The evidence provided by the Dutch Water Boards on imidacloprid contamination of surface water (attached) indicates that, in any case in the western part of the Netherlands, high concentrations of imidacloprid are diffused through the environment, which may kill or debilitate insects and possibly other arthropods. Attached is a map of Holland showing the agricultural areas where the use of imidacloprid is permitted.
The neonicotinoid insecticide imidacloprid is the first highly effective insecticide whose mode of action has been found to derive from almost complete and virtually irreversible blockage of postsynaptic nicotinergic acetylcholine receptors in the central nervous system of insects. The toxicity of imidacloprid to midges (Chironomus tentans) follows Haber’s rule, which is characterised by a linear relationship (on logarithmic coordinates) between exposure concentration and median time to effect, i.e. mortality. Similar dose : response relationships (in accordance with the Druckrey-Küpfmüller equation) have now also been demonstrated for the toxicity of imidacloprid to the freshwater ostracod Cypridopsis vidua and to Daphnia magna as well as for the toxicity of the neonicotinoid insecticide thiacloprid to Gammarus, Sympetrum and Simulium species, which indicates that exposure time may actually reinforce the toxicity of these substances to arthropods (recent articles attached).
The 96-h lethal imidacloprid concentration (LC50) value for for midges (Chironomus tentans) was determined to be 5,750 ng/L, but when the animals were continuously exposed for 28 days the LC50 value was much lower: 910 ng/L . The product of exposure concentration (c) and exposure time (t) remained approximately constant, i.e. c . t = constant, indicating that the total lethal imidacloprid dose remained virtually the same under acute and chronic exposure conditions. This points to cumulative blockage of critical receptors. Indeed, imidacloprid is the first highly effective insecticide whose mode of action has been found to derive from almost complete and virtually irreversible blockage of postsynaptic nicotinergic acetylcholine receptors in the central nervous system of insects.
Such dose : response relationships (c.t = constant) are known as Haber's rule, after the German chemist Fritz Haber who in the early 1900s characterized the acute toxicity of nerve gases used in chemical warfare . Haber's rule was subsequently (in the 1940s) shown to apply to the carcinogenicity of 4-dimethylaminoazobenzene (4-DAB) in rats (the time up to the appearance of liver cancer was found to be inversely proportional to the daily dose), which led to a crucially important theoretical explanation of Haber's rule , as follows:
denoting the initial concentration of specific receptors that 4-DAB reacts with as R, the concentration of receptors that 4-DAB has reacted with as CR, and the mean 4-DAB concentration at the site of action as C, the reaction kinetics in the case of a bimolecular reaction are:
dCR / dt = K (R - CR) C – CR / TR (1)
where K is the reaction constant for association and TR the time constant for dissociation. Since the carcinogenic action of 4-DAB was irreversible, and TR → ∞, we obtain
dCR / dt = K (R - CR) C (2)
Now, assuming that up to the time of action CR « R, which appears reasonable, then R remains practically constant, therefore
dCR / dt = K R C (3)
Since the dose level was kept constant throughout the study, C probably remained constant as well. Integration yields
CR = K R C t (4)
which is Haber’s Rule.
Thus, Haber’s Rule points to cumulative blockage of critical receptors. Indeed, imidacloprid is the first highly effective insecticide whose mode of action has been found to derive from almost complete and virtually irreversible blockage of postsynaptic nicotinergic acetylcholine receptors in the central nervous system of insects.
Clark further expanded Haber’s rule to characterise the action of a number of drugs, and pointed to an additional aspect of Haber’s Rule that is highly relevant in toxicological terms :
(c – x) (t – y) = constant (5)
where x = a threshold concentration, and y = a minimum time of response. Clark commented at the time
“The formula ct = constant is indeed an impossible one in the case of drugs acting on biological material because it implies that an infinitely small concentration of a drug will produce the selected action in infinite time, and conversely that a sufficiently high concentration will produce an instantaneous effect. In some cases ct = constant gives an approximate fit, but this merely implies that x and y are so small as not to produce a measurable error”.
So, an approximate fit of Haber's rule to the action of a compound indicates not only cumulative blockage of critical receptors but also that the threshold concentration (x) is very small. Haber’s rule is characterised by a linear relationship (on logarithmic coordinates) between exposure concentration and median time to effect, i.e. mortality, and such relationships have now also been demonstrated for the toxicity of imidacloprid to the freshwater ostracod Cypridopsis vidua and to Daphnia magna as well as for the toxicity of thiacloprid to Gammarus, Sympetrum and Simulium species. Exposure time may actually reinforce the toxicity of these substances to arthropods. Thus, low environmental concentrations of these insecticides (that may not be acutely toxic) could be detrimental to many invertebrate species in the long term, in particular because these compounds are persistent in soil and stable to breakdown by water.
Nicotinic acetylcholine receptors (nAChRs) play roles in many cognitive processes. At sub-lethal doses imidacloprid can alter honey bee foraging and learning. Imidacloprid has been detected at levels of 5.7 µg/kg in pollen from French hives and foraging honey bees reduced their visits to a syrup feeder when it was contaminated with 3 µg/kg of imidacloprid . Mayflies of the genera Baetis and Epeorus showed a reduction in reproductive success when exposed to concentrations of imidacloprid as low as 100 ng/L .
The evidence indicates that, in any case in the western part of the Netherlands, high concentrations of imidacloprid are diffused through the environment, which may kill or debilitate insects and possibly other arthropods. There is supporting evidence. The number of butterflies in the Netherlands is presently at the lowest point ever recorded , and the lowest numbers of butterflies are being recorded in the western part of the country (apart from the coastal dunes) . The water beetle Graphoderus bilineatus, widely recorded in the Netherlands up to the 1980s, is now nearly extinct in the western province of South-Holland. In a comprehensive appraisal of the impact of neonicotinoid insecticides on bumblebees, honey bees and other non-target invertebrates, Kindemba also concluded that significant negative impacts of imidacloprid on bees and other non-target insecticides occur at levels predicted to be present in the UK countryside (based on imidacloprid application rates approved for use in the UK).
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Stoughton SJ et al. (2008) Arch Environ Contam Toxicol 54:662-673 (attached);
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van Swaaij CAM et al. (2009). Vlinders en libellen geteld. Jaarverslag 2008, Vlinderstichting (Butterfly Foundation) Wageningen & the Dutch Central Statistics Office (CBS), The Hague. Report No. VS2009.007;
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Kindemba V (2009) The impact of neonicotinoid insecticides on bumblebees, honey bees and other non-target invertebrates. Buglife Invertebrate Conservation Trust, UK.
|Imidacloprid Contamination Dutch Surface Water.doc||52 KB|
|Dutch Land Use and Imidacloprid.jpg||1.74 MB|
|Tennekes_Sanchez-Bayo_JEAT_2011_Review Article.pdf||2.58 MB|
|Stoughton et al 2008.pdf||156.97 KB|