Vitellogenin (VTG) is the egg-yolk precursor protein commonly measured in ecotoxicological tests in fish to identify the potential endocrine activity of chemicals. VTG data can be highly variable, meaning that additional fish testing may be required to address uncertainties in the VTG response. We formed a working group of experts from the pharmaceutical and agrochemical sectors to understand and address the causes of this variability, improve the robustness of VTG data and reduce unnecessary additional fish testing.
Harmonising measurement of VTG in fish
In 2021, in collaboration with an expert working group, we conducted an international survey of 16 laboratories with varying degrees of experience in conducting VTG assessment in regulatory studies. We surveyed sixteen laboratories from the UK, USA and EU, carrying out VTG analysis and identified technical challenges in measuring VTG and variation in interpreting results.
The survey results identified several aspects that contribute to variability in VTG and provides a basis for improving and harmonising the measurement of VTG in fish across the various relevant test guidelines. We are currently working on next steps to provide guidance for best practice to support the laboratories conducting this type of analysis, to reduce the incidences of equivocal VTG results and reduce unnecessary additional fish testing. Uptake of these recommendations will lead to more robust analysis and avoid unnecessary repeated testing or additional tests in fish.
Alongside this, we participated in a general review of VTG measurements in fish based on study data with 106 substances. This showed that VTG is a reliable biomarker for endocrine activity, but highlighted high variability between studies and laboratories which could trigger additional unnecessary tests in fish. This work also builds the evidence base supporting application of New Approach Methodologies (NAMs) to predict VTG responses in fish to support a reduction in animal testing, by demonstrating that in vitro tests using mammalian cell lines are predictive of the in vivo VTG response.
