Neonicotinoid#History

The precursor to nithiazine was first synthesized by Henry Feuer, a chemist at Purdue University, in 1970.{{cite journal |vauthors=Feuer H, Lawrence JP |date=1969 |title=The alkyl nitrate nitration of active methylene compounds. VI. A new synthesis of α-nitroalkyl heterocyclics. |journal=Journal of the American Chemical Society |volume=91 |issue=7 |pages=1856–1857 |doi=10.1021/ja01035a049}}{{cite book |vauthors=Jeschke P, Nauen R |chapter=Chapter 3: Neonicotinoid insecticides |veditors=Gilbert LI, Gill S |title=Insect Control: Biological and Synthetic Agents |location=London, England |publisher=Academic Press |date=2010 |chapter-url=https://books.google.com/books?id=nd2euFHjQyQC&pg=PA62 |page=62 |isbn=978-0-12-381450-0}}{{cite book |vauthors=Schaefer B |translator=Smith D, Janssen B |title=Natural Products in the Chemical Industry |location=Berlin, Germany |publisher=Springer Verlag |date=2015 |url=https://books.google.com/books?id=DbO4CQAAQBAJ&pg=PA734 |page=734 |isbn=978-3-642-54461-3}}

Shell researchers found in screening that this precursor showed insecticide potential and refined it to develop nithiazine.

In 1984 nithiazine's mode of action was found to be as a postsynaptic acetylcholine receptor agonist,{{Cite journal |vauthors=Schroeder ME, Flattum RF |doi=10.1016/0048-3575(84)90084-1 |title=The mode of action and neurotoxic properties of the nitromethylene heterocycle insecticides |journal=Pesticide Biochemistry and Physiology |volume=22 |issue=2 |pages=148–160 |year=1984|bibcode=1984PBioP..22..148S }} the same as nicotine. Nithiazine does not act as an acetylcholinesterase inhibitor, in contrast to the organophosphate and carbamate insecticides. While nithiazine has the desired specificity (i.e. low mammalian toxicity), it is not photostable—that is, it breaks down in sunlight and thus is not commercially viable.

In 1985, Bayer (Shinzo Kagabu) patented imidacloprid as the first commercial neonicotinoid.{{cite journal | vauthors = Tomizawa M, Casida JE | title = Neonicotinoid insecticide toxicology: mechanisms of selective action | journal = Annual Review of Pharmacology and Toxicology | volume = 45 | pages = 247–268 | year = 2005 | pmid = 15822177 | doi = 10.1146/annurev.pharmtox.45.120403.095930 | s2cid = 33621512 }}

During the late 1990s, imidacloprid became widely used.{{specify|reason=where, on which crops, against which pests|date=March 2015}} Beginning in the early 2000s, two other neonicotinoids, clothianidin and thiamethoxam, entered the market{{where|date=March 2015}}. {{As of|2013}}, virtually all US corn was treated with one of these two insecticides.{{cite journal | vauthors = Stokstad E | title = Pesticides under fire for risks to pollinators | journal = Science | volume = 340 | issue = 6133 | pages = 674–676 | date = May 2013 | pmid = 23661734 | doi = 10.1126/science.340.6133.674 | df = dmy-all | bibcode = 2013Sci...340..674S }} {{As of| 2014}}, about a third of US soybean acreage was planted with neonicotinoid-treated seeds, usually imidacloprid or thiamethoxam.{{cite web |work=U.S. Environmental Protection Agency |date=15 October 2014 |url=http://www2.epa.gov/sites/production/files/2014-10/documents/benefits_of_neonicotinoid_seed_treatments_to_soybean_production_2.pdf |title=Benefits of Neonicotinoid Seed Treatments to Soybean Production |archive-url=https://web.archive.org/web/20141017035702/http://www2.epa.gov/sites/production/files/2014-10/documents/benefits_of_neonicotinoid_seed_treatments_to_soybean_production_2.pdf |archive-date=17 October 2014}}

{{Update section|date=February 2022}}

Neonicotinoids have been registered in more than 120 countries. With a global turnover of €1.5 billion in 2008, they represented 24% of the global insecticide market. The market grew from €155 million in 1990 to €5.50 billion in 2023.{{Cite web |title=Neonicotinoid Pesticide Market by Type (Imidacloprid, Thiacloprid, Thiamethoxam, Acetamiprid), By Crops (Cereals, Oilseed, Pulses, Fruits, Vegetables and Others) and Region, Global trends and forecast from 2024 to 2030 |url=https://exactitudeconsultancy.com/reports/38308/neonicotinoid-pesticide-market/ |access-date=2024-03-14 |website=Exactitude Consultancy |language=en-US}} Neonicotinoids make up as much as 43% of insecticide weight applied to seeds,{{Cite web |url=https://academic.oup.com/bioscience/article/70/5/390/5805569 |access-date=2024-11-13 |journal=BioScience |doi=10.1093/biosci/biaa019 |title=Sowing Uncertainty: What We do and Don't Know about the Planting of Pesticide-Treated Seed |date=2020 |last1=Douglas |first1=Margaret R. |last2=Esker |first2=Paul D. |last3=Wechsler |first3=Seth |last4=Code |first4=Aimee |last5=Smith |first5=David J. |last6=Hitaj |first6=Claudia |volume=70 |issue=5 |pages=390–403 }} and accounted for 80% of all seed treatment sales in 2008.{{cite journal | vauthors = Jeschke P, Nauen R, Schindler M, Elbert A | title = Overview of the status and global strategy for neonicotinoids | journal = Journal of Agricultural and Food Chemistry | volume = 59 | issue = 7 | pages = 2897–2908 | date = April 2011 | pmid = 20565065 | doi = 10.1021/jf101303g | bibcode = 2011JAFC...59.2897J }}

As of 2011, seven neonicotinoids from different companies were on the market.

Imidacloprid is effective against sucking insects, some chewing insects, soil insects, and fleas on domestic animals. It is systemic with particular efficacy against sucking insects and has a long residual activity. Imidacloprid can be added to the water used to irrigate plants. Controlled-release formulations of imidacloprid take 2–10 days to release 50% of imidacloprid in water.{{cite journal | vauthors = Adak T, Kumar J, Shakil NA, Walia S | title = Development of controlled release formulations of imidacloprid employing novel nano-ranged amphiphilic polymers | journal = Journal of Environmental Science and Health, Part B | volume = 47 | issue = 3 | pages = 217–225 | year = 2012 | pmid = 22375594 | doi = 10.1080/03601234.2012.634365 | bibcode = 2012JESHB..47..217A | s2cid = 8121408 }}

It is applied against soil pests, seed, timber, and animal pests as well as foliar treatments.

{{as of| 2013}} neonicotinoids were used in the U.S. on about 95 percent of corn and canola crops, the majority of cotton, sorghum, and sugar beets and about half of all soybeans. They have been used on the vast majority of fruit and vegetables, including apples, cherries, peaches, oranges, berries, leafy greens, tomatoes, and potatoes, to cereal grains, rice, nuts, and wine grapes.{{cite web |vauthors=Grossman E |title=Declining Bee Populations Pose A Threat to Global Agriculture |url=http://e360.yale.edu/feature/declining_bee_populations_pose_a_threat_to_global_agriculture/2645/ |website=Yale Environment 360 |publisher=Yale School of Forestry & Environmental Studies |access-date=9 November 2014 |date=30 April 2013 |url-status=live |archive-url=https://web.archive.org/web/20141109090509/http://e360.yale.edu/feature/declining_bee_populations_pose_a_threat_to_global_agriculture/2645/ |archive-date=9 November 2014 |df=dmy-all}} Imidacloprid was possibly the most widely used insecticide, both within the neonicotinoids and in the worldwide market.

In agriculture, usefulness of neonicotinoid seed treatments for pest prevention depends upon the timing of planting and pest arrival. For soybeans, neonicotinoid seed treatments typically are not effective against the soybean aphid, because the compounds break down 35–42 days after planting, and soybean aphids typically are not present or at damaging population levels before this time.{{cite letter |vauthors=Myers C |recipient=Neil Anderson |subject=Benefits of Neonicotinoid Seed Treatments to Soybean Production |date=15 October 2014 |url=http://www2.epa.gov/sites/production/files/2014-10/documents/benefits_of_neonicotinoid_seed_treatments_to_soybean_production_2.pdf |publisher=US EPA |access-date=6 November 2014 |url-status=live |archive-url=https://web.archive.org/web/20141017035702/http://www2.epa.gov/sites/production/files/2014-10/documents/benefits_of_neonicotinoid_seed_treatments_to_soybean_production_2.pdf |archive-date=17 October 2014 |df=dmy-all}}{{cite journal | vauthors = Ragsdale DW, Landis DA, Brodeur J, Heimpel GE, Desneux N | title = Ecology and management of the soybean aphid in North America | journal = Annual Review of Entomology | volume = 56 | pages = 375–399 | date = September 2010 | pmid = 20868277 | doi = 10.1146/annurev-ento-120709-144755 | url = http://www.entomology.umn.edu/prod/groups/cfans/@pub/@cfans/@ento/documents/asset/cfans_asset_343751.pdf | access-date = 7 November 2014 | df = dmy-all | archive-url = https://web.archive.org/web/20141107055727/http://www.entomology.umn.edu/prod/groups/cfans/@pub/@cfans/@ento/documents/asset/cfans_asset_343751.pdf | archive-date = 7 November 2014 }}{{cite journal |vauthors=Hodgson EW, McCornack BP, Tilmon K, Knodel JJ |title=Management Recommendations for Soybean Aphid (Hemiptera: Aphididae) in the United States. |journal=Journal of Integrated Pest Management |volume=3 |pages=E1–E10 |date=2012 |doi=10.1603/IPM11019 |df=dmy-all |doi-access=free}} Neonicotinoid seed treatments can protect yield in individual cases such as late-planted fields or in areas with large infestations much earlier in the growing season.

Overall yield gains are not expected from neonicotinoid seed treatments for soybean insect pests in the United States, and foliar insecticides are recommended instead when insects do reach damaging levels.

Health Canada estimated that neonicotinoids provide benefits equivalent to over 3% of the national farm gate value of corn and 1.5% to 2.1% of the national farm gate value of soybean in 2013 .{{cite web |url=http://www.hc-sc.gc.ca/cps-spc/pest/part/consultations/_rev2016-03/rev2016-03-eng.php |title=Re-evaluation Note REV2016-03, Value Assessment of Corn and Soybean Seed Treatment Use of Clothianidin, Imidacloprid and Thiamethoxam |date=6 January 2016 |archive-url=https://web.archive.org/web/20160125002842/http://www.hc-sc.gc.ca/cps-spc/pest/part/consultations/_rev2016-03/rev2016-03-eng.php |archive-date=25 January 2016}}

The US EPA operates a 15-year registration review cycle for all pesticides.{{cite web |publisher=U.S. Environmental Protection Agency |url=http://www2.epa.gov/pesticide-reevaluation/registration-review-process |title=Registration Review Process |archive-url=https://web.archive.org/web/20140711185359/http://www2.epa.gov/pesticide-reevaluation/registration-review-process |archive-date=11 July 2014 |date=17 April 2014 |access-date=7 June 2014}} The EPA granted a conditional registration to clothianidin in 2003.{{cite web |work=U.S. Environmental Protection Agency |url=http://www.epa.gov/opp00001/chem_search/reg_actions/registration/fs_PC-044309_30-May-03.pdf |title=Pesticide Fact Sheet: Clothianidin |quote=Conditional Registration, Issued 30 May 2003 |archive-url=https://web.archive.org/web/20140326133528/http://www.epa.gov/opp00001/chem_search/reg_actions/registration/fs_PC-044309_30-May-03.pdf |archive-date=26 March 2014}} The EPA issues conditional registrations when a pesticide meets the standard for registration, but there are outstanding data requirements.{{cite web |work=U.S. Environmental Protection Agency |url=http://www2.epa.gov/pesticide-registration/conditional-pesticide-registration |title=Conditional Pesticide Registration |archive-url=https://web.archive.org/web/20140914044836/http://www2.epa.gov/pesticide-registration/conditional-pesticide-registration |archive-date=14 September 2014 |date=17 April 2014 |access-date=7 June 2014}} Thiamethoxam is approved for use as an antimicrobial pesticide wood preservative and as a pesticide; it was first approved in 1999.{{cite web |work=U.S. Environmental Protection Agency |date=21 December 2011 |url=http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2011-0581-0002 |title=Thiamethoxam Summary Document Registration Review Initial Docket |archive-url=https://web.archive.org/web/20150503044719/http://www.regulations.gov/ |archive-date=3 May 2015}} Imidacloprid was registered in 1994.{{cite web |work=U.S. Environmental Protection Agency |date=17 December 2008 |url=http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2008-0844-0002 |title=Imidacloprid Summary Document |archive-url=https://web.archive.org/web/20150503044719/http://www.regulations.gov/ |archive-date=3 May 2015}}

As all neonicotinoids were registered after 1984, they were not subject to reregistration, but because of environmental concerns, especially concerning bees, the EPA opened dockets to evaluate them.{{cite web |work=U.S. Environmental Protection Agency |url=http://www2.epa.gov/pesticide-reevaluation/groups-pesticides-registration-review#neonic |title=Groups of Pesticides in Registration Review: Neonicotinoids |archive-url=https://web.archive.org/web/20140711161759/http://www2.epa.gov/pesticide-reevaluation/groups-pesticides-registration-review |archive-date=11 July 2014 |date=17 April 2014 |access-date=7 June 2014}} The registration review docket for imidacloprid opened in December 2008, and the docket for nithiazine opened in March 2009. To best take advantage of new research as it becomes available, the EPA moved ahead the docket openings for the remaining neonicotinoids on the registration review schedule (acetamiprid, clothianidin, dinotefuran, thiacloprid, and thiamethoxam) to FY 2012. The EPA said that it expected to complete the review for the neonicotinoids in 2018.{{cite web |work=Press release: Pesticide Action Network, Center for Food Safety, and Beyond Pesticides |date=21 March 2013 |url=http://www.panna.org/press-release/beekeepers-and-public-interest-groups-sue-epa-over-bee-toxic-pesticides |title=Beekeepers and Public Interest Groups Sue EPA Over Bee-Toxic Pesticides |archive-url=https://web.archive.org/web/20140701154426/http://www.panna.org/press-release/beekeepers-and-public-interest-groups-sue-epa-over-bee-toxic-pesticides |archive-date=1 July 2014}}

In March 2012, the Center for Food Safety, Pesticide Action Network, Beyond Pesticides and a group of beekeepers filed an Emergency Petition with the EPA asking the agency to suspend the use of clothianidin. The agency denied the petition. In March 2013, the US EPA was sued by the same group, with the Sierra Club and the Center for Environmental Health joining, which accused the agency of performing inadequate toxicity evaluations and allowing insecticide registration based on inadequate studies.{{cite news |vauthors=Carrington D |title=US government sued over use of pesticides linked to bee harm |url=https://www.theguardian.com/environment/2013/mar/22/us-government-sued-pesticides-bee-harm |access-date=25 March 2013 |newspaper=The Guardian |date=22 March 2013 |url-status=live |archive-url=https://web.archive.org/web/20140212110231/http://www.theguardian.com/environment/2013/mar/22/us-government-sued-pesticides-bee-harm |archive-date=12 February 2014 |df=dmy-all}} The case, Ellis et al v. Bradbury et al, was stayed as of October 2013.{{cite web |work=Justia Dockets & Filings |url=http://dockets.justia.com/docket/california/candce/3:2013cv01266/264413 |title=Ellis et al v. Bradbury et al |archive-url=https://web.archive.org/web/20150519023213/http://dockets.justia.com/docket/california/candce/3:2013cv01266/264413 |archive-date=19 May 2015 |access-date=7 June 2014}}

On 12 July 2013, Rep. John Conyers, on behalf of himself and Rep. Earl Blumenauer, introduced the "Save American Pollinators Act" in the House of Representatives. The Act called for the suspension of the use of four neonicotinoids, including the three recently suspended by the European Union, until their review is complete, and for a joint Interior Department and EPA study of bee populations and the possible reasons for their decline.{{cite web |url=http://www.oregonlive.com/environment/index.ssf/2013/07/legislation_to_restrict_pestic.html |title=Legislation to restrict pesticide use proposed by Rep. Blumenauer |publisher=The Oregonian at 'OregonLive' |date=12 July 2013 |access-date=17 July 2013 |url-status=live |archive-url=https://web.archive.org/web/20130903083934/http://www.oregonlive.com/environment/index.ssf/2013/07/legislation_to_restrict_pestic.html |archive-date=3 September 2013 |df=dmy-all}} The bill was assigned to a congressional committee on 16 July 2013 and did not leave committee.{{cite web |work=Govtrack.us |url=https://www.govtrack.us/congress/bills/113/hr2692 |title=H.R. 2692: Saving America's Pollinators Act of 2013 |archive-url=https://web.archive.org/web/20140928153613/https://www.govtrack.us/congress/bills/113/hr2692 |archive-date=28 September 2014 |access-date=7 June 2014}}

The US EPA has taken a variety of actions to regulate neonicotinoids in response to concerns about pollinators.{{cite web |title=EPA Actions to Protect Pollinators |url=https://www.epa.gov/pollinator-protection/epa-actions-protect-pollinators |website=US EPA |access-date=24 March 2019 |language=en |date=3 September 2013}} In 2014, under the Obama administration, a blanket ban was issued against the use of neonicotinoids on National Wildlife Refuges in response to concerns about off-target effects of the pesticide, and a lawsuit from environmental groups. In 2018, the Trump administration reversed this decision, stating that decisions on neonicotinoid usage on farms in wildlife refuges will be made on a case-by-case basis.{{cite web |title=Trump administration lifts ban on pesticides linked to declining bee numbers |url=https://www.theguardian.com/environment/2018/aug/04/trump-administration-lifts-ban-on-pesticides-linked-to-declining-bee-numbers |website=The Guardian |access-date=24 March 2019 |date=4 August 2018}} In May 2019, the Environmental Protection Agency revoked approval for a dozen pesticides containing clothianidin and thiamethoxam as part of a legal settlement.{{cite news |vauthors=Allington A |date=21 May 2019 |title=EPA Curbs Use of 12 Bee-Harming Pesticides |url=https://news.bloombergenvironment.com/environment-and-energy/epa-curbs-use-of-12-bee-harming-pesticides |work=Bloomberg | access-date=1 July 2019}}

The first neonic was approved in the EU in 2005.{{cite web |website=Food Safety |url=https://ec.europa.eu/food/plants/pesticides/approval-active-substances/renewal-approval/neonicotinoids_en |title=Neonicotinoids |access-date=July 24, 2021}}

In 2008, Germany revoked the registration of clothianidin for use on seed corn after an incident that resulted in the death of millions of nearby honey bees.{{cite news |vauthors=Benjamin A |url=https://www.theguardian.com/environment/2008/may/23/wildlife.endangeredspecies |title=Pesticides: Germany bans chemicals linked to honeybee devastation |work=The Guardian | date=23 May 2008 |url-status=live |archive-url=https://web.archive.org/web/20130902082632/http://www.theguardian.com/environment/2008/may/23/wildlife.endangeredspecies |archive-date=2 September 2013 |df=dmy-all}} An investigation revealed that it was caused by a combination of factors:

• 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.{{cite web |url=http://www.epa.gov/oppfead1/cb/csb_page/updates/2008/bees-act.htm |title=EPA Acts to Protect Bees | Pesticides | US EPA |publisher=Epa.gov |access-date=11 October 2011 |archive-url=https://web.archive.org/web/20110204045731/http://www.epa.gov/oppfead1/cb/csb_page/updates/2008/bees-act.htm |archive-date=4 February 2011 |df=dmy-all}}

In Germany, clothianidin use was also restricted in 2008 for a short period on rapeseed. After it was shown that rapeseed treatment did not have the same problems as maize, its use was reinstated under the condition that the pesticide be fixed to the rapeseed grains by an additional sticker, so that abrasion dust would not be released into the air.{{cite web |url=http://www.bvl.bund.de/EN/08_PresseInfothek_engl/01_Presse_und_Hintergrundinformationen/2008_07_15_hi_Bienensterben_en.html?nn=1414138 |title=Background information: Bee losses caused by insecticidal seed treatment in Germany in 2008 |publisher=German Federal Office of Consumer Protection and Food Safety (BVL) |date=15 July 2008 |url-status=live |archive-url=https://web.archive.org/web/20111005203508/http://www.bvl.bund.de/EN/08_PresseInfothek_engl/01_Presse_und_Hintergrundinformationen/2008_07_15_hi_Bienensterben_en.html?nn=1414138 |archive-date=5 October 2011 |df=dmy-all}}

In 2009, the German Federal Office of Consumer Protection and Food Safety decided to continue to suspend authorization for clothianidin use on corn. It had not yet been fully clarified to what extent and in what manner bees come into contact with the active substances in clothianidin, thiamethoxam and imidacloprid when used on corn. The question of whether liquid emitted by plants via guttation, which bees ingest, posed an additional risk was unanswered.{{cite web |url=http://www.bvl.bund.de/EN/08_PresseInfothek_engl/01_Presse_und_Hintergrundinformationen/2009_02_09_pi_Maissaatgut_Mesurol_en.html?nn=1414138 |title=Maize seed may now be treated with "Mesurol flüssig" again |publisher=German Federal Office of Consumer Protection and Food Safety (BVL) |date=9 February 2009 |url-status=live |archive-url=https://web.archive.org/web/20111005203622/http://www.bvl.bund.de/EN/08_PresseInfothek_engl/01_Presse_und_Hintergrundinformationen/2009_02_09_pi_Maissaatgut_Mesurol_en.html?nn=1414138 |archive-date=5 October 2011 |df=dmy-all}}

Neonicotinoid seed treatment is banned in Italy, but foliar use is allowed.{{When|date=July 2021}} 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 based its decision on the known acute toxicity of these compounds to pollinators.{{cite web |title=Colony Collapse Disorder: European Bans on Neonicotinoid Pesticides – Pesticides – US EPA |website=epa.gov |date=June 23, 2010 |url=http://www.epa.gov/opp00001/about/intheworks/ccd-european-ban.html |archive-url=https://web.archive.org/web/20110904234638/http://www.epa.gov/opp00001/about/intheworks/ccd-european-ban.html |archive-date=September 4, 2011 |access-date=July 24, 2021}}{{cite magazine |url=https://www.wired.com/wiredscience/2010/12/epa-clothianidin-controversy/ |title=Leaked Memo Shows EPA Doubts About Bee-Killing Pesticide |magazine=Wired | date=13 December 2010 | vauthors = Keim B |url-status=live |archive-url=https://web.archive.org/web/20120602213044/http://www.wired.com/wiredscience/2010/12/epa-clothianidin-controversy |archive-date=2 June 2012 |df=dmy-all}}

In France, sunflower and corn seed treatment with imidacloprid are suspended; imidacloprid seed treatment for sugar beets and cereals are allowed, as is foliar use.{{When|date=July 2021}}

In 2012, the European Commission asked the European Food Safety Authority (EFSA) to study the safety of three neonicotinoids, in response to growing concerns about the impact of neonicotinoids on honey bees. The study was published in January 2013, stating that neonicotinoids pose an unacceptably high risk to bees and that the industry-sponsored science upon which regulatory agencies' claims of safety have relied may be flawed and contain data gaps not previously considered. Their review concluded, "A high acute risk to honey bees was identified from exposure via dust drift for the seed treatment uses in maize, rapeseed, and cereals. A high acute risk was also identified from exposure via residues in nectar and/or pollen."{{cite journal |publisher=European Food Safety Authority |year=2013 |title=Conclusion on the peer review of the pesticide risk assessment for bees for the active substance clothianidin |journal=EFSA Journal |volume=11 |issue=1 |page=3066 |doi=10.2903/j.efsa.2013.3066 |doi-access=}}{{cite journal |publisher=European Food Safety Authority |year=2012 |title=Assessment of the scientific information from the Italian project 'APENET' investigating effects on honeybees of coated maize seeds with some neonicotinoids and fipronil |journal=EFSA Journal |volume=10 |issue=6 |page=2792 |doi=10.2903/j.efsa.2012.2792 |doi-access=free}} EFSA reached the following conclusions:[http://www.efsa.europa.eu/en/press/news/130116?wtrl=01 EFSA identifies risks to bees from neonicotinoids] efsa.europa.eu 16 January 2013.{{cite journal |publisher=European Food Safety Authority |year=2013 |title=Conclusion on the peer review of the pesticide risk assessment for bees for the active substance clothianidin |url=http://www.efsa.europa.eu/en/efsajournal/pub/3066 |journal=EFSA Journal |volume=11 |issue=1 |page=3066 |doi=10.2903/j.efsa.2013.3066 |doi-access=|url-access=subscription }}

• Exposure from pollen and nectar. Only uses on crops not attractive to honey bees were considered acceptable.
• Exposure from dust. A risk to honey bees was indicated or could not be excluded, with some exceptions, such as use on sugar beet and crops planted in glasshouses, and for the use of some granules.
• Exposure from guttation. The only completed assessment was for maize treated with thiamethoxam. In this case, field studies showed an acute effect on honey bees exposed to the substance through guttation fluid.

EFSA's scientists identified several data gaps and were unable to finalize risk assessments for some uses authorized in the EU. EFSA also highlighted that risk to other pollinators should be further considered. The UK Parliament asked manufacturer Bayer Cropscience to explain discrepancies in the evidence they submitted.{{cite web |vauthors=Carrington D |date=16 January 2013 |url=https://www.theguardian.com/environment/2013/jan/16/insecticide-unacceptable-danger-bees |title=Insecticide 'unacceptable' danger to bees, report finds |archive-url=https://web.archive.org/web/20130824121909/http://www.theguardian.com/environment/2013/jan/16/insecticide-unacceptable-danger-bees |archive-date=24 August 2013 |work=The Guardian}}

In response to the study, the European Commission recommended a restriction on their use across the European Union. On 29 April 2013, 15 of the 27 EU member states voted to restrict the use of three neonicotinoids for two years starting 1 December 2013. Eight states voted against the ban, while four abstained. The law restricted the use of imidacloprid, clothianidin, and thiamethoxam for seed treatment, soil application (granules), and foliar treatment in crops attractive to bees. Temporary suspensions had previously been enacted in France, Germany, and Italy. In Switzerland, where neonicotinoids were never used in alpine areas, neonics were banned because of accidental poisonings of bee populations and the relatively low safety margin for other beneficial insects.{{cite web |title=Insektizide und Bienen: Was soll die Einschränkung der Neonicotinoide bringen? - NZZ.ch |website=Neue Zürcher Zeitung |date=May 8, 2013 |url=https://www.nzz.ch/wissen/wissenschaft/was-soll-die-einschraenkung-der-neonicotinoide-bringen-ld.1046509 |archive-url= |archive-date= |url-status=|language=de |access-date=July 24, 2021}}

Environmentalists called the move "a significant victory for common sense and our beleaguered bee populations" and said it is "crystal clear that there is overwhelming scientific, political, and public support for a ban." The UK, which voted against the bill, disagreed: "Having a healthy bee population is a top priority for us, but we did not support the proposal for a ban because our scientific evidence doesn't support it." Bayer Cropscience, which makes two of the three banned products, remarked, "Bayer remains convinced neonicotinoids are safe for bees when used responsibly and properly … clear scientific evidence has taken a back-seat in the decision-making process."{{cite news |title=Bee-harming pesticides banned in Europe |work=The Guardian |vauthors=Carrington D |date=29 April 2013 |url=https://www.theguardian.com/environment/2013/apr/29/bee-harming-pesticides-banned-europe |access-date=1 May 2013 |url-status=live |archive-url=https://web.archive.org/web/20130820230126/http://www.theguardian.com/environment/2013/apr/29/bee-harming-pesticides-banned-europe |archive-date=20 August 2013 |df=dmy-all}} Reaction in the scientific community was mixed. Biochemist Lin Field said the decision was based on "political lobbying" and could lead to the overlooking of other factors involved in colony collapse disorder. Zoologist Lynn Dicks of Cambridge University disagreed, saying "This is a victory for the precautionary principle, which is supposed to underlie environmental regulation." Simon Potts, Professor of Biodiversity and Ecosystem Services at Reading University, called the ban "excellent news for pollinators", and said, "The weight of evidence from researchers clearly points to the need to have a phased ban of neonicotinoids."

The decision came up for review in 2016. In March 2017, The Guardian printed an article that claimed that they had obtained information that indicated that the European Commission wanted a complete ban and cited "high acute risks to bees". A vote on the ban was expected in 2017 but delayed until early 2018 to assess the scientific findings.{{cite news |vauthors=Carrington D |title=Europe poised for total ban on bee-harming pesticides |url=https://www.theguardian.com/environment/2017/mar/23/europe-poised-for-total-ban-on-bee-harming-pesticides |newspaper=The Guardian |access-date=July 4, 2017 |url-status=live |archive-url=https://web.archive.org/web/20170630202116/https://www.theguardian.com/environment/2017/mar/23/europe-poised-for-total-ban-on-bee-harming-pesticides |archive-date=30 June 2017 |df=dmy-all |date=2017-03-23}}{{cite web |vauthors=Stokstad E |title=European agency concludes controversial 'neonic' pesticides threaten bees |url=https://www.science.org/content/article/european-agency-concludes-controversial-neonic-pesticides-threaten-bees |website=Science Mag |access-date=4 April 2018 |url-status=live |archive-url=https://web.archive.org/web/20180307192943/http://www.sciencemag.org/news/2018/02/european-agency-concludes-controversial-neonic-pesticides-threaten-bees |archive-date=7 March 2018 |df=dmy-all |date=2018-02-28}}{{Cite web |title=French firm breeds plants that resist climate change |url=https://www.eib.org/en/stories/breeding-plants-climate-change |access-date=2023-01-25 |website=European Investment Bank |language=en}}

On 27 April 2018, member states of the European Union agreed upon a total ban on neonicotinoid insecticide use, except within closed greenhouses, to be imposed from the end of 2018.{{cite news |vauthors=Carrington D |title=EU agrees total ban on bee-harming pesticides |url=https://www.theguardian.com/environment/2018/apr/27/eu-agrees-total-ban-on-bee-harming-pesticides |work=The Guardian |access-date=27 April 2018 |url-status=live |archive-url=https://web.archive.org/web/20180427101618/https://www.theguardian.com/environment/2018/apr/27/eu-agrees-total-ban-on-bee-harming-pesticides |archive-date=27 April 2018 |df=dmy-all}} The ban applies to the three main neonicotinoid active compounds: clothianidin, imidacloprid and thiamethoxam.{{cite news |title=EU to fully ban neonicotinoid insecticides to protect bees |url=https://www.reuters.com/article/eu-environment-bees/eu-to-fully-ban-neonicotinoid-insecticides-to-protect-bees-idUSS8N1QI00F |access-date=29 April 2018 |work=Reuters |date=27 April 2018}} Use of the three compounds had been partially restricted in 2013.{{cite news |vauthors=McGrath M |title=EU member states support near-total neonicotinoids ban |url=https://www.bbc.com/news/science-environment-43910536 |access-date=29 April 2018 |work=BBC |date=27 April 2018}} The vote on the proposed ban followed a February 2018 report from the European Food Safety Authority which concluded that neonicotinoids posed a high risk to both domestic and wild bees.{{cite journal |title=EU expected to vote on pesticide ban after major scientific review |journal=Nature |date=February 28, 2018 |doi=10.1038/d41586-018-02639-1 | vauthors = Butler D |volume=555 |issue=7695 |pages=150–151 |bibcode=2018Natur.555..150B |doi-access=free}} Voting on the issue had previously been postponed on multiple occasions. The ban had strong public support, but faced criticism from the agrochemical industry, and from certain farmers' groups.

The ban on neonicotinoids caused pseudo-jaundice virus devastation in certain sugar beet fields, reducing harvests in one of the world's largest beet sugar producers and endangering the industry. {{Citation needed|date=April 2025}} France subsequently extended the ban until 2023.{{Cite web |date=2023-01-25 |title=Sugar beet farmers cry foul after French U-turn on bee-killing pesticide |url=https://www.rfi.fr/en/france/20230125-sugar-beet-farmers-cry-foul-after-french-u-turn-on-bee-killing-pesticide-neonicotinoid |access-date=2023-01-25 |website=RFI |language=en}}{{Cite web | vauthors = Kiš N |date=2023-01-25 |title=French farmers warn pesticide u-turn will impact output |url=https://brusselsmorning.com/french-farmers-warn-pesticide-u-turn-will-impact-output/29999/ |access-date=2023-01-25 |website=Brussels Morning Newspaper |language=en-GB}}

In January 2013, the Humboldt Forum for Food and Agriculture e. V. (HFFA), a non-profit think tank, published a report on the value of neonicotinoids in the EU. On their website HFFA lists as their partners/supporters: BASF SE, the world's largest chemical company; Bayer CropScience, makers of products for crop protection and nonagricultural pest control; E.ON, an electric utility service provider; KWS Seed, a seed producer; and the food company Nestlé.

The study was supported by COPA-COGECA, the European Seed Association and the European Crop Protection Association, and financed by neonicotinoid manufacturers Bayer CropScience and Syngenta. The report looked at the short- and medium-term impacts of a complete ban of all neonicotinoids on agricultural and total value added (VA) and employment, global prices, land use, and greenhouse gas (GHG) emissions. In the first year, agricultural and total VA would decline by €2.8 and €3.8 billion, respectively. The greatest losses would be in wheat, maize, and rapeseed in the UK, Germany, Romania, and France. 22,000 jobs would be lost, primarily in Romania and Poland, and agricultural incomes would decrease by 4.7%. In the medium-term (5-year ban), losses would amount to €17 billion in VA, and 27,000 jobs. The greatest income losses would affect the UK, while most job losses would occur in Romania. Following a ban, the lowered production would induce more imports of agricultural commodities into the EU. Agricultural production outside the EU would expand by 3.3 million hectares, leading to additional emissions of 600 million tons of carbon dioxide equivalent.{{cite web |vauthors=Noleppa S, Hahn T |url=http://www.neonicreport.com/wp-content/uploads/2013/01/HFFA%20Report.pdf |title=The value of Neonicotinoid seed treatment in the European Union: A socio-economic, technological and environmental review. |archive-url=https://web.archive.org/web/20131015131734/http://www.neonicreport.com/wp-content/uploads/2013/01/HFFA%20Report.pdf |archive-date=15 October 2013 |work=Humboldt Forum for Food and Agriculture (HFFA) |date=2013}} {{citation needed|date=April 2018}}

When the report was released, Peter Melchett, policy director of the Soil Association, which has been working to ban neonicotinoids in the UK, commented that since the report was funded by Bayer Crop Sciences and Syngenta, "it was probably unlikely to conclude that neonicotinoids should be banned". The spokesperson further stated: "On the one hand, the chemical companies say we risk the additional costs to farmers amounting to £630 million. On the other, the possible cost of losing pollinating insects is thought to be worth three times as much (£1.8 billion*) to UK farmers."{{cite web |url=http://www.sacert.org/news/newsandfeatures/articleid/4826/soil-association-comment-the-humboldt-forum-for-food-and-agriculture-report |title=Soil Association comment: The Humboldt Forum for Food and Agriculture report |archive-url=https://web.archive.org/web/20140714182420/http://www.sacert.org/news/newsandfeatures/articleid/4826/soil-association-comment-the-humboldt-forum-for-food-and-agriculture-report |archive-date=14 July 2014 |date=15 January 2013 |work=Soil Association Certification}}

The use of pesticides in Canada is a matter of federal jurisdiction. In 2016, Health Canada proposed phasing out imidacloprid over the next three to five years.{{cite web |url=http://www.cbc.ca/news/canada/british-columbia/health-canada-imidacloprid-neonicotinoid-1.3864450 |title=Ban on controversial pesticide proposed by Health Canada | work = CBC News |access-date=2018-02-24 |url-status=live |archive-url=https://web.archive.org/web/20180214231353/http://www.cbc.ca/news/canada/british-columbia/health-canada-imidacloprid-neonicotinoid-1.3864450 |archive-date=14 February 2018 |df=dmy-all}} The government has voiced concerns regarding the impact of neonics on bees, invertebrate waterspecies, and birds.

In Ontario, nearly all corn seeds and a majority of soybeans get treated with neonicotinoids. In the summer of 2015, the province passed a law to reduce the presence of neonicotinoids. Ontario's regulations were written to reduce the percentage of seeds and beans covered with neonicotinoids to 20 percent within two years.{{cite news |title=Ontario wants 80% reduction of bee-killing neonicotinoid use in 2 years |url=http://www.cbc.ca/news/canada/toronto/ontario-wants-80-reduction-of-bee-killing-neonicotinoid-use-in-2-years-1.3106666 |access-date=29 September 2015 |work=CBC News |publisher=CBC/Radio-Canada |date=9 June 2015 |location=Toronto, Ontario, Canada |url-status=live |archive-url=https://web.archive.org/web/20150917154549/http://www.cbc.ca/news/canada/toronto/ontario-wants-80-reduction-of-bee-killing-neonicotinoid-use-in-2-years-1.3106666 |archive-date=17 September 2015 |df=dmy-all}}

On 10 December 2015, Montreal banned all neonicotinoids – without exception – on all properties within the city limits, including the Botanical Garden, all agricultural areas, and all golf courses.{{cite news |title=Montreal neonicotinoid ban |url=http://ville.montreal.qc.ca/portal/page?_pageid=5798,42657625&_dad=portal&_schema=PORTAL&id=26124&ret=http://ville.montreal.qc.ca/pls/portal/url/page/prt_vdm_fr/rep_annonces_ville/rep_communiques/communiques |access-date=10 December 2015 |work=City of Montreal |date=10 December 2015 |url-status=live |archive-url=https://web.archive.org/web/20180427151714/http://ville.montreal.qc.ca/portal/page?_pageid=5798%2C42657625&_dad=portal&_schema=PORTAL&id=26124&ret=http%3A%2F%2Fville.montreal.qc.ca%2Fpls%2Fportal%2Furl%2Fpage%2Fprt_vdm_fr%2Frep_annonces_ville%2Frep_communiques%2Fcommuniques |archive-date=27 April 2018 |df=dmy-all}} Agricultural businesses opposed Montreal's ban.{{cite news |title=CropLife Canada highlights safety of neonics amid Montreal's pesticide ban |url=http://cropprotectionnews.com/stories/510549206-croplife-canada-highlights-safety-of-neonics-amid-montreal-s-pesticide-ban |access-date=29 September 2015 |work=Crop Protection News |date=12 June 2015 |url-status=live |archive-url=https://web.archive.org/web/20150930124147/http://cropprotectionnews.com/stories/510549206-croplife-canada-highlights-safety-of-neonics-amid-montreal-s-pesticide-ban |archive-date=30 September 2015 |df=dmy-all}}

In July 2016, British Columbia's largest city, Vancouver, banned the use of neonicotinoids within Vancouver city limits, where it was primarily being used to kill off chafer beetles living under home lawns.{{cite web |url=http://www.cbc.ca/news/canada/british-columbia/vancouver-bans-neonicotinoids-1.3675572 |title=Bee-killing pesticides banned in Vancouver | work = CBC News |access-date=2018-02-24 |url-status=live |archive-url=https://web.archive.org/web/20180306160847/http://www.cbc.ca/news/canada/british-columbia/vancouver-bans-neonicotinoids-1.3675572 |archive-date=6 March 2018 |df=dmy-all}}

On 11 October 2019, the Fiji government announced a ban on imidacloprid, effective 1 January 2020.{{Cite web |url=https://fijisun.com.fj/2019/10/11/paraquat-imidacloprid-pesticide-to-be-banned-from-january-2020/ |title=Paraquat, Imidacloprid Pesticide To Be Banned From January, 2020 |language=en-US |access-date=2019-10-11}}

Neonicotinoids, like nicotine, bind to nicotinic acetylcholine receptors (nAChRs) of a cell and trigger a response by that cell. In mammals, nicotinic acetylcholine receptors are located in cells of both the central nervous system and peripheral nervous systems. In insects, these receptors are limited to the central nervous system.

Nicotinic acetylcholine receptors are activated by the neurotransmitter acetylcholine.

While low to moderate activation of these receptors causes nervous stimulation, high levels overstimulate and block the receptors,{{cite web |vauthors=Gervais JA, Luukinen B, Buhl K, Stone D |publisher=National Pesticide Information Center | title=Imidacloprid Technical Fact Sheet |date=April 2010 |url=http://npic.orst.edu/factsheets/imidacloprid.pdf |access-date=12 April 2012 |url-status=live |archive-url=https://web.archive.org/web/20120411203109/http://npic.orst.edu/factsheets/imidacloprid.pdf |archive-date=11 April 2012 |df=dmy-all}}

causing paralysis and death. Acetylcholinesterase breaks down acetylcholine to terminate signals from these receptors. However, acetylcholinesterase cannot break down neonicotinoids and their binding is irreversible. Neonicotinoids were assigned to IRAC group 4A.

{{multiple image

| direction = vertical

| width = 200

| footer = R-nicotine (top) and desnitro-imidacloprid are both protonated in the body

| image1 = R-nicotine.svg | alt1 = R-nicotine

| image2 = Desnitro-imidacloprid.svg | alt2 = Desnitro-imidacloprid

}}

Mammals and insects have different compositions of the receptor subunits and the structures of the receptors.{{Cite journal |vauthors=Tomizawa M |title=Neonicotinoids and Derivatives: Effects in Mammalian Cells and Mice |doi=10.1584/jpestics.29.177 |journal=Journal of Pesticide Science |volume=29 |issue=3 |pages=177–183 |year=2004 |doi-access=free}} Because most neonicotinoids bind much more strongly to insect neuron receptors than to mammal neuron receptors, these insecticides are more toxic to insects than mammals.{{cite book |vauthors=Tomizawa M, Latli B, Casida JE |chapter=Structure and Function of Insect Nicotinic Acetylcholine Receptors Studied with Nicotinic Insecticide Affinity Probes |pages=271–292 |veditors=Yamamoto I, Casida JE |editor2-link=John E. Casida |title=Nicotinoid Insecticides and the Nicotinic Acetylcholine Receptor |publisher=Springer-Verlag |location=Tokyo |year=1999 |isbn=978-4-431-70213-9}}

The low mammalian toxicity of imidacloprid has been explained by its inability to cross the blood–brain barrier because of the presence of a charged nitrogen atom at physiological pH. The uncharged molecule can penetrate the insect blood-brain barrier.

Other neonicotinoids have a negatively charged nitro or cyano group, which interacts with a unique, positively charged amino acid residue present on insects, but not mammalian nAChRs.{{cite journal | vauthors = Tomizawa M, Casida JE | title = Selective toxicity of neonicotinoids attributable to specificity of insect and mammalian nicotinic receptors | journal = Annual Review of Entomology | volume = 48 | pages = 339–364 | year = 2003 | pmid = 12208819 | doi = 10.1146/annurev.ento.48.091801.112731 }}

However, the breakdown product desnitro-imidacloprid, which is formed in a mammal's body during metabolism as well as in environmental breakdown of imidacloprid,{{cite web |vauthors=Koshlukova S |date=9 February 2006 |title=Imidacloprid: Risk Characterization Document: Dietary and Drinking Water Exposure |publisher=California Environmental Protection Agency, Department of Pesticide Regulation |url=http://www.cdpr.ca.gov/docs/risk/rcd/imidacloprid.pdf |access-date=11 April 2012 |url-status=live |archive-url=https://web.archive.org/web/20111227193836/http://www.cdpr.ca.gov/docs/risk/rcd/imidacloprid.pdf |archive-date=27 December 2011 |df=dmy-all}} has a charged nitrogen and shows high affinity to mammalian nAChRs. Desnitro-imidacloprid is quite toxic to mice.{{Cite journal |vauthors=Chao SL, Casida JE |doi=10.1006/pest.1997.2284 |title=Interaction of Imidacloprid Metabolites and Analogs with the Nicotinic Acetylcholine Receptor of Mouse Brain in Relation to Toxicity |journal=Pesticide Biochemistry and Physiology |volume=58 |pages=77–88 |year=1997|issue=1 |bibcode=1997PBioP..58...77L }}

Toxic action may result from the active ingredient itself or from its residue. {{visible anchor|6-chloronicotinic acid}} is a common degradation product of multiple neonicotinoids.{{cite journal | vauthors = Blacquière T, Smagghe G, van Gestel CA, Mommaerts V | title = Neonicotinoids in bees: a review on concentrations, side-effects, and risk assessment | journal = Ecotoxicology | volume = 21 | issue = 4 | pages = 973–992 | date = May 2012 | pmid = 22350105 | pmc = 3338325 | doi = 10.1007/s10646-012-0863-x | publisher = Springer Science+Business Media | bibcode = 2012Ecotx..21..973B }}

Most neonicotinoids are water-soluble and break down slowly in the environment, so they can be taken up by the plant and provide protection from insects as the plant grows.{{Cite journal |last1=Giorio |first1=Chiara |last2=Safer |first2=Anton |last3=Sánchez-Bayo |first3=Francisco |last4=Tapparo |first4=Andrea |last5=Lentola |first5=Andrea |last6=Girolami |first6=Vincenzo |last7=van Lexmond |first7=Maarten Bijleveld |last8=Bonmatin |first8=Jean-Marc |date=March 2021 |title=An update of the Worldwide Integrated Assessment (WIA) on systemic insecticides. Part 1: new molecules, metabolism, fate, and transport |journal=Environmental Science and Pollution Research |language=en |volume=28 |issue=10 |pages=11716–11748 |doi=10.1007/s11356-017-0394-3 |issn=0944-1344 |pmc=7920890 |pmid=29105037|bibcode=2021ESPR...2811716G }}

Independent studies show that the photodegradation half-life time of most neonicotinoids is around 34 days when exposed to sunlight. However, it might take up to 1,386 days (3.8 years) for these compounds to degrade in the absence of sunlight and micro-organism activity. Some researchers are concerned that neonicotinoids applied agriculturally might accumulate in aquifers.{{cite web |url=http://www.delo.si/brez%20kategorije/intervju-z-mikrobiologom-ta-prostor-je-prestreljen-z-lobisti-multinacionalk.html |title=Interview with microbiologist: "This place is filled with multinational lobbyists" |publisher=Delo.si |date=14 May 2011 |access-date=11 October 2011 |url-status=live |archive-url=https://web.archive.org/web/20110920021804/http://www.delo.si/brez%20kategorije/intervju-z-mikrobiologom-ta-prostor-je-prestreljen-z-lobisti-multinacionalk.html |archive-date=20 September 2011 |df=dmy-all}}

{{See also|Colony collapse disorder|Pollinator decline|Pesticide toxicity to bees|Bees and toxic chemicals}}

A dramatic rise in the number of annual beehive losses noticed around 2006 spurred interest in factors potentially affecting honeybee health.{{cite news |vauthors=Copping J |date=1 April 2007 |title=Flowers and fruit crops facing disaster as disease kills off bees |url=https://www.telegraph.co.uk/news/uknews/1547243/Flowers-and-fruit-crops-facing-disaster-as-disease-kills-off-bees.html |work=The Telegraph |url-status=live |archive-url=https://web.archive.org/web/20171020071833/http://www.telegraph.co.uk/news/uknews/1547243/Flowers-and-fruit-crops-facing-disaster-as-disease-kills-off-bees.html |archive-date=20 October 2017 |df=dmy-all}}{{cite journal | vauthors = Vanengelsdorp D, Evans JD, Saegerman C, Mullin C, Haubruge E, Nguyen BK, Frazier M, Frazier J, Cox-Foster D, Chen Y, Underwood R, Tarpy DR, Pettis JS | display-authors = 6 | title = Colony collapse disorder: a descriptive study | journal = PLOS ONE | volume = 4 | issue = 8 | pages = e6481 | date = August 2009 | pmid = 19649264 | pmc = 2715894 | doi = 10.1371/journal.pone.0006481 | veditors = Brown J | doi-access = free | bibcode = 2009PLoSO...4.6481V }} Many biological factors influence colony collapse disorder, including varroa mite infestation and Israeli acute paralysis virus (IAPV).{{cite journal |vauthors=Watanabe M |title=Colony Collapse Disorder: Many Suspects, No Smoking Gun |journal=BioScience |volume=58 |issue=5 |pages=384–388 |date=May 2008 |doi=10.1641/b580503 |s2cid=85798698 |doi-access=free}}{{cite report |author=USDA |date=17 October 2012 |title=Report on the National Stakeholders Conference on Honey Bee Health National Honey Bee Health Stakeholder Conference Steering Committee |url=http://www.usda.gov/documents/ReportHoneyBeeHealth.pdf |access-date=4 June 2014 |archive-url=https://web.archive.org/web/20140520063250/http://www.usda.gov/documents/ReportHoneyBeeHealth.pdf |archive-date=20 May 2014 |df=dmy-all}} Despite much speculation on the role of neonicotinoids, many collapsing colonies show no trace of them.{{cite journal | vauthors = Cepero A, Ravoet J, Gómez-Moracho T, Bernal JL, Del Nozal MJ, Bartolomé C, Maside X, Meana A, González-Porto AV, de Graaf DC, Martín-Hernández R, Higes M | display-authors = 6 | title = Holistic screening of collapsing honey bee colonies in Spain: a case study | journal = BMC Research Notes | volume = 7 | page = 649 | date = September 2014 | pmid = 25223634 | pmc = 4180541 | doi = 10.1186/1756-0500-7-649 | doi-access = free }}

A review article (Carreck & Ratnieks, 2015) concluded that while laboratory-based studies have demonstrated adverse sub-lethal effects of neonicotinoid insecticides on honey bees and bumble bees, these same effects have not been observed in field studies, which is likely due to an overestimation of three key dosage factors (concentration, duration, and choice) in many laboratory-based studies.

In 2017, researchers demonstrated the combined effects of nutritional stress and low doses of common, widely used neonicotinoid pesticides (clothianidin, thiamethoxam) found in nectar and pollen. Their results provided the first demonstration that neonicotinoids and nutrition levels can synergistically interact and cause significant harm to animal survival, showing the complexity of neonicotinoid effects. In addition, the combined exposure reduced bee food consumption and hemolymph (bee blood) sugar levels.{{cite journal | vauthors = Tosi S, Nieh JC, Sgolastra F, Cabbri R, Medrzycki P | title = Neonicotinoid pesticides and nutritional stress synergistically reduce survival in honey bees | journal = Proceedings. Biological Sciences | volume = 284 | issue = 1869 | page = 20171711 | date = December 2017 | pmid = 29263280 | pmc = 5745400 | doi = 10.1098/rspb.2017.1711 }} Declines in managed and wild bee populations have been attributed, in part, to the combination of direct and indirect effects of neonicotinoids that render them vulnerable to pathogens.{{cite journal | vauthors = Sánchez-Bayo F, Goulson D, Pennacchio F, Nazzi F, Goka K, Desneux N | title = Are bee diseases linked to pesticides? - A brief review | journal = Environment International | volume = 89-90 | pages = 7–11 | year = 2016 | pmid = 26826357 | doi = 10.1016/j.envint.2016.01.009 | publisher = Elsevier BV | bibcode = 2016EnInt..89....7S }}

Almost all research into the negative effects of neonicotinoids has been conducted on honey bees, with little research investigating other bees such as bumblebees. However, some research has shown neonicotinoids affecting mason bees and bumblebees more negatively than honey bees, which are inconsistently affected.

Research suggests potential toxicity to honey bees and other beneficial insects even with low levels of exposure, with sublethal effects that negatively impact the survival of colonies. In lab studies, neonicotinoids were shown to increase mortality rates{{cite web |title=Neonicotinoids |website=Pollinator Network @ Cornell |url=https://pollinator.cals.cornell.edu/threats-wild-and-managed-bees/pesticides/neonicotinoids/ |access-date=2019-05-10}} and negatively affect the ability to fly{{cite journal | vauthors = Tosi S, Burgio G, Nieh JC | title = A common neonicotinoid pesticide, thiamethoxam, impairs honey bee flight ability | journal = Scientific Reports | volume = 7 | issue = 1 | page = 1201 | date = April 2017 | pmid = 28446783 | pmc = 5430654 | doi = 10.1038/s41598-017-01361-8 | bibcode = 2017NatSR...7.1201T }} and forage in exposed bees.{{cite web |url=http://citybugs.tamu.edu/factsheets/ipm/what-is-a-neonicotinoid/ |title=What is a neonicotinoid? Insects in the City |archive-url=https://web.archive.org/web/20130515044301/http://citybugs.tamu.edu/factsheets/ipm/what-is-a-neonicotinoid/ |archive-date=15 May 2013 |work=Citybugs.tamu.edu |access-date=2 May 2013}} Neonicotinoids may also be responsible for detrimental effects on the bumblebee, another important pollinator.{{cite journal | vauthors = Whitehorn PR, O'Connor S, Wackers FL, Goulson D | title = Neonicotinoid pesticide reduces bumble bee colony growth and queen production | journal = Science | volume = 336 | issue = 6079 | pages = 351–352 | date = April 2012 | pmid = 22461500 | doi = 10.1126/science.1215025 | s2cid = 2738787 | bibcode = 2012Sci...336..351W | doi-access = free }}{{cite journal | vauthors = Rundlöf M, Andersson GK, Bommarco R, Fries I, Hederström V, Herbertsson L, Jonsson O, Klatt BK, Pedersen TR, Yourstone J, Smith HG | display-authors = 6 | title = Seed coating with a neonicotinoid insecticide negatively affects wild bees | journal = Nature | volume = 521 | issue = 7550 | pages = 77–80 | date = May 2015 | pmid = 25901681 | doi = 10.1038/nature14420 | s2cid = 4468879 | bibcode = 2015Natur.521...77R }} In general, however, despite the fact that many laboratory studies have shown the potential for neonicotinoid toxicity, the majority of field studies have found only limited or no effects on honey bees.{{cite journal |doi=10.3896/IBRA.1.53.5.08 |title=The dose makes the poison: have "field realistic" rates of exposure of bees to neonicotinoid insecticides been overestimated in laboratory studies? |volume=53 |issue=5 |journal=Journal of Apicultural Research |pages=607–614 |year=2014 | vauthors = Carreck NL |bibcode=2014JApiR..53..607C |s2cid=15038464 |url=http://sro.sussex.ac.uk/53342/1/Carreck_%26_Ratnieks_%282014%29.pdf}} Studies have shown a variety of sublethal effects of neonicotinoids on bumblebees, including lower reproduction rates, production of fewer workers and queens, and numerous behavioral changes. Sublethal exposure of bumblebee colonies to neonicotinoids alters foraging behaviors, often causing bees to forage less effectively and lowering colony growth and reproduction rates.

In April 2015 EASAC conducted a study of the potential effects on organisms providing a range of ecosystem services like pollination and natural pest control which are critical to sustainable agriculture. The resulting report concludes "there is an increasing body of evidence that the widespread prophylactic use of neonicotinoids has severe negative effects on non-target organisms that provide ecosystem services including pollination and natural pest control."{{cite web |author=EASAC |url=http://www.easac.eu/fileadmin/Reports/Easac_15_ES_web_complete.pdf |title=Ecosystem services, agriculture and neonicotinoids |quote=There is an increasing body of evidence that the widespread prophylactic use of neonicotinoids has severe negative effects on non-target organisms that provide ecosystem services including pollination and natural pest control. |access-date=10 April 2015 |date=8 April 2015 |url-status=live |archive-url=https://web.archive.org/web/20150415155001/http://www.easac.eu/fileadmin/Reports/Easac_15_ES_web_complete.pdf |archive-date=15 April 2015 |df=dmy-all}}

A 2015 systematic review (Lundin et al., 2015) of the scientific literature on neonicotinoids and bees concluded that despite considerable research efforts, there are still significant knowledge gaps concerning the impacts of neonicotinoids on bees.{{cite journal | vauthors = Lundin O, Rundlöf M, Smith HG, Fries I, Bommarco R | title = Neonicotinoid Insecticides and Their Impacts on Bees: A Systematic Review of Research Approaches and Identification of Knowledge Gaps | journal = PLOS ONE | volume = 10 | issue = 8 | pages = e0136928 | date = 2015 | pmid = 26313444 | pmc = 4552548 | doi = 10.1371/journal.pone.0136928 | doi-access = free | bibcode = 2015PLoSO..1036928L }}

A 2017 survey covering every continent with honeybees found neonicotinoids in three-fourths of honey samples, albeit in every case at levels considered safe for human consumption.{{cite web |url=https://www.sciencenews.org/article/much-worlds-honey-now-contains-pesticides-harm-bees |title=Much of the world's honey now contains bee-harming pesticides; Global survey finds neonicotinoids in three-fourths of samples |vauthors=Hamers L |date=5 October 2017 |website=Sciencenews.org | access-date=6 October 2017 |url-status=live |archive-url=https://web.archive.org/web/20171007120030/https://www.sciencenews.org/article/much-worlds-honey-now-contains-pesticides-harm-bees |archive-date=7 October 2017 |df=dmy-all}}

Neonicotinoids have adverse effects on bird populations.{{Cite journal |last1=Molenaar |first1=Elke |last2=Viechtbauer |first2=Wolfgang |last3=van de Crommenacker |first3=Janske |last4=Kingma |first4=Sjouke A. |date=October 2024 |title=Neonicotinoids Impact All Aspects of Bird Life: A Meta-Analysis |journal=Ecology Letters |language=en |volume=27 |issue=10 |pages=e14534 |doi=10.1111/ele.14534 |pmid=39385588 |issn=1461-023X|doi-access=free |bibcode=2024EcolL..27E4534M }} Neonicotinoid dust intended for plants and seed coatings can spread throughout the air and seep into the water, which unintentionally affects non-target wildlife.{{cite journal | vauthors = Goulson D | title = Ecology: Pesticides linked to bird declines | journal = Nature | volume = 511 | issue = 7509 | pages = 295–296 | date = July 2014 | pmid = 25030159 | doi = 10.1038/nature13642 | s2cid = 4448389 | bibcode = 2014Natur.511..295G }}

Globally, 60% of neonicotinoids are used as seed coatings.{{cite journal | vauthors = MacDonald AM, Jardine CM, Thomas PJ, Nemeth NM | title = Neonicotinoid detection in wild turkeys (Meleagris gallopavo silvestris) in Ontario, Canada | journal = Environmental Science and Pollution Research International | volume = 25 | issue = 16 | pages = 16254–16260 | date = June 2018 | pmid = 29704179 | pmc = 5984634 | doi = 10.1007/s11356-018-2093-0 | bibcode = 2018ESPR...2516254M }} Some seed-eating bird species can be poisoned by neonicotinoid-coated seeds.{{cite journal | vauthors = Millot F, Decors A, Mastain O, Quintaine T, Berny P, Vey D, Lasseur R, Bro E | display-authors = 6 | title = Field evidence of bird poisonings by imidacloprid-treated seeds: a review of incidents reported by the French SAGIR network from 1995 to 2014 | journal = Environmental Science and Pollution Research International | volume = 24 | issue = 6 | pages = 5469–5485 | date = February 2017 | pmid = 28028702 | pmc = 5352772 | doi = 10.1007/s11356-016-8272-y | publisher = Springer Science and Business Media LLC | doi-access = free | bibcode = 2017ESPR...24.5469M }} There have been reports of developmental abnormalities and reduced eggshell thickness, fertilization success, and embryo size with direct exposure to pesticides including neonicotinoids.{{cite journal | vauthors = Gibbons D, Morrissey C, Mineau P | title = A review of the direct and indirect effects of neonicotinoids and fipronil on vertebrate wildlife | journal = Environmental Science and Pollution Research International | volume = 22 | issue = 1 | pages = 103–118 | date = January 2015 | pmid = 24938819 | pmc = 4284370 | doi = 10.1007/s11356-014-3180-5 | bibcode = 2015ESPR...22..103G }} Some studies suggest burying neonicotinoid seeds used for agriculture below the surface of the soil will prevent birds from eating them.

Neonicotinoids can have non-direct impacts on birds by disrupting the food chain. The main goal of neonicotinoids is to target pests. However, this negatively affects insectivorous bird populations that rely on these insects for food.{{Cite journal |vauthors=Humann-Guilleminot S, Binkowski ŁJ, Jenni L, Hilke G, Glauser G, Helfenstein F |date=2019 |title=A nation-wide survey of neonicotinoid insecticides in agricultural land with implications for agri-environment schemes |journal=Journal of Applied Ecology |volume=56 |issue=7 |pages=1502–1514 |doi=10.1111/1365-2664.13392 |s2cid=133107567|doi-access=free |bibcode=2019JApEc..56.1502H }}{{cite journal | vauthors = Hallmann CA, Foppen RP, van Turnhout CA, de Kroon H, Jongejans E | title = Declines in insectivorous birds are associated with high neonicotinoid concentrations | journal = Nature | volume = 511 | issue = 7509 | pages = 341–343 | date = July 2014 | pmid = 25030173 | doi = 10.1038/nature13531 | s2cid = 4464169 | bibcode = 2014Natur.511..341H | hdl = 2066/130120 | hdl-access = free }}{{cite journal | vauthors = Brain RA, Anderson JC | title = The agro-enabled urban revolution, pesticides, politics, and popular culture: a case study of land use, birds, and insecticides in the USA | journal = Environmental Science and Pollution Research International | volume = 26 | issue = 21 | pages = 21717–21735 | date = July 2019 | pmid = 31129901 | pmc = 6647523 | doi = 10.1007/s11356-019-05305-9 | bibcode = 2019ESPR...2621717B }}{{cite journal | vauthors = Bowler DE, Heldbjerg H, Fox AD, de Jong M, Böhning-Gaese K | title = Long-term declines of European insectivorous bird populations and potential causes | journal = Conservation Biology | volume = 33 | issue = 5 | pages = 1120–1130 | date = October 2019 | pmid = 30912605 | doi = 10.1111/cobi.13307 | bibcode = 2019ConBi..33.1120B | s2cid = 85517845 }}

Neonicotinoids can also leach into soil, accumulating in bodies of water that normally incubate insects.{{cite web |title=The Same Pesticides Linked to Bee Declines Might Also Threaten Birds |publisher=National Audubon Society | date=2017-03-24 |url=https://www.audubon.org/magazine/spring-2017/the-same-pesticides-linked-bee-declines-might |access-date=2021-01-14 |vauthors=Royte E}} A 2014 observational study conducted in the Netherlands correlated declines in some bird populations with environmental imidacloprid residues, although it stopped short of concluding that the association was causal.

In March 2013, the American Bird Conservancy published a commentary on 200 studies on neonicotinoids calling for a ban on neonicotinoid use as seed treatments because of their toxicity to birds, aquatic invertebrates, and other wildlife.{{cite web |title=The Impact of the Nation's Most Widely Used Insecticides on Birds |url=http://www.abcbirds.org/abcprograms/policy/toxins/Neonic_FINAL.pdf |work=Neonicotinoid Insecticides and Birds |publisher=American Bird Conservancy |access-date=19 March 2013 |vauthors=Mineau P, Palmer C |date=March 2013 |url-status=live |archive-url=https://web.archive.org/web/20130418010024/http://www.abcbirds.org/abcprograms/policy/toxins/Neonic_FINAL.pdf |archive-date=18 April 2013 |df=dmy-all}}

A 2013 Dutch study found that water containing allowable concentrations of imidacloprid had 50% fewer invertebrate species compared with uncontaminated water.{{cite journal | vauthors = Van Dijk TC, Van Staalduinen MA, Van der Sluijs JP | title = Macro-invertebrate decline in surface water polluted with imidacloprid | journal = PLOS ONE | volume = 8 | issue = 5 | pages = e62374 | date = 1 May 2013 | pmid = 23650513 | pmc = 3641074 | doi = 10.1371/journal.pone.0062374 | doi-access = free | bibcode = 2013PLoSO...862374V }}{{cite web |url=https://www.theguardian.com/environment/2013/may/01/study-links-insecticide-invertebrate-die-off |title=Study links insecticide use to invertebrate die-offs |publisher=www.guardian.com |date=1 May 2013 |access-date=3 September 2013 |url-status=live |archive-url=https://web.archive.org/web/20130824142640/http://www.theguardian.com/environment/2013/may/01/study-links-insecticide-invertebrate-die-off |archive-date=24 August 2013 |df=dmy-all}} A later study found the analysis was confounded with other co-occurring insecticides and did not show imidacloprid directly affected invertebrate diversity.{{cite journal | vauthors = Vijver MG, van den Brink PJ | title = Macro-invertebrate decline in surface water polluted with imidacloprid: a rebuttal and some new analyses | journal = PLOS ONE | volume = 9 | issue = 2 | pages = e89837 | date = 28 February 2014 | pmid = 24587069 | pmc = 3938502 | doi = 10.1371/journal.pone.0089837 | doi-access = free | bibcode = 2014PLoSO...989837V }}

A 2014 review took a broader look at the ecological impact of neonicotinoids and fipronil, finding negative effects on invertebrates, but not microbes or fish.{{cite web |url=http://www.tfsp.info/worldwide-integrated-assessment/ |title=Worldwide Integrated Assessment of the impact of Systemic Pesticides on biodiversity and ecosystems (WIA) |publisher=The Task Force on Systemic Pesticides |date=10 October 2014 |access-date=27 November 2014 |url-status=live |archive-url=https://web.archive.org/web/20141204222936/http://www.tfsp.info/worldwide-integrated-assessment/ |archive-date=4 December 2014 |df=dmy-all}} Although not yet conclusive, there is increasing evidence that neonicotinoids can have negative effects on pollinating insects other than bees, including monarch butterflies. Some evidence has linked neonicotinoids to reduced numbers of monarch eggs that are hatched.{{cite web | vauthors = Weber B |title=Monarch butterflies harmed by common neonic pesticides, study suggests |url=https://www.cbc.ca/news/science/monarch-butterflies-neonics-1.6024834}}{{cite web |url=https://monarchjointventure.org/faq/what-to-do-if-you-have-neonicotinoid-treated-plants-and-how-to-avoid-them |title=What should I do if plants that I've purchased were treated with neonicotinoids or other pesticides? How should I avoid purchasing treated plants in the future? |work=FAQ (Frequently Asked Questions) |publisher=Monarch Joint Venture |year=2021 |access-date=August 2, 2021 |archive-url=https://web.archive.org/web/20210802171051/https://monarchjointventure.org/faq/what-to-do-if-you-have-neonicotinoid-treated-plants-and-how-to-avoid-them |archive-date=August 2, 2021 |url-status=live}}{{cite web |url=https://i0.wp.com/www.compoundchem.com/wp-content/uploads/2015/04/Neonicotinoid-Pesticides-Their-Effect-on-Bee-Colonies-The-Facts.png?ssl=1 |title=Neonicotinoid Pesticides – The Facts |work=Neonicotinoid Pesticides & Bee Colonies |date=April 2015 |publisher=Compound Interest: Explorations of everyday chemical compounds |access-date=August 2, 2021 |archive-url=https://web.archive.org/web/20210802173045/https://i0.wp.com/www.compoundchem.com/wp-content/uploads/2015/04/Neonicotinoid-Pesticides-Their-Effect-on-Bee-Colonies-The-Facts.png?ssl=1 |archive-date=August 2, 2021 |url-status=live |quote=Can accumulate in soil; low concentrations found in nectar of treated crops. .... Negative impacts on monarch butterly populations in the USA have recently been suggested.}}{{cite journal | vauthors = James DG | title = A Neonicotinoid Insecticide at a Rate Found in Nectar Reduces Longevity but Not Oogenesis in Monarch Butterflies, Danaus plexippus (L.). (Lepidoptera: Nymphalidae) | journal = Insects | volume = 10 | issue = 9 | page = 276 | date = September 2019 | pmid = 31480499 | pmc = 6780620 | doi = 10.3390/insects10090276 | publisher = MDPI (Multidisciplinary Digital Publishing Institute) | doi-access = free | oclc = 9113208907 }} However, the effects of neonicotinoids on butterflies and moths have been studied very little.

A 2024 study found that non-target freshwater amphipods (Gammarus roeselii and Hyalella azteca) exposed to the neonicotinoid thiacloprid developed increased tolerance over successive generations. The findings suggest that developmental plasticity plays a key role in their rapid adaptive response, raising concerns about how neonicotinoid exposure may drive evolutionary changes in aquatic ecosystems.{{cite journal | vauthors = Jourdan J, Abdel Fadil SE, Oehlmann J, Hupało K | title = Rapid development of increased neonicotinoid tolerance in non-target freshwater amphipods | journal = Environment International | volume = 183 | page = 108368 | date = 2024 | doi = 10.1016/j.envint.2023.108368 | doi-access = free }}

Rodents exposed chronically or acutely to neonicotinoids suffer major damage to their nervous systems, likely due to impairment of their neurotransmitter mechanisms. Laboratory studies showed that such major neurological damage resulted both when the exposure occurred during the embryonic period and when the exposure occurred during adulthood. Impairments to cognitive ability and to memory were observed. Neonicotinoid exposure at an early age was shown to impair neuronal development, with decreases in neurogenesis and induced neuroinflammation. Adult exposure induced neurobehavioral toxicity and resulting changes in neurochemicals.Carmen Costas-Ferreira and Lilian R. F. Faro, International Journal of Molecular Science, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395098/ "Neurotoxic Effects of Neonicotinoids on Mammals: What Is There beyond the Activation of Nicotinic Acetylcholine Receptors?—A Systematic Review"], 2021 Aug 22(16): 8413, Published online 2021 Aug 5

Neonicotinoids have been identified systemically in many human subjects. They have been identified in children, adults and neonates. Multiple neonicotinoids have been found in human blood, tissue, urine, semen, bile and brain matter. Additionally they have been found in breast milk and neonate first urine samples.Yuanyuan Zhang, Wanxuan Zhu, Ying Wang, Xueli Li, Jianxin Lv, Jiaoyang Luo, Meihua Yang,

Insight of neonicotinoid insecticides: Exploring exposure, mechanisms in non-target organisms, and removal technologies,

Pharmacological Research,

Volume 209,

2024,

107415,

ISSN 1043-6618,

https://doi.org/10.1016/j.phrs.2024.107415.

• Decline in amphibian populations
• Decline in insect populations

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Category:Insecticides