Morbidity and mortality resulting from acute inhalation exposures to hydrogen fluoride and carbonyl fluoride in rats

Abstract

Objective: Experiments were undertaken to compare morbidity and mortality from brief inhalation exposures to high levels of hydrogen fluoride (HF) and carbonyl fluoride (COF₂).

Methods: Rats from both sexes were exposed for durations of 5 and 10 min to nominal concentrations of 10,000 to 57,000 ppm HF or 500 to 10,000 ppm COF₂. Respiration was monitored before, during, and after exposure. Animals were observed up to 6 days post-exposure. Terminal blood samples were collected for routine clinical chemistry and hematology. Post-mortem lung fluoride concentrations and lung weights were measured, and gross pathology noted.

Results: Both gases produced respiratory depression independent of concentration or exposure duration with minute ventilation decreasing to approximately 50% of baseline. Estimated mixed-gender HF and COF₂ 10-min LC₅₀’s were 48,661 ppm and 1083 ppm, respectively. HF mortalities were generally delayed 3 to 4 days post-exposure, while COF₂ mortalities occurred during or briefly after exposure. Lung fluoride levels increased with COF₂ dose, though elevated lung weights occurred only at the mid-level exposures. Lung weights were unaffected in the HF-exposed animals, and their lung fluoride concentrations were variable. Clinical chemistry and hematology had few consistent trends with the exception of hemoconcentration primarily in HF-exposed males. These short-term exposure experiments conclude that COF₂ is nearly 45 times more lethal than HF in rats.

Conclusions: These experiments suggest that hydrolysis to HF cannot solely explain COF₂ toxicity. Although HF and COF₂ may have common injury mechanisms, they are expressed to markedly different degrees and temporal occurrence.

Keywords:

• Hydrogen fluoride
• carbonyl fluoride
• inhalation
• rats
• toxicity
• LC₅₀

Acknowledgements

The study would not have been possible without the help and support Robyn Lee (APHC) and Brian C. Veety (Aberdeen Test and Evaluation Center). The authors also gratefully acknowledge Dr. Mark S. Johnson for the technical review of this report. The opinions or assertions contained herein are the private views of the authors, and are not to be construed as official, or as reflecting true views of the Department of the Army or the Department of Defense. The studies reported herein were performed in animal facilities fully accredited by the American Association for the Accreditation of Laboratory Animal Care.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research was funded by the United States Army Research Development and Engineering Command.