Interspecies: 3. Based on LC50 values in the same studies, the rat was approximately three times less sensitive than the mouse to the lethal effects of hydrogen fluoride; however, the delivery of hydrogen fluoride directly to the trachea via oral cannulation is a conservative model.

Intraspecies: 3. Oral cannulation maximizes the dose to the lungs and is relevant to mouth breathing humans.

30-min and 1-, 4-, and 8-h AEGL-2 values

Total uncertainty factor: 3

Interspecies: 1. Based on LC50 values, the mouse was the most sensitive of three tested species; of several studies involving the mouse, this study had the lowest lethal values.

Intraspecies: 3. Application of a greater uncertainty factor would reduce concentrations to those found only slightly irritating in human studies.

Modifying factor: For 30-min and 1-, 4-, and 8-h AEGL-2 values, 2. The highest non-lethal value was close to the LC50 value

Animal to human dosimetric adjustment: Insufficient data

Time-scaling: Cn×t=k where n=2 based on regression analysis of rat LC50 studies conducted at time periods of 5, 15, 30, and 60 min. A second study using rabbits and guinea pigs and conducted over time periods of 5 min to 6 h resulted in the same value for n (reported in a third study). End points for the second study were both irritation and death. Because the time-scaled 8-h AEGL-3 value of 15 ppm was inconsistent with results of longer-term studies with monkeys and rodents, the 8-h value was set equal to the 4-h value.

Data adequacy: There is considerable support for the AEGL-3 values as the database for hydrogen fluoride is extensive with multiple studies of lethality conducted at several exposure durations and involving five species of mammals (monkey, rat, mouse, guinea pig, and rabbit). Studies with multiple dosing regimens generally showed a clear dose-response relationship. A few longer-term studies were also available and served as supporting data. Tissue and organ pathology indicated that the toxic mechanism was the same across species. Difficulties in maintaining/measuring exposure concentrations were encountered in some of the studies; studies in which these difficulties were described were not used to derive AEGL values.

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