# Presentation: 563803

## Content developed by
Suzanne M. Snedeker, Ph.D. 
Associate Director 
for Translational Research

			Cornell University
			Program on Breast Cancer and 
			Environmental Risk Factors (BCERF)

**Content developed by**
**Suzanne M. Snedeker, Ph.D.**** **
**Associate Director **
**for Translational Research**
***	******	******	******Cornell University***
**	****	****	****Program on Breast Cancer and **
**	****	****	****Environmental Risk Factors (BCERF)**
**	****	****	**

**Pieces of the Puzzle:**** Does Atrazine Affect the ****Risk of Cancer?**

## Do environmental chemicals affect the risk of cancer?
1995 Cornell University Program on Breast Cancer and Environmental Risk Factors was founded to address these concerns
Launched a new translational research program

**1995 Cornell University Program on Breast Cancer and Environmental Risk Factors was founded to address these concerns**
**Launched a new translational research program**

**Translational cancer research****	*****– expanding your knowledge***

**Notes:**
 Do environmental chemicals affect the risk of cancer?
 This is a question being asked by scientists, cancer advocates, educators, policy makers, and those exposed to environmental chemicals in their homes and workplaces.
 In 1995 the Cornell University Program on Breast Cancer and Environmental Risk Factors was founded because concerned citizens and policy makers wanted to know if there was a relationship between pesticides and higher than average breast cancer rates in many New York State counties.
 This new translational research program was launched to provide science-based information on environmental risk factors and cancer.

## Address the relationships between environmental factors and cancer risk

**Translational cancer research****	*****– expanding your knowledge ***

**Notes:**
In this approach we:
 Address the relationships between environmental factors and cancer risk.

## Address the relationships between environmental factors and cancer risk
Critically evaluate the current scientific evidence

**Critically evaluate the current ****scientific evidence**

**Translational cancer research****	*****– expanding your knowledge***

**Notes:**
 Critically evaluate the current scientific evidence using a strength of evidence approach.

## Address the relationships between environmental factors and cancer risk
Critically evaluate the current scientific evidence
Translate this science-based data into information individuals can use to expand their knowledge and reduce their risk of cancer

**Critically evaluate the current ****scientific evidence**
**Translate this science-based data into information individuals can use to expand their knowledge and reduce their risk of cancer**

**Translational cancer research****	*****– expanding your knowledge***

**Notes:**
 Translate this science-based data into information individuals can use to expand their knowledge and reduce their risk of cancer.

## Address the relationships between environmental factors and cancer risk
Critically evaluate the current scientific evidence
Translate this science-based data into information individuals can use to expand their knowledge and reduce their risk of cancer
Recommend promising avenues of new research

**Critically evaluate the current ****scientific evidence**
**Translate this science-based data into information individuals can use to expand their knowledge and reduce their risk of cancer**
**Recommend promising avenues of new research**

**Translational cancer research****	*****– expanding your knowledge***

**Notes:**
 However, we do not always have clear answers.  So, we also recommend promising avenues of new research to help clarify any uncertainties.
 In this module we will explore why consumers are concerned about pesticides and cancer risk.  This will include learning more about how cancers, in this case, breast cancer develops.  We will also explore the Environmental Protection Agency’s cancer risk assessment of the herbicide atrazine and the types of exposures that may be of concern for both pesticide applicators and the general consumer.
 First, let’s talk about breast cancer risk and ways pesticides can affect the risk of breast and other cancers.

## Breast cancer statistics for the US	– projections for the year 2002

**New Cases in Women: ****	****203,500**
**New Cases in Men: ****	****    ****	****    1,500**
*** US estimates for 2002 from the American Cancer Society,  *****Cancer Facts & Figures 2002***

**Notes:**
 The American Cancer Society has estimated that in the year 2002, 203,500 new cases of breast cancer will be diagnosed in American women, and 1,500 new cases will be diagnosed in men.  
 Over one-fifth of the women and one-third of the men diagnosed with breast cancer will die of the disease.

## The puzzle of breast cancer

**The puzzle of breast cancer**

**Very complex disease**

**Notes:**
 The puzzle of breast cancer
 Breast cancer is a very complex disease.  

## Very complex disease
No one single factor associated with causing the disease

**Very complex disease**
**No one single factor associated with causing the disease**

** **

**The puzzle of breast cancer**

**Notes:**
 There is no one single factor associated with causing the disease.

## Very complex disease
No one single factor associated with causing the disease
Breast cancer develops over a long period of time, usually 10 to 30 years

**Very complex disease**
**No one single factor associated with causing the disease**
**Breast cancer develops over a long period of time, usually 10 to 30 years**

**The puzzle of breast cancer**

**Notes:**
 Breast cancer develops over a long period of time.  It can take 10 to 30 years for a normal cell to develop into a detectable tumor.

## The puzzle of breast cancer	– how does breast cancer occur?

**The puzzle of breast cancer****	****– *****how does breast cancer occur?***

**There are many steps**

**Notes:**
 How does breast cancer occur?  The development of breast cancer is a long process that has many steps.

## The puzzle of breast cancer 	– how does breast cancer occur?

**The puzzle of breast cancer ****	****– *****how does breast cancer occur?***

**There are many steps**
**Occurs as a result of a cell accumulating changes in key genes that control the cell’s ability to divide, mature and die**

**Notes:**
 Breast cancer occurs as a result of accumulating changes in key genes that control a cell’s ability to divide, mature and die.  

## The puzzle of breast cancer 	– how does breast cancer occur?

**The puzzle of breast cancer ****	****– *****how does breast cancer occur?***

**There are many steps**
**Occurs as a result of a cell accumulating changes in key genes that control the cell’s ability to divide, mature and die**
**The result is an abnormal cell that divides out of control and forms a tumor**

**Notes:**
 These changes can  result in an abnormal cancer cell that divides out of control and forms a tumor.

## The puzzle of breast cancer 	– how does breast cancer occur?

**The puzzle of breast cancer ****	****– *****how does breast cancer occur?***

**As the tumor grows, it may invade surrounding or distant tissues**

**  ****Cancer cells can break off from the primary tumor and travel to distant sites invading vital organs**
**  ****Early**** detection is important**

**Notes:**
 As the tumor grows in size, it may invade surrounding or distant tissues.  
 If cancer cells break off from the primary tumor they may travel to distant sites in the body, invading vital organs such as the brain, bone, liver or lung, and establish new tumors.  When these vital organs fail, it can be fatal.  
 That is why early detection and treatment are so important.  It increases the chances of removing the tumor when it is small, before it has grown and invaded other tissues.

## Risks related to breast cancer

**Notes:**
 What affects a person’s risk of breast cancer?  Breast cancer risk factors are like puzzle pieces.  We know how some of the puzzle pieces fit together and affect risk.  For other risk factors, we are just learning about the role they may play. 
 Gender is the main factor that affects risk.  Women have higher breast cancer  rates than men. 
 Advancing age, the age when a girl gets her first period, the age when a woman stops menstruating, a higher consumption of alcohol, and the use of hormone replacement therapy also affects breast cancer risk.  These factors may increase exposure to certain reproductive hormones, such as estrogen and progesterone, which can stimulate breast cells to divide and grow.  
 A dividing cell is more prone to making mistakes when copying its genetic material, leading to a higher rate of “by chance” or spontaneous mutations.  A mutation can also be induced by an environmental chemical.  Normally, our cells are very efficient at repairing these damaging mutations.  However, a spontaneous or an induced mutation can be made permanent and be passed on to new daughter cells during cell division.  

## Risks related to breast cancer

**Risks related to breast cancer**

**Notes:**
 A close relative with breast cancer (a mother, sister or grandmother), and having certain breast cancer susceptibility genes only accounts for five to seven percent of breast cancer risk.  Therefore, most women who are diagnosed with breast cancer have no family history.  
 The age when a woman has her first child also influences breast cancer risk.  About 30% of breast cancer risk is explained by having a child late in life after 30 years of age, or never having children.  Having children early in life causes immature breast cells to change and become resistant to the effects of cancer-causing chemicals.  
  Other factors associated with an increased risk of breast cancer include certain types of benign breast disease, and exposure of the breast to ionizing radiation.  

## Risks related to breast cancer

**Notes:**
 For many other factors, we are just beginning to understand their role in breast cancer risk. 
 A diet rich in fruits, vegetables and fiber may be associated with a lower risk of breast cancer.  As was previously mentioned, a higher consumption of alcohol has been associated with more exposure to the hormone estrogen and a higher risk of breast cancer.
 Being overweight after menopause is associated with higher breast cancer risk.  That is why regular exercise is important to help control body weight. 
 There is concern that exposures to certain environmental chemicals may lead to a higher risk of breast cancer.  This includes some types of dyes, flame retardants, solvents, passive cigarette smoke, certain pharmaceutical drugs and several pesticides.

## Pesticides

**Pesticides**
**	*****– ******potential for exposure***

**Cropland**

**Gardens**

**Recreation**

**Insect Control**

**Notes:**
 Why is there a concern among consumers that pesticides may play a role in cancer risk?  There is concern because of the potential for exposure. 
 We use pesticides :
     - In agriculture to raise crops and livestock		
     - In the home and garden to  control weeds, structural insects and       animal pests 
    - To control pests in recreational areas like golf courses, parks, playgrounds        and athletic fields, and 
     - For large scale insect control against vector-borne diseases. 
 The Environmental Protection Agency estimated that in 1997 nearly one billion pounds of pesticides were used in the United States alone.  About 79% was used in agriculture, 14% for industrial, commercial and governmental use, and seven percent in the home and garden.

## Pesticides and breast cancer risk	– possible mechanisms

**“****Complete” carcinogen**

**Notes:**
 Researchers have identified several ways that pesticides may affect breast cancer risk. 
 Some pesticides may act as “complete” carcinogens.  A complete carcinogen is capable of taking a normal cell through the entire multi-step process to form an invasive tumor.  Only a few pesticides have been identified as “complete” carcinogens.

## Pesticides and breast cancer risk	– possible mechanisms

**“****Complete” carcinogen**
**Co-carcinogen / tumor promoter**

**Notes:**
 Another way is to act as a tumor promoter.  A tumor promoter may give an existing tumor a growth advantage, promoting its further growth and development. 
 The insecticide DDT has been identified as a tumor promoter in  laboratory animals.  When given with or after a known cancer-causing chemical (called a carcinogen), a tumor promoter can cause a higher number or earlier appearance of breast tumors than if only the cancer-causing chemical is given.

## Endocrine disruptor (Hormonally Active Agent)
Mimics other hormones
Affects formation or breakdown of other hormones
Supports the growth of a hormone-dependent tumor
EPA is developing tests to identify which pesticides are endocrine disruptors

**Mimics other hormones**
**Affects formation or breakdown of other hormones**
**Supports the growth of a hormone-dependent tumor**
**EPA is developing tests to identify which pesticides are endocrine disruptors**

**Pesticides and breast cancer risk****	****– *****possible mechanisms***

**Notes:**
 Other pesticides may affect breast cancer risk by acting as “endocrine disruptors,” also called “hormonally active agents.”  These chemicals may mimic a known hormone, such as estrogen, or in another way affect the formation or breakdown of hormones that regulate cell division.  
 Pesticides that mimic the effect of estrogen may be able to support the growth of an existing estrogen-dependent breast tumor.  We know that over half of all breast tumors depend on estrogen for growth.  
 Scientists are only starting to identify which pesticides are endocrine disruptors, including estrogen mimics.  The insecticides DDT and methoxychlor are weak estrogen mimics.  The 1996 Food Quality and Protection Act mandates that the Environmental Protection Agency develop screening tests to identify which pesticides act as endocrine disruptors.

## Atrazine

**Atrazine**

**Pieces of the Puzzle: Does Atrazine Affect the Risk of Cancer? Cornell University BCERF, Snedeker 2002**

**Notes:**
 What is the evidence that certain pesticides affect cancer risk? 
 The  Environmental Protection Agency has been evaluating the cancer risk of atrazine since the 1980s.

## Most widely used herbicide in the US
First registered for use in 1959
Annual crop land usage 
Up to 77.3 million lbs active ingredient*

*Source:  Asplein, 1999

**First registered for use in 1959**
**Annual crop land usage **
**Up to 77.3 million lbs active ingredient***
*******Source:  Asplein, 1999**

**Atrazine****	****– *****usage***

**Notes:**
 Atrazine is one of the most widely used herbicides in the United States.  
 It was first registered for use in 1959.
 Up to 77 million pounds of atrazine, as the active ingredient, were used per year during the 1990s. 

## Atrazine	– usage

**Agricultural crops**
**Primary crops **
**Field and sweet corn, sorghum and sugarcane**** **

**Notes:**
 About 98% of atrazine usage is on agricultural crops.
 Its primary use is as a pre- and post-emergent herbicide on field and sweet corn, especially in the Midwestern corn-belt states. 
 According to the US Department of Agriculture, about 69% of the corn crop was treated with atrazine in 1998 and about 82% of sorghum was treated with atrazine.  
 Atrazine is also used for weed control on sugarcane fields. 

## Atrazine	– usage

**Agricultural crops**
**Primary crops **
**Field and sweet corn, sorghum and sugarcane **
**Other crops **
**Winter wheat, guava and macadamia nuts**
**Hay for animal fodder**
**Fallow land**
**Christmas tree farms**

**Notes:**
 It is used to a lesser extent for weed control on other crops including winter wheat, guava and macadamia nuts, and on hay for animal feed and fodder, and to control weeds on fallow land.
 It is also used to control weeds on Christmas tree farms. 

## Other weed control uses
Turf – golf courses, home lawn care(Southeastern US, St. Augustine and Bermuda grass)
Right-of-ways

**Turf – golf courses, home lawn care****(Southeastern US, St. Augustine and Bermuda grass)**
**Right-of-ways**

**Atrazine****	****– *****usage***

**Notes:**
 Non-agricultural uses only make up about two percent of atrazine’s usage.  This includes weed control: 
     - On turf, including golf courses and home lawn care in the Southeastern US.       Atrazine is used for weed control on St. Augustine and Bermuda grass.
     - And on roadways and right-of-ways in some Midwestern and Western states.

## Application rates vary
Field corn, 1 lb to 2.5 lbs per acre
Sugarcane, up to 10 lbs per acre
Turf*, 2.0 lbs or less per acre
    (* Southeastern US)

**Field corn, 1 lb to 2.5 lbs per acre**
**Sugarcane, up to 10 lbs per acre**
**Turf*, 2.0 lbs or less per acre**
**    ****(* Southeastern US)**

**Atrazine****	****– *****usage***

**Notes:**
 Application rates for atrazine vary according to its use.
 In agriculture, the average field corn application rate is one pound of active ingredient per acre, while the maximum rate of application is two and a half pounds of active ingredient per acre.  
 For sugarcane, the maximum application rate is ten pounds per acre, while on turf in the Southeastern US, application rates are usually two pounds or less per acre.
 Always refer to the product label for correct application rates. 

## Atrazine 	– cancer risk in women

**Breast cancer**_** **_
**Two “ecological” studies from Kentucky**
**Study #1: higher rate of breast cancer in counties with:**
**Higher use of corn herbicides**
**Higher levels of triazine herbicides in water supplies**
**Study criticized because of crude methods used to estimate atrazine exposures**

**Notes:**
 Is there evidence that atrazine exposure can affect breast cancer risk in women exposed to this herbicide?  There are few studies of women that have attempted to answer this question.  Unfortunately, there are no well-controlled human studies that have evaluated breast cancer risk in women exposed to atrazine compared to women not exposed to this herbicide. 
 Two “ecological” studies have been conducted in Kentucky.  Ecological studies approximate exposures of a population within a certain geographic area rather than evaluating exposures of individuals.  
 In the first study researchers found higher breast cancer rates in women living in counties with: 
     - A higher use of corn herbicides and 
     - Higher levels of triazine  herbicides in water supplies.
 This study did not estimate actual exposures to atrazine, but used surrogate measures, like number of acres of corn grown, to estimate atrazine exposure. 
 This may have introduced inaccuracies, since many herbicides besides atrazine are used as corn herbicides.

## Atrazine 	– cancer risk in women

**Breast cancer**_** **_
**Two “ecological” studies from Kentucky**
**Study #2, a 5-year follow-up study: **
**Breast cancer risk **_**not**_** associated with**
**Acres of corn planted **
**Atrazine sales **
**Atrazine levels in water supplies**
**But, study did not measure skin exposures, drift, or levels inside farm homes**

**Notes:**
 In a recently published five-year follow-up study, breast cancer risk was not associated with:	
     - Number of acres of corn planted
     - Atrazine sales 
     - Atrazine levels in the water supplies.
 But, this begs the question, what is the best way to estimate exposure to atrazine?  For instance, what is sold in one county may be applied in another county.  This study did not use more accurate, direct measures of exposure to atrazine, such as skin exposures, estimates of drift, or actual levels of atrazine in the air or dust of farm homes.  Unfortunately, ecological studies can only give us very limited information. 

## Atrazine  	– cancer risk in lab animals

**Breast Cancer**
**Increased number or earlier appearance of mammary (breast) tumors in one type of female rat**
**Not all types of laboratory animals are affected**
**No mammary tumors seen in other rat strains or in mice fed atrazine**

**Notes:**
 What is the evidence that atrazine affects the risk of mammary cancer in experimental animal studies? 
 Atrazine was fed at high levels over long periods of time to female rats in several studies.  Atrazine caused a higher number or earlier appearance of mammary tumors in one type of female rat.  
 But not all types of laboratory animals were affected.
 In other strains of rats and in mice, atrazine treatment did not induce breast tumors.

## Breast Cancer
Atrazine is not an estrogen mimic
May disrupt other hormonal pathways that affect mammary cancer in rats
Decreases luteinizing hormone
Increases prolactin levels

**Atrazine is not an estrogen mimic**
**May disrupt other hormonal pathways that affect mammary cancer **_**in rats**_
**Decreases luteinizing hormone**
**Increases prolactin levels**

**Atrazine  ****	*****– cancer risk in lab animals***

**Notes:**
 While atrazine is not an estrogen mimic, the results of some studies suggest that atrazine may affect breast cancer risk by disrupting certain hormonal pathways in susceptible laboratory animals.
 We do know there are two hormonal pathways that are affected.  Atrazine can decrease levels of luteinizing hormone, and increase levels of a hormone called prolactin.  Both of these hormones are important for reproduction in laboratory animals.

## Breast Cancer
Atrazine is not an estrogen mimic
May disrupt other hormonal pathways that affect mammary cancer in rats
Decreases luteinizing hormone
Increases prolactin levels
These two hormonal pathways may not be as important in human breast cancer

**Atrazine is not an estrogen mimic**
**May disrupt other hormonal pathways that affect mammary cancer **_**in rats**_
**Decreases luteinizing hormone**
**Increases prolactin levels**
**These two hormonal pathways may not be as important in human breast cancer**

**Atrazine  ****	*****– cancer risk in lab animals***

**Notes:**
 Disruption of these two pathways can lead to hormonal changes that increase the number of breast tumors in certain strains of atrazine-treated female rats.
 However, many scientists feel that these two hormonal pathways may not be as important in human breast cancer.  For instance, elevated prolactin levels are known to increase the number of mammary tumors in rats.  However, prolactin levels have little influence on the development of human breast cancer. 

## Atrazine 	– cancer risk in women

**Ovarian cancer**
**Study of Italian women **
**Exposed to triazine herbicides **
**Atrazine and simazine**
**Risk of ovarian cancer higher in exposed women**

**Notes:**
 What about other types of cancer? 
 The results from a study of Italian women suggests that women exposed to the triazine herbicides atrazine and simazine had a higher risk of ovarian cancer than women with little or no exposure. 
 No other studies have been done to see if ovarian cancer rates are higher in American women exposed to atrazine.  
 So, we do not have strong evidence that atrazine causes breast or ovarian cancer in women.  But, it should be pointed out that this is based on very few studies.  
 While there are other studies of cancer rates in farm women and female farm workers, they usually have not measured exposures to specific pesticides.  

## Stomach cancer
Emerging area of research
Study in Ontario, Canada
Higher rates of stomach cancer seen in areas with higher levels of atrazine in the drinking water

**Emerging area of research**
**Study in Ontario, Canada**
**Higher rates of stomach cancer seen in areas with higher levels of atrazine in the drinking water**

**Atrazine ****	*****– cancer risk in men***

**Notes:**
 What about cancer risk in men?
 There is emerging research from Ontario, Canada, suggesting higher rates of stomach cancer in agricultural regions where there were higher levels of atrazine in the drinking water.  
 More research is needed to confirm this study’s findings.

## Atrazine 	– cancer risk in men

**Non-Hodgkin’s lymphoma (NHL)**
**Inconsistent results in studies of Midwestern male farmers **
**Studies in Iowa, Minnesota, and Ontario, Canada did not see a higher risk of NHL **
**Studies in Nebraska and Kansas saw higher risk of NHL**
**When they controlled for other pesticides (e.g. 2,4-D), atrazine-effect not as strong**

**Notes:**
 Can atrazine exposure affect the risk of non-Hodgkin’s lymphoma (NHL) in men?
 The results have not been consistent.  Some have and other studies have not observed a higher risk of non-Hodgkin’s lymphoma in atrazine-exposed Midwestern male farmers.
 Studies conducted in Iowa, Minnesota and a recent study from Ontario,Canada did not see a higher risk of non-Hodgkin’s lymphoma in atrazine-       exposed men.
 While studies conducted in Nebraska and Kansas did see a higher risk ofnon-Hodgkin’s lymphoma in male farmers exposed to this herbicide.
 The researchers then looked at the other pesticides the men were exposed        to, and controlled for exposures to these other pesticides.  When they didthis, the atrazine-effect on non-Hodgkin’s lymphoma was not as strong,        and only a small risk was observed from atrazine exposure.

## Atrazine 		– EPA’s cancer risk assessment

**1988**
**EPA rated atrazine as a ‘possible human carcinogen’ **
**1994 to present**
**EPA placed atrazine under “Special Review” **
**December 1999 **
**EPA’s preliminary cancer risk assessment, rated as ‘probable human carcinogen’**

**Notes:**
 The Environmental Protection Agency first rated atrazine as a possible human carcinogen in 1988 based on evidence of mammary (breast tumors) in female laboratory rats fed high levels of atrazine for most of their lives.
 In 1994 atrazine and two other triazine herbicides simazine and cyanazine were placed under “Special Review” by the Environmental Protection Agency because of concerns about their potential cancer-causing effects.  The Environmental Protection Agency also expressed concern because of risks resulting from exposure through contaminated water and food, and exposures in workers during mixing, loading and application of this herbicide. 
 In December 1999, the Environmental Protection Agency released a preliminary cancer risk assessment, rating atrazine as a ‘probable human carcinogen’.

## 2000
Scientific Advisory Panel (SAP) did not agree with EPA draft report
New research on relevancy of rat data available
Atrazine caused reproductive changes in one strain of rats that influenced levels of hormones important in rat mammary (breast) cancer 

**Scientific Advisory Panel (SAP) did not agree with EPA draft report**
**New research on relevancy of rat data available**
**Atrazine caused reproductive changes in one strain of rats that influenced levels of hormones important in rat mammary (breast) cancer **

**Atrazine**** ****	****	****– *****EPA’s cancer risk assessment***

**Notes:**
 A panel of scientists did not agree with the Environmental Protection Agency’s draft report. 
 At this time new research was emerging on the way atrazine induced breast tumors in rats and whether this was relevant to human breast cancer.  
 Atrazine caused reproductive changes in one strain of rats that influenced levels of hormones important in rat mammary (breast) cancer. 

## 2000 (continued)
These reproductive changes seen in atrazine-treated rats probably would not occur in women
SAP concluded that it is unlikely that atrazine would affect human breast cancer risk

**These reproductive changes seen in atrazine-treated rats probably would not occur in women**
**SAP concluded that it is unlikely that atrazine would affect human breast cancer risk**

**Atrazine**** ****	****	****– *****EPA’s cancer risk assessment***

**Notes:**
 The advisory panel concluded that the types of reproductive changes seen in atrazine-treated rats probably do not occur in women, because of species differences.  
 Therefore, the Scientific Advisory Panel concluded that it is unlikely that atrazine would affect human breast cancer risk.

## June 2000 
Based on SAP recommendations the EPA changed atrazine’s cancer classification to: “not likely to be a carcinogen in humans”
EPA’s reregistration decision expected in 2003

**Based on SAP recommendations the EPA changed atrazine’s cancer classification to: ****“not likely to be a carcinogen in humans”**
**EPA’s reregistration decision expected ****in 2003**

**Atrazine**** ****	****	****– *****EPA’s cancer risk assessment***

**Notes:**
 In June of 2000, based on the Scientific Advisory Panel’s recommendations, the Environmental Protection Agency changed atrazine’s cancer classfication to: “not likely to be a carcinogen in humans”.
 The Environmental Protection Agency’s reregistration decision is expected in 2003.

## Atrazine 	– effects on wildlife

**Sexual development in frogs**
**Male tadpoles exposed to atrazine **
**All had abnormal sexual development**
**Up to 20% had both testes and ovaries**
**Males were more like females**

**Notes:**
 There is some emerging data that has identified an effect of atrazine in wildlife that may be linked to hormone disruption.  A study from the University of California at Berkeley has shown that atrazine can affect the sexual development of African clawed frogs.  
 The male tadpoles were exposed to a wide range of atrazine levels from very low to high.  All of the atrazine-exposed tadpoles had abnormal sexual development.  
 There were no abnormalities in the control frogs that were not exposed to atrazine.
 In the atrazine-exposed male frogs, up to 20% had both testes, the male sex organ, and ovaries, the female sex organ.  These frogs are called “inter-sex” or hermaphrodite frogs.  
 Also, the male frogs were more like female frogs.  Atrazine had a demasculinizing effect on the male frogs.
 Female frogs were not affected. 

## Sexual development in frogs
Male tadpoles exposed to atrazine 
All had abnormal sexual development
Up to 20% had both testes and ovaries
Males were more like females
Occurred at very low levels of atrazine

**Male tadpoles exposed to atrazine **
**All had abnormal sexual development**
**Up to 20% had both testes and ovaries**
**Males were more like females**
**Occurred at very low levels of atrazine**

**Atrazine ****	*****– effects on wildlife***

**Notes:**
 These effects occurred at very low levels of atrazine, levels commonly seen in lakes, rivers and streams in agricultural areas where atrazine is used for crop protection.
 The effects were seen as low as 0.1 part per billion.  This is 30 times lower than the maximum level for atrazine allowed by the Environmental Protection Agency in public drinking water supplies, which is 3.0 parts per billion.

## Sexual development in frogs
Male tadpoles exposed to atrazine 
All had abnormal sexual development
Up to 20% had both testes and ovaries
Males were more like females
Occurred at very low levels of atrazine
Adult frogs had low levels of the male hormone testosterone

**Male tadpoles exposed to atrazine **
**All had abnormal sexual development**
**Up to 20% had both testes and ovaries**
**Males were more like females**
**Occurred at very low levels of atrazine**
**Adult frogs had low levels of the male hormone testosterone**

**Atrazine ****	*****– effects on wildlife***

**Notes:**
 The researchers also measured levels of sex hormones in adult frogs.  They found that adult male frogs that had been exposed to atrazine had very low levels of the male hormone testosterone.

## Sexual development in frogs
Atrazine may increase levels of an enzyme called aromatase
This enzyme converts testosterone to estrogen
Would explain why blood levels of testosterone in  atrazine-treated male frogs are so low
More research is needed to confirm this “aromatase” hypothesis

**Atrazine may increase levels of an enzyme called aromatase**
**This enzyme converts testosterone to estrogen**
**Would explain why blood levels of testosterone in  atrazine-treated male frogs are so low**
**More research is needed to confirm this “aromatase” hypothesis**

**Atrazine ****	*****– effects on wildlife***

**Notes:**
 What could be the explanation?
 The researchers’ theory is that atrazine may increase the levels of an enzyme called aromatase.  This enzyme converts testosterone, the male sex hormone, to estrogen, the female sex hormone.
 This would explain why blood levels of testosterone in atrazine-treated male frogs are so low.
 But, this hypothesis needs to be tested to see if aromatase levels are actually higher in atrazine-treated frogs.
 Does this potential hormone disruption have any implication for humans?

## Atrazine 	– effects on aromatase

**Are levels of the aromatase enzyme or sex  hormones changed in humans exposed to atrazine? **
**Not known**

**Notes:**
 In humans, testosterone can be converted to estrogen by the same aromatase pathway.
 Do we know if atrazine can affect levels of sex hormones or the aromatase enzyme in humans?
 This is not known.  However, it is important to determine if atrazine can affect the levels of aromatase in other non-frog species, including humans.  

## Atrazine & its breakdown products	– exposures of concern

**Workplace exposures:**
**Handling, mixing, loading or applying to row crops or right-of-ways**

**Notes:**
 Are there any exposures of concern that have been identified by the Environmental Protection Agency?  
 During the Special Review of atrazine, the Environmental Protection Agency has identified several exposures of concern.
 While there is little concern for short-term exposures of workers with proper protective clothing, there are concerns for those who have higher exposures from handling large amounts of this herbicide. 
 The highest potential for exposure to atrazine occurs in those who handle, mix, load or apply atrazine to large acreage of crops.  Decreased application rates and the use of closed cabs has reduced exposure during agricultural applications.  Many uses of atrazine to control weeds on right-of-ways have been eliminated over the years.  However, in recent studies, the Environmental Protection Agency found exposures of concern in 30% of the applicators who used the proper personal protective equipment.

## Workplace exposures:
Handling, mixing, loading or applying to row crops or right-of-ways
Post-application field work (sugarcane)

**Handling, mixing, loading or applying to row crops or right-of-ways**
**Post-application field work (sugarcane)**

**Atrazine ****&**** its breakdown products****	****– *****exposures of concern***

**Notes:**
 Those who enter treated fields after atrazine has been applied also have the potential for exposure.  The Environmental Protection Agency has expressed concern for exposures of workers who reenter atrazine-treated fields to scout sugarcane.

## Workplace exposures:
Handling, mixing, loading or applying to row crops or right-of-ways
Post-application field work (sugarcane)
Aerial application or hand spraying 	

**Handling, mixing, loading or applying to row crops or right-of-ways**
**Post-application field work (sugarcane)**
**Aerial application or hand spraying**** ****	**

**Atrazine ****&**** its breakdown products****	****– *****exposures of concern***

**Notes:**
 Those who are involved with aerial application and hand spraying activities, or who are flaggers for aerial applicators potentially also have higher exposures to atrazine.

## Workplace exposures:
Turf application
Use of “belly grinders”
Proper protective clothing is needed when applying atrazine to treat turf in playgrounds, golf courses and residential lawns. 	

**Turf application**
**Use of “belly grinders”**
**Proper protective clothing is needed when applying atrazine to treat turf in playgrounds, golf courses and residential lawns. ****	**

**Atrazine ****&**** its breakdown products****	****– *****exposures of concern***

**Notes:**
 Application of atrazine to turf, especially by the use of “belly grinders” (hand-held broadcast spreaders) was another type of exposure of concern identified by the Environmental Protection Agency. 
 Those who apply atrazine to turf in the Southeastern US (playgrounds, golf courses, residential lawns) may have potential exposures of concern if proper protective clothing is not worn.  In this situation, exposure is possible by breathing mists, sprays or powder, or by exposure to unprotected skin on the face, neck and hands.

## Rural families
Drift from treated fields

**Rural families**
**Drift from treated fields**

**Atrazine ****&**** its breakdown products****	****– *****exposures of concern***

**Notes:**
 Rural families also have the potential for higher exposures to this pesticide. This includes exposure to atrazine as drift from treated fields. 

## Rural families
Drift from treated fields
Tracking into homes

**Rural families**
**Drift from treated fields**
**Tracking into homes**

**Atrazine ****&**** its breakdown products****	****– *****exposures of concern***

**Notes:**
 Tracking atrazine into living and food preparation areas of their homes.  Atrazine does not breakdown easily without exposure to sunlight or bacteria.

## Rural families
Drift from treated fields
Tracking into living & food preparation areas
Handling soiled work clothes

**Drift from treated fields**
**Tracking into living & food preparation areas**
**Handling soiled work clothes**

**Atrazine ****&**** its breakdown products****	****– *****exposures of concern***

**Notes:**
 Through the handling of soiled work clothes, when removing or while laundering the clothes.

## Rural families
Drift from treated fields
Tracking into living & food preparation areas
Handling soiled work clothes
Drinking water from contaminated wells or contaminated community water supplies

**Drift from treated fields**
**Tracking into living & food preparation areas**
**Handling soiled work clothes**
**Drinking water from contaminated ****wells or contaminated community ****water supplies**

**Atrazine ****&**** its breakdown products****	****– *****exposures of concern***

**Notes:**
 Or by drinking water from contaminated wells or contaminated community water supplies.  
 When drinking contaminated water, exposure may be to atrazine as well as to its breakdown products.  Two of the most commonly detected atrazine breakdown products are deethylatrazine (DEA) and deisopropylatrazine (DIA).

## Atrazine levels in water supplies 		– trends

**1980s**
_***Frequent detection***_*** *****of atrazine in groundwater and surface water**

**Notes:**
 What have been the trends in the levels of atrazine in water supplies? 
 During the 1980s, atrazine was frequently detected in groundwater and especially in surface water in Midwestern, Western, and Eastern states and in Florida.  

## 1980s
Frequent detection of atrazine in groundwater and surface water 
Levels greater than the EPA ‘Maximum Contaminant Level’ (MCL) of 3 g/L
Levels detected exceeded 20 g/L 

_***Frequent detection***_*** *****of atrazine in groundwater and surface water **
**Levels greater than the EPA ‘Maximum Contaminant Level’ (MCL) of 3 ********g/L**
**Levels detected exceeded 20 ********g/L **

**Atrazine levels in water supplies ****	****	*****– trends***

**Notes:**
 Levels of atrazine frequently exceeded  the Maximum Contaminant Level (MCL) of 3 micrograms per liter allowed in public water supplies.  This level is set by the Environmental Protection Agency.  It is the highest level of a contaminant allowed in public drinking water. 
 Levels of atrazine detected often exceeded 20  micrograms per liter.  The Environmental Protection Agency, in their most recent risk assessment for atrazine, stated that the greatest concern in water supplies for human or ecological health is when concentrations were 10 to 20 micrograms per liter or greater.  

## 1980s
Surface water levels – influenced by surface run-off from spring rains after application

**Surface water levels – influenced by surface run-off from spring rains after application**

**Atrazine levels in water supplies ****	****	*****– trends***

**Notes:**
 Levels in surface water are influenced by surface run-off from spring rains after application.  This can result in transient levels that “spike” after a heavy rainfall in the late spring and early summer.

## 1990-2000s
Still see high frequency of detection
Now have very sensitive methods
Analytical ability to detect atrazine has improved 	
However, levels are lower, usually below MCL allowed in drinking water 
But, there is concern that in some agricultural areas, still see atrazine levels exceeding the MCL	

**Still see high frequency of detection**
**Now have very sensitive methods**
**Analytical ability to detect atrazine has improved ****	**
**However, **_***levels are lower***_***, *****usually below MCL allowed in drinking water **
**But, there is concern that in some agricultural areas, still see atrazine levels exceeding the MCL****	**

**Atrazine levels in water supplies ****	****	*****– trends***

**Notes:**
 While atrazine remains one of the most frequently detected herbicides in water supplies in the US, the high frequency of detection is partially attributed to an increase in the sensitivity of analytical methods used to detect atrazine.
 The levels detected in the last ten years have usually been lower than the Maximum Contaminant Level (MCL) allowed in drinking water.  
 But, there is concern that atrazine levels in water of some areas, especially agricultural areas, is still in the 10-20 microgram per liter range.  In a recent study over five percent of the water samples from agricultural areas had atrazine levels that exceeded the 3.0 micrograms per liter, the Maximum Contaminant Level for atrazine in drinking water.  Levels as high as 120 micrograms of atrazine per liter were detected in this study.

## Residential - Recreational Exposure
Adults  
Mixing and applying atrazine to turf 
Contact with treated turf; residential lawns,  mowing, golf courses and parks
Tracking into living & food preparation areas
Children  
Playing on treated turf at home, playgrounds and parks
Hand to mouth behavior, and dirt eating

**Adults  **
**Mixing and applying atrazine to turf **
**Contact with treated turf; residential lawns,  mowing, golf courses and parks**
**Tracking into living & food preparation areas**
**Children  **
**Playing on treated turf at home, playgrounds and parks**
**Hand to mouth behavior, and dirt eating**

**Atrazine ****&**** its breakdown products****	****– *****exposures of concern***

**Notes:**
 In Southeastern states, especially Florida, atrazine is used for weed control on St. Augustine and Bermuda grass. 
 Some situations where adults can come into contact with atrazine include when they mix or apply atrazine to turf, or
 When they come into contact with recently treated turf from walking, playing on or mowing residential lawns, or using golf courses or parks. 
 Tracking atrazine on shoes and clothes into living and food preparation areas of the home is also of concern.  
 Of special concern is the exposure of children to atrazine.  This includes exposures when playing on treated turf at home, in playgrounds and in parks. 
 Children can easily get residues from the treated grass on their hands.  Children often lick their fingers or exhibit other “hand to mouth” behavior, including putting toys or other objects into their mouths or even eating dirt. 

## Atrazine and cancer risk	– the unanswered questions

**Is the risk of breast or ovarian cancer increased in women? **
**Is the risk of stomach cancer or Non-Hodgkin’s lymphoma (NHL) increased in men?**

**Notes:**
 What are some of our unanswered questions?
 We still lack human studies evaluating the cancer-causing potential of atrazine.  
 We still need more information on whether the risk of breast or ovarian cancer is increased in women, or whether the risk of stomach cancer or non-Hodgkin’s lymphoma is increased in men exposed to atrazine. 

## Do low levels of  atrazine have an impact on wildlife ecology and declining amphibian populations?
Does atrazine increase levels of the aromatase enzyme and affect sex hormone levels in humans?

**Does atrazine increase levels of the aromatase enzyme and affect sex hormone levels in humans?**

**Atrazine and cancer risk****	*****– the unanswered questions***

**Notes:**
 We need more information on whether low levels of atrazine commonly found in surface and groundwater can have an impact on wildlife ecology and declining amphibian populations.
 Whether atrazine can increase levels of the aromatase enzyme and affect sex hormone levels in humans is still an unanswered question.  Whether this has implications for human breast cancer risk is not known at this time.  

## What are the trends in levels of atrazine and its breakdown products in surface water, rural drinking water wells and rainfall?
Can atrazine breakdown products affect human health?
Can exposure to atrazine affect sensitive populations such as children or developing wildlife?

**Can atrazine breakdown products affect human health?**
**Can exposure to atrazine affect sensitive populations such as children or developing wildlife?**

**Atrazine and cancer risk****	*****– the unanswered questions***

**Notes:**
 What are the trends in water levels of atrazine and its breakdown products?  
 We need to continue to monitor water supplies for atrazine and its breakdown products in surface water, rural drinking water wells, and rainfall. 
 One of the needs that still has not been adequately addressed is whether atrazine breakdown products can affect  human health.  No Maximum Contaminant Levels in drinking water have been set for atrazine breakdown products.  
 There is still concern that seasonably high levels of atrazine in water supplies could affect sensitive populations, including children and developing wildlife.

## Pesticides and health outcomes	– emerging research

**Agricultural Health Study**
**Evaluating whether exposure to agrochemicals affects the health of farm families**
**Ten-year study sponsored by the ****National Institutes of Health**
**Includes 57,000 men  and  32,000 women from farm families in Iowa and North Carolina**

**Notes:**
 Where will we be able to find more answers?
 The Agricultural Health study is one of the largest studies ever designed to evaluate whether exposure to agrochemicals, including pesticides, diesel exhaust, etc. affects the health of farm families.  
 This long-term ten-year study, sponsored by the National Institutes of Health, has over 57,000 men and 32,000 farm women enrolled from the states of Iowa and North Carolina.  

## Pesticides and health outcomes	– emerging research

**Agricultural Health Study**
**Health endpoints to be evaluated**
**Breast and Prostate Cancer**
**Parkinson’s disease**
**Thyroid disease**
**Reproduction**
**Asthma**
**Osteoperosis**
**Childhood diabetes**

**For more information http://www.aghealth.org/**

## Summary

**Breast cancer is a complex disease and environmental factors may play a role in determining its risk**
**Atrazine is widely used in agriculture for crop protection especially for corn, sorghum, sugarcane, and hay crops, and on turf in the Southeastern US**

**Notes:**
 Breast cancer is a complex disease and environmental factors may play a role in determining its risk.
 Atrazine is widely used in agriculture for crop protection especially for corn, sorghum, sugarcane, and hay crops, and on turf in the Southeastern US.

## Summary

**Atrazine causes mammary tumors in some types of laboratory animals**
**We do not have strong evidence that atrazine affects the risk of cancer in humans**
**The EPA has concluded atrazine is not a human carcinogen**
**Low levels of atrazine in water can cause harmful effects on the sexual development of frogs**

**Notes:**
 Atrazine causes mammary tumors in some types of laboratory animals.
 We do not have strong evidence that atrazine affects the risk of cancer in humans.
 The Environmental Protection Agency has concluded that atrazine is not a human carcinogen.
 Low levels of atrazine in water can cause harmful effects on the sexual development of frogs.

## Summary	

**There are exposures of concern to atrazine in both workplace and residential settings**
**Atrazine is widely detected at low levels in water supplies, and there is some concern that levels above drinking water standards persist in some agricultural areas**
**More research is needed to monitor levels in water supplies, determine human health risks including cancer risk, and effects on wildlife**

**Notes:**
 There are exposures of concern to atrazine in both workplace and residential settings.
 Atrazine is widely detected at low levels in water supplies, and there is some concern that levels above drinking water standards persist in some agricultural areas.
 More research is needed to monitor levels in water supplies, determine human health risks including cancer risk, and effects on wildlife.

## Resources on Pesticides   – http://envirocancer.cornell.edu 

**Cancer maps**
**Fact sheets on cancer risk and chemicals**
**Bibliographies on environmental risk factors**
**Searchable Bibliographic Database**
**Newsletter  “*****The Ribbon”***
**Links to:**
**Information on health effects of pesticides, ****policy and legislation, and new research ****studies**

##  BCERF on the Webhttp://envirocancer.cornell.edu

***Cornell University*****Program on Breast Cancer and ****Environmental Risk Factors****in New York State ****(BCERF)**

## Acknowledgments	– funding

**	****This material is based upon work supported by ****Smith Lever funds from the Cooperative State Research,  Education, and Extension Service, ****US Department of Agriculture and a grant from ****the New York State Departments of Health and Environmental Conservation. **
**	****Any opinions, findings, conclusions, or recommendations expressed in this module are those of the author and do not reflect the view ****of the grantors.**
** **

**Notes:**
This material is based upon work supported by Smith Lever funds from the Cooperative State Research,  Education, and Extension Service, US Department of Agriculture and a grant from the New York State Departments of Health and Environmental Conservation.  
Any opinions, findings, conclusions, or recommendations expressed in this module are those of the author and do not reflect the view of the grantors.

## Acknowledgements	– production and design

**Graphics & Animation:****  -   Mari Stewart ****  -   Sean Gardner ****  -   Jason Hernandez**
**Narration:****  -   Mari Stewart**
**Guidebook Formatting: ****  -   Neil Rotach****  -   Carin Rundle****  -   Mari Stewart**

**Notes:**
Graphics & Animation:
     Mari Stewart     Sean Gardner and      Jason Hernandez
Narration:
     Mari Stewart
Guidebook Formatting:
     Neil Rotach      Carin Rundle and     Mari Stewart