Data on percent
tumors in male rats after administration of
methyl eugenol, obtained from the National Toxicology Program, or
tamoxifen were plotted on a linear scale for percent
tumors against the dose on a logarithmic scale. Data on (32)P-postlabelled
DNA adducts were plotted on the same graphs for each of these two compounds in order to correlate adduct formation and
tumor incidence with dose. The resulting graph for
methyl eugenol showed a linear response for both adduct formation and
tumor incidence. The threshold dose of administered
methyl eugenol for adduct formation (zero adducts) was 10(19.3) molecules of
methyl eugenol/kg/day, which compared with a threshold of 10(20.1) molecules of
methyl eugenol/kg/day for
tumor formation; however, 30 adducts/10(8)
nucleotides was the threshold for
tumor formation. The dose of
tamoxifen for adduct formation fit an exponential plot slightly better than a linear plot, but reached minimal values close to the threshold of 10(18.7) molecules of
tamoxifen/kg/day for
tumor formation. These data confirm that
tumor formation coincides with adduct formation and that both have thresholds, or at least reach minimal values, above levels to which humans are exposed. Although the threshold dose for
tumor formation from
tamoxifen is only about 10x above the dose received by women at risk for
breast cancer, this should be an adequate safety margin. The safety factor for
methyl eugenol is several orders of magnitude; therefore, there should be no cause for concern for humans at current levels of exposure.