Karstadt M, Haseman J K
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
Am J Ind Med. 1997 May;31(5):485-94. doi: 10.1002/(sici)1097-0274(199705)31:5<485::aid-ajim1>3.0.co;2-t.
It has been suggested that, for mechanistic reasons, certain tumors found in experimental animals should be discounted when evaluating carcinogenic effects. The questioned tumors are: mouse liver, rat thyroid follicular cell, bladder and kidney (male rat), forestomach (mouse and rat, gavage route), and lung (mouse and rat, inhalation of particles). We sought to determine the effects of discounting those tumors on classification of chemicals as carcinogens in animals. We looked at carcinogenicity data for chemicals studied in NCI-NTP bioassays and/or reviewed in IARC monographs and we found that deleting the questioned tumors would have significant impact on evaluations of carcinogenicity in animals. Fifty-six of 234 (24%) chemicals determined to be carcinogenic in the NCI-NTP bioassay program would no longer be considered carcinogenic: 102 (44%) would have weaker evidence of carcinogenic effects. Thirty-three of 361 (9%) chemicals determined by IARC to have "limited" or "sufficient" evidence of carcinogenicity would no longer be considered carcinogenic; 119 (33%) would have weaker evidence of carcinogenic effects. Because such a large number of chemicals currently considered carcinogenic would be affected by categorical deletion of tumors and because we are not aware of data that would justify such categorical deletions, it would be preferable to consider mechanistic justifications for discounting tumors on a case-by-case basis for each individual chemical. Deletion of tumors on a categorical basis has serious implications for regulation of toxic chemicals and for public health.
有人提出，出于机制方面的原因，在评估致癌作用时，实验动物身上发现的某些肿瘤应不予考虑。受到质疑的肿瘤包括：小鼠肝脏、大鼠甲状腺滤泡细胞、膀胱和肾脏（雄性大鼠）、前胃（小鼠和大鼠，灌胃途径）以及肺（小鼠和大鼠，吸入颗粒物）。我们试图确定不考虑这些肿瘤对化学品在动物体内致癌性分类的影响。我们查看了在NCI-NTP生物测定中研究和/或在IARC专论中审查的化学品的致癌性数据，发现删除这些受到质疑的肿瘤将对动物致癌性评估产生重大影响。在NCI-NTP生物测定项目中被确定为致癌的234种化学品中，有56种（24%）将不再被视为致癌物：102种（44%）的致癌作用证据将减弱。在IARC确定具有“有限”或“充分”致癌证据的361种化学品中，有33种（9%）将不再被视为致癌物；119种（33%）的致癌作用证据将减弱。由于目前被视为致癌物的大量化学品会受到肿瘤分类删除的影响，而且我们不知道有哪些数据可以证明这种分类删除是合理的，因此最好针对每种化学品逐一考虑基于机制的理由来不考虑某些肿瘤。按类别删除肿瘤对有毒化学品的监管和公众健康具有严重影响。
