Anna Maria Seppäläinen

Subclinical Neuropathy at “Safe” Levels of Lead Exposure

Electrophysiological methods revealed subclinical neuropathy in 26 workers, exposed from 1 to 17 years to lead and whose blood lead (PbB) values had never exceeded 70mu/100ml, as ascertained by checking the monitor reports of the factory and by careful exposure history. The PbB determinations had been tested repeatedly and had been found valid. The main findings were slowing of the maximal motor conduction velocities of the median and ulnar nerves and particularly the conduction velocity of the slower fibers of the ulnar nerve. Electromyographical abnormalities comprised fibrillations, diminution of the number of motor units on maximal contraction, and an abnormally long duration of the units. Earlier similar measurements from heavily exposed workers had been even more abnormal. Thus, a dose-response relationship exists on a group basis. Since the regular monitoring of PbBs in most workers during their entire period of exposure excludes the possibility of a body burden out of proportion to the PbB slight neurological damage is produced at exposures hitherto regarded as quite safe.

n-HEXANE-INDUCED CHANGES IN VISUAL EVOKED POTENTIALS AND ELECTRORETINOGRAMS OF INDUSTRIAL WORKERS

Visual evoked potentials (VEPs) and averaged extraocular electroretinograms (ERGs) were recorded from 15 workers occupationally exposed to n-hexane for 5-21 years and from 10 healthy control persons. The amplitude of the VEP components was clearly smaller among the exposed subjects with the exception of N0, which tended to be larger. In addition, the latencies of P1 and N1 were longer among the exposed workers, while that of P2 was slightly shorter. The peak-to-peak amplitude of the ERGs was also diministed among the exposed subjects. The changes were interpreted to indicate cerebral dysfunction, probably conduction block in intracerebral axons. n-Hexane is an aliphatic hydrocarbon found in gasoline and used in various industrial applications. It has been shown to cause axonal neuropathy of the dying-back type in both experimental animals and humans. According to the present findings the central nervous system is alos susceptible to the toxic effects of n-hexane.

Changes induced by xylene and alcohol in human evoked potentials

Neurotoxic effects of industrial solvents have recently aroused great interest. Few studies have applied evoked potential methods to test acute or chronic neurotoxicity of solvents or alcohol. Eight young healthy male volunteers were exposed for 4 h to about 1200 or 700 mg/m3 of xylene alone or in combination with alcohol 0.8 g/kg. Single doses of 0.4 g/kg and 0.8 g/kg alcohol were also used as test substances, and the subjects stayed for 4 h in the exposure chamber also during 3 control days. Tests were conducted single-blind and the subjects acted as their own controls. Visual (VEPs) and somatosensory (SEPs) evoked potentials as well as electroretinograms (ERGs) were recorded in the mornings before the exposure and in the afternoons immediately after exposure stopped. A single dose of alcohol 4 h prior to recording increased the latencies of P50, N60, P115 and N155 of VEP dose-dependently. Alcohol alone did not change significantly the amplitude of VEP, but xylene 1200 mg/m3 in combination with alcohol 0.8 g/kg decreased significantly the amplitude of N60-P115. The lower concentration of xylene in combination with alcohol as well as xylene 1200 mg/m3 alone tended to have similar effects. Concerning the latency changes simultaneous xylene exposure tended to counteract the effect of alcohol. No significant effects on ERGs could be shown in any of situations. The effects of SEPs were minor or lacking, and the lower exposure levels were associated with more statistically significant changes than higher exposure levels.

Effects of short-term m-xylene exposure and physical exercise on the central nervous system.

SummaryEight male volunteers were exposed on 5 consecutive days and 1 day after the weekend to m-xylene vapour at either a constant (Study I) or a periodically varying (Study Il) concentration of 3.7–8.2 μmol/1(90–200 ppm, time-weighted average). The effects of the exposure on psychophysiological functions, such as reaction time, manual coordination and body balance, and EEG were studied. The same tests were completed on 2 non-exposure days for control purposes in both studies, in which physical exercise of 10O W was included.An inhalation exposure to m-xylene already at a concentration of 3.7 μmol/1 (90 ppm) had acute deleterious effects on the above mentioned psychophysiological functions of non-adapted subjects. EEG indicated lowered vigilance during exposure to varying concentrations with peak exposures of 8.2 μmol/l. Slight exercise, especially at the beginning of the exposure, seemed to antagonize the effects of xylene, particularly when the concentration fluctuated. Tolerance against the observed effects developed over one working week, but some effects were again discernible in the following week. A dose-response relationship between blood m-xylene concentrations and the effects of m-xylene was not found. This was probably due to tolerance.

Changes in the electroretinogram and visual evoked potentials during general anaesthesia.

Ten patients (one male and nine females), aged 33.2±12.0 years, were given electrophysiological studies before and during general anaesthesia. A mixture of thiopentone sodium, halothane, and nitrous oxide was used for anaesthesia. Electroretinogram (ERG) and visual evoked potentials (VEP) were recorded with scalp electrodes, and an averaging technique was used to improve signal-noise ratio. The recordings were made under standard conditions 15 to 20 min after induction of the anaesthesia. The amplitudes of the a- and b-waves of the ERG were significantly diminished whereas their latencies remained unchanged. The peak-to-peak amplitudes of the early components N1 and P2 of the VEP were significantly lowered, and the latencies of N0, P1 and N1 were prolonged by anaesthesia. These modifications are suggested to reflect metabolic changes in the sensitive layers of the retina and in the optic tract. Bei zehn Patienten (ein Mann und neun Frauen) mit einem durchschnittlichen Alter von 33.2±12.0 Jahren wurde das Elektroretinogramm (ERG) sowie die visuell evozierten Potentiale (VEP) unter Standardbedingungen vor und während Allgemeinanästhesie mit einer Thiopenton Natrium-Halothan-Lachgas-Mischung registriert. Die Ableitungsstelle lag 2 cm über dem Inion (00 des internationalen 10–20 Systems) in der okzipitalen Mittellinie. Zur Mittelwertbildung wurde ein Summationselektronenrechner (Nokia) angewandt. Die Aufzeichnungen wurden während konstanter Bedingungen 15–20 min nach Induktion der Anästhesie durchgeführt. Die Amplituden der a- und b-Wellen des ERGs waren signifikant erniedrigt. Die Latenzen verblieben dagegen unverändert. Die Höhe der Amplitude (Spitze zu Spitze) der frühen VEP Komponente n1 und P2 waren signifikant erniedrigt, und die Latenzen von no0 p1 und n1 während der Anästhesie verzögert. Diese Veränderungen scheinen metabolische Ursachen sowohl in der Neuroretina wie auch im Nervus und Tractus opticus zu haben.

Peripheral neuropathy and vibration syndrome

SummaryHundred and three patients with suspected or diagnosed vibration syndrome caused by the prolonged use of chain saws were examined during 1978–1980. Neurological or neurophysiological examinations revealed slight changes suggesting polyneuropathy in the lower extremities of 42 patients. Peripheral neuropathy in the upper extremities was only detected in 39 patients. No evidence of peripheral neuropathy was found for 22 patients. The polyneuropathic patients did not significantly differ from the non-polyneuropathic patients with regard to other clinical symptoms and signs, laboratory findings, or data on exposure. We concluded that patients with neuropathic diathesis tend to be selected into groups of patients with suspected vibration syndrome. This study emphasizes the need for the careful neurological examination of each patient with suspected vibration syndrome.

Changes induced by short-term xylene exposure in human evoked potentials

SummaryNine healthy male volunteers were exposed to m-xylene for 3 h in the morning and 40 min in the afternoon with a 40-min break in between. The atmospheric m-xylene concentrations were either stable at 8.2 μmol/l (200 ppm) or they fluctuated (5.2–16.4 μmol/1; 135–400 ppm) with peaks of 16.4 μmol/1 and duration of 20 min at the beginning of each exposure session. The subjects were either sedentary or exercised at 100 W for 10 min at the beginning of each session during both exposure types. The two control days, with and without exercise, were similar to the exposure days but without exposure. Evoked potentials were recorded in the morning before the exposure and immediately after the morning and afternoon sessions. Visual evoked potentials were studied to a pattern reversal stimulus (pattern VEP) and to a light flash (flash VEP). For pattern VEPs the latencies of P50, N70, P100, N135 and P170 as well as the peak-to-peak amplitude of N70 to P100 were measured. For flash VEPs the latencies of P50, N70, P100, N150 and P200 as well as the peak-to-peak amplitude of P100 to N150 were measured. Short-latency auditory evoked potentials arising in the brainstem (BAEP) were recorded for a click stimulus. The peaks 1, II, III, IV and V were identified from the grand averages. The effect of various exposure paradigms was evaluated by comparing the individual changes on an exposure day to those during the control days. The latency N135 of the pattern VEP decreased in exposure at 400 ppm with exercise, and the latency P210 in the flash VEP decreased both at the stable and fluctuating exposure with exercise. The results might suggest some activation of the arousal level of the subjects after the most intensive exposure situations.

Diphenyl poisoning in fruit paper production. A new health hazard.

Production of diphenyl-impregnated fruit wrapping paper under poor hygienic conditions caused the death of one man and the poisoning of eight other workers. The diphenyl concentrations in the air had been much in excess of the present threshold limit value of 1 mg/cu m. The clinical picture of diphenyl poisoning is characterized by central and peripheral nervous damage and liver injury. The cause of death in the fatal case was acute yellow liver atrophy. In three of the eight men with poisoning, there was histological evidence of liver injury. Changes in the results of blood analysis or renal function did not occur. The prognosis of diphenyl poisoning is still unknown, but some patients showed deterioration when seen after one year.

ELECTROENCEPHALOGRAPHIC FINDINGS DURING EXPERIMENTAL HUMAN EXPOSURE TO M-XYLENE

Aromatic hydrocarbon solvents, used widely in industry, cause central nervous system symptoms in exposed workers. Acute effects of m-xylene were studied in nine voluntary subjects exposed experimentally to stable or varying concentrations of m-xylene at rest or while exercising. Each subject participated in four exposure and two control sessions in a single-blind fashion. The time-weighted average (TWA) m-xylene concentration was always 200 parts per million (ppm) (8.2 mumol/l) during the 4-h exposure period, complying to a TWA of 4.1 mumol/l.8 h, which is equivalent to the hygienic limit allowed in work situations. The short-term peak concentrations were 400 ppm or less. Electroencephalography was recorded at the beginning of exposure, during exposure, and after exposure was stopped. Eighteen 60-s EEG samples for each subject on each experimental day were analyzed automatically. Exercise increased theta percentage and delta power and percentage; these changes were more prominent in the control session without exposure. Exposure increased the dominant alpha frequency and alpha percentage during the early phase of exposure and also counteracted the effects of exercise. The effects of short-term m-xylene exposure on EEG were minor, and no deleterious effects were noted. Perhaps alpha activation is indicative of stimulating and excitatory effects induced by m-xylene exposure, which has been noted heretofore in the absorption phase of alcohol intake.

Changes in the Electroretinogram and Visual Evoked Potentials During General Anaesthesia Using Enflurance

Fourteen female patients 27.7 ± 10.0 years of age were studied by electrophysiological means before and during general anaesthesia. A mixture of thiopentone sodium, enflurane and nitrous oxide was used for anaesthesia. Electroretinogram (ERG) and visual evoked potentials (VEP) were recorded with electrodes placed on the lower lid and scalp and an averaging technique was used. The recordings were made under standard conditions with the pupils dilated, the eyes adapted to the dark and after 15–20 min stable anaesthesia.The latency of the a-wave did not change, whereas the b-wave was delayed (P<0.01). The amplitude of the a-wave tended to decrease; however, an increase of amplitude was also present. Therefore the change was not significant. The b-wave was unchanged.Changes induced by anaesthesia were often noted in the shape of P130, where a change from V to W-form took place or the reverse. The latencies of the late components N180 and P220 were increased during anaesthesia (P=0.006 andP=0.001, respectively). No statistically significant change occurred in the N180 and P220 amplitudes. The amplitudes of N60 and P130 became smaller (P=0.002 andP=0.0003, respectively) during anaesthesia. The effect of enflurane on the components of the VEP seems to indicate a cortical site of action.ZusammenfassungBei vierzehn Frauen mit einem durchschnittlichen Alter von 27.7 ± 10.0 Jahren wurden das Elektroretinogramm (ERG) sowie die visuell evozierten Potentiale (VEP) unter Standardbedingungen vor und während der Allgemeinanästhesie mit einer Thiopenton Natrium-Enfluran-Lachgas-Mischuing registriert. Die Ableitungsstelle für die VEP lag 2 cm über dem Inion (O0 des internationalen 10–20 Systems) in der okzipitalen Mittellinie. Die Ableitungselektrode für das ERG befand sich am Unterlid. Zur Mittelwertbildung wurde ein Summationselektronenrechner (Nokia) angewandt.Die Aufzeichnungen wurden unter konstanten Bedingungen mit erweiterter Pupille sowie Dunkeladaptation des Auges 15–20 Minuten nach Verabreichung der Anästhesie durchgeführt. Die Latenz der a-Welle des ERGs blieb unverändert während sich die der b-Welle verlängerte (P<0.01). Die Amplitude der a-Welle tendierte zu einer Erniedrigung, jedoch kann auch eine erhöhte a-Welle vorkommen. Eine Signifikanz lag deshalb nicht vor. Die Amplitude der b-Welle blieb unverändert.P130 der VEP zeigte eine Veränderung der Form von V in W Form und entgegengesetzt. Die späten Komponenten N180 und P220 waren verzögert (P=0.006 undP=0.001). Eine statistisch signifikante Veränderung der Amplituden von N180 und P220 konnte nicht festgestellt werden. Die Amplituden von N60 und P130 wurden kleiner (P=0.002 undP=0.003). Die Veränderungen der späten Komponente der visuell evozierten Potetentale während der Allgemeinanaesthesie mit Enfluran deuten auf einen kortikalen Einfluß hin.