Chlorothalonil (2,4,5,6-tetrachloroisophthalonitrile) is an

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. The ...

mainly used as a broad spectrum, nonsystemic

fungicide Fungicides are biocidal chemical compounds or biological organisms used to kill parasitic fungi or their spores. A fungistatic inhibits their growth. Fungi can cause serious damage in agriculture, resulting in critical losses of yield, quality, ...

, with other uses as a wood protectant,

pesticide Pesticides are substances that are meant to control pests. This includes herbicide, insecticide, nematicide, molluscicide, piscicide, avicide, rodenticide, bactericide, insect repellent, animal repellent, microbicide, fungicide, and lampri ...

acaricide Acaricides are pesticides that kill members of the arachnid subclass ''Acari'', which includes ticks and mites. Acaricides are used both in medicine and agriculture, although the desired selective toxicity differs between the two fields. Termino ...

, and to control

mold A mold () or mould () is one of the structures certain fungus, fungi can form. The dust-like, colored appearance of molds is due to the formation of Spore#Fungi, spores containing Secondary metabolite#Fungal secondary metabolites, fungal seco ...

mildew Mildew is a form of fungus. It is distinguished from its closely related counterpart, mould, largely by its colour: moulds appear in shades of black, blue, red, and green, whereas mildew is white. It appears as a thin, superficial growth consi ...

bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...

algae Algae (; singular alga ) is an informal term for a large and diverse group of photosynthetic eukaryotic organisms. It is a polyphyletic grouping that includes species from multiple distinct clades. Included organisms range from unicellular mic ...

. Chlorothalonil-containing products are sold under the names Bravo, Echo, and Daconil. It was first registered for use in the US in 1966. In 1997, the most recent year for which data are available, it was the third most used fungicide in the US, behind only

sulfur Sulfur (or sulphur in British English) is a chemical element with the symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms form cyclic octatomic molecules with a chemical formula ...

and

copper Copper is a chemical element with the symbol Cu (from la, cuprum) and atomic number 29. It is a soft, malleable, and ductile metal with very high thermal and electrical conductivity. A freshly exposed surface of pure copper has a pinkis ...

, with used in agriculture that year. Including nonagricultural uses, the

United States Environmental Protection Agency The Environmental Protection Agency (EPA) is an independent executive agency of the United States federal government tasked with environmental protection matters. President Richard Nixon proposed the establishment of EPA on July 9, 1970; it be ...

(EPA) estimates, on average, almost were used annually from 1990 to 1996.Reregistration Eligibility Decision for chlorothalonil
US EPA, 1999.

Uses

In the US, chlorothalonil is used predominantly on

peanut The peanut (''Arachis hypogaea''), also known as the groundnut, goober (US), pindar (US) or monkey nut (UK), is a legume crop grown mainly for its edible Seed, seeds. It is widely grown in the tropics and subtropics, important to both small ...

s (about 34% of usage),

potato The potato is a starchy food, a tuber of the plant ''Solanum tuberosum'' and is a root vegetable native to the Americas. The plant is a perennial in the nightshade family Solanaceae. Wild potato species can be found from the southern Unit ...

es (about 12%), and

tomato The tomato is the edible berry of the plant ''Solanum lycopersicum'', commonly known as the tomato plant. The species originated in western South America, Mexico, and Central America. The Mexican Nahuatl word gave rise to the Spanish word ...

es (about 7%), although the EPA recognizes its use on many other crops. It is also used on golf courses and lawns (about 10%) and as a preservative additive in some paints (about 13%), resins, emulsions, and coatings. Chlorothalonil is commercially available in many different formulations and delivery methods. It is applied as a dust, dry or water-soluble grains, a

wettable powder A wettable powder (WP) is an insecticide or other pesticide formulation consisting of the active ingredient in a finely ground state combined with wetting agents and sometimes bulking agents. Wettable powders are designed to be applied as a dil ...

, a liquid spray, a fog, and a dip. It may be applied by hand, by ground sprayer, or by aircraft.

Mechanism of action

Chlorothalonil reduces and thereby deactivates

glutathione Glutathione (GSH, ) is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by sources such as reactive oxygen species, free radicals, pero ...

. Its mechanism of action is similar to that of trichloromethyl sulfenyl fungicides such as

captan Captan is a general use pesticide (GUP) that belongs to the phthalimide class of fungicides. It is a white solid, although commercial samples appear yellow or brownish. Applications Although it can be applied on its own, Captan is often add ...

and

folpet Folpet is the tradename for the organic compound with the formula C6H4(CO)2NSCCl3. It is a fungicide derived from phthalimide (C6H4(CO)2N-) and trichloromethylsulfenyl chloride. The compound is white although commercial samples can appear bro ...

Toxicity

Acute

According to the EPS, chlorothalonil is a toxicity category I eye irritant, producing severe eye irritation. It is in toxicity category II, "moderately toxic", if inhaled (inhaled 0.094 mg/L in rats.) For skin contact and ingestion, chlorothalonil is rated toxicity category IV, "practically nontoxic", meaning the oral and dermal is greater than 10,000 mg/kg.

Chronic

Long-term exposure to chlorothalonil resulted in

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...

damage and tumors in animal tests.

Carcinogenic

Chlorothalonil is a Group 2B "possible human

carcinogen A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive substan ...

" (N.B. : in the Group 2A of International Agency for Research on Cancer IARC are the "probable human

" substances), based on observations of

cancers Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Poss ...

and

tumors A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

of the kidneys and

forestomach The rumen, also known as a paunch, is the largest stomach compartment in ruminants and the larger part of the reticulorumen, which is the first chamber in the alimentary canal of ruminant animals. The rumen's microbial favoring environment allow ...

s in laboratory animals fed diets containing chlorothalonil. To give context, the IARC evaluates Pickled vegetables (traditional Asian) as a Group 2B possible human carcinogen, and night shift work and drinking very hot beverages as Group 2A probable human carcinogen substances.

Environmental

Chlorothalonil was found to be an important factor in the decline of the honey bee population, by making the bees more vulnerable to the gut parasite ''

Nosema ceranae ''Nosema ceranae'' is a microsporidian, a small, unicellular parasite that mainly affects ''Apis cerana'', the Asiatic honey bee. Along with '' Nosema apis'', it causes the disease nosemosis, the most widespread of the diseases of adult honey b ...

''. Chlorothalonil is highly toxic to fish and aquatic invertebrates, but not toxic to birds.Environmental Health Criteria 183

World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...

, 1996. At a concentration of 164 μg/L, chlorothalonil was found to kill a species of frog within a 24-hour exposure.

Contaminants

Common chlorothalonil synthesis procedures frequently result in contamination of it with small amounts of

hexachlorobenzene Hexachlorobenzene, or perchlorobenzene, is an organochloride with the molecular formula C6Cl6. It is a fungicide formerly used as a seed treatment, especially on wheat to control the fungal disease bunt. It has been banned globally under the Sto ...

(HCB), which is toxic. US regulations limit HCB in commercial production to 0.05% of chlorothalonil. According to the EPA report, "post-application exposure to HCB from chlorothalonil is not expected to be a concern based on the low level of HCB in chlorothalonil.

2,3,7,8-Tetrachlorodibenzodioxin 2,3,7,8-Tetrachlorodibenzo-''p-''dioxin (TCDD) is a polychlorinated dibenzo''-p-''dioxin (sometimes shortened, though inaccurately, to simply 'dioxin')Tuomisto, Jouko (2019) Dioxins and dioxin-like compounds: toxicity in humans and animals, s ...

being one of the most potent carcinogens known is also a known contaminant".

Environmental contamination

Chlorothalonil has been detected in ambient air in

Minnesota Minnesota () is a state in the upper midwestern region of the United States. It is the 12th largest U.S. state in area and the 22nd most populous, with over 5.75 million residents. Minnesota is home to western prairies, now given over to ...

and

Prince Edward Island Prince Edward Island (PEI; ) is one of the thirteen Provinces and territories of Canada, provinces and territories of Canada. It is the smallest province in terms of land area and population, but the most densely populated. The island has seve ...

, as well as in

groundwater Groundwater is the water present beneath Earth's surface in rock and soil pore spaces and in the fractures of rock formations. About 30 percent of all readily available freshwater in the world is groundwater. A unit of rock or an unconsolidate ...

Long Island, New York Long Island is a densely populated island in the southeastern region of the U.S. state of New York, part of the New York metropolitan area. With over 8 million people, Long Island is the most populous island in the United States and the 18th ...

and

Florida Florida is a state located in the Southeastern region of the United States. Florida is bordered to the west by the Gulf of Mexico, to the northwest by Alabama, to the north by Georgia, to the east by the Bahamas and Atlantic Ocean, and to ...

. In the first three cases, the contamination is presumed to have come from potato farms. It has also been detected in several fish kills in

. The main breakdown product of chlorothalonil is hydroxy-2,5,6-trichloro-1,3-dicyanobenzene (SDS-3701). It has been shown to be 30 times more acutely toxic than chlorothalonil and more persistent in the environment. Laboratory experiments have shown it can thin the eggshells of birds, but no evidence supports this happening in the environment. In 2019, a review of the evidence found that "a high risk to amphibians and fish was identified for all representative uses", and that chlorothalonil breakdown products may cause DNA damage. Around the same time, research indicated chlorothalonil and other fungicides to be the strongest factor in bumblebee population decline. File:2,4,5-trichloro-6-hydroxyisophthalonitrile.svg, 2,4,5-trichloro-6-hydroxyisophthalonitrile (SDS-3701) File:R417888.svg, Chlorothalonil sulfonic acid (R417888) File:R471811.svg, R471811

Gag order

Syngenta sued to stop communication by Swiss health authorities with the Swiss public regarding the "relevance" of specific metabolites of chlorothalonil that Swiss authorities detected in high concentrations in the groundwater from which hundreds of thousands of Swiss people obtain drinking water. The court banned Swiss health authorities from communicating with the public about the dangers posed by some of the metabolites.

Bans

In March 2019, as a result of the previously mentioned research, the European Union banned the use of chlorothalonil dated to take effect May 20, 2020. Switzerland followed in December 2019.

Removal

The removal of chlorothalonil and its metabolites is usually achieved by very expensive, technically complex and unecological methods such as reverse osmosis, nano- or microfiltration. In addition, dilution is achieved by mixing with uncontaminated water. However, this only reduces the concentration, the substances still remain in the water. In technologies based on membrane technology, the membranes must be cleaned regularly with chemicals, which is expensive and not ecological. Recent research results from a Swiss company show very good results for the removal of chlorothalonil and its metabolites. In contrast to the conclusion described in the Eawag fact-sheet, it was also possible to remove the metabolites R471811 and chlorothalonil sulfonic acid from water using a filter material based on activated carbon. The first measurements did not even reach the detection limit. Thus, it was shown that it is possible to completely remove the pesticide residues.

Production

Chlorothalonil can be produced by the direct chlorination of

isophthalonitrile Isophthalonitrile is an organic compound with the formula C6H4(CN)2. Two other isomers exist, phthalonitrile and terephthalonitrile. All three isomers are produced commercially by ammoxidation of the corresponding xylene isomers. Isophthalonitr ...

or by dehydration of tetrachloroisophthaloyl amide with

phosphoryl chloride Phosphoryl chloride (commonly called phosphorus oxychloride) is a colourless liquid with the formula . It hydrolyses in moist air releasing phosphoric acid and fumes of hydrogen chloride. It is manufactured industrially on a large scale from phosp ...

. It is a white solid. It breaks down under basic conditions, but is stable in neutral and acidic media. Technical grade chlorothalonil contains traces of

dioxins Dioxin may refer to: * 1,2-Dioxin or 1,4-Dioxin, two unsaturated heterocyclic 6-membered rings where two carbon atoms have been replaced by oxygen atoms, giving the molecular formula C4H4O2 *Dibenzo-1,4-dioxin, the parent compound also known as ...

and

, a

persistent organic pollutant Persistent organic pollutants (POPs), sometimes known as "forever chemicals", are organic compounds that are resistant to environmental degradation through chemical, biological, and photolytic processes. They are toxic chemicals that adversely ...

banned under the

Stockholm Convention Stockholm Convention on Persistent Organic Pollutants is an international environmental treaty, signed on 22 May 2001 in Stockholm and effective from 17 May 2004, that aims to eliminate or restrict the production and use of persistent organic ...

References

External links

Extension Toxicology Network: Chlorothalonil Pesticide Information Profile
* * *{{cite web , title=2017 Pesticide Use Maps - High , website=Water Resources , publisher=

United States Geological Survey The United States Geological Survey (USGS), formerly simply known as the Geological Survey, is a scientific agency of the United States government. The scientists of the USGS study the landscape of the United States, its natural resources, ...

, url=http://water.usgs.gov/nawqa/pnsp/usage/maps/show_map.php?year=2017&map=CHLOROTHALONIL&hilo=H , access-date=2021-03-16 Fungicides Nitriles Chloroarenes IARC Group 2B carcinogens