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Occupational Neuroepidemiology

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Olav Axelson*

*Adapted from Axelson 1996.

Early knowledge about the neurotoxic effects of occupational exposures appeared through clinical observations. The observed effects were more or less acute and concerned exposure to metals such as lead and mercury or solvents like carbon disulphide and trichloroethylene. With time, however, more chronic and clinically less obvious effects of neurotoxic agents have been assessed through modern examination methods and systematic studies of larger groups. Still, the interpretation of the findings has been controversial and debated such as the chronic effects of solvent exposure (Arlien-Søborg 1992).

The difficulties met in interpreting chronic neurotoxic effects depend on both the diversity and vagueness of symptoms and signs and the associated problem of defining a proper disease entity for conclusive epidemiological studies. For example, in solvent exposure, the chronic effects might include memory and concentration problems, tiredness, lack of initiative, affect liability, irritability, and sometimes dizziness, headache, alcohol intolerance, and reduced libido. Neurophysiological methods have also revealed various functional disturbances, again difficult to condense into any single disease entity.

Similarly, a variety of neurobehavioural effects also seems to occur due to other occupational exposures, such as moderate lead exposure or welding with some exposure to aluminium, lead, and manganese or exposure to pesticides. Again there are also neurophysiological or neurological signs, among others, polyneuropathy, tremor, and disturbance of equilibrium, in individuals exposed to organochlorine, organophosphorus and other insecticides.

In view of the epidemiological problems involved in defining a disease entity out of the many types of neurobehavioural effects referred to, it has also become natural to consider some clinically, more or less well-defined neuropsychiatric disorders in relation to occupational exposures.

Since the 1970s several studies have especially focused on solvent exposure and the psycho-organic syndrome, when of disabling severity. More recently also Alzheimer’s dementia, multiple sclerosis, Parkinson’s disease, amyotrophic lateral sclerosis, and related conditions have attracted interest in occupational epidemiology.

Regarding solvent exposure and the psycho-organic syndrome (or toxic chronic encephalopathy in clinical occupational medicine, when exposure is taken into diagnostic account), the problem of defining a proper disease entity was apparent and first led to considering en bloc the diagnoses of encephalopathia, dementia, and cerebral atrophy, but neurosis, neurasthenia, and nervositas were also included as not necessarily distinct from each other in medical practice (Axelson, Hane and Hogstedt 1976). Recently, more specific disease entities, such as organic dementia and cerebral atrophy, have also been associated with solvent exposure (Cherry, Labréche and McDonald 1992). The findings have not been totally consistent, however, as no excess of “presenile dementia” appeared in a large-scale case-referent study in the United States with as many as 3,565 cases of various neuropsychiatric disorders and 83,245 hospital referents (Brackbill, Maizlish and Fischbach 1990). However, in comparison with bricklayers, there was about a 45% excess of disabling neuropsychiatric disorders among white male painters, except spray painters.

Occupational exposures also seem to play a role for disorders more specific than the psycho-organic syndrome. Hence, in 1982, an association between multiple sclerosis and solvent exposure from glues was first indicated in the Italian shoe industry (Amaducci et al. 1982). This relationship has been considerably strengthened by further studies in Scandinavia (Flodin et al. 1988; Landtblom et al. 1993; Grönning et al. 1993) and elsewhere, so that 13 studies with some information on solvent exposure could be considered in a review (Landtblom et al. 1996). Ten of these studies provided enough data for inclusion in a meta-analysis, showing about a twofold risk for multiple sclerosis among individuals with solvent exposure. Some studies also associate multiple sclerosis with radiological work, welding, and work with phenoxy herbicides (Flodin et al. 1988; Landtblom et al. 1993). Parkinson’s disease seems to be more common in rural areas (Goldsmith et al. 1990), especially at younger ages (Tanner 1989). More interestingly, a study from Calgary, Canada, showed a threefold risk for herbicide exposure (Semchuk, Love and Lee 1992).

All the case persons who recalled specific exposures reported exposure to phenoxy herbicides or thiocarbamates. One of them recalled exposure to paraquat, which is chemically similar to MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), an inducer of a Parkinson-like syndrome. Paraquat workers have not yet been found to suffer from such a syndrome, however (Howard 1979). Case-referent studies from Canada, China, Spain, and Sweden have indicated a relation with exposure to unspecified industrial chemicals, pesticides, and metals, especially manganese, iron and aluminium (Zayed et al. 1990).

In a study from the United States, an increased risk of motor neuron disease (encompassing amyotrophic lateral sclerosis, progressive bulbar palsy and progressive muscular atrophy) appeared in connection with welding and soldering (Armon et al. 1991). Welding also appeared as a risk factor, as did electricity work, and also work with impregnating agents in a Swedish study (Gunnarsson et al. 1992). Hereditability for neurodegenerative and thyroid disease, combined with solvent exposure and male gender, showed a risk as high as 15.6. Other studies also indicate that exposure to lead and solvents could be of importance (Campbell, Williams and Barltrop 1970; Hawkes, Cavanagh and Fox 1989; Chio, Tribolo and Schiffer 1989; Sienko et al. 1990).

For Alzheimer’s disease, no clear indication of any occupational risk appeared in a meta-analysis of eleven case-referent studies (Graves et al. 1991), but more recently an increased risk was connected with blue-collar work (Fratiglioni et al. 1993). Another new study, which included also the oldest ages, indicated that solvent exposure could be a rather strong risk factor (Kukull et al. 1995). The recent suggestion that Alzheimer’s disease might be related to exposure to electromagnetic fields was perhaps even more surprising (Sobel et al. 1995). Both these studies are likely to stimulate interest in several new investigations along the indicated lines.

Hence, in view of the current perspectives in occupational neuroepidemiology, as briefly outlined, there seems to be a reason for conducting additional work-related studies of different, hitherto more or less neglected, neurological and neuropsychiatric disorders. It is not unlikely that there are some contributing effects from various occupational exposures, in the same manner as we have seen for many cancer types. In addition, as in etiologic cancer research, new clues suggesting ultimate causes or triggering mechanisms behind some of the serious neurological disorders may be obtained from occupational epidemiology.



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