Neonicotinoids

Neonicotinoids (also known as chloronicotinyls) are a new class of insecticides that are analogs of nicotine. Unlike nicotine, these insecticides are relatively nontoxic to mammals. Currently, there are several important insecticides in this class. 

Imidacloprid is a systemic insecticide with contact and stomach poison activity for control of sucking insects including aphids, leafhoppers, planthoppers, thrips, and whiteflies, and soil insects, termites, and some species of biting insects. It has an oral LD30 in rats of 450 mg/kg. 

Acetamiprid is a systemic insecticide used for control of aphids, Colorado potato beetles, leafhoppers, leafminers, thrips, and whiteflies. Its oral LD30 in rats is 417 mg/kg. 

Thiacloprid is a broad-spectrum systemic insecticide for use as a seed treatment and for foliar use to control aphids, leafminers, whiteflies, and other sucking and biting insects. Its oral LD50 in rats is 444-836 mg/kg. 

---

Imidacloprid is a widely used neonicotinoid insecticide that kills pests by targeting their central nAChRs. Levamisol is used to kill nematodes by acting on nAChRs in the worm s muscles. 

Many pesticides are not as novel as they may seem. Some, such as the pyre-throid and neonicotinoid insecticides, are modeled on natural insecticides. Synthetic pyrethroids are related to the natural pyrethrins (see Chapter 12), whereas the neo-nicotinoids share structural features with nicotine. In both cases, the synthetic compounds have the same mode of action as the natural products they resemble. Also, the synthetic pyrethroids are subject to similar mechanisms of metabolic detoxication as natural pyrethrins (Chapter 12). More widely, many detoxication mechanisms are relatively nonspecific, operating against a wide range of compounds that... 

Nicotine Acts on nicotinic receptor Neonicotinoids An insecticide in its own... 

Nicotine is a component of Nicotiana tabacum, the tobacco plant. It is toxic to many insects because of its action upon the nicotinic receptor of acetyl choline. It has served as a model for a new range of insecticides, the neonicotinoids, which also act upon the nicotinic receptor (Salgado 1999). 

It is very clear, therefore, that there have been many examples of neurotoxic effects, both lethal and sublethal, caused by pesticides in the field over a long period of time. Far less clear, despite certain well-documented cases, is to what extent these effects, especially sublethal ones, have had consequent effects at the population level and above. Interest in this question remains because neurotoxic pesticides such as pyre-throids, neonicotinoids, OPs, and carbamates continue to be used, and questions continue to be asked about their side effects, for example, on fish (Sandahl et al. 2005), and on bees and other beneficial insects (see, for example, Barnett et al. 2007). 

Speaking generally, many laboratory studies have shown behavioral effects in vertebrates or invertebrates or both exposed to organochlorine, carbamate, OP, pyre-throid, and neonicotinoid insecticides. However, the critical questions are (1) to what extent have these effects been demonstrated at normal levels of exposure in the field and (2), if such effects have occurred in the field, have there been knock-on effects at the population level These issues will be returned to in Section 16.7. 

At a more subtle level, behavioral disturbances may make it more difficult for animals to find food. Pyrethroids, carbamates, OPs, and neonicotinoids can disturb the foraging activity of bees (Thompson 2003). Interestingly, effects have been shown upon the wagtail dance of bees, and this disrupts communication between individuals as to the location of nectar-bearing plants. Also, the neonicotinoid imidacloprid has been shown to adversely affect conditioned responses such as proboscis extension of honeybees (Guez et al. 2001). Nicotinoids can disturb the functioning of cholinergic synapses, which are involved in the operation of the proboscis reflex as... 

Neonicotinoids are potent broad-spectrum insecticides that exhibit contact, stomach and systemic activity. Acetamiprid, imidacloprid, nitenpyram, thiamethoxam and thiacloprid are representatives of the neonicotinoid insecticides (Figure 1). The mechanism of action is similar to that of nicotine, acting on the central nervous system causing irreversible blocking of postsynaptic nicotinic acetylcholine receptors (nAChR). Neonicotinoid insecticides are often categorized as antagonists of the... 

Neonicotinoids are generally polar, nonvolatile crystals with high water solubility. They are nonionized at environmentally relevant pH and are stable to heat and sunlight. Neonicotinoids are stable to acid hydrolysis. Except for thiacloprid, they are susceptible to alkaline hydrolysis. 

Tolerances for pesticide residue and/or standard withholding registration of neonicotinoids in Japan are shown in Table 1. 

Residue analytical methods for neonicotinoids in crops, soil and water samples have been developed. The basic principle of these methods consists of the following steps extraction of the crop and/or soil samples with acetone or the other organic solvent, cleanup by liquid-liquid partition or column chromatography, and quantitative analysis by high-performance liquid chromatography with ultraviolet detection (HPLC/UV). Simple column cleanup procedures are used to improve the accuracy and sensitivity of these methods. 

In general, neonicotinoids (except for nitenpyram) are metabolized slowly in plants, and remain mainly as the parent compounds. The definition of crop residues is for the acetamiprid and imidacloprid parent molecule. The definition of crop... 

Several determination methods such as GC, HPLC, gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS) are used for the analysis of neonicotinoid residues. The applications of GC/MS and LC/MS are of increasing importance. The application of HPLC to the determination of neonicotinoids residues is limited, especially when metabolites (such as acetamiprid and nitenpyram) can be easily determined by GC after derivatization. 

HPLC and LC/MS. HPLC methodology coupled with ultraviolet (UV), fluorescence (FL), photodiode-array (PDA) and/or a mass spectrometry (MS) detection has been developed. In general, neonicotinoids can be determined by HPLC/UV. Typical HPLC operating conditions are given in Table 2. 

Table 2 HPLC and LC/MS operating conditions for the determination for neonicotinoids... 

Quantitation is performed by the calibration technique. A new calibration curve with neonicotinoid standard solutions is constructed for each set of analyses. The peak area or peak height is plotted against the injected amount of neonicotinoid. The injection volume (2 qL) should be kept constant as the peak area or peak height varies with the injection volume. Before each set of measurements, the GC or HPLC system is calibrated by injecting more than one standard solution containing ca 0.05-2 ng of neonicotinoid. Recommendation after constmcting the calibration curve in advance, standard solutions and sample solutions are alternately injected for measurement of actual samples. 

The LOD is an important criterion of the efficiency of an analytical method. It defines the smallest value of the concentration of a compound in the analytical sample. Detectable amounts of neonicotinoid insecticides range from 0.5 to 1 ng by HPLC. The LOQ ranges from 0.005 to 0.01 mg kg for vegetables, fruits and crops. 

HPLC determination can be carried out for most of the neonicotinoids. The average recoveries of imidacloprid in the various crops by the HPLC/PDA method were 88-94% at a fortification level of 0.25 mg and 96-99% at a fortification level of 0.05 mg kg . The overall average recovery for 30 samples was 95% with an RSD of 4.7%.12... 

The amount of neonicotinoids insecticide residue (R, mg kg ) in the sample is calculated by the following equation ... 

Wi = amount of neonicotinoid insecticide for Vj read from calibration curve (ng)... 

Extraction of neonicotinoid from crop materials is often performed using the classical methods, which include the coagulation of the oily material on a solid support prior to extraction. 

The polar character of neonicotinoids makes them, in general, potentially mobile in soil. Acetamiprid and nitenpyram have short soil persistence. Imidacloprid and thi-amethoxam, however, are sufficiently persistent in soil to be used for soil treatment. The definition of soil residues for the various neonicotinoid compounds except for imidacloprid are the parent compound and it metabolites. The metabolites of acetamiprid are lM-1-2, lM-1-4 and lC-0 (Figure 6). The metabolites of nitenpyram are 2-[N-(6-chloro-3-pyridyl-methyl)-A-ethyl]amino-2-methyliminoacetic acid (CPMA) and A-(6-chloro-3-pyridylmethyl)-Ai-ethyl-A -methylformamidine] (CPMF). 

Extraction of neonicotinoid residues from soil is much more difficult than their extraction from plant or water samples. Soil residues could exist as bound residue . Various extraction methods such as organic solvent extraction, supercritical fluid extraction (SEE), Soxhlet extraction and sonication have been used. Some extraction methods are described in the following. 

The definition of water residue for the neonicotinoid insecticides except for niten-pyram and thiacloprid is the parent molecule. For nitenpytram and thiacloprid both the parent and its metabolites are determined. These metabolites are 2-[A-(6-chloro-3-pyridylmethyl)-A-ethyl]amino-2-methyliminoacetic acid (CPMA) and... 

Solvent extraction. Extraction of neonicotinoid insecticides from water is a simple process involving saturation with sodium chloride and extraction with diethyl ether, dichloromethane or ethyl acetate. This extraction procedure will allow the simultaneous extraction of all neonicotinoids. 

Acetamiprid is a neonicotinoid insecticide with outstanding systemic activities and a broad insecticidal spectrum. Acetamiprid controls diverse soil and foliar insect pests infesting cotton, sugar beet, vegetables, fruits and other major food crops by both contact and stomach action... 

---