Lush Prize 2018 | Berlin

The Global
Trend inEnding
AnimalTesting

Troy Seidle
Vice President
Research & Toxicology
tseidle@hsi.org
hsi.org40+ different animal tests entrenchedin guidelines & regulations… and more indevelopment

Endocrine disruption

Nano-toxicology

Complex patchwork of regulations
across sectors & countries

Cosmetics

Calls for global ban
on animal testing &trade

Chemicals

Pesticides & Food

New & revised laws
impacting ~80K existing+ hundreds of new
substances each year

Extensive pre-market
testing required for
new active ingredients& formulations

Pharmaceuticals

Vaccines

Extensive pre-market
testing, including
primates & dogs

Redundant &sometimes lethal
batch-release testingNumerous ‘1R’ approaches available» NAMs, IATA, waivers, read-across, in silico…

Achieving replacement in practice» 1 test / regulation / country at a time

• All major markets
must agree to changeà even 1 holdout means
animal testing will continueAchieving replacement in practice» 1 test / regulation / country at a time
Deletion of 1-year dog test•

First scientific redundancy analysis
published in late 1990s•

Test requirement deleted in US, India,EU & Canada between 2007 -16•

Japan and S Korea took action in 2018•

Brazil is the last major market to move

è Nearly 20 years to delete 1 test !!

Achieving replacement in practice» encourage major markets to move en bloc
Abnormal Toxicity Test &Target Animal Batch Safety
Test for Vaccines

Consensus report & roadmapfor implementation(barriers to change& how to overcome)

MODERN APPROACH
Application of ‘consistency approach’

European precedent(2019 deletion)
Multi-national consensus workshop(include developing economies)

Global agreement & eliminationof ATT & TABST requirements

Legislative reforms» growth of mandatory alternatives laws
European Union• Requirement to use available alternatives
established in 1986 Animal Experiments
Directive and subsequent regulations

Brazil• 2014 CONCEA Resolution establishes 5 -year
mandatory phase-out for animal tests withgovernment-recognized replacement

United States• 2016 TSCA Reform Act introduced
unprecedented animal protective language
in a federal chemical statute

South Korea• 2017 ‘K-REACH’ Reform Bill introduced
established first-in-Asia animal protective
language in a national chemical law

Legislative reforms» cosmetic animal testing & sales bans
37 national bans
already in force

8 state bans inforce in Brazil & USA

10+ similar laws
in development• Australia• Brazil• Canada• Chile• Japan• Mexico• South Africa• Sri Lanka• United States• ASEAN region ofsouth-east Asia

Progress in China» official commitment to AT phase-out
3 NAMs adopted
since 2017; morein pipeline
Workgroup on
cosmetic alts.
research & valid’nestablished aheadof ChCVAM
Major policy
reform expected
this year with newcosmetic regul’n‘Tox21’ paradigm shift» are we there yet??!

Tox21 paradigm shift» human biology is complex & non-linear
Tox21 to-do list:
à Consolidate global expertise ofhuman patho/physiology in OECDknowledgebase

à Identify major modes of actionof human toxicity & rate-limiting‘key events’ and biomarkers
à Develop human based microphysiological (molecular/cell) tests
to detect changes in biomarkers
à Integrate quantitative outputs
from in vitro tests to buildcomplex systems biology models
à Define thresholds of adversity
à Incorporate exposure(magnitude, duration, time of life,etc.)

Tox21 paradigm shift» animal-free human risk assessmente.g.
ALZHEIMER’S(or otherenvironmental/ lifestylefactors)

AUTISM
PARKINSON’SLUNG CANCERASTMHA

Adapted from Dr AH Piersma, “Evolution vs Revolution in Innovating Regulatory Toxicity Testing”, 15 June 2018, RIVM

‘Tox21’ paradigm shift» bridging the silos
More multidisciplinary
collaboration(clinicians,big data)

Describe humanphysiology in thefrom of AOPs

Build models aroundhuman patho/
physiology(AOPs)

Human microphysiologicalsystems

Computationalmodels forprediction

Excelsior!

(ever upward)