proceedings of the international workshop “synergistic ... · combined effects of noise and...

Proceedings of the International Workshop “Synergistic exposure to noise, vibrations and

ototoxic substances”

Rome, Italy – Università Urbaniana 30th September 2010

Edited by P. Nataletti, R. Sisto

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Proceedings of the International Workshop “Synergistic exposure to noise, vibrations and

ototoxic substances”

Rome, Italy – Università Urbaniana 30th September 2010

With the sponsorhip of:

Supported by:

Svantek Italia Svantek International

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CONTENTS

Forewords

Contributions

WIESLAV J.SULKOWSKY Combined effects of noise and carbon disulfide occupational exposure on auditory and vestibular function 1

MATS HAGBERG, ANDREAS JONSSON The different combinations of exposure to noise and hand-arm vibration in the Swedish work force affect health outcomes 15

TOPPILA ESKO Synergistic effects of noise and solvents - what we know and future research needs 25

TOPPILA ESKO Impulse noise and impulsive noise in the framework of the European noise directive 36

THAIS MORATA, ANN-CHRISTIN JOHNSON Chemical interactions in the auditory system: implications for occupational health 47

PIERRE CAMPO, CÉCILE RUMEAU, THOMAS VENET Combined effects of noise and solvent on hearing: animal experiments 61

Proceedings of the International Workshop Synergistic exposure to noise, vibrations and ototoxic substances

Rome, 30th September 2010

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FOREWORDS

The new 2003/10/EC Directive of the European Parliament and of the Council, replacing the previous Directive 86/188/EEC, has increased health and safety requirements regarding the exposure of workers to the risks arising from noise, with special emphasis on hearing-related damage. Indeed, noise is still the cause of the first occupational illness being indemnified in Europe in general and in Italy in particular. While on the one hand these requirements aim to safeguard the health and safety of each worker as an individual, on the other hand they set out to create a minimum protection policy for all community workers which avoids possible distortions of competition.Current scientific knowledge relating to the impact of risk exposure on health and safety does not allow accurate levels of exposure to be defined in respect of all health and safety risks, primarily as regards the non-hearing effects of noise.The 2003/10/EC Directive places special emphasis on the innovative topic concerning the assessment of all the effects on the workers’ health and safety arising from the impulsive content of noise, interaction between noise and ototoxic substances connected with the work being performed and between noise and vibrations, the latter being covered under Directive 2002/44/EC.Current scientific knowledge does not yet allow the synergistic contribution of these risk factors to the impact of noise on the workers’ health and safety to be assessed, such contribution being useful for risk assessment and managing the requirements set forth in the Directive.This workshop “Synergistic exposure to noise, vibrations, and ototoxic substances” has been initially organised by the National Institute of Occupational Prevention and Safety (ISPESL), as part of the IOHA 8th International Scientific Conference 2010 in Rome, with the sponsorship of the Italian Acoustic Association (AIA) – Noise and Vibration at Work Group, and of the International Commission on Occupational Health (ICOH) - Vibration & Noise Scientific Committee.Recently the ISPESL has been suppressed and incorporated into the Italian Workers’ Compensation Autority (INAIL).The purpose of the workshop is to provide a platform for leading international experts to exchange viewpoints on noise and the synergistic effects between noise, impulsive noise-and ototoxic substances and vibrations, so as to outline the state of the art of research and scientific and technological knowledge. Hopefully, this workshop will provide not only work and cooperation ideas and inputs for the researchers who are involved in the above areas, but also guidelines and practical advice for the assessment and management of these synergistic risks by the different stakeholders who are called upon to deal with prevention, with special reference to employers.

Pietro Nataletti, Renata SistoItalian Workers’ Compensation Autority, Rome, Italy

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CONTRIBUTIONS

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COMBINED EFFECTS OF NOISE AND CARBON DISULFIDE

OCCUPATIONAL EXPOSURE ON AUDITORY AND VESTIBULAR

FUNCTION1

Wieslaw J. Sulkowski

Nofer Institute of Occupational Medicine, Department of Occupational Diseases and

Toxicology, Lodz, Poland

e-mail: [email protected]; [email protected]

INTRODUCTION

It is well-known that most work environments consist of a myriad of physical and

chemical agents that are potentially risky to health. Study results of isolated workplace

hazards however are often used to develop occupational safety criteria that may not be

adequate for protecting workers in plants where sequential exposures to a variety of agents

occur.

Accordingly to the recent estimations around 30 million people in Europe work in

noise conditions that are dangerous to hearing and an additional 10 million work with

industrial chemicals considered to be ototoxic, and a great number of them may be

simultaneously exposed to the both.

A lot of data have been collected over the last two decades that synergistic effect is

observed in those having combined exposures to noise and chemicals, particularly to noise

and solvents such as toluene, styrene, xylene, trichloroethylene and their mixtures. In

addition to the synergistic effects on hearing, solvents may also affect balance and auditory

central nervous system function in a way not expected from noise exposure alone.

1 The invited paper presented at the 8th International Scientific Conference of IOHA, Rome, 28.09-02.10.2010



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A considerable much less research have been conducted on a joint effect of noise and

carbon disulfide (CS2), the organic solvent also known from ototoxic properties.

The summary of knowledge on the CS2 impact on auditory system (the risk for hearing

loss from noise is well recognized) and review of information on its interaction with noise are

therefore the main objective and contents of this paper.

CS2 APPLICATIONS AND TOXICITY SUMMARY

Carbon disulfide (CS2) – at present listed as an extremely hazardous substance - in its

pure form is a colorless liquid with a smell similar to chloroform. The commonest form used

in industry is impure and yellowish in color with an unpleasant odor, made by combining

carbon and sulfur at very high temperatures.

Carbon disulfide evaporates at room temperature and is highly inflammable.

It has played an important role in industry since the 1800s and was first recognized as

an occupational hazard in 1843 when cold vulcanization (a strengthening process for rubber)

was introduced.

Several incidences of neurotoxicity were noted in a number of countries using the

process, and as a result carbon disulfide was eliminated from the process.

Carbon disulfide has many useful properties and was previously used in many

extraction processes. Prior to 1985, it was used as a grain fumigant. Now its most important

industrial use is in the manufacturing process for viscose rayon and cellophane and as a

solvent for fats, lipids, resins, rubbers.

Worldwide annual production is estimated to be approximately 1 million tones.

Carbon disulfide is extensively absorbed by inhalation, but also via the skin. It is

metabolized to several metabolites including 2-thiothiazolidine-4-carboxylic acid which can

be measured in urine and which forms the basis for biomonitoring of exposure in the work

place.

Based on the results of studies of workers exposed to carbon disulfide, the nervous

system appears to be the critical target for carbon disulfide induced toxicity, manifested most

often by reduced conduction velocity in the peripheral nerves and impaired performance in

psychomotor testing.

Other effects for which there is considerable weight of evidence in humans exposed to

carbon disulfide include alterations in serum lipids and blood pressure that are associated with

increased risk of cardiovascular diseases, systemic eye pathologies such as color vision and

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damage to the blood vessels of the retina, and with higher exposures increased mortality from

heart disease.

No evidence of carcinogenicity has been observed in limited epidemiological studies.

There are several reports of decreased libido and or impotence among males

occupationally exposed to high concentrations of carbon disulfide, but there is no consistent

evidence based on limited study of other adverse reproductive effects in humans.

Acute and chronic forms of poisoning can result from exposure; at very high levels, it

can be life threatening because of the effects on the heart and nervous system. The effects of

exposure are nonspecific and require a diagnosis based on exposure history, signs or

symptoms and exclusion of other diseases.

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OVERVIEW OF LITERATURE DATA ON THE INFLUENCE OF CARBON

DISULFIDE ALONE VS IN CONCERT WITH NOISE ON THE AUDITORY AND

BALANCE SYSTEM

Table 1. Animal studies on the effects of carbon disulfide on the auditory system*

References Research findings

Rebert, Sorenson and Pryor

(1986)

Experiments on Fischer-344 rats exposed to carbon disulfide

(172, 286 and 400 mg/kg, 5 days/week, 11 weeks) administered

intraperitoneally resulted in prolonged ABR latencies in wave V

but not in wave I, indicating an effect on conduction within the

central auditory pathway. No histological data was reported.

Rebert and Becker (1986) ABR results from Long-Evans rats exposed to carbon disulfide

(400 or 800 ppm, 7 h/day, 7 days/week for 11 weeks) were

consistent with a retrocochlear pattern of hearing loss. Inter-peak

latencies (IPL) were prolonged and amplitudes reduced. An

additional peripheral loss of a conductive nature was suspected,

possibly due to effects on Eustachian tube function.

Clerici and Fechter (1991) No significant effect was noted on pure-tone thresholds in rats

exposed to carbon disulfide (500 ppm 6 h/day, 5 days/week for

12 weeks). At this exposure level, severe neuromuscular

compromise occurred, highlighting the fact that pure-tone

audiometry (PTA) is not sensitive to the early action of carbon

disulfide exposure.

Hirata et al. (1992) In female rats exposed to 800 ppm of CS2 for 15 weeks the ABR

showed the delay of III-V IPL and I-V PL, which began at the

end of the 3rd week and became stable at the end of the 9th week.

* The effects of carbon disulfide on the vestibular system or the effect of simultaneous

exposure to noise and carbon disulfide has not been well documented in animals.

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Table 2. Human studies on the effects of carbon disulfide on the hearing and balance


Batson (1938) Pure tone audiometric tests in 120 viscose rayon workers in

Pennsylvania, US pointed out 4000 Hz notch in 50% of them

Levey (1941) A study of neurological symptoms in 50 workers exposed to chronic

industrial carbon disulfide absorption revealed – among others in

part of them (?) - the 4000 Hz notch and spontaneous nystagmus.

Valerio (1959) Otoneurologic investigation of 86 viscose rayon industry workers

indicated a perceptive hearing loss of various degree in 12% as well

as vestibular dysfunction in 5%.

Cis and Perani (1964) In eighteen cases of chronic carbon disulfide poisoning

(encephalopathies or polyneuropathies) diagnosed in Clinica del

Lavoro the sensorineural hearing loss was found in 61%, and

vestibular damage as much as in 83%.

Molinari, Saia and

Mercer (1974)

Of 71 patients with chronic carbone disulfide poisoning, 45.1% had

sensorineural heating loss, 39.4% experienced vertigo confirmed by

asymmetry or hyporeflexicity of reactions in bicaloric test, as well as

by presence of spontaneous nystagmus in 4.2%.

Sulkowski (1979) Three groups of subjects were studied, using PTA, Bekesy

audiometry, SISI test and electronystagmography (ENG): 259

viscose fibre spinning room workers exposed to CS2 concentrations

changing with time i.e. to 140 mg/m3 in the 60 s and gradually

lowered later to 10-35 mg/m3, 101 past workers disabled due to

diagnosed chronic CS2 poisoning, and 60 controls non-exposed to

CS2 but employed in the same noise levels of 86 dB-A. The

sensorineural hearing loss was found respectively in the groups: 60%

(42% retrocochlear), 81% (63% retrocochlear) and 46% (33%

cochlear). It was accompanied by vestibular disorders, usually of

central origin respectively 60%, 89% and 13%.

Sulkowski (1990) In the ENG tests including 159 viscose fibre factory workers

exposed to CS2 concentrations >35 mg/m3 vs. 60 age-matched non-

exposed employees the signs of vestibular damage typical for the

central site of dysfunction were identified in 60% vs. 1.3%.

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Sulkowski et al. (1992) The posturographic testing in the group of 37 patients suffering from

chronic CS2 intoxication manifested by encephalopathy,

polyneuropathy or psychoorganic syndrome complaining for vertigo

revealed the postural stability disorder in 72.9%, which correlated

with ENG results confirming central vestibular lesion.

Hirata et al. (1992) In the ABR examinations of 74 present and past viscose spinning

workers exposed to CS2 ranged from 3.3 to 8.2 ppm (average 4.76

ppm) vs. 40 unexposed controls, significantly altered ABRs

(prolonged latencies of wave V and I-V and III-V IPL) were found,

greater in workers with longest and more excessive exposure

histories suggesting the damage of ascending auditory tract in the

brainstem.

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Table 3. Combined effects of noise and carbon disulfide on the auditory and vestibular

function


Morata (1989) In the study 258 Brazilian viscose rayon plant workers exposed

simultaneously to noise levels of 86-89 dB(A) and carbon disulfide

concentrations of 89-92 mg/m3 (30 ppm) the PTA results showed a

large proportion of those with hearing loss exposed for 6 years or

longer, namely 71%; percentage of hearing losses were higher than

would by predicted from noise exposure of these levels and than

expected for all age groups; there were relationships between hearing

loss and balance disturbance discovered in the simple balance tests

(Unterberger and Babinski-Weil).

Kowalska, Sulkowski

and Sinczuk-Walczak

(2000)

Three groups of subjects were examined: 40 viscose fibre spinning

mill workers with clinically observed chronic carbon disulfide

poisoning and 40 workers without symptoms of poisoning, both

groups of similar age (mean 52.3 ± 6.2 years) and duration of

employment (mean 20.3 ± 5.4 years) exposed to continuous noise

levels of 88-92 dB(A) and to CS2 levels of 10-35 mg/m3 (mean 25.8

mg/m3), and 40 controls exposed to similar levels of noise ranging

from 86 to 93 dB(A) but without contact with CS2. The PTA, SISI

test, impedance audiometry, ABR, posturography and

electronystagmography revealed retrocochlear hearing impairment

associated with signs of central vestibular disturbances in the

exposed groups, respectively 97.5% and 45% versus cochlear

hearing loss typical of noise-induced acoustic trauma without

concomitant balance disorders in the control group.

Chang et al. (2003) In the audiometric survey of 131 Taiwan viscose rayon plant

workers exposed to carbon disulfide (1.6-20.1 ppm) and noise (80-91

dB(A)), 105 men exposed to noise only (83-90 dB(A)) and 110 men

exposed to lower noise levels (75-82 dB(A)) hearing loss > 25 dB

HL was found respectively in 67.9%, 32.4% and 23%; the noise-only

group had a stronger effect at 4000 Hz.

Sulkowski (2005) The study covered 70 viscose rayon production plant workers:

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43 spinners exposed only to CS2 vapors of 30-35 mg/m3 vs. 27

locksmiths exposed simultaneously to CS2 and noise levels of 88-90

dB(A), the both groups employed over 30 years, and the age-

matched controls consisted of 30 unexposed white collars and 20

ironworkers exposed to noise. The battery of tests used (PTA,

impedance audiometry, ABR, DPOAE, VNG) proved the

sensorineural hearing loss of different degrees in 75% of viscose

rayon plant employees and statistically significant increase in

hearing thresholds was observed in those exposed to CS2 and noise

vs. evidently lower increase in subjects exposed only to noise or only

to CS2. The auditory disorders were accompanied by vestibular

dysfunction revealed in VNG examination as canal paresis (32%) or

directional preponderance and other signs of central balance lesion

(48%); there were not vestibular changes in the controls.

To illustrate the above data the results of audiological/otoneurological examinations in

one case of CS2 chronic intoxication, diagnosed in our Clinic of Occupational Diseases is

shown in Fig 1; the workmen developed, among other complaints, vertigo, balance disorders

and hypoacusis.

CONCLUSIONS

The studies reviewed confirm the direct ototoxic actions of CS2 proved in the animal

experiments and neurotoxic/ototoxic in clinical investigations carried out in the viscose rayon

manufacture workers; in the latter - besides the sensorineural hearing losses mostly

retrocochlear – also the damage of vestibular part of the inner ear or predominantly of central

part of the balance system were observed. The changes were demonstrated by pathological

nystagmus and/or another abnormal vestibulo-oculomotor reflexes and problems with

postural sway.

The high prevalence of such symptoms have appeared especially in the cases of

chronic CS2 poisoning under the form of encephalopathy and/or polyneuropathy.

As concerns the combined CS2 and noise exposure there is a lack of animal evidence

however the cited human studies seen to indicate a synergistic effect.

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The retrocochlear pattern of hearing damage located in the cochlear nerve and

brainstem cochlear nuclei (see Fig. 2) mirrors that due to CS2 exposure rather than noise but is

more enhanced than would by expected from exposure to noise and CS2 alone. In some cases

however a cochlear structure involvement was noted. The variabilities seen in subjects

exposed simultaneously to the both agents are probably due to individual susceptibility to its

harmful impact as well as probably due to the prevailing dose of particular agent.

There are also some evidence emerging to suggest that hearing loss and balance

disturbances can occur at levels below existing permitted levels of exposure (see Tab. 4).

If confirmed in further studies, these results could have far-reaching implications for

industrial hygiene in terms of possible changes in the work environment to reduce levels of

single/combined exposures or to limit its duration.

Therefore, if the noise regulations have to be made more effective, it is necessary to

develop a better understanding of its interaction with ototoxic substances such as carbon

disulfide, which may exacerbate a size of noise-induce hearing impairment.

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Table 4. Maximum allowable concentrations of CS2 in different countries vs. exposure

limit values and exposure action values for noise

CS2 Noise*

mg/m3 ppm Lower Exposure

Action Value

Upper Exposure

Action Value

Exposure Limit

Value

Austria (2006) 30 10

Belgium (2002) 31 10

Denmark (2002) 15 5

Finland (2005) 16 5

LEX,8h 80 dB(A)

PPeak 135 dB(C)

(112 Pa)

LEX,8h 85 dB(A)

PPeak 137 dB(C)

(140 Pa)

LEX,8h 87 dB(A)

PPeak 140 dB(C)

(200 Pa)

France (2006) 30 10

Germany (2009) 16 5

Italy (1979) 30 -

Ireland (2002) 30 10

Japan 31 10

New Zeeland 31 10

Poland (2002) 18 -

Sweden (2005) 16 5

Switzerland 16 5

USA:

ACGIH (2008)

OSHA

NIOSH

3.13

60

3

1

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UK (2005) 32 10

EU proposal 15 5

* Control of Noise at Work Regulations 2005 (Directive 2003/10/EC 6th Feb. 2003)

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REFERENCES

1.Batson OV: Otological aspects of CS2 intoxication. In: Bashore RM, Staley AL, eds. Survey

of carbon disulphide and hydrogen sulphide hazards in viscose rayon industry.

Commonwealth of Pennsylvania, Harrisburg, PA 1938

2.Chang S-J, Shih T-S, Chou T-C, Chen C-J, Chang H-Y, Sung F-C: Hearing loss in workers

exposed to carbon disulfide and noise. Environ Health Perspect 2003, 111: 1620-24

3.Cis C, Perani G: L’apparato cocleo-vestibolare nell’avvelenamento cronico da solfuro di

carbonico. Med Lavoro 1964, 55: 198-211 (in Italian)

4.Clerici WJ, Fechter LD: Effects of chronic carbon disulfide inhalation on sensory and motor

function in the rat. Neurotoxicol Teratol 1991, 13: 249-55

5.Fechter LD: Mechanisms of ototoxicity by chemical contaminants: Prospects for

intervention. Noise Health 1999, 2: 10-24

6.Hirata M, Ogawa Y, Okayama A, Goto S: A cross-sectional study on the brainstem auditory

evoked potential among workers exposed to carbon disulfide. Int Arch Occup Environ

Health 1992, 64: 321-24

7.IPCS, International Programme on Chemical Safety: Document No 46 – Carbon Disulfide.

World Health Organization, Geneva, 2002

8.Kowalska S, Sulkowski WJ, Sinczuk-Walczak H: Assessment of the hearing system in

workers chronically exposed to carbon disulfide and noise. Med Pracy 2000, 51: 123-38

(in Polish)

9.Levey FH: Neurological, medical and biochemical signs and symptoms indicating chronic

industrial carbon disulphide absorption. Ann Int Med 1941, 15: 869-74

10.Molinari GA, Saia B, Mercer G: Rilievi otovestibolari in operai intossicati da tossici

industriali. Nuovo Arch Ital Otol 1974, 2: 315-28 (in Italian)

11.Morata TC: Study of the effects of simultaneous exposure to noise and carbon disulfide on

workers’ hearing. Scand Audiol 1989, 18: 53-58

12.Prasher D, Hodgkinson L: Effects of industrial solvents on hearing and balance. A review.

Noise Health 2006, 8: 114-33

13.Prasher D, Morata T-C, Campo P, Fechter L, Johnson A-C, Lund SP, Pawlas K, Starck J,

Sulkowski WJ, Sliwinska-Kowalska M: An European Commission research project on the

effects of exposure to noise and industrial chemicals on hearing and balance. Int J Occup

Med Environ Heath 2002, 15: 5-11

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14.Rebert CS, Becker E: Effects of inhaled carbon disulfide on sensory-evoked potentials of

Long-Evans rats. Neurobehav Toxicol Teratol 1986, 8: 533-41

15.Rebert CS, Sorenson SS, Pryor GT: Effects of intraperitoneal carbon disulfide on sensory-

evoked potentials of Fischer-344 rats. Neurobehav Toxicol Teratol 1986, 8: 543-49

16.Sulkowski WJ: Clinical usefulness of audiometry and electronystagmography in the

diagnosis of chronic carbon disulphide poisoning. Med Pracy 1979, 30: 135-45 (in Polish)

17.Sulkowski WJ: Exposition professionnelle au sulfure de carbone (CS2) et

dysfonctionnements du système vestibulaire – Une ètude clinique. Cahiers Note Document

1990, 139: 472-75 (in French)

18.Sulkowski WJ: The effects of simultaneous occupational exposure to carbon disulfide and

noise on the auditory and vestibular function. The 7th EFAS Congress, 19-22.06.2005,

Gıteborg. Abstract Book, p. 63

19.Sulkowski WJ, Kowalska S, Matyja W, Guzek W, Wesolowski W, Szymczak W,

Kostrzewski P: Effects of occupational exposure to a mixture of solvents on the inner ear:

A field study. Int J Occup Med Environ Health 2002, 15: 247-56

20.Sulkowski WJ, Kowalska S, Sobczak Z, Jozwiak Z: The statokinesiometry in evaluation of

the balance system in persons with chronic carbon disulphide intoxication. Pol J Occup

Med Environ Health 1992, 5: 265-76

21.Śliwińska-Kowalska M, Zamyslowska-Szmytke E: Organic solvent exposures and

occupational hearing loss. In: Noise and Its Effects, eds. Luxon L, Prasher D, John Wiley

and Sons Ltd., Chichester 2007 pp. 477-97

22.Valerio M: Indagini otoneurologiche su operai esposti ad inalazione tossica del solfuro di

carbonio. Riv Audiol Prat 1959, 9: 127-31 (in Italian)

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Figure 1. The results of the auditory and vestibular tests battery in the case of the CS2

chronic intoxication-induced encephalopathy.

(Patient J.P., 55 years old, locksmith in the viscose rayon production plant for 24 years; CS2

concentrations ab. 30-40 mg/m3, continuous noise levels of ab. 90 dB(A))

PTA: binaural sensorineural hearing loss;

ART: high thresholds 85-100 dB;

ABR (exemplified by the right ear records): prolonged peak and interpeak latencies;

VNG: irregular saccades,

disturbed eye-tracking,

square waves in the gaze nystagmus test,

weakened optokinetic nystagmus

right-sided canal paresis in the bicaloric test

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Figure 2. Schematic drawing of the retrocochlear auditory pathway (reproduced with

permission from Swartz et al., Am J NeuroRadiol, 1996, 17:1479-81)

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THE COMBINATIONS OF EXPOSURE TO NOISE, VIBRATION AND

ERGONOMIC STRESSORS IN THE SWEDISH WORK FORCE

AFFECT HEALTH OUTCOMES

Mats Hagberg, Andreas Jonsson

Occupational and Environmental Medicine, University of Gothenburg

Abstract

This was a cross-sectional study based on surveys conducted in 1997, 1999, 2005, 2007 and

2009 by Statistics Sweden (SCB) representing the Swedish work force. Data concerning

working environment was collected by phone interview and questionnaire. The response rate

for the phone interview was 88% (12546 employed persons) and for questionnaire there was

a 69% response rate (9798 employed persons). These responders were the study population in

the analytical study of risk factors for musculoskeletal and hearing disorders. Noise exposure

had an effect on musculoskeletal symptoms in the Swedish work force even when controlling

for ergonomic stressors. Ergonomic stressors were related to hearing problems in the Swedish

work force even when controlling for noise exposure. No inference on the relation between

chemical exposure and hearing problems was possible in the Swedish work force in this

study.



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INTRODUCTION

Exposure to vibration both hand-arm vibration (HAV) and whole-body vibration (WBV) is

mechanical energy oscillations which are transferred to the human body. These mechanical

oscillations also cause noise. Thus workers exposed to vibrations are also exposed to noise.

Furthermore workers exposed to WBV and HAV are often simultaneously exposed to other

ergonomic stressors such as awkward postures and manual material handling (lifting) [1].

In a study of the Swedish work-force from a survey conducted in 1999, 2001 and 2003 by

Statistics Sweden we found that when the exposure factors lifting and frequent bending were

added to a multivariate analysis, there was surprisingly a low magnitude of association

between low back symptoms and whole body vibration exposure [2]. Interestingly the

relation between whole body vibration exposure and symptoms in the neck, shoulder/arm and

hand had the same or higher magnitude of association even when the possible confounders

were in the model. For the neck, low back and shoulder/arm there was a visible increase in

prevalence ratio (as high as 5 times) when combined exposures of whole body vibration,

lifting, frequent bending, twisted posture and noise were included in the analysis [2].

There are few studies of combination of exposure to noise and vibration on possible health

effects such as musculoskeletal disorders and hearing problems. It has been proposed that

sympathetic vasoconstriction causes hearing impairment as an explanation to the finding of

an association between hearing problems and Raynauds disease [3]. If so there would also be

a possibility of an association between ergonomic stressor and hearing problems since it has

been hypothesized that chronic muscle pain conditions are associated an increased

sympathetic activity.

AIM

To study the combinations of exposure to noise, vibration and ergonomic stressors in the

Swedish work force and the effect on self reported health outcomes such as musculoskeletal

symptoms and hearing problems

METHODS

The occurrence of exposure to noise in working environment was considered for surveys

conducted in 1997, 1999, 2005, 2007 and 2009 by Statistics Sweden (SCB), by order of the

National Board of Occupational Safety and Health. Exposure to noise is defined as “Exposed

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at least 1/4 of the time to noise so that you cannot speak in a normal tone” in these surveys.

The description of occurrence for exposure to noise is stratified according to occupation

(Table 1). All together the sample for these surveys is over 44000 employed persons.

This cross-sectional working environmental study is based on material from a survey

conducted in 1999 by Statistics Sweden (SCB), by order of the National Board of

Occupational Safety and Health. Data concerning working environment was collected by

phone interview and questionnaire. The response rate for the phone interview was 88%

(12546 employed persons) and for questionnaire there was a 69% response rate (9798

employed persons). These responders were the study population in the analytical study of risk

factors for musculoskeletal and hearing disorders. For individual questions the level of non-

response was between 1% and 3%

Vibration and noise exposure

The definition of exposure to whole body vibration (WBV), hand transmitted vibration

(HTV) and noise was based on three different questions, “Are you at work exposed to

vibrations that make your whole body vibrate (e.g. tractor, truck or other working

machines)?”, “Are you at work exposed to vibration from hand held machines (e.g.

compressed air machines, jigsaw or similar)?” and “Are you at work exposed to noise that is

so high that you cannot talk in a normal tone?”. All questions had the same six response

alternatives, “Almost all the time”, “About 3/4 of the time”, “At least half the time”, “About

1/4 of the time”, “Slightly (maybe 1/10 of the time)” and “Not at all”. Exposure cutoff was

set to “At least half the time”.

Symptoms and other risk factors

The regions for musculoskeletal symptoms considered were low back, neck, shoulder/arm

and hand. There were different categories of duration of symptoms. The definition of

musculoskeletal symptoms used was, having pain in the specific region ‘‘More than one day

per week’’. Hearing symptoms was defined by “During the last 12 months have you had

problems with your hearing due to work?”. Manual material handling was addressed by two

questions ‘‘Do you have to lift loads heavier than 25 kg multiple times per day, more than 1

day per week?’’ and ‘‘Do you have to lift loads between 15 and 25 kg multiple times per day,

more than one day per week?’’. Awkward postures were defined as frequent bending and

rotation of the trunk and working with the trunk in a rotated position. Frequent bending was

defined by the question ‘‘Does it occur in your work that you bend or twist your body in the

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same way many times per hour during several hours the same day, at least 1 day per week?’’

Twisted posture was defined as ‘‘Do you sometimes work with your body in a twisted

posture, at least half the time?’’. Chemical fumes was defined as “Do you smell gases,

vapors, solvents, pesticides at your workplace, exposure cutoff was set to “at least half the

time”. Gender and age (years) was also considered as risk factors.

Risk combinations

Combination of risk factors was also examined and the effect on prevalence ratios between

exposed and not exposed persons. Six different risk combinations was defined from previous

used risk factors, i.e. WBV, HTV, noise, manual material handling, frequent bending, twisted

posture and noise. Contrast used for risk combination factors between exposed and not

exposed persons was exposed to all risk factors included compared to not being exposed to

any risk factor included.

Statistics

Descriptive statistics for symptoms, vibration exposure, noise exposure, other risk factors and

age stratified for gender. The effect measure used for all analysis was prevalence ratios (PR)

with 95% confidence intervals (CI). A proportional hazard model with time set to one was

used to assess PR. All analysis was adjusted for gender and age. The relation between

symptoms and noise exposure was examined. A multivariate model assessing the relation

between risk factors, exposure and symptoms was analyzed. Risk factors included in the

multivariate model was significant in a univariate model assessing the relation between

factors and symptoms. Relationship between variables was considered with Spearman’s rank

correlation to avoid multicollinearity and variables with a correlation > 0.7 was not included

in the same model. Risk combination factors were analyzed one at a time adjusted for gender

and age. Statistical significance was set to p ≤ 0.05 or equivalent, the 95% CI for PR not

including one. All analysis was performed with SAS 9.1. The multivariate analysis models

used PROC PHREG.

RESULTS

Exposure to noise in the Swedish work-force has not decreased the last ten years. Craft, trade

workers, miners and construction workers are heavily exposed to noise (61 percent) Table 1.

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23

In the sample of 12546 persons representing the Swedish work force 19 percent of the men

and 10 percent of the women were exposed to noise at least half of the time (Table 2).

Exposure to ergonomic stressors such as lifting and bending was frequent among both men

and women whereas vibration exposure both HAV and WBV was frequent among men

(around 6 percent) but less than one percent among women (Table 2).

Table 1. Employed individuals (percent) exposed to noise (at least 1/4 of the working

time so high that you cannot talk in a normal tone) in the Swedish work force (16-64

years) by occupation.

Occupation 1999 2009

1. Managers, legislators, senior officials 6 ..

2. Professionals, e.g. teachers, computer technicians 11 10

3. Technicians and associated professionals 12 12

4. Clerks, warehouse workers 9 9

5. Service and shop sales workers 17 17

6. Skilled agricultural, forestry and fishery workers1 48

7. Craft, trade workers, miners, construction workers 53 61

8. Plant and machine operators 50 49

9. Elementary occupations, e.g. cleaners, janitors 32 .. 1 No numbers present for occupational category 2009

28

24

Table 2. Descriptive statistic of age, symptoms and exposure stratified for gender, data

are given as numbers and percent (%) n=12546.

Variable Men Women

Age

16-24 510 (8%) 416 (7%)

25-34 1495 (25%) 1270 (22%)

35-44 1501 (25%) 1520 (26%)

45-54 1571 (26%) 1691 (29%)

≥55 950 (16%) 951 (17%)

Neck 640 (15%) 1417 (30%)

Low back 546 (13%) 867 (19%)

Shoulder/arm 635 (15%) 1265 (28%)

Hand 299 (7%) 631 (14%)

Hearing problems 128 (2%) 121 (2%)

Lifting (15-25 kg) 1277 (29%) 942 (20%)

Lifting (>25 kg) 773 (18%) 462 (10%)

Frequent bending 1528 (35%) 1878 (39%)

Twisted posture 635 (15%) 757 (16%)

Whole body vibration (WBV) 271 (6%) 35 (1%)

Hand-arm vibration (HAV) 295 (7%) 47 (1%)

Noise 834 (19%) 483 (10%)

WBV and Noise 189 (4%) 23 (0.5%)

WBV and no Noise 81 (2%) 12 (0.3%)

WBV and HAV 91 (2%) 9 (0.2%)

WBV and no HAV 175 (4%) 25 (0.5%)

HAV and Noise 211 (5%) 20 (0.4%)

HAV and no Noise 82 (2%) 27 (0.6%)

Chemical fumes 356 (8%) 188 (4%)

Chemical fumes and Noise 185 (4%) 60 (1%)

Chemical fumes and no Noise 169 (4%) 127 (3%)

Reporting exposure to noise at least half of the working time was a risk factor for hearing

problems with a prevalence ratio of 5 (Table 3). Musculoskeletal symptoms in the low back,

neck, shoulder/arm and hand was also related to noise exposure (Table 3).

29

25

Table 3. The relation between musculoskeletal symptoms, hearing symptoms and

exposure to noise at least half of the working time. Prevalence ratios (PR) with 95%

confidence interval (CI) are adjusted for age and gender.

Exposed (Noise) Not exposed PR (95% CI)

Cases Non-cases Cases Non-cases

Low back 327 904 1066 6484 2.1 (1.8, 2.4)

Neck 422 835 1612 6008 1.9 (1.7, 2.1)

Shoulder/arm 402 838 1476 6081 1.9 (1.7, 2.2)

Hand 246 971 669 6769 2.7 (2.3, 3.1)

Hearing problems 79 1099 107 6995 5.0 (3.7, 6.7)

Interestingly when performing the multivariate analyses including possible confounders noise

still had an effect on musculoskeletal symptoms (Table 4). Furthermore ergonomic variables

such as WBV, lifting and frequent bending were related to hearing problems (Table 4).

When combining different risk factors additional factors to noise increased the prevalence

ratios of hearing problems (Table 5) Ergonomic risk factors added to the model for

musculoskeletal symptom a substantial increase of prevalence ratios were seen (Table 5).

Table 4. Multivariate analysis of musculoskeletal symptoms and hearing symptoms in

relation to ergonomic stressors and individual factors. Data are given as prevalence

ratios (PR) with 95% confidence interval (CI).

Variables Low back Neck Shoulder/arm Hand Hearing

PR 95% CI PR 95% CI PR 95% CI PR 95% CI PR 95% CI

Gender (women/men) 1.5 1.4 1.8 2.1 1.9 2.3 2.0 1.8 2.2 2. 3 2.0 2.654

1.3 0.97 1.8

Age 1.02 1.01 1.02 1.02 1.01 1.02 1.03 1.03 1.04 1.03 1.03 1.04 1.06 1.04 1.07

Whole body vibration 1.2 0.91 1.5 1.2 0.99 1.6 1.4 1.1 1.7 1.4 1.0 1.8 1.2 0.69 2.2

Lifting (15-25 kg) 1.4 1.2 1.6 1.1 1.0 1.3 1.4 1.21 1.5 1.4 1.2 1.6 1.4 1.0 2.0

Frequent bending 2.0 1.8 2.3 1.9 1.7 2.1 2.14 1.91 2.4 2.3 2.0 2.7 1.7 1.2 2.4

Twisted posture 1.5 1.3 1.7 1.4 1.3 1.6 1.4 1.21 1.5 1.3 1.1 1.6 1.1 0.73 1.5

Noise 1.4 1.2 1.6 1.3 1.2 1.5 1.2 1.1 1.4 1.6 1.3 1.9 3.9 2.8 5.5

Hand-arm vibration 0.95 0.73 1.2 1.1 0.91 1.4 1.2 0.99 1.5 1.5 1.1 1.9 0.76 0.40 1.4

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26

Table 5. Multivariate analysis of musculoskeletal symptoms, hearing problemss in

relation to risk combinations of ergonomic stressors adjusted for gender and age. Data

are given as prevalence ratios (PR) with 95% confidence intervals (CI) or as percent.

Combination of stressors

Exposed1

Not exposed1 Low back Neck Shoulder/arm Hand

Hearing problems

% % PR 95% CI PR 95% CI PR 95% CI PR 95% CI PR 95% CI

Noise+WBV 1.7 62 3.0 2.3 3.9 2.8 2.2 3.5 3.2 2.5 4.0 5.2 3.9 6.9 5.5 3.0 9.8

Noise+WBV+HAV 0.7 61 3.2 2.2 4.8 3.3 2.3 4.65 3.8 2.7 5.2 7.0 4.8 10.2 4.7 1.9 11.78

Noise+WBV+HAV+ Frequent bending 0.5 41 5.7 3.6 8.8 4.8 3.2 7.15 6.7 4.6 9.7 12.3 7.9 19.3 6.2 2.2 17.8Noise+WBV+HAV+ Frequent bending+Lifting (15-25 kg) 0.5 36 6.1 3.8 9.6 5.2 3.5 7.9 7.9 5.4 11.713.7 8.5 22.0 6.6 2.0 22.0Noise+WBV+HAV+ Frequent bending+Lifting (15-25 kg)+Twisted posture 0.3 35 6.7 4.1 11.0 5.6 3.6 8.7 8.5 5.6 12.914.2 8.6 23.6 7.6 2.3 25.41 Based on the phone interview study population (n=12546)

Exposure to chemical fumes and hearing problems

The association between exposure to chemical fumes and hearing problems had a prevalence

ratio of 2.2 (95% confidence interval 1.4-3.5) adjusted for age and gender. This association

disappeared when controlling for noise exposure (Table 6). However there was still an

association between hearing problems and the ergonomic stressors lifting, frequent bending,

twisted posture and hand arm vibration (Table 6).

Table 6. Multivariate analysis of hearing problems in relation to ergonomic stressors

and individual factors. Data are given as prevalence ratios (PR) with 95% confidence

interval.

Variables Modell 1 Modell 2 PR 95% CI PR 95% CI

Gender (women/men) 1.3 0.99 1.8 1.6 1.4 1.8 Age 1.06 1.04 1.07 1.02 1.01 1.02 Whole body vibration 1.2 0.92 1.5 Lifting (15-25 kg) 1.4 1.2 1.6 Frequent bending 2.0 1.8 2.3 Twisted posture 1.5 1.3 1.7 Noise 5.1 3.7 6.9 1.4 1.2 1.6 Hand-arm vibration 0.95 0.73 1.2 Chemical fumes 1.2 0.72 1.9 1.000 0.82 1.2

31

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DISCUSSION

Noise exposure at least half of the time at levels approximately at 80-85 dB(A) is common in

the Swedish work force. The question used for self report of noise exposure has been

validated as reflecting noise level of 85 dB(A). The relation between self report of noise

exposure and hearing problems is natural. Noise exposure had also a relation to

musculoskeletal symptoms possibly explained by ergonomic stressor being prevalent in noisy

environments. However when we controlled for ergonomic stressor noise still had an effect

on musculoskeletal disorders. This may be explained by that the magnitude of the ergonomic

stressors are particular high in noisy environment and/or that noise itself adds to the burden of

musculoskeletal symptoms.

Ergonomic stressors were also related to hearing problems even when controlling for noise

exposure. A possible explanation for this could be that when ergonomic stressors are present

the noise exposure to character and magnitude may be more hazardous than if not. An

example would be high transients when objects fall to the floor. Another possibility would be

the hypothesed relation between increased sympathetic activity in musculoskeletal disorders

that would influence hearing. Whether musculoskeletal pain causes or are caused by

increased sympathetic activity is still obscure [4].

There was an association between the exposure to chemical fumes and hearing problems but

this relation disappeared when controlling for noise exposure. Since the self report on

exposure to chemical fumes is diffuse no inference can be made on toxic otoneuropathy This

study was supported by the Swedish Council for Working Life and Social Research in the

present study.

CONCLUSION

Noise exposure had an effect on musculoskeletal symptoms in the Swedish work force even

when controlling for ergonomic stressors.

Ergonomic stressors were related to hearing problems in the Swedish work force even when

controlling for noise exposure.

No inference on the relation between chemical exposure and hearing problems was possible

in the Swedish work force in this study.

32

28

ACKNOWLEDGEMENT

This study was supported by the Swedish Council for Working Life and Social Research

REFERENCES

1. Palmer, K.T., M.J. Griffin, H.E. Syddall, B. Pannett, C. Cooper, D. Coggon, The relative

importance of whole body vibration and occupational lifting as risk factors for low-back

pain. Occup Environ Med, 2003. 60(10): p. 715-21.

2. Hagberg, M., L. Burstrom, A. Ekman, R. Vilhelmsson, The association between whole

body vibration exposure and musculoskeletal disorders in the Swedish work force is

confounded by lifting and posture. Journal of Sound and Vibration, 2006. 298(3): p. 492-

498.

3. Palmer, K.T., M.J. Griffin, H.E. Syddall, B. Pannett, C. Cooper, D. Coggon, Raynaud's

phenomenon, vibration induced white finger, and difficulties in hearing. Occup Environ

Med, 2002. 59(9): p. 640-2.

4. Sjors, A., B. Larsson, J. Dahlman, T. Falkmer, B. Gerdle, Physiological responses to low-

force work and psychosocial stress in women with chronic trapezius myalgia. BMC

Musculoskelet Disord, 2009. 10: p. 63.

33 29

SYNERGISTIC EFFECTS OF NOISE AND SOLVENTS - WHAT WE

KNOW AND FUTURE RESEARCH NEEDS

Esko Toppila

Finnish Institute of Occupational Health - Helsinki - Finland

Abstract

The noise directive requires that in the risk assessment the combined effect of noise and

ototoxic chemicals must be taken into account. All chemicals that are neurotoxic are

potentially ototoxic. As a consequence there are over 700 groups of potentially ototoxic

chemicals.

Ototoxicity is often related to vestibulotoxicity as both organs are located in the inner ear.

Ototoxicity is an underestimated risk.

NIOSH evaluates that in USA 22 million people are exposed to harmful noise levels and

nine million people are exposed the levels that can be hazardous to hearing.

Solvents are perhaps the most studied group of ototoxic chemicals. Experiments with rats

have shown that combined exposure to noise and solvents such as toluene, styrene, ethyl

benzene and trichloroethylene have induced synergistic adverse effects on hearing.

A number of epidemiological studies have demonstrated the relationship between hearing

impairments and co-exposure to both noise and industrial solvents. Due to confounding

factors, straightforward conclusions can not be easily drawn. New analysis suggests that the

synergistic effect is negligible if the noise exposure is less than 80-85 dB(A).

Still there are many open questions concerning the synergistic effects of noise and solvents:



34

30

- The combined effect is evaluated using audiometry. However this may not be a good

measure for the effects since the solvent may damage the auditory nerve and auditory

brainstem too.

- The combined effect vestibulotoxicity and noise needs to be studied. It may affect to

increased accident risk.

- The noise directive requires that workers belonging to particularly sensitive risk groups

are identified. This techniques need to be developed.

- Mechanism studies are needed to improve the risk assessment.

- The risk can be identified for humans but the quantification of the problem cannot be

solved with cross-sectional studies.

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31

INTRODUCTION

The new noise directive (2003/10/EC) was introduced in 2003 to reduce the health effects

of noise especially the induced hearing loss (NIHL). One of the new requirements for the

risk assessment is to evaluate the combined effect noise and work-related ototoxic substances.

The risks of ototoxicity are also recognized in US. NIOSH evaluates that in USA 22 million

people are exposed to harmful noise levels and nine million people are exposed the levels of

chemicals that can be hazardous to hearing. This indicates that ototoxicity is an

underestimated risk.

This requirement has produced at least two comprehensive handbooks (Campo et al,

2009; Johnson et Morata, 2010) of the current knowledge of ototoxic effects of chemicals.

An addition at least a Canadien web-site on the topic exist (Vyskocil). A critical review of

the ototoxicity is given be Lawton et al (2006).

The purpose of this paper is to provide a short presentation of the current knowledge of the

ototoxic chemicals especially to solvents. Also some practical recommendations are given.

OTOTOXICITY

All substances that may affect the structures and/or the function of the inner ear (auditory

plus vestibular apparatus) and the connected neural pathways can be considered ototoxic. In

other words, both cochleotoxicants and vestibulotoxicants are ototoxicants (Campo et al

2009).

Typically the ototoxicants agents causes degeneration of hair cells but also the auditory

pathways and/or auditory cortex may be affected. The damage in the cochlea is supposed to

be caused by the formation of reactive oxygen metabolites (ROM). In the other hand the

acoustical overstimulation by noise damages the hear cell by several mechanisms (Pyykkö

et al, 2007). Some of the mechanisms are mainly metabolic and some are mainly mechanical.

In metabolic mechanisms the ROMs and other highly reactive endogenous substances play a

significant role in the noise induced hearing loss (NIHL). The metabolic mechanisms is

dominant at lower sound pressure levels where as the mechanical mechanism is dominant at

high noise levels. The actual hear cell death occurs via apoptosis or via necrosis. Necrosis is

related to the mechanical injuries of the cochlea. Ototoxicity and noise may have a

synergistic effect. However these interactions are not yet well understood.

3632

Potentially all neurotoxic substances are ototoxic. Thus there are over 700 different groups

of potentially ototoxic chemicals. Ototoxicity of these chemicals is not tested

comprehensively. Solvents are best known ototoxic chemicals.

Above are listed the ototoxicants with strong evidence of ototoxicity (Campo et al, 2009).

Drugs

Antibiotics, amino glycosides, certain other antibiotics, certain antineoplastics and certain

diuretics.

Life style factors

Smoking seems to be a risk factor for hearing impairment (Toppila et al., 2000, 2001;

Dudarewicz et al, 2010). However the risk caused by smoking may be aggravated by the

presence of other factors (use of painkillers, elevated blood pressured, high cholesterol levels)

related to life style ( Starck et al, 1999).

Industrial chemicals

Several industrial chemicals have strong evidence of ototoxicity.

Solvents

Toluene, ethylbenzene, n-propylbenzene, styrene and methylstyrenes, trichloroethylene, p-

Xylene, n-Hexane,carbon disulfide.

Asphyxiants

Carbon monoxide, hydrogen cyanide and its salts (cyanides).

Metals

Lead and lead compounds, mercury (methyl mercury chloride, mercuric sulfide), Tin,

germanium (germanium dioxide).

Nitriles

Acrylonitrile, 3,3-Iminodipropionitrile, 3-Butenenitrile and 3-Butenenitrile. In addition

there are several chemical with fair evidence of ototoxicity (cadmium, arsenic, bromates,

halogenated hydrocarbons). Suspected ototoxicants include insecticides, alcydic compounds

and manganese.

37 33

COMBINED EFFECTS WITH NOISE

Pharmaceuticals

Some studies indicate that the administration of ototoxic drugs such as aminoglycosides

produces increased susceptibility to noise-induced damage. Salicylate-induced temporary

threshold shifts may exacerbate temporary noise effects due to the reduced comprehension of

speech and difficulty to detect acoustic alarms in noisy environments So far, it is not known

whether salicylates in combination with environmental noise would promote permanent

noise-induced hearing loss.

Solvents

Experiments with rats have shown that combined exposure to noise and solvents such as

toluene, styrene, ethylbenzene, trichloroethylene.

A number of epidemiological studies have investigated the relationship between hearing

impairments and co-exposure to both noise and industrial solvents (Johnson et al., 2006 ;

Morata et al., 2010). Due to confounding factors, straightforward conclusions could not be

easily drawn. Given the difficulty in (1) extrapolating the animal findings and (2) analysing

the data obtained in humans, regulators have to pay attention to both experimental and

epidemiological studies. Overall, in combined exposure to noise and organic solvents,

interactive effects may be observed depending on the parameters of noise (intensity,

impulsiveness) and the solvent exposure concentrations.

Dudarewicz et al (2010) have shown that in order to have a combined effect with noise

and solvents, the noise levels should be above 83 dB(A). The effect increases with noise

levels. This threshold is so far the only available for the combined effect in human. For

solvents the limits seems to be around present threshold values.

Smoking

Smokers may have an increased risk of noise-induced hearing impairment (Dudarewicz et

al, 2010). The additional risks seem to start when daily exposure is 83-85 dB(A).

CURRENT SITUATION

At present the combined effect of solvents and noise is a generally recognized

phenomenon but debates of its importance is still going on. For the final answer dose-

38

34

response relation curves are needed. This has proven to be complicated. First the solvent

exposure cannot be determined accurately. The first threshold values above, which the

combined exposure may cause combined effect, have been recently determined. So far it

seems to be that for solvents the level is near the present threshold values. For noise the daily

exposure must be over 83 dB(A). This result is valid for solvents and smoking only

(Dudarewicz et al, 2010).

The solvents are neurotoxic, which means that they all have other effects to nervous

system; in fact for all of them the critical effect, which is the base for the threshold value, is

not ototoxicity (WHO, 2000). Theoretically it is possible that the combined effect of noise

and the ototoxicant can make the cochlea the critical organ. No strict answer can be given,

as for none of the ototoxicants, the combined noise-dose relationship is available.

Many solvents have an impact in addition the cochlea, to the auditory nerve and/or to the

auditory cortex. The golden standard for hearing test, is the audiogram. It is testing only the

cochlea function and thus the result may severely underestimate the impact of the combined

effect of noise and ototoxicants to hearing.

Altogether ototoxicity of solvents is a problem, which needs to be taken care at least

because of the precautionary principle.

3935

MAJOR USES OF SOLVENTS IF INDUSTRY

The major uses are shown in Table 1 (Campo et al, 2009).

Table 1: Major uses/sources of exposure to solvents

CHEMICAL

AGENT

MAJOR USES

Toluene Production of benzoic acid, benzaldehyde, explosives, dyes, and many

other organic compounds; solvent for paints, lacquers, gums, resins;

extracting agent; petrol and naphtha constituent; additive; fabric and

paper coating, artificial leather and detergent manufacture.

Toluene is often found together with other solvents.

Ethylbenzene Almost exclusively used for the production of styrene. Only a small

proportion is used as a solvent.

n-Propylbenzene Textile dying, solvent for cellulose acetate.

Styrene Manufacture of plastics, rubber articles, glass fibres; synthetic rubber;

insulators; used as a chemical intermediate, particularly in the resin and

plastics production, component in agricultural products and stabilising

agent.

Methylstyrene Manufacture of modified polyester and alkyd resins. Low-molecular

polymers are viscose liquids that are used as softener in polymers, paints

and waxes.

Trichloroethylene Solvent for a variety of organic materials. Trichloroethylene is a cleaning

and degreasing agent and a means of extraction.

p-Xylene Manufacture of resins, paints, varnishes, general solvent for adhesives; in

aviation kerosene; protective coatings; synthesis of organic chemicals;

solvent (e.g. for paints, coatings, adhesives and rubber); used in

production of quartz crystal oscillators, perfumes, insect repellents,

epoxy resins, pharmaceuticals, and in the leather industry. Used as a

solvent in phenoxyalkanoic herbicides.

n-Hexane Used as a cleaning agent in textile, furniture, and leather industries;

laboratory reagent; component of many products associated with the

petroleum and petrol industries; solvent, especially for vegetable oils;

40

36

low-temperature thermometers; calibration; polymerisation reaction

medium; paint diluent; alcohol denaturant. Used as reaction medium in

manufacture of polyolefins, elastomers, pharmaceuticals and as a

component of numerous formulated products.

n-Heptane Used as a solvent in laboratories and for quick-drying glossy paints and

glues.

Carbon disulfide Manufacture of rayon, soil disinfectants, electronic vacuum tubes and

carbon tetrachloride. Used as solvent for lipids, sulfur, rubber,

phosphorus, oils, resins and waxes.

PRACTICAL CONSIDERATIONS

In REACH there is no R-phrase for labelling ototoxic endpoints (Sliwinska-Kowalska, et

al 2007). As a consequence the possibility of ototoxicity may be neglected in practical work

in occupational health care and in occupational hygiene. To identify the risk, ototoxicity

must to checked from other sources.

When exposed to both noise and ototoxicant one practical question is how to protect the

workers against the synergist effects. The limited amount of data available suggests, that in

such situation, hearing protection should be mandatory if noise levels exceeds to lower action

limit value of 80 dB(A). By ensuring that the exposure to noise is below 80 dB(A), no

combined effect is to be expected and situation reduces to a simple single agent problem.

Vestibulotoxicity reduces the balance control and thus may increase the accident risk

(Toppila et al, 2006). The noise directive recognises the impact of noise to accident risk, but

there is regulations how to treat vestibulotoxicity.

FUTURE RESEARCH NEEDS

Unfortunately, the published data on the combined health effects of ototoxic substances

and noise are rather limited (Campo et al, 2009). There is a lack of data concerning the health

risks of combined exposures to ototoxic substances, noise and vibration. The techniques to

understand and/or perform the effects of combined exposures are not well developed.

Complex mathematical analysis is needed.

4137

The individual ototoxic substances rated “suspected” or “questionably ototoxic” today

obviously need a research on their ototoxicity. This work cannot be done in random, but

understanding the mechanism how these agents harm the hearing.

Typically these studies are cross-sectional. They can identify the problem but they fail to

quantify it. The reason is the healthy worker phenomenon. Susceptible workers are removed

from the workforce through early retirement, unemployment or just by changing the job and

are thus not properly recorded.

To overcome this, well-designed longitudinal studies are needed to evaluate the impact of

noise and work-related ototoxic substance exposure in humans. “Well-designed” means in

this context that the social impacts and other confounders as well as all aspects of hearing

impairment are included in the study. As an example, styrene may affect vision, balance and

hearing.

In most EU countries, hearing handicap testing is confined to hearing impairment instead

of measuring a loss of communication skills. This is also true for the majority of relevant

epidemiological studies. Although hearing impairment is simple to measure, this approach

causes problems that have a strong bearing on combined exposure to noise and ototoxic

chemicals because several organs may be affected. If only physiological changes are

measured, there is a lack of information on the psycho-social consequences for everyday life

and the impairment of communication skills may be highly underestimated.

Essential for a risk assessment is the identification of risk groups. Gene-research may

reveal genes causing susceptibility to noise or to solvents. In addition databases and

mathematical modelling is needed to find out all aspects of this complicated question.

Data obtained from animal models cannot be neglected and should serve as a basis for

precautionary measures. They make it possible to assess the specific effect of several

substances or factors studied in controlled and proper experimental conditions. Therefore,

they contribute significantly to the determination of effect thresholds for humans.

CONCLUSIONS

The synergistic effect of noise and solvents is an underestimated risk. It is hard to

recommend direct action because the dose-response relationships are not well established. To

do this research is needed on the effect on man and on the mechanisms. At present the

educated guess is that combined effects are not relevant for solvents, if the daily noise

exposure is below 83 dB.

4238

REFERENCES

Pierre Campo, Katy Maguin, Stefan Gabriel, Angela Möller, Eberhard Nies,María Dolores

Solé Gómez, Esko Toppila, COMBINED EXPOSURE TO NOISE AND OTOTOXIC

SUBSTANCES, EO OSHA reviews, 2009, 60 pp,

http://osha.europa.eu/en/publications/literature_reviews

Dudarewicz A, Toppila E, Pawlaczyk-Luszcynska MAWLACZYK–

ŁUSZCZYNSKA(1), Mariola Sliwisnska-Kowalska M, The Influence of Selected Risk

Factors on the Hearing Threshold Level of Noise Exposed Employees, Arch. Acoust., 35, 3,

131–142 (2010).

Johnson, A.C., Morata, T.C., Lindblad, A.C., Nylén, P.R., Svensson, E.B., Krieg, E.,

Aksentijevic, A., Prasher, D., ‘Audiological findings in workers exposed to styrene alone or

in concert with noise’, Noise Health 8, 2006, pp. 45-57.

Johnson AC, Morata T, Occupational exposure to chemicals and hearing impairment, The

Nordic Expert Group for Criteria Documentaton of Health Risks form Chemicals , Arbete

och Hälsa nr 2010;44(4), Gothenburg, Sweden.

Lawton, B.W., Hoffmann, J., Triebig, G., ‘The ototoxicity of styrene: a review of

occupational in-vestigations’, Int. Arch. Occup. Environ. Health 79, 2006, pp. 93-10.

Morata T, Sliwinska-Kowalska, M, Johnson AC, Starck J, Pawlas K, Zamyslowska-

Szmytke Z, Nylen P, Toppila E, Krieg E, Prasher D, A multicenter study on the audiometric

findings of styrene-exposed workers, submitted for publication, Ear and Hearing, 2010

Pyykkö I, Toppila E, Zou J, Jacobs H, Kentala E, Noise related hearing impairment, (91-

109), Genes, Hearing and Deafness, From Molecular Biology to Clinical Practice Editors

Alessandro Martini, Dafydd Stephens, Andrew Read, Informa Healthcare, 2007

Sliwinska-Kowalska M, Prasher D, Rodrigues CA, Zamysłowska-Szmytke E, Campo P,

Henderson D, Lund SP, Johnson AC, Schäper M, Odkvist L, Starck J, Toppila E, Schneider

E, Möller C, Fuente A, Gopal KV. Ototoxicity of organic solvents - from scientific evidence

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39

to health policy.International Journal of Occupational Medicine and Environmental Health

2007;20(2):215 – 222

Toppila E, Forsman P, Pyykko I, Starck J, Tossavainen T, Uitti J, Oksa P. Effect of

styrene on postural stability among reinforced plastic boat plant workers in Finland. J Occup

Environ Med. 2006 Feb;48(2):175-80.

Toppila E, Prasher D, NoiseChem: Ein projekt der Europäischen Kommission zu den

Auswirkungen von Lärm und Chemikalien auf Gehör und Gleichgewicht. Fachveranstaltung.

Ototoxizität - eine neue Herausforderung bei der Prävention von Gehörsschäden? 2006 Jul 4-

5; Berufsgenossenschaftliche Akademie Hennef (BGA), Deutschland.

Vyskocil A, Truchon G, Leroux T, Lemay F, Gendron M, Gagnon F, Botez S, El

Majidi N, Lim S, Émond C, Viau C, Effets ototoxiques de substances industrielles,

ttp://www.irsst.qc.ca/fr/utoto.htm

WHO, Air Quality Guidelines for Europe, WHO Regional Publications, European Series,

No. 91, 2000

4540

IMPULSE NOISE AND IMPULSIVE NOISE IN THE FRAMEWORK OF

THE EUROPEAN NOISE DIRECTIVE

Esko Toppila

Finnish Institute of Occupational Health - Helsinki - Finland

Abstract

The noise directive sets action and limit values to continuous noise and peak levels. For peaks

the lower action value is 135 dB(C), the upper action level value is 137 dB(C) and the limit

value is 140 dB(C). These peak levels are seldom exceeded in industrial environment.

Typical sources are shots, blasts and explosions. Apart from military applications these high

peak levels are most often found in the music and entertainment sector. In addition the noise

directive requires that the risk assessment must include the effect of impulsive noise.

Impulsive noise refers to noise which contains peaks of short duration, less than 1 ms.

Typically these peaks are found in welding and forging in metal industry. Music is a source

of impulsive noise too. Impulsive and impulse noises are often called non-continuous noises.

For impulse noise the ISO 1999 model does not apply. For impulsive noise the ISO 1999

model can be applied by using a correction factor. In addition to chronic hearing impairment

non-continuous noises can cause acute acoustic trauma (AAT), for which no dose-response

relationship is available.

The non-continuous noises destroy hear cells with a different mechanism than continuous

noise. There is a necrotic component involved whereas continuous noise destroys hear cell by

apoptosis. This difference may explain the higher incidence of tinnitus among people exposed

to non-continuous noises.



46

41

Hearing protectors work well against impulsive noise. They reduce the level and

impulsiveness of the noise. As a consequence impulsive noise is seldom a problem when

hearing protectors are properly used. For impulse noise the protection is a more complicated

issue. The attenuation of hearing protectors becomes non-linear when noise levels increase.

With high peak levels the attenuation may be reduced to half. This is a problem related to

special effects in music and entertainment sector. These impulses may cause AAT in the

audience too.

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42

Introduction

In 2003 the European Union introduced the new noise directive to protect the workers against

the adverse effects of noise. This directive sets the following limits to the peak levels:

(a) Exposure limit value ppeak = 200 Pa (140 dB(C))

(b) upper exposure action value ppeak = 140 Pa (137 dB(C))

(c) lower exposure action value ppeak = 112 Pa (135 dB(C))

In addition the directive requires that in the risk assessment particular attention shall be given

to impulsive noise.

Normally the standard ISO 9612 (2009) is used to evaluate the noise exposure. It is based on

the equal energy principle, which works fine with steady state noise (fig 1A). However if the

noise contains fast peaks (fig 1B) the equal energy principle underestimates the effect of

noise to man. Typical sources of impulsive noise are music, welding and hammering. The

third type of noise is impulse noise, where the noise consists of one high peak (fig 1C).

Typical sources of impulse noise are shots and blasts. Impulse noise can cause acute acoustic

trauma in addition to chronic acoustic trauma.

Impulsive noise seldom exceeds the levels set to the peak levels. Thus the impulse noise is in

practice the only noise type to which peak limit values apply.

The purpose of this presentation is present the current knowledge about the impulsive and

impulse noise. The mechanisms behind the trauma, and current status of risk assessment are

presented. Also typical workers exposed to impulse and impulse noise and best practices to

protect the workers are discussed.

48

43

Figure 1. Different noise sources and types of noise

Biological mechanism behind noise induced hearing loss

Figure 2. Hear cell death by noise

A) steady state noise

B) Impulsive noise

C) Impulse noise

4944

There are several mechanisms leading to cellular damage after acoustical overstimulation

(Fig. 2 ). The damages can be repaired or they can be irreversible leading to cell death. Some

of the mechanisms are mainly related to metabolic changes, e.g., oxidative stress, synaptic

hyperactivity, and altered cochlear blood flow, while others are predominantly mechanical. It

is likely, however, that the resulting damage to the auditory system is partly mediated by

similar mechanisms irrespective of the cause. Although definite evidence of a common final

pathway is missing, experimental data suggest that free radicals and other highly reactive

endogenous substances play a significant role in noise-induced hearing loss. The mechanisms

causing cell death through necrosis are fundamentally different from those in apoptosis.

At SPLs of less than 125 dB, sound-induced overstimulation and overactivity of the cochlea

can result in disturbed cochlear homeostasis and subsequent functional impairment in the

absence of direct and immediate mechanical damage. Experimental evidence suggests a

critical level about 125 dB SPL, at which the cause of damage changes from predominantly

metabolic to mechanical (Scheibe et a, 1992). Thus, at moderate SPLs, damage would mainly

be caused by metabolic mechanisms while at higher levels, mechanical mechanisms would

predominate (Pyykkö et al, 2007). As changes in homeostasis may also occur in mechanical

trauma and the effects of metabolic stress are also likely to be expressed as mechanical

damage, it is not meaningful to make a strict separation between metabolic and mechanical

causes of noise induced hearing loss.

Tinnitus is often experienced after an exposure to a very sudden loud noise, such as an

explosion or gunshot. In most instances, the tinnitus is accompanied by a high-tone HL. The

tinnitus usually disappears in a few days. If permanent hearing loss has occurred, tinnitus

may persist for many years. It is evaluated that 20-40 % of people exposed to occupational

industrial noise have permanent tinnitus. The same applies to musicians. The occurrence of

continuous tinnitus among people exposed to impulse noise is 63-70 %.

Risk assessment

The risk of NIHL is higher in occupations where workers are exposed to impulsive noise. In

many occupations, the impulses are so brief that they contribute only a small increase to the

energy content of noise. Comparative studies showed that, for example, shipyard workers

who are exposed to impulse noise had 10 dB greater hearing loss than was predicted by the

ISO 1999 model. (Starck et al. 1988).

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45

For impulsive noise there is no generally accepted method. The standard ISO 9612 does not

recommend any method to evaluate the additional risk. Thus the only way is to observe the

presence of impulses and state that the exposure evaluation provides lower limit to the risk.

For high level impulse noise the situation is complex. There are several methods available

for risk assessment. The existing methods can be divided into two categories: the peak level

methods and energy attenuation methods. With the peak level methods (Pfander 1975,

CHABA 1968) the risk for hearing loss is related to the peak level and duration. These

methods do not provide a way of combining different gunfire exposures or gunfire exposure

with work noise exposure to a single exposure index. The latest approach is to apply the

energy attenuation of the impulse in risk assessment (Patterson and Johnson, 1996).

According to Pekkarinen et al (1993) even with hearing protection shooting impulses are still

deteriorating hearing. It should be noted that the noise directive itself assumes that no

impulses over 140 dBC are allowed in the ear.

Both impulsive and impulse noise are suspected to cause acute acoustic trauma too.

Sometimes after discos and concerts people are complaining about permanent tinnitus and/or

hearing loss. At present the mechanism behind a single event acoustic trauma caused by

impulsive noise is unclear. For high level impulses the acute acoustic trauma the mechanism

is clear.

Group of workers exposed to impulse noise

Amazingly the group most probably exposed to impulse noise is working in the entertainment

sector. In this sector the use of special effects is the main cause of exposure to high level

impulses (fig. 3). Peak levels in shooting scenes are up to 155 dB with hand arms (fig. 3A)

and up to 165 dB with canons (fig. 3C). In addition to shooting there are other pyrotechnical

devices with extremely high peak levels (fig. 3B). Unfortunately there are no good statistics

about the prevalence of acute acoustic trauma in the entertainment sector. Still I know about

20 cases only in the Helsinki region which has occurred during the past few years.

In industry peak exceeding 140 dB are found seldom. A typical case is force hammering,

where peak levels may exceed 140 dB (Suvorov et al, 2001).

5146

Groups exposed to impulsive noise

Again the entertainment sector is one important sector. The exposure to impulsive noise is

due to exposure to music. As a consequence in the entertainment sector the prevalence of

tinnitus and hyperacusia are high compared to normal population.

In industry the exposure to impulsive noise is common in metal industry. Actually in Finland

the top-10 list of occupations causing noise induced hearing loss are populated by occupation

with exposure to impulse or impulsive noise.

a) Bullet hit b) suicide bomber c) Replica canon from the

year 1790

Figure 3. Different exposure schemes in the entertainment sector. Peak level in fig. a)

154 dB and in b) and c) over 165 dB.

Protection against impulse and impulsive noise

Protection against impulsive noise using hearing protective device (HPD) is quite simple.

The HPDs attenuate industrial impulsive noise even more effectively than steady state

continuous noise. This is due to the high frequency contents of impulses, which are

attenuated effectively in earmuffs. In addition the additional damage caused by impulses is

reduced when the peak levels become lower. Toppila et al (2000) observed that at low level

impulsive noise is not more dangerous than steady-state noise.

On the contrary protection against high level impulse noise is complicated. The attenuation

of HPDs depend highly on the frequency contents of impulse. When the amount of explosive

material increases the attenuation of HPDs decreases (fig. 4). The reduced attenuation can

already be seen with moose rifle (Toppila et Starck, 1995) or with high level low frequency

industrial impulses (Starck et al, 2002).

52

47

0

5

10

15

20

25P

eak

leve

l att

enu

atio

n (

dB)

Peltor Silenta Super Supermil+EAR

Protector

Antiaircraft cannon

122 mm cannon

1 kg TNT

Figure 4. The attenuation of selected HPDs against different blasts (Toppila et al, 2004)

Special considerations

High level impulses may have a permanent impact on the auditory brain stem responses

(ABR) of the fetus. A safe limit is regarded to be 155 dBC (Pierson, 1996). The significance

of the finding is somewhat unclear. For the fetus there is no way of protecting the hearing.

Thus the precautionary principle suggests that pregnant women should not be exposed to high

level impulses.

Discussion

The impulsive and impulse noise are a special problem recognised by the noise directive.

The additional damage is caused by necrosis of the hear cells. In addition to NIHL this type

of noise increases the prevalence of the tinnitus and hyperacusia.

Often it is not realized that impulse noise is a high risk in the entertainment sector. As the

use of special effects is continuously increasing the possibility of hearing damage is

increasing too. Although safety in the field of pyrotechnics is well established, for some

reason the protection of hearing is almost completely forgotten.

For practical work the present situation is frustrating. There are no risk assessment methods

available. The limit values given in the directive do not protect against the adverse effects of

impulsive noise. They probably prevent from acute effects of high level impulses.

A second problem is the presence of these noise types in the entertainment sector. Artists are

extremely reluctant to use HPDs and still they are very sensitive to hearing damage (Laitinen,

53

48

2005). Partly this problem is due to the fact that the risks are not properly identified, but

mostly it is a question of attitude.

Special care must be taken in the use HPDs. As long as the noise is not low frequency noise

the standard methods for the evaluation of the attenuation of HPD provide acceptable results.

This is not true for low frequency noise. In these cases the only way is to do Microphone In

Real Ear (MIRE) measurements.

However the situation is not hopeless. The problems are known, which means the solutions

can be found. Quantitative validation of the solutions is not possible. However qualitative

risk assessment can be done.

54 49

References

CHABA. Proposed Damage-risk criterion for impulse noise (Gunfire) Report of working

group 57, National Academy of Sciences National

ISO 9612:2009, ACOUSTICS. DETERMINATION OF OCCUPATIONAL NOISE

EXPOSURE. ENGINEERING METHOD, CEN, Belgium, 2009

DIRECTIVE 2003/10/EC OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL

of 6 February 2003 on the minimum health and safety requirements regarding the exposure,

European comission, 2003

ISO 1999. (1990). Acoustics - Determination of occupational noise exposure and estimation

of noise induced hearing impairment. International Organization for Standardization,

Geneva..

Johnson D. Prediction of NIPTS due to continuous noise exposure Rep No AMRL-TR-73-91,

US Air Force July, 1973.

Laitinen H, Factors Affecting the Use of Hearing Protectors among Classical Music Players,

Noise & Health 2005, 7;26, 21-29

Pfander F. Das Knalltrauma. Berlin, Heidelberg, New York Springer Verlag, 1975

Pekkarinen J, Iki M, Starck J, Pyykkö I. (1993). Hearing loss risk from exposure to shooting

impulses in workers exposed to occupational noise, Brit J Audiol 27:175-182.

Pierson LL. Hazards of Noise Exposure on Fetal Hearing, Seminars in Perinatology, Vol 20,

No 1 (February), 1996: pp 21-29.

Pyykkö I, Toppila E, Zou J, Kentala E, Pharmacotherapy of the inner ear, (220-238), Genes,

Hearing and Deafness, From Molecular Biology to Clinical Practice Editors Alessandro

Martini, Dafydd Stephens, Andrew Read, Informa Healthcare, 2007

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50

Scheibe F, Haupt H, Ludwig C. Intensity-dependent changes in oxygenation of cochlear

perilymph during acoustic exposure. Hear Res 1992; 63(1–2):19–25.

Starck J, Pekkarinen J, Pyykkö I. (1988). Impulse noise and hand-arm vibration in relation to

sensory neural hearing loss. Scand J Environ Health 14:265-271.

Starck J, Toppila E, Laitinen H, Suvorov G, Haritonov V, Grishina T. The attenuation of

hearing protectors against high-level industrial impulse noise; comparison of predicted and in

situ results. Applied Acoustics 2002;63:1-8.

Suvorov G, Denisov E, Antipin V, Kharitonov V, Starck J, Pyykkö I, Toppila E. Effects of

peak levels and number of impulses to hearing among forge hammering workers. Applied

Occupational and Environmental Hygiene.2001;16(8):816-22

Toppila E, Starck,The attenuation of hearing protectors against high-level shooting impulses

(2004), Archives of Acoustics, 29:4,275-283

Toppila E, Pyykkö I, Starck J, Kaksonen R, Ishizaki H. Individual Risk Factors In The

Development Of Noise-Induced Hearing Loss. Noise&Health 2000;8:59-70.

Toppila E, Starck J. The attenuation of hearing protectors against military impulse noise,

People and work, Research reports 3, 1995:35-9.

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51

CHEMICAL INTERACTIONS IN THE AUDITORY SYSTEM:

IMPLICATIONS FOR OCCUPATIONAL HEALTH

Thais C. Morata1, Ann-Christin Johnson2

1National Institute for Occupational Safety and Health, Cincinnati, OH , USA 2Karolinska Institute, Stockholm, Sweden

Abstract

Several factors have been studied to try to understand why the prevalence and degree of

noise-induced hearing loss can vary so much within a group and among groups. Some of the

factors studied include variations in exposure, age, gender, race, and general health

indicators, such as blood pressure and use of certain medications. The focus of the present

paper will be on the ototoxicity (the toxic effects on hearing), industrial chemicals and, their

interaction with noise. We will also briefly discuss other factors that can affect susceptibility

to hearing loss.

Environmental or work-related chemical exposures that have been specifically studied for

their potential ototoxicity include solvents, metals, asphyxiants, PCBs and pesticides. While

noise exposure is particularly damaging to the peripheral auditory system, the cochlea,

ototoxic chemicals tend to affect both the cochlear structures and the central auditory system.

Reduced blood flow and free radical formation are important ototoxic mechanisms shared by

noise and chemical exposures. Solvents and asphyxiants may also disrupt intrinsic anti-

oxidant defences and make the ear more vulnerable to the effects of e.g. noise exposure.

Some of the solvents and the asphyxiants interact synergistically with noise or potentiate

noise effects on the auditory system. Combinations of chemical exposure with noise and



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other stressors such as physical activity during exposure may lower the concentration of the

chemical exposure necessary for induction of an auditory effect.

As combined exposure (e.g. chemical and noise) is currently not taken care of in the

regular occupational exposure limit (OEL) setting procedure, a noise notation has been

proposed to indicate an increased risk of hearing loss after exposure to the chemical at a level

close to the OEL with concurrent noise exposure.

Keywords: auditory, hearing, metal, noise, occupational exposure limit, ototoxicants, review,

solvent

5953

RISK OF HEARING IMPAIRMENT FROM WORK-RELATED CHEMICAL

EXPOSURES

Robust evidence from a large number of animal studies has demonstrated that toluene,

styrene, solvent mixtures, lead, and carbon monoxide (the latter only in combination with

noise) are toxic to the auditory system, or ototoxic (Johnson & Morata, 2010). For these

substances, the number of existing studies is relatively large, and comprehensive approaches

have been taken in investigating their ototoxicity (testing of different exposure parameters

and combinations of agents, attempting benchmark dose calculations, testing of hypothesis

for the inhibition of the observed effects).

Other chemicals that have been studied in less detail with respect to ototoxicity include

xylenes, ethylbenzene, chlorobenzene, trichloroethylene, n-hexane, n-heptane, carbon

disulphide, mercury, organotins, hydrogen cyanide, acrylonitrile, IDPN, pesticides and PCBs.

Hitherto, the existing evidence indicates that also these substances have ototoxic properties

(in some cases, only with concurrent noise).

For chemicals such as n-hexane, n-heptane, carbon disulphide, lead and mercury, the

auditory effect is connected to the neurotoxic effect of these substances. Thus, they exhibit

more central neurotoxic effects than pure ototoxic effects.

Although less investigated than other chemicals, also trichloroethylene, carbon disulphide,

mercury, and some pesticides have been associated with auditory effects in humans.

Observed auditory effects of n-hexane have been interpreted as a sign of its well-known

central nervous system toxicity. No human studies on the ototoxicity of xylenes,

ethylbenzene, chlorobenzene, n-heptane, organotins, hydrogen cyanide, acrylonitrile, IDPN

and PCBs were identified, even though xylene, ethylbenzene and chlorobenzene are common

components in solvent mixtures that has been shown to be ototoxic in humans (Johnson &

Morata, 2010).

Early reports on solvents suggested that the exposure levels needed to cause an auditory

effect in experimental animals were rather high in relation to occupational exposure limits

(OELs). In contrast, several occupational reports (on styrene, toluene, solvent mixtures and

lead) indicated that much lower levels in industrial settings were sufficiently high to be

associated with hearing deficits. The reasons for the difference between the lowest levels that

cause an effect in humans and in animals, respectively, are not understood. However, recent

research in animals has demonstrated that addition of other stressors (such as impact or

continuous noise, other chemicals or drugs, or keeping the animals active during chemical

60 54

exposure) reduces the lowest solvent exposure level needed to elicit an auditory effect

(Lataye et al., 200; Lund & Kristianen, 2004, 2008).

In contrast to experimental animals, human factors are characterised by great individual

variability. Consequently, it is quite challenging to characterise risk and to separate the

effects of each agent in a combined exposure scenario, and to measure with precision the

interaction between agents such as noise and chemicals. When investigating causal

associations of a certain factor, it is of utmost importance to determine known medical factors

such as e.g. past diseases, intake of certain ototoxic drugs, noise or head trauma accidents as

well as non-medical risk factors such as e.g. leisure time or past occupational noise and/or

chemical exposures and life-style factors associated with the outcome to be investigated.

Given all these limitations, a large body of knowledge shows that hearing losses are more

common in work settings where certain chemical exposures occur. Chemical-induced hearing

losses are often moderate to severe, as is also the case with noise-induced hearing loss. The

audiometric high-frequency “notch” common in noise-induced hearing loss, is often present

following long-term chemical exposures, although some reports indicate that a wider range of

audiometric frequencies are affected when compared to the range of frequencies affected by

noise.

GROUPS AT INCREASED VULNERABILITY

There is no firm evidence to identify groups of humans at extra risk for developing hearing

impairment. However, factors that have been shown to influence the occurrence and degree

of hearing loss other than noise and chemicals include age, foetal and neonatal development,

gender, race, socio-economic and life-style factors, physical work load, and use of

medications (Toppila et al., 2000; Ecob et al., 2008).

Age

Age is an important factor to consider when examining hearing disorders. Animal

experiments suggest that young animals are more susceptible to the effects of noise than older

ones (Ohlemiller, Wright & Heidbreder, 2000; Kujawa & Liberman, 2006). Similarly, young

rats (14 weeks of age) were more vulnerable to the effects of styrene (Campo et al., 2003).

Toluene and noise were found to accelerate the age-related hearing loss in mice with a

genetic predisposition for age-induced hearing loss, but not in mice from a strain without this

predisposition (Li et al., 1992). These studies suggest that younger populations may be more

6155

susceptible to hearing loss, but that has not yet been clearly demonstrated in humans. On the

other hand, toughening of ears through low intensity noise exposures has been demonstrated

in animals and might make young ears more resistant to noise (Subramaniam et al., 1992;

Rabinowitz et al., 2006).

Foetal and neonatal development

The ototoxic effects of chemical exposure of rats during pregnancy and early lactation (a

period in which the auditory system develops rapidly in rats) were investigated for toluene,

lead, mercury, IDPN and PCBs and were demonstrated in the offspring (Goldey, Kehn &

Crofton, 1993; Goldey et al., 1995; Lasky et al., 1995; Herr, Goldey & Crofton, 1996; Rice,

1998; Hougaard et al., 1999; Crofton & Rice, 1999; Herr et al., 2004). Similar findings have

not been reported in humans.

Gender and race

Gender and race seem to be associated with susceptibility to noise-induced hearing loss.

Studies conducted with groups with similar jobs and exposures have indicated that Caucasian

males have poorer auditory thresholds and higher prevalence of noise-induced hearing loss,

while African American females have the lowest prevalence of hearing loss (Szanto &

Ionescu, 1983; Driscoll & Royster, 1984). The issue of gender is not fully understood since

both environmental and occupational noise exposure histories can be heavily influenced by

gender. The issue of race and susceptibility to noise could be explained by the protective role

played by the presence of melanine in the inner ear (Barrenas & Lindgren, 1991; Barrenas,

1997). Regarding solvents, albino and pigmented rats have been used in ototoxicity

experiments and both species are susceptible to auditory effects, but no formal investigation

compared species for this specific feature. Eastman, Young and Fechter (1987) examined the

role of melanine following animal exposures to trimethyltin and did not observe significant

effects.

Socio-economic and life-style factors

Low social class in childhood and adulthood was also found to be associated with poorer

hearing thresholds (Ecob et al., 2008) and is likely to interact with occupational risks, leisure

noise or non-occupational chemical exposures, and medical history factors such as middle ear

disease, lack of appropriate treatment or use/abuse of medication.

Studies on the interaction between hearing loss and smoking indicate that heavy smoking

can affect hearing (Sharabi et al., 2002; Burr et al., 2005; Wild, Brewster & Banerjee, 2005)

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and interact with noise, thus causing a more severe hearing loss in humans (Itoh et al., 2001;

Mizoue, Miyamoto & Shimizu, 2003; Starck, Toppila & Pyykkö, 1999; Toppila et al., 2000).

Other epidemiological investigations of solvents have controlled for smoking and no

significant associations were reported (Morata et al., 1993, 1997; 2002; Śliwińska-Kowalska

et al., 2001; 2003). Similarly, epidemiological studies (Itoh et al., 2001; Morata et al., 1993,

1997, 2002; Śliwińska-Kowalska et al., 2001, 2003) have not confirmed that alcohol

consumption potentiates the effect of solvent exposure on hearing as demonstrated in animals

(Campo & Lataye, 2000). Information about alcohol consumption can be considered sensitive

and is thereby difficult to obtain in human studies.

Physical work load

Physical exercise has also been shown to increase the susceptibility to noise (Dengerink et al.,

1987; Lindgren & Axelsson, 1988). It has also been demonstrated that styrene concentrations

required to induce auditory damage are much lower for active rats in comparison to sedentary

rats (Lataye et al., 2005). Studies indicate that the total absorbed styrene dose can be

increased six-fold with physical work and increased respiratory rate (Engström, Åstrand &

Wigaeus, 1978). It has been suggested that auditory effects of solvents may be observed at

lower concentrations in humans because humans are generally exposed to solvents in

combination with a multitude of other factors (several combined exposures, physical

demands, etc.) whereas animal experiments typically involve isolated chemical exposures

(Lataye et al., 2005).

Medication

Finally, the ototoxicity of therapeutic drugs has been recognised for a long time, but their

interaction with work-related risk factors has rarely been examined. A synergistic interaction

between acetyl salicylic acid and toluene was shown by Johnson. Acetyl salicylic acid did not

cause hearing loss but potentiated the ototoxic effect caused by toluene (Johnson, 1992).

These results might be of interest since pain killers of this type in lower doses are likely to be

used by workers including those exposed to toluene.

6357

BEST PRACTICES, INTERNATIONAL STANDARDS AND LEGISLATIONS

REGARDING CHEMICAL EXPOSURE IN THE WORKPLACE

In its 1996 National Occupational Research Agenda, the US NIOSH identified both hearing

loss and multiple exposures as research priorities for the occupational safety and health

community. In two publications, NIOSH also argued for broadening the scope of risk

assessment of hearing risks and preventive initiatives (NIOSH, 1996, 1998). NIOSH and the

American College of Occupational and Environmental Medicine both recommend that

hearing loss prevention programs take chemical exposures into account when monitoring

hazards, assessing hearing, and controlling exposures (ACOEM, 2003; NIOSH, 1996, 1998).

These recommendations do not include specific information on exposure levels of concern.

Since 1998, the American Conference of Governmental Industrial Hygienists (ACGIH)

states that periodic audiograms are advised and should be carefully reviewed in setting where

there may be exposures to noise and to carbon monoxide, lead, manganese, styrene, toluene,

or xylene. Other substances under investigations for ototoxic effects include arsenic, carbon

disulphide, mercury, and trichloroethylene (ACGIH, 2009).

Also in 1998, the US Army started requiring consideration of ototoxic chemical exposures

for inclusion in hearing conservation programmes, “particularly when in combination with

marginal noise” (US Army, 1998).

The most detailed and specific recommendation to date is one offered in 2003 by the US

Army. Since the exposure threshold for ototoxic effects is not known, audiometric monitoring

is necessary to find out if the substance is affecting the hearing of exposed workers. Yearly

audiograms are recommended for workers whose airborne exposures (without regard to the

use of respiratory protection) are at 50 % of the most stringent criteria for OELs (either of the

OSHA permissible exposure limit or ACGIH threshold limit value) for toluene, xylene, n-

hexane, organic tin, carbon disulphide, mercury, organic lead, hydrogen cyanide, diesel fuel,

kerosene fuel, jet fuel, JP-8 fuel, organophosphate pesticides, or chemical warfare nerve

agents, regardless of the noise level (US Army, 2003).

Best practice guidelines recommending hearing tests for those exposed to ototoxic agents

were also published in Australia and New Zealand, without information on exposure levels

(Australian/New Zealand Standard, 2005). Legislation regarding compensation for hearing

loss associated with chemical exposure at work has changed in Australia (Australian

Standard, 2002) and Brazil (Brazil, 1999) making it possible for workers to apply for

compensation for hearing loss because of exposure to ototoxic chemicals in the workplace.

64 58

In February 2003, the European Parliament published the Directive 2003/10/EC on

minimum health and safety requirements regarding the exposure of workers to the risks

arising from noise. In the Directive, it is stated that when carrying out risk assessments,

employers should “…give particular attention to: any effects on workers’ health and safety

resulting from interactions between noise and work-related ototoxic substances…” (European

Parliament, 2003). Finally, in April 2004, because of its demonstrated ototoxicity, toluene

was labelled as R48/20: “Danger of serious damage to health by prolonged exposure through

inhalation.” R48/20 is justified because toluene causes several types of serious toxic

effects after inhalation. Toluene-induced chronic impairment of auditory function has been

demonstrated in a number of animal studies. This has been substantiated by morphological

evidence of cell loss in the rat cochlea. Existing data suggest that humans are sensitive to this

effect at exposure levels which may be encountered in the working environment.” (European

Parliament, 2003; European Commission, 2004).

Comprehensive evaluations of ototoxic substances (Vyskocil et al., 2010) and of the

hazards of combined workplace exposure to noise and ototoxic chemical substances

(European Agency for Safety and Health at Work, 2009; Johnson & Morata, 2010) have

recently been published by other bodies.

The approach used by the Canadian Occupational Health and Safety Research Institute

IRSST (Vyskocil et al., 2010) used a time-limited period for review, a limited range of

exposure concentrations, exclusion of human data and data on the interaction between noise

and chemicals. Still, it classified lead and inorganic compounds, toluene, styrene and

trichloroethylene as “ototoxic substances.” The report on Combined Exposure To Noise and

Ototoxic Substances published by the European Agency for Safety and Health at Work

(2009) used a broader approach and data set (not limiting the time period in the search of

documents and including studies on humans, and noise interactions) as did the Johnson and

Morata 2010 document, and focused on the qualitative properties of chemicals to induce

ototoxic effects. The list of chemicals included is slightly different in the two documents as

is the rating strategy used. Still, conclusions are in agreement. The report from the European

Agency also highlighted policies from specific member states.

In 2008, Hoet and Lison proposed a “noise notation,” inspired by the widely used “skin

notation” (skin notation criteria were introduced almost 50 years ago as a qualitative indicator

of a hazard related to dermal absorption at work). They suggested that “a noise notation”

could be added to OELs of chemical agents for which there is significant concern about a

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59

possible ototoxic effect, e.g. when experimental data suggest that ototoxicity is the critical

health effect or that ototoxic effects occur at a level close to the OEL (Hoet & Lison, 2008).

As combined exposure (e.g. chemical and noise) is currently not taken care of in the

regular OEL setting procedure, a noise notation can be used to indicate an increased risk of

hearing loss after exposure to the chemical with concurrent noise exposure.

DISCLAIMER

The findings and conclusions in this report are those of the author(s) and do not necessarily

represent the views of the US National Institute for Occupational Safety and Health.

6660

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agents and biological exposure indices. Cincinnati, Ohio: American Conference of

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Australian Standards. Workcover guides for the evaluation of hearing impaired. Canberra,

Australia, June 2002.

Australian/New Zealand standard. Occupational noise management/informative appendix

on ototoxic agents. AS/NZS 1269:2005. 2nd ed. Canberra, Australia, 2005.

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COMBINED EFFECTS OF NOISE AND SOLVENT ON HEARING:

ANIMAL EXPERIMENTS

Pierre Campo, Cécile Rumeau, Thomas Venet.

Institut National de Recherche et de Sécurité. Rue du Morvan. CS 60027. 54519 Vandœuvre

Cédex. France; Tel: +33 3 83 50 21 55; Fax: 33 3 83 50 20 96; [email protected]

Abstract

Human and animal studies have shown that certain aromatic solvents can cause hearing loss

and even worsen the effects of noise. However, the mechanism responsible for the synergistic

effects of co-exposure has not yet been completely elucidated. Animal studies have shown

that solvents can inhibit acetylcholine receptors and alter the function of N- and P/Q-type

voltage-dependent Ca2+ channels in the auditory nerve centres involved in the ear protective

reflex (EPR). To study the effects of toluene (Tol) on the EPR, rat hearing was evaluated by

measuring 2f1-f2 distortion otoacoustic emissions prior to, during and after EPR activation.

The noise suppressor (NS) tone activating the EPR was delivered either contralaterally or

ipsilaterally. The efficiency of EPR during injection of different Tol concentrations into the

carotid was measured. Results showed that Tol could modify EPR efficiency. These findings

provide a basic framework for better understanding the EPR's physiological function. Based

on this and its expected consequences in terms of hearing conservation, we propose hearing

protection recommendations for workers exposed to both noise and solvents.

Keywords: Solvent, Noise, Combined exposure, Middle-ear reflex, Hearing conservation.



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1. INTRODUCTION

While noise is the predominant occupational hazard to hearing, research into hearing

conservation has shown that noise is often present in occupational settings where chemical

exposure occurs (3). Although aromatic solvents are proven ototoxicants which can

exacerbate the effects of noise exposure in both animals (6) and humans (15), neither the

European directive (2003/10/EC) nor the American noise standards take complex exposures

including chemicals into consideration. We have shown that toluene (Tol) can antagonise

neuronal acetylcholine receptors (8) and block neuronal voltage-dependant Ca2+ channels

(11). Because of these effects, Tol could be considered to be a pharmacological agent capable

of depressing the auditory nervous system which drives the ear-protective reflexes (EPR);

and in particular the middle-ear reflex (MER).

In mammals, the auditory efferent system is a centrifugal pathway, which has its source in

the vicinity of the superior olivary complex (SOC). While some motoneurons located outside

the SOC are involved in control of the MER muscles (13), most of those responsible for

contraction of the stapedius and tensor tympani muscles are located in the vicinity of the

facial or trigeminal nerve nuclei (9). Because of the structure of the efferent system, the MER

can be elicited bilaterally by sound-evoked efferent feedback (16). Thus, through stimulation

of the facial and trigeminal nerve nuclei involved in the MER, a contralateral sound may

influence activity in the opposing cochlea (2, 11). The effects of aromatic solvents on MER

efficiency can be evaluated by measuring 2f1-f2 distortion product otoacoustic emissions

(DPOAEs). These are reliable indicators of outer hair cell function (10) and are also very

sensitive to any type of hearing loss caused by changes to middle-ear impendency.

Consequently, DPOAEs are ideally suited to the study of solvent effects on the MER in both

animals and humans. Today, we are developing a non-invasive audiometric tool to study the

auditory receptor in its entirety. Based on recent findings obtained with this new experimental

approach, we have formulated a hypothesis to explain how the input coming from the various

nerve centres is integrated to generate an appropriate MER. From a practical point of view,

we propose adjustments to hearing conservation practices in order to better protect workers'

hearing, particularly during exposure to the combined effects of both noise and solvents.

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2. MATERIAL AND METHODS

2.1. Animals

Adult Long-Evans rats were used in this study (n = 21). Food and tap water were available

ad libitum. While conducting the research described in this article, the investigators adhered

to the Guide for Care and Use of Laboratory Animals as promulgated by the French Conseil

d'Etat through decree No. 87,848, published in the French Journal Officiel on October 20th

1987.

2.2. Anaesthesia

Levomepromazine (12.5 mg/kg) was given to animals by i.p. injection 15 min prior to

DPOAE measurements. Anaesthesia was induced by injection of a mixture of ketamine (50

mg/kg) and xylazine (6 mg/kg).

2.3. Reflex measurement

DPOAE recording

The DPOAE probe consisted of 2 transducers generating the primary tones: f1 = 8000 Hz

and f2 = 9600 Hz and a microphone measuring the acoustic pressure within the outer ear

canal. f1 and f2 were emitted at 65 and 60 dB SPL, respectively, and delivered to the left ear.

The ratio of f1 to f2 was 1.2, which is suitable both for rats (5) and humans (4). The primary

tone signals were produced by frequency synthesizers (Pulse, B&K 3110) and emitted by two

miniature speakers (Microphone, B&K type 4191). DPOAE amplitude was measured by an

FFT analyzer (B&K PULSE 3110).

The contralateral noise (noise suppressor: NS) was an 800 Hz band noise centred at 4 kHz,

emitted at 100 dB SPL. Each tone burst lasted 2.5 s and was followed by a 9.5 s silent

window before the next tone burst.

The ipsilateral NS was a 3.5 kHz sinus emitted at an intensity of 75 dB SPL, so as not to

disturb the 2f1-f2 DPOAEs measured in the same ear. The signal was synthesized by a B&K

Pulse 3110 and emitted by one of the transducers included in the probe. In fact, f1 and f2

were generated by one transducer and the noise suppressor (NS) tone by the other one.

Catheter implantation

A circular custom-made catheter (8), filled with a solution of NaCl 0.9% and heparin (50

UI/ml), was fitted into the carotid artery. Once inserted, the catheter was filled with Intralipid.

All injections were performed with a syringe pump calibrated to deliver a 266 µL bolus over

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80 s (Figure 1). Three concentrations of Tol were tested in this investigation: 58.4, 87.4 and

116.2 mM.

2.4 Data recording

DPOAE changes were measured with (NS) and without (noNS) noise suppression. The

MER metric could be modelled as follows: MER = DPOAE(noNS) – DPOAE(NS) (Figure

2). Prior to injection, four MER values were recorded. The average magnitude of the MER

(avgMER) was calculated for all animals using the four values recorded prior to injection.

During solvent injection, the increase in MER amplitude was called the "N" (for negative)

component. This corresponds to a decrease in the acoustic energy reaching the cochlea. In

contrast, an increase in the acoustic energy penetrating into the cochlea results from a

decrease in MER amplitude, this was therefore called the "P" (for positive) component.

An ANOVA was run to test the significance of DPOAE amplitude vs. experimental

conditions. Post hoc analysis was performed using Bonferroni's method.

3. RESULTS

3.1. Contralateral acoustic stimulation

When measuring solvent effect in the contra ear, DPOAE amplitudes were approximately

30 dB SPL (Figure 3A, B). Prior to injection, the avgMER values were 12 dB for animals

receiving 58 mM toluene (Figure 3A) and 16 dB (range, 30-14) for animals receiving 116

mM toluene (Figure 3B). Injection of Tol at 58 mM elicited one N-component, of

approximately 8 dB amplitude. The amplitude of this component was increased for the first

30 s of the injection, it then remained constant up to the end of the period of interest.

Injection of Tol at 116 mM induced two successive components: an N-component (3 dB)

followed by a P-component (11 dB) (Figure 3B). While the N-component lasted 30 s, the P-

component interacted with the N-component from about 20 s. As a result, the N-component

was masked by the P-component when 116 mM Tol was injected. P-component amplitude

peaked at the end of the injection period.

The changes of N-component amplitude vs. Tol concentration were significant for

amplitudes measured at 0 and 58 mM [F(3,14) = 3.4; p = 0.048]. At 87 and 116 mM

concentrations, N-component amplitudes were masked by the presence of the P-component,

however there was a significant difference between the effects of Tol injections at 116 mM

and lower concentrations for the P-component [F(3,14) = 6.4; p = 0.006]. Thus, it is clear that

the concentration of solvent injected directly affects MER efficiency.

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3.2. An ipsilateral acoustic stimulation

When measuring solvent effect on the ipsi ear, injection of Tol at 58 mM induced only one

P-component (Figure 4A). In contrast, 116 mM Tol provoked two successive components

having a different time- course from that shown in Figure 4B: first, P-component, then, N-

component. Thus, depending on the side to which the NS tone was applied, opposing effects

of Tol injections were observed.

The P-component amplitude obtained in the ipsi ear was slightly greater than 1 dB

[F(2,14) = 4.98; p = 0.03]. The amplitude of the N-component was also low, ranging from 2

to 2.5 dB. Lower amplitudes were expected in this series of experiments because of the NS

intensities used, 75 dB as compared to 100 dB in contra experiments. The significant

reduction of NS intensity was required in the ipsi side to avoid skewing of the 2f2-f1 DPOAE

measurements, performed in the same ear. The N-component amplitude obtained with 116

mM toluene was greater than 2.5 dB [F(2,14) = 20.57; p < 0.001]. Bonferroni post hoc

analysis shows significant differences between 116 and [0 or 58mM].

4. DISCUSSION

The main physiological functions of the MER are to protect the inner ear from high-

intensity noises. Because of its role in hearing protection, high-intensity noises presented to

either ear activate the MER on both ears. This bilateral characteristic is used by clinicians to

diagnose ear or even facial-nerve pathologies (12, 14, 17). MER efficiency can be evaluated

non-invasively by measuring its impact on 2f1-f2 DPOAEs. In the present study, DPOAEs

were recorded while the MER was activated by an NS tone emitted in the ipsi or contra ear of

the rat being studied. Using this audiometric approach, we were able to evaluate the function

of the peripheral auditory system as a whole. As expected from previous experiments (2, 11),

a bolus of 116 mM Tol injected into the carotid artery provoked temporary inhibition of

contractions of the stapedius and tensor tympani muscles elicited by contra acoustic

stimulation. Surprisingly, exposure to 58 mM Tol and noise can cause stronger contraction of

the middle-ear muscles than noise alone. Thus, depending on its concentration, an aromatic

solvent can affect the auditory nerve centres differently, either increasing or decreasing MER

efficiency. When the NS tone was delivered to the ipsi ear, opposing effects of solvent

concentration on MER contraction were observed. As a result, the side to which the NS burst

is delivered appears to be a key parameter in determining the order of N- and P-components,

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either N then P, or P then N. These results can be explained by Tol effects on interneurons

linking the nuclei to the cerebellar trunk. Basically, the dorsal and ventral cochlear nuclei and

the SOC are all involved in the MER (1, 9, 13). The interneurons and neurons from auditory

nuclei are capable of interpreting different afferent spikes coming from both ears to generate

an integrated response eliciting the MER. Therefore, through interneurons, the auditory

nuclei can adjust the MER response depending on the intensities recorded in both ears. Our

findings also reveal that solvent intoxication and resultant brainstem damage can disturb

MER adaptation.

Recommendations

This research program raised the level of concern about chemical exposure in combination

with noise as a risk factor for occupational hearing loss. Despite progress made in

understanding the toxic processes involved in combined exposures, it must be admitted that

the occupational health community is only dimly aware of the risk to hearing posed by

chemical hazards. Standard hearing conservation practices always focus on noise and do not

take the increased risk of combined exposure to noise and solvents into consideration. In the

European Directive 2003/10/EC, which focuses on the effects of noise on hearing, employers

are advised to pay particular attention to the risks faced by workers when they are exposed to

work-related ototoxic substances, without clearly mentioning chemicals. Through inhibiting

the EPR, ototoxic solvents cause a higher acoustic energy to penetrate the cochlea, making

noise more damaging. This results in synergistic adverse effects on hearing when there is co-

exposure to these solvents and noise. The risks encountered by people exposed to both noise

and solvents in the workplace could be easily reduced by requiring the use of hearing

protectors from the lower exposure action value: LEX,8h = 80 dB(A).

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Figure 1: Study schedule. Hearing tests were carried out with Long-Evans rats using

2f1-f2 DPOAEs. Primaries: f1 = 8000 Hz at 65 dB SPL and f2 = 9600 Hz at 60 dB SPL;

f1/f2 = 1.2. The contralateral noise suppressor was an 800 Hz band noise centred at 4

kHz, whereas the ipsilateral noise suppressor was a 3.5 kHz sinus.

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Figure 2: Decrease in DPOAE amplitude provoked by the protective reflexes. Each

noise suppressor (NS) tone lasted 2.5 s and was emitted at 100 dB SPL. Left Y-axis:

DPOAE amplitude. Right Y-axis: DPOAE NS-induced variation. Open circle: DPOAE

measured for 500 ms without NS. Black circle: mean of 18 DPOAE measured in the

absence of NS. Open triangle: DPOAE measured for 500 ms during NS burst emission.

Black triangle: mean of 4 measurements performed during NS burst emission. Cross:

DPOAE measurements excluded from calculations. Grey squares correspond to the

reflex amplitude: difference between the mean of the 2 black circles and the black

triangle for each series of measurements.

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Figure 3: Variations of 2f1-f2 DPOAE amplitude and MER efficiency in the

contralateral ear prior to, during and after toluene injection (A) 58 mM; (B) 116 mM

toluene injection. A 266 µL bolus of vehicle containing appropriate concentrations of

toluene was injected over 80 s (grey triangles). Primary tones f1 = 8000 Hz and f2 = 9600

Hz were emitted at L1 = 65dB SPL and L2 = 60 dB SPL, respectively. Frequency ratio

was 1.2. The contralateral noise suppressor was an 800-Hz band noise centred at 4 kHz

and emitted at 100 dB SPL. N-component: decrease of the acoustic energy entering the

cochlea. P-component: increase of the acoustic energy entering the cochlea.

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Figure 4: Variations of 2f1-f2 DPOAE amplitude and MER efficiency in the ipsilateral

ear prior to, during and after injection of toluene. (A) 58 mM toluene; (B) 116 mM

toluene. A 266 µL bolus of vehicle containing the appropriate toluene concentration was

injected over 80 s (grey triangles). Primary tones f1 = 8000 Hz and f2 = 9600 Hz were

emitted at L1 = 65dB SPL and L2 = 60 dB SPL, respectively. Frequency ratio was 1.2.

The ipsilateral noise suppressor was a 3.5 kHz sinus emitted at 75 dB SPL. P-

component: increase of the acoustic energy penetrating into the cochlea. N-component:

decrease of the acoustic energy penetrating into the cochlea.

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