By Elke Anklam and Maurice Whelan - 12th October 2012
Cosmetics companies are faced with a considerable challenge - how to ensure product safety when validated alternative methods that cover the spectrum of relevant adverse health effects are simply not available
Elke Anklam and Maurice Whelan
Elke Anklam and Maurice Whelan discuss whether there are effective alternative non-animal tests available and whether they can realistically replace animal testing
The testing of cosmetic ingredients on animals in the EU has been banned since March 2009. From that date the cosmetics directive also prohibits the marketing of cosmetics which have been tested on animals outside the EU, for the purpose of determining their potential to cause topical effects such as skin or eye irritation. From March 2013, this marketing ban will extend to more complex health effects, including chronic systemic toxicity, skin sensitisation and reproductive toxicity. Cosmetics companies are therefore faced with a considerable challenge – how to ensure product safety when validated alternative methods that cover the spectrum of relevant adverse health effects are simply not available.
The state of play regarding the availability of alternative methods was thoroughly reviewed by the European commission between April 2010 and May 2011. At the request of the commission’s health and consumers DG, the EU reference laboratory for alternatives to animal testing (EURL ECVAM), part of the institute for health and consumer protection of the commission’s joint research centre (JRC) coordinated an evaluation exercise aimed at gaining a broad and objective picture of the progress being made towards the development of alternative methods for toxicological assessment of complex health effects. Upwards of 40 experts were brought together following nominations from member states, the commission’s scientific committee on consumer safety, the European cosmetics association, the European federation for cosmetic ingredients and the European coalition to end animal experiments. The outcome, published on the JRC-IHCP website and in a scientific journal, formed the basis for the commission’s report to the European parliament and the council on the availability of alternatives in this area. Simply put, in most cases the scientific opinion was that full replacement of current animal tests would not be available for at least another 10 years. Only in the case of skin sensitisation was the outlook more optimistic.
Although validation and regulatory acceptance of alternative methods can be challenging, the central issue is clearly the lack of credible and comprehensive solutions based on alternative methods that address the toxicological effects of most concern. This is despite a considerable research effort where over the last two decades the EU has spent roughly €200m in direct funding to research organisations, €65m of that under the seventh framework programme. In 2011, the largest single research initiative ever undertaken in the EU was launched to specifically tackle the development of alternatives for assessing repeated dose systemic toxicity. The resulting safety evaluation ultimately replacing animal testing, phase 1 (SEURAT-1) initiative comprises a cluster of six complimentary research projects facilitated by a dedicated coordination action and is funded to the tune of €50m, equally financed by the commission and Cosmetics Europe. The JRC-IHCP is playing a substantial role in SEURAT-1 both as a research partner and in the overall scientific coordination. The expectation is that at the end of the five year programme, the collective effort of the 70 institutions involved will have delivered a number of prototype systems for predicting aspects of systemic toxicity that will be based on the integration of innovative in vitro technologies with advanced computational models. Proving key scientific concepts underpinning the research strategy of SEURAT-1 will provide the blueprint for expanding on the toxicological effects and the chemical domains that can be assessed.
The current lack of alternative methods suitable for the safety assessment of chemicals and cosmetics might seem surprising considering the array of highly sophisticated tools at the disposal of the research and development community. For example, never before have we been able to probe biology to such an extent using an in vitro setting, with cells of human origin and measurement systems that report on a myriad of processes at the molecular, cellular and tissue levels. The problem is however, that developing more methods for the ‘tool box’ is not going to be enough. What’s needed is a determined shift towards a safety assessment paradigm that relies on understanding toxicity rather than simply observing its effects. Reducing our reliance on animal testing will only be possible if we ‘think before we test’. Recently, the OECD took an important step to facilitate this transitioning towards knowledge-driven approaches by proposing a programme for the development and application of adverse outcome pathways (AOP), a conceptual and analytical tool to formally capture and report on toxicological processes. The AOP programme builds on many aspects of mode-of-action thinking developed and described by the international programme on chemical safety of the World Health Organisation, and has much in common with toxicity pathways as described in the ‘Toxicity testing in the 21st century’ report, issued by the US national research council in 2007. A well described AOP that is accompanied by evidence of its validity provides a sound scientific foundation on which to base various integrated test and assessment systems used to support regulatory decision making, including integrated testing strategies, chemical categories, read-across and weight-of-evidence approaches.
As the in-house science service of the commission, the JRC conducts an extensive research programme of its own in the area of alternatives and safety assessment. Under directive 2010/63 for the protection of animals used for scientific purposes EURL ECVAM broadened its remit to not only address the validation of alternative methods, but also to guide research, promote acceptance within the regulatory community and facilitate uptake of innovative solutions by end-users.
The research needs in the area of alternatives have never been greater and requires coupling of pan-European efforts with those of international partners. Success will ultimately depend on the effective operation of large scale networks and the guaranteed synergy and continuity between different research programmes The JRC-hosted ECVAM is ideally placed to provide an organisational hub and scientific reference point for the growing alternatives community who strive to make animal-free safety assessment a reality.
Elke Anklam is director of the institute for health and consumer protection of the commission's joint research centre
Maurice Whelan is head of the institute's system toxicology unit and of the European Union reference laboratory for alternatives to animal testing