Penninks A H, Seinen W
Food Chem Toxicol. 1982 Dec;20(6):909-16. doi: 10.1016/s0015-6264(82)80227-7.
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.
在一项为期2周的喂养研究中，比较了酯锡化合物双（β-羧丁氧基乙基）二氯化锡（CBETC）和双（β-羧甲氧基乙基）二氯化锡（CMETC）及其水解产物双（β-羧乙基）二氯化锡（CETC）与二烷基锡化合物二正辛基二氯化锡（DOTC）和二正丁基二氯化锡（DBTC）的经口毒性。在日粮水平为450 ppm时，酯锡对体重没有影响，但在相对较高的1350 ppm水平时，二者均导致生长迟缓，肝脏相对重量出现统计学显著下降，而CBETC还降低了胸腺和脾脏的相对重量。肝脏糖原含量减少是在这些器官中观察到的唯一与处理相关的组织病理学变化。在高达1350 ppm的水平下，CETC未引起任何毒性迹象。饲喂50 ppm DBTC或150 ppm DBTC或DOTC的大鼠体重增加略有下降，但饲喂二烷基锡的大鼠的主要影响是淋巴器官重量减少。在饲喂150 ppm DBTC或DOTC 2周的大鼠中，胸腺相对重量与对照值相比下降了70%以上，胸腺尤其是胸腺皮质以及脾脏中依赖胸腺的淋巴区域出现淋巴细胞耗竭。经肠外暴露显示这些组之间在毒性方面也存在类似差异；单次腹腔注射或静脉注射2.5 mg DBTC/kg体重会导致体重增加略有下降和严重的胸腺萎缩，而CBETC和CETC即使在10 mg/kg时也没有这种作用。然而，在体外，酯锡的活性与二烷基锡相似。在淋巴细胞代谢研究中，所有这些化合物均诱导葡萄糖消耗呈剂量依赖性刺激，DBTC和CBETC在5 microM水平时刺激作用最大，DOTC和CMETC在120 microM水平时刺激作用最大。在更高的暴露水平下，葡萄糖消耗急剧下降，氧气消耗减少，淋巴细胞活力受损。由于二羧基锡化合物CETC在体外细胞代谢、细胞活力或胚细胞转化研究中未诱导淋巴细胞毒性迹象，因此推测CBETC和CMETC在大鼠体内水解为CETC是酯锡化合物体外淋巴细胞毒性活性与体内暴露后无淋巴萎缩之间差异的可能解释，也是CMETC和CBETC在大鼠中比二烷基锡化合物DBTC和DOTC毒性小得多这一发现的原因，DBTC和DOTC在体外和体内均诱导淋巴细胞毒性。
