Abdo K M, Huff J E, Haseman J K, Alden C J
Food Chem Toxicol. 1986 Oct-Nov;24(10-11):1091-7. doi: 10.1016/0278-6915(86)90293-0.
Chronic toxicity and carcinogenicity studies were conducted on D-mannitol and propyl gallate in F344 rats and B6C3F1 mice. Groups of 50 rats and 50 mice of each sex were maintained on diets containing either 0, 2.5 or 5.0% D-mannitol or 0, 0.6 or 1.2% propyl gallate for 103 wk. D-Mannitol had no effect on survival or mean body weight of rats and mice, and feed consumption was approximately the same in control and treated groups in each species. Gastric fundal gland dilation occurred at a higher incidence in treated female rats than in controls. A mild nephrosis characterized by focal vacuolization of the renal tubular epithelium was observed in an increased incidence in treated mice. No significant increase in tumour incidence was observed in any of the treated groups in comparison with the corresponding controls. Survival of rats and mice given propyl gallate was similar to that of the controls. Mean body weights were lower in chemically exposed animals, and more so for females. Male rats exposed to propyl gallate showed an increased incidence of hepatic cytoplasmic vacuolization and suppurative inflammation of the prostate gland. Tumours of the preputial gland, islet-cell tumours of the pancreas, and phaeochromocytoma of the adrenal gland occurred at a significantly (P less than 0.05) higher incidence in the low-dose male rats. Malignant lymphoma occurred with a positive trend in male mice (control 1/50, low dose 3/49 and high dose 8/50), and the incidence in the high-dose group was significantly (P less than 0.05) higher than in the control group. However, since the incidence in the control group was much less than the historical control rate (36/398 or 9%) in this laboratory, this apparent increase was not considered to be related to propyl gallate administration. Under the conditions of these studies, neither D-mannitol nor propyl gallate was considered to be carcinogenic to F344 rats or B6C3F1 mice of either sex.
对F344大鼠和B6C3F1小鼠进行了D - 甘露醇和没食子酸丙酯的慢性毒性和致癌性研究。每组50只各性别的大鼠和小鼠，分别喂食含0%、2.5%或5.0%D - 甘露醇或0%、0.6%或1.2%没食子酸丙酯的饲料，持续103周。D - 甘露醇对大鼠和小鼠的存活率及平均体重无影响，各物种的对照组和处理组的饲料消耗量大致相同。经处理的雌性大鼠胃底腺扩张的发生率高于对照组。在经处理的小鼠中，观察到以肾小管上皮细胞局灶性空泡化为特征的轻度肾病的发生率增加。与相应对照组相比，任何处理组的肿瘤发生率均未显著增加。给予没食子酸丙酯的大鼠和小鼠的存活率与对照组相似。化学暴露动物的平均体重较低，雌性更明显。暴露于没食子酸丙酯的雄性大鼠肝细胞质空泡化和前列腺化脓性炎症的发生率增加。低剂量雄性大鼠的包皮腺肿瘤、胰腺胰岛细胞瘤和肾上腺嗜铬细胞瘤的发生率显著（P小于0.05）高于对照组。雄性小鼠恶性淋巴瘤的发生率呈上升趋势（对照组1/50，低剂量组3/49，高剂量组8/50），高剂量组的发生率显著（P小于0.05）高于对照组。然而，由于对照组的发生率远低于本实验室的历史对照率（36/398或9%），这种明显的增加不被认为与没食子酸丙酯的给药有关。在这些研究条件下，D - 甘露醇和没食子酸丙酯均未被认为对任何性别的F344大鼠或B6C3F1小鼠具有致癌性。
