Peak exposures to organic solvents

Exposures at work to volatile organic solvents may cause chronic toxic encephalopathy (CTE), a disease characterised by brain disturbances, concentration loss, fatigue, mental inertia, headache, depression and irritability. Volatile organic solvents are a vast class of hydrocarbons, including oxygenated and halogenated compounds. Many of the solvents on the market are mixtures specially produced for the different outlets such as paints, inks, glues, cleaning agents and many others.

The occurrence of CTE was first described in Scandinavian literature for painters, car mechanics, metalworkers and workers in the boat building industry in the late 1970's. The biological mechanism explaining the relationship between solvent exposures and the development of CTE has not been elucidated. At present there is consensus among occupational toxicologists that chronic exposures to concentrations below the occupational exposure limits (OEL's) will not enhance the risk of developing CTE. This is in agreement with the results of the toxicological and neurotoxicological assessments made for the main components in organic solvents. Epidemiological studies on workers from the relevant professions often report experiences like 'feelings of drunkenness' directly following exposures to organic solvents. On this basis it has been hypothesised that repeated short-term high exposures (so-called peak exposures) may be an important factor in the development of CTE.

In this light the State Secretary for Social Affairs an Employment requested the Health Council to report on the implications of peak exposure to organic solvent vapours, in particular in relation to the development of CTE, whether a limitation of peak exposure is necessary and whether there exists a generic methodology to determine short-term limit values that may assist in limiting the risks of peak exposures. The TNO Food and Nutrition Organisation was requested to report on latest developments in the literature on peak exposure and the development of CTE. The TNO report has been attached to the present report as an appendix. It provides relevant information on experiments with human volunteers, on epidemiological studies, on health effects with glue-sniffers, on animal studies, and on the occurrence of peak exposures to solvent vapours at work. In addition physiologically based pharmacokinetic modelling was carried out to describe the biochemical fate of four important solvent molecules in the human body (so called PBPK studies).

The overall conclusion in the TNO report confirms the premise that data that could explain specifically the relationship between peak exposures to organic solvent vapours and the occurrence of chronic neurotoxicological effects, including CTE, are not available. Occupational hygiene data show that peak exposures for solvent molecules do occur and the maximum concentration in the peaks sometimes are ten times or more the existing OEL limits. PBPK studies show the internal concentrations of a substance in blood and the brain follow the development of the external concentration with a certain lag-time. Information obtained on glue-sniffers indicate there could be a relationship between acute physiological effects immediately following sniffing of solvents from the glue and the development of chronic neurological effects. With glue-sniffers the health effects are much more serious than the CTE effects observed in workers.

The committee concluded there probably is a relationship between peak exposures to organic solvents and the development of CTE, however a biological mechanism explaining this relationship is not available. This assumption, however plausible, can neither be denied nor accepted on the basis of the available information. In case peak exposures clearly cause CTE it still is not clear whether the total dose or the maximum concentration determines the development of CTE. Further complicating factors in the interpretation of the available data are the complex composition of many solvents and differences in susceptibility of individuals to exposure to organic solvents. Notwithstanding the committee is of the opinion that peak exposures would provide an important additional source of exposure to organic solvents and its reduction may contribute to the reduction of the risk for CTE.

The committee recommends to further specify the present guidance on short-term exposure in the guideline of the Labour Inspectorate:

- a peak exposure should be defined as the mean exposure over a period of 15 minutes
- a peak exposure above two times the OEL value should not occur
- within a peak exposure the maximum concentration should not exceed a value of ten times the OEL-value
- during a working day the number of peak exposures should be limited to only four and the interval between two peak exposures should at least be one hour.
The committee advises to study more closely the characteristic exposure patterns for solvent vapours in the different professions. Better understanding of the causes of CTE such as the development of peak exposures, could help the management as well as workers in preventing exposures. The committee is of the opinion that attention should be given to early diagnosis of symptoms of CTE among workers, to prevent further development of CTE. This may be important for those with a higher susceptibility. PBPK studies on the relationship between peak exposures and the biochemical fate of the components of a solvent mixture in the body fluids of the human body could help in understanding the mechanisms that may lead to neurotoxicological effects, including CTE.