Pulmonary absorption and disposition of [14C]thiophene in rats following nose-only inhalation exposure.

Abstract

The absorption, disposition, and metabolism of [14C]thiophene was investigated in rats following nose-only inhalation exposure at 8000 ppm for 1 h. Under these exposure conditions, it was estimated that approximately 16.3% (493 mumol) of the inhaled thiophene was absorbed from the respiratory system. Within 72 h following exposure, a total of 488 mumol of thiophene equivalents (99% of that retained) was excreted, of which 360.4 mumol (73.9% of the total excreted radioactivity) was in expired air, 120.7 mumol (24.8%) was in urine, 3 mumol (0.6%) was in feces, and 3.7 mumol (0.8%) was in the cage wash. Excretion took place primarily within the first 8 h, during which 91% of the total radioactivity excreted was collected. The thiophene equivalents remaining in tissues at 72 h were estimated to total 5.1 mumol (1.0% of the retained radioactivity). Exhaled radioactivity was identified as thiophene. No 14CO2 was detected in the expired air. After 1 h following exposure, the elimination of thiophene equivalents from plasma was monophasic, with a half-time of 3.6 h. The elimination of thiophene equivalents from blood cells was biphasic, with half-times of 2.9 h and 9.1 d. The blood cells/plasma concentration ratios of thiophene equivalents ranged from 3 to 13, with the higher ratio observed at the 12-h time interval. At 72 h after exposure, blood cells contained the highest concentration of thiophene equivalents, approximately fourfold higher than that of the liver, which contained the second highest concentration. Kidney, heart, and lung contained similar but lower concentrations than liver, while brain, fat, and skeletal muscles contained the lowest concentrations. In summary, this study demonstrates that thiophene was absorbed from the respiratory system, and the majority of the absorbed thiophene was eliminated unchanged in the exhaled air, while a smaller fraction was metabolized and eliminated in urine.