DDT

''For other uses: see DDT (disambiguation).

DDT (from its trivial name, Dichloro-Diphenyl-Trichloroethane) is one of the best known synthetic pesticides. It was originally synthesized in 1874 but its insecticidal properties were not discovered until 1939. In the early years of World War II DDT was used with great effect to combat mosquitoes spreading malaria, typhus, and other insect-borne diseases among both military and civilian populations. 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, Houghton Mifflin published Silent Spring by American biologist Rachel Carson. 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 use of DDT being banned in the US in 1972. DDT was subsequently banned for agricultural use worldwide, 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 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, and is producted by the reaction of chloral (C2HCl3O) with chlorobenzene (C6H5Cl) in the presence of a sulfuric acid catalyst. The major product of this reaction is the p,p isomer pictured in this article, but the o,p isomer (in which one of the chlorine atoms is shifted around the aryl group) is also generated in significant amounts. Commercial DDT is actually a mixture of several closely related compounds, with p,p-DDT generally comprising 77% of the formulation, o,p-DDT 15%, and the related compounds making up the balance. The major metabolites and breakdown products of DDT in the environment are dichlorodiphenyldichloroethylene (DDE) which produced by the dehydrohalogenation of DDT, and dichlorodiphenyldichloroethane (DDD). Both DDE and DDD are found in small amounts in commercial DDT samples.

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

Trade or other names for DDT include Anofex, Cesarex, Chlorophenothane, Dedelo, p,p-DDT, Dichlorodiphenyltrichloroethane, Dinocide, Didimac, Digmar, ENT 1506, Genitox, Guesapon, Guesarol, Gexarex, Gyron, Hildit, Ixodex, Kopsol, Neocid, OMS 16, Micro DDT 75, Pentachlorin, Rukseam, R50 and Zerdane.

History
DDT was first synthesized in 1874 by Othmar Zeidler, but its 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. It was used extensively during World War II by Allied troops in Europe and the Pacific as well as certain civilian populations to control insect typhus and malaria vectors (nearly eliminating typhus as a result). Civilian suppression used a spray on interior walls, which kills mosquitoes that rest on the wall after feeding to digest their meal; resistant strains are repelled from the area. Entire cities in Italy were dusted to control the typhus carried by lice. DDT also sharply reduced the incidence of biting midges in Great Britain, and was used extensively as an agricultural insecticide after 1945.

DDT contributed to the final eradication of malaria in Europe and North America, although malaria had already been eliminated from much of the developed world in the early 20th century through the use of a range of public health measures and generally increasing health and living standards. "Malaria's decline in the United States and Europe in the late 1800s was due mainly to draining swamps and removing mill ponds". Even in countries without these advances, it was critical in their eradication of the disease. "Malaria was eradicated from Brazil and Egypt, largely due to extensive DDT spraying."

In 1955, the World Health Organization commenced a program to eradicate malaria worldwide, relying largely on DDT. Though this program was initially highly successful worldwide (reducing mortality rates from 192 per 100,000 to a low of 7 per 100,000), 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.

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. Furthermore, mosquitoes were developing resistance to DDT. Efforts were shifted from spraying to the use of bednets impregnated with insecticides.

Concerns about environmental effects
Concerns about DDT's environmental effects grew out of direct personal observations, usually involving a marked reduction in bird life, later supplemented by scientific investigation. The first recorded group effort against the chemical involved several citizens, including one or more scientists, in Nassau County, NY. Their unsuccessful struggle to have DDT regulated was reported in the New York Times in 1957, and thereby came to the attention of the popular naturalist-author, Rachel Carson. New Yorker editor William Shawn urged her to write a piece on the subject, which developed into Silent Spring, her famous 1962 bestseller. Despite the uproar surrounding Silent Spring, DDT remained in use.

A few years later, Carol Yannacone witnessed a fish kill at Yaphank Ponds following spraying by the Suffolk County Mosquito Control Commission. She convinced her husband Victor Yannacone, an attorney, to sue; their suit resulted in a local ban on DDT. Charles Wurster, a professor at nearby State University of New York at Stony Brook, had earlier noticed that the use of DDT on elms in New Hampshire killed birds without saving trees. A Bellport school teacher, Art Cooley, meanwhile was observing the decline of ospreys and other large birds around the Carmans River, and he too correctly suspected a DDT connection—the specific effect being extremely thin and fragile shells that prevent reproduction. The Yannacones joined forces with Wurster and Cooley to form the EDF in 1967, and launched a wider campaign against DDT. David Peakall measured DDE levels in Peregrine eggs collected in Alaska from 1969 to 1973, and showed a strong inverse relationship between DDE content and eggshell thickness. The chemical industry claimed that shell thinning occurred too rapidly after the introduction of DDT in 1946 for DDT to be the cause. Peakall filled blown peregrine eggs collected from the critical period with solvent and measured DDE in the extracted lipids. DDE was present in sufficient concentrations to account for significant eggshell thinning in 1946 in Great Britain and as early as 1948 in California. Later, he would apply similar methods to California Condor eggshell fragments as evidence that this species was extremely sensitive to DDE. The efforts of this group of people eventually led to the US ban, and a spectacular recovery in once-endangered osprey and eagle populations.

Restrictions on usage
In the 1970s and 1980s, agricultural use of DDT was banned in most developed countries, and DDT was replaced in most antimalarial uses by less persistent, and more expensive, alternative insecticides. DDT was first banned in Norway and Sweden in 1970 and the US in 1972, but was not banned in the United Kingdom until 1984.

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 for controlling malaria, the public health use of DDT was exempted from the ban until such alternatives are developed. Regular updates on the continued need to use DDT and on global DDT production and use is available from the Stockholm Convention. Malaria Foundation International states:
 * The outcome of the treaty is arguably better than the status quo going into the negotiations over two years ago. 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.

As of 2006, DDT continues to be used in other (primarily tropical) countries where mosquito-borne malaria and typhus are serious health problems. Use of DDT in public health to control mosquitoes is primarily done inside buildings and through inclusion in household products and selective spraying; this 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 the whole country of Guyana, covering an area of 215,000 km², the required amount is roughly equal to the amount of DDT that might previously have been used to spray 4 km² of cotton during a single growing season.

U.S. ban
In 1962, Rachel Carson's book Silent Spring was published. The book argued that pesticides, especially DDT, were poisoning both wildlife and the environment and were also endangering human health. Public reaction to Silent Spring launched the modern environmental movement in the United States, and DDT became a prime target of the growing anti-chemical and anti-pesticide movements during the 1960s.

During the late 1960s, pressure grew within the United States to effect a ban on DDT. In January 1971, the U.S. District Court of Appeals ordered William Ruckelshaus, the EPA's first Administrator, to begin the de-registration procedure for DDT. Initially, after a six-month review process, Ruckelshaus rejected an outright ban, 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 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 a ban on most uses of DDT in the U.S., where it was classified as an EPA Toxicity Class II substance. An exemption was allowed for public health uses under some conditions, but it appears that this exemption has never been invoked. Despite the domestic ban on its use, DDT continued to be produced in the US for foreign markets until as late as 1985, when over 300,000 kg were exported.

The 1970s ban in the U.S. took place amid a climate of public mistrust of the scientific and industrial community, following such fiascoes as Agent Orange and use of the hormone diethylstilbestrol (DES). In addition, the placement of the bald eagle on the endangered species list was also a strong factor leading to its being banned in the United States. The overuse of DDT was found to be a major factor in the bald eagle population decline, a point confirmed in later studies and in the dramatic recovery of the eagle once DDT concentrations in their food were reduced&mdash;though the claim is disputed by latter-day DDT advocates including Steven Milloy.

The ban and Carson's book have subsequently been vigorously criticized by pro-DDT advocates, including Steven Milloy, Roger Bate and Richard Tren, whose critiques draw on the work of the late San Jose State University entomologist J. Gordon Edwards, a witness at the hearings who stated that there was no evidence to substantiate the claims that DDT posed a threat to human health. They report that, at the end of the hearings, hearing examiner Edmund Sweeney ruled that the scientific evidence provided no basis for banning DDT. In the summer of 1972, Ruckelshaus reviewed evidence collected during the agency's hearings as well as reports prepared by two DDT study groups (the Hilton and Mark Commissions) that had come to the opposite conclusion. Milloy and Edwards claimed that Ruckelshaus did not actually attend any of the EPA commission's hearings, and (citing unnamed aides) that he did not read any transcripts of the hearings. However, generally administrative law under both the Administrative Procedures Act and the EPA's own rules suggest the EPA director should not attend such hearings since the director would be in a position of taking administrative appeals; similar to the way the Supreme Court justices do not attend criminal arraignment hearings or criminal trials, Ruckelshaus's not attending the hearings is no problem legally. Ruckelshaus overturned Sweeney's ruling, arguing that the pesticide was "a warning that man may be exposing himself to a substance that may ultimately have a serious effect on his health." Ruckelshaus's action was contested by DDT manufacturers in court; had Ruckelshaus acted without sound reason, under administrative law the courts should have overturned his ruling. The court cases were decided in EPA's favor, and appeals got no traction, suggesting that Ruckelshaus's actions were solidly based on science.

Environmental impact
DDT is a persistent organic pollutant with a half life of 2-15 years, and is immobile in most soils. Its half life is 56 days in lake water and approximately 28 days in river water. Routes of loss and degradation include runoff, volatilization, photolysis and biodegradation (aerobic and anaerobic). These processes generally occur slowly. Breakdown products in the soil environment are DDE (1,1-dichloro-2,2-bis(p-dichlorodiphenyl)ethylene) and DDD (1,1-dichloro-2,2-bis(p-chlorophenyl)ethane), which are also highly persistent and have similar chemical and physical properties. These products together are known as total DDT.

DDT and its metabolic products DDE and DDD magnify through the food chain, with apex predators such as raptors having a higher concentration of the chemicals, stored mainly in body fat, than other animals sharing the same environment. In the United States, human blood and fat tissue samples collected in the early 1970s showed detectable levels in all samples. A later study of blood samples collected in the latter half of the 1970s (after the U.S. DDT ban) showed that blood levels were declining further, but DDT or metabolites were still seen in a very high proportion of the samples. Biomonitoring conducted by the CDC 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 certain range of phyla. In particular, DDT is a major reason for the decline of the bald eagle in the 1950s and 1960s  as well as the peregrine falcon. DDT and its breakdown products are toxic to embryos and can disrupt 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 thinness remains 10–12 percent thinner than pre-DDT thicknesses. 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. In addition to acute toxic effects, DDT may bioaccumulate significantly in fish and other aquatic species, leading to long-term exposure to high concentrations.

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. It is not considered to be acutely toxic, and in fact it has been applied directly to clothes or used in soap. Indeed, 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.
 * In one 1969 study, 24 cynomolgus monkeys and rhesus monkeys fed up to 16 mg/kg/day of DDT for 130 months were compared to a control group of 17 monkeys. Six animals in the dosed group died, and the study demonstrated "clear evidence of hepatic and CNS toxicity following long-term DDT administration." Although the exposed group developed two malignancies and three benign tumors, compared to zero in the control group, statistically this is still "inconclusive with respect to a carcinogenic effect of DDT in nonhuman primates."
 * In another study, humans voluntarily ingested 35 mg of DDT daily for about two years, and were then tracked for several years afterward. Although there was "suggestive evidence of adverse liver effects", no other adverse effects were observed.
 * Farmers exposured to DDT occupationally have an increased incidence of non-allergic asthma.
 * 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.

Cancer

 * The EPA, in 1987, classified DDT as class B2, a probable human carcinogen based on "Observation of tumors (generally of the liver) in seven studies in various mouse strains and three studies in rats. DDT is structurally similar to other probable carcinogens, such as DDD and DDE." Regarding the human carcinogenicity data, they stated "The existing epidemiological data are inadequate. Autopsy studies relating tissue levels of DDT to cancer incidence have yielded conflicting results. Three studies reported that tissue levels of DDT and DDE were higher in cancer victims than in those dying of other diseases (Casarett et al., 1968; Dacre and Jennings, 1970; Wasserman et al., 1976). In other studies no such relationship was seen (Maier-Bode, 1960; Robinson et al., 1965; Hoffman et al., 1967). Studies of occupationally exposed workers and volunteers have been of insufficient duration to be useful in assessment of the carcinogenicity of DDT to humans."
 * 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.

Breast cancer
Several studies have looked for associations between breast cancer and DDT exposure. Almost all studies have measured DDT or DDE blood levels at the time of breast cancer diagnosis or after. While individual studies have yielded conflicting results, taken as a whole, the studies of this design "do not support the hypothesis that exposure to DDT is an important risk factor for breast cancer." These types of studies have been extensively reviewed:


 * In 2007, the journal Cancer published a review of all of the epidemiological studies on breast cancer and DDT and DDE published between 2000 and 2006. The authors state that "Positive findings for well-controlled studies in the early 1990s of associations between breast cancer risk and the insecticide DDT, its breakdown product DDE, and PCBs prompted additional study. Snedeker reviewed studies of DDT/DDE and dieldrin, concluding that existing research strategies provided conflicting and mostly negative evidence…Updating the picture to 2006 provides…essentially unchanged conclusions for DDT/DDE…[I]n light of these findings, additional study of incident breast cancer in association with biological measures of DDE/DDT levels near the time of diagnosis is not a promising avenue."


 * A 2005 review in The Lancet, states that "In a study in 1993, 37 breast cancer patients had higher serum DDE concentrations (11.8 μg/L) than controls (7.7 μg/L), and results from several subsequent studies supported such an association. However, large epidemiological studies and subsequent pooled and meta-analyses failed to confirm the association."


 * A 2004 meta-analysis of studies on the association of p,p'-DDE and breast cancer concluded that "Overall, these results should be regarded as a strong evidence to discard the putative relationship between p,p'-DDE and breast cancer risk. Nevertheless, the exposure to DDT during critical periods of human development—from conception to adolescence—and individual variations in metabolizing enzymes of DDT or its derivatives are still important areas to be researched in regard to breast cancer development in adulthood.

A new study in Environmental Health Perspectives 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 the studies discussed in the reviews cited above, this was prospective study in which blood samples were collected from young California mothers in the 1960s while DDT was still in use, and their breast cancer status was then tracked. (As discussed above, previous studies measured exposure more recently, long after DDT was banned in the US.) 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 of women 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 it is chemically similar enough to estrogen to trigger hormonal responses in contaminated animals. This hormonal-mimicking 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.
 * A review article in The Lancet concludes:
 * ''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.
 * Future perspectives: Although acute toxic effects are scarce, toxicological evidence shows endocrine-disrupting properties; human data also indicate possible disruption in semen quality, menstruation, gestational length, and duration of lactation. The research focus on human reproduction and development seems to be appropriate. DDT could be an effective public-health intervention that is cheap, longlasting, and effective. However, various toxic-effects that would be difficult to detect without specific study might exist and could result in substantial morbidity or mortality. Responsible use of DDT should include research programmes that would detect the most plausible forms of toxic effects as well as the documentation of benefits attributable specifically to DDT. Although this viewpoint amounts to a platitude if applied to malaria research in Africa, the research question here could be sufficiently focused and compelling, so that governments and funding agencies recognise the need to include research on all infant mortality when DDT is to be used. 


 * 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 infant deaths in areas where DDT is used for malaria control, and thus offset any benefit derived from its anti-malarial effects.
 * 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 another study from the same year found that even low-level concentrations of DDT in serum from the umbilical cord at birth were associated with a decrease in 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.

DDT use against malaria
Malaria afflicts between 300 million and 500 million people every year. The World Health Organization estimates that around 1 million people die of malaria and malaria-related illness every year, with about 90% of these deaths occur in Africa, mostly to children under the age of 5.

Most prior use of DDT was in agriculture, but the controlled use of DDT continues to this day for the purposes of public health. Current use for disease control requires only a small fraction of the amounts previously used in agriculture, and at these levels the pesticide is much less likely to cause environmental problems. Residual house spraying involves the treatment of all interior walls and ceilings with insecticide, and is particularly effective against mosquitoes, which favour indoor resting before or after feeding. Advocated as the mainstay of malaria eradication programmes in the late 1950s and 1960s, DDT remains a major component of control programmes in southern African states, though many countries have abandoned or curtailed their spraying activities. South Africa, Swaziland, Mozambique and Ecuador are examples of countries that have very successfully reduced malaria infestations with DDT.

Indeed, the problems facing health officials in their fight against malaria neither begin nor end with DDT. Experts tie the spread of malaria to numerous factors, including the resistance of the malaria parasite itself to the drugs traditionally used to treat the illness and a chronic lack of funds in the countries worst hit by malaria.

The growth of resistance to DDT and the fear that DDT may be harmful both to humans and the environment led the U.N., donor countries, and various national governments to restrict or curtail the use of DDT in vector control. At the same time, use of DDT as an agricultural insecticide was often unrestricted, and restrictions were often evaded, especially in developing countries where malaria is rife, so that resistance continued to grow.

A commentary on the current state of global malaria control was published in the May 2007 issue of the Journal of the American Medical Association. The authors identify "3 critical factors that are currently absent or in too short supply" for making progress in the fight against malaria: "leadership, management, and money," while making no mention of restrictions limiting the use of DDT. They also single out resistance of the malaria parasite to chloroquine as the cause of increasing malaria mortality in sub-Saharan Africa, not restrictions on DDT.

Today there is debate among professionals working on malaria control concerning the appropriate role of DDT. The range of disagreement is relatively narrow: Few believe either that large scale spraying should be resumed or that the use of DDT should be abandoned altogether. The debate focuses on the relative merits of DDT and alternative pesticides as well as complementary use of interior wall spraying, insecticide-treated bed-nets, and other mosquito control techniques.

Since the appointment of Arata Kochi as head of its anti-malaria division, the WHO has shifted its position in this controversy, from primary reliance on bed-nets to a policy more favorable to DDT. Until an announcement made on 16 September 2006, the policy had recommended indoor spraying of insecticides in areas of seasonal or episodic transmission of malaria, but a new policy also advocates it where continuous, intense transmission of the disease causes the most deaths. In 2007, the WHO clarified its position, saying it is "very much concerned with health consequences from use of DDT" and reaffirmed its commitment to phasing out the use of DDT.

Overall effectiveness of DDT against malaria
In the period from 1934-1955 there were 1.5 million cases of malaria in Sri Lanka, resulting in 80,000 deaths. After the country invested in an extensive anti-mosquito program with DDT, there were only 17 cases reported in 1963. Thereafter the program was halted, and malaria in Sri Lanka rebounded to 600,000 cases in 1968 and the first quarter of 1969. Although the country resumed spraying with DDT, many of the local mosquitoes had acquired resistance to DDT in the interim, presumably because of the continued use of DDT for crop protection, so the program was not nearly as effective as it had been before. Switching to the more-expensive malathion in 1977 reduced the malaria infection rate to 3,000 by 2004. A recent study notes, "DDT and Malathion are no longer recommended since An. culicifacies and An. subpictus has been found resistant."

A 2004 editorial in the British Medical Journal argues that the campaign against malaria is failing, that funding of malaria control should therefore be increased, and that use of DDT should be considered since DDT has "a remarkable safety record when used in small quantities for indoor spraying in endemic regions."

One insecticide supply company states on its website:
 * DDT is still one of the first and most commonly used insecticides for residual spraying, because of its low cost, high effectiveness, persistence and relative safety to humans. [...] In the past several years, we supplied DDT 75% WDP to Madagascar, Ethiopia, Eritrea, Sudan, South Africa, Namibia, Solomon Island, Papua New Guinea, Algeria, Thailand, and Myanmar for Malaria Control project, and won a good reputation from WHO and relevant countries' government.

According to DDT advocate Donald Roberts, malaria cases increased in South America after countries in that continent stopped using DDT. Only Ecuador, which has continued to use DDT, has seen a reduction in the number of malaria cases in recent years. Other mosquito-borne diseases are also on the rise. Roger Bate claims that until the 1970s, DDT was used to eradicate the Aedes aegypti mosquito from most tropical regions of the Americas. The reinvasion of Aedes aegypti since has brought devastating outbreaks of dengue fever, dengue hemorrhagic fever, and a renewed threat of urban yellow fever.

Mosquito resistance to DDT
Although the publication of Silent Spring undoubtedly influenced the U.S. ban on DDT in 1972, the reduced usage of DDT in malaria eradication began the decade before because of the emergence of DDT-resistant mosquitoes. Paul Russell, a former head of the Allied Anti-Malaria campaign, observed that eradication programs had to be wary of relying on DDT for too long as "resistance has appeared [after] six or seven years."

In some areas DDT has lost much of its effectiveness, especially in areas such as India where outdoor transmission is the predominant form. According to one article by V.P. Sharma, "The declining effectiveness of DDT is a result of several factors which frequently operate in tandem. The first and the most important factor is vector resistance to DDT. All populations of the main vector, An. culicifacies have become resistant to 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."

Due to this DDT resistance, in Sri Lanka, parts of India, Pakistan, Turkey and Central America, DDT has already been replaced by organophosphate or carbamate insecticides, e.g. malathion or bendiocarb.

According to a pesticide industry newsletter, DDT is obsolete for malarial prevention in India not only owing to concerns over its toxicity, but because it has largely lost its effectiveness. Use of DDT for agricultural purposes was banned in India in 1989, and its use for anti-malarial purposes has been declining. Use of DDT in urban areas of India has halted completely. Food supplies and eggshells of large predator birds still show high DDT levels. Parasitology journal articles confirm that malarial vector mosquitoes have become resistant to DDT and HCH in most parts of India. Nevertheless, DDT is still manufactured and used in India. One study concludes "The overall results of the study revealed 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."

The initial appearance of this resistance was largely due to the much greater quantity of DDT which had been used for agricultural spraying, rather than the relatively insignificant amounts used for disease prevention. According to one study which attempted to quantify the lives saved due to banning agricultural use of DDT and thereby slowing the spread of DDT resistance: "Correlating the use of DDT in El Salvador with renewed malaria transmission, it can be estimated that at current rates each kilo of insecticide added to the environment will generate 105 new cases of malaria."

Advocates for continuing use of DDT against malaria state that "Limited use of DDT for public health has continued to be effective in areas where it is used inside homes. As DDT's chief property is repellency, mosquitoes often avoid the DDT treated homes altogether. In so doing, they avoid the exposure that promotes resistance as well. DDT resistance exists in West Africa and in other malarial areas, such as India. Isolated occurrences of DDT resistance have occurred in South Africa, and South Africa continues to monitor for resistance. As the various Departments of Health that use it carefully control DDT use, it is unlikely that resistance will emerge as a major problem."

Studies of malaria-vector mosquitoes trapped while exiting windows 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."

The avoidance of DDT-sprayed walls by mosquitoes is sometimes touted as a beneficial aspect of DDT. For example, a 2007 study published in PLoS ONE reported that DDT-resistant mosquitoes still avoided DDT-treated huts, while entering huts treated with other insecticides to which they were not resistant. 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 develope resistance to. Others have argued that the avoidance of DDT sprayed walls by moosquitoes 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."

Residents' resistance to use of DDT
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 lambdacyhalothrin 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.

As a result, says Dr. Avertino Barreto, chief of infectious disease control in Mozambique, 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.' "

In areas where resistance from the residents prevents a high percentage of the homes being effectively sprayed, it reduces the "chance of reaching a level of coverage at which the vectorial capacity of the mosquito population will be lowered to a point at which malaria transmission will be interrupted."

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 a region 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.

Criticism of restrictions on DDT use
There are claims 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 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." Paul Driessen, author of Eco-Imperialism: Green Power, Black Death, argues that the epidemic of malaria in Africa not only takes the lives of 2 million people a year, but leaves those who survive malaria unable to contribute to the economy while sick and more vulnerable to subsequent diseases that might kill them.

These arguments have been called "outrageous" by former WHO scientist Socrates Litsios. 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." Restrictions on DDT use for vector control were imposed by various national governments, donor countries and international aid agencies, in response to pressure from environmentalists. It has been suggested that DDT treatments were used long enough to eliminate insect-borne diseases in the West, but now that it is only needed in poorer nations in Africa, Asia and elsewhere, it has been banned or otherwise restricted. Some environmental groups have been strongly criticized for trying to ban all use of DDT. According to Amir Attaran, many environmentalist groups fought against the public health exception of DDT in the 2001 Stockholm Convention, against the objections of third world governments and many malaria researchers. "Greenpeace, World Wildlife Fund, Physicians for Social Responsibility and over 300 other environmental organizations advocated for a total DDT ban, starting as early as 2007 in some cases." In an opinion piece in Nature Medicine he strongly objected to what would have been a de facto ban and stated: "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 for being "a current source of significant injury to...humans."

Criticisms of a ban on DDT often refer specifically to the 1972 US ban (with the implication that this constituted a worldwide ban), while ignoring that DDT has not been banned for public health use in most areas of the world where malaria is endemic. Reference is also often made to Rachel Carson's Silent Spring even though she never pushed for a ban on DDT. In fact, she devoted a page of the book to consideration of the relationship between DDT and malarial mosquitoes, with cognizance of the development of resistance in the mosquito, 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.'"

However, the fact that DDT is not formally banned in developing nations does not necessarily mean that those nations have the option to use it. Developing nations are typically heavily dependent on aid from agencies that made the aid contingent upon non-usage of DDT. The British Medical Journal of March 11, 2000, reports that the 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." Many African nations have been dissuaded from to using DDT in part because the European Union has said that their agricultural exports may not be accepted if spraying was "widespread."

According to the USAID website, "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 Indoor Residual Spraying (IRS) in general – with DDT or any other insecticide – as an effective malaria prevention strategy in tropical Africa." But the pro-DDT advocacy group Africa Fighting Malaria maintains that USAID and some other international donor organizations have refused to fund public health DDT programs. Similarly, Roger Bate of 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, and that Belize and Bolivia have gone on record to say that they gave in to pressure on this issue from the US Agency for International Development. 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.

However, USAID "favored" DDT alternatives in its funding:


 * Contrary to popular belief, USAID does not "ban" the use of DDT in its malaria control programs. From a purely technical point of view in terms of effective methods of addressing malaria, USAID and others have not seen DDT as a high priority component of malaria programs for practical reasons. In many cases, indoor residual spraying of DDT, or any other insecticide, is not cost-effective and is very difficult to maintain. In most countries in Africa where USAID provides support to malaria control programs, it has been judged more cost-effective and appropriate to put US government funds into preventing malaria through insecticide-treated nets, which are every bit as effective in preventing malaria and more feasible in countries that do not have existing, strong indoor spraying programs.

Alternatives to DDT
Before DDT, malaria was successfully eradicated or controlled 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.

Those who advocate for increased use of DDT claim that the alternatives to DDT are generally more expensive, more toxic to humans and not always as effective at controlling malaria and insect-borne diseases, and that the petrochemical companies which patent those alternatives push(ed) for DDT's ban simply for their own profits; DDT had entered the public domain, their patented insecticides have not. Actual data on the cost-effectiveness of DDT versus other insecticides and/or means of fighting malaria is, in fact, lacking. One complicating factor is that the relative costs of various measures vary, depending on geographical 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.

Organophosphate or carbamate insecticides, e.g. malathion or bendiocarb, are considerably more expensive than DDT, and malathion requires more frequent respraying. Pyrethroids such as deltamethrin and lambdacyhalothrin are also more expensive than DDT, but due to their much greater coverage per unit weight, the net cost per house is about the same.

There are some insecticide alternatives to DDT, including methoxychlor and pyrethroids. The environmental and health effects of alternatives are also under scrutiny. Under the Stockholm Convention, these are issue to be addressed when investigating and promoting alternative chemicals. A recent study has found that DDT as well as pyrethroid residues, such as permethrin and deltamethrin, were present in breast milk from a malaria controlled area in South Africa. The DDT was derived from malaria control, but the pattern of pyrethoid pollution indicated exposure via agricultural use, where mothers frequently work in cotton fields, as well as from domestic use of insecticide dusts in vegetable gardens.

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 impregnated bednets cannot easily replace DDT spraying without substantial increase in incidence, but impregnated nets do permit a substantial reduction in the amount of 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 EPA

 * EPA press release - December 31, 1972
 * EPA on DDT

Toxicity

 * DDT Technical Fact Sheet - National Pesticide Information Center
 * DDT General Fact Sheet - National Pesticide Information Center
 * Agency for Toxic Substances and Disease Registry: ToxFAQs for DDT, DDE and DDD
 * CDC ATSDR DDT toxicity reference list (PDF)
 * EXTOXNET: Pesticide Information Profiles&mdash;DDT
 * Oregon State University EXTOXNET DDT toxicity reference list
 * Scorecard: The Pollution Information Site&mdash;DDT

Environmental impact

 * Microbial Degradation of Pesticides
 * US Fish and Wildlife Service Historic News Releases - DDT
 * DDT and its Derivatives - Environmental Aspects
 * Aerobic pathway of DDT metabolization
 * Anaerobic pathway of DDT metabolization
 * Pesticide residues in food 2000 : DDT
 * Pesticide residues in food&mdash;1984
 * Environmental Fate Evaluation of DDT, Chlordane and Lindane
 * EPA: Pesticides and Public Health

Politics and DDT

 * DDT, Eggshells, and Me Article from Reason magazine
 * DDT: The Bald Eagle Lie Article from FrontPageMag.com
 * Rachel Carson, Mass Murderer?: The creation of an anti-environmental myth. Aaron Swartz, Extra!, September/October, 2007.
 * Rachel Carson's Birthday Bashing, Kirsten Weir, Salon.com, June 29, 2007.

Malaria and DDT

 * "If Malaria's the Problem, DDT's Not the Only Answer", a Washington Post column by entomologist May Berenbaum
 * WHO gives indoor use of DDT a clean bill of health for controlling malaria The current position of the World Health Organization
 * "The Mosquito Killer", a New Yorker article about Fred Soper by Malcolm Gladwell
 * '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
 * Malaria and DDT
 * Putting Myths to Bed
 * The Kill Malarial Mosquitoes NOW! coalition, a project of the international NGO Africa Fighting Malaria
 * DDT Ban Myth Bingo
 * Nets for fighting malaria

Chemical
ДДТ DDT DDT DDT DDT DDT Dichlorodiphényltrichloroéthane Diclorodifeniltricloroetano די די טי DDT (insecticide) DDT DDT DDT DDT DDT ДДТ Dichlórdifenyltrichlóretán ДДТ DDT DDT 滴滴涕