “… a reasonable evidence base for a biologically plausible causal relationship between the [endocrine mode of action] and the adverse effects seen in intact organism studies.”
This is not an unreasonable barrier to surmount, unless the proponents doubt they have sufficient quality evidence on their side to make their case. The EC rightfully rejected a much higher standard of conclusive evidence of causality which would require observing direct evidence of harm already in humans and wildlife.
Many stakeholders, including industry, agriculture and some member states, have advocated for the inclusion of potency in the proposed EU criteria. They make the point that to ignore potency will lead to an over-identification of chemicals as EDCs. Thus far, the EC has rejected the inclusion of potency in their criteria.
Allegation #7 — (Note: this is not so much an allegation but rather a recommendation to establish an expert organization modeled after the Intergovernmental Panel on Climate Change (IPCC) to review and assess the weight of evidence on EDCs.) “We therefore call for the development and implementation of effective measures that address both endocrine disrupting chemicals and climate change in a coordinated fashion. An effective way of achieving this would be by creating an organization within the United Nations with the same international standing and charge as the Intergovernmental Panel on Climate Change. This body would review the science to be used by decision makers in the public interest and would protect our science from the influence of vested interests.”
Response to Allegation #7
There is some irony in the co-signatories making this recommendation. On the one hand their article asserts the science on EDCs is compelling enough to take urgent action now, and on the other their recommendation to convene a group of global experts to review the science would seem to be an admission that it needs a fresh look from an independent group. So which is it?
The IPCC model may have merit, although many could legitimately question whether the science on EDCs is sufficiently strong to warrant this level of attention and commitment from governments. Frankly, it is difficult to imagine that such a group would come to a different conclusion than “the evidence provides hints of possible associations, but is insufficient to conclude that they are causal.”
Also, what would be the scope of such an organization’s work? Would it be limited to a review of the evidence linking specific chemicals to selected diseases and disorders or would it also tackle knottier issues such as existence of thresholds, the low dose hypothesis, and non-monotonic dose response relationships? If so, the group would soon reach the limits of scientific discourse on these topics and would have to be strongly counseled to avoid making policy recommendations as per below.
By way of background, IPCC authored papers are policy-relevant but not policy-prescriptive: they may present projections of future climate change based on different scenarios and the risks that climate change poses and discuss the implications of response options, but they do not tell policymakers what actions to take. This stands in stark contrast to the heavy policy activism practiced by the co-signatories to the Le Monde op-ed.
Another potential strength of the IPCC model is that members and authors of reports are chosen based on their expertise and participation is welcomed by non-profit and industry scientists who, according to the IPCC, “bring a valuable perspective to the assessment.”
We note again, with some irony, that such a constructive attitude towards the participation by industry stands in stark contrast to the allegations made in the Le Monde article.
So, I'll now again ask you the reader to decide who's really manipulating the science on EDCs?