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|Year : 2000 | Volume
| Issue : 9 | Page : 49--57
Noise and solvent, alcohol and solvent : Two dangerous interactions on auditory function
P Campo, R Lataye
Institut National de Recherche et de Sécurité‚ Laboratoire Multinuisances, Vandoeuvre, France
Institut National de Recherche et de Sécurité‚ Laboratoire Multinuisances, Avenue de Bourgogne, BP 27, 54501 Vandoeuvre
While noise exposure is the most significant contributor to occupational hearing loss, recent evidence points to solvents and their interactions as additional contributors to occupational deafness. Furthermore, due to the metabolic competitive inhibition between aromatic solvents and ethanol, the solvent toxicity can be even enhanced in certain circumstances. So, two dangerous interactions: noise and solvents, solvents and ethanol deserve to be taken into consideration in an exhaustive preventive policy. Based on the investigations reviewed in the present study, it appears that the combined effects of an exposure to noise and solvent exceed the summation of the damage produced by each agent alone. Such a statement can be also made for a combined exposure to solvent and ethanol. It is therefore important to bear in mind that noise effects can be exacerbated by non-acoustic agents. Thus, if our noise regulations have to be more effective, it is necessary to take into consideration the ototoxic effects of noise in a multifactorial environment.
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Campo P, Lataye R. Noise and solvent, alcohol and solvent : Two dangerous interactions on auditory function.Noise Health 2000;3:49-57
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Campo P, Lataye R. Noise and solvent, alcohol and solvent : Two dangerous interactions on auditory function. Noise Health [serial online] 2000 [cited 2022 May 22 ];3:49-57
Available from: https://www.noiseandhealth.org/text.asp?2000/3/9/49/31770
Despite efforts to eliminate hazardous noise sources in many factories, occupational hearing loss is still one of the most common occupational disease in France. Most research on the etiology of occupational hearing loss has focused on the damaging effects of noise on hearing. While noise exposure is undoubtedly the most significant contributor to occupational hearing loss, recent evidence points to aromatic solvents and their interactions with noise as additional significant contributors to occupational hearing disorders (Morata et al., 1993 and 1995). Toluene (C7H 8 ) and styrene(C 8 H 8 ) are both widely used in a broad variety of processes and activities in many factories (Miller et al., 1994, Morata et al., 1993;1994; Ukai et al., 1997). Thus, the effects of these two organic and aromatic solvents need to be studied and better understood as part of the hearing conservation policy. Furthermore, due to the metabolic competitive inhibition between aromatic solvents and alcohol (ethanol), the solvent toxicity on the auditory system can be enhanced in certain circumstances. Indeed, it is well known that ethanol has both stimulating and inhibiting effects on the metabolism of solvents. Inhibition of aromatic solvent metabolism in humans has been found during solvent exposures after acute oral intake of ethanol (Wallen et al., 1984). On the other hand, chronic ethanol consumption exacerbates the enzymes involved in the metabolic breakdown of solvents (Coccini et al., 1996). Interestingly, the effect disappears almost completely after one day withdrawal of ethanol, suggesting that only recently ingested ethanol plays a decisive part in stimulating the enzyme activity involved in the metabolism of the solvents. Therefore, ethanol must also be considered as a substance involving a potential degree of risk (depending on the level) for hearing function especially when combining with aromatic solvents such as toluene or styrene.
To better understand the auditory risks encountered by individuals exposed to dangerous combinations such as solvent (toluene or styrene) and noise or solvent and ethanol, the main objective of the present paper will be to review the experiments carried out with an animal model, the Long-Evans rats, which was chosen because of its metabolic similarities with humans. The exposure was an octave band noise (OBN) centered at 8 kHz (8kHz,OBN) directly generated inside the inhalation chamber (Lataye et al., 1997). The centre frequency of the noise was chosen to cause noise-induced hearing loss in the partition area where auditory sensitivity is the highest (Heffner et al., 1994). Delivery of ethanol (4g/kg) was ensured by gastric intubation to better control the intake. In addition, the metabolism of solvent, and more important, the metabolic effects of the combination of solvent and ethanol was monitored by measuring the urinary metabolites which are the end products of oxidation of the aromatic solvent side chain (Campo et al., 1998). Auditory function was tested by recording near field auditory evoked potentials picked up from the inferior colliculus. With such a technique, each animal serves as its own control and therefore the auditory permanent threshold shifts (PTS) can reliably be documented over several months.
Solvent-induced hearing loss versus Noise induced hearing loss
In all the experiments reported in the present paper, the duration of exposure to both the noise and the solvents was identical: 6 hours per day, 5 days per week, for 4 consecutive weeks (6h/d, 5d/w, 4w). The PTS values were collected 6week post exposure. As a result, the comparison of the effects of the different experimental conditions on hearing is straight forward.
Solvent-induced hearing loss
Since both toluene and styrene are organic and aromatic solvents which have been reported as ototoxic agents in animals (Crofton et al., 1994; Loquet et al., 1999) and also in humans (Morata et al., 1993; 1997; Calabrese et al., 1996), the concept of solvent-induced hearing loss will be restricted in the present paper to the cochlear impairments caused either by toluene or by styrene. Toluene- like styrene-induced hearing losses seem to be caused by similar cochlear damages, even though styrene appears to be much more ototoxic than toluene. In fact, inhaled styrene would be roughly 2.3 time more ototoxic than inhaled toluene (Loquet et al., 1999) in identical experimental conditions (6h/d, 5d/w, 4w). Despite the fact that styrene is more ototoxic than toluene (perhaps because of the air/blood absorption ratio) the mechanism, or at least the sequence of histopathological events is quite similar for the two solvents (Loquet et al., 1999). Basically, the main characteristics of aromatic solvents induced hearing losses are: - the tonotopicity of the trauma or the location of the cochlear trauma induced by solvents is spread out from the middle (16 kHz) to the upper turn (2-4 kHz) of the cochlea, or in other words from the mid- to the mid-low frequency regions (Campo et al., 1997; Lataye et al., 1999); - the centripetal intoxication route which can be illustrated by the fact that the outer hair cells from the third row are more sensitive than those from the second row which are themselves more sensitive than those belonging to the first row. Moreover, the outer sulcus, and more specifically the Hensen's and Deiters' cells represents the major intoxication route taken by the solvents (Campo et al; 1999). Basically, the intoxication route taken by the organic solvents is caused by a tissue intoxication (the outer sulcus) rather than by a fluid contamination.
Noise-induced hearing loss
The ototraumatic effects of overstimulation are different from those obtained from solvent- treated rats (Chan et al., 1998). In the following experiments, the intensities of the OBN exposures were moderate (92-97 dB SPL) and the centre frequency (8 kHz) of the noise was chosen to generate noise-induced hearing loss in the cochlear partition area where auditory sensitivity is the highest. As a result, the noise-induced hearing losses were located around 1016 kHz. Such noises generate very few losses of outer hair cells, but rather injure the stereocilia and more precisely the stereocilia of the first row of outer hair cells and the row of inner hair cells (Lataye et al; 1997, 1999). Of course, these are not the only effects induced by the noise exposure, the stereocilia pathology can also be associated with a swelling of afferent dendrites beneath the inner hair cells (Robertson, 1983) or/and with an increase of the total membrane content such as vesicles and tubulovesicular cisternae (Canlon et al., 1992; Saunders et al., 1985). Nevertheless, the mechanism involved in the acoustic trauma is very different from the "poisoning" mechanism caused by solvents. There are thus two different mechanisms which underlie the cochlear lesions: the mechanical and poisoning mechanisms.
Combined effects of a simultaneous exposure to noise and solvent
The OBN exposure was always carried out inside the inhalation chamber so that the exposures to noise and solvent were simultaneous and not sequential.
Toluene and Noise
The toluene concentration inside the inhalation chambers was 2000ppm and the intensity of OBN was 92 dB for this first combination.
[Figure 1] illustrates the permanent threshold shifts (PTS) versus frequencies obtained with first, a group of 2000ppm toluene-treated animals, second, a group of 92dB OBN-exposed animals and third, a group of animals exposed to both noise and toluene. The combined exposure caused PTS amplitudes significantly larger (~35dB) than those obtained with the toluene (~23dB) or with the noise exposure alone (~10dB). As a result, a simultaneous exposure to both noise and toluene caused a more severe trauma from the sum of both agents. A similar conclusion was also reached by Johnson and collaborators (1988) with sequential exposures.
Styrene and Noise
Due to the more potent toxicity of styrene compared to that of toluene, the concentration of styrene (6h/d, 5d/w, 4w) inside the inhalation chambers was deliberately lower (750ppm) than that used with toluene (2000pppm). Moreover, a 750ppm concentration is close to the liver potency for detoxification the styrene (Filser et al., 1993). In contrast, the intensity of the OBN was a bit higher: 97 dB SPL, for this second combination. Once again, the combination of the two agents caused a more severe trauma than that obtained only from each agent [Figure 2]. In fact, the auditory deficit induced by the combined exposure (~25.7dB) exceeded the summated losses caused by styrene alone (~8dB) and by noise alone (~16.6dB) within a wide range of frequencies.
The outcomes of the combined exposures to noise and solvents can be described using terminology suggested by Johnson and Nylen (1995) or by Fechter (1995). Since the combined effects exceed the simple summation of the damage produced by each agent alone, such combinations can be considered as synergistic, even though the poisoning and mechanical mechanisms involved in the cochlear lesions are very different. From a practical or clinical perspective, it is important to bear in mind that the effects of noise in the workplace can be exacerbated by other non-acoustic agents such as industrial solvents.
Combined effects of a simultaneous exposure to solvent and ethanol
The gavage with ethanol (4g/kg) was always done approximately 10 minutes before the start of the solvent exposures. No significant effect of the ethanol intake alone was found on the auditory function in our experimental conditions.
Toluene and Ethanol
[Figure 3] illustrates the detoxification process of toluene in the rat. From a general point of view, three main steps for toluene catabolism can be observed : the microsomal ethanol-oxidising system (MEOS) which involves a specific form of cytochrome P450 (CYP2E1), the alcohol (ADH) and the aldehyde dehydrogenase (AlDH).
The combination of toluene with ethanol changes the kinetics of the toluene detoxification process. In fact, ethanol is a known competitive inhibitor of toluene catabolism (Sato et al., 1981). Thus, an acute exposure to ethanol slows the clearance of toluene and therefore prolongs internal exposure to toluene. Given that toluene induced ototoxicity is caused by toluene itself (Pryor et al., 1991), it is reasonable to assume that ethanol may increase the toluene effects on the auditory function. Such an assumption was verified in a recent experiment (Campo et al., 1998) in which the amount of missing outer hair cells following a simultaneous exposure to both ethanol and toluene was larger than that obtained after a single exposure to toluene [Figure 4].
Styrene and Ethanol
[Figure 5] illustrates the detoxification process of styrene. Although the three steps involved in the detoxification process are not radically different from those involved for the toluene, nevertheless the cytochromes P450 are different (CYP2E1 and major forms CYP2C11, CYP2B1) and the formation of mercapturic acids is greater.
Consequently, a consumption of ethanol can generate different metabolic consequences when combined with styrene. Similarly to toluene, ethanol can slow down the clearance of styrene and prolong the internal exposure to the solvent. In fact, the effects of a simultaneous exposure to ethanol and styrene are much more noticeable than those seen with toluene. As shown in [Figure 6], the synergetic effect is impressively large. Such a synergism requires a more detailed commentary. First of all, it is well established that the ototoxicity of styrene itself is more potent than that of toluene. Secondly, if toluene is the only ototoxic agent (Pryor et al., 1991), the metabolites of styrene, such as styrene oxide, styrene glycol are also neurotoxic (Kohn et al., 1995; Ladefoged et al., 1998). So, it is reasonable to think that the presence of a neurotoxic agent within a sensitive target can last much longer after a styrene inhalation than after a toluene inhalation.
Finally, ethanol consumption is associated with changes in blood lipids (Lieber, 1994), resulting in "alcoholic hyperlipemia". The lipophilicity of styrene being larger than that of toluene, extra styrene can be trapped and therefore the rate of delivery of styrene to the cochlea by the bloodstream could be increased.
The outcomes of the combined exposure to ethanol and solvents are not as clear as those obtained previously with noise. If the ethanol intake increases the effects of toluene, only the combination of ethanol and styrene can clearly be considered as synergistic. Indeed, in the latter combination, the ototoxic effects exceed the simple summation of the damage produced by each agent alone.
From a practical point of view, it is important to bear in mind that the effects of noise in the workplace can be exacerbated by other nonacoustic agents such as industrial solvents and the effects of solvents can be enhanced by an ethanol ingestion as well. Thus, if our noise regulations have to be made more effective, it is necessary to develop a better understanding of the ototoxic effects of noise in a multifactorial environment.
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