Metabolic fate of chlorinated paraffins: Degree of chlorination of [1−¹⁴C]-chlorododecanes in relation to degradation and excretion in mice

Abstract

The disposition of three [1−¹⁴C]-chlorododecanes (MCDD, PCDD I and PCDD II; 17.4%, 55.9%, and 68.5% chlorination) was studied in C57Bl mice. [1−¹⁴C]-lauric acid (LA) was studied as reference compound. Fifty-two percent (MCDD), 32% (PCDD I), and 8% (PCDD II) of the radioactive doses were exhaled as ¹⁴CO₂ during 12 h after i.v. injection. Similar results were obtained after p.o. administration. In addition to a marked labelling of the liver and fat, the distribution patterns observed at 24 h after administration revealed an uptake of radioactivity in tissues with high cell turnover/high metabolic activity, e.g., intestinal mucosa, bone marrow, salivary glands and thymus. The concentration of radioactivity in these sites and the exhalation of ¹⁴CO₂, which were inverse to the degree of chlorination, indicate that the chloroalkanes are degraded to metabolites which can be utilized in the intermediary metabolism. A similar, although more pronounced, distribution pattern and ¹⁴CO₂-exhalation (70% of i.v. dose) was observed after LA administration. The long time retention of heptane-soluble radioactivity in liver and fat (indicating unmetabolized substance) increased with degree of chlorination. On the contrary, the administration of LA and the chlorododecanes MCDD and PCDD I, but not of PCDD II, resulted in a selective labelling of the central nervous system 30–60 days after injection.