INTRODUCTION
DDT (dichlorodiphenyltrichloroethane) it is a colorless, crystalline, tasteless and almost odorless organochloride known for its insecticidal properties. DDT has been formulated in almost every conceivable form, including solutions in xylene or petroleum distillates, emulsifiable concentrates, water-wettable powders, granules, aerosols, smoke candles and charges for vaporisers and lotions.
DDT was banned because it persists in the environment , accumulates in fatty tissues and can cause adverse health effects on wildlife . In addition, resistance occurs in some insects (like the house fly) who develop the ability to quickly metabolize the DDT.
CHEMICAL CHARACTERISTICS
IUPAC name: 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane
Molecular formula: C14H9Cl5
Molar mass: 354.49 g/mol
Density: 0.99 g/cm³
Melting point: 108.5 °C; 227.3 °F; 381.6 K
Boiling point: 260 °C; 500 °F; 533 K (decomposes)
LD50: 113 mg/kg (rat)
PROPERTIES
It is an excellent reagent for maintaining SH groups in reduced state;
it quantitatively reduces disulfides. DTT is effective in sample buffers for reducing protein disulfide bonds prior to SDS-PAGE. DTT can also be used for reducing the disulfide bridge of the cross-linker N,N′-bis(acryloyl)cystamine to break apart the matrix of a polyacrylamide gel. DTT is less pungent and is less toxic than 2-mercaptoethanol.
Chemical properties
HISTORY
The discovery of the insecticidal properties of DDT in 1939 by the Swiss chemist Paul Muller was probably the most significant development in the history of pest control. DDT appeared to be the ideal insecticide, very toxic to most pest insects but relatively harmless to man. It could be made in unlimited quantities, was cheap to produce and retained toxicity for a considerable period. Following its introduction a large number of other chlorinated hydrocarbon insecticides were developed and marketed, one of the most successful being methoxychlor. The first full-scale reported use of DDT was during World War II. A typhus epidemic in Naples, Italy in December 1943 was brought under control within a period of a few weeks by a mass treatment of over 2.5 million people with 10% DDT powder, which killed the body lice responsible for transmitting the disease. However, the outstanding property of DDT is its effectiveness as a residual surface film following spray application. This revolutionized malaria control in the 1950s as it enabled cheap, safe, effective, targeted treatments, especially spraying of indoor residential surfaces. Initial spraying programmes in Italy, Cyprus, and Greece were so successful that a bold decision was made to try to eradicate malaria from all of Europe. The campaign was orchestrated and funded by several agencies, including the World Health Organization, the United Nations, the Rockefeller Foundation and the US Public Health Service. By 1961, eradication had already been achieved in many countries, and the entire European continent was finally declared free of endemic malaria in 1975. During the same period DDT spraying programmes in Africa, in India and other countries of the Far East substantially decreased the death rate from malaria in these regions.
Since the 1970s, DDT and most other chlorinated hydro-carbon compounds have been restricted or banned for agricultural use in most countries, due in part to their unacceptably long persistence in the environment and also because of increased concerns arising from their fat solubility (having a high partition coefficient in lipids versus water) and resultant long-term accumulation in fatty tissues of non-target organisms . However, DDT continues to be used in limited quantities in the control of insect vectors for public health purposes.
CURRENT USES
The only remaining legal use of DDT is to control malaria-carrying mosquitoes. A devastating disease, malaria kills more than 800,000 people every year, the majority of deaths among children in Sub-Saharan Africa. Indoor spraying with DDT is one of a number of tools being used to control malaria around the world.
DDT is still used today in South America , Africa , and Asia (for example Thailand and South Africa) for this purpose
The DDT Story
MOLECULAR MECHANISM
DDT affects mainly the peripheral nervous system , initial contact with the insecticide causing neurons to fire spontaneously causing muscles to twitch, with resulting tremors throughout the body and appendages, the so-called ‘DDT jitters’. Eventually, over the course of a few hours or days, DDT exposure leads to excitatory paralysis and consequent death of the insect. Compared with some insecticides DDT is rather slow acting. Its effects at a neuromuscular junction are brought about by depolarization due to an increased frequency of miniature post-synaptic potentials due to an accelerated spontaneous release of neurotransmitter. If depolarization continues the neuromuscular junction becomes blocked due to depletion of neurotransmitter. With DDT only a small fraction of the sodium channel population needs to be modified for the generation of repetitive discharges. After modification by DDT the channels remain open as the insecticide impedes channel closing either by inactivation or deactivation, and the sodium channels retain the ability to conduct Na+. However, the membrane potential is shifted so that the nerve cells function in a new, and relatively stable, state of abnormal hyperexcitability. In insects this produces an incapacitating, but sublethal effect, known as ‘knockdown’. The amplitude of the sodium current continues undiminished until the level of hyperexcitability overwhelms the capacity of the cell to maintain the activity of the sodium pump. Higher lipophilicity gives better knockdown rates as the pyrethroid penetrates to the target more quickly. However, such compounds may not give good ‘kill’ due to a tendency to dissociate from the target.
DDT, Pyrethrins, Pyrethroids and Insect Sodium Channels. 2007
METABOLISM
DDT tends to accumulate in the fatty tissues of insects, wildlife, and people, but produces no known toxic effects while it is stored in the fat.
DDT is metabolized into various breakdown products in the body including DDE, DDD4 and DDA5. When fat stores are used during periods of starvation the breakdown products of DDT are released into the blood where they may be toxic to the liver and the nervous system . Once DDT has accumulated in the body, it is excreted in the urine, feces, or breast milk. Breast milk is often used to measure a population’s exposure to DDT.
DDT general factsheet. 1999
CLINICAL
ACUTE POISONING
Acute effects likely in humans due to low to moderate exposure may include nausea, diarrhea, increased liver enzyme activity, irritation (of the eyes, nose or throat), disturbed gait, malaise and excitability; at higher doses, tremors and convulsions are possible. While adults appear to tolerate moderate to high ingested doses of up to 280 mg/kg, a case of fatal poisoning was seen in a child who ingested one ounce of a 5% DDT:kerosene solution.
Acute toxicological effects of DDT
LONG TERM EFFECTS
FERTILITY
Exposure to pesticides affects many body organs including reproductive system. Pesticides are one of the compounds that might reduce the semen quality in the exposed workers according to current knowledge. Although many underlying mechanisms have been proposed, the mechanisms of action are not clarified yet. Majority of pesticides including organophosphoruses affect the male reproductive system by mechanisms such as reduction of sperm density and motility, inhibition of spermatogenesis, reduction of testis weights, reduction of sperm counts, motility, viability and density, and inducing sperm DNA damage, and increasing abnormal sperm morphology. Reduced weight of testes, epididymis, seminal vesicle, and ventral prostate, seminiferous tubule degeneration, change in plasma levels of testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH), decreased level and activity of the antioxidant enzymes in testes, and inhibited testicular steroidogenesis are other possible mechanisms. Moreover, DDT and its metabolites have estrogenic effects on males.
Occupational exposure to pesticides and consequences on male semen and fertility: A review.Pubmed 2014
PRENATAL AND POSTNATAL EXPOSURE
DDT's long half-life makes it persistent in the environment and, consequently, almost everyone has DDT residues in the body. Human milk constitutes an ideal non-conventional matrix to investigate environmental chronic exposure to organochlorine compounds (OCs) residues.
DDT is present in breast milk of women at the time of delivery. Residual levels and the spread from countries still using DDT explain DDT detection from vegetables and from animal origin food. The presence of this compound in breast milk represents a pre- and postnatal exposure hazard for foetuses and infants due to chronic bioaccumulation and poor elimination, with possible deleterious effects on health. This data should be used to raise awareness of the risks of OCs exposure and to help establish health policies in order to avoid its use worldwide and thus, to prevent its propagation.
Prenatal and Postnatal Exposure to DDT by Breast Milk Analysis. Pubmed 2014
ENDOCRINE EFFECTS
Prevalence of subclinical hyperthyroidism and the presence of TPOAb antibodies were higher than those described for euthyroid populations elsewhere.
Total T3 levels were associated with lower concentrations of endosulphan 2 in men and with higher alpha-chlordane, p,p'-dichlorodiphenyltrichloroethane (DDT), endosulphan 2, and methoxychlor in women. Levels of free T4 showed inverse association with beta-hexachlorocyclohexane (HCH) and p,p'-DDT in men, and were positively associated with hexachlorobenzene (HCB), heptachlor, o,p'-DDT, and p,p'-DDT in women. TSH levels were associated with higher beta-HCH in men. A positive association was observed between exposure methoxychlor in males and presence of TPOAb, but no association with TPOAb was found in women. These results suggest that OC pesticides can affect the thyroid system through gender-specific mechanisms that may differ among compounds.
Long-term exposure to organochlorine pesticides and thyroid status in adults in a heavily contaminated areas. Pubmed 2013
Low-dose organochlorine (OC) pesticides have recently been associated with type 2 diabetes in several non-Asian general populations.As there is currently epidemic type 2 diabetes in Asia, the associations between OC pesticides and type 2 diabetes in Koreans have been investigated. Most OC pesticides showed strong associations with type 2 diabetes after adjusting for age, sex, BMI, alcohol consumption, and cigarette smoking. By using a small sample, low-dose background exposure to OC pesticides was strongly associated with prevalent type 2 diabetes in Koreans even though absolute concentrations of OC pesticides were no higher than in other populations. Asians may be more susceptible to adverse effects of OC pesticides than other races.
The results from the present case-control study, including a follow-up design, confirms that p,p'-DDE exposure can be a risk factor for type 2 diabetes.
Strong associations between low-dose organochlorine pesticides and type 2 diabetes. Pubmed 2010
CANGEROGENIC EFFECTS
Clorodiphenyltrichloroethane (DDT) is a persistent organic pollutant, involved in the progression of many cancers, including liver cancer .
The impact of p,p'-DDT on the growth of hepatocellular carcinoma using both in vitro and in vivo models has been evaluated
The present data indicated that the proliferation of HepG2 cells was strikingly promoted after exposed to p,p'-DDT for 4 days. In addition, reactive oxygen species (ROS) content was significantly elevated, accompanied with inhibitions of γ-glutamylcysteine synthetase (γ-GCS) and superoxide dismutase (SOD) activities.
Interestingly, the levels of β-catenin and its downstream target genes (c-Myc and CyclinD1) were significantly up-regulated, and co-treatment of NAC, the ROS inhibitor, inhibited these over-expressed proteins. Moreover, the p,p'-DDT-stimulated proliferation of HepG2 cells could be reversed after NAC or β-catenin siRNA co-treatment. Likewise, p,p'-DDT treatment increased the growth of tumor in nude mice, stimulated oxidative stress and Wnt/β-catenin pathway. Current data indicates that low doses p,p'-DDT exposure promote the growth of hepatocellular carcinoma via Wnt/β-catenin pathway which is activated by oxidative stress. The finding suggests an association between low dose DDT exposure and liver cancer growth.
Dichlorodiphenyltrichloroethane exposure induces the growth of hepatocellular carcinoma via Wnt/β-catenin pathway. Pubmed 2014
The biological basis for investigating dichlorodiphenyltrichloroethane (DDT) exposure and breast cancer risk stems from in vitro and animal studies indicating that DDT has estrogenic properties. The existing information does not support the hypothesis that exposure to DDT/DDE increases the risk of breast cancer in humans.
DDT/DDE and breast cancer: a meta-analysis. Pubmed 2013
LIVER DAMAGE
Hirmi Valley liver disease was first reported in 2001 in Tigray, Ethiopia. 591 cases, including 228 deaths, were reported up to December 2009. The pyrrolizidine alkaloid acetyllycopsamine was detected in stored grain and residents reported adding the pesticide DDT (dichlorodiphenyldichloroethylene) directly to their food stores.
Clinical presentation included epigastric pain, abdominal swelling, bloody diarrhoea, hepatomegaly, splenomegaly, and ascites . Histology revealed acute injury characterised by centrilobular necrosis or chronic injury with bile ductular reaction, cytomegaly and fibrosis but no hepatic vein occlusion.
This novel form of disease appears to be caused by co-exposure to acetyllycopsamine and DDT.
Hirmi Valley liver disease: a disease associated with exposure to pyrrolizidine alkaloids and DDT. Pubmed 2014
ALZHEIMER'S DISEASE
The causes of late-onset Alzheimer disease (AD) are not yet understood but likely include a combination of genetic, environmental, and lifestyle factors. Limited epidemiological studies suggest that occupational pesticide exposures are associated with AD. serum levels of dichlorodiphenyldichloroethylene (DDE), the metabolite of the pesticide dichlorodiphenyltrichloroethane (DDT), were found to be elevated in a small number of patients with AD (n=20). The association between serum levels of DDE and AD and whether the apolipoprotein E (APOE) genotype modifies the association have been studied.
Levels of DDE were 3.8-fold higher in the serum of those with AD (mean [SEM], 2.64 [0.35] ng/mg cholesterol) when compared with control participants (mean [SEM], 0.69 [0.1] ng/mg cholesterol; P < .001).Elevated serum DDE levels are associated with an increased risk for AD and carriers of an APOE4 ε4 allele may be more susceptible to the effects of DDE. Both DDT and DDE increase amyloid precursor protein levels, providing mechanistic plausibility for the association of DDE exposure with AD. Identifying people who have elevated levels of DDE and carry an APOE ε4 allele may lead to early identification of some cases of AD.
Elevated Serum Pesticide Levels and Risk for Alzheimer Disease. Pubmed 2014
Elena Osella
Eleonora Rutto
