DDT and Its Metabolites in Mexico

DDT (dichlorodiphenyltrichloroethane) was first synthesized in 1874, and its insecticidal properties were discovered in 1939 by Paul Hermann Muller (Stapleton 1998). The U.S. military began using DDT extensively for mosquito control in 1944, particularly in the Pacific, where much of the action of World War II took place in highly malarious areas (Stapleton 1998). In 1955, the World Health Organization (WHO) started a global malaria control program with DDT; by 1958, 75 countries had joined and, at the peak of the campaign, 69,500 tons of pesticides mainly DDT [1,1,1-trichloro-2,2-bis(pchlorophenyl)ethane] were applied to 100 million dwellings each year (Wijeyaratne, 1993). For the control of malaria, houses were sprayed twice a year with DDT wettable powder to kill resting mature Anopheles mosquito. Later, the Stockholm Convention on Persistent Organic Pollutants, which came into force on 17 May 2004, outlawed the use of 12 chemicals including DDT (UNEP, 2004). However, one exemption clause allows malaria-endemic nations to use DDT, strictly for disease vector control. The United Nations Environment Program estimates that about 25 countries will use DDT under exemptions from the DDT pesticide ban (POPs, 2009). Thus, in regard to presence of DDT around the world can be divided into three scenarios: Sites where DDT is still in use; sites where the presence is due to DDT sprayed several years ago, and sites where the presence of DDT is the result of a long-range transport of the insecticide to areas where it was never used like the Antarctic. In Mesoamerica (Mexico, Costa Rica, El Salvador, Guatemala, Honduras, Mexico, Nicaragua and Panama) DDT was used until the year 2000, Mexico and Nicaragua being the last nations that applied the insecticide in agriculture and for the control of malaria. Table 1 lists the period and the total amount of DDT used in each Mesoamerican country by the malaria control programs. The amount used (approximately 85,000 tons between 1946 and 1999) together with the high environmental persistence of DDT and its metabolites, provide the necessary conditions for DDT to become a contaminant of concern for this region of the world (ISAT, 2002). Taking into account the environmental persistence and the toxicity of DDT, a program for the control of malaria without using insecticides in Mesoamerica was developed between 2004 and 2007, with assistance from the Pan American Health Organization [PAHO; (Chanon et al., 2003; PAHO, 2008)]. The phase-out of DDT in Costa

Rica, El Salvador, Guatemala, Honduras, Mexico, Nicaragua and Panama was part of a regional proposal supported by the Global Environment Facility (GEF) and the United Nations Environmental Program with the participation of the North American Commission for Environmental Cooperation (CEC).

DDT in Mexico
In 1944, and for the first time, houses were sprayed with DDT in Temixco, Morelos, Mexico (Stapleton 1998). The spray was applied to the walls and ceilings of residences. Studies done two months after the spraying, showed that there was a 99% reduction in the incidence of Anopheles (Stapleton 1998). In 1947-48, the spraying of DDT began in other Mexican regions, such as Veracruz, Mexico City and Baja California (Stapleton 1998). By 1948, the first clear evidence of malaria control appeared in the areas first sprayed with DDT; the overall parasite rate in the state of Morelos was found to be 10%, and the rate in the sprayed towns was found to be 1% (Stapleton 1998). In 1936 it was estimated that half of the Mexican population lived in endemic regions and was subject to a malaria mortality rate of 0.5%, or about 36,000 deaths per year (Stapleton 1998).During the 1930s and 1940s, malaria became the third cause of death in the country. However, the antimalaria campaign was not generalized until 1956 (CCE 1998). The success of DDT was outstanding, malaria cases decreased from 41,000 in 1955 to 4,000 in 1960 (Fernández de Castro 1998); in 1970 the campaign was relaxed and the cases increased to 57,000 (Fernández de Castro 1998). However, this was also the time in which DDT production peaked in Mexico, with more than 80 thousand tonnes produced annually (CCE 1998). In recent years, the incidences of malaria have declined significantly, to less than 5,000 cases. Since 1982 there have been no deaths from this disease. As, showed, Malaria is a longstanding public health problem that has inhibited development in large areas of the country. Approximately 60% of the Mexican territory, representing an area inhabited by close to 45 million people, provides an environment suitable for malaria transmission. This includes the Pacific coast, the Gulf of Mexico slopes, the Yucatan peninsula and interior basins of the high plateau. (CCE 1998). In actuality, Mexico operates a malaria control program that has substantially reduced the incidence of this disease. In 1995, Mexico initiated an integrated pest management approach for malaria to reduce the heavy dependence on pesticides. Much of the success of Mexico's malaria control program (there have been no recorded deaths from malaria since 1982) is due to improvements in sanitation, increased disease surveillance, and integrated pest management schemes that focus pesticide applications on critical habitats and stages in the mosquito's life cycle (Government of Mexico 1998). Since 1998, DDT was substituted with pyrethroids in the malaria control program. In other hand, In the area of agriculture, as much as 1,000 tonnes per year were used (CCE 1998).Application rates in the north of Mexico, were among the highest in the world (CCE 1998). However, the growing concern about DDT persistence has had a significant impact on agricultural practices in Mexico. During the early 1970s the US Food and Drug Administration (USFDA) began rejecting the importation of commodities due to high residue levels, especially of DDT (CCE 1998). Therefore, some agricultural areas changed to newer pesticides in order to comply with the USFDA regulations. By 1990, DDT was limited to campaigns addressing public sanitation (CCE 1998). In recognition of DDT's environmental and human health effects, Mexico shifted the emphasis of its anti-malarial campaigns away from DDT beginning in the 1980s and 1990s, and the use of the pesticide was gradually reduced. In 1997, the Intergovernmental Forum on Chemical Safety agreed there was sufficient evidence to take international action to restrict and reduce the use of DDT.

Environmental pathways of exposure to DDT
The physicochemical properties of DDTs (Table 2) show the extent of their volatility and the high KOW/KOA value shows that they are more likely to partition into environmental sectors which exhibit greater organic phases (biota, soil, and sediment). The concentration of DDTs in the water samples may be limited due to characteristically low water solubility. In other hand, the exposure pathways are the processes by which DDT may be transported from the pollution source to living organisms. In the malaria areas, the source of DDT was the household-spraying of the insecticide. Since the beginning of the control program of malaria, DDT was sprayed on the ceilings and walls, both indoors and outdoors. Therefore, after spraying, indoor dust (or indoor soil in some cases), and the external surface soil in those areas next to the dwellings, were the media first to become contaminated with DDT. From these points, the insecticide could be transported from one medium to another by different processes.

Soil and Dust
Several  Tables 3 and 4 show DDT levels in outdoor and indoor surface soils, respectively. Taking into account the guideline for DDT in residential soil: 0.7 mg/kg from Canada (Environment Canada, 2007) different scenarios have been observed in Mexico. Regarding outdoor levels, in general lower levels were found in household outdoor samples (Table 3). With exception of levels found in Chiapas and Oaxaca, that have levels lower than Canadian guide (Table  3). In other hand, high levels are recorded in indoor levels in different regions of Mexico, generally higher than Canadian guideline (Table 4). Also, we can note that the higher levels of DDT in those environment media were found in indoor dust samples, generally with levels above the Canadian guideline (Table 5). Moreover, the data in Tables 3, 4 and 5 indicate high levels of total DDT in soil and dust in all regions studied in Mexico when compared with studies around the world.

Water
DDT, DDD and DDE (DDTs) are only slightly soluble in water, with solubilities of 3.4 ppb, 160 ppb and 120 ppb, respectively (ATSDR 2010). In this regard, sedimentation is the most important factor for the disappearance of DDT from water. However, it has also been suggested that contaminated sediments are a main source of DDT inputs to the water column (Zeng 1999). In order to study the degree of pollution in water bodies www.intechopen.com located in tropical areas, DDTs were quantified in a relatively small stream. The levels of total DDT found in the tropical area was 280 pg/L (Carvalho et al. 2009). In other hand, levels of total DDT found in the tropical area in United states of America was 10300 pg/L (California 1999)

Sediments
As stated above, sediments act as the primary reservoir for excess quantities of DDT. Therefore, it is very important to analyze the concentrations in this medium. In Table 6 it is shown that DDT concentrations in Mexican samples are lower than those detected in other countries, where DDT was used either for the control of malaria or for agricultural practices. Whether this difference can be explained by an increased degradation or by a DDT mass reduction caused by water currents carrying suspended DDTs out of the contaminated area, are issues that deserve further research. However, we cannot exclude another explanation. The Mexican studies, results of which are shown in Table 6, were not designed to assess the amount of DDT in sediments due to spraying. In fact, a sediment sample collected in a river near an area where the insecticide was used intensively for vector control, had DDT concentrations of up to 70.0 mg/kg (

Food and Biota
Due to their lipophilic attributes and high persistence, the DDTs may bioaccumulate significantly in animal species (Fisher 1995). Furthermore, biomagnification has been observed; for example, DDT concentration increased with each successive trophic level in a food chain (Fisher 1995).Taking into account these properties, food ingestion can be considered a pathway of exposure. In Mexico, studies have been done in different food items, such as fish, hen's egg, butter and cow's milk and muscle. In Table 7, total DDT levels in different food items are presented. Considering fish, the concentrations of DDT, in organisms collected in Mexico, are above normal values. As is shown in Table 8, where DDTs levels in Fish are depicted for different countries. We can note that the food item with high levels of DDT are food rich in fat as butter and cow´s milk (Table 7).

Air
Because DDTs have a Henry's Law constant value of 10-4/10-5 atm m3 mol, they are considered moderate volatile compounds [5]. Therefore, these compounds can be transported by air, either in the gaseous phase or adsorbed to atmospheric particles [5].Photodegradation of DDT occurs slowly; thus, residues of these pesticides are ubiquitous in the atmosphere, although at lower concentrations. Information on the atmospheric levels of OCs in Mexico is scarce. Previous studies in southern Mexico found that DDT and toxaphene concentrations in air were 1-2 orders of magnitude above levels in the Laurentian Great Lakes and arctic regions (24-26). Atmospheric levels in southern Mexico were generally higher than those in central Mexico (27) In other hand, a biomarker of exposure is a xenobiotic substance or its metabolite (s), that is measured within a compartment of an organism. The preferred biomarkers of exposure are generally the substance itself or substance-specific metabolites in readily obtainable body fluid(s) or excreta. DDT and its metabolites DDD,DDE, DDA, and MeSO2-DDE (3methylsulphonyl-DDE), can be measured in adipose tissue, blood serum, urine, feces, semen, or breast milk .

Breast Milk
Psychological and medical studies have underlined the benefits of nursing which raises immunological defenses and provides a healthier development of the baby. Parallel findings have increased concern about the excretion of drugs and environmental contaminants contained in breast milk, since it is considered the main route for eliminating deposited organochlorine pesticides from a mother's body (Jensen and Slorach 1991; Sonawane 1995; Cupul-Uicab et al. 2008). Because of their lipophilic nature and high persistence, DDT and its metabolites accumulate in lipophilic human body parts, particularly in lipid-rich tissues such as adipose tissue and subsequently translocated and excreted through milk fat. A major concern is that milk is the first (and in some areas the only) food for the newborn child.
Concentrations of DDTs (DDT, DDD and DDE) in human milk have been shown to be higher in communities exposed to this insecticide, than in non-exposed populations (Table  10). For example, levels from a cotton area where DDT was used for agricultural purposes (Coahuila) were higher or similar to those obtained in samples collected in a malarious area (Veracruz, Yucatan) where DDT was extensively used (Table 10). And both were higher than the concentrations quantified in urban areas (Mexico DF), where DDT has never been used.
The World Health Organization's Acceptable Daily Intake (ADI) for DDTs is 20 mg/kg/day (Lu 1995

Serum
In this document, we presented data regarding DDT and its metabolites levels in children (Table 11) and adults (Table 12) Children appear to be particularly suitable for a monitoring program, as they are not directly exposed to occupational pollution; thus, children normally reflect present trends of environmental exposure more accurately than do adults (

Adipose tissue
Adipose tissue biopsy has been used in epidemiological studies to assess chronic exposure to DDT. This is a logical choice because the DDTs are accumulated in adipose tissue due to its lipid solubility. The half-life of DDT in human adipose tissue is approximately seven years (Woodruff et al. 1994). As in serum, DDTs in adipose tissue are a good biomarker of exposure for communities exposed to DDT. When compared to an urban non-exposed community [46], the levels of DDTs (especially those of DDE), were higher in the exposed population (Table 9). In the same table it can be observed that the concentrations of DDT in adipose tissue from workers of the malaria program were higher than the levels found in people living in an agricultural area or in malarious areas. In the workers, a linear model that included an index of chronic exposure, the use of protective gear,and recent weight loss explained 55% of the variation of www.intechopen.com p,p′-DDE conncentrations in adipose tissue. The index of chronic exposure was constructed according to worker position and based on the historical duration and intensity of DDT application [48]. When the concentrations of DDTs in adipose tissue were expressed by age group, two groups were identified as the most exposed. Those groups were children and elderly people [49]. The levels in elderly people can be explained by the accumulation of DDT in a chronic exposure scenario,whereas the concentration in children may be the result of an exposure to multiple pathways (soil, household dust, air, water, food, etc.). It is interesting that the group less exposed to DDT was the 0-2 years, a group that may be exposed to DDT through lactation [49].  Table 11. Total DDT levels in serum (ng/g lipid) of children living in different Mexican Regions.
A monitoring program of DDTs in adipose tissue is needed in order to assess the body burden, now that in Mexico this insecticide has been eliminated from the malaria program. However, due to ethical constraints, it is not always possible to obtain adipose tissue samples form healthy individuals. Therefore, alternative matrices are needed; for example, a good correlation between adipose tissue concentration and levels in human milk [50] or human serum [51] has been reported .When the geometric DDE levels in lipid bases are used for the estimation of the adipose tissue/serum DDE ratio, a value near unity is obtained [51].  In addition to the differences in the comparison of cases and controls, the difference in the serum DDE levels among the women studied is remarkable. Participants from both studies came from similar hospitals, and there were no apparent differences between case and control selection that could explain this divergence. Differences in laboratory procedures is the most feasible explanation.

Endocrine disruption
DDT is known to have adverse effects on wildlife via endocrine disruption.Clear effects include thinning of the eggshell, feminization, reproduction impairment and development effects [60]. In Mexico two studies in humans have reported findings in this area. Gladen and Rogan [61] found that DDE might affect women's ability to lactate in a study conducted in an agricultural town in northern Mexico. Two hundred and twenty-nine women were followed from childbirth until weaning or until the child reached 18 months of age.DDE was measured in breast milk samples taken at birth, and women were followed to see how long they lactated.Median duration was 7.5 months in the lowest DDE group and 3 months in the highest. The effect was confined to those who had lactated previously -but not for first pregnancies -and it persisted after statistical adjustment for other factors. Rodriguez et al.
[ These associations suggest direct toxicity to the testicles, especially the Leydig cells, as observed with antineoplasic drugs.

Genotoxicity
Some studies have reported genotoxic effects in humans heavily exposed to DDT [8]. Therefore, this area has been studied in Mexico. Studies were done in workers from the control program of malaria, and in women living in malarious areas. Herrera et al. ) had a mean frequency of chromosomal translocations (5.1¥1000 metaphases), two times higher than that observed in workers occupationally exposed to 0.5 Gy of radiation.A positive relationship between the duration of exposure to DDT, measured as years working for the vector control program, and chromosomal translocations was observed (Fig.2). These results suggest an increased risk for diseases with a genetic component, such as cancer. Yañez et al.
[64] evaluated the association of blood DDT levels and DNA damage using the single cell gel electrophoresis assay. A group of 53 postpartum women were selected from two different areas in San Luis Potosí to assure different exposure levels, one with antecedents of malaria and DDT spraying and the other without malaria. Mean and range levels of DDT, DDE and DDD in whole blood were 5.57 ppm (0.02-20.69), 6.24 ppm (0.04-39.16) and 1.16 ppm (0.01-5.63), respectively. The significant correlation of DNA damage, measured as DNA migration with the logarithm of DDT,DDE and DDD was 0.60, 0.62 and 0.43, respectively. Fig. 3 shows the shape of the association of DNA migration with DDE concentration in whole blood, as obtained by the regression: DNA migration= 71.58+7.62(logDDE), this association was not modified by age, smoking habits, nutrition or occupation. This observational finding in the epidemiological study with postpartum women was reevaluated in an in vitro study.Human blood cells were exposed to three doses of DDT, DDD and DDE.DNA damage was assessed by two different techniques: single-cell electrophoresis and flow cytometry. Results obtained by either technique showed that DNA damage was induced by the three organochlorides and a dose-response was observed with