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Priorities for Research on Alternative Methods

Since 1992, Colipa and its member companies have been committing funds and resources to a large research programme on Alternative Approaches to Animal Testing (AAT).

The cosmetics industry is determined to find replacements to animal tests as soon as it is scientifically possible. Human safety still remains the overriding consideration.
The research programme’s immediate objective is to support the development, validation and acceptance of alternative testing approaches in the light of the 7th Amendment to the Cosmetics Directive which phases in a ban on use of animals in testing.

The work of Colipa’s Steering Committee on AAT is based on collaboration between cosmetics manufacturers and other parties providing the relevant scientific expertise and/or with a legitimate interest in the outcome of research.

Each area under research is guided by a Colipa project team. Current priorities fall into four areas:

 

Eye irritation

 Colipa’s programme for development of in vitro eye irritation assays incorporates three core elements:
integrated research projects that are conducted in collaboration with academia;
continued development/optimisation of existing assays to validation
collaborative activities with external partners.

 

Research Programme

The research programme which builds on the experience of earlier validation studies and scientific workshops is focused on identification of in vitro endpoints related to the dynamics of injury and recovery that are more predictive of the in vivo human response to chemical injury. This will enable the development of prediction models for pre-validation of new or improved/optimised in vitro methods that could proceed to formal validation.

The focus of the ongoing research programme is based on the outcomes of the original research programme which was composed of three integrated research projects. These projects were:
  1. development of an in vitro model of excised corneas maintained in culture to allow observation of injury/recovery after chemical exposure;
  2. development of sequentially built bioengineered 3-D multi-layer corneal constructs consisting of epithelium, stroma and endothelium
  3. a preliminary genomics project using a pattern recognition approach to identify new endpoints for injury and repair that builds on corneal models.
With the availability of a basic 3-D, 2-layer bioengineered corneal construct composed of a 3-D barrier-forming epithelium and non-activated stromal cells in a collagen matrix from project 2, work is currently ongoing for the continued standardisation, development/optimisation of this model to enable further research. This further research and development work will be focused on definition of the prediction model and identification of the domain of applicability through evaluation of chemicals that span the range of irritancy from none to severe and which are derived from a wide range of chemical classes.

 

Development/Optimisation of Existing Methods

Colipa’s activities related to method development/optimisation of current in vitro assays is focused on Human Reconstituted Tissue (HRT) models. Several HRT models are available with some being more advanced in both development and availability than others. Two of the most advanced models currently available are the MatTek Epiocular™ and SkinEthic Human Corneal Epithelium (HCE) models. Most recently, protocol optimisation has been led by industry in collaboration with the owners/producers of the models. This work within industry using the optimised protocols to expand the data available for predictive capacity and reliability (within and between laboratory variability) is completed. Submissions have been made to ECVAM for consideration of these assays to proceed to formal validation. As such, a validation study is currently in the planning/design phase (Q4 2008).

 

External collaborations

Collaboration between industry, academia, external scientific organisations and regulators is equally important for achieving validated in vitro methods. Colipa is participating actively in the ECVAM eye irritation Task Force and is supporting post-hoc statistical analysis of current in vitro methods via the funding of an independent biostatistician.

 

Genotoxicity

 Current standard in vitro tests allow the sensitive detection of carcinogens but they lead to a high percentage of false positive results (i.e show a low specificity). The genotoxicity project team aims to improve the specificity of those in vitro genotoxicity tests and to develop new in vitro assays with higher relevance for the dermal route of exposure.

In order to achieve this, the project team genotoxicity has been analysing key causes for the differences observed between in vitro and in vivo genotoxicity testing and is carrying out experimental work to address this. The respective project aims at improving the specificity of current standard assays which will avoid unnecessary in vivo follow-up testing.

For cosmetics the most likely exposure is via the skin. Therefore the second focus area of the PT is the development of genotoxicity assays on the basis of 3-dimensional human skin equivalents. Using 3D skin equivalents should allow a more realistic hazard/risk assessment as they take into account the bioavailability of the substance in question as well as its metabolic fate. This project goes along with a research programme on skin metabolism which should give us insight in how the metabolic competency of 3D skin equivalents compares to that of human skin.

The above mentioned projects are run in collaboration with academia and ECVAM.

 

Skin sensitisation

 The Skin Tolerance project team is working to strengthen our understanding of how chemicals react with the skin and activate the body’s immune system to cause skin allergy. The goal is to develop in vitro assays capable of measuring different chemical and biological parameters that are believed to be key to the induction of skin sensitisation in vivo. Ultimately, the aim is to integrate data from these different assays to predict the potential risk that a new chemical ingredient could induce skin allergy when used in a cosmetic product.

The belief that not one but several in vitro assays will be required to replace the animal testing for the skin sensitisation endpoint stems from our understanding of the biology of chemical-induced skin allergy. Several key parameters are believed to be critical for induction of skin sensitisation and consequently Colipa’s approach has been to fund research and method development across a number of areas. These approaches range from developing computer-based models to predict epidermal bioavailability, to investigating how chemicals are converted within the skin (protein binding, skin metabolism) and characterising how chemicals activate skin immune cells (investigating Dendritic cell intracellular signalling pathways, gene and receptor expression changes). The knowledge and understanding generated by this work has been used and will continue to be used to refine existing in vitro assay systems and identify novel assay systems.

In addition following several years of collaborative method development and evaluation activities within Colipa three in vitro assays are planned to enter into a formal ECVAM pre-validation activity in Q1 2009, as follows:
  • Human Cell Line Activation Test (h-CLAT)
  • Myeloid U937 Skin Sensitisation Test (MUSST)
  • Direct Peptide Reactivity assay
Two of these approaches (hCLAT and MUSST) aim to predict Dendritic cell activation events while the third (Direct Peptide Reactivity assay) aims to model the modification of skin proteins by chemical binding. The next challenge will be to analyse how data from these three in vitro approaches (and potentially other in vitro or in silico approaches) can be integrated to inform consumer safety risk assessment decisions.

 

Further scientific information can be requested by emailing This e-mail address is being protected from spambots. You need JavaScript enabled to view it .
The following items are available:

- The Colipa Strategy for Developing and Evaluating Animal Alternatives for Skin Sensitisation Testing

- The Colipa Strategy for Developing and Pre-validating in Vitro Alternatives for Skin Sensitisation

- The Colipa Strategy for Developing and Evaluating non-animal test methods for risk assessment

 

The Colipa TF AAT Skin Tolerance is organizing its  annual multidisciplinary workshop on the 21st-22nd of June in Brussels to bring together experts to discuss the scientific progress associated with activities supported by Colipa in that field. Click here to see the Workshop agenda

Conference Themes

  • Advancements and challenges of the Colipa research strategy
  • Optimization of the roadmap through integration and cross-fertilization between the research groups and the Colipa management.
  • Elaboration of a strategy for a full replacement of animal tests for skin sensitization, including definition and understanding of the possible role of the developed technologies in an Integrated Test Strategy (ITS)

 

Systemic toxicity

 A new project is developing a scientific strategy for researching alternatives to animal testing in the area of systemic toxicity.

The project team is identifying key scientists in the field to work on the research.

Colipa is funding research in order to help achieve the progress needed by 2013 in accordance with the 7th Amendment to the Cosmetics Directive.