Method development

EOGRT

Bureau REACH contributed to a project within the Organisation for Economic Co-operation and Development (OECD) to improve the implementation of an important test guideline: the extended one-generation reproductive toxicity (EOGRT; OECD TG 443) study.

This test guideline provides important information on the potential effects of chemical substances on the immune system and brain function, the endocrine system, reproduction, and the development of the unborn child. In 2023, the European Chemicals Agency (ECHA), in collaboration with several EU Member States including the Netherlands, reviewed the first 55 EOGRT studies submitted under REACH. This review showed that improvements could be made in several areas.

As a result, the Netherlands, together with Denmark and ECHA, proposed improvements to this test guideline. The revised protocol has been published on the OECD website. It includes, among other things, adjustments for testing effects on the immune system and endocrine system. The associated guidance document (GD 151) is currently being updated in line with these changes.

Article: mutagenicity of Annex VII substances

For determining the mutagenicity of a substance, a distinction is made between (1) inducing mutations and (2) causing chromosomal damage. For identifying mutagenic substances registered under REACH at 1–10 tonnes per registrant per year (Annex VII), only the Ames test is required. If a substance tests positive, further investigation is required. In the case of a negative result, additional testing is only required at higher tonnage levels. As the Ames test only measures mutation formation, not all mutagenic substances are identified with the Annex VII requirements.

Using a battery of (Q)SAR models, Denmark and the Netherlands jointly investigated how many potentially mutagenic substances under Annex VII may not be identified. The publication shows that only around a quarter of these substances have a positive experimental Ames test result. To address this gap, it is recommended to add the in vitro micronucleus test, which can detect chromosomal damage, to the Annex VII requirements.

Article: impact of (very) persistent substances

Emissions of (very) persistent chemical substances can lead over time to an increasing environmental burden. Depending on their persistence, the environmental stock may remain high even after emissions have fully ceased. The effects on ecosystems and human health are linked to this stock in the environment, whereas policy effectiveness is typically assessed based on emission reductions. However, emission estimates do not provide insight into changes in environmental stock resulting from persistence.

As part of an integrated project, a dynamic model was developed that translates emission trends into changes in environmental stock across different environmental compartments, both at national and global scale. Using PFOA emissions in Western Europe as a case study, the development of environmental stock was mapped across three periods: before policy intervention, during the transition, and after implementation of policy measures.

Different historical and hypothetical intervention scenarios were also compared, varying in timing and stringency of measures. The analysis shows that the reduction in environmental stock is not directly proportional to emission reduction. Calculating the (cumulative) environmental stock is therefore essential for a proper assessment of the benefits (or effectiveness) and costs of emission reduction measures. The results also show that the effectiveness of measures decreases or may even become negligible if interventions are delayed, for example through the granting of derogations.

This approach is broadly applicable to various persistent and very persistent substances and can be used to prioritise risk management measures under different regulatory frameworks, such as REACH or the EU Biocidal Products Regulation. The analyses are currently under review for publication in a scientific journal.