available toxicity studies are indicative of contact irritation (lacrimation and signs of nasal irritation), as well as systemic effects (testicular atrophy, central nervous system depression and neuromuscular dysfunction, weight loss, and renal dysfunction).

Neither qualitative nor quantitative data were available for development of AEGL-1 values for HFA, so no values were established.

Few studies on HFA relevant to AEGL-2 effects were available. Several studies reported reproductive toxicity in male rats after acute inhalation exposure to HFA, and developmental toxicity after female rats were exposed during gestation. Testicular atrophy observed in male rats appeared to be reversible after exposure was stopped. Developmental toxicity was selected as the critical effect for developing AEGL-2 values because those effects occurred at concentrations lower than those linked with testicular effects. Specifically, exposure of pregnant rats to HFA at 1 ppm for 6 h/day on gestation days 7-16 resulted in a slight decrease in mean fetal weight. In the absence of notable maternal toxicity, these findings suggest that the fetus is more sensitive to HFA exposure. A concentration of 1 ppm was selected as the point of departure for calculating AEGL-2 values, under the assumption that a single 6-h exposure during gestation could be responsible for the observed effects. A total uncertainty factor of 30 was applied. A factor of 10 was use to account for uncertainties associated with extrapolating animal data to human exposure conditions. An uncertainty factor of 3 was used for intraspecies variability because HFA does not appear to undergo significant metabolism and because the fetus is considered a sensitive target. Further adjustment was considered unnecessary because of the assumption that the observed effects were the result of a single 6-h exposure during the 10-day gestational exposure period. Time scaling from the 6-h experimental duration to AEGL-specific durations was performed using the equation Cn × t = k; n = 1 was empirically determined from available data (ten Berge et al. 1986). Because of the uncertainty associated with extrapolating a 6-h point of departure to a 10-min exposure duration, the 10-min AEGL-2 value was set equivalent to the 30-min value (NRC 2001).

Studies in rats by E. I. du Pont de Nemours & Co. provided the most comprehensive data from which to develop AEGL-3 values. Two reports (E. I. du Pont de Nemours & Co. 1962a,b) showed that 4-h exposure of rats to HFA at 200 ppm (300 ppm for the nonahydrate) was without lethality and that mortality increased to 50% at 300 ppm (50-75% at 400 ppm for the HFA nonahydrate). The concentration of 200 ppm was selected as the point of departure for AEGL-3 development. An uncertainty factor of 3 was applied to account for uncertainties associated with extrapolating animal data to human exposure conditions. A factor of 3 was used for intraspecies variability because HFA does not appear to undergo significant metabolism. Further adjustment in calculating the AEGL-3 values did not appear justified because the values would similar to or below concentrations shown to be nonlethal in 13-week rat and dog studies (E. I. du Pont de Nemours & Co. 1971). Time scaling from the 4-h experimental duration to AEGL-specific durations was performed using the equation Cn × t = k; n = 1



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