Clothianidin

Clothianidin
IUPAC name 1-(2-Chlor-1,3-thiazol-5-ylmethyl)-3-methyl-2-nitroguanidine[1]
Identifiers
CAS number	210880-92-5 (E) N
PubChem	213027 (E)
ChemSpider	184723 (E) Y
KEGG	C18508 Y
MeSH	Clothianidin
ChEBI	CHEBI:39178 N
ChEMBL	CHEMBL259727 Y
Beilstein Reference	9196326, 8620724 (E)
Jmol-3D images	Image 1 Image 2
SMILES CNC(Nn(:o):o)=NCc1cnc(Cl)s1 CNC(N[N+]([O-])=O)=NCC1=CN=C(Cl)S1
InChI InChI=1S/C6H8ClN5O2S/c1-8-6(11-12(13)14)10-3-4-2-9-5(7)15-4/h2H,3H2,1H3,(H2,8,10,11) Y Key: PGOOBECODWQEAB-UHFFFAOYSA-N Y InChI=1/C6H8ClN5O2S/c1-8-6(11-12(13)14)10-3-4-2-9-5(7)15-4/h2H,3H2,1H3,(H2,8,10,11) Key: PGOOBECODWQEAB-UHFFFAOYAT
Properties
Molecular formula	C6H8ClN5O2S
Molar mass	249.68 g mol−1
Exact mass	249.008722922 g mol-1
Appearance	Colorless crystals
Density	1.61 g cm-3
Melting point	179 °C, 452 K, 354 °F
Solubility in water	327 mg dm-3 (at 20 °C)
log P	0.732
Acidity (pKa)	7.472
Basicity (pKb)	6.525
N (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Clothianidin is an insecticide developed by Takeda Chemical Industries and Bayer AG. Similar to thiamethoxam and imidacloprid, it is a neonicotinoid. Neonicotinoids are a class of insecticides which act on the central nervous system of insects with lower toxicity to mammals. According to the Environmental Protection Agency, "the fate and disposition of clothianidin in the environment suggest a compound that is a systemic insecticide that is persistent and mobile, stable to hydrolysis, and has potential to leach to ground water, as well as runoff to surface waters."^[2] Neonicotinoid insecticides are among the most widely used insecticides worldwide, but recently the uses of some members of this class have been restricted in some countries due to a possible connection to honey bee colony collapse disorder.

Clothianidin was first given conditional registration for use as a pesticide by the United States Environmental Protection Agency in April of 2003,^[2][3] pending the completion of additional study of its safety to be done by December of 2004 (later extended to May of 2005).^[4] The study was not completed until August of 2007.^[5] Clothianidin was granted an unconditional registration for use as a seed treatment for corn and canola on April 22, 2010.^[6] However, on November 2, 2010, after a review of the studies supplied by the manufacturer, the EPA released a memorandum in which they stated that the Bayer field study submitted did not appear to be adequate and it was reclassified as "supplemental".^[7][8][9]

Environmental impact

According to the United States Environmental Protection Agency (EPA) clothianidin generally poses less risk to agricultural workers and fish and wildlife when compared to the organophosphate and carbamate insecticide alternatives. Laboratory data shows that clothianidin is toxic to honey bees. Current labels for clothianidin products used as foliar treatments (e.g. spray applications) include bee hazard statements^[10] that prohibit use when plants are flowering and bees are in the area. The EPA states that they are not aware of any data demonstrating that bee colonies are subject to elevated losses due to long-term exposure to this compound.^[11]

Based upon acute toxicity studies, the EPA has classified clothianidin as Toxicity Category III.^[12] It is classified as a “not likely” human carcinogen. There are no to low concerns and no residual uncertainties with regard to pre- and/or postnatal toxicity from clothianidin. However, due to evidence of effects on the rat immune system and that juvenile rats appear to be more susceptible to these effects, and due to the lack of a developmental immunotoxicity study, a 10X database uncertainty factor is applied to all dietary exposure endpoints. Available data indicate that clothianidin on corn and canola should result in minimal acute toxic risk to birds. However, assessments show that exposure to treated seeds through ingestion may result in chronic toxic risk to non-endangered and endangered small birds (e.g., songbirds) and acute/chronic toxicity risk to non-endangered and endangered mammals. Clothianidin has the potential for toxic chronic exposure to honey bees, as well as other nontarget pollinators, through the translocation of clothianidin residues in nectar and pollen. Clothianidin should not present a direct acute or chronic risk to freshwater and estuarine/marine fish, or a risk to terrestrial or aquatic vascular and nonvascular plants.^[2]

In 2008 Germany revoked the registration of clothianidin for use on seed corn after an incident that resulted in the death of hundreds of nearby honey bees.^[13] Investigation of the incident revealed that it was caused by a combination of factors including the failure to use a polymer seed coating known as a "sticker", weather conditions that resulted in late planting when nearby canola crops were in bloom, a particular type of air-driven equipment used to sow the seeds which apparently blew clothianidin-laden dust off the seeds and into the air as the seeds were ejected from the machine into the ground. dry and windy conditions at the time of planting that blew the dust into the nearby canola fields where honey bees were foraging.^[14]and a higher application rate which had been authorized for a severe root worm infestation. Clothianidin was also restricted for a short period for use on rapeseed, however after evidence had shown that the problems resulting from maize seed were not transferable to rapeseed its use was reinstated under the condition that the pesticide be fixed to the rapeseed grains by means of an additional sticker, so that abrasion dusts would not be released into the air.^{[15] [16]}

In 2009 the German Federal Office of Consumer Protection and Food Safety decided to continue to suspend authorization for the use of clothianidin on corn because it has not yet been fully clarified to what extent and how bees come into contact with the active substances in the pesticides belonging to the neonicotinoid group (clothianidin, thiamethoxam and imidacloprid) when used on corn. In addition, on the basis of new findings, the question arose as to whether drops of liquid from plants which are taken in by bees pose an additional risk.^[17]

Neonicotinoid seed treatment uses are banned in Italy, but foliar uses are allowed. This action was taken based on preliminary monitoring studies showing that bee losses were correlated with the application of seeds treated with these compounds; Italy also based its decision on the known acute toxicity of these compounds to pollinators.^[18][19]

In August 2008, the Natural Resources Defense Council sued the EPA after the latter agency failed to provide records related to studies regarding clothianidin's possible effects on bees.^[20][21][22] When the study was ultimately released, it was criticized for lacking proper control groups; bee colonies were placed within fields of clothianidin-treated canola and untreated canola that were located within easy foraging range of each other, permitting each colony to feed from both fields.^[6][23] An internal EPA memo from November 2010 indicated several EPA researchers have also concluded the study was flawed, with deficiencies sufficient to render it of only "supplemental" value.^[24] According to the memorandum:

Clothianidin’s major risk concern is to nontarget insects (that is, honey bees). Clothianidin is a neonicotinoid insecticide that is both persistent and systemic. Acute toxicity studies to honey bees show that clothianidin is highly toxic on both a contact and an oral basis. Although EFED does not conduct RQ based risk assessments on non-target insects, information from standard tests and field studies, as well as incident reports involving other neonicotinoids insecticides (e.g., imidacloprid) suggest the potential for long term toxic risk to honey bees and other beneficial insects. An incident in Germany already illustrated the toxicity of clothianidin to honeybees when allowed to drift off-site from treated seed during planting.^[25]

Also in the memo:

A previous field study (MRID 46907801/46907802) investigated the effects of clothianidin on whole hive parameters and was classified as acceptable. However, after another review of this field study in light of additional information, deficiencies were identified that render the study supplemental. It does not satisfy the guideline 850.3040, and another field study is needed to evaluate the effects of clothianidin on bees through contaminated pollen and nectar. Exposure through contaminated pollen and nectar and potential toxic effects therefore remain an uncertainty for pollinators.^[24][26][27]

See also

• Colony collapse disorder
• Imidacloprid effects on bee population

References

1. ^ PubChem 213027
2. ^ ^{a b c} Clothianidin, Pesticide Fact Sheet, United States Environmental Protection Agency
3. ^ http://www.epa.gov/oppfead1/international/naftatwg/projects/jointreview/conventional-chem.pdf
4. ^ http://www.epa.gov/pesticides/chemical/foia/cleared-reviews/reviews/044309/044309-2003-03-11a.pdf
5. ^ http://www.epa.gov/pesticides/chemical/foia/cleared-reviews/reviews/044309/044309-2007-11-16a.pdf
6. ^ ^{a b} Philpott, Tom (10 Dec 2010). "Leaked document shows EPA allowed bee-toxic pesticide despite own scientists’ red flags". Grist. http://www.grist.org/article/food-2010-12-10-leaked-documents-show-epa-allowed-bee-toxic-pesticide-. 
7. ^ http://www.epa.gov/pesticides/chemical/foia/cleared-reviews/reviews/044309/044309-2010-11-02a.pdf
8. ^ http://www.epa.gov/pesticides/chemical/foia/cleared-reviews/reviews/044309/044309-2010-11-02b.pdf
9. ^ http://www.epa.gov/pesticides/chemical/foia/cleared-reviews/reviews/044309/044309-090201-113501-079801-2010-12-22a.pdf
10. ^ http://www.epa.gov/oppfead1/labeling/lrm/chap-08.pdf
11. ^ http://www.epa.gov/pesticides/about/intheworks/clothianidin-registration-status.html#international
12. ^ http://www.epa.gov/pesticides/regulating/labels/pest-label-training/module2/page2.html
13. ^ http://www.guardian.co.uk/environment/2008/may/23/wildlife.endangeredspecies
14. ^ http://www.epa.gov/oppfead1/cb/csb_page/updates/2008/bees-act.htm
15. ^ http://www.bvl.bund.de/EN/08_PresseInfothek_engl/01_Presse_und_Hintergrundinformationen/2008_07_15_hi_Bienensterben_en.html?nn=1414138
16. ^ "Background information: Bee losses caused by insecticidal seed treatment in Germany in 2008". German Federal Office of Consumer Protection and Food Safety (BVL). 2008-07-15. http://www.bvl.bund.de/EN/08_PresseInfothek_engl/01_Presse_und_Hintergrundinformationen/2008_07_15_hi_Bienensterben_en.html?nn=1414138. 
17. ^ "Maize seed may now be treated with "Mesurol flüssig" again". German Federal Office of Consumer Protection and Food Safety (BVL). 2002-02-09. http://www.bvl.bund.de/EN/08_PresseInfothek_engl/01_Presse_und_Hintergrundinformationen/2009_02_09_pi_Maissaatgut_Mesurol_en.html?nn=1414138. 
18. ^ http://www.epa.gov/opp00001/about/intheworks/ccd-european-ban.html
19. ^ Brandon Keim (Dec 13, 2010). "Leaked Memo Shows EPA Doubts About Bee-Killing Pesticide". Wired. http://www.wired.com/wiredscience/2010/12/epa-clothianidin-controversy/. 
20. ^ http://www.wired.com/wiredscience/2010/12/epa-clothianidin-controversy/
21. ^ http://www.nrdc.org/media/2008/080818a.asp
22. ^ "Lawsuit Seeks EPA Pesticide Data". San Francisco Chronicle. August 19, 2008. http://www.commondreams.org/archive/2008/08/19/11070/. 
23. ^ http://www.fastcompany.com/1709448/interview-with-a-bee-leaker-beekeeper-tom-theobald-discusses-the-epas-bee-toxic-pesticide-co
24. ^ ^{a b} Joseph DeCant, Michael Barrett (November 2, 2010). "Clothianidin Registration of Prosper T400 Seed Treatment on Mustard Seed (Oilseed and Condiment) and Poncho/Votivo Seed Treatment on Cotton.". United States Environmental Protection Agency. http://www.panna.org/sites/default/files/Memo_Nov2010_Clothianidin.pdf. 
25. ^ http://www.panna.org/sites/default/files/Memo_Nov2010_Clothianidin.pdf
26. ^ http://www.epa.gov/pesticides/about/intheworks/clothianidin-petition2.pdf
27. ^ http://www.epa.gov/pesticides/about/intheworks/clothianidin-registration-status.html

External links

• Cutler, G. Christopher; Scott-Dupree, Cynthia D. (2007). "Exposure to Clothianidin Seed-Treated Canola Has No Long-Term Impact on Honey Bees". Journal of Economic Entomology (Entomological Society of America) 100 (3): 765–772. doi:10.1603/0022-0493(2007)100[765:ETCSCH]2.0.CO;2. http://www.grist.org/i/assets/bees_Guelph.pdf.