ChronicHealthEffects_PesticidesPresentation_0.ppt

Health hazard due to chemicals

1. The Long Term Effects of Pesticide Exposure on
Human Health
An Update on Recent Studies
Study IssuesStudy Issues
Skin ProblemsSkin Problems
Respiratory Problems Respiratory Problems
Reproduction Reproduction
Nervous System Nervous System
CancersCancers
Helen Murphy, FNP-MHS
Pacific Northwest Agricultural Safety and Health Center
University of Washington

2. Problems Studying
Long Term Effects
Time delay between exposure and health Time delay between exposure and health
outcome outcome
Attribution: is it from pesticides or something Attribution: is it from pesticides or something
else?else?
–Other factors Other factors
Poor exposure assessment Poor exposure assessment
– by locationby location
– by job classification by job classification
– recall biasrecall bias
Incomplete information on health outcomesIncomplete information on health outcomes
What goes unpublished? What goes unpublished?

3. Studying Long Term Effects
Exposure
1.Location
2.Job Title
3.Equipment Sales
4.Use questionnaire
5.Biological monitoring
Health
Problem
1.Questionnaires
2.Medical Records
3.Cancer Registries
4.Clinical Measurements
Intervening Factors
Diet
Genetics
Illnesses
Smoking
Other Chemicals
Environmental Factors

Intervening
Factors

4. How do we study the long term
health effects of pesticides?
Case series
cases seen by a doctor cases seen by a doctor
Ecological
comparing two geographic regionscomparing two geographic regions
Cross sectional
snap shot surveysnap shot survey
Case-control
compare exposures of people with and without a health problemcompare exposures of people with and without a health problem
Cohort
follow exposed and unexposed people to see who gets the health problemfollow exposed and unexposed people to see who gets the health problem
Randomized controlled trial (RCT)
experimental - animalsexperimental - animals

5. Random
assignment
Non-random
assignment
Analytic:
comparison group
OBSERVATIONAL: No control
over who is exposed and non-
exposed
EXPERIMENTAL: Control
over who is exposed and non-
exposed
* Clinical trials (e.g. symptoms
from spray with toxic pesticide vs.
spray with non-toxic pesticide)
* Community intervention
studies (e.g. community’s health
after IPM vs. after pesticide use)
Descriptive: no
comparison group
Observational vs. Experimental

6. Descriptive Studies
-no comparison group-
Case reviews: Investigate cases of
pesticide poisoning (e.g. LNI investigated
cholinesterase depressions)
Surveillance: Report cases of poisoning
(e.g. Pesticide Incidence Reporting and Tracking PIRT
program)
Survey: Pesticide use and health
problems

7. Analytic: Comparison Group
Case Control: Select
cases with or without the
health problem and look
back to compare their
exposures or non-
exposure
Cohort: Select exposed and
non exposed (pregnant
sprayers and pregnant non-
sprayers) then follow over
time to determine health
outcome
Cross Sectional:
Compare present
health problem and
exposures at one
point in time
Retrospective Cohort: Select groups (cohorts) who are
exposed and unexposed (sprayers vs non-sprayers) and look
back at their health outcomes (pregnancies)
ECOLOGICAL: Compare rates of a pesticide health
problem in 2 populations by exposure areas
Community LevelCommunity Level
Past Future
RETROSPECTIVE PROSPECTIVE
Now
Individual LevelIndividual Level

8. Information Sources
Pesticide Literature Review 1990 – 2003Pesticide Literature Review 1990 – 2003
– 12, 061 papers: 30 reviews/254 primary12, 061 papers: 30 reviews/254 primary
– Rated by quality scoring 1-7Rated by quality scoring 1-7
– Summary conclusions and evaluationSummary conclusions and evaluation
Mother-Child Pair StudiesMother-Child Pair Studies
– Exposures measured with bio-markers Exposures measured with bio-markers
(urine, blood, personal air monitors)(urine, blood, personal air monitors)
– Data on intervening factors (smoking etc)Data on intervening factors (smoking etc)
– Clinical measurements on childrenClinical measurements on children

9. Sources
US Agriculture Health Study n=89,658

Sample: recruited from Sample: recruited from 1993 – 1997
–Private applicators: 52,395
–Spouses: 32,347
–Commercial applicators: 4,916
Detailed questionnaires: (validated)
– Pesticides: kinds, frequency, application practices
– Lifestyle: diet, exercise, smoking, alcohol
– Medical history: personal and family
–Other farm exposures: solvents etc….
Cancer and non-cancer outcomes:
–Cancer registries
–Vital statistics
–Interviews

10. Skin ProblemsSkin Problems

11. Skin Problems
Skin: Skin: Primary Primary
exposure route of exposure route of
pesticidespesticides
Most common effect Most common effect
is contact dermatitis is contact dermatitis
– AllergicAllergic
– IrritantIrritant
• 15-25% pesticide 15-25% pesticide
illness reports illness reports

12. Coexisting Factors in Agricultural
Workplace
Plant materialsPlant materials
SolventsSolvents
FuelsFuels
RubberRubber
CleansersCleansers
CreamsCreams
MoistureMoisture
Cold temperaturesCold temperatures
Physical abrasionsPhysical abrasions

13. Skin Problems
Fungicide induced irritant or allergic Fungicide induced irritant or allergic
dermatitisdermatitis
 DithiocarbamatesDithiocarbamates
•Maneb Maneb (MANEX, PENTATHLON)(MANEX, PENTATHLON)
•Mancozeb Mancozeb (DITHANE)(DITHANE)
•Thiram Thiram (ROOTONE, PROSPER)(ROOTONE, PROSPER)
•Zineb Zineb (NR)(NR)
 SulfurSulfur
 Benomyl (nr)
 Captan (BONIDE, ENHANCE )
 Chlorothalonil (APPLAUSE ,
BRAVO )

Source: M.A. O’Malley, Skin reactions to pesticides, Occup Med
State Art Rev 12 ([1997]2): 327–45.

14. Skin Problems
InsecticidesInsecticides
Miticide: propargite Miticide: propargite
OP’s: skin sensitizersOP’s: skin sensitizers
•Intermittent dermatitis reports in Wa and Ca Intermittent dermatitis reports in Wa and Ca
•Malathion and ChlorpyrifosMalathion and Chlorpyrifos
Carbamates: Reported cases in Wa with Carbamates: Reported cases in Wa with
carbaryl carbaryl
 Pyrethroids – Topical (skin surface) Pyrethroids – Topical (skin surface)
irritation and paresthesiasirritation and paresthesias

15. Skin Problems
Soil fumigants can cause irritant Soil fumigants can cause irritant
dermatitis and chemical burnsdermatitis and chemical burns
– methyl bromide methyl bromide (TRI-CON)(TRI-CON)
– metam sodium metam sodium (VAPAM) (VAPAM)
Herbicides - induced irritant or allergic Herbicides - induced irritant or allergic
dermatitisdermatitis
– paraquat – diquat – highly irritating – 53% paraquat – diquat – highly irritating – 53%
paraquat applicators had a rash or burn in paraquat applicators had a rash or burn in
one study* one study*
* Source: Castro-Gutierrez N, McConnell R, Andersson K, Pacheco-Anton F, Hogstedt,C. Respiratory symptoms, spirometry and
chronic occupational paraquat exposure. Scand J Work Environ Health 1997;23:421–427.

16. Severe Contact Dermatitis
Cartap + [Fenobucarb, Dimethoate and Methyl Parathion x 20 yrs]

17. Respiratory Problems
•A few pesticides are ‘sensitizers’ causing A few pesticides are ‘sensitizers’ causing
allergic reactions along with OTHER triggersallergic reactions along with OTHER triggers
–dusts, pollens, animals, diesel, molds, grains, hay, dusts, pollens, animals, diesel, molds, grains, hay,
disinfectantsdisinfectants
Organophosphates and carbamates inhibit Organophosphates and carbamates inhibit
cholinesterase resulting in cholinesterase resulting in
–Constriction of the bronchial tubesConstriction of the bronchial tubes
–Increased secretionsIncreased secretions
–Difficulty in breathingDifficulty in breathing

18. Respiratory Problems
Insecticide related wheezing with*: Insecticide related wheezing with*:
–parathion (NR) parathion (NR)
–Chlorpyriphos (Lorsban/Dursban)Chlorpyriphos (Lorsban/Dursban)
–malathion malathion ((MAXIDE)MAXIDE)
Herbicide related wheezing with*: Herbicide related wheezing with*:
–paraquatparaquat
–Atrazine (Shotgun…95 labels)Atrazine (Shotgun…95 labels)
–Alachlor (Lasso)Alachlor (Lasso)
–chlorimuron ethyl (NR) chlorimuron ethyl (NR)
–EPTC EPTC ((EPTAM, ERADICANE) EPTAM, ERADICANE)
*Source: Hoppin JA et al (2006). Pesticides and Adult Respiratory Outcomes in the
Agricultural Health Study. Ann. New York Academy of Sciences. 1076:343-354.

19. Chronic Bronchitis in Farm Women and
Pesticides
InsecticidesInsecticides
Dichlorvos Dichlorvos (Fulex/ (Fulex/
Vapona) Vapona)
DDTDDT
HerbicidesHerbicides
Cyanazine Cyanazine (Bladex)(Bladex)
ParaquatParaquat
FumigantFumigant
methyl bromidemethyl bromide
Source: Valcin M, et al. Chronic bronchitis among nonsmoking farm women in the agricultural health study. J Occup
Environ Med. 2007 May;49(5):574-83.
Controlling for:
• Smoking
• 2
nd
hand smoke
• Asthma
• Usual suspects:
dust, solvents,
manure

20. Reproductive
Menstrual CyclesMenstrual Cycles
Birth defectsBirth defects
Time to pregnancyTime to pregnancy
Small for Age at BirthSmall for Age at Birth
MiscarriagesMiscarriages

21. Women using pesticides have 1.5 x Women using pesticides have 1.5 x
increased odds of *increased odds of *
Longer cyclesLonger cycles
Missing a periodMissing a period
Hormonally active pesticides increase Hormonally active pesticides increase
odds of missed periods, long cycles, odds of missed periods, long cycles,
bleeding mid cycle. bleeding mid cycle.
LindaneLindane
AtrazineAtrazine
Mancozeb or ManebMancozeb or Maneb
Source: Farr SL, Cooper GS, Cai J, Savitz DA, Sandler DP. Pesticide use and menstrual cycle
characteristics among premenopausal women in the Agricultural Health Study. (2004). American
Journal of Epidemiology, 160(12):1194-204.
Menstrual Cycle ChangesMenstrual Cycle Changes

22. Birth Defects:
Study Design Issues
Indirect exposure measurements Indirect exposure measurements
without biomarkers:without biomarkers:
Work recordsWork records
Places of residencePlaces of residence
DatabasesDatabases
QuestionnairesQuestionnaires
Only cases that survive birth are Only cases that survive birth are
counted ( miscarried fetuses? )counted ( miscarried fetuses? )

23. Birth Defects
Consistent findings with Consistent findings with
Limb reductions - Uro-genital defectsLimb reductions - Uro-genital defects
Central nervous systemCentral nervous system
Cleft palates/lips: marginal significant w/maternal Cleft palates/lips: marginal significant w/maternal
exposure exposure
Eye – heart defectsEye – heart defects
Not definitive until better exposure analysis Not definitive until better exposure analysis
with the US Children’s Health Studywith the US Children’s Health Study
Source: Sanborn M, Cole D, Kerr K, Vakil C, Sanin LH, Bassil K. Pesticides Literature Review. Ontario
College of Family Physicians. Toronto 2004.

24. Time to Pregnancy
SStudies tudies suggestsuggest that occupational that occupational
exposure increase time needed to become exposure increase time needed to become
pregnantpregnant
20% 20%  in women engaged in pesticide in women engaged in pesticide
activities + husband also engaged in same– activities + husband also engaged in same–
but but impreciseimprecise due to small numbers due to small numbers
Associated with dicamba, glyphosate, 2,4-Associated with dicamba, glyphosate, 2,4-
D, thiocarbamates, OP’s although not D, thiocarbamates, OP’s although not
statistically significant statistically significant
Source: Curtis KM, Savitz DA, Weinberg CR, Arbuckle TE. The effect of pesticide exposure on time to
pregnancy. Epidemiology. 1999 Mar;10(2):112-7.

25. Probable linkProbable link
Fetal and maternal blood Fetal and maternal blood
samples for OP by-products and samples for OP by-products and
newborn lengthsnewborn lengths
Chlorpyrifos and diazinon Chlorpyrifos and diazinon [by-[by-
products measured in fetal and maternal products measured in fetal and maternal
blood]blood] associated to lower birth associated to lower birth
weight and length*weight and length*
Small for Age at Birth
* Whyatt RM et al. Biomarkers in assessing residential insecticide exposures during pregnancy
and effects on fetal growth.Tox Applied Pharm 206 (2): 246-254 AUG 7 2005

26. Miscarriages

SStudies suggest an association tudies suggest an association
Critical exposure windows and certain Critical exposure windows and certain
pesticides pesticides
One - four months before conception One - four months before conception
Non use of PPE increased risk 5 fold in one studyNon use of PPE increased risk 5 fold in one study
Study Method ProblemsStudy Method Problems
No data on miscarriage rates in general populationNo data on miscarriage rates in general population
High % go undetectedHigh % go undetected
?? Role of other farm toxins (animal viruses, heavy ?? Role of other farm toxins (animal viruses, heavy
metals) largely unknown in studiesmetals) largely unknown in studies
Sources: Arbuckle et al 1999 and 2001; Garry VF et al 2002

27. Health Risks to Children
Asthma Asthma
Cancers Cancers
Neuro-developmental Neuro-developmental
problems problems
Small for age at birth Small for age at birth
Congenital defects Congenital defects

28. Asthma
Children exposed to herbicides Children exposed to herbicides
in 1in 1
stst
year of life 4.5x greater year of life 4.5x greater
risk of developing asthma risk of developing asthma
before age 5. insecticides 2.4x before age 5. insecticides 2.4x

Source: Salam MT, Li YF, Langholz B, Gilliland FD. Early-life environmental risk factors for asthma: findings
from the Children's Health Study. Environ Health Perspect. May 2004;112(6):760-765.

29. The Agriculture Health Study
Cancers in Children
All cancer incidence: a third higher than rates in All cancer incidence: a third higher than rates in
general populationgeneral population
All lymphomas 2 x higher - Hodgkin's 2.5 x higherAll lymphomas 2 x higher - Hodgkin's 2.5 x higher
Exposure risks Exposure risks
  risk if father NOT use chemically resistant glovesrisk if father NOT use chemically resistant gloves
 NOT associated to parental application frequency NOT associated to parental application frequency
  risk with aldrin (2.66) but not a known carcinogenrisk with aldrin (2.66) but not a known carcinogen
• Limitations: only 5 year follow up and small numbersLimitations: only 5 year follow up and small numbers
Source: Flower KB, Hoppin JA, Lynch CF, Blair A, Knott C, Shore DL, Sandler DP. Cancer risk and parental pesticide application in children
of Agricultural Health Study participants. Environ Health Perspect. 2004 Apr;112(5):631-5.

30. Nervous System

Mental HealthMental Health
Neurological Symptoms Neurological Symptoms
Parkinson’s DiseaseParkinson’s Disease

31. Mental Health
Depression, emotional disorders and suicides*Depression, emotional disorders and suicides*
–Earlier poisonings ~ minor depression Earlier poisonings ~ minor depression
–Canada suicides ~ pesticide useCanada suicides ~ pesticide use
US Agriculture Health Study – wives of US Agriculture Health Study – wives of
pesticide applicators pesticide applicators
–Self report or MD diagnosed depression in women Self report or MD diagnosed depression in women
3.26 x higher risk if earlier poisoning**3.26 x higher risk if earlier poisoning**
** Beseler C, et al. Depression and Pesticide Exposures in Female Spouses of Licensed
Pesticide Applicators in the Agricultural Health Study Cohort. J Occ Env Med •Volume 48,
Number 10, October 2006.
* Sanborn M, Cole D, Kerr K, Vakil C, Sanin LH, Bassil K. Pesticides Literature Review. Ontario College
of Family Physicians. Toronto 2004.

32. Adult Nervous System Problems
Subtle diminished function of nervous systemSubtle diminished function of nervous system
– Occur after severe acute poisonings (OPIDN)Occur after severe acute poisonings (OPIDN)
– Chronic low level exposureChronic low level exposure
Self-reported neurologic symptoms Self-reported neurologic symptoms
associated with cumulative exposure to associated with cumulative exposure to
moderate levels of fumigants, moderate levels of fumigants,
organophosphates, organochlorines*organophosphates, organochlorines*
* Kamel F, et al Neurologic Symptoms in Licensed Private Pesticide Applicators in the
Agricultural Health Study. Environ Health Perspect 113:877–882 (2005).

33. Parkinson’s and Pesticides
New cases among applicators associated to overall New cases among applicators associated to overall
use, cumulative days (years x frequency) of pesticide use, cumulative days (years x frequency) of pesticide
application (2.3 risk), hazardous practices, and some application (2.3 risk), hazardous practices, and some
specific pesticides. specific pesticides.
–High exposure event (spill) and not bathing w/in 1 hourHigh exposure event (spill) and not bathing w/in 1 hour
–Use of PPE was protectiveUse of PPE was protective
Evidence shows an association but questions remainEvidence shows an association but questions remain
– Is it a causal relationship?Is it a causal relationship?
– Is it related to any particular pesticide? Is it related to any particular pesticide?
– Is it a combination of a pesticide and another toxicant?Is it a combination of a pesticide and another toxicant?
Kamel F. et al. Pesticide Exposure and Self-reported Parkinson’s Disease in the
Agricultural Health Study. Am J Epidemiol 2007;165:364–374

34. Cancers
Brain TumorsBrain Tumors
BreastBreast
PancreaticPancreatic
LymphomasLymphomas
Leukemia Leukemia
KidneyKidney
ProstateProstate
LungLung
OvarianOvarian

35. Brain Tumors
5 Cohort Studies (all retrospective cohorts) 5 Cohort Studies (all retrospective cohorts)
all +all +
Exposure estimations problematicExposure estimations problematic
 Association membershipAssociation membership
 Pesticide licensees: use or notPesticide licensees: use or not
 Pesticide and application equipment purchases*Pesticide and application equipment purchases*
 Residence in high pesticide using areasResidence in high pesticide using areas
Norwegian Study*: one type of tumor Norwegian Study*: one type of tumor (non-(non-
astrocytic neuroepithelial)astrocytic neuroepithelial) >3 x risk >3 x risk
Kristensen P et al. Cancer in offspring of parents engaged in agricultural
activities in Norway: incidence and risk factors in the farm environment.
International Journal of Cancer. 1996; 65: 39–50.

36. Breast Cancer
Previous studies: mixed results – some studies Previous studies: mixed results – some studies
positive and some negative positive and some negative
–Case/control ; 1.8 x risk if in field during spraying , 2.0 x if Case/control ; 1.8 x risk if in field during spraying , 2.0 x if
not use PPE not use PPE
US Agriculture Health Study US Agriculture Health Study unclearunclear risk* : risk* :
–Proximity of farm to areas of pesticide application Proximity of farm to areas of pesticide application
–Husband’s use of 2,4,5-TP and possibly dieldrin, captan, and Husband’s use of 2,4,5-TP and possibly dieldrin, captan, and
2,4,5-T 2,4,5-T
New DDT study - 5 fold risk with exposure to DDT *New DDT study - 5 fold risk with exposure to DDT *
–p,p´-DDT measured exposure at < age 20
**Cohen et al. (2007) DDT and Breast Cancer in Young Women: New Data on the Significance of Age at
Exposure. EHP. 115(10) 1406-1414.
*Engel L, et al (2005). Pesticide Use and Breast Cancer Risk among Farmers' Wives in the
Agricultural Health Study American Journal of Epidemiology, 161: 121-135.

37. Other Cancers
Pancreatic: Pancreatic: Aerial applicators (9,961) 2.71x Aerial applicators (9,961) 2.71x
risk than flight instructors (9,969) risk than flight instructors (9,969)
Non Hodgkin’s Lymphoma Non Hodgkin’s Lymphoma [[Immunologic + Immunologic +
environmental factors]environmental factors]:: 23/27 studies positive.23/27 studies positive.
2-4 D a precipitant.2-4 D a precipitant.
Leukemia: Leukemia: 14/16 studies positive14/16 studies positive
KidneyKidney: : Increased mortality rates on Increased mortality rates on
pentachlorophenol chemical company workerspentachlorophenol chemical company workers
Source: Sanborn M, Cole D, Kerr K, Vakil C, Sanin LH, Bassil K. Pesticides Literature Review. Ontario
College of Family Physicians. Toronto 2004.

38. US Agriculture Health Study Cancer
Outcomes
Prostate: Prostate: 5,322 male applicators 3.75 risk > age 50 5,322 male applicators 3.75 risk > age 50
with methyl bromide or chlorinated pesticides with methyl bromide or chlorinated pesticides
((organochlorines like DDT or endosulfan)organochlorines like DDT or endosulfan)
Lung: Lung: (non smokers)(non smokers) Dose-response with 2 herbicides Dose-response with 2 herbicides
and 2 insecticidesand 2 insecticides
–metolachlor (OR) = 5.0 in highest exposure groupmetolachlor (OR) = 5.0 in highest exposure group
–pendimethalin (OR) = 4.4 pendimethalin (OR) = 4.4
–chlorpyrifos (OR) = 1.9 chlorpyrifos (OR) = 1.9
–diazinon (OR) = 3.7 diazinon (OR) = 3.7
Ovarian: Ovarian: Female applicators 3 x more cases than Female applicators 3 x more cases than
general population general population

39. THE END
&

40. Research Websites
The US Agricultural Health StudyThe US Agricultural Health Study
http://aghealth.nci.nih.gov/http://aghealth.nci.nih.gov/
Columbia Center for Children’s Environmental Health Columbia Center for Children’s Environmental Health
http://www.mailman.hs.columbia.edu/ccceh/pesticides.htmlhttp://www.mailman.hs.columbia.edu/ccceh/pesticides.html
CHAMACOS CHAMACOS Center for the Health Assessment of Mothers and Children Center for the Health Assessment of Mothers and Children
of Salinas of Salinas
http://ehs.sph.berkeley.edu/chamacos/http://ehs.sph.berkeley.edu/chamacos/
The National Children’s StudyThe National Children’s Study
http://www.nationalchildrensstudy.gov/http://www.nationalchildrensstudy.gov/

41. Pesticide Information Websites
PICOL-Pesticide Information Center On PICOL-Pesticide Information Center On
Line WSULine WSU
http://picol.cahe.wsu.edu/LabelTolerance.hhttp://picol.cahe.wsu.edu/LabelTolerance.h
tmltml

PAN Pesticides Database:PAN Pesticides Database:
http://www.pesticideinfo.org/index.htmhttp://www.pesticideinfo.org/index.htm
CDMS Agro Chemical DatabaseCDMS Agro Chemical Database
http://www.cdms.net/LabelsMsds/http://www.cdms.net/LabelsMsds/
LMDefault.aspxLMDefault.aspx

42. http://creativecommons.org/licenses/by-nc-sa/3.0/http://creativecommons.org/licenses/by-nc-sa/3.0/
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0
Unported License.Unported License.