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Age-Related Susceptibility to Carcinogenesis Analysis

Investigating measures of sensitivity to cancer incidence across age groups using statistical methods to account for dosage variations. Research data includes fetal, pre-weaning, weaning, and adult periods in animals of different weights. Outcome comparisons for ionizing radiation dosing.

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Age-Related Susceptibility to Carcinogenesis Analysis

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  1. 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

  2. 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).

  3. Results for the Combined Continuous and Discrete Dosing Data Per BW^3/4, Separated by Sex

  4. Results for All Ionizing Radiation Dosing Experiments (per Gray) (based on a total of 274 group tumor incidence observations for 6 chemicals)

  5. The Bottom Line for Mutagenic Carcinogens Based on Comparisons of Body Weights at Sexual Maturity

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