Thiamethoxam

Thiamethoxam was developed by Ciba-Geigy (now Syngenta) in 1991 and launched in 1998; a patent dispute arose with Bayer which already had patents covering other neonicotinoids including imidacloprid 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 to give N-methyl nitroguanidine. This intermediate is used in a Mannich reaction with formaldehyde in formic acid to give 3-methyl-4-nitroimino-1,3,5-oxadiazinane. In the final step, the heterocycle is N-alkylated with a thiazole derivative to give a mixture of E and Z isomers of the final product. : ==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 in the central nervous system, 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, 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 (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 tests. In bioassays of aquatic organisms, fish, aquatic primary producers, mollusks, worms, and rotifers are often largely insensitive to thiamethoxam concentrations found in surface waters, but insects, such as chironomid larvae are especially susceptible. Sublethal 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 pesticide, wood preservative and as an 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. , 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 voted for a two-year restriction on neonicotinoid insecticides. The ban restricts the use of imidacloprid, clothianidin, and thiamethoxam on crops that attract bees. In February 2018, the European Food Safety Authority published a new report indicating that neonicotinoids pose a serious danger to both honey bees and wild bees. In April 2018, the member states of the European Union decided to ban the three main neonicotinoids (clothianidin, imidacloprid and thiamethoxam) for all outdoor uses. Other countries Thiamethoxam is approved for a wide range of agricultural, viticultural(vineyard), and horticultural uses. Emergency use In January 2021 the UK allowed this pesticide to be used to save sugar beet plants in danger of damage from beet yellows virus 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. The UK made similar decisions in 2022, 2023, and 2024 but in these three years the predicted incidence level of yellow virus was met, and in March 2024 it was announced that the use of Cruiser SB (a pesticide which contains thiamethoxam) would be allowed for a third consecutive year. ==References==