NTP DATABASE SUMMARIZATION AND EVALUATION

点击翻译按钮获取中文摘要

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.