Clofenotane

# Overview
DDT (dichlorodiphenyltrichloroethane) is a colorless, crystalline, tasteless and almost odorless organochloride known for its insecticidal properties. DDT has been formulated in almost every conceivable form, including solutions in xylene or petroleum distillates, emulsifiable concentrates, water-wettable powders, granules, aerosols, smoke candles and charges for vaporizers and lotions.
First synthesized in 1874, DDT's insecticidal action was discovered by the Swiss chemist Paul Hermann Muller in 1939. It was then used in the second half of World War II to control malaria and typhus among civilians and troops. After the war, DDT was made available for use as an agricultural insecticide and its production and use duly increased. Muller was awarded the Nobel Prize in Physiology or Medicine "for his discovery of the high efficiency of DDT as a contact poison against several arthropods" in 1948.
In 1962, the book Silent Spring by American biologist Rachel Carson was published. It cataloged the environmental impacts of indiscriminate DDT spraying in the United States and questioned the logic of releasing large amounts of potentially dangerous chemicals into the environment without a sufficient understanding of their effects on ecology or human health. The book claimed that DDT and other pesticides had been shown to cause cancer and that their agricultural use was a threat to wildlife, particularly birds. 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 the agricultural use of DDT in the United States. A worldwide ban on its agricultural use was later formalized under the Stockholm Convention, but its limited use in disease vector control continues to this day and remains controversial, because of its effectiveness in reducing deaths due to malaria, countered by environmental and health concerns.
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 (the national bird of the United States) and the peregrine falcon from near-extirpation in the contiguous United States.

# Properties and chemistry
DDT is similar in structure to the insecticide methoxychlor and the acaricide dicofol. Being highly hydrophobic, it is nearly insoluble in water but has 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 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 a mixture of several closelyrelated 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 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, 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 have been produced globally since the 1940s. In the U.S., where 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 (1.35 billion lbs) were applied in the U.S. before the 1972 ban. Usage peaked in 1959 at about 36,000 tonnes.
In 2009, 3314 tonnes were produced for the control of malaria and visceral leishmaniasis. India is the only country still manufacturing DDT, with China having ceased production in 2007. India is the largest consumer.

## Mechanism of insecticide action
In insects it opens 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 other 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 metabolism of the toxin into inactive metabolites.

# 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 Muller, 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. 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 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 a high degree of 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 it played a role in the final elimination of malaria in Europe and North America.
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 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, failure to sustain the program, increasing resistance of mosquito to DDT, and increasing parasite resistance led to a resurgence. In many areas early victories 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 applied at all in sub-Saharan Africa due to these perceived difficulties. 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.
The goal of eradication was abandoned in 1969 and attention was 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. Efforts shifted from spraying to the use of bednets impregnated with insecticides and other interventions.

## 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 up to a fairly thorough-going vindication of Rachel Carsons 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, who 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 19711972, with scientists giving evidence both for and against the use of DDT. The hearings produced a 113-page decision, in which Hearing Examiner Edmund Sweeney wrote: DDT is not a carcinogenic, mutagenic, or teratogenic hazard to man. The uses under regulations involved here do not have a deleterious effect on fresh water fish, estuarine organisms, wild birds, or other wildlife. The evidence in this proceeding supports the conclusion that there is a present need for essential uses 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. He later wrote, in a letter to American Farm Bureau President Allan Grant, that in such decisions the ultimate judgement remains political. Immediately after the cancellation was announced, both EDF and the DDT manufacturers 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.
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 tons were exported.

## Restrictions on usage
In the 1970s and 1980s, agricultural use was banned in most developed countries, beginning with Hungary in 1968 then in Norway and Sweden in 1970, Germany and the United States in 1972, but not in the United Kingdom until 1984. By 1991 total bans on the use of DDT, including in disease control, were in place in at least 26 countries; for example Cuba in 1970, Singapore in 1984, Chile in 1985 and the Republic of Korea in 1986.
The Stockholm Convention, which took effect in 2004, outlawed several persistent organic pollutants, and restricted DDT use to vector control. The Convention has been ratified by more than 170 countries and is endorsed by most environmental groups. Recognizing that total elimination in many malaria-prone countries is currently unfeasible because there are few affordable or 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 the World Health Organization to the Stockholm Convention's aim of reducing and ultimately eliminating the use of 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 as of 2008.
Today, about 3,000 to 4,000 tonnes of DDT are produced each year for disease vector control. 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 40 hectares (98.8421524 acres) of cotton during a typical U.S. growing season requires the same amount of chemical as roughly 1,700 homes.

# 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 contributing to terrestrial organisms. 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. Due to hydrophobic properties, in aquatic ecosystems DDT and its metabolites are absorbed by aquatic organisms and adsorbed on suspended particles, 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. 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.
Because of its lipophilic properties, DDT has a high potential to bioaccumulate, especially in predatory birds. 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 very lipophilic and are stored mainly in body fat. DDT and DDE are very 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 in the US. Estimated dietary intake has also declined, although FDA food tests commonly detect it.
Marine macroalgae (seaweed) help reduce soil toxicity by up to 80% within six weeks.

## Effects on wildlife and eggshell thinning
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, through its metabolite DDE (dichlorodiphenyldichloroethylene), caused eggshell thinning and resulted in severe population declines in multiple North American and European bird of prey species. Eggshell thinning lowers the reproductive rate of certain bird species by causing egg breakage and embryo deaths. DDE related eggshell thinning is considered a major reason for the decline of the bald eagle, brown pelican, peregrine falcon, and osprey. However, different groups of birds vary greatly in their sensitivity to these chemicals. Birds of prey, waterfowl, and song birds are more susceptible to eggshell thinning than chickens and related species, and DDE appears to be more potent than DDT. Even in 2010, more than forty years after the U.S. ban, California condors which feed on sea lions at Big Sur which in turn feed in the Palos Verdes Shelf area of the Montrose Chemical Superfund site seemed to be having continued thin-shell problems. Scientists with the Ventana Wildlife Society and others are intensifying studies and remediations of the condors' problems.
The biological thinning mechanism is not entirely known, but there is strong evidence that p,p'-DDE inhibits calcium ATPase in the membrane of the shell gland and reduces the transport of calcium carbonate from blood into the eggshell gland. This results in a dose-dependent thickness reduction. There is also evidence that o,p'-DDT disrupts female reproductive tract development, impairing eggshell quality later. Multiple mechanisms may be at work, or different mechanisms may operate in different species. Some studies show that although DDE levels have fallen dramatically, eggshell thickness remains 1012 percent thinner than before DDT was first used.

# Effects on human health
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. The DDT metabolite DDE acts as an antiandrogen, 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 United States National Toxicology Program (NTP) and "moderately hazardous" by the World Health Organization (WHO), based on the rat oral Template:LD50 of 113 mg/kg. DDT has on rare occasions been administered orally as a treatment for barbiturate poisoning.

## Chronic toxicity

### Developmental toxicity
DDT and 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 in mice and rat toxicological studies, and available epidemiological evidence indicates that these effects may be occurring in humans as a result of DDT exposure. The US Environmental Protection Agency states that DDT exposure damages the reproductive system and reduces reproductive success. These effects may cause developmental and reproductive toxicity:
- A review article in The Lancet states, "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."
- Other studies document decreases in semen quality among men with high exposures (generally from IRS).
- Studies generally find that high blood DDT or DDE levels do not increase time to pregnancy (TTP.)Error creating thumbnail: File missingThis article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed.  (October 2014) (Learn how and when to remove this template message) There is some evidence that the daughters of highly exposed women may have more difficulty getting pregnant (i.e. increased TTP).Error creating thumbnail: File missingThis article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed.  (October 2014) (Learn how and when to remove this template message)
- DDT 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."Error creating thumbnail: File missingThis article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed.  (October 2014) (Learn how and when to remove this template message) The median serum DDE level of study group was lower than that typically observed in women living in homes sprayed with DDT.Error creating thumbnail: File missingThis article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed.  (October 2014) (Learn how and when to remove this template message)
- A Japanese study of congenital hypothyroidism concluded that in utero DDT exposure may affect thyroid hormone levels and "play an important role in the incidence and/or causation of cretinism."Error creating thumbnail: File missingThis article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed.  (October 2014) (Learn how and when to remove this template message) Other studies have also found that DDT or DDE interfere with proper thyroid function.Error creating thumbnail: File missingThis article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed.  (October 2014) (Learn how and when to remove this template message)

## Carcinogenicity
In 2002, the Centers for Disease Control reported that "Overall, in spite of some positive associations for some cancers within certain subgroups of people, there is no clear evidence that exposure to DDT/DDE causes cancer in humans." The NTP classifies it as "reasonably anticipated to be a carcinogen," the International Agency for Research on Cancer classifies it as a "possible" human carcinogen, and the EPA classifies DDT, DDE, and DDD as class B2 "probable" carcinogens. These evaluations are based mainly on the results of animal studies.
A Lancet review of epidemiological studies concluded that that DDT causes cancers of the liver, and pancreas, that there is mixed evidence that it causes cancers of the testes, and that it probably does not contribute to cancers of the rectum, prostate, endometrium, lung, or stomach. A second review, whose co-authors included persons engaged in DDT-related litigation, reached broadly similar conclusions, but also found possible associations with breast cancer, leukemia, lymphoma, and testicular cancer.

### Breast cancer
The question of whether DDT or DDE are risk factors in breast cancer has not been conclusively answered. Several meta analyses of observational studies have concluded that there is no overall relationship between DDT exposure and breast cancer risk. 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 using archived blood samples found that breast cancer risk was increased 5-fold among women who were born prior to 1931 and who had high serum DDT levels in 1963. Reasoning that DDT use became widespread in 1945 and peaked around 1950, they concluded that the ages of 14-20 were a critical period in which DDT exposure leads to increased risk. This study, which suggests a connection between DDT exposure and breast cancer that would not be picked up by most studies, has received variable commentary in third party reviews.  One review suggested that "previous studies that measured exposure in older women may have missed the critical period." A second review suggested a cautious approach to the interpretation of these results given methodological weaknesses in the study design. The 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"

# Use against malaria
Malaria remains a major public health challenge in many countries. 2008 WHO estimates were 243 million cases, and 863,000 deaths. About 89% of these deaths occur in Africa, and mostly to children under the age of 5.  DDT is one of many tools that public health officials use to fight the disease. Its use in this context has been called everything from a "miracle weapon  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 fighting malaria. 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. Today, a variety of usually simultaneous interventions is the norm. These include antimalarial drugs to prevent or treat infection; improvements in public health infrastructure to quickly diagnose, sequester, and treat infected individuals;  bednets and other methods intended to keep mosquitoes from biting humans; and vector control strategies such as larvaciding 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 all interior walls and ceilings with insecticides, and is particularly effective against mosquitoes, since many species rest on an indoor wall before or after feeding. DDT is one of 12 WHOapproved IRS insecticides.
WHO's anti-malaria campaign of the 1950s and 1960s relied heavily on DDT and the results were promising, though temporary. Experts tie the resurgence of malaria to multiple factors, including poor leadership, management and funding of malaria control programs; poverty; civil unrest; and increased irrigation. The evolution of resistance to first-generation drugs (e.g. chloroquine) and to insecticides exacerbated the situation. Resistance was largely fueled by often unrestricted agricultural use. Resistance and the harm both to humans and the environment led many governments to restrict or curtail the use of DDT in vector control as well as agriculture. In 2006 the WHO reversed a longstanding policy against DDT by recommending that it be used as an indoor pesticide in regions where malaria is a major problem.
Once the mainstay of anti-malaria campaigns, as of 2008 only 12 countries used DDT, including India and some southern African states, though the number is expected to rise.

## Initial 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 and rapid treatment and diagnosis to break the transmission cycle, was initially very successful as well. For example, in Sri Lanka, the program reduced cases from about one million per year before spraying to just 18 in 1963 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.
Today, DDT remains on 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 has reaffirmed its commitment to eventually 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. The WHO plans to implement alternatives to DDT to achieve this goal.
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. 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
In some areas resistance has greatly 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, a former head of the Allied Anti-Malaria campaign, observed in 1956 that "resistance has appeared after six or seven years." Resistance has been detected in 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 also largely lost its effectiveness. Agricultural uses were banned in 1989 and its anti-malarial use has been declining. Urban use has halted completely. Nevertheless, DDT is still manufactured and used, 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."
DDT can still be effective against resistant mosquitoes, and the avoidance of DDT-sprayed walls by mosquitoes is an additional benefit of the chemical. For example, a 2007 study reported that resistant mosquitoes avoided 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 mosquitoes out of the three test chemicals) because the others pesticides worked primarily by killing or irritating mosquitoes  encouraging the development of resistance to these agents. Others argue that the avoidance behavior slows the eradication of the disease. 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." 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."  Genomic studies in the model genetic organism Drosophila melanogaster have revealed that high level DDT resistance is polygenic, involving multiple resistance mechanisms.

## Residents' concerns
IRS is effective if at least 80% of homes and barns in a residential area are sprayed. Lower coverage rates can jeopardize program effectiveness. Many residents resist DDT spraying, objecting to the lingering smell, stains on walls, and the potential exacerbation of problems with other insect pests. Pyrethroid insecticides (e.g. deltamethrin and lambda-cyhalothrin) can overcome some of these issues, increasing participation.

## Human exposure
A 1994 study found that compared to contemporaries living where DDT is not used, South Africans living in sprayed homes have levels that are several orders of magnitude greater. Breast milk from South African mothers contains high levels of DDT and DDE. It is unclear to what extent these levels arise from home spraying vs. residues in food. There is some evidence that these levels are associated with neurological abnormalities in babies.
Most studies of DDT's human health effects have been conducted in developed countries where DDT is not used and exposure is relatively low. Many experts urge that alternatives be used instead of IRS.
Illegal diversion to agriculture is also a concern as it is almost impossible 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 being 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 recent bans in several tropical countries. Adding to this problem is a lack of skilled personnel and supervision.

## Criticism of restrictions on DDT use
Critics argue that limitations on DDT use for public heath purposes have caused unnecessary morbidity and mortality from vector borne diseases, with some claims of malaria deaths ranging as high as the hundreds of thousands, and millions. Robert Gwadz of the US National Institutes of Health said in 2007, "The ban on DDT may have killed 20 million children." In his novel State of Fear, author Michael Crichton wrote "Banning DDT killed more people than Hitler." These arguments have been dismissed as "outrageous" by former WHO scientist Socrates Litsios. May Berenbaum, University of Illinois entomologist, says, "to blame environmentalists who oppose DDT for more deaths than Hitler is worse than irresponsible." Investigative journalist Adam Sarvana and others characterize this notion as a "myth" promoted principally by Roger Bate of the pro-DDT advocacy group Africa Fighting Malaria (AFM).
Criticisms of a DDT "ban" often specifically reference the 1972 US ban (with the erroneous implication that this constituted a worldwide ban and prohibited use of DDT in vector control). Reference is often made to Rachel Carson's Silent Spring, even though she never pushed for a ban on DDT specifically. John Quiggin and Tim Lambert wrote, "the most striking feature of the claim against Carson is the ease with which it can be refuted."
It has also been alleged that donor governments and agencies have refused to fund DDT spraying, or made aid contingent upon not using DDT. According to 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 asserts, "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 ."
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 did 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." 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  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.

## Alternatives

### Other 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 (0.020.3 g/m2 vs 12 g/m2), so the net cost per house is about the same over 6 months.

### 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 filling or applying oil to standing water. These methods have seen little application in Africa for more than half a century. According to the United States 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 (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 WHO study released in January 2008 found that mass distribution of insecticide-treated mosquito nets and artemisininbased drugs cut malaria deaths in half in Rwanda and Ethiopia, countries with high malaria burdens. IRS with DDT did not play an important role in mortality reduction in these countries.
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 against malaria have been so successful that the Mexican DDT manufacturing plant ceased production due to lack of demand.
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 frontline drug 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 programs.
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 lambda-cyhalothrintreated 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 consider ecological damage and negative aspects of insecticide use on human health. 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.