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HYDROFLUOROCARBON-404A 45 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.
HYDROFLUOROCARBON-404A 46 The subcommittee divided the NOAEL by an uncertainty factor of 10 to account for interspecies variability, because there are no human data on HFC-143a, for a 1-hr EEGL of 25,000 ppm. TABLE 4-1 Summary of Noncancer Toxicity Information for HFC-143a Species Exposure End Point NOAEL, LOAEL, Reference Frequency ppm ppm and Duration Acute Toxicity Rat 4 hr No 540,000 ND Brock et significant al. 1996 effect Dogs 10 min Cardiac 250,000 300,000 Brock et sensitization al. 1996 Subchronic Toxicity Rat 6 hr/d, 5 Testicular ND 2,000a Brock et d/wk for changes al. 1996 4wk Rat 6 hr/d, 5 No 40,000 ND Brock et d/wk for significant al. 1996 4wk effect Rat 6 hr/d, 5 No 40,000 ND Brock et d/wk for significant al. 1996 90 d effect Developmental Toxicity Rat 6 hr/d, Maternal 40,000 ND Brock et gestation toxicity al. 1996 d 6-15 Fetal 40,000 ND toxicity Rabbit 6 hr/d, Maternal 40,000 ND Brock et gestation toxicity al. 1996 d 6-18 Fetal 40,000 ND toxicity 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.