Micronucleated erythrocyte frequency in peripheral blood of B6C3F(1) mice from short-term, prechronic, and chronic studies of the NTP carcinogenesis bioassay program

The mouse peripheral blood micronucleus (MN) test was performed on samples collected from 20 short-term, 67 subchronic, and 5 chronic toxicity and car cinogenicity studies conducted by the National Toxicology Program (NTP). Da ta are presented for studies not previously published. Aspects of protocol that distinguish this test from conventional short-term bone marrow MN test s are duration of exposure, and absence of repeat tests and concurrent posi tive controls. Furthermore, in contrast to short-term bone marrow MN tests where scoring is limited to polychromatic erythrocytes (PCE), longer term s tudies using peripheral blood may evaluate MN in both, or either, the normo chromatic (NCE) or PCE populations. The incidence of MN-PCE provides on ind ex of damage induced within 72 hr of sampling, whereas the incidence of MN in the NCE population at steady state provides an index of average damage d uring the 30-day period preceding sampling. The mouse peripheral blood MN t est has been proposed as a useful adjunct to rodent toxicity tests and has been effectively incorporated as a routine part of overall toxicity testing by the NTP. Data derived From peripheral blood MN analyses of dosed animal s provide a useful indication of the in vivo potential for induced genetic damage and supply an important piece of evidence to be considered in the ov erall assessment of toxicity and health risk of a particular chemical. Alth ough results indicate that the test has low sensitivity for prediction of c arcinogenicity, a convincingly positive result in this assay appears to be highly predictive of rodent carcinogenicity. (C) 2000 Wiley-Liss, Inc.