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An experimental study of the effects of lead acetate on hearing Cochlear microphonics and action potential of the guinea pig
Toxicology Letters, 21 (1984) 41-47 Elsevier
41
TOXLett , 1172 AN EXPERIMENTAL STUDY OF THE EFFECTS OF LEAD ACETATE ON HEARING COCHLEAR MICROPHONICS AND ACTION POTENTIAL OF THE GUINEA PIG (Lead acetate: CM; AP)
KOHTAROH YAMAMURA, RBIKO KISHI*, NAOKI MAEHARA, TERUKAZU SADAMOTO* and EIGI UCHINO** Department of Hygiene, Asahikawa Medical College, Asahikawa, Hokkaido, * Department of Public Health, Sapporo Medical College, Sapporo, Hokkaido and ** Hokkaido Institute of Public Health, Sapporo, Hokkaido (Japan) (Received August 26th, 1983) (Revision received November Znd, 1983) (Accepted December 6th, 1983)
SUMMARY Guinea pigs were poisoned with repeated i.p. injections of 1% lead acetate. After 5 weeks, the animals were examined electrophysiologic~ly by using cochlear microphonics (CM) and action potential (AP). The thresholds of ma~mum voltage of Nt in the AP of the animats injected with a total of 100 mg lead acetate were elevated about 15 dB and increased Ni latency was also observed. However, no significant changes in those of CM were found. The results suggest that lead acetate not only induces damage to the peripheral nerves, but also to the cranial nerves.
INTRODUCTION
Demyelination of motor nerves induced by lead exposure is well known in man 21 and animals [3-51. This damage may involve the cranial nerves, since vertigo and sensory neuronal deafness have been reported among lead workers [6, 71. The effects of lead acetate exposure on the cochlea and the VIII nerve have been investigated by using the CM and AP in the guinea pig. [l ,
Abbreviations:
AP, action potential; CM, cochlear microphonics; VDL, visual detection level.
0378-4274/84/~ 03.00 0 Elsevier Science Publishers B.V.
42
MATERIALS
AND METHODS
Animals and dosing procedures 6-10 naive male albino Hartley guinea pigs, 9 week of age, were used. The mean body weight was 320 g for experiment 1 (control: n = lo), 516 g for experiment 2 (n = lo), 467 g for experiment 3 (n = 6), and 488 g for experiment 4 (n = 6). The room temperature was 25” f 2°C. Exposure Animals were randomly assigned to 4 dose groups: 0 mg (control), 10 mg, 15 mg, and 20 mg lead acetate. A 1% solution of lead acetate was administered by i.p. injection, once a week for 5 consecutive weeks. In Experiment 1, the CM and AP of guinea pigs over 300 g in body weight were measured. Measurements of AP and CA4 The room used for these CM and AP measurements was 4 m x 5 m x 3.5 m and it was acoustically sealed. An electrically shielded box (950 mm x 700 mm x 950 mm) was set up on a wooden desk in the center of the room, and physiological examinations were carried out in this box. Sodium pentobarbital (0.4 ml/kg) was injected into the abdominal cavity of the guinea pigs; they were then fixed face upward and 0.5 ml/kg succinylcholine chloride was injected into the leg muscle. With the use of a respirator, surgical operations involving opening of the bulla and exposure of the cochlea were performed and an endotracheal vinyl tube was inserted. Using a microscope, small holes, approx. 50-100 pm in diameter, were made with a dental reamer at the Scala vestibuli and Scala tympani in the basal turn of the cochlea. (A) Measurement of CM potential Measurement of CM followed the method of vestibulotympanal differential recording [8]. Silver wires (approx. 30 pm in diameter) were introduced into the small holes using a micromanipulator. The CM response from a pair of these electrodes was introduced into a high-impedance amplifier and a synchroscope. An audiometer was used as the apparatus of sound stimulus to the guinea pigs. To prevent electrical induction, an iron cover was placed over the receiver of this audiometer and a vinyl tube was inserted into a small hole in the iron cover. Finally, the tip of the vinyl tube was introduced into the external acoustic meatus. The stimulus sound level (dB) was observed from the audiometer, and the intensity function of the CM was measured (test frequency: 4 kHz). An intensity of 0 dB
43
(VDL) was used since this wasthe stimulus intensity level of 4 kHz which was obtained for CM potentials below 30 PV in the control guinea pigs on the CRoscillator. This level was about 40 dB on the audiometer. In this experiment, therefore, 40 dB was considered as 0 dB or the pseudo-threshold. (B) Measurement of action potential (AP) The measurement of AP was performed by the method of Tasaki [8]. AP was induced from the electrode inserted into the small hole of the Scala vestibuli, and an indifferent electrode made of silver wire was placed in the neck muscle of the guinea pig. AP was obtained using digital memory and a synchroscope. The stimulus sound was as follows. The rise-decay time was 1 ms, whereas the decay time was 2.5 ms with a pure tone of 7 kHz [9]. The instruments used for this impulse noise (one pulse/s) were the following: (1) generator; (2) electronic switch; (3) amplifier (combination of pre-main type); (4) audiometer; (5) receiver with iron cover. The peak level of impulse sound was obtained from the dial value of the audiometer. The pseudo-threshold was 40 dB.
1ooo-
s3
500-.-
5 %
voltage (Exp. 1)
regression Exp. 1
line
output voltage of Exp. 2 (lead acetate 50 m-3 injection)
loo-
_____ regression Exp.
s P 5 0
of
__a__. ‘CM
.o $
CM output of Control
50-...-.-.-
10 5
I
I
I
I
I
I
I
I
I
10
15
20
25
30
35
40
45
50
dB (above
Visual
Detection
Level)
Fig. 1. Intensity function of cochlear microphonics (CM).
line
of
2
g,Mp.yt
ut voltage acetate Plead 75 mg injection)
of
CM out ut voltage EXP. 4 Plead acetate 100 mg injection)
of
regression EXP. 4
line
of
44
(C) Measurement of lead concentration in blood Samples of blood were obtained from the animals after examination of electrophysiological studies 2 or 3 days after the last lead acetate injection. Analyses were performed by using a Varian AA175 type flameless atomizer equipped with a DZ lamp background collector. A mixture of nitric acid and perchloric acid was used for the wet digestion of samples. The standard addition method was applied for the determination to eliminate matrix interferences. RESULTS
Experiment 2. The body weight of the guinea pigs changed from 538 g to 516 g during the 5 weeks of lead injection and 3 guinea pigs out of 13 died during the 5 weeks. Experiment 3. The mean body weight of the guinea pigs changed from 420 g to 467 g during the 5 weeks of injection and 4 guinea pigs out of 10 died during the 5 weeks. Experiment 4. The body weight of the guinea pigs changed from 421 g to 488 g and 14 guinea pigs out of 20 died during the above injection period. The variations in CM output voltage and regression lines are shown in Fig. 1 (Experiments l-4). The ordinate was CM output voltage &V: peak to peak value) and the abscissa was dB of 4 kHz sound stimulus above the visual detection level of CM (40 dB (SL) on the audiometer).
-
AP output of Exp. 1
voltage (Control)
-
regression Exp. 1
line
--o---
AP output voltage of Exp. 2 (lead acetate 50 mg injection)
-----
regression Exp. 2
-I-
AP
line
of
of
output voltage 3 (lead acetate 75 mg injection)
of
EXP.
-
regression Exp. 3
-.a.-
AP output voltage Exp. 4 (lead acetate 100 mg injection)
-.-.-
regression 4
EXP.
10
I
5
10
dB
Fig. 2. Output
15
(above
voltage
20
25
Visual
of action
30
35
Detection
potential
40
45 Level)
(AP: NI).
50
line
line
of
of
of
In all experiments (Experiments l-4), regressions between the intensity of sound stimulus and the logarithm of CM output voltage were significant (P < 0.01). Intensity function was obtained in all experiments. However, significant differences in CM output voltages among Experiments l-4 by analysis of variance were not observed. The mean Ni values of AP to sound stimulus and regression in each experiment, respectively, are shown in Fig. 2. The regressions between the intensity (dB) of stimulus sound and logarithm of Nr of AP output voltage &V) in each examination (Experiments 1-4) were significant (P < 0.01). The mean Nr of maximum output voltage of AP in Experiment 4 was equal to those obtained below 10 or 15 dB in Experiments l-3. Examples of maximum AP wave form in Experiment 3 and Experiment 4 are shown in Fig. 3, A and B, respectively. These photographs of AP were obtained at a sound stimulus of 50 dB above the detection level. It was observed that the voltage of peak Ni and N2 in Experiment 3 were greater than those in Experiment 4. The results of the latency of Ni were as follows. In control (n = 5), it was 2.8 + 0.61 ms. In Experiment 2 (n = 8), in Experiment 3 (n = 7) and in Experiment 4 (n = 5), they were 3.4 -t 0.22 ms, 3.4 f 0.21 ms and 3.3 * 0.22 ms, respectively. There were significant differences between the latency of Nl in Experiment 1 and that of Experiment 4 (t = 4.651, P < 0.01). However, significant differences were not obtained in the latency of N1 in Experiment 2, and Experiments 3 and 4. The concentrations of blood lead were 30 + 14 kg/100 ml, in controls (n = 6), 154 f 40 pg/lOO ml, in Experiment 3 (n = 6), and 153 + 46 kg/100 ml, in Experiment 4 (n = 4). DISCUSSION
Gozdzik-iolierkiewicz [7] injected a 1% water solution of lead acetate into the abdominal cavity of guinea pigs and examined the inner ear and the VIII nerve A
2 ms/div
6
2 ms/div
Fig. 3. (A) AP wave form in Exp. 3; (B) AP wave form in Exp. 4.
46
histologically. Although the sensory cells of the inner ear appeared to be normal, the VIII nerve showed segmental demyelination and axonal degeneration, The blood lead level was from 310 pg to 420 @g/100 ml. It was considered that this toxic effect induced by lead acetate was probably the result of a disturbance of the enzymic content of the myelin sheath. Demyelination of the motor nerves induced by lead acetate is well known. Fullerton [3] investigated the guinea pig motor nerve by histological examination, measured conduction velocity of the plantar nerve electrophysiologically, and observed correlation between the extent of histological change and the conduction velocity of the motor nerve. Three lead acetate exposure conditions were investigated. As it is generally known that the sensory cells of the inner ear have a rather strong resistance to lead exposure, lead acetate exposures did not induce changes in CM, in either pseudothreshold or maximum output voltages. In Experiment 4, a total of 100 mg exposure to lead acetate did not induce change in the CM intensity function. Davis [I 1) reported that the changes in CM (detection level and maximum output voltages) with a pathological change in the sensory cells was proportionate to CM of the normal inner ear obtained below 15-20 dB sound stimulus. For this reason, pathological changes of sensory cells were not considered. However, it was found that the input-output function of AP [lo] was changed by lead exposure. The maximum output voltage of AP (Ni) in Experiment 4 was smaller than that under other experimental conditions. As the results in Fig. 2 show, the mean Nr voltage of AP at 50 dB sound stimulus in Experiment 4 was approximately equaf to those obtained below lo-15 dB sound stimulus in other experiments. Decreases of Nl potential in AP were considered to be the impairment of the VIII nerve [9, 121. In Gozdzik-iolierkiewicz’s report (with 300 mg/kg of lead acetate exposure) showed demyelination of the VIII nerve. Such an exposure condition resembles that of the authors’ Experiment 4, with lead exposure of approx. 250 mg/kg. Because both signs (a decrease in the maximum output voltage of Ni potential and increase of Ni peak latency) were observed in Experiment 4, the results might be considered as an indicator of demyelination of the VIII nerve. Paradoxical relations between the decrease of NI potential and the increase of Ni peak latency are well known [13]. REFERENCES 1 G. Ursan and I. Sueiu, Notes on modern aspects of neurotoxicosis in chronic industrial lead poisoning, J. Hyg. Epidemiol. Microbial. Immunol., (1965) IX, 409-420. 2 M.J. Catton, M.J.G. Harrison, P.M. Fullerton and G. Kazantzis, Subclinical neuropathy in lead workers, Br. Med. J., 11 (1970) 80-82. 3 P.M. Fullerton, Chronic peripheral neuropathy produced by lead poisoning in guinea-pigs, J. ~europathol. Exp. Neuroi., 25 (1965) 214-236. 4 CD. Knecht, J. Crabtree and A. Katherman, Clinical, clinicopathologic, and electroencephalo-
47
graphic features of lead poisoning in dogs, J. Am. Vet. Med. Assoc., 175 (1979) 196-201. 5 A. Ohnishi and P.J. Dyck, Retardation of Schwann cell division and axonal regrowth following nerve crush in experimental lead neuropathy, Ann. Nemo]., 10 (1981) 469-477. 6 E. Ciurlo and A. Ottoboni, Variations of the internal ear in chronic lead poisoning, Ext. Med., 9 (1956) 60. 7 T. Gozdzik-iolnierkiewicz and B. Moszyiski, VIII nerve in experimental lead poisoning, Acta Otolaryng., 68 (1969) 85-89. 8 I. Tasaki, H. Davis and J.P. Legouix, The space-time pattern of the cochlear microphonics (guinea pig), as recorded by differential electrodes, J. Acoust. Sot. Am., 24 (1952) 502-519. 9 D.C. Teas, D.H. Eldredge and H. Davis, Cochlear responses to acoustic transients: an interpretation of whole-nerve action potentials, J. Acoust. Sot. Am., 34 (1962) 1438-1459. 10 6. iizdamar and P. Dallos, Input-output functions of cochlear whole-nerve action potentials: interpretation in terms of one population of neurons, J. Acoust. Sot. Am., 59 (1976) 143-147. 11 H. Davis, Acoustic trauma in the guinea pig, J. Acoust. Sot. Am., 25 (1953) 1180-1189. 12 C. Mitchell, Susceptibility to auditory fatigue: comparison on changes in cochlear nerve potentials in the guinea pig and chinchilla, J. Acoust. Sot. Am., 60 (1976) 418-422. 13 N. Yoshie, Auditory nerve action potential responses to clicks in man, Laryngoscope, 78 (1968) 198-213.
41
TOXLett , 1172 AN EXPERIMENTAL STUDY OF THE EFFECTS OF LEAD ACETATE ON HEARING COCHLEAR MICROPHONICS AND ACTION POTENTIAL OF THE GUINEA PIG (Lead acetate: CM; AP)
KOHTAROH YAMAMURA, RBIKO KISHI*, NAOKI MAEHARA, TERUKAZU SADAMOTO* and EIGI UCHINO** Department of Hygiene, Asahikawa Medical College, Asahikawa, Hokkaido, * Department of Public Health, Sapporo Medical College, Sapporo, Hokkaido and ** Hokkaido Institute of Public Health, Sapporo, Hokkaido (Japan) (Received August 26th, 1983) (Revision received November Znd, 1983) (Accepted December 6th, 1983)
SUMMARY Guinea pigs were poisoned with repeated i.p. injections of 1% lead acetate. After 5 weeks, the animals were examined electrophysiologic~ly by using cochlear microphonics (CM) and action potential (AP). The thresholds of ma~mum voltage of Nt in the AP of the animats injected with a total of 100 mg lead acetate were elevated about 15 dB and increased Ni latency was also observed. However, no significant changes in those of CM were found. The results suggest that lead acetate not only induces damage to the peripheral nerves, but also to the cranial nerves.
INTRODUCTION
Demyelination of motor nerves induced by lead exposure is well known in man 21 and animals [3-51. This damage may involve the cranial nerves, since vertigo and sensory neuronal deafness have been reported among lead workers [6, 71. The effects of lead acetate exposure on the cochlea and the VIII nerve have been investigated by using the CM and AP in the guinea pig. [l ,
Abbreviations:
AP, action potential; CM, cochlear microphonics; VDL, visual detection level.
0378-4274/84/~ 03.00 0 Elsevier Science Publishers B.V.
42
MATERIALS
AND METHODS
Animals and dosing procedures 6-10 naive male albino Hartley guinea pigs, 9 week of age, were used. The mean body weight was 320 g for experiment 1 (control: n = lo), 516 g for experiment 2 (n = lo), 467 g for experiment 3 (n = 6), and 488 g for experiment 4 (n = 6). The room temperature was 25” f 2°C. Exposure Animals were randomly assigned to 4 dose groups: 0 mg (control), 10 mg, 15 mg, and 20 mg lead acetate. A 1% solution of lead acetate was administered by i.p. injection, once a week for 5 consecutive weeks. In Experiment 1, the CM and AP of guinea pigs over 300 g in body weight were measured. Measurements of AP and CA4 The room used for these CM and AP measurements was 4 m x 5 m x 3.5 m and it was acoustically sealed. An electrically shielded box (950 mm x 700 mm x 950 mm) was set up on a wooden desk in the center of the room, and physiological examinations were carried out in this box. Sodium pentobarbital (0.4 ml/kg) was injected into the abdominal cavity of the guinea pigs; they were then fixed face upward and 0.5 ml/kg succinylcholine chloride was injected into the leg muscle. With the use of a respirator, surgical operations involving opening of the bulla and exposure of the cochlea were performed and an endotracheal vinyl tube was inserted. Using a microscope, small holes, approx. 50-100 pm in diameter, were made with a dental reamer at the Scala vestibuli and Scala tympani in the basal turn of the cochlea. (A) Measurement of CM potential Measurement of CM followed the method of vestibulotympanal differential recording [8]. Silver wires (approx. 30 pm in diameter) were introduced into the small holes using a micromanipulator. The CM response from a pair of these electrodes was introduced into a high-impedance amplifier and a synchroscope. An audiometer was used as the apparatus of sound stimulus to the guinea pigs. To prevent electrical induction, an iron cover was placed over the receiver of this audiometer and a vinyl tube was inserted into a small hole in the iron cover. Finally, the tip of the vinyl tube was introduced into the external acoustic meatus. The stimulus sound level (dB) was observed from the audiometer, and the intensity function of the CM was measured (test frequency: 4 kHz). An intensity of 0 dB
43
(VDL) was used since this wasthe stimulus intensity level of 4 kHz which was obtained for CM potentials below 30 PV in the control guinea pigs on the CRoscillator. This level was about 40 dB on the audiometer. In this experiment, therefore, 40 dB was considered as 0 dB or the pseudo-threshold. (B) Measurement of action potential (AP) The measurement of AP was performed by the method of Tasaki [8]. AP was induced from the electrode inserted into the small hole of the Scala vestibuli, and an indifferent electrode made of silver wire was placed in the neck muscle of the guinea pig. AP was obtained using digital memory and a synchroscope. The stimulus sound was as follows. The rise-decay time was 1 ms, whereas the decay time was 2.5 ms with a pure tone of 7 kHz [9]. The instruments used for this impulse noise (one pulse/s) were the following: (1) generator; (2) electronic switch; (3) amplifier (combination of pre-main type); (4) audiometer; (5) receiver with iron cover. The peak level of impulse sound was obtained from the dial value of the audiometer. The pseudo-threshold was 40 dB.
1ooo-
s3
500-.-
5 %
voltage (Exp. 1)
regression Exp. 1
line
output voltage of Exp. 2 (lead acetate 50 m-3 injection)
loo-
_____ regression Exp.
s P 5 0
of
__a__. ‘CM
.o $
CM output of Control
50-...-.-.-
10 5
I
I
I
I
I
I
I
I
I
10
15
20
25
30
35
40
45
50
dB (above
Visual
Detection
Level)
Fig. 1. Intensity function of cochlear microphonics (CM).
line
of
2
g,Mp.yt
ut voltage acetate Plead 75 mg injection)
of
CM out ut voltage EXP. 4 Plead acetate 100 mg injection)
of
regression EXP. 4
line
of
44
(C) Measurement of lead concentration in blood Samples of blood were obtained from the animals after examination of electrophysiological studies 2 or 3 days after the last lead acetate injection. Analyses were performed by using a Varian AA175 type flameless atomizer equipped with a DZ lamp background collector. A mixture of nitric acid and perchloric acid was used for the wet digestion of samples. The standard addition method was applied for the determination to eliminate matrix interferences. RESULTS
Experiment 2. The body weight of the guinea pigs changed from 538 g to 516 g during the 5 weeks of lead injection and 3 guinea pigs out of 13 died during the 5 weeks. Experiment 3. The mean body weight of the guinea pigs changed from 420 g to 467 g during the 5 weeks of injection and 4 guinea pigs out of 10 died during the 5 weeks. Experiment 4. The body weight of the guinea pigs changed from 421 g to 488 g and 14 guinea pigs out of 20 died during the above injection period. The variations in CM output voltage and regression lines are shown in Fig. 1 (Experiments l-4). The ordinate was CM output voltage &V: peak to peak value) and the abscissa was dB of 4 kHz sound stimulus above the visual detection level of CM (40 dB (SL) on the audiometer).
-
AP output of Exp. 1
voltage (Control)
-
regression Exp. 1
line
--o---
AP output voltage of Exp. 2 (lead acetate 50 mg injection)
-----
regression Exp. 2
-I-
AP
line
of
of
output voltage 3 (lead acetate 75 mg injection)
of
EXP.
-
regression Exp. 3
-.a.-
AP output voltage Exp. 4 (lead acetate 100 mg injection)
-.-.-
regression 4
EXP.
10
I
5
10
dB
Fig. 2. Output
15
(above
voltage
20
25
Visual
of action
30
35
Detection
potential
40
45 Level)
(AP: NI).
50
line
line
of
of
of
In all experiments (Experiments l-4), regressions between the intensity of sound stimulus and the logarithm of CM output voltage were significant (P < 0.01). Intensity function was obtained in all experiments. However, significant differences in CM output voltages among Experiments l-4 by analysis of variance were not observed. The mean Ni values of AP to sound stimulus and regression in each experiment, respectively, are shown in Fig. 2. The regressions between the intensity (dB) of stimulus sound and logarithm of Nr of AP output voltage &V) in each examination (Experiments 1-4) were significant (P < 0.01). The mean Nr of maximum output voltage of AP in Experiment 4 was equal to those obtained below 10 or 15 dB in Experiments l-3. Examples of maximum AP wave form in Experiment 3 and Experiment 4 are shown in Fig. 3, A and B, respectively. These photographs of AP were obtained at a sound stimulus of 50 dB above the detection level. It was observed that the voltage of peak Ni and N2 in Experiment 3 were greater than those in Experiment 4. The results of the latency of Ni were as follows. In control (n = 5), it was 2.8 + 0.61 ms. In Experiment 2 (n = 8), in Experiment 3 (n = 7) and in Experiment 4 (n = 5), they were 3.4 -t 0.22 ms, 3.4 f 0.21 ms and 3.3 * 0.22 ms, respectively. There were significant differences between the latency of Nl in Experiment 1 and that of Experiment 4 (t = 4.651, P < 0.01). However, significant differences were not obtained in the latency of N1 in Experiment 2, and Experiments 3 and 4. The concentrations of blood lead were 30 + 14 kg/100 ml, in controls (n = 6), 154 f 40 pg/lOO ml, in Experiment 3 (n = 6), and 153 + 46 kg/100 ml, in Experiment 4 (n = 4). DISCUSSION
Gozdzik-iolierkiewicz [7] injected a 1% water solution of lead acetate into the abdominal cavity of guinea pigs and examined the inner ear and the VIII nerve A
2 ms/div
6
2 ms/div
Fig. 3. (A) AP wave form in Exp. 3; (B) AP wave form in Exp. 4.
46
histologically. Although the sensory cells of the inner ear appeared to be normal, the VIII nerve showed segmental demyelination and axonal degeneration, The blood lead level was from 310 pg to 420 @g/100 ml. It was considered that this toxic effect induced by lead acetate was probably the result of a disturbance of the enzymic content of the myelin sheath. Demyelination of the motor nerves induced by lead acetate is well known. Fullerton [3] investigated the guinea pig motor nerve by histological examination, measured conduction velocity of the plantar nerve electrophysiologically, and observed correlation between the extent of histological change and the conduction velocity of the motor nerve. Three lead acetate exposure conditions were investigated. As it is generally known that the sensory cells of the inner ear have a rather strong resistance to lead exposure, lead acetate exposures did not induce changes in CM, in either pseudothreshold or maximum output voltages. In Experiment 4, a total of 100 mg exposure to lead acetate did not induce change in the CM intensity function. Davis [I 1) reported that the changes in CM (detection level and maximum output voltages) with a pathological change in the sensory cells was proportionate to CM of the normal inner ear obtained below 15-20 dB sound stimulus. For this reason, pathological changes of sensory cells were not considered. However, it was found that the input-output function of AP [lo] was changed by lead exposure. The maximum output voltage of AP (Ni) in Experiment 4 was smaller than that under other experimental conditions. As the results in Fig. 2 show, the mean Nr voltage of AP at 50 dB sound stimulus in Experiment 4 was approximately equaf to those obtained below lo-15 dB sound stimulus in other experiments. Decreases of Nl potential in AP were considered to be the impairment of the VIII nerve [9, 121. In Gozdzik-iolierkiewicz’s report (with 300 mg/kg of lead acetate exposure) showed demyelination of the VIII nerve. Such an exposure condition resembles that of the authors’ Experiment 4, with lead exposure of approx. 250 mg/kg. Because both signs (a decrease in the maximum output voltage of Ni potential and increase of Ni peak latency) were observed in Experiment 4, the results might be considered as an indicator of demyelination of the VIII nerve. Paradoxical relations between the decrease of NI potential and the increase of Ni peak latency are well known [13]. REFERENCES 1 G. Ursan and I. Sueiu, Notes on modern aspects of neurotoxicosis in chronic industrial lead poisoning, J. Hyg. Epidemiol. Microbial. Immunol., (1965) IX, 409-420. 2 M.J. Catton, M.J.G. Harrison, P.M. Fullerton and G. Kazantzis, Subclinical neuropathy in lead workers, Br. Med. J., 11 (1970) 80-82. 3 P.M. Fullerton, Chronic peripheral neuropathy produced by lead poisoning in guinea-pigs, J. ~europathol. Exp. Neuroi., 25 (1965) 214-236. 4 CD. Knecht, J. Crabtree and A. Katherman, Clinical, clinicopathologic, and electroencephalo-
47
graphic features of lead poisoning in dogs, J. Am. Vet. Med. Assoc., 175 (1979) 196-201. 5 A. Ohnishi and P.J. Dyck, Retardation of Schwann cell division and axonal regrowth following nerve crush in experimental lead neuropathy, Ann. Nemo]., 10 (1981) 469-477. 6 E. Ciurlo and A. Ottoboni, Variations of the internal ear in chronic lead poisoning, Ext. Med., 9 (1956) 60. 7 T. Gozdzik-iolnierkiewicz and B. Moszyiski, VIII nerve in experimental lead poisoning, Acta Otolaryng., 68 (1969) 85-89. 8 I. Tasaki, H. Davis and J.P. Legouix, The space-time pattern of the cochlear microphonics (guinea pig), as recorded by differential electrodes, J. Acoust. Sot. Am., 24 (1952) 502-519. 9 D.C. Teas, D.H. Eldredge and H. Davis, Cochlear responses to acoustic transients: an interpretation of whole-nerve action potentials, J. Acoust. Sot. Am., 34 (1962) 1438-1459. 10 6. iizdamar and P. Dallos, Input-output functions of cochlear whole-nerve action potentials: interpretation in terms of one population of neurons, J. Acoust. Sot. Am., 59 (1976) 143-147. 11 H. Davis, Acoustic trauma in the guinea pig, J. Acoust. Sot. Am., 25 (1953) 1180-1189. 12 C. Mitchell, Susceptibility to auditory fatigue: comparison on changes in cochlear nerve potentials in the guinea pig and chinchilla, J. Acoust. Sot. Am., 60 (1976) 418-422. 13 N. Yoshie, Auditory nerve action potential responses to clicks in man, Laryngoscope, 78 (1968) 198-213.