DeMerlis C C, Schoneker D R, Borzelleca J F
Colorcon, West Point, PA, USA.
Food Chem Toxicol. 2005 Sep;43(9):1355-64. doi: 10.1016/j.fct.2005.03.008.
Surelease Aqueous Ethylcellulose Dispersion is an excipient used as a modified release coating for beads, granules, non-pariels, drug crystals and tablets and for taste masking applications for drug products and dietary supplement products. A study was conducted to assess the toxicity of spray-dried Surelease when administered orally, via dietary admixture, to Sprague-Dawley CD rats (20/sex/group) at dose levels of 0, 2000, 3500, and 5000 mg/kg/day for a period of at least 3 months. After 3 months of treatment, all rats scheduled for terminal sacrifice were killed and selected organs were weighed. Complete macroscopic examinations and histopathological evaluation of selected tissues were conducted on all animals. Neuropathological evaluations were performed on 5 animals/sex/group. No mortality occurred during the study. Clinical observations, ophthalmology, body weight and food consumption, hematology, coagulation, clinical chemistry, urinalysis, functional observational assessments, motor activity, organ weights and ratios and macroscopic and microscopic observations did not reveal any significant, consistent, dose-dependent test article-related adverse effects. The NOAEL (no-observed-adverse-effect-level) is 5000 mg/kg/day, the highest dose tested. A series of genotoxicity tests were conducted with Surelease. Surelease showed no evidence of mutagenic activity in the bacterial reverse mutation test with and without metabolic activation and in the in vitro cell mutation assay under the experimental conditions employed. Surelease did not show any evidence of causing chromosome damage or bone marrow cell toxicity when administered by gavage in the mouse micronucleus in vivo test procedure. These findings support the safety of Surelease for use as an excipient.
Surelease水性乙基纤维素分散体是一种辅料，用作微丸、颗粒、非那西丁、药物晶体和片剂的缓释包衣，以及用于药品和膳食补充剂产品的掩味应用。进行了一项研究，以评估喷雾干燥的Surelease通过饮食混合经口给予斯普拉格-道利CD大鼠（每组雌雄各20只）时的毒性，剂量水平为0、2000、3500和5000mg/kg/天，为期至少3个月。治疗3个月后，所有预定进行终末处死的大鼠均被处死，并对选定的器官进行称重。对所有动物的选定组织进行了完整的大体检查和组织病理学评估。对每组雌雄各5只动物进行了神经病理学评估。研究期间未发生死亡。临床观察、眼科检查、体重和食物消耗、血液学、凝血、临床化学、尿液分析、功能观察评估、运动活动、器官重量和比值以及大体和显微镜观察均未发现任何与受试物相关的显著、一致、剂量依赖性不良反应。无观察到不良反应水平（NOAEL）为5000mg/kg/天，即测试的最高剂量。对Surelease进行了一系列遗传毒性试验。在有和无代谢活化的细菌回复突变试验以及在所采用的实验条件下的体外细胞突变试验中，Surelease均未显示出诱变活性的证据。在小鼠体内微核试验程序中，通过灌胃给予Surelease时，未显示出任何导致染色体损伤或骨髓细胞毒性的证据。这些发现支持Surelease作为辅料使用的安全性。
