LRI-ECO34: Rapid assessment for uptake and biotransformation pathways using multiple lines of in vitro evidence – Deadline: 6 September 2015

Background

Recently a CEFIC-LRi and ECHA workshop on recent developments in bioaccumulation research (Helsinki, September, 2014) concluded that the biotransformation rate constant represents the principal source of uncertainty in the bioaccumulation assessment of most chemicals and that in vitro to in vivo extrapolation to estimate clearance and biotransformation offers a promising path forward.  Several research groups, for instance, have expanded their empirical tools beyond simply assessing liver metabolism, and have developed methods to measure fish gut and gill metabolism. These tools can add to a weight of evidence assessment of bioaccumulation and might be used with other indicators of bioaccumulation potential in a tiered approach for deciding the need for in vivo bioaccumulation testing. Consequently, it is believed that the development of in vitro screening tools to assess biotransformation, and that extend the applicability domain of tests, can enable improvements in the regulatory assessment of bioaccumulation.

Furthermore, by combining empirical data on the biotransformation of a chemical with internal concentration models, a more robust method for linking toxicokinetics with toxicodynamics is possible, which could be useful in strengthening mechanistic understanding of adverse outcome pathways.  It is expected that the development of a suite of in vitro tools aimed at quantifying biotransformation pathways could thus support the development of mechanistic tools for estimating internal concentrations that will result in more ecologically relevant chemical risk assessment.