October 17, 2023 by Becky Brown

wca are pleased to announce the publication of two new open access papers concerning the assessment of the vitellogenin protein (a pivotal protein biomarker for endocrine activity of chemicals) in fish. These papers are a collaboration between scientists from wca, the agrochemical industry and the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs). The papers discuss some of the challenges in conducting vitellogenin analysis and in interpreting the results for regulatory purposes.

The first paper (Are changes in vitellogenin concentrations in fish reliable indicators of chemical-induced endocrine activity?) is a general review of vitellogenin measurements in fish based on studies with 106 substances. It confirms high intra-study and inter-laboratory variability in vitellogenin measurements and issues associated with outliers. Despite this, vitellogenin is generally a good biomarker for oestrogen agonist activity (specifically induction in male fish) and aromatase inhibition (based on the inhibition of vitellogenin in female fish). Although interpretation of the vitellogenin data were sometimes confounded by a potential alternative (endocrine) mechanism of action, it was rare for substances without endocrine activity in vitro to cause a concentration-dependent vitellogenin response in fish in the absence of systemic toxicity.

The second paper summarises the results from a survey of laboratories conducting vitellogenin analysis in fish (An international cross-laboratory survey on fish vitellogenin analysis: Methodological challenges and opportunities for best practice). Sixteen laboratories responded to the survey which identified several technical challenges for measurement of vitellogenin and interpretation of the results. There were issues associated with sampling, storage, analyses of vitellogenin protein concentrations, data handling and data acceptability criteria. The paper concludes that there is a need to improve and further harmonise guidance on the measurement of vitellogenin for regulatory testing purposes.

We hope these papers will raise awareness around the issues with variability of vitellogenin measurement and highlight the importance of reporting all data (e.g., from individual fish) alongside the proficiency criteria of the relevant method and Test Guideline. The papers also include insights on interpretation of the results from vitellogenin measurements which could be used to avoid potentially unnecessary repeat, or higher tier fish testing. The ambition is that this work may lead to the development of more consolidated and harmonised guidance for vitellogenin measurements in regulatory fish testing.

These papers were co-authored by Dr Becky Brown (becky.brown@wca-consulting.com) and Dr Grace Panter (grace.panter@wca-consulting.com) from wca. These and another publication on anti-androgenic activity in fish demonstrate a commitment to improving the interpretation of regulatory fish tests for endocrine assessment.

Becky and Grace lead work on endocrine disruptor assessments at wca. Please contact us if you have any questions on the above publications or enquiries on how we can help with an endocrine disruptor assessment for your substance.

Photo Credit: iStock.com/GlobalP.