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Title: The biological fate of some chlorofluoroalkanes
Author: Cox, Peter John
ISNI:       0000 0001 3393 7180
Awarding Body: University of Surrey
Current Institution: University of Surrey
Date of Award: 1972
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The literature on the toxicology and biochemical effects of chlorofluoroalkanes and closely related compounds of toxicological interest has been reviewed. The chlorofluoroalkanes used in aerosol propellant mixtures were the subject of this study. A simple, accurate quantitative g. l. c. assay was developed for the measurement of trichlorofluoromethane and 1,2-dichloro-1,1,2,2-tetrafluoroethane in extracts of tissues and the expired air. The separation and quantitation of mixtures of chlorofluoroalkanes was investigated. The distribution and excretion of trichlorofluoro-methane and 1,2-dichloro-1,1,2,2-tetrafluoroethane was determined after administration of these compounds by the oral route. Attempts were made to detect metabolism of trichloro-fluoromethane in in vitro incubations. Although it was feasible to detect 0.2% of a possible metabolite (dichloro-fluoromethane), no formation of this metabolite was detected in incubations of trichlorofluoromethane with microsomal preparations from several rodent species. Lipid peroxidation was investigated as a measure of free radical formation. Trichlorofluoromethane was found to have little effect on this parameter. Simple toxicological experiments showed the chlorofluoroalkanes to be relatively non-toxic even at very high dose levels. Total tissue lipid was not affected by trichlorofluoromethane. The chlorofluoroalkanes gave spectral interactions with cytochrome P-450, both in the oxidised and reduced states. The chlorofluoroalkanes did not affect type I substrate metabolism. The effects on type II substrate metabolism were inhibition (zoxazolamine hydroxylation) and activation (acetanilide and aniline 4-hydroxylations). The results are discussed in relation to the low toxicity of the chlorofluoroalkanes, and in comparison to the hepatotoxin, carbon tetrachloride.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available