Lung cancer in rats from prolonged exposure to high concentrations of carbonaceous particles: Implications for human risk assessment
Lung cancer in rats from prolonged exposure to high concentrations of carbonaceous particles: Implications for human risk assessment
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DOI：
10.1080/02726359608906688
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发表时间：
1996-04-01
影响因子：
2.5
通讯作者：
McClellan, RO
中科院分区：
文献类型：
--
作者：
McClellan, RO
在一些研究中观察到肺癌的高发病率，在这些研究中，老鼠通过吸入高浓度的柴油发动机废气和碳黑颗粒而慢性暴露。这些颗粒物此前被认为与苯并[a]芘等其他颗粒物相比相对无害，这些颗粒物因其特定的化学性质而致癌。对暴露在类似浓度的柴油废气中的小鼠和叙利亚仓鼠进行的研究没有产生过量的肺癌，也没有产生可疑的结果。柴油机排放的烟尘和碳黑颗粒很容易被吸入并沉积在肺部区域，由于它们的低溶解度，它们在那里保留了很长的半衰期。大量证据表明，肺癌发病率的增加是由于肺内积累了大量的颗粒物，改变了对肺部颗粒物的清除，持续的炎症，细胞周转增加，以及诱导肺上皮细胞突变。这些突变和随后的谣言被假设为持续的炎症和细胞周转增加的结果，而不是粒子的化学成分与肺细胞DNA直接相互作用的结果。在大鼠身上观察到的影响似乎是阈值现象，只有在长期暴露于高浓度颗粒物的情况下才会发生。因此，不应使用通常用作评估化学物质致癌风险的默认假设的线性化多阶段模型将高浓度的大鼠肺癌结果外推到低浓度。本文回顾了过去评估柴油废气和碳黑致癌风险的方法，并提出了表征其人类致癌风险的替代方法。
High incidences of lung cancers have been observed in a number of studies in which rats were chronically exposed by inhalation to high concentrations of diesel engine exhaust and carbon black particles. These particles have previously been viewed as being relatively innocuous compared with other particles such as benzo[a]pyrene that are carcinogenic because of specific chemical properties. Studies with mice and Syrian hamsters exposed to similar concentrations of diesel exhaust did not produce an excess of lung cancer or yielded equivocal outcomes. Diesel exhaust soot and carbon black particles are readily inhaled and deposited in the pulmonary region, where they are retained with a long half-life because of their low solubility. Substantial evidence indicates that the increased incidence of at lung cancers results from the accumulation of large burdens of particles in the lungs, altered clearance of particles from the lungs, persistent inflammation, increased cell turnover, and induction of mutations in lung epithelial cells. The mutations and subsequent rumors are hypothesized to occur as a result of persistent inflammation and increased cell turnover rather than as a result of direct interaction of chemical constituents of the particles with DNA of lung cells. The observed effects in rats appear to be threshold phenomena that occur only with prolonged exposure to high concentrations of particles. Thus the rat lung cancer findings at high concentrations should not be extrapolated to low concentrations using the linearized multistage model typically used as a default assumption for assessing the cancer risk of chemicals. This article reviews past approaches to evaluating the carcinogenic risk of diesel exhaust and carbon black and suggests alternative approaches to characterizing their human cancer risk.