The European Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) has published its recommendation on the performance of the 3T3 Neutral Red Uptake (NRU) in vitro test method for acute oral toxicity.The recommendation says that 3T3 NRU could be used to identify chemicals that do not require classification as toxicants, so called "negative" substances. This, EURL ECVAM says, will be useful for industrial chemicals under REACH, where information on acute oral toxicity is one of two health effects requiring animal tests at low production levels.The recommendation summarzses the overall performance of the 3T3 NRU test method, its applicability and limitations, and provides guidance for proper scientific use. It also suggests ways of tackling some remaining gaps to provide more complete characterisation of substances using the test method. For more information, please follow the link and visit the EURL ECVAM website.
Registration Deadline May 15 for Scientific Roadmap for the Future of Animal-free Systemic Toxicity Testing Workshop
Register to see a presentation and participate in discussions on a scientific roadmap for the future of animal-free systemic toxicity testing, at a workshop on May 30-31, 2013 at the U.S. Food and Drug Administration's Wiley Building in College Park, Maryland. The scientific roadmap was the product of an October 2011 workshop held under the auspices of the transatlantic think tank for toxicology (t4). The program includes an opportunity for public discussion of the roadmap, as well as its possible updating in light of more recent developments. Please visit the link above for the agenda, registration information, and a list of the organizing committee.
An appeal has overturned the European Chemicals Agency’s (ECHA) request for additional animal toxicity testing on the automotive air-conditioning refrigerant 2,3,3,3-tetrafluoropropene (HFO-1234yf). ECHA requested that Honeywell, manufacturers of HFO-1234yf, conduct extended safety studies in rabbits. Honeywell countered that such studies would not provide the agency with the information they were looking for and that safety could be confirmed by analyzing the current data. ECHA's board of appeal has rulled that the requested test would oppose the ECHA’s responsibility under the Reach (registration, evaluation, authorisation and restriction of chemicals) regulation to ensure that animal tests are only undertaken as a last resort, and that any testing involves the minimum number of animals. Read more by following the link above.
BCOP and ICE Assays Accepted for use to Identify Non-Irritating Materials in the Field of Eye Irritation
The OECD has revised the test guidelines for the Bovine Corneal Opacity and Permeability (BCOP) test and the Isolated Chicken Eye (ICE) test to extend the applicability domain of two in vitro methods. This is the first time that in vitro methods are accepted for the identification of non-irritant chemicals in the field of eye irritation. The revision of the two test guidelines was adopted at the OECD meeting of the Working Group of National Coordinators of the Test Guideline Programme held in Paris on 9 to 11 April 2013. They had originally been adopted in 2009 for the identification of serious eye damage/eye irritation of chemicals further to retrospective validation by the US Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) in collaboration with EURL ECVAM and the Japanese Center for the Validation of Alternative Methods (JaCVAM). Additional validation of the two tests showed their usefulness also for the identification of chemicals not requiring classification for serious eye damage/eye irritation (i.e. non-irritant chemicals), thus leading to the revision of the test guidelines under the co-lead of EURL ECVAM and the Netherlands. Please follow the link above to read the full story on the EURL ECVAM website.
Chemicals company BASF has teamed up with life sciences company Promega to jointly develop an alternative method to animal testing to detect allergic reactions in the skin to certain substances. Dr. Robert Landsiedel, head of the short term Toxicology unit at BASF states, "Combining the new method with two additional alternative methods to investigate skin sensitization allows us not only to significantly reduce the number of animal studies, but also to predict a possible allergic potential more reliably than before." This new method has been submitted to ECVAM (The European Center for the Validation of Alternative Methods) for evaluation.
Swedish researchers at Lund University have developed various in vitro test strategies to replace animal testing when determining skin allergens, thanks to a special special gene expression analysis software. To read the article on Cosmetics Design Europe's website, please follow the link above.
The latest PanAmerican Society for Pigment Cell Research (PASPCR) Newsletter is now available online.
Dr. Gertrude-Emilia Costin, Study Director at IIVS, serves as Editor of the PanAmerican Society for Pigment Cell Research (PASPCR) Newsletter which is published three times a year and is intended to serve as a regular means of communication for the members the Society. The April number is now available by following the link above.
PETA is presenting a new award—the Laurie and Carlee McGrath Award, which includes a $5,000 cash prize—to the MatTek Corporation for its development of sophisticated non-animal tests. The award is named in honor of Laurie McGrath and her mother, Carlee McGrath, whose San Diego–based McGrath Family Foundation supports PETA's work to replace animals in laboratories with non-animal methods. IIVS and MatTek have collaborated over many years and we congratulate MatTek for being recognized for their work in developing 3-dimensional human cell based tissue constructs that can be used in place of animals for various types of toxicity tests. Please follow the link above to read the full article.
The Alternatives Research & Development Foundation is currently soliciting research proposals for its 2013 Alternatives Research Grant Program. For nearly 20 years, this program has created opportunities for scientists who have interest and expertise in alternatives research.
Up to $40,000 in funding available to support individual projects
Preference given to U.S. universities and research institutions
Preference given to projects that use pathway-based approaches as exemplified by the 2007 National Academy of Sciences report, Toxicity Testing in the Twenty-first Century: A Vision and A Strategy
Deadline: Applications must be electronically submitted or postmarked by Tuesday, April 30, 2013
Recipients notified: Tuesday, July 16, 2013
Potential to significantly replace or reduce laboratory animals
Scientific merit and feasibility
To apply, please download the Guidelines for submission and Application cover page Applicants must notify ARDF via email of intent to submit a proposal by April, 23, 2013. Please see instructions in Grant Guidelines.
As the final animal testing ban deadline went into effect in Europe last week, Chinese regulatory bodies in their efforts to follow closely behind the West, have organized a workshop on in vitro alternative methods to further educate industry professionals on the Asia Pacific region. IIVS, along with two Chinese agencies, served as organizers for the event taking place March 19, 2013. Follow the link above to read more detail on the Cosmetics Design Asia website.
European Union regulators announced today that the ban on the import and sale of cosmetics containing ingredients tested on animals has gone into effect. This ban follows the EU ban on animal testing of finished cosmetic products that went into effect in 2004. Today's ban removes extensions to the deadline allowing continued use of animal testing for those endpoints for which a suitable in vitro alternative has not been found. Through this action, the EU has also pledged to put forth a greater effort to push other parts of the world, like China, to accept alternatives. To read more about this ban, please click on the link above.
The Drug Controller General of India (DCGI) is said to have called for the fast-tracking of the deletion of two animal-tests from the regulatory safety standards governing cosmetics.Products ranging from eye-liners and lipsticks to shampoos and face-washes will be affected by this change. Companies wanting to test cosmetic products or ingredients for specific effects will have to submit a non-animal testing proposal to the DCGI for approval. It is expected that the Indian cosmetic standard IS4011 will be amended to reflect the changes, as directed by DCGI. To read the full article, please follow the link above.
US scientists have created a tiny device that simulates a working human lung and could reduce the need for testing pharmaceutical compounds in animals. The “lung-on-a-chip” contains hollow channels lined with living human cells that mimic the interface between the air sacks in the lung and the blood vessels beneath, allowing scientists to study the body’s response to lung infections and diseases. The chip’s inventors at the Wyss Institute for Biologically Inspired Engineering at Harvard University have received an annual international prize for the device’s potential to gradually reduce the use of animals in drug testing. Please click on the link above to read more at The Engineer.
Read about the activities and planned future work of the Evidence-based Toxicology Collaboration in there newsletter (linked above). The newsletter includes information on recent publications, a satellite meeting during the SOT meeting, and a summary of their 2012 meeting titled "Evidence-based Toxicology: Opportunities and Challenges".
Content includes information on the Short Time Exposure Assay (and our upcoming webinar on the same topic), a synopsis on our recent activities in China and Brazil, details concerning the LUSH prize for training, our MOU with the EPAA, and much more.
Queen Mary, University of London, has created a professorial chair in animal replacement science. The position is funded by the Dr Hadwen Trust, a charity that funds investigation into ways of replacing animals in research. According to the trust, the chair will "see the UK spearhead a collaborative global search for more ethical, human-relevant alternatives to animal testing". The professor will be based at Queen Mary's Blizard Institute, where researchers already are already working on developing in vitro models using human cells and tissue. Read more by following the link above.
A new animal- and cell-free method has been developed to measure the toxic activity of Botulinum neurotoxin (BoNT), e.g. Botox. The invention will avoid the use of mouse LD50 tests for toxicity testing, e.g. in BoNT-containing pharmaceutical products such as Botox.The method uses functionalized liposomes to determine the toxin’s activity under physiological conditions. Read more by following the link above.
In a development that could lead to faster and more effective toxicity tests for airborne chemicals, scientists from Rice University and the Rice spinoff company Nano3D Biosciences have used magnetic levitation to grow some of the most realistic lung tissue ever produced in a laboratory. The research is part of an international trend in biomedical engineering to create laboratory techniques for growing tissues that are virtually identical to those found in people's bodies. In the new study, researchers combined four types of cells to replicate tissue from the wall of the bronchiole deep inside the lung. The research is available online and scheduled to appear in a future issue of the journal Tissue Engineering Part C: Methods. Read more by following the link above.
Via Frame -
Amendments to the Animals (Scientific Procedures) Act 1986 came into force on January 1. The amended version of ASPA has been introduced to align UK legislation with European Directive 2010/63/EU. The Home Office has produced guides for researchers to help them with the changes.The ‘quick start’ guide provides advice on what the revised ASPA covers and guidance to holders of establishment licences, project licences and personal licences and new licence applicants. It also provides guidance on severity classification, humane killing and the accommodation and care of animals. More detailed draft guidance, covering more topics, will be published later in January for consultation.
A transitional guide sets out details of changes that researchers must make immediately in order to comply with the new regulations. It also details changes that will happen automatically.The new law requires re-authorisation for some activities and some types of animal, and the transitional guide sets out details of those amendments. For example, all cephalopods (octopus, squid, cuttlefish and nautilus) are now protected. Under the old regulations only Octopus vulgaris was included. The new rules also increase control of breeding of some frog species and zebra fish. Increased use of fish in regulatory testing accounted for a significant rise in the number of animals used for toxicology (safety testing) in the last Home Office statistics on the use of animals in laboratories in the UK.
The next IVTIP meeting titled '2013: State of the art on alternatives from an industrial point of view: ready for regulation?' will be held in Southampton (UK) on May 14-16, 2013 hosted by British American Tobacco at their GR&D facility. Authors wishing to submit an abstract should send it to email@example.com (1 page, title in bold, authors with affiliations, presenting author to be underlined, 350 words maximum, Arial 10, please indicate “oral” or “poster” presentation). Deadline for submission is February 1, 2013. Please consider the meeting program on the IVTIP website (www.ivtip.org) to make sure your paper falls within the scope of this event. Authors will be informed about the acceptance of their abstracts by February 20. All accepted abstracts will be included in the IVTIP Abstract Book and distributed to all participants. Please note that all presenters will be required to register for the conference.
Exhibition spaces available
A 2010 law passed by Israel took effect January 1, 2013 banning animal testing on cosmetic products imported into the country. Much like the European Cosmetics Directive, this law governs cosmetics, toiletries and detergents and includes a ban on the marketing of cosmetics that have been tested on animals in foreign countries as well. For more information on this law, please visit the website above.
This issue contains information on the election of board of directors and a summary of the first annual meeting.
The European Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) is inviting public comments on its latest recommendation concerning the 3T3 Neutral Red Uptake cytotoxicity test method. The deadline for receipt of these comments is January 31, 2013. The assay was recently validated by EURL ECVAM for its possible use to support the identification of substances not requiring classification for acute oral toxicity. The present recommendation outlines the assay's principle, its performance characteristics (based on available information and, mainly, evidence generated during validation) and the assay's limitations and makes recommendations for its implementation within an Integrated Testing Strategy (ITS) based primarily on non-animal approaches including structure-activity relationships and biokinetic modelling. The recommendation is based on the opinion of the ECVAM EURL Scientific Advisory Committee (ESAC) which peer-reviewed the validation study (the ESAC opinion is annexed to the recommendation document). Please visit the ECVAM website for downloadable pdfs of the relevant documents and instructions on how to submit your comments.
Mathematical modelling has the potential to solve biological questions, provide new insights which benefit science and medicine, and reduce reliance on animal models. Submit a problem to the NC3Rs Maths Study Group for the opportunity to work with mathematicians in addressing your research questions.
If you are interested in participating in the Study Group please submit a proposal describing your biological problem by 14 January 2013. Proposals should be no longer than two A4 pages and should include:
A brief background to the problem
Details of the problem
Any available data for informing possible mathematical models
Questions you would like to see answered
The potential impact on animal use
Any relevant references
Proposals for problems for the Study Group to consider at the workshop should be submitted to the NC3Rs at firstname.lastname@example.org.
The U.S. Environmental Protection Agency Office of Pesticide Programs (U.S. EPA/OPP) and Health Canada’s Pest Management Regulatory Agency (PMRA) have cooperated on the development of a guidance document on the use of Quantitative Structure Activity Relationships [(Q)SAR] for pesticide risk assessors. This document has been developed under a North American Free Trade Agreement Technical Working Group (NAFTA TWG) project, 21st Century Toxicology: Integrated Approaches to Testing and Assessment.
The NAFTA TWG (Q)SAR Guidance Document provides an introduction to (Q)SAR and a flexible framework to assist with problem formulation for (Q)SAR, assessing the adequacy of predictions, and incorporating predictions into weight of evidence based assessments of pesticides. While the (Q)SAR Guidance Document was not designed to be a step-by-step manual, it provides useful guidance to evaluators who are reviewing predictions included in pesticide submissions or who are using (Q)SAR to help identify additional data requirements for pesticides, metabolites or degradates. Moreover, it also supplements, but does not replace, existing (Q)SAR guidance documents from the Organisation for Economic Cooperation and Development (OECD), the European Chemicals Bureau and other agencies.The NAFTA TWG (Q)SAR Guidance Document is currently available for download at the link above.
The Hamner Institutes for Health Sciences launched a partnership designed to advance a systems biology approach to the study of toxicity testing in pre-competitive research phases. Hamner said the partnership will develop human cell-based assays that map and model key cell signaling pathways in order to evaluate dose response, using toxicity pathway case studies with the goal of speeding implementation of recommendations from the National Research Council report “Toxicity Testing in the 21st Century: A Vision and a Strategy.” Partners sponsoring the research include Agilent Technologies, Illumina, Dow Chemical, Dow Corning, ExxonMobil, Unilever, and CropLife America, while the Long-Range Research Initiative of the American Chemistry Council supported earlier stages. Please click the link above to read the full article.
EU Health Commissioner Designate Receives Endorsements from ECEAE and HSI, and Criticism from the Personal Care Trade Association
Earlier this month prospective EU Health Commissioner Tonio Borg expressed his support for the current March 2013 deadlines on animal testing put in place by the European Cosmetics Directive. "The ECEAE agrees with Mr. Borg's comments that industry would not find alternative means of testing if the marketing ban is not implemented as 'necessity is the mother of invention", it says in a statement. Likewise, HSI's senior EU policy adviser, Emily McIvor, agreed. "Tonio Borg's stated aim of overseeing full implementation of the 11 March 2013 ban represents a huge step forward..." Read more about ECEAE and HSI backing of Tonio Borg.
In contrast, Cosmetics Europe has urged caution over Tonio Borg's comments saying it may 'jeopardize' progress and undermine EU leadership in global animal welfare. Organization president Fabio Franchina comments, "[Borg's] sweeping statements threaten to remove that impetus and undermine the EU's hard-won leadership in driving the development of alternatives to animal testing. Furthermore, it is completely incompatible with the EU's existing Innovation 2020 strategy." Read more about Cosmetic Europe's concerns with Borg's remarks.
Marking its commitment to international cooperation, the European Partnership for Alternative Approaches to Animal Testing (EPAA) Co‐chairs signed a Memorandum of Understanding with the Institute for In Vitro Sciences (IIVS) President Rodger Curren during their 8th annual meeting on November 16th. EPAA and IIVS have agreed to establish a strategic partnership dedicated to the international dissemination of alternative techniques for safety evaluation. EPAA will provide sponsorship of up to €100,000 over the next two years to IIVS to support training activities in key regions, including China and Brazil. R. Curren stated that “EPAA’s efforts to promote international cooperation on 3Rs will be greatly complemented by our joint activities and solid international network.” To read more about the MOU and the EPAA annual meeting, please click on the link above. You can also view a signed copy of the MOU between EPAA and IIVS.
“Strong international cooperation is the future of alternatives to animal testing”
‐ Memorandum of Understanding with US‐based Institute for In Vitro Sciences signed
‐ Researcher from Germany‐based Helmholtz Centre for Environmental Research awarded with the 3Rs Science Award 2012
16th November 2012, Brussels Centre de Conferences Albert Borschette: Today, the European Partnership for Alternative Approaches to Animal Testing (EPAA) organized its 8th Annual Conference in Brussels. EPAA is a unique collaboration between five EU Commission services and seven industry sectors ‐ animal health, chemicals, cosmetics, crop protection, fragrances, pharmaceuticals, soaps & detergents. Finding future alternatives to animal testing and ensuring their use in regulatory contexts will require stronger and greater international cooperation, delegates at the Annual European Partnership for Alternative Approaches to Animal Testing (EPAA) conference in Brussels heard today. Speaking at the conference, DG Enterprise and Industry’s Deputy Director General, Antti Peltomäki – speaking on behalf of European Commission Vice President Antonio Tajani ‐ stressed that while Europe has pioneered efforts in the 3Rs of replacing, reducing and refining animal testing, further progress for the sustainable development of innovative products worldwide lies in strengthened international cooperation.
DG Enterprise and Industry’s Director and EPAA Commission Co‐Chair, Gwenole Cozigou, echoed these remarks, concluding that 2012 has been a turning point for the EPAA. While EPAA remains committed to and works on promoting alternative approaches in Europe, it has to be ready for the global stage, and will also work towards developing synergies with other regions. In her keynote presentation, Dr Julia Scheel, EPAA’s Industry Co‐Chair, highlighted the relevance of international cooperation from an industry perspective, as reflected in EPAA’s 2012 lead theme. She reported on a number of promising activities developed or launched during 2012, such as reducing animal numbers in vaccines batch testing and advancing 3Rs in other dedicated areas of regulatory toxicology including carcinogenicity and skin sensitization.
Marking this commitment to international cooperation, the EPAA Co‐chairs signed a Memorandum of Understanding with the US based Institute for In Vitro Sciences (IIVS) President Rodger Curren. EPAA and IIVS have agreed to establish a strategic partnership dedicated to the international dissemination of alternative techniques for safety evaluation. EPAA will provide sponsorship of up to €100,000 over the next two years to IIVS to support training activities in key regions, including China and Brazil. R. Curren stated that “EPAA’s efforts to promote international cooperation on 3Rs will be greatly complemented by our joint activities and solid international network.”
The conference which attracted around 150 delegates, also heard from the US Food and Drug Administration, the Chinese State Food and Drug Administration, the OECD and European Chemicals Agency. Speakers highlighted both the potential benefits as well as the main challenges arising from implementing increased collaboration on the 3Rs. EPAA also honoured Dr Nils Klüver from the German‐based Helmholtz Centre for Environmental Research with the annual 3Rs Science Award for 2012, for his project “Systematic approach to investigate outliers of the fish embryo test to increase its predictive capacity and applicability domain for acute fish toxicity and beyond”. Dr Klüver will now further develop his method in collaboration with EPAA partners, thanks to a €100,000 grant.
The European Partnership for Alternative Approaches to Animal Testing (EPAA) is a joint initiative from the European Commission, European trade associations from seven industry sectors and individual companies (see partners here). It was launched in November 2005 with the purpose to promote the development and implementation of new 3Rs methods (replace, reduce, refine) in the field of safety testing. For further information on the EPAA or its projects
The Institute for In Vitro Sciences, Inc. is a non‐profit research and testing laboratory dedicated to the advancement of in vitro (non‐animal) methods worldwide. Founded in 1997, IIVS has worked with industry, academic laboratories and government agencies to implement in vitro testing strategies that limit animal use while supplying key information for product safety and efficacy decisions. For further information on IIVS and its programs
At an award ceremony being held in London today, two groups shared the £50,000 Lush Training Prize for making ‘outstanding contributions’ to training researchers in non-animal methods.
The winners were:
The Institute for In Vitro Sciences, USA – for their work on training researchers from Brazil to China
InterNICHE, co-ordinated from the UK – for their training work in former Soviet states, South America and Africa
The new annual Lush Training Prize, a joint project between the global handmade cosmetics company and Ethical Consumer magazine, is designed to bring forward the date when products and chemicals are no longer tested on animals.
The Training Prize provides a useful illustration of the extent of animal testing in emerging economies and the importance for campaigners of moving into these new regions.
Rob Harrison from the Lush Prize said:
“Lush Prize winners in 2012 have included scientists, campaigners, lobbyists, training specialists and young researchers from eight countries. All these people play a vital role in the global movement to replace animal testing with methods that are now widely accepted to be both more humane and effective.”
Every year, it is estimated that more than 100 million animals – including mice, rabbits and rats – are used in testing laboratories around the world.
Gaithersburg, MD, November 16, 2012: The Institute for In Vitro Sciences (IIVS), a non-profit laboratory, received the first annual Lush Training Prize during an award ceremony in London yesterday. The prize is a joint project between the global handmade cosmetics company and Ethical Consumer magazine. Designed to bring forward the date when products and chemicals are no longer tested on animals, the prize recognizes individuals or organizations who have excelled in establishing training programs to make scientists aware of the range of available non-animal testing methods.
“At IIVS we believe the change to non-animal testing methods will be hastened through education and training. Seeing, touching, using these methods firsthand and understanding the results will change perceptions and practices,” said Rodger Curren, President of IIVS, during the awards ceremony in London. “Our trainings change the fuzzy image of ‘alternatives’ into the reality of better science and the removal of animal pain and suffering.”
The Lush Training Prize is one of 5 categories the cosmetics company is recognizing. Others include the Science Prize, Young Researcher Prize, the Public Awareness Prize and the Lobbying Prize. Over 180 nominations were submitted and a panel of 10 independent judges picked the winners from a short-list compiled by the Lush Prize Team.
IIVS shares the award with InterNICHE, an international network focusing on animal use and alternatives within biological sciences, medical and veterinary medical education.
IIVS is a non-profit organization wholly dedicated to the promotion of rapid and innovative non-animal testing methods. Founded in 1997, IIVS is recognized as a leading provider of in vitro testing in support of toxicological safety evaluations. Rigorous scientific programs coupled with educational and outreach initiatives have established IIVS as a global leader in the advancement of alternatives to animal testing. For more information please visit www.iivs.org.
The European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) is renewing membership of its Scientific Advisory Committee (ESAC). ESAC is a key contributor to EURL ECVAM's workflow, notably through providing published ESAC opinions summarizing peer review advice on validation studies. ESAC opinions form the basis for issuing formal ECVAM Recommendations, summarizing the validity of alternative methods, their limitations and appropriate use.
EURL ECVAM is now launching an open call for applications for membership in the ESAC. Interested scientists with relevant competences are invited to apply. A Selection Committee composed of EURL ECVAM staff and external scientists will assess all applications for eligibility and will shortlist suitable candidates using defined selection criteria. The Selection Committee may also draw on the reserve lists created after the 2009 call for applications. Experts who are currently on the reserve list of the 2009 call do not need to reapply, unless their competence profile has changed considerably. All relevant details pursuant to the call can be found on ECVAM's website The deadline for applications is 30th November 2012.
IIVS staff recently returned from a training trip to China funded by a grant through PETA. Last week students and staff of the Beijing Technical and Business University attended a training session with IIVS that included education on the Bovine Corneal Opacity and Permeability Test. The students and staff were very enthusiastic to be part of the training. More information on the training session and the acceptance of non-animal test methods in China can be found in the article above.
The OECD QSAR toolbox is software that can be used to group chemicals into categories to help fill some of the gaps in the toxicity or ecotoxicity testing data needed to perform hazard assessment on chemicals. This tool could be a valuable addition to a tiered testing strategy that could also include follow-on in vitro testing. Version 3.0 of the software can be downloaded from the website link above.
The Organisation for Economic Co-operation and Development (OECD) has officially adopted two test guidelines for identification of substances with the potential to cause eye injury. One of these (OECD TG 405), an updated test guideline for the traditional rabbit eye test, incorporates specific procedures to avoid or minimize animal pain and distress when it necessary to use animals to identify substances with the potential to cause eye injuries. The other test guideline (OECD TG 460)provides a new method to identify substances that may cause serious eye injuries without using animals. Both guidelines, along with all of the current OECD test guidelines for the testing of chemicals) can be viewed on the OECD website by clicking on the link above.
Contents include: 3Rs Prize, David Sainsbury Fellowship Scheme, Project and Pilot Study grants and CRACK IT Challenges registration deadline. Please click on the link above to view the newsletter on the NC3R website.
Content includes information on the EPA's in vitro testing pilot program for ocular irritation testing on antimicrobial cleaning products (and our upcoming webinar on the same topic), a synopsis on our educational activities, information on a practical methods workshop for delegates from Russia, a dermal absorption workshop, and much more.
LUDWIGSHAFEN, Germany and GAITHERSBURG, Md., Oct. 23, 2012 /PRNewswire-USNewswire/ —
BASF SE, the world’s leading chemical company, has provided U.S. based Institute for In Vitro Sciences (IIVS) with equipment critical to replacing the use of animals for eye irritation testing of certain chemicals. IIVS will place the units at each of its newly developed training laboratories in Xi’an, Beijing, and Guangzhou, China.
With a long history in the development and use of non-animal methods, BASF engineered and produced the instrument, known as an opacitometer, to provide a reliable, state-of the art, and commercially available platform for the Bovine Corneal Opacity and Permeability (BCOP) assay. “We determined that development of this equipment was necessary to standardize the BCOP assay for our own internal use. Realizing that it could help scientists around the world implement this important non-animal method, we made it commercially available in 2010 at production cost,” says Dr. Susanne Kolle, Head of Applied Alternative Methods at BASF SE. “We are proud to support IIVS’ efforts to promote the use of non-animal methods in China by providing three opacitometer kits.”
IIVS, a non-profit, laboratory-based organization, has recently expanded its international outreach and training program. Dr. Rodger Curren, President of IIVS, comments on the importance of the donation. “The three BASF opacitometer kits allow our staff to rapidly train Chinese scientists and regulators using state-of-the art equipment. The BCOP assay provides a predictive and cost effective alternative to the use of live animals for eye irritation testing.”
BASF has been a contributor to IIVS since 2010 and the two organizations have collaborated on several projects including inter-laboratory validation studies of non-animal methods.
BASF is the world’s leading chemical company. Our portfolio ranges from chemicals, plastics, performance products and crop protection products to oil and gas. We combine economic success, social responsibility and environmental protection. Through science and innovation we enable our customers in almost all industries to meet the current and future needs of society. Our products and system solutions contribute to conserving resources, ensuring healthy food and nutrition and helping to improve the quality of life. We have summed up this contribution in our corporate purpose: We create chemistry for a sustainable future. BASF posted sales of about €73.5 billion in 2011 and had more than 111,000 employees as of the end of the year. BASF shares are traded on the stock exchanges in Frankfurt (BAS), London (BFA) and Zurich (AN). Further information on BASF is available on the Internet at www.basf.com. To find out more about BASF’s activities on alternatives to animal testing please visit www.alternatives.basf.com.
IIVS is a non-profit organization wholly dedicated to the promotion of rapid and innovative non-animal testing methods. Founded in 1997, IIVS is recognized as a leading provider of in vitro testing in support of toxicological safety evaluations. Rigorous scientific programs coupled with educational and outreach initiatives have established IIVS as a global leader in the advancement of alternatives to animal testing. For more information please visit www.iivs.org.
The U.S. Consumer Product Safety Commission (CPSC) has added a page to its website titled "Recommended Procedures Regarding the CPSC's Policy on Animal Testing." The page summarizes the CPSC policy on animal testing and their suggestions 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 and approvals regarding animal testing policy. Please contact us to discuss strategies for implementing the CPSC's recommendations within your in vitro testing program. Click on the link above to view the page on the CPSC website.
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 (Europe, Canada, Japan and the United States). The report describes the current regulatory climate in each region and it discusses a number of currently available OECD validated non-animal testing methods, such as for skin irritation testing and phototoxicity testing. It also outlines the use of tiered-testing approaches to safety assessment and the necessity of this type of testing paradigm as the focus is shifted to the use of non-animal testing methods. Click on the link above to read the report on the FDA website.
Congratulations to Dr. Horst Spielmann for receiving this year's Björn Ekwall Memorial Award. Dr. Spielmann has significantly contributed to the field of in vitro toxicology by developing non-animal tests aimed at reducing the number of animals used in experimentation such as the 3T3 phototoxicity assay and the embryonic stem cell test (EST) for determining embryotoxicity. Dr. Spielmann collaborated with Dr. Björn Ekwall over the course of several years. The Björn Ekwall Memorial Award will be awarded at the ESTIV 2012 meeting where Dr. Spielmann will deliver the Björn Ekwall Memorial Lecture titled Today Björn Ekwall would endorse the concept "Toxicology in the 21st Century".
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. Click on the link above to view the full article.
This international workshop features presentations by representatives from around the globe who will speak on validation studies performed on the HET-CAM assay and their experiences in working with a number of materials in the assay. Registration is open to the public, but limited to 40 participants. More information, including links to the web page of the International Workshop on the HET-CAM Assay can be found by following the link above.
The Lush Training Prize aims to reward individuals and organizations involved in training researchers in non-animal methods. The training prize recognizes that many scientists involved in chemicals testing are not aware of the range of non-animal methods available or trained in using them. Establishing training programs around the world makes a huge difference to the field. The prize wishes therefore to reward individuals, teams, or organizations who have excelled in this field. The three groups on the short list are:
Institute of In Vitro Sciences
The International QSAR Foundation
The winner will be announced October 15.
Forsby, Norman et al. Article on Eye Sting Editor's Highlight in the Current Issue of Toxicological Sciences
The paper chosen for the Editor's Highlight in the October 2012, Vol. 129, No. 2 issue of Toxicological Sciences is "Using Novel In Vitro NociOcular Assay Based on TRPV1 Channel Activation for Prediction of Eye Sting Potential of Baby Shampoos" by Anna Forsby, Kimberly G. Norman, Johanna EL Andaloussi-Lilja, Jessica Lundqvist, Vincent Walczak, Rodger Curren, Katharine Martin, and Neena K. Tierney.
Editor, Michael L. Cunningham notes that "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."
The National Center for the Replacement, Refinement, and Reduction of Animals in Research's (NC3Rs) latest newsletter is available on the web. The 47th issue includes information on the 3Rs prize, a call for fellowships, information on current vacancies, the CRACK IT 2012 Challenges launch, and two new CRACK IT Solutions. Please click on the link above for access to this newsletter.
From the ESTIV2012 Organizing Committee - This is a friendly reminder that the Registration Deadline (15th September) for ESTIV2012 is fast approaching. This year the congress will take place October 16-19 in Lisbon, and will be co-hosted by AP Tox. ESTIV2012 will focus on the new developments in toxicity testing and the mechanism of action of chemicals and nanomaterials with a special emphasis on the following themes:
Innate immune responses in toxicity
Reproductive & developmental testing
Computational toxicity & toxicokinetics
Additional information and program is available online
Abstracts for the EUSAAT Annual Congress 2012 are now available to download from the FRAME website. The Congress (5 - 8 September) will focus on new approaches and methodologies — for example, disease models, non-animal tools for basic biomedical research, ‘-omics’ techniques and advanced 3D models. More details can be found on the FRAME website by following the link above. There is also a link to a pdf document of all of the conference abstracts on this page. The abstracts will also appear in a future issue of FRAME's scientific journal ATLA (Alternatives to Laboratory Animals)
The European Union Reference Laboratory for Alternatives to Animal Testing (EURL-ECVAM), the Institute for Health and Consumer Protection, has published two calls for grantholder positions to support EURL-ECVAM in the assessment and validation of alternative methods:
Deadline for the applications is 7 October 2012.
Subscribers to FRAME's Alternatives to Laboratory Animals (ATLA) journal may download the contents. Non-subscribers may purchase the entire issue. In addition, there are a number of free articles for review including: Editorial: The International Transport of Laboratory Animals: No Excuse for Biased Extremism of Any Kind, The Forthcoming Launch of Perspectives in Laboratory Animal Science (PiLAS), and the announcement of the Dorothy Hegarty Award Winners.
Rodger Curren Addresses Scientists at the 244th National Meeting & Exposition of the American Chemical Society
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) yesterday 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 modelled for use in the safety assessment of other consumer products, thus supporting the 3Rs approach and avoiding new animal experimentation. To read more from speakers at the meeting, please follow the link above.
People for the Ethical Treatment of Animals (PETA) and the Physicians Committee for Responsible Medicine (PCRM) have submitted public comments on the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM)'s draft 5 year plan. They have listed specific areas in which ICCVAM is not meeting its Congressional mandate to facilitate the acceptance of nonanimal testing methods government-wide. Please follow the link above to view a synopsis of their findings.
The 17th European Congress on Alternatives to Animal Testing (LINZ2012) and the 14th Annual Congress of the European Society for Alternatives to Animal Testing (EUSAAT 2012) are being held September 5-8 at the University of Linz, Austria. Early bird registration ends on Monday, August 13th. The preliminary program is available for review online. Please follow the link above to register for the event.
The August 2012 Issue of the PanAmerican Society for Pigment Cell Research (PASPCR) Newsletter is Now Available Online
Dr. Gertrude-Emilia Costin, Study Director at IIVS, serves as editor of the PanAmerican Society for Pigment Cell Research (PASPCR) Newsletter which is published three times a year and is intended to serve as a regular means of communication for the members the Society. The August issue is now available at the link above.
U.S. National Institutes of Health Awards Grants to Fund Development of Tissue Chips to Help Predict Drug Safety
The U.S. National Institutes of Health (NIH) has awarded 17 grants aimed at creating 3-D chips with living cells and tissues that accurately model the structure and function of human organs such as the lung, liver and heart. The grants were announced in a July 24th NIH news release (available on the NIH website by clicking on the link above). Once developed, these tissue chips will be tested with compounds known to be safe or toxic in humans. Data from these tests will help identify the most reliable drug safety signals, ultimately advancing research to help predict the safety of potential drugs in a faster, more cost-effective way. The initiative marks the first interagency collaboration launched by the NIH's recently created National Center for Advancing Translational Sciences.
More than 30 percent of promising medications have failed in clinical trials because they are determined to be toxic despite promising preclinical studies in animal models. Tissue chips, which are a newer human cell-based approach, may enable scientists to predict more accurately how effective a therapeutic candidate would be in clinical studies. Tissue chips merge techniques from the computer industry with modern tissue engineering by combining miniature models of living organ tissues on a transparent microchip. Ranging in size from a quarter to a house key, the chips are lined with living cells and contain features designed to replicate the complex biological functions of specific organs.
NIH's newly funded "Tissue Chip for Drug Screening" initiative is the result of collaborations that focus the resources and ingenuity of the NIH, the Defense Advanced Research Projects Agency, and the U.S. Food and Drug Administration. NIH's Common Fund and the National Institute of Neurological Disorders and Stroke led the trans-NIH efforts to establish the program. The NIH plans to commit up to $70 million to the program over five years.
Tissue chips are an example of innovative tools and methodologies that can be used to identify whether substances are likely to be safe or toxic to humans. In its draft 2013-2017 Five-Year Plan, the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) identifies "Promoting the Application and Translation of Innovative Science and Technology" as one of its core strategies to support the development of predictive alternative test methods. Innovative testing approaches such as tissue chips have the potential to more accurately and efficiently identify substances that may present human health hazards, while reducing and ultimately replacing animal use for this purpose.
In an article on AltTox, Nicholas Ball of The Dow Chemical Company describes the connection between REACH testing requirements and the obligation to utilize animal tests only as a last resort. Without simply adopting an unnecessarily conservative assessment of hazards, registrants must make the best use of the various options to reduce the need for new animal studies, and regulatory authorities must take into consideration the animal welfare aspects when reviewing dossiers and deciding on the need for additional studies. All of this must at the same time provide sufficient comfort that the hazards of substances are being identified and addressed as necessary so that human and environmental safety are not adversely impacted. Please follow the link above to AltTox to read the article in its entirety.
An article on Scientist Live discusses the progress made toward replacing animal test methods with alternatives at a recent meeting. 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 found in cosmetics and personal care products, the methodology and tools being developed by SEURAT-1 scientists are intended for application in a variety of fields. Some of the latest results of SEURAT-1were presented at the Euroscience Open Forum (ESOF) in Dublin on 14 July. The new SEURAT-1 report on progress and related international efforts was launched on this occasion. Please follow the link above to read the entire article and learn more about what was presented in Dublin.
With China poised to accept its first ever non-animal test method for cosmetics by late summer, Dr. Brian Jones of IIVS says don't be surprised by how quickly the authorities accept and implement more. In an article in Cosmetics Design's new series "Voice of the Industry", the Director of Education and Outreach Programs discusses IIVS's role in helping to shape China's attitude to non-animal testing alternatives. Please follow the link above to view the entire article on the cosmetics design website.
The National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) is planning to convene an independent scientific peer review panel to assess the validation status of in vitro tests and integrated non-animal testing strategies proposed for identifying eye injury hazard potential of chemicals and products. The panel will be convened in collaboration with the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM).
NICEATM requests nominations of scientific experts who can be considered for the panel. NICEATM also requests data from substances tested in in vitro tests for identifying eye injury hazard potential. Of particular interest are data generated in the short time exposure (STE) and isolated rabbit eye (IRE) tests and data from approaches using two or more in vitro tests. However, NICEATM also requests data from other in vitro tests, as well as corresponding in vivo data from any ethical human or animal studies or accidental human exposures. For more information about the NICEATM-ICCVAM evaluation of the STE, IRE, and other eye safety test methods and strategies; submission of data; and nominations of scientific experts, please visit the NICEATM-ICCVAM website linked above.
Italy may soon become the European country with the most restrictive legislation on animal experimentation, if a draft law due for discussion in the Senate July 11th is approved in its current form. The Italian government says that it considers the draft “a good balance point”, but scientists fear that the restrictions would hamper biomedical research and damage the country's pharmaceutical industry. The draft being discussed in Italy contains several prohibitions that are not in the parent EU legislation, and that were not part of Italy’s regulations before the directive was adopted. It bans the breeding of primates, cats and dogs for laboratory use, and requires the government to impose “sufficiently cautious” norms for the authorized use of transgenic animals. It also bans experimentation on “anthropomorphic apes”, cats and dogs, unless the tests are mandatory for new drugs to be approved, or are aimed at “improving human health”. Finally, it prohibits all experiments without anaesthesia that cause pain to an animal. For more information, please follow the link above to the article.
Abstracts are being accepted now through July 31st for poster presentations during the first annual meeting of the American Society for Cellular and Computational Toxicology. The meeting will be held Sept. 21 at the Lister Hill Auditorium, National Library of Medicine, NIH in Bethesda, Md. and will feature a plenary lecture by Dr. Melvin Andersen, Associate Director of The Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, and ASCCT Board Member. Abstracts describing original research or policy analyses related to the development or implementation of in vitro and/or in silico toxicological testing methods are being accepted now until July 31. E-mail abstracts of 250 words or less as Microsoft Word documents using an Ariel 10 font to the ASCCT Secretary, Kristie Sullivan. Please include title, all authors (underline presenting author's name) and affiliations following the format of the sample Abstract here. Include email contact information for presenting author. A select number of abstracts will be chosen for oral presentations. Authors will be notified by Aug. 10. For more information on the society or their first annual meeting, please visit the link above
The European Union Reference Laboratory for alternatives to animal testing (EURL ECVAM) has received a Good Laboratory Practice accreditation from the Organization for Economic Co-operation and Development (OECD) for its work in developing alternative methods and approaches. Formally established last year due to the increasing need for new methods to be proposed for validation in the EU, the lab is active in testing topical, systemic and strategic toxicity activities. The OECD, an intergovernmental organization representing 29 industrialized countries in North America, Europe and the Pacific, provide GLP certification to laboratories meeting its guidelines of uniformity, consistency, reliability, reproducibility, quality, and integrity of non-clinical safety tests for chemicals from physio-chemical properties to kinetic and dynamic toxicity. Please click on the link above for more information.
The National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) in collaboration with the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) has developed a draft updated NICEATMICCVAM Five-Year Plan. This document will provide strategic direction for NICEATM and ICCVAM during 2013 to 2017. It outlines how, consistent with ICCVAM's statutory duties and purposes, NICEATM and ICCVAM will contribute to the transformation of safety testing by fostering and promoting the incorporation of scientific advances and innovative technologies into new improved test methods and integrated testing and decision strategies. As announced in the Federal Register, NICEATM and the National Institute of Environmental Health Sciences (NIEHS) request public comments on the draft 2013-2017 Five-Year Plan, which is available on the NICEATMICCVAM website at the link above. Comments are requested by August 13, 2012 and may be submitted online.
Content includes the announcement of our next webinar on skin irritation testing strategies using 3D tissue constructs, an article on the conduct of validation studies, a special workshop in Japan and much more.
Content includes the announcement of our next webinar on skin irritation testing strategies using 3D tissue constructs, an article on the conduct of validation studies, a special workshop in Japan and much more.
Registration for the First Annual Meeting of the American Society for Cellular and Computational Toxicology (ASCCT) is now open! Join your fellow ASCCT members for plenary and member lectures, poster presentations, the election of members to the board of directors, and a social cocktail event at the first annual scientific and business meeting.Abstracts describing original research or policy analyses related to the development or implementation of in vitro and/or in silico toxicological testing methods are being accepted now until July 15. Please visit the ASCCT website for details on registering for the meeting, submitting an abstract, and becoming an ASCCT member.
“Has this method been validated?” “Can you help validate our test?”
At IIVS, we are often asked these and similar questions for a variety of reasons. Sometimes clients would like to know whether a certain in vitro protocol has been validated (is it reproducible and reliable) and will it meet their testing goals. Sometimes they inquire if it is validated for regulatory use. Other times they would like assistance in validating a protocol to screen their unique product candidates. We are also frequently called upon by industry consortia and methods developers to participate in or lead a formal multi-laboratory validation of methods for potential regulatory use. What is assay validation, and what are the goals of a validation? Validation is a planned, detailed, fully documented process for the experimental and statistical evaluation of a proposed method, including the associated prediction model, within the constraints of its intended purpose. Simply put: Does the method do what it is intended to do? Please read the attached article for additional information.
Dr. Brian Jones of IIVS has written an article published at AltTox concerning the current state of cosmetic testing regulations in China. The article discusses the rapid progression of cosmetic regulations from their beginnings in 1990 to the current moves toward acceptance of alternative methods in place of animal testing. To read about the Chinese regulations and the need for sustained effort to assist them in moving towards acceptance of non-animal testing methods, please read the article above.
The Proceedings of the Eighth World Congress on Alternatives and Animal Use in the Life Sciences have now been published and can be accessed on the ALTEX website above. The organizers hope that it will serve as a lasting reminder of the excellent presentations and discussions that took place in Montréal last August. They hope that you will find the papers contained in these Proceedings to be inspiring, and that you will use them to stimulate the further implementation of the Three Rs in your own work. Finally, we look forward to building on the work presented and to meeting each of you again in Prague in 2014 for WC9.
IIVS is happy to partner with MatTek, manufacturers of 3-D reconstructed human epidermis models, to provide special discounted pricing for select OECD approved testing methods. We will be discounting $750 off the total study cost for assays conducted on groups of at least 5 test materials in the Skin Irritation Test (SIT) (OECD TG 439) or the Skin Corrosion Test (OECD TG 431). Follow the link above to read about the program in MatTek's recent newsletter. Please contact one of our study directors today to discuss how this special pricing may be applied to your projects. (MatTek terms and conditions apply.)
The DB-ALM of the European Union Reference Laboratory on Alternatives to Animal Testing (EURL ECVAM) wants to remind you, as previously announced by the European Partnership for Alternative Approaches to animal testing (EPAA), that a second survey has been launched on the use of alternative methods in the industry for the assessment of reproductive toxicity of compounds and/or formulations covering Reduction and Refinement (2Rs) methods applied for both regulatory and non-regulatory purposes. Follow the link above to the EPAA website and download the EPAA questionnaire. The deadline for responding has been extended to May 18th.
The survey has been launched in the context of the EPAA thematic review project to provide an overall picture on available alternative methods at all stages of development, validation and/or regulatory acceptance covering the 3Rs in the topic area of reproductive toxicity testing. This project was based on an extensive bibliographic review and the full content published in 2011 on the DB-ALM together with the first survey results.This second survey, in fact, follows and complements the first one that covered Replacement methods providing in this way a full picture on the use of all the 3Rs methods in industry for reproductive toxicity testing. For more information, please visit the EPAA website and the ECVAM DB-ALM website
ESTIV is welcoming the submission of abstracts for presentation as posters or oral papers during their annual meeting October16-19 in Lisbon, Portugal. Authors wishing to submit an abstract are requested to follow the abstract submission guidelines available from the ESTIV2012 website (linked above). Please consider the preliminary program to make sure your paper falls within the scope of this event. Authors will be informed about the acceptance of their abstracts to be presented as an oral or poster presentation by the 30th June 2012. All accepted abstracts will be included in the ESTIV2012 Abstract Book and distributed to all participants. Please note that presenters (poster & oral) will be required to pay registration fees. Please review the attached pdf for additional information and the preliminary program.
British American Tobacco’s (BAT) Group Research & Development (GR&D) Centre has become the newest member of the Scientific Advisory Panel of the Institute for In Vitro Sciences (IIVS). “We rely on the expertise of our panel members to help determine the direction and focus of our scientific activities,” said Dr. Rodger Curren, President of IIVS. “As companies such as BAT dedicate significant resources to the implementation and use of alternative methods, we assist them in evaluating the technology and introducing these methods to the regulatory community.” “We fully support the development and application of in vitro methods as alternatives to limit the use of in vivo studies,” said Dr. Marianna Gaca, BAT’s IIVS Scientific Advisory Panel representative. “ We hope the in vitro models we are developing will help facilitate the understanding of the biological effects of tobacco smoke and, in the future, help support the assessment of conventional and modified risk tobacco products,” she said. To read the entire press release, open the document above.
The DB-ALM of the European Union Reference Laboratory on Alternatives to Animal Testing (EURL ECVAM) wants to remind you, as previously announced by the European Partnership for Alternative Approaches to animal testing (EPAA), that a second survey has been launched on the use of alternative methods in the industry for the assessment of reproductive toxicity of compounds and/or formulations covering Reduction and Refinement (2Rs) methods applied for both regulatory and non-regulatory purposes. Please click on the pdf document above to download and answer the survey.
This questionnaire survey is part of an EPAA-initiated activity to review the state-of-the-art of development, acceptance and use of 3Rs in Reproductive Toxicity testing. A previous survey conducted in 2010 covered Replacement or non-animal in vitro methods used in industry. The present questionnaire follows and complements that survey and covers the 2Rs (Reduction and Refinement) as applicable to in vivo methods used either as stand-alone methods or as part of Integrated Testing Strategies (ITS) using a combination of in vivo and in vitro methods. It addresses the ways that the 2Rs are applied for both regulatory and non-regulatory purposes. Therefore, together with the previous questionnaire, this survey aims to provide a full picture of all the 3Rs methods used in the assessment of Reproductive Toxicity of compounds (chemicals, drugs, etc.) and/or formulations (including biologicals, i.e. proteins and vaccines).
Deadline to respond to this survey is April 13th.
The U.S. Department of Agriculture (USDA) Center for Veterinary Biologics (CVB) regularly seeks public comment on drafts of proposed guidance documents concerning all aspects of veterinary vaccines production, testing, and distribution. Draft Notice 465, which is currently available for comment, provides proposed guidance on the use of humane endpoints and methods in animal testing of biological products. The draft document includes specific guidance regarding the use of humane endpoints in biological products testing, including guidance on humane endpoints for the rabies challenge test. The draft guidance also strongly encourages the use of anesthesia for intracerebral inoculation of mice during rabies vaccine testing.
The draft guidance incorporates recommendations for refinement of rabies vaccine testing made by participants at the October 2011 NICEATM-ICCVAM workshop on alternative methods for rabies vaccine potency testing. Information about the workshop is available on the NICEATM-ICCVAM website. A summary of the workshop is posted here.
Comments on the draft proposed guidance document should be submitted by April 23, 2012, via email to email@example.com. Draft proposed CVB guidance documents and additional information about submitting comments are available on the USDA website above.
The US Department of Transportation Pipeline and Hazardous Materials Safety Administration (PHMSA) Office of Hazardous Materials Safety has updated all guidance documents and references on its webpage to reflect the currently accepted practice of using in vitro corrosion test methods wherever possible. Due in large part to efforts by PETA, PHMSA's website, letters of interpretation and all other materials on this issue have been updated to reflect recent amendments made to the United Nations Recommendations on the Transport of Dangerous Goods Model Regulation and OECD guidance documents. Previously-issued letters and positions have been replaced by the current position which promotes to the extend possible the use of in vitro skin corrosion test methods.
Shaping science and driving innovation: 2011 NC3Rs Annual Report
The NC3Rs has recently published its Annual Report for 2011. The report describes the work the NC3Rs as done within the scientific community to support the 3Rs and the Coalition Government's pledge to work to reduce the use of animals in science. To read the report please visit the link above.
Abstracts are currently being accepted for poster and oral presentations during the 2012 EUSAAT/Linz conference. Topics to be covered include:
21st century non-animal tools for basic and biomedical research (e. g. humane disease pathways, specific disease models, transgenic animals, xenotransplantation, teratoma assays to prove pluripotency of stem cells)
Implementing of the Directive 2010/63/EU on the protection of animal used for scientific purposes (incl. position of the EU Commission, of EU member states and of animal welfare organisations, examples for the implementation)
Progress in 3Rs research: EU FP6 & FP7 projects on alternatives and member state research funding. (e. g. status national and EU: Research topic overview and future funding policy)
7th amendment of EU Cosmetics Directive: Cosmetics and animal testing - an end in sight (e. g. skin regulatory acceptance, eye regualtory accaptance, sensitisation, skin models and open source)
Chemicals: REACH and animal welfare (e. g. report on use of alternatives, views of companies, animal welfare, methods, search engines)
3Rs progress in other sectors (e. g. vaccine testing, replacing mouse bioassays)
Inhalation toxicology & toxicology of nanomaterials
3R goes 3D! Implementation of 3D methods in toxicity testing
GCCP - Good cell culture practice
Ethical and & legal issues
To submit your lecture or your poster please use the ONLINE SUBMISSION FORM! The deadline for the submission of lectures is April 30th and the deadline for the submission of posters is May 31st.
The US Occupational Safety and Health Administration (OSHA) has released the final rule establishing its new Hazard Communication Standard that incorporates provisions of the Globally Harmonized System (GHS) of Classification and Labeling of Chemicals specifically in the workplace. The updated standard that includes GHS labeling, hazard categorization, and safety data sheet requirements, will be phased in over the next four years. It is due to be published in the Federal Register on 26 March. Read a summary of the news in Chemical Watch or click on the link above for information directly from the US Department of Labor website.
The draft recommendations for three Cell Transformation Assays (CTAs), the Syrian Hamster Embryo (SHE) CTA at pH 6.7, the SHE CTA at pH 7.0, and the BALB/c 3T3 CTA for in vitro carcinogenicity was developed following the ESAC (ECVAM Scientific Advisory Committee) opinion (No. 2011.01). Please follow the link above to view the recommendation in it's entirety. IIVS President, Dr. Rodger Curren, is currently serving on the ESAC and participated in the formation of the published opinion document that has lead to this recommendation.
The U.S. Environmental Protection Agency and L’oréal cosmetic company announced a research collaboration designed to determine if EPA’s chemical toxicity forecaster (ToxCast) can be used in systemic toxicity tests. EPA is using ToxCast to screen chemicals to understand their potential impact on processes in the human body that lead to adverse health effects. L’oréal is providing EPA $1.2 million in collaborative research funding plus robust safety data from a set of representative substances from the cosmetic sector, expanding the types of chemical use groups assessed by ToxCast. EPA will compare the ToxCast results to the L’oréal data to determine if the reliability and the relevance are appropriate for use in the safety assessment of chemicals in cosmetics. Please follow the link above to view the entire article.
Guiding Principles for the Implementation of Non-animal Safety Assessment Approaches for Cosmetics: Skin Sensitization
A new paper published in Regulatory Toxicology and Pharmacology elaborates on guiding principles for a non-animal safety assessment concept for skin sensitization of cosmetic ingredients. to purchase the complete article, follow the link above. Please visit the skin sensitization section of our website for information specifically on the KeratinoSens Assay for Identification of Skin Sensitizers. We also have several KeratinoSens posters and manuscripts available on our Publications page.
Characterisation of skin sensitisation potential is a key endpoint for the safety assessment of cosmetic ingredients especially when significant dermal exposure to an ingredient is expected. At present the mouse local lymph node assay (LLNA) remains the ‘gold standard’ test method for this purpose however non-animal test methods are under development that aim to replace the need for new animal test data. COLIPA (the European Cosmetics Association) funds an extensive programme of skin sensitisation research, method development and method evaluation and helped coordinate the early evaluation of the three test methods currently undergoing pre-validation. In May 2010, a COLIPA scientific meeting was held to analyse to what extent skin sensitisation safety assessments for cosmetic ingredients can be made in the absence of animal data. In order to propose guiding principles for the application and further development of non-animal safety assessment strategies it was evaluated how and when non-animal test methods, predictions based on physico-chemical properties (including in silico tools), threshold concepts and weight-of-evidence based hazard characterisation could be used to enable safety decisions. Generation and assessment of potency information from alternative tools which at present is predominantly derived from the LLNA is considered the future key research area.
The next time you use shampoo, air freshener, or moisturizing cream, consider this: How do you know it's safe? In all likelihood, whatever toxicologic screening its component ingredients were subjected to involved laboratory animals, the method of choice for decades and the industry's reigning "gold standard." Yet as Bob Dylan once put it, the times, they are a-changing. Animal-based testing is expensive and time-consuming, morally and ethically troubling, and most significantly, often a poor predictor of human toxicity. Animals aren't going anywhere just yet. But their numbers are dropping. Driven both by legislative mandate and scientific need, a new suite of in vitro and cell culture-based animal-free methods are gaining a foothold in toxicology labs. Read the full article at sciencemag.org by clicking on the link above.
SkinEthic is running two training sessions covering the use of their tissue and the validated methods they are used in. Their training sessions are build up to allow in one hand, any new users to be able to feel comfortable in the 3D screening tool approaches and possibilities,and on the other hand, already trained professionals in the field of in vitro alternatives, to be updated on current validated protocols. SkinEthic’s one-day training sessions will run on March 27 and April 24. One-on-one interaction is fostered by limiting the maximum participants to 5.These sessions will be held in Lyon, France and cost € 1000 – (lunch included) VAT excluded. Please click on the link above for the registration form. Contact us Alain Alonso with questions or to register at firstname.lastname@example.org.
Cambridge research that created liver cells from stem cells has been recognized with a national prize by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs). These cells, known as human induced pluripotent stem cells (hIPSCs), have already attracted attention for the possibilities they offer to regenerate damaged tissues and organs. But it is their potential to reduce the number of animals used for screening potential drug treatments that led to Dr. Vallier receiving the Centre’s 3Rs prize for 2011.
The prize, sponsored by GlaxoSmithKline, of a £2,000 personal award and a £18,000 research grant, is for the scientific paper published in the last three years that contributes most to the advancement of the 3Rs (Replacement, Reduction and Refinement). Dr Vallier’s winning paper was published in The Journal of Clinical Investigation in 2010. He received his prize from Professor Paul Matthews OBE of GlaxoSmithKline at the NC3Rs Annual Science Review Meeting in London on 28 February.
London – Seeking to maximise the value of computational modelling in avoiding animal testing for the European Union's Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), the People for the Ethical Treatment of Animals (PETA) Foundation has produced a free resource for potential registrants, identifying sources of information and expertise on the use of Quantitative Structure Activity Relationships (QSARs). The short brochure "QSARs and REACH: A Guide to Sources of Information and Advice" was produced in consultation with leading experts in the field and lists publicly available online resources and selected contact points for individuals and organisations that can offer support to REACH registrants and consultants on the use of QSARs.
QSARs predict chemical behaviour directly from chemical structure and simulates adverse effects in cells, tissues and lab animals, minimising the need to use animal tests to comply with regulatory requirements for human health and ecotoxicology endpoints. The REACH regulation promotes the use of alternative methods and states that animal testing should be a last resort. The use of QSAR is specifically encouraged. However, while QSARs have already been used in many registrations, it is clear from the European Chemicals Agency's (ECHA) 2011 report, "The Use of Alternatives to Testing on Animals for the REACH Regulation", that many opportunities to use them have been missed and that, in some cases, registrants have not submitted QSAR data in accordance with REACH's requirements, leading to potential failure at the REACH compliance check, additional costs, and increased animal testing.
"QSARs, used in the context of intelligent testing strategies and in combination with a chemical category approach, have the potential to replace many animal tests for REACH – but registrants must feel confident both with the use of the technology and with integrating it into weight-of-evidence arguments that ECHA will accept", says PETA policy adviser Alistair Currie. "It's clear from our discussions with companies that those less familiar with its use feel cautious about using it to replace testing. This resource answers the need to link the experts in QSAR use for REACH with the registrants who need that expertise." The list was compiled by PETA in consultation with PETA US and contacts within industry and academia, and selection and inclusion was based entirely on expert judgment – the list contains no paid advertising. The resource is currently being distributed gratis to chemical companies, consultants and other stakeholders and is available online at the link above.
The Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) recommended to Federal agencies that the murine local lymph node assay, or LLNA, may be used to categorize the potency of chemicals causing allergic contact dermatitis (ACD) in humans. Specifically, ICCVAM recommended that the LLNA may be used to categorize some substances as strong sensitizers, thus identifying those substances considered to have a significant potential for causing skin hypersensitivity resulting in ACD.
In today's Federal Register, the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) announced availability of Federal agency responses to the ICCVAM recommendations. Regulatory agencies, including FDA, EPA, CPSC, and OSHA, have indicated that they will take actions in response to the ICCVAM recommendations to encourage use of the LLNA for this purpose where appropriate.
According to the U.S. Bureau of Labor Statistics, skin diseases are the most common type of occupational illness. Many of these cases arise from repeated exposures to skin-sensitizing substances, which can lead to ACD, an immunologically mediated hypersensitivity reaction. Studies have shown that ACD has a significant adverse impact on quality of life in affected individuals.
For over 10 years, the LLNA has been accepted worldwide as a valid alternative to traditionally accepted guinea pig test methods for assessing ACD hazard potential for most testing applications. The new ICCVAM recommendation provides guidance on how to use the LLNA to categorize some chemicals and products as strong skin sensitizers. However, since only half of the known strong human skin sensitizers can be identified in this way (52% or 14 out of 27), additional testing or information will be necessary to conclude that substances are not strong skin sensitizers.
Substances with the potential to cause ACD can also be categorized with the traditional test methods using guinea pigs. However, the LLNA uses fewer animals than guinea pig test methods, requires less time to perform, provides dose-response information, and, in most cases, eliminates the potential for pain and distress in the test animal. In accordance with Animal Welfare Act regulations and the Public Health Service Policy on Humane Care and Use of Laboratory Animals, the LLNA should be routinely considered when planning animal studies that evaluate whether chemicals and products are strong sensitizers in order to minimize animal use and to avoid pain and distress.
The ICCVAM evaluation is detailed in a report entitled ICCVAM Test Method Evaluation Report: Usefulness and Limitations of the Murine Local Lymph Node Assay for Potency Categorization of Chemicals Causing Allergic Contact Dermatitis in Humans (NIH Publication No. 11-7709). In June 2011, ICCVAM forwarded recommendations to Federal agencies and made these recommendations available to the public (76 FR 18639). In accordance with the ICCVAM Authorization Act of 2000 (42 U.S.C. 285l-3), agencies have notified ICCVAM in writing of their findings, and ICCVAM is making these responses available to the public.
NICEATM and ICCVAM are also currently evaluating several in vitro and in chemico methods for their potential to further reduce and eventually replace the use of animals for ACD safety testing.
The Federal agency responses to the ICCVAM recommendations and more information about the ICCVAM evaluation of the LLNA for potency categorization can be found on the NICEATM-ICCVAM website. The ICCVAM Test Method Evaluation Report is also available. In addition, the Federal Register notice announcing the availability of Federal agency responses to the ICCVAM recommendations is available.
Allergan is pleased to announce the company has received two positive opinions regarding its fully in vitro, cell-based assay for use in the stability and potency testing of BOTOX(R) and VISTABEL(R) (Allergan's botulinum toxin type A products). he first positive opinion, from Agence Francaise de Securite Sanitaire des Produits de Sante (AFSSAPS), relates to VISTABEL(R) and paves the way for approval in 29 countries in the European Union. The second positive opinion was granted by the Irish Medicines Board (IMB) for BOTOX(R) and covers 14 European Union countries involved in the Mutual Recognition Process. The Medicines and Healthcare products Regulatory Agency (MHRA) have already approved the assay for BOTOX(R) vials sold in the UK. Once approval is finalized, the new assay will be utilized to release the product for sale in the relevant countries.
The China State Food and Drug Administration have issued a draft proposal for an alternative method to animal experiments when testing cosmetic ingredients for acute phototoxic effects on the skin.
Single Generation Reproductive Toxicology Test May Be Accepted in the EU under REACH, Saving Millions of Animals
ECHA (the European Chemical Agency) has announced that it is in favor of accepting the Extended One-Generation Reproductive Toxicity Study (EOGRTS) for reproductive toxicity. This test allows just one generation of animals to be used, with additional tests on a second generation required only if the first round raised concerns. The agency says that the streamlined test will, “under certain conditions”, provide sufficient safety information to replace the two-generation reproductive toxicity study. It says it has already received around 230 proposals from companies to carry out the new test.
The Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) recently evaluated the usefulness of a non-animal test method that can identify substances with the potential for interacting with the estrogen receptor in vitro. As announced in today's Federal Register, ICCVAM recommended to Federal agencies that this test method, the BG1Luc ER TA, can be used as a screening test to identify substances with in vitro estrogen agonist and antagonist activity.
This issue includes how to use use in vitro methods as a pre-screen for clinical testing, international educational and outreach activities in Russia, China, and Brazil and more.
This issue includes how to use in vitro methods as a pre-screen for clinical testing, international educational and outreach activities in Russia, China, and Brazil and more.
Recognizing the urgent need to drive regulatory change in those countries that still require animal testing for cosmetic and personal care products, the Institute for In Vitro Sciences, Inc (IIVS) is expanding its international outreach program. The expanded program will be designed to demonstrate to regulators and industry in these countries how alternative testing strategies for cosmetic products can be integrated into a regulatory acceptance program.
NICEATM announces availability of the report on the "International Workshop on Alternative Methods To Reduce, Refine, and Replace the Use of Animals in Vaccine Potency and Safety Testing: State of the Science and Future Directions." The report was published as a dedicated issue of the journal Procedia in Vaccinology (Volume 5, pp 1-266, 2011) and is publicly available online.
The European Coalition to End Animal Experiments (ECEAE) has issued a statement suggesting that the European Commission is likely to propose an exemption to the animal testing ban for products that contain "significant added value".
Dr. Patric Amcoff is the new Operational Manager of the European Union Reference Laboratory for Alternative Methods to Animal Testing (EURL ECVAM) as of mid-November. Before joining the European Commission, Dr. Amcoff worked for nine years at the Organization for Economic Co-operation and Development (OECD) in Paris, where he was responsible for driving the regulatory acceptance at international level of alternative testing methods and approaches for chemical and nano-safety. The mission of ECVAM is to promote the development and use of alternatives to animal testing, for use as research tools and for supporting regulatory safety assessment. ECVAM will continue to coordinate validation studies at European level and act as a focal point for exchange of information on alternative methods to animal testing in the EU. Follow the link above fore more information on Dr. Amcoff available on the ECVAM website.
ECVAM Recommendation on the Cell Transformation Assays (CTA) using Syrian Hamster Embryo Cells (SHE) and the BALB/c 3T3 Mouse Fibroblast Cell Line Open for Public Comment
ECVAM fully endorses the ESAC Opinion of these methods and has additionally provided some further suggestions concerning the CTAs.The ECVAM Recommendation is now out for public consultation until 31 December 2011. The documents that are open for public commenting are divided into two separate parts. Please note that the ESAC Opinion (Annex 1 of Part 1) and the documents in Part 2 are finalised and will not be revised or changed following this open commenting round. Please visit the IHCP Website above for instructions on submitting comments.
Dr. Gertrude-Emilia Costin, Study Director at IIVS, has been recently elected as a member of the PanAmerican Society for Pigment Cell Research (PASPCR) Council for the 2012-2014 term. More info on PASPCR Council and its activities can be found at http://paspcr.med.umn.edu/paspcr.htm.
The latest issue of PanAmerican Society for Pigment Cell Research Newsletter (PASPCR) is now available online
Dr. Gertrude-Emilia Costin, IIVS Study Director, serves as editor of the PanAmerican Society for Pigment Cell Research (PASPCR) Newsletter. The Newsletter is published three times a year and is intended to serve as a regular means of communication for the members of the Society.
The latest issue of the AltTox newsletter is now available for review online. IIVS and American Society of Cellular and Computational Toxicology (ASCCT) president Rodger Curren as well as Kate Willett, Director, Regulatory Toxicology, Risk Assessment and Alternatives for the HSUS, have been named new members of the AltTox Management Team. The newsletter also includes links to recent forum postings and upcoming events. Please click on the link above to view the full newsletter.
Proteome Sciences announces that it has developed a number of novel in vitro tests for chemical compounds and substances that induce allergies when they come into contact with the skin or the respiratory system. Testing for these allergens in products including chemicals, pharmaceuticals, cosmetics and detergents will become mandatory under EU legislation. Proteome Sciences presented data from eight assays at the Sens-it-iv Scientific Congress in Brussels, 24-25 November 2011. Sens-it-iv is a European Commission project which began in 2005 and brings together companies and academic institutions with the aim of developing in vitro alternatives to animal tests, which are currently used for the risk assessment of potential skin or lung sensitizers. As well as reducing the use of animal testing, the program is aimed at improving consumer safety and benefiting the environment.
As of 28 November 2011, Novo Nordisk will no longer use living animals to test the quality of the batches of medicine coming out of Novo Nordisk's production lines. These tests have for years been required by health authorities as part of their approval of the products. "Today's achievement is a milestone in our ongoing commitment to animal ethics in Novo Nordisk. We have been working for more than a decade, in close collaboration with regulatory authorities around the world, to eliminate obsolete tests or develop and certify new laboratory assays that can be used instead of animals to evaluate the consistent quality of our marketed products," says Executive Vice President and Chief Science Officer, Mads Krogsgaard Thomsen. Novo Nordisk has a commitment to the 3R principles to 'Reduce', 'Refine' or 'Replace' the use of animal testing within the pharmaceutical industry. Therefore, a task force was established more than ten years ago with the ambitious aim to eliminate all redundant product control tests in living animals or replace them with other test methods that would guarantee the same product safety. To read more, please click on the link above.
Click the link above for links to both free and subscription downloadable content including: Editorial: Toxicity Testing: The Need for New Maps for the Future, News & Views, and articles including "Assessing the Search for Information on Three Rs Methods, and their Subsequent Implementation: A National Survey among Scientists in The Netherlands" and "A Critical Evaluation of the 2011 ECHA Reports on Compliance with the REACH and CLP Regulations and on the Use of Alternatives to Testing on Animals for Compliance with the REACH Regulation".
The NIEHS and the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) request public comments that can be considered by the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and agencies' program offices in updating The NICEATM-ICCVAM Five-Year Plan (2008-2012) (ICCVAM, 2008). The current plan addresses: (1) Identification of areas of high priority for new and revised non-animal and alternative assays to reduce, refine (enhance animal well-being and lessen or avoid pain and distress), and replace the use of animals in testing and (2) research, development, translation, and validation of new and revised non-animal and other alternatives assays for integration of relevant and reliable methods into Federal agencies' testing programs. Please follow the link above for more information and for information on how to submit your comments.
Content includes the announcement of our next webinar on the BCOP assay, strategies for identification of skin irritants and corrosives in vitro, a special workshop in Brazil, information on our January Practical Methods for In Vitro Toxicology Workshop and much more.
Content includes the announcement of a new member to our Science Advisory Panel, a scientific article on the cytosensor microphysiometer assay, announcement of our September webinar on skin sensitization and the KeratinoSens assay, a synopsis of our recent trip to the California EPA, and more.
Content of the June 2011 newsletter includes information on a non-animal test method for skin sensitization (KeratinoSens), a summary of our recent training meetings in China, and registration for and details on the expanded program for the 2012 Practical Methods for In Vitro Toxicology Workshop.
IIVS goes paperless with its first digital, e-newsletter. Content includes an overview of our re-designed website, details on our assay designed to look at topical antioxidant materials, our participation in the ECVAM ESAC committee, and more. Please let us know what you think of the new format.
The IIVS Fall/Winter 2010 newsletter contains a wrap-up of the October In Vitro Alternatives Forum, IIVS' skin sensitization program, the Axlr8 program, the founding of the American Society for Cellular and Computational Toxicology, and more.
The IIVS Summer 2010 newsletter contains valuable information on the proposed TSCA reform, the 2010 In Vitro Alternatives Forum, a formation of a new scientific society and much more.
This newsletter contains information about: * The Mouse Embryonic Stem Cell Test: Technical Challenges and Recent Advances * 2010 In Vitro Alternatives Forum * IIVS Training Workshops * and much more!
The Institute's Fall/Winter 2009 Newsletter contains information on: * Mucosal Irritation * Upcoming Events * Draize Replacement * Considering Alternatives Meeting * ECHA Clarification * 5th IWGT Workshop * ZEBET Anniversary * SAP and contributors, and * Eye Irriation Update!
This newsletter contains information about: * Alternatives Highlights - 1st Half 2009 * FRAME Celebrates 40 Years and More * OECD Draft Guideline for Skin Irritation * Meeting report - Forinvitox: from innovation to market success * and more!
Topics covered in this Institute Update include: the importance of conducting work according to GLPs, the profile of a new IIVS contributor, information on the upcoming SOT meeting and Practical Methods Workshop, and a look at the potentially promising year ahead.
View the pdf to read about recent skin irritation events, highlights from the 2008 In Vitro Alternatives Forum meeting (Spotlight on Ingredients) and the EPAA annual meeting, current progress for eye irritation models, and more.
The summer edition of IIVS Update has been mailed. Take a look at the pdf file to see our improved layout and information on the October Spotlight on Ingredients Forum, the June BCOP Histopathology Workshop, the annual Practical Methods for In Vitro Toxicology Workshop, and much more!
The IIVS Newsletter contains information on our current outreach programs, technical notes on the phototoxicity assay and information on future Institute activities. The Institute Update is published 3 times per year.
This quarters newsletter includes information on:
* ICCVAM 5 year plan, * Moscow Seminar, * Technical Notes, * QA Initiatives, * ECEAE Workshop, * Alternatives Forum, * SAP Member Highlight, * Two New IIVS Contributors, * What’s New at Our House
Take a look at our March 2007 newsletter: * 3-D Human Skin Models – The Next Generation of Tools for the In Vitro Toxicologist * Society of Toxicology Annual Meeting, * SAP Member Highlight - Dr. Marilyn Aardema, * SkinInVitro 2007 Meeting, * Development of Genotoxicity Assays in 3D Human Skin Models, * CELEBRATING 10 YEARS!, * POM Wonderful Supports IIVS’ Mission to Develop In Vitro Methods to Replace Animal Research.
Checkout our November newsletter: The Importance of Outreach, INVITOX 2006, Remembering William Russell, CAAT 25th Anniversary, Doris Day Animal League Merges with HSUS.
- Expert Users Workshop Review of the OECD Guidelines of Percutaneous Absorption (PA) In Vitro
- 13th Congress on Alternatives to Animal Testing
- Use of An Adenosine Triphosphate (ATP) Cytotoxicity Assay in Normal Human Epidermal Keratinocytes (NHEK)to Predict Systemic Toxicity In Vitro
- Practical Methods Workshop
- and more!
Have you wondered how IIVS provides reliable, reproducible in vitro testing services? Or how IIVS fosters scientific optimization, validation and implementation of alternatives to animal testing or who sponsors these activities? Learn about our Test System Monitoring and Good Laboratory Practices programs, some of our scientific outreach program activities and our sponsors in the March 2006 Newsletter.
IIVS progress on optimization of Alternative Tests, ICCVAM Expert Panel Reviews BRD Addenda, Standards for In Vitro Tests, and more.
IIVS news on
- In vitro eye irritation testing of antimicrobial products and the EPA,
- ECVAM eye irritation expert meeting,
- ICCVAM project on severe eye irritation,
- World Congress on Alternatives & Animal Use in the Life Sciences Practical Training Workshop on In Vitro Eye Irritation Methods
- and more!
Choosing the Appropriate Solvent for Solid Materials Tested in the Bovine Corneal Opacity and Permeability (BCOP) In Vitro Assay
In compliance with OECD Test Guideline 437 for eye irritation (BCOP assay), non-surfactant solid materials are typically tested as 20% dilutions prepared in 0.9% sodium chloride solution, distilled water, or other solvent that has been demonstrated to have no adverse effects on the test system. However, the limited solubility of some chemicals adds technical challenges in finding a vehicle that would ensure the material’s availability to the excised corneas and that itself would not affect the test system. In this study, we evaluated five solvents frequently used in the BCOP assay: distilled water, mineral oil, corn oil, polyethylene glycol (PEG)-400, and methocel solution (0.5%). Based on the available classification systems, our preliminary data showed that water, methocel, mineral oil and corn oil were predicted as non-irritants, while PEG-400 was predicted as a mild irritant. To demonstrate the influence of the type of solvent on the outcome/prediction of the BCOP assay for solid materials, we tested a 20% suspension of benzoic acid (BA) prepared in these solvents. BA has a non-polar benzoic ring that would preferably dissolve in non-polar solvents and a polar acidic group with affinity for polar solvents, thus making it a good model for testing its effect on corneas when dissolved in various solvents. Previous animal tests reported moderate to severe eye irritation induced by BA. Our results demonstrated that when mixed in water, mineral oil, corn oil, or methocel, BA was predicted to be a corrosive/severe irritant, while it was predicted to be a moderate irritant when mixed in PEG-400. These results support the need for further investigation of the solvent’s influence in the BCOP assay to allow the correct prediction of the irritation potential of solid materials.
Application of the KeratinoSens Assay for Prediction of Dermal Sensitization Hazard for Botanical Cosmetic Ingredients
An essential step in the safety review of cosmetic/personal care ingredients is hazard assessment for a series of endpoints, including dermal sensitization potential. In vitro methods have been developed to identify allergic (haptenic) potential for individual chemicals based on electrophilic interaction with marker peptides or cellular target systems. These assays generally use a specific molar ratio of the test chemical to the test system. Botanical extracts are used increasingly in formulas and, as mixtures, specific molar ratios cannot be determined for these assays. Often, the botanical extract portion is a relatively small portion of the complete ingredient. To assess these mixtures, the KeratinoSens assay was selected because it operates over a wide dose range and sets cytotoxicity limits on doses used to measure marker gene expression (Emter et al, 2010 ). In the KeratinoSens assay, the induction of a luciferase gene, under the control of the antioxidant response element (ARE) derived from the human gene AKR1C2 gene, is measured. In parallel, cytotoxicity is assessed by both Neutral Red Uptake (NRU) and MTT assays. Test concentrations ranged up to 1000 μg/mL (of complete ingredient) and a test concentration was considered positive if the relative viability was ≥ 70% and the fold induction of luciferase was 1.5x relative to the solvent controls. The goal of the study was to measure the activity of 3 known sensitizers (gluteraldehyde (GA) [strong], dimethyl maleate (DM) [moderate] and cinnamic aldehyde (CA) [moderate] spiked into four different botanical ingredients (each with a different excipient solvent systems). The “spiked” botanical ingredients were used as the test article as no sensitizing botanical ingredient was available. Activity of the spiked sample was measured relative to the EC1.5 of the neat sensitizer as a function of sensitizer concentration and extract composition. Three independent trials were performed on each test material. No appreciable cytotoxicity was observed with any of the samples. The recovery of the GA spike required at least a ~3 fold increase in concentration relative to the chemical alone and botanical ingredient #3 reduced the activity below detection. The DM and CA showed activity at about the same effective concentrations as the neat chemical although the DM showed reduced activity in botanical ingredient #3 as well. These data suggest that the KeratinoSens assay has the potential to identify electrophile allergens within a botanical ingredient matrix.
The Bovine Corneal opacity and Permeability (BCOP) assay can be used for predicting mild, moderate, and severe ocular irritation through quantitative assessment of the changes in opacity and permeability of the bovine cornea. In addition, histological evaluation of the corneas can be performed to assess the depth of damage. The BCOP assay with histology was used to determine the ocular irritation potential of prototype cleaning products with antimicrobial claims according to the guidance provided by the EPA-Office of Pesticide Program (OPP). Several prototype cleaners with similar formulation were evaluated along with a reference material. The results of the BCOP assay showed noticeable differences among the products. The in vitro score, determined by changes in opacity and permeability, of the corneas treated with products ranged from ~15 to 80. These scores indicate mild, moderate, and severe irritation according to the guideline provided in the EPAOPP document. In addition, the histological evaluation of the corneas showed differences in the depth of damage between moderate and severe category products, confirming the in vitro score.
The assay distinguished ocular irritation potential among similar prototypes demonstrating its effectiveness during product development. Additionally, the results demonstrate the utility of the BCOP assay with histology as a stand-alone assay for eye irritancy evaluation in the EPAOPP program.
Screening of Cosmetics Ingredients for Phototoxic Potential Using the In Vitro 3T3 Neutral Red Uptake Phototoxicity Test
Phototoxicity is an acute toxic response after exposure to a phototoxicant and either UV radiation or visible light (UV/VIS). Phototoxicity from substances applied topically typically occurs at the site of photo-irradiation. Phototoxicity is the result of direct cellular damage caused by a non-immunological inflammatory response. Clinically, phototoxicity resembles an exaggerated sunburn (erythema, increased skin temperature, pruritis and edema). Phototoxicity reactions have been reported for both synthetic substances and those which occur naturally (e.g., botanical extracts). Although symptoms generally subside quickly, the potential for substances used in topical products to cause phototoxicity is clearly of concern for manufacturers of cosmetics, personal care and other consumer products. Historically, the potential to cause phototoxicity from substances applied topically was evaluated by utilizing various animal models. However in 1997 the 3T3 Neutral Red Uptake Phototoxicity Test (3T3 NRU PT) was validated by ECVAM’s Scientific Advisory Committee as an in vitro method for evaluating the phototoxic potential of chemicals shown to absorb in the UV/VIS range. To illustrate the utility of the 3T3 NRU PT as a useful screening tool in the safety evaluation of potential cosmetic ingredients, the results of the evaluation of 42 botanical extracts and 25 synthetic chemicals found to absorb in the UV/VIS range are reported. Most substances evaluated were found not to be phototoxic in vitro; however, 9 substances were identified as potentially/probably phototoxic in the 3T3 NRU PT and were eliminated from further consideration for use as cosmetic ingredients. Several substances found to be non-phototoxic in the 3T3 NRU PT were formulated with other ingredients in a prototype cosmetic formulation and subject to clinical testing. No manifestations of phototoxicity were observed in any of the test subjects in the prototype formulation containing any of the substances identified as non-phototoxic in vitro.
Surfactant Responses in the Bovine Corneal Opacity and Permeability Assay: Points to Consider for In Vitro Eye Irritation Testing
The Bovine Corneal Opacity and Permeability (BCOP) assay is an ex vivo test used to evaluate the ocular irritation of a broad range of chemicals. In the regulatory classification and labeling arena, BCOP can be used to identify severe and corrosive eye irritants according to the OECD Test Guideline (TG) 437. However, BCOP has historically under-predicted certain anionic surfactants, when tested according to the standard liquid protocol. TG 437 specifies that liquid surfactants may be tested as 10% aqueous dilutions for 10 minutes (although alternate dilutions and exposure times may be conducted with scientific rationale), and the relevant guidance document (GD) No. 160 suggests that solid and concentrated liquid surfactants may be diluted to 10% for testing. However, GD No. 160 further directs that surfactant-based formulations are usually tested neat, but could be diluted with justification, imparting some confusion in identifying the most appropriate test methods. Since neither the basis for selecting the appropriate surfactant test methods, nor the justification for modifications are clearly presented in TG 437 or GD No. 160, we present on the testing of sodium lauryl sulfate (SLS) in the BCOP assay, using standard and modified dilutions and exposures, to elucidate the impact of these variables on eye irritation prediction. For example, in vitro scores of 20.7, 28.4, and 28.3 were obtained when testing SLS at concentrations of 50, 20, and 10% for 10 minutes, showing that irritation responses were not fully concentrationdependent, but demonstrated optimally at intermediate doses. When tested using modified exposure times, SLS showed time-related responses, with improvements in irritation predictions at the 20 and 30 minute exposures. Histopathology was performed to assess the surfactant-induced corneal changes. Based upon these results, a framework for testing surfactants, and surfactant-based formulations is proposed.
The inter-laboratory reproducibility of the STE test for assessing eye irritation of cosmetic products
STE test is an in vitro eye irritation test using cell viability as an end point in SIRC cells following just a 5 minute treatment, and the good correspondence has been confirmed between the STE irritation categories (non irritant [NI] and irritant [I]) and GHS categories (NC and category 1 [Cat. 1]/category 2 [Cat. 2]). Generally, cytotoxicity tests using cultured cells have an advantage of being simple, a quick procedure, and a low evaluation cost. The STE test has the advantages not only easy-to-use but also evaluable the eye irritation potential of water insoluble substances by using mineral oil as test vehicle. The STE test is planned for peer review in 2013 and may be accepted as an OECD test guideline for classifying ocular irritation. In this study, the technical transferability and inter-laboratory reproducibility of the STE test were evaluated in 3 contract research laboratories as a naive laboratory.
Validation of In Vitro and Clinical Safety Assessment of Leave-On Body Lotions Using Post-Marketing Adverse Event Data
Behentrimonium chloride (BTC) is a straight-chain alkyltrimonium chloride compound commonly used as an antistatic, hair conditioning, emulsifier, or preservative agent in personal care products. Although the European Union restricted the use of alkyltrimonium chlorides and bromides as preservatives to ≤0.1%, these compounds have been safely used at ≤5% in hundreds of cosmetic products for other uses than as a preservative. In vitro, clinical, and controlled consumer usage tests in barrier-impaired individuals were conducted to determine if whole body, leave-on skin care products containing 1-5% BTC cause dermal irritation or any other skin reaction with use. BTC-containing formulations were predicted to be non-irritants by the EpiDerm®* skin irritation test and the bovine corneal opacity and permeability (BCOP)/chorioallantoic membrane vascular assay (CAMVA) ocular irritation test battery. No evidence of allergic contact dermatitis or cumulative dermal irritation was noted under the exaggerated conditions of confirmatory human occlusive patch tests. No clinically assessed or self-reported adverse reactions were noted in adults or children with atopic, eczematous, and/or xerotic skin during two-week and four-week monitored home usage studies. These results were validated by post-marketing data for five body lotions, which showed only 0.69 undesirable effects (skin irritation) reported per million shipped consumer units during 2006-2011. No serious undesirable effects were reported during in-market use of the products. Therefore, if formulated in appropriate conditions at 1-5%, BTC will not likely cause dermal irritation or delayed contact sensitization when used in a whole-body, leave-on product.
Using Novel In Vitro NociOcular Assay Based on TRPV1 Channel Activation for Prediction of Eye Sting Potential of Baby Shampoos
The transient receptor potential vanilloid type 1 (TRPV1) channel is one of the most well-characterized pain-inducing receptors. The purpose of this study was to predict human eye stinging of 19 baby bath and shampoo formulations by studying TRPV1 activity, as measured by increase in intracellular free Ca2+. The NociOcular test, a novel recombinant neuronal in vitro model with high expression of functional TRPV1 channels, was used to test formulations containing a variety of surfactants, preservatives, and fragrances. TRPV1-specific Ca2+ influx was abolished when the TRPV1 channel antagonist capsazepine was applied to the cells prior to shampoo samples. The positive control, an adult shampoo that contains cocamide monoethanolamine (CMEA), a known stinging ingredient, was the most active sample tested in the NociOcular test. The negative control, a marketed baby shampoo, was negative in the NociOcular and human tests. Seven of the formulations induced stinging in the human test, and of those six were positive in the NociOcular test. Twelve formulations were classified as nonstinging in the human test, and of those ten were negative in the NociOcular test. There was no correlation between the clinical stinging results for the baby formulations and the data generated from other in vitro eye irritation assays (cytosensor microphysiometer, neutral red uptake, EpiOcular, transepithelial permeability). Our data support that the TRPV1 channel is a principal mediator of eye-stinging sensation induced by baby bath and shampoo formulations and that the NociOcular test may be a valuable in vitro tool to predict human eye–stinging sensation.
COLIPA validation of the Reconstructed Human Skin Micronucleus Assay (RSMN): A novel micronucleus assay in a 3D human skin model
Current mammalian cell in vitro genotoxicity assays induce a high level of false positive results leading to a large number of costly and time consuming followup in vivo genotoxicity studies. As of March 2009, the 7th Amendment to the EU Cosmetics Directive prohibits the use of in vivo genotoxicity tests in safety assessments for cosmetics, greatly impacting the assessment of genotoxicity of new ingredients. To address this, the European Cosmetic Toiletry and Perfumery Association (COLIPA) initiated an international project to establish and evaluate more predictive in vitro genotoxicity assays using 3D human tissues. One focus has been on the 3D human skin micronucleus assay (RSMN) in EpiDermTM. Since skin is the first site of contact with maximum exposure to many different products including cosmetics, the RSMN assay offers the potential for a more realistic application/metabolism of test compounds for evaluating genotoxicity (1,2,3). The COLIPA RSMN project is a multi-lab initiative involving Procter & Gamble (US), LOreal (France), Henkel (Germany), and the Institute for In Vitro Sciences (IIVS, US). Intra-laboratory and inter-laboratory reproducibility have been investigated with model genotoxins mitomycin C and vinblastine sulfate as well as a variety of chemicals that require metabolic activation. In addition studies with coded chemicals are in progress. This model is a promising new in vitro method for detecting micronuclei induction in human skin. This work is funded by the European Cosmetic Industry Association COLIPA.
The Utilization of the EpiOcular™ Human Tissue Model to Assess and Compare the Irritation Potential of Multiple Surfactant Systems Used In Shampoos And Facial Cleansers
Assuring the safety of cosmetics and personal care products without testing in animals is a primary goal for Alberto-Culver Company. In addition, the Seventh Amendment to the Cosmetics Directive requires that after 2009, animal testing cannot be used to assess the eye or skin irritation potential of either cosmetic formulations or ingredients. To address these issues, we have developed an in vitro irritation assessment program to support the ocular safety evaluation of multiple surfactant systems used in shampoos and facial cleansers. This is particularly important as eye irritation is a foreseeable occurrence in the use of these cosmetics and personal care products. The program relies on the results of a topical application of formulations to the surface of a three-dimensional, human cell-derived model of the corneal epithelium (EpiOcular™, MatTek Corp., Ashland, MA, USA) and monitoring time to toxicity. 35 finished products and 15 prototype formulations with a range of multiple surfactant systems have been tested at dilutions of 2% and 10% (w/v in water). Two surfactant reference standards with well established safety profiles in commerce were tested along with these materials at same dilutions of 2% and 10%. The irritation potential of materials was then assessed by comparison to these benchmark materials. At these dilutions, we determined that the irritancy potential for most of the prototype shampoos fell in the mild to no irritation range shown as similar and less cytotoxic responses compared to the Reference materials. The effectiveness of this in vitro test system was evaluated by comparing the in vitro test results with consumer experience information.