A quick search of uses didn’t disclose clinical treatment on humans but some risk studies have been done.
One is presented here:
“Summary of Health EffectsIn acute toxicity studies, technical imidacloprid was moderately toxic via the oral routeand of low toxicity via the inhalation and dermal routes of exposure. It was non-irritatingto the skin and eyes and it was not a skin sensitizer.Short-term toxicity studies via the oral, dermal and inhalation routes did not reveal anyadverse toxicological effects. Increased levels of mixed function oxidase were observedat high doses but in the absence of any other treatment-related findings, this was notconsidered to be an adverse effect. Summary evaluation of acute and subchronicneurotoxicity studies conducted with imidacloprid revealed no evidence ofneuropathology.Chronic toxicity studies did not result in any specific overt signs of intoxication, andthere was no evidence of oncogenicity. In a battery of genotoxicity studies, the weight ofthe evidence suggests that imidacloprid is not genotoxic.In reproductive and developmental toxicity studies, there was no evidence of adversereproductive or teratogenic effects. Fetotoxicity was observed in rats and rabbits. Inrabbits, the observed changes occurred at maternally toxic doses, and hence wereconsidered to be secondary to maternal systemic toxicity. In rats, a slight increase in theincidence of a common observation (wavy ribs) was not deemed toxicologicallysignificant.In toxicokinetic studies, imidacloprid was rapidly excreted, with approximately 90% ofthe administered dose excreted within 24 hours. Urinary excretion accounted for 70-80%of the dose while faecal excretion accounted for 17-25% of the dose. There was nosignificant accumulation in the tissues at 48 hours and only trace amounts were detectedin expired air.Occupational and bystander exposure assessments have been conducted to estimatepotential exposure to imidacloprid. For the turf use, for example, passive dosimetrymonitoring of adults during a choreographed routine on treated turf, as well asdetermination of residues available for transfer, were reviewed. The results of thesestudies provided estimates of dermal, inhalation and non-dietary ingestion exposure forchildren contacting treated turf during play.The PMRA has conducted dietary and occupational/bystander risk assessments forregistered uses of imidacloprid and risk levels are acceptable.
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Regulatory Note - REG2001-11Page 3In October, 1999, the U.S. EPA published a Data Call-In for pesticides thought to haveneurologic effects. Imidacloprid is among a class of insecticides, the neonicotinoids,whose mode of action is via a neurologic mechanism in insects. In their assessment, theU.S. EPA concluded that although there was no evidence of sensitivity in fetuses ascompared to maternal animals following in utero exposure in rats and rabbits, theadditional Food Quality Protect Act safety factor would be retained but reduced to 3×with a requirement for the registrant to conduct a developmental neurotoxicity study. ThePMRA will harmonize with this requirement by requesting the data at the same time.Summary of Environmental EffectsAs indicated in REG97-01, Admire, the Agency requested more data regarding theenvironmental impact of imidacloprid including studies on its toxicity to birds andaquatic organisms, terrestrial field dissipation, runoff modelling and groundwatermonitoring studies. Additional data have been received and reviewed. These data confirminitial findings regarding the persistence, potential mobility and toxicity to non-targetorganisms of imidacloprid. With respect to the groundwater monitoring studies, interimreports have been provided and final reports are anticipated. PMRA will continue toreview this additional information as well as any other studies that are submitted and willreport any new findings.Imidacloprid is classified as persistent under agricultural field crop conditions accordingto the classification scheme of Goring et al. (1975), with a DT50in soil in the order of1-2 years. The term DT50refers to the time it takes for 50% of the applied pesticide todissipate in the soil.By way of comparison, atrazine, with a DT50of 120 days, is classified as moderatelypersistent; diazinon, with a DT50of 40 days, is classified as slightly persistent; andacephate, with a DT50of 3 days, is classified as non-persistent using the sameclassification scheme (see Table 1).With a DT50of 21-33 days in turf-covered soils such as golf course/orchard settings,persistence of imidacloprid in soil is reduced in comparison to agricultural field cropconditions. The time for 90% of the applied imidacloprid to dissipate in turf-covered soil(i.e., DT90), however, was in the order of 1.2-2 years. This result indicated that, whileimidacloprid may be classified as slightly persistent in turf based on the DT50values, theDT90values indicate higher persistence and a potential for carryover in turf-covered soil.Imidacloprid is strongly bound to soils in which it has been allowed to age for 4-8 weeksafter application. The persistence of imidacloprid may lead to accumulation of residuesfrom repeat applications. It is assumed that soils do not have an infinite capacity to bindimidacloprid. Therefore if the binding capacity of the soil is reached, aged imidaclopridmay leach into groundwater. Bayer recognizes the complexity of the soil sorption issuessurrounding imidacloprid and is currently evaluating its own experimental database and
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Regulatory Note - REG2001-11Page 4published literature related to binding of imidacloprid by soil. Bayer will provide theresults of this analysis to the PMRA.The compound is highly soluble in water. Thus, freshly applied or unbound imidaclopridis subject to initial runoff. The physical/chemical properties of imidacloprid suggest ahigh leaching potential. Modelling systems, such as the Expert System for PesticideRegulatory Evaluations and Simulations (EXPRES), that incorporate productcharacteristics including solubility, persistence, and binding to soil can be used tocompare the leaching attributes of imidacloprid with registered pesticides whosecharacteristics have become recognized through long years of use.Although the U.S. EPA reached similar conclusions, they have taken a different approachin terms of acceptable use expansions requiring that groundwater monitoring studies beconducted to measure leaching under actual use conditions. Bayer is nearing completionof prospective groundwater studies over 4.5 years in California and Michigan withinvolvement of the U.S. EPA. The studies were performed in sandy agricultural fields inSalinas Valley, California, and Vestaberg, Michigan, overlying shallow groundwater, andtherefore reflect mobility and potential for groundwater contamination in highlyvulnerable settings. Bayer is also working with officials in Suffolk County, Long Island toconduct a general groundwater monitoring program in areas of agricultural andhorticultural use.Interim results submitted in 1998 by the registrant indicate that, after three years of use,low concentrations of imidacloprid and its metabolites were detected at sites in New Yorkand Michigan. Bayer will provide final study reports to the PMRA when available. Thereis no practical remedial action that can be taken once groundwater is contaminated with apesticide. This is of concern because groundwater can recharge wetlands and surfacewaters, especially in areas with a shallow groundwater table.Groundwater monitoring studies conducted in Ontario and Quebec in 1996 and 1997 bythe provincial authorities did not indicate leaching of imidacloprid or its metabolitesthrough the soil. Trace concentrations of imidacloprid, however, were detected ingroundwater from a single well adjacent to a potato field in Prince Edward Island.However, more recent sampling has not shown any additional detections of the chemicalin that well.Studies on experimental test plots and spot sampling of commercial agriculturaltreatments in the Atlantic provinces show concentrations of imidacloprid in runoff water.Ad hoc monitoring of tile drains in Ontario also have shown low concentrations ofimidacloprid in surface runoff water. Surface runoff potential is relevant to aquatic non-target organisms. The concentrations of imidacloprid detected in surface runoff water inthe Atlantic provinces in studies mentioned above have the potential to impact aquaticinvertebrate indicator species in streams and ponds.
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Regulatory Note - REG2001-11Page 5Imidacloprid has a broad spectrum of activity against a wide range of arthropodsincluding pests, parasites, predators of pests, and aquatic invertebrates.Although recognized as a highly persistent material in field crop settings, imidaclopriddoes not bioaccumulate as do chlorinated hydrocarbons. Imidacloprid is toxic to birds onan acute and reproductive effects basis. Precautionary statements regarding toxicity tobirds are required on product labels.PMRA’s initial review concluded that, although pollinators could be at risk because ofhigh toxicity of imidacloprid to bees exposed to direct treatment, or residues on bloomingcrops or weeds, this risk could be mitigated by a label statement contraindicatingapplication of the product to blooming crops when bees are visiting the treatment area.Since that time, the question of whether systemic residues of imidacloprid may occur innectar and pollen of flowering crops at concentrations harmful to bees has been the focusof an extensive research program. PMRA will be reviewing as a priority relevant studiesfrom the published literature and elsewhere to determine whether imidacloprid is thecause of adverse effects and mortalities of commercial pollinators.Table 1A comparison of persistence, solubility and mobility characteristics ofimidacloprid with selected pesticides, using the EXPRES model.Ranked in order ofDT50(days)Solubility(g/L)Leaching Potential¶(score)Leaching Index§(score)Imidacloprid(426)Acephate(650)Acephate(1.42 X 106)Acephate(4.25 X 106)Dimethoate(122)Dimethoate(25)Imidacloprid(9.96 X 103)Imidacloprid(4.24 X 106)Atrazine(120)Imidacloprid(0.51)Dimethoate(1.14 X 103)Dimethoate(1.39 X 105)Diazinon(40)Malathion(0.15)Atrazine(5.45 X 100)Atrazine(6.54 X 102)Acephate(3)Diazinon(0.040)Malathion(1.59 X 10-2)Diazinon(8.42 X 10-2)Malathion(1)Atrazine(0.033)Diazinon(2.11 X 10-3)Malathion(1.59 X 10-2)Notes:¶Potential to migrate through unsaturated zone to the water table.§Based on extent of the potential migration distance of the pesticide, i.e. how far it will migrate before degrading.
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Regulatory Note - REG2001-11Page 6Summary of Regulatory Rationales for Approved Uses of ImidaclopridA number of additional uses for imidacloprid have been approved since the initialregistration of this insecticide in 1995. These uses and the rationales for their approval arediscussed here and summarised in the attached Appendix I. Other uses also have beenproposed but were found not to meet the criteria outlined in REG97-01, Admire.Colorado Potato Beetle in Potato, Tomato; Spotted Tentiform Leafminer in Apple:The initial imidacloprid registration was granted for control of the CPB in potato ineastern Canada and secondly for control of spotted tentiform leafminer (STLM) in applein response to severe widespread insecticide resistance to registered products in thesepests. Registration was subsequently extended to include tomato, another host of CPBand to allow these uses across Canada. A maximum of a single in-furrow application(in potatoes) or two foliar applications per season and other precautionary measures wereincorporated into use directions of the product label to preclude or delay the developmentof CPB and STLM resistance to imidacloprid.Aphid in Field Lettuce: Use to control aphid pests, particularly lettuce aphid, was firstapproved in British Columbia as no effective alternative product was available. Withouteffective treatment, losses of up to 25% of the crop can be expected. This use was alsoextended across Canada as other lettuce-growing areas in Canada experienced similarneeds.Aphid and Whitefly in Greenhouse-Grown Plants (vegetable and ornamental); FleaAdulticide (cats and dogs): Limited risk of environmental exposure was anticipated withthese uses allowing consideration of Merit and Impower for greenhouse use andAdvantage for use on domestic pets.Seed Treatment in Canola, Corn: The insecticide lindane which was widely used as aprophylactic flea beetle seed treatment has come under international regulatory scrutinyand is under special review in Canada. Initially, the PMRA granted registration ofimidacloprid as a lindane replacement for treatment of canola seed for export only.Registration was then extended for use on canola seed planted in Canada on the conditionthat additional supervised residue trials be conducted. This condition has now been met.An assessment of the potential risk to birds from seed treatment use of imidaclopridindicated lower risk to birds compared to granular insecticides. The relatively lowapplication rates (grams active ingredient per hectare) associated with seed treatmentswere also taken into consideration in permitting this use. Registration for control of cornflea beetle on field corn was granted in May 2001.
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Regulatory Note - REG2001-11Page 7European Chafer, Japanese Beetle in Turf in Ontario and Quebec: The currentlyregistered alternative products for this use are the organophosphate insecticides,chlorpyrifos and diazinon and the carbamate, carbaryl. These insecticides are not aseffective as imidacloprid for a number of reasons including their shorter persistence andthe probable resistance in the target pests to these insecticides. Additional concerns suchas the relative potential for bystander and applicator exposure and the redundantapplication of diazinon and chlorpyrifos by users trying to overcome the performancelimitations of these products were also considered.ConclusionImidacloprid has value in controlling pests which have become resistant to otherinsecticides and as a potential replacement to insecticides that are under reevaluation.Nevertheless its potential to disrupt established integrated pest management (IPM)programs, to engender resistance in some species if used to excess, its broad spectrum ofactivity and its potential for mobility and persistence in the environment have led thePMRA to adopt the current regulatory approach to this insecticide. Imidacloprid useexpansions are considered only in the context of sustainable pest management programsand where mitigative measures can be incorporated into product labelling. The PMRArecognizes the contribution that provincial regulatory and extension personnel and otherexpert advisors can make to user compliance with these measures.The PMRA acknowledges the importance of working in partnership with growerorganizations and experienced extension specialists as well as pesticide manufacturers, tostrengthen IPM programs and manage the use of this insecticide.Regulatory limitations have been imposed with respect to imidacloprid because of itspotential to leach into surface and groundwater and to persist in soil. Review of additionaldata and information indicates that these regulatory limitations continue to be necessary.The PMRA will continue its judicious regulatory approach to imidacloprid. PMRA willcontinue to review additional information as well as any other studies that are submittedand will report any new findings.In conclusion, imidacloprid use expansions will continue to be considered only for uses inlow environmental risk situations or critical need uses in the context of sustainable pestmanagement programs and where mitigative measures can be incorporated into productlabelling.ReferencesGoring, C. A. I., D. A. Laskowski, J. H. Hamaker, and R. W. Meikle. 1975. Principles ofpesticide degradation in soil. pp. 135-172 in R. Haque and V. H. Freed, eds.Environmental Dynamics of Pesticides. Plenum Press, New York.
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Appendix IRegulatory Note - REG2001-11Page 8Appendix I Summary of approved uses of imidaclopridCropPestRateDate FirstRegistered /Renewal DateCommentsAdmire 240 F, Reg. No. 24094potatoColorado potatobeetle48 (foliar)-312(in-furrow) g a.i./haMaximum 312 g a.i.in-furrow or 2 foliar(2 X 48 g a.i.)applications perseason.April 28, 1995 -Dec 31, 2001First registered for use tocontrol CPB in potatoes ineastern Canada in 1995. Approved for use inpotatoes across Canada,April 21, 1999.appleapple; rosy appleaphidswhite appleleafhoppermullein bugtentiformleafminer55 g a.i./ha48 g a.i./ha91 g a.i./ha91 g a.i./haMaximum 2 foliarapplications perseason.July 27, 1997 -Dec 31, 2001First registered for useQuebec and Ontario,addition of BC in 1998.lettuceaphid48 g a.i./ha (foliar);156 - 312 (soildrench) g a.i./ha or2.5 g a.i./1000seedlings as transplantplug drench.Maximum 312 g infurrow or 2 foliarapplications perseasonAugust 20, 1999 -Dec 31, 2001First approved for use onfield lettuce in BritishColumbia August 20, 1999and extended for use inother lettuce-growing areasin Canada Dec. 17, 1999.tomatoColorado potatobeetle48 (foliar)-312(in-furrow) g a.i./haMaximum 312 g infurrow or 2 foliarapplications perseasonApril 15, 1996 -Dec 31, 2001Approved for use on fieldtomato in eastern Canadaonly.Gaucho 75 ST, Reg. No. 25556Gaucho 480 F, Reg. No. 26124mustard,canolaflea beetle394-787 g a.i./100 kgseedOct 26, 1999 -Dec 31, 2001Treatment of seed forexport to the US withGaucho 75 ST was firstregistered 1998.Treatment of seed for use inCanada, 1999.
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Appendix ICropPestRateDate FirstRegistered /Renewal DateCommentsRegulatory Note - REG2001-11Page 9field corncorn flea beetle254 g a.i./100 kg seedMay 10, 2001Gaucho 480 F approved fortemporary use on corn seeduntil July 2001.Merit 60 WP Greenhouse Insecticide, Reg. No. 25636Impower 60 WP Greenhouse Insecticide, Reg. No. 25658cucumber,tomato,vegetable(greenhouse)aphidwhitefly9.6 g a.i./1000 plantsin 1000 L waterJuly 21, 1998 -Dec 31, 2003Limited environmental risk.ornamentalplants(containergrown)aphidwhitefly8.0 g a.i./1000 L0.002-0.003 g a.i./potJuly 21, 1998 -Dec 31, 2003Limited environmental risk.Merit Solupak Insecticide 75 % WP, Reg. No. 25932Merit 0.5 G Insecticide, Reg. No. 25933airport,recreationalarea, lawn,turfEuropean chaferJapanese beetle330 g a.i./haJune 30, 1999 -Dec 31, 2001Approved for use inOntario and Quebec only.Registration grantedconditional on providingenvironment fate data inurban settings.Advantage Flea Adulticides, Reg. Nos. 25127, 25128, 24129, 25130, 25131, 25132cats, dogsadult fleasJune 23, 1997 -Dec 31, 2002Limited environmental risk;full registration...”