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HBM2.2-ITC: Development of a computer program with a multi-level modelling tool for the estimation of biomonitoring equivalent guidance values for chemical agents related to health based exposure rates for inhalation, oral intake and/or skin exposure.

Principal Investigator

Dr. Frans Jongeneelen
University Business Center
PO Box 31070
NL-6503 CB Nijmegen
The Netherlands
Tel: +31 24 3528842
Fax: +31 24 3540090

Collaborators

Dr W.F. ten Berge - Santoxar, Westervoort, The Netherlands
Dr R. Vermeulen - IRAS, Utrecht University, The Netherlands
Dr J.G.M. van Rooij - IndusTox Consult, Nijmegen, The Netherlands

Description

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.

Timeline: January 2008 > November 2011

LRI funding: €289,000

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