The fate of inhaled ~(14)C-labeled PCB11 and its metabolites in vivo

摘要

Background: The production ban of polychlorinated biphenyl (PCB) technical mixtures has left the erroneous impression that PCBs exist only as legacy pollutants. Some lower-chlorinated PCBs are still being produced and contaminate both indoor and ambient air. Objectives: To inform PCB risk assessment, we characterized lung uptake, distribution, metabolism and excretion of PCB11 as a signature compound for these airborne non-legacy PCBs. Methods: After delivering [ ~(14)C]PCB11 to the lungs of male rats, radioactivity in 34 major tissues and 5 digestive matter compartments was measured at 12,25,50,100,200 and 720 min postexposure, during which time the excreta and exhaled air were also collected. [~(14)C)PCB11 and metabolites in lung, liver, blood, digestive matter, urine, feces, and adipose tissues were extracted separately to establish the metabolic profile of the disposition. Results: [~(14)C]PCB11 was distributed rapidly to all tissues after 99.8% pulmonary uptake and quickly underwent extensive metabolism. The major tissue deposition of [~(14)C]PCB11 and metabolites translocated from liver, blood and muscle to skin and adipose tissue 200 min postexposure, while over 50% of administered dose was discharged via urine and feces within 12 h. Elimination of the [~(14)C]PCB11 and metabolites consisted of an initial fast phase (t_(1/2) = 9-33 min) and a slower clearance phase to low concentrations. Phase Ⅱ metabolites dominated in liver blood and excreta after 25 min postexposure. Conclusions: This study shows that PCB11 is completely absorbed after inhalation exposure and is rapidly eliminated from most tissues. Phase Ⅱ metabolites dominated with a slower elimination rate than the PCB11 or phase Ⅰ metabolites and thus can best serve as urine biomarkers of exposure.