Disposition of phenolic and sulfated metabolites after inhalation exposure to 4-chlorobiphenyl (PCB3) in female rats.

Chemical research in toxicology

PubMedID: 24988477

Dhakal K, Uwimana E, Adamcakova-Dodd A, Thorne PS, Lehmler HJ, Robertson LW. Disposition of phenolic and sulfated metabolites after inhalation exposure to 4-chlorobiphenyl (PCB3) in female rats. Chem Res Toxicol. 2014;.
Lower chlorinated PCBs, such as PCB3, are air contaminants in buildings and outdoors. Metabolites of PCB3 are potential endocrine disrupting chemicals and genotoxic agents. We studied the disposition of phenolic and sulfated metabolites after acute nose-only inhalation exposure to airborne PCB3 for 2 h in female rats. Inhalation exposure was carried out in three groups. In the first group, rats exposed to an estimated inhaled dose of 23 µg/rat were euthanized at 0, 1, 2, and 4 h after exposure. Highest concentrations of phenols and sulfates were observed at 0 h, and the values were 7±1 and 560± 60 ng/mL in serum, 213±120 and 842± 80 ng/g in liver, 31±27 and 22±7 ng/g in lung, and 27±6 and 3±0 ng/g in brain, respectively. First order serum clearance half-lives of 0.5 h for phenols and 1 h for sulfates were estimated. In the second group, rats exposed to an estimated inhaled dose of 35 µg/rat were transferred to metabolism cages immediately after exposure for the collection of urine and feces over 24 h. Approximately 45±5% of the dose was recovered from urine and consisted mostly of sulfates, and 18±5% of the dose recovered from feces was exclusively phenols. Unchanged PCB3 was detected in both urine and feces but accounted only for 5±3% of the dose. Peak excretion of metabolites in both urine and feces occurred within 18 h post exposure. In the third group, three bile-cannulated rats exposed to an estimated dose of 277 µg/rat were used for bile collection. Bile was collected for 4 h immediately after 2 h exposure. Biliary metabolites consisted mostly of sulfates, some glucuronide, and lower amounts of the free phenol. Control rats in each group were exposed to clean air. Clinical serum chemistry values, serum T4 level, and urinary 8-hydroxy-2'-deoxyguanosine were similar in treated and control rats. These data show that PCB3 is rapidly metabolized to phenols and conjugated to sulfates after inhalation and both of these metabolites are distributed to liver, lungs and brain. The sulfates elaborated into bile are either reabsorbed or hydrolyzed in the intestine and excreted in the feces as phenols.