Chapter 9:Novel Data Streams in the Assessment of Mutagenicity and Carcinogenicity: Implications for Cancer Hazard Assessment

Carcinogenic hazard identification refers to an assessment of whether an agent causes cancer. In identifying causes of human cancer, hazard assessment does not predict the magnitude of cancer risks, but does consider all relevant information in evaluating the likelihood of cancer causation. This chapter will discuss the data streams and processes used to assess mutagenicity, carcinogenicity and other relevant toxicity. It will focus specifically on implications for cancer hazard assessment. When human evidence is less than sufficient, integrating across multiple data streams can help to reach hazard conclusions. Mechanistic data can be critical in the process. Challenges and opportunities in evaluating selected compounds in the context of the International Agency for Research on Cancer Monographs programme are presented. A discussion follows on how predictive modeling can aid in agent prioritization and in filling data gaps in carcinogenicity evaluations. This includes chemo-informatics approaches to prioritizing and grouping agents, as well as systematic approaches to identifying and presenting mechanistic evidence in human health assessments. Progress in addressing human variability is discussed and future directions in the evaluation of mechanistic data are explored. These discussions should be of interest to individuals engaged in the assessment of carcinogenic risk to humans.