Although airborne chemicals can cause a number of harmful effects, the most common effect is sensory irritation (De Ceaurriz et al. 1981). Exposure to a sensory irritant may stimulate the trigeminal nerve endings and laryngeal receptors, eliciting any one or a combination of the following symptoms: burning sensation of the eyes, nose, or throat, as well as coughing sensations (Alarie et al. 2000). Sensory irritation is also the most common end point for occupational exposure levels (OELs). For one specific OEL measure, threshold limit values (TLVs) [developed by the American Conference of Governmental Industrial Hygienists (ACGIH 2006)] are calculated based on sensory or pulmonary irritation for > 50% of the compounds. Kane et al. (1979) reported that approximately two-thirds of the compounds for which they found a TLV acted as sensory irritants. A qualitative evaluation of sensory irritants indicated that sensory irritation responses in the mouse are predictive of responses in humans (Alarie 1973a). In 1966, Alarie initially proposed the use of an animal test to evaluate the potency of airborne sensory irritants. The bioassay uses male Swiss-Webster mice to measure decreases in respiratory frequency resulting from exposure to a geometric series of concentrations of airborne irritants (Alarie 1966). The concentration inducing a 50% decrease in respiratory frequency is termed the RD50. From these measured RD50s, Alarie (1981b) ranked irritant potencies and found a good correlation (R2) between RD50s and TLVs. The Alarie test evolved over the years and was adopted in 1984 as a standard test by the American Society for Testing and Materials (ASTM 2004). The “RD50 test” or the “Standard Test Method for Estimating Sensory Irritancy of Airborne Chemicals” (ASTM 2004) quantitatively measures irritancy as indicated by the reflex inhibition of respiration in mice exposed to sensory irritants. For the test, four mice are first acclimatized to the chamber and are then simultaneously exposed to the airborne chemical. A sufficient number of groups are exposed to a geometric series of concentrations so that a concentration–response curve can be constructed from the analysis. The mice are placed in a body plethysmograph attached to an exposure chamber so that only the head is exposed to the test material. The plethysmographs are connected to pressure transducers, which sense changes created by inspiration and expiration. The amplified signals are transmitted to a polygraph recorder. The concentration of airborne irritant that produces an RD50 is determined from the concentration–response curve constructed from the various data points obtained with a series of concentrations. Sensory irritation is a reflex reaction from stimulation of the trigeminal or laryngeal nerve endings (Boylstein et al. 1996). The sensory irritant response is mediated through binding to the trigeminal nerve receptors and appears to follow Michaelis-Menten receptor kinetics. Although the RD50 concentration has been described as “intolerable” to humans, as indicated in the ASTM standard, “the test method will detect irritation effects at concentrations far below those at which pathological changes are observed” (Alarie 2000; ASTM 2004). Further, as demonstrated by Barrow et al. (1986), pathologically detectable responses are expected only after prolonged repeated exposure. RD50s are a basis, at least partially, for a number of OELs by ACGIH (ACGIH 2006). The calculation methodology is based on Kane et al. (1979), who evaluated data from 11 sensory irritants and concluded that a level one-hundredth of the RD50 would produce “minimal or no sensory irritation” in humans. The current suggestion of setting OELs at 0.03 RD50 comes from Alarie (1981a, 1981b), because 0.03 RD50 is halfway between 0.1 RD50 and 0.01 RD50 on a logarithmic scale. Alarie (1981a) reported a strong correlation (R2 = 0.89) between 0.03 RD50 and OELs for the 26 chemicals tested. Subsequently, both analyses, one using 41 chemicals (Alarie and Luo 1986) and most recently another using 89 chemicals (Schaper 1993), resulted in a lower but still strong correlation (R2 = 0.78). Although most of the applications of the RD50 have focused on OELs, Nielsen et al. (1995) found that protection against indoor sensory irritation effects could be achieved at a level of 0.025–0.25 of the OEL. Multiple studies show strong correlations between RD50s and OELs, supporting the continued use of the Alarie test for establishing OELs (Kane et al. 1979, 1980; Schaper 1993). In this study we examined the relationship between RD50s 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. We also analyzed the relationship between RD50s and OELs for identified human sensory irritants. Finally, we evaluated the relationship between RD50s and acute reference exposure levels (RELs) developed to protect the public (Collins et al. 2004). RELs are defined as “[t]he concentration level at or below which no adverse health effects are anticipated for a specified exposure duration [1 hr for the acute RELs]. … RELs are based on the most sensitive, relevant, adverse health effect reported in the medical and toxicological literature.” A strong correlation between RD50s and LOAELs, TLVs, and acute RELs will support the use of RD50s in establishing guidance levels to protect the public from sensory irritants.