Clothianidin
Encyclopedia
Clothianidin is an insecticide
Insecticide
An insecticide is a pesticide used against insects. They include ovicides and larvicides used against the eggs and larvae of insects respectively. Insecticides are used in agriculture, medicine, industry and the household. The use of insecticides is believed to be one of the major factors behind...

 developed by Takeda Chemical Industries and Bayer AG. Similar to thiamethoxam
Thiamethoxam
Thiamethoxam is an insecticide in the class of neonicotinoids. It has a broad spectrum of activity against many types of insects.-History:Thiamethoxam was developed by Syngenta but a patent dispute arose with Bayer which already had patents covering other neonicotinoids including imidacloprid...

 and imidacloprid
Imidacloprid
Imidacloprid is a nicotine-based, systemic insecticide, which acts as a neurotoxin and belongs to a class of chemicals called the neonicotinoids. Although it is now off patent, the primary manufacturer of this chemical is Bayer CropScience,...

, it is a neonicotinoid. Neonicotinoids are a class of insecticides which act on the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

 of insects with lower toxicity to mammals. According to the Environmental Protection Agency, "the fate and disposition of clothianidin in the environment suggest a compound that is a systemic
Systemic
Systemic refers to something that is spread throughout, system-wide, affecting a group or system such as a body, economy, market or society as a whole. Systemic may also refer to:-In medicine:...

 insecticide that is persistent and mobile, stable to hydrolysis
Hydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...

, and has potential to leach to ground water, as well as runoff to surface waters." Neonicotinoid insecticides are among the most widely used insecticides worldwide, but recently the uses of some members of this class have been restricted in some countries due to a possible connection to honey bee colony collapse disorder
Colony Collapse Disorder
Colony collapse disorder is a phenomenon in which worker bees from a beehive or European honey bee colony abruptly disappear. While such disappearances have occurred throughout the history of apiculture, the term colony collapse disorder was first applied to a drastic rise in the number of...

.

Clothianidin was first given conditional registration for use as a pesticide by the United States Environmental Protection Agency
United States Environmental Protection Agency
The U.S. Environmental Protection Agency is an agency of the federal government of the United States charged with protecting human health and the environment, by writing and enforcing regulations based on laws passed by Congress...

 in April of 2003, pending the completion of additional study of its safety to be done by December of 2004 (later extended to May of 2005). The study was not completed until August of 2007. Clothianidin was granted an unconditional registration for use as a seed treatment for corn and canola on April 22, 2010. However, on November 2, 2010, after a review of the studies supplied by the manufacturer, the EPA released a memorandum in which they stated that the Bayer field study submitted did not appear to be adequate and it was reclassified as "supplemental".

Environmental impact

According to the United States Environmental Protection Agency
United States Environmental Protection Agency
The U.S. Environmental Protection Agency is an agency of the federal government of the United States charged with protecting human health and the environment, by writing and enforcing regulations based on laws passed by Congress...

 (EPA) clothianidin generally poses less risk to agricultural workers and fish and wildlife when compared to the organophosphate
Organophosphate
An organophosphate is the general name for esters of phosphoric acid. Phosphates are probably the most pervasive organophosphorus compounds. Many of the most important biochemicals are organophosphates, including DNA and RNA as well as many cofactors that are essential for life...

 and carbamate
Carbamate
Carbamates are organic compounds derived from carbamic acid . A carbamate group, carbamate ester, and carbamic acids are functional groups that are inter-related structurally and often are interconverted chemically. Carbamate esters are also called urethanes.-Synthesis:Carbamic acids are derived...

 insecticide alternatives. Laboratory data shows that clothianidin is toxic to honey bees. Current labels for clothianidin products used as foliar treatments (e.g. spray applications) include bee hazard statements that prohibit use when plants are flowering and bees are in the area. The EPA states that they are not aware of any data demonstrating that bee colonies are subject to elevated losses due to long-term exposure to this compound.

Based upon acute toxicity studies, the EPA has classified clothianidin as Toxicity Category III. It is classified as a “not likely” human carcinogen. There are no to low concerns and no residual uncertainties with regard to pre- and/or postnatal toxicity from clothianidin. However, due to evidence of effects on the rat immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...

 and that juvenile rats appear to be more susceptible to these effects, and due to the lack of a developmental immunotoxicity study, a 10X database uncertainty factor is applied to all dietary exposure endpoints.
Available data indicate that clothianidin on corn and canola should result in minimal acute toxic risk to birds. However, assessments show that exposure to treated seeds through ingestion may result in chronic toxic risk to non-endangered and endangered small birds (e.g., songbirds) and acute/chronic toxicity risk to non-endangered and endangered mammals. Clothianidin has the potential for toxic chronic exposure to honey bees, as well as other nontarget pollinators, through the translocation of clothianidin residues in nectar and pollen. Clothianidin should not present a direct acute or chronic risk to freshwater and estuarine/marine fish, or a risk to terrestrial or aquatic vascular and nonvascular plants.

In 2008 Germany revoked the registration of clothianidin for use on seed corn after an incident that resulted in the death of hundreds of nearby honey bees. Investigation of the incident revealed that it was caused by a combination of factors including the failure to use a polymer seed coating known as a "sticker", weather conditions that resulted in late planting when nearby canola
Canola
Canola refers to a cultivar of either Rapeseed or Field Mustard . Its seeds are used to produce edible oil suitable for consumption by humans and livestock. The oil is also suitable for use as biodiesel.Originally, Canola was bred naturally from rapeseed in Canada by Keith Downey and Baldur R...

 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.and a higher application rate which had been authorized for a severe root worm infestation. Clothianidin was also restricted for a short period for use on rapeseed
Rapeseed
Rapeseed , also known as rape, oilseed rape, rapa, rappi, rapaseed is a bright yellow flowering member of the family Brassicaceae...

, however after evidence had shown that the problems resulting from maize
Maize
Maize known in many English-speaking countries as corn or mielie/mealie, is a grain domesticated by indigenous peoples in Mesoamerica in prehistoric times. The leafy stalk produces ears which contain seeds called kernels. Though technically a grain, maize kernels are used in cooking as a vegetable...

 seed were not transferable to rapeseed its use was reinstated under the condition that the pesticide be fixed to the rapeseed grains by means of an additional sticker, so that abrasion dusts would not be released into the air.
In 2009 the German Federal Office of Consumer Protection and Food Safety decided to continue to suspend authorization for the use of clothianidin on corn because it has not yet been fully clarified to what extent and how bees come into contact with the active substances in the pesticides belonging to the neonicotinoid group (clothianidin, thiamethoxam
Thiamethoxam
Thiamethoxam is an insecticide in the class of neonicotinoids. It has a broad spectrum of activity against many types of insects.-History:Thiamethoxam was developed by Syngenta but a patent dispute arose with Bayer which already had patents covering other neonicotinoids including imidacloprid...

 and imidacloprid
Imidacloprid
Imidacloprid is a nicotine-based, systemic insecticide, which acts as a neurotoxin and belongs to a class of chemicals called the neonicotinoids. Although it is now off patent, the primary manufacturer of this chemical is Bayer CropScience,...

) when used on corn. In addition, on the basis of new findings, the question arose as to whether drops of liquid from plants which are taken in by bees pose an additional risk.

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

In August 2008, the Natural Resources Defense Council
Natural Resources Defense Council
The Natural Resources Defense Council is a New York City-based, non-profit, non-partisan international environmental advocacy group, with offices in Washington DC, San Francisco, Los Angeles, Chicago, and Beijing...

 sued the EPA after the latter agency failed to provide records related to studies regarding clothianidin's possible effects on bee
Bee
Bees are flying insects closely related to wasps and ants, and are known for their role in pollination and for producing honey and beeswax. Bees are a monophyletic lineage within the superfamily Apoidea, presently classified by the unranked taxon name Anthophila...

s. When the study was ultimately released, it was criticized for lacking proper control groups; bee colonies were placed within fields of clothianidin-treated canola
Canola
Canola refers to a cultivar of either Rapeseed or Field Mustard . Its seeds are used to produce edible oil suitable for consumption by humans and livestock. The oil is also suitable for use as biodiesel.Originally, Canola was bred naturally from rapeseed in Canada by Keith Downey and Baldur R...

and untreated canola that were located within easy foraging range of each other, permitting each colony to feed from both fields. An internal EPA memo from November 2010 indicated several EPA researchers have also concluded the study was flawed, with deficiencies sufficient to render it of only "supplemental" value. According to the memorandum:
Clothianidin’s major risk concern is to nontarget insects (that is, honey bees). Clothianidin is a neonicotinoid insecticide that is both persistent and systemic. Acute toxicity studies to honey bees show that clothianidin is highly toxic on both a contact and an oral basis. Although EFED does not conduct RQ based risk assessments on non-target insects, information from standard tests and field studies, as well as incident reports involving other neonicotinoids insecticides (e.g., imidacloprid) suggest the potential for long term toxic risk to honey bees and other beneficial insects. An incident in Germany already illustrated the toxicity of clothianidin to honeybees when allowed to drift off-site from treated seed during planting.


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