Roller Markus
Advisory Office for Risk Assessment, Doldenweg 14, Dortmund, Germany.
Exp Toxicol Pathol. 2007 Aug;58(6):393-405. doi: 10.1016/j.etp.2007.02.003. Epub 2007 Jun 8.
The article presents a comparison of two opposing evaluations and interpretations of the carcinogenicity study with 19 granular dusts. It is one of the two responses to a Letter to the Editor of Exp Toxicol Pathol by Morfeld and Borm(1), who had analysed selected data from the primary source of our study [Borm et al., Inhal Toxicol 2000;12(Suppl 3):225-31; Borm et al., Int J Cancer 2004;110:3-14; Morfeld et al., Inhal Toxicol 2006:18:215-25]. In contrast, our statistical analyses are based on the authentic and complete results of the study published with a detailed description of materials, methods and results [Pott and Roller, Eur J Oncol 2005,10:249-81; Mohr et al. Exp Toxicol Pathol 2006;58:13-20; Roller and Pott, Ann NY Acad Sci 2006,1076:266-80]. Analysis of the tumor incidences from non-specifically toxic dusts in terms of a usual multistage model leads to reasonable dose-response curves and to the finding that tumor risk depends on the retained dust volume and on mean particle size. The model is adequate because survival of the groups included in the analysis was not reduced. In contrast to this analysis, Morfeld et al. (2006) calculated an implausible threshold of 10mg instilled total dust per rat and a saturation dose of 20mg. These values are not compatible with the data because three dose groups with highly significantly increased tumor incidences (up to 67%) lie within the 95% confidence interval of the threshold dose of Morfeld et al. (2006). The claim of Morfeld [Zbl Arbeitsmed 2004;54(7):246-58] to consider as "of interest" only carcinogenicity tests with doses similar to current occupational exposure limit values would make it impossible to identify the carcinogenicity of non-specifically toxic dusts even if the excess risk is higher than 1 in 100.
本文对19种颗粒粉尘致癌性研究的两种相反评估和解释进行了比较。这是对Morfeld和Borm致《实验毒理学与病理学》编辑信（1）的两种回应之一，他们分析了我们研究原始资料中的部分数据[Borm等人，《吸入毒理学》2000年；12（增刊3）：225 - 31；Borm等人，《国际癌症杂志》2004年；110：3 - 14；Morfeld等人，《吸入毒理学》2006年：18：215 - 25]。相比之下，我们的统计分析基于已发表研究的真实完整结果，该研究详细描述了材料、方法和结果[Pott和Roller，《欧洲肿瘤学杂志》2005年，10：249 - 81；Mohr等人，《实验毒理学与病理学》2006年；58：13 - 20；Roller和Pott，《纽约科学院学报》2006年，1076：266 - 80]。根据常用的多阶段模型分析非特异性有毒粉尘的肿瘤发生率，可得出合理的剂量 - 反应曲线，并发现肿瘤风险取决于粉尘的留存量和平均粒径。该模型是合适的，因为分析中所纳入组的存活率并未降低。与这种分析相反，Morfeld等人（2006年）计算出每只大鼠注入总粉尘量为10毫克时出现了不合理的阈值以及20毫克的饱和剂量。这些值与数据不相符，因为三个肿瘤发生率显著升高（高达67%）的剂量组处于Morfeld等人（2006年）阈值剂量的95%置信区间内。Morfeld[《职业医学文献》2004年；54（7）：246 - 58]声称仅将与当前职业接触限值相似剂量的致癌性试验视为“有意义”，这将使得即使过量风险高于1/100，也无法识别非特异性有毒粉尘的致癌性。
