Interlaboratory comparison of the CB6F1-Tg rasH2 rapid carcinogenicity testing model

Several genetically engineered mouse models are currently being examined fo r potential use in cancer hazard identification. We have undertaken an inte rlaboratory comparison of the performance of the CB6F1-Tg rasH2 transgenic mouse in cancer bioassays concurrently conducted in the United States and J apan. Chemicals selected for study included known human carcinogens (melpha lan and cyclosporin A) and known rodent carcinogens (p-cresidine and vinyl carbamate) tested at carcinogenic doses, and non-carcinogens (p-anisidine a nd resorcinol) tested at appropriate high doses. Because of abdominal adhes ions caused by the intraperitoneal dosing vehicle, melphalan was excluded f rom the study results. The remaining five studies showed similar results be tween the two laboratories conducting each study. Vinyl carbamate gave the strongest positive response inducing lung adenomas and carcinomas and splen ic hemangiosarcomas. p-Cresidine was considered positive for urinary bladde r transitional neoplasia, Cyclosporin A, p-anisidine, and resorcinol were n egative in all studies. Although only five chemicals were successfully test ed in this interlaboratory comparison, there was good concordance in outcom e for the strong carcinogens and for the non-carcinogens. Successful testin g of chemicals with less carcinogenic potential may require modifications i n study design to include more animals and longer study duration. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.