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.

Neuropharmacological and cochleotoxic effects of styrene. Consequences on noise exposures.

Occupational noise exposure can damage workers' hearing, particularly when combined with exposure to cochleotoxic chemicals such as styrene. Although styrene-induced cochlear impairments only become apparent after a long incubation period, the pharmacological impact of styrene on the central nervous system (CNS) can be rapidly measured by determining the threshold of the middle-ear acoustic reflex (MER) trigger. The aim of the study was to evaluate the effects of a noise (both continuous and impulse), and a low concentration of styrene [300ppm<(threshold limit value×10) safety factor] on the peripheral auditory receptor, and on the CNS in rats. The impact of the different conditions on hearing loss was assessed using distortion product oto-acoustic emissions, and histological analysis of cochleae. Although the LEX,8h (8-hour time-weighted average exposure) of the impulse noise was lower (80dB SPL sound pressure level) than that of the continuous noise (85dB SPL), it appeared more detrimental to the peripheral auditory receptors. A co-exposure to styrene and continuous noise was less damaging than exposure to continuous noise alone. In contrast, the traumatic effects of impulse noise on the organ of Corti were enhanced by co-exposure to styrene. The pharmacological effects of the solvent on the CNS were discussed to put forward a plausible explanation of these surprising results. We hypothesize that CNS effects of styrene may account for this apparent paradox. Based on the present results, the temporal structure of the noise should be reintroduced as a key parameter in hearing conservation regulations.

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.

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.

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.

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.