Overview of the neurotoxic effects in solvent …

1 Arch Public Health2002, 60, 217-232 Overview of the neurotoxic effects in solvent - exposed workersbyViaene exposed to solvents are at risk to develop a chronic toxicencephalopathy, although effects (promoting or etiological) on other cen-tral and peripheral nervous system diseases may be possible. Carefulmonitoring of exposure (environmental monitoring and bio-monitoring) butalso bio- effect monitoring is strictly needed. A review of the literature isgiven. This text is the summary of the report made for the Fund forOccupational Diseases (Fonds voor de Beroepsziekten), Belgium, syndromes, organic solvents , chronic toxic Viaene, MD, PhD, Neuropsycho-Toxicological Expertise Centre,Governmental Psychiatric Hospital (OPZ), Pas 200, 2440 Geel, Tel: 014/ 57 91 11, of Occupational Medicine, Catholic University of Leuven, UZ.

2 St. Rafa l,Kapucijnenvoer 35, 3000 Leuven, Tel: 016/ 33 70 solvents represent a group of aliphatic and aromatic organiccompounds which are usually lipophilic and more or less volatile. Historically,some solvents ( trichloroethylene and chloroform) were used in medi-cine as anesthetics because of their narcotic properties. Propofol (2,6-di-isopropylphenol) is still widely used in this respect. However, in industrynumerous chemical or technical processes rely on specific properties oforganic solvents which may cause substantial exposure to these substancesin the work force. Although the acute neurotoxic potentials of most solventswere known for a long time, it was not earlier than the second half of the20thcentury that chronic or delayed neurotoxicity due to occupational sol-vent exposure became a scientific issue.

3 Since then, case-reports, case-control studies, cross-sectional and follow-up investigations documenteda variety of exposure conditions (aromatic or aliphatic solvents , or solventmixtures) which may cause clinical neurological or neurophysiologicaleffects, neuropsychological deficits, influence on neuro-endocrinologicalfunction or neuro-radiological changes (1-3). Pre-narcotic symptoms evolv-ing to coma with or without residual neurobehavioral sequels have beendescribed as resulting from acute exposure, while invalidating diseasessuch as organic encephalopathy (or organic psycho-syndrome, OPS),depression, psychosis, sleep apnoea, multiple sclerosis, dementia,Parkinson s disease, and amyotrophic lateral sclerosis were consideredas chronic or delayed effects of long-term solvent exposure (1-4).

4 Minorproblems such as dyschromatopsia, loss of hearing and smell, and vestibu-lar dysfunction were also reported in chronic exposure conditions with avariety of solvents (1-3). It appeared thus that exposure to most solventscould induce deterioration of different central nervous system functions aswell as peripheral nervous functions. The characterization of the exposureconditions (exposure intensity, exposure duration, type of solvent ), how-ever, was mostly insufficient and therefore frequently led to controversy orconfusion. This review attempts to give an Overview of what is known aboutthe neurotoxic effects of occupational solvent exposure in humans and theimplications of this knowledge to early detection and Nervous System EffectsOrganic psycho-syndrome due to solvent exposureAcute effectsIn most cases there is no discussion about the etiology of this diseasewhen the time-lag between the intoxication and the clinical symptoms is219 Overview of the neurotoxic effects in solvent exposed workersnot more than a few hours (5).

5 In cases of acute or subacute intoxicationwith organic solvents , symptoms of eye and nose irritation, a feeling ofdrunkenness, dyspnea, nausea, headache, ataxia, in the worst caseseventually leading to myoclonus, confusion, somnolence, coma and con-vulsions have been described (6-8). These symptoms have been repro-duced in human and animal experiments which required very high expo-sure levels, especially if the exposure duration was limited in time (9-10).In the occupational setting high airborne solvent concentrations, whichmay increase the risk of acute intoxication, can be encountered when theworking conditions are related to confined spaces ( cleaning of tanksor reactors) without personal protection, when large quantities are to beapplied on broad surfaces, when the ventilation flow is in the direction ofthe breathing zone, or when solvent containing products are sprayed orapplied in warm environments or are heated.

6 In the acute stage of intox-ication no special clinical, neurophysiological (EEG, evoked potentials) orradiological signs (CT, MRI) were found except if concomitant hypoxiawas present, resulting in cerebral edema or infarction. Afterwards a dis-crete cortical-subcortical atrophy on CT or MRI scanning was reported insome cases (11). Slowing of EEG activity was frequently seen in the acutestage. Only in such cases persistent cognitive deficit remained afterwards(12) and the presence of deficits in neuropsychological testing shortly afterthe intoxication seemed to predict a bad prognosis (6, 8). In conclusion,recovery after an acute intoxication with solvents can be uneventfully, butin several cases persisting mild to severe chronic encephalopathic syn-dromes were described (6-8).

7 Therefore, timely testing of basic neuro-psychological functions ( concentration ability, memory, psychomotoraccuracy and speed, and conceptual ability and speed) is necessary foran adequate evaluation of these patients. Acute solvent intoxication inwhich the solvent is metabolized to carbon monoxide ( methylene chlo-ride or methanol) produces the typical pattern of retinal degeneration andinfarction in the basal ganglia in addition to the encephalopathy alreadydescribed (13).Chronic effectsIn contrast to the acute intoxication situation, the debate about chronicneurotoxic effects of daily low to moderate solvent exposures is not yetsettled.

8 Gamberale and Hultengren (10) concluded that in occupationalexposures not only the level of exposure, but also the duration of expo-sure must be crucial because in healthy volunteers a much higher con-centration was needed in acute exposure conditions to induce the samesymptoms. Organic psycho-syndromes with concentration and memorydifficulties, diminished psychomotor speed, decreased mental flexibility,220 Viaene changes, changes in personality, diffuse pain, and sleeping difficul-ties are usually described in workers who experienced working conditionswhich caused at least once symptoms of acute intoxication (14-16).

9 Someof these cases had also signs of spasticity, ataxia, tremor or polyneuropathy(2, 7). But, numerous cross-sectional studies in healthy subjects exposedto solvents have shown dose-dependent subclinical effects on concen-tration, memory and psychomotor function (17-18), central and peripheralnerve conduction velocities (19), vestibular functioning (20), and slightlyabnormal clinical neurological examinations (intentional and posturaltremor, diminished distal peripheral reflexes, positive glabella reflex,increased body sway) (21-22). Even long-term exposure to low airborneexposure concentrations are likely to produce slight pre-narcotic or irrita-tion symptoms like headache, nausea, inappropriate laughing or angri-ness, dizziness, imbalance, and eye irritation (23).

10 In addition, like foracute intoxications, chronic exposure conditions may lead to cortical andsubcortical atrophy on CT-scan and diffuse diminished blood flow on SinglePhoton Emission Tomography (SPECT) examination (15). No differencewas seen in the clinical picture regardless exposure had been to mixturesor to aromatic or aliphatic hydrocarbons (15-16, 24). The odds ratio thatexposed workers develop a neuropsychiatric disease is estimated to bebetween to and increases with increasing duration and intensityof the exposure (25-29). Mikkelsen et al. (25) calculated that the risk startsto increase after 6 years of a time weighted average exposure (TWA) to100 ppm white spirit.