Impact case study database

The consensus reached at the Berlin workshop put European Commission decision makers in a position to deliver on legal obligations to protect the 445,000,000 EU citizens against the harmful effects of EDCs in pesticides and biocides. This provided the foundations for improving the safe use of such products where endocrine disruption was not previously considered as a form of harm. It gives manufacturers the certainty needed for developing safer products in compliance with EU law on biocides and pesticides.

As the European Commission takes steps not only to deal with pesticides and biocides, but also to regulate endocrine disrupting properties of industrial chemicals and substances used as food additives or personal care product ingredients, the new regulatory principles for EDCs begin to radiate out into other regulatory domains.

In 2013, the European Commission started the regulatory process with an impact assessment on defining the scientific criteria, in which several regulatory options were set out (Comm 2016). The impact assessment was not completed in time to meet a legally binding deadline (December 2013) and even continued until 2016, leading to a case brought by Sweden to the European Court of Justice.

The April 2016 “Berlin consensus” initiated by Kortenkamp and Jobling created an environment in which it became possible to realise the protection of people from harmful effects of EDCs. The President of the German Federal Institute of Risk Assessment, Professor Andreas Hensel, declared the consensus a “ breakthrough in the scientific discussion on endocrine disruptors and of great importance for the consumer health protection in Europe” (S1).

As an immediate and direct consequence of the consensus, the European Commission abandoned one option (option 4) of their impact assessment. If not withdrawn, this option would have weakened protection from EDCs in the EU. A Commission executive summary of the impact assessment, published as a staff document (S2) noted (page 2): “ Recent scientific consensus made evident that Option 4 could no longer be pursued from a scientific point of view, although it is supported by some stakeholders and member states”.

The way was free to implement science-based regulatory criteria for EDCs and to provide the foundations for protection of human health and the environment from harmful effects of EDCs in pesticides and biocides.

In replacing intermediate regulatory criteria for EDCs which targeted substances classed as carcinogens or reproductive toxicants, the consensus improved the quality of the regulation by providing the principles for directly addressing endocrine disruption. The intermediate criteria would have led to restrictions for many chemicals which in fact do not pose endocrine disrupting harm. This situation would have compromised acceptance of EU law and would have disoriented manufacturers.

The new criteria were enshrined in the form of Delegated Regulations, first for biocides in 2017 (S3), then for pesticides in 2018 (S4).

The Delegated Regulations implemented the provisions for health protection against EDCs that are laid down in the EU Biocidal Product Regulation and the Plant Protection Product Regulation. These provisions stipulate that manufacturers can only place active biocidal or pesticidal substances with endocrine disrupting properties on the EU market if risks (biocides) or exposures (pesticides) are minimal. Without the development of regulatory criteria for EDCs these legal obligations could not have been realized and the protection of human health and the environment from harm through EDC exposures would have been delayed.

Very few EU chemical regulations currently mandate the consideration of cocktail effects in risk assessment, chief among them the regulations for plant protection products and for biocides. But even here the legal mandates are currently not implemented due to a lack of agreed mixture risk assessment methods (Ref 2). May other chemical regulations relevant to the mixtures issue currently do not require mixture risk assessments, for example those relevant to food contaminants, food contact materials, industrial emissions and many others.

The new EU Chemical Strategy for Sustainability (S1) acknowledges these regulatory gaps and intends to establish provisions for mixture risk assessment in regulations for all chemicals, not only pesticides and biocides. It commits the EU to accelerate work on pesticides so that existing legal mandates can be implemented in practice. There is also a commitment to introduce Mixture Assessment Factors which will lower exposure limits for chemicals, thereby protecting against mixture risks.

Brunel’s work has contributed significantly to this policy shift. A European Commission Staff Working Document (S2) accompanying the Chemical Strategy contains a compilation of recommendations from EU member states, scientists, and other stakeholders (Box 7, p 40) that explicitly references Kortenkamp and Faust (Ref 2). The paper called for the introduction of legal requirements for mixture risk assessment in all relevant regulations, and for a framework to ensure coordination of mixture risk assessment across various regulatory areas.

The Staff Document (p 6) also refers to Brunel’s work that exposed the insufficient protection against mixture risks through traditional single chemical safety margins (Ref 3). This supports the idea of introducing additional safety margins leading to lower exposure limits (Mixture Assessment Factors).

To highlight the need for introducing additional regulations that can deal with mixtures composed of chemicals across different regulatory areas (e.g. combinations of plant protection products, biocides, industrial chemicals and pharmaceuticals), the document (p 17) refers to Evans et al. (Ref 4). The paper called for extending the scope of activities across regulatory areas.

In support of making default additivity assumptions in mixture risk assessments based on existing single chemical toxicity data, which will make such assessments feasible in regulatory practice, the document (p 30) cites Brunel researchers’ recent systematic review on synergism (Ref 5). This work demonstrated that synergisms are rare and show the usefulness of default additivity assumptions.

In the first example of a regulatory action where the underlying risk assessment considered mixture exposures to several chemicals, the European Chemicals Agency (ECHA) in 2017 introduced restrictions for a group of four phthalates used as plasticisers in consumer articles (S3). When making such restrictions, ECHA is obliged to demonstrate that the envisaged measures have socio-economic benefits by avoiding a minimum number of infertility cases. In making this case, ECHA referred to Brunel’s work which showed that infertility attributable to phthalates was close to 9% in 2010 (Ref 6).

ECHA estimated that in 2014 approximately 5% of all newborn boys in the EU (130,000 boys) were at risk through phthalate exposure in prenatal life, and 15.5% of newborn boys (400,000) through direct exposure in postnatal life. On the basis of these statistics, ECHA concluded that without the restrictions for phthalates the exposures to these chemicals would not be adequately controlled.

The prevailing need to better address chemical mixtures in relevant regulations requires the delivery of practicable approaches for the assessment of mixture risks. Kortenkamp made substantial contributions to developing mixture risk assessment guidance by the European Food Safety Authority (EFSA) (More et al. 2019). This guidance (S4) provides a firm basis for procedures of how to assess chemical mixture risks.