more than 4 h resulted in shortness of breath and wheezing as well as serious pulmonary function changes (Rotman et al. 1983). In the D’Alessandro et al. (1996) study, there was a significant fall in FEV₁ and airway resistance immediately after exposure at 1.0 ppm in both healthy and asthmatic subjects, but the fall among asthmatic subjects was greater. Two of the subjects with airway hyper-reactivity experienced undefined respiratory symptoms following the exposure. Those subjects were not specifically identified as asthmatics. The 2-ppm concentration tested by Anglen (1981) reached nuisance levels by 4 h and was accompanied by transient changes in pulmonary functions. Joosting and Verberk (1974) did not find differences in pulmonary function after exposure at 2 ppm for 2 h; concentrations at 4 ppm for 2 h were irritating, but pulmonary function measurements were not made. Subjective sensory irritation of the throat reached an average level of “nuisance” (distinctly perceptible to offensive) at 4 ppm for 2 h; irritation of the nose and the desire to cough averaged “distinctly perceptible” (range, up to nuisance). No sensory response was reported as unbearable during these exposures. Although airflow resistance, the major pulmonary effect found in the Rotman et al. (1983) study, was not measured by Joosting and Verberk (1974), Anglen (1981) reported that the changes in other pulmonary parameters at 2 ppm for 4 or 8 h were completely reversible by the next day.

Alarie (1981), the author of the ASTM (1981) RD₅₀ test, considered the RD₅₀ for male Swiss-Webster mice to be intolerable to humans but nonlethal over a period of hours. The RD₅₀ of male Swiss-Webster mice was 9.3 ppm, as reported by Barrow et al. (1977). Lesions were present in the nasal passages, and some changes were present in the lower respiratory tract of rats exposed at 9.1 ppm for 6 h (Jiang et al. 1983). Mice “tolerated” that concentration 6 h/d for 5 d without deaths (Buckley et al. 1984). No gross or microscopic lung changes occurred in rabbits following a 30-min exposure at 50 ppm (Barrow and Smith 1975).