Academic journal article Environmental Health Perspectives

Evaluation and Application of the [RD.Sub.50] for Determining Acceptable Exposure Levels of Airborne Sensory Irritants for the General Public

Academic journal article Environmental Health Perspectives

Evaluation and Application of the [RD.Sub.50] for Determining Acceptable Exposure Levels of Airborne Sensory Irritants for the General Public

Article excerpt

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 [RD.sub.50]. From these measured [RD.sub.50]s, Alarie (1981b) ranked irritant potencies and found a good correlation ([R.sup.2]) between [RD.sub.50]s 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 "[RD.sub.50] 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 [RD.sub.50] 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 [RD.sub.50] 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.

[RD.sub.50]s 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 [RD.sub.50] would produce "minimal or no sensory irritation" in humans. The current suggestion of setting OELs at 0.03 [RD.sub.50] comes from Alarie (1981a, 1981b), because 0.03 [RD.sub.50] is halfway between 0.1 [RD.sub.50] and 0.01 [RD.sub.50] on a logarithmic scale. Alarie (1981a) reported a strong correlation ([R. …

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