Concordance of carcinogenic response between rodent species: potency dependence and potential underestimation.
The use of average qualitative concordance between two bioassay endpoints is considered, with emphasis directed at agreement between rats and mice from results of long-term carcinogenicity studies. It is noted that concordance varies as a function of the underlying potency or toxicity of the chemicals over which the averaging is performed. Thus, the averaging process dilutes large observed concordances from potent chemicals, and possibly inflates lower observed concordances from weakly active chemicals. Stratification over some measure of potency is suggested as a method for taking these effects into account. Statistical simulations of concordance analyses limited to low-potency ranges are employed to examine the concordance measure in greater detail. It is seen that at low potencies, observed concordance is consistently underestimated, reaching maximum levels of only about 80%.
Piegorsch
W W
WW
Division of Biometry and Risk Assessment, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Carr
G J
GJ
Portier
C J
CJ
Hoel
D G
DG
D000818:Animals; D001681:Biological Assay / Q000706:statistics & numerical data; D015197:Carcinogenicity Tests / Q000706:statistics & numerical data*; D002273:Carcinogens / Q000633:toxicity; D003198:Computer Simulation; D016208:Databases, Factual; D051379:Mice; D051381:Rats; D012306:Risk; D013045:Species Specificity
D002273:Carcinogens