Nomiracle WP 4.1: Modelling Effects of mixtures of compounds
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Transcript of Nomiracle WP 4.1: Modelling Effects of mixtures of compounds
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Nomiracle WP 4.1: Modelling Effects of mixtures of compounds
EU Integrated project NoMiracle: http://nomiracle.jrc.it Novel Methods for Integrated Risk assessment of
Cumulative Stressors in Europe EU-theme "Global Change and Ecosystems"
topic “Development of risk assessment methodologies”Coordination: Dr. Hans Løkke, NERI, DK-8600 Silkeborg, Denmark
Interim-report: Modelling effects of binary mixtures on survival in time
Jan Baas (2005/10/01 – 2009/10/01) Tjalling Jager & Bas Kooijman (VU-Theor Biol)
In collaboration with Mieke Broerse, Kees van Gestel (VU-Ecol, EU-project NoMiracle) Daniel Bontje, Bob Kooi (VU-Theor Biol, EU-project Modelkey)
contract No. 003956
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Biology based methods
Effects based on internal concentrations One compartment accumulation-elimination
Hazard rate or physiological target parameter is linear in internal concentration (small effects only) Dynamic Energy Budget theory is used to identify potential target parameters translate change in parameter to change in endpoint
Interaction of compounds in mixture product of internal concentrations similar to analysis of variance
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Suppose that the elimination rate large
internal conc is fast at equilibrium, hazard rate is constant
Conclusion:
effect on survival concentration exposure time
well known in
pharmacology
desinfection of buildings, green houses
Hazard model
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Effect on survival for single compound
Effects of Dieldrin on survival of Poecilia
NEC 4.49 g l-1
killing rate 0.038 l g-1 d-1
elimination rate 0.712 d-1
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Effect on survival for mixture
Model for survival in time for a binary mixture: 8 parameters in total using data for all observation times control mortality rate, interaction parameter 2 (NEC, killing rate, elimination rate)
Model tested for 6 binary mixtures of metals (Cu, Cd, Pb & Zn) on Folsomia candida (Collembola)
Survival measurements daily for 21 days 6 6 concentrations 22 6 6 = 792 data points for each mixture
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Cd & Cu survival of Folsomia
Data: Bart van HouteTheory: Bas KooijmanFit: Jan BaasMovie: Jorn Bruggeman
Interaction Cu,Cd, Pb, Zn: Cu & Pb: slightly antagonistic Other combinations: nill
Folsomia candida
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Results for NoMiracle RP 3 & 4• New model is available for analysis of data for effects of mixtures of
compounds on the survival of organisms
• This model is shown to be realistic, has few parameters and has attractive statistical properties
• Software DEBtool is available to make the application of this model feasible http://www.bio.vu.nl/thb/deb/deblab/
• Standard deviations are available to judge accuracy
• Parameters quantify effects in ways that do not depend on exposure time. OECD encourages the development of exposure-time-explicit methods (Braunschweig, 1996)
• Scaling relationships are available that can help filling gaps in knowledge
• NECs can be used in risk-assessments to replace NOECs
RP 3
RP 4
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Publication output
• Kooijman, S. A. L. M., Baas, J., Bontje, D., Broerse, M., Jager, T. , Gestel, C. van and Hattum, B. van (2006) Scaling relationships based on partition coefficients and body sizes have similarities and interactions. SAR and QSAR in Environ. Res, to appear
• Baas, J., Houte, B. P. P. van, Gestel, C. A. M. van and Kooijman, S. A. L. M. (2006) Modelling the effects of binary mixtures on survival in time. Environmental Toxicology & Chemistry, submitted
• Baas, J. and Kooijman, S. A. L. M. (2006) Statistical properties of NEC estimates if values scatter among individuals. Water Research, in prep
Start: 2005/10/01
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Future plans
Research• Application of results to (some) NoMiracle data• Effects of pH (conc dependent mixtures of molecular & ionic forms)• Sublethal effects of mixtures• Mixtures of a large number of chemical compounds (frequency distributions of tox parameter values)
• Effects of metabolic transformations (if time allows)
Education• DEBtox tele-course 2006 Feb-Mar• JRC-ECB workshop on biology-based methods in environmental risk assessment• DEB tele-course 2007 Feb-April
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DEB tele course 2007
http://www.bio.vu.nl/thb/deb/
Free of financial costs; some 200 h effort investment
Feb-April 2007; target audience: PhD students
We encourage participation in groups that organize local meetings weekly French group of participants of the DEB tele course 2005 wrote special issue of J. Sea Res. 2006 on DEB applications to bivalves
Software package DEBtool for Octave/ Matlab freely downloadable
Slides of this presentation are downloadable from http://www.bio.vu.nl/thb/users/bas/lectures/
Cambridge Univ Press 2000
Audience: thank you for your attention
Organizers: thank you for the invitation