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

WHO I WORK FOR?

20101981

ANIMAL TESTING HISTORICAL

RETROSPECTIVE

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

CHALLENGING THE 3000Yrs OF TRADITION

WORLDWIDE

SOME US FIGURES

•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

US REGULATORY FRAMEWORK

AWA - 76

US PERSPECTIVES-

Tox21Tools

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. “

"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.”

LOW COST & TIME

=X

$10 millions US + 5 years time

X =

$10,000 US + 2 weeks vs. 6 months

TOX21 REG. OUTPUTS

Tox-21c Reg. Outputs

ToxCast Substances

HTP assay

s

Phase 12007-2009

300 500

Phase 22010-2013

2000 700

EDSP20

$6 millions / ingredient

EDSP21 =

in vitro HTSin silico

Full replacement

for Tier 1$30,000 / ingredient

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

INTERNATIONAL CONTEXT & THE BAN

ShampooPerfume

SunscreenAnti-wrinkle

Sao Paulo

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WHY AREN’T WE DONEWITH ANIMAL TESTING?

•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

EU FUNDING IN ALTERNATIVES TO ANIMAL TESTING

•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%...