Dose-dependent enantiomeric enrichment of 2,2',3,3',6,6'-hexachlorobiphenyl in female mice.

Nineteen of the 209 possible polychlorinated biphenyl (PCB) congeners are chiral and stable to racemization at ambient temperature. Chiral PCB congeners are important components of technical and environmental PCB mixtures, and some are highly toxic. Both environmental and laboratory studies have shown that these chiral PCB congeners undergo enantiomeric enrichment in many species; however, the processes and factors influencing the extent of this enantiomeric enrichment are poorly understood. We hypothesized that the exposure levels are an important factor affecting the extent of enantiomeric enrichment. To test this hypothesis, we investigated the levels and enantiomeric fractions of (+/-)-PCB 136 in selected tissues, feces, and urine of female C57Bl/6 mice 3 d after oral administration of 2.5, 10, or 50 mg/kg body weight of (+/-)-PCB 136. The PCB 136 tissue levels typically increased with increasing dose. The extent of the enrichment of (+)-PCB 136 in tissues and feces, however, decreased with increasing dose, an observation that suggests a saturation of the disposition process responsible for the enantiomeric enrichment. Overall, the present study demonstrates that in addition to species, exposure source, exposure frequency, and other factors, levels of PCB exposure are an important determinant of the enantiomeric enrichment of PCBs in mice and, most likely, other species.