Last week the German Federal Institute for Risk Assessment (BfR) released a consensus statement on criteria for identifying endocrine disrupting chemicals (EDCs) that could input to the European Commission’s mandate to develop and implement criteria for EDC identification as required by both the EU Plant Protection Products Regulation (PPPR) and Biocidal Products Regulation (BPR).
As described by BfR, the statement was the result of a meeting of scientists who were convened by BfR, and who had previously publicly disagreed about the topic. Such disagreement among the experts was apparently causing enough confusion within the EU Commission (EC) that they were struggling on how best to proceed.
Although I have serious reservations about the lack of transparency regarding the selection of meeting participants, and the conduct of the meeting itself — transparency being not only virtuous for its own sake, but also to preserve scientific integrity — attempts to find common ground among scientists to reduce public confusion should generally be applauded. In this instance, the scientists were able to reach consensus on a number of principles, whereas disagreement on some other important ones persists.
So, on which principles did they agree and how does their agreement advance efforts to develop criteria for identifying and regulating EDCs within the EU?
In general, and as explained in greater detail below, the scientists found important consensus on those principles that would support a risk-based approach to regulating EDCs, similar to how the U.S., Canada and Japan are already regulating EDCs.
However – and this is ironic and unfortunate – both the PPPR and the BPR dictate that the EC must apply a hazard-only based approach to regulating EDCs. In fact, the only way the BfR could coax consensus from the scientists was to convince them to equate EDC identification to the hazard identification step of a risk assessment and to ignore subsequent steps, especially including the pivotal hazard characterization step where critical information about the dose levels that produce adverse effects is integrated into the risk equation.
We’ll discuss this shortcoming more fully toward the end of this blog.
Definition of an EDC
There was consensus to use the WHO definition of an EDC: “An ED is an exogenous substance or mixture that alters the function(s) of the endocrine system and consequently causes adverse effects in an intact organism, or its progeny, or (sub) populations.” Thus, to be an EDC, a chemical must cause an adverse effect via alteration of the endocrine system. If a chemical alters the functioning of the endocrine system, but this does not result in an adverse effect, by definition, it cannot be identified as an EDC.
An adverse effect is defined as “a change in morphology, physiology, growth, reproduction, development or lifespan of an organism which results in impairment of functional capacity or impairment of capacity to compensate for additional stress or increased susceptibility to the harmful effects of other environmental influences”.
Distinction Between Endocrine Active and Endocrine Disruptor
Related to the definition of EDC above, the BfR statement also makes a critical distinction between a chemical being only endocrine active and it being an endocrine disruptor. The endocrine system strives to maintain homeostasis in the body and many substances that interact with it may cause only transitory alterations that have no adverse consequences, or may even have beneficial consequences. The BfR statement is unequivocal on this point: endocrine activity on its own is insufficient to identify a chemical as an EDC.
Disputes About NMDR and the Low Dose Hypothesis Shouldn’t Delay EDC Criteria
The statement acknowledges the lack of scientific consensus on Non-Monotonic Dose-Response (NMDR) relationships and data supporting the so-called low dose hypothesis that have been inconsistently reported in the literature. The scientists concluded that consensus was unlikely to be achieved on these controversial topics anytime soon, but that it wasn’t required to establish criteria for the identification of EDCs. By extension one can then also conclude that programs such as the U.S. EPA’s Endocrine Disruptor Screening Program (EDSP) should continue to move forward and be used to screen and test for endocrine disruption.
A Weight-of-the-Evidence Approach
The statement reinforces the point that the identification of a chemical as an endocrine disruptor must rely on a weight-of-evidence (WoE) evaluation of both adversity and mode of action together. WoE approaches consider all available relevant and reliable evidence and take into account the strengths and weaknesses of the underlying study methods and quality of the data.
The EU Should Update its Legislation to Include Relevant and Validated Screens and Tests
The statement acknowledges that current EU legislation has not been updated to include all relevant and validated tests for endocrine disruption. This presents the EU with an unprecedented opportunity to now incorporate the validated screens and tests currently used in the US EPA’s EDSP and to apply the results obtained from the EDSP on specific chemicals in the EU weight-of-the-evidence classification of EDCs. The new high throughput assays pioneered in the EDSP, which are insufficient alone for classification purposes, can nevertheless be used along with exposure information for prioritization of chemicals and integrated with toxicity results for weight of evidence determinations.
Potency: Important for Hazard Characterization but Not for Identifying an EDC
Potency refers to the amount of a substance required to produce a given effect. A chemical that can produce a biological effect at lower doses is said to be more potent than one which produces effects only at higher doses. The BfR statement concludes that potency does matter when characterizing the hazard of EDCs and when assessing and managing their risks; however, it concludes that potency does not need to be considered only in identifying which chemicals meet the definition of an EDC (hazard identification).
The International Program on Chemical Safety (IPCS) defines hazard identification as: “The identification of the type and nature of adverse effects that an agent has an inherent capacity to cause in an organism, system, or (sub)population. Hazard identification is the first of four steps in risk assessment.”
IPCS defines hazard characterization as: “The qualitative and, wherever possible, quantitative description of the inherent property of an agent or situation having the potential to cause adverse effects. This should, where possible, include a dose–response assessment and its attendant uncertainties. Hazard characterization is the second of four steps in risk assessment. The remaining steps in a risk assessment are exposure assessment and risk characterization.”
The problem here isn’t necessarily with the consensus statement, but with the fact that, under the current EU law, if a pesticide or biocide is identified as an EDC – no further steps in a risk assessment are done. It doesn’t even make it to hazard characterization, exposure assessment or risk characterization. There’s no consideration of potency or dose-response, of real-world exposure scenarios or probability of real-world effects.
According to the logic driving this “hazard-only” approach to regulation that ignores potency and real world exposure levels, substances such as water and many foods we eat would potentially be banned because they contain naturally occurring EDCs at some level:
- soy based products
- other vegetables
- some fruits
- meat products
- cereals and breads
- nuts and oil seeds
- alcoholic beverages
- coffee and tea
It’s senseless, and it’s the epitome of what’s wrong with a hazard-only approach to regulating EDCs.
Hazard-Only Based Approaches to Chemicals Risk Management Fall Short
It is unfortunate that the EU has chosen to take a hazard-only based approach to regulating crop protection chemicals and biocides identified as EDCs. The BfR consensus statement notes this is contrary to the risk-based approach taken for EDCs in other parts of the world. It also conflicts with the risk-based approach taken in nearly every other piece of EU chemicals legislation and regulation.
Banning a substance based on its hazard properties alone can also create utter confusion between the EU and the rest of the world and within the marketplace and result in unwanted consequences, including creating serious potential public health gaps, unnecessarily increasing costs for consumers and reducing consumer choice, without actually reducing the societal disease burden attributable to EDCs.
For example, hazard-based approaches could encourage the substitution of new chemistries into existing products that may make them less efficacious or more harmful, because the safety information, given the shorter time the new chemical has been studied, may be more limited.
The scientists convened by BfR seemed to understand this, despite having been constrained by their remit to restrict themselves to the hazard identification step of risk assessment. As noted above, their statement includes many principles that reinforce the importance of taking a risk-based rather than hazard-only based approach to regulating EDCs.