Christopher N Connolly 1, Stephen P H Alexander 2, Jamie A Davies 3, Michael Spedding 4
1Independent, 2School of Life Sciences, University of Nottingham, Nottingham, UK. 3Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK. 4Spedding Research Solutions, Le Vésinet, France.
Loss of biodiversity is a major challenge for the environment, much attributable to a worldwide decline in insects (1), and the use of pesticides.
In 2020, 13 million kgs of different pesticides were used in the UK but there is little pharmacological knowledge about their action, although toxicology (eg LD50s) is well described. However, the agents may act at pharmacological doses which are much lower than toxicological doses and we have proposed that treating pesticides in a similar way as medicines would be imperative for a healthy environment. For example, there is almost no information on synergies between different pesticides, despite synergies being a pillar of modern medicine. There are very few data on potency at site of action, or selectivity between pests and bystander species, although neonicotinoids may have affinities in the low nM range. IUPHAR has thus proposed, in a far-ranging article (2), that pharmacology should complement toxicology by treating pesticides in a parallel manner to drugs in terms of affinities, distribution, synergies etc. We are discussing joint interactions with IUTOX. We would need to extend the IUPHAR databases to cover pesticides and we have made a variety of propositions(2). Quantification of the total doses, taking into account the affinities of pesticides for their sites of action, compared with concentration of the agents in the biosphere, and taking into account mechanistic synergies, may lead to a very different picture as to how the environment should be dosed.
We are actively seeking funding, and partners to further explore this extension of pharmacology. Please contact michael@speddingresearchsolutions.fr for questions.
To improve relevance of pesticide safety testing we propose:
- The use of binding affinities to relevant target tissues of multiple target and bystander species (and man) as an index of potency.
- The creation of an independent series of experts, linked to a database of pesticide targets and affinities (as in IUPHAR/BPS guidetopharmacology.org) with expert subcommittees on each pesticide target,
- Funding for a CRO to set up binding assays for multiple targets for pesticides.
- Sánchez-Bayo F, Wyckhuys KAG. Worldwide decline of the entomofauna: A review of its drivers. Biol Conserv. 2019 Apr 1;232:8–27.
- Connolly CN, Alexander SPH, Davies JA, Spedding M. Environmental pharmacology-Dosing the environment: IUPHAR review 36. Br J Pharmacol. 2022 Aug 16;
