EC Releases Endocrine-Disruptor Criteria, Drawing Heavily On WHO Definitions

The European Commission’s newly released criteria for identifying endocrine disruptors in the plant-protection and biocidal product sectors have no direct regulatory impact on cosmetics, but could signal the approach the EC will take in other areas as it works to manage endocrine-disruptor risks. A review of the Cosmetics Regulation’s applicability to endocrine disruptors is nearing completion, the EC says.

The European Commission has released regulatory criteria for identifying substances with endocrine-disrupting properties in selected product areas, part of its broader strategy for addressing endocrine-disruptor risks and concerns that includes a review of the EU Cosmetics Regulation.

That review is "close to completion," the EC says, with plans to present results by year-end.

Meanwhile, the criteria set out in two draft legal acts required by EU regulations concerning plant-protection and biocidal products provide an indication of the approach that may be taken by the EC and other European authorities in other regulated product areas.

In a June 15 Communication to the European Parliament and Council, the EC explains the legislative and regulatory background for its work on endocrine disruptors and highlights key definitions and positions developed by other health and regulatory bodies that the EC has folded into in its criteria.

The commission is adopting a 2002 definition established by the International Programme on Chemical Safety, a collaboration between United Nations bodies including the World Health Organization, which identifies an endocrine disruptor as:

• “An exogenous substance or mixture that alters function(s) of the endocrine system and consequently causes adverse health effects in an intact organism, or its progeny, or (sub)populations.”

According to an EC “roadmap” steering its endocrine-disruptor work, the WHO/IPSC definition has commanded “general consensus” among scientists and regulators worldwide, if not wide support from industry.

“The issue faced by the Commission in this exercise is to establish criteria to determine what is or is not an endocrine disruptor for the purposes of plant-protection products and biocidal products – not to decide how to regulate these substances.”

As to what constitutes an adverse effect, the EC embraces another definition provided by IPCS: “change in the morphology, physiology, growth, development, reproduction [or] life span of an organism, system, or (sub)population that results in an impairment of functional capacity, an impairment of the capacity to compensate for additional stress, or an increase in susceptibility to other influences."

With regard to effects seen in testing at the sub-organ (molecular or cellular) level, the EC recognizes the challenge investigators likely will face in assessing potential adversity. Here, it refers to the position taken by the European Food Safety Authority – whose activities support the EC, Parliament and European member states – in a scientific opinion published in March 2013.

EFSA’s solution was to make a distinction based on degree, calling for “expert judgment” to determine the toxicological relevance of changes on a case-by-case basis. “In general, transient, inconsistent and minor fluctuations at the biochemical and molecular level may be considered adaptive (i.e. non-adverse), whilst sustained, consistent and permanent changes at the cell, organ- or organism-level, resulting in pathology or functional impairment in vivo, as well as altered timing of development, may be considered adverse.”

The EC says this is the tack it is taking in its proposed regulations regarding plant-protection and biocidal products and the conditions under which chemical manufacturers should determine a substance an endocrine disruptor.

There remains the issue of causality. The commission underscores the importance of “endocrine mode of action” in determining whether an observed adverse health effect reflects the impact of what should be considered an endocrine disruptor.

But the WHO/IPSC definition, which links an endocrine system-altering action to a resulting adverse effect, pivots on the word “consequently,” raising questions as to “the extent to which this link should be clearly established – the degree to which a strict causality should be required,” the EC notes.

The commission again refers to reasoning set out by EFSA in its 2013 opinion. EFSA asserted that there must be "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.”

The EC says it intends to follow this concept of reasonable evidence, as opposed to a more rigid approach requiring “conclusive evidence” of a relationship between endocrine mode of action and adverse effect to characterize a substance as an endocrine disruptor. Conclusive evidence would be very difficult to demonstrate, it says.

Stakeholders React: No One’s Happy

The EC’s rejection of a conclusive-evidence standard for determining causality may factor in the backlash being seen from the agricultural and pesticides industries. The criteria’s heavy reliance on the WHO/IPSC definition, which industry generally has opposed in its narrow wording, also has ruffled feathers.

Notably, the commission sidestepped the issue of potency, which industry wanted to see enshrined in its criteria. While the EC notes that typically chemical safety assessments and related regulations take into account “safe thresholds,” or dosages below which no adverse event is expected to occur, it declines to address the subject in its criteria, suggesting that such considerations fall outside of its immediate task.

“Answering the question of whether a threshold exists is neither necessary nor appropriate when defining scientific criteria for determining what is an endocrine disruptor,” the EC asserts.

It also says that questions about whether safe thresholds can be established for endocrine disruptors, or left to case-by-case risk assessment, are matters of controversy and ongoing debate.

Vying with industry’s protests are objections from NGOs and Members of European Parliament who see the EC’s criteria, and the manner in which causality is addressed therein, as inadequate to capture endocrine disruptors in its regulatory net.

Some have suggested that it shifts EU biocides and pesticides regulation from a hazard- to a risk-based system.

In reality, as the EC notes in its Communication, European chemicals regulations vary as to their risk or hazard basis depending on the overarching legislation. In the case of legislation for plant-protection and biocidal products, endocrine disruptors are banned if they are hazards regardless of any risk or exposure considerations, with some room for exceptions.

Again, the EC emphasizes that “the issue faced by the Commission in this exercise is to establish criteria to determine what is or is not an endocrine disruptor for the purposes of plant-protection products and biocidal products – not to decide how to regulate these substances.”

Cosmetic ‘Screening Exercise’ Nears Completion

The proposed delegated regulations released by the EC require adoption through standard procedures involving the EU Parliament and Council.

In any event, they have no direct bearing on the cosmetics sector or others outside of plant-protection and biocidal products. For those two areas, legislation expressly required the EC to develop criteria for application specifically within their perimeters.

However, the EC notes that it and other agencies already are addressing endocrine-disruptor risks in other regulated sectors and currently are reviewing endocrine-disruptor data requirements across their respective jurisdictions.

It notes that the European Cosmetics Regulation – which entered into force in July 2013, replacing the Cosmetics Directive of 1976 – includes a mandate for the EC to “review this Regulation with regard to substances with endocrine-disrupting properties.”

The review was supposed to happen “at the latest” by Jan. 11, 2015.

The EC acknowledges that its review is overdue. “A screening exercise of certain cosmetic ingredients that has been contracted by the Commission is close to completion. The Commission will present the review by the end of the year,” it says.

The EC also will present by year-end on its review of REACH regulations and whether endocrine disruptors should be candidates for authorization on the basis of their socio-economic benefits in the absence of suitable alternatives.

The EC-advising Scientific Committee on Consumer Safety has noted that identifying endocrine disruptors in the cosmetics sector could be challenging due to the EU animal-testing ban in place for ingredients since 2013 (Also see "ID’ing Endocrine Disruptors Without Animal Tests ‘Extremely Difficult’ – SCCS" - HBW Insight, 15 Jan, 2015.).

The marketing ban prohibits the sale of cosmetics containing animal-tested ingredients after its date of enactment. However, a pending decision from the European Court of Justice could permit cosmetics to enter the EU market with ingredients tested on animals to meet REACH requirements, fulfill third-country regulatory requirements or for any other reason, provided that the data is not used to substantiate product safety under the European Cosmetics Regulation (Also see "Cruelty Free Optimistic About Legal Opinion On EU's Marketing Ban" - HBW Insight, 22 Mar, 2016.).

The EU notes that it is working with the European Chemicals Agency, which oversees the EU’s Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) program, on endocrine-disruptor oversight issues and the relevance of its newly issued criteria to REACH administration.

Specifically, the EC points out that under REACH, chemicals for which no safe threshold can be established can still receive authorization for market use if their socio-economic benefits are shown to outweigh risks to human health or the environment and no suitable alternative substances are available.

The commission is required to review REACH to assess whether endocrine disruptors should be considered in the context of such authorizations. “Following the presentation of scientific criteria today, this review can be finalized,” the EC says, targeting the end of 2016 for its presentation of those findings as well.