The Use of Information on Upper Respiratory Tract Irritation and Acute Central Nervous System Depression to Set Occupational Exposure Limits for Hydrocarbon Solvents

Hydrocarbon solvents are liquid hydrocarbon fractions, often with complex compositions. Because of the potential for human exposure, primarily to the more volatile solvents, considerable effort has been directed towards the development of occupational exposure recommendations. Because of the complex and variable nature of these substances, the recommended approach is to calculate occupational exposure levels (OELs) using an adaptation of the mixture formula developed by the ACGIH® in which “group guidance values” are assigned to similar constituents. This approach is supported by the results of toxicological studies of hydrocarbon solvents and their constituents which have shown that, with a few, well characterized exceptions, exposures to these substances do not cause toxicologically important systemic effects. Accordingly, the effects that seem most appropriate for use in setting OELs are upper respiratory tract irritation and acute central nervous system (CNS) depression. In early studies, volunteers were exposed to these substances over a range of concentrations to identify exposure levels suitable for occupational settings. In more recent years, for ethical reasons, there has been a shift to the use of animal data to characterize these effects, particularly the potential for acute CNS effects, with volunteer studies now being used primarily to confirm that the recommended exposure levels are below effect levels. Using the data from animal studies, along with physiologically-based pharmacokinetic (PBPK models), it is possible to predict no effect levels in humans, and to then compare the predictions to empirical evidence from human studies. These comparisons provide evidence that the recommended approach to setting OELs for complex hydrocarbon solvents yields recommendations that are below the no effect levels for acute effects while also providing protection from longer term effects associated with the more problematic constituents.