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首页> 外文期刊>Archives of Toxicology >Small difference in carcinogenic potency between GBP nanomaterials and GBP micromaterials
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Small difference in carcinogenic potency between GBP nanomaterials and GBP micromaterials

机译：GBP纳米材料和GBP微型材料的致癌潜能差异很小

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Materials that can be described as respirable granular biodurable particles without known significant specific toxicity (GBP) show a common mode of toxicological action that is characterized by inflammation and carcinogenicity in chronic inhalation studies in the rat. This study was carried out to compare the carcinogenic potency of GBP nanomaterials (primary particle diameter 1–100 nm) to GBP micromaterials (primary particle diameter >100 nm) in a pooled approach. For this purpose, the positive GBP rat inhalation carcinogenicity studies have been evaluated. Inhalation studies on diesel engine emissions have also been included due to the fact that the mode of carcinogenic action is assumed to be the same. As it is currently not clear which dose metrics may best explain carcinogenic potency, different metrics have been considered. Cumulative exposure concentrations related to mass, surface area, and primary particle volume have been included as well as cumulative lung burden metrics related to mass, surface area, and primary particle volume. In total, 36 comparisons have been conducted. Including all dose metrics, GBP nanomaterials were 1.33- to 1.69-fold (mean values) and 1.88- to 3.54-fold (median values) more potent with respect to carcinogenicity than GBP micromaterials, respectively. Nine of these 36 comparisons showed statistical significance (p < 0.05, U test), all of which related to dose metrics based on particle mass. The maximum comparative potency factor obtained for one of these 9 dose metric comparisons based on particle mass was 4.71. The studies with diesel engine emissions did not have a major impact on the potency comparison. The average duration of the carcinogenicity studies with GBP nanomaterials was 4 months longer (median values 30 vs. 26 months) than the studies with GBP micromaterials, respectively. Tumor rates increase with age and lung tumors in the rat induced by GBP materials are known to appear late, that is, mainly after study durations longer than 24 months. Taking the different study durations into account, the real potency differences were estimated to be twofold lower than the relative potency factors identified. In conclusion, the chronic rat inhalation studies with GBP materials indicate that the difference in carcinogenic potency between GBP nanomaterials and GBP micromaterials is low can be described by a factor of 2–2.5 referring to the dose metrics mass concentration.
机译：可以描述为可呼吸的颗粒状生物耐用颗粒而没有已知的显着比毒性（GBP）的材料显示出一种常见的毒理作用模式，其特征是在大鼠的慢性吸入研究中具有炎症和致癌性。这项研究以汇总的方式比较了GBP纳米材料（一次粒径为1-100 nm）和GBP微型材料（一次粒径> 100 nm）的致癌能力。为了这个目的，已经评估了GBP大鼠吸入致癌性的阳性研究。由于假定致癌作用的方式相同，因此也包括了对柴油机排放物的吸入研究。由于目前尚不清楚哪种剂量指标最能解释致癌性，因此已考虑了不同的指标。与质量，表面积和初级颗粒体积有关的累积暴露浓度以及与质量，表面积和初级颗粒体积有关的累积肺负荷指标都已包括在内。总共进行了36次比较。包括所有剂量指标，GBP纳米材料在致癌性方面的功效分别比GBP微材料高1.33至1.69倍（平均值）和1.88至3.54倍（中值）。这36个比较中有9个显示出统计学意义（p <0.05，U检验），所有这些均与基于颗粒质量的剂量指标有关。对于这9个剂量度量比较中的一个，基于颗粒质量获得的最大比较效价因子为4.71。柴油发动机排放的研究对效价比较没有重大影响。使用GBP纳米材料进行致癌性研究的平均持续时间分别比使用GBP微材料进行的研究长4个月（中值分别为30个月和26个月）。肿瘤发生率随年龄增长而增加，已知由GBP材料诱发的大鼠肺肿瘤出现较晚，也就是说，主要是在研究持续时间超过24个月之后。考虑到不同的研究时间，估计实际效能差异比确定的相对效能因子低两倍。总之，用GBP物质进行的慢性大鼠吸入研究表明，GBP纳米材料和GBP微型材料之间的致癌潜能差异很小，可以用剂量系数质量浓度的2–2.5来描述。

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