In general, living near farms increases the risk of birth defects in children (see below). When looking at specific crops, researchers at Purdue University found a significantly higher risk of arm and leg birth defects in children born to mothers living less than 500 meters (approx 1/3rd mile) from corn agriculture. A dose response effect was found showing each 10 hectacre increase in cornfields increased birth defects by 47%. Higher birth defects were not found in families living close to soybean production suggesting different pesticides used on crops were responsible. Below is the concluding quote from study authors:

Hugo Ochoa-Acuna, Cristina Carbajo
Department of Comparative Pathobiology
Purdue University

Babies born to families living near wheat growing agricultural areas using chemical pesticides were found to have a 65% greater risk of having birth defects related to the circulatory/respiratory system. The pesticide category believed to be the culprit is known as chlorophenoxy herbicides that contain the chemical 2,4-D. Chlorophenoxy herbicides are used to kill a variety of weeds and are also commonly used by city and county maintenance departments for grass and weed control along roads, canals etc. Other conclusions of the study found there was more than double an increase in respiratory/circulatory birth defects in babies if heart malformations were excluded. When looking at musculoskeletal/intergumental anomalies for both sexes in the high-wheat growing counties, there was a 50% increased risk of these types of defects. Infant deaths for male babies (from congenital anomalies related to the birth defects) was over 2.5 times higher than normal. Scientists also found that infants conceived from April-June (the time of primary pesticide application) had a 75% increased risk of being diagnosed with birth defects - compared to birth defect rates for conception during other times of the year. In conclusion, the scientists stated:

Dina M. Schreinemachers
National Health and Environmental effects Research Laboratory
Office of Research and Development
U.S. Environmental Protection Agency, Research Triangle Park, North Carolina

Living within 1 mile of agriculture resulted in increased risk of fetal death due to major birth defects, according to a study conducted by the School of Public Health, University of North Carolina. The most important factor increasing fetal death rate was the timing of pesticide exposure. If pesticide exposure occurred between the 3rd and 8th week of pregnancy, there was a 40% increase in major birth defects ending in fetal death. If pesticide exposure was from halogenenated hydrocarbons, during the 3rd and 8th week, there was more than double the rate of death from birth defects. Organ and limb formation occurs in the developing child between weeks 3 and 8, and therefore, would be more vulnerable to harm.

Department of Epidemiology
School of Public Health,
University of North Carolina, Chapel Hill, NC

High brain cancer rates were found for people living near a cranberry agricultural growing area in Cape Cod, Massachusetts.  Researchers from the Boston University School of Public Health compared the home locations of approximately 1000 cancer patients to the home locations of 1000 patients dying of illnesses not related to cancer. Results showed that living within 2600 feet of the cranberry growing area resulted in twice the risk for all brain cancers and nearly a 7-fold increased risk for a type of brain cancer known as astrocytoma. (Astrocytomas are in the family of "glioma" cancers which begin in the glial tissue (glial tissue are the cells which hold the other brain cells together).

For more information on brain cancer and neuroblastoma see:
www.chem-tox.com/cancerchildren - brain cancer research summaries
www.chem-tox.com/neuroblastoma - neuroblastoma research summaries

Drs. A. Aschengrau, D. Ozonoff, P.Coogan, R. Vezina, T. Heeren
Department of Epidemiology and Biostatistics
Boston University School of Public Health

Rates for Autism Spectrum Disorder (ASD) were more than 6 times higher for children whose mothers were exposed to certain pesticides during a specific time-window in pregnancy. 465 children were identified with ASD in the Sacramento River Valley and San Joaquin River Valley air basin of California. Residences were identified and proximity to pesticide sprayed farms was determined through state mandated agriculture pesticide use reporting files. Results showed that the risk of having a child with Autism Spectrum Disorder was 7.6 times higher than normal if certain conditions were present. This included:

Further support for these findings is shown by the fact that the risk of ASD increased with the pounds of pesticide used and decreased with distance from the treated fields.

CHEM-TOX COMMENT: Also of significance, the human brain begins growing at over 4,000 cells per second beginning in the 4th week of pregnancy, thereby suggesting this would be a highly vulnerable time period.

Eric Roberts, Paul English, Judith Grether, Galye Windham,
Lucia Somberg, Craig Wolff
Public Health Institute, Oakland, CA, USA
California Department of Health Services, Richmond, CA
School of Public Health, University of California, Berkeley, CA

Living within 1 mile of food crops grown using pesticides was shown to result in a higher rate of autism and developmental disorders in children. The background statement of this research states exposure to several common agricultural pesticides during pregnancy can induce developmental neurotoxicity in humans, and has been associated with developmental delay and autism. The researchers involved in this study evaluated whether residential proximity to agricultural pesticides during pregnancy was associated with autism spectrum disorders (ASD) or developmental delay (DD) in the Childhood Autism Risks from Genetics and Environment (CHARGE) study.

The study included 970 participants, commercial pesticide application data from the California Pesticide Use Report (1997–2008) were linked to the addresses during pregnancy. Pounds of active ingredient applied for organophophates, organochlorines, pyrethroids, and carbamates were aggregated within 1.25-km, 1.5-km, and 1.75-km buffer distances from the home. Multinomial logistic regression was used to estimate the odds ratio (OR) of exposure comparing confirmed cases of ASD (n = 486) or DD (n = 168) with typically developing referents (n = 316).

Results: Approximately one-third of CHARGE study mothers lived, during pregnancy, within 1.5 km (just under 1 mile) of an agricultural area treated with pesticides. Proximity to organophosphates at some point during gestation was associated with a 60% higher risk for ASD, higher for third-trimester exposures (OR = 2.0; 95% CI: 1.1, 3.6), and second-trimester chlorpyrifos applications (OR = 3.3; 95% CI: 1.5, 7.4). Children of mothers residing near pyrethroid insecticide applications just before conception or during third trimester were at greater risk for both ASD and DD, with ORs ranging from 1.7 to 2.3. Risk for DD was increased in those near carbamate applications, but no specific vulnerable period was identified.

Conclusions: This study of ASD strengthens the evidence linking neurodevelopmental disorders with gestational pesticide exposures, particularly organophosphates, and provides novel results of ASD and DD associations with, respectively, pyrethroids and carbamates.

Department of Public Heatlh Sciences (University of Calfornia, Davis)
Division of General Medicine, Department of Pediatrics,
School of Medicine, Univ. California
Department of Neurology, University of California, Los Angeles, CA

Children living near fruit orchard farms were found to have 5x higher levels of organophosphate pesticides in their bodies than other children. The study was conducted by the Department of Environmental Health, University of Washington.

109 children (ages 9 months to 6 years) from 75 families were tested for their exposure to pesticides. Children lived in areas with small family orchards that typically grow apples, cherries, pears and peaches. To determine pesticide exposure, samples were taken from urine, hand wipes and household dust.

The study consisted of 35 families who lived within 50 feet from a pesticide treated orchard - 12 families who lived between 50 and 200 feet and 4 families who lived between 200 feet and 1/4 mile from pesticide treated orchards. For comparison, pesticide levels were measure in 14 reference families who lived more than 1/4 mile from the pesticide treated orchard.

Results showed that families living within 1/4 mile from the orchards had house dust concentrations 7 times higher than found in the reference homes. Pesticide levels in urine were 5 times higher than in children living more than 1/4 mile away. Children living within 200 feet of pesticide sprayed groves had the highest blood levels of pesticides and contaminated house dust.

The researchers concluded by stating:

These findings indicate that children living with parents who work with agricultural pesticides, or who live in proximity to pesticide-treated farmland, have higher exposures than do other children living in the same community

Department of Environmental Health
School of Public Health & Community Medicine
University of Washington, Seattle, Washington

The risk of fetal death from birth defects is higher for those living near farming areas. This was the conclusion of a study conducted at the University of North Carolina at Chapel Hill. The study, which involved almost 700 women in 10 California counties, showed that pregnant mothers who lived near food crops where certain pesticides were sprayed faced significantly increased rates of miscarriage due to birth defects.

To break this down further - Women who lived within 2 miles of a place where halogenenated pesticides were used during the first 2 months of pregnancy (when fetal organs are formed), were more than twice as likely to have a miscarriage caused by fetal defects. Other common pesticides (organophosphates and carbamates), raised the risk of miscarriage by 40%.

According to the scientists,

Our study showed a consistent pattern with respect to timing of exposure," said Dr. Erin Bell, who earned her doctorate with the research at the University of North Carolina (UNC) School of Public Health. "The largest risks for fetal death due to birth defects were from pesticide exposure during the third week to the eighth week of pregnancy.

"The risks appeared to be strongest among pregnant women who lived in the same square mile where pesticides were used," she said.

"This is the first study to our knowledge of pesticides and pregnancy in which exposures were in close proximity to the subjects and the verification of pesticide use was objective, not relying on people's memories of what they might have been exposed to," Hertz-Picciotto said.

Erin Bell (Ph.D.)
University of North Carolina
School of Public Health

The human brain is protected from harm by a defense system known as the blood brain barrier. The first stage of the blood brain barrier is made from exceptionally "tight-junctions" between cells that line the blood vessels supplying nutrients to the brain. These tight-junctions prevent larger toxic molecules from squeezing-through and entering the brain cell network. Unfortunately, the tight-junctions can become "lose" after exposure to some chemicals in the environment - thereby, allowing toxic chemicals into the brain cell network resulting in elevated damage to the brain. Chemicals now being found to damage the blood brain barrier take on new interest as research over the past decade has found defects in blood brain barrier function in people with Psychosis(1), Epilepsy(2), Alzheimers(3) and Parkinson's Disease(4).

In this 1999 research, scientists exposed 10 day old rat pups to three separate pesticides. This included quinalphos (an organophosphate pesticide) - cypermethrin (a pyrethoid pesticide) and the chemical Lindane (an organochlorine pesticide). Exposure levels were 1/50th the amount that would kill 50% of the animals. To determine if the pesticides were damaging the blood brain barrier, animals were injected with a radioactive tracer. Normally, the tracer would be blocked by the blood brain barrier and not enter the brain. However, 2 hours after exposure to the pesticides, the tracer had entered the brain, thereby demonstrating blood brain barrier dysfunction. The three pesticides had disrupted blood brain barrier permeability by 130, 80, and 50% respectively. Defects in blood brain barrier function was also seen at exposure levels of only 1/100th the amount needed to kill 50% of the animals. Of significant interest, 15 day old rat pups had less barrier damage than the 10 day old rat pups. Adult rats showed no evidence of blood brain barrier damage whatsoever. Extrapolating these results to humans, we would then expect younger children to receive far more harm from pesticide exposure than adolescents or adults. Unfortunately, allowable levels of pesticide exposure are currently set from research done with healthy adult animals.

1. British Journal of Psychiatry Volume 141(3):273-281, September, 1982
2. Epilepsia, Volume 47(11):1761-1774, November, 2006
3. Neurobiology of Aging, Volume 28(7):977-986, July, 2007
4. Annals of Neurology, Volume 57:176–179, 2005

Predictive Toxicology Research Group
Industrial Toxicology Research Center
Lucknow, India

BACKGROUND: In the last two decades reports from different countries emerged associating pesticide and herbicide use with Parkinson's disease (PD). California growers use approximately 250 million pounds of pesticides annually, about a quarter of all pesticides used in the US.

METHODS: The scientists in this study employed a proportional odds mortality design to compare all cases of PD recorded as underlying causes of death (1984-1994) or associated causes of death (1984-1993) occurring in California with all deaths from ischaemic heart disease (ICD-9 410-414) during the same period. Based on pesticide use report data, scientists divided California counties into several pesticide use categories. Agricultural census data allowed them to create measures of percentage of land per county treated with pesticides. Employing logistic regression models, the scientists estimated the effect of pesticide use controlling for age, gender, race, birthplace, year of deaths, and education. RESULTS: Mortality from PD as the underlying cause of death was higher in agricultural pesticide-use counties than in non-use counties. A dose response was observed for insecticide use per county land treated when using 1982 agricultural census data, but not for amounts of restricted pesticides used or length of residency in a country prior to death.
CONCLUSIONS: Data shows an increased Parkinson's Disease mortality in California counties using agricultural pesticides.

Ritz B, Yu F
Department of Epidemiology
Center for Occupational and Environmental Health
School of Public Health, UCLA, Los Angeles, CA 90095-1772, USA.

A combination of two commonly used agricultural pesticides, are showing the ability to cause the same pattern of brain damage seen in Parkinson's disease. Mice exposed to the weed killer paraquat and the fungicide maneb showed clear signs of Parkinson's, a progressive and incurable brain illness, according to Deborah Cory-Slechta and colleagues at the University of Rochester School of Medicine and Dentistry. What is interesting about this study is that neither chemical alone works to create the distinctive pattern of brain damage. The findings add to a growing body of evidence that exposure to chemicals such as pesticides may at least contribute to the brain damage seen in Parkinson's.

"No one has looked at the effects of studying together some of these compounds that, taken by themselves, have little effect. This has enormous implications," Cory-Slechta said in a statement. Dr. Eric Richfield, a neurologist who worked on the study, said it may mean that no one will ever be able to predict who is at risk of Parkinson's based on exposure to chemicals.

Parkinson's disease, which affects an estimated 500,000 people in the United States alone, is a progressive and incurable disease that involves the destruction of brain cells that produce dopamine, an important message-carrying chemical linked with movement. Patients start out with tremors and can become paralyzed and die. There is no cure and treatments can delay the disease for a while but eventually stop working. Perhaps the best-known patient is Pope John Paul II, whose doctor admitted on Wednesday the pontiff had the disease. Actor Michael J. Fox also has Parkinson's, and boxer Muhammad Ali has symptoms of the disease. Researchers suspect that a combination of genetic vulnerability and exposure to something in the environment may be responsible. One major suspect is organophosphate pesticides, which are known to affect the nervous system.

Writing in the Dec. 15 issue of the Journal of Neuroscience, Cory-Slechta's team said they studied the effects of a mixture of paraquat and maneb. Both are used on millions of acres of crops such as potatoes, tomatoes, lettuce, corn, soybeans, cotton and fruit.

Mice exposed to one or the other alone showed no ill effects, but when the combination was given they showed clear patterns of brain damage. The mice moved around much less than normal and had lower levels of an enzyme known as tyrosine hydroxylase that is used as a measure of the health of the dopamine system. The mice had nearly four times as many "reactive astrocytes,'' brain cells that suggest they are damaged, they had about 15 percent fewer dopamine neurons, and they produced 15 percent less dopamine than normal mice.

University of Rochester School of Medicine

In research to determine the amount of air contamination following application of pesticides, it was found that the levels of the pesticide Dursban drop to one-sixth of its original 1 hour level four days after application. Dursban was previously used as a common indoor and lawn pesticide but because of research finding damage to the immune system, it was banned and is now only allowed in agriculture (under the name Lorsban). Unfortunately, families living near agriculture could receive significantly higher exposure levels depending on size of farming areas and wind direction.

The dangers of pesticides are typically calculated by looking at only one pesticide at a time. However, this is not what occurs in real life situations for people working around pesticides or families living in homes within 1/2 to 1 mile of farming areas. For example, On one day, pesticide "A" can be applied - and the next day pesticide "B." Some pesticides emit vapors for weeks after application. Others have been found to react with sunlight, and through a process known as photolysis, form even more toxic compounds. In this study, researchers investigated the effects of a combination of six common pesticides used in agriculture. This included atrazine, metribuzine, endosulfan, lindane, aldicarb and dieldren. The concentrations of these chemicals were equal to what is typically found in the enviroment of the southwest region of the province of Quebec. The purpose of the study was to determine how the pesticide combination affected the immune systems of two amphibian frog species. Results showed that the combination caused a reduction in the ability of certain immune system cells to "engulf" (consume) pathogens (bacteria, viruses, fungi) and slowed the immune system's ability to multiply cells needed for removing pathogens. In conclusion, the researchers stated,

Taken together, these results indicate that agricultural pesticides can alter some aspects of the immune response in frogs and could contribute to their global decline by rendering them more susceptible to certain infections.

Department of Biology, Concordia University, Montreal, Conada
Vanderbilt University Medical Center, Nashville, TN

Chem-Tox Comment: While the pesticide chlorpyrifos was banned for indoor use in 2000 (under the name Dursban), it is still used in agriculture under the name Lorsban. This results in high exposure for families living near agriculture. Lorsban is used frequently in citrus agriculture in Florida and California.

The following research was conducted at the Department of Pharmacology, Duke University Medical Center, Durham, North Carolina. The first paragraph below is the abstract taken from the original research article:

Researchers administered chlorpyrifos to neonatal rats in apparently subtoxic doses that caused no mortality and little or no weight deficits and examined developing brain regions (cerebellum, forebrain, brainstem) for signs of interference with cell development. One day old rats given 2 mg/kg of chlorpyrifos showed significant inhibition of DNA synthesis in all brain regions within 4 hours of treatment; equivalent results were obtained when a small dose (0.6 ug) was introduced directly into the brain via intracisternal injection, indicating that the actions were not secondary to systemic toxicity. Inhibition of DNA synthesis was also seen at 8 days of age; however, at this point, there was regional selectivity, with sparing of the cerebellum... These results indicate that low doses of chlorpyrifos target the developing brain during the critical period in which cell division is occurring, effects which may produce eventual cellular, synaptic, and behavioral aberrations after repeated or prolonged subtoxic exposures."

In summary the researchers stated,

In extrapolating findings in the developing rat brain to man, it is important to note that the first 10 days of postnatal life in the rat represent stages of neurodevelopment corresponding to the last trimester of gestation in man; thus, our finding of a much greater sensitivity to chlorpyrifos in the neonate, in terms of both systemic toxicity and targeting of DNA and protein synthesis within the brain, emphasize the need for caution in assigning safety standards. Further study of acute and chronic exposure to chlorpyrifos should be undertaken to evaluate the cellular, synaptic, and behavioral consequences of low-level exposures.

K. D. Whitney, F. J. Seidler, T.A. Slotin
Department of Pharmacology
Duke University Medical Center
Durham, North Carolina

Children who live in homes where indoor or outdoor pesticides are used face a far greater chance of developing leukemia (leukemia is a cancer in which exceptionally high levels of blood cells are formed in the blood). The study, published in July's 1987 issue of the Journal of the National Cancer Institute, studied 123 Los Angeles children with leukemia and 123 children without the malignancy. The results showed the children living in the pesticide treated homes had nearly 4 times greater risk of developing the disease. If the children lived in homes where pesticides were used in the garden as well, the risk of developing leukemia was 6.5 times greater. All of the children in the study were 10 years of age or younger.

CHEM-TOX COMMENT: Although this study measured risk for only home and lawn use of the chemical, families living in close proximity to farming areas could potentially be exposed to significantly higher levels of the chemical.

Dr. John Peters
University of Southern California

A study of 3,827 Florida pesticide applicators employed for 20 or more years found they had nearly 3 times the risk for developing lung cancer. The same study also showed the pesticide applicators had twice the risk for brain cancer. There was not any increased cancer risk when applicators were studied for only 5 years implying it takes over 5 years to accumulate enough damage to the genetic structure to develop the cancers.

A type of kidney cancer known as Wilms' tumor occured nearly 60% higher than expected in children whose fathers worked around pesticides. Job occupations included farmers, agricultural workers, agricultural machinery drivers, gardeners and foresters. Wilms' tumor is a type of kidney cancer that is the fourth most common childhood cancer, accounting for approximately 6% of all malignancies diagnosed before 15 years of age). Child exposure can occur from pesticides on the father being inhaled and transferred to the child.

Cancer Epidemiology Unit, Imperial Cancer Research Fund, Oxford
Leukaemia Research Fund, Center for Clinical Epidemiology, University of Leeds

The human brain is protected from harm by a defense system known as the blood brain barrier. The first stage of the blood brain barrier is made from exceptionally "tight-junctions" between cells that line the blood vessels supplying nutrients to the brain. These tight-junctions prevent larger toxic molecules from squeezing-through and entering the brain cell network. Unfortunately, the tight-junctions can become "lose" after exposure to some chemicals in the environment - thereby, allowing toxic chemicals into the brain cell network with potential for causing elevated damage to the brain. Chemicals now being found to damage the blood brain barrier take on new interest as research over the past decade has found defects in blood brain barrier function in people with Psychosis (1), Epilepsy (2), Alzheimers (3) and Parkinson's Disease (4).

One of several compounds found to weaken and damage the blood brain barrier is the chlorophenoxy herbicide MCPA. This pesticide is used to kill broadleaf weeds and is used when growing alfalfa, barley, clover, flax, lespedeza, oats, grass, peas, rice, rye, sorghum, trefoil, triticale, and wheat. It is also used on sod farm turf, golf courses, public walkways, pastures, rangelands and residential lawns. EPA estimates that 4.6 million pounds of MCPA are used each year in agricultural and residential applications.

To determine if the weed killer could damage the blood brain barrier, rats were given single doses of MCPA at 100, 250, and 500 mg/kg at various intervals before sacrifice. A blue dye was injected into the animals to determine if staining occurred to the brain. Staining occurs when the blood brain barrier is not working properly (as a properly working barrier would block the dye from entering the brain). Blood brain barrier damage was observed with the 250 and 500 mg/kg doses. Most severe damage occurred 4.5 hr after administration of 250 mg/kg MCPA. After approximately 24 hours, no evidence of blue dye could be observed.

1. British Journal of Psychiatry Volume 141(3):273-281, September, 1982
2. Epilepsia, Volume 47(11):1761-1774, November, 2006
3. Neurobiology of Aging, Volume 28(7):977-986, July, 2007
4. Annals of Neurology, Volume 57:176–179, 2005

Department of Biomedical Sciences, University of Tampere,
Box 607, SF-33101 Tampere 10, Finland

Men who mixed or applied the weed killer 2,4-D experienced a 50% higher rate of the cancer known as Non-Hodgkin's Lymphoma (also called NHL). The risk of NHL was dose-dependent and increased with the frequency of use of the pesticide. For example, men who were exposed to the weed killer 20 or more days per year had over a 3 times greater chance of developing the disease. Non-Hodgkin's Lymphoma is the name given to a group of blood cell cancers that develop from lymphatic cells within the lymph nodes. Lymph nodes are oval or bean shape structures that range in size from 1/16th up to 1 inch and located under the arm pits, stomach and many other areas in the body. Lymph nodes contain high concentrations of immune system cells which can attack and eliminate bacteria, viruses and even cancer cells. The image at left shows a lymph node that has become cancerous resulting in uncontrolled growth of lymphatic cells inside the lymph node.

CHEM-TOX COMMENTS: Of significant concern regarding 2,4-D, it contains the chemical Dioxin (TCDD) as a contaminant. Dioxin has been found to weaken the immune system of mammals at exremely low levels (parts per billion). The incidence rate of NHL has been rising 3-4% a year. In the United States, the annual incidence rate for NHL was 5.9 per 100,000 people in 1950 - In 1975, it had risen to 9.3 per 100,000 people. By 1989 it had reached 13.7 per 100,000. (This was reported in the Annals of Oncology, Vol. 5(1):S19-S24, 1994). After 1989 it had risen further and is currently at appoximately 20 new cases per 100,000 people (more than 3 times the rate as in 1950). According to researchers Devesa and Fears at the the National Cancer Institute in Bethesda, Maryland, the incidence rates for NHL have increased at about 3-4% per year (Cancer Research, 1;52(Suppl 19):5432s-5440s, October, 1992).

The chemical chlorpyrifos (Lorsban) is commonly used in agriculture as an insecticide. In 2000, it was banned for indoor use after being linked with a variety of health disorders, however, it is still permitted in agriculture settings. In a study by the Department of Health Science at California State University, 12 individuals, which included a teacher, six housewives, a retail owner, a musician and an engineer, were studied for 1 to 4.5 years after they became ill when their home or place of employment was treated with the pesticide. The researchers were investigating for any abnormalities in immune system function. Immediately following each patient's exposure to the pesticide, common complaints included an initial flu-like illness followed by chronic complaints of fatigue, headaches, dizziness, loss of memory, upper and lower respiratory symptoms, joint and muscle pain and gastrointestinal disturbances. The subjects were found to have an elevated number of CD26 cells and a higher rate of autoimmune problems, compared with two other control groups. (Autoimmune disorders occur when the person's own immune system mistakenly makes antibodies which attack their own body.) Autoantibodies were found toward smooth muscle, parietal cell, brush border, thyroid gland, myelin, and ANA. 83% of the pesticide exposed people were found to have autoantibodies in their blood, in comparison to only 15% for non-pesticide exposed control group. 50% of the pesticide exposed people were also found to have two or more autoantibodies in comparison to only 4% for the non-exposed group.

In conclusion the researchers stated,

The presence of several different types of autoantibodies, e.g., antimyelin, antismooth muscle, anti brush boarder, and antimicrosomal, indicates that generalized tissue injury has occurred. Moreover, these identical observations have been made in additional chlorpyrifos patients (research in progress). Thus, chlorpyrifos (Dursban), as used in pesticide spray, should be examined more closely as a probable immunotoxin.

Jack D. Thrasher Ph.D., Roberta Madison, Alan Broughton
Department of Health Science, California State University

Lupus is an autoimmune disease in which the body's immune system mistakenly attacks a person's healthy tissue including the heart, lungs and brain. Rheumatoid arthritis is an autoimmune disease in which the body's immune system mistakenly attacks tissues of the joints. Dr. Christine G Parks of the National Institute of Environmental Health studied health reports from nearly 77,000 women participating in the Women's Health Initiative. The strongest association between pesticides and these autoimmune disorders appeared in women who lived on a farm and reported personally applying pesticides.

Dr. Christine G. Parks
National Institute of Environmental Health

Although this study ws done regarding home pesticide use, we are including it as it is related to pesticide exposure and could be applied to an agricultural setting.

One of the largest studies to date has found that pesticide use around the home can more than double the chance of a child developing neuroblastoma.

Neuroblastoma accounts for approximately 10% of all childhood tumors. There are 550 new cases in the United States each year, with an annual incidence rate of 9.2 cases per million children under 15 years of age. This works out to approximately 1 per 100,000 children under age 15 on a national level. (These rates were reported in the book "Principles and Practice of Pediatric Oncology, Lippincott-Raven, 1997). Neuroblastoma is a very serious cancer as approximately 60% of children over age 1 who develop neuroblastoma do not live more than 3 years even when receiving treatments of radiation and chemotherapy. Children under age 1 have a more positive prognosis. As statistics show that neuroblastoma rates have increased over the past 50 years, it is reasonable to assume environmental factors are involved.

One of the largest collaborative efforts among 7 Universities and medical facilities worked together to determine what extent pesticide use in the home could increase child neuroblastoma rates. 390 neuroblastoma children and 460 non-cancer controls were included in the study. Investigators questioned both parents regarding use of pesticides in and around the home.

Results showed that using pesticides in and around the home resulted in a 60% increased likelihood of children developing the disease (Odds Ratio=1.6). Looking at pesticide use for the lawn and garden resulted in an increased risk of 120% (Odds Ratio=2.2) when the mother had applied pesticides in the yard and 50% higher (Odds Ratio=1.5) when the father had applied pesticides in the yard. (Chem-Tox Note: Outdoor pesticides are much different from indoor pesticides as they include fungicides and herbicides some of which have been reported to contain dioxin).

Julie L. Daniels, Andrew F. Olshan, Kay Teschke, Irva Hertz-Picciotto, Dave A. Savitz, Julie Blatt, Melissa L. Bondy, Joseph P. Neglia, Brad H. Pollock, Susan L. Cohn, A. Thomas Look, Robert C. Seeger, Robert P. Castleberry
Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, University of British Columbia, University of Texas, University of Minnesota, University of Florida, Northwestern University, Department of Experimental Oncology, St. Jude Children's Research Hospital and University of Alabama

The pesticide chlorpyrifos (called Lorsban in agriculture) is showing evidence of causing immune system disorders in people. In a study by the Department of Health Science at California State University, 12 individuals, which included a teacher, six housewives, a retail owner, a musician and an engineer, were studied for 1 to 4.5 years after they became ill when their home or place of employment was treated with the pesticide. The researchers were investigating for any abnormalities in immune system function. Immediately following each patient's exposure to the pesticide, common complaints included an initial flu-like illness followed by chronic complaints of fatigue, headaches, dizziness, loss of memory, upper and lower respiratory symptoms, joint and muscle pain and gastrointestinal disturbances. The subjects were found to have an elevated number of CD26 cells and a higher rate of autoimmune problems, compared with two other control groups. (Autoimmune disorders occur when the person's own immune system mistakenly makes antibodies which attack their own body.) Autoantibodies were found toward smooth muscle, parietal cell, brush border, thyroid gland, myelin, and ANA. 83% of the pesticide exposed people were found to have autoantibodies in their blood, in comparison to only 15% for non-exposed control group. 50% of the pesticide exposed people were also found to have two or more autoantibodies in comparison to only 4% for the non-exposed group. 

In conclusion the researchers stated, 

"The presence of several different types of autoantibodies, e.g., antimyelin, antismooth muscle, anti brush boarder, and antimicrosomal, indicates that generalized tissue injury has occurred. Moreover, these identical observations have been made in additional chlorpyrifos patients (research in progress). Thus, chlorpyrifos (Lorsban), as used in pesticide spray, should be examined more closely as a probable immunotoxin."

Jack D. Thrasher Ph.D., Roberta Madison, Alan Broughton
Department of Health Science, California State University

Of the many different types of pesticides (which include insecticides, herbicides and fungicides), it was found that the common fungicide "cyproconazole" caused serious defects when administered to test animals. This chemical is reported to be widely used in agriculture and is a member of the family of fungicides known as triazole fungicides. It's closely related family members include the fungicides triadimefon, triadimenol, bitertanol, flusilazole, 1,2,4-triazole, and propiconazole. Each of these pesticides were reported in this article as being capable of causing birth defects in test animals when administered at doses as low as 30 mg/kg. These chemicals are far more toxic than even standard insecticides. The "No Observable Effect Level" (which means the maximum amount of the chemical that test animals can be exposed to without seeing any adverse effects) is reported to be only 2 mg/kg for flusilazole.

The study on the effects of cyproconazole (lets call it CPZ for simplicity) was headed by Dr. K. Machera, at the Laboratory of Pesticide Toxicology in Athens, Greece. Dr. Machera exposed 10 pregnant animals to different levels of CPZ ranging from 20-75 mg/kg from the 6th to the 16th day of pregnancy. On the 21st day of pregnancy the animals were sacrificed and the number of implantations, resorption sites and live and dead fetuses were recorded. The fetuses were weighed and examined for abnormalities. 

Results showed the number of resorptions (similar to an early miscarriage) was over 8 times greater for the animals exposed to the 50 and 75 mg/kg doses. The fetal length was significantly smaller in doses from 50 mg/kg up. The fetal body weight was significantly less even at the lowest dose of 20 mg/kg. 

Cleft Palate did not occur in any of the 100 offspring not exposed to CPZ. However, cleft palate did occur in 2% of animals exposed to 20 mg/kg of CPZ, 20% of animals exposed to 50 mg/kg of CPZ and 91% of animals exposed to the highest 100 mg/kg dose. 

The same trend was also seen with hydrocephalus - 0% for the animals not exposed to CPZ, 6% for animals exposed to 20 mg/kg, 19% for animals exposed to 50 mg/kg, 32% for animals exposed to 75 mg/kg and 100% for the 12 animals exposed to the 100 mg/kg level. 

These studies demonstrate the definite potential for pesticides in the triazole family to increase the risk of lower birthweight, lower body length, as well as strongly increasing the risk of cleft palate and hydrocephalus. With results such as this in test animals, it would certainly be worthwhile to investigate the incidence of these conditions among people living in close proximity to agricultural areas. Dr. Machera did not state if these chemicals were used on residential lawns as an anti-fungal agent. Keep in mind that these studies were looking for physical defects and were not looking for neurological defects in offspring (which typically occur at much lower levels). 

Dr. K. Machera  
Laboratory of Pesticide Toxicology
Benaki Phytopathological Institute, Athens, Greece

The pesticide malathion is one of the most widely applied pesticides. It is often said to be a "safer" pesticide because it requires a larger exposure to cause death in test animals. However, malathion can cause many serious health disorders other than death. Investigators surveyed 933 pregnancies identified through hospitals in the Sanfrancisco Bay area, in relation to exposure to the pesticide malathion that was applied aerially to control the Mediterranean fruit fly. No association was found between malathion exposure and spontaneous abortion, intrauterine growth retardation, stillbirth, or most categories of congenital abnormalities. However, it was found that mothers exposed to malathion during the second trimester of pregnancy had children with 2 1/2 times more gastrointestinal disorders (affecting the stomach and small intestines) in comparison to children not exposed to malathion during pregnancy. This study is being included as malathion is sometimes sprayed aerially (and repeatedly) over crops in agriculture districts. Of great significance, this birth defect occurred after only one exposure to the chemical.

Department of Preventive Medicine
University of Sourthern California, Los Angeles

The Natural Resource Defense Council completed an extensive report on the health dangers faced by children who live on a farm. Highlights of the report include the following:

Autism has been shown to occur more frequently among children living near agriculture (two reports at the top of this page). The weed killer (herbicide) known as Glyphosate (also called Round-Up) is the most popular herbicide used in agriculture world-wide. In this 2013 study, published in the journal Entropy, by Anthony Samsel and Dr. Stephanie Seneff (Massachusetts Institute of Technology), the researchers show how the chemical glyphosate is linked to increasing autism rates by causing changes in body chemistry that affect important enzyme and biological systems critical in brain development and maintaining brain integrity. According to Dr. Seneff, the autism rate has risen from 1 in 10,000 in 1970 to 1 in 68 in 2012. At current trends, Dr. Seneff, predicts a 50% autism rate by 2025. The table below summarizes 2 ways that the pesticide glyphosate can damage body systems and increase the likelihood of Autism and Alzheimers.

This study was conducted to investigate the link between exposure to environmental pesticides and childhood obesity. A total of 6,770 subjects aged 6-19 were selected from the National Health and Nutrition Examination Survey (NHANES). Exposure to pesticides was based on concentrations in urine samples. Results showed a dose-dependent increase in the rates of obesity for the pesticide "2,5-DCP." This pesticide is used as a soil fumigant in agricultural settings and is highly volatile after application. According to the Centers for Disease Control Biomonitoring Summary, 2,5-Dichlorophenol is a likely carcinogen. Median levels of 2,5-DCP in adults in a non-agricultural setting were 6.6 to 10/4 mcg/l (NHANES 2003-2008). Levels of the pesticide in pregnant women living in an agricultural region of Califoria had median urinary levels 2 to 3 times higher at 21.5 and 18.5 micrograms/liter (mcg/l) and 95th percentile values of approximately 1950 mcg/l (Castorina et al., 2010).

The authors concluded by stating -

"This study suggests a possible relationship between exposure to 2,5-DCP and obesity in children."

Department of Community Medicine
Mercer University School of Medicine
Macon, GA 31207

Children with even the lowest detectable levels of pyrethroid pesticides were twice as likely to have ADHD (Attention Deficit Hyperactive Disorder) than children with no detectable pesticides in their bodies. 687 children were tested for urinary levels of the pyrethroid pesticide metabolite called "3-PBA." (Metabolites occur after the original pesticide is processed by the liver). Along with the doubling of ADHD for children testing positive for the pesticide, every 10-fold increase in 3-PBA resulted in an additional 50% increase in hyperactive-impulsive behavior.

CHEM-TOX COMMENT: This study is of concern as pyrethroid pesticides are commonly used in agriculture and have replaced previously banned organophosphate pesticides. Along with use in agriculture, these chemicals are the used in school pest control - home pest control and community mosquito control applications from trucks and planes. The pesticide is also found in commercially grown foods but not in organically grown foods. 

Cincinatti Children's Hospital Medical Center, Cincinatti, Ohio
Rutgers Robert Wood Johnson Medical School and 
Environmental & Occupational Health Sciences Institute.
Brown University of Public Health, Providence, RI

329 mothers took part in a study to determine if pesticide exposure during pregnancy could result in lowering IQ scores in children. 44% of mothers performed agricultural work during pregnancy, while others lived close to an agricultural setting. The first stage of the study determined the mother's level of pesticide exposure through urine analysis looking for a metabolite called dialkylphosphate (DAP). This chemical is a breakdown product from the liver's interaction with organophosphate pesticides. Urine tests of mothers were done during week 13 of pregnancy and week 26. Results were recorded to a database for future reference. After 7 years - all mothers were contacted and their children tested for intellectual performance using the Wechsler Intelligence Scale for Children, 4th edition. Results showed that mothers whose pesticide levels were in the lowest 25% of all mothers tested had children whose IQ scores were 7 points higher than children whose mothers were in the highest quartile (top 25%) of pesticide exposure. Deficits for the higher pesticide exposed children occurred over all four cognitive domains on the Wechsler IQ Test.

Providing an explanation, authors stated, "Developing fetal nervous systems may be more vulnerable to (OP) pesticides because of the many unique processes occurring during this stage of development, such as cell division, migration, differentiation, formation of synapses, pruning of synapses, apoptosis, and myelination (Tau and Peterson 2010)."

In concusion, the authors stated:

Our findings suggest that prenatal exposure to OP pesticides, as measured by urinary DAP metabolites in women during pregnancy, is associated with poorer cognitive abilities in children at 7 years of age.

University of California-Berkeley
Center for Environmental Research and Children's Health
School of Public Health, Berkeley, California

Does eating chemically grown commercial food increase the rate of diabetes in children? This was one of several questions researchers at Mansoura University Childrens Hospital in Egypt wanted to answer. The study was started with 75 young children, all under age 10, who were recently diagnosed with type-1 diabetes. Blood samples were taken from 75 children with diabetes and 35 control children who did not have diabetes. Blood samples in both groups were then tested for nine different pesticides. This included the head-lice and farming pesticide lindane, the farming/food pesticides malathion and chlorpyrifos and also the farming pesticides DDT and its metabolite DDE. Most people assume DDT is no longer used, but this is incorrect as some countries in Africa and South America still use DDT in agriculture, and these foods are frequently imported into Europe and the United States, especially during the winter months. Another source of DDT in foods comes from a little known fact that the legal pesticide dicofol (routinely used on citrus) contains DDT as an unintended by-product during manufacture.

By comparing the pesticide test results between children with and without diabetes, doctors could easily see if a pattern exists. For example, if pesticide levels were the same in both groups, it suggests that pesticides do not harm the body in a way that increases diabetes. However, if pesticide levels are higher in children with diabetes, we then begin painting a picture that eating conventionally grown pesticide foods, living near agriculture or using pesticides in the home, may very well be a major contributing factor to diabetes.

Below are the results of the tests, and as can be seen, there was a very strong association found between child diabetes and pesticides - suggesting that eating conventionally grown food increases the rate of diabetes in children. All measurements are in what is called nanograms per milliliter of blood

1. Healthy children had no mesureable levels of the pesticide lindane,
but diabetes children had a level of 0.54.

2. Healthy children had no measureable levels of the pesticide DDT, 
but diabetes children had levels of 0.20

3. Healthy children had no measurable levels of the pesticide DDE, 
but diabetes children had levels of 0.37

The same pattern was seen with the common pesticides chlorpyrifos and malathion.

4. Health children had chlorpyrifos levels of .02,
but diabetic children had levels of .24.
Therefore, diabetes children had 12 times higher levels of this common pesticide.

The same pattern was also seen for the pesticide malathion.

Healthy non-diabetic children had malathion levels of .03,
but children with diabetes malathion blood levels 15 times higher at .54.

When using these numbers to determine increased risk from the pesticides, the researchers found that children with high levels of malathion in their blood had a 4 times greater risk of developing diabetes than children with low levels of malathion.

In a related study described below, researchers found that switching to organic food resulted in a dramatic drop in malathion levels in children. When results of both of these studies are viewed together, it provides strong support for the importance of switching to a 100% organic diet for the 38% of the U.S. population with pre-diabetes and also for children with newly diagnosed with type-1 diabetes.

Also, of concern, children living near farming areas can receive considerably higher levels of pesticide exposure after these same pesticides are sprayed on food crops.

As found in the above study, children with diabetes had considerably higher blood levels of several types of pesticides when compared to children who did not have diabetes.

In this study, researchers found that when children switched to organic food (foods grown without pesticides), the levels of pesticides in their bodies dropped dramatically.

Conducted in part by the Centers for Disease Control, scientists studied the effects of eating organic (non-pesticide) food among 23 elementary school children ages 3 to 11. Each child was tested daily for pesticide levels over 15 consecutive days. During the first 5 days (called phase 1) - children consumed their typical (pesticide) food diets. During phase 2 (days 6 to 10) - children ate only organic foods. In phase 3 (days 11 to 15), all children switched back to eating conventional foods grown with pesticides.

RESULTS: After switching from the chemically grown to organic foods during phase 2, all children showed a dramatic drop in levels of the pesticides chlorpyrifos and malathion (see chart above). Average levels of malathion metabolites was approximately 1.2 micrograms per liter (of urine) while eating conventional foods, but after switching to organic foods, it dropped to about less then 0.1 micrograms/liter. This represents a 12-fold decrease in pesticide levels in children. For the pesticide chlorpyrifos (which has been linked to many health disorders affecting the brain and weakening of the immune system), levels were approximately 6 micrograms/liter on conventional foods and then dropped to 2 micrograms per liter after eating organic (a 3-fold reduction). Both malathion and chlorpyrifos are used extensively in agriculture with chlropyrifos also being used in home pest and termite control prior to 2002.

In conclusion, the researchers stated,

We were able to demonstrate that an organic diet provides a dramatic and immediate protective effect against exposures to organophosphorus pesticides that are commonly used in agricultural production....The persistent existence of OP pesticide metabolites in urine during the conventional diet periods raises a concern of the possible chronic exposures to OP pesticides in children. 

Rollins School of Public Health, Emory University, Atlanta, Georgia, USA
University of Washington, Seattle, Washington, USA
Centers for Disease Control and Prevention, Atlanta, Georgia, USA

CHEM-TOX COMMENT:  It is important that people realize that so-called safe levels of exposure are based upon studies done on "adults." Children have far lower levels of important liver enzymes that remove pesticides from the blood (i.e. paraoxanase) and this level can vary dramatically from one child to the next.. Therefore, chidren have pesticides remain in their blood for longer periods and at higher levels than adults. Also, critics of this study (such as those funded by agricultural interests) do not take into account that EPA guidelines on pesticide safety consider only at one pesticide at a time, however, children (and all of us) are exposed to many pesticides in food simulneously. This has been shown to result in far more harm than one pesticide alone, and can sometimes result in an exponential effect (1+1=100). Also, current EPA pesticide safety guidelines do not consider what is called subtle neurotoxicity (effects on learning/behavior) - subtle immune system effects (increased autoimmunity - lowering of white blood count - natural killer cell effects, etc.). The bottom line is that pesticides are designed specifically to kill - and our children are being exposed to small levels of these continuously in food. A follow-up study now needs to be done to determine if natural killer cells and autoimmunity are affected by these levels of pesticides.

The common pesticide chlorpyrifos (also called dursban or lorsban) was shown to damage the ability of the body to properly control iron levels in the blood. Although the pesticide was banned for home and yard pest control in the United States in 2000, it is still used extensively in agriculture and is routinely a contaminant in non-organic food sources and can be found in homes treated with the pesticide in the 80's and 90's.

While iron is essential for many functions in the body (i.e., liver enzymes and hemoglobin for oxygen carrying red blood cells), too much iron can cause accelerated damage to organs, including the liver and heart. In a condition known as hemochromatosis, iron levels above 1000 ng/mL typically require the individual to endure periodic "bloodletting" (removal of blood) to bring iron levels down to a normal range. While some people have mutations of cells that predispose them to the disease, it now appears that low level exposure to the pesticide chlorpyrifos can accelerate or worsen this condition by impairing the liver's ability to produce the hormone hepcidin. Under normal circumstances, when iron levels become too high in the blood, the liver responds by producing the hormone hepcidin. As hepcidin levels increase in the blood, the small intestines react by blocking iron from being re-absorbed back into the body.

Scientists at the Research Center for Eco-Environmental Sciences in China found that low levels of the common pesticide chlorpyrifos (also called dursban or lorsban) caused a highly significant 50% decrease in the amount of hepcidin produced by the liver. Of great concern, the effects on the liver occurred at very small levels of pesticide exposure which did not cause liver cell death or changes in liver cell appearance. In other words, even very low levels of the pesticide was able to weaken the genes in liver cells controlling hepcidin levels in the blood (without affecting other parts of the cell). This would suggest that the pesticide could also cause an accelerated worsening of the condition for individuals who already have an inherited form of the disease.

In conclusion the researchers stated,

We have demonstrated that chlorpyrifos exposure significantly altered the expression of central iron genes (i.e., chlorpyrifos elevates ferroportin expression in macrophages (which uptake iron for transfer to red blood cells) and represses hepcidin expression in hepatocytes (liver cells).

State Key Laboratory of Environmental Chemistry and Ecotoxicology
Research Center for Eco-Environmental Sciences
Chinese Academy of Sciences, Haidian, Beijing, China

Microcephaly is a medical condition in which the brain is considerably smaller than normal, resulting in decreased intelligence and behavior problems. Although the research described here is not directly linked to living near agriculture, it does show how common pesticides can cause microcephaly. The chemical dichlorvos is formed within hours after application of the commonly used mosquito control pesticide dibrom (also referred to as naled).

The photograph above shows the brain of a normal guinea (left) and the brain of guinea pig that was exposed to the chemical trichlorfon found in the mosquito control pesticide dibrom (right). In this current study, the chemical trichlorfon was found to cause a - severe reduction - in brain weight and shape of test animals.   The timing of exposure appeared to be the key factor in determining brain damage.  Brain damage was observed when guinea pigs were exposed to a non-lethal dose of the pesticide between 42-46 days of gestation at levels of 15 mg/kg. Scientists say this time period correlates with the brain growth spurt period for the animal.

The powerful neurotoxic nature of the pesticide was further emphasized when the scientists found that these brain abnormalities did not occur when animals were exposed to the other pesticides tested - soman - TOCP and ethyl-trichlorfon.

Scientists concluded by stating they suspect the nervous system abnormality occurred due to direct damage to DNA at a time when the animals' repair systems are not developed.

CHEM-TOX COMMENT:  The fact that this study shows neurological damage can easily occur in animals (who are often less sensitive than humans to harmful neurological effects) is enough to warrant serious re-evaluation regarding the use of this toxic chemicals over populated areas.

University of Oslo, Institute of Biology
Department of Molecular Cell Biology, Oslo, Norway
Norwegian Defense Research Establishment
Division for Environmental Toxicology, Kjeller, Norway

Rates of diabetes and pre-diabetes were found to be 11 times higher in 116 men employed as pesticide sprayers from public mosquito vector control programs in Bolivia. The prevalence of diabetes and prediabetes was 61% among men employed to spray pesticides and only 8% among 92 non-exposed controls. A dose-response was also found showing that sprayers reporting the highest number of hours spraying pesticides had diabetes and prediabetes rates 14x greater.

Section for Environment, Occupation and Health
Department of Public Health
Aarhus University, Aarhus, Denmark

Having higher levels of pesticides in the blood has now been linked to increasign rates of diabetes. Saudi Arabia has one of the highest rates of diabetes in the world. Nearly 30% of adult population had diabetes in a sample of 1,792 people in 2011 (Annals of Saudi Medicine). This is 2-3 times higher than seen in other developed countries. Investigators at King Saud University measured blood levels of the pesticide DDT and its metabolites among 280 Saudi adults - 136 with diabetes and 144 contols who did not have diabetes. Results showed that higher levels of the breakdown product of DDT (DDE) was associated with increased risk of diabetes.

CHEM-TOX COMMENT:  Primary exposure routes for organochlorine pesticides is living in homes built before 1980 and consuming non-organic food. DDT is still found in commercially grown non-organic foods due to its continued use in South America and imports into other countries.

College of Applied Medical Sciences
King Saud University
Riyadh, Saudi Arabia

43 farmers who had been using pesticides for 15 years were studied to determine if immune system abnormalities could be identified (thereby, increasing risk for cancer and viral infections). Results were compared to a control group of 30 individuals without a history of pesticide exposure.

Results showed farmers had significantly lower levels of lymphocytes known as "B-Cells." These are immune system white blood cells involved in making antibodies against pathogens such as viruses and bacteria. Along with this, farmers also had lower levels of regulatory B-cells that function to suppress overactive immunity (needed to suppress autoimmune conditions).

Pro-inflammatory IL-6 (interleukin-6) was also significantly elevated in farmers compared to controls. Researchers also stated CD4 T and B cells that process antigens are possibly undergoing proliferative exhaustion. which would explain the depletion of mature B-cell subpopulations. Of course, lowering of any of these critical immune defenses would eventually lead to increased risk for future illness, including viral infections.

Postgraduate Program in Pharmacy of the Federal University of Santa Catarina (UFSC), Florianopolis, SC, 88040-900, Brazil.