Michael Alavanja, Dr.P.H. Captain, USPHS Senior Investigator, Division of Cancer Epidemiology and Ge

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
Study Tuesday, August 211030 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 1970s.
• 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 (lt2).
• 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 gt35,000 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
(No Transcript)
11
(No Transcript)
12
(No Transcript)
13
Types of Pesticide Exposure

• Acute exposure events. High exposure dose, short
  term.
• Chronic exposure. Low exposure dose, long term.

14
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.

15
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.

16
Acute Exposure

17
Determinants of High Pesticide Exposure Events
(HPEE)

18
Determinants of High Pesticide Exposure Events
(HPEE)

19
Chronic Exposure

20
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 46245-260, 2002.
21
Questionnaire Evaluation Monitoring Visits
22
Questionnaire Evaluated with Field Measurements
of 2,4-D and Other Pesticides
Technician observations MLA
Questionnaire

Day 1 Day 2 Day
34

• 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
23
Comparison of Questionnaire Based Intensity
Scores and Field Measurements 2,4-D(Thomas et
al., in review)
24
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

25
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
26
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
27
Hygiene PracticesAHS Phase II Interviews
28
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
29
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
30
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
31
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
32
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
33
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 Pgtchi2 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
Prgtchi2 0.0000
34
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.

35
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.

36
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

37
Thank you for listening AHS Research Team