Occupational and Environmental Medicine 1 996;53:520-525

Abnormalities on neurological examination amongsheep farmers exposed to organophosphorouspesticides

Jeremy R Beach, Anne Spurgeon, Richard Stephens, Tom Heafield, Ian A Calvert,Leonard S Levy, J Malcolm Harrington

AbstractObjectives-Organophosphates are effec-tive pesticides which are frequently usedin several agricultural settings. Althoughtheir acute effects are well characterised,it remains unclear whether long termexposure can damage the human nervoussystem. This study sought to investigatetheir long term effects by comparingabnormalities on neurological examina-tion between groups ofworkers exposed toorganophosphates and an unexposedgroup.Methods-146 exposed sheep farmers and143 unexposed quarry workers wererecruited into a cross sectional study ofsymptoms and neuropsychological effectsof long term exposure to organophos-phates in sheep dip. From a symptomquestionnaire given immediately afterdipping the 10 most symptomatic and 10least symptomatic farmers were selected.Several months later each of these, alongwith 10 of the unexposed quarry workers,underwent a standardised neurologicalexamination similar to that which mightbe used in clinical practice, at a time asremote as possible from recent exposureto organophosphates so as to exclude anyacute effects.Results-All 30 selected subjects agreed toparticipate. The components ofthe exam-ination which showed a significant differ-ence were two point discrimination on thedorsum of the hand (symptomatic farm-ers 22 mm; asymptomatic farmers 13mm; quarry workers 8 mm) and the dor-sum of the foot (symptomatic farmers 34mm; asymptomatic farmers 10 mm;quarry workers 11 mm), and mean calfcircumference (symptomatic farmers35-0 cm; asymptomatic farmers 36*3 cm;quarry workers 38-6 cm). Overall theprevalence of neurological abnormalitieswas low.Conclusions-The differences in neuro-logical examination detected betweengroups were subtle and their clinical sig-nificance was unclear. However, they dosuggest evidence of an adverse neurologi-cal effect from exposure to organophos-phates. Further, larger scale studies willbe required before it is possible to con-firm or refute the differences detected.

(Occup Environ Med 1996;53:520-525)

Keywords: sheep farmers; organophosphates; neuro-logical examination

Organophosphate based pesticides havebecome widely used throughout the world,with applications in many areas of agriculture.Although the acute toxicity of these com-pounds is relatively well known from knowl-edge of the mechanism of their actions andfrom published reports of acute poisoning,recent concerns have been expressed that longterm low level exposure may also result inadverse effects upon the human nervous sys-tem.' Anecdotally, there are reports thatexposed people may experience poor mentalhealth and other neurological problems,notably difficulties with cognitive functionsincluding memory and concentration. How-ever, objective scientific evidence of this puta-tive effect is scarce, as most studies involvedassessment at a time when acute effects mightstill have been present, or reported long termsequelae of acute poisoning incidents ratherthan long term low level exposure.48

Particular concern has been voiced amongsheep farmers, many of whom are exposed toorganophosphates through the practice ofsheep dipping to control sheep scab and otherparasites. This involves total immersion of theanimals in a solution of a pesticide, and duringthis procedure there may be considerableexposure from the splashing of dip ontoexposed areas of skin, particularly as the use ofprotective clothing by many farmers in this sit-uation has been found to be very limited.9Thus, sheep farmers comprise a representativegroup of agricultural workers with potentiallysubstantial exposure to organophosphates.The study reported here comprised part of a

larger study carried out to assess whether longterm low level exposure to organophosphatesis associated with chronic effects on thehuman nervous system. In the main study atotal of 146 sheep farmers, and 143 quarryworkers with no exposure to organophos-phates, underwent extensive neuropsychologi-cal testing, the results of which have beenreported elsewhere.'0 Quarry workers wereselected as an appropriate comparison groupfor the farmers as they are largely outdoorworkers situated geographically in the sameareas of Britain as the sheep farmers beingtested, but are unlikely to be exposed to agri-cultural chemicals (providing those with parttime farm jobs are excluded). This paperreports the results from a detailed clinical neu-

Institute ofOccupational HealthJ R BeachA SpurgeonR StephensI A CalvertL S LevyJM HaringtonDepartment ofNeurology, UniversityofBirminghamT HeafieldCorrespondence to:Dr A Spurgeon, Institute ofOccupational Health,University of Birmingham,Edgbaston, BirminghamB15 2fT.Accepted 14 March 1996

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rological examination of a subgroup of thispopulation, comprising 10 sheep farmers withacute symptoms suggestive of organophos-phate effects at the time of dipping, 10 sheepfarmers without such symptoms, and 10quarry workers not occupationally exposed toorganophosphates.

Subjects and methodsSUBJECTSMale farmers were recruited into the mainstudy by selecting every 10th name on regis-tration lists for the Wool Marketing Boardwithin three areas of Britain (Devon,Cumbria, and North Wales). Initial contactwas by letter. However, this initially produced alow response (33%) and raised concerns thatthe study population might not be representa-tive of the sheep farming population as awhole. A further sample was thereforerecruited with a telephone call for the initialcontact, so producing a better response rate(69%). Subsequent comparison of the twosamples on a range of demographic and expo-sure variables showed no significant differ-ences except for mean age (telephone samplefive years younger) so largely allaying fears ofany substantial recruitment bias. Subjects withany known previous neurological disease, orsystemic illness with neurological effects-forexample, diabetes-were excluded, as weresubjects who had had a head injury which hadresulted in loss of consciousness for greaterthan one hour.

Quarry workers were selected from quarriessituated in the same geographical areas asthose of the sheep farmers. Any who hadhelped on sheep farms, been involved in dip-ping, or been otherwise occupationallyexposed to organophosphates-for example,spraying to control pests on fruit crops or onverges-were excluded. Although quarryworkers might intuitively seem to be an inap-propriate control group because of a risk ofexposure to agricultural chemicals, it is inter-esting to note that only 12 possible recruitshad to be excluded because of organophos-phate exposure or working with sheep.

It was thought that it would be logisticallyimpossible to perform a detailed clinical neu-rological examination of all sheep farmers tak-ing part in the neuropsychological assessmentas each examination required a visit to thesubjects home, often several hundred milesfrom Birmingham, at a prearranged appoint-ment time. Consequently 30 subjects (20sheep farmers and 10 quarry workers) wereselected from within the study population toundergo further examination. All subjects gavewritten informed consent to their inclusion inthe study.The main study comprised two stages: the

administration of a symptom questionnaireimmediately before and 24 hours after dippingto identify symptoms similar to those previ-ously described in reports of organophosphatetoxicity; and a neuropsychological assessmentcarried out as long after the previous year'sdipping as possible and before the current

year's dipping (when there had been no recentexposure). To maximise the probability ofidentifying any abnormalities that might beattributable to organophosphate exposure, the10 sheep farmers with the highest symptomscores 24 hours after dipping were recruited,as well as the 10 with the lowest scores.Although these were not necessarily the 10with the highest exposure, we none the lessthought that they represented the group mostlikely to display neurological abnormalities.Ten quarry workers were also recruited from asingle quarry site. The neurological examina-tions themselves were carried out as part of thesecond stage of the investigation, at a timeremote from recent exposure to organophos-phates.

METHODSNeurological examinationBased upon a neurological examination asused in clinical practice, a format was designedto allow a standardised and systematic exami-nation of all subjects. As examinations wereusually to take place in the subjects' ownhomes in the case of sheep farmers and at thequarries in the case of quarry workers, this wasdesigned to require only relatively simple androbust equipment, and was deliberately tai-lored to detect the types of abnormalitieswhich could be detected by most physicians.The neurological examination was included ina pilot study to establish that the intendedstudy methods were feasible in practice, andwas thought to fulfil its intended aims.

Individual appointments were made withsubjects by telephone and confirmed by letter.All examinations were performed by a singleinvestigator (JRB) who was unaware, at thetime of examination, which farmers were inthe symptomatic group, and which the asymp-tomatic group, although the quarry workerswere identifiable. Before examination severalstandardised questions were included to finddetails of any relevant current or previous ill-nesses, medications, family history of neuro-logical illness-for example, musculardystrophies, hereditary spinocerebellar degen-erative diseases, hereditary myopathies,Huntington's chorea-intake of alcohol, orexposure to other potential neurotoxins-forexample, other pesticides and farmyard chemi-cals, lead, mercury, and thallium. The mainelements of the examination included:

sensory and motor examination of cranialnerves including:visual acuity-assessed by Jaeger chartvisual fields-assessed by confrontationfundoscopy-with hand held ophthalmo-scopesensory examinationfine touchpinprick (face bilaterally in each of the divi-sions of the trigeminal nerve: medial andlateral aspects of arm, forearm, palm ofhand: dorsum of hand: tips of fingers:medial, lateral, and posterior aspects ofthigh calves: dorsal and plantar surfaces offoot: tips of toes: full length of trunk bilater-ally)

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vibration-sternum, wrist, anklejoint position sense-index finger, big toetwo point discrimination at tip of index fin-ger, dorsum ofhand, tip of big toe, and dor-sum of footmotor examinationmuscle bulk-measured with a tape mea-sure at:upper arm (15 cm above lateral epicondyle)thigh (15 cm above upper border of patella)calf (15 cm below lower border of patella)muscle tonepower of all main muscle groupsreflexes-biceps, triceps, supinator, knee,ankle, plantarcoordination and balancegaitcerebellar abnormalitiesThe farmers were seen in their own homes

at individual appointments throughout theworking day. Upon arrival the investigatorconfirmed that the subject had given consentand explained the nature of the intendedexamination. A suitable private room forexamination was then selected which wascomfortably warm and included a couch orbed. Occasionally it was necessary to ask sub-jects to heat a room so that it would be com-fortably warm, so ensuring temperaturevariations would not affect the examination.Subjects were asked to undress to their under-

Table 1 Characteristics of three subject groups

Symptomatic Asymptomatic Quarry workersfarmers (n = 10) farmers (n = 10) (n = o0)

Age (mean (SD)) 47-0 (10-6) 49-2 (14-0) 40 4 (12-8)Righthanded(n) 10 10 9Alcohol (median (range),

units/week) 1-5 (0-16) 5 0 (0-30) 13 5 (4-30)Taking prescribed medication 3 2 2Family history of

neurological disease 1 0 0Previous exposure toneurotoxic chemicals 5 5 0

Table 2 Results of neurological examination for three subject groupsSymptomatic Asymptomatic Quanry workersfarmers (n = 10) farmers (n = 10) (n = o0)

Cranial nerves abnormality (n) 2 3 1Sensory system abnormality (n):

Fine touch - objective 1 0 0Fine touch - subjective 2 0 1Vibration 1 0 0Joint position sense 1 0 0

Two point discrimination(mm, median (range)):

Index finger 3-50 (3-10) 3 00 (3-5) 3-25 (3-10)Dorsum hand 21-75 (6-85) 12-50 (3-38) 7 50 (4-20)Big toe 8-75 (4-23) 7 50 (4-16) 7-25 (3-10)Dorsum foot 33-75 (13-85) 10-25 (5-27) 11-25 (4-18)Motor system:Limb circumference(cm, mean (SD))Upper arm 27-5 (2 0) 28-8 (2-1) 28-9 (3-2)Thigh 46-9 (2 8) 48-0 (3 3) 48-1 (6-7)Calf 35-0 (2-1) 36-3 (2-3) 38-6 (4-0)Abnormality (n):Muscle power 0 0 0Reflexes 0 0 0Gait 1 0 0Coordination 0 0 0Rombergism 1 0 0

Reflex score (median (range))Biceps 2 (1-3) 2 (1-3) 2 (1-3)Triceps 2 (1-3) 2 (1-3) 1 (1-2)Supinator 2 (1-3) 1-5 (1-3) 1 (1-2)Knee 2 (1-3) 2 (1-3) 2 (1-3)Ankle 2 (1-3) 2 (1-3) 2 (2-3)

wear before the examination. Each examina-tion took about 60 minutes. Once the exami-nation was completed the investigatordiscussed any abnormalities with the individ-ual subject and suggested if appropriate thatthey visit their own general practitioner.A surrogate measure of cumulative expo-

sure was estimated for all subjects. This wascalculated as: the average number of sheep intheir flock x number of dips a year x numberof years using organophosphates (total num-ber of sheep dipped in organophosphate). Thiswas used to assess differences in average expo-sure between the three study groups. Giventhe relatively crude nature of this estimate, thesmall numbers in the sample, and the way thesample had been selected on the basis ofsymptomatology, we thought it inappropriateto try to correct for other variables and esti-mate an exposure response relation with thesedata.

Data handling and analysisAs soon as possible after completion, dataforms were returned to the Institute ofOccupational Health. Data were subsequentlyentered onto a personal computer and verified.Statistical analysis was undertaken with thestatistical software package 'Minitab' (StateCollege, PA 16801-3008 USA). For mostanalyses the study population was categorisedinto three groups and comparisons were madecontrasting the symptomatic sheep farmers,the asymptomatic sheep farmers, and thequarry workers. Where statistical probabilitiesare quoted they were calculated with X2 forcategorical data, and analysis of variance forcontinuous data. A non-parametric analysis ofvariance (Kruskal Wallis test) was used whereappropriate.

ResultsThirty subjects were selected with the criteriadefined in the protocol, and all agreed to takepart in this element of the investigation. Table1 shows some characteristics of subjects ineach group. The mean ages of the three groupswere not significantly different (F2,27 = 1-34,P > 0 1), and the three groups were not signif-icantly different for right or left handedness,there was only one left handed subject whowas one of the quarry workers (X2 2-069, df 2,P > 0-1). There were no significant differencesbetween the groups for the number of subjectstaking prescribed medication, or the numberwith a family history of neurological disease.Median alcohol consumption was significantlyhigher among the quarry workers than eithergroup of sheep farmers (H 11'03, df 2, P =

0.004), whereas exposure to other toxic chem-icals was less frequently reported by the quarryworkers than by either group of sheep farmers(x2 7.500, df 2, 0-05 > P > 0*01).Table 2 shows results from the neurologicalexaminations. The overall prevalence of cra-nial nerve abnormalities was low and therewere no significant differences between thethree groups. No consistent pattern of cranialnerve abnormality was noted in any group.

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All the sensory examinations except twopoint discrimination showed no significant dif-ferences between groups. In contrast two pointdiscrimination on the dorsum of the hand andthe dorsum of the foot did show significantdifferences between groups. On the dorsum ofthe hand median distance between two pointsbefore they could be discriminated as separatewas 22 mm for the symptomatic sheep farm-ers, 13 mm for the asymptomatic sheep farm-ers, and 8 mm for the quarry workers (H 9 07,df 2, P = 0-011); and on the dorsum of thefoot the corresponding figures were 34 mm forthe symptomatic sheep farmers, 10 mm for theasymptomatic sheep farmers, and 11 mm forthe quarry workers (H 13-22, df 2, P < 0.001).Two point discrimination was also tested on

the index finger and the big toe, and here toothe symptomatic sheep farmers required thegreatest median distance between two pointsbefore they could be discriminated as separate,although these differences were not significant(for index finger H 1-28, df 2; P > 0-1; for bigtoe H 2 15, df 2; P> 0 1).

Muscle power was normal for all subjects,and reflexes showed no definite abnormality.No obvious muscle wasting or hypertrophywas noted. Mean calf circumference differedsignificantly between groups, being 35-0 cmfor the symptomatic sheep farmers, 36-3 cmfor the asymptomatic sheep farmers, and 38-6cm for the quarry workers (F2,27 3-87, P =

0 033). Mean circumferences of the upper

arm and thigh were not significantly differentbetween groups. Tendon reflexes were scoredfrom 0 to 3 and the median score showed no

significant difference between the three subjectgroups for any of the reflexes tested. No sub-ject had an abnormal plantar reflex, and no

subject showed any abnormalities of coordina-tion to suggest a cerebellar abnormality.One subject in the group of symptomatic

farmers had an abnormal wide based gait, andthe same subject also displayed rombergismand abnormal joint position sense. Contactwith his general practitioner showed that hehad been seen some 10 years previously by a

consultant neurologist with the same physicalsigns, but that no cause had been identified atthe time, and there had been little if any clinicaldeterioration in the interim. He had continuedto work normally throughout. The clinical sig-nificance of these abnormalities was, therefore,not clear.The change in symptom scores between the

questionnaires administered immediatelybefore and 24 hours after dipping was calcu-lated for each group of subjects. The sympto-matic group showed an increase in mediansymptom score in the interval between thesetwo tests from 22-5 to 33 0, whereas theasymptomatic group showed a decrease from a

median symptom score of 3-0 to 1-0. The

change in symptom scores was not signifi-cantly different between the two groups ofsheep farmers.The surrogate estimate of cumulative expo-

sure, not surprisingly, showed a clear differ-ence between the study groups, as all quarryworkers with exposure to organophosphates

had been excluded (H 17 7, df 2, P < 0 00 1).Median (range) exposure for quarry workerswas 0 (0-0) sheep dipped in organophosphate,for the symptomatic sheep farmers 14 500(1200-180 000), and for the asymptomaticsheep farmers 15 000 (300-81 000). How-ever, once the quarry workers were excluded,there were no significant differences in expo-sure between the two groups of sheep farmers.

DiscussionThis study has identified significant differ-ences between the three subject groups,although these were limited to two point dis-crimination on the dorsum of the hand andthe foot, and the circumference of the calf 15cm below the lower border of the patella. Noother significant differences were identified inthe other variables assessed.The differences in two point discrimination

were significant at two sites, and results at theother two sites tested also showed a non-sig-nificant trend with the symptomatic sheepfarmers requiring the greatest median differ-ence between two points before they could beperceived as separate. Thus, these data areconsistent with the suggested abnormality intwo point discrimination in the symptomaticfarmers. However, the evidence of an effect onmuscle mass is rather less convincing, withonly one of three sites tested showing a signifi-cant difference between the study groups.Also, data on weight was not available for allsubjects and so it was impossible to allow forthe effect of body mass index on these mea-surements. Consequently we would be lessconfident that this result represents a mean-ingful difference between groups.A clear relation was not found between

exposure and the neurological abnormalitiesdetected within the groups of farmers.Although there were differences detected inthe neurological tests between the two groupsof farmers, differences in exposure were notsignificant. However, the estimate of exposureused was relatively crude, and it may also bethat individual susceptibility to the effects oforganophosphates was an important factor indetermining outcomes, in a similar way thatatopy is important in determining the develop-ment of occupational asthma in some settings.Variation in susceptibility to the effects oforganophosphates between people has beennoted to be considerable.' For this study, thesymptomatic farmers were selected deliber-ately because they were the group most likelyto have neurological abnormalities, so makingthe study as sensitive as possible. However, itmay be that the differences in neurologicaloutcome reflect constitutional differencesbetween the groups of farmers as well as differ-ences in exposure between the farmers andquarry workers.

There is little evidence that the differencesbetween the groups could have been due to anartefact or to confounding. All examinationswere carried out by a single investigator whowas unaware of the symptom score of thefarmers, and a standardised examination for-

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mat was used for all subjects. Subjects withcurrent or previous disease likely to cause neu-rological abnormalities were specificallyexcluded from the study population. Themean ages of the groups were not significantlydifferent, and there were no differencesbetween groups in the prevalence of a familyhistory of neurological disease, or use of pre-scribed medication. Although the quarryworkers were all seen at the workplace ratherthan their own homes, the room used was pri-vate and kept at a comfortable temperature.As with the sheep farmers, examinations werecarried out throughout the day. Also, thesheep farmers drank less alcohol than thequarry workers and so should have had fewerabnormalities which could be attributed to thisparticular cause. Significantly more of thesheep farmers had worked with other poten-tially toxic chemicals than the quarry workers,most had carried out occasional knapsackspraying of weeds or treating livestock withother chemicals or drugs, for example, equip-ment cleaning by dairy farmers. The use ofthese chemicals was however no more preva-lent among the symptomatic than the asymp-tomatic sheep farmers (five subjects in eachgroup recorded their use) although there wereclear differences in two point discriminationbetween the two groups. Consequently itseems unlikely that differences between groupsin the use of other chemicals could explain thedifferences in two point discrimination. Thus,the differences between groups would seem tobe genuine, and seem most likely to be due toexposure to organophosphates.Two point discrimination is the ability to

perceive two simultaneous stimuli composedof two blunt points applied to the skin.Normally the ability to measure two points asseparate varies between parts of the body,from around 5 mm for most people on the fin-gers, but up to about 50 mm on the dorsum ofthe foot. In the presence of normal peripheralnerve function disturbance of two point dis-crimination indicates parietal cortex dysfunc-tion, much like the complex sensation ofgraphaesthesia." In our subjects graphaesthe-sia was not tested but there were no other fea-tures suggesting parietal dysfunction, and so aperipheral and neuropathic aetiology seemsthe most likely explanation for the differencesdetected in two point discrimination. Musclewasting is usually a consequence of abnormal-ity in the lower motor neurone, the neuromus-cular junction, or the muscle itself (outside thecentral nervous system). It could therefore bepostulated that both abnormalities could beascribed to a peripheral neuropathy caused bydemyelination or an axonopathy (as has beendescribed before in association with organo-phosphate compounds).812 However, if this isthe mechanism, it is difficult to understandwhy only two point discrimination should beaffected and not other sensory functions, norwhy two point discrimination at other siteswas not affected, if such a mechanism were thebasis of the abnormalities. It may be that thisdiscrepancy is due to the small number of sub-jects and hence lack of power in the study,

particularly when trying to identify abnormali-ties in the other sensory functions, none ofwhich were measured as a continuous variable.

Acute symptoms of organophosphate poi-soning are generally held to be due to inhibi-tion of cholinesterase enzymes. Classically thesymptoms of acute intoxication include non-specific symptoms such as headache, giddi-ness, nausea; autonomic symptoms such asblurred vision, miosis, salivation, sweating,and bradycardia; and symptoms related toover-reactivity of volountary muscle-tremorsand impaired coordination'3. The pathogene-sis of any putative chronic effects is not so wellcharacterised, and few previous studies haveincluded a neurological examination of sub-jects exposed to organophosphate pesticides.When this has taken place the examination israrely described in detail, and only one hasreported two point discrimination.61214-17Because of a lack of standardisation it is diffi-cult to perform comparative analysis of thesefindings, although several abnormalities havebeen described.

Davignon et al found a greater proportion ofsubjects with miosis, weakening or loss ofreflexes, tremors, and disturbances of equilib-rium among those with contact with insecti-cides than those without such contact in theirstudy.'4 Tabershaw and Cooper in their followup of 114 subjects with a previous episode ofacute toxicity due to organophosphates foundfew long term neurological sequelae althoughthey noted that a high proportion of subjectscomplained of visual problems.'5 Most of thesecomplaints however consisted of blurredvision, were in subjects aged 40-55, and con-sisted solely of presbyopia. The authors con-cluded that the evidence "leads us to discountthe likelihood of any causal relation in thesecases between organic phosphate intoxicationand permanently disturbed vision". Metcalfand Holmes, although unable to show anyclear excess of neurological abnormalities intheir group of subjects exposed to organophos-phates concluded "It is our impression thatexposed men show more so-called "soft" neu-rological signs such as minor coordinationdeficits and oculomotor imbalance".'6 Lotti etal described a delayed neurotoxic effect oforganophosphates characterised by a distalmotor polyneuropathy, whereas Senanayakeand Karalliedde described an intermediatesyndrome characterised again by motor abnor-malities, predominantly muscle weakness butwith changes in reflexes and dystonia alsoreported in some patients.'2 17 Savage et al didreport two point discrimination in 100 sub-jects at a variable interval after acute organo-phosphate intoxication, and 100 controls.6However, no significant differences werefound between cases and controls for any testof the sensory system, the only differencefound being for one test of motor reflexes.There are no other reports of disturbances ofthe kind reported here in a chronically exposedpopulation.Where neurological abnormalities have

been found, either acutely, in the intermediatesyndrome, or as a part of a delayed polyneu-

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ropathy, they have primarily involved themotor system rather than the sensory system,and this study is unusual in that the majordeficit seems to be sensory rather than motor.Most published work reports a motor neuro-pathic deficit and myelopathy which areknown to predominate clinically in cases ofacute intoxication. However, there were signif-icant differences between previous populationsstudied, and the population in this investiga-tion, particularly the nature of exposure ofsubjects in this study. Most previous investiga-tions have studied subjects after an episode ofacute intoxication, usually sufficient to requiremedical attention, whereas for this study suchsubjects were specifically excluded. It may behowever, that some of the sheep farmers hadsustained effects from subclinical episodes ofacute intoxication rather than having only longterm low level exposures. From these datathere is no way to differentiate the effects ofthese two separate patterns of exposure, and itmay be that either or both are capable of caus-ing the changes we have documented.

Although the number of subjects examinedin this study is relatively small, these abnor-malities cannot easily be dismissed as inconse-quential. The combination of findings,although they do not easily fit into any charac-teristic pattern of neurological disease, aresuggestive of neurological dysfunction of aprobable neuropathic and peripheral aetiol-ogy, although they may represent a combina-tion of both neuropathic and spinal corddysfunction. Regardless, they suggest thatsome neurological changes, albeit relativelysubtle, had occurred as a consequence of longterm exposure to organophosphate sheep dipat concentrations which had never inducedsufficient symptoms that medical attentionwas sought. Sequential examination and addi-tional neurophysiological testing in this groupwould be of great interest. It may also be help-ful to further characterise the exact nature of

this neurological abnormality, and determinewhether this damage is associated ultimatelywith any clinical disease.

This work was funded by a grant from the Health and SafetyExecutive.

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2 Davies JE. Neurotoxic concerns of human pesticide expo-sures. Am _J Ind Med 1990;18:327-31.

3 Mearns J, Dunn J Lees-Haley PR. Psychological effects oforganophosphate pesticides: a review and call forresearch by psychologists. J Clin Psychol 1994;50:286-94.

4 Maizlish N, Schenker M, Weisskopf C, Sieber J, SamuelsS. A behavioural evaluation of pest control workers withshort-term, low level exposure to the organophosphatediazinon. Am 7 Ind Med 1987;12:153-72.

5 Rodnitsky RL, Levin HS, Mick DL. Occupational expo-sure to organophosphate pesticides. Arch Environ Health1975;30:98-103.

6 Savage EP, Keefe TJ, Mounce LM, Heaton RK, Lewis JA,Burcar PJ. Chronic neurological sequelae of acuteorganophosphate pesticide poisoning. Arch EnvironHealth 1988;43:38-45.

7 Rosenstock L, Keifer M, Daniell WE, McConnel R,Claypoole K. The pesticide health effects study group.Chronic CNS effects of acute organophosphate intoxica-tion. Lancet 1991;338:223-7.

8 Steenland K, Jenkins B, Ames R, O'Mallery M, Chrislip D,Russo J. Chronic neurological sequelae to organophos-phate pesticide poisoning. Am J Public Health 1994;84:731-6.

9 Niven KJM, Scott AJ, Hagen S, Waclawski ER, Lovett M,Cherrie B, et al. Occupational hygiene assessment of sheepdipping practices and processes. Edinburgh: Institute ofOccupational Medicine, 1993. (IOM report TM/93/03.)

10 Stephens R, Spurgeon A, Calvert IA, Beach J, Levy LS,Berry H, Harrington JM. Neuropsychological effects oflong-term exposure to organophosphates in sheep dip.Lancet 1995;345:1135-9.

11 Bickerstaff ER, Spillane JA. Neurological examination in clin-ical practice, 5th ed. Oxford: Blackwell Sci Publ, 1989.

12 Lotti M, Becker CE, Aminoff MJ. Organophosphatepolyneuropathy: pathogenesis and prevention. Neurology1984;34:658-62.

13 Health and Safety Executive. Biological monitoring of workersexposed to organo-phosphorous pesticides, 2nd ed. London:HSE Books, 1987. (Guidance note MS17.)

14 Davignon LF, St-Pierre J, Charest G, Tourangeau H;. Astudy of the chronic effects of insecticides in man. CanMed AssocJ 1965;92:597-602.

15 Tabershaw IR, Cooper CW. Sequelae of acute organo-phosphate poisoning. J Occup Med 1966;8:5-20.

16 Metcalf DR, Holmes JH. EEG, psychological, and neuro-logical alterations in humans with organophosphateexposure. Ann NYAcad Science 1969;160:357-65.

17 Senanayake N, Karalliedde L. Neurotoxic effects oforganophosphorous insecticides. An intermediate syn-drome. N EnglJt7Med 1987;316:761-3.

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