Enantioselective disposition of PCB 136 (2,2′,3,3′,6,6′‐hexachlorobiphenyl) in C57BL/6 mice after oral and intraperitoneal administration

Abstract

Studies of xenobiotic disposition in rodents often employ experimental designs using differing routes of administration. In an effort to investigate the effects of route of administration on enantioselective disposition of xenobiotics, a chiral polychlorinated biphenyl (PCB), racemic PCB 136, was administered as a single dose (50 mg/kg body weight) to male or female C57BL/6 mice either orally or via intraperitoneal injection. Mice were sacrificed after either 3 or 6 days, and blood and organs were collected for PCB analysis. Intraperitoneal injection of PCB 136 produced statistically higher PCB levels in blood and organs than did the oral administration. Tissue levels were higher after 3 days than those after 6 days. Enantioselective analysis showed that (+)-PCB 136 was enriched in most organs, with the most pronounced enrichment found in the liver and the brain of animals dosed orally or by intraperitoneal injection, respectively. Significantly higher retained enantiomeric fractions of PCB 136 were found in the oral treatment groups compared with those found in intraperitoneal treatment groups, possibly as a result of the lower PCB levels in oral treatment groups. Therefore, the choice of administration route may well have implications for the enantioselective disposition of PCB 136 and other chiral substances.

The effect of dietary glycine on the hepatic tumor promoting activity of polychlorinated biphenyls (PCBs) in rats

“…PCBs 77 and 153 were extracted from liver samples using an Accelerated Solvent Extractor ASE 200 (Dionex Corporation, Sunnyvale, CA) as described previously (Kania-Korwel et al 2007). A recovery standard solution consisting of PCBs 14, 65, and 166 (50 μL; 4 mg PCB/L in hexane) was added to the extraction cells prior to extraction using hexane:acetone.…”

“…The PCB extract was concentrated to 1 mL and an internal standard solution consisting of PCBs 30 and 204 (300 μL; 100.8 μg PCB/L in hexane) was added. Sulfur impurities were removed using standard EPA procedures prior to PCB analysis (Kania-Korwel et al 2005;Kania-Korwel et al 2007;Lehmler et al 2003). …”

“…Lipids were extracted from tissue samples with a chloroform:methanol mixture (2:1 v/v) using an Accelerated Solvent Extractor ASE 200 (Dionex Corporation, Sunnyvale, CA) as described previously (Kania-Korwel et al 2007). The lipid content was determined gravimetrically after evaporation of the solvents and used to calculate lipid adjusted PCB levels in the liver.…”

Chirality as an Environmental Forensics Tool

“…biotransformation, excretion, and/or differential tissue retention) occurred during the initial distribution. In similar experiments, this strain of mice also enriched (þ)-PCB 136 enantioselectively in adipose, spleen, kidney, liver, brain, uterus, and testes tissues [274]. Animals given PCB 136 via oral administration generally had more nonracemic residues by roughly 0.1 EF units [274], indicating that route of exposure affects enantiomer-specific toxicokinetics.…”

“…In similar experiments, this strain of mice also enriched (þ)-PCB 136 enantioselectively in adipose, spleen, kidney, liver, brain, uterus, and testes tissues [274]. Animals given PCB 136 via oral administration generally had more nonracemic residues by roughly 0.1 EF units [274], indicating that route of exposure affects enantiomer-specific toxicokinetics. However, absorption processes did not appear to be enantioselective, as EFs of PCB 136 in mice tissues did not change with increasing dietary fat [275].…”