New ANSES expert appraisals on SDHIs in plant protection products
ANSES is publishing two opinions on the safety of succinate dehydrogenase inhibitors (SDHIs). These active substances are used in plant protection products to combat fungi that are harmful to crops. After reviewing all the available data, the Agency recommends adjusting certain toxicity reference values intended to protect human health. These conclusions will be presented at European level. ANSES has also assessed the risks to consumers associated with residues of various SDHIs in food. It does not highlight any health concerns arising from the cumulative ingestion of residues in food in light of the adjusted toxicity values.
Substances in the SDHI class inhibit succinate dehydrogenase, an enzyme found in human mitochondria. They are used in agriculture as fungicides. To date, 11 SDHI substances have been approved at European level for plant protection purposes.
Following a report from scientists in 2019, which had already given rise to an opinion that concluded there was no health alert, ANSES carried out additional expert appraisals on its own initiative:
- on the revision of the safety values used to assess the risks associated with exposure
- on exposure to SDHI residues by ingestion
It is publishing the results in the form of two opinions.
Proposed changes to certain toxicity reference values
ANSES reviewed the toxicity reference values (TRVs) for SDHIs in light of all the available data, including the most recent data. It examined 14 active SDHI substances, including 11 that are approved in the European Union, two that are no longer approved, and one that is currently under assessment. This work involved an in-depth review of 39 TRVs.
TRVs are the amounts of chemicals that should not be exceeded in order to protect human health, for a given route of exposure and a given duration (short, medium or long term). Modes of action that can cause mitochondrial toxicity were particularly taken into account.
The group of experts convened by ANSES reviewed the data published in the scientific literature and the data in the dossiers submitted as part of applications, made available by the Agency, for the approval of plant protection products containing SDHIs. It should be noted that the literature search carried out by the experts did not find any additional epidemiological data published since the INSERM collective expert review on the health effects of pesticides of 2021.
The expert appraisal carried out by ANSES does not call into question 28 existing TRVs. Following its review of the available scientific data, the Agency recommends lowering 11 of the 39 TRVs analysed, by moderately reducing their current value by factors ranging from 1.5 to 3.3.
These proposed adjustments, which are intended to provide greater protection, will be recommended by ANSES at European level so that they can be taken into account when the active substances concerned are re-assessed. These TRVs are used to assess risks by considering all routes of exposure for consumers, local residents, workers and operators. The assessment methodologies used take account of both acute and chronic health effects.
The Agency is also issuing several methodological and research recommendations to continue improving knowledge on the modes of action of SDHIs and their potential health consequences. Some of these recommendations will be brought to the attention of the OECD and EFSA to help define testing strategies and study protocols to be used when assessing active substances.
Cumulative dietary exposure to SDHI substances
In its 2019 expert appraisal, ANSES concluded that the level of chronic dietary exposure associated with each SDHI substance was low, in light of the toxicity reference values for each active substance taken individually. To supplement this analysis, the Agency assessed the risks associated with cumulative dietary exposure to all SDHI substances.
The assessment adopted the most recent methodologies recommended by EFSA and also took account of the scientific and technical advances identified in the case studies published at European level. Two assessment methods were used, including both “worst case” scenarios and the TRV adjustments proposed by ANSES.
The results showed that the safety thresholds for consumer health were not exceeded, even with the TRVs revised downwards by ANSES, for cumulative exposure to all active SDHI substances.
Research is under way to further explore the effects of SDHIs
To continue improving knowledge on levels of exposure to SDHIs in the population, ANSES has already included these substances in the following:
- the third French Total Diet Study (TDS), which is currently being implemented with the aim of estimating people's exposure to chemicals in food
- an INRAE campaign to measure plant protection products in soils.
The Agency is also funding studies exploring data from the national register of hereditary paraganglioma, a disease caused by a mutation in one of the genes coding for succinate dehydrogenase (SDH) in humans, in an attempt to determine whether changes in the incidence of this type of disease could be linked to exposure to SDHIs. These studies will supplement the limited epidemiological data available for these substances.
Two other research projects are also under way, with funding from the Ecophyto plan and ANSES’s National Research Programme for Environmental and Occupational Health (PNR EST), to gain a better understanding of the effects of SDHI fungicides on living cells, using toxicological and mechanistic approaches.