Endocrine disruptors under the spotlight: what EFSAs latest findings mean for chemical manufacturers

25 Nov 2025

Despite the structured ECHA/EFSA Guidance for the identification of endocrine disruptors, both human health and non-target organism studies continue to face challenges related to study design, methodological limitations and variable data quality.

The European Food Safety Authority (EFSA), the independent body that provides scientific advice on food, nutrition, animal health and other related risks, recently identified recurring and regulatory challenges in evaluating the endocrine-disrupting properties of pesticide active substances (EFSA Technical Report EFSA-Q-2025-00204).

Across human health assessments

Several recurring problems were identified that affect the robustness and interpretability of the data. EFSA highlighted that many inconclusive or equivocal results originated from deficiencies in study conduct, wide biological variability between runs, and inconsistent application of test guideline criteria.

For instance, in laboratory tests used to measure the presence, amount or functional activity of a specific substance or entity – such as the H295R steroidogenesis test (OECD TG 456) – variability in cell passages, inadequate evaluation of solubility and stability, and contradictory solvent use across studies often resulted in an inability to reliably confirm actual cell exposure to the test substance.

In the case of thyroid effects, hormonal changes observed without corresponding histopathological effects make interpretation particularly challenging and sometimes require more complex investigative studies to substantiate. Overall, inconsistent reporting, limited mechanistic insight, and gaps in datasets often forced reliance on additional testing to reach a conclusion.

Non-target organisms

The assessments were similarly hindered by methodological and technical limitations. Establishing maximum tolerated concentrations remained a common difficulty, partly due to limited guidance on distinguishing systemic toxicity effects beyond mortality, often resulting in inconclusive tests and the need to repeat studies. Several tests were found to be poorly suited for detecting certain modes of action, such as anti-androgenic effects, leading to uncertainty in the weight-of-evidence evaluation. Furthermore, biomarkers like vitellogenin showed high variability and were frequently accompanied by incomplete methodological reporting, complicating their interpretation and sometimes rendering their statistical power insufficient to detect endocrine-related effects reliably. Data limitations, where there is a reliance on single studies or species, and insufficient progression to higher tier tests when warranted further contributed to uncertainty. Together, these issues underscore the need for improved study design, clearer guidance and more consistent data generation to ensure reliable hazard identification in non-target organism assessments.

Guidance for manufacturers

The EFSA outlined key recommendations to ensure the scientific validity of endocrine disruptor evaluations:

Generation of comprehensive and robust datasets to avoid inconclusive results and enable the derivation of toxicological reference values (TRV).
Provision of well-substantiated justifications for waiving endocrine disruptor assessment, which must not be based solely on assumptions of low or short-term exposure.
Conduct of preliminary range-finding studies to establish appropriate test concentrations for definitive endocrine disruptor assessment.

To ensure a scientifically robust and comprehensive endocrine disruptor assessment, it is strongly recommended that companies apply the ECHA/EFSA Guidance for the identification of endocrine disruptors in conjunction with the ECHA Guidance on the implementation of CLP criteria.

Pesticide active substances already considered endocrine disruptors under the Legislation on Plant Protection Products (PPP) will be classified as endocrine disruptor Category 1 under CLP. However, for pesticide active substances that do not meet the endocrine disruptor criteria according to the ECHA/EFSA Guidance may be classified as Category 1, 2 or given no classification, depending on the data available when reassessed under CLP.

At Ricardo, we are committed to assisting companies in achieving scientifically sound and regulatory-compliant assessments for endocrine disruptor, persistence, bioaccumulation and other challenges. Our chemical experts have extensive experience in endocrine disruption and can provide reliable, tailored guidance at every stage of the process.

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