Summary of an international methods validation study, carried out in nine laboratories, on the immunological assessment of cyclosporin A in the Fischer 344 rat.
In evaluating the adverse effects of chemicals on the immune response, the mouse has been the predominant animal species of choice. The acceptance of the mouse as a validated animal model has been the result, in part, of the studies conducted by the US National Toxicology Program (NTP). In these studies functional and host-resistance assays were developed and validated using five compounds and four testing laboratories. In toxicological evaluations of drugs and chemicals, the rat has been the rodent species of choice of the worldwide toxicology community. The current study was designed to begin the validation of the rat as a model for immunotoxicology assessment. Nine laboratories participated in the study, including laboratories from Canada, France, the United States and The Netherlands. Before the study began a detailed protocol was prepared and standard operating procedures were developed. Cyclosporin A was selected as the prototype immunosuppressive compound, and was administered orally to male Fischer 344 rats. Data were collected on standardized forms and submitted to a central laboratory for statistical analysis. Similar dose-response trends were observed between the various laboratories. In the natural killer cell assay and concanavalin A mitogen assay similar results were observed in at least 63% of the laboratories. In the T-dependent antibody-plaque forming cell assay, and the mixed leucocyte response, 100% of the laboratories that conducted the assays had statistically similar results. The results from this study support the usefulness of the rat as a model species for immunotoxicity assessment and represent a beginning for international interlaboratory validation of immunotoxicology assays in this species.
White
K L
KL
Department of Pharmacology and Toxicology and Biomedical Engineering Program, Medical College of Virginia/Virginia Commonwealth University, Richmond, VA 23298, USA.
Gennings
C
C
Murray
M J
MJ
Dean
J H
JH