11

Genotoxic Effects of Military Fuel Vapors

The genotoxicity of several military fuels has been tested in bacterial and mammalian cells. Tests for genotoxicity in experimental animals have also been conducted to determine the potential of military fuel vapors to produce germ-cell effects.

ASSAY TESTING FOR GENOTOXICITY

JP-4, JP-5, JP-8, and fuels were tested for genotoxicity in a battery of assays (Brusick and Matheson, 1978). (No data are available on the genotoxicity of DFM.) In the tests on JP-8, in vitro assays used microbial and mammalian cells in culture, and in vivo assays measured potential germ-cell effects in mice and rats. JP-8 fuel did not induce mutagenicity in Salmonella typhimurium in the Ames assay; however, it did have toxic effects in most of the bac-



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Permissible Exposure Levels for Selected Military Fuel Vapors 11 Genotoxic Effects of Military Fuel Vapors The genotoxicity of several military fuels has been tested in bacterial and mammalian cells. Tests for genotoxicity in experimental animals have also been conducted to determine the potential of military fuel vapors to produce germ-cell effects. ASSAY TESTING FOR GENOTOXICITY JP-4, JP-5, JP-8, and fuels were tested for genotoxicity in a battery of assays (Brusick and Matheson, 1978). (No data are available on the genotoxicity of DFM.) In the tests on JP-8, in vitro assays used microbial and mammalian cells in culture, and in vivo assays measured potential germ-cell effects in mice and rats. JP-8 fuel did not induce mutagenicity in Salmonella typhimurium in the Ames assay; however, it did have toxic effects in most of the bac-

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Permissible Exposure Levels for Selected Military Fuel Vapors terial strains at concentrations above 1 µg per plate. In the mouse lymphoma assay, JP-8 did not induce gene mutations in L5178Y mouse lymphoma cells at the TK locus but did induce moderately toxic effects at 0.16 µL/mL. JP-8 induced significant increases of 3H-thymidine in WI-38 cells. The genotoxicity was moderate and not dose-related. There was clear evidence of cytotoxicity at 5.0 µL/mL. JP-8 was found to be negative in the dominant lethal assays in both mice and rats (Brusick and Matheson, 1978). Mice were administered 0.13, 0.4, or 1.3 mL/kg of body weight per day for 5 days. The concentrations administered to rats were 0.1, 0.3, or 1.0 mL/kg per day for 5 days. Brusick and Matheson (1978) concluded that JP-8 fuel produces a moderate increase in unscheduled DNA synthesis in WI-38 cells. That finding suggests that JP-8 could interact with DNA, producing nonspecific lesions. However, there was no evidence of mutagenicity or significant genetic risk in any of the tests. Brusick and Matheson (1978) also evaluated the genotoxicity of JP-4 fuel in the same battery of assays. JP-4 was tested for mutagenicity in the Ames assay with Salmonella typhimurium TA-1535, TA-1537, TA-1538, TA-98, and TA-100 at concentrations of 0.001, 0.01, 0.1, 1.0, or 5.0 µL per plate with and without metabolic activation. The results showed that JP-4 is not mutagenic in the Ames assay. JP-4 was also tested for mutagenicity in L5178Y mouse lymphoma cells. The cells were exposed to JP-4 at concentrations of 0.005 to 0.24 µL/mL with and without metabolic activation. JP-4 was not found to be mutagenic to the mouse lymphoma cells. JP-4 was also examined for its ability to induce unscheduled DNA synthesis in WI-38 cells (Brusick and Matheson, 1978). The cells were exposed to JP-4 at concentrations of 0.1-5.0 µL/mL with and without metabolic activation. Although JP-4 was found to alter DNA and form repairable DNA lesions, these lesions are not necessarily mutagenic. In the dominant lethal assay, JP-4 was tested at concentrations of 0.01, 0.03, or 0.09 mL/kg in mice and at concentrations of

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Permissible Exposure Levels for Selected Military Fuel Vapors 0.09, 0.3, or 0.9 mL/kg in rats. No significant dominant lethality was observed in any of the measurements. Tests on JP-5 also did not result in evidence of mutagenicity. JP-5 was tested in the Ames assay with Salmonella typhimurium TA-1535, TA-1537, TA-97, TA-98, and TA-100 at concentrations of 100-10,000 µg per plate in the presence or absence of metabolic activation systems from rat or hamster liver (NTP, 1986). CONCLUSIONS The subcommittee does not consider the vapors of the fuels JP-5, JP-8, and DFM to constitute an important genotoxic hazard.