Module 3: Toxicology - Section 17:

TOX17.1: Organic Solvent Neurotoxicity

INTRODUCTION

Occupational neurotoxicity is a difficult area both from an epidemiologic and a clinical point of view. There is inconsistency in research findings and clinical approaches. For example, in some countries (particularly in Scandinavia) chronic solvent encephalopathy is recognised as a disease or injury by the medical profession and by the compensation system, while in other countries it is controversial or not recognised. Similarly, the scientific literature contains studies that show exposure-response relationships for neurotoxic exposures while others do not.

There is no doubt that there are overt clinical cases of irreversible neurotoxicity involving both the central and peripheral nervous systems associated with exposure to neurotoxins. This is best established occupationally for heavy metals such as mercury, lead and manganese and for a monomer such as styrene. In the case of solvents, neurotoxicity is most widely accepted non-occupationally in the case of solvent (toluene) sniffers. Neurotoxicity has been more difficult to demonstrate consistently in the occupational setting where exposures are lower and over long periods. Where findings have been positive, a mixture of solvents has been implicated.

The ability to make a clinical diagnosis of solvent related neurological disease requires:

• an ability to take an occupational and exposure history based on an understanding of the ways solvents are used and may be absorbed into the body
• an understanding of the neurological effects associated with solvent exposure including exposure-response relationships
• the ability to carry out or to obtain by referral a full neurological evaluation, including the exclusion of non-occupational disease
• the ability to obtain by referral neurobehavioural testing, ideally from someone with an interest in occupational neurotoxicity.

Activity:

Read the articles from the ILO Encyclopaedia on "Chemical neurotoxic agents" by Arlien-Soborg and Simonsen, and on "Manifestations of acute and chronic early poisoning" by Mergler.  All the tables and figures referred to below are to be found in the ILO Encyclopaedia.

There is some overlap between these two articles, but together they provide a useful general review of the subject of chemical neurotoxicity. They cover acute and chronic poisoning, and the whole range of neurotoxins (not only solvents).

Figure 7.7    summarises the effects of chemicals on the nervous system.  Table 7.6  lists organic solvents that have been associated with neurotoxicity (acute and chronic; central and peripheral).

 Table 7.2 posits a spectrum of effect from early/mild/reversible to late/severe/irreversible changes. An equivalent schema for staging clinical findings  is in use.

Table 7.9 shows a questionnaire for evaluation of symptoms of neurotoxicity in both clinical and epidemiological approaches. This is an extension of the Swedish Q16 questionnaire (which has 16 questions) which has been shown in studies to be a useful instrument although lacking somewhat in both sensitivity and specificity.

Table 7.10 shows a profile of neurobehavioural deficits linked to neurotoxic exposures. It is apparent that organic solvent neurotoxicity involves almost all modalities of central nervous functioning as well as effects on the peripheral nervous system.

Activity:

Read the article from the ILO Encyclopaedia on "Measuring neurotoxic deficits" by Mergler.

Table 7.12 shows two examples of test batteries for measuring some of the outcomes of neurotoxic exposures on the central nervous system. Of particularly interest is the World Health Organsation Neurobehavioural Core Test Battery (WHO-NCTB) which was specifically developed to assist comparison of epidemiologic studies and to be of use both in the developing country and developed country settings.

Activity:

• Read the article by Nell et al. which covers the social determinants of performance with neurobehavioural tests and the impact of culture, language, educational level and level of development in general, which all effect individual and group performance in neurobehavioural tests. This makes it difficult to use many of the test batteries as they are culturally embedded and do not transfer easily for use in other settings.
   
• View brief descriptions of selected tests from the WHO-NCTB in computer and "pencil and paper" format.
   
• See also the comparative table for the mean performance of different groups of exposed workers on important tests modalities for subjects in countries with high and low levels of development.

At the individual level, clinical diagnosis is also made difficult by considerable variability. Additionally, when confronted by one individual it is always difficult to interpret neurobehavioural test results, even if there are appropriate reference values or norms that may be applicable in the case of that individual. Ultimately, clinicians will need to rely on the diagnostic skills and judgement of an experienced neuropsychologist. A useful rule of thumb for clinical diagnosis of an abnormal test result where reference values (e.g. the table and the literature) are available is to use the mean value plus or minus 2 standard deviations to recognize outliers.

REFERENCES:

Required Readings:

1. Arlien-Soborg P, Simonsen L. Chemical neurotoxic agents. International Labour Organisation (ILO) Encylcopaedia of Occupational Health and Safety. Fourth Edition. JM Stellman (Ed). 2000. Volume 1. pp 7.8 - 7.13.
2. Mergler D. Manifestations of acute and early chronic poisoning. International Labour Organisation (ILO) Encylcopaedia of Occupational Health and Safety. Fourth Edition. JM Stellman (Ed). 2000. Volume 1. pp. 7.13- 7.17.
3. Mergler D. Measuring neurotoxic deficits. International Labour Organisation (ILO) Encyclopaedia of Occupational Health and Safety. Fourth Edition. JM Stellman (Ed). 2000. Volume 1. pp 7.20 - 7.22.
4. Nell V, Myers J, Colvin M, Rees D. Neuropsychological assessment of organic solvent effects in South Africa: Test selection, adaptation, scoring and validation issues. Environ Res 1993; 63:301-318.
5. Feldman RG, Ratner MH, Ptak T. Chronic toxic encephalopathy in a painter exposed to mixed solvents. Environ Health Perspectives 1999; 107:417-422.

Optional Readings:

1.  Myers JE, Nell V, Colvin M, Thompson ML. Neuropsychological function in solvent exposed South African paintmakers. Journal of Occupational and Environmental Medicine 1999;41(11):1011-1018.
   
   This study of paint manufacturing workers exposed to mixed organic solvents illustrates how exposures can be measured and related to neurobehavioural test results.

Postgraduate Diploma in Occupational Health (DOH) - Modules 3: Occupational Medicine & Toxicology (Basic) by Profs Mohamed Jeebhay and Rodney Ehrlich, Health Sciences UCT is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 2.5 South Africa License. Major contributors: Mohamed Jeebhay, Rodney Ehrlich, Jonny Myers, Leslie London, Sophie Kisting, Rajen Naidoo, Saloshni Naidoo. Source available from here. For any updates to the material, or more permissions beyond the scope of this license, please email healthoer@uct.ac.za or visit www.healthedu.uct.ac.za. Last updated Jan 2007.
Disclaimer note: Some resources and descriptions may be out-dated. For suggested updates and feedback, please contact healthoer@uct.ac.za.