Int Arch Occup Environ Hlth 36,267-274 (1976)
International Archives of
(kupational
all Elironmenlal Health © by Springer-Verlag 1976
E.M G Voltage and Motor Nerve Conduction Velocity in Organophosphorus Pesticide Factory Workers D V ROBERTS Department of Physiology, University of Liverpool, P O Box 147, Liverpool, England
Summary Organophosphorus pesticide factory workers have been examined electromyographically and a relation between work with organophosphorus compounds and low voltage E M G in response to supra-maximal ulnar nerve stimulation has been demonstrated Workers with low voltage E M G also have, on average, low conduction velocities in both fastest and slowest motor nerve fibres A comparison of the maximum conduction velocity of motor nerve fibres in control and organophosphorus workers showed that the latter group had, on average, velocities 10 % less than the control group. Key words: Organophosphorus conduction velocity.
Pesticide
Electromyography
Motor-nerve
Chronic exposure to anti-cholinesterase compounds may result in neuropathy (Cavanagh, 1973), myopathy (Fenichel et al , 1972), structural changes at the motor end plate (Engel et al , 1973), and reduced output of acetylcholine from motor-nerve endings (Roberts and Thesleff, 1969) For these reasons it is important that factory workers concerned with the manufacture and formulation of organophosphorus (O P ) compounds should be protected from exposure to these compounds during their work It is equally important that the efficiency of this protection should be checked periodically. Hitherto, the method used to monitor exposure of workers to anti-cholinesterase compounds has been based on the measurement of cholinesterase enzyme activity in plasma and/or erythrocytes. Thus a lower than normal level of activity has been taken as evidence that absorption of an inhibitor compound has taken place Conversely, a normal enzyme level has been thought to indicate that no exposure has occurred or that recovery from a previous exposure is complete However, for a number of reasons, these simple criteria do not always provide a reliable indication of chronic exposure to anti-cholinesterase compounds. For instance, the considerable physiological variation in levels of enzyme activity makes it difficult to assess the significance of small deviations from the expected normal values.
267
Moreover, under some circumstances, chronic exposure to anticholinesterase compounds such as neostigmine results in an increase in the total amount of enzyme present in plasma, so that the activity of the uninhibited portion of the enzyme may lie within normal limits even when the plasma contains a substance with inhibitor activity (Buckley and Heading, 1972) Similar increases in enzyme activity have been found to occur as a result of low-level exposure to parathion (Rider et al , 1958 ; Locker and Siedeck, 1952), schradan (OMPA) (McPhillips and Coon, 1966), dimefox and mipafox (Locker and Siedeck, 1952). A further disadvantage of a monitoring system based on plasma or erythrocyte cholinesterase levels of activity stems from the fact that the signs and symptoms produced by anti-cholinesterase compounds are due, in part, to inhibition of the enzymes of the nervous system, secretory glands and muscle, and not to the coincident inhibition of blood enzymes (Grob and Harvey, 1953) The rates of recovery of these various enzyme systems after inhibition are not necessarily identical and so a normal plasma or erythrocyte cholinesterase value may give a false impression of the functional state of cholinesterase enzymes elsewhere in the body For example, after a period of exposure to neostigmine, stellate ganglion cholinesterase was found to be still inhibited at a time when the plasma enzyme had fully recovered its normal level of activity (Buckley and Heading, 1972). Finally, if O P compounds have actions other than those due to inhibition of cholinesterase enzymes, there is no reason why such actions should not take effect at exposure levels insufficient to produce a detectable reduction in blood cholinesterase activity. In view of these disadvantages of the use of blood cholinesterase measurements as the sole means of monitoring exposure to anti-cholinesterase compounds, there would appear to be a strong case for examining and, if possible, measuring some physiological functions in which acetylcholinesterase plays a part To this end, electromyography (E M G ) has been used to study peripheral neuromuscular function in factory workers engaged in the manufacture and formulation of organophosphorus pesticides (Jager et al , 1970) It was found that these workers had a high incidence of E M G abnormalities similar to those observed in myasthenia gravis patients overtreated with the carbamate compounds neostigmine and pyridostigmine (Roberts and Wilson, 1969) These abnormalities consisted of repetitive activity and low voltage in response to single supramaximal stimulation of a motor-nerve, and a further decrease in voltage after a short period (10 sec) of maximal voluntary activity in the muscle under test.
268
METHODS OF
INVESTIGATION AND SUBJECTS USED
E.M G records were made as described previously (Jager et al , 1970) Measurements of maximum conduction velocities and conduction velocities of the slowest motor nerve fibres were effected with the techniques described by Hodes et al (1948) and by Hopf (1962) The core temperature of the arm was not measured during the conduction velocity investigations but all subjects were examined at rest in a room temperature of 20-22 0 C. The pesticide factory workers examined in this study were engaged in the manufacture or formulation of either diethyl and dimethyl 4-nitrophenyl phosphorothionates, or 2-chloro-l-( 2,4dichlorophenyl)-vinyl diethyl phosphate, or O,O-diethyl 0-( 3,5,6trichloro-2-pyridyl)-phosphorothioate Exposure levels could not be measured and so no dose-response relationships can be established. The control subjects were taken from the same factory as the corresponding pesticide workers and had similar ages and duties. Only male subjects were examined in this investigation.
DAY-TO-DAY VARIABILITY OF E M G IN NON-EXPOSED INDIVIDUALS
VOLTAGE
In order to assess the significance of changes in the E M G. voltage of exposed workers it is necessary to know what variation may be expected in non-exposed individuals For this reason, 7 non-exposed workers were examined electromyographically, daily for 20 days The coefficients of variation of individual workers were calculated, and the mean coefficient of variation for this group was found to be 7 7% with a standard error of the mean of 0 3% The factors contributing to this variability were not investigated but they will no doubt include physiological variation in the subjects' nerve and muscle function as well as small errors in the positioning of the recording electrodes llarge errors may be excluded by inspection of the E M G record (Desmedt, 1961)l. The coefficient of variation may be used to evaluate the probability that any deviation from an individual's mean preexposure E M G voltage is due to normal variation Thus, for a worker whose pre-exposure mean is equal to 12 O m V, the odds against a voltage of 10 0 m V being due to normal variability are greater than 40 to 1 If the same worker's voltage decreases further to 9 0 m V the chance that this is due to normal variation is less than 1 in 100 When such low E M G voltages are found on successive examinations, normal variability may be excluded and further investigations are needed to determine the cause of the low voltage Clearly, in view of previously published work, exposure to organophosphorus compounds is one poss-
269
ible cause but neuromuscular disorders and the effects of drugs should also be considered The causal factor may be indicated more clearly when a correlation can be established between working with organophosphorus compounds and the occurrence of low voltage E M G.
COMPARISON OF PRE E.M G VOLTAGES
AND POST-VACATION
Of 56 men examined before and after a 3-week vacation 14 had voltages less than 10 mV before vacation but after the vacation, the voltage had increased in every one of these 14 workers The means (SEM) for this group of 14 men before and after vacation were 8 57 (0 32) m V and 10 19 (0 49) m V respectively and the difference is significant at the P = 2% level The remaining 42 men with voltages equal to or more than 10 m V before vacation showed no significant change in group mean voltage after the vacation although the E M G voltage increased in some individuals, decreased in others and in some, remained constant These results suggest that the E M G voltages of the 14 men were depressed by some factor associated with their work and that the effect of this diminished during their absence from the plant while on vacation.
EFFECT OF WORK PATTERN ON E M G
VOLTAGE
A group of 17 men were examined electromyographically and then were classified into 2 subgroups on the basis of their probable contact with O P compounds at all stages of the organophosphorus manufacture process Thus there were 8 shift supervisors with a high probability of contact and 9 men in a mixed function group with a low probability of contact The contact probability was assessed by the production manager in relation to the nature of each man's work, the frequency of visits to or duration of work on the production plant, and the particular part of the plant at which a man worked. The mean (SEM) E M G voltage of the 9 men in the mixed function (low contact) group was 13 06 (0 47) m V while that of the 8 shift supervisors (high contact) was only 10 71 (0 79) mV. This difference is significant at the P = 2% level and provides further evidence of functional changes in nerve and/or muscle which are related to work with O P compounds.
270
Table 1 Conduction velocity in motor nerve fibres in relation to E M G
voltage
recorded from the adductor pollicis muscle in response to supramaximal ulnar nerve stimulation
E.M G voltage less than 10 mV
Max conduction velocity (m/s) mean (SEM)
Conduction velocity of slowest fibres (m/s) mean (SEM)
57 3 (O 9)
43 6 (O 8)
61 5
47 7 (O 7)
(n = 53)
E.M G voltage equal t/more than 10 ul mV t/ han l
mV
(O 7)
(n = 49)
Significance level
E.M G
P less than O 1%
P less than O 1%
VOLTAGE AND MOTOR NERVE CONDUCTION VELOCITY
At present, little is known about the mechanism by which the E.M G voltage is reduced in some organophosphorus pesticide workers A type of neuromuscular junctional block, similar to that found in myasthenia gravis or after the administration of tubocurarine, can, however, be excluded, because none of the low-voltage pesticide workers so far examined exhibited the characteristic decline in action potential amplitude in response to repetitive motor nerve stimulation Another possible reason for reduced E M G voltage is an increase in the temporal dispersion of the various components of the compound action potential due to a reduction in motor nerve conduction velocity On this basis, workers with low E M G voltages should also have low conduction velocities The following investigation was carried out to test this hypothesis. 102 organophosphorus pesticide factory workers were examined electromyographically and E M G voltage, maximum and minimum motor nerve conduction velocities were measured The mean (SEM) E.M G voltage in these workers was found to be 9 97 (0 3) m V which may be compared with the corresponding values of 12 73 (0.3) mV found in a control group of 75 factory workers not involved in the use or production of organophosphorus compounds. The difference between these two groups is significant at the P less than O 1% level. The organophosphorus workers were separated on the basis of their E M G voltages, 53 with voltages less than 10 m V and the remaining 49 with voltages equal to or more than 10 m V The
271
mean conduction velocities found in these subgroups were then compared statistically and the results, which are given in Table 1, indicate that there is a relation between E M G voltage and conduction velocity in motor nerve fibres Those workers with E M G voltages equal to or more than 10 m V have, on average, normal conduction velocities whereas those with voltages below 10 m V have conduction velocities about 10 % below normal.
MAXIMUM MOTOR NERVE CONDUCTION VELOCITIES IN PESTICIDE AND NONPESTICIDE FACTORY WORKERS In view of the relation between low voltage E M G and work with organophosphorus compounds, and between low voltage E M G and low conduction velocity, a comparison was made of the conduction velocities in two groups of workers Group 1 consisted of 8 nonpesticide factory workers and group 2 consisted of 8 workers engaged in the development, manufacture and formulation of an organophosphorus pesticide Each subject was examined on 5 occasions over a period of 3 weeks and the average maximum conduction velocity calculated for each group In the control group the mean (SEM) conduction velocity was 58 8 (0 93) m/s, whereas in the pesticide group the values were 53 7 (O 81) m/s Thus, on average, conduction velocities in the pesticide group were approximately 10% less than those in the control group, the difference being significant at the P less than 0 1% level.
DISCUSSION These results confirm the previous observations that disturbances of normal nerve and muscle function may be found by electromyographic examination in men working with organophosphorus compounds They also strengthen the case for using functional tests such as electromyography as part of the procedure for monitoring the effects of work with and possible exposure to organophosphorus compounds The ways in which organophosphorus compounds produce these functional changes have not yet been established but recent work suggests that excessive amounts of acetylcholine in the vicinity of the endplate region may play a major role (Fenichel et al , 1974) This would not of course explain the slower conduction velocity in motor nerve fibres, and for this attention should be given to the report of a cholinergic link between the squid axon and its surrounding Schwann cells (Villegas, 1975) This link is sensitive to tubocurarine and to eserine when these compounds are applied in an acute experiment A study on the effect of chronic exposure to antichol-
272
inesterase compounds on Schwann cell function may serve to explain some of the functional changes seen in the peripheral nervous system of organophosphorus pesticide workers. Acknowledgements The author wishes to thank Dr J E Burgess and Dr C F Ottevanger for their help with the conduction velocity studies.
REFERENCES Buckley, G A , Heading, C : Persistence of neostigmine-like activity in tissues of the rat after prolonged oral administration Brit J Pharmacol. 44, 336 p (1972) Cavanagh, J B : Peripheral neuropathy caused by chemical agents CRC Critical Reviews in Toxicology 2, 365-417 (1973) Desmedt, J E : In: Myasthenia Gravis Proceedings of the Second International Symposium (H R Viets, ed ), pp 150-178 Springfield, Ill : Thomas 1961 Engel, A G , Lambert, E H , Tetsuji Santa: Studies of long-term anti-cholinesterase therapy Effects on neuromuscular transmission and on motor end-plate fine structure Neurology (Minneap ) 23, 1273-1281 (1973) Fenichel, G M , Dettbarn, W -D , Newman, T M : An experimental myopathy secondary to excessive acetylcholine release Neurology (Minneap ) 24, 41-45 (1974) Fenichel, G M , Kibler, W B , Olson, W H , Dettbarn, W D : Chronic inhibition of cholinesterase as a cause of myopathy Neurology (Minneap ) 22, 1026-1033 (1972) Grob, D , Harvey, A M : The effects and treatment of nerve gas poisoning. Amer J Med 14, 52-63 (1953) Hodes, R , Larrabee, M G , German, W : The human electromyogram in response to nerve stimulation and conduction velocity of motor axons Arch Neurol. Psychiat (Chic ) 60, 340-365 (1948) Hopf, H Ch : Untersuchungen ber die Unterschiede in der Leitgeschwindigkeit motorischer Nervenfasern beim Menschen 579-588 (1962)
Dtsch Z Nervenheilk
183,
Jager, K W , Roberts, D V , Wilson, A : Neuromuscular function in pesticide workers Europ J Pharmacol 6, 281-285 (1970) Locker, A , Siedek, H : Uber Aktivierung von Cholinesterasen durch Alkylphosphate in vivo Experienta 8, 146-148 (1952) McPhillips, J J , Coon, J M : Adaptation to octamethylpyrophosphoramide in rats Toxicol Applied Pharmacol 8, 66-76 (1966) Rider, J A , Moeller, H C , Swader, J , Weilerstein, R W : Effect of parathion on human red blood cell and plasma cholinesterase A M A Arch. industr Hlth 18, 441-445 (1958) Roberts, D V , Thesleff, S : Acetylcholine release from motor-nerve endings in rats treated with neostigmine Europ J Pharmacol 6, 281-285 (1969)
273
Roberts, D V , Wilson, A : Electromyography in diagnosis and treatment In: Myasthenia Gravis (R Greene, ed ), pp 29-42 London: Heinemann 1969 Villegas, J : Effects of cholinergic compounds on the axon-Schwann cell relationship in the squid nerve fibre Fed Proc 34, 1370-1373 (1975)
Received December 5, 1975 / Accepted December 8, 1975
274
International Archives of
(kupational
all Elironmenlal Health © by Springer-Verlag 1976
E.M G Voltage and Motor Nerve Conduction Velocity in Organophosphorus Pesticide Factory Workers D V ROBERTS Department of Physiology, University of Liverpool, P O Box 147, Liverpool, England
Summary Organophosphorus pesticide factory workers have been examined electromyographically and a relation between work with organophosphorus compounds and low voltage E M G in response to supra-maximal ulnar nerve stimulation has been demonstrated Workers with low voltage E M G also have, on average, low conduction velocities in both fastest and slowest motor nerve fibres A comparison of the maximum conduction velocity of motor nerve fibres in control and organophosphorus workers showed that the latter group had, on average, velocities 10 % less than the control group. Key words: Organophosphorus conduction velocity.
Pesticide
Electromyography
Motor-nerve
Chronic exposure to anti-cholinesterase compounds may result in neuropathy (Cavanagh, 1973), myopathy (Fenichel et al , 1972), structural changes at the motor end plate (Engel et al , 1973), and reduced output of acetylcholine from motor-nerve endings (Roberts and Thesleff, 1969) For these reasons it is important that factory workers concerned with the manufacture and formulation of organophosphorus (O P ) compounds should be protected from exposure to these compounds during their work It is equally important that the efficiency of this protection should be checked periodically. Hitherto, the method used to monitor exposure of workers to anti-cholinesterase compounds has been based on the measurement of cholinesterase enzyme activity in plasma and/or erythrocytes. Thus a lower than normal level of activity has been taken as evidence that absorption of an inhibitor compound has taken place Conversely, a normal enzyme level has been thought to indicate that no exposure has occurred or that recovery from a previous exposure is complete However, for a number of reasons, these simple criteria do not always provide a reliable indication of chronic exposure to anti-cholinesterase compounds. For instance, the considerable physiological variation in levels of enzyme activity makes it difficult to assess the significance of small deviations from the expected normal values.
267
Moreover, under some circumstances, chronic exposure to anticholinesterase compounds such as neostigmine results in an increase in the total amount of enzyme present in plasma, so that the activity of the uninhibited portion of the enzyme may lie within normal limits even when the plasma contains a substance with inhibitor activity (Buckley and Heading, 1972) Similar increases in enzyme activity have been found to occur as a result of low-level exposure to parathion (Rider et al , 1958 ; Locker and Siedeck, 1952), schradan (OMPA) (McPhillips and Coon, 1966), dimefox and mipafox (Locker and Siedeck, 1952). A further disadvantage of a monitoring system based on plasma or erythrocyte cholinesterase levels of activity stems from the fact that the signs and symptoms produced by anti-cholinesterase compounds are due, in part, to inhibition of the enzymes of the nervous system, secretory glands and muscle, and not to the coincident inhibition of blood enzymes (Grob and Harvey, 1953) The rates of recovery of these various enzyme systems after inhibition are not necessarily identical and so a normal plasma or erythrocyte cholinesterase value may give a false impression of the functional state of cholinesterase enzymes elsewhere in the body For example, after a period of exposure to neostigmine, stellate ganglion cholinesterase was found to be still inhibited at a time when the plasma enzyme had fully recovered its normal level of activity (Buckley and Heading, 1972). Finally, if O P compounds have actions other than those due to inhibition of cholinesterase enzymes, there is no reason why such actions should not take effect at exposure levels insufficient to produce a detectable reduction in blood cholinesterase activity. In view of these disadvantages of the use of blood cholinesterase measurements as the sole means of monitoring exposure to anti-cholinesterase compounds, there would appear to be a strong case for examining and, if possible, measuring some physiological functions in which acetylcholinesterase plays a part To this end, electromyography (E M G ) has been used to study peripheral neuromuscular function in factory workers engaged in the manufacture and formulation of organophosphorus pesticides (Jager et al , 1970) It was found that these workers had a high incidence of E M G abnormalities similar to those observed in myasthenia gravis patients overtreated with the carbamate compounds neostigmine and pyridostigmine (Roberts and Wilson, 1969) These abnormalities consisted of repetitive activity and low voltage in response to single supramaximal stimulation of a motor-nerve, and a further decrease in voltage after a short period (10 sec) of maximal voluntary activity in the muscle under test.
268
METHODS OF
INVESTIGATION AND SUBJECTS USED
E.M G records were made as described previously (Jager et al , 1970) Measurements of maximum conduction velocities and conduction velocities of the slowest motor nerve fibres were effected with the techniques described by Hodes et al (1948) and by Hopf (1962) The core temperature of the arm was not measured during the conduction velocity investigations but all subjects were examined at rest in a room temperature of 20-22 0 C. The pesticide factory workers examined in this study were engaged in the manufacture or formulation of either diethyl and dimethyl 4-nitrophenyl phosphorothionates, or 2-chloro-l-( 2,4dichlorophenyl)-vinyl diethyl phosphate, or O,O-diethyl 0-( 3,5,6trichloro-2-pyridyl)-phosphorothioate Exposure levels could not be measured and so no dose-response relationships can be established. The control subjects were taken from the same factory as the corresponding pesticide workers and had similar ages and duties. Only male subjects were examined in this investigation.
DAY-TO-DAY VARIABILITY OF E M G IN NON-EXPOSED INDIVIDUALS
VOLTAGE
In order to assess the significance of changes in the E M G. voltage of exposed workers it is necessary to know what variation may be expected in non-exposed individuals For this reason, 7 non-exposed workers were examined electromyographically, daily for 20 days The coefficients of variation of individual workers were calculated, and the mean coefficient of variation for this group was found to be 7 7% with a standard error of the mean of 0 3% The factors contributing to this variability were not investigated but they will no doubt include physiological variation in the subjects' nerve and muscle function as well as small errors in the positioning of the recording electrodes llarge errors may be excluded by inspection of the E M G record (Desmedt, 1961)l. The coefficient of variation may be used to evaluate the probability that any deviation from an individual's mean preexposure E M G voltage is due to normal variation Thus, for a worker whose pre-exposure mean is equal to 12 O m V, the odds against a voltage of 10 0 m V being due to normal variability are greater than 40 to 1 If the same worker's voltage decreases further to 9 0 m V the chance that this is due to normal variation is less than 1 in 100 When such low E M G voltages are found on successive examinations, normal variability may be excluded and further investigations are needed to determine the cause of the low voltage Clearly, in view of previously published work, exposure to organophosphorus compounds is one poss-
269
ible cause but neuromuscular disorders and the effects of drugs should also be considered The causal factor may be indicated more clearly when a correlation can be established between working with organophosphorus compounds and the occurrence of low voltage E M G.
COMPARISON OF PRE E.M G VOLTAGES
AND POST-VACATION
Of 56 men examined before and after a 3-week vacation 14 had voltages less than 10 mV before vacation but after the vacation, the voltage had increased in every one of these 14 workers The means (SEM) for this group of 14 men before and after vacation were 8 57 (0 32) m V and 10 19 (0 49) m V respectively and the difference is significant at the P = 2% level The remaining 42 men with voltages equal to or more than 10 m V before vacation showed no significant change in group mean voltage after the vacation although the E M G voltage increased in some individuals, decreased in others and in some, remained constant These results suggest that the E M G voltages of the 14 men were depressed by some factor associated with their work and that the effect of this diminished during their absence from the plant while on vacation.
EFFECT OF WORK PATTERN ON E M G
VOLTAGE
A group of 17 men were examined electromyographically and then were classified into 2 subgroups on the basis of their probable contact with O P compounds at all stages of the organophosphorus manufacture process Thus there were 8 shift supervisors with a high probability of contact and 9 men in a mixed function group with a low probability of contact The contact probability was assessed by the production manager in relation to the nature of each man's work, the frequency of visits to or duration of work on the production plant, and the particular part of the plant at which a man worked. The mean (SEM) E M G voltage of the 9 men in the mixed function (low contact) group was 13 06 (0 47) m V while that of the 8 shift supervisors (high contact) was only 10 71 (0 79) mV. This difference is significant at the P = 2% level and provides further evidence of functional changes in nerve and/or muscle which are related to work with O P compounds.
270
Table 1 Conduction velocity in motor nerve fibres in relation to E M G
voltage
recorded from the adductor pollicis muscle in response to supramaximal ulnar nerve stimulation
E.M G voltage less than 10 mV
Max conduction velocity (m/s) mean (SEM)
Conduction velocity of slowest fibres (m/s) mean (SEM)
57 3 (O 9)
43 6 (O 8)
61 5
47 7 (O 7)
(n = 53)
E.M G voltage equal t/more than 10 ul mV t/ han l
mV
(O 7)
(n = 49)
Significance level
E.M G
P less than O 1%
P less than O 1%
VOLTAGE AND MOTOR NERVE CONDUCTION VELOCITY
At present, little is known about the mechanism by which the E.M G voltage is reduced in some organophosphorus pesticide workers A type of neuromuscular junctional block, similar to that found in myasthenia gravis or after the administration of tubocurarine, can, however, be excluded, because none of the low-voltage pesticide workers so far examined exhibited the characteristic decline in action potential amplitude in response to repetitive motor nerve stimulation Another possible reason for reduced E M G voltage is an increase in the temporal dispersion of the various components of the compound action potential due to a reduction in motor nerve conduction velocity On this basis, workers with low E M G voltages should also have low conduction velocities The following investigation was carried out to test this hypothesis. 102 organophosphorus pesticide factory workers were examined electromyographically and E M G voltage, maximum and minimum motor nerve conduction velocities were measured The mean (SEM) E.M G voltage in these workers was found to be 9 97 (0 3) m V which may be compared with the corresponding values of 12 73 (0.3) mV found in a control group of 75 factory workers not involved in the use or production of organophosphorus compounds. The difference between these two groups is significant at the P less than O 1% level. The organophosphorus workers were separated on the basis of their E M G voltages, 53 with voltages less than 10 m V and the remaining 49 with voltages equal to or more than 10 m V The
271
mean conduction velocities found in these subgroups were then compared statistically and the results, which are given in Table 1, indicate that there is a relation between E M G voltage and conduction velocity in motor nerve fibres Those workers with E M G voltages equal to or more than 10 m V have, on average, normal conduction velocities whereas those with voltages below 10 m V have conduction velocities about 10 % below normal.
MAXIMUM MOTOR NERVE CONDUCTION VELOCITIES IN PESTICIDE AND NONPESTICIDE FACTORY WORKERS In view of the relation between low voltage E M G and work with organophosphorus compounds, and between low voltage E M G and low conduction velocity, a comparison was made of the conduction velocities in two groups of workers Group 1 consisted of 8 nonpesticide factory workers and group 2 consisted of 8 workers engaged in the development, manufacture and formulation of an organophosphorus pesticide Each subject was examined on 5 occasions over a period of 3 weeks and the average maximum conduction velocity calculated for each group In the control group the mean (SEM) conduction velocity was 58 8 (0 93) m/s, whereas in the pesticide group the values were 53 7 (O 81) m/s Thus, on average, conduction velocities in the pesticide group were approximately 10% less than those in the control group, the difference being significant at the P less than 0 1% level.
DISCUSSION These results confirm the previous observations that disturbances of normal nerve and muscle function may be found by electromyographic examination in men working with organophosphorus compounds They also strengthen the case for using functional tests such as electromyography as part of the procedure for monitoring the effects of work with and possible exposure to organophosphorus compounds The ways in which organophosphorus compounds produce these functional changes have not yet been established but recent work suggests that excessive amounts of acetylcholine in the vicinity of the endplate region may play a major role (Fenichel et al , 1974) This would not of course explain the slower conduction velocity in motor nerve fibres, and for this attention should be given to the report of a cholinergic link between the squid axon and its surrounding Schwann cells (Villegas, 1975) This link is sensitive to tubocurarine and to eserine when these compounds are applied in an acute experiment A study on the effect of chronic exposure to antichol-
272
inesterase compounds on Schwann cell function may serve to explain some of the functional changes seen in the peripheral nervous system of organophosphorus pesticide workers. Acknowledgements The author wishes to thank Dr J E Burgess and Dr C F Ottevanger for their help with the conduction velocity studies.
REFERENCES Buckley, G A , Heading, C : Persistence of neostigmine-like activity in tissues of the rat after prolonged oral administration Brit J Pharmacol. 44, 336 p (1972) Cavanagh, J B : Peripheral neuropathy caused by chemical agents CRC Critical Reviews in Toxicology 2, 365-417 (1973) Desmedt, J E : In: Myasthenia Gravis Proceedings of the Second International Symposium (H R Viets, ed ), pp 150-178 Springfield, Ill : Thomas 1961 Engel, A G , Lambert, E H , Tetsuji Santa: Studies of long-term anti-cholinesterase therapy Effects on neuromuscular transmission and on motor end-plate fine structure Neurology (Minneap ) 23, 1273-1281 (1973) Fenichel, G M , Dettbarn, W -D , Newman, T M : An experimental myopathy secondary to excessive acetylcholine release Neurology (Minneap ) 24, 41-45 (1974) Fenichel, G M , Kibler, W B , Olson, W H , Dettbarn, W D : Chronic inhibition of cholinesterase as a cause of myopathy Neurology (Minneap ) 22, 1026-1033 (1972) Grob, D , Harvey, A M : The effects and treatment of nerve gas poisoning. Amer J Med 14, 52-63 (1953) Hodes, R , Larrabee, M G , German, W : The human electromyogram in response to nerve stimulation and conduction velocity of motor axons Arch Neurol. Psychiat (Chic ) 60, 340-365 (1948) Hopf, H Ch : Untersuchungen ber die Unterschiede in der Leitgeschwindigkeit motorischer Nervenfasern beim Menschen 579-588 (1962)
Dtsch Z Nervenheilk
183,
Jager, K W , Roberts, D V , Wilson, A : Neuromuscular function in pesticide workers Europ J Pharmacol 6, 281-285 (1970) Locker, A , Siedek, H : Uber Aktivierung von Cholinesterasen durch Alkylphosphate in vivo Experienta 8, 146-148 (1952) McPhillips, J J , Coon, J M : Adaptation to octamethylpyrophosphoramide in rats Toxicol Applied Pharmacol 8, 66-76 (1966) Rider, J A , Moeller, H C , Swader, J , Weilerstein, R W : Effect of parathion on human red blood cell and plasma cholinesterase A M A Arch. industr Hlth 18, 441-445 (1958) Roberts, D V , Thesleff, S : Acetylcholine release from motor-nerve endings in rats treated with neostigmine Europ J Pharmacol 6, 281-285 (1969)
273
Roberts, D V , Wilson, A : Electromyography in diagnosis and treatment In: Myasthenia Gravis (R Greene, ed ), pp 29-42 London: Heinemann 1969 Villegas, J : Effects of cholinergic compounds on the axon-Schwann cell relationship in the squid nerve fibre Fed Proc 34, 1370-1373 (1975)
Received December 5, 1975 / Accepted December 8, 1975
274
