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Suggested Citation:"Genotoxicity." 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-23 32 Developmental Toxicity Munley (1997) exposed groups of 25 mated female rats to HFC-23 at concentrations of 5,000 ppm, 20,000 ppm, or 50,000 ppm on days 7 to 21 of gestation for 6 hr per day. No evidence of any maternal or developmental toxicity was observed at any exposure concentration tested. No compound- related effects were observed on maternal body weights, weight changes, food consumption, clinical observations, or post-mortem findings. No compound- related developmental effects were observed. The end points evaluated were mean fetal weight, mean litter size, measures of pre- and post-implantation embryo lethality, and the incidences of fetal malformations and variations. Thus, the no-observed-adverse-effect level (NOAEL) is 50,000 ppm for developmental and maternal effects. Therefore, the results of this study indicate that HFC-23 is not toxic to the rat conceptus. Genotoxicity Foltz and Fuerst (1974) exposed Drosophila melanogaster to a presumably high, but unknown, concentration of HFC-23 for 10 min to assess its mutagenic potential. HFC-23 was found to significantly increase mutation rates in Drosophila progeny over the control rates. However, the investigators state that an undetermined part of the observed mutagenic effects of the gas might be due to anoxia and warrants further investigation. Lee et al. (1983) in a report of the U.S. Environmental Protection Agency gene-tox program reviewed a large number of studies on the sex-linked recessive lethal (SLRL) test for mutagenesis in D. melanogaster, including the study by Foltz and Fuerst (1974) cited above. The report categorized HFC-23 as a compound that could not be classified as positive or negative for mutagenic activity in the Drosophila SLRL test because of inadequate sample size. Andrews (1996a) conducted an Ames Salmonella typhimurium reverse mutation assay on HFC-23 by exposing five strains of the bacteria to concentrations ranging from 100,000 to 1,000,000 ppm for 24 hr. The results indicate a negative mutagenic response in all five strains both in the presence and in the absence of metabolic activation. Longstaff et al. (1984) also conducted an Ames Salmonella reverse mutation assay on HFC-23 at concentrations up to 500,000 ppm and obtained negative results in four strains of the bacteria, with and without metabolic activation.

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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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