In Vitro Mass Balance Model (IV-MBM)

Toxicity testing in the 21st Century is shifting towards more in vitro based experiments to obtain empirical data for different decision-making contexts, e.g., ToxCast, Tox21, Safety Evaluation Ultimately Replacing Animal Testing (SEURAT). Generally speaking, in vitro toxicity and bioactivity dose-response curves are reported using (initial) nominal concentrations in the test medium, i.e., the amount of chemical added divided by the volume of medium.  However, the use of nominal concentrations can be problematic for the interpretation and use of in vitro data for hazard and risk evaluations because nominal concentrations do not account for the behaviour of the chemical in the test system.

To address these concerns, the In Vitro Mass Balance Models (IV-MBM) were designed to simulate the distribution of organic chemicals in in vitro test systems based on i) the physical-chemical properties of the chemical and ii) the properties (e.g., volume fraction of serum albumin in the test medium) and dimensions of the in vitro test system.  Two versions of the model are available here, i) IV-MBM EQP v2.1 and ii) IV-MBM DP v1.0.  The EQP version is a “static” model which simulates the in vitro disposition of neutral and ionizable organic chemicals (IOCs) at equilibrium.  The DP version is a “kinetic” model which simulates the in vitro disposition of neutral organic chemicals over time (i.e., a time-variant implementation). 

IV-MBM has been used by regulatory agencies (EPA, NTP) in the United States (e.g., Casey et al., Environ Health Persp 2018).   Full details of the IV-MBM EQP and IV-MBM DP models are available in the following publications:


– Armitage, J. M.; Wania, F.; Arnot, J. A. 2014. Application of mass balance models and the chemical activity concept to facilitate the use of in vitro toxicity data for risk assessment. Environ. Sci. Technol. 48, (16), 9770-9779. DOI: 10.1021/es501955g

– Armitage J. M.; Sangion A.; Parmar R.; Looky A. B.; Arnot J. A. 2021. Update and Evaluation of a High-Throughput In Vitro Mass Balance Distribution Model: IV-MBM EQP v2.0. Toxics 9:315. Open Access – DOI: 10.3390/toxics9110315


– Bloch S.; Arnot J.A.; Kramer N.; Armitage J.M.; Verner M-A. 2022.  Dynamic mass balance modeling for chemical distribution over time in in vitro systems with repeated dosing.  Front. Toxicol. doi: 10.3389/ftox.2022.911128

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