Chronic Neurological Effects of Pesticides

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					Chronic Neurological
 Effects of Pesticides

            Summary of
           Selected Studies

            September 2002

                Prepared by
           Marion Moses M.D.

          Pesticide Education Center
P.O. Box 225279, San Francisco CA 94122-5279
  Telephone 415-665-4722, Fax 4215-665-2396
Chronic Neurological Effects of Pesticides. - Marion Moses M.D.

                                                        Table of Contents

Explanation of Tables . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-2

Parkinson’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-7

Other Neurological Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7-12

References - Parkinson’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12-13

References - Other Neurological Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14-15

Footnotes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15-16
Chronic Neurological Effects of Pesticides. - Marion Moses M.D.                                               2

                                                  Some Notes on the Table
This table is a selective summary of studies of long term effects on the nervous system in adults with
potential occupational and environmental exposure to pesticides . Most are from articles published in English
in peer-reviewed journals. The studies are listed in chronological order by author – the most recent first.
        The source of pesticide exposure could be their occupation as farmers, agricultural workers, sprayers,
exterminators, formulators, or other jobs. The exposure could be from household, lawn/garden, pet, or other
pesticide use. Or it could be from potential pesticide exposures from living on a farm, in an agricultural spray
area, near a pesticide factory, or other environmental exposures.

                                                How The Studies Are Done
Epidemiology is the study of diseases and their causes in human populations. It compares groups of people
with an exposure or a disease to those without it.
        In the studies in this table, groups of people with Parkinson’s disease* or other neurological disease,
or with pesticide exposure are the “cases”. Groups of people without Parkinson’s or other neurological
diseases, or without poesticide exposure are the “controls”.
        The aim is to find out if the people with neurological disease (the cases) are more likely to have
exposure to pesticides than the people without neurological disease (the controls). Or to find out if the
people with pesticide exposure (the cases) are more likely to have neurological disease than those with
pesticide exposure (the controls).

                                            How Study Results are Reported
        Study results are reported as risk ratios. These ratios indicate whether the people with neurological
disease were more likely to have been exposed to pesticides (at increased risk), equally likely to have had
pesticide exposure (no difference in risk), or less likely to have had pesticide exposure (decreased risk) than
the people without neurological disease .
        Or whether the people with pesticide exposure were more likely to have neurological disease (at
increased risk), equally likely to have neurological disease (no difference in risk), or less likely to have
neurological disease (decreased risk) than the people without pesticide exposure.

         For example: In a study of Parkinson’s disease, the cases would be people with Parkinson’s, and
the controls people without it. There are three possible outcomes. The people with Parkinson’s could be more
likely, equally likely, or less likely to have pesticide exposure.
         1. More likely: If the ratio is greater than 1 (> 1), this means that the people with Parkinson’s were
more likely to have pesticide exposure – that pesticide exposure increases the risk of Parkinson’s. The size
of the ratio indicates how much the risk is increased. The larger the number the greater the risk. A ratio of
1.4 means a 40% increase in risk. A ratio of 2.0 means a doubling of the risk, or a 200% increase. At least
a doubling of the risk is considered more important than ratios less than 2.
         2. Equally likely: If the ratio is equal to one ( = 1) this means that there was no difference in
pesticide exposure found in the people with or without Parkinson’s – pesticides did not increase the risk of
Parkinson’s in the study.
         3. Less likely: If the ratio is less than one (< 1), this means that people with Parkinson’s were less
likely to have pesticide exposure than people without it, or the risk was decreased. The smaller the number
the lower the risk. A ratio of 0.80 means that people with Parkinson’s are 20% less likely to have been
exposed to pesticides. A ratio of 0.40, that they are 60% less likely.

         When studying humans, it is impossible to determine every factor that might influence the results
of a study. It might have occurred anyway, by chance. It is possible that any increase in risk was not from
pesticides, but something else. This could be something the researcher didn’t think of, or didn’t even ask
Chronic Neurological Effects of Pesticides. - Marion Moses M.D.                                                            3

about. Or it could be from pesticide exposure in combination with other unknown or unstudied factors.
Therefore, finding an increase in risk does not mean that pesticides “cause” Parkinson’s.
         This is why it is common to report increase in risk by stating that “pesticide exposure increases
the risk of Parkinson’s”, or “pesticide exposure is a risk factor for Parkinson’s”, and not that pesticides
“cause” Parkinson’s.

                                         Are the Study Results “Significant”?
There are methods to determine how strong the link or associations between neurological diseases and
pesticides are, or if they occurred by chance. They are called tests of statistical significance. The statistical
part is usually left out, and the results reported as “significant” or “not significant”. The two most common
tests are the “p” value, and confidence intervals.

         1. “p” value: This tests whether the findings could have occurred by chance 5% of the time or less.
The 5% is converted to a fraction and written as 0.05. For example, you will see the results as “p = 0.05"
(read as p equals point 0 5 ), or “p < 0.05" (read as p less than point 0 5), or “p # 0.05" (read as p less than
or equal to point 0 5).
         If the “p” value is less than or equal to 0.05, the findings are considered to be statistically
significant; that is, they are unlikely to have occurred by chance. The smaller the “p” value the more
significant the findings. For example” p # 0.01" (read as p less than or equal to point 0 1) means that it could
have occurred by chance 1% of the time or less.

         2. Confidence intervals: Another widely used test is called the confidence interval. It shows how
close the risk ratio found in the study is to the “true” or expected value. The chosen level is usually 95%.
This means that 95% of the time the study results will lie within the calculated interval. Another way of
saying this is that 5% of the time they will not.
          Because it is an interval, there are two numbers, with the lower number written first. If the lower
number of the confidence interval is less than or equal to one (# 1), than the increase in risk is “not
significant” or “non-significant”. If the lower number of the interval is greater than one (> 1) then the
increase in risk is considered “significant”.
         If the number of cases is small, the confidence interval can be very wide. When there is a very wide
interval between the lowest and the highest number, the less confidence you have in the findings. It usually
means that the number of cases found were very small.
         The larger the number of people in the study (the sample size), the narrower the confidence interval,
and the more significant the findings.

                                                    Commonly Used Ratios
          FR         Fecundability Ratio                          SM R    Standard ized M ortality Ratio
          OR         Od ds Ratio                                  SHR     Standardized Hospital Ratio
          PM R       Pro portionate Mortality Ratio               SM bR   Standardized M orbidity Ratio
          PC MR      Proportionate Cancer M ortality Ratio        SIR     Standardized Incidenc e Ratio
          PR         Prevalenc e Ratio                            SPR     Stand ard P roportional Ratio
          RR         Relative Risk (or Rate Ratio)                SRR     Stand ardized R ate Ratio

* Parkinson’s disease is used as an example, but the discussion refers to all of the neurological diseases listed in the
Chronic Neurological Effects of Pesticides. - Marion Moses M.D.                                                        4

                                                     Parkinson’s Disease

       Location             Source of Exposure                                     Findings (95% CI)                 Ref.

 US                         Age of PD 1 onset sibling pairs                                                         2002
 Case-control                 Pesticide exposure                         No differences seen                        Maher

 Taiwan                     Young onset PD1 (before age 40)                                                          2002
 Case-control                  Well water drinking                       Increased risk                              Tsai

 Italy                      Parkinso n’s disease                                           OR                        2002
 Case-control                  Farming as an occupation                  7.7 (1.4-44) p = 0.02                      Zorzon
                               We ll water use                           2.0 (1.1-3.6) p = 0.03

 Bra zil                     Parkinsonian syndrome                                   Follow-up                      2001
 Case report                   Glyphosate spray accident 54 y man        Syndrome develop ed 1 month later.        Barbosa

 India                      Parkinso n’s disease                                            OR                       2001
 Case-control                  Well water more than 10 yrs               Increased risk - signif.                   Behari

 US                         Parkinson’s disease - orchard workers                   Pre valence Ra tio              2001
 W ash. State                  Highest tertile yrs pest. exposure        2.0 (1.0 to 4.2)                           Engel
 Case-control                  Middle tertile yrs pest. exposure         1.9 ( 0.9 to 4.0) trend not sig.
                               Specific pesticide use                    No increased risk
                               Farming                                   No increased risk
                               Well water use                            No increased risk

 Israel                     Parkinson’s disease                                                                     2001
 Rura l south                   Pesticide exposure                       Strong predictor                         Herishanu

 US                         Parkinso n’s disease                                          OR                        2001
 Michigan                       Agricultural occupation                  1.74 (0.85- 3.60)                          Kirkey

 Meta-analysis              Parkinso n’s disease                         OR All Studies        OR U.S, Only          2001
 55 studies                    Rural re sidence.                         1.56 (1.18-2.07)      2.17 (1.54-3.06)   Priyadarshi
                               Well water use                            1.26 (0.97-1.64       1.44(0.92-2.24 )
                               Farming                                   1.42 (1.05-1.91)      1.72(1.20-2.46)
                               Pesticide exposure                        1.85(1.31-2.60)        2.16(1.95-2.39)

 Meta-analysis              Parkinso n’s disease                                           OR                        2000
 19 studies                    Pesticide exposure - all studies          1.94 (1.49-2.53)                         Priyadarshi
                               Pesticid e exp o. all studies U.S. only    2.15 (1.14-4.05)
                               Duration exposure to pesticides           No sig. dose-response found
                               Type of pesticide                         No specifics found

 US                         Parkinson’s disease mo rtality                             M ortality                    2000
 California                    Counties using agric. pesticides          Increased                                   Ritz
                               Insecticide use b y county2               Increased - dose-response

 Denmark                    Parkinso n’s disease                         Standardized Hospitalization Ratio         2000
                               Agricult / horticult.- men & wo men       1.32 (1.11-1.6)                           Tuchsen
                               Agricult / horticult.- me n only          1.34 (1.1-1.6)
                               Farmers                                   1.3 (1.03-1.6)

 India                      Parkinsonism syndrome                        4 patients recovered completely            1999
 Mumbai                        5 cases of OP 3 poisoning                 1 had repeated episodes w re-exposure      Bhatt
Chronic Neurological Effects of Pesticides. - Marion Moses M.D.                                                         5

 Sweden                     Parkinson’s disease                                              OR              1999
 Southern                      Agricultural work                        Increased risk                       Fall
                               Pesticide exposure                       Increased risk

 Finland                    Parkinson’s disease                                              OR              1999
                               Farming                                  No association                      Kuopio
                               Drinking well water                      No association
                               Pesticide/herbicide exposure             No association

 Australia                  Parkinson’s disease                                            OR                1999
 Rural                         Rural residence                          1.8 p < 0.001                       McCann
                               Herbicide / pesticide exposure           No significant difference

 US                         Parkinson’s disease                                             OR               1999
 New England                   Well-water use                           Inverse association (lower risk)     Taylor
 Case-control                  Pesticide / herbicide exposure           No association

 China                      Parkinson’s disease                                                              1998
 Hong Kong                     Number years exposed pesticides          Increased risk p= 0.10               Chan

 US                         Parkinsonian syndrome                                                          1998 Davis
 Case report                   Crop duster pilot poisoned OP 3          Possibly pesticide induced

 US                         Parkinson’s disease                                              OR              1998
 Detroit                       Occupational exposure herbicides         4.10 (1.37- 12.24)                   Gorell
 Case-control                  Occupational exposure insecticides       3.6 (1.8-7.2)
                               Farming as occupation                    2.8 (1.03- 7.6)

 Israel                     Pre-Parkinsonism syndrome                                                        1998
 Kkibbutzim                    Field crop exposure, espc. cotton        Increase risk p = 0.0007           Herishanu
                               Landscape work.                          Weaker association

 US                         Parkinson’s disease                                             OR              1998
 Multiethnic rural             Rural living                             Increased risk in blacks            Marder
 community                     Farming                                  Decreased risk in Hispanics
                               Drinking unfiltered water                Increased risk entire cohort

 Italy                      Parkinson’s disease                                              OR              1998
                               Well water use                           2.8 (1.5-5.3)                      Smargiassi
                               Pesticide / herbicide exposure           1.15 (0.6-2-46)

 China                      Parkinson’s disease                                             OR               1997
 Taiwan                        Paraqua t/ other herb/pesticide expos.   Increased risk - dose response       Liou
                               Hrb/pest. other than paraquat expos.     Decreased risk

 Italy                      Parkinson’s disease                                              OR              1996
 Sicily                        Lived most of life as farmer             0.6 (0.3-1.3 )                       Rocca

 Germany                    Parkinson’s disease                                             OR               1996
                               Pesticide use                            Increases risk - signif.            Seidler
                               Wood preservative exposure               Increased risk - signif.
                               Rural factors                            No association

 US                         Postmortem brain samples                    PD1 Alzeimers Controls               1994
 Miami                          Dieldrin detection                      30 % 14.3 %    0%      p=.03        Fleming

 Canada                     Parkinson’s disease - fruit farmers                            OR               1994
 British Columbia.             Pesticide handling or direct contact     Increased risk                     Hertzman
                                Type/class of pesticide                 No specific associations
Chronic Neurological Effects of Pesticides. - Marion Moses M.D.                                                                 6

 Canada                     Parkinson’s disease                                             OR                       1994
 British Columbia.             Working in orchards                      3.69 sig.                                    Kelly
 Okanaga Valley                Occupational exposure to pesticides      2.03, 2.3
                               Paraquat, azinophosmethyl, ferbam        >1
                               Contact with paraquat                    Sig. assoc. with postural tremors

 Italy                      Extrapyramidal symptoms                     2 yr latency between exposure and onset      1994
 case report                    Occ. expos. maneb fung. 37 y %                                                       Meco

 Spain                      Parkinson’s disease                                             OR                       1994
 Caceres                       Pesticide exposure                       Increased - borderline signif.              Morano
                               Agricultural work                        No association

 US                         Young onset PD1 (< age 50)                                          OR                  1993
 Washington State             Insecticide exposure                      5.75    p   <   0.001                     Butterfield
                              Herbicide exposure                        3.22    p   =   0.033
                              Residenc fumigated house                  5.25    p   =   0.046
                              Rural residence4
                                                                        2.72    p   =   0.027

 US                         Parkinso n’s disease                                                                    1993
 Rural Kansas                  Pesticide use                            Significant predictor o f risk             Hubble

 Canada                     Parkinso n’s disease                                                                    1992
 Calgary                       Occupational herbicide use               Significant predictor o f risk              Hubble

 Canada                     Parkinso n’s disease                                                OR                  1993
 Calgary                       Occup ational herbicide use              Increased risk                             Semchuk

 Canada                     Parkinso n’s disease                                                OR                  1991
 Calgary                       Rural living                             No increase                                Semchuk
                               Farm living                              No increase
                               Well water use                           No increase

 Spa in                     Parkinso n’s disease                                         OR                         1992
 Madrid                        Well water exposure $30 years            Increased risk p < 0.02                    Jimenez
                               Past exposure to pesticides              No association

 Italy                      Severe P arkinson’s                               Follow-up 4 months later               1992
 Case report                   72 yr old farmer acute onset             CT scan, MRI abnormalities6                  Sechi
                                Post 10% Diquat spill on hands5         Persistent signs / symptoms 7

 Italy                      Parkinso n’s disease                                Incidence / yr / 100,000            1991
 Ferrara                       Early onset cases urb an areas            3.1                                       Granieri
                               Early onset cases rural areas             6.32
                               All cases 1967-1987                      10.01
                               All cases in agricultural workers        20.6

 US                          PD 1 young (< 40) & old (> 60) onset                               OR                   1991
 Case-control                    Well water use                         No associations                              Stern
                                  Herbicide / pesticide exposure        No associations
                                  Residential history of rural living   No associations

 US                         Parkinso n’s disease                                                OR                  1991
 W ashington State             Farm job                                 3.1 (0.3-35)                               W echsler
                               Occup. or home pe sticide exposure       No clear trends
Chronic Neurological Effects of Pesticides. - Marion Moses M.D.                                                                7

 US                         Parkinso n’s disease                                         OR                       1991
 Kansas                         Rural living                           Increased risk signif.                     W ong
 Case-control                   Drinking well water                    Increased risk signif.
                                Farming                                No increased risk
                                Herbicide exposure                     No increased risk

 Canada                     Parkinson’s disease                                          OR                        1990
 British Columbia              Wo rking in orchard s                   3.69 (1.34-10.27)                         Hertzman
                               Contact with paraquat                   Positive association p = 0.01

 US                         Parkinso n’s disease                                         OR                       1990
 Kansas                         Rural living                           Increased risk signif.                     Koller
                                Drinking well water                    Increased risk signif.
                                Farming                                No increased risk
                                Herbicide / pesticide exposure         No increased risk

 Canada                     Parkinso n’s disease                                             OR                   1990
 Quebec                        Residence in rural areas                0.31 p = 0.05                              Zayed
                               Occupational exposure Mn, Fe, Al8       2.28 p = 0.07
                               Exposure more than 30 yrs               13.64 p # 0.05
                               Pesticide exposure                      No association
                               Farm work                               No association
                               We ll water use                         No association

 Hong K ong                 Parkinson’s disease                                              OR                    1989
 China                         Long time residence rural areas         Increased   risk   signif.                   Ho
                               Farming occupation                      Increased   risk   signif.
                               Herbicide / pesticide use               Increased   risk   signif.
                               Habitual consump. raw vegetables        Increased   risk   signif.

 China                      PD 1 onset before 47 yr (vs 54 or older)                    OR                        1987
                                Rural residence                        Increased risk p # 0.01                    Tanner
                                Drinking well water                    Increased risk p # 0.01

 Italy                      Parkinso n’s disease                                                                   1986
 Case repo rts                  41 yr old farmer                       Author claim s 1 st reported cases PD 1   Bo cchetta
                               38 yr pest. manuf. worker               directly trelated to pesticide use

 Canada                     Parkinson’s disease early onset                             OR                         1986
                               Raised in rural areas                   Increased p = 0.015                         Rajput

                                                 Other Chronic Neurological Effects
        Location                         Source of Exposure                        Findings (95% CI)                Ref.

 England                     Sheep dipping farmers OP3 exposure                 Neuro pathy Symp toms               2002
                                 Group with normal NCV 9                 7%                                        Jamal
                                 Group with abnormal NCV 9               52 %
                                 Motor and sensory NCV 9                 Sensory deficits, mainly small fibers
                                 Neuro spsychological tests              Increased anxiety, depression

 Sri Lanka                   Regular sprayers OP 3 pesticides                           NCV 9                       2002
                                Sensory nerves                           Decreased farmers p = 0.01              Peiris-John
                                Motor nerves                             Decreased fisherman p = 0.04
Chronic Neurological Effects of Pesticides. - Marion Moses M.D.                                                                   8

 Netherlands                 Farmer sprayers OP 3                             Between growing season                   2002
                                Senso ry nerve cond uction velocity      Reduced sig p=.04                          Peiris-John
                                Mo tor nerve co nduc tion velocity       Reduced sig p=.04
                                                                               During growing season
                                 Senso ry nerve cond uction velocity     Reduced farmers p <.01
                                 Mo tor nerve co nduc tion velocity      Reduced fishers p=.04

 Costa Rica                  Banana wo rkers10                                     Poisoned Group                     2002
                                Psycho moto r and visuom otor skills     Poorer performance                         W esseling
                                Language skills, affect                  Poorer performance
                                Digit-Symbol test                        Poorer performance - sig diff.
                                Neuropsychiatric symptoms                Marked increase
                                Expos. che inhib. 11 prior 3 m onths     Poorest performance

 France                      Vineyard workers exposed pesticides 12                     OR                             2001
 1977-1978                       Neuropsychiatric testing.               Poorer performance $ 2                        Baldi

 Michigan - Dow              2,4-D M anufacturing workers                                   OR                        2001
                                ALS 13 deaths                            3.45 (1.1-11.1)                              Burns

 England                     Chronic OP 3 expos. sheep farmers                        Findings                         2001
                                Vibration thresholds                     Higher in concentrate handlers14           Pilkington

 US                          Hispanic children                                     Cognitive tests                    2001
                                Agricultural vs nonagricultural          Lower performance                           Rohlman

 Costa Rica                  DD T expo sure - malaria workers                           Findings                      2001
 1950-97                       Neurobehav. tests overall perform.        20 % decrease (mean)                       VanW end
                               Verbal attn, visuomot. spd, seqnce        Differed most between groups
                                Increase risk attributable yrs expo s.   5 mo tor, sens., cognit. tests sig. diff
                                Increase neuropsyc/psychiat. symp        3.98 (1.02-15.6)

 Belgium                     Aging study mild cognitive dysfunction                                                   2000
 Maa stricht                    Farmers and gardeners                    Increased risk                               Bosma

 India                       Pesticide exposed workers 15                      Neuro behaviora l Tests                 2000
                                 Memory, learning , vigilance            Poorer performance                         Srivastava

 US                          Exterminators - total population                           Findings                       2000
                                 Postural sway                           Poorer performance - sig. diff.             Steenland
                                 Pegboard turning                        Poorer performance - sig. diff
                                 Nerve con duction velocity              No sig. differences
                                 Vibro tactile sensitivity               No sig. differences
                                 Smell, vision                           No sig. differences
                                 No sig. differences                     No sig. differences
                                 Visual/m otor skill                     No sig. differences
                             Chlorpyrifos poisoned workers
                                 Postural sway, pegboard                 Poorer performance - sig. diff.
                                 2 of 6 ne urob ehavioral tests          Poorer performance - sig. diff
                                 5 of 5 m ood scale tests                Poorer performance - sig. diff

 Poland                      Women greenhouse wrkrs OP 3 expos.                      WH O NCTB 20                      1999
                               Reaction times                            Increased                                  Bazylewicz
                               Mo tor steadiness                         Reduced
                               Tension, depression, fatigue              Mo re prevalent

 US                          Multiple System Atrophy                                                                  1999
 Record review                 Envirojhmental toxin exposure 16          11/100 cases                                 Hanna
Chronic Neurological Effects of Pesticides. - Marion Moses M.D.                                                                 9

 NY State                    Male pesticide applicators OPs3                     Findings                           1999
                                Vibration sensitivity                  Increased17                                 Ho rowitz
                                Electrophysiological abnormalities     One case
                                Acute or subacute symptoms             None found

 Germany                     Severe acute pyrethroid poisoning                          Sequelae                    1999
 Case rprt                      Persistent chro nic effects 18         Clinical picture 2 years later              Muller-M

 Germany                     Long term occup. exposure to WPC 19         Association PCP32 bloo d levels             1999
 15 & /controls                 Paired-associate learning              Poorer performance - signif..                 Peper
                                Benton                                 Poorer performance - signif..
                                Read ing/nam ing speed.                Poorer performance - signif..

 US                          Cortical blindness                        Case report                                  1998
 Tennessee                     Intentional carbofuran ingestion                                                     Baban

 US                          Structural fumigation workers36                        Performance                      1998
 Florida                          Pattern Memory                       W orse sulfuryl fluroride grp sig.           Calvert
                                  Olfactory testing                    W orse all fumigant expo sed sig
                                  Santa Ana Dexterity dom. hand        W orse all fumigant expo sed sig

 US                          Hispanic farmworkers low OP3 expos.                       NCV 9                         1998
                                Sural nerve latency and amplitude      No signif. differences                        Engel
                                Ulnar nerve cond uction velocity       No signif. differences
                                Ulnar neuromuscular junct. function    No signif. differences

 Chile                       Men chronic methyl brom ide expo s.                    Findings                        1997
                                Vibration senso ry thresholds          Increased 2.4 to 2.85 sec                    Acuna
                                Dynamometry                            Reduced 51 .4 to 47.2 kg
                                Nothingham -       Increased 11.2 to 13 .6.

 Ecuador                     Farmer memb ers of cooperative                        WH O NCTB 20                    199 7 Cole
                                Visual-spatial                         Mo st sensitive

 France                      Methyl bromide poisoning cases                          Findings                       1997
 1973-1994                      Review and follow-up                   2 developed p eripheral neuropathy21        DeHaro

 US                          Male fruit farmers heavy expos. OPs3            Neuro behavio ral Tests                 1997
                                Reaction time, dominant hand           Slower - signif.                             Fiedler
                                Other tests                            No signif. differences

 South Africa                Fruit farm/sprayers chronic OP 3 expos.             WH O NCTB 20                        1997
 1993                           Pursuit-Aiming                         Small associations                           London
                                Santa Ana sub test                     Small associations
                                Vibration sense                        No loss found

 Germany                     “Chronic” pyrethroid illness 22                 Nervo us System Effects                 1996
 1993                          Causal link acute sym. 6 of 23 cases    All reversible.                             Altenkirch

 UK                          OP 3 exposed sheep dipp ers               Symptoms      No symptoms        Controls     1996
                                2 point discrimin. dorsum of hand       22 mm            13 mm            8 mm       Beach
                                2 point discrim in. dorsum o f foot     34 mm            10 mm           11 mm
                                Mean calf circumference                 35.0 cm          36.3 cm         38.6 cm

 England                     OP 3 exposure                                                                          1996
                                Reported symptoms / chronic effects    No evidence o f any association             Stephens

 California                  Cho linesterase-inhibited sub jects 23                  Findings                        1995
 Case-control                  Serial digits                              Better performance sig.                    Ames
Chronic Neurological Effects of Pesticides. - Marion Moses M.D.                                                            10

 US                          Chlordane exposure - nonoccupational                      OR                        1995
                                Balance                                 Poorer performance signif.              Kilburn
                                Reaction time                           Poorer performance signif
                                Digit smb ol,                           Poorer performance signif
                                Trail-making                            Poorer performance
                                Verb al recall                          Poorer performance
                                Mo od-state                             No difference
                                Long-term memo ry                       No difference

 England                     OP 3 exposed sheep farmers                                   OR                     1995
                                  Sustained attention                   Poorer performance signif.             Stephens
                                  Speed of information processing       Poorer performance signif.
                                  Short-term memory and learning        No difference
                                  Psychiatric disorders                 Gre ater vulnerab ility

 New Y ork                    Farmer pesticide applicators                 Vibration se nsitivity thresho ld     1995
                                Long term exposures                     Increased dom. hand          p<.001     Stokes
                                                                        Increased non-dom. hand p<.04

 Nicaragua                   Males methamidop hos poisoning 24                  Findings                        1994
                               Vibrotactile thresholds                  > 25 % abnormal thresholds             McC onn

 India                       Agric. sprayers exposed fenthion 16                Psychom etric Tests              1994
                               Benton                                   Poorer performance signif.               Misra
                               Memo ry                                  Poorer performance signif.
                               Lexand                                   Poorer performance signif.
                               Passalong                                Poorer performance signif.
                               ERPs25 - P3 amplitude                    No significant diffeence

 US                          Methyl bromide acute poisoning                           Sequelae                   1994
 Case report                   Concentration, learning , memory         Impaired                                 Reidy

 Netherlands                 Flower farm ers pesticide exp os. 20 yrs                  NCV 9                     1994
                               Median motor                             -1.1 m/s decrease                       Ruijten
                               Median sensory                           -1.4 m/s decrease
                               Sural sensory                            -0.9 m/s
                               Peroneal motor                           -1.2 m/s -1.3 m/s de crease
                               Refractory period sural and peroneal     Increased

 California                  Severe OP 3 poisoning group                             Findings                    1994
 1982-90                         Sustained visual attention             Poorer performance signif.             Steenland
                                 Mood scales                            Poorer performance signif.
                             Vibrotactile sensitivity finger, toe
                                Che 26 inhibition group (not hosp)      Poorer performance
                                 Hospitalization OP p oisoning          Poorer performance

 US Case repo rt 3           Occup. exposure to ethylene oxide          Bilateral foot-drop and denervation      1993
 young adults                  Subacute polyneuropathy                  potentials on electromyography 27       Finelli

 US                          Apple orchard applicators OPs 9                Pre-season vs Post-season            1992
 Washington                     Neuropsychiatric tests                  No differences                          Daniell

 Netherlands                 Pesticide exposed bulb growers                              OR                     1992
                                Neurological exam                       No sig. difference                     DeW eerd
                                 Visual evoke d po tentials             No sig. difference
                                 Electroencephalogram                   More fast (beta ) activity
Chronic Neurological Effects of Pesticides. - Marion Moses M.D.                                                                   11

 US                          Chronic ethylene oxide exposure             Author conclusion: Cognitive             1992 Dretchen
 Case report                    29 y female records review               dysfunc tion of p sychiatric etiology.     see Crystal

 Netherlands                 Flower growers exposed pesticides                                                        1992
                                EEG findings                             Changes mean sp ectral frequencies         Jonkman

 US                          Ethylene oxide expos. hospital wrkrs                       Findings                      1991
                                 Nerve Co nduc tion V elocity            No sig. differences                         Estrin
                                 EEG                                     No sig. differences
                                 Neuropsychiatric test scores            No sig. differences

 US                          Heavy exp osure to dico fol                             Sequelae                        1991
 Case report                    12 yr male poisoned                      Cognitive/emotional probs. 18 mos         Lessenger

 US 60 cases/ctls            Multiple system atrophy                                                                1991 Nee
                                 Pesticide exposure                      Increase risk signif.

 Nicaragua 1986-88           Hospitalization OP 3 poisoning                        WH O NCTB 20                      1991
 agricultural workers           2 yrs after hosp.                        Sig. wo rse5/6 subtests 28                Rosenstock
                                 Mo tor steadiness and dexterity         Sig. wo rse than contro ls

 Bulgaria                    Pre/post season OP 3 agric. spraying               Post Season Findings                  1990
                                Evoked potentials                        Increased amp litude - signif.              Datsov
                                Median nerve conduction velocity         Decreased
                                Pero neal nerve co nduc tion velocity    Decreased

 US                          Soil fumigation wo rkers                                 Sequelae                        1990
 Case repo rts                  Methyl bromide poisoning                 Neuropsych. symp. several wks              Herzstein

 Netherlands                 Flower gro wers pesticide use > 10 yrs                     Findings                     1990
                                Nerve con duction velocity               Sma ll differences - signif.               VerB erk
                                EEG beta-activity                        Sma ll differences - signif.
                                Attention, perceptual coding             Sma ll differences - signif.

 California                  Optic atrophy (blindness)                              Sequelae                          1988
 Case report                   Methyl bromide expo s. 32 yr m ale        No improvement 1 yr later                   Chavez

 US                          ETO 29 occupational exposure                             Sequelae                    198 8 Crystal
 Case report                   29 yr old wo man for 10 yrs               Cognitive dysfunction disputed           see Dretchen

 India                       Agric.sprayers exposed fenthion 30                      Peroneal Nerve                  1988
                                 Cond uction velocity                    Slowing      p 0.05                         Misra
                                 Median latency                          Increased    p< 0.1
                                 Peroneal latency                        Increased    p < 0.05
                                 F min.H reflex. latency                 Increased    p < 0.01

 US                          Former OP 3 poisoned                                      Findings                       1988
                                Memory, abstraction, mood                No significant difference                   Savage
                                Halstead-Reitan Battery scores           Consistent w.cerebral damage/dysfxn
                                MMPI 31                                  Increased distress
                                PRAP FI 32                               Increased com plaints o f disability
                                Audiom etry, vision, EEG s               No significant differences

 Bhopal                      MIC 33 victims 34 severe/moderate exp os.           Psychom etry Results                 1987
 India                          Learning, motor speed, precision         Impaired p< 0.01                             Misra
                                Motor speed and precision tests          Disability score, r = 0.68 sig.
Chronic Neurological Effects of Pesticides. - Marion Moses M.D.                                                                       12

 Germany                     Men/women occup. expos. PCP 35                                  NCV 9                           1987
 1980-1984                     Ulnar, median nerves                          W ithin normal range                           Triebig
                               Peroneal, sural nerves                        W ithin normal range

 California                  Structural and soil fumigators35                      M ethyl Bromide Group                    1986
                                 Behavioral tests battery                    Poorer performance 23 of 27                    Anger
                                 Finger sensitivity                          Poorer performance signif.
                                 1 cognitive pe rformance test.              Poorer performance signif.

 Japan                       Multiple neuropathy                                                                            1986
 4 case reports                Ethylene-oxide (ET O) poisoning 36            Sensory disturbance lower limbs              Fukushima
                               Chronic ETO occupational exposure             Gait disturbance in all affected

 Yugoslavia                  Occupational ethylene oxide exposure                         Findings                          1984
 Case report                   19 yr male heavy exposure                     Polyneuropathy - lower limbs                   Kovac

 US                          2,4-D, 2,4,5-T manuf. workers                      Nerve C onduction V elocity                  1984
 Arkansas                        One or more slowed NCV                      46% expo sed vs 5% contro ls                   Singer
                                 Sural nerve below first perce ntile         48% expo sed vs 10% contro ls
                                 Sural NCV 9 1.3 SD 37 below cntls           Mea n slowing - 5.2 m eters m/s 38
                                 Median mo tor nerve                         Mea n slowing -1.9 m /s

 Japan                       Occupational ethylene oxide exposure                         Findings                          1983
 Case repo rts                 2 sterilizer workers                          Polyneuropathy 39                            Kuzuhara

 California                  OPs 3 reentry poisoning 19 wo rkers                           Follow-up                        1983
 farm workers                 Recovery time from acute poisoning             2 to 3 months                                 Whorton
                              Norm al cholinesterase 29                      Persistent 4 months later
                              Eye symptoms                                   Persistent 4 months later

 US                          Dieldrin occupational exposure                               Findings                          1981
                                Psycho logical. tests                        Poorer performance 5 / 58                     Sandifer
                                Pycho moto r tests                           Poorer performance 47 /58 p # .0540

 Germany                     Agricultural pesticide handlers                             Peroneal NCV 9                     1976
                                Exposed 3 years or more                      Decreased                                      Roder

 France                      Methyl bro mide leakage fire exting .                         Follow-up                         1975
 Case report                   Severe poisoning w myoclonus                  Lived 5 yrs in a stuporous state 41            Goulon

 US                          Agricultural pilots                                                                             1964
 Case repo rts                  Chronic OP 3 pesticide poisoning             Psychiatric sequelae                            Dille

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1. Parkinson’s disease.
2. Based on 1982 pesticide use reporting data. At that time not all pesticide use was required to be reported .
3. Organophosphate insecticides.
4. At the time of diagnosis.
5. 10 minutes later developed erythema, hyperkeratosis, conjunctival injection, diffuse hyperemia and tearing. These irritative
symptoms cleared up in 4 days.
6. CT: 2 small areas hypodensity left periventricular area near homolateral ventricular wall. MRI: small multiple, bilateral
symmetric areas high signal intensity caudate nuclei, putamen, cerebral white matter near ventricular wall.
7. Dysphonia, bradykinesis, and rigidity developed over the next 5 days, stabilized after 1 week and persisted until the time of
8. Mn - manganese; Fe - iron; Al - aluminum.
9. Nerve conduction velocity.
10. 81 workers treated for mild poisoning (not requiring hospitalization) from cholinesterase inhibiting pesticides
(organophosphates and N-methyl carbamates) compared to 130 who did not seek treatment for pesticide symptoms.
11. Cholinesterase inhibiting insecticides. This includes organophosphates and N-methyl carbamates.
12. 528 directly through mixing/spraying (mean exposure duration: 22 years), 173 indirectly through contact with treated plants,
216 were never exposed.
13. Amyotrophic lateral sclerosis (Lou Gehrig’s disease). All 3 case worked in manufacture /formulation of 2,4-D (1947-49,
1950-51, 1968-86), for varying durations of time (1.3, 1.8, and 12.5 years).
14. No association with cumulative exposure.
15. Quinalphos manufacturing workers.
16. One case had occupational exposure to high concentrations of malathion, diazinon, and formaldehyde.
17. In four with peripheral neuropathy.
18. Cerebro-organic disorders; sensomotor- polyneuropathy; vegetative nervous disorders ; cellular, humoral immune defects
19. Wood-preserving chemicals containing solvents, pentachlorophenol (PCP), and (-hexachlorocyclohexane ( lindane), and
other neurotoxicants.
20. World Health Organization's Neurobehavioral Core Test Battery. These information-processing tests were designed for use
in subjects with minimal education.
21. In one patient, symptoms improved within five months. In the other, paresthesia still present two years later, associated with
visual after-effects.
22. Exposure from carpets, moth killers, pesticide sprays and wood preservatives.
23. History of reduction of RBC cholinesterase activity less than or equal to 70% of baseline ; or reduction of plasma
cholinesterase less than or equal to 60% of baseline. Reductions were present without symptoms of frank poisoning.
24. Study done 10 to 34 months after hospitalization. Stratified as: 1) never poisoned; 2) poisoned with organophosphates other
than methamidophos and 3) poisoned with methamidophos, a known peripheral neurotoxin.
25. Event related potentials.
26. Acetylcholinesterase. Inhibition of this enzyme occurs in organophosphate poisoning.
27. Gradual and complete return of strength in the lower extremities occurred 4 to 7 months after removal from exposure.
28. Verbal/visual attention and memory, visuo-motor speed, sequencing, problem solving.
29. Ethylene oxide: TWA (time weighted average) 2.4 ppm , 4.2ppm around sterilizer. OSHA stand. 1.0 ppm.
30. No clinical evidence of peripheral neuropathy or muscle weakness.
Chronic Neurological Effects of Pesticides. - Marion Moses M.D.                                                                17
31. Minnesota Multiphasic Personality Inventory.
32. Patient's and Relative's Assessment of Patient Functioning Inventories .
33. Methylisocyanate, toxic chemical released in explosion at factory manufacturing carbaryl (Sevin) in Dec.1984.
34. 15 severely, 14 moderately, and 23 mildly affected ; mean age 38.2 (15-65);30 males. Neurological examination was normal.
35. Exposure to the fumigants methyl bromide and sulfuryl fluoride (Vikane).
36. Overexposure problems included the reverse flow of an exhaust fan, a choked air conditioner filter and the lack of protective
masks in the sterilizing facility.
37. Standard deviation.
38. Sural slowing significantly correlated with duration of employment.
39. Confirmed by sural nerve biopsies.
40. Author notes most did not correlate with dieldrin blood levels, and were within the normal range.
41. Autopsy of brain: necrosis inferior colliculi, gliosis in the upper brain stem reticular formation, moderate changes in the
dentate and pontine nuclei.

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Description: Chronic Neurological Effects of Pesticides