Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Université Catholique de Louvain (UCL), Brussels, Belgium.
Toxicol Lett. 2012 Aug 13;213(1):122-8. doi: 10.1016/j.toxlet.2011.07.004. Epub 2011 Jul 8.
The industrial uses of indium, a rare metal with no known physiological role in humans, have increased dramatically over the past 15 years. The results of animal toxicity studies showing pulmonary and systemic effects as well as some reports in workers have created a growing concern about the possible occurrence of toxic effects in exposed workers. Validated biomarkers to assess exposure to indium are not available.
This work aimed at investigating the kinetics of indium in urine (In-U) and plasma (In-Pl) in workers manufacturing In ingots and mainly exposed to hardly water-soluble In compounds. All nine workers from the In department of a large metallurgical concern participated in the study as well as 5 retired workers and 20 controls.
Personal breathing zone air was collected throughout the work shift on Monday and Friday. Blood and urine samples were collected, before and after the shift, on the same day as the air sampling and on preshift the next Monday after a non-working week-end. Moreover, rats were given either InCl(3) by intraperitoneal injection or In(2)O(3) by pharyngeal aspiration, In was followed in plasma during 120 days and measured in tissues 120 days after exposure.
Higher In-Pl and In-U concentrations were found in both current (range 0.32-12.61 μg/L plasma; 0.22-3.50 μg/g creat) and former (0.03-4.38 μg/L plasma; 0.02-0.69 μg/g creat) workers compared with controls (<0.03 μg/L plasma; <0.02 μg/g creat). Both biological parameters were highly correlated but no correlation was found between In-air (10-1030 μg/m(3)) and In-Pl or In-U. Normalizing In-U by the urinary creatinine concentration reduced the inter- (from 90% to 70%) and intra-individual variability (from 54% to 35%). In-Pl remained remarkably stable along the working week (inter- and intra-individual variability: 89% and 10%, respectively). Neither In-U nor In-Pl significantly increased during the day or the week. A week-end without occupational exposure was not sufficient to reach the background In-Pl and In-U levels measured in controls. The results of the experimental investigations confirmed the hypothesis that inhalation of hardly soluble In compounds may cause accumulation of In in the body leading to a prolonged "endogenous exposure" from both a lung depot of "insoluble" particles that are progressively absorbed and from a retention depot in other internal organs.
This study shows that in workers exposed to hardly soluble In compounds, In-U and In-Pl are very sensitive to detect exposure and mainly reflect long-term exposure. In-Pl levels are particularly stable for a given individual. In-U might be more influenced than In-Pl by recent exposure. Both parameters remained high years after withdrawal from exposure, indicating a possible endogenous exposure and a prolonged risk of pulmonary and systemic diseases even after work exposure has ceased.
作为一种在人体中没有已知生理作用的稀有金属,铟在过去 15 年中的工业用途急剧增加。动物毒性研究结果表明,铟会对肺部和全身产生影响,以及一些工人的报告,这引起了人们对暴露于铟的工人可能发生毒性作用的日益关注。目前还没有经过验证的生物标志物来评估铟暴露情况。
本研究旨在调查制造铟锭的工人尿液(In-U)和血浆(In-Pl)中铟的动力学,这些工人主要接触难溶于水的铟化合物。来自一家大型冶金公司铟部门的所有 9 名工人以及 5 名退休工人和 20 名对照者都参加了这项研究。
在周一和周五的整个工作班次期间,通过个人呼吸区空气采集器收集空气样本。在同一工作日,在空气采样后以及非工作日周末后的下周一,采集血液和尿液样本。此外,大鼠通过腹腔注射给予氯化铟(InCl(3))或通过咽吸入氧化铟(In(2)O(3)),在 120 天内监测血浆中的铟,并在暴露后 120 天测量组织中的铟。
与对照组相比,当前(范围 0.32-12.61μg/L 血浆;0.22-0.69μg/g 肌酐)和以前(0.03-4.38μg/L 血浆;0.02-0.69μg/g 肌酐)的工人血浆(0.03-4.38μg/L 血浆;0.02-0.69μg/g 肌酐)中的铟-Pl 和铟-U 浓度均较高。这两个生物参数高度相关,但空气中的铟(10-1030μg/m(3))与铟-Pl 或铟-U 之间没有相关性。通过尿肌酐浓度对尿铟进行标准化降低了个体间(从 90%降至 70%)和个体内(从 54%降至 35%)的变异性。铟-Pl 在整个工作周内保持相当稳定(个体间和个体内的变异性分别为 89%和 10%)。无论是白天还是一周内,尿铟和血浆铟都没有显著增加。非工作日的周末不足以使对照组测量的背景铟-Pl 和铟-U 水平达到。实验研究的结果证实了这样一种假设,即吸入难溶性铟化合物可能导致铟在体内积累,从而导致从肺部“不可溶”颗粒的储存库中逐渐吸收以及从其他内部器官的储存库中保留的“内源性暴露”,从而导致长时间的“内源性暴露”。
本研究表明,在接触难溶性铟化合物的工人中,尿铟和血浆铟非常敏感,可以检测到暴露情况,主要反映长期暴露情况。对于给定的个体,铟-Pl 水平特别稳定。与血浆铟相比,尿铟可能更容易受到近期暴露的影响。这两个参数在停止暴露多年后仍保持较高水平,表明即使工作暴露已经停止,仍可能存在内源性暴露和肺部及全身疾病的长期风险。