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铀体内清除动力学-退役核燃料工人的长期随访研究。

Uranium Body Clearance Kinetics-A Long-term Follow-up Study of Retired Nuclear Fuel Workers.

机构信息

Department of Medical Radiation Physics, and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.

Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.

出版信息

Health Phys. 2024 Oct 1;127(4):520-535. doi: 10.1097/HP.0000000000001861. Epub 2024 Jul 24.

Abstract

Nuclear industry workers exposed to uranium aerosols may risk kidney damage and radiation-induced cancer. This warrants the need for well-established dose and risk assessments, which can be greatly improved by using material-specific absorption parameters in the ICRP Human Respiratory Tract Model. The present study focuses on the evaluation of the slow dissolution rate ( s s , d -1 ), a parameter that is difficult to quantify with in vitro dissolution studies, especially for more insoluble uranium compounds. A long-term follow-up of urinary excretion after the cessation of chronic inhalation exposure can provide a better estimate of the slow-rate dissolution. In this study, two workers, previously working for >20 y at a nuclear fuel fabrication plant, provided urine samples regularly for up to 6 y. One individual had worked at the pelletizing workshop with the known presence of uranium dioxide (UO 2 ) and triuranium octoxide (U 3 O 8 ). The second individual worked at the conversion workshop where multiple compounds, including uranium hexafluoride (UF 6 ), uranium dioxide (UO 2 ), ammonium uranyl carbonate, and AUC [UO 2 CO 3 ·2(NH 4 ) 2 CO 3 ], are present. Data on uranium concentration in urine during working years were also available for both workers. The daily excretion of uranium by urine was characterized by applying non-linear least square regression fitting to the urinary data. Material-specific parameters, such as the activity median aerodynamic diameter (AMAD), the respiratory tract absorption parameters, rapid fraction ( f r ,), rapid dissolution rate ( s r , d -1 ), and slow dissolution rate ( s s , d -1 ) and alimentary tract transfer factor ( f A ) acquired from previous work along with default absorption types, were applied to urine data, and the goodness of fit was evaluated. Thereafter intake estimates and dose calculations were performed. For the ex-pelletizing worker, a one-compartment model with a clearance half-time of 662 ± 100 d ( s s = 0.0010 d -1 ) best represented the urinary data. For the ex-conversion worker, a two-compartment model with a major [93% of the initial urinary excretion (A 0 )] fast compartment with a clearance half-time of 1.3 ± 0.4 d ( s r = 0.5 d -1 ) and a minor (7% of A 0 ) slow compartment with a half-time of 394 ± 241 d ( s s = 0.002 d -1 ) provided the best fit. The results from the data-fitting of urinary data to biokinetic models for the ex-conversion worker demonstrated that in vitro derived experimental parameters (AMAD = 20 μm, f r = 0.32, s r = 27 d -1 , s s = 0.0008 d -1 , f A = 0.005) from our previous work best represented the urinary data. This resulted in an estimated intake rate of 0.66 Bq d -1 . The results from the data-fitting of urinary data to biokinetic models for the ex-pelletizing worker indicated that the experimental parameters (AMAD = 10 μm and 20 μm, f r = 0.008, s r = 12 d -1 , f A = 0.00019) from our previous dissolution studies with the slow rate parameter step-wise optimized to urine-data ( s s = 0.0008 d -1 ) gave the best fit. This resulted in an estimated intake rate of 5 Bq d -1 . Experimental parameters derived from in vitro dissolution studies provided the best fit for the subject retired from work at the conversion workshop, where inhalation exposure to a mix of soluble (e.g., AUC, UF 6 ) and relatively insoluble aerosol (e.g., UO 2 ) can be assumed. For the subject retired from work at the pelletizing workshop, which involved exposure to relatively insoluble aerosols (UO 2 and U 3 O 8 ), a considerably higher s s than obtained in dissolution studies provided a better representation of the urinary data and was comparable to reported s s values for UO 2 and U 3 O 8 in other studies. This implies that in vitro dissolution studies of insoluble material can be uncertain. When evaluating the results from the retrospective fitting of urine data, it is evident that the urine samples acquired after cessation of exposure provide less fluctuation. Long-term follow-up of uranium excretion after cessation of exposure is a good alternative for determining absorption parameters and can be considered the most viable way for determining the slow rate for more insoluble material.

摘要

核工业工人接触铀气溶胶可能有肾脏损伤和辐射诱导癌症的风险。这就需要建立完善的剂量和风险评估体系,而使用 ICRP 人类呼吸道模型中的特定物质吸收参数可以大大提高评估效果。本研究重点评估了缓慢溶解率( s s, d -1 ),这是一个很难通过体外溶解研究来定量的参数,特别是对于更难溶解的铀化合物。长期追踪慢性吸入暴露停止后尿液排泄情况,可以更好地估计缓慢溶解率。在这项研究中,两名在核燃料制造厂工作了超过 20 年的工人定期提供尿液样本,最长可达 6 年。其中一名在球团车间工作,已知存在二氧化铀(UO 2 )和三氧化铀八(U 3 O 8 )。第二个人在转化车间工作,那里存在多种化合物,包括六氟化铀(UF 6 )、二氧化铀(UO 2 )、碳酸铀酰铵和 AUC[UO 2 CO 3 ·2(NH 4 ) 2 CO 3 ]。对于这两名工人,我们也有他们在工作期间尿液中铀浓度的数据。通过对尿液数据进行非线性最小二乘回归拟合,描述了铀在尿液中的每日排泄情况。应用以前工作中获得的特定物质参数,如活性中值空气动力学直径(AMAD)、呼吸道吸收参数、快速分数( f r,)、快速溶解率( s r, d -1 )、缓慢溶解率( s s, d -1 )和肠转移系数( f A )以及默认吸收类型,对尿液数据进行拟合,并评估拟合优度。然后进行摄入量估计和剂量计算。对于前球团工人,半衰期为 662±100d( s s = 0.0010 d -1 )的单室模型能更好地代表尿液数据。对于前转化工人,半衰期为 1.3±0.4d( s r = 0.5 d -1 )的主要(93%的初始尿液排泄量[A 0 ])快速隔室和半衰期为 394±241d( s s = 0.002 d -1 )的次要(7%A 0 )缓慢隔室的两室模型提供了最佳拟合。从转化工人尿液数据到生物动力学模型的数据拟合结果表明,从我们之前的工作中获得的体外衍生的实验参数(AMAD=20μm, f r = 0.32, s r = 27 d -1 , s s = 0.0008 d -1 , f A = 0.005)能最好地代表尿液数据。这导致估计的摄入量为 0.66Bq d -1 。从球团工人尿液数据到生物动力学模型的数据拟合结果表明,实验参数(AMAD=10μm和 20μm, f r = 0.008, s r = 12 d -1 , f A = 0.00019)和逐步优化到尿液数据的缓慢溶解率参数( s s = 0.0008 d -1 )提供了最佳拟合。这导致估计的摄入量为 5Bq d -1 。从体外溶解研究中获得的实验参数为从转化车间退休的工人提供了最佳拟合,在那里可以假设吸入暴露于可溶性(例如 AUC、UF 6 )和相对不溶性气溶胶(例如 UO 2 )的混合物。对于从球团车间退休的工人,涉及到相对不溶性气溶胶(UO 2 和 U 3 O 8 )的暴露,从溶解研究中获得的较高的 s s 值能更好地代表尿液数据,与其他研究中报道的 UO 2 和 U 3 O 8 的 s s 值相当。这意味着对不溶性物质的体外溶解研究可能不确定。在评估尿液数据回顾拟合的结果时,显然暴露停止后获得的尿液样本波动较小。停止暴露后长期追踪铀排泄情况是确定吸收参数的好方法,也可以被认为是确定更不溶性物质的缓慢溶解率的最可行方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebff/11460735/311ab29d58e0/hpj-127-520-g001.jpg

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