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.