Fomesafen is the

ISO ISO is the most common abbreviation for the International Organization for Standardization. ISO or Iso may also refer to: Business and finance * Iso (supermarket), a chain of Danish supermarkets incorporated into the SuperBest chain in 2007 * 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 contrast ...

for 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 ...

used as an

herbicide Herbicides (, ), also commonly known as weedkillers, are substances used to control undesired plants, also known as weeds.EPA. February 201Pesticides Industry. Sales and Usage 2006 and 2007: Market Estimates. Summary in press releasMain page fo ...

. It acts by inhibiting the enzyme

protoporphyrinogen oxidase Protoporphyrinogen oxidase or protox is an enzyme that in humans is encoded by the ''PPOX'' gene. Protoporphyrinogen oxidase is responsible for the seventh step in biosynthesis of protoporphyrin IX. This porphyrin is the precursor to hemoglobin, ...

which is necessary for

chlorophyll Chlorophyll (also chlorophyl) is any of several related green pigments found in cyanobacteria and in the chloroplasts of algae and plants. Its name is derived from the Greek words , ("pale green") and , ("leaf"). Chlorophyll allow plants to a ...

synthesis Synthesis or synthesize may refer to: Science Chemistry and biochemistry *Chemical synthesis, the execution of chemical reactions to form a more complex molecule from chemical precursors ** Organic synthesis, the chemical synthesis of organ ...

Soybean The soybean, soy bean, or soya bean (''Glycine max'') is a species of legume native to East Asia, widely grown for its edible bean, which has numerous uses. Traditional unfermented food uses of soybeans include soy milk, from which tofu an ...

s naturally have a high tolerance to fomesafen, via metabolic disposal by glutathione ''S''-transferase. As a result, soy is the most common crop treated with fomesafen, followed by other

bean A bean is the seed of several plants in the family Fabaceae, which are used as vegetables for human or animal food. They can be cooked in many different ways, including boiling, frying, and baking, and are used in many traditional dishes th ...

s and a few other crop types. It is not safe for maize/corn or other

Poaceae Poaceae () or Gramineae () is a large and nearly ubiquitous family of monocotyledonous flowering plants commonly known as grasses. It includes the cereal grasses, bamboos and the grasses of natural grassland and species cultivated in lawns an ...

History

The nitrophenyl ethers are a well-known class of herbicides, the oldest member of which was

nitrofen Nitrofen is an herbicide of the diphenyl ether class. Because of concerns about its carcinogenicity, the use of nitrofen has been banned in the European Union and in the United States since 1996. It has been superseded by related protoporphyrino ...

, invented by Rohm & Haas and first registered for sale in 1964. This area of chemistry became very competitive, with the Mobil Oil Corporation's filing in 1969 and grant in 1974 of a patent to the

structural analog A structural analog (analogue in modern traditional English; Commonwealth English), also known as a chemical analog or simply an analog, is a compound having a structure similar to that of another compound, but differing from it in respect to a ce ...

with a COOCH₃ group adjacent to the nitro group of nitrofen. This product, bifenox, was launched with the

brand name A brand is a name, term, design, symbol or any other feature that distinguishes one seller's good or service from those of other sellers. Brands are used in business, marketing, and advertising for recognition and, importantly, to create an ...

Mowdown in 1981. Meanwhile Rohm & Haas introduced acifluorfen (as its sodium salt with brand name Blazer) in 1980, having developed it under the code number RH-6201. It had much improved properties including a wider spectrum of herbicidal effect and good safety to soybean crops. The first patent for the material was published in December 1975, although an earlier Belgian patent published in September 1973 had described related chemistry. File:Nitrofen.svg, Nitrofen File:Bifenox-flip.svg, Bifenox File:Acifluorfen structure.svg, Acifluorfen Chemists at the

Imperial Chemical Industries Imperial Chemical Industries (ICI) was a British chemical company. It was, for much of its history, the largest manufacturer in Britain. It was formed by the merger of four leading British chemical companies in 1926. Its headquarters were at M ...

(ICI) research site at

Jealott's Hill Jealott's Hill is a village in the county of Berkshire, England, within the civil parish of Warfield. The settlement is on the A3095 road approximately north of Bracknell. The nearest railway station is in . The name of the hill is reported to ...

, UK, investigated this area to attempt to find their own

intellectual property Intellectual property (IP) is a category of property that includes intangible creations of the human intellect. There are many types of intellectual property, and some countries recognize more than others. The best-known types are patents, cop ...

and develop a proprietary material that could compete in the market. The idea which proved successful was to replace the carboxylic acid in acifluorfen with a

group A group is a number of persons or things that are located, gathered, or classed together. Groups of people * Cultural group, a group whose members share the same cultural identity * Ethnic group, a group whose members share the same ethnic ide ...

that could mimic it (by having similar pK_a and overall solubility, for example) but could not

metabolise Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

to acifluorfen and potentially infringe the competitor's patents. Patent filings on this invention, where the replacement for COOH was a CONHSO₂CH₃ group were made in January 1978. Fomesafen was developed under the code number PP021 and first sales were in Argentina in 1983, with the brand name Flex.

Synthesis

As described in the ICI patent, fomesafen can be made from acifluorfen by reaction with

thionyl chloride Thionyl chloride is an inorganic compound with the chemical formula . It is a moderately volatile, colourless liquid with an unpleasant acrid odour. Thionyl chloride is primarily used as a chlorinating reagent, with approximately per year bein ...

to form the

acid chloride In organic chemistry, an acyl chloride (or acid chloride) is an organic compound with the functional group . Their formula is usually written , where R is a side chain. They are reactive derivatives of carboxylic acids (). A specific example o ...

and then with methanesulfonamide, in pyridine as solvent. :Ar-COOH + SOCl₂ → ArCOCl :Ar-COCl + CH₃SO₂NH₂ → ArCONHSO₂CH₃

Mechanism of action

The detailed mechanism of action for fomesafen and related nitrophenyl ether herbicides was unknown at the time they were invented. The effects visible on whole plants are

chlorosis In botany, chlorosis is a condition in which leaves produce insufficient chlorophyll. As chlorophyll is responsible for the green color of leaves, chlorotic leaves are pale, yellow, or yellow-white. The affected plant has little or no ability to ...

and

desiccation Desiccation () is the state of extreme dryness, or the process of extreme drying. A desiccant is a hygroscopic (attracts and holds water) substance that induces or sustains such a state in its local vicinity in a moderately sealed container. ...

: several hypotheses were advanced regarding the molecular-level interactions which might explain these symptoms. The now-accepted explanation for the damage is that these compounds inhibit the enzyme protoporphyrinogen oxidase, which leads to an accumulation of

protoporphyrin IX Protoporphyrin IX is an organic compound, classified as a porphyrin, that plays an important role in living organisms as a precursor to other critical compounds like heme (hemoglobin) and chlorophyll. It is a deeply colored solid that is not sol ...

in the plant cells. This is a potent

photosensitizer Photosensitizers produce a physicochemical change in a neighboring molecule by either donating an electron to the substrate or by abstracting a hydrogen atom from the substrate. At the end of this process, the photosensitizer eventually returns to ...

which activates oxygen, leading to

lipid peroxidation Lipid peroxidation is the chain of reactions of oxidative degradation of lipids. It is the process in which radical (chemistry), free radicals "steal" electrons from the lipids in cell membranes, resulting in cell damage. This process proceeds by ...

. Both light and oxygen are required for this process to kill the plant.

Usage

In the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...

, the

Environmental Protection Agency A biophysical environment is a biotic and abiotic surrounding of an organism or population, and consequently includes the factors that have an influence in their survival, development, and evolution. A biophysical environment can vary in scale f ...

(EPA) is responsible for regulating pesticides under the

Federal Insecticide, Fungicide, and Rodenticide Act The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) is a United States federal law that set up the basic U.S. system of pesticide regulation to protect applicators, consumers, and the environment. It is administered and regulated by t ...

(FIFRA), the

Food Quality Protection Act The Food Quality Protection Act (FQPA), or H.R.1627, was passed unanimously by Congress in 1996 and was signed into law by President Bill Clinton on August 3, 1996. The FQPA standardized the way the Environmental Protection Agency (EPA) would man ...

(FQPA) and the Pesticide Registration Improvement Act (PRIA). A pesticide can only be used legally according to the directions on the label that is included at the time of the sale of the pesticide. The purpose of the label is "to provide clear directions for effective product performance while minimizing risks to human health and the environment". A label is a legally binding document that mandates how the pesticide can and must be used and failure to follow the label as written when using the pesticide is a federal offence. Fomesafen is normally applied postemergence (when weeds are visible in the crop) but may also be used preemergence. It controls or suppresses broadleaf weeds, grasses and sedges in soybeans and is effective on a very wide range of weed species including ''

Abutilon theophrasti ''Abutilon theophrasti'' (velvetleaf, velvet plant, velvetweed, Chinese jute, China jute, crown weed, buttonweed, lantern mallow, butterprint, pie-marker, or Indian mallow) is an annual plant in the family Malvaceae, native to southern Asia. It' ...

'', '' Acalypha ostryifolia'', '' Acanthospermum hispidum'', '' Amaranthus palmeri'', ''

Ambrosia artemisiifolia ''Ambrosia artemisiifolia'', with the common names common ragweed, annual ragweed, and low ragweed, is a species of the genus '' Ambrosia'' native to regions of the Americas. Taxonomy The species name, ''artemisiifolia'', is given because the le ...

'', ''

Anoda cristata ''Anoda cristata'' is a species of flowering plant in the Malvaceae, mallow family known by many common names, including spurred anoda, crested anoda, and violettas. It is native to North and South America. It is known throughout the rest of th ...

'', ''

Barbarea vulgaris ''Barbarea vulgaris'', also called wintercress (usual common name), or alternatively herb barbara, rocketcress, yellow rocketcress, winter rocket, yellow rocket, and wound rocket, is a biennial herb of the genus ''Barbarea'', belonging to the fam ...

'', '' Brassica kaber'', ''

Calystegia sepium ''Calystegia sepium'' (hedge bindweed, Rutland beauty, bugle vine, heavenly trumpets, bellbind, granny-pop-out-of-bed and many others) is a species of flowering plant in the family Convolvulaceae. It has a cosmopolitan distribution, subcosmopolit ...

'', ''

Cannabis sativa ''Cannabis sativa'' is an annual Herbaceous plant, herbaceous flowering plant indigenous to East Asia, Eastern Asia, but now of cosmopolitan distribution due to widespread cultivation. It has been cultivated throughout recorded history, used as ...

'', ''

Cardiospermum halicacabum ''Cardiospermum halicacabum'', known as the lesser balloon vine, balloon plant or love in a puff, is a climbing plant widely distributed across tropical and subtropical areas of Africa, Australia, and North America that is often found as a weed a ...

'', '' Cassia obtusifolia'', ''

Chenopodium album ''Chenopodium album'' is a fast-growing weedy annual plant in the genus ''Chenopodium''. Though cultivated in some regions, the plant is elsewhere considered a weed. Common names include lamb's quarters, melde, goosefoot, wild spinach and fat-h ...

'', '' Citrullus vulgaris'', ''

Convolvulus arvensis ''Convolvulus arvensis'', the field bindweed, is a species of bindweed that is rhizomatous and is in the morning glory family (Convolvulaceae), native to Europe and Asia. It is a climbing or creeping herbaceous perennial plant with stems growing ...

'', '' Croton glandulosus'', ''

Cucumis melo ''Cucumis melo'', also known as melon, is a species of ''Cucumis'' that has been developed into many cultivated varieties. The fruit is a pepo. The flesh is either sweet or bland, with or without a musky aroma, and the rind can be smooth (such as ...

'', ''

Cyperus esculentus ''Cyperus esculentus'' (also called chufa, tiger nut, atadwe, yellow nutsedge, and earth almond) is a species of plant in the Cyperaceae, sedge family widespread across much of the world. It is found in most of the Eastern Hemisphere, including S ...

'', ''

Datura stramonium ''Datura stramonium'', known by the common names thorn apple, jimsonweed (jimson weed), devil's snare, or devil's trumpet, is a poisonous flowering plant of the nightshade family Solanaceae. It is a species belonging to the ''Datura'' genus a ...

'', ''

Digitaria ''Digitaria'' is a genus of plants in the Poaceae, grass family native to tropical and warm temperate regions but can occur in tropical, subtropical, and cooler temperate regions as well. Common names include crabgrass, finger-grass, and fonio. ...

'', ''

Echinochloa crus-galli ''Echinochloa crus-galli'' is a type of wild grass originating from tropical Asia that was formerly classified as a type of panicum grass. It is commonly known as cockspur (or cockspur grass), barnyard millet, Japanese millet, water grass, common ...

'', ''

Eleusine indica ''Eleusine indica'', the Indian goosegrass, yard-grass, goosegrass, wiregrass, or crowfootgrass, is a species of grass in the family Poaceae. It is a small annual grass distributed throughout the warmer areas of the world to about 50 degrees lat ...

'', '' Euphorbia heterophylla'', ''

Helianthus annuus The common sunflower (''Helianthus annuus'') is a large annual forb of the genus ''Helianthus'' grown as a crop for its edible oily seeds. Apart from cooking oil production, it is also used as livestock forage (as a meal or a silage plant), as b ...

'', ''

Hibiscus trionum ''Hibiscus trionum'', commonly called flower-of-an-hour, bladder hibiscus, bladder ketmia, bladder weed, modesty, puarangi, shoofly, and venice mallow, is an annual plant native to the Old World tropics and subtropics. It has spread throughout s ...

'', ''

Ipomoea quamoclit ''Ipomoea quamoclit'', commonly known as cypress vine, cypress vine morning glory, cardinal creeper, cardinal vine, star glory, star of Bethlehem or hummingbird vine, is a species of vine in the family Convolvulaceae native to tropical regions o ...

'', '' Melochia corchorifolia'', ''

Mollugo verticillata ''Mollugo verticillata'', the green carpetweed (also known as Indian chickweed), is a rapidly spreading annual plant from tropical Americas, America. In eastern North America, it is a common weed growing in disturbed areas. It forms a prostrate ...

'', ''

Polygonum pensylvanicum ''Persicaria pensylvanica'' (syn. ''Polygonum pensylvanicum'') is a species of flowering plant in the buckwheat family, Polygonaceae. It is native to parts of North America, where it is widespread in Canada and the United States. It has also been ...

'', ''

Portulaca oleracea ''Portulaca oleracea'' (common purslane, also known as little hogweed, or pursley) is an annual (actually tropical perennial in USDA growing zones 10–11) succulent in the family Portulacaceae. Description The plant may reach in height. It ...

'', '' Richardia scabra'', '' Sesbania exaltata'', ''

Setaria faberi ''Setaria faberi'', the Japanese bristlegrass, nodding bristle-grass, Chinese foxtail, Chinese millet, giant bristlegrass, giant foxtail or nodding foxtail, is an Asian grass. It is a summer annual, with plants emerging from seeds in the spring, ...

'', ''

Solanum carolinense ''Solanum carolinense'', the Carolina horsenettle, is not a true nettle, but a member of the Solanaceae, or nightshade family. It is a perennial herbaceous plant, native to the southeastern United States, though its range has expanded throughou ...

'', ''

Sorghum halepense Johnson grass or Johnsongrass, ''Sorghum halepense'', is a plant in the grass family, Poaceae, native to Asia and northern Africa. The plant has been introduced to all continents except Antarctica, and most larger islands and archipelagos. It re ...

'', ''

Striga asiatica ''Striga asiatica'', the Asiatic witchweed or the red witchweed, is a hemiparasitic plant in the family Orobanchaceae. It is native to Asia and sub-Saharan Africa, but has been introduced into other parts of the world including Australia and th ...

'' and ''

Xanthium strumarium ''Xanthium strumarium'' (rough cocklebur, clotbur, common cocklebur, large cocklebur, woolgarie bur) is a species of annual plants of the family Asteraceae. Some sources claim it originates in southern Europe and Asia, but has been extensively na ...

''. The product is typically used at application rates of 0.3 lb a.i. per acre. Fomesafen use USA

The estimated annual use of fomesafen in US agriculture is mapped by the US Geological Service and shows that in 2018, the latest date for which figures are available, approximately were applied — mainly in soybean. The compound is not registered for use in 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 des ...

, although a closely related nitrophenyl ether, bifenox, is available there.

Human safety

The LD₅₀ of fomesafen is 1250 mg/kg (rats, oral), which means that it is moderately toxic by oral ingestion. The US Code of Federal Regulations records the maximum residue tolerances for fomesafen in various food products.

Effects on the environment

The environmental fate and

ecotoxicology Ecotoxicology is the study of the effects of toxic chemicals on biological organisms, especially at the population, community, ecosystem, and biosphere levels. Ecotoxicology is a multidisciplinary field, which integrates toxicology and ecology. ...

of fomesafen are summarised in the Pesticide Properties database The compound was used in a case study that developed methods for conducting nationwide endangered species assessments in the USA.

Resistance

Resistance to fomesafen has developed including in ''

Amaranthus retroflexus ''Amaranthus retroflexus'' is a species of flowering plant in the family Amaranthaceae with several common names, including red-root amaranth, redroot pigweed, red-rooted pigweed, common amaranth, pigweed amaranth, and common tumbleweed. page 47 ...

'' in

Northeast China Northeast China or Northeastern China () is a geographical region of China, which is often referred to as "Manchuria" or "Inner Manchuria" by surrounding countries and the West. It usually corresponds specifically to the three provinces east of t ...

, ''Amaranthus palmeri'' in

Arkansas Arkansas ( ) is a landlocked state in the South Central United States. It is bordered by Missouri to the north, Tennessee and Mississippi to the east, Louisiana to the south, and Texas and Oklahoma to the west. Its name is from the Osage ...

, and ''Euphorbia heterophylla'' in

Brazil Brazil ( pt, Brasil; ), officially the Federative Republic of Brazil (Portuguese: ), is the largest country in both South America and Latin America. At and with over 217 million people, Brazil is the world's fifth-largest country by area ...

References

External links

* {{PPDB, 355 PPO herbicides Benzamides Trifluoromethyl compounds Diphenyl ethers Sulfonamides