High-Throughput
Toxicokinetics and
Read-Across

Read-across is a science-driven approach that predicts the toxicity and behavior of data-poor (target) chemicals using information from similar, well-studied (source) compounds. This method relies on the principle that structurally similar chemicals share comparable physicochemical and ADME profiles, leading to similar effects.

By leveraging read-across, toxicokinetic behavior can be inferred without extensive in vivo testing, aiding risk assessment and safety profiling. Physiologically Based Kinetic (PBK) models enhance this process by mechanistically describing ADME processes, allowing for quantitative extrapolation across species, exposure routes, and even formulation types.

PBK models also facilitate QIVIVE, enabling animal-free safety assessments. When combined with structural and metabolic similarity analyses, PBK-based read-across strengthens scientific justification and improves regulatory confidence. Read-across accelerates evaluations, supports Next Generation Risk Assessment (NGRA) goals, and enhances human relevance in toxicology by reducing animal testing.

Physiologically based biopharmaceutics modeling (PBBM) is a specific field of PBPK model applications that aims to establish the link between the formulation’s properties and in vivo performance.

This field of application of PBPK modeling is evolving at a fast-pace and offers the link between in vivo and in vitro to support pharmaceutical development in the selection of the best drug substance and product, as well as later in development in the establishment of manufacturing quality and controls.
Dissolution testing is often a key input in PBBM. Results from in vitro experiments characterizing drug substances and the formulation behavior (e.g., solubility, particle size, dissolution) can be linked to key ADME parameters and integrated into full PBPK models to predict PK exposure in plasma and/or specific tissues or organs.

These models can also be linked to Pharmacodynamic (PD) relationships to derive the impact of physicochemical, drug and formulation properties on safety and efficacy. The role of Physiologically Based Biopharmaceutics Modeling (PBBM) in drug development spans multiple stages, including supporting patient-centric design, guiding life cycle management, informing regulatory submissions, streamlining development processes, optimizing dosing strategies, enhancing study design, and aiding in formulation development and developability assessment.

Figure adapted from Paini, A., Worth, A., Kulkarni, S., Ebbrell, D., Madden, J., 2021.
Assessment of the predictive capacity of a physiologically based kinetic model using a read-across approach.
Computational Toxicology 18, 100159. RA: read-across.
https://doi.org/10.1016/j.comtox.2021.100159 

What we can offer

ESQlabs specializes in developing tailored PBK models for data-poor chemicals with no or limited in vivo TK data by using read-across approaches. Our expertise includes parameterization of PBK models using data from structurally and functionally similar analogues, supporting quantitative predictions even when target-specific data are scarce. PBK models allow for quantitative, mechanistic insights into the ADME of untested chemicals, helping to bridge data gaps and reduce the reliance on animal testing in chemical safety evaluations.

We also support hybrid strategies combining read-across and in vitro kinetics for improved model calibration and greater confidence in QIVIVE outcomes.

Scenarios and simulations:

  • Single chemicals
  • Defined Mixtures
  • Aggregate exposure 
  • Sensitive populations

Our Read-Across for Toxicokinetics service is useful for:

  • Chemical risk assessment: Providing insights into the potential impacts of chemical exposure
  • Safety profiling of new or data-poor compounds: Supporting the evaluation of novel or data-limited substances for their safety and toxicity
  • QIVIVE within NGRA: Facilitating Quantitative In Vitro to In Vivo Extrapolation (QIVIVE) as part of Next-Generation Risk Assessment (NGRA) approaches
  • Sustainable product development: Helping drive the design of safer and more sustainable chemicals through effective toxicokinetic insights

Related Platforms

High-Throughput Screening and ADMET-PBPK

Integrating automated PBPK model development with ADMET data pipelines for HT pharmacology and safety screening.
Find out more 

Large Molecules, Biologics and Novel Modalities

Advancing PBPK-based solutions for (Bi-specific) antibodies, conjugated drugs, gene therapy, and other novel modalities.
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Small Molecules and Chemicals

Advancing PBPK-based solutions for small molecules and chemicals across all services.
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Related publications and initatives

Using Read-Across to build Physiologically-Based Kinetic models: Part 2. Case studies for atenolol and flumioxazin
Using read-across to build physiologically-based kinetic models: Part 1. Development of a KNIME workflow to assist analogue selection for PBK modelling
Towards best use and regulatory acceptance of generic physiologically based kinetic (PBK) models for in vitro-to-in vivo extrapolation (IVIVE) in chemical risk assessment
See all publications 

Meet the Team

Lara Lamon

Senior Scientist
Consultant
Google Scholar

Lara Lamon is an Environmental Scientist with a solid drive to investigate the unknowns of chemical exposure and enhance model simulations aimed at protecting human health and the environment.

She worked at ECVAM within the JRC on the grouping and read-across of nanomaterials. Lara contribiuted to applying the read-across framework released by ECHA to support nanomaterials dossiers submissions under the REACH regulation. She further advanced this expertise in the H2020 GRACIOUS project. Additionally, she has developed and applied modeling approaches to estimate environmental emissions and concentrations of environmental and emerging pollutants, including uncertainty analysis (Monte Carlo and sensitivity analysis).

Lara obtained her Ph.D. in Environmental Science at the Ca’ Foscari University of Venice at the Environmental Chemistry and Risk Assessment Unit. During her Ph.D., she was a visiting scholar at the Safety and Environmental Technology group at ETH Zürich, where she collaborated with Martin Scheringer and Matthew Macleod at the Safety and Technology group.

Marco Siccardi

Principal Scientist
Lead Toxicology & PBPK
Google Scholar

Marco is a Clinical Biologist by training with a PhD in molecular pharmacology and PK/PD modelling. He spent over 15 years at the University of Liverpool working on the topic of pharmacogenetics and in developing PBPK approaches for the optimisation of drug delivery, including HIV therapy optimisation.

Marco has most recently been working with CROs in taking this approaches for modelling and simulation approaches and PKTK (Systems Toxicology) models across a number of disease areas.

Marco leads the Systems Toxicology team with the aim to promote collaborative innovation and to develop novel modeling approaches to streamline the toxicological assessment.

Stella Fragki

Senior Scientist
Consultant
Google Scholar

Styliani (Stella) Fragki is a Senior Scientist in Systems Toxicology at ESQlabs, where she applies physiologically based kinetic (PBK) modeling in chemical risk assessment. Her work focuses on integrating New Approach Methodologies (NAMs) within the framework of Next-Generation Risk Assessment (NGRA), with the aim of supporting human-relevant and animal-free safety evaluations.

She is a certified European Registered Toxicologist and has been active in the field of toxicological risk assessment since 2010, supporting the (agro)chemical industry with dossier preparation for plant protection products, biocides, and REACH-regulated substances.

Stella holds a degree in Biology from Thessaloniki, Greece, and an MSc in Food Safety from Wageningen University in the Netherlands. Her PhD research focused on quantitative in vitro to in vivo extrapolation (QIVIVE) using physiologically based kinetic (PBK) modeling, integrating data from both in vitro and in silico sources. Stella is also a certified European Registered Toxicologist.

Susana Proença

Scientist
Consultant
Google Scholar

Susana Proença is a biologist and toxicologist dedicated to the leveraging in vitro and in silico data for parameterizing PBPK models and to perform chemical safety assessment. She is focused on developing frameworks and case-studies for IVIVE, extrapolation of ADME properties from in vitro to in vivo, and on QIVIVE, extrapolating in vitro effect concentrations to in vivo doses. She has experience in working with PBPK models both in OSP and in R.

Before joining ESQlabs, she worked at Wageningen University, Toxicology division under Dr. Nynke Kramer supervision. There she worked on evaluating in vitro kinetics of chemical related to different toxicological ontologies (such as cholestasis and development neurotoxicity) and developing strategies for performing QIVIVE for these chemicals. Before this she underwent an internship at ECVAM-JRC on in silico modelling of in vitro kinetics, which was followed by a stint automating chemical data curation from REACH dossiers, also in JRC.

Susana obtained her Master’s degree in Bio-Pharmaceutical Sciences from Faculty of Pharmaceutical Sciences, Lisbon University (Portugal). For her PhD thesis, she studied the in vitro kinetics in complex in vitro models and (Q)IVIVE of highly lipophilic chemicals. The thesis was supervised by Dr. Nynke Kramer at the Institute for Risk Assessment Sciences at Utrecht University. The work was multidisciplinary, envolving setting in vitro experiments, analytical methods, transcriptomics analysis and in silico modelling. Her PhD thesis will be submitted soon.