European perspective on the use of QSAR for chemicals management

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European perspective on the use of QSAR for
chemicals management

• Joanna Jaworska
• Procter Gamble
• European Technical Center , Brussels

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Overview

• Role of QSARs in REACH Commission view vs.
  Industry view
• What is happening to reconcile the differences-
  OECD QSAR Work program

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EU chemicals policy REACH

• Registration 30,000 substances gt 1 t / y
• Evaluation 5,000 substances gt 100 t / y
• substances of concern
• Authorisation 1,400-2,000 substances of very
  high concern (e.g. CMR, PBTs)
• Restriction 300-400 substances

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Council Conclusions on the White Paper

• The Commission is invited to
• develop screening procedures to effectively
  identify chemicals with potentially harmful
  properties or uses of concern for the purposes of
  prioritising substances for which further
  information is urgently needed (Conclusion 40)
• develop procedures to simplify the
  identification of the relevant testing strategies
  and reduce the need for animal testing, including
  the use of decision trees and specific screening
  methods for all chemicals, such as validated
  computer modelling(Conclusion 43)

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Regulatory Uses of QSARs

• 1. To support priority setting of chemicals
• 2. To guide experimental design (e.g. selection
  of tests / doses)
• 3. To provide mechanistic information
• 4. To group chemicals into chemical categories
• 5. To fill in data gaps for classification and
  labelling
• 6. To fill in data gaps for risk assessment

Reduction
Replacement
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Use of QSARs under REACH (Annex IX)

• Acceptance of QSAR results - BOTH positive and
  negative results will be accepted if
• Models have been validated
• Models are adequately documented and meet
  acceptance criteria for a given application-
  fit for purpose concept
• (Q)SARs may support grouping of chemicals
  Chemical categories and minimise testing
• Animal testing is conducted as a last resort

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When will we need QSARs for REACH ?
Valid QSARs will be needed before implementation
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Impact of QSARs on testing costs

• Testing costs are 98 costs of REACH

Pedersen et al.(2003). Assessment of additional
testing needs under REACH.
http//ihcp.jrc.cec.eu.
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Impact of REACH on Testing (2)

• Average use of QSARs
• Based on current models, but need validation and
  regulatory implementation
• Maximal use of QSARs
• New models required, followed by validation and
  implementation
• Cost-saving potential 700 940 M EURO

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ECETOC TF assessment of current predictive
capabilities in silico
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The Chemical Category concept and supporting role
of (Q)SARs
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ECVAM changing focus

• Provide effective support for REACH
• ECVAM is developing capacity in computational
  toxicology, QSARs to augment its portfolio of
  approaches to reduce animal testing, especially
  that these approaches have been more promising
  than in vitro studies alone.

Position of JRC in relation to REACH and the
European Chemicals Agency K. van Leeuwen
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JRC/ECVAM long term strategy

• development and validation of testing strategies
  for chemical substances based on decision support
  approach where
• the user follows a logical process to decide on
  the set of relevant information derived from
  different sources in vitro data , QSAR analysis,
  read- accross, in vivo data
• The user is advised how to combine and interpret
  this information ( example batteries)

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OECD activity on promoting Regulatory Acceptance
of (Q)SARs

• Special Session on (Q)SARs at 34th Joint Meeting
  (Paris, November 2002)
• Establishment of OECD Expert Group
• 1st Meeting of Expert Group hosted by JRC 2003
• 2nd Meeting of Expert Group, Paris, Sept 2004
• JRC/ECVAM is leading

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OECD Work Program

• evaluation of Setubal principles of (Q)SAR
  validity and acceptance
• Concept of fit for purpose
• development of technical guidance
• validation of (Q)SARs
• regulatory use of (Q)SARs
• use of batteries of (Q)SARs
• making (Q)SARs readily available
• data base of valid/accepted (Q)SARs

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Summary

• Need to use (Q)SARs is explicit in legislative
  proposal for REACH
• Future regulatory use of (Q)SARs will be
  controlled by various acceptance and validity
  criteria
• ECVAM validation process is being adapted for
  (Q)SARs
• There is a need tools to make (Q)SARs readily
  available (e.g. databases, decision support
  system)
• There is a need to develop integrated chemical
  assessment strategies that combine use of
  exposure, (Q)SARs, in vitro and in vivo tests
  (REACH implementation projects)
• JRC plans to play a leading role, in
  collaboration with its partners