The use of 2,4,5,2',4',5'-hexachlorobiphenyl (6-CB) as an unmetabolizable lipophilic model compound.
2,4,5,2',4'5'-Hexachlorobiphenyl (6-CB)--a polychlorinated biphenyl (PCB) congener resistant to metabolism in most species--has become a major residue in the biosphere including human adipose tissue. Its use as a model of unmetabolizable lipophilic compounds and as a tool in toxicokinetics in the last two decades is reviewed. This extremely water-insoluble compound is transported in plasma by albumin and lipoproteins. Binding to these plasma proteins appears to be important for uptake and release processes in different tissues. The redistribution kinetics of 6-CB as well as its pronounced adipose tissue storage and a very slow excretion with the faeces has been established in long-term animal studies. Excretion is strongly influenced by an increasing or diminishing adipose storage compartment size. Other minor pathways of elimination, e.g., via hair, become also important in the absence of metabolism and renal excretion. 6-CB has revealed the possibility of an almost quantitative transfer of the maternal body burden to the offspring via milk. The use of 6-CB in studies with tissue preparations in vitro is providing insight into transport mechanisms of uptake and release.
Mühlebach
S
S
Department of Pharmacology, Berne, Switzerland.
Wyss
P A
PA
Bickel
M H
MH
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D011078:Polychlorinated Biphenyls / Q000493:pharmacokinetics* / Q000633:toxicity
D011078:Polychlorinated Biphenyls; C014024:2,4,5,2',4',5'-hexachlorobiphenyl