NTP DATABASE SUMMARIZATION AND EVALUATION

工作总结：一个数据库评估检查了决策制定 NTP在长期啮齿动物评估中使用的过程 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， NTP长期研究中的低水平。 评估假阴性率 由于生物测定的灵敏度有限， 检测细微的致癌作用 间质细胞瘤 雄性F344大鼠睾丸组织中的DNA含量显著高于雄性F344大鼠（p<0.05）。 偶然发生率高于预期，但没有一个被认为 与化学有关。 然而，这些的生物学意义 增加是不确定的，因为肿瘤的高背景率 （>90%）。 啮齿类动物致癌作用机制的研究进展 一些研究人员得出结论， 肿瘤与人类的相关性值得怀疑。 我们进行了 NTP和IARC数据库的详细评估，发现这些 肿瘤部位构成致癌作用的重要部分 在啮齿动物研究中观察到。自从确定了 行动可能很困难，我们建议考虑机械 在化学物质的基础上对肿瘤进行折扣的理由。

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.