Detoxification of the estertin stabilizer bis-([beta]-carbobutoxyethyl)tin dichloride in rats by hydrolysis of the ester bond

Abstract

In a previous comparative toxicity study with alkyltin and estertin stabilizers, it was recognized that estertim 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. The discrepancy between the in vitro and in vivo toxicity of estertin compounds prompted us to study the metabolism of the estertin compound bis-(β-carbobutoxyethl)tin dichloride (CBETC) in rats.

The hydrolysis product bis-(β-carboxyethl)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 adminstration of relatively large amounts of 20 mg CETC/kg body weight indicated that this compound is not metabolized by rapidly excreted in urine, probably because of its hydrophilic nature.

Daily gavage of 15 mg CBETC/kg body weight resulted in the excretion of apprecable 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 compund CBETC is effectively detoxified by hydrolysis of the ester bond.