Thomas Venet

Neuronal Circuits Involved in the Middle-Ear Acoustic Reflex

Human and animal studies have shown that certain aromatic solvents such as toluene can cause hearing loss and can exacerbate the effects of noise. The latter effects might be due to a modification of responses of motoneurons controlling the middle-ear acoustic reflex. In the present investigation, the audition of Long-Evans rats was evaluated by measuring cubic (2f1 - f2) distortion otoacoustic emissions (f1 = 8000 Hz; f2 = 9600 Hz; f1/f2 = 1.2) prior to, during, and after activation of the middle-ear acoustic reflex. A noise suppressor was used to modify the amplitude of the 2f1 - f2 distortion otoacoustic emissions. It was delivered either contralaterally (band noise centered at 4 kHz), or ipsilaterally (3.5 kHz sine wave) to test the role played by the central auditory nuclei. This audiometric approach was used to study the physiological efficiency of the middle-ear acoustic reflex during an injection of a bolus of Intralipid (as a vehicle) containing 58.4, 87.4, or 116.2mM toluene via the carotid artery. The results showed that toluene could either increase or decrease middle-ear acoustic reflex efficiency, depending on the toluene concentration and the ear receiving noise suppressor. A new neuronal circuit of the middle-ear acoustic reflex has been proposed to explain findings obtained in this investigation. Finally, the depressing action of toluene on the central auditory nuclei driving the middle-ear acoustic reflex might explain the synergistic effects of a co-exposure to noise and aromatic solvents.

Impact of noise or styrene exposure on the kinetics of presbycusis

Presbycusis, or age-related hearing loss is a growing problem as the general population ages. In this longitudinal study, the influence of noise or styrene exposure on presbycusis was investigated in Brown Norway rats. Animals were exposed at 6 months of age, either to a band noise centered at 8 kHz at a Lex,8h = 85 dB (86.2 dB SPL for 6 h), or to 300 ppm of styrene for 6 h per day, five days per week, for four weeks. Cubic distortion product otoacoustic emissions (2f1-f2 DPOAEs) were used to test the capacity of the auditory receptor over the lifespan of the animals. 2f1-f2DPOAE measurements are easy to implement and efficiently track the age-related deterioration of mid- and high-frequencies. They are good indicators of temporary auditory threshold shift, especially with a level of primaries close to 60 dB SPL. Post-exposure hearing defects are best identified using moderate, rather than high, levels of primaries. Like many aging humans, aging rats lose sensitivity to high-frequencies faster than to medium-frequencies. Although the results obtained with the styrene exposure were not entirely conclusive, histopathological data showed the presbycusis process to be enhanced. Noise-exposed rats exhibit a loss of spiral ganglion cells from 12 months and a 7 dB drop in 2f1-f2DPOAEs at 24 months, indicating that even moderate-intensity noise can accelerate the presbycusis process. Even though the results obtained with the styrene exposure are less conclusive, the histopathological data show an enhancement of the presbycusis process.

Inhaled toluene can modulate the effects of anesthetics on the middle-ear acoustic reflex

Toluene (Tol) is an organic solvent widely used in the industry. It is also abused as an inhaled solvent, and can have deleterious effects on hearing. Recently, it was demonstrated that Tol has both anticholinergic and antiglutamatergic effects, and that it also inhibits voltage-dependent Ca(2+) channels. This paper describes a study of the effects of inhaled Tol on rats anesthetized with isoflurane, pentobarbital, or a mixture of ketamine/xylazine. Hearing was tested using distortion product oto-acoustic emissions (DPOAEs) associated with a contralateral noise to evaluate contraction of the middle-ear muscles. This allowed us to assess the interactions between the effects of Tol and anesthesia on the central nervous system (CNS). Although both anesthetics and Tol are known to inhibit the middle-ear acoustic reflex, our data indicated that inhaled Tol counterbalances the effects of anesthetic in a dose-dependent manner. In other terms, Tol can increase the amplitude of the middle-ear reflex in anesthetized rats, whatever the nature of the anesthetic used. This indicates that inhaling Tol (a Ca(2+)-channel-blocking drug) modifies the potency of anesthesia, and thereby the amplitude of the middle-ear reflex.

The tonotopicity of styrene-induced hearing loss depends on the associated noise spectrum

The neuropharmacological and cochleotoxic effects of styrene can exacerbate the impact of noise on the peripheral auditory receptor. The mechanisms through which co-exposure to noise and styrene impairs hearing are complex as the slowly developing cochleotoxic process can be masked in the short-term by the rapid pharmacological effect on the central nervous system. The current investigation was therefore designed to delineate the auditory frequency range sensitive to noise, to styrene, and to noise and styrene combined. In case of different frequency ranges targeted by noise and styrene, it would be possible to point out the main factor responsible for cases of deafness by looking at the location of the audiometric deficits. Male Brown-Norway rats were exposed to 600-ppm styrene, to an octave band noise centered at 8 kHz, or to both noise and styrene. The noise exposure was of two different types: impulse noise with a LEX,8h (equivalent continuous noise level averaged over 8 h) of 80 dB and continuous noise with a LEX,8 h of 85 dB SPL. Hearing was tested using a non-invasive technique based on distortion product otoacoustic emissions. Hearing data were completed with histological analysis of cochleae. The results showed that exposure to styrene alone caused outer hair cell losses in the apical cochlear region, which discriminates low frequencies. In contrast, noise-induced hearing loss was located at half an octave above the central frequency of the spectrum, around 10-12 kHz. Damage due to impulse noise was significantly exacerbated by styrene, and the noise spectrum defined the location of the cochlear trauma. Combined exposure caused greater cell losses than the sum of losses measured with the impulse noise and styrene alone. The fact that the tonotopicity of the styrene-induced damage depends on the associated noise spectrum complicates the diagnosis of styrene-related hearing loss with a tone-frequency audiometric approach. In conclusion, there is not really a frequency specificity of impairments due to styrene.

Toluene Effect on the Olivocochlear Reflex

Animal studies have shown that toluene can cause hearing loss and can exacerbate the effects of noise by inhibiting the middle ear acoustic reflex. In this investigation, carried out in Long-Evans rats, the tensor tympani tendon was cutoff and the stapedius muscle was electrocoagulated in one or both middle ears. Rat hearing was evaluated by measuring cubic distortion otoacoustic emissions (2f1-f2; f1 = 8000 Hz; f2 = 9600 Hz; f1/f2 = 1.2) prior to, during, and after activation of the olivocochlear (OC) reflex. A band noise centered at 4 kHz was used as suppressor noise. It was delivered contralaterally to decrease 2f1-f2 amplitude. The strength of the inner ear acoustic reflex was tested by increasing contralateral noise intensity, and toluene injected into the carotid artery was used to study physiological efficacy. Results showed that the protective effect of the OC reflex is intensity dependent. In addition, the OC reflex was found to be less sensitive to toluene than the middle ear acoustic reflex. This may be because the efferent neurons involved in inner ear and middle ear reflexes are located differently. In conclusion, the synergistic effects on hearing of co-exposure to noise and aromatic solvents are because of solvents depressing the central nuclei, which mainly drive the middle ear acoustic reflex.

One-day measurement to assess the auditory risks encountered by noise-exposed workers

Abstract Noise is one of the most pervasive hazards in the workplace. Despite regulations and preventive measures, noise-induced hearing loss is common. The current reference test is pure-tone air-conduction audiometry (PTA), but this test cannot be used to detect early hearing loss. Objective: In this study, we assess one-day auditory fatigue using both PTA and efferent reflexes (ER) measured using DPOAEs associated with contralateral acoustic stimulation (CAS DPOAEs). Design: The noise exposure history, PTA, and ER detection were performed in seven different companies where the LEX,8h was 85 dB(A). Hearing was tested before and at the end of the working day. Study sample: Forty-six volunteers were selected to carry out this study. Results: After a single working day, a greater impact of noise was measured using ER thresholds than PTA or DPOAEs. ER measurements are objective, easy to perform, and do not require a sound-attenuated booth. Conclusion: Screening workers by periodically measuring ER thresholds using CAS DPOAEs helps detect early changes in hearing status, before the onset of noise-induced hearing loss. These tests can be readily applied as part of a hearing conservation program.

Toluene-induced hearing loss in the guinea pig.

Toluene is a high-production industrial solvent, which can disrupt the auditory system in rats. However, toluene-induced hearing loss is species dependent. For instance, despite long-lasting exposures to high concentrations of aromatic solvent, no study has yet succeeded in causing convincing hearing loss in the guinea pig. This latter species can be characterized by two metabolic particularities: a high amount of hepatic cytochrome P-450s (P-450s) and a high concentration of glutathione in the cochlea. It is therefore likely that the efficiency of both the hepatic and cochlear metabolisms plays a key role in the innocuousness of the hearing of guinea pigs to exposure to solvent. The present study was carried out to test the auditory resistance to toluene in glutathione-depleted guinea pigs whose the P-450 activity was partly inhibited. To this end, animals on a low-protein diet received a general P-450 inhibitor, namely SKF525-A. Meanwhile, they were exposed to 1750 ppm toluene for 4 weeks, 5 days/week, 6 h/day. Auditory function was tested by electrocochleography and completed by histological analyses. For the first time, a significant toluene-induced hearing loss was provoked in the P-450-inhibited guinea pigs. However, the ototoxic process caused by the solvent exposure was different from that observed in the rat. Only the stria vascularis and the spiral fibers were disrupted in the apical coil of the cochlea. The protective mechanisms developed by guinea pigs are discussed in the present publication.

Membrane fluidity does not explain how solvents act on the middle-ear reflex

Some volatile aromatic solvents have similar or opposite effects to anesthetics in the central nervous system. Like for anesthetics, the mechanisms of action involved are currently the subject of debate. This paper presents an in vivo study to determine whether direct binding or effects on membrane fluidity best explain how solvents counterbalance anesthesias depression of the middle-ear reflex (MER). Rats were anesthetized with a mixture of ketamine and xylazine while also exposed to solvent vapors (toluene, ethylbenzene, or one of the three xylene isomers) and the amplitude of their MER was monitored. The depth of anesthesia was standardized based on the magnitude of the contraction of the muscles involved in the MER, determined by measuring cubic distortion product oto-acoustic emissions (DPOAEs) while triggering the bilateral reflex with contralateral acoustic stimulation. The effects of the aromatic solvents were quantified based on variations in the amplitude of the DPOAEs. The amplitude of the alteration to the MER measured in anesthetized rats did not correlate with solvent lipophilocity (as indicated by logKow values). Results obtained with the three xylene isomers indicated that the positions of two methyl groups around the benzene ring played a determinant role in solvent/neuronal cell interaction. Additionally, Solid-state Nuclear Magnetic Resonance (NMR) spectra for brain microsomes confirmed that brain lipid fluidity was unaffected by solvent exposure, even after three days (6h/day) at an extremely high concentration (3000ppm). Therefore, aromatic solvents appear to act directly on the neuroreceptors involved in the acoustic reflex circuit, rather than on membrane fluidity. The affinity of this interaction is determined by stereospecific parameters rather than lipophilocity.

Continuous exposure to low-frequency noise and carbon disulfide: combined effects on hearing

HIGHLIGHTSCarbon disulfide temporarily potentiates the effects of low‐frequency noise on cochlear function.Low‐frequency noise provokes hearing loss in a frequency range wider than expected.No evidence of cochlear toxicity due to carbon disulfide. ABSTRACT Carbon disulfide (CS2) is used in industry; it has been shown to have neurotoxic effects, causing central and distal axonopathies.However, it is not considered cochleotoxic as it does not affect hair cells in the organ of Corti, and the only auditory effects reported in the literature were confined to the low‐frequency region. No reports on the effects of combined exposure to low‐frequency noise and CS2 have been published to date. This article focuses on the effects on rat hearing of combined exposure to noise with increasing concentrations of CS2 (0, 63,250, and 500 ppm, 6 h per day, 5 days per week, for 4 weeks). The noise used was a low‐frequency noise ranging from 0.5 to 2 kHz at an intensity of 106 dB SPL. Auditory function was tested using distortion product oto‐acoustic emissions, which mainly reflects the cochlear performances. Exposure to noise alone caused an auditory deficit in a frequency area ranging from 3.6 to 6 kHz. The damaged area was approximately one octave (6 kHz) above the highest frequency of the exposure noise (2.8 kHz); it was a little wider than expected based on the noise spectrum.Consequently, since maximum hearing sensitivity is located around 8 kHz in rats, low‐frequency noise exposure can affect the cochlear regions detecting mid‐range frequencies. Co‐exposure to CS2 (250‐ppm and over) and noise increased the extent of the damaged frequency window since a significant auditory deficit was measured at 9.6 kHz in these conditions.Moreover, the significance at 9.6 kHz increased with the solvent concentrations. Histological data showed that neither hair cells nor ganglion cells were damaged by CS2. This discrepancy between functional and histological data is discussed. Like most aromatic solvents, carbon disulfide should be considered as a key parameter in hearing conservation régulations.

158 Coachbuilding and painting shop workers’ co-expositionto noise and ototoxic substances. risk evaluation and prevention

Introduction Coachbuilding and painting shop workers are co-exposed to noise and ototoxic substances thereby producing synergistic adverse effects on hearing, which might increase the risk of professional hearing loss. A previous investigation showed that most of employers and workers ignore those risks due to occupational activities, or negligences. Methods 60 volunteers were measured in 24 shops. We used dosimeters for evaluating the noise exposures, and passive badges for the amount of solvents inhaled by each worker during a workday. CAS DPOAE suppression (Echoscan) allowed auditory fatigue to be assessed by summing several sources: metabolic fatigue from hair cells, afferent and efferent fibres, central nuclei (SOC and facial), and obviously from middle-ear muscles. The trigger threshold variations of workers exposed to both noise and solvents were measured with Echoscan twice a day. In the meantime, the wearing of auditory and respiratory individual protectors was monitored. Results The Lex8h measurements were higher than 80, 85, 87 dB(A) for 33, 17, 12% of tested workers, respectively. Toluene, ethylbenzene and xylene constituted the most used ototoxics. These findings are in agreement with the data collected in the French database COLCHIC for carshops’ workers. Taken separately each solvent exposure was inferior to its legal threshold limit value, but an exposure to a chemical cocktail may affect the hair cells or the central nuclei. Results showed that data obtained with Echoscan were sensitive both to noise and solvents. At the end of a working day, trigger threshold variations of workers exposed to both noise and solvents were significantly lower than those measured in workers exposed to noise only. Workers and shop observation showed significant neglects in collective and individual prevention. Conclusion Difficulties to characterise workers’ effective exposure are numerous in car shops. Regarding employers and workers’ awareness, a primary prevention has been launched through information sessions. Auditory fatigue depends on the nature of the exposure. A co-exposure impacts the trigger threshold variations of CAS DPOAEs.