Application of Transcriptional Benchmark Dose Values in Quantitative Cancer and Noncancer Risk Assessment

• DOI: 10.1093/toxsci/kfq355
• Publication Date: 2010-11-23T02:48:39Z
• Authors: Russell S. Thomas; Harvey J. Clewell; Bruce C. Allen; Scott C. Wesselka...; Nina Ching Y. Wang; Jason C. Lambert; Janet K. Hess-Wilson; Q. Jay Zhao; Melvin E. Andersen
• Keywords: 0301 basic medicine; Lung Neoplasms; Dose-Response Relationship, Drug; Carcinogenicity Tests; Endpoint Determination; Body Weight; Gene Expression; Mice, Inbred Strains; Environmental Exposure; Organ Size; Carcinogens, Environmental; 3. Good health; Mice; 03 medical and health sciences; Liver Neoplasms, Experimental; Liver; Data Interpretation, Statistical; Neoplasms; Animals; Humans; Female; Lung; Oligonucleotide Array Sequence Analysis

The traditional approach for estimating noncancer and cancer reference values in quantitative chemical risk assessment is time resource intensive. extent nature of the studies required under has limited number chemicals with published assessments. In this study, female mice were exposed 13 weeks to multiple concentrations five that positive a 2-year bioassay. Traditional histological organ weight changes evaluated, gene expression microarray analysis was performed on target tissues. histological, changes, original tumor incidences bioassay analyzed using standard benchmark dose (BMD) methods identify points departure, respectively. dose-related also BMD responses grouped based cellular biological processes. A comparison transcriptional those apical endpoints showed high degree correlation specific For human exposure data, used calculate margin exposure. margins ranged from 1900 54,000. Both between suggest may be as potential departure assessment.