Introduction

Humane Society International (HSI), and its affili-ates, together constitute one of the world’s largestand most effective forces for animal protection.HSI is widely respected as an authority on animalresearch and testing issues, and is frequentlycalled upon by governments, corporations andother official bodies for its advice and expert opin-ion. Its team of scientists, policy experts, campaignprofessionals, investigators and supporters spansthe globe, acting as a voice for humane andhuman-relevant testing and research that movesbeyond outdated animal models by using the mostadvanced tools that 21st century science has tooffer.

HSI Strategy and Accomplishments

Be Cruelty-Free: Ending cosmetics animaltesting worldwide

HSI played a leading role in driving Europeaninstitutions to follow through on their commitmentto ban the sale of newly animal-tested cosmetics,

which became effective on 11 March 2013. Years ofhigh-level political negotiations were coupled withhigh-profile public campaigning — includingrecruitment of top celebrity supporters such as SirPaul McCartney, Leona Lewis, Ricky Gervais andmany others, and a corporate partnership withLush cosmetics, through which hundreds of thou-sands of petition signatures were collected in mereweeks — to achieve the celebrated victory: aEurope free from cosmetics animal cruelty. Yet solong as powerful emerging markets such as Chinacontinue to require animal testing, not only fornew cosmetic ingredients, but also for each newproduct formulation (1), HSI’s efforts could notremain limited to Europe.

Be Cruelty-Free was born from the recognitionthat the global nature of the cosmetics industry, cou-pled with differing regional regulatory requirements(2), necessitated a coordinated, multinational strat-egy, if a worldwide end to animal testing for cosmet-ics was to be achieved. In April 2012, HSI and itsaffiliates, in partnership with Lush and animal pro-tection groups in Australia, Brazil, Canada, India,Korea, New Zealand, Russia and the USA, launchedBe Cruelty-Free, with the goal of making cruelty-freecosmetics the global mainstream by replicating theEuropean animal testing and sales bans across all

Humane Society International’s Global Campaign to EndAnimal Testing

Troy Seidlea

Research & Toxicology Department, Humane Society International, Toronto, ON, Canada

Summary — The Research & Toxicology Department of Humane Society International (HSI) operates a mul-tifaceted and science-driven global programme aimed at ending the use of animals in toxicity testing andresearch. The key strategic objectives include: a) ending cosmetics animal testing worldwide, via the multi-national Be Cruelty-Free campaign; b) achieving near-term reductions in animal testing requirementsthrough revision of product sector regulations; and c) advancing humane science by exposing failing ani-mal models of human disease and shifting science funding toward human biology-based research and test-ing tools fit for the 21st century. HSI was instrumental in ensuring the implementation of the March 2013European sales ban for newly animal-tested cosmetics, in achieving the June 2013 cosmetics animal test-ing ban in India as well as major cosmetics regulatory policy shifts in China and South Korea, and in secur-ing precedent-setting reductions in in vivo data requirements for pesticides in the EU through the revisionof biocides and plant protection product regulations, among others. HSI is currently working to exportthese life-saving measures to more than a dozen industrial and emerging economies.

Key words: adverse outcome pathway, animal testing, AXLR8, chemical, cosmetic, data requirements,Horizon 2020, HSI, Human Toxicology Project, OECD, pesticide, REACH, regulatory alignment, Three Rbest practices.

Address for correspondence: Troy Seidle, Humane Society International, 506–460 Sainte CatherineOuest, Montréal, QC H3B 1A7, Canada.E-mail: tseidle@hsi.org

ATLA 41, 453–459, 2013 453

aThe author was a member of the 2012 Lush Prize judging panel.

key global cosmetics markets. A global online pledgewas launched at hsi.org/becrueltyfree and in morethan 700 Lush shops in 48 countries, to educate con-sumers and provide them with an avenue to supportthe campaign. Be Cruelty-Free has since expandedalso into China, Japan and Taiwan, for a total of 12concurrent regional campaigns (Figure 1).

A partial list of Be Cruelty-Free’s achievementsto date include the following:— In India, being instrumental in convincing pol-

icymakers to delete the last remaining animaltests from the country’s cosmetics standard(3), thereby effectively banning cosmetics test-ing involving animals. Today, HSI–India isholding top-level meetings with Governmentofficials to achieve an extension of the ban toprohibit also the sale of cosmetics that havebeen subject to new animal testing in otherparts of the world.

— In Brazil, influencing the revision of nationalcosmetics safety assessment guidelines, whichwere updated following an HSI workshop inDecember 2012, and now provide for acceptanceof all Three Rs test guidelines promulgated bythe Organisation for Economic Co-operationand Development (OECD; 4). In September2013, HSI filed a regulatory proposal withBrazil’s Conselho Nacional de Controle deExperimentação Animal (CONCEA) calling fora national cosmetics animal testing ban, withthe backing of more than 150 Brazilian federalparliamentarians.

— In China, HSI and the Humane Society of theUnited States (HSUS) have awarded an$80,000 grant to the Institute for In VitroSciences (IIVS) to provide hands-on training togovernment regulators, and academia andindustry scientists, on the use and interpreta-tion of non-animal OECD test guideline meth-ods. In previous years, HSI has co-fundedsimilar IIVS training courses for Brazilian andRussian stakeholders. Since the launch of BeCruelty-Free in China, the China Food andDrug Administration has announced the firstrevision of the country’s cosmetics frameworkregulation in 20 years.

— In South Korea, intensive political, regulatoryand corporate engagement prompted theMinistry of Food and Drug Safety to announcea significant policy shift to formally recognisenon-animal test results for assuring the safetyof sunscreens, anti-wrinkle creams and other‘functional’ cosmetics. Additionally, the govern-ment has committed to invest 166 billion Won(approx. $145 million) to establish Korea’s firstCentre for Alternatives to Animal Testing.

— In New Zealand, HSI delivered a similar sub-mission to the Parliament, as it reviews thecountry’s Animal Welfare Act. HSI and our NZ

cam paign partner have also launched anational advertising campaign calling for KiwiPrime Minister John Key to ‘hop to it’ and bananimal testing for cosmetics (Figure 2).

HSI and its partners are also working to influencenew and revised laws and regulations governingthe trade and testing of chemicals (similar to theEurope’s Registration, Evaluation, Authorisationand Restriction of Chemicals [REACH] system,discussed further below) to prevent the creation ofloopholes that would allow, or even require, newanimal testing for cosmetic raw ingredients. Inmany parts of the world, Be Cruelty-Free has putthe animal testing issue on the public policyagenda for the very first time. Yet, from theAmericas to Asia and Oceania, opinion pollsfunded by HSI and its partners have revealedunprecedented levels of public support for nation-wide bans on cosmetics animal testing (5), and BeCruelty-Free is helping to drive public policy dis-cussions in Brazil, China, New Zealand, SouthKorea and beyond, with first-of-their-kind legisla-tive proposals arguing the case for cosmetics ani-mal testing bans.

Revision of product sector regulatory datarequirements

The efficient uptake of ‘Three Rs best practices’, toachieve practical, near-term reduction in animaluse in product sectors (pesticides, industrial chem-icals, medicinal products, etc), is hampered bycomplex and highly regionalised regulatory frame-works and data requirements. Progress requires asector-specific and region-specific approach, andoften upwards of two years of detailed scientificnegotiations with regulators, industry and otherstakeholders are necessary to achieve a revisedregulation that fulfils the objectives of: a) adoptingall available OECD Three Rs test guidelines andguidance; b) providing flexibility to enable the useof the most efficient testing strategies to reduceanimal use to the greatest possible extent withoutcompromising human health or environmentalprotection; and c) laying the groundwork for atransition toward a future adverse outcome path-way (AOP)-based testing and risk assessment par-adigm (6).

Pesticides

Today, testing to meet regulatory requirements fora new pesticide active ingredient can consumemore than 10,000 rodents, rabbits, fish, birds, dogsand other animals, in dozens of separate toxicityand ecotoxicity studies. Animal testing is also car-ried out on all finished products, and is often

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required for the re-registration of existing activeingredients. Overt redundancies abound, includ-ing, for some endpoints, the requirement for thesame study via multiple exposure routes (e.g.acute, subacute and subchronic testing via oraland/or dermal and/or inhalation routes), or in morethan one species (e.g. subchronic and chronic test-ing in rodents and dogs, prenatal developmentaltoxicity in rodents and rabbits, carcinogenicity inrats and mice, fish acute studies in two or morespecies, etc).

Between 2010 and 2013, HSI and its partnersundertook to influence technical and political nego-tiations around the scheduled revision of Europeandirectives for plant protection and biocidal prod-ucts (i.e. agricultural and non-agricultural pesti-cides, respectively). Working from regulatoryproposals drafted by the European Commission,HSI identified more than 100 opportunities torevise toxicological data requirements for biocides,in order to remove redundancies and incorporatenew OECD Three Rs guideline methods and other

Figure 2: Be Cruelty-Free national advertising campaign in New Zealand

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Humane Society International’s global campaign 457

innovative testing strategies. In the case of acutetoxicity, HSI collaborated with the EuropeanCentre for the Validation of Alternative Methods(ECVAM) to carry out a new data analysis to objec-tively examine the regulatory value of testing viamultiple exposure routes (7).

The political process involved multiple rounds ofnegotiations with Commission scientists, Parlia -mentary rapporteurs and Member State regula-tors. Ultimately, more than 80 amendments putforward by HSI were adopted in the new EUBiocidal Products Regulation (8), including:— deletion of the dog chronic toxicity study; — uptake of the new OECD Extended One-gener-

ation Reproductive Toxicity Study; — downgrading several second route/species study

types to conditional requirements;— a requirement to consider combining two or

more endpoints within the framework of a sin-gle repeated-dose toxicity study (e.g. the addi-tion of neuro/immuno endpoints and/or thepresence of micronuclei for genotoxicity assess-ment); and

— broad provision for ‘classification by calculation’for formulations and finished products.

These and other measures, when taken together,represent possibly the largest one-time reductionin in vivo data requirements in a regulated productsector, and are the bases on which HSI wasawarded the 2012 Lush Prize for lobbying (lush-prize.org). A number of similar measures have alsobeen taken up in new EU regulations setting outdata requirements for plant protection products (9,10). Since achieving these regulatory precedents inthe EU, HSI has begun active outreach to pesticideregulators in Canada, India, Brazil and the USA,with an eye to extending these Three Rs best prac-tices globally, and already some progress has beenachieved (11).

Chemicals

In addition to advocating global uptake of Three Rsbest practices within the pesticide sector, HSI isalso actively pressing the EU to revise datarequirements under the REACH chemical regula-tions (12). Millions of animals could be spared suf-fering and death, if EU chemical regulators wouldsimply accept the same Three Rs best practicesthat have already been taken up by their pesticideregulatory counterparts, for the tens of thousandsof substances that fall within the scope of REACH.Not only is this the responsible and humaneoption, it is also a legal requirement under REACHthat animal testing be carried out only as a lastresort (Article 25.1), and that data requirementsbe updated “as soon as possible” and “with a view

to reducing testing on vertebrate animals” (Article13.2). Yet, despite this mandate, and that morethan 18 months have passed since HSI presentedits proposal to update REACH data requirements,meaningful action on the part of the EuropeanCommission remains conspicuously absent.European progress in this area is also consequen-tial for other countries that have chosen to emulateREACH as a model for their own domestic chemi-cal regulations (e.g. China REACH, and K-REACHin South Korea). HSI and its regional partners areactively working to influence new and revisedchemical regulations, particularly in theAsia–Pacific region, to ensure that contemporaryThree Rs best practices are taken up in lieu ofalignment with the now outdated EU REACH reg-ulations.

Advancing humane science

AXLR8 and the Human Toxicology Project

The view that conventional animal models ofhuman safety and efficacy are time-intensive andresource-intensive, restrictive in the number ofsubstances that can be tested, of limited use in pro-viding mechanistic understanding, and of evenmore limited relevance to human biology, has gonefrom being dismissed as anti-vivisectionist rheto-ric, to being embraced as a compelling driver for afundamental paradigm shift in toxicology (13). TheUS National Academy of Sciences 2007 report (14)has not only inspired a number of regional andmultinational research efforts aimed at advancing‘21st century toxicology’ — from the US intera-gency Tox21 collaboration (epa.gov/ncct/tox21), tothe European SEURAT-1 project (seurat-1.eu) andthe OECD global initiative to map AOPs(bit.ly/1hFUYl6) — it has also shifted the discus-sion from whether animal testing can be replaced,to how quickly this goal can be achieved (15).

Leading universities, research institutes andcompanies have joined HSI under the EU 7thFramework project, AXLR8 (axlr8.eu), to develop aroadmap to guide 21st century toxicology-relatedEU research investment under the forthcomingfunding programme, Horizon 2020 (16). In addi-tion, through the Human Toxicology ProjectConsortium (htpconsortium.org), HSI, HSUS andcorporate partners are working hand-in-hand on aglobal basis, to dramatically increase public andprivate research funding in this important area(Figure 1). HSI also serves on a number of govern-mental expert and stakeholder advisory bodies,including at European and OECD levels, where wecontribute to high-level discussions regardingprocesses for the validation and regulatory accept-ance of novel testing tools. HSI is honoured also to

have two of its scientists serving as judges for theLush Prize, to help promote and award tangibleprogress toward animal replacement.

Disease models in biomedical research

In contrast to the relatively rapid shift under wayin toxicology, the inertia in the wider biomedicalresearch community — which accounts for morethan 80% of all animal use for scientific purposes— is more pronounced. Intolerance persists ofquestions, or criticisms, regarding the validity andvalue of animal models of human disease, despitea scant and painstakingly slow rate of progress incrucial disease areas and an ever-growing body ofpublished evidence pointing to the need for a shiftin research paradigm (17–22). As noted by the for-mer US National Institutes of Health director,Elias Zerhouni:

“We have moved away from studying human dis-ease in humans… We all drank the Kool-Aid onthat one, me included… The problem is that it hasn’tworked, and it’s time we stopped dancing aroundthe problem… We need to refocus and adapt newmethodologies for use in humans to understanddisease biology in humans.” (23)

In the interests of stimulating further constructivedebate within the biomedical research community,HSI and HSUS scientists have begun contributingscholarly reviews in several disease areas, includ-ing asthma (24), Alzheimer’s disease, Parkinson’sdisease, and Amyotrophic Lateral Sclerosis (K.Willett, personal communication, 01.11.13). Rec -ently, HSI launched a grant programme to sponsorreviews and publications by independent academicscientists that critically examine animal models ina particular disease area, and propose a forward-looking scientific ‘roadmap’ for the disease areabased on 21st century human biology-based (non-animal) tools. Interventions from HSI in politicalnegotiations for Horizon 2020 have alreadyachieved new directional language to better-focusfuture EU health research funding on human-rele-vant approaches (in lieu of more genetically-modi-fied mice), with emphasis on AOP discovery andbioinformatics, expanded development of humanbiology-based cellular and computational tools,and funding for new research infrastructures suchas high-throughput in vitro screening and super-computing capacity. HSI will provide funding forits disease model grant recipients to present theirpublications at key scientific conferences world-wide, and will organise high-level briefings fornational public and private research funding bod-ies, with an eye to shifting resources away fromfailing models in the interests of more-humaneinvestments and better returns for human health.

Conclusions

Investment in the science needed to replace theuse of animals in testing and research is muchmore than a political objective driven by ethicalconsiderations; it is an opportunity to improve ourfundamental understanding of human biology as ameans of achieving optimal health and being ableto effectively treat — and ideally prevent — dis-ease. In the interim, incremental, yet significant,reductions in animal use can be achieved throughmore-robust application of established Three Rsbest practices across regulated product sectorsglobally, laying the groundwork for a more sub-stantial methodological shift over the longer-term.In emerging economies, an initial focus on cosmet-ics provides an effective gateway through which toinform and engage the public and policymakersand put the animal testing issue on the govern-ment agenda.

Acknowledgements

HSI would like to thank Lush Cosmetics for itsgenerous financial and campaign support for BeCruelty-Free, and all our regional Be Cruelty-Freepartners around the globe for their collaboration.AXLR8 is a coordination and support projectfunded by the European Commission under the7th European Framework Programme on Researchand Innovation (Grant No. 241958). All work onHorizon 2020 political negotiations was carried outby using grant funds generously provided by theWorld Society for the Protection of Animals. HSIwould also like to thank WSPA for funding a por-tion of its disease models initiative.

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