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 14CO-2-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.

The Distribution of 14C–Chloramphenicol in the Japanese Quail (Coturnix coturnix japonica)

“…incorporated in fatty acids (Darnerud et al 1982). The high and persistent concentration of chloramphenicol and/ or its metabolites in the koilin lining of the gizzard has not been reported earlier and may be important from the residue point of view since the gizzard is mostly also used as food for humans.…”

“…The chemical nature of this radioactivity is not known, but could be due t o intermediate metabolism pathway(s) leading t o labelled carbon fragments e.g. incorporated in fatty acids (Darnerud et al 1982). This assumption is supported by the fact that I4COz-exhalation could be registered after the administration of ''C-chIoramphenicol.…”

Pitfalls in the Interpretation of Whole‐Body Autoradiograms: Long‐time Retention in Brain and Adrenal Cortex Caused by Metabolic Incorporation of 14C from Various Labelled Xenobiotics

“…Davison & Wajda 1959;Kabara & Okita 1961;Webster 1961;Cuzner et al 1965), and proteins (Davison 1961). acetate, glucose and amino acids, can serve as building blocks for substances with slow turn-over in the brain, such as cholesterol, polar lipids (e.g.…”

“…acetate, glucose and amino acids, can serve as building blocks for substances with slow turn-over in the brain, such as cholesterol, polar lipids (e.g. Davison & Wajda 1959;Kabara & Okita 1961;Webster 1961;Cuzner et al 1965), and proteins (Davison 1961). The present study shows that degradation products from several xenobiotics also have the ability to be building block donors for endogenous compounds with long time retention in the brain and adrenal of mice.…”

Studies on Implantation and Embryonic Development in Mice Given a Highly Chlorinated Hexadecane

“…Safe 1984), separate CP preparations differ in their biological properties (e.g. Darnerud et al 1982;Nilsen & Toftgird 1981;Bengtsson & Baumann Ofstad, 1982). Therefore, it is necessary to study the reproductive effects of other chloroalkane analogues or CP preparations before the reproductive toxicity of CPs can be accurately assessed.…”