Pharmacokinetics in rats of 2,4,5,2′,4′,5-hexachlorobiphenyl, an unmetabolizable lipophilic model compound

Abstract

1. Pharmacokinetics of the unmetabolizable lipophilic model compound, 2,4,5,2′,4′,5′-hexachlorobiphenyl (6-CB) was studied in rats, using g.l.c. and ¹⁴C methods.

2. After single i. v. doses of 0·6 and 3·6 mg/kg, 16% dose was excreted in 40 weeks in the faeces; the value for infinite time was 17% dose. This limited excretion was first-order with a half-life of 100 days for the terminal component. Urinary excretion was nearly complete after 1 week and amounted to 0·8% dose.

3. 6-CB was redistributed from blood to liver, muscle, skin, and adipose tissue. The latter contained a constant level of about 75% dose from 6 to 40 weeks, while the total lean tissue level fell to 6% dose; only 6-CB in the lean tissue compartment was available for excretion.

4. In rats given six oral doses of 0·6 mg/kg at weekly intervals, excretion and distribution patterns were similar to the single-dose situation, and were thus independent of dose, route of administration, and dose regimen.

5. It is concluded that in rats under physiological conditions, about 75% of every dose of 6-CB is irreversibly stored in adipose tissue and that excretion is limited to 18% dose. 6-CB in rats exhibit novel pharmacokinetics of unmetabolizable lipophilic compounds.