Friedman M A, Dulak L H, Stedham M A
Cytec Industries Incorporated, West Paterson, New Jersey 07424, USA.
Fundam Appl Toxicol. 1995 Aug;27(1):95-105. doi: 10.1006/faat.1995.1112.
A lifetime oncogenicity study in Fischer 344 rats was conducted to accurately characterize the carcinogenic potency of acrylamide. Acrylamide was administered in drinking water throughout the 106-week study at concentrations required to provide a dose of 0, 0.1, 0.5, or 2.0 mg/kg/day to males or 0, 1.0, or 3.0 mg/kg/day to females. Complete necropsy and gross pathology examinations were performed on all study animals. Histopathology examinations were conducted on selected tissues of all high-dose and control animals. Selected tissues from intermediate and low-dose groups were subjected to histopathological examinations as required to clarify high- and control-dose group observations. There was no visual observation of neurotoxicity in any study animal but sciatic nerve degeneration was observed in the male and female high-dose groups. Increased mortality related to acrylamide was observed in the high-dose male group from Month 17 to the end of the study and in the high-dose females during Month 24. Mesotheliomas of the testicular tunic were significantly increased in the high-dose male group. The combined incidence of mammary gland adenocarcinomas and fibroadenomas was significantly increased in both acrylamide-dosed female groups. Males and females in the high-dose groups as well as females of the low-dose group had significantly (p < 0.001) increased thyroid follicular cell adenomas and adenocarcinomas. A variety of other tumor types observed with increased incidence in a previous acrylamide oncogenicity study (i.e., combined CNS glial neoplasms, papillomas of the oral cavity, adenomas of the clitoral gland, and uterine adenocarcinomas) were not observed to be present at increased incidence in this study. This study confirms previously described acrylamide induction of benign tumors of the thyroid and mammary glands as well as mesotheliomas of the testis. By using a larger number of animals with an unbalanced study design, this study showed that acrylamide did not induce glial tumors and demonstrated that the no-observable-effect level for scrotal mesotheliomas is 0.5 mg/kg. It also demonstrated that the increased incidence of mammary tumors was again within historical control ranges.
在Fischer 344大鼠中进行了一项终生致癌性研究，以准确表征丙烯酰胺的致癌效力。在为期106周的研究中，通过饮用水给予丙烯酰胺，浓度需达到给雄性大鼠提供0、0.1、0.5或2.0毫克/千克/天的剂量，或给雌性大鼠提供0、1.0或3.0毫克/千克/天的剂量。对所有研究动物进行了完整的尸检和大体病理学检查。对所有高剂量和对照动物的选定组织进行了组织病理学检查。根据需要对中剂量和低剂量组的选定组织进行组织病理学检查，以澄清高剂量和对照组的观察结果。在任何研究动物中均未观察到神经毒性的视觉表现，但在高剂量雄性和雌性组中观察到坐骨神经变性。在高剂量雄性组中，从第17个月到研究结束观察到与丙烯酰胺相关的死亡率增加，在高剂量雌性组中，在第24个月期间观察到死亡率增加。高剂量雄性组中睾丸鞘膜间皮瘤显著增加。在两个丙烯酰胺给药的雌性组中，乳腺腺癌和纤维腺瘤的合并发生率显著增加。高剂量组的雄性和雌性以及低剂量组的雌性甲状腺滤泡细胞腺瘤和腺癌显著增加（p < 0.001）。在先前的丙烯酰胺致癌性研究中观察到的多种其他肿瘤类型（即中枢神经系统神经胶质瘤合并瘤、口腔乳头状瘤、阴蒂腺腺瘤和子宫腺癌）在本研究中未观察到发生率增加。本研究证实了先前描述的丙烯酰胺诱导甲状腺和乳腺良性肿瘤以及睾丸间皮瘤。通过使用大量动物且研究设计不平衡，本研究表明丙烯酰胺不会诱导神经胶质瘤，并证明阴囊间皮瘤的无观察到效应水平为0.5毫克/千克。它还表明乳腺肿瘤发生率的增加再次在历史对照范围内。
