PRINCIPLES OF TOXICOLOGY

300 CHEMICAL CARCINOGENESIS
TABLE 13.9 Correlations across Species of Positive Cancer Bioassays
Observed Outcome Percent
concordance
Comparison + +– –+ Total (++ or ––)
Intraspecies Comparisons
Male rats vs. female rats 74 25 12 111 67%
Male mice vs. female mice 78 10 23 111 70%
Interspecies Comparisons
Male rats vs. male mice 46 43 36 125 37%
Male rats vs. female mice 59 33 36 128 46%
Female rats vs. male mice 46 32 37 115 40%
Female rats vs. female mice 57 23 39 119 48%
Rats vs. mice 208 131 148 487 43%
This, in turn, suggests that the number of animals tested might be reduced (i.e., eliminate
the testing of male mice and female rats).
• The high concordance between rats and mice supports the view that extrapolation of
carcinogenicity outcomes to other species (humans) is appropriate.
However, the high degree of concordance in this analysis stems from the fact that about half of the
studies are negative and the chemical being tested manifested no carcinogenic activity. When a slightly
different questions is asked—regarding how reliably positive test results can be extrapolated across
species—a much different answer is reached. In Table 13.9 the noncarcinogens have been removed
and the comparisons across sexes and species have been reanalyzed. Figure 13.9 contains the same
Figure 13.9