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Year : 2002  |  Volume : 4  |  Issue : 14  |  Page : 63--71

Solvents impair balance in man

Susan Aylott, Deepak Prasher 
 Institute of Laryngology and Otology, University College London, London, United Kingdom

Correspondence Address:
Deepak Prasher
Institute of Laryngology and Otology, University College London, 330 Gray’s Inn Road, London WC1X 8EE
United Kingdom

Abstract

Solvents are commonly used in many industries and therefore exposure to multiple solvents is a common occupational hazard. A myriad of peripheral and central nervous system toxic effects can be produced by both acute and chronic low level exposures. Dizziness is often an early symptom of solvent exposure but has only in recent times been investigated specifically. The indications from the studies reviewed are that vestibular disturbances are common in workers exposed to solvents and dose-response relationships need to be established for early detection of vestibulo-toxicity.



How to cite this article:
Aylott S, Prasher D. Solvents impair balance in man.Noise Health 2002;4:63-71


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Aylott S, Prasher D. Solvents impair balance in man. Noise Health [serial online] 2002 [cited 2022 Jun 24 ];4:63-71
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Full Text

 Introduction



Many commonly used chemicals such as toluene, styrene, n-hexane, xylene and many others used to dissolve or disperse substances are called solvents and are used in a wide range of industries including engineering, construction, chemicals, printing, rubber, plastics, pharmaceuticals, footwear, textiles, foods, woodworking, dry cleaning, paint and ink manufacture. They are found in paints, lacquers, varnishes, paint-removers, cleaning and degreasing materials, adhesives, inks and ink removers, pesticides, and toiletries. It is thought that some 10 million workers in the EU and a similar number in the USA are exposed to solvents in the occupational environment. High volatility of solvents leads to absorption largely through inhalation but also in liquid form through direct contact with skin. Increased physical activity and temperature in the occupational setting increase the rate of solvent vapour absorption. Trapping solvents between wet clothing and skin also increases absorption through trans-dermal routes. It is considered that a worker using a highly volatile solvent will inhale four times more vapour than a less volatile agent or vegetable oil based cleaning agent. The Health and Safety Commission (HSC) is proposing changes in the occupational exposure limits in order to meet the requirements of the European Commission's (EC) First Indicative occupational Exposure limit values (IOELV) directive, which had to be implemented by the end of 2001.

Solvents with the same threshold limit values (TLV) or permissible exposure limits (PEL) may present two distinctly different health hazards owing to their different vapour pressures. Vapour pressure of a solvent is an important indicator of the health hazard as it is directly related to the airborne concentration. Vapour hazard index is an indicator of a solvent's toxicity and potential for exposure.

 Solvent health effects



Health effects are dependent upon the toxicity of the solvent, which relates to the physiochemical properties, inherent toxicity, metabolites and clinical pharamokinetics. For the individual worker, the route of exposure, exposure concentration, absorbed dose, length of exposure, individual worker's susceptibility, toxic metabolites, previous medical conditions and combination with other chemical exposures are relevant to the associated risk. Exposure to multiple solvents is a common occupational hazard.

With chronic exposure to multiple solvents, a myriad of neurological symptoms may be present signifying peripheral and central nervous system toxicity. In considering the diagnosis it is important to consider dose-response relationships, time between exposure and development of symptoms and signs and their change over time. Variations in symptoms may be due to varying degrees of involvement of the metabolic, nutritional, inflammatory, or degenerative processes. Common peripheral nerve toxicants include n-hexane, methyl n-butyl ketone. Central nervous system toxicity may present with various symptoms including altered cognition to balance disturbances, co-ordination, and motor dysfunction.

Initially acute or pre-narcotic symptoms include feelings of intoxication, headache, vertigo, disequilibrium, nausea or euphoria and concentration difficulties, also irritability, fatigue and mucous membrane symptoms may develop. Chronic symptoms with longstanding exposure include memory loss, lowered ability to concentrate, fatigue, abnormal tiredness, lowered stress tolerance, intellectual reduction, affective lability, vegetative symptoms, lowered activity levels and disequilibrium. Such symptoms are slow to develop and within the first few years, tend to be reversible (Odkvist et al 1992).

Psychological performance tests have been used to evaluate the effects of CTE in large-scale studies in occupational settings but the findings remain somewhat controversial as concerns have been expressed regarding the methodological quality and validity and significance of the data. But a recent systematic review by Anne Spurgeon (2001) of the studies on this subject reveal that around 80% of the studies reported statistically significant effects of long term low level solvent exposure on some aspects of cognitive functioning, furthermore exposure­effect relationships were observed in 50% of the studies.

The diagnosis of CTE syndrome at present is slow and may be confused with a multitude of alternative diagnoses, thus it may not be recognized until the damage is irreversible. Impaired function may well exist after the exposure is terminated. It has been suggested that the test procedure should consist of a thorough case history, solvent exposure level and time, physical examination, psychological testing and oto-neurological tests including dynamic posturography and auditory tests (Odkvist et al 1992).

Recent studies (Niklasson et al, 1998) examining the balance system in subjects with chronic low level solvent exposure suggest that such an evaluation may provide an early indication of solvent induced chronic toxic encephalopathy.

This review examines the effects of solvent exposure on the human balance system.

 Balance systems



Vestibular system and connections

Angular motion or turning is sensed by the semicircular canals in the inner ear. The three canals at right angles to each other sense motion in the three dimensions. There are also contributions from the visual system and sensation from the body, which influence the perception of motion.

The vestibular branch of the eighth nerve innervates the cristae ampularris of the superior, posterior and horizontal semicircular canals (responding to angular acceleration- e.g. head turning) and the maculae of the utricle and saccule (respond to linear acceleration- e.g. translational movements back/forth, side/side etc).

The first order vestibular neurones terminate in the vestibular nuclei in the lower brainstem from where they connect to

vestibulo-spinal tract in the spinal cord for postural reflexescerebellum for reflexive and neuro­muscular orientationreticular formation of the midbrain and brainstem for integration with other sensory systemsoculo-motor nuclei- for control of horizontal eye movements compensating for head turntemporal lobe for awareness of head motionvestibular sense organ via the efferent pathway for control of input to vestibular nuclei Thus many interconnecting pathways are involved in the maintenance of balance.

Posture

The main purpose of the vestibular system is to maintain posture, therefore assessment of the vestibular system must include gait and stance. If a person stands on a small platform with feet together, the extent of body sway is slightly increased when the eyes are closed. Subjects with central vestibular lesions are usually unsteady with eyes open or closed whereas those with peripheral lesions are more unsteady with eyes closed than open. The system can be further stressed by having the subject stand on a foam thereby reducing proprioceptive as well as visual input.

Vertigo

Vertigo is an illusion of a rotatory motion either of the individual or their surrounding and may result from an acute vestibular lesion. Continuing imbalance or dizziness may be due to lack of complete central compensation from that lesion. It may occur in episodes as central compensation reduces the effect or the offending cause dissipates. A slowly developing unilateral vestibular pathology or bilateral involvement may not typically produce vertigo. Changes in symptoms with certain visual inputs may be result from alteration in the visual-vestibular interaction. Rapid head movements may induce vertigo as this may accentuate the imbalance in the vestibular pathways. Vertigo can result from a disturbance from the inner ear, the neck, vestibular/visual interaction centres in the brainstem and cerebellum, and in the subjective sensation pathways in the thalamus or cortex (Baloh 1998). Vertigo which is induced by lying on one side and is short lived is considered to be benign positional paroxysmal vertigo and that due to neck extension may be due to vertebro­basilar ischaemia and therefore less likely to be induced by solvent exposure.

Some subjects may be made very unsteady without any visual input, as in the dark. Removal of proprioceptive input may also worsen the unsteadiness as for example by standing on a mattress. Thus eyes closed standing on foam may provide the best indication of vestibular dysfunction.

Disorientation

Disorientation is another feature of vestibular disturbance with a subjective sensation of tilting or leaning or " not being one self". This sensation may also result in increased sway on postural testing.

Eye Movements

All of the eye movements may be examined using electro-nystagmographic (ENG) recordings, which rely on the corneo-retinal potential. The semi-circular canals can be tested by rotational or thermal stimuli. The caloric test with hot and cold water irrigation has the advantage of testing one side at a time whereas the rotational test examines horizontal canals together.

In order to establish whether the cause of dizziness is vestibular in origin and whether its site is peripheral or central, electronystagmo­graphic recordings of eye movements are essential. Normally the afferent nerves from the otolith organs and the semicircular canals of each inner ear maintain a balanced tonic rate of firing into the vestibular nuclei. Any asymmetry in the activity of the vestibular systems leads to a sense of vertigo.

Nystagmus

Examination of eye movements can also reveal effects of solvents on the vestibulo-ocular system. It is important to establish visual acuity, conjugate eye movements and presence of any squints before examination. Observation of eyes in the primary position may reveal the presence of any spontaneous nystagmus. Nystagmus or repetitive eye movements with a fast and slow phase may occur spontaneously in the primary gaze position as a result of vestibular dysfunction or may be evoked by placing eyes in lateral gaze. Spontaneous nystagmus of peripheral origin does not change direction (which is defined by the fast phase) with change in gaze position to either side although it

increases in amplitude with gaze in the direction of the fast phase and reduces in the gaze in the opposite position (Alexander's law). It is also inhibited with fixation. In contrast spontaneous nystagmus of central origin typically changes direction when the subject looks away from the direction of the fast phase. If the slow phase velocity of the horizontal nystagmus is greater than 7 degrees per second, it is considered pathological and if it is greater with eyes closed than with eyes open, it tends to be indicative peripheral vestibular pathology. If it is greater with eyes open than with eyes closed it tends to indicate central involvement. Vertical nystagmus is central in origin (Baloh, 1998).

Saccades

Saccades are rapid voluntary eye movements from target to target location. Ocular dysmetria resulting from hypo or hypermetric saccades require additional corrective adjustments to reach target after under or over shooting. This is usually associated with cerebellar pathology. Ocular flutter with spiky overshoots is consistent with brainstem dysfunction as is slowing of the velocity of saccades. The velocity and accuracy of saccades are an indication of the effect on the vestibulo-ocular system.

Smooth Pursuit

Smooth pursuit movements may also be examined by a slowly moving target in the horizontal and vertical planes. Central lesions of the cerebellum and basal ganglia produce deranged pursuit.

Visual Suppression

Vestibulo-ocular reflex (VOR) is responsible for maintaining a stabilised image on the retina with movement of the head and compensatory eye movements. Dysfunction of VOR results in illusion of objects moving up and down for example during walking but normal when stationary. Abnormalities of VOR and VOR suppression with fixation provide a valuable indication of solvent induced disturbance of head/eye co-ordination.

Imbalance is always associated with vertigo but tends to be worse with central causes.

Solvent effects on balance

It is important in the assessment of balance that a detailed family and work history is taken to exclude many other causes of disturbance of balance other than solvent exposure.

As solvents are lipid soluble they enter organs with a high fat content, including the lipid-rich areas of the white matter, for example the brainstem. Most are excreted directly through the lungs or via urine after hepatic metabolism. As a result of occupational exposure to solvents, disturbances in both the peripheral and central nervous system are apparent, not only at high concentrations but also at levels close to the threshold limit value (Xiao et al 2000). The term chronic toxic encephalopathy is used to describe permanent residual neuro-cognitive defects and neurological impairment (Sullivan and vanErt 2001), previously termed psycho-organic syndrome (Odkvist et al 1992). The early symptoms may range from disequilibrium, vertigo, nausea and mood changes to chronic CNS lesions with fully developed CTE (Odkvist et al 1992).The primary effects of chronic exposure include encephalopathy, cerebellar degeneration, and disorders of equilibrium (Knox and Nelson (1966) Sasa et al (1978). Cerebellar dysfunction has been observed in long-term abusers of pure toluene (NTP, 1990) and vestibular deficits in clinical studies of toluene sniffers were reported by Winneke (1982).MRI findings in chronic toluene abusers include abnormalities in the middle cerebellar peduncle, thalamus, basal ganglia and in cerebral and cerebellar white matter (Kojima et al (1993).

Occupational studies by Yin et al (1987) and Lee et al (1988) reported subjective symptoms including dizziness following exposure to approximately 100ppm toluene. Controlled exposure effects on volunteers produced dizziness at 100 ppm of toluene Andersen et al 1983). Disturbances of vestibulo-ocular responses has been demonstrated in subjects exposed to concentrations of toluene ranging from 103-140ppm for more than 2 hours while doing light work (Hyden et al 1983).

Subjects exposed to mixed xylene at 690 ppm for 15 minutes experience dizziness (Laine et al 1993). Peripheral neuropathy has been associated with xylene exposure (Ruitjen et al, 1994).

Workers exposed to styrene vapours between 4 and 165ppm complained of dizziness and tinnitus (Geuskens et al 1992). Ledin et al 1989 and Moller et al 1990 have shown disturbances in equilibrium testing in workers exposed to styrene whilst others (Feldman 1999) have indicated that styrene interferes with cerebellar inhibition of the vestibulo-ocular system.

Specific deficits in the balance systems are detailed below and summarised in [Table 1].

Postural sway

Postural control in an upright stance is dependant upon the projection of the centre of gravity within the area of support. Postural muscles generate acceleration forces acting upon the body segments. Displacement of the centre of pressure between feet and ground depends on gravity and acceleration forces. The cerebellum acts as an integrating organ and corrects equilibrium disturbances. The cerebellum uses information from the vestibular, visual and proprioceptive systems to maintain postural control (Odkvist LM, 1978, Rubin AM et al 1978).

These systems all contribute to the postural control and damage to any of them or to the cerebellum will influence the common output of the postural system (Diener HC et al 1984, Nashner LM et al 1982).

The cerebellum contributes to the inhibition of the vestibulo-ocular reflex, presumably by visual suppression. It is possible that the same system is used together with proprioception to maintain adequate equilibrium. This could explain the correlation between the impaired ability to visually suppress the vestibulo-ocular reflex and the pathological posturographic findings in solvent exposed individuals (Ledin T et al 1989). In solvent exposed individuals posturographic findings suggest vestibular abnormalities.

Several studies demonstrate an increased sway area in the eyes open and/or eyes closed tests (Ledin T et al 1989, Moller C et al 1990, Yokoyama K et al 1997, Smith LB et al 1997, Pospiech L et al 1998).

The cerebellar, brainstem and vestibular functions have been suggested to be sensitive early indicators for organic solvent effects (WHO et al 1985). It is possible that xylene inhibits the effect of n-hexane on postural balance (Yokoyama et al 1997). Using dynamic posturography workers exposed to solvents showed a significantly impaired equilibrium performance on the sensory organization element of the test (Odkvist LM et al 1992). A positive relationship between changes in postural balance variables and exposure to constituents of jet fuel has been observed. An increased exposure level showed an increase in postural sway, implying poorer postural balance. Also routine low-level doses of neurotoxic solvents have shown a cumulative effect (Smith LB et al 1997).

Calorics

Normal caloric results indicate normal peripheral vestibular function. In a study of workers exposed purely to styrene normal calorics were obtained in all workers (Moller C et al 1990)

Visual suppression

The Vestibuar Ocular Reflex (VOR) provides compensatory eye movements during head rotation and therefore stabilizes visual fixation of a steady target. However, if the target is moving with the head, the VOR has to be suppressed in order for a stable image to be produced on the retina. The cerebellum is probably of crucial importance in systems providing inhibitory signals to the VOR (Cohen B 1974). The inability to suppress this reflex indicates a disturbance of cerebellar function. Decreased VOR suppression in solvent induced workers with a confirmed diagnosis of Psycho-Organic Syndrome (POS) has been observed (Moller C et al 1989). Increasing gain in the visual suppression test using styrene and toluene exposure indicates that these solvents act on the VOR by blocking inhibitory mechanisms presumably from the cerebellum. The transmitter involved in the cerebellar inhibition of the vestibular pathways is possibly gamma-amino butyric acid (GABA) (Odkvist et al 1983)

Saccades

The saccadic system is thought to originate and be controlled by the brainstem-cerebellum and saccadic abnormalities have previously been found in patients with cerebellar lesions (Leigh J et al 1983). Latency time is significantly higher in individuals exposed to styrene (Moller C et al 1989)

Smooth pursuit

In patients with CTE, the smooth pursuit test displays lower gain, using both sinusoidal and pseudo-randomised tests, possibly indicating impaired cerebellar function. It is postulated that these two tests; sinusoidal and pseudorandomised tests may unveil the CNS lesion before the CTE has become permanent (Odkvist LM et al 1992).

A phase lag during sinusoidal tests and a depression of gain during pseudorandomised stimulation was observed in workers exposed to styrene (Moller C et al 1989). The smooth pursuit pathways engage several systems within the CNS namely the optic accessory tract, the cerebral hemispheres, the brainstem and the cerebellar flocculus (Leigh J et al 1983). The reduction of gain during pseudorandomised stimulation in the styrene-exposed workers demonstrates that the overall ability to perform smooth pursuit eye movement was reduced. The increase in phase lag during sinusoidal stimulation indicates disturbances of central motor programs for anticipating stimulus patterns (Moller C et al 1989).

The existence of positional or spontaneous nystagmus in some patients indicates a disturbance of the CNS. Styrene and toluene exposure did not elicit any positional nystagmus (Odkvist L M 1983).

 Conclusions



It is clear that both acute and chronic exposures to solvents produce symptoms of dizziness. Early studies have documented these with neuropsychological disturbances due to chronic low level exposure but did not test specifically for the vestibular disturbances. The studies which have evaluated the balance mechanisms in workers exposed to solvents indicate that these may provide an early indication of solvent exposure effects and need to be studied in clear dose-response manner to observe the relationship.[44]

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