EFFECT OF ENVIRONMENTAL TEMPERATURE ON THE TOXICITY OF CAFFEINE AND DEXTROAMPHETAMINE IN MICE

¹ Environmental Biology Division, Ames Research Center, NASA, Moffeft Field, California

The effects of environmental temperature and dehydration, individually and in combination, on the toxicity of caffeine and dextroamphetamine were studied in mice. LD05's were compared at 22°C(normal), 30°C(warm) and 15°C (cool), with and without dehydration. No statistically significant difference in LD50's (P < .05) could be shown between acute (one hour) and subacute (three days) preinjection exposures. A 7-8° alteration in temperature on either side of 22°C significantly changed the toxicity of both drugs. At 15°C the toxicity of dextroamphetamine decreased 10-fold, and the animals were protected from its toxic effects; at 30°C toxicity increased 2- to 3-fold. Both warming and cooling appeared to increase the toxicity of caffeine. Dehydration caused a marked decrease in the LD50's of both drugs. This decrease was more pronounced at the higher temperatures, with the exception of dextroamphetamine at 15°C where cooling appeared to mask the increase in toxicity otherwise produced by dehydration. The combination of dehydration and change in temperature showed an additive effect on the toxicity of caffeine at 15°C and dextroamphetamine at 30°C, whereas a marked potentiation occurred with caffeine at 30°C. These results indicate that alterations of the environmental temperature markedly affect drug toxicity. They emphasize that such alterations do not have to be particularly drastic but that "mild" variations in temperature are effective.