Acute Exposure Guideline Levels for Selected Airborne Chemicals Volume 13 (2012) / Chapter Skim
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4 Hexafluoroacetone
4 Hexafluoroacetone
Pages 112-138
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From page 112... ...
Both the document and the AEGL values were then reviewed by the National Research Council (NRC) Committee on Acute Exposure Guideline Levels.
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From page 113... ...
Airborne concentrations below the AEGL-1 represent exposure concentrations that could produce mild and progressively increasing but transient and nondisabling odor, taste, and sensory irritation or certain asymptomatic, nonsensory effects. With increasing airborne concentrations above each AEGL, there is a progressive increase in the likelihood of occurrence and the severity of effects described for each corresponding AEGL.
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From page 114... ...
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.
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From page 115... ...
. Because of uncertainties associated with extrapolating a 4-h point of departure to a 10min exposure duration, the 10-min AEGL-3 was set equivalent to the 30-min value (NRC 2001)
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From page 116... ...
Nonlethal Toxicity No definitive data were available regarding nonlethal effects in humans following inhalation exposure to HFA. It is likely that inhaling HFA would be irritating but quantitative data are only available from an abstract reporting that exposure at 4 ppm was irritating to the upper respiratory tract (Kuznetsova 1972)
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From page 117... ...
The acute lethal toxicity of HFA and HFA nonahydrate was evaluated using groups of four ChR-CD rats exposed for 4 h (E.
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1962b. TABLE 4-4 Lethal Toxicity of Hexafluoroacetone in Male Rats After Acute Inhalation Exposure Concentration (ppm)
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From page 119... ...
1988) to determine exposures for assessing the developmental toxicity of HFA, four of six female rats exposed at 60 ppm for 6 h per day for 2 days had to be killed in extremis.
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Subsequent studies at Haskell Laboratory examined the course of testicular effects in rats exposed to HFA by inhalation (E.
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All female rats survived to scheduled sacrifice on gestation day 22, although a significant (p ≤ 0.05) decrease in body weight change relative to controls was found in the high-dose group on gestation days 17-22.
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From page 122... ...
The most prevalent nonlethal responses to HFA after inhalation exposure were lacrimation and salivation during exposure and developmental effects in rats when dams were exposed to HFA for several days during gestation. Exposure of male rats to HFA consistently resulted in testicular degeneration after multiple exposures at 12 ppm or a single 4-h exposure at 200 ppm.
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From page 123... ...
Studies described in Section 3 indicate contact irritation effects (lacrimation and signs of nasal irritation) and systemic effects (testicular atrophy, central nervous system depression, neuromuscular dysfunction, weight loss, and renal dysfunction)
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From page 124... ...
Evidence of developmental toxicity in rats occurred at lower concentrations than did testicular effects and were selected as the critical effect for development of AEGL-2 values for HFA. Exposure of dams to HFA at 6.9 ppm for 6 h/day on gestation days 7-16 resulted in a significant decrease in the number of live fetuses per litter, total resorptions per litter, and mean fetal weight, and exposure at 1 ppm resulted in a slight decrease in mean fetal weight (E.
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From page 125... ...
For time scaling from the 6-h experimental duration to AEGL-specific durations, the equation Cn × t = k was applied. The value of n was empirically determined from the available data to be 1 (ten Berge et al.
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From page 126... ...
A factor of 3 was applied to account for uncertainties associated with extrapolating animal data to human exposure conditions. A factor of 3 was applied to account for individual variability, because HFA does not appear to undergo significant metabolism.
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From page 127... ...
Additionally, the Health Council of the Netherlands Committee on Updating of Occupational Exposure Limits developed an occupational exposure limit of 0.05 mg/m3 (≈0.0075 ppm) for HFA and its hydrates on the basis of HFA-induced developmental toxicity (Health Council of the Netherlands 2001)
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From page 128... ...
c TLV-TWA (threshold limit value - time weighted average, American Conference of Governmental Industrial Hygienists [ACGIH 2003]
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From page 129... ...
1988. Pilot Developmental Toxicity Study of Hexafluoroacetone in the Rat - Summary of Reproductive Outcome with Attached Letter and Receipt Dated April 13, 1988 and Cover Letter Dated 122988.
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From page 130... ...
2001. Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals.
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From page 131... ...
Critical effect: A significant (p ≤ 0.05) decrease in live fetuses per litter, total resorptions per litter, and mean fetal weight was observed in pregnant rats exposed to HFA at 6.9 ppm for 6 h/day on gestation days 7-16.
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From page 132... ...
Critical effect: No lethality in male rats exposed at 200 ppm for 4 h.
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From page 133... ...
. 3 for intraspecies variability; HFA does not appear to undergo significant metabolism and a larger adjustment would result in exposure concentrations below those shown to be nonlethal in multiple-exposure rat and dog studies (E.
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From page 134... ...
. According to this concept, exposure concentration and exposure duration may be reciprocally adjusted to maintain a cumulative exposure constant (k)
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From page 135... ...
(1986) of LC50 data for certain chemicals revealed chemical-specific relationships between exposure concentration and exposure duration that were often exponential.
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From page 136... ...
Uncertainty factors/Rationale: Total uncertainty factor: 30 Interspecies: 10 to account for extrapolating animal data to human exposure conditions. Intraspecies: 3 for intraspecies variability, because HFA does not appear to undergo significant metabolism and because the fetus is considered a sensitive target.
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From page 137... ...
Uncertainty factors/Rationale: Total uncertainty factor: 10 Interspecies: 3 was applied to account for uncertainties associated with extrapolating animal data to human exposure conditions; no irreversible effects were observed in studies of rats and dogs exposed to HFA at 12 ppm for up to 13 weeks (6 h/day, 5 days/week)
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From page 138... ...
Because of uncertainties in extrapolating from the experimental exposure durations to 10 min, the 30-min AEGL-2 and AEGL-3 values were set equivalent to the respective 30min values. AEGL-1 values were not recommended because of insufficient data.
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