REGULATION & LEGISLATION
“The Animal Testing Ban – What is next?”
A Retrospective look at the full day In-Cosmetics Hamburg 1. April 2014 Workshop
Steven L. Hanft, M.A., President, CONUSBAT & co-organizer of this workshop, et al.
On April 1st, in the Chicago room at Hamburg’s Exhibition Center,
the workshop „The Animal Testing Ban – What is next?” occurred.
CONUSBAT once again had been asked to organize the full-day
(2-sessions) regulatory event for Reed Exhibition, which it had gladly
accepted.
The 2 sessions addressed the following issues:
Part 1 Session: Why should the Animal Testing Ban be the end of
innovation in cosmetics? Learning about new in-vitro, in-silico and
in-chemico methods that form the elements of the new toolbox for
assessing ingredient safety.
Part 2 Session: Gaining insight about multi-tier alternative strategies for the example of skin sensitization. Explore the biochemical
mechanisms behind the effect, how these are addressed by alternative methods and see the way information is put together like mosaic
pieces for sensitization assessment. What are the consequences for
the industry in supporting existing and new ingredients within the
European regulatory processes?
The In-Cosmetics Animal Testing Ban’s list
of esteemed speakers and panelists
with their topics were:
Workshop, part 1, morning session
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O
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Dr. Annelie Struessmann, Technical Director, CONUSBAT,
Aachen, Germany and co-organizer of this workshop Animal
Q Animal Testing for Cosmetics in a World-wide Perspective
Historical Background for Animal Protection
Dr. Patric Amcoff, Interim Director Science & Research,
Cosmetics Europe, Brussels, Belgium
Q The EU’s Animal Testing Ban
In order to know where we are headed with the ban on animal
testing for cosmetics and cosmetic ingredients in the EU, it is important to know from where the ban gained its origins. Stemming its
roots in the Animal Rights Movement, no one can give an exact date
as to when this movement was founded.
Dr. Joop de Knecht, Environment Directorate, OECD, Paris,
France
Q Implementing Altenatives to Animal Testing
Dr. Christian Pellevoisin, Scientific Coordinator, SkinEthic
Academy (L’Oreal), Lyon, France
Q Existing Alternative for Skin Irritation / Corrosion
However, it could be argued that the initial link for the Animal
Rights Movement was the link to religion and more specifically to
the Hindu religion. After all, the earliest Hindu Veda (meaning
‘knowledge’) scriptural texts show that vegetarianism has always
been a mainstream thought. In the Mahabharata, the great warrior
Bhishma explains to Yudhisthira, eldest of the Pandava princes,
“that the meat of animals is like the flesh of one's own son, and that
the foolish person who eats meat must be considered the vilest of
human beings.” The Atharva Veda proclaims, ”Those noble souls
who practice meditation and other yogic ways, which are ever
careful about all beings, who protect all animals, are committed to
spiritual practices.“
Mr. Des Caves, Toxicologist & Account Manager Early Development Services, Bioreliance, UK
Q 3D Tissue for Genotoxicity – A Validation Scenario
Workshop, part 2, afternoon session
O
Dr. Nava Dayan, Nava Dayan LLC, Fairlawn, NJ, USA
Skin Toxicology: Biochemical Mechanisms and their Reflection
in Toxicological Testing
Q
O
Dr. Reinhard Kreiling, Clariant, Sulzbach, Germany
Skin Sensitization as Example of a Comprehensive Testing
Strategy
Q
O
As for Western thought, in 1875, Ms. Frances P. Cobbe (born in
Dublin, Ireland, and a leading woman’s suffragist) founded the UKbased National Anti-Vivisection Society (NAVS), which was the
world’s first NGO opposing experiments on animals. The NAVS
gathered many notable people of the day to support its cause, one
was Queen Victoria. Many of the social reformers of the day, working
for children's rights and women's rights, supported the aims of the
NAVS.
Ms. Ellen Pfrommer, BASF, Ludwigshafen, Germany
Animal Testing Ban / Marketing Ban – Consequences for
Cosmetic Ingredients
Q
O
Dr. Theresa Callaghan, CCI (claims expertise), Hamburg,
Germany
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EURO COSMETICS
REGULATION & LEGISLATION
O
By 1876, the British Parliament passed the first anti-vivisection
law, the ‘Cruelty to Animals Act’. In 1883, the readers of ‘Science’,
the organ of the American Association for the Advancement of
Science (AAAS), were warned that American scientists in the US
faced a similar legislation and thus issues of using animals for testing.
In view of this threat, the author advised the medical profession to
“inform the laity” how and why animal experimentation was used in
scientific research. Inspired by Ms. Cobbe, the American Anti-Vivisection Society (AAVS; Philadelphia, Pennsylvania, USA) was
founded in 1883 with the goal of regulating the use of animals in
science and society.
Background to the Animal Test Ban
in Europe for Cosmetics
The 11. March 2013 deadline ‘came and went’ for the final implementation of the animal testing ban for cosmetics products in the
EU. The last step for the ban applied towards marketing of cosmetic
products and their ingredients when tested on animals for the most
complex human health effects: skin sensitization, carcinogenicity,
repeated-dose systemic toxicity, reproductive toxicity and toxicokinetics. At the time of final implementation, the EU Commissions
stated, ‘The testing and marketing bans in the Cosmetics Regulation
apply even in case alternative methods to animal testing are not yet
available’.
The ideology continuously evolved over millennia, but many
animal activists point to the publication of “Animal Liberation” by
Professor Peter Singer in 1975 as the catalyst for the modern American animal rights movement. Singer, whose family hails from Vienna
(due to Nazi persecution, the family left Austria in 1938 to Australia)
now heads up a bioethics chair at Princeton University, Princeton,
NJ, USA.
On that day, the animal test ban news even made into the New
York Times, which is considered America’s most widely read newspaper. Considering that Europe (incl. Switzerland and Norway) possesses the world’s largest share of the cosmetic sector at € 72billion
(US$ 91billion), the newspaper was citing global cosmetics manufacturers, stating, that increasing efforts exist in the companies seeking
global acceptance for products with proof of safety not relying on
animal tests. However, the NY Times also cited representatives of
the European cosmetics industry, who were criticizing the EU Commission for putting a ban into effect before alternatives existed for
some of the most complex tests.
NGOs as drivers of the Animal Test Ban
Many animal rights protection agencies/organizations espouse a
number of approaches, and are bitterly divided on the issue of direct
action and violence, with very few activists or writers publicly advocating the latter tactic as a justified method to use. It should be also
noted, that the animal rights movement has other cause célèbre,
which included stopping the sale of animal furs (seals, mink, etc.) or
to end humans waging bets in cock (roosters) or dog fighting. Each
NGO has n organization structure, staff and its own campaign to
support; thus, monetary donations are their key source to achieving
their goals.
As such, these representatives were contributing to an already
‘hot topic’, as in their view, the ban would mean jeopardizing the
cosmetic industry’s ability towards innovation. Accordingly, consumers in Europe would not have access to new products because
the industry cannot assure the safety for some of the ingredients
without having access to suitable and adequate testing.
Whether liked or disliked, the NGOs and their members are the
main drivers for the Animal Test Ban, some of whom hail from rock
star status (i.e., Paul McCartney) to VIP’s from the entertainment
world (TV, film, etc.). The following Animal Right’s NGOs are considered as the being mostly in the main stream:
O
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NAVS - National Anti-Vivisection Society; founded in 1875, London,
UK
While the discussions are often emotional or narrowed in their
objectivity, certainly hurdles do exist. However, it is often overlooked how many impressive alternative approaches to proving the
safety of ingredients and products exist already. Based on extensive
efforts and money being put into the research of alternatives for this
nascent science area of human toxicology, an array of new in-silico,
in-chemico and in-vitro methods has evolved. Also, tools for new
multi-tiered testing strategies were designed, which are based on the
awareness that one alternative test cannot cover the complexity of
human biochemical mechanisms. Presenting key results obtained
from past year’s research and depicting strategies for assessing cosmetics by alternative approaches was the goal of the regulatory
workshop in Hamburg.
AAVS - American Anti-Vivisection Society; founded in 1883, Jenkintown, Pennsylvania, USA
The Humane Society, also sometimes referred to as the Society for
the Prevention of Cruelty to Animals (SPCA); founded in 1954,
Washington, DC, USA (European office: London, UK)
WWF - World Wildlife Fund (directed more towards protecting
endangered species and concern towards pollution, climate
change); found in 1961, Gland (near Geneva), Switzerland
PETA - People for the Ethical Treatment of Animals; founded in
1980, Norfolk, Virginia, USA
6-2014
Cruelty Free International (claims to be ‘the only global organization working solely to end animal testing for cosmetics and consumer products’); offices in London/UK, Boston, Massachusetts/
USA & Singapore
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EURO COSMETICS
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Animal Test Ban – Implementation Deadlines
Date
Testing ban on finished cosmetic products
Testing ban on ingredients or combination of ingredients
Marketing ban when tested for human health effects with the exception of the specific effects of
repeated-dose toxicity, reproductive toxicity and toxicokinetics
Marketing ban when tested on the specific effects
The ban applies irrespectively on the availability of alternative non-animal tests
11. Sept. 2004
11. March 2009
Key Results from the Workshop in Hamburg Contents and Quotations from the
Esteemed Speakers
Dr. Annelie Struessmann opened the day by looking into the status
worldwide on existence of animal testing bans for consumer product
areas. She concluded that the EU took the lead and banning of animal
testing for cosmetics is under review worldwide. During the past
years, major moves happened in various countries, including, the
implementation of animal testing bans and the introduction of programs for research of test alternatives. Dr. Struessmann predicted
that with alternatives becoming completely available animal testing
11. March 2009
11. March 2013
on cosmetics will be phased out on a worldwide scale. A main hindrance at this time are outstanding replacement methods for
complex toxicological endpoints, the REACH testing requirements
and the European Chemicals Agency’s (ECHA) role in interpretation
of the compliance criteria towards these, as well as, still existing
different views in some major markets on the needs for testing of
cosmetics.
The second speaker was Dr. Patric Amcoff from the industry association Cosmetics Europe (Brussels, Belgium), formerly known as
Colipa. He provided an overview of the EU Commission’s and the
cosmetic industry’s goals and programs on research for testing
alternatives. The joint program under the Steering Committee on
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project and toolbox, which is attempting to identify similarities in
structural characteristics and mechanisms for chemicals and subsequent use of existing experimental data in read-across approaches.
Finally, Joop de Knecht reported on the OECD’s activities in the area
of Adverse Outcome Pathways (AOPs) with a current work plan of
about twenty AOP projects for the different assays, endpoints or
databases, including the implementation of AOPs into the (Q)SAR
Toolbox.
Alternatives to Animal Testing (AAT)’s for the time phase from 20082016 will be followed up by a long range science strategy 2016-20 via
the European Partnership for Alternative Approaches to Animal
Testing (EPAA), the International Cooperation on Cosmetic Regulation (ICCR), and other sector organisations. The new approach will
focus exclusively on test replacements, while before the 3R principal
of replacement, refinement and reduction formed the base for
research. His conclusions were, that new internationally agreed
tools and testing approaches such as AOP (Adverse Outcome
Pathway), ITS (Integrated Testing Strategies), IATA (Integrated
Approaches to Testing and Assessment), etc., will form the basis for
reseach and a conceptual change in performing safety assessments
based on mechanistical understanding will be the consequence. An
issue in his view is the time required for validation of methods and
their regulatory acceptance, e.g. for the SCCS’ ingredient evaluation
process. This issue will considerably increase the total time period
until availability of the completed new toxicology toolbox.
Another part of Dr. Amcoff’s speech covered the EC’s Interpretation on use of animal testing data after the 2013 deadline. Accordingly, tests performed after March 2013 on ingredients exclusively
used in cosmetics trigger the ban. Animal data generated for third
country cosmetics regulations cannot be used for EU safety assessments; however, use of non-cosmetics data generated for EU- and
non-EU regulatory regimes is allowed with an interpretation from
the European Court of Justice still pending. No derogative scheme
exists for new cosmetics-unique ingredients, but current Member
State derogation schemes for existing ingredients remain valid.
Dr. Christian Pellevoisin introduced two existing alternative and
fully validated methods, OECD TG 431 is an in vitro method for skin
corrosion and OECD TG 439 is an in vitro method for skin irritation.
Using reconstructed human epidermis (RhE) as a biological model,
both tests are accepted as full replacement methods. Predictive
methods have been developed for efficacy and toxicity testing of
ingredients and validation was achieved for safety testing. RhE predictivity methods with can also be used for determining the skin
irritation potential of finished cosmetic products.
The last speaker for the morning session was Des Cave, who
depicted the validation scenario in progress for the 3D skin micronucleus assay, a promising and relevant new non-animal approach for
genotoxicity evaluation of cosmetics. In the three-step validation
process, the method showed usefulness for following up chemicals
which are positive in the standard in-vitro genotoxicity assays.
Results from the validation steps showed that the test can be readily
transferred to new laboratories, it is robust enough for standard GLP
testing, and it allows establishing inter and intra-laboratory reproducibility. At this point global validation of the method appears as
being very promising.
Dr. Joop de Knecht introduced the OECD’s tools and programs in
the area of testing alternatives and started with available guidelines
for in-vitro tests, which include, but are not limited to skin corrosion, phototoxicity, skin absorption, eye corrosion, genotoxicity and
endocrine disruption. Further efforts address integrated approaches;
draft OECD guidance, which is in the reviewing phase, exists on
how to integrate all existing information on corrosion and irritation
potentials for final decisions on classification and labelling of chemicals. Another alternative approach uses grouping of chemicals for
read-across, promoting use of data from analogue substances to fill
data gaps. Existing guidance has recently been augmented with
examples encountered in the OECD Cooperative Chemicals Assessment Program; publication of the update is anticipated for 2014. The
eChemPortal is a global portal with information on chemical substances and provides direct links to information from a large number
of data sources. Another alternative OECD approach is the (Q)SAR
Dr. Nava Dayan opened up the afternoon session by exposing the
complexity of the human body’s largest immune response organ, the
skin, and the difficulty of addressing the toxicological responses in
testing procedures. She evaluated the biochemical mechanisms
leading to the induction of skin sensitization reactions and the
various types of hypersensitization and their attributes. While
looking into the functionality of cosmetic ingredients in inducing
sensitization reactions it was reminded that the risks determined do
not consider the final cosmetic formulations. Gaps for risk assessment result also from current skin sensitization testing approaches
which do not address all different biochemical responses sufficiently
and also, most often, do not consider accumulation for chemical
exposure. Animal testing is limited due to the differences between
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animal and human skin which is easily expressed by the difference
in number of follicles. Finally, in addressing replacement for animal
test she emphasized to further investigate the use of gene expression
and proteomics, methods frequently used in pharmaceutical testing.
As an example of a comprehensive testing strategy, Dr. Reinhard
Kreiling addressed AOPs for skin sensitization. Traditionally, quantitative potency estimates for contact dermatitis were based on the
in-vivo Local Lymph Node Assay (LLNA). Current integrated evaluation methods use a stepwise process integrating all relevant information and approaches on a case-by-case basis to reach science-based
decisions in a weight-of-evidence (WoE) assessment. Adverse
outcome pathways (AOPs) reflect the shift towards knowledgedriven approaches to toxicological hazard & risk assessment. Important for establishing AOPs are the identification of key targets and
events for a given endpoint, the development of assessment tools
(alternative assays) and the development of extrapolation tools to
translate mechanistic data into reliable predictions of in vivo outcomes. According to Dr. Kreiling, skin sensitization strategies need
to address both, the potential and the potency for a skin sensitizer.
Integrated Testing Strategies (ITS) in form of combination(s) of (test)
methods may allow the identification and classification of skin sensitization hazard but lack to date the information on potency. Including addressing this gap in an IATA, he generally sees the need for an
OECD wide agreed guidance on the significance and application of
IATA (Integrated Approaches to Testing and Assessment) for all relevant regulatory objectives.
all
Ellen Pfrommer spoke from the ingredient supplier’s perspective
about consequences from the animal testing ban / marketing ban.
For Europe, ingredient suppliers need to address two key regulatory
areas, one is chemicals’ legislation and consequently compliance
with REACH. At the same time, support for cosmetic product manu-
facturers in their compliance with the Cosmetic Product Regulation
is requested. Therefore, two different sets of testing requirements
exist, with REACH requiring defined testing standards. Issues arising
from this situation include the status on availability of alternative
test methods, as such the questions if tests are accepted under
REACH. Also critical is in case of animal tests performed, how to
document in the PIF that they were generated for non-cosmetic
purposes, etc. Ms. Pfrommer concluded, that for break-through
innovations animal testing so far is not avoidable and serious risks
exist for ingredient manufacturers in developing long-term R&D
strategies for these. Therefore, her statement and general conclusion
was: ‘avoiding animal tests is key; however, no general rule exists
and strategies need to be developed in case-by-case decision’.
The workshop concluded with a panel discussion interacting with
a highly energetic audience. The outlook for the industry included
that the Animal Testing Ban will not vanish. The presence depicts an
interim phase where extensive input into research on still missing
alternatives is made. The future will provide alternative approaches
for all toxicological endpoints – new tools and testing approaches
will lead to a conceptual change in performing safety assessments.
While amazing progress for test alternatives has been made, and
further results are in the pipeline, existing key issues remain, as
such:
O
a lack of methods for complex toxicological endpoints
O
long time frames for validation processes
O
reluctant approach towards alternative data by authorities
O
extensive requirements on professionals while gaining
experience with the complex new methods.
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