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Chemical Exposure as a Risk Factor for Hearing Loss: Implications for Occupational Health

Thais C. Morata, Ph.D.Hearing Loss Prevention Team

tmorata@cdc.govThe findings and conclusions in this presentation are those of the author and do not necessarily represent the views of the National Institute for Occupational Safety and Health.

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No systematic research effort on auditory effects of chemicals, but isolated reports:

- Poisoning: accidents or abuse- Occupational exposures (painters,

printers, metal, chemical, leather industry workers, etc.)

- Environmental exposures (air and water contamination)

Before the 1980’s

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Schacht J, Hawkins JE. 2006 Sketches of otohistory. Part 11: Ototoxicity: drug-induced hearing loss. Audiol Neurootol. 2006;11(1):1-6.

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Bergstrom & Nystrom, 1986

Division N %HL dBA

Chemical 47 23 80-90

Paper pulp 123 8 95-100

Sawmill 41 5 95-100

Maintenance 84 6 95-100

Scand Audiol. 1986;15(4):227-34.

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Features of NIHL/Ototoxicity

• Bilateral, symmetrical, and irreversible• Onset in the high-frequency range,

progress rate determined by risk factors• Cochlear, or with a cochlear component• History of exposure

General descriptors

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Ototoxicity of therapeutic drugs

• Antimalarial• Non-steroidal anti-inflammatory• Aminoglycosides• Antimicrobial• Loop diuretics• Antineoplastic• Chelating agents

Mostly: Vastly studied Effects restricted to cochlea Use monitored, i.e., knowledge of intake

Approaches: Substitution Antioxidants

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Ototoxicity of environmental chemical

exposures Mostly: Relatively few studies Effects not restricted to the cochlea Use poorly monitored, i.e., poor knowledge of exposure history Confounded by noise

Approaches:Substitution/control of exposureAntioxidants

• Metals

• Solvents• Asphyxiants• Pesticides

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• Metals– Trimethyltin (Fechter et al, Crofton et al.)

– Methyl mercury (Konshi et al., Ison et al., Rice et al.)

– Lead (Discalzi et al)

– PesticidesPerry & May J Agromedicine.

2005;10(2):49-55.

Selected key publications reporting

effects

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• Chemical asphyxiants– Carbon Monoxide (CO) + noise (Fechter

et al)

– Hydrogen Cyanide + noise (Fechter et al)

– Potassium Cyanide (Konishi et al., Evans & Klinke, Fechter et al. )

• Acrylonitrile (Fechter et al., Pouyatos et al.)

Selected key publications reporting

effects

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• Organic solvents– Toluene (Pryor et al., Sullivan et al., Johnson et al.,

Crofton et al, Campo et al., Morata et al., Fechter et al.)– Ethyl benzene (Cappaert et al.)

– Styrene (Campo et al., Crofton et al., Pryor et al., Morata et al, Sliwinska-Kowalska et al )

– Xylene (Pryor et al., Crofton et al, 1994)

– Trichloroethylene (Crofton et al., Fechter et al., Muijser et al.)

– N- Hexane (Rebert et al., Nylen et al.,)

– Carbon disulfide (Sulkowski, Morata, Chang et al.)

– Solvent mixtures (Rebert et al., Crofton et al., Morata et al., Jacobsen et al., Kim et al., Sliwinska-Kowalska et al)

Selected key publications reporting

effects

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ICOH Milano• Special Session (June 14th)• Mini-Symposium (June 15th)• Other presentations dispersed in

noise or chemical sessions

2006

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In the 1990’s

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1998-2006

TLVs® and BEIs®: Notes, Noise“Exposure to certain chemicals may also result in hearing loss. In settings in which there may be exposure to noise as well as toluene, lead,… ….periodic audiograms are advised and should be carefully reviewed.”

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ACOEM Noise-induced Hearing Loss EVIDENCE-BASED STATEMENT, JOEM 45(6) 2003

“Clinicians evaluating cases of possible noise-inducedhearing loss should keep in mind the followingclinical concerns:……Coexposure to ototoxic agents, such as solvents, heavy metals and tobacco smoke, may act in synergy with noise to cause hearing loss”.

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Australia-New Zealand AS/NZS 1269:2005 Occupational Noise Management/Informative Appendix on Ototoxic Agents requiring hearing tests for those exposed to ototoxic agentshttp://www.standards.com.au/catalogue/script/search.asp

Standards

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US Army Regulation 1998-2004

Dept. of the Army Pamphlet 40-501 Hearing Conservation Program: Requires consideration of ototoxic chemical exposures (including toluene) for program inclusion, particularly when in combination with marginal noise (¶ 3-3).

https://134.11.61.26/CD4/Publications/DA/DA%20Pam/DA%20Pam%2040-501%2019981210.pdf

Fact Sheet 51-002-0903 suggests Action Level for chemicals for inclusion in Hearing Conservation Program.

http://chppm-www.apgea.army.mil/documents/FACT/51-002-0903.pdf

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Legislation

The European Community directive on noise (2003/10 EC noise) requires that the interaction between noise and work-related ototoxic substances, and noise and vibration be taken into account in the risk assessment of exposed populations (Article 4 of Section II)

.http://europa.eu.int/eur-lex/pri/en/oj/dat/2003/l_042/l_04220030215en00380044.pdf

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Countries (Australia, New Zealand, Brazil) started to accept link between chemical exposure and hearing loss in compensation casesBrazil Decree no. 3048/ May 6, 1999Australiahttp://www.workcover.nsw.gov.au/Publications/WorkersComp/InjuryManagement/Permimpair.htm

Legislation

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Remaining challenges

Lab studiesDamage MechanismAdministration Route

Field StudiesPriority List &

RationaleIdentify Risk Populations

Data over Exposure Range

Rationale: Magnitude of exposed populations, chemical’s ototoxicity, general toxicity, as well as nephro- or neurotoxicity.

1- Number of chemicals and combinations

Morata et al., 2003

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Remaining challenges

2- Dose-response, NOEL, LOEL, Action Level, Response Level

• Chronic effect/ role of peak exposures• Biomarkers

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Groups:

• Distribution of hearing loss to be compared from groups with different exposure conditions

• Comparing mean thresholds between groups does not always allow distinction between the effect of each agent (noise or chemical); risk ratios are needed.

Remaining challenges2- Analysis strategies

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• Pure tone audiometry– Requires large population, or– Requires complaint of speech difficulty or other

difficulty inconsistent w/ thresholds

• Need to consistently define hearing loss and change from baseline

• Need good reference data from unexposed populations

• Criteria for excluding age/confounders• Consideration of non-occupational exposures

2- Analysis strategies

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Individual cases: • Ototoxicity or neurotoxicity/Cochlear vs.

retrocochlear? Tests to complement pure-tone audiometry are needed

• Complaints of hearing difficulties not compatible with audiometric result

• Other complaints associated with neurotoxicity (balance, vision, etc).

3. Appropriate metrics

Remaining challenges

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• Length of test• Administration time• Ease of analysis• Sensitivity/specificity (validity)• Utility for retrospective vs. prospective or longitudinal studies

Availability of gold standard or screening tests? Not yet (Morata and Little, 2002)

3. Appropriate metrics

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Impact on Preventive Practices & Research

• Recommended limits have not taken ototoxic properties or combined exposures into consideration

• Controlling noise and hearing protectors insufficient for preventing hearing loss

• Eligibility to Hearing Loss Prevention Programs

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Remediation

• Reduce hazardous exposures– Engineering controls– Protective equipment

(e.g. respirators, gloves)

• Education of the potentially affected population

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NIOSH, Publication Disseminationhttp://www.cdc.gov/niosh/homepage.html

pubstaft@cdc.gov

http://www2a.cdc.gov/niosh-comments/nora-comments/input.asp