2,4-Dichlorophenoxyacetic acid

2,4-Dichlorophenoxyacetic acid
IUPAC name (2,4-dichlorophenoxy)acetic acid
Other names 2,4-D hedonal trinoxol 2',6'-Diethyl-N-butoxymethyl-2-chloroacetanilide[1]
Identifiers
CAS number	94-75-7 Y
PubChem	1486
ChemSpider	1441 Y
UNII	2577AQ9262 N
KEGG	C03664 Y
ChEBI	CHEBI:28854 Y
ChEMBL	CHEMBL367623 Y
Jmol-3D images	Image 1
SMILES Clc1cc(Cl)ccc1OCC(=O)O
InChI InChI=1S/C8H6Cl2O3/c9-5-1-2-7(6(10)3-5)13-4-8(11)12/h1-3H,4H2,(H,11,12) Y Key: OVSKIKFHRZPJSS-UHFFFAOYSA-N Y InChI=1/C8H6Cl2O3/c9-5-1-2-7(6(10)3-5)13-4-8(11)12/h1-3H,4H2,(H,11,12) Key: OVSKIKFHRZPJSS-UHFFFAOYAM
Properties
Molecular formula	C8H6Cl2O3
Molar mass	221.04 g mol−1
Appearance	white to yellow powder
Melting point	140.5 °C; 284.9 °F; 413.6 K
Boiling point	160 °C; 320 °F; 433 K (0.4 mm Hg)
Solubility in water	900 mg/L
Related compounds
Related compounds	2,4,5-T, Dichlorprop
N (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
Infobox references

2,4-Dichlorophenoxyacetic acid (usually referred to by its abbreviation, 2,4-D) is a common systemic pesticide/herbicide used in the control of broadleaf weeds. It is one of the most widely used herbicides in the world, and is the third most commonly used herbicide in North America.^[2] 2,4-D is a synthetic auxin (plant hormone), and as such it is often used in laboratories for plant research and as a supplement in plant cell culture media such as MS medium. It was a major ingredient in Agent Orange alongside its chemically similar relative, 2,4,5-T (2,4,5-trichlorophenoxyacetic acid).

History

2,4-D was co-discovered independently in both the US and the UK in 1941. The two teams involved were "Templeman and Colleagues at ICI" (USA) and "Nutman and Collaborators at Rothamsted Experimental Station" (UK). In both cases the researchers were part of a clandestine wartime effort by their governments, to create chemical warfare agents for use in WWII. For further reading, see section 7.1 of "Herbicides and Plant Physiology By Andrew H. Cobb, John P. H. Reade"

The new chemical's ability to kill weeds was entirely accidental and not the aim of the research in either country. Because of war-time defense security reasons as well as for international legal reasons, research of this sort was never done openly. Research, production and use of chemical warfare agents were illegal actions under the Geneva Protocol and many other international treaties signed by both the USA and the UK. This meant that a plausible cover story was needed to hide the actual nature of any chemical warfare research. For both the Allies and the Axis powers, the civilian label of agricultural was often used to conceal illegal and/or secret chemical warfare research.

Experimentation had become quite common in the fashion of British team at Rothamsted Experimental Station, under the leadership of Judah Hirsch Quastel. Some discoveries were able to be eventually used to increase crop yields, although 2-4D was not used until 1945 near the end of WWII.^[3] When it was commercially released in 1946, it became the first successful selective herbicide and allowed for greatly enhanced weed control in wheat, maize (corn), rice, and similar cereal grass crops, because it kills dicots (broadleaf plants), but not most monocots (grasses).

Genetically modified crops

Dow has demonstrated soybean resistance to 2,4-D due to insertion of a bacterial aryloxyalkanoate dioxygenase gene.^[4] This is intended as an alternative to Roundup Ready crops due to the increasing prevalence of glyphosate resistant weeds. Department of Agriculture approval is pending for a 2,4-D resistant corn.^[5]

Mode of action

2,4-D is a synthetic auxin, which is a class of plant hormones. It is absorbed through the leaves and is translocated to the meristems of the plant. Uncontrolled, unsustainable growth ensues, causing stem curl-over, leaf withering, and eventual plant death. 2,4-D is typically applied as an amine salt, but more potent ester versions exist as well.

Effect of 2-4-d foliar application.

Manufacture

2,4-D is a member of the phenoxy family of herbicides, which include:

• 2,4,5-Trichlorophenoxyacetic acid (2,4,5-T)
• 2-Methyl-4-chlorophenoxyacetic acid (MCPA)
• 2-(2-Methyl-4-chlorophenoxy)propionic acids (mecoprop, MCPP)
• 2-(2,4-Dichlorophenoxy)propionic acid (dichlorprop, 2,4-DP)
• (2,4-Dichlorophenoxy)butyric acid (2,4-DB)

Containers of 2-4 D(ow) weed killer, ca. 1947

2,4-D is manufactured from chloroacetic acid and 2,4-dichlorophenol, which is itself produced by chlorination of phenol. Alternatively, it may be produced by the chlorination of phenoxyacetic acid. The production processes creates several contaminants including isomers, monochlorophenol, and other polychlorophenols and their acids.^[6]

Dioxin impurities

Some preparations of 2,4-D are contaminated with dioxins due to the manufacturing process.^[7] Tetrachlorodibenzo-p-dioxin (TCDD) is classified as "carcinogenic to humans" by International Agency for Research on Cancer.^[8]

Contamination is predominantly of the type with 2 or 3 chlorine atoms. Another form of dioxin, 2,7-dichlorodibenzo-p-dioxin (2,7-DCDD) was found to be equipotent to dioxin TCDD in its toxic effect on the immunity of mice. TCDD received all the publicity while the DCDD component was largely forgotten. To this day, DCDD is not regulated or monitored by the EPA and PMRA, even though DCDD levels could be at much higher levels than TCDD.^{[citation needed]} The typical smell of 2,4-D is the breakdown product 2,4-dichlorophenol. 2,4-D is toxic to the liver at small dosages. There have been reports of increases in jaundice, acute hepatitis, lobular and portal inflammation indicative of a toxic reaction, as well as reports of permanent liver damage leading to cirrhosis in exposed golfers.^[9][10][11]

The defoliant and herbicide Agent Orange, used extensively throughout the Vietnam War, contained 2,4-D. The controversies associated with the use of Agent Orange were associated with a contaminant (dioxin) in the 2,4,5-T component.^[12]

Applications

2,4-D is primarily used as an herbicide.^[13] It is sold in various formulations under a wide variety of brand names. 2,4-D can be found in lawn herbicide mixtures such as "Weed B Gon MAX", "PAR III", "Trillion", "Tri-Kil", "Killex" and "Weedaway Premium 3-Way XP Turf Herbicide". All of these mixtures typically contain three active ingredients: 2,4-D, mecoprop and dicamba. Over 1,500 herbicide products contain 2,4-D as an active ingredient.^{[citation needed]}

2,4-D is most commonly used for:

• Weed control in lawns and other turf
• No-till burndown
• Control of weeds and brush along fences and highway and railroad rights of way
• Conifer release (control of broad-leaf trees in conifer plantings)
• Grass hayfields and pastures
• Cereal grains
• Corn and sorghum (occasionally)
• As a synthetic auxin analog

2,4-D continues to be used, where legal, for its low cost. However, where municipal lawn pesticide bylaws exist, such as in Canada,^[14] alternatives such as corn gluten meal and vinegar-based products are increasingly being used to combat weeds.

Toxicity

Manufacturing processes

It was assumed that because of improved manufacturing processes that there were no longer any dangerous dioxins in 2,4-D, however, a July 2013 Four Corners investigation found "elevated levels" of dangerous dioxins in a generic version of 24D, one of Australia's most widely used herbicides. One scientist said the product tested by Four Corners, which was imported from China, had "one of the highest dioxin readings for 24D in the last 10 to 20 years, and could pose potential health risks."^[15]

Cancer risk

Studies have yielded conflicting results, and different organizations have taken different stances, with regard to the cancer risk of 2,4-D. In 1987, the International Agency for Research on Cancer (IARC) concluded that the phenoxy acid herbicides including 2,4-D, MCPA and 2,4,5-T as a group were classified as a class 2B carcinogen - "possibly carcinogenic to humans".^[16] A 1990 study of farmers in Nebraska, even when adjusting for exposure to other chemicals, found that 2,4-D exposure substantially increased the risk of non-Hodgkin's lymphoma (NHL).^[17]

A 1995 panel of 13 scientists reviewing studies on the carcinogenicity of 2,4-D had divided opinions. None of the scientists thought the weight of the evidence indicated that 2,4-D was a “known” or “probable” cause of human cancer. The predominant opinion indicated that it is possible that 2,4-D can cause cancer in humans, although not all of the panelists believed the possibility was equally likely: one thought the possibility was strong, leaning toward probable, and five thought the possibility was remote, leaning toward unlikely. Two panelists believed it unlikely that 2,4-D can cause cancer in humans.^[18]

A 2000 study of 1517 former employees of Dow Chemical Company who had been exposed to the chemical in manufacturing or formulating 2,4-D found no significant increase in risk of mortality due to NHL following 2,4-D exposure, but did find an increase in risk of mortality due to amyotrophic lateral sclerosis.^[19] On August 8, 2007, the U.S. Environmental Protection Agency issued a ruling that stated that existing data do not support a link between human cancer and 2,4-D exposure.^[20]

Other

The LD₅₀ determined in an acute toxicity rat study is 639 mg/kg.^[21] Single oral doses of 5 and 30 mg/kg body weight did not cause any acute toxic effects in human volunteers. This chemical has been associated with the risk of amyotrophic lateral sclerosis.^[22]

The amine salt formulations can cause eye damage (blindness) on contact; ester formulations are considered non-irritating to the eyes.

One study found that occupational exposure to 2,4-D caused male reproductive problems, including dead and malformed sperm.^[23]

Concerns regarding neurotoxicity have been voiced with increased sensitivity to amphetamine and thus concerns of increased risk of drug addiction among those exposed.^[24]

Treatment

While urinary alkalinisation has been used in acute poisonings, evidence to support its use is poor.^[25]

Environmental behavior

Owing to the longevity and extent of use, 2,4-D is among the most thoroughly studied herbicides with respect to environmental properties. 2,4-D applied at 1.16 lb/acre to bluegrass turf in a laboratory experiment had a half-life of ten days. Other studies found half-life figures between 1.5 and 16 days. Soil microbes are primarily responsible for its disappearance in soil. Studies in Alaska and Canada failed to detect leaching in 22 weeks or from spring to fall,^[26] but 2,4-D has been included on the EPA list of compounds that are likely to leach from soil. ^{[citation needed]}

In aquatic environments microorganisms readily degrade 2,4-D and breakdown by sunlight is not a major reason for loss. Rates of breakdown increase with increased nutrients, sediment load and dissolved organic carbon. Under oxygenated conditions the half-life can be short, in the order of one week to several weeks. 2,4-D interferes with normal plant growth processes. Uptake of the compound is through leaves, stems and roots; however, it is, in general, nonpersistent. In one study when 2,4-D was applied to grass, there were 80 ppm at day zero, 45 ppm at 14 days, and 6 ppm at 56 days. Breakdown in plants is by a variety of biological and chemical pathways.^[27]

A number of 2,4-D-degrading bacteria have been isolated and characterized from a variety of environmental habitats.^[28][29] Metabolic pathways for the compound’s degradation have been available for many years, and genes encoding 2,4-D catabolism have been identified for several organisms. As a result of the extensive metadata on environmental behavior, physiology and genetics, 2,4-D was the first herbicide for which the bacteria actively responsible for in situ degradation was demonstrated.^[30] This was accomplished using the technique of DNA-based stable isotope probing, which enables a microbial function (activity), such as degrading a chemical, to be linked with the organism’s identity without the need to culture the organism involved.^[31] This advancement has been particularly beneficial for the study of soil microorganisms, since only a very small fraction of the thousands of species present in highly diverse soil bacterial communities can be isolated in pure culture.

Despite its short half-life in soil and in aquatic environments, the compound has been detected in groundwater supplies in at least five States and in Canada.^[32] It has also been detected in surface waters throughout the United States at very low concentrations.

Legal issues

2,4-D has been evaluated by the European Union and included on its list of approved herbicides, stating inter alia that "the review [of 2,4-D] has established that the residues arising from the proposed uses, consequent on application consistent with good plant protection practice, have no harmful effects on human or animal health."^[33] Concern over 2,4-D is such that it is currently not approved for use on lawns and gardens in Sweden,^[34] Denmark, Norway, Kuwait and the Canadian provinces of Québec^[35] and Ontario.^[36] 2,4-D use is severely restricted in the country of Belize. In 2005, the United States Environmental Protection Agency approved the continued use of 2,4-D.^[37] On July 10, 2013 the Pest Management Regulatory Agency in Canada updated the re-evaluation notice of 2,4-D stating that the 2,4-D registrants provided the PMRA with required data submissions and deemed such data acceptable.^[38] On April 18, 2012, EPA denied the petition filed November 6, 2008 by the Natural Resources Defense Council (NRDC) to revoke all tolerances and to cancel all registrations of 2,4-D. EPA stated that recent new study and EPA’s comprehensive review confirmed EPA’s previous finding that the 2,4-D tolerances are safe.^[39][40]

References

External links

Government and academic references

• 2,4-D Technical Fact Sheet - National Pesticide Information Center
• 2,4-D Pesticide Information Profile - Extension Toxicology Network
• EPA 2,4-D Reregistration Eligibility Decision
• 2,4-D RED Facts
• CDC - NIOSH Pocket Guide to Chemical Hazards
• Biomonitoring Data for 2,4-Dichlorophenoxyacetic Acid in the US and Canada: Interpretation in a Public Health Risk Assessment Context Using Biomonitoring Equivalents, Environmental Health Perspectives online 12. 8. 2009
• Burns et al.: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1740039/?tool=pubmed

Industry website

• Industry Task Force II on 2,4-D

Health and environmental references

• Highlights of Major Problems with PMRA's Feb. 21, 2005 Review on 2,4-D Herbicide
• Overview of the toxic effects of 2,4-D
• 2,4-D: The Wrong Symbol for Pesticides