Age-Related Differences in Susceptibility to Carcinogenesis—Toward a Quantitative Analysis of Empirical Data Researchers: Dale Hattis, Principal Investigator Rob Goble, Research Professor Abel Russ, Research Associate Jen Ericson and Jill Mailloux, Student Research Assistants Margaret Chu, EPA Project Monitor
Innovative Aspects of the Analysis • Compares measures of intrinsic sensitivity, rather than uncorrected cancer incidence, among groups. • Where dosage spans multiple age groups, uses dummy variables to represent the observed tumor risk as the sum of cancer contributions from dosing in different periods: • The periods are fetal (gd 12-19), pre-weaning (1-21 d), weaning - 2 mo, and adult (2 mo - 2 yr). • Where continuous dosing occurs in only a fraction of a period, that fraction is used as the corresponding “dummy” rather than 1. • Uses likelihood methods to derive appropriate statistical weighting of the different observations and to avoid bias from excluding “0” points. • Expresses dosage for animals of different weights on a metabolically consistent basis (either concentration in air or food, or per unit body weight3/4).
Results for the Combined Continuous and Discrete Dosing Data Per BW^3/4, Separated by Sex
Results for All Ionizing Radiation Dosing Experiments (per Gray) (based on a total of 274 group tumor incidence observations for 6 chemicals)
The Bottom Line for Mutagenic Carcinogens Based on Comparisons of Body Weights at Sexual Maturity