Graduate Thesis Or Dissertation
 

The in vivo metabolism of ethyl-N, N,-di-n-propylthiolcarbamate in rats

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  • The metabolism of ¹⁴C-labeled ethyl -N, N-di-n- propylthiolcarbamate (EPTC- ¹⁴C) was studied in adult female rats. Single oral doses of EPTC-¹⁴C ranging from 0. 6 to 100. 6 mg were given and the elimination pattern of ¹⁴C was determined. Results of 18 experiments showed that increasing the doses of EPTC- ¹⁴C led to a decrease in the ability of rats to catabolize the herbicide into respiratory carbon dioxide. The excretion through renal route, however, was enhanced. Thus, recovery of radioactivity in ¹⁴CO₂ decreased from 84. 6% for the 0. 6 mg dose to 38. 2% for the 100.6mg dose while recovery in the urine increased from 8.4% for the 0. 6 mg dose to 35. 6% for the 100. 6 mg dose. The rate of elimination of ¹⁴C was markedly delayed by increasing the doses. ¹⁴CO₂ elimination was completed within 15 hours for 0. 6 mg to 20, 6 mg doses but extended to approximately 35 hours for 50. 6 and a 100.6 mg dose. Likewise, the time for complete elimination of radioactivity through urinary excretion was considerably extended. The pattern of ¹⁴CO₂ elimination showed a multiple peaked formation. This multiplicity of peaks was more pronounced with higher doses. Paper chromatography and autoradiography revealed six major radioactive metabolites and three minor ones in the urine. Two dimensional thin layer chromatography and autoradiography, however, showed a total of 20 urinary radioactive metabolites, seven of which are the major ones. One of the major metabolites was tentatively identified as urea. Attempts to isolate the individual metabolites through ion exchange chromatography or extraction with organic solvents has not been successful, These procedures, as well as elution of metabolites from the paper chromatograms, demonstrated the labile nature of some metabolites.
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