title: Comparative toxicity of alkyltin and estertin stabilizers.
abstract: In a 2-wk feeding study the oral toxicities of the estertin compounds bis-(beta-carbobutoxyethyl)-tin dichloride (CBETC) and bis-(beta-carbomethoxyethyl)tin dichloride (CMETC) and their hydrolysis products bis-(beta-carboxyethyl)tin dichloride (CETC) were compared with those of the dialkyltin compounds di-n-octyltin dichloride (DOTC) and di-n-butyltin dichloride (DBTC). At a dietary level of 450 ppm the estertins did not affect weights, but at the relatively high level of 1350 ppm both caused growth retardation and a statistically significant decrease in the relative weight of the liver, while CBETC also reduced the relative weights of the thymus and spleen. A diminished amount of liver glycogen was the only treatment-related histopathological change observed in these organs. CETC caused no signs of toxicity up to a level of 1350 ppm. Slightly decreased body-weight gains were recorded in rats fed 50 ppm DBTC or 150 ppm DBTC or DOTC, but the main effect in dialkyltin-fed rats was a decrease in lymphoid-organ weights. In rats fed 150 ppm DBTC or DOTC for 2 wk, the relative thymus weight was decreased by more than 70% compared with the control value and there was lymphocyte depletion in the thymus, especially the thymic cortex, and in thymus-dependent lymphoid areas of the spleen. Parenteral exposure demonstrated a similar difference in toxicity between these groups; a single ip or iv injection of 2.5 mg DBTC/kg body weight caused a slight reduction in body-weight gain and severe thymic atrophy, whereas CBETC and CETC had no such effects even at 10 mg/kg. However, in vitro the activities of the esterins were similar to those of the dialkyltins. In lymphocyte metabolism studies, all these compounds induced a dose-dependent stimulation of glucose consumption, with maximum stimulation occurring at a level of 5 microM with DBTC and CBETC and at 120 microM with DOTC and CMETC. At higher exposure levels, glucose consumption fell sharply, oxygen consumption was reduced and lymphocyte viability was impaired. Since the dicarboxyltin compound CETC induced no signs of lymphocytotoxicity in the in vitro cell-metabolism, cell-viability or blast-transformation studies, hydrolysis of CBETC and CMETC to CETC in the rat is suggested as a possible explanation for the discrepancy between the lymphocytotoxic activity of the estertin compounds in vitro and the absence of lymphoid atrophy following in vivo exposure, and for the finding that in the rat CMETC and CBETC are much less toxic than the dialkyltin compounds DBTC and DOTC, which induce lymphocytotoxicity both in vitro and in vivo.
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D009947:Organotin Compounds / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen / Q000473:pathology; D013950:Thymus Gland / Q000473:pathology
chemical_list: D009947:Organotin Compounds; D005947:Glucose