National Research Centre for the Working Environment, Copenhagen, Denmark.
Part Fibre Toxicol. 2020 Jul 16;17(1):32. doi: 10.1186/s12989-020-00364-0.
In response to the Letter to the Editor by Kevin Driscoll et al., we certainly agree that particle clearance halftimes are increased with increasing lung burden in rats, hamsters and mice, whereas complete inhibition of particle clearance has only been observed in rats, and only at high particle concentrations (50 mg/m). Where we disagree with Kevin Driscoll and colleagues, is on the implications of the increased clearance halftimes observed at higher lung burden. We argue that it does not hamper the extrapolations from relatively high dose levels to lower dose levels.Furthermore, we highlight, again, the challenges of detecting particle-induced lung cancer in epidemiological studies where occupational, particle-induced lung cancer has to be detected on top of the background lung cancer incidence. Almost all available epidemiological studies on carbon black and titanium dioxide suffer from a number of limitations, including lack of control for smoking, the use of background population cancer rates as reference in the US studies, lack of information regarding particle size of the exposure, and incomplete follow-up for cause of death of the study population.
针对 Kevin Driscoll 等人的来信,我们当然同意在大鼠、仓鼠和小鼠中,颗粒清除半衰期随肺部负荷的增加而延长,而只有在高颗粒浓度(50mg/m)下才观察到完全抑制颗粒清除。我们与 Kevin Driscoll 和同事们的分歧在于,对更高肺部负荷下观察到的清除半衰期延长的影响的理解。我们认为,这并不妨碍从相对高剂量水平到低剂量水平的推断。此外,我们再次强调,在流行病学研究中检测职业性、颗粒诱导性肺癌的挑战,在这些研究中,必须在背景肺癌发病率的基础上检测颗粒诱导性肺癌。几乎所有关于炭黑和二氧化钛的可用流行病学研究都存在一些局限性,包括缺乏对吸烟的控制、在美国研究中使用背景人群癌症发病率作为参考、缺乏关于暴露颗粒大小的信息以及对研究人群死亡原因的不完全随访。