DDT
Dichlorodiphenyltrichloroethane 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 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.
By October 1945, DDT was available for public sale in the United States. Although it was promoted by government and industry for use as an agricultural and household pesticide, there were also concerns about its use from the beginning. Opposition to DDT was focused by the 1962 publication of Rachel Carson's book Silent Spring. It talked about environmental impacts that correlated with the widespread use of DDT in agriculture in the United States, and it questioned the logic of broadcasting potentially dangerous chemicals into the environment with little prior investigation of their environmental and health effects. The book cited claims that DDT and other pesticides caused cancer and that their agricultural use was a threat to wildlife, particularly birds. Although Carson never directly called for an outright ban on the use of DDT, its publication was a seminal event for the environmental movement and resulted in a large public outcry that eventually led, in 1972, to a ban on DDT's agricultural use in the United States. Along with the passage of the Endangered Species Act, the United States ban on DDT is a major factor in the comeback of the bald eagle and the peregrine falcon from near-extinction in the contiguous United States.
The evolution of DDT resistance and the harm both to humans and the environment led many governments to curtail DDT use. A worldwide ban on agricultural use was formalized under the Stockholm Convention on Persistent Organic Pollutants, which has been in effect since 2004. Recognizing that total elimination in many malaria-prone countries is currently unfeasible in the absence of affordable/effective alternatives for disease control, the convention exempts public health use within WHO guidelines from the ban.
DDT still has limited use in disease vector control because of its effectiveness in killing mosquitos and thus reducing malarial infections, but that use is controversial due to environmental and health concerns. DDT is one of many tools to fight malaria, which remains the primary public health challenge in many countries. WHO guidelines require that absence of DDT resistance must be confirmed before using it. Resistance is largely due to agricultural use, in much greater quantities than required for disease prevention.
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. DDT has been marketed under trade names including Anofex, Cezarex, Chlorophenothane, Dicophane, Dinocide, Gesarol, Guesapon, Guesarol, Gyron, Ixodex, Neocid, Neocidol and Zerdane; INN is clofenotane.Isomers and related compounds
Commercial DDT is a mixture of several closely related compounds. Due to the nature of the chemical reaction used to synthesize DDT, several combinations of ortho and para arene substitution patterns are formed. The major component is the desired p,''p isomer. The o'',p isomeric impurity is also present in significant amounts. Dichlorodiphenyldichloroethylene and dichlorodiphenyldichloroethane make up the balance of impurities in commercial samples. DDE and DDD are also the major metabolites and environmental breakdown products. DDT, DDE and DDD are sometimes referred to collectively as DDX.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. More than 600,000 tonnes were applied in the US before the 1972 ban. Usage peaked in 1959 at about 36,000 tonnes.
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. DDT resistance is also conferred by up-regulation of genes expressing cytochrome P450 in some insect species, 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
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.Use in the 1940s and 1950s
DDT is the best-known of several chlorine-containing pesticides used in the 1940s and 1950s. During this time, the use of DDT was driven by protecting American soldiers from diseases in tropical areas. Both British and American scientists hoped to use it to control spread of malaria, typhus, dysentery, and typhoid fever among overseas soldiers, especially considering that the pyrethrum was harder to access since it came mainly from Japan. Due to the potency of DDT, it was not long before America's 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 American government's advertising campaigns of posters depicting Americans fighting the Axis powers and insects and through media publications celebrating its military uses. In the South Pacific, it was sprayed aerially for malaria and dengue fever control with spectacular effects. While DDT's chemical and insecticidal properties were important factors in these victories, advances in application equipment coupled with competent organization and sufficient manpower were also crucial to the success of these programs.In 1945, DDT was made available to farmers as an agricultural insecticide and played a role in the elimination of malaria in Europe and North America. 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.
DDT was also a way for American influence to reach abroad through DDT-spraying campaigns. In the 1944 issue of Life magazine there was a feature regarding the Italian program showing pictures of American public health officials in uniforms spraying DDT on Italian families.
In 1955, the World Health Organization commenced a program to eradicate malaria in countries with low to moderate transmission rates worldwide, relying largely on DDT for mosquito control and rapid diagnosis and treatment to reduce transmission. The program eliminated the disease in "North America, Europe, the former Soviet Union", and in "Taiwan, much of the Caribbean, the Balkans, parts of northern Africa, the northern region of Australia, and a large swath of the South Pacific" and dramatically reduced mortality in Sri Lanka and India.
However, failure to sustain the program, increasing mosquito tolerance to DDT, and increasing parasite tolerance led to a resurgence. In many areas early successes partially or completely reversed, and in some cases rates of transmission increased. 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 were curtailed due to concerns over safety and environmental effects, as well as problems in administrative, managerial and financial implementation. Efforts shifted from spraying to the use of bednets impregnated with insecticides and other interventions.