Parameters influencing auditory fatigue among professionals working in the amplified music sector: noise exposure and individual factors.

OBJECTIVE: Hearing disorders are common among music professionals, as they are frequently exposed to sound levels exceeding 100 dB(A). By assessing auditory fatigue, situations that are deleterious for hearing could be identified, allowing the deployment of preventive measures before permanent impairment occurs. However, little is known about the factors contributing to auditory fatigue. The objective is to determine the exposure parameters most influencing auditory fatigue during occupational exposure to amplified music. DESIGN: Auditory fatigue was defined as variations of both pure tone auditory (ΔPTA) and efferent reflex thresholds (ΔER) during the workday. Noise exposure was monitored and information on the volunteers was gathered using a questionnaire. STUDY SAMPLE: The population consisted of 43 adult volunteers exposed to amplified music (sound, light or stage technicians, security agents, barmen) and 24 unexposed administrative agents. RESULTS: ΔPTA and ΔER were positively correlated with the energy of noise exposure and its stability over time, i.e a steady noise tends to create more auditory fatigue. CONCLUSION: In addition to a global decrease of music levels and a systematic use of hearing protection, our results advocate for the provision of quiet periods within noise exposures as they reduce auditory fatigue accumulation and long-term risks for hearing.

Measuring the middle-ear reflex: A quantitative method to assess effects of industrial solvents on central auditory pathways.

Volatile organic solvents are frequently present in industrial atmospheres. Their lipophilic properties mean they quickly reach the brain following inhalation. Acute exposure to some solvents perturbs the middle ear reflex, which could jeopardize cochlear protection against loud noises. As the physiological mechanisms involved in this protective reflex are highly complex, in vivo rodent models are required to allow rapid and reliable identification of any adverse effects of solvents on the middle ear reflex (MER). In this study, MER amplitude was measured in anesthetized Brown-Norway rats by monitoring the decrease in distortion product otoacoustic emissions (DPOAEs) caused by a contralateral stimulation. Our screening test consisted in measuring the impact of inhalation of solvent vapors at 3000 ppm for 15 min on the MER amplitude. We had previously studied a selection of aromatic solvents with this model; here, we extended the analysis to volatile compounds from other chemical families. The results obtained shed light on the mechanisms involved in the interactions between solvents and their neuronal targets. Thus, benzene and chlorobenzene had the greatest effect on MER (≥ + 1.8 dB), followed by a group composed of toluene, styrene, p-xylene, m-xylene, tetrachloroethylene and cyclohexane, which had a moderate effect on the MER (between + 0.3 and + 0.7 dB). Finally, trichloroethylene, n-hexane, methyl-ethyl-ketone, acetone, o-xylene, and ethylbenzene had no effect on the MER. Thus, the effect of solvents on the MER is not simply linked to their lipophilicity, rather it depends on specific interactions with neuronal targets. These interactions appear to be governed by the compound's chemical structure, e.g. the presence of an aromatic ring and its steric hindrance. In addition, perturbation of the MER by a solvent is independent of its toxic effects on cochlear cells. As the MER plays a protective role against exposure to high-intensity noises, these findings could have a significant impact in terms of prevention for subjects exposed to both noise and solvents.

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 anesthesia's 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.

Measurement of ketamine and xylazine in rat brain by liquid-liquid extraction and gas chromatography-mass spectrometry.

INTRODUCTION: In human and veterinary medicine, the injectable drugs ketamine and xylazine are mainly used in combination to induce, and then maintain general anaesthesia; they also provide pain and stress relief. Some side-effects have been reported on the auditory brainstem response, a method is therefore required to determine their concentrations in the brain. METHODS: This paper presents a method to determine nanogramme quantities of ketamine and xylazine in rat brain using liquid-liquid extraction and gas chromatography-mass spectrometry in selective ion monitoring mode. The technique requires only 0.5 g of sample, and uses xylazine d6 as an internal standard. RESULTS: The method was linear between 0.86 and 34.4 µg/g of brain. Limits of quantification were 378 and 87 ng (approximately 0.76 and 0.17 µg/g of brain) for ketamine and xylazine, respectively. The reliability of the method in terms of accuracy, within-day and between-day precision was also demonstrated. For xylazine, bias and intra-day precision were good (<3.0%), as was between-day precision (<10.5%); the equivalent values for ketamine were 7%, 11.1% and 20.9%, respectively. Stability of the analytes in the matrix at -80 °C was assessed over five months; both compounds were found to be stable for at least 1 month, even at very low concentrations. The procedure was successfully applied to determine (for the first time) the in vivo brain levels of both drugs in animals following systemic administration. DISCUSSION: The procedure will be useful in future studies of the side-effects of these drugs, and their interactions with other compounds.

Influence of water dilution on percutaneous absorption of N-vinyl-2-pyrrolidone in vivo and ex vivo in rats and ex vivo in humans.

N-vinyl-2-pyrrolidone (NVP) is mainly used as a monomer in the production of polyvinylpyrrolidone or copolymers. Percutaneous absorption is an important source of exposure in the work environment. However, few studies have investigated this route of absorption. In this study, percutaneous absorption of neat or aqueous NVP solutions was measured in vivo and ex vivo in rats, and ex vivo in humans. Penetration and absorption fluxes were very similar following in vivo exposure to neat NVP (0.54 and 0.43 mg/cm(2)/h, respectively). Exposing rats to a 50% aqueous solution of NVP increased both fluxes threefold (to 1.48 and 1.55 mg/cm(2)/h, respectively). Ex vivo, the absorption flux increased with solutions from 10 to 25% of NVP, reached a plateau (between 25 and 50% in rat, 25 and 75% in human) and then decreased with neat NVP. In vivo and ex vivo absorption fluxes measured using rat skin were similar, supporting the hypothesis that the ex vivo measurements were a good representation of what was observed in vivo. Thus, for humans, the ex vivo measurements are likely the same as would be determined in vivo.

In vivo and ex vivo percutaneous absorption of [14C]-bisphenol A in rats: a possible extrapolation to human absorption?

Bisphenol A (BPA) is a monomer used mainly in the synthesis of polycarbonates and epoxy resins. Percutaneous absorption is the second source of exposure, after inhalation, in the work environment. However, studies on this route of absorption are lacking or incomplete. In this study, percutaneous BPA absorption was measured in vivo and ex vivo in the rat, and ex vivo in humans. An approximately 12-fold difference in permeability between rat skin and human skin was found, with permeability being higher in the rat. In addition, inter- and intra-individual variability of up to tenfold was observed in humans. No accumulation of BPA in the skin was found during exposure. The skin clearance rate following exposure was estimated at 0.4 µg/cm²/h. Ex vivo and in vivo percutaneous absorption fluxes of BPA in the rat were in the same range (about 2.0 µg/cm²/h), suggesting that extrapolation to the in vivo situation in humans may be possible. The European tolerable daily intake (TDI) of BPA is 50 µg/kg body weight. However, many research projects have highlighted the significant effects of BPA in rodents at doses lower than 10 µg/kg/day. A 1-h occupational exposure over 2,000 cm² (forearms and hands) may lead to a BPA absorption of 4 µg/kg/day. This is 8% of the European TDI and is very close to the value at which effects have been observed in animals. This absorption must therefore be taken into account when evaluating risks of BPA exposure, at least until more relevant results on the toxicity of BPA in humans are available.

3-Hydroxybenzo(a)pyrene as a biomarker of dermal exposure to benzo(a)pyrene.

The aim of this study was to determine the percutaneous absorption flux of BaP (20 microg/cm(2) in ethanol) and the usefulness of urinary 3-OHBaP as a bio-indicator of dermal exposure to BaP. The percutaneous absorbed dose and absorption flux were estimated by comparison with intravenous administration of BaP (0.01 and 0.05 mg/kg in Cremophor) as reference way. A percutaneous absorption flux of 0.37 microg/cm(2)/h was determined by killing groups of rats, following exposure time of 4.5 and 24 h. [(14)C] skin content was 3.1 microg/cm(2), after 24 h exposure to BaP. Total urinary 3-OHBaP accounted for 0.4% of the real absorbed dose, which was fourfold higher than the percentage of an intravenous dose excreted as 3-OHBaP. This finding reveals that percutaneous absorption of BaP, based on the ratio of urinary excretion of 3-OHBaP following percutaneous exposure compared to percutaneous absorption following intravenous administration of BaP, is overestimated in the rat. In vitro, BaP was intensively metabolised by rat skin. Unchanged BaP and 3-OHBaP in receptor fluid accounted for 50 and 30% of the total radioactivity. This percutaneous first past effect of BaP in rats could, in part, explain the higher urinary excretion ratio of 3-OHBaP compared to the value based on intravenous administration of BaP. Conversely, BaP was largely lower metabolised as 3-OHBaP during percutaneous absorption by humans, so BaP absorption flux should be overestimated to a lesser extent in humans than in rats.