FOURTEEN DAY ORAL RANGEFINDING STUDIES AND TWENTY-EIGHT

美国国家癌症研究所癌症预防部化学预防剂开发研究小组指导了一项研究性化学预防剂开发计划，以确定和开发预防，延迟或逆转致癌过程的药物。 为了评估研究性新药的安全性，必须对其毒理学潜力进行评价。 各种动物研究被用来评估候选新药在治疗人类时所带来的潜在风险。 首先，在一种啮齿动物种属（通常为大鼠）中进行毒性研究，从经口剂量范围探索研究和短期经口毒性研究开始。 这些数据将被纳入向FDA提交的研究性新药（IND）申请中，这是在启动人体临床试验之前所需的。 一系列试验将包括监测大体运动和行为活动、摄食量、体重、可观察到的外观变化、与供试化合物药理学和毒理学相关的临床体征、血液学、临床化学、检眼镜检查以及肉眼和显微镜组织检查。 将从快速获得预防干预开发（RAPID）计划中选择研究化合物。 这些研究应符合支持NDA申请的毒理学研究的现行行业标准，并应根据FDA药物非临床研究质量管理规范（GLP）法规在AAALAC认证的、NIH/OPRR和USDA注册的实验室（具有活跃的机构动物护理和使用委员会（IACUC））中进行。

The National Cancer Institute, Division of Cancer Prevention, Chemopreventive Agent Development Research Group directs an investigational chemopreventive agent development program to identify and develop drugs that will prevent, delay, or reverse the process of carcinogenesis. In order to assess safety of investigational new agents, they must be evaluated for their toxicological potential. A variety of animal studies are used to assess the potential risk posed by candidate new drugs in treating humans. Initially, toxicity studies are conducted in one rodent species (typically rat) starting with oral rangefinding studies and short term oral toxicity studies. The data will be included in an Investigational New Drug (IND) application to FDA which is required prior to initiation of human clinical trials. The battery of tests will include monitoring of gross motor and behavioral activity, food consumption, body weight, observable changes in appearance, clinical signs related to pharmacology and toxicology of the test compound, hematology, clinical chemistry, ophthalmoscopic examination, and macroscopic and microscopic tissue examination. Compound selection for the study will be made from the Rapid Access to Preventive Intervention Development (RAPID) Program. The studies shall fulfill current industry standards for toxicology studies supporting NDA application and shall be conducted under FDA Good Laboratory Practice (GLP) regulations in AAALAC accredited, NIH/OPRR & USDA registered laboratories with active Institutional Animal Care and Use Committee (IACUC).