SETAC Spotlight: Experience to date deriving endpoints for birds and mammals using the EFSA updated guidance (2023)

In 2021 the European Food Safety Authority (EFSA) released a new draft guidance for estimating the risk for wild birds and mammals exposed (or potentially exposed) to Plant Protection Products, which must be assessed in accordance with EU Regulation (EC) 1107/2009. This was followed by the release of a final, revised bird and mammal guidance in 2023.

According to EFSA (2023), benchmark dose modelling must now be attempted to determine whether valid 10% effect levels (BMD₁₀) can be calculated. If they can, these must be used in the risk assessment instead of the NOAEL. An online tool provided by EFSA is available to perform calculations, which uses a Bayesian approach. An online workshop on the use of the BMD approach and the new tool was hosted by EFSA in February 2023.

Our experience to date with BMD modelling has highlighted the following issues:

• In general, standard bird and mammal toxicity studies are not suitable for generating BMDs, as they are designed to generate NOAELs. The use of more dose levels (even with fewer individuals in each dose level) would allow for a better curve to be fitted, a fact which is acknowledged in the EFSA (2023) guidance.
• Calculating BMDs can be very time consuming, a fact which is not helped by the difficulty of extracting data from old studies (which may need to be done manually, or at least checked for correctness if done automatically). Running the BMD calculations can then be time-consuming, depending on the number of endpoints needed.
• It is still unclear whether expert ‘common sense’ can be used when selecting endpoints for BMD modelling, or whether regulators will require all endpoints from a study to be run.
• The guidance leans heavily on the selection of a BMD₁₀ over the NOAEL for the bird and mammal endpoints, however it has been our experience that it is very rare to achieve a ‘sensible’ BMD₁₀ endpoint from this activity (with modelling often failing due to a lack of effects occurring or due to the limited number of doses).

The EFSA 2023 revised guidance provides some advice on deriving ecologically relevant toxicity endpoints for birds and mammals. This requires reviewing the effects observed in the toxicity studies to determine which are population relevant and which aren’t, with the guidance providing some advice on how to make these decisions.

Our experience with deriving ecologically relevant toxicity endpoints has highlighted the following issues:

• A focus is still made on ‘≥10%’ effects being the most relevant, regardless of effect type (in line with the BMD₁₀-focussed approach). Though no evidence for the relevance of this to wild populations is provided in EFSA (2023). In reality, it is unlikely that that the different effect types would have comparable impacts on populations at the same magnitude (e.g. pup survival Vs. pup weight).
• The guidance states that effects don’t have to be statistically significant to be ecologically relevant but equally, effects which are statistically significant may not be ecologically relevant (e.g. if <10%).
• Some specific examples of ecological relevance are provided in EFSA (2023), e.g. mammal body weight effects of ≥10% are considered relevant, but body weight gain is stated to be less relevant. However, other than the few specific examples, the approach for determining ecological relevance is similar to EFSA (2009) – a case-by-case assessment of any effects observed is required, which includes specific argumentation/data to support ecological (ir)relevance of effects.

The new EFSA (2023) Bird and Mammal guidance has not yet been notified at the EU level, therefore technically it is not required to be used for current active substance or product submissions. However, there is every indication that the guidance will be noted some time in 2024. So, use of this guidance is potentially just around the corner.

Further discussion on this topic is available in the poster presented at SETAC 2023. The poster is available for free download.

If you would like to discuss any of the topics raised in this article, feel free to contact us.

You can find all of the other posters that CEA presented at SETAC Dublin here. You can also find all of our publications from previous conferences and links to journal articles we have authored on our library page.

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