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HYDROFLUOROCARBON-404A 44 mental variations in the fetuses were not statistically significant. However, there was a significant increase in the mean percentage per litter of visceral variations due to retarded development in all the test groups. When these anomalies were combined for visceral, skeletal, and external variations, a statistically significant increase was found only at the highest concentration. However, the increase appeared to be a reflection of an unusually low incidence (1.6%) of variations in the control group (the range in historical controls was 6.8% to 16.2%). Because of that, the investigators did not consider the observed anomalies to be compound related. No external variations were observed in any group. In a study with rabbits, groups of 24 pregnant animals were exposed to HFC-143a at concentrations of 0, 2,000, 10,000, or 40,000 ppm for 6 hr per day on days 6 to 18 of gestation (Brock et al. 1996). There were no signs of maternal toxicity during or after exposure, nor were there any significant changes in body weight, body-weight gains, or food consumption throughout the study. However, there was a slight increase in the incidence of combined malformations, expressed as mean percentage per litter, in the litters of the 2,000-ppm and 40,000-ppm groups. The increase appeared to be primarily due to increases in skeletal malformations (expressed as percentage incidence per litter); increases of 1.5%, 7.5%, 3.4%, and 6.3% were found in the control, 2,000-ppm, 10,000-ppm, and 40,000-ppm groups, respectively. Because no clear concentration response was found, however, in either the types or the numbers of malformations and the incidence was within the range of historical controls (0-12.9%), the investigators did not consider the malformations to be compound related. No statistically significant increase in the incidence of soft tissue or external malformation was found compared with controls. Genotoxicity Ames Salmonella reverse mutation assays were conducted in three independent laboratories using a modified experimental design for testing HFC-143a gas (Longstaff et al. 1984; Brock et al. 1996). In one laboratory, HFC-143a was mutagenic in two of four Salmonella strains tested (TA1535 and TA100). HFC-143a was not mutagenic in tests performed at the other two laboratories that used four to five Salmonella strains, including TA1535 and TA100. It was also negative in an Escherichia coli strain (WP2uvrA) assay system which detects DNA damage and repair. HFC-143a was negative in a cell-transformation (Styles) assay using BHK21