Journal of Occupational and Environmental Hygiene ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/uoeh20 Exposure to lead, mercury, styrene, and toluene and hearing impairment: Evaluation of dose- response relationships, regulations, and controls Ehsan Hemmativaghef To cite this article: Ehsan Hemmativaghef (2020): Exposure to lead, mercury, styrene, and toluene and hearing impairment: Evaluation of dose-response relationships, regulations, and controls, Journal of Occupational and Environmental Hygiene, DOI: 10.1080/15459624.2020.1842428 To link to this article: https://doi.org/10.1080/15459624.2020.1842428 Published online: 04 Dec 2020. Submit your article to this journal View related articles View Crossmark data Full Terms & Conditions of access and use can be found at https://www.tandfonline.com/action/journalInformation?journalCode=uoeh20 JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HYGIENE https://doi.org/10.1080/15459624.2020.1842428 REVIEW Exposure to lead, mercury, styrene, and toluene and hearing impairment: Evaluation of dose-response relationships, regulations, and controls Ehsan Hemmativaghef Faculty of Medicine, School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada ABSTRACT KEYWORDS The risk of hearing loss from exposure to ototoxic chemicals is not reflected in occupational Biological exposure index; exposure limits and most jurisdictions. The aims of this research were to investigate dose- blood lead level; ototoxic response relationships between exposure to lead, mercury, toluene, and styrene and hearing chemicals; pure impairment based on current epidemiological evidence, conduct cross-jurisdictional compar- tone audiometry isons, and investigate control measures for exposure to ototoxic chemicals. Ovid Medline and Ovid Embase databases were used to find relevant publications. A total of 86 epidemio- logical studies met the eligibility criteria for final evaluation. When significant associations between exposure and outcome were identified, exposure levels were evaluated to deter- mine whether No Observed Adverse Effect Level (NOAEL) and Lowest Observed Adverse Effect Level (LOAEL) could be identified. Cross-jurisdictional comparisons included the U.K., U.S., Canada, and Australia occupational health and safety legislations. The majority of lead (75%), styrene (74%), and toluene (77%) studies showed significantly increased risks of hear- ing loss from exposure to these substances, although numerous studies on toluene (70%) and styrene (16%) compared auditory function between “solvent mixture” or “noise and solvent mixture” exposed groups and controls and not necessarily on groups exposed to a single agent. Based on five studies, blood lead ranges of 1–1.99 lg/dL to 2.148–2.822 lg/dL were identified as NOAELs while blood lead levels of 2 lg/dL up to 2.823–26.507 lg/dL were identified as LOAELs for hearing loss. Except for general duty clauses, the U.S., Canadian, and Australian jurisdictions have set no enforceable regulations specific to ototoxic chemical exposures. A biological exposure index of 2 lg/dL is recommended for prevention of hear- ing impairment from lead exposure. Based on Safe Work Australia, noise exposure limits may be reduced to 80 dB(A) for 8 hr. Other recommendations include performing audiomet- ric testing and controlling exposure through all routes of entry. Introduction “confirmed” ototoxic substances including pharma- Hearing loss is the fourth most prevalent disabling ceuticals, solvents, asphyxiants, nitriles, and metals. disease in the world (IHME 2017). The number of The classification was based on a weight of evidence people with disabling hearing loss is estimated to be approach obtained from at least two well-documented 466 million or 6.1% of the world’s population. This animal studies or a single comprehensive and reliable number is expected to grow over the coming years animal study providing consistent and coherent evi- and could rise to 630 million by 2030 and over 900 dence of ototoxic effects (Campo et al. 2009). million in 2050, unless preventive actions are taken The mechanism of damage to hearing varies (WHO 2018). depending on the chemical substance. An acute or Although loud noise has detrimental effects on chronic neurotoxic effect of exposure to aromatic sol- auditory function, it is not the only source of work- vents such as toluene and styrene is central nervous related hearing impairment. Exposure to ototoxic system (CNS) depression (NIOSH 1987;Moller€ et al. chemicals can increase the risk of hearing loss with or 1990; Greenberg 1997) while chronic exposures affect without concurrent noise exposure (Fechter and the inner ear (Pryor et al. 1983; 1987) causing irre- Pouyatos 2005; Gagnaire and Langlais 2005). The versible hearing impairment by poisoning cochlear European Agency for Safety and Health at Work clas- hair cells and disorganizing their membranous struc- sified several chemicals in five groups of substances as tures (Johnson and Canlon 1994; Campo et al. 2001). CONTACT Ehsan Hemmativaghef [email protected] E Mall, 2206 E Mall, Vancouver, BC V6T 1Z3, Canada. ß 2020 JOEH, LLC 2 E. HEMMATIVAGHEF Solvents may directly affect the cells of the organ of Examination Survey (NHANES) data collected from Corti forming chemically and biologically reactive 1999–2004 (Tak et al. 2009). Over 30 M U.S. workers intermediates including reactive oxygen species, which are exposed to hazardous chemicals in their workpla- may trigger the death of these cells (Chen et al. 2007). ces, some of which might be ototoxic and hazardous While exposures to solvents such as styrene and solv- to hearing (OSHA 2004; NIOSH 2018). ent mixtures are associated with disorders in the cen- The American Conference of Governmental V tral auditory pathway (Abbate et al. 1993; Morata Industrial Hygienists (ACGIH R ), in its Threshold et al. 1993; Greenberg 1997; Johnson et al. 2006), Limited Values and Biological Exposure Indices V exposure to lead and mercury may affect both the coch- (TLVs R and BEIs) publication, has included a note lea (Rice and Gilbert 1992;Rice1997) and the central entitled “Ototoxicant” under Definitions and auditory pathways (Discalzi et al. 1993;OttoandFox Notations. The note explains that the designation 1993;Lasky,Maier,Snodgrass,Hecox,Laughlin1995; “OTO” in the “Notations” column indicates the Lasky, Maier, Snodgrass, Laughlin, Hecox 1995). Similar potential for a chemical to cause hearing impairment to aromatic solvents, the hearing-damaging effects of from exposure to the chemical alone or in interaction lead and mercury are caused by a neurotoxic mechan- with noise of even below 85 dBA. The OTO notation ism (Discalzi et al. 1993; Counter and Buchanan 2002; is reserved for chemicals which adversely affect audi- Hwang et al. 2009). Lead exposure affects cognitive and tory capacity including permanent audiometric thresh- central auditory nervous system function and peripheral old shifts as well as difficulties in processing sounds nerve conduction (Araki et al. 1992). Blood lead levels based on animal studies or human experience. The are associated with adverse effects in conduction in the note also states that “Some substances may act syner- distal auditory nerve and are found to impair conduc- gistically with noise, whereas others may potentiate tion in the auditory nerve and pathway in the lower noise effects. The OTO notation is intended to focus brainstem (Bleecker et al. 2003). Dimethylmercury poi- attention, not only on engineering controls, adminis- soning is shown to damage the auditory neural system trative controls and personal protective equipment (Musiek and Hanlon 1999)andexposuretomethyl needed to reduce airborne concentrations, but also on mercury chloride causes nerve conduction hypersensitiv- other means of preventing excessive combined expo- ity in the brainstem (Wassick and Yonovitz 1985). sures with noise to prevent hearing disorders. Carbon monoxide and hydrogen cyanide deprive oxy- Specifically, affected employees may need to be genwithinthecochlea(Campoetal.2013) impairing enrolled in hearing conservation and medical surveil- the cochlear function under extreme exposure condi- lance programs to more closely monitor auditory cap- tions but have reversible auditory effects when exposure acity, even when noise exposures do not exceed the levels are low (Campo et al. 2009). Aminoglycosides TLV for Audible Sound” (ACGIH 2019). Although penetrate the outer hair cells causing a reaction which employers are required to control risks of chemical generates the release of reactive oxygen species (ROS), exposures by the general duty clauses such as that resulting in death of cells (Rybak and Ramkumar 2007). contained in section 5(a)(1) of the U.S. OSH Act, Anti-neoplasticdrugscauselossofcochlearhaircells however, in most jurisdictions, they are not explicitly and cells of the spiral ganglion (Hamers et al. 2003). required to control the risks of hearing loss arising Exposure to nitriles is shown to cause cochlear hair cell from exposure to ototoxic chemicals. In addition, losses and spiral ganglion cell losses in animal studies these risks are not reflected in occupational exposure (Crofton et al. 1994;Soler-Martınetal.2007). limits. These issues have been linked to a lack of data In a recent study on the Australian workforce, on dose-response relationships and effects of exposure more than 80% of workers who were exposed to noise to ototoxic chemicals on hearing threshold shifts