2,4-Dichlorophenoxyacetic acid

2,4-D was first reported in 1944 by Franklin D. Jones at the C. B. Dolge Company in Connecticut. The biological activity of 2,4-D as well as the similar hormone herbicides 2,4,5-T, and MCPA were discovered during World War II, a case of multiple discovery by four groups working independently under wartime secrecy in the United Kingdom and the United States: William G. Templeman and associates at Imperial Chemical Industries (ICI) in the UK; Philip S. Nutman and associates at Rothamsted Research in the UK; Franklin D. Jones and associates at the American Chemical Paint Company; and Ezra Kraus, John W. Mitchell, and associates at the University of Chicago and the United States Department of Agriculture. All four groups were subject to wartime secrecy laws and did not follow the usual procedures of publication and patent disclosure. In December 1942, following a meeting at the Ministry of Agriculture the Rothamsted and ICI workers pooled resources and Nutman moved to Jealott's Hill to join the ICI effort. The first scientific publication describing the 2,4-D structure and plant growth regulating activity was by Percy Zimmerman and Albert Hitchcock at the Boyce Thompson Institute, who were not the original inventors. The precise sequence of early 2,4-D discovery events and publications has been discussed. William Templeman found that when indole-3-acetic acid (IAA), a naturally occurring auxin, was used at high concentrations, it could stop plant growth. In 1940, he published his finding that IAA killed broadleaf plants within a cereal field. MCPA was discovered at about that time by his ICI group. In the United States, a similar search for an acid with a longer half life, i.e., a metabolically and environmentally more stable compound, led to 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), both phenoxy herbicides and analogs of IAA. Robert Pokorny, an industrial chemist for the C.B. Dolge Company in Westport, Connecticut, published their synthesis in 1941. and in the 1950s it was registered in the United States to control size and enhance skin color in potatoes without affecting yields. The first publication of 2,4-D's use as a selective herbicide came in 1944. The ability of 2,4-D to control broadleaf weeds in turf was documented soon thereafter, in 1944. Starting in 1945, the American Chemical Paint Company brought 2,4-D to market as an herbicide called "Weedone". It revolutionized weed control, as it was the first compound that, at low doses, could selectively control dicotyledons (broadleaf plants), but not most monocotyledons — narrowleaf crops, such as wheat, maize (corn), rice, and similar cereal grass crops. 2,4-D is one of the ingredients in Agent Orange, an herbicide that was widely used during the Malayan Emergency and the Vietnam War. ==Manufacture==

2,4-D is a member of the phenoxy family of herbicides. ==Mode of action==

2,4-D is a synthetic auxin that induces uncontrolled growth and eventually death in susceptible plants. 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. '' == Applications ==

2,4-D is primarily used as a selective herbicide that kills many terrestrial and aquatic broadleaf weeds, but not grasses. 2,4-D can be found in commercial lawn herbicide mixtures, which often contain other active ingredients including mecoprop and dicamba. Over 1,500 herbicide products contain 2,4-D as an active ingredient. A variety of sectors use products containing 2,4-D to kill weeds and unwanted vegetation. In agriculture, it was the first herbicide for selective killing of weeds but not crops. It has been used since 1945 to control broad-leafed weeds in pastures, orchards, and cereal crops such as corn, oats, rice, and wheat. Cereals, in particular, have excellent tolerance to 2,4-D when it is applied before planting. 2,4-D is the cheapest way for farmers to control winter annual weeds by spraying in the fall, often at the lowest recommended rate. This is particularly effective before planting beans, peas, lentils, and chickpeas. The estimated use of 2,4-D in US agriculture is mapped by the US Geological Survey. In 2019, the latest date for which figures are available, this reached annually. In domestic lawn and garden maintenance, 2,4-D is commonly used. In forestry, it is used for stump treatment, trunk injection, and selective control of brush in conifer forests. Along roadways, railways, and power lines, it is used to control weeds and brush which might interfere with safe operation and damage equipment. Along waterways, it is used to control aquatic weeds that might interfere with boating, fishing, and swimming or clog irrigation and hydroelectric equipment. It is often used by government agencies to control the spread of invasive, noxious, and non-native weed species and prevent them from crowding out native species, and also to control many poisonous weeds such as poison ivy and poison oak. A 2010 monitoring study conducted in the US and Canada found that "current exposures to 2,4-D are below applicable exposure guidance values." 2,4-D has been used in laboratories for plant research as a supplement in plant cell culture media such as MS medium since at least 1962. 2,4-D is used in plant cell cultures as a dedifferentiation (callus induction) hormone. It is classified as an auxin plant hormone derivative. ==Health effects==

Men who work with 2,4-D are at risk for abnormally shaped sperm and thus fertility problems; the risk depends on the amount and duration of exposure and other personal factors. Acute toxicity According to the U.S. Environmental Protection Agency, "The toxicity of 2,4-D depends on its chemical forms, including salts, esters, and an acid form. 2,4-D generally has low toxicity for humans, except certain acid and salt forms can cause eye irritation. Swimming is restricted for 24 hours after application of certain 2,4-D products applied to control aquatic weeds to avoid eye irritation." Urinary alkalinisation has been used in acute poisoning, but evidence to support its use is poor. Cancer risk The International Agency for Research on Cancer classifies 2,4-D as a possible carcinogen to humans while the United States Environmental Protection Agency does not. The International Agency for Research on Cancer (IARC), said 2,4-D was classified as "possibly carcinogenic to humans (Group 2B), based on inadequate evidence in humans and limited evidence in experimental animals". In June 2015 the World Health Organization's International Agency for Research on Cancer confirmed its 1987 classification of 2,4-D as a possible carcinogen. On August 8, 2007, the EPA issued a ruling that existing data do not support a link between human cancer and 2,4-D exposure. 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. In a prior 1987 report the IARC classified some chlorphenoxy herbicides including 2,4-D, MCPA and 2,4,5-T as a group as class 2B carcinogens - "possibly carcinogenic to humans". 2,4-D has been linked to lymphoma and bladder cancer in dogs. Contaminants A July 2013 Four Corners investigation found elevated levels of dioxins in a generic version of 2,4-D, one of Australia's most widely used herbicides. Samples imported from China had "one of the highest dioxin readings for 2,4-D in the last 10 to 20 years, and could pose potential health risks." ==Metabolism==

When radioactively labeled 2,4-D was fed to livestock, 90% or more of the total radioactive residue (TRR) was shed in urine unchanged or as conjugated forms of 2,4-D. A relatively small portion of 2,4-D was metabolized into dichlorophenol, dichloroanisole, 4-chlorophenoxyacetic acid (6.9% of the TRR in milk), and 2,4-dichlorophenol (5% of the TRR in milk; 7.3% of the TRR in eggs and 4% of the TRR in chicken liver). Residue levels in kidney were the highest. ==Environmental behavior==

Owing to the longevity and extent of use, 2,4-D has been evaluated several times by regulators and review committees. 2,4-D amine salts and esters are not persistent under most environmental conditions. The degradation of 2,4-D is rapid (half life of 6.2 days) in aerobic mineral soils. 2,4-D has been detected in streams and shallow groundwater at low concentrations, in both rural and urban areas. Breakdown is pH dependent. "The ester forms of 2,4-D can be highly toxic to fish and other aquatic life. 2,4-D generally has moderate toxicity to birds and mammals, is slightly toxic to fish and aquatic invertebrates, and is practically nontoxic to honeybees" per EPA. Microbial breakdown A number of 2,4-D-degrading bacteria have been isolated and characterized from a variety of environmental habitats. 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 were demonstrated. 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. ==Regulation ==

Maximum residue limits were first set in the EU in 2002 and re-evaluated in 2011 by the European Food Safety Authority, which concluded that the codex maximum residue limits were "not expected to be of concern for European consumers". The total chronic exposure represented less than 10% of the acceptable daily intake (ADI). and Ontario. 2,4-D use is severely restricted in the country of Belize. In 2008, Dow AgroScience, LLC, sued the Canadian government for allowing Quebec to ban 2,4-D, but settled in 2011. In 2012, EPA denied the petition filed November 6, 2008, by the Natural Resources Defense Council to revoke all tolerances and to cancel all registrations of 2,4-D. EPA stated that new study and EPA's comprehensive review confirmed EPA's previous finding that the 2,4-D tolerances are safe at anticipated exposure. The estimated annual use of 2,4-D in US agriculture is mapped by the US Geological Service. In October 2014, the US EPA registered Enlist Duo, an herbicide containing the less volatile 2,4-D choline salt, glyphosate, and an antidrift agent, for use in six states: Illinois, Indiana, Iowa, Ohio, South Dakota, and Wisconsin. In November 2015, the EPA attempted to withdraw its own approval of Enlist Duo, as a result of legal actions against both the agency and Dow by two U.S. groups. However, while it was implied that the approval was "gone" because of the action, in fact, Enlist Duo was still approved pending a decision by the courts. On January 25, 2016, the US Ninth Circuit Court of Appeals denied EPA's motion to vacate its Enlist Duo registration. Dow stated the product would be available in 15 US states and Canada for the 2016 crop season. On August 21, 2013, the Australian Pesticides and Veterinary Medicines Authority (APVMA) banned selected 2,4-D high volatile ester (HVE) products due to their environmental hazards. HVE 2,4-D products had already been banned in Europe and North America for 20 years; low volatile ester products continue to be available in Australia and worldwide. In July 2013 APVMA published their report findings. ==Genetically modified crops==

In 2010, Dow published that it had created genetically modified soybeans made resistant to 2,4-D by insertion of a bacterial aryloxyalkanoate dioxygenase gene, aad1. Dow intended it to be used as an alternative or complement to Roundup Ready crops due to the increasing prevalence of glyphosate-resistant weeds. As of April 2014, genetically modified maize and soybeans resistant to 2,4-D and glyphosate have been approved in Canada. ==See also==

• CDC - NIOSH Pocket Guide to Chemical Hazards • Overview of the toxic effects of 2,4-D Sierra Club Canada January 2005 • "Review of 2,4-dichlorophenoxyacetic acid (2,4-D) biomonitoring and epidemiology" Review of the literature by Dow scientists Crit Rev Toxicol. Oct 2012 • PPDB Pesticides Properties database entry for 2,4-D • 2,4-D on Pubchem