Evaluation of the Effect of Implanted Depleted Uranium (DU) on Adult Rat Behavior and Toxicological Endpoints

Abstract

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 × 2 mm); 20 DU pellets of size 1 × 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 aminotransferse 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.

This work was made possible by a grant from the U.S. Army Medical Research Acquisition Activity (USAMRAA), 820 Chandler Street, Fort Detrick, MD 21702–5014. The views expressed in this article are those of the authors and do not necessarily reflect the official position or policy of the Department of the Navy, Department of the Army, Department of Defense, the U.S. government, or the Wisconsin Department of Health and Family Services. This article is approved for public release, distribution unlimited.

The experiments reported here were conducted according to the principles set forth in the “Guide for the Care and Use of Laboratory Animals,” Institute of Laboratory Animal Resources, National Research Council, DHHS, Publication No. (NIH) 86–23 (1996). All procedures involving live animals were approved by the WPAFB Institutional Animal Care and Use Committee (IACUC) as protocol number F-WA-2002-0064-A.

Notes

Organization of Economic Co-operation and Development. 2000. Guidance Document on the Recognition, Assessment, and Use of Clinical Signs as Humane Endpoints for Experimental Animals Used in Safety Evaluation. OECD Environmental Health and Safety Publications Series on Testing and Assessment. No. 19. Environment Directorate, Organization for Economic Co-Operation and Development, Paris.