Intravenous Safety Study in Rats Given Paramagnetic, Polystyrene Beads with Covalently Bound Sheep Anti-Mouse Immunoglobulin G (IgG)

The potential for acute toxicity from Dynabeads1 M-450 Sheep Anti-Mouse IgG ST (SAM-Beads) administered once intravenously to male and female rats was assessed. SAM-Beads in saline containing 0.5% plasma protein fraction (PPF) was intravenously administered at dosages of 9.6 times 104 or 8.3 times 108 beads/kg at a rate of ≥2.5 ml/min/kg. Rats administered 9.6 times 104 beads/kg were killed 14 days posttreatment. Rats administered 8.3 times 108 beads/kg were killed either 14 or 42 days posttreatment. Saline containing 0.5% PPF served as the control article. Treatment groups were statistically compared with respect to clinical chemistry, hematology parameters, and body weight data. No significant group differences were detected (α = 0.01) with respect to any statistically analyzed data. No SAM-Beads were detected in urine samples collected overnight posttreatment. No test beads were found in any of the tissues from animals administered 9.6 times 104 beads/kg. The SAM-Beads were evident in the lung, liver, spleen, lymph nodes, kidney, and sternal bone marrow of rats administered 8.3 times 108 beads/kg and killed 14 or 42 days posttreatment. The SAM-Beads observed were recognized as a foreign body and were phagocy-tized by cells of the reticuloendothelial system. The majority of the SAM-Beads were found in the lung, liver, and spleen and were slightly more numerous among animals who were killed at 14 days. There was also a trend toward an increased incidence and/or distribution of phagocytized beads in the bone marrow of animals killed 42 days posttreatment when compared with the 14-day killed animals. A few extracellular beads were present in the lymph nodes, kidneys, and sternal bone marrow. Under the conditions of this study, intravenous administration of Dynabeads M-450 Sheep Anti-Mouse IgG ST did not result in any adverse test-article-related macroscopic, clinical pathologic, or histopathologic changes.