Thiamethoxam is the ISO

common name In biology, a common name of a taxon or organism (also known as a vernacular name, English name, colloquial name, country name, popular name, or farmer's name) is a name that is based on the normal language of everyday life; and is often contra ...

for a mixture of ''cis-trans'' isomers used as a systemic insecticide of the

neonicotinoid Neonicotinoids (sometimes shortened to neonics ) 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, din ...

class. It has a broad spectrum of activity against many types of insects and can be used as a

seed dressing In agriculture and horticulture, a seed treatment is any additional material added to the seed. By the amount of material added, it can be divided into: * A seed dressing, typically containing a "protectant" ( pesticide) applied to the seed and po ...

History

Thiamethoxam was developed by

Ciba-Geigy Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-loc ...

(now

Syngenta Syngenta AG is a provider of agricultural science and technology, in particular seeds and pesticides with its management headquarters in Basel, Switzerland. It is owned by ChemChina, a Chinese state-owned enterprise. Syngenta was founded ...

) in 1991 and launched in 1998; a patent dispute arose with

Bayer Bayer AG (, commonly pronounced ; ) is a German multinational pharmaceutical and biotechnology company and one of the largest pharmaceutical companies in the world. Headquartered in Leverkusen, Bayer's areas of business include pharmaceutica ...

which already had patents covering other neonicotinoids including

imidacloprid Imidacloprid is a systemic insecticide belonging to a class of chemicals called the neonicotinoids which act on the central nervous system of insects. The chemical works by interfering with the transmission of stimuli in the insect nervous system ...

and clothianidin. In 2002 the dispute was settled, with Syngenta paying Bayer $120 million in exchange for worldwide rights to thiamethoxam.

Synthesis

Thiamethoxam was first prepared by chemists at Ciba Geigy in 1991. S-Methyl-N-nitro-isothiourea is treated with

methylamine Methylamine is an organic compound with a formula of . This colorless gas is a derivative of ammonia, but with one hydrogen atom being replaced by a methyl group. It is the simplest primary amine. Methylamine is sold as a solution in methanol, ...

to give N-methyl nitroguanidine. This intermediate is used in a

Mannich reaction In organic chemistry, the Mannich reaction is a three-component organic reaction that involves the amino alkylation of an acidic proton next to a carbonyl () functional group by formaldehyde () and a primary or secondary amine () or ammonia (). ...

with

formaldehyde Formaldehyde ( , ) ( systematic name methanal) is a naturally occurring organic compound with the formula and structure . The pure compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde (refer to section ...

formic acid Formic acid (), systematically named methanoic acid, is the simplest carboxylic acid, and has the chemical formula HCOOH and structure . It is an important intermediate in chemical synthesis and occurs naturally, most notably in some ants. Est ...

to give 3-methyl-4-nitroimino-1,3,5-oxadiazinane. In the final step, the heterocycle is N-alkylated with a

thiazole Thiazole, or 1,3-thiazole, is a heterocyclic compound that contains both sulfur and nitrogen. The term 'thiazole' also refers to a large family of derivatives. Thiazole itself is a pale yellow liquid with a pyridine-like odor and the molecular fo ...

derivative to give a mixture of ''E'' and ''Z'' isomers of the final product. : Thiamethoxam synthesis route

Mechanisms of action

Thiamethoxam is a broad-spectrum, systemic insecticide, which means it is absorbed quickly by plants and transported to all of its parts, including pollen, where it acts to deter insect feeding. An insect can absorb it in its stomach after feeding, or through direct contact, including through its tracheal system. The compound gets in the way of information transfer between nerve cells by interfering with

nicotinic acetylcholine receptors Nicotinic acetylcholine receptors, or nAChRs, are receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the central and peripheral ne ...

in the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...

, and eventually paralyzes the muscles of the insects. Syngenta asserts that thiamethoxam improves plant vigor by triggering physiological reactions within the plant, which induce the expression of specific "functional proteins" involved in various stress defense mechanisms of the plant allowing it to better cope under tough growing conditions, such as "drought and heat stress leading to protein degradation, low pH, high

soil salinity Soil salinity is the salt content in the soil; the process of increasing the salt content is known as salinization. Salts occur naturally within soils and water. Salination can be caused by natural processes such as mineral weathering or by the ...

, free radicals from UV radiation, toxic levels of aluminum, wounding from pests, wind, hail, etc, virus attack".

Toxicity

The selective toxicity of neonicotinoids like thiamethoxam for insects versus mammals is due to the higher sensitivity of insects' acetylcholine receptors. The

Food and Agriculture Organization The Food and Agriculture Organization of the United Nations (FAO)french: link=no, Organisation des Nations unies pour l'alimentation et l'agriculture; it, Organizzazione delle Nazioni Unite per l'Alimentazione e l'Agricoltura is an intern ...

(FAO) of the U.N. assessed thiamethoxam as "moderately hazardous to humans (WHO class III)", because it is harmful if swallowed. It found it to be no skin or eye irritant, and not mutagenic in any ''in vitro'' and ''in vivo''

toxicology Toxicology is a scientific discipline, overlapping with biology, chemistry, pharmacology, and medicine, that involves the study of the adverse effects of chemical substances on living organisms and the practice of diagnosing and treating expos ...

tests. FAO described thiamethoxam as non-toxic to fish, daphnia and algae, mildly toxic for birds, highly toxic to midges and acutely toxic for bees. The

Globally Harmonized System of Classification and Labelling of Chemicals The Globally Harmonized System of Classification and Labelling of Chemicals (GHS) is an internationally agreed-upon standard managed by the United Nations that was set up to replace the assortment of hazardous material classification and labelli ...

(GHS) classification is: "Harmful if swallowed. Very toxic to aquatic life with long lasting effects".

Sublethal Non-lethal weapons, also called nonlethal weapons, less-lethal weapons, less-than-lethal weapons, non-deadly weapons, compliance weapons, or pain-inducing weapons are weapons intended to be less likely to kill a living target than conventional ...

doses of thiamethoxam metabolite clothianidin (0.05–2 ng/bee) have been known to cause reduced foraging activity since at least 1999, but this was quantified in 2012 by RFID tagged honeybees. Doses of equal or more than 0.5 ng/bee caused longer foraging flights.

Regulation and use

United States

Thiamethoxam has been approved for use in the US as an

antimicrobial An antimicrobial is an agent that kills microorganisms or stops their growth. Antimicrobial medicines can be grouped according to the microorganisms they act primarily against. For example, antibiotics are used against bacteria, and antifungals ...

pesticide, wood preservative and as a insecticide; it was first approved in 1999. It is still approved for use in a wide range of crops. On September 5, 2014 Syngenta petitioned the EPA to increase the legal tolerance for thiamethoxam residue in numerous crops. It wanted to use thiamethoxam as a leaf spray, rather than just a seed treatment, to treat late to midseason insect pests. Thiamethoxam use USA

The estimated annual use of the compound in US agriculture is mapped by the US Geological Service and showed an increasing trend from its introduction in 2001 to 2014 when it reached . However, use from 2015 to 2019 dropped sharply following concerns about the effect of neonicotinoid chemicals on pollinating insects. In May 2019, the Environmental Protection Agency revoked approval for a number of products containing thiamethoxam as part of a legal settlement. However, certain formulations continue to be available.

Neonicotinoids banned by the European Union

In 2012, several peer reviewed independent studies were published showing that several neonicotinoids had previously undetected routes of exposure affecting bees including through dust, pollen, and nectar; that sub-nanogram toxicity resulted in failure to return to the hive without immediate lethality, the primary symptom of

colony collapse disorder Colony collapse disorder (CCD) is an abnormal phenomenon that occurs when the majority of worker bees in a honey bee colony disappear, leaving behind a queen, plenty of food, and a few nurse bees to care for the remaining immature bees. Whi ...

; and showing environmental persistence in agricultural irrigation channels and soil. However, not all earlier studies carried out before 2014 have found significant effects. These reports prompted a formal peer review by the

European Food Safety Authority The European Food Safety Authority (EFSA) is the agency of the European Union (EU) that provides independent scientific advice and communicates on existing and emerging risks associated with the food chain. EFSA was established in February 2002 ...

, which stated in January 2013 that neonicotinoids pose an unacceptably high risk to bees, and that the industry-sponsored science upon which regulatory agencies' claims of safety have relied on may be flawed and contain several data gaps not previously considered. In April 2013, the

European Union The European Union (EU) is a supranational political and economic union of member states that are located primarily in Europe. The union has a total area of and an estimated total population of about 447million. The EU has often been ...

voted for a two-year restriction on neonicotinoid insecticides. The ban restricts the use of

, clothianidin, and thiamethoxam on crops that attract bees. In February 2018, the

published a new report indicating that neonicotinoids pose a serious danger to both

honey bee A honey bee (also spelled honeybee) is a eusocial flying insect within the genus ''Apis'' of the bee clade, all native to Afro-Eurasia. After bees spread naturally throughout Africa and Eurasia, humans became responsible for the current cosmop ...

s and wild

bee Bees are winged insects closely related to wasps and ants, known for their roles in pollination and, in the case of the best-known bee species, the western honey bee, for producing honey. Bees are a monophyly, monophyletic lineage within the ...

s. In April 2018, the member states of the

decided to ban the three main neonicotinoids ( clothianidin,

and thiamethoxam) for all outdoor uses.

Other countries

Thiamethoxam is approved for a wide range of agricultural,

viticultural Viticulture (from the Latin word for ''vine'') or winegrowing (wine growing) is the cultivation and harvesting of grapes. It is a branch of the science of horticulture. While the native territory of ''Vitis vinifera'', the common grape vine, ran ...

(vineyard), and horticultural uses.

Emergency use

In January 2021 the UK allowed this pesticide to be used to save

sugar beet A sugar beet is a plant whose root contains a high concentration of sucrose and which is grown commercially for sugar production. In plant breeding, it is known as the Altissima cultivar group of the common beet ('' Beta vulgaris''). Together ...

plants in danger of damage from

beet yellows virus Beet yellows virus (BYV) is a plant pathogenic virus of the family '' Closteroviridae''. Beet yellows virus is transmitted by multiple species of aphid and causes a yellowing disease in ''Beta vulgaris'' and ''Spinacia oleracea Spinach ('' ...

which is transmitted by aphids. However due to lower levels of this disease than was expected, it was announced in March 2021 that the conditions for emergency use had not been met.

References

{{Portal bar, Chemistry, Insects Insecticides Nitroguanidines Thiazoles Chloroarenes Neonicotinoids