neonicotinoid neonicotinoid neonicotinoids (sometimes shortened to neonics /ˈniːoʊnɪks/) are a class of neuro-active insecticides chemically similar to nicotine, developed by scientists at shell and bayer in the 1980s. the neonicotinoid family includes acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, nithiazine, thiacloprid and thiamethoxam. imidacloprid has been the most widely used insecticide in the world from 1999 through at least 2018. compared to organophosphate and carbamate insecticides, neonicotinoids are less toxic to birds and mammals. because they affect the central nervous system of insects, neonicotinoids kill or deleteriously affect a wide variety of both target and non-target insects. they are often applied to seeds before planting as a prophylactic treatment against herbivorous insects. neonicotinoids are water-soluble, so when the seed sprouts and grows, the developing plant absorbs the pesticide into its tissues as it takes in water. neonicotinoids can also be applied to the soil directly. once absorbed, neonicotinoids become present throughout the plant, including in its leaves, flowers, nectar, and pollen. neonicotinoid use has been linked to adverse ecological effects, including honey-bee colony collapse disorder (ccd), bumblebee decline, and declining populations of insect-eating birds. neonicotinoids widely contaminate wetlands, streams, and rivers, and due to their widespread use, pollinating insects are chronically exposed to them. sublethal effects from chronic low-level exposure to neonicotinoids in the environment are thought to be more common in bees than directly lethal effects. these effects upon bees include difficulty navigating, learning, and foraging, suppressed immune response, lower sperm viability, shortened lifespans of queens, and reduced numbers of new queens produced. furthermore, organisms unaffected by, resistant to, or exposed to sublethal doses of neonicotinoid pesticides retain the pesticides in their bodies when they feed upon neonicotinoid-treated plants, which can then kill predatory insects that consume the contaminated prey. in 2013, the european union and some neighbouring countries restricted the use of certain neonicotinoids. in 2018 the eu banned the three main neonicotinoids (clothianidin, imidacloprid and thiamethoxam) for all outdoor uses, but in 2020, france re-allowed the use of neonicotinoids on sugar beet crops. several us states have restricted neonicotinoids out of concern for pollinators and bees. history the precursor to nithiazine was first synthesized by henry feuer, a chemist at purdue university, in 1970. 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, 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. during the late 1990s, imidacloprid became widely used. beginning in the early 2000s, two other neonicotinoids, clothianidin and thiamethoxam, entered the market. as of 2013, virtually all us corn was treated with one of these two insecticides. as of 2014, about a third of us soybean acreage was planted with neonicotinoid-treated seeds, usually imidacloprid or thiamethoxam. market 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 €957 million in 2008. neonicotinoids made up 80% of all seed treatment sales in 2008. as of 2011, seven neonicotinoids from different companies were on the market. namecompanyproductsturnover in million us$ (2009) imidaclopridbayer cropscienceconfidor, admire, gaucho, advocate1,091 thiamethoxamsyngentaactara, platinum, cruiser627 clothianidinsumitomo chemical/bayer cropscienceponcho, dantosu, dantop, belay439 acetamipridnippon sodamospilan, assail, chipcotristar276 thiaclopridbayer cropsciencecalypso112 dinotefuranmitsui chemicalsstarkle, safari, venom79 nitenpyramsumitomo chemicalcapstar, guardian8 agricultural usage efficacy 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. 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. imidacloprid was possibly the most widely used insecticide, both within the neonicotinoids and in the worldwide market. seed coatings 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. 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 . regulation united states the us epa operates a 15-year registration review cycle for all pesticides. the epa granted a conditional registration to clothianidin in 2003. the epa issues conditional registrations when a pesticide meets the standard for registration, but there are outstanding data requirements. thiamethoxam is approved for use as an antimicrobial pesticide wood preservative and as a pesticide; it was first approved in 1999. imidacloprid was registered in 1994. 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. 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. 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. the case, ellis et al v. bradbury et al, was stayed as of october 2013. 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 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. the bill was assigned to a congressional committee on 16 july 2013 and did not leave committee. the us epa has taken a variety of actions to regulate neonicotinoids in response to concerns about pollinators. 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. in may 2019, the environmental protection agency revoked approval for a dozen pesticides containing clothianidin and thiamethoxam as part of a legal settlement. european union the first neonic was approved in the eu in 2005. 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. 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. 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 dusts would not be released into the air. 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. neonicotinoid seed treatment is banned in italy, but foliar use is 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 based its decision on the known acute toxicity of these compounds to pollinators. 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. eu restrictions on use 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, oilseed rape and cereals. a high acute risk was also identified from exposure via residues in nectar and/or pollen." efsa reached the following conclusions: 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 a number of 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. in response to the study, the european commission recommended a restriction of 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