REPRODUCTIVE TOXICITY TEST SYSTEM

生殖毒性测试系统

• 批准号: 2308443
• 负责人: BRUCE C BRIGGS
• 金额: $ 120.81万
• 依托单位: NORTHRUP GRUMMAN INFORM TECH CORP
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-06-30 至 1996-06-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2308443
• 关键词: REPRODUCTIVE; TOXICITY; TEST; SYSTEM

As part of the National Toxicology Program one of our mandates is to determine the reproductive toxicity of industrial and environmental chemicals/agents/conditions in order to protect the public from reproductive health hazards. In order to accomplish this goal we have devised a test for reproductive toxicity called Reproductive Assessment by Continuous Breeding (RACB). It is similar enough to conventional multigeneration studies to be useful to regulatory agencies but also has additional endpoints which will identify a toxicant which does not specifically alter fertility. It also provides an indication of the site of action to aid in the design of follow-up experiments on the site and mechanism of action of toxicants. This RACB protocol improved over the conventional fertility tests by dosing breeding pairs over 98 days (mice) which resulted in up to five litters being produced thereby significantly increasing the sensitivity of the test. In addition, it contains histological assessment of the testis and epididymis, measurement of epididymal sperm number, motility and morphology, and weight of the testis, epididymis, seminal vesicles, and prostate in order to assess any change in spermatogenesis. A crossover mating trial is used to determine the sex affected. An assessment of the second generation with a complete necropsy including histology, sperm assessment and reproductive organ weights also improves the sensitivity of the test. This RACB protocol will be used in this contract to identify chemicals/agents/conditions of environmental and industrial origin which are reproductive toxicants. This information will then be used by government regulatory agencies to aid in their decision making process and by the NTP as a starting point for continued studies on the site and mechanism of action of these toxicants.

作为国家毒理学计划的一部分，我们的任务之一是 确定工业和生物制品的生殖毒性 环境化学品/试剂/条件，以保护 公众免受生殖健康危害。 为了实现 为了这个目标，我们设计了一种生殖毒性测试，称为 连续育种繁殖评估 (RACB)。 这是 与传统的多代研究足够相似，很有用 监管机构，但也有额外的端点，这将 确定一种不会特别改变生育能力的毒物。 它还提供了行动地点的指示，以帮助 后续实验部位和作用机制的设计 有毒物质。该RACB协议比传统协议有所改进 通过在 98 天的时间内对繁殖配对（小鼠）给药进行生育力测试 导致产生多达五窝幼崽，从而显着 提高测试的灵敏度。 此外，它还包含 睾丸和附睾的组织学评估、测量 附睾精子的数量、活力和形态以及重量 睾丸、附睾、精囊和前列腺，以便 评估精子发生的任何变化。 交叉交配试验是 用于确定受影响的性别。 对第二个的评价 一代进行完整的尸检，包括组织学、精子 评估和生殖器官重量也改善了 测试的敏感性。 该 RACB 协议将在本合同中用于识别 环境和工业来源的化学品/试剂/条件 它们是生殖毒物。 该信息随后将被 政府监管机构用来帮助他们做出决定 制定过程并以 NTP 作为持续的起点 研究这些毒物的作用部位和机制。