DDT (insecticide)

DDT (from its trivial name, Dichloro-Diphenyl-Trichloroethane) is one of the best known synthetic pesticides. It is a chemical with a long, unique, and controversial history.

First synthesized in 1874, DDT's insecticidal properties were not discovered until 1939. In the second half of World War II, it was used with great effect among both military and civilian populations to control mosquitoes spreading malaria and lice transmitting typhus, resulting in dramatic reductions in the incidence of both diseases. The Swiss chemist Paul Hermann Müller of Geigy Pharmaceutical 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." After the war, DDT was made available for use as an agricultural insecticide, and soon its production and use skyrocketed.

In 1962, Silent Spring by American biologist Rachel Carson was published. The book catalogued the environmental impacts of the indiscriminate spraying of DDT in the US and questioned the logic of releasing large amounts of chemicals into the environment without fully understanding their effects on ecology or human health. The book suggested that DDT and other pesticides may cause cancer and that their agricultural use was a threat to wildlife, particularly birds. Its publication was one of the signature events in the birth of the environmental movement. Silent Spring resulted in a large public outcry that eventually led to most uses of DDT being banned in the US in 1972. DDT was subsequently banned for agricultural use worldwide under the Stockholm Convention, but its limited use in disease vector control continues to this day in certain parts of the world and remains controversial.

Along with the passage of the Endangered Species Act, the US ban on DDT is cited by scientists as a major factor in the comeback of the bald eagle in the contiguous US.

Properties and chemistry
DDT is an organochlorine insecticide, similar in structure to the pesticides dicofol and methoxychlor. It is a highly hydrophobic, colorless, crystalline solid with a weak, chemical odor. It is nearly insoluble in water but has a good solubility in most organic solvents, fats, and oils. DDT does not occur naturally, but is produced by the reaction of chloral (CCl3CHO) with chlorobenzene (C6H5Cl) in the presence of sulfuric acid, which acts as a catalyst. Trade names that DDT has been marketed under include Anofex, Cezarex, Chlorophenothane, Clofenotane, Dicophane, Dinocide, Gesarol, Guesapon, Guesarol, Gyron, Ixodex, Neocid, Neocidol, and Zerdane.

Isomers and Related Compounds
Commercial DDT is actually a mixture of several closely related compounds. The major component (77%) is the p,p isomer which is pictured at the top of this article. The o,p'  isomer (pictured to the right) is also present in significant amounts (15%). Dichlorodiphenyldichloroethylene (DDE) and dichlorodiphenyldichloroethane (DDD) make up the balance. DDE and DDD are also the major metabolites and breakdown products of DDT in the environment. The term "total DDT" is often used to refer to the sum of all DDT related compounds (p, p-DDT, o, p-DDT, DDE, and DDD) in a sample.

Production and use statistics
From 1950 to 1980, when DDT was extensively used in agriculture, more than 40,000 tonnes were used each year worldwide, and it has been estimated that a total of 1.8 million tonnes of DDT have been produced globally since the 1940s. In the U.S., where it was manufactured by Ciba, Montrose Chemical Company and Velsicol Chemical Corporation, production peaked in 1963 at 82,000 tonnes per year. More than 600,000 tonnes (1.35 billion lbs) were applied in the U.S. before the 1972 ban, with usage peaking in 1959 with about 36,000 tonnes applied that year.

Today, 4-5,000 tonnes of DDT are used each year for the control of malaria and visceral leishmaniasis, with India being the largest consumer. India, China, and North Korea are the only countries still producing and exporting it, and production is reportedly on the rise.

Mechanism of action
DDT is moderately toxic, with a rat LD50 of 113 mg/kg. It has potent insecticidal properties, where it kills by opening sodium ion channels in the neurons, causing them to fire spontaneously leading to spasms and eventual death. Insects with certain mutations in their sodium channel gene are resistant to DDT and other similar insecticides. DDT resistance is also conferred by up-regulation of genes expressing cytochrome P450 in some insect species.

History
First synthesized in 1874 by Othmar Zeidler, DDT's insecticidal properties were not 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 a number of chlorine-containing pesticides used in the 1940s and 1950s. With pyrethrum in short supply, DDT was used extensively during World War II by the Allies to control the insect vectors of typhus—nearly eliminating the disease in many parts of Europe. In the South Pacific, it was sprayed aerially for malaria control with spectacular effects. While DDT's chemical and insecticide properties were important factors in these victories, advances in application equipment coupled with a high degree of organization and sufficient manpower were also crucial elements in the success of these wartime spray programs. In 1945, it was made available to farmers as an agricultural insecticide.

DDT played a small role in the final elimination of malaria in Europe and North America, as malaria had already been eliminated from much of the developed world before the advent of DDT through the use of a range of public health measures and generally increasing health and living standards. One CDC physician involved in the United States' DDT spraying campaign said of the effort that "we kicked a dying dog." But in countries without these advances, it was critical in their eradication of the disease.

In 1955, the World Health Organization commenced a program to eradicate malaria worldwide, relying largely on DDT. The program was initially highly successful, eliminating the disease 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 reducing mortality in Sri Lanka and India. However resistance soon emerged in many insect populations as a consequence of widespread agricultural use of DDT. In many areas, early victories against malaria were partially or completely reversed, and in some cases rates of transmission even increased. The program was successful 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 not pursued at all in sub-Saharan Africa due to these perceived difficulties, with the result that mortality rates in the area were never reduced to the same dramatic extent, and now constitute the bulk of malarial deaths worldwide, especially following the resurgence of the disease as a result of microbe resistance to drug treatments and the spread of the deadly malarial variant caused by Plasmodium falciparum. The goal of eradication was abandoned in 1969, and attention was 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, but mostly because mosquitoes were developing resistance to DDT. Efforts were shifted from spraying to the use of bednets impregnated with insecticides and other interventions.

Silent Spring and the U.S. ban
As early as the 1940s, scientists in the U.S. had begun expressing concern over possible hazards associated with DDT, and in the 1950s the government began tightening some of the regulations governing its use. However, these early events received little attention, and it was not until 1957, when the New York Times reported an unsuccessful struggle to restrict DDT use in Nassau County, New York, that the issue came to the attention of the popular naturalist-author, Rachel Carson. William Shawn, editor of The New Yorker, urged her to write a piece on the subject, which developed into her famous book Silent Spring, published in 1962. The book argued that pesticides, including DDT, were poisoning both wildlife and the environment and were also 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 Kennedy ordered his Science Advisory Committee to investigate Carson's claims. The report the committee issued "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". DDT became a prime target of the growing anti-chemical and anti-pesticide movements, and in 1967 a group of scientists and lawyers founded the Environmental Defense Fund (EDF) with the specific goal of winning a ban on DDT. Victor Yannacone, Charles Wurster, Art Cooley and others associated with inception of EDF had all witnessed bird kills or declines in bird populations and suspected that DDT was the cause. In their campaign against the chemical, EDF petitioned the government for a ban and filed a series of lawsuits. Around this time, toxicologist David Peakall was measuring DDE levels in the eggs of peregrine falcons and California condors and finding that increased levels corresponded with thinner shells.

In response to an EDF suit, the U.S. 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 to human health and wildlife. However, the findings of these staff members were criticized, as they were performed mostly by economic entomologists inherited from the United States Department of Agriculture, whom many environmentalists felt were biased towards agribusiness and tended to minimize concerns about human health and wildlife. The decision not to ban thus created public controversy.

The EPA then held seven months of hearings in 1971-1972, with scientists giving evidence both for and against the use of DDT. In the summer of 1972, Ruckelshaus announced the cancellation of most uses of DDT—an exemption allowed for public health uses under some conditions. Immediately after the cancellation was announced, both EDF and the DDT manufactures filed suit against the EPA, with the industry seeking to overturn the ban, and EDF seeking a comprehensive ban. The cases were consolidated, and in 1973 the U.S. Court of Appeals for the District of Columbia ruled that the EPA had acted properly in banning DDT.

The U.S. DDT ban took place amid a climate of growing public mistrust of industry, with the Surgeon General issuing a report on smoking in 1964, the Cuyahoga River catching fire in 1969, the fiasco surrounding the use of diethylstilbestrol (DES), and the well-publicized decline in the bald eagle population.

Some uses of DDT continued under the public health exemption. For example, in June 1979, the California Department of Health Services was permitted to use DDT to suppress flea vectors of bubonic plague. DDT also continued to be produced in the US for foreign markets until as late as 1985, when over 300 tonnes were exported.

Restrictions on usage
In the 1970s and 1980s, agricultural use of DDT was banned in most developed countries. DDT was first banned in Hungary in 1968 then in Norway and Sweden in 1970 and the US in 1972, but was not banned in the United Kingdom until 1984. The use of DDT in vector control has not been banned, but it has been largely replaced by less persistent, and more expensive, alternative insecticides.

The Stockholm Convention, ratified in 2001 and effective as of 17 May 2004, outlawed several persistent organic pollutants, and restricted the use of DDT to vector control. The Convention was signed by 98 countries and is endorsed by most environmental groups. Recognizing that a total elimination of DDT use in many malaria-prone countries is currently unfeasible because there are few affordable or effective alternatives, the public health use of DDT was exempted from the ban until alternatives are developed. The 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 on agricultural use of DDT, its use in this context continues in India North Korea, and possibly elsewhere.

About 4-5,000 tonnes of DDT per year is still used today in some countries where malaria is a serious health problem. In this context, DDT is applied to the inside walls of homes to kill or repel mosquitos entering the home. This intervention, called indoor residual spraying (IRS), greatly reduces environmental damage compared to the earlier widespread use of DDT in agriculture. It also reduces the risk of resistance to DDT. This use only requires a small fraction of that previously used in agriculture; for example, the amount of DDT that might have been used on 100 acres (0.4 km²) of cotton during a typical growing season in the U.S. is estimated to be enough to treat roughly 1,700 homes.

Environmental impact
DDT is a persistent organic pollutant that is extremely hydrophobic and strongly absorbed by soils. Depending on conditions, its soil half life can range from 22 days to 30 years. Routes of loss and degradation include runoff, volatilization, photolysis and aerobic and anaerobic biodegradation. When applied to aquatic ecosystems it is quickly absorbed by organisms and by soil or it evaporates, leaving little DDT dissolved in the water itself. Its breakdown products and metabolites, DDE and DDD, are also highly persistent and have similar chemical and physical properties. These products together are known as "total DDT". DDT and its breakdown products are transported from warmer regions of the world to the Arctic by the phenomenon of global distillation, where they then accumulate in the region's food web.

DDT, DDE, and DDD magnify through the food chain, with apex predators such as raptors having a higher concentration of the chemicals than other animals sharing the same environment. They are stored mainly in body fat. In the United States, human blood and fat tissue samples collected in the early 1970s showed detectable levels in all samples. A study conducted in the late 1970s after the U.S. DDT ban found that blood levels were declining, but DDT or metabolites were still found in a high proportion of samples. Biomonitoring conducted by the Centers for Disease Control as recently as 2002 shows that more than half of subjects tested had detectable levels of DDT or metabolites in their blood, and of the 700+ milk samples tested by the USDA in 2005, 85% had detectable levels of DDE.

DDT is a toxicant across a range of phyla. DDT was a major reason for the decline of the bald eagle in North America in the 1950s and 1960s as well as the brown pelican and the peregrine falcon. DDT and its breakdown products are toxic to embryos and disrupts calcium absorption, thereby impairing eggshell quality. Studies in the 1960s and 1970s failed to find a mechanism for the hypothesized thinning. However, more recent studies in the 1990s and 2000s have laid the blame at the feet of DDE. Some studies have shown that although DDE levels have fallen dramatically, eggshell thickness remains 10–12 percent thinner than before DDT was first used. DDT is also highly toxic to aquatic life, including crayfish, daphnids, sea shrimp and many species of fish. DDT may be moderately toxic to some amphibian species, especially in the larval stages.

Effects on human health
The effects of DDT on human health are disputed since studies have yielded conflicting results.

Acute

 * DDT is classified as "moderately toxic" by the US National Toxicological Program and "moderately hazardous" by WHO, based on the rat oral LD50 of 113 mg/kg. It is not considered to be acutely toxic, and in fact it has been applied directly to clothes and/or used in soap. DDT has on rare occasions been administered orally as a treatment for barbiturate poisoning.

Chronic

 * Occupational exposure to DDT was associated with reduced verbal attention, visuomotor speed, sequencing, and with increased neuropsychological and psychiatric symptoms in a dose-response pattern (ie, per year of DDT application) in retired workers aged 55–70 years in Costa Rica. DDT or DDE concentrations were not determined in this study.
 * Farmers exposed to DDT occupationally have an increased incidence of non-allergic asthma.
 * Organochlorine compounds in general and DDE specifically have been linked to diabetes. A study of Native Americans exposed to DDE primarily from eating contaminated fish found that elevated blood DDE levels were associated with an increased incidence of diabetes. These results are consistent with previous studies on diabetes incidence and organochlorine exposure. A recent study of Mexican Americans yielded similar results.

Cancer

 * The United States National Toxicology Program classified DDT as "reasonably anticipated to be a human carcinogen", and the EPA classifies DDT, DDE, and DDD as a class B2 "probable" human carcinogens. The International Agency for Research on Cancer classifies a Group 2B, "possible" human carcinogen. These evaluations are based mainly on the results for animal studies.
 * A study of malaria workers who handled DDT occupationally found an elevated risk of cancers of the liver and biliary tract. Another study has found a correlation between DDE and liver cancer in white men, but not for women or black men. An association between DDT exposure and pancreatic cancer has been demonstrated in a few studies, but other studies have found no association. Several studies have looked for associations between DDT and multiple myeloma, and testicular, prostate, endometrial, and colorectal cancers, but none conclusively demonstrated any association.
 * A Canadian study from 2007 found a positive association between DDE and non-Hodgkin Lymphoma.
 * A recent study in the Journal of the National Cancer Institute concluded that DDE exposure may be associated with testicular cancer. The incidence of seminoma in men with the highest blood levels of DDE was almost double that of men with the lowest levels of DDE.

Breast cancer
The question of whether DDT or its metabolites can cause breast cancer has been the subject of numerous investigations. While individual studies have come to conflicting conclusions, the most recent review of all the evidence concludes that exposure to DDT before puberty increases the risk of breast cancer later in life. Until recently, almost all studies measured DDT or DDE blood levels at the time of breast cancer diagnosis or after. This study design has been criticized, since the levels of DDT or DDE at diagnosis do not necessarily correspond to the levels present in a woman's body at the time when her cancer first started. Such studies have thus yielded conflicting results and taken as a whole "do not support the hypothesis that exposure to DDT is an important risk factor for breast cancer." The studies of this design have been extensively reviewed.

In contrast to studies which measured DDT or DDE late in life, a recent study was able to assess DDT exposure early in life and track the breast cancer status of the women later in life. This study found a strong association between exposure to the p, p-isomer of DDT early in life and breast cancer later in life. Exposure to the o, p'-isomer was negatively correlated with breast cancer (i.e. a protective effect was observed), and no association was observed for DDE. Unlike previous studies, this was prospective cohort study in which blood samples were collected from young mothers in the 1960s while DDT was still in use, and their breast cancer status was then monitored. In addition to suggesting that exposure to the p, p-isomer of DDT is the more significant risk factor of breast cancer, the study also suggests that the timing of exposure is critical. For the subset of women born more than 14 years prior to the introduction of DDT into US agriculture, there was no association between DDT levels and breast cancer. However, for women born more recently—and thus exposed earlier in life—the most p, p-DDT exposed third had a fivefold increase in breast cancer incidence over the least exposed third, after correcting for the protective effect of o, p-DDT.

Developmental and reproductive toxicity
DDT and its breakdown product DDE, like other organochlorines, have been shown to have xenoestrogenic activity; meaning they are chemically similar enough to estrogens to trigger hormonal responses in animals. This endocrine disrupting activity has been observed when DDT is used in laboratory studies involving mice and rats as test subjects, and available epidemiological evidence indicates that these effects may be occurring in humans as a result of DDT exposure. In areas where DDT is used for malaria control, infants can be exposed via breastmilk in levels that exceed the W.H.O's acceptable daily intake value for DDT.


 * A review article in The Lancet concludes that, "research has shown that exposure to DDT at amounts that would be needed in malaria control might cause preterm birth and early weaning … toxicological evidence shows endocrine-disrupting properties; human data also indicate possible disruption in semen quality, menstruation, gestational length, and duration of lactation."


 * Human epidemiological studies suggest that DDT exposure is a risk factor for premature birth and low birth weight, and may harm a mother's ability to breast feed. Some researchers argue that these effects may cause increases in infant deaths in areas where DDT is used for malaria control, and thus offset any benefit derived from its anti-malarial effects.  A recent study, however, failed to confirm the association between exposure and difficulty breastfeeding.


 * Several recent studies demonstrate a link between in utero exposure to DDT or DDE and developmental neurotoxicity in humans. For example, a 2006 study conducted by the University of California, Berkeley suggests children who have been exposed to DDT while in the womb have a greater chance of experiencing development problems, and other studies have found that even low-levels of DDT or DDE in umbilical cord serum at birth are associated with decreased attention at infancy and decreased cognitive skills at 4 years of age. Similarly, Mexican researchers have demonstrated a link between DDE exposure in the first trimester of pregnancy and retarded psychomotor development.


 * A 2007 study documented decreases in semen quality among South African men from communities where DDT is used to combat endemic malaria. The researchers found statistically significant correlations between increased levels of DDT or DDE in blood plasma and decreases in several measures of semen quality including ejaculate volume, certain motility parameters, and sperm count. The same researchers reported similar results in 2006 from a study of men in Mexico. A review of earlier studies noted that "Studies of populations with a much lower exposure than that seen in current malaria-endemic areas have shown only weak, inconsistent associations between DDE and testosterone amounts, semen quality, and sperm DNA damage."


 * One recent study suggests that women exposed to DDT while in the womb have more difficulty getting pregnant as adults than non-exposed women. On the other hand, prenatal DDE exposure increased the probability of pregnancy.


 * DDT exposure is associated with early pregnancy loss, a type of miscarriage. A prospective cohort study of Chinese textile workers found "a positive, monotonic, exposure-response association between preconception serum total DDT and the risk of subsequent early pregnancy losses." The median serum DDE level of study group was lower than that typically observed in women living in homes sprayed with DDT, suggesting that these finding are relevant to the debate about DDT and malaria control.


 * A case-control study of congenital hypothyroidism in Japan concluded that in utero DDT exposure may affect thyroid hormone levels and "play an important role in the incidence and/or causation of cretinism." Other studies have also found the DDT or DDE interfere with proper thyroid function.

DDT use against malaria
Malaria remains a major public health challenge in many parts of the world. The World Health Organization estimates that there are 250 million cases every year, resulting in almost 1 million deaths. About 90% of these deaths occur in Africa, and mostly to children under the age of 5. Spraying DDT is one of many public health interventions currently used 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 the advent of DDT, aggressive campaigns to eliminate mosquito breeding grounds by drainage or poisoning with Paris green or pyrethrum were used, sometimes successfully, to fight the disease. In many parts of the world, rising standards of living resulted in the elimination of malaria as a collateral benefit of the introduction of window screens and improved sanitation. Today, a variety of interventions are used, and usually many are used simultaneously. These include the use of antimalarial drugs to prevent or treat malaria infections; improvements in public health infrastructure to quickly diagnose, sequester, and treat infected individuals; the distribution of bednets and other methods intended to keep mosquitos from biting humans; and vector control strategies. These include larvaciding with appropriate insecticides, ecological controls such as draining mosquito breeding grounds or introducing fish to eat larva, and indoor residual spraying (IRS) with DDT or other insecticides. IRS involves the treatment of all interior walls and ceilings with insecticides, and is particularly effective against mosquitoes, since many species will rest on an indoor wall before or after feeding. The contemporary DDT debate revolves around how much of a role the chemical should play in the mix of malaria control strategies.

Once the mainstay of anti-malaria campaigns, as of 2006 only 13 countries were still using DDT, including India and some southern African states. The WHO's anti-malaria campaign in the 1950s and 1960s relied heavily on the chemical and initially the results were promising, though short lived. Experts tie the resurgence of malaria to numerous factors, including poor leadership and management of malaria control programs, a chronic lack of funds in the countries worst hit by malaria, and the resistance of the malaria parasite itself to the drugs traditionally used to treat the illness. According to Richard Tren, "Malaria surged through Africa in the 1990s, fueled by resistance to chloroquine and other historically effective drugs." Resistance of mosquitoes to DDT has also been a factor, which was exacerbated by the often unrestricted use of DDT in agriculture. This, coupled with the awareness that DDT may be harmful both to humans and the environment led governments to restrict or curtail the use of DDT in vector control.

Overall effectiveness of DDT against malaria
When it was first introduced in World War II, DDT was very effective in reducing malaria morbidity and mortality. The WHO's anti-malaria campaign, which consisted mostly of spraying DDT, was initially very successful as well. For example, in Sri Lanka, the program reduced cases from about 3 million per year before spraying to just 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 spraying, but it was largely ineffective because mosquitoes had acquired resistance to the chemical in the interim, presumably because of its continued use in agriculture. The program was forced to switch to malathion, which though more expensive, proved effective.

Today, DDT is still included in the WHO's list of insecticides recommended for IRS. Since the appointment of Arata Kochi as head of its anti-malaria division, WHO's policy has shifted from recommending IRS only in areas of seasonal or episodic transmission of malaria, to also advocating it in areas of continuous, intense transmission. The WHO remains, however, "very much concerned with health consequences from use of DDT" and it has reaffirmed its commitment to eventually phasing it out. South Africa is one country that 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.

According to DDT advocate Donald Roberts, malaria cases increased in South America after countries in that continent stopped using DDT. Research data shows a significantly strong negative relationship between DDT residual house sprayings and malaria rates. In a research from 1993 to 1995, Ecuador increased its use of DDT and resulted in a 61% reduction in malaria rates, while each of the other countries that gradually decreased its DDT use had large increase in malaria rates.

Mosquito resistance to DDT
The evolution of resistance to DDT in mosquitos has greatly reduced its effectiveness in many parts of the world, and current WHO guidelines require that before the chemical is used in an area, susceptibility of local mosquitos to DDT must be confirmed. The appearance of DDT-resistance is largely due to its use in agriculture, where it was used in much greater amounts than the relatively small quantities used for disease prevention. According to one study that attempted to quantify the lives saved by banning agricultural uses of DDT and thereby slowing the spread of resistance, "it can be estimated that at current rates each kilo of insecticide added to the environment will generate 105 new cases of malaria."

Resistance was noted early in spray campaigns, with Paul Russell, a former head of the Allied Anti-Malaria campaign, observing in 1956 that eradication programs had to be wary of relying on DDT for too long as "resistance has appeared [after] six or seven years." DDT has lost much of its effectiveness in many parts of the world including Sri Lanka, Pakistan, Turkey and Central America, and it has largely been replaced by organophosphate or carbamate insecticides, e.g. malathion or bendiocarb.

In many parts of India, DDT has largely lost its effectiveness. Agricultural uses were banned in 1989, and its use for anti-malarial purposes has been declining. Its use in urban areas has been halted completely. Nevertheless, DDT is still manufactured and used in the country, and one study had 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 (the WHO susceptibility standard), in 63% of the samples, compared to the average of 86.5% 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."

It has been argued that DDT can still be effective against resistant mosquitos, and that the avoidance of DDT-sprayed walls by mosquitoes is an additional benefit of the chemical. For example, a 2007 study reported that DDT-resistant mosquitoes still avoided DDT-treated huts. The researchers argued that DDT was the best pesticide for use in IRS (even though it did not afford the most protection from mosquitos out of the three test chemicals) because the others pesticides worked primarily by killing or irritating mosquitoes—modes of action the authors presume mosquitoes will develop resistance to. Others have argued that the avoidance of DDT sprayed walls by mosquitoes is detrimental to the actual eradication of the disease. Unlike other insecticides such as pyrethroids, DDT requires a long period of contact before mosquitoes pick up a lethal dose; however its irritant property makes them fly off before this occurs. "For these reasons, when comparisons have been made, better malaria control has generally been achieved with pyrethroids than with DDT." In India, with its outdoor sleeping habits and frequent night duties, "the excito-repellent effect of DDT, often reported useful in other countries, actually promotes outdoor transmission."

Residents' resistance to use of DDT
For IRS to be effective, at 80% of homes and barns in an area must be sprayed, and enough residents refuse spraying, the effectiveness of the whole program can be jeopardized. Many residents resist spraying of DDT for various reasons. For instance, the smell lingers, and DDT leaves a stain on the walls. While that stain makes it easier to check whether the room has been sprayed it causes some villagers to avoid spraying of their homes or to resurface the wall, which eliminates the residual insecticidal effect of the spraying. "Pyrethroids such as deltamethrin and lambda-cyhalothrin are … much more acceptable to householders because they leave no visible deposit on walls… therefore rates of refusal of spraying by householders are lower with pyrethroids than with DDT."

In addition, DDT is not suitable for this type of spraying in Western-style plastered or painted walls, only traditional dwellings with unpainted walls made of mud, sticks, dung, thatch, clay, or cement. As rural areas of South Africa become more prosperous, there is a shift towards Western style housing, leaving fewer homes suitable for DDT spraying, and necessitating the use of alternative insecticides.

Other villagers object to DDT spraying because it does not kill cockroaches or bedbugs; rather, it excites such pests making them more active,    so that often use of another insecticide is additionally required. Pyrethroids such as deltamethrin and lambdacyhalothrin, on the other hand, are more acceptable to residents because they kill these nuisance insects as well as mosquitoes. DDT has also been known to kill beneficial insects, such as wasps that kill caterpillars that, unchecked, destroy thatched roofs.

As a result, Mozambique's chief of infectious disease control, Avertino Barreto, says that resistance to DDT spraying is "homegrown", not due to "pressure from environmentalists". "They only want us to use DDT on poor, rural black people," he says. "So whoever suggests DDT use, I say, 'Fine, I'll start spraying in your house first.'"

Human exposure associated with DDT spraying for disease vectors
In the low income areas where malaria eradication is necessary, it is almost impossible to ensure that DDT intended for disease prevention does not get diverted to use on crops, on a totally unregulated basis. "The consequent insecticidal residues in crops at levels unacceptable for the export trade have been an important factor in recent bans of DDT for malaria control in several tropical countries". Adding to this problem is a lack of skilled personnel and supervision.

Evidence for exposure to DDT is seen in South Africa, where in contrast to areas where DDT use has ceased (even where it was used heavily), in areas where DDT is currently in use ostensibly in small amounts for malaria prevention only, DDT levels in men and women were significantly higher than the allowable daily intake. Breast milk from regions where DDT is used for malaria control contains enough DDT to greatly exceed the allowable daily intake of breast feeding infants. These levels have been associated with neurological abnormalities in babies ingesting relatively large quantities of DDT in their milk although toxicity via this mode of intake has not been proved.

Some researchers have suggested that the negative health effects of exposure to DDT might outweigh the health benefits afforded by anti-malarial properties. For example, scientists with the US National Institute of Environmental Health Sciences argued in The Lancet that "Although DDT is generally not toxic to human beings and was banned mainly for ecological reasons, subsequent research has shown that exposure to DDT at amounts that would be needed in malaria control might cause preterm birth and early weaning, abrogating the benefit of reducing infant mortality from malaria...DDT might be useful in controlling malaria, but the evidence of its adverse effects on human health needs appropriate research on whether it achieves a favourable balance of risk versus benefit."

Criticism of restrictions on DDT use
Critics claim that restrictions on the use of DDT in vector control have resulted in substantial numbers of unnecessary deaths due to malaria. Estimates for the number of deaths that have been caused by an alleged lack of availability of DDT range from hundreds of thousands, according to Nicholas Kristof, to much higher figures. Robert Gwadz of the National Institutes of Health said in 2007 that "The ban on DDT may have killed 20 million children." These arguments have been called "outrageous" by former WHO scientist Socrates Litsios and May Berenbaum, a professor of entomology at the University of Illinois at Urbana-Champaign, says that "to blame environmentalists who oppose DDT for more deaths than Hitler is worse than irresponsible." Criticisms of a "ban" on DDT often specifically reference the 1972 US ban (with the erroneous implication that this constituted a worldwide ban). Reference is often made to Rachel Carson's Silent Spring even though she never pushed for a ban on DDT. John Quiggin and Tim Lambert have written that "the most striking feature of the claim against Carson is the ease with which it can be refuted." Carson actually devoted a page of her book to considering the relationship between DDT and malaria, warning of the evolution of DDT resistance in mosquitoes and concluding:

"It is more sensible in some cases to take a small amount of damage in preference to having none for a time but paying for it in the long run by losing the very means of fighting [is the advice given in Holland by Dr Briejer in his capacity as director of the Plant Protection Service]. Practical advice should be 'Spray as little as you possibly can' rather than 'Spray to the limit of your capacity.'"

According to Amir Attaran, many environmental groups fought against the public health exception of DDT in the 2001 Stockholm Convention, over the objections of third world governments and many malaria researchers. Attaran strongly objected to an outright ban, writing, "Environmentalists in rich, developed countries gain nothing from DDT, and thus small risks felt at home loom larger than health benefits for the poor tropics. More than 200 environmental groups, including Greenpeace, Physicians for Social Responsibility and the World Wildlife Fund, actively condemn DDT..."

It has also been argued that donor governments and agencies have refused to fund DDT spraying, or made aid contingent upon not using DDT. According a report in the British Medical Journal, use of DDT in Mozambique "was stopped several decades ago, because 80% of the country's health budget came from donor funds, and donors refused to allow the use of DDT." Roger Bate of the pro-DDT advocacy group Africa Fighting Malaria (AFM), asserts that "many countries have been coming under pressure from international health and environment agencies to give up DDT or face losing aid grants: Belize and Bolivia are on record admitting they gave in to pressure on this issue from [USAID]."

The United States Agency for International Development (USAID) has been the focus of much criticism. While the agency is currently funding the use of DDT in some African countries, in the past it has not. When John Stossel accused USAID of not funding DDT because it wasn't "politically correct," Anne Peterson, the agency's assistant administrator for global health, replied that "I believe that the strategies we are using are as effective as spraying with DDT … So, politically correct or not, I am very confident that what we are doing is the right strategy." USAID's Kent R. Hill states that the agency has been misrepresented: "USAID strongly supports spraying as a preventative measure for malaria and will support the use of DDT when it is scientifically sound and warranted." With regard to decision to start funding the use of the chemical, the Agency's website states that "USAID has never had a 'policy' as such either 'for' or 'against' DDT for IRS. The real change in the past two years [2006/07] has been a new interest and emphasis on the use of IRS in general—with DDT or any other insecticide—as an effective malaria prevention strategy in tropical Africa." The website further explains that in many cases alternative malaria control measures were judged to be more cost-effective that DDT spraying, and so were funded instead.

DDT versus other insecticides
Advocates of increased use of DDT in IRS claim that alternative insecticides are more expensive, more toxic, or not as effective. As discussed above, susceptibility of mosquitos to DDT varies geographically and the same is true for alternative insecticides, so its effectiveness vis-a-vis other chemicals varies. With regard to toxicity and cost-effectiveness versus other insecticides, actual data is, in fact, lacking. The relative costs of employing various insecticides vary by location and ease of access, the habits of the particular mosquitoes prevalent in each area, the degrees of resistance to various pesticides exhibited by the mosquitoes, and the habits and compliance of the population, among other factors. Furthermore, the choice of insecticide has little impact on the overall cost of a round of spraying, since insecticide costs are only a fraction total budget for an IRS campaign. However to be effective, IRS needs to be maintained throughout the malaria season, and DDT lasts longer than alternative insecticides, so needs to be applied less frequently.

Organophosphate, carbamate, insecticides, e.g. malathion or bendiocarb, 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 is about the same per 6 months.

DDT versus non-chemical vector control
Before DDT, malaria was successfully eradicated or curtailed in several tropical areas by removing or poisoning the breeding grounds of the mosquitoes or the aquatic habitats of the larva stages, for example by filling or applying oil to places with standing water. These methods have seen little application in Africa for more than half a century.

The relative effectiveness of IRS (with DDT or alternative insecticides) versus other malaria control techniques (e.g. bednets or prompt access to anti-malarial drugs) varies greatly and is highly dependent on local conditions.

A study by the World Health Organization released in January 2008 found that mass distribution of insecticide-treated mosquito nets and artemisinin based drugs cut malaria deaths in half in Rwanda and Ethiopia, countries with very high malaria burdens. IRS with DDT was determined to not have played an important role in the reduction of mortality.

Vietnam is an example of a country that has seen a continued decline in malaria cases after switching in 1991 from a poorly funded DDT-based campaign to a program based on prompt treatment, bednets, and the use of pyrethroid group insecticides. Deaths from malaria dropped by 97%.

In Mexico, the use of a range of effective and affordable chemical and non-chemical strategies against malaria has been so successful that the Mexican DDT manufacturing plant ceased production voluntarily, due to lack of demand. Furthermore, while the increased numbers of malaria victims since DDT usage fell out of favor would, at first glance, suggest a 1:1 correlation, many other factors are known to have contributed to the rise in cases.

A review of fourteen studies on the subject 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 the first line drug for treatment, found decision making limited by the gross lack of information on the costs and effects of many interventions, the very small number of cost-effectiveness analyses available, 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; furthermore, the resulting estimates may not be good predictors of cost-effectiveness in current programmes.

However, a study in Thailand found the cost per malaria case prevented of DDT spraying ($1.87 US) to be 21% greater than the cost per case prevented of lambdacyhalothrin-treated nets ($1.54 US), at very least casting some doubt on the unexamined assumption that DDT was the most cost-effective measure to use in all cases. The director of Mexico's malaria control program finds similar results, declaring that it is 25% cheaper for Mexico to spray a house with synthetic pyrethroids than with DDT. However, another study in South Africa found generally lower costs for DDT spraying than for impregnated nets.

A more comprehensive approach to measuring cost-effectiveness or efficacy of malarial control would not only measure the cost in dollars of the project, as well as the number of people saved, but would also take into account the negative aspects of insecticide use on human health and ecological damage. One preliminary study regarding the effect of DDT found that it is likely the detriment to human health approaches or exceeds the beneficial reductions in malarial cases, except perhaps in malarial epidemic situations. It is similar to the earlier mentioned 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 have generally proved susceptible to pyrethroids. Thus far, pyrethroid resistance in Anopheles has not been a major problem.

US Government

 * A Persistent Controversy, a Still Valid Warning - May Berenbaum, head of the entomology department at University of Illinois, Urbana-Champaign
 * EPA on DDT

Toxicity

 * DDT Technical Fact Sheet - National Pesticide Information Center
 * EXTOXNET: Pesticide Information Profiles&mdash;DDT
 * Scorecard: The Pollution Information Site&mdash;DDT
 * Interview with Barbara Cohn, PhD about DDT and breast cancer

Environmental impact

 * Microbial Degradation of Pesticides
 * US Fish and Wildlife Service Historic News Releases - DDT
 * Aerobic pathway of DDT metabolization
 * Anaerobic pathway of DDT metabolization
 * Pesticide residues in food 2000 : DDT
 * Environmental Fate Evaluation of DDT, Chlordane and Lindane

Politics and DDT

 * DDT, Eggshells, and Me Article from Reason magazine
 * Rachel Carson, Mass Murderer?: The creation of an anti-environmental myth. Aaron Swartz, Extra!, September/October, 2007.

Malaria and DDT

 * "If Malaria's the Problem, DDT's Not the Only Answer", a Washington Post column by entomologist May Berenbaum
 * 'Andrew Spielman, Harvard School of Public Health, discusses environmentally friendly control of Malaria and uses of DDT Freeview video provided by the Vega Science Trust
 * The DDT ban myth
 * Malaria and the DDT Story
 * Ugandan farmers push for DDT ban. Dated 31 May 2008 ABC News

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