Cooperation Between the US EPA and Industry to Develop an In Vitro Ocular Hazard Testing Strategy
The majority of cleaning products in the US do not undergo a pre-market registration process. However, once an "anti-microbial" claim is made for the product, it is regulated by the US Environmental Protection Agency's Office of Pesticide Programs (US EPA OPP), and animal testing for hazard identification is required before the product can be sold.
Investigation of whether an in vitro approach for evaluating the safety of anti-microbial cleaning products (AMCP) could replace some of the required animal tests was suggested by OPP's Pesticide Program Dialog Committee. Both the EPA and industry recognized that many essentially identical products had been marketed safely for years - without the anti-microbial claims and without animal testing. All parties believed that eye irritation should be the first animal test replaced. They agreed that a predictive, conservative in vitro testing strategy to label for eye irritation hazard had the potential to satisfy industry's need for non-animal testing while providing necessary data for regulatory approval. Key approaches which ultimately led to the success of the program were:
- Agreement by all parties on the purpose and goals of the study
- Toxicity mechanisms were addressed whenever possible
- Data collection and analysis were done with utmost transparency
Sharing Knowledge - IIVS, a Learning Organization in the Spirit of Science
"Sharing knowledge is not about giving people something, or getting something from them. That is only valid for information sharing. Sharing knowledge occurs when people are genuinely interested in helping one another develop new capacities for action; it is about creating learning processes." These are the words of Peter Senge, Director of the Center for Organizational Learning at MIT Sloan School of Management, known for his extensive work in the field of organization learning (Senge, 1994)
More than just being a leader in in vitro testing, IIVS also recognizes the value of sharing knowledge. IIVS' scientists share their unique perspective and expertise regarding the use of in vitro methods with researchers from academia, industry and government agencies. IIVS educational programs provide for the continued communication of ideas and information to advance the understanding and application of in vitro methods. While you may be familiar with IIVS' scientists sharing their knowledge through participation in meetings or as members of various boards and committees, there are many other educational activities our staff are involved in that are less visible. At IIVS we share knowledge with our clients, collaborators and stakeholders as part of our mission to provide the scientific community with the tools needed to help advance the field. Examples of these activities can be seen below:
Over the last decade, IIVS has successfully coordinated the review of grant proposals for The Alternatives Research & Development Foundation (ARDF), an organization which funds the development of alternatives to the use of laboratory animals in research, testing and education.Working with a wide network of scientists on a yearly basis, IIVS coordinates the review and works closely with ARDF's President, Sue Leary, to create opportunities for scientists who have compelling research initiatives in the area of non-animal research. Drs. Gertrude-Emilia Costin, Kimberly Norman, and Brian Jones, also with IIVS, have been involved in the review of grants awarded by ARDF to scientists who are developing alternatives or seeking to incorporate animal welfare issues into their studies.
Dr. Rodger Curren is a board member for The International Foundation for Ethical Research (IFER), an organization also dedicated to supporting the development and implementation of scientifically valid alternatives that refine, reduce or replace the use of live animals in research, product testing, and classroom education. He and other IFER board members invest their time to ensure that the highest quality research proposals that address the 3Rs criteria are funded.
Another example is the work of Dr. Costin who, in recognition of her expertise, was invited to review grants as part of the research programs funded by the Romanian Government through the National Council for Scientific Research. This program finances joint experimental research and technological development projects, resulting in products, technologies and innovative services aimed at resolving and implementing solutions to complex socio-economic problems of national priority.
IIVS' scientists currently serve as editors or reviewers for several renowned scientific journals as part of our mission to contribute to the public availability of quality science. Dr. Curren is section editor for ATLA and Dr. Jones is a section editor for the journal Dermatitis. Dr. Costin is currently serving as Editor of the PanAmerican Society for Pigment Cell Research (PASPCR) Newsletter and is also part of the scientific board of the Romanian Journal of Rare Diseases. Our scientists are reviewers on a regular basis for ATLA, Toxicology In Vitro, Journal of Investigative Dermatology, Journal of Dermatology, and Journal of Dermatological Science. Our staff are also invited as expert reviewers for journals such as Cutaneous and Ocular Toxicology, Mutation Research, Journal of Bioengineering and Biomedical Science, and Journal of Biological Chemistry.
Scientific Societies Membership
Advancing science and disseminating knowledge is often best done as part of societies. Therefore IIVS encourages its scientists to become members and hold board positions within societies such as Society of Toxicology (SOT), Society of Quality Assurance (SQA), American Society for Cellular and Computational Toxicology (ASCCT), PanAmerican Society for Pigment Cell Research (PASPCR), American Academy of Dermatology (AAD), Society for In Vitro Biology (SIVB), Society for Investigative Dermatology (SID), Society of Cosmetic Chemists (SCC), European Society for Toxicology In Vitro (ESTIV) and the In Vitro Testing Industrial Platform (IVTIP).
As outlined above, IIVS strives to excel as a learning organization through interaction with its partners in order to advance the field of in vitro toxicology. The goal we seek is well stated by Senge, "learning organizations are those organizations where people continually expand their capacity to create the results they truly desire, where new and expansive patterns of thinking are nurtured, where collective aspiration is set free, and where people are continually learning to see the whole together." (Senge, 1990)
Senge, M. P. et al. (1994) The Fifth Discipline. Strategies and tools for building a learning organization. Fieldbook. New York: Crown Business.
Senge, P. M. (1990) The Fifth Discipline. The art and practice of the learning organization. London: Random House.
IIVS Workshop for Russian Delegates
Furthering its goal to technically assist in the adoption of non-animal tests in countries where animal testing has historically been required, IIVS hosted a four day workshop for eleven attendees from Russia. Through a combination of lectures and hands-on laboratory training, the delegates gained firsthand knowledge of how non-animal test methods can be used to assess the safety of cosmetic and personal care products.
"Scientists in Russia are interested in learning more about non-animal test methods. This course gave an extremely useful technical overview and also highlighted how the data from these methods can be incorporated into a product safety testing program." said Tatiana Puchkova, Chairman of the Board of Perfumery and Cosmetic Association of Russia which organized this training for Russian authorities and leading toxicologists. "This is the beginning of an extensive collaboration with IIVS to establish non-animal safety testing in Russia. This effort is extremely important for further harmonization and plans to enter the OECD."
Although several non-animal tests have been formally validated and accepted by the OECD, the corresponding Test Guidelines often lack sufficient detail for users to execute the new methods or interpret resulting data. The workshop is one example of many educational and training activities in IIVS' International Outreach Program focusing on bridging information gaps to make non-animal test methods more readily adoptable by scientists around the world. Generous support from The Alternatives Research & Development Foundation, The Colgate Palmolive Company, and Humane Society International enabled IIVS to provide the workshop for the Russian attendees. Additional IIVS training programs are being planned for Russia as well as the US, China and Brazil.
|IIVS staff and Russian regulators and delegates who participated in the June Workshop|
Dermal Absorption Workshop
In May of this year IIVS and the Physicians Committee for Responsible Medicine hosted a cadre of international scientific and North American regulatory experts in dermal absorption, for a workshop intended to pave the way for the adoption of an in vitro method for pesticide risk assessment. Despite the adoption of OECD Test Guideline 428 on in vitro dermal absorption techniques in 2004, pesticide regulators in North America often do not accept data generated using human skin in vitro; a technology commonly used to evaluate dermal absorption of ingredients in personal care products. Regulators cite the inconsistency of experimental protocols historically submitted for regulatory review as a major reason behind the lack of acceptance of in vitro data. There are several key elements that can vary between protocols, such as skin thickness, species, and preparation procedures, receptor fluid composition, and tape stripping or other post-exposure procedures. Any of these could contribute to differences in results between laboratories.
Steering group members from IIVS, PCRM, California EPA, and Canada PMRA planned the workshop to ensure that discussion of these and other key variables would be supported by data collected in top laboratories and agrochemical companies. The workshop participants discussed each variable and made several recommendations for "best practices" for the conduct of in vitro dermal absorption studies. The workshop also determined reporting guidelines to ensure companies provide enough detail for regulators to interpret submitted in vitro studies. While the recommendations are not binding, participants agree that studies conducted according to them will improve acceptability and comparability of data across studies and laboratories, paving the way for broad acceptance of the in vitro method. Finally, participants encouraged the conduct of a meta-analysis of existing in vitro and in vivo dermal absorption data with agrochemicals. A workshop report detailing the recommendations and reporting guidelines is in process.
News & Upcoming Events
IIVS Welcomes Two New Board Members
IIVS is pleased to announce the addition of Dr. Richard Kouri, NC State University, and Dr. John "Jack" Fowle, formerly of the EPA, to the IIVS Board of Directors. Dr. Kouri brings extensive entrepreneurial, management, and biological research background to the board. Dr. Fowle is well known in the in vitro alternatives community for his work at EPA, OECD and involvement with ICCVAM. His background in working with both regulatory and industry scientists will lend itself perfectly to his function on the board. We look forward to working with both Dr. Kouri and Dr. Fowle in the coming years.
FDA Publishes Final ICCR Report on Alternatives
The FDA has published a report following its most recent International Co-operation on Cosmetics Regulation meeting (ICCR-5), in which it outlines the applicability of animal testing alternatives in the four ICCR jurisdictions. Click Here to read the report on the FDA website.
European Society for Toxicology In Vitro International Conference
October 16 - 19, 2012, Lisbon, Portugal
ESTIV 2012 will cover a broad range of topics addressing systemic toxicity, local toxicity, and developmental toxicity with emphasis on physiologically relevant markers, marker profiles, molecular mechanisms and pathways. Rodger Curren will give a keynote presentation titled "Can non-animal methods supply the data that regulators need?"
October 29 - 30, 2012, Berlin, Germany
The BfR is co-organizing with Services & Consultation on Alternative Methods (SeCAM) an international workshop on the HET-CAM assay, co-sponsored by the BfR and the European Partnership for Alternative Approaches to Animal Testing (EPAA). The aim of this workshop is to make recommendations on the most relevant HET-CAM protocol(s) and prediction model(s) for top-down and bottom-up approaches for ocular safety assessment.
CAAT-Europe Joint Information Day: Organotypic 3D-cell culture models and engineered tissues
October 25, 2012, Konstanz, Germany
This information day will focus on the applicability of 3D systems to model human physiology and pathophysiology with particular focus on toxicological risk assessment. The systems presented will include hepatic, neuronal, lung and skin models. For more information please visit the website.
Harmonization of Techniques for Safety Evaluation of Cosmetics and Their Ingredients
December 3 - 6, 2012, Brasilia, Brazil
This course aims to consolidate knowledge of those involved in cosmetic product development and those who perform safety evaluations of ingredients and cosmetics.
Special attention will be drawn to modern test methodologies and the impact of safety
assessment of ingredients, specific cosmetic categories and stability testing. Dr. Rodger Curren will give two presentations addressing the use of in vitro methods for skin and ocular safety assessment.
International Conference of Alternatives to Animal Experimentation (ICAAE)
January 26 - 27, 2013, Fórum Romeu Correia, Almada, Portugal
This Conference will promote the discussion and sharing of information regarding the use of 3Rs policies. Replacement of animal models for suitable and ethical alternatives, such as in vitro and in silico models, and the use of alternative experimental designs will be highlighted. For further information, registration and poster submission, please visit their website.
A. Forsby, K. Norman, J.El Andaloussi-Lilja, J. Lundqvist, V. Walczak, R. Curren, K. Martin, and N.Tierney. Using Novel In Vitro NociOcular Assay Based on TRPV1 Channel Activation for Prediction of Eye Sting Potential of Baby Shampoos. Toxicological Sciences, Vol. 129, No. 2, October 2012
This article on eye sting was selected as the Editor's Choice. Editor, Michael L. Cunningham notes, "Replacing animal testing for pain induction by chemicals is a goal of animal welfare research. Forsby et al. make a significant advancement in this field by the development of the NociOccular test for baby bath and shampoo formulations. This assay is a recombinate neuronal in vitro model of activation of the Transient Receptor Potential Vanilloid type 1 channel, a well characterized pain-inducing receptor. This research opens the way for the development of future assays to predict pain induction without the use of animals."
I. Baldea, G.-E. Costin, A. Filip, R.M. Cosgarea, D.A. Norris, S.A. Birlea. Biphasic pro-melanogenic and apoptotic effects of all-trans-retinoic acid on human melanocytes - time course study. Pigment Cell Melanoma Res. 25 (5), 692 (2012).
IIVS Congratulates Prof. Dr. med Horst Spielmann on receiving the 2012 Bjorn Ekwall Memorial Award
Professor Dr. med. Horst Spielmann, has significantly contributed to the field of in vitro toxicology by developing of non-animal tests aiming reduction of animal experiments. The alternative models for toxicity testing developed by Dr. Spielmann are used world-wide, e.g. use of mouse fibroblasts for the estimation of phototoxicity and chemical toxicity, and the embryonic stem cell test (EST), which is an in vitro embryotoxicity test using two permanent mouse cell lines: 3T3 fibroblasts and embryonic stem cells.
Practical Methods for In Vitro Toxicology Workshop
January 14-17, 2013
Join us at IIVS for a three and a half day training session on in vitro toxicology. Both lecture and hands-on laboratory material will be presented.
Would you like to learn more about IIVS' technical capabilities or training opportunities? Send us an email or visit our web-site at www.iivs.org
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Help IIVS promote the acceptance of in vitro methods as replacements for animal testing
Rodger Curren Addresses Scientists at the American Chemical Society Annual Meeting
Dr. Rodger Curren, President of IIVS, stated that transparency, data sharing and active communication between scientists, industry and regulators is the best way to ensure the intelligent application of science to regulatory policy during a meeting of the American Chemical Society (ACS) in August in Philadelphia. Dr. Curren described how such an approach was key to the successful use and acceptance of new in vitro ocular models for hazard testing of anti-microbial cleaning products. He said this approach could be modeled for use in the safety assessment of other consumer products, thus supporting the 3Rs approach and avoiding new animal experimentation.
1st Latin American Congress Of Alternative Methods for Use Of Animals In Education, Research and Industry
November 25 - 29, 2012 Niteroi (RJ), Brazil
Styled after the World Congress on Alternatives and Animal Use in the LIfe Sciences, this event aims to provide a forum for groups of Latin American countries interested in alternative methods. IIVS' Dr. Rodger Curren will present "The Use of 3 Dimensional Tissue Constructs for Genotoxicity". Additional themes of the congress are ethics, teaching methods, refinement and applications in industry. IIVS is proud to be a Bronze level supporter of this event. Please visit the congress website for more information.
SEURAT -1 Report Presented at Euroscience Open Forum
The Euroscience Open Forum (ESOF) was held in Dublin on July 14th and included a presentation on the new SEURAT-1 report. This report followed progress made toward the creation and validation of non-animal testing methods and related international efforts. SEURAT-1 is the first phase of a longer term research initiative aiming at Safety Evaluation Ultimately Replacing Animal Testing. Although there is an initial focus on chemicals used in cosmetics and personal care products, the methodology and tools being developed are intended for application in a variety of fields.
CPSC Webpage on Animal Testing Policy
The U.S. Consumer Product Safety Commission (CPSC) has added a section titled "Recommended Procedures Regarding the CPSC's Policy on Animal Testing".
The page summarizes the CPSC policy on animal testing and emphasizes the CPSC's support for the use of existing information and scientifically validated alternatives to animal testing in hazard assessment. The page also lists acceptable alternative methods for acute toxicity testing, ocular irritation testing, dermal irritation testing, and skin sensitization testing, and provides links to CPSC votes or approvals with respect to animal testing policy.
CPSC is a member agency of the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), which is administered and supported by the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM).
American Society for Cellular and
First Annual Meeting a Success
The first annual meeting of ASCCT was held on September 21st at the Lister Hill Auditorium on the campus of NIH. Presentations included a Plenary Lecture titled "Computational Cellular Pathway Modeling: Combining Key In Vitro and In Silico Tools to Enhance Modern Safety Assessment" given by Melvin Andersen, of the The Hamner Institutes for Health Sciences. Additional presentations were made and posters were presented on current topics in the fields of cellular and computational toxicology. The event concluded with a business meeting and election of the board for the following year. Visit the website for more information.
Congratulations to Dr. Melvin Andersen, Associate Director of The Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, and ASCCT Board Member; who was Awarded the William and Elenore Cave Award.
For more information on both Events please visit