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Suggested Citation:"Developmental Toxicity." National Research Council. 2000. Submarine Exposure Guidance Levels for Selected Hydrofluorocarbons: HFC-236fa, HFC-23,and HFC-404a. Washington, DC: The National Academies Press. doi: 10.17226/9815.
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HYDROFLUOROCARBON-404A 43 ered incidental. The only remarkable finding was degenerative changes in the testes of male rats in all exposure groups. No evidence of toxicity was observed in female rats. Excessive temperature conditions and problems with the proper fit of the nose-only restraint system on the animals were reported. To investigate whether the testicular changes might have been an artifact of the excessive temperature conditions, which are known to adversely affect the testes of rats and humans (Van Demark and Fre 1970), or the stress of the restraint system, another 4-week study was conducted in male rats using the same HFC-143a concentrations under normal chamber temperature conditions and without restraint (i.e., whole-body exposure system) (Brock et al. 1996). No adverse testicular effects or adverse clinical signs were observed at any exposure concentration in the study. Because of the absence of testicular changes in this study as well as in a 90-day study (discussed below), the subcommittee believes that the testicular changes observed in the first 4-week study were not caused by exposure to HFC-143a. Four groups of rats (20 of each sex) were exposed (whole body) for 6 hr per day, 5 days per week for 90 days to 0, 2,000, 10,000, or 40,000 ppm (Brock et al. 1996). Clinical signs, body weights, food consumption, clinical pathology, organ weights, and tissue histopathology were evaluated. Liver β-oxidation activity, an indicator of peroxisomal proliferation, was also measured. There were no HFC-143a-related adverse effects at any exposure level. Reproductive Toxicity No reproductive toxicity studies of HFC-143a are currently available. Developmental Toxicity Two inhalation studies, one in rats and one in rabbits, were conducted to evaluate the developmental toxicity of HFC-143a. Brock et al. (1996) exposed groups of 25 pregnant rats to HFC-143a at concentrations of 0, 2,000, 10,000, or 40,000 ppm for 6 hr per day on days 6 to 15 of gestation. 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. The number of corpora lutea and implants and the incidence of malformations and develop

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As part of the effort to phase out the use of stratospheric ozone-depleting substances, such as chlorofluorocarbons (CFCs), the U.S. Navy is considering hydrofluorocarbons (HFCs) as replacements for the CFC refrigerants used aboard its submarines. Before using the HFCs, the Navy plans to set emergency exposure guidance levels (EEGLs) and continuous exposure guidance levels (CEGLs) to protect submariners from health effects that could occur as a result of accidental releases or slow leaks.

In this report, the Subcommittee on Exposure Guidance Levels for Selected Hydrofluorocarbons of the National Research Council's (NRC 's) Committee on Toxicology independently reviews the scientific validity of the Navy's proposed 1-hr and 24-hr EEGLs and 90-day CEGLs for two of the candidate refrigerants-HFC-236fa and HFC-404a. In addition, the subcommittee reviews the the EEGLs and CEGL for HFC-23, one of the combustion products of HFC-236fa. This NRC report is intended to aid the Navy in using HFCs safely.

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