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Journal of Occupational & Environmental Medicine:
Original Articles

Neuro-Ototoxicity in Andean Adults With Chronic Lead and Noise Exposure

Counter, S. Allen DMSc, PhD; Buchanan, Leo H. PhD

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Author Information

From the Department of Neurology, Massachusetts General Hospital, Harvard Medical School, The Biological Laboratories, Cambridge (Dr Counter); and the Audiology Department, Harvard University Health Services, Shriver Center UAP LEND Program, Waltham (Dr Buchanan); Massachusetts.

Address correspondence to: Dr. S. Allen Counter, Harvard University, The Biological Laboratories, 16 Divinity Avenue, Cambridge, MA 02138; allen_counter@harvard.edu.

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Abstract

Brainstem auditory evoked responses and audiological thresholds were used as biomarkers for neuro-ototoxicity in adults with chronic lead (Pb) intoxication from long-term Pb exposure in ceramic-glazing work. Venous blood samples collected from 30 adults (15 men and 15 women) indicated a mean blood Pb level of 45.1 μg/dL (SD, 19.5; range, 11.2 to 80.0 μg/dL) and in excess of the World Health Organization health-based biological limits (men, 46.2 μg/dL; SD, 19.6; range, 18.3 to 80.0 μg/dL; women, 44.0 μg/dL; SD, 20.1; range,11.2 to 74.2 μg/dL). Mean auditory thresholds at frequencies susceptible to ototoxicity (2.0, 3.0, 4.0, 6.0, and 8.0 kHz) revealed sensory-neural hearing loss in men, which may be attributable to occupational noise exposure in combination with Pb intoxication. Bilateral brainstem auditory evoked response tests on participants with elevated blood Pb levels (mean, 47.0 μg/dL) showed delayed wave latencies consistent with sensory-neural hearing impairment. The results suggest that environmental noise exposure must be considered an important factor in determining sensory-neural hearing status in occupationally Pb-exposed adults.

Lead (Pb) poisoning in adults remains a serious occupational health problem in many developing countries and in factories of some industrialized nations. 1–4 Chronic Pb intoxication is reported to cause pervasive physiological abnormalities and to induce neurosensory, neuromotor, and neurocognitive impairment in children and adults. 5–7 At the cellular level, Pb interferes with neuronal development and synaptogenesis and blocks the action of neural cell adhesion molecules. 8,9 It has also been suggested that Pb exposure impairs neural functioning by disrupting calcium regulated intracellular activity, including protein kinase C regulation at the synapse, and reduces cellular enzymatic activity below critical levels. 10,11 Segmental demyelination and axonal degeneration are the hallmarks of Pb-induced neuropathy, manifested clinically by distinct wrist and ankle drop and extensor muscle palsy. 12 Exposure to toxic levels of Pb may have both acute and long-term physiological consequences, because Pb has a half-life of approximately 18 days in the blood and years to decades in bones, the major reservoir of the Pb body burden. 13 However, the complete range of neurobiological changes resulting from long-term high Pb intoxication in adults has not been fully elucidated. Furthermore, Pb-induced neurotoxicity is variable in its effects on individuals and in its dose-response relationship, and it is affected by several factors. 14

One adverse neurophysiological effect that has been reported to be associated with Pb intoxication is auditory impairment, as revealed by sensory-neural hearing loss and abnormal neural transmission in the tracts and nuclei of the auditory brainstem of animals and humans. 15–20 On the basis of findings of these and other previous auditory studies, it may be predicted that the inner ear and contiguous eighth nerve and brainstem neurons of chronically Pb-intoxicated adults would be permanently impaired or, at best, severely compromised. The conclusions regarding the neuro-ototoxicity of Pb have been based primarily on measures of far-field potentials from the brainstem auditory pathway and audiological tests of cochlear (sensory-neural) function, both of which are presumed to have utility in neuro-ototoxicity testing. 21–25 Thus, the findings of several widely cited studies would suggest that measures of auditory sensory-neural function might serve as a reliable noninvasive biomarker for Pb intoxication. Although the specific neuro-ototoxic effects of Pb poisoning on the auditory brainstem and cochlea of adults are not fully understood, it is reported that Pb exposure, even at low levels, impairs the inner ear receptor cells and neuronal function in the ascending auditory brainstem tracts. 21,24 However, some investigators have not found a relationship between Pb exposure and auditory function, raising questions regarding evidence for Pb-induced neuro-ototoxicity. 26,27 A recent study has reported a relationship between decreased hearing and long-term ambient Pb and noise exposure but no effects on hearing after short-term (defined by PbB levels) exposure. 28

In previous investigations of the prevalence of Pb poisoning in children living in highly Pb-contaminated Ecuadorian villages where small-scale Pb glazing of ceramic tiles is the primary livelihood, we have found extensive and chronic Pb intoxication with indications of Pb-induced anemia in the children. 29,30 The high blood lead (PbB) levels not withstanding, we found no evidence of inner ear ototoxicity or auditory brain impairment in the children of this study area. 31,32 One question that arises is whether there is a cumulative effect of chronic Pb exposure, such that significant auditory impairment may not be evident until adulthood. Furthermore, our previous research has shown that the adults of the same area also have chronic Pb poisoning, with many presenting with PbB levels in excess of the World Health Organization (WHO) health-based biological limits. 33 It is conceivable that because of the possible cumulative effect of Pb exposure, adults may demonstrate Pb-related auditory dysfunction while the Pb-exposed children do not. However, the Pb-intoxicated adults in the study area have not been the subject of a systematic investigation of the neuro-ototoxic effects of their chronic Pb exposure.

If auditory thresholds and auditory brainstem neural conduction times are reliable biomarkers for neuro-ototoxicity, it would be expected that auditory abnormalities would be reflected in these behavioral and electrophysiological measures, especially in cases of chronic Pb intoxication. The objective of this field study was to measure the auditory brainstem and cochlea function in a group of adult men and women with long-term occupational Pb exposure and to determine whether their auditory function is related to PbB levels. A second aim was to determine the hearing health status of the adult Pb-glazing workers who participated in the study and report the findings to the patients and the local health authorities.

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Materials and Methods

Participants and Location

The participants in this study were 30 adult Pb-glazing workers (15 women and 15 men) aged 17 to 55 years (median, 35.2 years) and living in the village of La Victoria, in Cotapaxi Province, Ecuador, approximately 125 km south of Quito at an altitude of approximately 2800 m above sea level, and in the village of Racar, located at an altitude of 2500 m and approximately 15 km west of the southern Ecuadorian city of Cuenca. The inhabitants of both villages are mainly indigenous Quechua “Indians” (descendants of the Incas) and Mestizos (persons of mixed Spanish and indigenous Indian backgrounds), most of whom have lived all of their lives in the Pb-contaminated areas. The study areas are sites of extensive Pb glazing of ceramic roof tiles and artisan crafts as a cottage industry, with men and women participating in the Pb extraction, mixing, coating, and baking operations. Discarded automobile Pb-acid storage batteries purchased from local vendors are the primary source of Pb exposure in the area. 30,32 All participants in this study received a medical examination and medical treatment for complaints when indicated. Informed consent was obtained from each participant before testing. This study was approved by the Human Studies Committee of the Universidad San Francisco de Quito Medical School, and it was conducted under the auspices of the Universidad San Francisco de Quito Medical School in Quito, Ecuador.

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Blood Pb Level

Venous blood samples were obtained for measurements of PbB levels at the same time that the electrophysiological and audiological data were acquired. The concentration of Pb in whole blood was determined by drawing 2 to 4 mL of blood from the antecubital vein of 30 adults in the Pb study areas (using evacuated Li-heparinized blood collecting tubes) after thorough cleaning of the skin with water and isopropanol swabs. All whole blood samples were refrigerated and analyzed within 1 week for Pb concentrations by inductively coupled plasma-mass spectrometry at the Channing Laboratory of the Harvard School of Public Health. Four empty tubes from the same batch used at the test site were tested for metal contamination. Quality control samples of blood were analyzed on 0.5 mL of the collected samples by Graphite Furnace Atomic Absorption Spectroscopy at the Boston Children’s Hospital Chemistry Laboratory. The WHO (International Programme on Chemical Safety, 1995) health-based biological exposure limits for PbB of ≥40 μg/dL (1.92 μmol/L) for men, and PbB levels ≥30 μg/dL (1.44 μmol/L) for women, were used as references. Recent US National Institute for Occupational Safety and Health regulations, however, indicate that occupational PbB levels >25 μg/dL are considered elevated in occupationally exposed adults.

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Audiological Examination

An audiological case history was taken on each subject at the time of examination. Comprehensive audiological evaluations were performed in the field on 15 men and 15 women who engaged in Pb-glazing activities. The tests were conducted on Pb-exposed adults in the study area who were available for audiological testing. Data were not included in the present study for two subjects found to have bilateral conductive pathological conditions as determined by audiological and otoscopic examinations. Audiological tests were obtained in a quiet area and consisted of pure-tone air and bone conduction threshold data and tympanometry. Pure-tone air conduction threshold data were obtained from both ears at 0.25, 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, and 8.0 kHz using the Interacoustics (model AD 12, Copenhagen, Denmark) portable audiometer with standard TDH 39 earphones, which were housed in otocups for additional sound attenuation. In addition to an analysis of the thresholds for the individual frequencies in the 1- to 8-kHz range, thresholds were averaged across the 4- to 8-kHz range to assess overall high-frequency sensitivity. Bone conduction thresholds were obtained if a hearing loss was detected. Pure-tone thresholds were obtained using the conventional descending-ascending threshold crossing technique. Threshold was defined as the minimum hearing level at which the participant responded at least two times on ascending trials. A priori intratest reliability was set at ±5 dB at 1 kHz. Audiological threshold measurements were used to evaluate the integrity of the sensory receptors in the inner ear. In the data analysis, the frequencies of 0.25 and 0.5 kHz were excluded because of their sensitivity to ambient noise levels, and because these frequencies are less susceptible to ototoxic exposure. The ototoxicity literature suggests that the high-frequency area of the inner ear (≥2 kHz) is most vulnerable to ototoxic chemicals and noise. The securely packed audiometer was transported to the test site in the Andes Mountains by vehicle and by foot. Hearing thresholds of ≤20 dB hearing level were considered normal. Verbal instructions were given to the participants in Spanish. Each participant responded by raising his or her hand when a tone was heard. Tympanometric results were obtained using the GSI-33 tympanometer. Tympanometry, in combination with the otolaryngological examination, was used to rule out a middle-ear pathological state.

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Brainstem Auditory Evoked Response Measurements

Electrophysiological brainstem auditory evoked response (BAER) examinations were conducted in the field with the instrumentation being transported to the test site in the Andes Mountains by vehicle, or by foot when vehicular transportation could not be used. The BAER equipment was carefully packed in rubber foam and bubble plastic packing and was housed in a specially designed fiberglass carrying case for transport. The electrophysiological averager was checked for functionality, cleaned on arrival at the test site in the Andes, and, subsequently, checked on a daily basis. BAER measures were used to examine the functional integrity of the ascending auditory brainstem tracts and nuclei, including summated response latency and neural transmission capacity. 34–36 Complete BAER measures were obtained on Pb-exposed adults in the study area who were available for testing. Each participant was tested in the supine position on a small bed or flat wooden surface. Standard bilateral BAER measures were conducted in the field on 12 adults (8 men and 4 women) in the Pb-glazing study areas using a Medlec/GSI 50 (Grason-Stadler, Inc, Milford, NH) electrophysiological system. The participants’ scalp, forehead, and ear lobes were thoroughly cleaned with swabs containing isopropanol, and gold-plated electrodes were placed at Cz, (active), A1, A2 (reference), and Fpz (ground), according to the 10-20 International Electrode System. The electrodes (vertex positive) were connected to a standard pre-amplifier (105), which was connected to the Medlec/GSI 50. Broad band monaural rarefaction click stimuli of 70 to 90 dB normal hearing level (nHL) and 100-μsec duration were delivered to the ear/side under test through TDH 39 earphones at rates of 10 per second (1024 to 2048 sweeps/trial) with contralateral masking. The BAER was bandpass-filtered between 100 and 3000 Hz. The intensity level of the click was increased in 10-dB steps (up to 100 dB nHL) when BAER morphological results were unclear at 70 dB HL. The absolute latencies (msec) of wave peaks I, III, and V, and the interwave peak latencies of I-III, III-V, and I-V, were measured and analyzed statistically. All measures were repeated for reliability. The average time for a complete BAER test on each patient in the field, from cleaning the scalp for electrode placement to post-test electrode removal was approximately 60 minutes.

The blood tests, electrophysiological and audiological measures were conducted in the field (in schools, churches, warehouses, and the local infirmary) using portable generator power, automobile battery power, or local electricity where available. All instruments used for the BAER and audiological measurements were calibrated to International Standards Organization 389 standards at Harvard University Biological Laboratories and were calibrated biologically in the field on a daily basis.

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Statistical Analysis

The mean, median, and range of the BAER absolute wave peak and interpeak latencies and pure-tone thresholds were determined for men and women in the study group. The differences in means were analyzed by t test and Mann-Whitney U test. Regression analyses were used to measure relations between auditory endpoints and PbB levels.

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Results

Blood Lead Level

The mean PbB level for 30 adult (15 men and 15 women) participants in the present study was 45.1 μg/dL (SD, 19.5; range, 11.2 to 80.0 μg/dL). The distribution of PbB levels for the 30 participants is shown in Fig. 1. The mean PbB levels for the 15 men and 15 women were 46.1 μg/dL (SD, 19.6; range,18.4 to 80.0 μg/dL) and 44.0 μg/dL (SD, 20.1; range, 11.2 to 74.2 μg/dL), respectively. The difference in mean PbB levels between men and women was not statistically significant (t test, −0.299;P = 0.767; Mann-Whitney U, P = 0.852).

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Audiological Examination

The PbB levels for the 30 adult Pb-glazing workers given audiological examinations ranged from 11.2 to 80.0 μg/dL. The mean mid- and high-frequency pure-tone thresholds for the right and left ears of the 15 men and 15 women are shown in Fig. 2. The results indicated that the men had significantly poorer high-frequency hearing sensitivity (Mann-Whitney U test, P ≤ 0.05) than the women in the right ear at 4.0, 6.0, and 8.0 kHz, and in the left ear at 3.0, 4.0, 6.0, and 8.0 kHz. The mean high-frequency average (hearing thresholds averaged across four frequencies: 3.0, 4.0, 6.0, and 8.0 kHz) was determined for men and women. The four frequency average thresholds for the men were 29.5 and 37.5 dB for the right and left ears, respectively. For the women, the four frequency average thresholds were 17.8 and 16.9 dB for the right and left ears, respectively. Nine men were found to have right and left ear four-frequency averages that were abnormal (>20 dB). Among the women, three were found to have abnormal right ear four-frequency averages, and two women had abnormal left ear four-frequency averages. In summary, 60% of the men had abnormal high-frequency hearing, whereas only 20% of the women had abnormal high-frequency thresholds. The regression curves of Fig. 3 show the relations between PbB level and auditory thresholds for the 30 subjects at 3.0, 4.0, 6.0, and 8.0 kHz. There was no statistically significant relationship between PbB level and pure-tone threshold at any frequency. However, sensory-neural hearing impairment was observed in several individual participants who had a history of occupational Pb and noise exposure (Figs. 5 through 7). For comparison, the audiogram of a normal 24-year-old woman with no history of Pb or noise exposure, who was tested on the same audiological equipment, is shown in Fig. 4, A.

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Brainstem Auditory Evoked Responses

Neurophysiological brainstem measurements from auditory tracts of 12 Pb-glazing workers (24 bilateral BAER tests) with PbB levels ranging from 18 to 80 μg/dL (mean, 47.0 μg/dL) showed a range of normal and abnormal BAER absolute latencies of waves peaks I, III, and V (Table 1), consistent with the patients’ peripheral hearing status. The delayed absolute latencies in peaks I, III, and V were unilateral in cases of unilateral peripheral hearing impairment and bilateral in instances of audiometrically determined bilateral hearing loss. The mean overall absolute latencies for the three primary wave peaks of I, III, and V were 1.69 msec (SD, 0.17), 3.83 msec (SD, 0.24), and 5.71 msec (SD, 0.26), respectively, and within the normal range. The mean interpeak latencies were 2.22 msec (SD, 0.14) for waves I-III, 1.84 msec (SD, 0.27) for waves III-V, and 4.06 msec (SD, 0.25) for waves I-V and were within normal limits. The BAER recordings (showing normal structure, latency, and amplitudes) from a neurologically normal person with no history of exposure to Pb, noise, or any other known ototoxic substance, who was tested on the same electrophysiological equipment, are shown in Fig. 4, B and C.

Table 1
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Case Profiles

The following cases are presented to illustrate the relations between PbB levels, BAER responses, and audiological thresholds in some of the Pb-intoxicated patients with PbB levels exceeding the WHO (International Programme on Chemical Safety, 1995) health-based biological exposure limits (≥40 μg/dL for men ≥30 μg/dL for women) and the US National Institute for Occupational Safety and Health regulations (>25 μg/dL).

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Case Profile 1

Case 1 is a 41-year-old man with a 25-year history of work in Pb-glazing operations and occupational noise exposure who has lived in the Pb-contaminated study area all of his life (Fig. 5). His PbB level was found to be 80 μg/dL and probably represents chronic Pb intoxication. He had no neurological, audiological, or other general medical complaints. Tympanometric tests for middle-ear abnormalities were negative, and the case history revealed no tinnitus. The audiogram of Fig. 5, A shows a mild high-frequency sensory-neural hearing loss in the right ear and a mild-to-severe high-frequency hearing loss in the left ear. The replicated unilateral BAER recordings of Fig. 5, B and C illustrate the latencies and amplitudes of the patient’s far-field brainstem potentials wave peaks. Absolute BAER wave peaks I, III, and V were slightly delayed on the right side (Fig. 5, B) but showed normal wave form structure. The BAER measures of the left side (Fig. 5, C) also revealed normal wave form structure but delayed absolute wave peak latencies of I, III, and V that were consistent with his peripheral hearing loss. The interpeak latencies and the V/I amplitude ratios were within the normal range bilaterally, suggesting that his hearing loss is related to noise exposure and not Pb exposure. The patient was counseled regarding his high-frequency hearing loss and was advised to avoid exposure to loud noise in the workplace and to use ear protectors if exposed.

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Case Profile 2

Case 2 is a 39-year-old man with a history of noise exposure who has worked for 25 years in Pb-glazing operations and has lived in the study area all of his life (Fig. 6). His PbB level was found to be 68 μg/dL. Although he had a history of chronic otitis media, the otoscopic examination, tympanometry, and pure-tone tests were negative for middle-ear abnormalities. The case history revealed no tinnitus. The audiogram of Fig. 6, A shows a bilateral, mild high-frequency sensory-neural hearing loss. The replicated unilateral BAER recordings of Fig. 6, B and C illustrate the latencies and amplitudes of the patient’s far-field brainstem potentials wave peaks. Replicate BAER measures revealed slightly delayed absolute wave latencies consistent with peripheral hearing loss, but normal interpeak latencies and V/I amplitude ratios bilaterally. The BAER wave form structure was normal for wave peaks I-V on both sides. Because the interpeak latencies were normal, this patient’s hearing loss was likely due to noise exposure rather than neuro-ototoxicity from Pb exposure.

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Case Profile 3

The patient is a 32-year-old man with a history of work in Pb-glazing operations for more than 15 years who has lived in the study area all of his life (Fig. 7). His PbB level was found to be 66 μg/dL. The patient had a history of noise exposure from operating a Pb-acid battery-grinding machine. He complained of recurrent high-pitch tinnitus bilaterally. He also reported a history of drainage from his right ear, which was last experienced 2 years before the present study. Tympanometry, otoscopic examination, and pure-tone tests showed no evidence of a current conductive pathological condition. The patient complained of frequent headaches, particularly in the presence of loud noise. There was no family history of hereditary hearing loss. The patient’s audiogram, shown in Fig. 7, A, reveals a severe high-frequency sensory-neural hearing loss in the right ear and a mild-to-severe high-frequency sensory-neural hearing loss in the left ear. The replicated unilateral BAER recordings of Fig. 7, B and C illustrate the latencies and amplitudes of the patient’s far-field brainstem potentials at 90 to 100 dB nHL in the right and left ears. Wave peak V in the right ear at 90 and 100 dB nHL is questionable, and the recorded positive deflection may represent neural summated activity that constitutes a prolonged wave IV discharge. The repeatable BAERs were present only at 90 to 100 dB in both ears, indicating elevated peripheral hearing thresholds bilaterally. The interpeak latencies and V/I amplitude ratios were found to be within normal limits at 100 dB on the right side and at 90 and 100 dB on the left side, suggesting that the patient’s hearing loss was related to noise exposure and not Pb exposure. The patient was counseled regarding his high-frequency hearing loss and was advised to avoid exposure to loud noise in the workplace and to use ear protectors if exposed.

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Case Profile 4

Case 4 is a 37-year-old woman who has lived in the study area all of her life and has a history of 20 years of work in Pb-glazing operations, primarily extracting Pb from Pb-acid batteries and producing clay tiles (Fig 8). Her PbB level was found to be 33 μg/dL and in excess of the WHO (International Programme on Chemical Safety, 1995) health-based biological exposure limits for PbB. She had no major neurological, audiological, or other general medical complaints and no history of noise exposure. Otoscopic examination, tympanometry, and pure-tone tests were negative for middle-ear pathological conditions. The case history revealed no tinnitus. The audiogram of Fig. 8, A shows normal hearing bilaterally. The replicated BAER recordings of Fig. 8, B and C illustrate the latencies and amplitudes of the patient’s brainstem wave peaks. Repeated BAER measures revealed normal absolute and interpeak latencies, as well as normal wave form structure and V/I amplitude ratios.

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Discussion

This study investigated Pb intoxication and neuro-ototoxic impairment in adults with a long history of occupational Pb exposure. Neuro-ototoxicity was assessed noninvasively by using auditory brainstem and cochlear function as biomarkers. The results show a high lead body burden in the adult men (mean, 46.1 μg/dL) and women (mean, 44.1 μg/dL) in the study areas, which places these Ecuadorian Pb-glazing workers at considerable neurological and general health risk. Although the elevated PbB levels observed reflect recent Pb exposures, the measured values are probably representative of the chronic Pb intoxication in participants living their entire lives in the highly Pb contaminated study areas.

High-frequency sensory-neural hearing loss reflects the loss or damage of inner ear receptor cells (outer hair cells) in the basal area of the cochlea, a common feature of occupational noise exposure and of neuro-ototoxicity. Several studies have suggested that Pb intoxication induces cochlear and retrocochlear impairment. 15–25 In contrast, a recent study showed that short-term Pb exposure had no effect on cochlear function, whereas long-term Pb exposure was significantly associated with hearing loss. 28 That study, which used only one frequency (4 kHz) as an index of hearing loss, further reported no enhancement of auditory impairment from combined Pb and noise exposure.

The present study, which measured auditory thresholds at five high frequencies (2.0, 3.0, 4.0, 6.0, 8.0 kHz) that are sensitive to neuro-ototoxic substances and noise, showed high-frequency sensory-neural hearing loss (cochlear impairment) in 60% of the men and 20% of the women with PbB levels in excess of the WHO health-based biological limits. This disparity in hearing loss between men and women is probably because the women are typically not exposed to the noise-producing aspects of the Pb-glazing operations. These results suggest that the sensory-neural hearing loss in the men is related more to noise exposure than Pb body burden. In addition, no significant correlation was found between hearing threshold and PbB level in the high-frequency range that is vulnerable to ototoxic insult. Although the evidence in the present study suggests that the high-frequency hearing loss among the men is related to noise exposure, enhancement of the auditory impairment due to the combination of Pb intoxication and noise exposure in the workplace cannot be completely ruled out. 37,38 For example, the 41-year-old man with a long history of occupational noise exposure from Pb-glazing equipment (case profile 1) also had a high PbB level (80 μg/dL). It is also possible that individual susceptibility to Pb-induced neuro-ototoxicity as a result of genetic or other environmental factors, or both, may contribute to the development of cochlear and retrocochlear damage.

Furthermore, the participants who were found to have sensory-neural hearing loss also had delayed absolute BAER wave latencies but normal interpeak (I-III, III-V, and I-V) latencies. These findings support peripheral hearing loss from cochlear impairment but the absence of retrocochlear neuronal damage in the ascending auditory tract. Wave peak I of the afferent auditory tract represents the integrity of the eighth cranial nerve, and waves III and V are believed to be generated by the cochlear nucleus-superior olivary complex and, possibly, the inferior colliculus, respectively. 39–41 The BAER interpeak intervals have been used clinically as a measure of neural conduction capacity in neurological disorders such as multiple sclerosis and in diagnosing neuronal function in persons with Pb intoxication. 15,25,26,36 The latency of the I-III interpeak interval represents neuronal transmission from the eighth nerve to the lower pons. The neural transmission time from the lower pons to the midbrain is reflected in the III-V interpeak interval. The latency of the I-V interpeak interval reflects the integrity of the ascending auditory tracts and nuclei from the eighth nerve to the lower midbrain. The BAERs recorded in adults with elevated PbB levels and sensory-neural hearing loss in this study suggest that the retrocochlear neural components of the auditory tract from the eighth nerve to the midbrain were unimpaired by Pb intoxication.

In conclusion, the findings of this investigation suggest that Pb exposure alone is not the cause of the sensory-neural hearing impairment found in this group of adult subjects with elevated PbB levels from occupational exposure in the ceramic Pb-glazing industry. Rather, the intense occupational noise levels or the combination of Pb intoxication and noise exposure may induce neuro-ototoxicity, particularly in susceptible individuals. Although it has been well established that Pb is a neurotoxic substance, the levels and parameters of exposure required to induce neuro-ototoxicity remain to be determined. Studies concerned with the effects of Pb exposure on the auditory system should consider each worker’s history of occupational noise exposure.

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Acknowledgments

This study was conducted as part of a series of lead-exposure studies in the La Victoria and Racar areas of Ecuador, under the auspices of the Universidad San Francisco de Quito Medical School in Quito, Ecuador. We thank Gonzalo Mantilla, MD, Dean of the Universidad San Francisco de Quito Medical School for support. We are grateful to Fernando Ortega, MD, internal and community medicine specialist at the Universidad San Francisco de Quito Medical School, and Göran Laurell, MD, otolaryngologist at the Karolinska Hospital, for their support and collaboration in the Ecuador Medical Projects. We thank nurses Ivonne Leon and Geovanna Segovia for their service. We appreciate the support of the Harvard University Biological Laboratories, David Rockefeller Center for Latin American Studies, the Shriver Center, and University of Massachusetts Medical School. We thank Anthony B. Jacobs for excellent technical and field assistance. We also thank Professor Erik Borg, MD, Keith Chiappa, MD, and Ernest J. Moore, PhD, for helpful advice and comments.

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