Imidacloprid - Expert overview - Bayer (2001)

With reference to Cox, Caroline (2001), Insecticide Factsheet / Imidacloprid, Northwest Coalition for Alternatives to Pesticides (NCAP),
Journal of Pesticide Reform, Vol. 21, No.1, pp.15-21
Bayer experts from different scientific fields compiled this position paper to allow a balanced assessment of imidacloprid. 

Introduction
In the NCAP fact sheet detailed information about imidacloprid has been compiled but with reference mainly to the intrinsic properties of the active ingredient. The whole article is therefore based mainly on the description of the hazards of imidacloprid. Presenting study results in this way is misleading and does not allow an objective overview or understanding.

Before a crop protection product can be marketed it has to pass a thorough investigation by each national regulatory authority. In this procedure, in all countries with high registration standards, a risk assessment is performed in line with internationally harmonised, standardised and validated testing guidelines. As a first step all studies are targeted to find out the intrinsic toxicity (hazard identification) of the compound and to establish dosages at which such an effect can not be observed (NOAEL = no-observed adverse effect level). These are the values which are mainly referred to in the NCAP fact sheet. In order to minimise or exclude any possible risk for the farmer, the consumer or the environment, it is important to collect information about the possible exposure. Even if a product is highly toxic for e.g. insects - if it is almost impossible that the insect will ever get in touch with this product these insects are not at risk! This is the second - and very important - step in a reasonable risk assessment that is often left out in the NCAP fact sheet. The NCAP fact sheet deals only with the intrinsic properties of imidacloprid (no real risk assessment of using the products), is citing studies without giving the whole picture and refers mainly to laboratory work, the results of which cannot directly be applied to practical field conditions.

In 1985, Bayer chemists synthesised imidacloprid for the first time. Because of its new mode of action controlling many important pests already resistant to other insecticides and its excellent systemic properties allowing a lot of innovative application techniques, farmers made this compound the most successful insecticide world wide within a decade. Today imidacloprid is marketed in more than 120 countries protecting more than 140 crops.

How does imidacloprid work?
Mode of action
Imidacloprid works differently to other insecticides presently being marketed (i.e. carbamates, organophosphates and pyrethroids). The mode of action is based on interference of the transmission of impulses in the nerve system of insects. Similar to the naturally occurring signal-transmitting acetylcholine, imidacloprid stimulates certain nerve cells by acting on a receptor protein. In contrast to acetylcholine, which is quickly degraded by the enzyme acetylcholine-esterase, imidacloprid is inactivated either very slowly or not at all. It has both contact and ingestion activity. The target pest’s feeding activity ceases within minutes to hours, and death occurs usually within 24 - 48 hours but can take up to 7 days depending on the mode of application. As to its performance: good reliable control, high selectivity, quick knock-down/protection and long residual activity are key features.

Systemic properties
Imidacloprid is characterised by its excellent systemic properties. The uptake of the active substance via the roots is an important prerequisite for soil-directed application, e.g. via irrigation systems (drench), in-furrow application, granular application including seedling-box application in rice, or seed treatment. Because of the excellent systemic activity and the low application rates, imidacloprid can be used as a seed dressing - trademark Gaucho® - as well as for foliar, soil and stem treatment - trademarks Confidor®, Admire®.

Biological spectrum
The biological spectrum of imidacloprid covers a broad range of target pests, such as:

  • sucking insects: aphids, whiteflies, leaf- and planthoppers, thrips, scales, mealy bugs, bugs, psyllids, phylloxera;
  • coleoptera (beetles): leaf beetles (e.g. Colorado potato beetle, rice water weevil), wireworms, grubs, flea beetles;
  • others: lepidopterous leaf­miners, some dipterous pests, termites, locusts, and fleas.

The trademarks for imidacloprid as a termiticide are Hachikusan® (Japan), Premise® (USA, Australia, Asia, world-wide). Under the trademark Advantage® it has been used commercially as a veterinary medicinal product for flea control on cats and dogs in the USA since 1996 and in Europe since 1997.

How toxic is imidacloprid?
Active ingredients to be used in plant protection must undergo an extensive battery of toxicological studies. The objective of these studies is to establish the toxicological hazard potential of the compound after single and repeated exposure so that an assessment can then be made of the risk to humans as users of the formulation and as consumers of the treated foodstuffs.

Accordingly, the toxicological testing performed with imidacloprid included a wide range of different study types:

  • The duration of compound administration to different species was increased progressively; from one single application (acute toxicity), through repeated feeding over several weeks (subacute/subchronic toxicity) to two year feeding (chronic toxicity).
  • All possible routes of administration were included (oral, dermal and inhalation).
  • The potential for specific toxic action such as developmental or reproduction toxicity, oncogenicity, neurotoxicity and genotoxicity, was checked.

From the results of these comprehensive studies it can be concluded that imidacloprid has a favourable toxicological profile for warm-blooded mammals. The symptoms observed following oral intake consisted of behavioural, respiratory and motility disturbances; narrowed palpebral fissures, transient trembling and spasms. They were reversible within six days. Imidacloprid was found to have practically no acute dermal toxicity and low acute inhalation toxicity. It is not irritating to skin or eyes and is not a skin sensitizer.

Mutagenity
No evidence of an oncogenic potential of imidacloprid was found in either the rat or the mouse long-term feeding studies. Imidacloprid exhibits no genotoxic or mutagenic potential under in vivo conditions.

Effects on reproduction
The reproductive toxicity of imidacloprid was investigated in a two-generation study in rats and in developmental toxicity studies in rats and rabbits. Reproduction behaviour and out­come were not negatively affected.

Overall the data show that imidacloprid has no primary reproductive toxicity and exerts no teratogenic potential.

Acute / Subchronic Toxicity
In an acute and a subchronic neurotoxicity screening study in rats investigating specific neuro-toxicological pa­rameters by a functional observation battery, by automated motor activity measurements, and by special neurohistopathology, no primary neurotoxic effects were found for imidacloprid. All effects observed were related to the general toxicity of this compound.

In conclusion, no specific areas of concern were identified in the toxicological profile for imi­dacloprid and no-observed adverse effect levels (NOAEL) were established. In a risk assessment using the lowest relevant NOAEL of the most sensitive species for a comparison with exposure values predicted for specific use scenarios always resulted in high margins of safety indicating that imidacloprid is safe for both, the operator and the consumer.

How toxic is imidacloprid for the environment ?
The ecotoxicological part of the NCAP article is implying hazards and risks to many groups of organisms by only mentioning the respective intrinsic toxicity values.

While it is acknowledged that imidacloprid is highly toxic to some groups of organisms e.g. insects, a high intrinsic toxicity alone does not mean a high risk.

With reference to the NCAP fact sheet the following examples of misleading wording are given.

Bird problems?
It is stated that "Other problems caused by imidacloprid in birds include ..... reduced egg production and hatching success (at exposures of 234 ppm in food).". It is, however, omitted that these effects occurred in a study where birds were fed the treated diet exclusively over a period of more than 20 weeks. Under natural conditions, such an exposure (at this level over such a long time) is completely unrealistic.

Egg shell thinning in birds?
In its first assessment EPA came to the conclusion that egg shell thinning was found in the avian reproduction study. It could be demonstrated, however, that this finding was due to an artefact in the measurements and that imidacloprid caused no eggshell thinning. This explanation was accepted by EPA thus it seems astonishing that the respective documentation is not cited in the NCAP paper, despite obviously detailed research and access to EPA internal communication documents.

Effects on earthworms
It is correct that imidacloprid is acutely toxic to earthworms. The sublethal effects shown in laboratory studies on e.g. sperm deformities or DNA damage must be seen in relation to exposure in the field. If these effects were relevant to natural conditions, they should also be detectable under practical conditions. Long-term field studies were performed under different agricultural conditions in which imidacloprid was applied over several years again and again. In no case did a long term-effect on earthworm populations occur. Thus, these laboratory-derived effects have no relevance to the field (due to lack of sufficiently high exposure or because they are not biologically relevant at the population level).

Effects on cats?
Linking the death of a cat, that was already ill with cancer to the treatment with a preparation containing imidacloprid is more than speculatory: in five years of world-wide monitoring of the use of imidacloprid preparations on cats, no single causal relationship between the death of a cat and the treatment with imidacloprid has been found. In addition the original paper states that imidacloprid was proven not to be the cause of death of this cat which also suffered from a final stage chronic cardiomyopathy.

Furthermore many millions of cats are treated yearly world-wide with imidacloprid preparations against fleas without any side effect. In several large, well-controlled GLP trials, cats - including weaned kittens at the age of eight weeks - received doses five-fold above the recommended therapeutic level with no signs of adverse effects.

How is the imidacloprid resistance management designed?
Since its introduction into the market more than ten years ago, and due to Bayer’s responsible care approach and strong support from the academic community, a strategy was designed to maintain this useful agricultural tool in the market for as long as possible, also with a view to future chloronicotinyls under development. Bayer has performed baseline susceptibility and cross-resistance studies for imidacloprid, and, on the basis of all these studies, guidelines were developed to prevent the development of possible resistance and cross-resistance (see Bayer AG (2000): Technical Information Brochure Confidor, Leverkusen).

There is an ongoing world-wide monitoring of critical field populations, which has shown no evident shift in sensitivity. Only two very local incidences of resistance related field failures (Long Island, USA, Colorado potato beetle; Almeria, Spain, whiteflies in greenhouses) have been reported.

Many studies have shown that there is no cross-resistance with any other class of insecticides, confirming imidacloprid’s unique mode of action. However, there is no doubt that, if any real resistance has been established in any pest(s), this problem cannot be solved by using other neonicotinoids.

What happens to imidacloprid in the environment?
The success of imidacloprid as a crop protection product would have been unthinkable had its short and long term impact on the environment brought about any adverse effects or irreversible changes. Assuming a use pattern which guarantees the desired protective effects, the behaviour in and between the compartments of the environment, biosphere, soil, water, and atmosphere, depends on physico-chemical and chemical properties defined principally by the chemical structure. Climatic differences and diversities of the soils must also be taken also into account. Which of the theoretical outcomes will predominate following application of a crop protection product, degradation, persistence, binding to soil, volatilisation, translocation into groundwater, runoff into surface due to rainfall after application, must be established either from physico-chemical data or by direct measurements.

In the case of imidacloprid it was proven beyond doubt that persistence of residues in soil due to repetitive application over several years; translocation into deeper soil horizons, groundwater, adjacent crops or surface waters; volatilisation; and transport through the air into other regions can be ruled out. This has been confirmed again and again by world-wide and long-term experience following its use in all major crops.

Degradation in soil
There is broad evidence from research at Bayer, as well as from independent sources that imidacloprid is degraded continuously though not very rapidly. Practical trials conducted under northern European conditions showed the half-life for dissipation to be less than six months.

Degradation ends with complete mineralization to carbon dioxide, though binding of intermediate degradates to soil also occurs. It is important to draw a line between relatively long lasting residence time and persistence in the soil. Imidacloprid cannot be classified as being persistent as it does not accumulate. Long-term trials under worst case conditions with the repeated use of imidacloprid over several years have demonstrated that maximum concentrations in soil will reach a plateau and will decline if no further applications occur.

Mobility in soil and leaching into groundwater
The translocation behaviour and particularly the leaching potential of a crop protection chemical from soil into groundwater is equivalent to its inclination for hydrophilic interactions or for interactions especially with water. Imidacloprid contains in its molecular structure substituents which cause a relatively high water solubility and a low affinity to hydrophobic structures found in ordinary organic matter. The parameters, which characterise this affinity, are the partition coefficient for the system octanol-water (Pow-value) and the soil adsorption coefficient normalised to the content of organic carbon (Koc-value). Pow and Koc-values are in a range where, translocation in soil and from soil is still negligible under ordinary conditions, but where the mobility is already sufficiently high for systemic action into the roots of plants or within plants for pest control.

Behaviour in water
Though imidacloprid is not intended to be applied directly in water, it nevertheless may enter water bodies due to spray drift or in extreme situations by runoff from treated fields after rainfall. It has been shown that no unacceptable harmful effects would occur under these circumstances as the substance will undergo complete elimination from water by photolytic reactions and by microbial activity. Though the substance is stable in sterile water in the dark, it decomposes readily under the influence of light. Biotic processes under the influence of microbes present in natural water and its sediments present another mechanism for the elimination of imidacloprid.

Behaviour in air
The principal feature of imidacloprid regarding its behaviour in air is its non-volatility. Its extremely low vapour pressure in combination with a relatively high water solubility precludes direct evaporation or evaporation driven by evaporating water from soil or plant surfaces. If the substance were to be found in air samples it could only be due to an aerosol resulting from spray application. Nevertheless, a transport of imidacloprid over larger distances in the air is negligible as its chemical life-time in the atmosphere is extremely short.

The use of imidacloprid in agriculture does not entail unacceptable harmful effects for the environment as the substance will disappear under all circumstances from the compartments soil, water and air.