clothianidin clothianidin 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 that are chemically similar to nicotine, which has been used as a pesticide since the late 1700s. clothianidin and other neonicotinoids act on the central nervous system of insects as an agonist of nachr, the same receptor as acetylcholine, the neurotransmitter that stimulates and activating post-synaptic acetylcholine receptors but not inhibiting ache. clothianidin and other neonicotinoids were developed to last longer than nicotine, which is more toxic and which breaks down too quickly in the environment. however, studies published in 2012 show that neonicotinoid dust released at planting time may persist in nearby fields for several years and be taken up into non-target plants, which are then foraged by bees, caterpillars, and other insects. clothianidin names iupac name 1-(2-chloro-1,3-thiazol-5-ylmethyl)-3-methyl-2-nitroguanidine identifiers cas number 210880-92-5 (e) y 3d model (jsmol) interactive image beilstein reference 9196326, 8620724 (e) chebi chebi:39178 n chembl chembl259727 y chemspider 184723 (e) y echa infocard 100.103.171 kegg c18508 y mesh clothianidin pubchem cid 86287519 (e) unii 2v9906abkq (e) y comptox dashboard (epa) dtxsid2034465 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) ykey: pgoobecodwqeab-uhfffaoysa-n yinchi=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 smiles cnc(n()=o)=ncc1=cn=c(cl)s1 properties chemical formula c6h8cln5o2s molar mass 249.67 g·mol−1 appearance colorless crystals density 1.61 g cm−3 melting point 179 °c (354 °f; 452 k) solubility in water 327 mg/l (at 20 °c) log p 0.732 acidity (pka) 7.472 basicity (pkb) 6.525 except where otherwise noted, data are given for materials in their standard state (at 25 °c , 100 kpa). n verify (what is yn ?) infobox references clothianidin is an alternative to organophosphate, carbamate, and pyrethroid pesticides. it poses lower risks to mammals, including humans, when compared to organophosphates and carbamates. it has helped prevent insect pests from building up resistance to organophosphate and pyrethroid pesticides. according to the environmental protection agency (epa), clothianidin's major risk concern is to nontarget insects (especially honey bees). information from standard tests and field studies, as well as incident reports involving other neonicotinoid insecticides (e.g., imidacloprid) suggest the potential for long term toxic risk to honey bees and other beneficial insects. in january 2013, the european food safety authority stated that neonicotinoids including clothianidin pose an unacceptably high risk to bees, concluding, "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." clothianidin is banned for all outdoor uses in the european union. authorized uses clothianidin is authorized for spray, dust, soil drench (for uptake via plant roots), injectable liquid (into tree limbs and trunks, sugar cane stalks etc.), and seed treatment uses, in which clothianidin coats seeds that take up the pesticide via the roots as the plant grows. the chemical may be used to protect plants against a wide variety of agricultural pests in many countries, of which the following are mentioned in citable english-language sources: australia, austria, belgium, bulgaria, canada, czech republic, denmark, estonia, france, finland, germany, greece, hungary, italy, ireland, japan, korea, lithuania, netherlands, new zealand, poland, portugal, serbia, slovakia, slovenia, spain, uk, and the united states. seed treatment uses of clothianidin, corn in particular, have been revoked or suspended in germany, italy and slovenia. the suspensions are reflective of e.u. pesticide law and are generally associated with acute poisoning of bees from pesticide dust being blown off of treated seeds, especially corn, and onto nearby farms where bees were performing pollinator services. clothianidin was prequalified for indoor residual spraying by the world health organization in 2017. background although nicotine has been used as a pesticide for over 200 years it degraded too rapidly in the environment and lacked the selectivity to be very useful in large-scale agricultural situations. however, in order to address this problem, the neonicotinoids (chloronicotinyl insecticides) were developed as a substitute of nicotine. clothianidin is an alternative to organophosphate, carbamate, and pyrethroid pesticides. it poses lower risks to mammals, including humans, when compared to organophosphates and carbamates. it also plays a key role helping to prevent the buildup in insect pests of resistance to organophosphate and pyrethroid pesticides, which is a growing problem in parts of europe. clothianidin was first given registration for use as a pesticide by the japan plant protection association in 2001. followed by conditional registration by the united states environmental protection agency in 2003, pending the completion of additional study of its safety to be done by december 2004. bayer did not complete the study on time and asked for an extension. the date was postponed to may 2005 and they also granted bayer the permission it had sought to conduct its study on canola in canada, instead of on corn in the united states. the study was not completed until 2007. in a november 2007 memo epa scientists declared the study “scientifically sound,” adding that it, “satisfies the guideline requirements for a field toxicity test with honeybees.” clothianidin continued to be sold under a conditional registration, and in april 2010 it was granted an unconditional registration for use as a seed treatment for corn and canola. however, in response to concerns raised by bee keepers, in november the epa released a memorandum in which they stated that some of the studies submitted did not appear to be adequate and the unconditional registration was withdrawn. in 2012, arguing that after more than 9 years the epa continues to maintain the registration status for clothianidin despite the fact that the registrant has failed to supply satisfactory studies confirming its safety, an alliance of beekeepers and environmental groups filed a petition on march 21 asking the epa to block the use of clothianidin in agricultural fields until they have conducted a review of the product. the petitioners state that they are aware that the epa has moved up its registration review of clothianidin and other neonicotinoids in response to concerns about their impacts on pollinators, however they note that this process is projected by the epa to take six to eight years and is thus grossly insufficient to address the urgency of the threat to pollinators. toxicity regulatory authorities describe the toxicological database for clothianidin as "extensive", and many studies have been reviewed to support registrations around the globe for this chemical. laboratory and field testing revealed that clothianidin shows relatively low toxicity to many test species but is highly or very highly toxic to others. toxicity varies depending on whether the exposure occurs on a short-term (acute) or long-term (chronic) basis. because it is systemic, persistent and highly toxic to honey bees, the canadian pest management regulatory agency has requested additional data to fully assess the potential effects of chronic exposure of clothianidin, resulting from its potential movement into plant pollen and nectar. mammals clothianidin is moderately toxic in the short-term to mammals that eat it, and long-term ingestion may result in reproductive and/or developmental effects. using laboratory test animals as surrogates for humans and dosages much higher than are expected from exposure related to actual use, rats showed low short-term oral, dermal, and inhalation toxicity to clothianidin. for mice, acute oral toxicity was moderate to high. rabbits showed little to no skin or eye irritation when exposed to clothianidin, and the skin of guinea pigs was not sensitized by it. when extrapolated to humans, these results suggest that clothianidin is moderately toxic through oral exposure, but toxicity is low through skin contact or inhalation. while clothianidin may cause slight eye irritation, it is not expected to be a skin sensitizer or irritant. clothianidin does not damage genetic material nor is there evidence that it causes cancer in rats or mice; it is unlikely to be a human carcinogen. permissible amounts of clothianidin residue on food and animal feed vary from crop to crop and nation to nation. however, regulatory authorities around the globe emphasize that when used according to the label instructions, clothianidin residues on food are not expected to exceed safe levels (as defined by each nation's laws and regulations). aquatic life in the 2003 united states epa assessment report it was stated that 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. it is considered to be toxic to aquatic invertebrates if disposal of wastes according to disposal instructions are not followed. the pest management regulatory agency of canada lists it as "very highly toxic" to aquatic invertebrates, but only slightly toxic to fish. in the 2003 epa report it was stated that although no water monitoring studies had been conducted, due to the extreme mobility and persistence of clothianidin in the environment, clothianidin has the properties of a chemical which could lead to widespread groundwater contamination should the registrant (e.g. bayer or takeda) request field uses involving direct application of clothianidin to the land surface. in a 2010 epa report, it was noted that the registrant (e.g. bayer or takeda) had recently added new uses on the labels, including using the pesticide directly applied to the soil surface/foliage at much higher application rate than as specified in 2003. as a result, the potential for clothianidin to move from the treated area to the nearby surface water body under the new uses is much greater than with use as a seed treatment. birds according to the epa, clothianidin is practically non-toxic to test bird species that were fed relatively large doses of the chemical on an acute basis. however, epa 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). bobwhite quail eggshell thickness was affected when the test birds were given a diet consisting of relatively large amounts of clothianidin-treated seeds. the pest management regulatory agency of canada lists clothianidin as "moderately toxic" to birds. bees and other insect pollinators