Toxicokinetics and biotransformation
Ad hoc OECD Expert Group on Toxicokinetics
Italian Expert: Emma Di Consiglio, Istituto Superiore di Sanità, Health and Environment Department
The availability and regulatory acceptance of New Approach Methodologies (NAMs) for the estimation of absorption, distribution, metabolism and excretion (ADME / biokinetics) are considered key elements in toxicological risk assessments for chemicals, including environmental and food contaminants, pesticides, biocides, pharmaceuticals, medical devices. To improve the predictivity and implementation of these approaches, the collaboration and involvement of experts from different fields (research, regulatory, industry) and expertise (toxicology, in silico methods) is required. Several NAMs have been identified for the study of biokinetic parameters to be used in the context of chemical safety assessment, such as the evaluation of inter- and intra-species variability or the quantitative in vitro-in vivo extrapolations.
The regulatory acceptance of these approaches, which involve kinetics, a key element is pivotal for their implementation. To this aim, the development of Test Guidelines (TG) for single tests and/or integrated testing strategies is essential.
The OECD expert group on toxicokinetics (TK), established in 2015, aims to evaluate TG proposals, useful for the evaluation of kinetic parameters, considered reliable, reproducible and relevant for humans, thus suitable to be applied in predictive models, such as PBK (Physiological based kinetic models). For the development and implementation of in vitro kinetic methods for regulatory use in human safety assessment, it is important to take into consideration the OECD TG on Good In vitro Method Practices (GIVIMP). GIVIMP provides scientific advices on how to perform in vitro methods, defining all critical aspects to be considered in the test design. In such a way, it is possible to reduce the uncertainties, to guarantee a univocal interpretation of the kinetic data produced, clearly addressing the acceptance criteria. Just as an example, OECD ad hoc expert Group on TK reviewed a proposed TG, on the use of human derived metabolic competent hepatic test systems to assess the potential of chemicals to induce (i.e. increase the synthesis and activity) some Phase I biotransformation enzymes, which are susceptible to induction and are highly expressed in human liver (project led by the European Commission).
OCSEProgramma Linee guida