NTP DATABASE SUMMARIZATION AND EVALUATION

工作总结：一项数据库评估审查了决策 NTP在评估长期啮齿动物时使用的程序 致癌性研究，以确定该程序是否 导致过多的假阳性或假阴性 结果。我们的评估表明，假阳性率相当高 长期研究的NTP水平较低。评估假阴性率更多 很难，因为生物测定的敏感性有限 检测微妙的致癌作用。卵巢间质细胞瘤 雄性F344大鼠的睾丸表现得更为显著(p&lt；0.05)。 偶然发生的事件比预期的要多，但没有一个被认为是 与化学物质有关。然而，这些生物的生物学意义 增长不确定，因为肿瘤的背景比率很高 (&gt；90%)。 对啮齿动物致癌作用机制的日益重视 研究导致一些调查人员得出结论，某些特定的地点 肿瘤与人类的相关性值得怀疑。我们开展了一项 对NTP和IARC数据库进行了详细评估，发现 肿瘤部位是致癌作用的重要组成部分。 在啮齿动物研究中观察到的。由于确定了最终的机制 行动可能很困难，我们建议考虑机械化 以化学为基础对肿瘤进行化学折扣的理由。

Summary of Work: One database evaluation examined the decision making process used by the NTP in its evaluation of long term rodent carcinogenicity studies to determine whether or not this procedure resulted in an excessive number of false positive or false negative outcomes. Our evaluation suggests that false positive rates are fairly low in NTP long term studies. Assessing false negative rates is more difficult because of the limited sensitivity of the bioassay for detecting subtle carcinogenic effects. Interstitial cell tumors of the testis in male F344 rats showed considerably more significant (p<0.05) increased incidences than expected by chance, yet none were considered to be chemically-related. However, the biological significance of these increases is uncertain because of the high background rate of neoplasia (>90%) for this target site. The increasing emphasis on mechanism of action in rodent carcinogenicity studies has led some investigators to conclude that certain site-specific tumors are of questionable relevance to humans. We carried out a detailed evaluation of the NTP and IARC databases and found that these tumor sites constitute a significant portion of the carcinogenic effects observed in rodent studies. Since determining definitive mechanisms of action may be difficult, we recommend considering mechanistic justifications for discounting tumors on a chemical by chemical basis.