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Suggested Citation:"Carcinogenicity." 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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Page 33

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HYDROFLUOROCARBON-23 33 Tice (1996a) conducted a mouse bone-marrow micronucleus assay on HFC-23 by exposing groups of five B6C3F1 mice per sex to concentrations ranging from 130,000 to 500,000 ppm for 6 hr per day for three consecutive days. That exposure was followed by a single sample time 24 hr after the final exposure. Positive and negative controls were included in the study. The results indicate that HFC-23 did not significantly increase the frequency of micronucleated polychromatic erythrocytes (PCEs) in the bone marrow of male or female mice or significantly affect the percentage of PCEs in either sex. Andrews (1996b) evaluated the ability of HFC-23 to induce gene mutations in the guanine phosphoribosyl-transferase (gpt) locus of cultured AS52 Chinese hamster ovary (CHO) cells in the presence or absence of metabolic activation. The cells were exposed to HFC-23 in concentrations ranging from 500,000 to 1,000,000 ppm for 5 hr. Positive and negative controls were included in the study. The results indicate that HFC-23, in either the presence or the absence of metabolic activation, did not induce a significant increase in the mutant frequency at the gpt locus in cultured AS52 cells. Tice (1996b) evaluated the potential of HFC-23 to induce structural chromosomal damage in cultured CHO cells in both the absence and the presence of metabolic activation. The cells were exposed to HFC-23 in concentrations ranging from 500,000 to 1,000,000 ppm for 4 hr. Positive and negative controls were included in the study. HFC-23 induced a significant increase in clastogenic damage at concentrations in air ranging from 800,000 to 1,000,000 ppm in the absence of metabolic activation. Under those same conditions, 100% nitrogen induced a significant increase in chromosomal damage to the same magnitude, suggesting the possibility that the response might reflect changes in oxygen concentrations rather than HFC-23 specifically. In the presence of metabolic activation, HFC-23 and 100% nitrogen induced an increase in chromosomal damage that was not statistically significant. On the basis of the available data, the subcommittee concludes that HFC-23 is not genotoxic and is unlikely to induce heritable effects in humans. Carcinogenicity No chronic exposure or carcinogenicity studies of HFC-23 are currently available.

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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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