Scientific Opinion on the developmental neurotoxicity potential of acetamiprid and imidacloprid


neonicotinoid, developmental neurotoxicity risk assessment, in vitro testing, nAChR agonists, pesticide approval regulations
First published in the EFSA Journal
17 dicembre 2013
21 novembre 2013
Last Updated
21 febbraio 2014. This version replaces the previous one/s.
Opinion of the Scientific Committee/Scientific Panel

The European Food Safety Authority asked the Panel on Plant Protection Products (PPR) and their residues to deliver a Scientific Opinion on the developmental neurotoxicity (DNT) potential of the neonicotinoid insecticides acetamiprid and imidacloprid. An in vitro study (Kimura-Kuroda et al., 2012) suggested that excitation and/or desensitisation of nicotinic acetylcholine receptors (nAChRs) by these compounds might affect developing mammalian nervous systems as occurs with nicotine. To evaluate the DNT potential of acetamiprid and imidacloprid, the PPR Panel scrutinised the open literature, the draft assessments reports and dossiers submitted for approval. The Panel concludes that both compounds may affect neuronal development and function, although several methodological limitations have been identified. Considering the available DNT studies for imidacloprid and acetamiprid, important uncertainties still remain and further in vivo studies following OECD test guideline (TG) 426 are required to robustly characterise a DNT potential and dose-response relationships, particularly for acetamiprid. The Panel considers that current ARfDs may not be protective enough for the possible DNT of acetamiprid and imidacloprid and no reliable conclusion can be drawn as regards the ADI for acetamiprid. More conservative reference values are proposed based on the analysis of the existing toxicological data. However, the current ADI for imidacloprid is considered adequate to protect against its potential developmental neurotoxic effects. Limitations of the in vitro system used by Kimura-Kuroda et al. (2012) prevent its current use as a screening tool in the regulatory arena. The PPR Panel encourages the definition of clear and consistent criteria at EU level to trigger submission of mandatory DNT studies, which could include development of an integrated DNT testing strategy composed of robust, reliable and validated in vitro assays and other alternative methods complementary to the in vivo TG 426 for assessing the DNT potential of substances.

Panel members at the time of adoption
Alf Aagaard, Theo Brock, Ettore Capri, Sabine Duquesne, Metka Filipic, Antonio Hernandez-Jerez, Karen Ildico Hirsch-Ernst, Susanne Hougaard Bennekou, Michael Klein, Thomas Kuhl, Ryszard Laskowski, Matthias Liess, Alberto Mantovani, Colin Ockleford, Bernadette Ossendorp, Daniel Pickford, Robert Smith, Paulo Sousa, Ingvar Sundh, Aaldrik Tiktak, Ton Van Der Linden
Panel on Plant Protection Products and their Residues
EFSA Journal 2013;11(12):3471 [47 pp.].
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