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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Hazard model

• 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

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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
Interaction Cu,Cd, Pb, Zn Cu Pb slightly
antagonistic Other combinations nill
Folsomia candida
Data Bart van Houte Theory Bas Kooijman Fit
Jan Baas Movie Jorn Bruggeman
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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
Start 2005/10/01

• 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

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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
Cambridge Univ Press 2000
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/
Audience thank you for your
attention Organizers thank you for the
invitation