Cochlear dysfunction is associated with styrene exposure in humans

RESEARCH ARTICLE Cochlear dysfunction is associated with styrene exposure in humans Mariola Sliwinska-Kowalska1, Adrian Fuente ID2,3*, Ewa Zamyslowska-Szmytke1 1 Department of Audiology and Phoniatrics, Nofer Institute of Occupational Medicine, Lodz, Poland, 2 Centre de recherche de l’Institut universitaire de gériatrie de Montréal, Québec, Canada, 3 École d’orthophonie et d’audiologie, Faculté de médecine, Université de Montréal, Québec, Canada * a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 Abstract Aim OPEN ACCESS Citation: Sliwinska-Kowalska M, Fuente A, Zamyslowska-Szmytke E (2020) Cochlear dysfunction is associated with styrene exposure in humans. PLoS ONE 15(1): e0227978. https://doi. org/10.1371/journal.pone.0227978 Editor: Paul Hinckley Delano, Universidad de Chile, CHILE Received: August 11, 2019 Accepted: January 3, 2020 Published: January 21, 2020 Copyright: © 2020 Sliwinska-Kowalska et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the manuscript and its Supporting Information files. Funding: MSK received funding from the 6th European Framework Project under the Marie Curie Host Fellowship for the Transfer of Knowledge ‘NOISEHEAR’ (Contract No. MTKD-CT-2004003137). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Occupational exposure to styrene has been shown to be associated with an increased probability of developing hearing loss. However, the sites of lesions in the auditory system in humans remain unknown. The aim of this study was to investigate the possible adverse effects of styrene exposure on the cochlea of human subjects. Design The hearing function of 98 styrene-exposed male workers from the glass fibre-reinforced plastics industry (mean concentration of 55 mg/m3) was evaluated bilaterally using puretone audiometry (1000–16000 Hz), distortion product otoacoustic emissions (DPOAEs), and auditory brainstem response (ABR). The results were compared to a group of 111 male workers exposed to noise (above 85 dBA) and 70 male white-collar workers exposed to neither noise nor solvents. Age and noise exposure levels were accounted for as confounding variables in all statistical models. Results Styrene exposure was significantly associated with poorer pure-tone thresholds (1–8 kHz), lower DPOAE amplitudes (5–6 kHz), and shorter wave V latencies in both ears compared to control-group subjects. Similar results were found among noise-exposed subjects. A further analysis with wave V latency showed that styrene-exposed subjects showed significantly shorter latencies than expected according to normative data. These results suggest that occupational exposure to styrene at moderate concentrations is associated with cochlear dysfunction, at least at high frequencies. DPOAEs may be considered a valuable diagnostic tool in hearing conservation programs in workers exposed to styrene. Competing interests: The authors have declared that no competing interests exist. PLOS ONE | https://doi.org/10.1371/journal.pone.0227978 January 21, 2020 1 / 23 Cochlear dysfunction associated with styrene exposure Introduction Styrene is an aromatic solvent that is widely used as a precursor for polystyrene plastics. Pure styrene is a colourless, easily evaporating liquid with a characteristic sweetish odour and is partially soluble in water. In the manufacturing industry, it is mainly used in the production of polyester laminates and plastics, synthetic rubber and insulating materials (such as polyurethane foam), and in the glass fibre-reinforced plastic product industry (e.g., yachts, lavatory pans and washbasins). The highest occupational exposure to styrene occurs when laminating large items such as boats. Styrene is absorbed through the respiratory airways and the skin. Its metabolites are mainly mandelic acid (MA) and phenylglyoxylic acid (PGA). The occupational exposure limit (OEL) for styrene in the U.S. is 426 mg/ m3 (100 parts per million (PPM)) as an 8-hour time-weighted average (TWA), according to the Occupational Safety and Health Administration (OSHA), and 87 mg/m3 (20 PPM) as an 8-hour TWA, according to the American Conference of Governmental Industrial Hygienists (ACGIH). In Poland, the OEL for styrene is 50 mg/m3 (12 PPM) as an 8-hour TWA. Chronic exposure to styrene has been associated with neurotoxicity [1,2], neuroendocrine alterations [3,4], nephrotoxicity [5], hepatotoxicity [6], acute myeloid leukemia [7], among other health problems. In addition, it has been suggested that styrene may adversely affect the hearing and balance systems [8,9]. Pryor et al. [10] were the first to report ototoxicity induced by styrene in an animal model. The adverse effect of styrene on human hearing was then initially reported by Muijser et al. [11], who found a statistically significant difference in hearing thresholds between workers directly exposed to styrene (at a mean concentration of 138 mg/m3) and workers indirectly exposed to styrene (at 61 mg/m3). However, Möller et al. [12], who examined a group of workers exposed to styrene at concentrations considerably lower than the Swedish OEL (i.e., 119 mg/m3 in 1990), did not find any significant hearing losses in the styrene-exposed group compared to non-exposed control subjects. Similarly, Calabrese et al. [13] found no hearing impairment in workers exposed to styrene concentrations of approximately 229 mg/m3. Some limitations, however, can be identified in these studies [12,13]. First, both studies [12,13] included a limited number of workers (18 and 20 subjects, respectively). Secondly, Calabrese et al. [13] did not use a control group; thus, the hearing test results for the styrene-exposed subjects were not compared to those of unexposed subjects. In addition, Calabrese et al. [13] did not provide details about the hearing tests utilised. Three different studies have found poorer hearing thresholds in workers exposed to styrene [14–16], than in unexposed workers. Morata et al. [15], found that styrene-exposed workers, despite being exposed to low airborne styrene concentrations (below 5 ppm; 12–16 mg/m3), showed poorer audiometric pure-tone thresholds for the frequencies 2–6 kHz in comparison to non-exposed control subjects. Mandelic acid concentration in urine and the odds ratio for hearing loss were significantly correlated [15]. Morioka et al. [14], showed that styrene exposure (mean exposure of approximately 229 mg/m3) was correlated with a poorer upper frequency limit of hearing [17]. In our previous study [16], we showed that styrene exposure at a mean concentration of 61.8 mg/m3 was significantly associated with a 5.2-fold increased odds ratio of hearing loss; (...truncated)