Safety evaluation of carbon tetrafluoride as an inert hyperbaric breathing gas in Sprague-Dawley rats

被引:1
作者
Makowski, Matthew S. [1 ]
Sproul, Christopher [2 ]
Swartz, Carol [2 ]
Everitt, Jeffrey, I [3 ]
Knaus, Darin A. [4 ]
Wilbur, Jed C. [4 ]
Moon, Richard E. [5 ,6 ]
机构
[1] Duke Univ, Dept Med, Sch Med, Div Pulm Allergy & Crit Care Med, 2301 Erwin Rd, Durham, NC 27710 USA
[2] Integrated Lab Syst LLC, 601 Keystone Pk Dr, Morrisville, NC 27560 USA
[3] Duke Univ, Dept Pathol, Sch Med, 6 Circuit Dr, Durham, NC 27710 USA
[4] Creare LLC, 16 Great Hollow Rd, Hanover, NH 03755 USA
[5] Duke Univ, Dept Anesthesiol, Sch Med, 2301 Erwin Rd, Durham, NC 27710 USA
[6] Duke Univ, Dept Med, Sch Med, 2301 Erwin Rd, Durham, NC 27710 USA
关键词
Carbon tetrafluoride; Tetrafluoromethane; Hyperbaric; Inert breathing gas; CONTRAST AGENT; POTENCY; DNA; HEMATOLOGY; BUBBLES; DAMAGE;
D O I
10.1016/j.taap.2022.116023
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Carbon tetrafluoride (CF4) is an inert gas with higher molecular weight and lower water solubility than commonly used hyperbaric breathing gases. These inert gas properties decrease time required to decompress and avoid decompression sickness after deep dives. To assess CF4 toxicity, Sprague-Dawley rats were exposed to 8 atm absolute (ATA) air (10 males, 10 females) or 8 ATA 79% CF4/21% O-2 (25 males, 25 females). Exposures were 30 min daily for 5 days. Rat behavior was normal throughout the testing period. There were no gross or microscopic pathology abnormalities following repeat dose exposure. Male body weight trends were similar between groups. Female body weight trends were 0.5 +/- 0.8% day(-1) for hyperbaric air exposure and - 0.2 +/- 0.8% day(-1) for hyperbaric CF4 exposure (P = 0.01) but remained within literature cited norms. Organ weights and hematologic indices remained within or near literature normal ranges. Clinical chemistry panels showed no signs of toxicity in renal or hepatic biomarkers. Polychromatic erythrocyte micronucleus frequency showed no chromosomal damage. Comet assay showed no DNA damage in lung tissue. Females exposed to CF4 had 2.5 times greater percent tail DNA in liver tissue than controls (P = 0.009). However this result remained within the normal range of local negative controls. A bacterial reverse mutation assay with exposure to 1 ATA 79% CF4/21% O-2 for 72 h was nonmutagenic in four strains of Salmonella typhimurium and one strain of Escherichia coli. Overall, there was no evidence that CF4 caused organ toxicity or genetic toxicity.
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页数:14
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