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In a previous comparative toxicity study with alkyltin and estertin stabilizers, it was recognized that estertin compounds displayed in vitro lymphocytotoxic effects comparable to the dialkyltin compounds, but did not induce lymphoid atrophy when administered in vivo to rats as was found for the dialkyltin compounds. This discrepancy between the in vitro and in vivo toxicity of estertin compounds prompted us to study the metabolism of the estertin compound bis-(beta-carbobutoxyethyl)tin dichloride (CBETC) in rats. The hydrolysis product bis-(beta-carboxyethyl)tin dichloride (CETC) was the only metabolite detectable using TLC. After daily intravenous administration of 20 mg CBETC/kg body weight CETC was detected in urine only, whereas no faecal excretion of organotin was found. Intravenous administration of relatively large amounts of 20 mg CETC/kg body weight indicated that this compound is not metabolized but rapidly excreted in urine, probably because of its hydrophilic nature. Daily gavage of 15 mg CBETC/kg body weight resulted in the excretion of appreciable amounts of CETC in urine, but CETC was also found in faeces together with the parent compound. In the gastrointestinal tract CETC would be formed locally probably by acid hydrolysis of CBETC as was shown also in vitro in acidified water. Esterases in the gastrointestinal tract, tissues and blood might also be responsible for the fast hydrolysis of CBETC. As shown in our previous study the hydrolysis product CETC did not cause any lymphocytotoxic effect. Therefore we conclude that in the rat the estertin compound CBETC is effectively detoxified by hydrolysis of the ester bond.

In this study the absorption, tissue distribution and excretion of 14C-labeled di-n-octyltin dichloride ([14C]DOTC) in rats were investigated after oral and intravenous (i.v.) administration. Although after i.v. administration with 1.2 mg [14C]DOTC/kg body weight the tissue radioactivity was about 3-4 times higher than after oral administration with 6.3 mg [14C]DOTC/kg body weight, the relative tissue accumulation was found to be the same after the oral and i.v. dosage. The highest amount of radioactivity was found in liver and kidney, and to a lesser degree in adrenal, pituitary and thyroid glands. The lowest activity was recovered from blood and brain. No selective accumulation was observed in thymus, although it has been reported that thymus atrophy is the most sensitive parameter of DOTC toxicity in rats. For all tissues a time dependent decrease in radioactivity was found, except for kidney. The excretion of radioactivity in feces and urine was determined after a single i.v. or oral dose of 1.2 and 2 mg [14C]DOTC, respectively. After i.v. administration most of the radioactivity was excreted in the feces which was characterized by a biphasic excretion pattern. In orally treated rats more than 80% of the radioactivity was already excreted in the feces during the first day after administration. This indicated that only a small part of the DOTC was absorbed, which was calculated to be approximately 20% of the dose. Similar half-life values of 8.3 and 8.9 days were obtained from the fecal excretion of radioactivity after the i.v. and oral administration, respectively. The urinary excretion of radioactivity appeared to be independent of the body burden, since the daily amount of radioactivity excreted in urine was nearly the same independent of the route of administration as well as the time after administration.

After single oral application of the organotin compound di-n-butyltindichloride (DBTC) to rats, a reversible dose-dependent thymus weight reduction is observed. This is maximal at day 4 and recovers to the control value approximately at day 9 after administration. In this study the changes in thymocyte subpopulations after a single oral dose of 15 mg DBTC/kg body weight were analysed by immunohistology. Thymus glands of exposed rats were collected at day 1,2,3,4,5,7 and 9 after DBTC dosing and frozen sections were screened for various thymocyte differentiation antigens. Staining by mAb HIS-44 that labels a subset of cortical thymocytes showed that the thymus atrophy was restricted to the cortex. Here a time-dependent decrease of labelling by CD2 (OX-34), CD8 (OX-8), CD4 (ER-2), and CD5 (OX-19) was observed. In contrast, the number of cortical OX-44+ cells increased from day 2 to day 5. This increase can reflect an increase of CD4-CD8- double-negative thymocytes or of macrophages. However, most of these OX-44+ cells were negative for acid phosphatase, which is present in most macrophages. We concluded that these OX-44+ cells were mainly CD4-CD8- thymocytes and that the thymocyte subpopulation of this phenotype, i.e. CD4-CD8-OX-44+, may be the target cell for DBTC. It is discussed whether DBTC might disturb the interaction of early thymocytes and thymic epithelium, probably by an interaction with the CD2 antigen.