Objective: Development of a tiered tool with compartmental and physiologically based toxicokinetic models, taken up in a software program, to derive Biomonitoring Equivalent Guidance Values (BEGV) based on existing health based acceptable daily doses or acceptable health based daily exposures.
Toxicokinetic modelling, either physiologically based or compartmental based, have already been used over a long period to estimate the impact of physiological, biochemical and anatomical factors on target dose and toxicity. Monte Carlo simulation makes it possible to estimate the impact of gender and individual variation in the human species. The aim is to develop a computer program based on kinetic models and possibly Quantitative Structure Activity relationships (QSAR’s) which make it possible to derive equivalent guidance values of parent chemical compounds and/or metabolites in blood and urine, derived from on existing toxicity screening criteria as Reference Dose (RfD), Occupational Exposure Limits (OEL’s) or Derived No-Effect Levels (DNELs).
The computer program will enable the user to select the most suitable model from the program database and calculate chemical specific concentrations in human biological media, equivalent to existing health screening criteria, regarding population variability. This tool follows a tiered approach in selecting the proper model. This program will allow a reliable interpretation of biomonitoring results of toxicity-data poor substances.
Jongeneelen F.J. and ten Berge W.F. (2011). A Generic, Cross-Chemical Predictive PBTK Model with Multiple Entry Routes Running as Application in MS Excel; Design of the Model and Comparison of Predictions with Experimental Results. The Annals of Occupational Hygiene. 55(8), 841-864.
Final report-User manual:
IndusChemFate: A multi-chemical PBTK-model in MS-Excel applicable for workers, consumers and experimental animals, user manual version 2.00 by F. Jongeneelen and W. ten Berge
Skin Absorption of (volatile) Liquids: A Skin-PBPK Model by W. ten Berge, D. Huizer and F. Jongeneelen
Simulation of blood and urine levels with a newly developed generic Physiologically Based ToxicoKinetic (PBTK)model by Frans J. Jongeneelen and Wil F. ten Berge
Simulation of blood and urine levels after exposure: Prediction with a chemical across predictive Physiologically Based Toxico-Kinetic (PBTK) model available as application in MS Excel by Frans J. Jongeneelen and Wil F. ten Berge