Elsevier

The Lancet

Volume 366, Issue 9487, 27 August–2 September 2005, Pages 763-773
The Lancet

Review
Health risks and benefits of bis(4-chlorophenyl)-1,1,1-trichloroethane (DDT)

https://doi.org/10.1016/S0140-6736(05)67182-6Get rights and content

Summary

DDT (bis[4-chlorophenyl]-1,1,1-trichloroethane) is a persistent insecticide that was used worldwide from the mid 1940s until its ban in the USA and other countries in the 1970s. When a global ban on DDT was proposed in 2001, several countries in sub-Saharan Africa claimed that DDT was still needed as a cheap and effective means for vector control. 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. Historically, DDT has had mixed success in Africa; only the countries that are able to find and devote substantial resources towards malaria control have made major advances. 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.

Section snippets

DDT exposure and concentration in human tissues

Technical-grade DDT contains 65–80% p,p′-DDT, 15–21% o,p′-DDT, and up to 4% p,p′-DDD (bis[4-chlorophenyl]-1,1,-dichloroethane).2 When sprayed, DDT can drift, sometimes for long distances. In the soil, the compound can evaporate or attach to wind-blown dust. In the environment, DDT breaks down to p,p′-DDE (bis[4-chlorophenyl]-1,1-dichloroethene),1 an extremely stable compound that resists further environmental breakdown or metabolism by organisms. DDE is the form usually found in human tissue in

Toxic effects of DDT

Toxic effects of DDT and its analogues have been extensively studied in laboratory animals. Acute exposure to a high dose of DDT can cause death.12 Exposure to DDT or DDE increases liver weight, induces liver cytochrome P450 (CYP) 2B and 3A and aromatase,21, 22, 23 and causes hepatic-cell hypertrophy and necrosis.12 DDT is insecticidal because of its neurological toxic effects. In laboratory animals, DDT causes hyperactivity, tremor, and seizures. DDT is carcinogenic in mice and rats, mainly

Neurobehaviour

DDT poisoning usually results in paresthesia, dizziness, headache, tremor, confusion, and fatigue.12 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.32 Although DDT or DDE concentrations were not determined in this study, they probably were very high. People who

Cancer

Although extensively studied, there is no convincing evidence that DDT or its metabolite DDE increase human cancer risk. Mainly on the basis of animal data, DDT is classified as a possible carcinogen (class 2B) by the International Agency for Research on Cancer (IARC)35 and as a reasonably anticipated human carcinogen by the US National Toxicology Program.36

Breast cancer has been examined most closely for an association with p,p′-DDE. In a study in 1993,37 breast cancer patients had higher

Reproductive health

Various reproductive and hormonal endpoints have been examined in both men and women, and although associations have been recorded, causal links have not been confirmed. In Chiapas, Mexico, where DDT was sprayed for malaria control, serum p,p′-DDE concentrations were inversely correlated with semen volume, sperm count, and bioavailable-to-total testosterone ratios in 24 young men not occupationally exposed to DDT.75 However, results from another study of South African malaria workers did not

Infant and child development

Although infant and child growth and neurodevelopment have been studied, no study has been large enough to show an effect on infant and child survival. In a German study,117 girls with the highest quartile of DDE concentration (>0·44 μg/L whole blood) were an average of 1·8 cm shorter at age 8 years than girls with the lowest quartile of DDE; the difference narrowed at age 9 years and disappeared at age 10 years. However, no such effect was seen in boys. Another study did not show any

Immunology and DNA damage

Increased plasma concentrations of DDE were associated with raised IgA in one study126 and with reduced IgG in another.127 Plasma p,p′-DDE was inversely associated with in-vitro secretion of tumour necrosis factor (TNF) α by umbilical cord-blood mononuclear cells.128 Do these effects translate into immunological disorders with clinical consequences? One study suggested that raised prenatal exposure of p,p′-DDE increased the risk of otitis media in Inuit infants,129 but this association was not

Efficacy and effectiveness of DDT for malaria control

Convincing historical evidence has shown that indoor residual house-spraying with DDT was the main method by which malaria was eradicated or greatly reduced in many countries worldwide in the 1940s to 1960s. However, these programmes had not been aimed to rigorously investigate the efficacy of individual components nor of local factors that might modify their effects. In sub-Saharan Africa, early pilot projects of malaria eradication also showed that the disease is highly responsive to vector

Debate and decision-making

Since evidence now indicates that DDT might have adverse effects on human health, it is prudent to consider currently available evidence of benefits and possible risks of DDT use in the context of modern malaria control. Infants are generally known to bear the burden of mortality from malaria worldwide (figure 3);138 most such mortality occurs in the first 5 years of life and in areas south of the Sahara (figure 4).139 The decision to use DDT would be straightforward if we had data from trials

Benefits of DDT spraying in sub-Saharan Africa

The success of the Malaria Eradication Campaign in 1955–69 was attributed to DDT.1 However, these programmes often included other components, such as provision of basic medical care, and were not designed to allow investigation of their individual parts. Thus, Giglioli140 showed large improvements in infant and all-cause mortality during three decades for employees of the sugar plantations in South America, but the quantitative role of DDT is impossible to specify. Without the appropriate

Risks of DDT spraying in sub-Saharan Africa

For indoor residual spraying to effectively prevent infant mortality from malaria, women of child-bearing age, pregnant women, and breastfeeding women will need to be exposed to DDT. Such spraying might be without the ecological effects that caused the ban (although more data are needed), but will unavoidably expose women to amounts of DDT that are associated with forms of toxic effects that might increase infant mortality. Of adverse effects to human health, reproductive outcomes are the major

Balance of benefits and risks from DDT use in malaria control

Malaria remains a difficult problem in Africa. Indoor residual spraying of DDT could be effective in some settings; the procedure is unlikely to lift the entire malaria mortality burden in infants and children. Additionally, if continuous DDT spraying does cause increased preterm births and shortened breastfeeding duration, infant deaths will occur, perhaps to the same extent as the deaths spraying would potentially prevent. Mothers would also carry a body burden of DDT, and even if they were

Future perspectives

DDT was originally banned because of ecological effects, such as eggshell thinning, and accumulation in the environment and organisms, including human beings. 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

Search strategy and selection criteria

We did a search of PubMed from the mid-1960s to February, 2005, for the use, body burden, and toxic and health effects of DDT. We used the keywords “DDT” and “DDE” and any of “malaria”, “mosquito”, “drug resistance”, “toxicity”, “health”, “cancer”, “reproduction”, “oestrogen”, “neurological”, and “development”. Of 3650 reports published on DDT, we gave preference to studies in the past 5 years on human health effects of DDT.

References (148)

  • N Rothman et al.

    A nested case-control study of non-Hodgkin lymphoma and serum organochlorine residues

    Lancet

    (1997)
  • L Hardell et al.

    Adipose tissue concentrations of p,p′-DDE and the risk for endometrial cancer

    Gynecol Oncol

    (2004)
  • MA Dalvie et al.

    The hormonal effects of long-term DDT exposure on malaria vector-control workers in Limpopo Province, South Africa

    Environ Res

    (2004)
  • MA Dalvie et al.

    The long-term effects of DDT exposure on semen, fertility, and sexual function of malaria vector-control workers in Limpopo Province, South Africa

    Environ Res

    (2004)
  • BA Cohn et al.

    DDT and DDE exposure in mothers and time to pregnancy in daughters

    Lancet

    (2003)
  • P Cocco et al.

    Reproductive outcomes in DDT applicators

    Environ Res

    (2005)
  • MP Longnecker et al.

    Maternal serum level of the DDT metabolite DDE in relation to fetal loss in previous pregnancies

    Environ Res

    (2005)
  • SA Korrick et al.

    Association of DDT with spontaneous abortion: a case-control study

    Ann Epidemiol

    (2001)
  • B Bercovici et al.

    Serum levels of polychlorinated biphenyls and some organochlorine insecticides in women with recent and former missed abortions

    Environ Res

    (1983)
  • JA O'Leary et al.

    Spontaneous abortion and human pesticide residues of DDT and DDE

    Am J Obstet Gynecol

    (1970)
  • V Leoni et al.

    PCB and other organochlorine compounds in blood of women with or without miscarriage: a hypothesis of correlation

    Ecotoxicol Environ Saf

    (1989)
  • MP Longnecker et al.

    Association between maternal serum concentration of the DDT metabolite DDE and preterm and small-for-gestational-age babies at birth

    Lancet

    (2001)
  • World Health Organization

    DDT and its derivatives. Environmental health criteria 9

    (1979)
  • Toxicological profile for DDT/DDD/DDE (update): US Department of Health and Human Services. Public Health Service

    (2002)
  • V Turusov et al.

    Dichlorodiphenyltrichloroethane (DDT): ubiquity, persistence, and risks

    Environ Health Perspect

    (2002)
  • PI Trigg et al.

    Commentary: malaria control in the 1990s

    Bull World Health Organ

    (1998)
  • Banned and non-authorised pesticides in the United Kingdom

  • DA Ratcliffe

    Decrease in eggshell weight in certain birds of prey

    Nature

    (1967)
  • A Attaran et al.

    Ethical debate: doctoring malaria, badly: the global campaign to ban DDT

    BMJ

    (2000)
  • DDT & malaria: answer to common questions

  • UN Environment Programme. Stockholm Convention on Persistent Organic Pollutants (POPs)

  • MS Wolff et al.

    Risk of breast cancer and organochlorine exposure

    Cancer Epidemiol Biomarkers Prev

    (2000)
  • K Jaga et al.

    Global surveillance of DDT and DDE levels in human tissues

    Int J Occup Med Environ Health

    (2003)
  • D Smith

    Worldwide trends in DDT levels in human breast milk

    Int J Epidemiol

    (1999)
  • SM Waliszewski et al.

    Organochlorine pesticide levels in maternal adipose tissue, maternal blood serum, umbilical blood serum, and milk from inhabitants of Veracruz, Mexico

    Arch Environ Contam Toxicol

    (2001)
  • H Bouwman et al.

    Levels of DDT and metabolites in breast milk from Kwa-Zulu mothers after DDT application for malaria control

    Bull World Health Organ

    (1990)
  • H Bouwman et al.

    Malaria control and levels of DDT in serum of two populations in Kwazulu

    J Toxicol Environ Health

    (1991)
  • L Rivero-Rodriguez et al.

    Exposure assessment for workers applying DDT to control malaria in Veracruz, Mexico

    Environ Health Perspect

    (1997)
  • HC Li et al.

    Induction of the hepatic CYP2B and CYP3A enzymes by the proestrogenic pesticide methoxychlor and by DDT in the rat. Effects on methoxychlor metabolism

    J Biochem Toxicol

    (1995)
  • A Sierra-Santoyo et al.

    Sex-dependent regulation of hepatic cytochrome P-450 by DDT

    Toxicol Sci

    (2000)
  • Bioassay of DDT, TDE, p,p′-DDE for possible carcinogencity. Carcinogenesis technical report series. no 131

    (1978)
  • S Takayama et al.

    Effects of long-term oral administration of DDT on nonhuman primates

    J Cancer Res Clin Oncol

    (1999)
  • HR Andersen et al.

    Comparison of short-term estrogenicity tests for identification of hormone-disrupting chemicals

    Environ Health Perspect

    (1999)
  • WR Kelce et al.

    Persistent DDT metabolite p,p′-DDE is a potent androgen receptor antagonist

    Nature

    (1995)
  • BD Banerjee

    Sub-chronic effect of DDT on humoral immune response to a thymus-independent antigen (bacterial lipopolysaccharide) in mice

    Bull Environ Contam Toxicol

    (1987)
  • BD Banerjee

    Effects of sub-chronic DDT exposure on humoral and cell-mediated immune responses in albino rats

    Bull Environ Contam Toxicol

    (1987)
  • SL Schantz et al.

    Impairments of memory and learning in older adults exposed to polychlorinated biphenyls via consumption of Great Lakes fish

    Environ Health Perspect

    (2001)
  • Report on carcinogens. 10th edn.

  • MS Wolff et al.

    Blood levels of organochlorine residues and risk of breast cancer

    J Natl Cancer Inst

    (1993)
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