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Metabolism and disposition of difluoromethane (HFC32) in the mouseZeneca Central Toxicology Laboratory, Alderley Park, Macclesfield, SK10 4TJ
Zeneca Central Toxicology Laboratory, Alderley Park, Macclesfield, SK10 4TJ
ICI Chemicals and Polymers Ltd., PO Box 13, Runcorn, WA8 4QF, UK
Zeneca Central Toxicology Laboratory, Alderley Park, Macclesfield, SK10 4TJ 1 Difluoromethane (HFC32) is under development as a replacement for chlorofluorocarbons (CFCs) in some refrigeration applications. 2 The metabolism and disposition of [14C]-difluoro methane ([14C]-HFC32) was determined in male Swiss mice as a consequence of a single 6 h inhalation exposure to atmospheres of 10 000 p.p.m. 3 Of the inhaled dose, about 1-2% was recovered in expired air, urine, faeces and carcass suggesting that systemic absorption of this hydrofluorocarbon from the alveolar air space of the lung into blood is poor. Upon cessation of exposure the majority of the systemically absorbed HFC32 was exhaled within 1 h. 4 Carbon dioxide was a major metabolite of HFC32. Carbon dioxide measured post-exposure accounted for about 0.3% of the inhaled dose. Urinary and faecal excretion of non-volatile metabolites accounted for about 0.34% and 0.07% of the inhaled dose, respec tively. 5 Carbon monoxide could not be detected. 6 Total metabolism, measured as the sum of the radio activity recovered in urine, faeces, as carbon dioxide and that retained in the carcass, amounted to about 0.8% of the inhaled dose, equivalent to 64% of the total radioactivity recovered. 7 Analysis of a range of tissues at 4 days post-exposure showed a relatively uniform distribution of radio activity with the highest concentration in the lung, liver and kidney. There was no evidence of a specific retention in any organ or tissue.
Key Words: difluoromethane inhalation mouse metabolism disposition
Human & Experimental Toxicology, Vol. 15, No. 7,
592-596 (1996) |
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