1. Center for Alternatives to Animal Testing (CAAT)
Johns Hopkins University, Baltimore, USA –
University of Konstanz, Germany
Francois Busquet, PhD
Toxicology for
the 21st
century
in USA

2. WHO I WORK FOR?

3. 20101981

5. ANIMAL TESTING
HISTORICAL
RETROSPECTIVE

6. Vth
B.C.
Hippocrate Aristotle
IInd
B.C.
Galen
XVIIth
Descartes
XIXth
Darwin Bernard
XVIIIth
Bentham
V. Bauman; Gene Therapy (2004) 11, S64–S66 & 2004 Nature Publishing Group
XXth
Russel & Burch

7. CHALLENGING THE
3000Yrs OF TRADITION
WORLDWIDE

10. SOME US FIGURES

11. •85 to 100 M Vertebrates used
worldwide – EU (11.5M)
•$3 billions Tox studies
regulates $10 trillions products
•Tox21 Budget $hundredsM
(ongoing)
•US Federal R&D budget Y13: $133
billions

12. US REGULATORY
FRAMEWORK

13. AWA -
76

14. US PERSPECTIVES
-
Tox21Tools

15. An atmosphere of departure in
toxicology 2007
New technologies from
biotech and
(bio-)informatics revolution
Mapping of pathways of
toxicity (PoT)
NAS vision report Tox-21c
“Traditional toxicological testing is based largely on the use of
laboratory animals. However, this approach suffers from low
throughput, high cost, and difficulties inherent to inter-species
extrapolation - making it of limited use in evaluating the very
large number of chemicals with inadequate toxicological data. “

16. "The Tox21 collaboration will transform our
understanding of toxicology with the ability to
test in a day what would take one year for a
person to do by hand."
“In FY 2014, the EPA will continue the multi-year
transition away from the traditional assays used
in the endocrine disruptor screening program
through efforts to validate and use computational
toxicology and high throughput screening methods.
This is expected to allow the agency to more
quickly, efficiently, and cost-effectively assess
potential chemical toxicity.”
“The NTP recognized that the dramatic technological advances in
molecular biology and computer science offered an opportunity to
use in vitro biochemical- and cell-based assays and non-rodent
animal models for toxicological testing.”

17. LOW COST & TIME
=X
$10 millions US + 5 years time
X =
$10,000 US + 2 weeks vs. 6 months

18. TOX21 REG. OUTPUTS

19. Tox-21c Reg. Outputs
ToxCast Substance
s
HTP
assay
s
Phase 1
2007-2009 300 500
Phase 2
2010-2013 2000 700

20. EDSP20
$6 millions /
ingredient
EDSP21
=
in vitro HTS
in silico
Full
replacement
for Tier 1
$30,000 / ingredient

21. http://en.wikipedia.org/wiki/Organ-on-a-chip
C. Zhang et al. (2009),
“Towards a human-on-chip:
Culturing multiple cell types
on a chip with
compartmentalized
microenvironments”
Human on a Chip Approach
Opportunities from
countermeasures to
bioterrorism
$200 million funding
program

22. INTERNATIONAL
CONTEXT & THE BAN

23. Shampoo
Perfume
Sunscreen
Anti-
wrinkle
Sao Paulo
??next??

24. WHY AREN’T WE DONE
WITH ANIMAL TESTING?

25. •3000 YEARS OF TRADITION = HUGE
KNOW HOW
•LACK OF CROs (CONTRACT RESEARCH
ORGANISATION)
•28 REGULATORY AGENCIES
•SHORTCOMINGS FOR IN VITRO
MODELS – DIFFICULT ENDPOINTS
•MANPOWER - R&D INVESMENTS

26. EU FUNDING IN
ALTERNATIVES TO
ANIMAL TESTING

27. •MEMBER STATES DUTIES REGARDING
ARTICLE 47 - DIRECTIVE
2010/63/EU
•13 MEMBER STATES ONLY
•AAT vs. national R&D
investments: 0.001 to 0.035%...