Joint Research Centre

1
Joint Research Centre REACH and the need for
intelligent testing strategies Kees van Leeuwen
2
(No Transcript)
3
Mission of the IHCP
is to provide scientific support to the
development and implementation of EU policies
related to health and consumer protection
such as risks posed by chemicals,
biocides, genetically modified organisms,
contaminants released from food contact materials
and consumer products
4
(No Transcript)
5
Purposes of animal experiments in 2002COM(2005)
7 final
total number in 2002 10.7 million
6
Purposes of animal experiments in 2002COM(2005)
7 final

• Total number 10,700,000 100
• Safety evaluations 1,060,000 10
• Agricultural chemicals 123, 000 1
• Industrial chemicals 136,000 1
• Cosmetics 2,700 0.025

7
Animals used in safety evaluations in
2002 COM(2005) 7 final
Total number 1.06 million (10 of total use)
8
REACH and the use of test animals

• Testing on vertebrate animals shall be undertaken
  only as a last resort (art. 23)
• Information may be generated by other means than
  tests, in particular through (Q)SARs and
  read-across (art 12)
• Legislative text guidance should limit use of
  animals and prevent box-ticking

9
REACH testing costs testing needs (Van der
Jagt et al., 2004 IHCP EUR report 21405)

• Direct testing costs 2,4 billion (max.
  scenario)
• Animals numbers 3,9 million (max. scenario)
• Time foreseen 11 years (http//ecb.jrc.it)
• This corresponds to a 3 increase of the total
  number of vertebrate test animals used if no
  alternative intelligent approaches are applied

10
REACH saving potential of ITS (Van der Jagt et
al., 2004 EUR report 21405)

• Testing costs 800-1130 million
• Number of animals 1.3-1.9 million
• The most likely scenario for REACH according to
  the JRC 2.6 million vertebrate animals and 1.5
  billion for testing (http//ecb.jrc.it/ )

11
Estimated test animal need for the different
endpoints (van der Jagt et al., 2004)
12
The principle of 3Rs (Directive 86/609/EEC)
Refinement reduce suffering and
distress Reduction reduce number of animals
needed to obtain equivalent information Replace
ment substitution of animal tests, either
completely or partially (certain chemical
types and/or endpoints)
13
Sequential Use of ITS Components
14
Components of Intelligent Testing Strategies
(Bradbury et al., 2004)

• (i) In-vitro tests
• (ii) Optimised in-vivo tests
• (iii) Thresholds of toxicological concern
• (iv) SARs and QSARs
• (v) Read-across and chemical categories
• (vi) Exposure assessment/exposure-based
• waiving

15
Components of Intelligent Testing Strategies(i)
In-vitro tests

• Complete replacement possible for example for
  skin irritation, corrosion and sensitisation, eye
  irritation and phototoxicity .
• In vitro tests for other endpoints can play an
  important role in reduction animal use
• Reduction and refinement alternatives

16
EC Timetables published 904 forcomplete
phasing-out cosmetics animal testing
Time estimates assuming that optimal conditions
are met
substantial reduction of animal use could be
achieved earlier
17
Components of Intelligent Testing Strategies(ii)
Optimised in-vivo tests (Combes et al., 2004)

• Only perform tests that provide relevant data
• Eliminate redundant tests
• Using one sex
• Apply some tests simultaneously
• Apply screening and preliminary testing
• Discussion on (regulatory) acceptability with MSs
  should start soon
• Coordination by OECD (Test Guidelines Programme)

18
Components of Intelligent Testing
Strategies(iii) Thresholds of toxicological
concern (TTC)

• TTCs are exposure threshold values for chemicals
  below which no significant risk is expected
• Developed for human health risk assessment (Kroes
  et al., 2002 and 2004)
• And for environmental risk assessment (De Wolf et
  al., 2005).
• Great potential use if combined with adequate
  information on exposure

19
Components of Intelligent Testing Strategies(iv)
SARs and QSARs

• 40,000 chemicals have been assessed in the USA
  TSCA on the basis of (Q)SARs (PMNs)
• Reliability for physicochemical properties and
  environmental effects is good for mammalian
  toxicology and biokinetics improvements are
  needed (OECD, 1994)
• QSAR decision support system estimated to cost
  appr. 10 million
• Application is proposed under REACH

20
Components of Intelligent Testing Strategies (v)
Read-across and chemical categories (USEPA,
2004)
21
Components of Intelligent Testing Strategies
(vi) Exposure assessment and exposure-based
waiving

• Increased realism in the exposure evaluation
  will allow stakeholders to give less priority to
  a higher number of substances that are of no
  concern, provided that a minimum set of hazard
  information is available

22
Intelligent Testing Strategies Conclusions

• It seems desirable to establish a concerted
  multi-stakeholder approach on how ITS are
  developed, adopted and implemented in the next
  decade.
• There is a need for rethinking and reframing the
  current 3-R strategy of replacement, reduction
  and refinement and possibly develop and implement
  a broader strategy for REACH by applying ITS

23
REACH Implementation Projects (RIPs)
Commissions preparations of REACH

• RIP 1 REACH Process Description
• RIP 2 REACH IT
• RIP 3 Technical Guidance and Tools for Industry
• RIP 4 Technical Guidance and Tools for
  Authorities
• RIP 5 Setting up the Pre-Agency
• RIP 6 Setting up the Agency
• RIP 7 Commission preparations for REACH

24
RIP 3.3 Guidance on Information Requirements

• Objective Guidance for industry on how they can
  fulfil the REACH information requirements on
  intrinsic properties (Annex IV to IX)
• Scoping study on-going developing the framework
  for Intelligent Testing Strategies
• Carried out by a consortium of Industry (CEFIC,
  ECETOC) and key MS authorities with broad
  stakeholder expert consultation
• Results, available July 2005, will determine
  future steps