Gebruiker:KvaraWolves88/Thiacloprid

Thiacloprid Thiacloprid (3-(6-Chloro-3-pyridinyl)methyl-2-thiazolidinylidene]] cyanamide) is a yellow crystalline powder that is part of a class of insecticides known as neonicotinoids[1]. Like other compounds in this class, thiacloprid acts as a potent agonist for nicotinic acetylcholine receptors (nAChRs) of the central nervous system (CNS) of a wide variety of chewing and sucking insects such as aphids, whiteflies, leaf- and planthoppers as well as a number of coleopteran pests[2,3]. Although in the past thiacloprid, along with other neonicotinoids, were considered highly selective for crop insects, it was not deemed toxic or carcinogenic to mammals and even humans[4]. However, more recent toxicological reviews are indicating the opposite, highlighting its potential adverse effects in humans[4]. One of the main routes of exposure is the accumulation of this compound in food and groundwater[4][BRON KIRILL 6]. Due to its toxic effects to aquatic life, carcinogenic, and teratogenic properties, an official ban of the use of the product for agricultures purposes was introduced by the EU in 2020[5].

History[bewerken | brontekst bewerken]

In the second half of the 1970’s, researchers from the Shell Chemical Company were conducting studies into more effective insecticides, namely nitromethylenes, which was considered as an innovative insecticide at the time. As the research progressed, chemists at Nihon Bayer Agrochem were researching the incorporation of 3-pyridylmethyl moiety to the heterocyclic structure of the nitromethylenes. Further research led to the production of imidacloprid, a precursor to thiacloprid. Since its launch in the 1991, derivatives of imidacloprid, which belongs to the chloropyridines of the neonicotinoid family, have been developed including thiacloprid in 2001[1][6][7]. Since then, the use of neonicotinoids including thiacloprid has increased drastically[7].

Structure and reactivity[bewerken | brontekst bewerken]

Structurally, thiacloprid is a synthetic molecule that closely resembles the molecular structure of nicotine[7]. Thiacloprid consists of an 2-chloropyridyl ring connected to a saturated nitrogen- and sulphur-containing 5-membered ring system bridged by a methylene group[2][8]. To this saturated ring, a conjugated N-cyanoimino group that is of great relevance for the reactivity of the compound with insect and non-target organism nAChRs[8]. In such a manner thiacloprid, like other neonicotinoids, has three structural sites where biotransformations can take place. The N¬-heterocyclylmethyl component can undergo oxidative cleavage in the form of a hydroxylation reaction to yield the corresponding amine and heterocyclic aldehyde. This part of the molecule also allows for GSH coupling via the chlorine atom. The thiazolidine spacer, which consists of the saturated nitrogen/sulphur ring can be hydroxylated or via sulfoxide intermediates metabolized to sulfonic acids and methylene sulfoxides. The last moiety, the electron-withdrawing N-cyanoimino group, can be cleaved to the descyano or N-carbamoylimine derivatives[9].

Synthesis[bewerken | brontekst bewerken]

To synthesize thiacloprid, a condensation reaction can be performed between 2-cyanoimine-1,3-thiazzolidine and 2-chloro-5-chloromethylpyridine in the presence of organic base (DBU) and iridium complex as a catalyst[10].

Mechanism of action[bewerken | brontekst bewerken]

Thiacloprid manages to distribute throughout the plant independent of the manner of application. This causes the plant to be toxic to all organisms that ingest it. Thiacloprid, a neonicotinoid generally does not affect organisms who do not have a CNS, since it selectively targets nAChRs[11]. When thiacloprid binds to nAChRs on the post-synaptic membrane, it acts as an agonist, causing ion channels to open. This causes continuous depolarization, which desensitizes the receptors. Eventually, the insect becomes paralyzed and dies. When comparing vertebrates and invertebrates, it is striking that neonicotinoids have a much higher toxicity for invertebrates. This is caused by the lower number of nicotinic receptors in vertebrates that have high affinity for neonicotinoids.

Related compounds[bewerken | brontekst bewerken]

All neonicotinoids target nAChRs, however their agonistic actions can change depending on small structural variations. Seven separate[11] neonicotinoid compounds are available commercially worldwide. These are imidacloprid, thiacloprid, clothianidin, thiamethoxam, acetamiprid, nitenpyram, and dinotefuran.

At the moment, tests are run on cis-isomers of current neonicotinoid compounds. All presently available neonicotinoids contain a cyano or nitro group in the trans position. However, it is known that for the cis-isomers a different level of toxicity and efficacy can be observed [11].

When comparing neonicotinoids, an important distinction can be made based on their hydrophilicity. Plants take up lipophilic compound more readily compared to hydrophilic compounds. A good uptake of an insecticide by a plant is crucial for it to be effective against insects. Research shows that water solubility, in terms of functional groups of insecticides, increases in the order: =C-NO2 > =N-CN > =N-NO2. Therefore, thiacloprid is less soluble in water than imidacloprid, with values of 0,185 g/L and 0,61 g/L respectively.

Metabolism[bewerken | brontekst bewerken]

Plants have varying mechanisms for metabolizing certain pesticides, including thiacloprid. Often, the method of insecticide-application influences the metabolism. Also, among different insect species and populations can the extent and efficiency of its metabolism vary [13]. One study advises against the use of thiacloprid, since it has a very short half-life (less than 2 days) for an insecticide. They also concluded that ~70% of thiacloprid gets converted into its metabolite thiacloprid amide. The study claims that this metabolite is less effective than its precursor, by yielding lower insecticidal activity. The metabolite does have an advantage over its parent, because it has a longer half-life[27].

Efficacy and side effects[bewerken | brontekst bewerken]

Considering the toxicokinetics of thiacloprid in the environment, the efficacy of the compound has been determined. In addition, the adverse effects after exposure to thiacloprid are demonstrated, indicating the risk regarding the compound.

Efficacy[bewerken | brontekst bewerken]

Thiacloprid is used as an effective reagent against insects and larvae. In 2017, Chinese researchers tested the efficacy of thiacloprid used on tomato crops infested with nematode (Meloidogyne incognita) and whitefly (B-biotype Bemisia tabaci). When thiacloprid was applied to the soil in two consecutive years, whitefly adults decreased by 37.8-75.4% within 60 days of treatment. The root-galling index was reduced by 31.8-85.2%. The optimum tomato plant growth maximum yields were observed when the soil was treated with 15 kg/ha of thiacloprid. The thiacloprid treatment indicates a high productivity, especially in comparison to other insecticides that were used, like abamectin. [14]

Adverse effects[bewerken | brontekst bewerken]

In 2020, thiacloprid faced a ban in the European Union due to its harmful effects on unborn organisms and the apprehension regarding groundwater contamination by carcinogenic metabolites. Additionally, its high toxicity to bees and other pollinators raised environmental concerns.[15]

Toxicity[bewerken | brontekst bewerken]

Neonicotinoid insecticides are considered to be less toxic to humans in comparison to older insecticides. In 2015, a fatal case of thiacloprid was reported by researchers in the United States. After deliberate ingestion, a 23-year-old man died after manifesting with status epilepticus, respiratory paralysis, rhabdomyolysis, metabolic acidosis and acute kidney injury.[16] These are the acute toxicities and NOAEL values that were derived from studies in rats:[17] Acute toxicity of thiacloprid in rats Acute oral toxicity Males: 621 mg/kg Females: 396 mg/kg Acute dermal toxicity Males: 2000 mg/kg Females: 2000 mg/kg Acute inhalation toxicity Males: >0.481 mg/L Females: >0.481 mg/L NOAEL of thiacloprid in rats Minimal risk level at a 90-day oral exposure Males: 7.3 mg/kg/day Females: 7.6 mg/kg/day Minimal risk level at chronic feeding/ carcinogenicity Males: 1.2 mg/kg/day Females: 1.6 mg/kg/day Minimum risk level for developmental neurotoxicity Maternal: 4.4 mg/kg/day Offspring: 4.4 mg/kg/day

Effects on animals and environment[bewerken | brontekst bewerken]

Thiacloprid has been proven to be toxic to non-target soil invertebrates and pollinators. Besides direct exposure to insects, the insecticide is also toxic to mammals, aquatic species and ecosystems via indirect admission.

Terrestrial animals[bewerken | brontekst bewerken]

Thiacloprid is toxic to non-target soil invertebrates like worms and lice, as well pollinators such as the honeybee and bumble bee, especially if the crops were sprayed after flowering[18]. These insects have adverse effects not just at a lethal dose, but recent studies suggest that sub-lethal doses have effects on the growth, maturation, survival and reproduction of animals[19, 20]. Small mammals that come in contact with plants sprayed with thiacloprid or insects that ingested thiacloprid bioaccumulate the toxic compound and may cause secondary poisoning in predators[21] and birds. A recent study conducted in rats, mice and dogs showed that while on short-term the liver was the target organ, toxicity in the dog prostate was additionally observed. Following 90 days (short-term) of study no-observed adverse effect level (NOAEL) of 7 mg/kg body weight per day was observed in rats. This was observed to be lower in a two-year study measuring a NOAEL of 1.2 mg/kg body weight in rats. Upon long-term exposure (two years) to thiacloprid, in addition to the aforementioned liver problems, effects were observed in thyroid, eye, nervous system and muscles of rats. For mice, besides liver effects, problems were observed in the adrenal glands, lymph nodes and ovaries[22]. This study found no long-term effects on the environment caused by thiacloprid.

Aquatic animals[bewerken | brontekst bewerken]

Thiacloprid often enters rivers and other aquatic environments via land water run-off after rains[23]. This leads to surface water pollution, which has detrimental effects on the environment. A lot of aquatic invertebrates are affected by the lethal and sub-lethal toxic effects of thiacloprid. Most notably the inability to eat, even after relocation to a clean environment. As the aquatic invertebrates play a huge role in the aquatic ecosystems as important decomposers and food base for higher trophic levels, they are used as biomarkers for the pollution of the rivers[24].

Regulation[bewerken | brontekst bewerken]

Due to the toxic, teratogenic and carcinogenic effects on humans and pollinators, as well its ability to remain in ground water, thiacloprid was prohibited in the EU and UK[25].

12 - References

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5. Should we allow residues of EU-banned Thiacloprid in imported food? [Internet]. PAN Europe. 2024 [cited 2024 Mar 1]. Available from: https://www.pan-europe.info/blog/should-we-allow-residues-eu-banned-thiacloprid-imported-food

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Use of AI AI, in particular Bing AI and Google Gemini LLMs were used in the writing of this report in the following ways: • Sharing a paper with the LLM and asking it to explain or reword a section in simpler terms, when a paper was difficult to understand. • Sharing a paper with the LLM and asking it to give papers, government reports that touch on the same topic. • When starting a new topic, LLMs were used to find initial information and first sources on the topic, from where the research could continue. AI was not used for the following: • LLMs were not tasked with writing pieces of text to directly incorporate into the report. • LLMs were not solely used for explaining a topic or as the source for a topic. • LLMs were not solely used to find sources for this report.

Links for Wikipedia Page 1. https://link.springer.com/book/10.1007/978-1-59259-132-9 DOI = https://doi.org/10.1007/978-1-59259-132-9 eBook ISBN: 978-1-59259-132-9

2. https://pubs.acs.org/doi/10.1021/jf101303g DOI = http://dx.doi.org/10.1021/jf101303g

3. https://onlinelibrary.wiley.com/doi/10.1002/ps.1631 DOI = http://dx.doi.org/10.1002/ps.1631

4. https://www.sciencedirect.com/science/article/pii/S0045653517317332?via%3Dihub DOI = http://dx.doi.org/10.1016/j.chemosphere.2017.10.149

5. https://www.pan-europe.info/blog/should-we-allow-residues-eu-banned-thiacloprid-imported-food

6. https://www.researchgate.net/publication/227596648_Molecular_Design_of_Neonicotinoids_Past_Present_and_Future DOI = http://dx.doi.org/10.1002/3527602038.ch16

7. https://pubs.acs.org/doi/10.1021/acs.est.7b06388 DOI = http://dx.doi.org/10.1021/acs.est.7b06388

8. https://onlinelibrary.wiley.com/doi/book/10.1002/3527602038 DOI = http://dx.doi.org/10.1002/3527602038

9. https://pubs.acs.org/doi/10.1021/jf102438c DOI = http://dx.doi.org/10.1021/jf102438c

10. https://worldwide.espacenet.com/patent/search/family/077538543/publication/CN113354632A?q=pn%3DCN113354632A

11. http://dx.doi.org/10.1007/s11356-014-3470-y

12. https://www.jstage.jst.go.jp/article/jpestics/33/2/33_G07-28/_pdf/-char/en