Submarine Exposure Guidance Levels for Selected Hydrofluorocarbons: HFC-236fa, HFC-23,and HFC-404a (2000)
Chapter: Exposure Guidance Levels for HFC-143a
cultures (Longstaff et al. 1984). HFC-143a was not clastogenic in in vitro tests with cultured human lymphocytes at exposure concentrations up to 35,000 ppm (Brock et al. 1996). There was no statistically significant increase in micronuclei in bone-marrow cells of male and female mice exposed to concentrations of up to 40,000 ppm for 6 hr per day for 2 consecutive days (Brock et al. 1996).
On the basis of the available data, the subcommittee concludes that HFC-143a is not genotoxic and is unlikely to induce heritable effects in humans.
Carcinogenicity
HFC-143a was one of five fluorocarbons tested for carcinogenicity in rats (36 of each sex) using a limited bioassay design (Longstaff et al. 1984). Each fluorocarbon was dissolved in corn oil and a dose of 300 mg/kg was administered by gavage for 5 days per week for 52 weeks. Control groups consisted of an undosed group (32 per sex) and two vehicle dosed groups (36-40 per sex). Clinical signs, body weights, gross abnormalities, and tissue (lungs, liver, spleen, kidneys, and brain) histopathology were evaluated. The study was terminated at week 125. Male rats receiving HFC-143a had lower mean body weights from weeks 28 to 88. Mortality in the exposed group was similar to that in the control groups. There was no significant increase in incidence of neoplasms in any organ in the HFC-143a exposure group.
Exposure Guidance Levels for HFC-143a
A summary of the noncancer toxicity studies on HFC-143a is presented in Table 4-1. On the basis of those data, the subcommittee calculated 1-hr and 24-hr EEGLs and a 90-day CEGL for HFC-143a. Because the submariner population is all male, young, and healthier than the general population, the subcommittee did not use an uncertainty factor to account for intraspecies differences in its calculations.
For a 1-hr EEGL, a cardiac-sensitization study in dogs (Brock et al. 1996) was found to be the most appropriate for determining a NOAEL of 250,000 ppm. Because absorption of hydrofluorocarbons via the inhalation route is rapid, reaching maximal concentrations in the blood within 5 min of exposure and equilibrium within the next 15 min (Azar et al. 1973; Trochimowicz et al. 1974; Mullin et al. 1979), the NOAEL identified for cardiac sensitization following a 10-min exposure can be used without time extrapolation.
TABLE 4-1 Summary of Noncancer Toxicity Information for HFC-143a
|
Species |
Exposure Frequency and Duration |
End Point |
NOAEL, ppm |
LOAEL, ppm |
Reference |
|
Acute Toxicity |
|||||
|
Rat |
4 hr |
No significant effect |
540,000 |
ND |
Brock et al. 1996 |
|
Dogs |
10 min |
Cardiac sensitization |
250,000 |
300,000 |
Brock et al. 1996 |
|
Subchronic Toxicity |
|||||
|
Rat |
6 hr/d, 5 d/wk for 4wk |
Testicular changes |
ND |
2,000a |
Brock et al. 1996 |
|
Rat |
6 hr/d, 5 d/wk for 4wk |
No significant effect |
40,000 |
ND |
Brock et al. 1996 |
|
Rat |
6 hr/d, 5 d/wk for 90 d |
No significant effect |
40,000 |
ND |
Brock et al. 1996 |
|
Developmental Toxicity |
|||||
|
Rat |
6 hr/d, gestation |
Maternal toxicity |
40,000 |
ND |
Brock et al. 1996 |
|
d 6-15 |
Fetal toxicity |
40,000 |
ND |
||
|
Rabbit |
6 hr/d, gestation |
Maternal toxicity |
40,000 |
ND |
Brock et al. 1996 |
|
d 6-18 |
Fetal toxicity |
40,000 |
ND |
||
|
aEnd point considered to be an artifact of exposure system (nose-only exposure and excessive temperature conditions), because repeated study under normal exposure (whole body) and temperature conditions did not cause similar effects. Abbreviation: ND, not determined. |
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