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|Year : 2002
: 4 | Issue : 16 | Page
|Effects of occupational exposure to mercury or chlorinated hydrocarbons on the auditory pathway
Moshe Shlomo1, Frenkel Avraham2, Hager Moshe3, Skulsky Mario4, Sulkis Jacklin5, Himelfarbe Mordechai5
1 Keren Ha-Yesod 15 st.,Givat-Shmuel 51905, Israel
2 The Ear Nose and Throat Department, Tel Aviv Medical Center, Sackler School of Medicine, Tel-Aviv University, Israel
3 Kupat-Holim Hakelalit, Occupational Department, Holon, Israel
4 The Israel National Insurance, Jerusalem, Israel
5 The Biostatistics Department, Beilinson Medical center, Petah-Tikva, Israel
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The purpose of this study was to examine the effects of industrial exposure to mercury and chlorinated hydrocarbons (CH) on the auditory pathway. To this effect, auditory brainstem responses (ABR) were recorded from 40 workers exposed to mercury, 37 workers exposed to CH and from a control group of 36 subjects that were never exposed to neurotoxic substances. The interpeak latency (IPL) of waves I-III, III-V and I-V were measured. The mean duration of exposure to mercury and CH was 15.5 (+6.4) and 15.8 (+7.2) years respectively. The air sample monitoring of mercury was 0.008 mg/m3 (0.32 of the Threshold Limit Value - TLV® as published by ACGIH 2000). The mean average air sample monitoring was found to be 98 ppm for TCE, 12.7 ppm for PCE and 14.4 ppm for TCA which is respectively between 0.28 - 0.51 of the TLV® of CH. The mean blood mercury (B-Hg) levels were found to be 0.5mgr% (+0.3mgr%), which is 0.13 of the upper range of the permitted biologic exposure index (BEI) published by the ACGIH 2000. The mean urine samples levels of trichloroacetic acid were between 0.11-0.2 of the permitted BEI for the CH workers. The percent of workers exposed to mercury and CH workers with abnormal prolongation of IPL I-III was higher than the control group (42.5% and 33.8% vs. 18.0% respectively p<0.02). These results are consistent with other studies and show that ABR may provide a sensitive tool for detecting subclinical central neurotoxicity caused by CH and mercury
Keywords: mercury, chlorinated hydrocarbons, trichloroethylene, trichloroethane, perchloroethylene, trichloroacetic acid, organic solvents, brainstem evoked response, neurotoxicity
|How to cite this article:|
Shlomo M, Avraham F, Moshe H, Mario S, Jacklin S, Mordechai H. Effects of occupational exposure to mercury or chlorinated hydrocarbons on the auditory pathway. Noise Health 2002;4:71-7
|How to cite this URL:|
Shlomo M, Avraham F, Moshe H, Mario S, Jacklin S, Mordechai H. Effects of occupational exposure to mercury or chlorinated hydrocarbons on the auditory pathway. Noise Health [serial online] 2002 [cited 2022 May 21];4:71-7. Available from: https://www.noiseandhealth.org/text.asp?2002/4/16/71/31825
| Introduction|| |
Evoked potentials are electrical signals recorded from the scalp in response to external stimulations of peripheral nerves or sensory organs. Auditory Brainstem Responses (ABR) are early Central Nervous System (CNS) evoked potentials recorded during the first 10 ms following click stimuli, generated along the auditory nerve and the brainstem auditory pathway. ABR abnormalities have been observed in a variety of neurological conditions such as multiple sclerosis, tumours and closed head injuries (Seppalainen, 1994; Discalzi et al., 1993).
ABR and other evoked potentials - Visual Evoked Potentials (VEP) and Somatosensory Evoked Potentials (SEP) have been used as relatively safe, easy and sensitive means to study the effects of long - term exposure to neurotoxic chemicals (Seppalainen, 1994; Discalzi et al., 1993). ABR studies of workers exposed to nhexane revealed prolonged wave V and waves IV Inter Peak Latencies (IPL) suggesting pathology of the auditory central pathways (Chang, 1987; Huang and Chus, 1989). SEPs have been used to detect peripheral neurologic deficits in workers exposed to n-hexane (Mutti et al., 1982), solvents and lead (Hazeman et al., 1983; Jeyarantnamy et al., 1985) and to mercury (Triebig et al., 1984; Langaver - Lewonica and Kazibutowska, 1988). VEP have been recorded in order to observe neurologic damage of the optic nerve due to exposure to lead (Sborgia et al., 1983; Armaki et al., 1986) zinc, copper (Sborgia et al., 1983) and mercury (Langaver - Lewonica and Kazibutowska, 1988).
Most of the studies of evoked potentials in occupational medicine were performed in symptomatic patients. The aim of our study was to verify the usefulness of ABR in detecting subclinical CNS effects of mercury and chlorinated hydrocarbons (CH) in asymptomatic workers exposed to safe levels of those substances, i.e., below recommend exposure limits.
| Material and Methods|| |
Three groups of male workers were evaluated - workers exposed to mercury (n=40), workers exposed to CH (n=37) and age-matched control group (n=36). Out of 37 exposed to CH, 7 workers were exposed to Trichloroethylene (TCE), 8 to Perchloroethylene (PCE) and 22 were exposed to Trichloroethane (TCA). The mean age of the workers was 49.7 ( + 6.4) years in mercury exposed group, 46.0 ( + 4.73) years in CH exposed group and 49.8 ( + 5.8) years in the control group. No cases of clinical mercury or CH poisoning were present. The workers were exposed during their daily work. There is a possibility that poor hygienic habits could cause exposure by ingestion or skin contact. Urinary mercury concentration was determined in a sample taken at the end of the work shift, on the day before the test. A urine sample of Trichloroacetic Acid (TCAA) was taken at the end of the shift, and at the end of the workweek. The control subjects were never exposed to neurotoxic substances, as indicated in the interview and industrial records.
At the first examination, a medical history was obtained for each subject. None of the subjects had a history of neurological, psychiatric, otologic or other chronic diseases. No subject reported consuming more than 70-cc alcohol per day. Otoscopy was used to examine the ear. In case cerumen occluded the external ear canal, it was removed by irrigation. Neurological tests of the subjects included examination of the cranial nerves and cerebellar function, using a clinical evaluation as recommended. No abnormality was indicated in any of the subjects. The puretone audiometric tests (obtained from their medical registry) showed no difference between the ears.
All the subjects underwent ABR testing (Screener, by Medelek). The acoustic stimuli consisted of clicks delivered at a rate of 11/s, alternating in polarity, and at an intensity of 85 dBHL. The responses to 1024 clicks were recorded from y scalp-electrodes, band-passed, filtered, amplified and averaged. The absolute latency of waves I, II, III, IV and V and the IPL I-III, III-V and I-V were calculated.
The means, standard deviations, median and ranges were calculated from the database collected in the occupational clinic. For the audiological results the mean values and the comparison between the different groups were analysed by Student's t and proportions tests. A confidence level of <0.05 was accepted as an indication of statistical significance.
| Results|| |
Biologic and environmental exposure levels results
The mean duration of exposure to mercury & CH was 15.5 ( + 6.4) and 15.8 ( + 7.2) years respectively. [Table - 1] represents the measured exposure levels of the different substances. The result of air sample monitoring was compared to the Threshold Limit Values (TLV®) published annually by the ACGIH (American Conference of Governmental Industrial Hygienists), 2000. The air sample monitoring of mercury was 0.008 mg/m 3 (0.32 of the TLV®). The mean level for TCE was 98 ppm, 12.7 ppm for PCE and 14.4 ppm for TCA. CH concentration was 0.28 - 0.51 of the TLV®. All Biologic Exposure Index (BEIs® which are published by the ACGIH) are the recommended values in the labour regulations published in Israel. Mean blood mercury (B-hg) levels were found to be 0.5gr% ( + 0.3gr%), which is 0.13 of the upper range of the BEI. The range of urine samples levels of TCAA were between 1%-80% of the BEI. The mean urine samples levels were between 0.110.2 of the permitted BEI for the CH. The measured BEI are detailed in [Table - 2] (ACGIH, 2000).
For both, study and control groups, thresholds at 0.25 kHz - 2 kHz ranged from 15 to 19 dB. At 4 kHz the average threshold in both ears was 25.0 dB HL in the mercury group, 28.8 dB HL in the CH group and 24.0 in the control group. The average threshold at 6 kHz in both ears was 23.2 dB HL in the mercury group, 30.3 dB HL in the CH group and 23.3 in the control group. For all tested frequencies the differences between the groups, for the right and left ears, were not statistically significant.
Auditory Brainstem Response (ABR) tests
[Table - 3] shows the ABR findings of for the right and left ears in the study groups respectively. The ABR recordings showed normal mean ABR absolute latencies for waves I to V, and normal IIII, III-V, and I-V inter peak latency (IPL) for right and left ears. No difference was found between the groups.
In order to find the proportion of abnormal ABR results we selected the upper limit of each IPL as 2.5 msec, 2.3 msec and 4.4 msec in I-III, III-V and I-V respectively. The upper limit of abnormal results of the IPL was determined according to the results of the control group and was defined above average + 1 SD. The proportion of abnormal ABR in the different IPL is demonstrated in [Table 4],[Table 5]. A significant difference was found in the IPL I - III in the study groups compared to the control group. The proportion of abnormal findings in IPL I-III was 42.5% in the mercury workers, 33.8% in the CH workers and 18.0% in the control group.
| Discussion|| |
This study examined the possible sub-clinical central nervous system (CNS) alterations in workers with long term exposure to low levels of mercury or CH. These workers were otherwise clear of neurological symptoms (such as tremor, or neuro behavioral alterations). ABR were recorded from 40 workers exposed to mercury, 37 workers exposed to CH and from a control of 36 subjects never exposed to neurotoxic substances. Subjects were matched by age and gender. The percent of mercury and CH workers with abnormal prolongation of IPL I-III was higher than for the control group (42.5% and 33.8% vs. 18.0%, p<0.01, p<0.02 respectively).
In recent years evoked potentials as SEP, VEP and ABR, became standard tools in occupational neuro-toxicological evaluation because they are non-invasive, can be used safely, and they provide objective indications of CNS disorders (Seppalainen, 1994). ABR tests serve as an objective method for evaluating the integrity of the ascending brainstem auditory tracts and nuclei, and measuring neural transmission capacity. The findings of this study suggest that the neural conduction time at the brainstem level were affected by exposure to mercury and CH. The statistically significant relationship between exposure to mercury and CH and the ABR I-III IPL prolongation may suggest a neurological effect at the level of the 8th nerve and the cochlear nuclear complex.
Several studies investigated ABR changes in mercury workers and exposed population. Lille et al (1988) reported normal ABR in patients exposed to mercury with mean BEI of 325 gr HgU. Discalazi et al (1993) evaluated the effects of occupational exposure to mercury and lead on ABR. Both mercury and lead exposed workers showed a significant prolongation of wave I-V IPL. The authors concluded that ABR may provide a sensitive tool for detecting subclinical central neurotoxicity caused by lead and mercury. Counter et al (1998) evaluated B-Hg and auditory neuro-sensory response in children and adults in the Namibija gold mining area of Ecuador. The ABR results on subjects in the study area showed a significant correlation between B-Hg and the I-III IPL on the right side. The results reported in the study are consistent with the results reported in the literature. These results show that ABR may provide a sensitive tool for detecting subclinical central neurotoxicity caused by mercury.
TCE was recognized as an industrial hazard over 50 years ago (Feldman, 1979). Unlike the peripheral neuropathies associated with carbon disulfide, n-hexane and methyl n-butyl ketone, TCE neuropathy is associated with sensory loss (facial dysesthesia and numbness) and motor weakness (muscles of mastication) in the distribution of the trigeminal nerve. Lower cranial and optic nerves may also be involved (Feldman, 1979). These types of cranial neuropathies are now attributed to a spontaneous decomposition product of TCE i.e. dichloroacetylene). Long-term, low-level exposure to TCE has also been reported to produce adverse neurological and neuropsychiatric effects, including tremor, giddiness, increased lacrimation, reddening of the skin, hypoesthesia, alcohol intolerance, neurasthenia and anxiety, bradycardia, and insomnia (Seppalainen, 1994). These disorders reportedly tend to become more severe with length of employment and degree of exposure. The ototoxicite associated with TCE exposure has been described as a high-frequency hearing loss in both humans (Szulc-Kuberska et al, 1976) and rats (Crofton & Zhao, 1993; Jaspers et al, 1993; Rebert et al, 1989). These reports suggests ototoxicity, characterized by hearing loss that progresses in a time-dependent manner, in a higher to lower frequency direction, and associated hair cell loss in the organ of corti. Of a variety of aromatic and halogenated hydrocarbons tested for their effects on vestibulo-ocular postrotatory nystagmus, it was noted that, with very few exceptions, the major determinant of excitation or inhibition of the reflex was the presence or absence of chemical double bonds. Unsaturated structures produced excitation.
PCE, now widely used as a substitute for TCE in dry cleaning of fabrics and degreasing of fabricated metal parts, reportedly produces similar neurasthenic effects, including longlasting changes in personality and recent memory (Seppalainen, 1994). Comparable changes, as well as trigeminal sensory defects, have been reported in individuals exposed to mixtures of TCE and PCE (Antti-poika et al., 1982). In this study we found that the percent of CH workers with abnormal prolongation of IPL I-III was higher than the control group (33.8% vs. 18.0% and p<0.01).
Abbate et al (1993) have investigated rotogravure printers chronically exposed to toluene without any hearing loss as shown by audiometry. They have shown alterations in ABR latency measured as effects of stimulation repetition rate. Chang et al (1987) have investigated the neurotoxic effects of n-Hexane on the human CNS by measuring evoked potential abnormalities in workers diagnosed with polyneuropathy. The ABR results showed prolongation of the wave I-V IPL corresponding with the severity of the polyneuropathy.
Chronic Mercury poisoning is what is meant when the term mercurialism is used. The chronic poisoning effect is also related to the physiochemical properties of the material inhaled or ingested. Spongous degeneration of the brain cortex has been reported as a late sequela to past severe exposure. Mercury granules were demonstrated histochemically in nerve cells, choroid plexus and phagocytes in the brains of both organic and inorganic mercury - treated rates, and in the ependyma of organic mercury - treated rats (Beliles, 1994).
The results of the present study suggest subclinical damage at the level of the lower brainstem after chronic exposure to mercury or solvents. The results correlate well with previous studies that investigated other organic solvents. However, this is the first study to investigate the influence of exposure to CH on the ABR of healthy workers. Moreover, the workers were exposed to mercury and CH levels that were less then half of the currently recommended exposure limits by the ACGIH 2000. Thus, it seems that even those levels of neurotoxic agents considered being safe and inert to worker's health might cause subclinical neurologic dysfunction in long-term exposures. It is justified, therefore, that biologic and environmental monitoring should be mandatory in this population of workers. ABR recordings appear to be a sensitive tool for detection of those subclinical CNS impairments and may be used also for monitoring the neurologic effects. Additional studies of human populations and experimental animals are required to evaluate if chronic occupational exposure to TCE and/or PCE precipitates irreversible changes in neurologic function. Large population with a range of mercury exposure levels must also be tested by ABR before conclusions can be drawn regarding the relationship between exposure and ABR effects.
| References|| |
|1.||Abbate C, Groigiani C, Munao F, Breciaroli R. (1993) Neurotoxicity induced by exposure to toluene. Am electrophysiologic study. Int Arch Occup Environ Health 64, 389-92. |
|2.||American Conference of Governmental Industrial Hygienist (ACGIH) (2000). Threshold Limit Value for chemical substances and physical agents - Biologic Exposure Indices. ACGIH Cincinnati OH. |
|3.||Antti-Poika M. (1982) Prognosis of symptoms in patients with diagnosed chronic organic solvent intoxication. Int Arch Occup Health 51, 81-89. |
|4.||Araki S, Murata K and Aono H. (1986) Subclinical cervico spinboulbar effect of lead: a study of short - latency somatosensory evoked potentials in workers exposed to lead zinc and copper. Am J Ind Med 10, 163-75. |
|5.||Beliles RP. The metals (Mercury). From Patty's Industrial Hygiene and Toxicology 4th ed. vol 2. (1994). John Willey and Sons Inc. New York, US. Pp2124-2146. |
|6.||Chang YC. (1987) Neurotoxic effects of n-Hexane on the human central nervous system: evoked potential abnormalities in n-Hexan polyneuropathy. J Neurol Neurosurg Psychiatry 50, 269-274. |
|7.||Counter SA, Buchanan LH, Laurell G, Ortega F. (1998) Blood mercury and auditory neuro-sensory response in children and adults in the Nambija gold mining area of Ecuador. Neurotoxicol 19,185-196. |
|8.||Crofton KM, Zhao X. (1993) Mid-frequency hearing loss in rats following inhalation exposure to trichloroethylene: evidence from reflex modification audiometry. Neurotoxicol Teratol 15, 413-23. |
|9.||Discalzi G, Donatella F, Meliga F. (1993) Effects of occupational exposure to mercury and lead on brainstem auditory evoked potentials. Int J Psychophysiology 14, 2125 . |
|10.||Feldman RG. (1979) Trichloroethylene. In: Vinken PJ, Bruyn GW, ed. Handbook of Clinical Neurology, intoxication of the nervous system, part 1. North-Holland Publishing co, Amsterdam, pp 457-464. |
|11.||Firth JB, Stuckey RE. (1945) Decomposition of trilene in closed circuit anesthesia. Lancet 1, 814-17. |
|12.||Hazemam P, Jeftic M ,Lille F. Somatosensory evoked potentials in alcoholic and patients occupationally exposed to solvents and lead. Electromyogra Clin Neurophysiol. |
|13.|| Huang, C.C. and Chus N.S. (1989) Evoked potentials in chronic n-Hexane intoxication. Clin Electroencephalogra 20, 162-168. |
|14.||Jaspers RMA, Muijser H, Lammers JHCM, Kulig BM. (1993) Mid-frequency hearing loss and reduction of acoustic startle responding in rats following trichloroethylene exposure. Neurotoxicol Teratol 15, 40712. |
|15.||Jeyarantnamy A., Devanthasan, G., Ong, C.N. Phoon W.O., Wong P.K. (1985) Neurophysiological studies on workers exposed to lead . Br J Ind Med 42, 173-177. |
|16.||Langaver - Lewonica, H. and Kazibutowska, Z. (1988) Multimodality evoked potentials in occupational exposure to metallic mercury vapor . Pol J Occup Med 2, 192-199. |
|17.||Lille, F., Hazemann, P., Garnier., R., Dally, S.(1988) Effects of lead and mercury intoxication on evoked potentials. Clin Toxicol 26, 103-116. |
|18.||Mutti, A., Ferri, F., Lommi, G. (1982) N-Hexane Induced Changes in conduction velocities and somatosensory evoked potentials. Int Arch Occup Environ Health 51, 4554. |
|19.||Rebert CS, Day VL, Matteucci MJ, Pryor GT. (1991) Sensory-Evoked potentials in rats chronically exposed to Trichloroethylene: predominant auditory dysfunction 13,83-90. |
|20.||Sagawa, K. (1973) Transverse lesion of the spinal cord after accidental exposure to trichloroethylene. Int Arch Arbeitsmed 31, 257-264. |
|21.||Sborgia, G, Assenato G.L, Abbate N, De Marinis I, Paci C, De Nicolo M, De Marinis G., Mantrone N, Ferrmini E, Specchio L, Masi G, Olivreri G. (1983) Comprehensive neurophysiological evaluation of lead exposed workers. In R Galilee MG, Cassitto and V Foa (Eds.) Neurobehavioral Methods in Occupational Health. Pergamon press London pp 283-294. |
|22.||Schaumburg, H.H., Spencer, P.S., Thomas, P.K. (1983) Disorders of Peripheral Nerves. FA Davis, Philadelphia, PA . |
|23.||Seppalainen, A.M. Occupational Neurotoxicology, in Zenz C. Occupational Medicine, 3rd Ed, (1994). Year Book Medical Publishers Inc Pp 790 - 799. |
|24.|| Spencer, P.S., Bischoff, M.C. (1982) Spontaneous remyelination of spinal cord plaques in rats orally treated with sodium dichloroacetate. J Neuropathol Exp Neurol 41, 373. |
|25.||Szulc-Kuberska J, Tronczynska J; Latkowski B. (1976) Oto-neurological investigations of chronic trichloroethylene poisoning. Minerva Otorhinolaringo 26, 108-112. |
|26.||Triebig, G., Giobet, T., Saure, E., Schaller, K.H., Weltle, D., Valentin. (1984) Investigation on neurotoxicity of chemical substances at the workplace. Longitudinal study in persons occupationally exposed to mercury. Int Arch Occup Environ Health 55, 19-31. |
Keren Ha-Yesod 15 st.,Givat-Shmuel 51905
Source of Support: None, Conflict of Interest: None
[Table - 1], [Table - 2], [Table - 3]
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