Chronic Neurological Effects of Pesticides Summary of Selected Studies Updated 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 firstname.lastname@example.org www.pesticides.org 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 table. 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 - neg.auto-perception 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 . 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J Toxicol Env VanWendelDeJoode B, et al. 2001 Chro nic Hlth 1 1(3):347-35 4. nervous-system effects of long-term occupational exposure to DDT . Lancet 357(9261 ):1012-1 015 . Footnotes 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 examination 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.