RANGE FINDING/ACUTE ORAL TOXICITY OF CHEMOPREVENTIVES

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化学预防剂开发计划，以确定和开发能够预防、延缓或逆转癌变过程的药物。为了评估试验性新药的安全性，必须对其毒理学潜力进行评估。各种各样的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。最初，毒性研究是在一种啮齿类动物（通常是大鼠）中进行的，从口腔范围研究和短期口腔毒性研究开始。这些数据将包括在开始人体临床试验之前向FDA提交的新药研究（IND）申请中。一系列测试将包括监测大运动和行为活动、食物消耗、体重、可观察到的外观变化、与试验化合物的药理学和毒理学相关的临床体征、血液学、临床化学、眼科检查以及宏观和微观组织检查。该研究的化合物选择将从快速获取预防干预发展（Rapid）计划中进行。该研究应符合支持NDA申请的毒理学研究的当前行业标准，并应在AAALAC认可的、NIH/OPRR和USDA注册的实验室（活跃的机构动物护理和使用委员会（IACUC））中按照FDA良好实验室规范（GLP）规定进行。

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).