INTRAVENOUS SAFETY STUDY IN RATS GIVEN PARAMAGNETIC, POLYSTYRENE BEADS WITH COVALENTLY BOUND SHEEP ANTI-MOUSE IMMUNOGLOBULIN-G (IGG)

The potential for acute toxicity from Dynabeads(1) M-450 Sheep Anti-Mo use IgG ST (SAM-Beads) administered once intravenously to male and fem ale rats was assessed. SAM-Beads in saline containing 0.5% plasma prot ein fraction (PPF) was intravenously administered at dosages of 9.6 x 10(4) or 8.3 x 10(8) beads/kg at a rate of similar to 2.5 ml/min/kg. R ats administered 9.6 x 10(4) beads/kg were killed 14 days posttreatmen t. Rats administered 8.3 x 10(8) beads/kg were killed either 14 or 42 days posttreatment. Saline containing 0.5% PPF served as the control a rticle. Treatment groups were statistically compared with respect to c linical chemistry, hematology parameters, and body weight data. No sig nificant group differences were detected (alpha = 0.01) with respect t o any statistically analyzed data. No SAM-Beads were detected in urine samples collected overnight posttreatment. No test beads were found i n any of the tissues from animals administered 9.6 x 10(4) beads/kg. T he SAM-Beads were evident in the lung, liver, spleen, lymph nodes, kid ney, and sternal bone marrow of rats administered 8.3 x 10(8) beads/kg and killed 14 or 42 days posttreatment. The SAM-Beads observed were r ecognized as a foreign body and were phagocytized by cells of the reti culoendothelial system. The majority of the SAM-Beads were found in th e lung, liver, and spleen and were slightly more numerous among animal s who were killed at 14 days. There was also a trend toward an increas ed incidence and/or distribution of phagocytized beads in the bone mar row of animals killed 42 days posttreatment when compared with the 14- day killed animals. A few extracellular beads were present in the lymp h nodes, kidneys, and sternal bone marrow. Under the conditions of thi s study, intravenous administration of Dynabeads M-450 Sheep Anti-Mous e IgG ST did not result in any adverse test-article-related macroscopi c, clinical pathologic, or histopathologic changes.