Pharmacokinetics and immunotoxicity

The possibilities of different actions of xenobiotics on the immunological system are described (different cells with immunocompetence in distinct stages of development, indirect action, pharmacokinetics and especially biotransformation). Results concerning the toxic action and biotransformation are given for DOTC. The atrophy of the thymus produced by DOTC was greater in the rat than in the mouse after intravenous, intramuscular and especially after oral administration. In vitro, the spontaneous movement of lymphocytes and macrophages in rats and mice was inhibited by similar concentrations of DOTC. In mice pretreated with SKF 525 A or CCl4 the atrophy of thymus was enhanced. Detection of DOTC in the thymus of rats and mice by means of electrothermal atomic absorption spectrophotometry showed a concentration of DOTC in the micromol range per Kilogram wet weight of the organ over a period of some days after administration of DOTC in doses producing atrophy of thymus. The possibilities of a direct or an indirect action of DOTC on the thymocytes were discussed.