Uptake, distribution, and elimination of carbon tetrachloride in rat tissues following inhalation and ingestion exposures.

摘要: Abstract Carbon tetrachloride (CCl 4 ) has been studied extensively for its hepatotoxic effects. There is a paucity of information, however, about tissue deposition following administration by different routes and patterns exposure. The specific objective this study was to delineate the uptake, distribution, elimination CCl in tissues rats subjected equivalent oral inhalation exposures. Male Sprague–Dawley (325–375 g) were exposed 1000 ppm 2 hr. total absorbed dose (179 mg /kg bw) administered other groups as single bolus or constant gastric infusion over period Animals terminated at selected time intervals during postexposure (liver, kidney, lung, brain, fat, skeletal muscle, spleen, heart, GI tract) removed measurement their content headspace gas chromatography. levels all much lower group than groups. Inhalation resulted relatively high concentrations, because inhaled chemicals enter arterial circulation are transported directly organs throughout body. It seems logical that liver should accumulate more ingestion inhalation. This did not prove be case when comparing AUC values Substantially concentrations animals appeared due very rapid metabolic clearance small amounts entering 2-hr period. hypothesized capacity first-pass hepatic pulmonary could exceeded, if given single, large bolus. Indeed, greater group. courses uptake governed largely tissue's rate blood perfusion lipid content. rapidly taken up, example, brain liver. These organs’ then diminished, metabolized redistributed adipose tissue. accumulated slowly, but fat remained elevated prolonged Thus, some may reflective levels. most appropriate measure internal acute hepatotoxicity appears area under concentration versus curve from 0 30 min. Tissue time–course data sets essential refinement validation physiological models volatile organic chemicals.