Abstract
Discussion and Summary
As with the rabbit, dog, and man, 2-thiophenecarboxylic acid in the rats was eliminated by route of urinary excretion. About 80% of the injected 2-TCA was recovered as metabolite by means of glycine conjugation and 20% remained unchanged. The conjugation process seemed to take place immediately after ingestion of the compound in the rats and the excretion of metabolites in urine was rapid. The peak rate of excretion occurred between 30 and 50 min after injection and was in company with a diuresis. After a shows that 2-TCA significantly increased excretion of urine during the 0-4 hr period compared to saline control animals. About 80% of the injected 2-TCA (2 or 4 mmoles/kg) was converted into 2-TG and the remaining 20% was excreted without conjugation. The ratio between 2-TG and 2-TCA recovered in each urine sample, however, varied with time after injection and also the injected dose. Urine samples collected in 4-24 hr periods contained mainly 2-TG. In rats receiving 2 mmoles/kg, 96% of the injected 2-TCA was recovered in urine collected in the 0-4 hr period. In rats injected with a larger dose of 2-TCA, 4 mmoles/kg, the recovery was nearly complete (98%) in their 24 hr urine collection.
When 2-TG was given to rats by a single oral dose of 12 mmoles/kg or daily injections of 2 mmoles/kg for consecutively 7 days, the animals showed no overt sign of toxic reaction as judged by the general appearance of animals and their growing weight. 2-TG single injection of 2-TCA (dose: 2 or 4 mmoles/kg), nearly all of the injected compound could be recovered in urine collected in a 10- or 24-hr period.
Since 2-thenoylglycine is virtually a nontoxic compound in rats, this mechanism of detoxification assured the nontoxicity of 2-thiophenecarboxylic acid in these animals.
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