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DDT

Dichlorodiphenyltrichloroethane (DDT) is a colorless, tasteless, and almost odorless crystalline chemical compound, an organochloride. Originally developed as an insecticide, it became infamous for its environmental impacts. DDT was first synthesized in 1874 by the Austrian chemist Othmar Zeidler. DDT's insecticidal action was discovered by the Swiss chemist Paul Hermann Müller in 1939. DDT was used in the second half of World War II to limit the spread of the insect-borne diseases malaria and typhus among civilians and troops. Müller was awarded the Nobel Prize in Physiology or Medicine in 1948 "for his discovery of the high efficiency of DDT as a contact poison against several arthropods". The World Health Organization's (WHO) anti-malaria campaign of the 1950s and 1960s relied heavily on DDT and the results were promising, though there was a resurgence in developing countries afterwards.

Properties and chemistry
DDT is similar in structure to the insecticide methoxychlor and the acaricide dicofol. It is highly hydrophobic and nearly insoluble in water but has good solubility in most organic solvents, fats and oils. DDT does not occur naturally and is synthesised by consecutive Friedel–Crafts reactions between chloral () and two equivalents of chlorobenzene (), in the presence of an acidic catalyst. File:P,p'-dichlorodiphenyltrichloroethane.svg|p,p-DDT(desired compound) File:O,p'-dichlorodiphenyltrichloroethane.svg|o,p-DDT(isomeric impurity) File:P,p'-dichlorodiphenyldichloroethene.svg|p,p-DDE(impurity) File:P,p'-dichlorodiphenyldichloroethane.svg|p,p-DDD(impurity) Production and use DDT has been formulated in multiple forms, including solutions in xylene or petroleum distillates, emulsifiable concentrates, water-wettable powders, granules, aerosols, smoke candles and charges for vaporizers and lotions. From 1950 to 1980, DDT was extensively used in agriculturemore than 40,000 tonnes each year worldwideand it has been estimated that a total of 1.8 million tonnes have been produced globally since the 1940s. In the United States, it was manufactured by some 15 companies, including Monsanto, Ciba, Montrose Chemical Company, Pennwalt, and Velsicol Chemical Corporation. Production peaked in 1963 at 82,000 tonnes per year. China ceased production in 2007, leaving India the only country still manufacturing DDT; it is the largest consumer. In 2009, 3,314 tonnes were produced for malaria control and visceral leishmaniasis. In recent years, in addition to India, just seven other countries, all in Africa, are still using DDT. Mechanism of insecticide action In insects, DDT opens voltage-sensitive sodium ion channels in neurons, causing them to fire spontaneously, which leads to spasms and eventual death. Insects with certain mutations in their sodium channel gene are resistant to DDT and similar insecticides. as greater quantities of some enzymes of this group accelerate the toxin's metabolism into inactive metabolites. Genomic studies in the model genetic organism Drosophila melanogaster revealed that high level DDT resistance is polygenic, involving multiple resistance mechanisms. In the absence of genetic adaptation, Roberts and Andre 1994 find behavioral avoidance nonetheless provides insects with some protection against DDT. The M918T mutation event produces dramatic kdr for pyrethroids but Usherwood et al. 2005 find it is entirely ineffective against DDT. Scott 2019 believes this test in Drosophila oocytes holds for oocytes in general. ==History==
History
Néocide (powder box, 50 g) containing 10% DDT, made in France. DDT was first synthesized in 1874 by Othmar Zeidler under the supervision of Adolf von Baeyer. It was further described in 1929 in a dissertation by W. Bausch and in two subsequent publications in 1930. The insecticide properties of "multiple chlorinated aliphatic or fat-aromatic alcohols with at least one trichloromethane group" were described in a patent in 1934 by Wolfgang von Leuthold. DDT's insecticidal properties were not, however, discovered until 1939 by the Swiss scientist Paul Hermann Müller, who was awarded the 1948 Nobel Prize in Physiology and Medicine for his efforts. Due to the potency of DDT, it was not long before the US War Production Board placed it on military supply lists in 1942 and 1943 and encouraged its production for overseas use. Enthusiasm regarding DDT became obvious through the US government's advertising campaigns of posters depicting US fighting the Axis powers and insects and through media publications celebrating its military uses. In 1945, DDT was made available to farmers as an agricultural insecticide Despite concerns emerging in the scientific community, and lack of research, the FDA considered it safe up to 7 parts per million in food. There was a large economic incentive to push DDT into the market and sell it to farmers, governments, and individuals to control diseases and increase food production. The program eliminated the disease in "North America, Europe, the former Soviet Union", and dramatically reduced mortality in Sri Lanka and India. The program succeeded in eliminating malaria only in areas with "high socio-economic status, well-organized healthcare systems, and relatively less intensive or seasonal malaria transmission". DDT was less effective in tropical regions due to the continuous life cycle of mosquitoes and poor infrastructure. It was applied in sub-Saharan Africa by various colonial states, but the 'global' WHO eradication program didn't include the region. Mortality rates in that area never declined to the same dramatic extent, and now constitute the bulk of malarial deaths worldwide, especially following the disease's resurgence as a result of resistance to drug treatments and the spread of the deadly malarial variant caused by Plasmodium falciparum. Eradication was abandoned in 1969 and attention instead focused on controlling and treating the disease. Spraying programs (especially using DDT) were curtailed due to concerns over safety and environmental effects, as well as problems in administrative, managerial and financial implementation. United States ban By October 1945 DDT was available for public sale in the United States, both as an agricultural pesticide and as a household insecticide. and had become an important part of the local economy. Citing research performed by Michigan State University in 1946, Robinson, a past president of the local Conservation Club, opined that: As its production and use increased, public response was mixed. At the same time that DDT was hailed as part of the "world of tomorrow", concerns were expressed about its potential to kill harmless and beneficial insects (particularly pollinators), birds, fish, and eventually humans. The issue of toxicity was complicated, partly because DDT's effects varied from species to species, and partly because consecutive exposures could accumulate, causing damage comparable to large doses. A number of states attempted to regulate DDT. In the 1950s the federal government began tightening regulations governing its use. In 1957 The New York Times reported an unsuccessful struggle to restrict DDT use in Nassau County, New York, and the issue came to the attention of the popular naturalist-author Rachel Carson when a friend, Olga Huckins, wrote to her including an article she had written in the Boston Globe about the devastation of her local bird population after DDT spraying. William Shawn, editor of The New Yorker, urged her to write a piece on the subject, which developed into her 1962 book Silent Spring. The book argued that pesticides, including DDT, were poisoning both wildlife and the environment and were endangering human health. Silent Spring was a best seller, and public reaction to it launched the modern environmental movement in the United States. The year after it appeared, President John F. Kennedy ordered his Science Advisory Committee to investigate Carson's claims. The committee's report "add[ed] up to a fairly thorough-going vindication of Rachel Carson's Silent Spring thesis", in the words of the journal Science, and recommended a phaseout of "persistent toxic pesticides". In 1965, the US military removed DDT from the military supply system due in part to the development of resistance by body lice to DDT; it was replaced by lindane. In the mid-1960s, DDT became a prime target of the burgeoning environmental movement, as concern about DDT and its effects began to rise in local communities. In 1966, a fish kill in Suffolk County, New York, was linked to a 5,000-gallon DDT dump by the county's mosquito commission, leading a group of scientists and lawyers to file a lawsuit to stop the county's further use of DDT. A year later, the group, led by Victor Yannacone and Charles Wurster, founded the Environmental Defense Fund (EDF), along with scientists Art Cooley and Dennis Puleston, and brought a string of lawsuits against DDT and other persistent pesticides in Michigan and Wisconsin. Around the same time, evidence was mounting further about DDT causing catastrophic declines in wildlife reproduction, especially in birds of prey like peregrine falcons, bald eagles, ospreys, and brown pelicans, whose eggshells became so thin that they often cracked before hatching. Toxicologists like David Peakall were measuring DDE levels in the eggs of peregrine falcons and California condors and finding that increased levels corresponded with thinner shells. Compounding the effect was DDT's persistence in the environment, as it was unable to dissolve in water, and ended up accumulating in animal fat and disrupting hormone metabolism across a wide range of species. In response to an EDF suit, the US District Court of Appeals in 1971 ordered the EPA to begin the de-registration procedure for DDT. After an initial six-month review process, William Ruckelshaus, the Agency's first Administrator rejected an immediate suspension of DDT's registration, citing studies from the EPA's internal staff stating that DDT was not an imminent danger. Industry sought to overturn the ban, while the EDF wanted a comprehensive ban. The cases were consolidated, and in 1973 the United States Court of Appeals for the District of Columbia Circuit ruled that the EPA had acted properly in banning DDT. DDT continued to be produced in the United States for foreign markets until 1985, when over 300 tons were exported. although in practice it continued to be used through at least 1970. This was followed by Norway and Sweden in 1970, West Germany and the US in 1972, but not in the UK until 1984. In contrast to West Germany, in the German Democratic Republic DDT was used until 1988. Especially of relevance were large-scale applications in forestry in the years 1982–1984, with the aim to combat bark beetle and pine moth. As a consequence, DDT-concentrations in eastern German forest soils are still significantly higher compared to soils in the former western German states. By 1991, total bans, including for disease control, were in place in at least 26 countries; for example, Cuba in 1970, the US in the 1980s, Singapore in 1984, Chile in 1985, and the Republic of Korea in 1986. The Stockholm Convention on Persistent Organic Pollutants, which took effect in 2004, put a global ban on several persistent organic pollutants, and restricted DDT use to vector control. The convention was ratified by more than 170 countries. Recognizing that total elimination in many malaria-prone countries is currently unfeasible in the absence of affordable/effective alternatives, the convention exempts public health use within World Health Organization (WHO) guidelines from the ban. Resolution 60.18 of the World Health Assembly commits WHO to the Stockholm Convention's aim of reducing and ultimately eliminating DDT. Malaria Foundation International states, "The outcome of the treaty is arguably better than the status quo going into the negotiations. For the first time, there is now an insecticide which is restricted to vector control only, meaning that the selection of resistant mosquitoes will be slower than before." Despite the worldwide ban, agricultural use continued in India, North Korea, and possibly elsewhere. DDT is applied to the inside walls of homes to kill or repel mosquitoes. This intervention, called indoor residual spraying (IRS), greatly reduces environmental damage. It also reduces the incidence of DDT resistance. For comparison, treating of cotton during a typical US growing season requires the same amount of chemical to treat roughly 1,700 homes. ==Environmental impact==
Environmental impact
DDT is a persistent organic pollutant that is readily adsorbed to soils and sediments, which can act both as sinks and as long-term sources of exposure affecting organisms.). Its breakdown products and metabolites, DDE and DDD, are also persistent and have similar chemical and physical properties. Medical researchers in 1974 found a measurable and significant difference in the presence of DDT in human milk between mothers who lived in New Brunswick and mothers who lived in Nova Scotia, "possibly because of the wider use of insecticide sprays in the past". Because of its lipophilic properties, DDT can bioaccumulate, especially in predatory birds. DDT is toxic to a wide range of living organisms, including marine animals such as crayfish, daphnids, sea shrimp and many species of fish. DDT, DDE and DDD magnify through the food chain, with apex predators such as raptor birds concentrating more chemicals than other animals in the same environment. They are stored mainly in body fat. DDT and DDE are resistant to metabolism; in humans, their half-lives are 6 and up to 10 years, respectively. In the United States, these chemicals were detected in almost all human blood samples tested by the Centers for Disease Control in 2005, though their levels have sharply declined since most uses were banned. Estimated dietary intake has declined, Despite being banned for many years, in 2018 research showed that DDT residues are still present in European soils and Spanish rivers. Eggshell thinning The chemical and its breakdown products DDE and DDD caused eggshell thinning and population declines in multiple North American and European bird of prey species. Both laboratory experiments and field studies confirmed this effect. The effect was first conclusively proven at Bellow Island in Lake Michigan during University of Michigan-funded studies on American herring gulls in the mid-1960s. DDE-related eggshell thinning is considered a major reason for the decline of the bald eagle, peregrine falcon and osprey. though DDT's role in the decline of the California condor is disputed. Other evidence indicates that o,p'-DDT disrupts female reproductive tract development, later impairing eggshell quality. Multiple mechanisms may be at work, or different mechanisms may operate in different species. ==Human health==
Human health
-carrying lice. hospital of Ziguinchor, 1973 is the build up of toxins in a food chain. The DDT concentration is in parts per million. As the trophic level increases in a food chain, the amount of toxic build up also increases. The X's represent the amount of toxic build up accumulating as the trophic level increases. Toxins build up in organism's tissues and fat. Predators accumulate higher toxins than the prey. DDT is an endocrine disruptor. It is considered likely to be a human carcinogen although the majority of studies suggest it is not directly genotoxic. DDE acts as a weak androgen receptor antagonist, but not as an estrogen. p,p-DDT, DDT's main component, has little or no androgenic or estrogenic activity. The minor component o,p-DDT has weak estrogenic activity. Acute toxicity DDT is classified as "moderately toxic" by the US National Toxicology Program (NTP) and "moderately hazardous" by WHO, based on the rat oral of 113 mg/kg. Indirect exposure is considered relatively non-toxic for humans. High-dose exposure to DDT can have effects on animals which could cause headaches, tremors, and convulsions. Laboratory animals were tested and were given a single oral dose of about 50mg DDT/kg a day. They were seen to have tremors, hyperactivity or a hunched appearance in doses as low as 27 mg DDT/kg. Similar effects have been seen across multiple species with exposure to higher dose ranges, including humans. In a controlled setting, humans were exposed to 6mg DDT/kg orally and were not seen to be ill, but did have perspiration, headaches, and nausea. At doses of 16mg DDT/kg or higher, convulsions were reported. At doses of around 22 mg DDT/kg, dizziness, confusion, tremors, headaches, and fatigue were all shown within 10 hours of dosing. The symptoms seemed to disappear within the next 24 hours after dosing. • Studies are inconsistent on whether high blood DDT or DDE levels increase time to pregnancy. • Indirect exposure of mothers through workers directly in contact with DDT is associated with an increase in spontaneous abortions. • Mothers with high levels of DDT circulating in their blood during pregnancy were found to be more likely to give birth to children who would go on to develop autism. Carcinogenicity In 2015, the International Agency for Research on Cancer classified DDT as Group 2A "probably carcinogenic to humans". Previous assessments by the US National Toxicology Program classified it as "reasonably anticipated to be a carcinogen" and by the EPA classified DDT, DDE and DDD as class B2 "probable" carcinogens; these evaluations were based mainly on animal studies. A 2009 review, whose co-authors included persons engaged in DDT-related litigation, reached broadly similar conclusions, with an equivocal association with testicular cancer. Case–control studies did not support an association with leukemia or lymphoma. The United States Institute of Medicine reviewed data on the association of breast cancer with DDT exposure in 2012 and concluded that a causative relationship could neither be proven nor disproven. A 2007 case-control study The US National Toxicology Program notes that while the majority of studies have not found a relationship between DDT exposure and breast cancer that positive associations have been seen in a "few studies among women with higher levels of exposure and among certain subgroups of women". ==Malaria control==
Malaria control{{anchor|Use_against_malaria}}
Malaria remains the primary public health challenge in many countries. In 2015, there were 214 million cases of malaria worldwide resulting in an estimated 438,000 deaths, 90% of which occurred in Africa. DDT is one of many tools to fight the disease. Its use in this context has been called everything from a "miracle weapon [that is] like Kryptonite to the mosquitoes", to "toxic colonialism". Before DDT, eliminating mosquito breeding grounds by drainage or poisoning with Paris green or pyrethrum was sometimes successful. In parts of the world with rising living standards, the elimination of malaria was often a collateral benefit of the introduction of window screens and improved sanitation. such as larviciding with insecticides, ecological controls such as draining mosquito breeding grounds or introducing fish to eat larvae and indoor residual spraying (IRS) with insecticides, possibly including DDT. IRS involves the treatment of interior walls and ceilings with insecticides. It is particularly effective against mosquitoes, since many species rest on an indoor wall before or after feeding. DDT is one of 12 WHO–approved IRS insecticides. Resistance was largely fueled by unrestricted agricultural use. Resistance and the harm both to humans and the environment led many governments to curtail DDT use in vector control and agriculture. Once the mainstay of anti-malaria campaigns, as of 2019 only five countries used DDT for IRS. Initial effectiveness When it was introduced in World War II, DDT was effective in reducing malaria morbidity and mortality. and 29 in 1964. Thereafter the program was halted to save money and malaria rebounded to 600,000 cases in 1968 and the first quarter of 1969. The country resumed DDT vector control but the mosquitoes had evolved resistance in the interim, presumably because of continued agricultural use. The program switched to malathion, but despite initial successes, malaria continued its resurgence into the 1980s. DDT remains on WHO's list of insecticides recommended for IRS. After the appointment of Arata Kochi as head of its anti-malaria division, WHO's policy shifted from recommending IRS only in areas of seasonal or episodic transmission of malaria, to advocating it in areas of continuous, intense transmission. WHO reaffirmed its commitment to phasing out DDT, aiming "to achieve a 30% cut in the application of DDT world-wide by 2014 and its total phase-out by the early 2020s if not sooner" while simultaneously combating malaria. WHO plans to implement alternatives to DDT to achieve this goal. South Africa continues to use DDT under WHO guidelines. In 1996, the country switched to alternative insecticides and malaria incidence increased dramatically. Returning to DDT and introducing new drugs brought malaria back under control. Malaria cases increased in South America after countries in that continent stopped using DDT. Research data showed a strong negative relationship between DDT residual house sprayings and malaria. In a research from 1993 to 1995, Ecuador increased its use of DDT and achieved a 61% reduction in malaria rates, while each of the other countries that gradually decreased its DDT use had large increases. Mosquito resistance In some areas, resistance reduced DDT's effectiveness. WHO guidelines require that absence of resistance must be confirmed before using the chemical. Resistance is largely due to agricultural use, in much greater quantities than required for disease prevention. Resistance was noted early in spray campaigns. Paul Russell, former head of the Allied Anti-Malaria campaign, observed in 1956 that "resistance has appeared after six or seven years". In many parts of India, DDT is ineffective. Agricultural uses were banned in 1989 and its anti-malarial use has been declining. Urban use ended. One study concluded that "DDT is still a viable insecticide in indoor residual spraying owing to its effectivity in well supervised spray operation and high excito-repellency factor." Studies of malaria-vector mosquitoes in KwaZulu-Natal Province, South Africa found susceptibility to 4% DDT (WHO's susceptibility standard), in 63% of the samples, compared to the average of 87% in the same species caught in the open. The authors concluded that "Finding DDT resistance in the vector An. arabiensis, close to the area where we previously reported pyrethroid-resistance in the vector An. funestus Giles, indicates an urgent need to develop a strategy of insecticide resistance management for the malaria control programmes of southern Africa." DDT can still be effective against resistant mosquitoes Others argue that the avoidance behavior slows eradication. Unlike other insecticides such as pyrethroids, DDT requires long exposure to accumulate a lethal dose; however its irritant property shortens contact periods. "For these reasons, when comparisons have been made, better malaria control has generally been achieved with pyrethroids than with DDT." Residents' concerns IRS is effective if at least 80% of homes and barns in a residential area are sprayed. Pyrethroid insecticides (e.g. deltamethrin and lambda-cyhalothrin) can overcome some of these issues, increasing participation. Illegal diversion to agriculture is also a concern as it is difficult to prevent and its subsequent use on crops is uncontrolled. For example, DDT use is widespread in Indian agriculture, particularly mango production and is reportedly used by librarians to protect books. Other examples include Ethiopia, where DDT intended for malaria control is reportedly used in coffee production, and Ghana where it is used for fishing. The residues in crops at levels unacceptable for export have been an important factor in bans in several tropical countries. These arguments were rejected as "outrageous" by former WHO scientist Socrates Litsios. Criticisms of a DDT "ban" often specifically reference the 1972 United States ban (with the erroneous implication that this constituted a worldwide ban and prohibited use of DDT in vector control). Reference is often made to Silent Spring, even though Carson never pushed for a DDT ban. John Quiggin and Tim Lambert wrote, "the most striking feature of the claim against Carson is the ease with which it can be refuted". Investigative journalist Adam Sarvana and others characterize these notions as "myths" promoted principally by Roger Bate of the pro-DDT advocacy group Africa Fighting Malaria (AFM). Alternatives Insecticides Organophosphate and carbamate insecticides, e.g. malathion and bendiocarb, respectively, are more expensive than DDT per kilogram and are applied at roughly the same dosage. Pyrethroids such as deltamethrin are also more expensive than DDT, but are applied more sparingly (0.02–0.3 g/m2 vs 1–2 g/m2), so the net cost per house per treatment is about the same. In 2019, the related compound difluorodiphenyltrichloroethane (DFDT) was described as a potentially more effective and therefore potentially safer alternative to DDT. Non-chemical vector control Before DDT, malaria was successfully eliminated or curtailed in several tropical areas by removing or poisoning mosquito breeding grounds and larva habitats, for example by eliminating standing water. These methods have seen little application in Africa for more than half a century. According to CDC, such methods are not practical in Africa because "Anopheles gambiae, one of the primary vectors of malaria in Africa, breeds in numerous small pools of water that form due to rainfall ... It is difficult, if not impossible, to predict when and where the breeding sites will form, and to find and treat them before the adults emerge." The relative effectiveness of IRS versus other malaria control techniques (e.g. bednets or prompt access to anti-malarial drugs) varies and is dependent on local conditions. Vietnam has enjoyed declining malaria cases and a 97% mortality reduction after switching in 1991 from a poorly funded DDT-based campaign to a program based on prompt treatment, bednets and pyrethroid group insecticides. In Mexico, effective and affordable chemical and non-chemical strategies were so successful that the Mexican DDT manufacturing plant ceased production due to lack of demand. A review of fourteen studies in sub-Saharan Africa, covering insecticide-treated nets, residual spraying, chemoprophylaxis for children, chemoprophylaxis or intermittent treatment for pregnant women, a hypothetical vaccine and changing front–line drug treatment, found decision making limited by the lack of information on the costs and effects of many interventions, the small number of cost-effectiveness analyses, the lack of evidence on the costs and effects of packages of measures and the problems in generalizing or comparing studies that relate to specific settings and use different methodologies and outcome measures. The two cost-effectiveness estimates of DDT residual spraying examined were not found to provide an accurate estimate of the cost-effectiveness of DDT spraying; the resulting estimates may not be good predictors of cost-effectiveness in current programs. However, a study in Thailand found the cost per malaria case prevented of DDT spraying (US$1.87) to be 21% greater than the cost per case prevented of lambda-cyhalothrin–treated nets (US$1.54), casting some doubt on the assumption that DDT was the most cost-effective measure. The director of Mexico's malaria control program found similar results, declaring that it was 25% cheaper for Mexico to spray a house with synthetic pyrethroids than with DDT. A more comprehensive approach to measuring the cost-effectiveness or efficacy of malarial control would not only measure the cost in dollars, as well as the number of people saved, but would also consider ecological damage and negative human health impacts. One preliminary study found that it is likely that the detriment to human health approaches or exceeds the beneficial reductions in malarial cases, except perhaps in epidemics. It is similar to the earlier study regarding estimated theoretical infant mortality caused by DDT and subject to the criticism also mentioned earlier. A study in the Solomon Islands found that "although impregnated bed nets cannot entirely replace DDT spraying without substantial increase in incidence, their use permits reduced DDT spraying". A comparison of four successful programs against malaria in Brazil, India, Eritrea and Vietnam does not endorse any single strategy but instead states, "Common success factors included conducive country conditions, a targeted technical approach using a package of effective tools, data-driven decision-making, active leadership at all levels of government, involvement of communities, decentralized implementation and control of finances, skilled technical and managerial capacity at national and sub-national levels, hands-on technical and programmatic support from partner agencies, and sufficient and flexible financing." DDT resistant mosquitoes may be susceptible to pyrethroids in some countries. However, pyrethroid resistance in Anopheles mosquitoes is on the rise with resistant mosquitoes found in multiple countries. == See also ==
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