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TABLE 1 |
|||||
|
Hazard
Identification and Dose-Response Relationships for Imidacloprid
in Acute and Subchronic Toxicity Tests with Rodents (4, 40-43)
|
|||||
|
Toxicity
Test & Exposure Route*
|
Number
of Days Exposed
|
Doses
Tested (mg/kg)†
|
LD50
or LOAEL (mg/kg)
|
NOAEL
(mg/kg)
|
Notable
Symptoms
|
|
Acute
Oral
|
1
|
Technical
formulation
|
LD50
= 454
|
Death;
typical nervous system effects
|
|
|
Flowable
formulation
|
LD50
= 4067
|
||||
|
Acute
Dermal
|
1
|
LD50
> 5000
|
No
effects
|
||
|
Acute
Inhalation‡
|
4
h
|
LD50
> 0.069 mg/L (aerosols); LD50 > 5.3 mg/L (dust)
|
No
effects
|
||
|
Acute
Neurotoxicity Oral
|
1
|
0,
42, 151, 307
|
42§
|
<
42
|
Death;
decreased rearing behavior, grip strength, response to stimuli,
motor activity; increased abnormalities in gait and righting reflex
|
|
Subchronic
Dermal
|
21
days; 6 hours per day
|
1000
|
1000
|
No
effects
|
|
|
Subchronic
Inhalation
|
28
days; 6 hours per day
|
0,
0.005, 0.31, 0.191 mg/L as dust
|
0.31
mg/L
|
0.005
mg/L
|
Decreased
body weight gain, thymus, and heart weight; increased liver weight;
induction of liver detoxification enzymes
|
|
Subchronic
Diet
|
90
|
0,
10, 66, 205
|
66
|
10
|
Decreased
weight gain; decreased forelimb grip strength
|
|
*Oral
exposure refers to a single dose given directly down the esophagus
of the animal while diet exposure referes to mixing imidacloprid
with the food and allowing the animal to eat freely (ad lib). Dermal
exposure refers to shaving the animal's fur and placing the chemical
directly in contact with the skin for six hours per day. For inhalation
exposures, animals were placed in enclosed chambers and dusts containing
imidacloprid were blown in.
†Average
of male and female dose.
‡The
highest feasible dose of aerosols in air was 0.069 mg/L; a dust
formulation is shown for comparison (from reference 27).
§Some
observable effects on female motor activity but not statistically
different than the 0 mg/kg dose level.
|
|||||
Bear in mind that the purpose of an acute oral toxicity study is to determine an LD50 (lethal dose to 50% of the tested rats) and to characterize the array of symptoms during intoxication. Such studies are not very informative about potential hazards following exposure to environmental residues (as the rates of exposure are much higher than would actually occur in a typical real-life situation), but they are useful for warning people who work with purified materials.
In the related acute neurotoxicity study, the objective is to determine whether high (but nonlethal) single doses to rats cause long term neurological impairment, including limb paralysis and/or behavioral impediments. The highest doses of imidacloprid (307 mg/kg) resulted in the death of some individuals; survivors had decreased motor skills and response to auditory stimuli. However, symptoms in surviving rats subsided five days after exposure (40). At the lowest dose (42 mg/kg), females but not males exhibited reduced locomotor activity (Table 1).
In other short-term toxicity tests, neither the technical nor the flowable formulation of imidacloprid caused skin or eye irritation or sensitization, whether rats were exposed to single doses or repeated doses (4, 41). Rats exposed to imidacloprid in air for four weeks reacted to the highest doses with decreases in body weight gain, increased liver weights, and induction of liver enzymes responsible for detoxification processes (4) (Table 1).
In chronic exposure tests over two years, dietary exposure resulted in no evidence of cancer (Table 2) (40-43). In eight of nine tests, imidacloprid caused no mutations or chromosomal breakage. The one test showing chromosomal aberrations was a test-tube-type study (in vitro) and the cells exhibited toxicity, which makes the outcome unreliable for judging gene damage (41).
Imidacloprid did not affect reproduction of rats in a two-generation study with constant exposure to high levels in the diet (Table 2). Lack of an effect in reproduction studies suggests that imidacloprid is not a hormonally active substance (i.e., an endocrine system disrupter). However, imidacloprid fed to pregnant rats and rabbits at high, maternally toxic doses (100 mg/kg or 72 mg/kg, respectively) caused skeletal malformations in a small percentage of fetuses (Table 2) (4, 40). The occurrence of maternal toxicity during pregnancy makes interpretatng the fetal effects difficult.
TABLE 2 |
|||||
|
Hazard
Identification and Dose-Response Relationships for Imidacloprid
in Developmental, Reproductive, and Chronic Toxicity Tests with
Rodents* (40-43)
|
|||||
| Toxicity Test & Exposure Route† |
Number
of Days Exposed
|
Doses
Tested (mg/kg/day)
|
LOAEL
(mg/kg/day)
|
NOAEL
(mg/kg/day)
|
Notable
Symptoms at LOAEL Dose or Higher
|
| Chronic Diet (dog) |
365
|
0,
6, 15, 41/72‡
|
72
|
41
|
Increased
in oxidative enzyme activity
|
| Chronic/ Carcinogenicity Diet |
728
|
0,
5.7, 16.9, 51.3 (males)
|
16.9
|
5.7
|
Decreased
weight gain in females; increased thyroid lesions in males; no evidence
of carcinogenicity
|
|
0,
7.6, 24.9, 73 (females)
|
|||||
| Carcinogenicity Diet (mouse) |
730
|
0,
20, 66, 208, 414 (males)
|
414
|
208
|
Decreased
body weight gain, food & water consumption; no evidence of carcinogenicity
|
|
0,
30, 104, 274, 424 (females)
|
|||||
| Developmental Oral |
10
|
0,
10, 30, 100 (pregnant rats)
|
10
(mother) 100 (fetus)
|
30
(fetus)
|
Mother:
decreased body weight gain and food consumption; 5% of fetuses with
wavy ribs
|
| Developmental Oral (rabbit) |
12
|
0,
8, 24, 72 (pregnant rabbits)
|
72
|
24
|
Decreased
body weight gain and increased abortions; fetus with skeletal abnormalities
|
| Reproductive Diet |
Two
generations
|
0,
7.3, 18.3, 52.0 (males)
|
52
|
18.3
|
Decreases
in body weight in both generations
|
|
0,
8.0, 20.5, 57.4 (females)
|
|||||
|
*All
tests with rats unless otherwise indicated. |
|||||
Once the array of possible adverse effects is delineated during the hazard identification phase, the relationship between dose and effect is examined: How much is safe? First, we determine the harmless dose, the No Observable Adverse Effect Level (NOAEL). The lowest NOAEL among all of the acute and the chronic toxicity tests indicates the most sensitive toxicological effect; these, therefore, become the toxicological endpoints of concern.
For imidacloprid, the acute neurotoxicity test (Table 1) and the chronic dietary carcinogenicity test (Table 2) revealed the most sensitive toxicological endpoints. Although a NOAEL of 5.7 mg/kg/day was definitively established for the carcinogenicity study, the lowest dose tested in the acute neurotoxicity study (42 mg/kg/day) still caused symptomology, albeit statistically non-significant (43).
As toxicological endpoints of concern, NOAELs form the basis for estimating the safe exposure level where there is a reasonable certainty of no harm. This “safe” level is called the reference dose (RfD) and is calculated by dividing the NOAELs by 100 to hedge bets against humans being more susceptible to imidacloprid than rats and to account for the possibility of significant differences in susceptibility among different age groups. Thus, the RfD for acute and chronic toxicity is 0.42 mg/kg/day and 0.057 mg/kg/day, respectively.
The Food Quality Protection Act requires EPA to divide the RfD by an extra safety (or uncertainty) factor of up to tenfold if infants and children are more susceptible or react differently to a given dose than adults (based on developmental and reproductive toxicity studies). The FQPA safety factor may also be applied when neurotoxic symptoms do not subside after dosing, or when the database is incomplete. The resulting new dose is called the population adjusted dose (PAD) (Table 3).
TABLE 3 |
||||
|
Acute
Dietary Exposure and Human Health Risk Characterization for Imidacloprid*
(43)
|
||||
| Population Subgroup |
PAD†
(mg/kg/day)
|
Dietary
Exposure (mg/kg/day)
|
%
of PAD
|
DWLOC‡
(ppb)
|
| U.S. Population |
0.14
|
0.0322
|
23
|
3900
|
| Infants (< 1 y) |
0.14
|
0.049
|
35
|
900
|
| Children (1-6 y) |
0.14
|
0.0644
|
46
|
760
|
| Females (13-50 y) |
0.14
|
0.0252
|
18
|
3600
|
| *Exposure
represents the 99th percentile; i.e., a person’s diet resulting in
the indicated dose is receiving exposures greater than 99% of the
rest of the population †Population Adjected Dose, based on an RfD of 0.42 mg/kg and an FQPA 3X safety factor ‡Drinking Water Level of Comparison, represents the level of imidacloprid in water that would cause the addition of dietary and drinking water exposure to exceed the PAD. The estimated environmental concentration was 17.4 ppb (µg/L). |
||||
EPA determined that an extra 3X safety factor should be applied to imidacloprid for several reasons (40-43). First, they felt the database for the acute neurotoxicity study was incomplete, therefore no valid NOAEL had been determined. Second, imidacloprid caused neurotoxic symptoms (decreased motor activity in females) that lasted well beyond dosing. Third, EPA considered that imidacloprid and nicotine bind to the same nerve receptor, and nicotine can adversely affect brain development in fetal rats.
Although EPA claims to use a weight-of-evidence approach, the agency seemed to discount the fact that there was no statistically significant decrease in rat motor activity at the Lowest Observable Adverse Effects Level (LOAEL) of 42 mg/kg/day, and therefore this is likely the NOAEL. Furthermore, biochemical toxicity studies show that imidacloprid binds very poorly to rat acetylcholine nerve receptors, and therefore it is unlike nicotine in its ability to induce adverse effects. Nevertheless, the EPA has the last word, so the question at hand becomes how much exposure to expect.
When calculating human risk, the FQPA mandates that EPA consider routes of exposure besides food. Therefore, possible exposures from drinking water and other uses around the home are added to the theoretical exposure a person might get through eating food containing residues of the subject chemical. Imidacloprid has not yet been routinely analyzed in public databases produced by the USDA, so we do not have actual residue data to work with. Acting conservatively, EPA defaulted to a calculation method known as Theoretical Maximum Residue Contribution (TMRC).
For acute dietary exposure (a one-day exposure), the agency
Chronic (lifetime) dietary exposure was handled differently. The residue values were cut back using estimates as to how many acres of crops were actually treated. Figures for median (i.e., 50th percentile) exposures were used. The highest level of exposure was again in one- to six-year-olds, in this case, 0.0097 mg/kg/day (Table 4).
TABLE 4 |
||||
|
Chronic
Dietary Exposure and Human Health Risk Characterization for Imidacloprid
(43)
|
||||
| Population Subgroup |
PAD*
(mg/kg/day)
|
Dietary
Exposure (mg/kg/day)
|
%
of PAD
|
DWLOC†
(µg/L)
|
| U.S. Population |
0.019
|
0.0046
|
24
|
490
|
| Infants (< 1 y) |
0.019
|
0.0072
|
38
|
120
|
| Children (1-6 y) |
0.019
|
0.0097
|
51
|
92
|
| Females (13-50 y) |
0.019
|
0.0034
|
18
|
450
|
| *Population
Adjusted Dose, based on an RfD of 0.057 mg/kg and an FQPA 3X safety
factor. †See Table 3 for explanation of DWLOC; the concentration was estimated as 15.8 ppb in surface water and 1.4 ppb in ground water. |
||||
Imidacloprid analysis has not yet been included in the U.S. Geological Survey (USGS) National Water Quality Assessment program pesticides database yet, so actual residues in water, if any, are unknown. However, EPA always uses a combination of computer models to estimate residues, even when data are available. The agency estimated that surface water would have residues of 15.8-17.4 ppb, and ground water would have residues of 1.4 ppb. These are inordinately high levels given the low application rates of imidacloprid products (typically 0.1 to 0.5 lb per acre). However, imidacloprid does have a comparatively high water solubility (500 mg/L), persistence in soil, and mobility potential. (See the following article, “Imidacloprid: Insecticide on the Move.")
Imidacloprid has several registered residential uses. Because there is no evidence of imidacloprid causing toxicity via dermal and inhalational exposure (the usual routes of exposure following home and lawn use), EPA waived consideration of adult residential exposure (42). For children, there was a chance of hand-to-mouth soil and grass ingestion; EPA estimated a worst-case exposure of 0.072 mg/kg/day. If a household pet had been treated for fleas, the estimated exposure to a child engaging in hand-to-mouth behavior would be 0.058 mg/kg.
To determine the likelihood of harm following exposure by food, water, or residential use, EPA divides the estimated exposure by the PAD. The result for each exposure source and all sources added together should be less than 100%. For drinking water, however, EPA just estimates the residue level in water that should not be exceeded to maintain an exposure less than 100% of the PAD when all sources of exposure are aggregated.
Results of the various risk characterization calculations showed dietary exposure to imidacloprid was 50% or less of the PAD (Tables 3 and 4, “% of PAD”), indicating no cause for concern. The estimated water concentrations for imidacloprid were 10 to 100 times less than any level of concern (Tables 3 and 4, “DWLOC”).
For children’s residential exposure, EPA aggregated risk by using the chronic dietary exposure values. The resulting potential exposure to children was less than the PAD and no cause for concern.
In summary, imidacloprid risk to humans seems nil even when all exposure sources are considered. Since imidacloprid poses no hazard by dermal and inhalational exposure, workers should face minimal risk as well.
Although imidacloprid seems
pretty innocuous to mammals, largely because it does not bind nerve receptors
sufficiently to trigger nervous activity, one of its known degradation
products, desnitro imidacloprid (DNIMI) behaves like a mirror image. DNIMI
binds very strongly to mammalian nerve receptors but not to insect nerve
receptors. It is not toxic to insects, but it is about four to five times
more toxic than imidacloprid to mice (6, 38). Such damning information
could put the skids on imidacloprid’s hopes for reduced-risk status,
but digging into the details shows this concern may be a tempest in a
teapot.
First, the ability to bind to nerve receptors tends to correlate with toxicity, but it is far from a perfect correlation. Absorption potential and metabolism rate will modify toxicity. When the toxicity of DNIMI was compared to imidacloprid, mice were injected directly with the substances. By this route of exposure, the LD50 of imidacloprid dropped to about 50 mg/kg, and that of DNIMI was about 10 mg/kg (38). Toxicity of DNIMI was never measured by oral or dermal exposure, the most likely routes in the environment.
Second, if DNIMI were a significant product of metabolism, the rat would have been exposed to it during high-dose toxicity tests by oral exposure. Conceivably, the rats react at high doses because of DNIMI generation. However, rat metabolism studies submitted for EPA’s risk assessment indicated very little, if any, DNIMI was generated (41).
Third, metabolism of imidacloprid is very quick. About 90% of the dose of imidacloprid is excreted within twenty-four hours, along with any possible metabolites. After forty-eight hours, residual material (less than 0.5% of the original dose) was found in the liver, as would be expected from the main organ of detoxification, but not in the brain (41). Furthermore, if DNIMI ever made it into the brain, biochemical studies show it is about as likely to bind to nerve receptors as nicotine, but it detaches (disassociates) from the receptors about eight times faster (10). Thus, imidacloprid interactions with the nerve endings are very transitory compared to nicotine.
Fourth, studies of imidacloprid metabolism in plants indicate approximately ten percent or less (depending on the crop) transforms into DNIMI (44). Thus, for all practical purposes human exposure to DNIMI is negligible.
Despite the rigors of high-dose testing and the assignment of an extra FQPA safety factor, imidacloprid smells like a rose, thanks in part to its low toxicity and low potential for human exposure. But EPA can still nix or severely restrict the use of a pesticide if residues exceed levels thought to harm nontarget organisms.
Perhaps the most studied aspect of ecological effects is aquatic toxicity. Just like mammals, fish and invertebrates seem pretty resistant to imidacloprid. For most of the aquatic species tested, imidacloprid falls into EPA’s category of practically nontoxic (LC50 greater than 100,000 ppb) to slightly toxic (LC50 between 10,000 and 100,000 ppb) (Table 5). The one exception is the saltwater shrimp, Mysidopsis, on which imidacloprid receives a very highly toxic rating: LC50 less than 100 ppb.
TABLE 5 |
|||
|
Toxicity
Parameters Risk Quotients for Exposure of Aquatic Organisms to Imidacloprid
(based on 9, 27, 31, 36)
|
|||
| Test Organism* |
Acute
LC50 (µg/L)
|
NOEC†
(µg/L)
|
Risk
Quotient‡
|
|
AQUATIC
INVERTEBRATES
|
|||
| Water flea (Daphnia) |
10,440
85,000
|
0.002-0.0002
|
|
| Water flea-reproduction (21-day) |
1800
3600
|
0.010-0.005
|
|
| Brine shrimp (Artemia) |
361,230
|
0.00005
|
|
| Mysid shrimp (Mysidopsis) |
37
|
0.47
|
|
| Hyalella azteca (crustacean) |
55
|
0.32
|
|
|
Mosquito
(Aedes)
|
13
|
1.34
|
|
|
FISH
|
|||
| Golden orfe |
237,000
|
0.00007
|
|
| Rainbow trout |
211,000
|
0.00008
|
|
| Carp |
280,000
|
0.00006
|
|
| Trout, 21-day |
29,000
62,000
|
0.0006-0.0003
|
|
| *Exposure
durations for all tests, unless otherwise indicated, were between
48-96 hours. †No Observable Effect Concentrate. ‡Calculated as the estimated environmental concentration (17.4 ppb based on EPA modeling studies, USEPA 2001) divided by the LC50 (for acute toxicity) or the NOEC (for chronic toxicity). Quotients below 0.5 and 0.05 pose no concerns for risk of acute toxicity for non-endangered and endangered species, respectively. Quotients below 1 pose no concerns for risk of chronic toxicity. |
|||
Of course, innate toxicity is only part of the ecological risk game, but published studies of imidacloprid water residues for estimating exposure are rare. Using computer simulation models, EPA estimated surface water residues of 16 to 17 ppb (43). As usual, reality paints a different picture. For example, one Canadian government study reported recoveries of 0.1 to 4.4 ppb imidacloprid in streams near potato fields (19), far less than the EPA estimates. Even if imidacloprid makes it into water bodies, several published studies show that it is susceptible to degradation by sunlight (25). Residues steadily degrade even in the dark, where they have a half-life of about thirty-five to forty days (32). Nevertheless, comparison of imidacloprid toxicity to aquatic organisms with EPA’s exaggerated surface water residues suggests that risks of adverse acute or chronic effects are extremely low, especially to endangered fish species (Table 5).
Some concern has been expressed that imidacloprid may be toxic to birds, especially because it is commonly used as a seed treatment (9). While birds, on a body weight basis, seem more susceptible to imidacloprid toxicity than rodents when force-fed the pesticide, the LC50s from dietary exposure are quite high, suggesting a low susceptibility by normal routes of exposure (Table 6). Furthermore, studies of how birds handle seeds show that some or all of the outer husk, which would contain the greatest amount of imidacloprid from a seed treatment, is actually removed prior to ingestion (3). Imidacloprid-treated seed also seems repellent to several bird species (1, 2). Thus, the reality of exposure from the diet belies the comparatively low LD50s for birds.
TABLE 6 |
||||
|
Toxicity
Parameters and Risk Quotients for Exposure of Nontarget Terrestrial
Organisms to Imidacloprid (toxicity and EEC data from 8, 9, 23,
27, 31 33)
|
||||
| Test Organism & Exposure Method |
Acute
Oral LD50 (mg/kg body weight) or LC50 (mg/kg soil or feed)
|
NOEC*
|
EEC†
|
Risk
Quotient‡
|
|
INVERTEBRATES
|
||||
| Earthworm (Eisenia), 14 days, soil |
2.3
10.7
|
0.239
|
0.104-0.022
|
|
| Earthworm (Eisenia), sperm deformities, soil exposure, 10 days§ |
0.1
|
0.239
|
2.4
|
|
|
Honey
bee (Apis mellifera), dietary**
|
0.14
1.57
|
0.02
|
0.005
|
0.25
0.036
|
|
MAMMALS
|
||||
| Mouse (force-fed) |
131
- 168
|
15.1
|
0.109-0.085
|
|
|
BIRDS
|
||||
| Canary (force-fed) |
25
- 50
|
0.054
|
0.109-0.054
|
|
| House sparrow (force-fed) |
41
|
0.054
|
0.066
|
|
| Pigeon (force-fed) |
25
- 50
|
0.054
|
0.109-0.054
|
|
| Japanese quail (force-fed) |
31
|
0.054
|
0.088
|
|
| Bobwhite quail (force-fed) |
152
|
0.054
|
0.018
|
|
| Bobwhite quail (5-day dietary) |
1420
|
26.8
|
0.019
|
|
| Bobwhite quail (reproduction, dietary) |
>243
|
26.8
|
0.107
|
|
| Mallard duck (5-day dietary) |
>5000
|
26.8
|
0.005
|
|
| Mallard duck (reproduction, dietary) |
125
|
26.8
|
0.208
|
|
| *NOEC,
No Observable Effects Concentration, mg/kg feed or soil; based on
a chronic feeding study, usually observing effects of repeated daily
exposure and/or reproductive potential. †EEC, estimated environmental concentration. Soil concentrations for the earthworm risk characerization reflect a maximum soil application rate of 0.312 kg/ha (0.278 lb/A) on potatoes. The EECs applied to the avian force-feeding studies represent milligrams imidacloprid on treated seeds per square foot assuming a seed application rate equivalent to 0.117 kg/ha (0.104 lbs/A) and solid seeding (based on 26). The EECs for the mouse study assumed a 0.125 kg/ha (0.112 lb/A) overspray, large insect/forage plant concentration of 15.1 mg/kg, based on EPA-recommended values published in (15), and a 15-gram mouse eating 95% of its body weight. The EECs for the avian dietary toxicity studies assume foliage is contaminated to a level of 26.8 ppm following a 0.125 kg/ha spray application to various vegetables (based on 27). ‡Risk Quotient, RQ; the estimated environmental concentration divided by the LD50, LC50, or the NOEC; value must be less than 0.5 or 0.1 to be of no concern for acute toxicity risk to non-endangered and endangered species, respectively. For chronic toxicity risk, values must be less than 1. Note that the RQ for the avian acute toxicity results (force fed studies) actually represents the number of LD50 equivalents per square foot. §After 10 days of exposure, sperm deformities were 3.5% in soil with 0.2 mg/kg imidacloprid compared to 1.7% in soil without imidacloprid (23). **The higher RQ for bees is based on the oral LC50, and the lower RQ is based on the NOEC. |
||||
When estimated residues caused by overspraying plant material (leaves, fruits, seeds) are compared to the dietary LC50s of several avian species, a low potential for acute and chronic adverse effects is indicated (Table 6). Similarly, the expected exposure of a very small twenty-gram bird to treated seeds planted as a solid set across a field with five percent of them left on the surface shows risks fall substantially below EPA’s level of concern, even for endangered species.
EPA also considers risk to pollinators such as bees. Beekeepers in Canada and Europe have swarmed to complain about declining bee populations in recent years, pointing to imidacloprid as the culprit (5). According to one Internet document (8), imidacloprid-treated sunflower seeds result in mature plants with detectable levels of imidacloprid in nectar, and a metabolite of imidacloprid may be toxic to bees.
Because the oral LD50 of imidacloprid lies somewhere between 4 and 41 nanograms per bee (33), EPA considers the compound to be highly toxic to bees.
Despite beekeeper protestations and a high bee toxicity rating, published experiments tend to lead to a conclusion of low hazard under actual environmental conditions. For example, the oral LD50 of imidacloprid translates to a nectar concentration of between 0.14 and 1.6 mg/kg (33). Yet nectar and pollen tested did not contain any imidacloprid above the analytical limit of detection, 0.0015 mg/kg (33). One of the insect-toxic metabolites, imidacloprid olefin, tested with an oral LD50 of >36 ng/bee (29), but its residues were not found in sunflower honey or nectar (33). Bumblebees (Bombus terrestris), which have a similar susceptibility to insecticides as honey bees, were not harmed by sunflowers grown from imidacloprid-treated seeds (37). Work at Washington State University showed that honey bees fed syrup with 2 mg/kg imidacloprid reduced their visits to the feeder by only 7% (24), hardly a significant impact considering the natural mortality factors in any colony. Based on the risk quotient calculated using published values for the dietary LC50 equivalent and the levels of residues in sunflower nectar reported by the French beekeeping industry, EPA is likely to also conclude low toxicity risk to honey bees (Table 6).
When imidacloprid was first introduced to the market, it was heavily touted as being soft on insect and mite predators and parasitoids (27). Pest management specialists are constantly searching for the holy grail of pesticides—something toxic to specific pests but harmless to biocontrol organisms known as pest natural enemies. Now that imidacloprid has been on the market for about eight years, and entomologists have had a greater opportunity to study it, compatibility with integrated pest management (IPM) is a “yes-and-no” story. For every paper suggesting little harm to natural enemies (7, 13, 14, 20, 21, 45), there seems to be another paper suggesting incompatibility (11, 16, 17, 18, 22, 35). To be sure, imidacloprid is much less toxic than the traditional organophosphorus, carbamate, and pyrethroid insecticides, but it is no magic bullet. Part of the problem in making a generalization about compatibility lies in the variation among pest control situations.
While we can’t say definitively that imidacloprid is compatible with IPM systems, it is clear that the ability to use imidacloprid as a systemic soil or seed treatment should have definite benefits in protecting predators and parasitoids. Internal plant residues should not be accessible to insects probing along the leaf surface or scraping the epidermis. However, directly sprayed predators could be at risk (18). What remains to be seen is whether these predators would also become intoxicated after walking on dried deposits on leaf surfaces. Fortunately, imidacloprid seems to have a very short persistence on tomato leaf surfaces. Fifty percent of residues dissipate within 1.4 days under cloudy conditions; dissipation is even quicker (fifty percent in 0.7 day) under sunny conditions (34).
Another aspect of compatibility with IPM systems is the rapidity with which a pest is likely to develop resistance and whether the new pesticide is likely to be compatible in chemical rotation schemes designed to delay resistance development. During the development of imidacloprid, numerous generations of the pest aphid Myzus persicae were repeatedly treated with different concentrations of imidacloprid (27). After ninety generations, resistance did not develop, giving hope that insects under field conditions would not develop resistance as readily as they did to the conventional pesticides.
Presently, full-blown resistance to imidacloprid does not seem to be a problem, but one study has indicated wide susceptibility differences among different populations of the Colorado potato beetle (CPB) (30). The comparatively more tolerant CPB populations existed before imidacloprid’s widespread use on potatoes. However, the tolerant populations were also resistant to the carbamate insecticide carbofuran, which suggested the possibility of cross-resistance. Another study has shown that a field-collected strain of the tobacco aphid (Myzus nicotianae) exhibited a strong antifeeding response that made it tolerant in comparison to a known susceptible laboratory strain of the aphid (28). Whatever the mechanism of tolerance, the existence of variability in susceptibility among different populations rings the alarm for careful management to avoid resistance development (12).
Imidacloprid has the appearance of a reduced-risk pesticide with its comparatively low hazards and low exposure potential for humans and nontarget organisms. Although the published experiments with bees downplay imidacloprid’s hazards suggested by its very low LD50, more research is definitely needed to assuage beekeepers’ fears that growers have not substituted yet another bee killer for the highly toxic organophosphorous insecticides. And the jury may still be out on imidacloprid’s compatibility with IPM systems.
Imidacloprid is already registered for a myriad of agricultural, urban, and veterinary uses. Achieving reduced-risk status would accelerate registration of new uses or formulations. It would also be an admission that innovation in pesticide technology was moving toward human and environmental safety long before the FQPA was conceived. If outstanding questions about bees and IPM compatibility are addressed in the near future, growers will be definitively reassured that they have another admirable tool that can be relied on for efficacy without harming their family, their workers, and their environment.
Dr. Allan S. Felsot is a frequent contributor to this newsletter. He can be reached at (509) 372-7365 or afelsot@tricity.wsu.edu.
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It’s Not Your Granddaddy’s NicotineImidacloprid has been touted as the synthetic analog of the botanical product nicotine. Actually it is the first commercial pesticide in a family of chemicals originally known as nitromethylene heterocycles but now called neonicotinoids. The association of imidacloprid with nicotine sticks because they have similar biochemical interactions with the nervous system.
Briefly, both imidacloprid and nicotine bind to nerve receptors called nicotinic acetylcholine receptors (nAChRs). One of several types of protein receptors, nAChRs are embedded in nerve endings in the brain and at the muscles. They bind acetylcholine, a neurotransmitter chemical that is released from adjacent nerve membranes. Acetylcholine crosses a microscopic space (the synapse) separating two nerve endings. When acetylcholine binds to the receptor, the membrane becomes permeable (i.e., more porous) to sodium and potassium ions, thereby kicking off a nervous impulse called the action potential. The action potential is like a wave of electricity that travels down the length of the nerve until it gets to the end where acetylcholine neurotransmitters are released, cross the synapse, and repeat the cycle of binding to the receptor and jumpstarting the action potential. So, imidacloprid, like nicotine, is a nerve toxin that mimics the action of acetylcholine, and thereby heightens nerve firing with increasing doses. But, unlike nicotine which is extremely toxic in very small doses (smokers, beware!), imidacloprid toxicity to vertebrates is extremely low. Fortunately for mammals, birds, and fish, imidacloprid in contrast to nicotine hardly binds to their nAChRs. Insects, especially sucking bugs, however, are not so lucky. Their nervous systems are not only rich with nAChRs, but imidacloprid is particularly “sticky.” The end result is essentially an insect nervous breakdown. |
Imidacloprid was one of the first commercial insecticides
to be registered in what has become a growing class of pesticides called
neonicotinoids. It is manufactured and sold by the Bayer Company in several
formulations, including those under the names of Admire, Provado, Gaucho,
and Marathon. Imida-cloprid has remarkably high insecticidal activity
against aphids, white flies, and leafhoppers, tiny plant-sap-sucking insects
in the order Homoptera. (See related article, “Homoptera and Neonicotinyls,”
below. ) Imidacloprid also has activity against fleas, the Colorado potato
beetle, and termites.
Imidacloprid is one of the most versatile insecticides around. Its high
biological activity is expressed whether it is sprayed directly on foliage,
coated on seeds, or placed directly into the soil. Imidacloprid can be
applied by diverse methods because it is highly systemic. The compound
is easily absorbed by plant roots and transmitted through the xylem (vascular
system) to all growing parts. Imidacloprid also has the ability to move
from the treated side of a leaf to the untreated side, a property called
translaminar movement. Applying imidacloprid to soil or seeds keeps residues
inside the foliage, avoiding surface residue and airborne drift that can
occur from spray application, greatly reducing the possibility of exposure
to insect predators and parasitoids and human field workers.
Water solubility and vapor pressure are two of the most important properties
driving environmental distribution of a compound and thus exposure potential.
Exposure potential is also strongly influenced by biodegradation rate
(speed of breakdown by soil bacteria, plants, and animals), which determines
how long pesticide residues are likely to stick around. Imidacloprid has
a comparatively high water solubility (510 mg/L) and very low vapor pressure
(1.9 x 10-9 mm Hg), so it is unlikely to evaporate from soil and plant
surfaces and become an air contaminant. On the other hand, its biodegradation
rate in soil has been characterized as moderately slow, with about 50%
of the applied residue dissipating in a range of 48-190 days.
Although imidacloprid has a comparatively low potential to cause adverse
effects in mammals, birds, and fish, its high water solubility combined
with its persistence in soil has raised a few concerns about groundwater
contamination. Indeed, in early studies of imidacloprid’s potential
for sorption (a measure of its ability to adhere to soil particles), the
compound looked like a leacher. Subsequent studies in the United States
and France showed that sorption potential increased as imidacloprid concentration
deceased and as its residues “aged” in soil.
When used as a systemic (applied to soil as opposed to sprayed on foliage),
imidacloprid is applied at a maximum rate of only 1/3 pound (150 grams)
per acre in comparison to the one to two pounds of the older organophosphate
insecticides. Also, it is applied in the plant row or by the base of individual
plants instead of over the whole field. Nevertheless, the EPA has reported
that groundwater monitoring turned up residues of imidacloprid of 0.1-0.2
ppb in California and Michigan, and 1.9 ppb in Long Island, New York.
While such levels indicate a need to better manage how imidacloprid is
used, they are hundreds to thousands of times lower than levels that EPA
said it would be concerned about.
Dr. Allan S. Felsot is an Environmental Toxicologist with Washington
State University’s Food and Environmental Quality Laboratory. He
can be reached at his office on the Tri-Cities campus at (509) 372-7365
or afelsot@tricity.wsu.edu.
Aphids, cicadas, leafhoppers, planthoppers, treehoppers, psyllids, whiteflies, mealybugs, phylloxera, and scale insects are “homopterans.” Homoptera are a particular suborder of insects that derive their name from the Greek “homo-” meaning uniform and “ptera” meaning wings. Most homoptera have wings with a uniform texture that fold tent-like over the body when the insect is at rest. They also have piercing/sucking mouthparts, enabling them to feed by withdrawing sap from vascular plants. This is where the trouble begins.
Economic damage is manifested by homopterans in several different and specific ways.
Homoptera populations are typically
regulated by natural enemies, with a wide range of arthropods acting as
biological control agents. These beneficial insects include parasitic
braconid and chacicoid wasps and generalist predators such as ladybird
beetles, lacewings, and syrphid flies. As with many insect pests, population
outbreaks of homoptera are often the result of disruption of the natural
checks and balances within the agronomic, landscape, or forest system.
Because natural biological control of homopterans is so successful, researchers
have investigated use of biocontrol under outbreak conditions; indeed,
classical biocontrol has been successful in suppressing pest homopteran
populations to densities below economically damaging levels. Such interventions
are most useful in situations where the homopterans are causing direct
damage through their feeding or excrement of honeydew. Unfortunately,
when homopterans vector disease, classical biological control may not
provide sufficient population suppression. Under these circumstances,
insecticidal control is common.
Chemical control efforts against homopterans focused primarily on the
application of organophosphate nerve toxins in the years between World
War II and the 1970s. Systemic organophosphate insecticides like demeton,
disulfoton, and TEPP (among several others) were applied widely to a range
of crops and provided good control of a number of pest homopterans. Most
uses of these products have been restricted or limited due to risks associated
with environmental contamination or human health.
Over the past fifteen years, chemical control of homopterans has shifted to emphasize chloronicotinyl (a.k.a. neonicotinyl) insecticides. (See related article on imidacloprid, “Admiring Risk Reduction,” above.) Chloronicotinyls kill susceptible insects by binding to the receptor site for the neurotransmitter acetylcholine. Unlike organophosphate and carbamate insecticides that inhibit acetlycholinesterase (the enzyme that normally breaks down the neurotransmitter acetylcholine), neonicotinyls specifically bind to an insect’s nicotinic receptor. This causes the exposed insect’s nerves to fire uncontrollably, eventually leading to death.
Nicotine is a natural plant product that can be applied for insect pest control. However, natural nicotine is expensive to produce, is highly toxic, and is rapidly degraded and rendered ineffective by sunlight. Imidacloprid, thiocloprid, acetimiprid, are among these neonicotinyls that are less toxic to vertebrates but persist long enough under field conditions to control insects. (See box, “It’s Not Your Granddaddy’s Nicotine,” above.)
Imidacloprid was the first of the neonicotinyls to gain widespread registration in the United States. It controls most sucking insects, including aphids and leafhoppers, but is generally less toxic to chewing insects and is ineffective against moth and butterfly caterpillar pests.
Homoptera control has been
in the news recently because of a critical event in California: introduction
and establishment of the glassy-winged sharpshooter (GWSS, Homalodisca
coagulata). GWSS is an efficient vector of Pierce’s disease (Xylella
fastidiosa), a lethal disease of grapevines. The half-inch-long GWSS
feeds on plants infested with X. fastidiosa, then transmits it
to healthy vines. The Xylella bacterium attacks a plant’s
water-conducting tissues, resulting in infections that eventually cut
off water and nutrient movement through the vine.
Scientists in California have long known that X. fastidiosa is
transmitted to grapevines by blue-green sharpshooters (Graphocephala
atropunctata), a species in a subfamily of homopterans known as sharpshooter
leafhoppers. Since blue-green sharpshooters are relatively weak fliers,
they are not efficient X. fastidiosa vectors. The GWSS is a much
stronger flier, making it a much more threatening, less controllable vector
for Pierce’s disease.
GWSS and the disease it vectors spread rapidly from Ventura, California,
to the Mexican border, causing catastrophic economic losses to that region.
Recently, the pest was found in California’s Central Valley, posing
a potentially greater threat to the $1 billion California grape industry,
as well as other agricultural commodities in that productive growing region.
While most homopterans are host-specific to a single plant or related
group of plants, GWSS thrives on a wide range of common plants. Adding
insult to injury, there are many strains of Xylella, too; the various
strains have been known to infect crops from plums and berries to apples
and citrus. The combination of vector mobility and multiple pathogen strains
make this pest situation formidable indeed. Fortunately for those of us
in the Pacific Northwest, Xylella does not tolerate cold temperatures
well.
The establishment of the GWSS in California has led to increased use of imidacloprid. It appears to be an effective chemical control, with the added benefit of being relatively “soft.” (See related article, “Admiring Risk Reduction,” above.) So far, resistance development does not seem significant, but there are some indications that beneficial insect populations may be adversely affected by use of this chemical. For now, many uses for imidacloprid have been approved and other uses are pending. As for the other neonicotinyls, thiocloprid has been registered for use on several crops (including apples) and registrations for several other products in this class are pending.
Dr. Doug Walsh is an Entomologist with WSU. His office is located at the Irrigated Agriculture Research and Extension Center in Prosser. He can be reached at (509) 786-2226 or dwalsh@tricity.wsu.edu.
Washington State University (WSU) provides pre-license and recertification training for pesticide applicators. Pre-license training provides information useful in taking the licensing exam.
