Chemical Exposure as a Risk Factor for Hearing

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

Chemical Exposure as a Risk Factor for Hearing Loss: Implications for Occupational Health Thais C. Morata, Ph. D. Hearing Loss Prevention Team [email protected] gov The 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. 1

Before the 1980’s No systematic research effort on auditory effects of chemicals, but isolated

Before the 1980’s 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) 2

Schacht J, Hawkins JE. 2006 Sketches of otohistory. Part 11: Ototoxicity: drug-induced hearing loss.

Schacht J, Hawkins JE. 2006 Sketches of otohistory. Part 11: Ototoxicity: drug-induced hearing loss. Audiol Neurootol. 2006; 11(1): 1 -6. 3

Bergstrom & Nystrom, 1986 Scand Audiol. 1986; 15(4): 227 -34. 4

Bergstrom & Nystrom, 1986 Scand Audiol. 1986; 15(4): 227 -34. 4

Features of NIHL/Ototoxicity General descriptors • Bilateral, symmetrical, and irreversible • Onset in the

Features of NIHL/Ototoxicity General descriptors • 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 5

Ototoxicity of therapeutic drugs • Antimalarial • Non-steroidal antiinflammatory • Aminoglycosides • Antimicrobial •

Ototoxicity of therapeutic drugs • Antimalarial • Non-steroidal antiinflammatory • Aminoglycosides • Antimicrobial • Loop diuretics • Antineoplastic • Chelating agents Mostly: ü Vastly studied ü Effects restricted to cochlea ü Use monitored, i. e. , knowledge of intake Approaches: ü Substitution ü Antioxidants 6

Ototoxicity of environmental chemical exposures Mostly: ü Relatively few studies • Metals ü Effects

Ototoxicity of environmental chemical exposures Mostly: ü Relatively few studies • Metals ü Effects not restricted to the cochlea • Solvents ü Use poorly monitored, i. e. , poor • Asphyxiants knowledge of exposure history • Pesticides ü Confounded by noise Approaches: üSubstitution/control of exposure üAntioxidants 7

Selected key publications reporting effects • Metals – Trimethyltin (Fechter et al, Crofton et

Selected key publications reporting effects • Metals – Trimethyltin (Fechter et al, Crofton et al. ) – Methyl mercury (Konshi et al. , Ison et al. , Rice et al. ) – Lead (Discalzi et al) – Pesticides Perry & May J Agromedicine. 2005; 10(2): 4955. 8

Selected key publications reporting effects • Chemical asphyxiants – Carbon Monoxide (CO) + noise

Selected key publications reporting effects • 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. ) 9

Selected key publications reporting effects • Organic solvents – Toluene (Pryor et al. ,

Selected key publications reporting effects • 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) 10

2006 ICOH Milano • Special Session (June 14 th) • Mini-Symposium (June 15 th)

2006 ICOH Milano • Special Session (June 14 th) • Mini-Symposium (June 15 th) • Other presentations dispersed in noise or chemical sessions 11

In the 1990’s 12

In the 1990’s 12

1998 -2006 TLVs® and BEIs®: Notes, Noise “Exposure to certain chemicals may also result

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. ” 13

ACOEM Noise-induced Hearing Loss EVIDENCE-BASED STATEMENT, JOEM 45(6) 2003 “Clinicians evaluating cases of possible

ACOEM Noise-induced Hearing Loss EVIDENCE-BASED STATEMENT, JOEM 45(6) 2003 “Clinicians evaluating cases of possible noise-induced hearing loss should keep in mind the following clinical concerns: … …Coexposure to ototoxic agents, such as solvents, heavy metals and tobacco smoke, may act in synergy with noise to cause hearing loss”. 14

Standards Australia-New Zealand AS/NZS 1269: 2005 Occupational Noise Management/Informative Appendix on Ototoxic Agents requiring

Standards Australia-New Zealand AS/NZS 1269: 2005 Occupational Noise Management/Informative Appendix on Ototoxic Agents requiring hearing tests for those exposed to ototoxic agents http: //www. standards. com. au/catalogue/ script/search. asp 15

US Army Regulation 1998 -2004 Dept. of the Army Pamphlet 40 -501 Hearing Conservation

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/CD 4/Publications/DA/DA%20 Pam%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 16

Legislation The European Community directive on noise (2003/10 EC noise) requires that the interaction

Legislation The European Community directive on noise (2003/10 EC noise) requires that the interaction between noise and workrelated 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_04220030215 en 00380044. pdf 17

Legislation Countries (Australia, New Zealand, Brazil) started to accept link between chemical exposure and

Legislation Countries (Australia, New Zealand, Brazil) started to accept link between chemical exposure and hearing loss in compensation cases Brazil Decree no. 3048/ May 6, 1999 Australia http: //www. workcover. nsw. gov. au/Publicati ons/Workers. Comp/Injury. Management/Permi mpair. htm 18

Remaining challenges 1 - Number of chemicals and combinations Lab studies Damage Mechanism Administration

Remaining challenges 1 - Number of chemicals and combinations Lab studies Damage Mechanism Administration Route Field Studies Priority List & Rationale Identify Risk Populations Data over Exposure Range Rationale: Magnitude of exposed populations, chemical’s ototoxicity, general toxicity, as well as nephro- or neurotoxicity. Morata et al. , 2003 19

Remaining challenges 2 - Dose-response, NOEL, LOEL, Action Level, Response Level • Chronic effect/

Remaining challenges 2 - Dose-response, NOEL, LOEL, Action Level, Response Level • Chronic effect/ role of peak exposures • Biomarkers 20

Remaining challenges 2 - Analysis strategies Groups: • Distribution of hearing loss to be

Remaining challenges 2 - Analysis strategies 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. 21

2 - Analysis strategies • Pure tone audiometry – Requires large population, or –

2 - Analysis strategies • 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 22

Remaining challenges 3. Appropriate metrics Individual cases: • Ototoxicity or neurotoxicity/Cochlear vs. retrocochlear? Tests

Remaining challenges 3. Appropriate metrics Individual cases: • Ototoxicity or neurotoxicity/Cochlear vs. retrocochlear? Tests to complement puretone audiometry are needed • Complaints of hearing difficulties not compatible with audiometric result • Other complaints associated with neurotoxicity (balance, vision, etc). 23

3. Appropriate metrics Availability of gold standard or screening tests? Not yet (Morata and

3. Appropriate metrics Availability of gold standard or screening tests? Not yet (Morata and Little, 2002) • Length of test • Administration time • Ease of analysis • Sensitivity/specificity (validity) • Utility for retrospective vs. prospective or longitudinal studies 24

Impact on Preventive Practices & Research • Recommended limits have not taken ototoxic properties

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 25

Remediation • Reduce hazardous exposures – Engineering controls – Protective equipment (e. g. respirators,

Remediation • Reduce hazardous exposures – Engineering controls – Protective equipment (e. g. respirators, gloves) • Education of the potentially affected population 26

NIOSH, Publication Dissemination http: //www. cdc. gov/niosh/homepage. html pubstaft@cdc. gov http: //www 2 a.

NIOSH, Publication Dissemination http: //www. cdc. gov/niosh/homepage. html [email protected] gov http: //www 2 a. cdc. gov/niosh-comments/nora-comments/input. asp 27