Endocrine disruptor assessments: Understanding Appendix E and Appendix I

Endocrine disruptor assessments are crucial for substances used in biocide and pesticide products, to gain market access. These assessments follow the guidance published in June 2018 by the European Chemicals Agency (ECHA) and the European Food Safety Authority (EFSA), and involve detailed evaluations of endocrine-disrupting properties based upon scientific criteria. This process is essential for compliance with the Biocidal Products Regulation (BPR) and the Plant Protection Products Regulation (PPPR). Due to the complexity of the assessment process, the ECHA and EFSA published tools to help you complete them, Appendix E in 2018, and Appendix I in 2019.

Appendix E

Appendix E helps users to gather and analyse data to assess the effects of substances on endocrine systems. When completed correctly, it captures all the relevant information from experimental studies and literature on the substance being assessed, including animal species, doses administered, exposure duration, and observed effects. It automatically reorganises the data into a matrix that summarises the collected information to provide the lines of evidence required for Appendix I and IUCLID. Accurate data input is crucial, as the summary data matrix in Appendix E plays a significant role in drawing final conclusions in the overall endocrine disruptor assessment.

Appendix E must be compiled by an (eco)toxicologist with a good understanding of endocrine systems. All of the substance-related study findings are entered into Appendix E and are assessed to decide whether they are due to an endocrine mode of action. If Appendix E is not properly compiled, data can be lost or omitted from the summary data matrix, which can result in incomplete datasets, skewing the analysis and leading to incorrect conclusions. As the summary data matrix and lines of evidence provide the critical analysis that informs decision making, inaccurate data entry risks inaccurate analysis and invalid conclusions leading to a potential non-approval decision.

Appendix I

Appendix I complements Appendix E and is a template for presenting the assessment of endocrine-disrupting properties by comprehensively summarising the data, including the lines of evidence from Appendix E, in a structured format. The format of Appendix I allows the (eco)toxicologists and the regulatory reviewer to draw appropriate conclusions on whether the substance is an endocrine disruptor.

The aim of Appendix I is to determine one of six scenarios once all data is considered. These can be collated into three groups:

• Scenarios 1a and 2a (ii): Sufficient investigations indicate that the criteria for endocrine disruption are not met, allowing the assessment to be concluded. The substance is not considered to be an endocrine disruptor
• Scenarios 1b, 2a (i), and 2b: Some data indicate effects that may be linked to endocrine disruption, requiring a Mode of Action (MoA) analysis
• Scenario 2a (iii): Available data are insufficient: additional investigations into endocrine activity are needed

Using Appendix I presents its own set of challenges. As a tool designed to summarise and analyse data from diverse sources, integrating information from various studies of different design and quality, with differing methodologies and conclusions, can be complex. Methodological differences among the studies can lead to variations in outcomes, making it difficult to compare and combine endpoints. Conflicting conclusions from these studies further complicate synthesis, requiring careful consideration to assess the overall weight of evidence. Expertise and experience are needed to ensure consistency and standardisation of approach across these datasets and are crucial for drawing comprehensive and accurate conclusions. Even if all the information from literature sources and regulatory studies are accurately compiled, interpreting the results of Appendix I correctly remains a significant challenge.

How Sagentia Regulatory can help

You don’t have to navigate the challenges of using Appendix E and I alone. Sagentia Regulatory’s team of experts has years of experience successfully tackling endocrine disruption assessments, including compiling Appendix E and Appendix I. They will meticulously assess all data, ensuring accurate conclusions for your endocrine disruption assessment.

Beyond completing this essential assessment, Sagentia Regulatory’s consultants are here to guide you through the necessary next steps of submission to the competent authorities, with excellent post-submission support, liaising on your behalf to provide further requested information or data waivers as required. We will help you achieve market access for your biocide and pesticide products; you don’t need to risk the consequences of non-compliance.  Get in touch at [email protected] to find out more about our endocrine disruption assessment services.