Short-term toxicity studies with triphenyltin compounds in rats and guinea-pigs

Abstract

Short-term toxicity studies have been carried out in rats and guinea-pigs fed diets containing triphenyltin acetate (TPTA), triphenyltin hydroxide (TPTH) or triethyltin hydroxide (TETH) for 90 days at levels ranging from 0 to 50 ppm.

The lowest dietary levels found to retard growth in rats and guinea-pigs respectively are as follows: 5 and 10 ppm for TETH; 25 and 5 ppm for TPTA; 50 and 20 ppm for TPTH. An increase in mortality was found in the following groups: rats on 10 ppm or more of TETH; guinea-pigs on 20 and 50 ppm TPTA and on 50 ppm TPTH. In rats and guinea-pigs given TETH, paralysis and pronation of the hindlegs developed. These toxic signs were not found in the TPTA- and TPTH-treated animals. This observation was correlated with the finding that only the TETH-treated animals developed interstitial oedema of the central nervous system. The water content of the brain and spinal cord was increased in rats and guinea-pigs at respective minimum levels of 5 and 10 ppm of TETH and in guinea-pigs on 20 ppm TPTA. In female rats given 50 ppm TPTA or TPTH the water content of the spinal cord was only increased.

The changes in organ weights which could be related to the administration of the organotin compounds were confined to an increase of brain weight in rats and guinea-pigs given TETH, and in guinea-pigs given 5 ppm or more of TPTA and a decrease of thymus and/or spleen weights in rats and guinea-pigs receiving TETH. Guinea-pigs given 5–20 ppm TPTA or 2·5–20 ppm TPTH displayed lymphopenia accompanied in a number of animals by histological changes in the lymphopoietic system, viz. atrophy of the white pulp of the spleen was found. This possibly induced a decrease of general resistance, so that a mycotic infection developed in the animals.

Hitherto, damage to the central nervous system was considered to be the most sensitive criterion for assessing the toxicity of organotin compounds, but the present work shows that the effect on lymphopoiesis is a more sensitive index of toxic action for triphenyltin compounds.