Occupational exposure limit variability and hazard characterization alignment—implications for protection from respiratory irritation

The primary purpose of this study was to examine patterns in the reliance on respiratory tract irritation as a toxicological basis for occupational exposure limits (OELs), focused on U.S.-based OELs. This study pursued three aims: (1) to evaluate the degree to which OELs are based on respiratory irritation, or more broadly, on respiratory effects; (2) to assess the variability in the OEL values across organizations; and (3) to determine how well surrogate endpoints align with respiratory irritation for OELs having respiratory tract effects as their critical effect. To address these aims, a database was developed that listed the chemical OELs from the German MAK (Maximale Arbeitsplatz-Konzentration) Commission, U.S. National Institute for Occupational Safety and Health (NIOSH), U.S. Occupational Safety and Health Administration (OSHA), California OSHA, American Conference of Governmental Industrial Hygienists (ACGIH®), and the Workplace Environmental Exposure Levels Committee (WEEL; initially derived under the American Industrial Hygiene Association (AIHA®), and after 2012 via Toxicology Excellence for Risk Assessment (TERA)). Information on inhalation toxicity, specifically respiratory irritation, was also included. Analyses of the collated data found the following. Most chemicals in the database with at least one OEL had three or four OELs from different organizations; there was variability among the OEL numeric values, but most chemicals differed by a factor of less than 10. The respiratory tract was the site of the critical or co-critical effect (i.e., the one occurring at the lowest concentration) for ∼50% of the chemicals in the database, illustrating the importance of consideration of this target organ in OEL development. Inconsistencies between GESTIS-curated Globally Harmonized System (GHS) Hazard (H) codes and OEL documentation regarding respiratory effects were identified, suggesting that the potential for respiratory effects may not be adequately addressed in assigning H codes. Neither skin nor eye irritation-related H codes are sufficiently sensitive to predict potential respiratory irritation, so other surrogate measures are needed to evaluate the potential to cause respiratory irritation of chemicals for which inhalation toxicity data are not available.