Evaluation and application of the RD50 for determining acceptable exposure levels of airborne sensory irritants for the general public

Abstract

Background: The RD(50) (exposure concentration producing a 50% respiratory rate decrease) test evaluates airborne chemicals for sensory irritation and has become an American Society for Testing and Materials (ASTM) standard method. Past studies reported good correlations (R(2)) between RD(50)s and the occupational exposure limits, particularly threshold limit values (TLVs).

Objective: The main purpose of this study was to examine the relationship between RD(50)s and human sensory irritation responses in a quantitative manner, particularly for chemicals that produce burning sensation of the eyes, nose, or throat, based on lowest observed adverse effect levels (LOAELs) reported for human subjects.

Methods: We compared RD(50)s with LOAELs and acute reference exposure levels (RELs). RELs, developed by the California Environmental Protection Agency's Office of Environmental Health Hazard Assessment, represent a level at which no adverse effects are anticipated after exposure. We collected RD(50)s from the published literature and evaluated them for consistency with ASTM procedures. We identified LOAELs for human irritation and found 25 chemicals with a corresponding RD(50) in mice.

Discussion: We found the relationship between RD(50)s and LOAELs as log RD(50) = 1.16 (log LOAEL) + 0.77 with an R(2) value of 0.80. This strong correlation supports the use of the RD(50) in establishing exposure limits for the public. We further identified 16 chemical irritants with both RD(50)s and corresponding acute RELs, and calculated the relationship as log RD(50) = 0.71 (log REL) + 2.55 with an R(2) value of 0.71. This relationship could be used to identify health protective values for the public to prevent respiratory or sensory irritation.

Conclusion: Consequently, we believe that the RD(50) has benefits for use in setting protective levels for the health of both workers and the general population.

Keywords: Alarie test; LOAEL; RD50; REL; TLV; exposure levels; sensory irritation.

Figure 1

Linear least-squares regression analysis for log RD₅₀ (for all mouse strains) vs. log LOAEL (human irritation end points) for 25 compounds, using 195 data points. Log RD₅₀ = 1.16(log LOAEL) + 0.77; R ² = 0.80.

Figure 2

Linear least-squares regression analysis for log RD₅₀ (mice) vs. log REL (set by OEHHA for airborne toxicants) for 16 compounds. Log RD₅₀ = 0.71(log REL) + 2.55; R ² = 0.71.

Figure 3

Linear least-squares regression analysis for log RD₅₀ (male mice) vs. log TLV for 24 compounds (no TLV for n-pentanol). Log RD₅₀ = 0.86(log TLV) – 1.13; R² = 0.86.