Insects and Insecticides

Written evidence submitted by the Nomenclature Committee of the International
Union of Pharmacologists

The Nomenclature Committee of the International Union of Pharmacology (NC-IUPHAR) is an authoritative independent body: IUPHAR reports to ICSU. We have >80 subcommittees working on the pharmacology of receptor systems. We were interested in the report of Gill et al1 which showed that chronic combinatorial exposure of bumblebees to two pesticides (imidacloprid, a neonicotinoid nicotinic receptor modulator, and -cyhalothrin, a pyrethroid which changes sodium channel kinetics), using levels expected to be those seen in the field, impaired foraging behavior, increasing worker mortality. There was evidence that combinatorial exposure to pesticides may increase colony failure. In the Nature commentary, J.L. Osborne2 carefully discussed the study, mentioned that regulatory requirements do not take into account exposure to multiple products, but then proposed a large number of field studies, without mentioning the important issue of combinatorial pharmacology as being potentially a crucial factor on the risk assessment. The pharmacology of pesticides is very clear – to pharmacologists; yet we were disconcerted to read that many more field trials may be needed, when the potential for pharmacological interactions is obvious. Modulating nicotinic receptors (cholinergic transmission is a major factor in insect cognition) while blocking sodium channels open (one of the major ion channels in neuronal action potential firing) at the same time will almost certainly have at least additive (and possibly even synergistic) effects on brain performance. This needs to be taken into account in risk assessment, and while the toxicological aspects clearly form part of the regulatory/advisory framework3, the underlying pharmacology is hardly taken into account.

Human clinical trials and drug mechanisms of action must take into account combinatorial pharmacology, which also may contribute to efficacy - this should also apply to pesticide studies. Field studies have multiple variables and in the key susceptible environmental nodes, where the combination may be particularly deleterious (or effective), potency may be hidden by complicated field studies. Osborne2 extensively lists these variables. In contrast, straightforward pharmacological studies can be clear – and much cheaper, albeit needing the careful studies of Gill et al1 to show the risks.

At no point do we wish to appear to criticize the industry, particularly at a point where the evergrowing pressures of the world population make the use and abuse of pesticides absolutely critical. But as pharmacologists with expertise in the mechanisms of action of these agents, we point out that the underlying pharmacological interactions are evident, potentially easy to show experimentally, and should be taken into account in risk, and efficacy analysis in conjunction with toxicological evaluation. Furthermore, such combinations may be used in a very different way to that at present, to the benefit of both industry and society.

1. Gill RJ, Ramos-Rodriguez O, Raine NE. Combined pesticide exposure severely affects individual- and colony-level traits in bees. Nature. 2012 Nov 1;491(7422):105-8

2. Osborne JL. Ecology: Bumblebees and pesticides. Nature. 2012 Nov 1;491(7422):43-5.

3. Fischer D, Moriarty T. Pesticide risk assessment for pollinators: summary of a SETAC Pellston workshop, Pensacola, Florida (Soc. Environ.Toxicol. Chem. 2011)

4 January 2013

Prepared 23rd January 2013