STUDIES ON S-CARBALKOXYTHIAMINE : (V) SUBACUTE AND CHRONIC TOXICITY OF S-CARBALKOXYTHIAMINE IN RATS

Abstract

Pathological study on the toxicity of S-carbethoxythiamine, S-carbobutoxythiamine and O, S-dicarbethoxythiamine was performed with the following results : The subacute LD_<50> of CET, CBT and DCET were estimated respectively to be 5.2 g/kg×5 and over, 4.8 g/kg×5 and 6.7 g/kg×5 p.o.. Large doses of CET and DCET, more than 3.5 g/kg×5,did not produce any specific pathological lesions in rats, but merely unspecific organ lesions similar to those of the animals in a catabolic phase of the post-aggressive oscillating reaction were found. Although some degenerative changes of the liver and kidney appeared in the rats administered a large dose of CBT (3.5 g/kg×5), these were experimentally demonstrated to be mainly caused by the toxic effect of butanol, a presumable metabolite of CBT. No pathological findings were noted in the rats administered CET, CBT and DCET in doses of either 785 mg/kg for 20 days or 20 mg/kg for 12 weeks.