Cefic-lri Programme | European Chemical Industry Council

B21 – In Vitro Data to Parameterise PBPK Models For Inhalation Exposure

Principal Investigator

Dr Katharina Schwarz
Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM)
Nikolai-Fuchs Strasse 1
30625 Hannover
Tel. + 49 511 5350 139


Dr. Tanja Hansen, Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hannover, DE, tanja.hansen@item.fraunhofer.de

Dr. Katharina Blümlein, Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hannover, DE, katharina.bluemlein@item.fraunhofer.de

Dr. Sylvia Escher, Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hannover, DE, Sylvia.escher@item.fraunhofer.de

Dr. Miyoung Yoon, Center of Excellence for 21st Century Toxicology, Toxstrategies, Inc., Cary, NC, USA, myoon@toxstrategies.com


Use of chemicals in the consumer and occupational environment requires a risk assessment considering the hazard of and exposure to a substance. In the workplace and for consumers, the inhalational route is of major importance. Due to absence/lack of in-vivo data describing systemic uptake, in-silico methods are required. Up to now, usually the inhaled dose, or the dose deposited in the respiratory tract is considered as relevant for the risk assessment process. This is a pragmatic but often very conservative assumption, not taking into account a variety of absorption and clearance processes in the respiratory tract influencing systemic availability of airborne substances.

For a more refined determination of the systemic available dose, relevant for potential toxicological effects, physiologically-based pharmacokinetic (PBPK) modelling recently has gained large interest but is still limited. Our approach aims at the generation and application of physiologically derived transport parameters in a PBPK model focusing on a more detailed description of substance uptake through the respiratory tract/via the inhalational route. This PBPK model is aimed to be universally applicable for the different forms of airborne substances (gases, soluble aerosols and poorly soluble particulates) and shall be designed as a publicly available model, that delivers information relevant for regulatory needs.

Permeation values for the trans-epithelial transport will be derived using suitable human cell or tissue barrier models. In addition, the applicability of other biological and physical parameters determined in vitro, such as intrinsic hepatic clearance or dissolution rates, will be investigated.

Timeline: April 2019 > September 2021

LRI funding: € 299 665

Cefic-Lri Programme Responsible Care

Terms and Conditions of Use | Privacy Policy | Cookie Policy | Coockie Settings

© Copyright 2017 Cefic | European Chemical Industry Council. All rights reserved.