THE TOXICITY AND EFFECT OF CERTAIN FLUORINATED DERIVATIVES OF PHENYLALANINE AND TYROSINE ON THE BASAL METABOLIC RATE OF THE RAT

¹ From the Department of Biochemistry, College of Agriculture, University of Wisconsin, Madison

The toxicity and effect of 3-fluorotyrosine, 3-fluorophenylalanine, 3-fluoro-5-iodotyrosine, and 3,5-difluorotyrosine on the basal metabolic rate were studied with the rat.

The M.L.D. of these compounds when given by subcutaneous injection was found to be 12.5 mg. per kilogram of body weight for 3-fluorotyrosine, 20 mg. per kilogram for 3-fluorophenylalanine, 65 mg. per kilogram for 3-fluoro-5-iodotyrosine, and slightly more than 40 mg. per kilogram for 3,5-difluorotyrosine. The acute toxic effects were similar for the four compounds and were characterized by periods of convulsion and hyperirritability followed by extreme lethargy.

When fed in the ration at levels as low as 0.0005 per cent 3-fluorotyrosine inhibited growth of young rats; 0.0025 per cent in the ration caused an inhibition of growth equivalent to that of 0.1 per cent sodium fluoride. Levels of 0.004 to 0.005 per cent fed in the ration were lethal.

The 3-fluorotyrosine and the 3-fluorophenylalanine had no effect on the B.M.R. of the rat, when given in amounts up to one-half of the M.L.D., 3,5-difluorotyrosine and 3-fluoro-5-iodotyrosine likewise had little or no effect on the B.M.R. and the latter did not prevent a calorigenic response to thyroxin. If the former was given in doses of approximately three-fourths of the M.L.D., a very slight drop in the B.M.R. was obtained.

The highly toxic nature of the compounds studied contra-indicates their use as therapeutic agents for the control of the B.M.R. in the rat under experimental conditions.