SDHIs: ANSES provides an update on the work initiated since the publication of its January 2019 opinion

On 14 January 2019, after being alerted by a group of scientists, ANSES published an opinion on the assessment of a warning signal regarding the toxicity of succinate dehydrogenase inhibitor (SDHI) fungicides. Based on a review of all the scientific data currently available, carried out by a group of independent experts, ANSES concluded that there was no health alert justifying the withdrawal of marketing authorisations for these fungicides. However, it called for vigilance at European and international level and stressed the need to step up research on potential toxicological effects in humans.

Work to examine this warning signal regarding SDHI fungicides has been continuing since January 2019 in three areas: the definition and funding of specific research, the detection by existing surveillance schemes of possible health effects that may be observed in the field, and lastly exchanges with research organisations and health agencies tasked with assessing these substances, in particular the European Food Safety Authority (EFSA).

The SDHI class includes 11 fungicidal substances that prevent the development of fungi and moulds affecting crops by blocking succinate dehydrogenase (SDH), an enzyme involved in cellular respiration. In April 2018, in an article published in the press, several scientists warned of the potential risks of these substances to human health.

The exhaustive examination of the available scientific data carried out by the expert group convened by ANSES did not provide any evidence to confirm this warning signal. Indeed, the level of dietary exposure is low in relation to the toxicological thresholds. Furthermore, these substances, none of which are classified as proven or presumed carcinogens in the European regulations, are rapidly metabolised and eliminated in humans. Moreover, in the sources consulted, none of the data suggest an increase in the incidence of cancers – particularly those associated with a hereditary SDH-deficiency – in line with the marketing of SDHI fungicides, particularly among farmers. Similarly, there are no data indicating that these fungicides have an impact on environmental organisms.

With a view to examining the warning signal in greater depth, ANSES has identified several research projects since January that respond to the independent expert group's recommendations to improve knowledge. The possibility of exploring data from the national register of hereditary paraganglioma associated with a mutation in one of the SDH genes has already attracted the Agency's attention, and it is committing funding to support this work in order to explain the trend in the incidence of this type of disease. Other research projects are in progress or have been presented as part of the 2019 call for projects of ANSES's National Research Programme for Environmental and Occupational Health (PNR-EST). They include toxicological and mechanistic studies to further investigate the mechanisms of action of SDHI fungicides. As soon as the working group reached its conclusions, ANSES also asked Inserm to consider the issue of the health effects of SDHIs as part of the ongoing collective expert appraisal aimed at updating knowledge of the health effects associated with pesticides.

ANSES is continuously improving its methods for assessing the risks associated with the use of plant protection products. In addition to the work in progress, in 2019 it issued an internal request to examine the question of cumulative dietary exposure to the various SDHIs. This work will be completed during the first half of 2020.

ANSES also remains vigilant regarding all adverse effects on human health and continues to collect field data through its multi-year national phytopharmacovigilance (PPV) programme. Ongoing and future studies on monitoring pesticide contamination of ambient air, soil and food will therefore take the study of SDHIs into account. Other surveillance schemes have also included SDHI fungicides in the list of substances to be monitored.

Lastly, as with all plant protection products, active substances are assessed at European level under the aegis of EFSA and the European Chemicals Agency (ECHA). The commercial products containing them undergo a specific assessment for each use by the Member States, with a view to obtaining marketing authorisation. Active substance approvals and marketing authorisations are regularly reviewed in light of advances in the available knowledge. As early as 2018, ANSES had informed the European authorities, Member States and its North American counterparts of the warning signal concerning SDHI fungicides and of its internal request to address the matter. In early 2019, ANSES forwarded its conclusions to EFSA, ECHA and the Member States for their consideration and to ask them to pay particular attention to any new data during ongoing assessment and re-assessment processes, such as the re-assessment of boscalid, the most widely used active substance in the SDHI class.

To date, no new evidence has been provided to confirm the existence of a health alert justifying the withdrawal of the marketing authorisations in force, in accordance with national and European regulations on plant protection products.