RANGE FINDING/ACUTE ORAL TOXICITY OF CHEMOPREVENTIVES

美国国家癌症研究所癌症预防和化学预防药物开发研究小组指导一项研究性化学预防药物开发计划，以确定和开发将预防、延缓或逆转癌症发生过程的药物。为了评估正在研究的新药的安全性，必须评估它们的毒理学潜力。各种动物研究被用来评估候选新药在治疗人类方面构成的潜在风险。最初，毒性研究是在一种啮齿动物物种(通常是大鼠)中进行的，首先是口服测距研究和短期口服毒性研究。这些数据将被包括在向FDA提交的新药研究(IND)申请中，这是启动人体临床试验之前所需的。该系列测试将包括监测大体运动和行为活动、食物消耗、体重、外观的可观察变化、与测试化合物的药理学和毒理学有关的临床体征、血液学、临床化学、眼底检查以及肉眼和显微组织检查。这项研究的化合物将从快速获得预防干预发展(RAPID)计划中进行选择。这些研究应符合当前支持NDA申请的毒理学研究的行业标准，并应在AAALAC认证、NIH/OPRR和美国农业部注册的实验室以及积极的机构动物护理和使用委员会(IACUC)中根据FDA良好实验室规范(GLP)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).