MIM26-Final+Project

Mark Mangir Mim26

**DDT: The Myths and Facts of its Consequences**

**Abstract:** Pesticides are commonly used all over the United States of America to help create a better crop yield, which leads to a large food supply and larger profits. Pesticides affect a large range of organisms, such as insects, fungi, and micro-organisms, in a variety of different ways including repellants and poisons. Repellants are usually less dangerous to humans, but do not remove the pest so it requires more treatments, while poisons are more toxic, they remove the pest and requires fewer treatments. (About Pesticides) Dichloro-diphenyl-trichloroethane (DDT) was one pesticide commonly used till the 1970’s in the United States, due to how effective it was at removing pests. But in 1972 it was banned because it was believed to cause toxic results in humans, such as breast cancer, loss of male fertility, non-Hodgkin’s lymphoma, and pancreatic cancer. Despite the initial findings, some of these accusations turned out to be false. DDT use does not correlate to the incidence of breast cancer and non-Hodgkin’s lymphoma. But unfortunately it has been linked to incidences of male sterility and pancreatic cancer. (Longnecker) So DDT is less toxic, and should still be allowed use in emergency situations. To help counter the side effects the company using DDT should be responsible for monitoring and treating the workers exposed for sterility and pancreatic cancer.

**Introduction:** Dichloro-diphenyl-trichloroethane (DDT) was a pesticide commonly used in the 1940’s in the United States and in the United States military. While it was a strong pesticide used for a variety of different purposes such as farming, DDT’s real notable trait was its extreme effect for killing mosquitoes. It was commonly used to prevent malaria and Typhus in military camps in Korea and Africa. (DDT) The U.S. department of Agriculture (which would later become the U.S. Environmental Agency in 1970) had determined that DDT was dangerous and limited asked for the limitation of the use of DDT, but the laws they put into effect only covered federal lands, such as national parks, and products that required USDA testing. The majority of the laws were written at the state level and ranged from a complete ban of its use, to only for use in emergency situations, to no mentioned restriction at all. (DDT Regulatory) Finally, the use of DDT in the United States was banned in the United States in 1972 due to severe negative ecological and toxicological effect. Only twice since 1972 has the Environmental Protection Agency approved the use of DDT in the United States. Both times a severe infestation had greatly threatened crop yields, and it was proven that no other unrestricted pesticide would remove the infestation.(DDT Regulatory) DDT is metabolized by the body into 1,1-dichloro-2,2-bis (//p// -chlorophenyl)ethylene (DDE). DDE is known to build up in fatty tissue over time, and is transferred from prey to predator when ingested, causing a faster build up in carnivorous animals. It also is found in to be present in breast milk and cow’s milk. (Snedeker) Now DDT is classified as a probable human carcinogen by the U.S. Environmental Protection agency, due to the incidence of liver cell tumors found in animals exposed to DDT. Despite all these risks, DDT has continued use in countries in Africa where the spread of malaria due to mosquitoes is a greater risk than the damaging toxic effects.(DDT)

**DDT’s link to Breast Cancer** DDT is classified as a Polychlorinated biphenyl (PCBs) within the organochloride pesticide group which acts similarly to estrogen. There have been studies that reported that some PCBs have a connection between their concentration and the development of Breast cancer. (Schecter) This correlation has brought up the idea that DDE in breast tissue would raise the risk in developing estrogen fed tumors. Many surveys were funded all over the world. The tests were performed by comparing the concentration of DDE within the breast tissue of women compared to the occurrence of breast cancer. Different groups were tested ranging from pre to post menopausal women, and included women from all the continents except Antarctica. The studies were all adjusted for many risk factors including age, location, body mass index, alcohol consumption, age at first birth, dietary factors, menopausal status, and ethnic and racial groups. One study published in the British Medical Journal in 1997 took sample populations from all over Europe including Germany, the Netherlands, Northern Ireland, Switzerland, and Spain, actually found that the concentration of DDE was inversely proportional to the risk of developing breast cancer in all of the people tested in each of these countries other than the Netherlands.(Van 't Veer) Another study which was published in the American Journal of Epidemiology in 1999 using data obtained from Connecticut provided similar results. In this case the women with breast cancer had slightly smaller DDE concentrations than the women who were counted as controls. The women with breast cancer had an average concentration of 736.5 ppb, while the women who were controls had an average concentration of 781.4 ppb.(Zheng) Also, this trend was found in a study published in the Environmental Contamination and Toxicology in 1997 used information gathered about women living in rural and urban Vietnam. But while the average was lower, the confidence intervals of the concentrations between the breast cancer cases and the controls overlap.(Schecter) This link is an extremely small difference, and it was not found in all of the other studies, so it cannot be verified. In fact, the study, published in Environmental Health Perspectives in 2001, that includes the largest compilation of data shows approximately an even distribution between the breast cancer cases having a higher concentration of DDE and the control cases having a higher concentration of DDE.(Snedeker) While this does not support its own conclusion, it does help approach a conclusion that DDT/DDE concentrations do not elevate the risk of breast cancer. Another study, which included data collected from all over the world, found that while there was no significant risk between DDE levels and breast cancer, the risk of breast cancer with high DDE concentrations greatly decreased in post-menopausal women compared to pre-menopausal women.(Snedeker) Despite the fact that the different research studies were located all over the globe, the studies came to the same conclusion: there is no correlation between DDE concentration in adipose breast tissue and the occurrence of breast cancer.

**DDT’s link to Non-Hodgkin’s Lymphoma** Another type of cancer that is believed to be associated with adipose DDT/DDE concentrations is non-Hodgkin’s Lymphoma. Studies have been done that shows that farmers in the United States who used a variety of pesticides at least five days during the year have been proven to have an increased incidence of non-Hodgkin’s Lymphoma. These studies were adjusted based on whether they smoked cigarettes and the subjects age.(Cantor) DDT is one of the pesticides included, so it has been interpreted that DDT causes an increased risk in non-Hodgkin’s Lymphoma, but this is not the case. It actually was caused by other pesticides used on the same land. In fact in one study published in 1992 in the Cancer Research Journal based off of male farmers in Iowa and Minnesota found that the only organo-pesticide that was proven to have a statistically significant effect on the risk of non-Hodgkin’s Lymphoma in their study was a pesticide called Malathion. (Cantor) Another study published in 1998 in the British Medical Journal based on data from Iowa, Minnesota, Kansas, and Nebraska had similar findings. They found when farmers who used DDT at least five days a year in combination with other pesticides had a higher incidence of non-Hodgkin’s Lymphoma (a 2.6 odds ratio), but once the data was compared to farmers who used a similar cocktail of pesticides that did not include DDT it was found that the incidence was the same (the odds ratio decreased down to 1.1). If DDT was a contributor to the risk factor of non-Hodgkin’s Lymphoma the first group would have developed non-Hodgkin’s Lymphoma at a higher rate, rather than both of the groups having a similar occurrence of the disease.(Baris) Also, a nested study of different pesticides used in Maryland published in 2004 in the Environmental Health Perspectives, using data that was collected in 1974. This survey found that while it could be proven that at least some PCB’s can raise the risk of non-Hodgkin’s Lymphoma, DDT itself could not be statistically linked to the rise in frequency of non-Hodgkin’s Lymphoma.(Rothman) One last study done on cadavers from all over the United States found that DDT actually did have a statistically significant effect on the occurrence, but this only happened in the highest quartile of concentrations, unlike many of the other pesticides they tested, such as Dieldrin and heptachlor epoxide, for that had significant elevations in incidence of non-Hodgkin’s lymphoma within all quartiles of concentration.(Quintana) None of the data from any of the areas in the United States showed a definite correlation between DDT use and non-Hodgkin’s Lymphoma.

**DDT’s link to Liver Cancer** They first type of cancer that has statistical evidence that DDT/DDE is a major risk factor is liver cancer. One study done in 2000 was based on data gathered on white and African American people within the United States. An interesting result occurred in this study. A correlation between DDT and the mortality rate of liver cancer could only be found within the white population in the study. DDT/DDE did not increase the incidence of liver cancer in the African American population.(Cocco) One more study published in 1974 in Germany found that mice that were given 250 ppm of DDT had similar results to rats that were exposed to DDT over their life time. Within this data, it was proven that there is a positive relationship between DDT concentration in the mice and their rate of developing hepatomas in the liver. Also, they found that male mice of certain species had a higher occurrence of these hepatomas than female mice of the same species.(Tomatis) Another study published in 2002 in Environmental Health Perspectives showed similar data to the previous study. The project found a high relation between DDT and liver cancer. This study was done in mice, and the mice dosed with 250 ppm first showed tumors after 50 weeks. This study also had an interesting conclusion. It seemed that the male mice were more susceptible to liver cancer than the female mice were. The male mice grew tumors sooner and more frequently than female mice did.(Turusov) Another study published in the Br. Journal of Cancer was performed in Sweden. The study found that organic solvents, including DDT, elevated the risk of developing hepatocellular carcinomas in the liver.(Hardell)

**DDT’s link to Pancreatic Cancer** The second type of cancer that actually has statistical evidence that DDT/DDE is a major risk factor is Pancreatic Cancer. These studies were all adjusted for cigarette smoke, alcohol consumption and age, as well as other factors that are already considered to be known factors of pancreatic cancer. One study published in 1992 in the Journal of the National Cancer Institute had compared different products made by chemical manufacturing workers, including DDT. The study found that while most of the products could not be independently linked to pancreatic cancer, DDT was one of the products that had a direct relation to the risk of pancreatic cancer. It was found that workers that helped manufacture DDT had a risk ratio of 4.8. DDT actually had the largest effect on pancreatic cancer risks in the study. The risk increased 7.4 times compared to people who had no exposure to DDT. The most interesting product of this study is that while DDT could be independently linked to pancreatic cancer, the metabolized form DDE was not found to be significantly linked to pancreatic cancer.(Garabrant) Another study published in The Lancet in 1999 on patients in five hospitals in eastern Spain. This study linked high concentrations of DDT/DDE to a mutation in the K-ras gene which is a known risk factor of pancreatic cancer. The highest concentration of DDT/DDT group actually had an eight fold greater likelihood to have the K-ras mutation than people who were not in contact with DDT/DDE. Though it is not clear whether its presence causes the mutation or if the mutation is enhanced and it helps the mutations grow into fully malignant cancer.(Li) Also the was a study published in Cancer Epidemiology in 2000, that studied subjects working in DDT manufacturing in the San Francisco Bay area between 1996 and 1998. Much like the first study presented in this section DDE was not found to be statistically linked to pancreatic cancer, while DDT levels were found to be significant. The study found similar data to the previous study, they found that DDT manufacturing workers had a seven fold increase in the occurrence in pancreatic cancer.(Hoppin) One last study published in The Lancet in 2004 also found evidence that DDT concentration is a direct risk factor of pancreatic cancer. This article has found proof that DDT and DDE have a noted impact on forcing the G to T conversion on the 12th codon in the K-ras gene. This mutation has already been linked to causing pancreatic cancer. All of the articles were able to link DDT concentrations to increased risk in pancreatic cancer, but oddly the same was not found for the metabolized form of the pesticide, DDE. This means that an increased risk would only come from direct contact of DDT which usually only happens through manufacturing or directly using DDT.

**DDT’s link to Male Fertility through Androgen Binding** In the male reproductive system, one of the major components is the androgen binding protein. Androgen binding protein facilitates the uptake of testosterone into epididymal cells in the testies. Without the presence of testosterone in these cells, spermatogenesis would not occur, and the male would be infertile. It has already been proven that synthetic estrogen can block this pathway and cause infertility.(Gerard) Also, it has been proven that DDE acts like estrogen, so it was a common worry that a buildup of DDT in males would cause infertility. While DDT does not bond as strongly to receptors, the fact that it persists much longer than estrogen in fatty tissue raises the worry about its concentration in humans.(Kelce) An article published in Aquatic Toxicology in 1996 discovered that DDT and DDE did have this estrogenic effect within young rainbow trout. In fact larger doses of DDT stopped vitellogenesis in the trout altogether. This is important to human activity because vitellogenesis uses the same mechanism as the human spermatogenesis. (Donohoe) Another article published in the Eur. J. Lipid Sci. Technol. in 2002 classified DDT and an endocrine disruptor. Originally it was found to block endocrine pathways in fish, such as steroid metabolism and the thyroid hormone receptor. But recently, it has been noticed to have this endocrine blocking in humans as well. The most common side effects found in humans were sperm count reduction, mutated sperm morphology, and reduced sperm mobility. It causes all of these side effects by blocking the ligands from binding to the androgen receptors.(Daxenberger) One final study that showed the androgen receptor blocking ability of DDT was published in the Obstetrical & Gynecological Survey in 1996. This article discussed that DDT did not incite a toxic reaction within the pathway, so instead it must have competitive inhibition with the ligands which normally bind there. But unlike the natural ligands, DDT does not cause the desired response when it binds to the androgen receptors. One extremely interesting development this study discovered was that DDT concentrations in male rats that had not yet reached puberty went through puberty significantly later than their non-dosed counter parts. (Kelce)

**Conclusion** While Dichloro-diphenyl-trichloroethane (DDT) has been proven to have different negative effects including carcinogenic properties, it does not have many of the factors that had caused the USDA to ban it in the first place. DDT was erroneously charged with raising the incidence of breast cancer. In actuality, the majority of the studies presented in this paper actually found an inversely proportional relationship between DDT exposure and breast cancer. Meaning women with higher levels of DDT in their adipose breast tissue actually had a lower occurrence of breast cancer. It also was incorrect when it was stated that DDT increased the risk of non-Hodgkin’s lymphoma. Instead it was found that it was not the one pesticide that raised the risk, but it was the combination of pesticides that had raised the incidence of non-Hodgkin’s Lymphoma. This was proven by comparing both farmers who had used DDT in their combination of pesticides versus farmers who did not use DDT in their combination of pesticides. On the other hand DDT has been found to elevate the risk of other different types of cancer. It has been found to increase the appearance of liver cancer. One study even narrowed it down to find that hepatocellular carcinomas were the type of liver cancer most prevalent after DDT exposure. One interesting piece of information that was found in these studies was that it seems that DDT has a greater impact on the health of whites than African Americans when it comes to liver cancer. Also, it was found that, at least in mice, male subjects exposed to DDT are more likely to develop liver cancer than the female subjects exposed to DDT. Also, DDT has been significantly linked to the occurrence of pancreatic cancer. The largest prevalent population to have this risk is workers who manufacture DDT. To help reduce this risk more and better safety protocols should be put into place to help lower this risk for current and future workers. Finally, it was proven that DDT blocks androgen binding in males lowering fertility by reducing sperm counts and causing more mutations during the spermatogenesis process. Overall, DDT is a hazardous material, but it has faced many untrue charges. And while it is dangerous in some ways the benefits it can provide sometimes out way the risks. Such as how it is still used in Africa today to prevent the spread of malaria. While some of the side effects of DDT are severe, these effects still allow for a longer life span than the average malaria patient. DDT still has a place in this world, but if it is used the three major consequences that need to be monitored are liver cancer, pancreatic cancer, and male androgen binding.

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