Arfsten D P, Wilfong E R, Bekkedal M Y-V, Johnson E W, McInturf S M, Eggers J S, Schaeffer D J, Still K R
Navy Drug Screening Laboratory, Naval Air Station, Jacksonville, Florida 32212-0113, USA.
J Toxicol Environ Health A. 2007 Dec;70(23):1995-2010. doi: 10.1080/15287390701550987.
In 2002, the Naval Health Research Center Toxicology Detachment began a study to determine the effects of surgically implanted depleted uranium (DU) pellets on adult rat (e.g., P1 generation) health and reproduction. In this report, the effect of implanted DU on adult rat behavior and health is described. Adult Sprague-Dawley (SD) rats, 8 wk of age, were surgically implanted with 0, 4, 8, 12, or 20 DU pellets (1 x 2 mm); 20 DU pellets of size 1 x 2 mm approximates to 0.22 kg (0.5 lb) of DU in a 70-kg (154 lb) person. Control animals were implanted with 12 or 20 tantallum (Ta) pellets. The animals were then housed for up to 150 d postimplantation or 20% of an assumed 2-yr life span for rats. The concentration of uranium in urine directly correlated with the number of implanted DU pellets, indicating that DU was migrating into the body from the implanted pellets. Three male and 4 female animals died during the 150-d period of causes apparently not related to DU implantation. Behavioral testing found no definitive evidence of neurobehavioral perturbations associated with DU implantation. Uranium translocated to tissues known to sequester uranium (bone, teeth, and kidneys), but uranium concentrations varied considerably within each dose group and did not follow a dose-response pattern as anticipated. Serum chemistry values were within normal ranges for the SD rat. However, alanine aminotransferase measurements were significantly lower for rats implanted with 20 DU pellets as compared to sham surgery controls but not when compared to animals implanted with Ta pellets only. Phosphate measurements were significantly lower for female rats implanted with 20 DU pellets as compared to both sham surgery controls and animals implanted with Ta pellets only. Monocyte ratios were higher in adult rats implanted with 20 DU pellets as compared to sham surgery controls but not when compared to animals implanted with 20 Ta pellets. Mean platelet volume was found to be significantly lower for rats implanted with 20 DU pellets as compared to sham surgery controls but not when compared to animals implanted with 20 Ta pellets. Gross necropsy found no obvious tissue abnormalities in implanted rats, and the weights of major tissues did not differ between Ta- and DU-implanted animals. Histopathologic analysis of major tissues from animals implanted with 0 pellets, 20 Ta pellets, or 20 DU pellets found no differences between treatment groups. The findings of this study indicate that implantation of up to 20 DU pellets in adult rats did not have a significant negative impact on their general health and neurobehavioral capacities when assessed after 150 d of pellet implantation. However, the growing body of data on the potential health effects associated with DU exposure warrants further studies involving higher embedded DU body burdens in conjunction with longer surveillance periods postimplantation.
2002年，海军健康研究中心毒理学支队开展了一项研究，以确定手术植入贫铀（DU）颗粒对成年大鼠（如P1代）健康和繁殖的影响。在本报告中，描述了植入DU对成年大鼠行为和健康的影响。选用8周龄的成年斯普拉格-道利（SD）大鼠，通过手术分别植入0、4、8、12或20颗DU颗粒（1×2毫米）；20颗1×2毫米大小的DU颗粒相当于70千克（154磅）人体中0.22千克（0.5磅）的DU。对照动物植入12颗或20颗钽（Ta）颗粒。然后将动物饲养至植入后150天，或大鼠假定2年寿命的20%。尿液中铀的浓度与植入的DU颗粒数量直接相关，表明DU正从植入的颗粒迁移到体内。在150天期间，有3只雄性和4只雌性动物死亡，死因显然与DU植入无关。行为测试未发现与DU植入相关的神经行为紊乱的确切证据。铀转移到已知会蓄积铀的组织（骨骼、牙齿和肾脏）中，但每个剂量组内铀浓度差异很大，且未呈现预期的剂量反应模式。血清化学值在SD大鼠的正常范围内。然而，与假手术对照组相比，植入20颗DU颗粒的大鼠丙氨酸转氨酶测量值显著降低，但与仅植入Ta颗粒的动物相比则无此差异。与假手术对照组和仅植入Ta颗粒的动物相比，植入20颗DU颗粒的雌性大鼠磷酸盐测量值显著降低。与假手术对照组相比，植入20颗DU颗粒的成年大鼠单核细胞比例更高，但与植入20颗Ta颗粒的动物相比则无此差异。发现与假手术对照组相比，植入20颗DU颗粒的大鼠平均血小板体积显著降低，但与植入20颗Ta颗粒的动物相比则无此差异。大体尸检未发现植入大鼠有明显的组织异常，Ta植入组和DU植入组动物的主要组织重量无差异。对植入0颗颗粒、20颗Ta颗粒或20颗DU颗粒的动物主要组织进行组织病理学分析，发现各治疗组之间无差异。本研究结果表明，在成年大鼠中植入多达20颗DU颗粒，在植入颗粒150天后进行评估时，对其总体健康和神经行为能力没有显著负面影响。然而，关于DU暴露潜在健康影响的越来越多的数据表明，有必要进一步开展研究，涉及更高的体内DU负荷以及植入后更长的监测期。
