Improving the development and use of biologically based dose response models (BBDR) in risk assessment

Biologically based dose-response (BBDR) models predict health outcomes (res ponse) resulting from the presence of a toxicant at a biological target (do se). The benefits of BBDR models are many, and research programs are increa singly focusing on mechanistic research to support model development; howev er, progress has been slow. Impediments to progress include the complexity of dose response modeling, the need for a multidisciplinary team and consis tent funding support, and difficulty in identifying and extracting the need ed data. Of immediate concern is the lack of transparency of published mode ls to the supporting data and literature, difficulty in accessing model cod e and simulation conditions sufficient to allow independent replication of results, and absence of well-defined quality criteria. Suggestions are pres ented to improve the development and use of BBDR models in risk assessment and to address the above limitations. Examples from BBDR models for methylm ercury neurotoxicity and 5-fluorouracil embryotoxicity are presented to ill ustrate the suggestions including what kinds of databases are needed to sup port model development and transparency, quality assurance for modeling, an d how the internet can advance database development and collaboration withi n the biological modeling community.