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DDT

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For other uses, see DDT (disambiguation).
DDT
Chemical structure of DDT
Image:DDT-3D-vdW.png
IUPAC name 4,4'-(2,2,2-trichloroethane-
1,1-diyl)bis(chlorobenzene)
Identifiers
CAS number [50-29-3]
SMILES Clc1ccc(cc1)C(c2ccc(Cl)cc2)C(Cl)(Cl)Cl
Properties
Molecular formula C14H9Cl5
Molar mass 354.49 g/mol
Density 1.55 g/cm³ [1]
Melting point

108.5–109 °C [1]

Boiling point

185–187 °C (at 7 Pa) [1]

Hazards
EU classification Yes
Main hazards T, N
R-phrases R25 R40 R48/25 R50/53
S-phrases (S1/2) S22 S36/37 S45 S60 S61
LD50 113 mg/kg (rat)
Except where noted otherwise, data are given for
materials in their standard state
(at 25 °C, 100 kPa)

Infobox disclaimer and references

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

First synthesized in 1874, DDT's insecticidal properties were not discovered until 1939. In the early years of World War II, DDT was used with great effect to control 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."[2] After the war, DDT was made available for use as an agricultural insecticide, and soon its production and use skyrocketed.[3]

In 1962, Silent Spring by American biologist Rachel Carson was published. The book catalogued the environmental impacts of the indiscriminate spraying of DDT in the US and questioned the logic of releasing large amounts of chemicals into the environment without fully understanding their effects on ecology or human health. The book suggested that DDT and other pesticides may cause cancer and that their agricultural use was a threat to wildlife, particularly birds.[4] Its publication was one of the signature events in the birth of the environmental movement. Silent Spring resulted in a large public outcry that eventually led to most uses of DDT being banned in the US in 1972.[5] 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.[6]

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.[7]

Contents

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 produced by the reaction of chloral (CCl3CHO) 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 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.[3]

DDT is moderately toxic, with a rat LD50 of 113 mg/kg,[8] 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.[9]

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

Image:DDT.jpg
Commercial product containing 5% DDT

First synthesized in 1874 by Othmar Zeidler,[10] DDT's insecticidal properties were not discovered until 1939 by the Swiss scientist Paul Hermann Müller, who was awarded the 1948 Nobel Prize in Physiology and Medicine for his efforts.[2]

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 the insect vectors for typhus and malaria (nearly eliminating typhus as a result). 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 played a small role in the final elimination of malaria in Europe and North America, as malaria had already been eliminated from much of the developed world before the advent of DDT through the use of a range of public health measures and generally increasing health and living standards.[11] One CDC physician involved in the United States' DDT spraying campaign said of the effort that "we kicked a dying dog."[12] But in countries without these advances, it was critical in their eradication of the disease.

In 1955, the World Health Organization commenced a program to eradicate malaria worldwide, relying largely on DDT. Though this program was initially highly successful worldwide (reducing mortality rates from 192 per 100,000 to a low of 7 per 100,000),[13] 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.[14] 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".[15]

DDT was less effective in tropical regions due to the continuous life cycle of mosquitoes and poor infrastructure. It was not pursued at all in sub-Saharan Africa due to these perceived difficulties, with the result that mortality rates in the area were never reduced to the same dramatic extent, and now constitute the bulk of malarial deaths worldwide, especially following the resurgence of the disease as a result of microbe resistance to drug treatments and the spread of the deadly malarial variant caused by Plasmodium falciparum. The goal of eradication was abandoned in 1969, and attention was focused on controlling and treating the disease. Spraying programs (especially using DDT) were curtailed due to concerns over safety and environmental effects, as well as problems in administrative, managerial and financial implementation, but mostly because mosquitoes were developing resistance to DDT.[14] Efforts were shifted from spraying to the use of bednets impregnated with insecticides.[16][15]

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.[4] The first recorded group effort against the chemical involved several citizens, including one or more scientists, in Nassau County, New York. 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.[17] 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.[18] 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. 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 use of DDT in vector control has not been banned, but it has been largely replaced by less persistent, and more expensive, alternative insecticides.

The Stockholm Convention, ratified in 2001 and effective as of 17 May 2004, outlawed several persistent organic pollutants, and restricted the use of DDT to vector control. The Convention was signed by 98 countries and is endorsed by most environmental groups. Recognizing that a total elimination of DDT use in many malaria-prone countries is currently unfeasible because there are few affordable or effective alternatives 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. [3] 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.[19]

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.[20] 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.[21]

U.S. ban

In 1962, Rachel Carson's book Silent Spring was published. The book argued that pesticides, including DDT, were poisoning both wildlife and the environment and were also endangering human health.[4] 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 latter 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.[22]

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—though the claim is disputed by latter-day DDT advocates including Steven Milloy.[23]

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.[24] 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,[25] and of the 700+ milk samples tested by the USDA in 2005, 85% had detectable levels of DDE.[26]

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[27][7] as well as the peregrine falcon. DDT and its breakdown products are toxic to embryos and can disrupt calcium absorption, thereby impairing eggshell quality.[28] Studies in the 1960s and 1970s failed to find a mechanism for the hypothesized thinning.[23] However, more recent studies in the 1990s and 2000s have laid the blame at the feet of DDE.[29][30] Some studies have shown that although DDE levels have fallen dramatically, eggshell thickness remains 10–12 percent thinner than before DDT was first used.[31] 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.

Toxicity

Acute

  • DDT is classified as "moderately toxic" by the US National Toxicological Program and "moderately hazardous" by WHO.[32] It is not considered to be acutely toxic, and in fact it has been applied directly to clothes or used in soap.[33] Indeed, DDT has on rare occasions been administered orally as a treatment for barbiturate poisoning.[34]

    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.[35]
      • 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."[36]
        • In an early 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.[37]
          • Farmers exposed to DDT occupationally have an increased incidence of non-allergic asthma. [38]
            • Organochlorine compounds in general and DDE specifically have been linked to diabetes.[39] 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.[40] A recent study of Mexican Americans yielded similar results.[41]

              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." [42]
                • 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.[16]
                  • A Canadian study from 2007 found a positive association between DDE and non-Hodgkin Lymphoma.[43]

                    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."[44] 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."[45]
                      • 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."[16]
                        • 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.[46]

                          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.[44][47]

                          Developmental and reproductive toxicity

                          DDT and its breakdown product DDE, like other organochlorines, have been shown to have xenoestrogenic activity; meaning they are chemically similar enough to estrogens to trigger hormonal responses in animals. This endocrine disrupting activity has been observed when DDT is used in laboratory studies involving mice and rats as test subjects, and available epidemiological evidence indicates that these effects may be occurring in humans as a result of DDT exposure. In areas where DDT is used for malaria control, infants can be exposed via breastmilk in levels that exceed the W.H.O's acceptable daily intake value for DDT.[48] [49]

                          • A review article in The Lancet concludes that, "research has shown that exposure to DDT at amounts that would be needed in malaria control might cause preterm birth and early weaning … toxicological evidence shows endocrine-disrupting properties; human data also indicate possible disruption in semen quality, menstruation, gestational length, and duration of lactation."[16]
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