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Behavioral Findings from the Agricultural Health Study Tuesday, August 21 10:30 AM

Michael Alavanja, Dr.P.H. Captain, USPHS Senior Investigator, Division of Cancer Epidemiology and Genetics, NCI 2007 North American Pesticide Applicator Certification & Safety Education Workshop August 20-23, 2007 Portland Maine.

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Behavioral Findings from the Agricultural Health Study Tuesday, August 21 10:30 AM

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  1. Michael Alavanja, Dr.P.H.Captain, USPHSSenior Investigator, Division of Cancer Epidemiology and Genetics, NCI2007 North American Pesticide ApplicatorCertification &Safety Education WorkshopAugust 20-23, 2007Portland Maine

  2. Behavioral Findings from the Agricultural Health StudyTuesday, August 2110:30 AM

  3. Do pesticides cause cancer ? • Few strong and consistent associations linking a single chemical to a single cancer. • Animal/laboratory studies show most pesticides in current use to be non-genotoxic. • Exposure assessment in previous epidemiologic studies was general weak, they were based on interviews and could suffer from case recall bias. • Studies of pesticide manufactures are generally too small to give meaningful results for cancer • Exposures among the general population in developed countries are relative low and effect hard to measure. • In summary: Neither animal studies nor human studies give a compelling case for an association.

  4. Background World-wide occupational exposures to pesticides exceed 1.8 billion people (World Bank estimate). • Everyone in the USA has some indirect exposure to pesticides (NHANES). • Agricultural Insecticides as a group labeled as probable (group 2A) human carcinogens by IARC. • Only arsenic and dioxin are listed as human carcinogens by IARC. • Vital public health need to identify human carcinogens on the market!

  5. Background • The Occupational & Environmental Epidemiology Branch, NCI has a history of ecological and case-control of farmers starting in the 1970’s. • A common critique- exposure assessment was weak. • I proposed the idea for a prospective cohort study of pesticide applicators in 1989- 1990. • In 1991 an extramural advisory group recommended the OES conduct the AHS. • The Agricultural Heath Study entered the field in December 12, 1993. • Other federal partners joined the team in 1994 (EPA), 1995 (NIEHS) and NIOSH (1997).

  6. Design AHS(www.aghealth.org) • Prospective cohort study of 89,658 pesticide applicators & spouses. • 82% of target population enrolled 1993-1997. • Little loss to follow-up (<2%). • Cancer incidence and mortality updated annually. • Comprehensive exposure assessment information on 82 pesticides collected at three points in time. • Questionnaire exposure assessment evaluated with field measurements of pesticides. • Buccal cells collected on >35,000 study subjects.

  7. Agricultural Health Study: Major Milestones in Time 85 manuscripts May 16,2007 1993 2000 2012 Jan 1, 2005: Third Interview & DNA Analyzed & Questionnaires validated: Disease Etiology Phase Jan 1, 1998: Second Interview & DNA Collection begins & Questionnaire validation begins Dec 13, 1993: First Interview

  8. Cumulative and Projected AHS Publications (as of 1/31/2007)

  9. Disease Etiology In the AHS Central Research Objectives: 1. Characterize exposures to the highest degree possible. 2. Identify pesticides and other agricultural exposures that increase the risk of cancer . 3. Identify the mode of action of agents causing disease.

  10. Types of Pesticide Exposure • Acute exposure events. High exposure dose, short term. • Chronic exposure. Low exposure dose, long term.

  11. Behavioral Findings from the Agricultural Health Study (Acute Exposures) • Pesticides spills, splashes and immersions resulting from equipment maintenance, spot spraying, mixing and loading have resulted in relatively high pesticides exposure (High Pesticide Exposure Events-HPEE). • During their working lifetime 14 percent of licensed pesticide applicators in the AHS cohort had “an incident or experience while using a pesticide which caused an unusually high personal exposure. • Long-term adverse health effects can result from exposures at levels associated with these events. • Studying the etiology of these events may help us construct effective prevention programs.

  12. Behavioral Findings from the Agricultural Health Study (Chronic Exposure) • The major routes of chronic pesticide exposure are being evaluated in the Agricultural Health Study. • Long-term adverse health effects have been observed with chronic exposures to pesticides. • Studying the etiology of diseases associated with chronic exposure can help us construct effective prevention programs.

  13. Acute Exposure

  14. Determinants of High Pesticide Exposure Events (HPEE)

  15. Determinants of High Pesticide Exposure Events (HPEE)

  16. Chronic Exposure

  17. Agricultural Health StudyPesticide Exposure Estimates Calculating Cumulative Exposure Index: Cumulative Exposure = Intensity * Duration Where: Intensity = Exposure scores obtained from algorithms Duration = Days/years * Years/life-time = days/life-time From: Dosemeci et al. Ann Occup Hyg 46:245-260, 2002.

  18. Questionnaire Evaluation: Monitoring Visits

  19. Questionnaire Evaluated with Field Measurements of 2,4-D and Other Pesticides Technician observations MLA Questionnaire } Day 1 Day 2 Day 3&4 • Mix Load Apply (MLA). • Hand wipes after MLA • Dermal patches • Air measurements Collect full first morning void 3. Collect each void from MLA through next morning void. Collect full first morning void

  20. Comparison of Questionnaire Based Intensity Scores and Field Measurements 2,4-D(Thomas et al., in review)

  21. Field Studies • AHS PES Study • Pre and Post-application urine, hand wash, dermal patch, and air measurements during 107 agricultural application days of 2,4-D or chlorpyrifos • NIOSH OFES Study • Pre and Post-application urine samples, hand rinse, air and dermal patch samples during 144 application days of fungicides to orchards

  22. Post-Application Urine Concentrations (ug/L):Number of measurements and geometric mean by type of glove and application method for 2,4-D applicators from PES 66-75% reduction for applicators who applied using gloves versus no gloves 33-51% reduction for applicators who applied using Broadcast versus Handspray

  23. Relative Geometric Mean Concentration of 2,4-D Detected in Urine, Hand Wash, Dermal Patch and Air Samples for Applicators Grouped by Tertiles of Algorithm Score

  24. Hygiene PracticesAHS Phase II Interviews

  25. 41. After mixing or applying pesticides, do (did) you usually bathe or shower before continuing with other farm activities? 1. Yes 37% 2. No 63% 42. Do (did) you usually wear the same work clothes you used to mix or apply pesticides two or more days without washing them? 1. Yes 5% 2. No 95% 43. Do (did) you usually take your work boots off before entering your home? 1. Yes 78% 2. No 21% 3. Do not wear 1%

  26. 44. Are (were) the clothes you use(d) when mixing or applying pesticides usually washed separately? 1. Yes 74% 2. No 26% 45. Are (were) agricultural or commercial pesticides ever stored (even temporarily) in your home or basement? 1. Yes 13% 2. No 87% 46. How far is your house from the nearest field or orchard where pesticides are applied? 1. No pesticides applied on farm 1% 2. Less than 50 feet 5% 3. 50-99 feet 11% 4. 100-199 feet 23% 5. 200-1/4 mile (1320 ft) 46% 6. GT 1/4 mile 13%

  27. 47. Does (did) the farm vehicle you usually use to apply pesticides have an enclosed cab? 1. Yes 64% 2. No 36% 48. Do (did) you usually spray with the windows closed? IF ANSWER IS “IT DEPENDS ON THE WEATHER”,THEN ASK: When it is (was) warm, what do you do? 1. Yes 94% 2. No 6% 49. Does (did) your cab have a charcoal filter? 1. Yes 27% 2. No 73%

  28. 50. Do (did) you usually repair your own spraying or mixing equipment? 1. Yes 93% 2. No 7% 52. For most of the herbicides, insecticides and fungicides that you use(d), do (did) you usually apply ... 1. less than the minimum recommended label rate 20% 2. more than the recommended label rate 1% 3. the recommended rate 79% 53. Have you substituted biological or cultural practices (resistant varieties, pheromones, Bt sprays, tillage, planting/harvesting date adjustments, etc.) for any of your chemical pesticide applications? 1. Yes 31% 2. No 69%

  29. Risk Perception Questions The next questions ask about your views regarding the occupation of farming. Do you agree or disagree with the following statements? 54. Farming is more dangerous than jobs in industry or manufacturing. 1. agree 64% 2. disagree 36% 55. Accidents are just one of the occupational hazards of farming that must be accepted if you are going to be in the business. 1. agree 54% 2. disagree 46% 56. During a normal work week, it's common for me, while doing farm work, to experience a number of 'close calls' that under different circumstances might have resulted in personal injury or property loss 1. agree 19% 2. disagree 81% 57. To make a profit, most farmers take risks that might endanger their health. 1. agree 32% 2. disagree 68%

  30. Odds for use of gloves when mixing by number of “Risky” responses: gloves no gloves odds [95% Conf. Interval] ------------------------------------------------------------ 20213 5534 3.65251 3.54550 3.76275 ------------------------------------------------------------ risk4 | gloves no gloves odds [95% Conf. Interval] ------------+------------------------------------------------------------- 0 | 3341 601 5.55907 5.09667 6.06341 1 | 6507 1481 4.39365 4.15259 4.64871 2 | 4661 1458 3.19684 3.01425 3.39050 3 | 1961 772 2.54016 2.33719 2.76075 4 | 272 125 2.17600 1.76068 2.68929 -------------------------------------------------------------------------- risk4 | Odds Ratio chi2 P>chi2 [95% Conf. Interval] ------------+------------------------------------------------------------- 0 | 1.000000 . . . . 1 | 0.790358 19.88 0.0000 0.712536 0.876680 2 | 0.575068 108.46 0.0000 0.517511 0.639028 3 | 0.456939 166.96 0.0000 0.404515 0.516157 4 | 0.391433 68.26 0.0000 0.310773 0.493027 -------------------------------------------------------------------------- Score test for trend of odds: chi2(1) = 247.56 Pr>chi2 = 0.0000

  31. Conclusions: From Exposure Algorithm Assessment • For 2,4-D applicators we observed a significant correlation between the questionnaire-based algorithm (intensity-factor) and post-application urine concentrations. • Important additional determinants of exposure have been identified to refine the exposure algorithm.

  32. Conclusions: From Exposure Algorithm Assessment • Proper glove use is the most influential item of personal protective equipment which mitigates chronic exposure. • Other personal protective equipment plays a role in mitigating exposure. • Methods of application result in quantifiable different rates of exposure. • Attitudes toward risk play an important role in chronic exposure. • Other determinants of chronic exposure are being identified and quantified.

  33. Conclusions: From Exposure Algorithm Assessment • Pesticides applied changed between Phase I and Phase II • Number of applicators who reported use in the last year increased for 3 and decreased for 18 of 22 pesticides listed in the enrollment questionnaire. • Use of chemically resistant gloves when mixing/applying pesticides has increased since enrollment. • AHS cohort: • 89% actively farmed since enrollment. • 85% reported use of pesticides

  34. Thank you for listening: AHS Research Team

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