data were considered adequate for deriving the three AEGL classifications for the five exposure periods. Regression analyses of the reported concentration-exposure durations for lethality in the animal species determined that the relationship between concentration and time is C2×t=k (where C=concentration, t=time, and k is a constant).
The AEGL-1 was based on an exposure at 3 parts per million (ppm) (range, 0.85–2.93 ppm) for 1 hour (h), which was the threshold for pulmonary inflammation, as evidenced by an increase in the percentage of several inflammatory parameters such as CD3 cells and myeloperoxidase in the bronchoalveolar lavage fluid of 20 healthy exercising adult subjects (Lund et al. 1999). There were no increases in neutrophils, eosinophils, protein, or methyl histamine at this or the next higher average exposure concentration of 4.7 ppm (range, 3.05–6.34 ppm). There were no changes in lung function and only minor symptoms of irritation at that concentration (Lund et al. 1997). Although healthy adults were tested, several individuals had increased immune factors, indicating atopy. The 3-ppm concentration was divided by an intraspecies uncertainty factor (UF) of 3 to protect susceptible individuals. Because there were no effects on respiratory parameters of healthy adults at concentrations up to 6.34 ppm in the Lund et al. (1997) study and at concentrations up to 8.1 ppm for 6 h/day (d) with repeated exposures in a supporting study (Largent 1960, 1961), the calculated AEGL-1 values will be protective of asthmatic individuals. Although the Lund et al. (1999) study duration was only 1 h, the longer exposures at higher concentrations in the supporting study (Largent 1960, 1961), and the fact that adaptation to mild sensory irritation occurs, support application of the 1-ppm concentration for up to 8 h.
The 10-minute (min) AEGL-2 was based on an absence of serious pulmonary or other adverse effects in rats during direct delivery of HF to the trachea at 950 ppm for an exposure period of 10 min (Dalbey 1996; Dalbey et al. 1998a). The reported concentration-exposure value of 950 ppm for 10 min was adjusted by a combined UF of 10–3 for interspecies variation, because the rat was not the most sensitive species in other studies (but direct delivery to the trachea is a sensitive model), and an intraspecies UF of 3 to protect susceptible individuals. The resulting 10-min value clearly is below the serious injury categories of data from tests in monkeys, rats, dogs, mice, guinea pigs, and rabbits.
The 30-min and 1-, 4- and 8-h AEGL-2 values were based on a study in which dogs exposed at 243 ppm for 1 h exhibited blinking, sneezing, and coughing (Rosenholtz et al. 1963). Rats exposed at a similar concentration (291 ppm) developed moderate eye and nasal irritation. The next higher