A method for determining the maximum tolerated dose for acute in vivo cytogenetic studies

A method for establishing a maximum tolerated dose for use in in vivo cytogenetic studies is proposed. Probit analyses were performed on acute (ip and po) LD50 studies for triethylenemelamine, chlorambucil, methyl methanesulphonate, glycidol, phenol, Triton X-15, and dimethylsulphoxide. The concentrations corresponding to the calculated LD30, LD10 and LD1 values were given both ip and po to groups of female and male rats. Half of the animals in each group were killed about 20 hr after treatment for bone marrow cytogenetic analyses, and body weights were recorded for 10 days for the other half. The following conclusions were drawn: (1) LD50 values and consequently the maximum tolerated dose (MTD) values differ for males and females; (2) the mitotic index is not a reliable indicator of toxicity; (3) the LD1 value approximates the MTD for these compounds; (4) this value and hence the MTD is not a fixed percentage of the LD50 value; (5) body-weight changes appear to be an accurate parameter for determining whether or not an animal received an MTD level.