Re-evaluation of the need for multiple sampling times in the mouse bone marrow micronucleus assay: results for DMBA.

Abstract

7,12-dimethylbenzanthracene (DMBA) is confirmed as active in the mouse bone marrow micronucleus assay 24 hr after dosing as a corn-oil homogenate via either oral gavage or intraperitoneal (ip) injection. These data are consistent with recent observations made by several investigators. However, when dosed via ip injection as a solution in DMSO, peak activity was evident 48 hr after dosing and a dramatic reduction in erythropoiesis was observed. The latter results are consistent with early observations made by Salamone and Heddle. The early observations of Salamone and Heddle were highlighted in the Gene-Tox review of this assay and led the OECD to recommend the use of 3 sampling times for this assay (between 12 and 72 hr). The present data indicate that this advice should be reviewed. In particular, it suggested that a maximum of two sampling times is adequate and that, as a consequence, the number of animals employed in the conduct of the test could be reduced with no loss of sensitivity. The present data also suggest that the use of a corn-oil homogenate of insoluble test agents may provide an efficient replacement for the use of ground suspensions or solutions in DMSO.