Brazil Proposes Amendments to the Cosmetics Bill to Strengthen the Ban of Animal Testing on New and Existing Cosmetics Ingredients
The cosmetics bill was adopted in June of this year and proposed a ban on animal tests for ingredients and finished cosmetic products when alternative testing methods are available. The amendments proposed to the bill include adding a deadline that three years after its publication no animal testing of cosmetics ingredients or the sale of cosmetics that used new animal testing will be permitted. A date for the vote on these amendments has not been determined. Please read the full article on the Chemical Watch website above for more information.
Dr. Kimberly Norman to Present on the Use of Non-Animal Methods for Eye and Skin Safety Assessments at PCPC's Science Symposium
Join IIVS Study Director Dr. Kimberly Norman October 20-21st at the Personal Care Products Council's Science Symposium and Expo in Newark, NJ. Dr. Norman will be presenting a talk on the "Current Approaches for Assessing Eye and Skin Safety of Cosmetics Using Non-Animal Methods". Additional IIVS staff will be at our booth in the Science Expo throughout the two day conference to answer any questions you may have about the effective use of in vitro test methods in your safety programs. Please plan to visit us.
The China Food and Drug Administration (CFDA) has submitted draft revisions to the regulations concerning the supervision and management of cosmetics in China. The revisions include reclassification of some materials to bring them into line with similar Western regulations. Some of these reclassifications could affect the regulation, circulation, and advertising of product classes. For additional information on the revised draft, please see the article in Cosmetic Design above.
The Russian State Duma (the lower house of the Federal Assembly of Russia) has offered to introduce a draft law banning the testing of cosmetic and perfume final formulations and ingredients on animals in the country. This new law proposal comes after Russian parliament placed harsher penalties against animal cruelty. It is hoped that by bringing the Russian perfume and cosmetics industry regulations in line with those of Europe, Russian-manufactured products would be allowed to enter the European market. Please read the article above for further information.
As of January 15th, 2016, it will be unlawful to test cosmetic ingredients and formulations on animals for endpoints for which there are validated alternative methods in place. The ban also affects the marketing of finished products that have been tested on animals after relevant alternative methods have been validated at the EU or OECD level. Please view the link above for additional information on Turkey's animal testing policies.
GAITHERSBURG, Md.- In an effort to reduce the number of animals used in the registration and testing of cosmetics in China, US non-profit laboratory, the Institute for In Vitro Sciences (IIVS), provided in-depth training for two scientists from the Zhejiang Food and Drug Administration’s Institute for Food and Drug Control (ZJFDA IFDC). The course focused on laboratory techniques using more predictive and human relevant test methods such as reconstructed human skin and eye models. The training was designed to assist the agency in adopting non-animal methods as a means to evaluate and monitor cosmetics products manufactured in the Zhejiang province.
ZJ FDA is responsible for the administration and supervision of food, drugs, medical devices and cosmetics in Zhejiang province, China. With a goal to incorporate non-animal methods into their regulatory framework, the scientists sought out training which would help them conduct the tests in their laboratory in China. Dr. Rong Kuang, Director of the Department of Biology of ZJFDA IFDC commented, “The training by IIVS will allow us to start conducting these tests in our new state-of-the-art laboratory. We are very appreciative of the assistance IIVS has given to our program.”
China’s scientific and regulatory community is starting to embrace the use of non-animal methods as is evident from a variety of scientific conferences organized in China on the topic. “We know it is essential that Chinese laboratories be able to provide non-animal testing methods before the CFDA will approve their use in regulatory submissions,” states Erin Hill, Co-Founder and President of IIVS. “The ZJFDA’s goal to be recognized as a Key Laboratory for non-animal methods presents a great opportunity and we are pleased to be able to support their notable efforts.”
The OECD has released two new guidelines for eye irritation testing using in vitro methods. OECD TG 491 covers the Short Time Exposure In Vitro Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage. The Short Time Exposure (STE) assay utilizes a rabbit corneal cell line to determine if a test substance has the potential to cause serious eye damage or if it is sufficiently mild to qualify for "no classification" labeling. The STE assay can be used in both a top-down and bottom-up tiered testing approach.
OECD TG 492 covers the use of the Reconstructed Human Cornea-like Epithelium (RhCE) Test Method for Identifying Chemicals Not Requiring Classification and Labeling for Eye Irritation or Serious Eye Damage. This covers the EpiOcular Eye Irritation Test (EIT) which uses a commercially available, 3D ocular tissue construct to determine the irritation potential of an undiluted test substance.
Please contact IIVS to see how these methods can be used in a tiered testing program for your materials. For additional information on the new OECD test guidelines and a link to a recent IIVS webinar overview of a number of in vitro assays, please follow the link above.
IIVS is honored to have been selected for inclusion on the shortlist of nominees for the 2015 LUSH Prize in the training category. The LUSH Prize for training recognizes the importance of educating the scientific and academic communities on the use of non-animal test methods. A judge's panel will meet in mid-September to determine the winner in each category and the awards will be distributed on November 20th at the LUSH Prize Conference. Please visit the LUSH Prize website for the complete shortlist and additional information on the prize and the November 20th conference and award ceremony.
Content includes a press release concerning the Antimicrobial Cleaning Products program, an introduction to our respiratory toxicology program, summaries of current workshops, webinars, and international activities, and more.
IIVS is pleased to announce that the Workshop Report for the Assessment of In Vitro COPD Models for Tobacco Regulatory Science meeting this past December is available for download on the IIVS website. Click here for a direct link to the Workshop Report. A manuscript is also in development.Questions regarding the workshop series or IIVS laboratory capabilities in respiratory toxicology can be directed to [Dr. Holger Behrsing][firstname.lastname@example.org].
Please save the date for the next in our workshop series:
# In Vitro Exposure Systems and Dosimetry Assessment Tools for Inhaled Tobacco Products # April 4-6, 2016
in Bethesda, Maryland
Integrated Approaches to Toxicity Testing Lead to New Challenges for Setting Regulatory Acceptance of Methods
In the last of the joint ChemicalWatch/PETA International Science Consortium (PISC) webinars focused on in vitro testing and REACH regulations. Karin Kilian, who is responsible for data requirements under REACH and test method regulation in the chemicals unit of the DG Environment, said that a "re-think" of the process of regulatory acceptance of chemical tests was in order and that "new processes are needed as a result of the paradigm shift in chemical testing according to an article written in Chemical Watch (linked below). Key questions that need to be addressed include:
How can information requirements be set for integrated testing approaches?
How can regulatory authorities assess submissions, based on such approaches, and what resources and expertise are needed?
Please follow the link to view the article in its entirety on the Chimical Watch website, or follow this link to view the recording of this and other webinars in the series on the PISC site.
Gaithersburg, MD – The Environmental Protection Agency has updated a policy which will result in fewer products required to be tested in the eyes of rabbits. The policy is the outcome of a multi-year project between industry, the EPA and the non-profit testing laboratory, the Institute for In Vitro Sciences (IIVS). Coordinated by The Accord Group, the project successfully identified three non-animal tests which can be used to in place of the rabbit test to determine the eye irritation potential of commonly used household cleaning products. The majority of cleaning products in the US do not undergo pre-market registration. However, those which carry anti-microbial claims are considered pesticides and animal testing is required by the EPA before they can be sold. “This policy illustrates the constructive way that industry and the regulatory community can work together to replace the use of animals in testing,” comments Dr. Rodger Curren, current CEO of IIVS and lead scientist on the project. “It took a lot of commitment and resources from industry and the EPA to turn this concept into a reality.” It is expected that these tests will provide useful information on the eye irritation of other types of products and result in even less animal testing in years to come.
Judicial Review of the European Marketing Ban on Cosmetic Products Containing Ingredients Tested on Animals Underway
"A European Court of Justice (ECJ) judicial review to interpret the marketing ban on cosmetic products, containing ingredients tested on animals under the EU cosmetics Regulation, is progressing, as relevant parties have submitted their statements on the case.
The European Federation for Cosmetic Ingredients (EFfCI) brought the case before the High Court in London, UK, in 2013, asking it to clarify whether the cosmetics industry is legally allowed to use in vivo data, generated for purposes that do not fall under the EU cosmetics Regulation. After the last hearing before the High Court, on 24 November, the case was referred to the ECJ (CW 16 December 2014).
The British Union for the Abolition of Vivisection (Buav) and the European Coalition to End Animal Experiments (ECEAE) have been accepted as case interveners."
Please visit the ChemicalWatch website above for the full article.
Experts from several EU regulatory bodies, member states, NGOs, and industry attended the European Partnership for Alternative Approaches to Animal Testing (EPAA) and Cosmetics Europe joint meeting on new skin sensitization testing strategies hosted by ECHA. The focus of the workshop was on the integration of the skin sensitization test methods recently receiving OECD test guidelines and how the information from these methods can be used in an integrated testing approach. Six case studies were presented during the workshop and the approaches were discussed. According to ChemicanWatch, David Basketter of DABMEB consultancy indicated that some of the strategies "could evolve towards a single decision tree". Follow the link above to view the complete article on the ChemicalWatch website.
The Alternatives Research & Development Foundation, a U.S. leader in the funding and promotion of alternatives to the use of laboratory animals in research, testing, and education, is currently soliciting research proposals for its 2015 Alternatives Research Grant Program. For over 20 years, this innovative 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 Thursday, April 30, 2015
Recipients notified: Wednesday, July 15, 2015
Potential to significantly replace or reduce laboratory animals
Scientific merit and feasibility
To apply, please visit the ARDF site above
People for the Ethical Treatment of Animals (PETA) India, have presented the Mahatma Gandhi-Doerenkamp Centre (MGDC), based in Tiruchirappalli, Tamil Nadu with a Humane Science Award for Alternatives to Use of Animals in Life Science Education. The award recognises the MGDC for its work in supporting humane legislation and reducing and eliminating animal testing through educational efforts. The MGDC has sponsored over 60 workshops at institutions across India over the past 5 years, educating teachers at the high school through university levels on modern digital dissection simulations. The MGDC has also paired with PETA to work with the University Grants Commission and Medical Council of India to promote changes to course curricula that would save many additional animals.
The human call line activation test (h-CLAT) has undergone validation by the European Commission's Joint Research Center (JRC) EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM). ECVAM is recommending the use of this method as part of an integrated testing strategy, which could also include data from other non-animal methods and in silico predictions. It is hoped that this position will strengthen discussions at the OECD aimed toward producing a test guideline on the h-CLAT method. Please read the information on the JRC website by following the link above.
As reported on the Cosmetics Europe website (link above), the Personal Care trade association is looking to further develop Alternatives to Animal Testing (AAT) by setting up a Research Consortium aimed at looking at different approaches and encouraging the industry to get involved. The consortium will focus on the areas of skin sensitization, eye irritation, genotoxicity, systemic toxicity and skin absorption and metabolism. Please visit the Cosmetics Europe website for further details.
According to press release by Cruelty-Free International, the Korean bill to end testing of cosmetics and their ingredients on animals will be formally proposed in March. Members of the animal welfare community are happy that the bill is being proposed this month and includes an implementation deadline of 2017. For further information, please visit the press release on the Cruelty Free International website by following the link above.
The Johns Hopkins Center for Alternatives to Animal Testing (CAAT) is soliciting projects that focus on the implementation of the NAS Report: Toxicity Testing in the 21st Century: A Vision and a Strategy in the following areas:
• Proposals Relating to Toxicology: Maximum grant amount is $25,000 per year. Projects should be developed to provide mechanistic understanding of computational systems biology approaches, focused on in vitroresponses to toxicants in human cells. Consideration should be given to the translation of this new method to evaluate/predict health outcomes.
• Proposal Relating to Refinement: See Science-Based Animal Welfare Awards – funded separately.
To apply for a CAAT grant, complete the preproposal form linked to above and be sure that the submission reaches the CAAT offices no later than March 27, 2015. The form may be returned via mail, fax, or e-mail.
• Mailing address: CAAT Grants Coordinator, 615 N. Wolfe St. W7032, Baltimore, MD 21205
• Fax number: 410-614-2871
• E-mail address: email@example.com
No other materials are required for this stage of the application process. ONLY ABSTRACTS USING THE APPROPRIATE FORMAT WILL BE REVIEWED. See the Preproposal Form for details and to submit. Applicants whose proposals meet the goals of the CAAT Grants Program will be invited to submit a complete grant application package. All responses will be forwarded by e-mail or U.S. mail. No telephone responses will be given.
Comments Requested on EPA Draft - Process for Establishing & Implementing Alternative Approaches to Traditional In Vivo Acute Toxicity Studies
The EPA is asking for comments on a new guidance to reduce the use of animals and increase relevant acute toxicity data on pesticides. The draft guidance, Process for Establishing & Implementing Alternative Approaches to Traditional In Vivo Acute Toxicity Studies, describes a transparent, stepwise process for evaluating and implementing alternative methods of testing for acute oral, dermal, and inhalation toxicity, along with skin and eye irritation and skin sensitization. In addition, there is a discussion of the three major phases of the process, and the implications for reporting information under section 6(a)(2) of the Federal Insecticide, Fungicide, and Rodenticide Act. Successfully putting this process into place will require an open dialogue with stakeholders, other regulatory organizations, and the scientific community.
Please submit any comments on the draft guidance by March 10, 2015 to Christopher Schlosser by email at firstname.lastname@example.org or regular mail at Christopher Schlosser, U.S.E.P.A, 1200 Pennsylvania Avenue, NW, MC 7509P, Washington, DC 20460.
This draft guidance is one step in the application of the Office of Pesticide Programs’ strategic vision for implementing the 2007 National Research Council report on Toxicity Testing in the 21st Century.
Content includes an announcement about a new management structure at IIVS, an article about the release of OECD test guidelines for two skin sensitization assays, summaries of recent training in China and here in the US, an overview of our December Inhalation toxicology workshop and more.
The European Partnership for Alternative Approaches to Animal Testing (EPAA), a collaboration between the European Commission and 35 major companies in the chemical, pharmaceutical, cosmetics, soap and detergent, crop protection, animal health, and fragrance sectors has been approved to continue until the year 2020. The EPAA was established in 2005 in an effort to harmonize efforts towards promoting the 3Rs (refinement, reduction, and replacement) in safety assessment. The EPAA signed an MOU with IIVS to allow for greater collaboration on international training efforts. We look forward to continuing our work with the EPAA to promote global acceptance of the 3Rs. To read the full article, please follow the link above to the Chemical Watch website.
The QSAR Application Toolbox was developed under the aegis of OECD to facilitate the use of the category approach and QSAR methods to fill data gaps in classification and labeling. Use of the Toolbox will save resources, reduce the need for animal testing, and greatly accelerate the hazard assessment process.
The Toolbox provides the ability to:
Make estimates of the relevant endpoints for single chemicals, linked to the CAS number or the chemical structure. Obtain summary information on the validation processes and results of the model so that the user can decide for which regulatory purpose the estimate can be used.
Obtain a list of analogues for a chemical, together with their experimental, or estimated environmental, toxic or health effects.
Obtain estimates for metabolite activation/detoxification information for the chemical.
Interface with IUCLID 5 with ability for automated submission of estimated values for registration purposes
Features of QSAR Toolbox 3.3:
Updated versions of six databases including REACH registration data from the REACH dissemination website;
IUCLID 5.5 compatibility;
Updated auto oxidation and rat liver metabolism simulators;
Updated versions of 12 profilers for grouping chemicals;
Enhanced user interface and other minor functionality improvements.
WHO SHOULD TAKE THIS OFFICIAL TRAINING?
QSAR Toolbox training is offered at two levels: Basic and Advanced. The Basic Training Course, which requires some knowledge of chemical structure, provides an overview of the Toolbox databases, modeling system, and use of QSAR methods for managing data and modeling, plus a hands-on introduction to filling data gaps for hazard assessment. The Advanced Training Course, for which the Basic Training Course is a prerequisite, is intended to provide the capability to make advanced hazard assessments for a wide variety of chemicals, along with documentation of the process in a form suitable for submission to regulatory agencies. Practicum training is offered for those who have completed the Basic and Advanced Training courses and wish to have additional practical work in applying the acquired skills to specific chemicals.
The Training Courses are designed for those charged with developing safety assessments for chemical manufacturers and distributors as well as for those charged with evaluating submitted assessments for new chemicals or those already in use in commerce. Those interested in or conducting research on QSAR tools and database development would also find the training useful.
FEES AND REQUIREMENTS
Course registration fee for each course is €1815 (includes 21% VAT) for industry trainees and €1210 (includes 21% VAT) for government and university trainees. Registration fee for Practicum is €907.50 (includes 21% VAT) for industry trainees and €605 (includes 21% VAT) for government and university trainees. This includes installation of the OECD Toolbox on each trainee’s laptop computer, all course materials, lunches, coffee breaks, and a Course Certificate. Language of the course is English. Trainees must provide their own laptop computers. Please visit the website above to register.
Congratulations to IVTIP on their newly revised website. The new site contains news items, and agenda of upcoming events, information on IVTIP member companies and publications. There is also a special "members only" area accessible to companies and individuals who have registered as IVTIP members. News items will be determined by IVTIP member companies. Check back often in the coming weeks as new features continue to go live.
Replacing Animals for Skin Sensitization Testing Gains Momentum as OECD Publishes Test Guidelines for Non-Animal Based Methods
GAITHERSBURG, MD - Determination of skin sensitization potential is a critical toxicological endpoint in the safety assessment of new chemicals. Although the Guinea Pig Maximization Test (GPMT) and in vivo Local Lymph Node assay (LLNA) have traditionally been used to assess skin sensitization, recent activity has focused on the development of novel non-animal assays for the endpoint. As a culmination of these efforts, the Organization for Economic Cooperation and Development (OECD) published the following test guidelines for non-animal skin sensitization testing on 5 February 2015: ARE-Nrf2 Luciferase Test Method (also referred to as the KeratinoSensTM Assay) (OECD TG 442D) and Direct Peptide Reactivity Assay (DPRA) (OECD TG 442C). The Institute for In Vitro Sciences (IIVS), a participating laboratory in the validation studies for the KeratinoSensTM assay, is pleased to offer each of these non-animal assays for detecting skin sensitizers.
The KeratinoSensTM assay is a cell-based reporter gene assay which identifies skin sensitizers by measuring the induction of luciferase under the control of the antioxidant response element (ARE) derived from the human AKR1C2 gene. In the proposed Adverse Outcome Pathway (AOP) leading to skin sensitization, this method addresses the second key event, gene expression in keratinocytes associated with the antioxidant/electrophile response element (ARE)-dependent pathway. The IIVS laboratory participated in the validation studies led by Givaudan to assess the KeratinoSensTM assay which demonstrated that the assay was transferable, reproducible, and predictive as compared to the historical animal data. Following extensive review of the data by EURL ECVAM, the assay was endorsed by ECVAM, and the OECD followed with a test guideline. Based on our experiences with the assay, IIVS has developed a GLP protocol for broader use, and since 2011 has offered the assay as a commercial service.
The DPRA is an in chemico assay that identifies dermal sensitizers based on their reactivity with synthetic peptides containing either lysine or cysteine. The assay models the first key event, protein reactivity, in the skin sensitization AOP. Through collaboration with the method developers at Procter & Gamble, IIVS scientists received training, successfully transferred the technology in-house, and are offering the assay as a commercial service. IIVS is currently exploring the use of the DPRA method in combination with the KeratinoSensTM assay to improve predictions.
Given the complex cascade of events leading to skin sensitization, it is generally thought that an integrated testing approach combining multiple assays and in silico predictive tools will be needed to fully replace the animal based methods. There is a significant effort underway to ascertain how the non-animal assays may be combined to both qualitatively and quantitatively assess skin sensitization most effectively. IIVS toxicologist Dr. Kimberly Norman served as a member of the OECD Expert Panel on skin sensitization, and IIVS offers both OECD approved methods for non-animal skin sensitization testing, as part of our GLP-compliant laboratory testing services. Please contact us for information on these skin sensitization assays and how they may be used as part of an integrated testing strategy within your existing testing program.
The Carcinogenicity Genotoxicity eXperience (CGX) dataset, previously hosted on the Lhasa Limited Site, is now available from the JRC/ EURL ECVAM website. The CGX dataset is a collection of publicly available data that can be used for a variety of scientific purposes including structural-based evaluation of chemical genotoxicity and the development of alternative approaches to animal testing such as Structure-Activity Relationships (SAR). This dataset, as well as the EURL ECVAM Genotoxicity and Carcinogenicity Consolidated Database of Ames Positive Chemicals are both available in the same location on the ECVAM website. Follow the link above for more information.
The Organization for Economic Cooperation and Development released their new test guidelines for skin sensitization testing using the KeratinoSens (OECD TG 442D) and Direct Peptide Reactivity Assay (DPRA) (OECD TG 442C) test methods. The KeratinoSens test method focuses on the second key event on the Adverse Outcome Pathway (AOP) leading to skin sensitization, the inflammatory response and gene expression in keratinocytes associated with the antioxidant/electrophile response element (ARE)-dependent pathways. The DPRA assay is in in chemico assay that addresses protein reactivity (a molecular initiating event leading to skin sensitization) by quantifying the reactivity of test chemicals towards synthetic peptides containing either lysine or cysteine. IIVS is pleased to have participated in the inter-laboratory study on KeratinoSens that was submitted to ECVAM and offers both the KeratinoSens and DPRA assays as part of our GLP-compliant laboratory testing services. Please contact us for information on the in vitro assays available for skin sensitization testing at IIVS.
The International Foundation for Ethical Research supports the development, validation, and implementation of innovative scientific methodologies that advance science and replace the use of animals in research, testing, and education. To that end, the foundation is accepting applications for the IFER Graduate Fellowship Program from graduate students whose program of study shows the greatest potential to replace the use of animals in science. Grants of up $15,000 will be awarded to students enrolled in master’s and doctoral programs in the sciences or human/veterinary medicine to support the development of alternatives to the use of animals in research, testing, and education. Fellowships are renewable annually for up to three years. Continued funding is dependent on student progress and the availability of funds. Fellowships will be considered for graduate students in fields such as education, psychology, humanities, journalism, and the law for projects that show promise to increase public awareness or promote changes in the legal system or public policy regarding the use of animals in research, testing, and education. See the IFER website (linked above) for program guidelines, information about previous grant recipients, and application guidelines.
The December newsletter of the European Network for Alternative Testing Strategies in Ecotoxicology (EUROECOTOX) focuses on a report from the SETAC Global Animal Alternatives Advisory Group (AAAG) of the organization. The report, linked above, discusses proposed updates of the fish early life stage test (OECD TG210), summarizes discussions from an Adverse Outcome Pathway (AOP) workshop titled "Advancing AOPs for Integrated Toxicology and Regulatory Applications", and updates from the NC3Rs center.
Korea's Ministry of Agriculture, Food, and Rural Affairs (MAFRA) plan to phase out the use of animal testing on finished cosmetic products and ingredients still needs final approval prior to implementation. The draft ban will be reviewed by the MFDA, the Ministry of Education and the Ministry of Science, ICT & Future Planning prior to finalization. There are also questions about the impact of the ban since no timeline has been proposed for implementation of the ingredients testing ban, among other things. For more information, please visit the full article (linked to above) on the Cosmetics Design website.
Slides Available from the PISC/Chemical Watch Webinar Series on the Use of Alternative Methods for REACH
Chemical Watch and the PETA International Science Consortium, Ltd. (PISC) co-sponsored a free series of REACH focused webinars. The webinars presented alternative methods and testing strategies that can be used to meet REACH requirements. IIVS Study Directors Dr. Emilia Costin and Dr. Kimberly Norman served as presenters on two of the topics in the series. Slides and recordings of these webinars have been made available on the PISC website and can be accessed via the link above.
EURL ECVAM Releases its Strategy for the Use of Alternative Methods for Acute Systemic Toxicity Testing
The European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) of the European Commission's Joint Research Center recently released a strategy on how to replace, reduce and refine the use of animals for acute mammalian systemic toxicity testing. Based on an assessment of regulatory needs across sectors and the scientific state-of-the art in the area, the strategy sets out strategic aims and associated objectives that are expected to deliver a significant 3Rs impact. In addition to gaining a better understanding of the mechanisms by which a substance can cause an acute systemically toxic effect, EURL ECVAM also recommends exploring methods by which the requirement for systemic toxicity testing could be waived for a substance. For additional information on EURL ECVAM's recommendation and a link to the pdf download of the recommendation, please follow the link above.
As part of a five year plan for animal welfare, the Korean Ministry of Agriculture, Food, and Rural Affairs has announced that a decision has been made to ban animal testing on finished cosmetic products in Korea. Korea has become the second country in Asia to implement such a ban, and they plan to consider banning the testing of ingredients to bring their legislation in line with that of the European Union. Please follow the link above to read more information about the Korean animal testing ban.
Two years ago, PETA logged a compliant with the EU stating that ECHA was not doing its duty to minimize animal testing under REACH, a chemical safety testing regulation. This week the European Ombudsman announced that after investigation, the claims made by PETA are true and that ECHA is not doing enough to minimize the use of animals in safety testing. In a 2011 report, 135 skin-irritation studies were conducted using animals even after a validated non-animal method was made available. ECHA has had talks with the ombudsman and has agreed to use its power to require the use of non-animal methods where validated alternatives are available. Please read the article above for additional information.
The Lush Prize is an initiative which uses resources to bring forward the day when safety testing takes place without the use of animals. The Lush Prize focuses pressure on toxicity testing for consumer products and ingredients in a way which complements the many projects already addressing the use of animals in medical testing. The prizes themselves consist of a £250,000 annual fund that is split between recipients in several categories. IIVS was honored to receive a joint award in the training category for 2012 and was among the groups short listed for the training prize in 2013 and again this year. Please follow the link above to view a list of all of the prize recipients from this year's awards, presented to the winners in a ceremony in London.
GAITHERSBURG, MD, BRUSSELS, BE - The European Partnership for Alternative Approaches to Animal Testing (EPAA) has partnered with US based Institute for In Vitro Sciences (IIVS) to produce a series of training videos on non-animal testing methods for the safety evaluation of products and ingredients. The first video in the series focuses on the Bovine Corneal Opacity and Permeability assay - a replacement for the Draize eye irritation test that utilizes live rabbits.
“Videos can be an effective and efficient means to provide training to an international audience. Filmed entirely in our laboratory using our highly proficient biologists, the 13 minute video provides an accurate demonstration of the Bovine Corneal Opacity and Permeability assay for eye irritation,” states Erin Hill, Vice President and Co-founder of IIVS. “We are grateful that EPAA has funded this project which will help scientists throughout the world to adopt replacements for animal testing.”
The series will focus on non-animal methods which have Test Guidelines developed by the international harmonizing body, the Organization for Economic Co-operation and Development (OECD).
The next video to be produced will highlight the 3T3 Phototoxicity Assay. Dr. Tzutzuy Ramirez, EPAA’s 2014 industry co-chair and Gwenole Cozigou, EPAA Commission co-chair commented, “One of EPAA’s primary goals is to pool knowledge and resources to facilitate the acceptance of alternative approaches to animal testing. Working with IIVS on this project is an a good example of combining resources to achieve a common goal at an international level.”
The first completed video, with English subtitles, is freely available on the EPAA website. Subtitled versions in Chinese and Portuguese will be available by the end of the year.
Media Contact: Erin Hill - email@example.com
Chemical Watch and the PETA International Science Consortium, Ltd. (PISC) are co-sponsoring a free series of REACH focused webinars. The webinars will present alternative methods and testing strategies that can be used to meet REACH requirements. They are intended for industry toxicologists, individuals who may be registering chemicals for the first time, and companies that would like to know more about the validated non-animal tests available and how they are currently used. Dr. Emilia Costin, Toxicologist at IIVS, will present on skin irritation and corrosion on November 11 at 11:00am EST. She will describe the in vitro methods that can be used to meet REACH data requirements for skin irritation and corrosion under Annexes VII and VIII. Dr. Costanza Rovide, of REACH Mastery and CAAT Europe, will explain how the in vitro methods can be used in an integrated approach to testing and assessment using specific examples. Dr, Kimberly Norman, also a Toxicologist at IIVS, will present in the webinar on December 4th covering topics of concern for eye irritation. Please follow the link above to the EURL-ECVAM website where the entire webinar series is discussed in more detail.
With funding provided by the EPAA, IIVS scientists have produced a 13 minute video that demonstrates how to perform the BCOP assay according to the Test Guidelines set forth for the assay by the Organization for Economic Co-operation and Development (OECD TG 437). The video focuses on steps that are critical to the success of the assay such as handling of the isolated cornea and removal of the test material from the cornea at the conclusion of the exposure time, and is now available for viewing on the EPAA website. Please follow the link above for direct access to the video.
Information re-published from the AltTox Digest newsletter -
If you rarely venture closer to AltTox.org than the AltTox Digest, we invite you to explore the "new" web site, relaunched on August 25 with a new design and organization. We've made the site easier to navigate, easier to read, and easier to use and share the hundreds of articles on toxicity testing endpoints, emerging technologies, and regulatory developments.
The “Toxicity Testing Resource Center” (TTRC) has been renamed and reorganized for user convenience; visit the “Methods, Approaches, Programs and Policies” (MAPP) section to see what we mean.
"The Way Forward" series of invited commentaries is now called "New Perspectives."
"In the Spotlight" will continue to feature brief reports on recent meetings, and technical and policy developments.
The “Meetings & Events” page remains one of the most comprehensive calendars of in vitro and in silico-specific conferences, workshops, and webinars on the Internet.
The highly informative “Resource Center” (previously called “Informational Resources”) was also updated.
The “AltTox Forum” will be moving soon to the “Community Blog.” When it does, we'll post details on where to access the AltTox Forum archives.
We've introduced a new feature, "Journal Watch," to highlight recently published articles on innovative, non-animal approaches to regulatory toxicity testing.
Visit the new AltTox website today to take a look at their exciting changes
India has put a new rule into effect that not only bans cosmetic testing on animals within the country, but bans importing cosmetic products that have been tested on animals after the November 13th effective date of this new rule. No new animal testing can be used on products manufactured in or imported into India, but testing performed prior to the effective date of this rule can continue to be used. They are the first south Asian country to have a ban like this in effect and brings their practices in line with those of the European Union and Israel. To read the full article, please follow the link above.
Predicting Eye Sting Using the Novel NociOcular Assay: Investigation Surfactant, Sunscreen, and Ophthalmic Product
The evaluation of ocular irritation potential is of primary importance for the safety assessment of products that are designed to be used in or around the eyes such as cosmetics, sunscreens, and ophthalmic products. In addition, testing for erythema, lacrimation, and the potential to cause stinging is often conducted on baby products such as shampoo and sunscreen to ensure the absense of irritation and pain associated with their use. Although several in vitro eye irritation assays are available, none of these assays can effectively predict the stinging potential of products which may come in contact with the eyes. In collaboration with Dr. Anna Forsby at Stockholm University and Johnson & Johnson Consumer and Personal Products Worldwide, IIVS has investigated the use of the NociOcular assay for eye sting prediction. Our initial investigation, which was focused on eye sting of baby bath products, demonstrated that the NociOcular assay may be used to distinguish stinging from non-stinging baby bath products, and supports that the NociOcular assay may serve as a simple bioassay to assess sensory response in the eye. An in vitro assay for eye sting prediction may be very beneficial as a pre-clinical screening tool. Also, since in vitro testing can be more readily conducted than clinical studies, it may be used as a tool to advance the understanding of the relative contributions to ocular sting of various ingredients within personal care products. With support from collaborators, IIVS has successfully transferred this technology and is now routinely performing the NociOcular assay. Our goal is to promote broader use of the assay so that we may further understand its applications and limitations.
The latest news from IIVS including the NociOcular assay, the creation of a BCOP training video, participation summaries from several industry events, and working links to pdfs of several recently presented posters.
The European Partnership for Alternative Approaches to Animal Testing (EPAA)'s May 2014 newsletter is available online. There is a great deal of information written in this newsletter concerning this year's activities in alternatives, including details on specific internationally focused interactions with IIVS on pages 9 and 10. Please follow the link above to view the complete newsletter.
The U.S. Environmental Protection Agency (EPA) has released the first beta version of the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore in vitro high-throughput data generated by the ToxCast and Tox21 projects. The video tutorial for using the iCSS Dashboard is available by following the link above. Information about the iCSS Dashboard is available on the EPA website. The iCSS Dashboard is best used with the Google Chrome or Mozilla Firefox web browsers. These resources are still under development, and EPA welcomes feedback on both the iCSS Dashboard and the training video.
The National Center for Advancing Translational Sciences (NCATS) is accepting submissions through November 14 for the 2014 Tox21 Data Challenge. The goal of the Challenge is to "crowdsource" analysis of Tox21 data by independent researchers to reveal how well they can predict compound interference in biochemical pathways using only chemical structure data. The computational models produced from the Challenge could become decision-making tools for government agencies in determining which environmental chemicals and drugs are of the greatest potential concern to human health. Information about the Challenge and a link to data downloads are available by following the link above. Challenge winners will be recognized on the NCATS website and via social media, and have an opportunity to submit a paper for publication in a special thematic issue of “Frontiers in Environmental Science.”
In support of European Union legislation on safety of chemicals, the European Commission Joint Research Centre (JRC) has published a state-of-the art review of test methods and computational approaches that help promote the replacement, reduction, and refinement of animal experiments in the safety assessment of chemicals. The report "Alternative Methods for Regulatory Toxicology – A State-of-the-Art Review" focuses on "non-standard" methods, i.e. those that are not included in current regulatory guidelines. The review was prepared by JRC's European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) in collaboration with the European Chemicals Agency (ECHA). A link to the review can be found above.
The Organisation for Economic Co-operation and Development (OECD) has launched the AOP Wiki, a resource for developing and sharing adverse outcome pathways (AOPs). The AOP Wiki is the first module of the OECD Adverse Outcome Pathways Knowledge Base, which will provide a focal point for AOP development and dissemination. Information about the AOP Wiki and a User Handbook is available on the OECD website by following the link above.
An overview of the AOP Wiki was presented at a workshop on “Adverse Outcome Pathways: From Research to Regulation” on September 3-5, which was organized by NICEATM and the Physicians Committee for Responsible Medicine. Materials from the workshop, including links to the plenary session videocasts and summaries of the breakout group discussions, are available on the NTP website.
Also on the NTP website is a link to the Adverse Outcome Pathways Community listserv, an email list managed by NICEATM to provide information about events and activities of interest to AOP developers and users. You may also subscribe to the list on the NIH website.
The deadline to submit your abstracts for the 3rd annual meeting of the American Society for Cellular and Computational Toxicology has been extended to October 10th. Email your abstracts to Kristie Sullivan, ASCCT Secretary at KSullivan@ascctox.org. They should be submitted in the following format:
Title in bold
Authors with affiliations, presenting author underlined
Presenting author's email address
350 words maximum, Arial 10 typeface
For meeting registration and to view a draft agenda, please follow the link above.
Cosmetics Design has made their SkinCare Ingredients 2014 webinar available on-demand on their website. During this webinar, Dr. Rodger Curren presents information on how IIVS is providing training to Chinese laboratories on in vitro methods with OECD Test Guidelines. He also speaks about the Memorandum of Understanding signed between IIVS and China's National Institute for Food and Drug Control (NIFDC), a subordinate agency of the China Food and Drug Administration (CFDA) and interactions with regulatory agencies in China in general. Follow the link above to register on the Cosmetics Design website and view Dr. Curren's presentation, along with a presentation by April Guo, Head of Cosmetics Regulatory Affairs at the Chemical Inspection and Regulation Service (CIRS).
Where Chemistry and Biology Meet: AOPs as a Framework for Advancing Toxicology
November 12, 2014 (8:30 am – 6:00 pm) Lister Hill Auditorium, NIH Campus, Bethesda, MD
Plenary Lecturer: Dr. Robert Kavlock, Environmental Protection Agency
To view the draft agenda, submit a poster abstract or register for the meeting, please visit the ASCCT Website of follow the link above. Questions? Please contact Erin Hill, Treasurer or Kristie Sullivan, Secretary
IIVS Study Director Dr. Emilia Costin will Present at the US/Global Biocides (Antimicrobials) Regulation Conference
This two day conference, September 25 & 26, will bring together experts from the USA and Europe to discuss latest developments in the regulation of Biocides (Antimicrobials)
The first day of the course covers new developments in the USA, including:
● New Data Requirements for Antimicrobials (implementation of 158W)
● Efficacy Testing for Public Health Products
● Testing - the Rise of Alternative Approaches
● Food contact and antimicrobials
Dr. Costin's presentation is titled "A New, Non-animal Based, Hazard Identification Strategy For Ocular Irritation of Antimicrobial Cleaning Products" and will cover:
- Original EPA hazard identification testing which required the rabbit eye test
- Description of how EPA hazard categories are determined and used
- Discussion of how many antimicrobial cleaning products have been safely marketed for years without the antimicrobial claim
- Background on how EPA has jurisdiction on cleaning products with an antimicrobial claim
The second day of the conference will expand the discussion globally and will end with a workshop covering the challenges of working in a global market. Attendees are welcomed from industry, regulatory agencies, consultants. Please follow the link above for additional details and registration information.
ARDF is pleased to announce that its 2014 Alternatives Research Grant Program has made its selections. ARDF has awarded $200,000 to scientists developing alternative methods in a variety of areas of medical research, testing and education. IIVS would like to congratulate this years' winners. Download the attached pdf to view the projects that the ARDF Alternatives Research Grant is funding this year.
The European Society of Toxicology In Vitro (ESTIV) in collaboration with The Portuguese Toxicology Association (AP Tox) is organizing a course titled "Applied in Vitro Toxicology" that will take place in Lisbon, Portugal during January 25-29 2015. This five day course is intended for post-docs wishing to begin in the field of in vitro toxicology, or for members of industry, academia, or regulatory agencies who have recently begun working in the field. Registration is now open. Please visit the website above for additional information.
Content includes a press release on the signing of an MOU with China FDA, recent training provided in Vietnam and China, lectures in Japan and Taiwan, the announcement of a new Principal Scientist at IIVS, and more.
The National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) and the Physicians Committee for Responsible Medicine (PCRM) will cosponsor a scientific workshop on “Adverse Outcome Pathways: From Research to Regulation.” The workshop proposes to explore and discuss how interaction and collaboration among stakeholders can be initiated and maintained so that scientific progress in adverse outcome pathway (AOP) concepts may improve regulatory assessment of chemical toxicity. The Society of Toxicology endorses this workshop.
The meeting will take place from September 3–5, 2014 at the William H. Natcher Conference Center, National Institutes of Health, Bethesda, Maryland, USA. This workshop is free as is the concurrent plenary presentations webcast. Registration for the workshop or webcast along with other information and a preliminary agenda are available by following the link above.
GAITHERSBURG, MARYLAND – The Institute for In Vitro Sciences (IIVS) last week signed a Memorandum of Understanding with the National Institute for Food and Drug Control (NIFDC), a subordinate agency of the China Food and Drug Administration (CFDA). The two organizations will work collaboratively on a number of projects focused on cosmetic safety testing designed to promote in vitro (non-animal) techniques in China.
In November 2013, IIVS held a week long training workshop at the NIFDC laboratory in Beijing to teach in vitro techniques for cosmetic safety testing to Chinese regulators including those from provincial agencies. Under the new memorandum, the NIFDC will coordinate with IIVS to hold an annual training workshop titled “Techniques for In Vitro Assays for Cosmetics Testing”. Additionally the NIFDC agrees to participate in validation projects of new models or techniques developed within China.
The MOU was signed by Dr. Wang Youchun, Deputy Director-General of NIFDC and Erin Hill, Co-founder and Vice President of IIVS. “The NIFDC has a great responsibility to introduce in vitro techniques to a large number of regulators within China” states Ms. Hill. “IIVS is honored to assist them in achieving this goal. Additionally our expertise in validation projects will be helpful as new in vitro methods are developed within China.”
Since 2012, the Institute for Food and Cosmetic Control (IFCC) within the NIFDC has been responsible for the testing of cosmetics for pre-market approval, post market surveillance, and investigations in response to consumer complaints. A new in vitro laboratory is currently under construction which will be used for, among other things, hands-on training. Dr. Wang Gangli, Director of the IFCC commented, “With our expanded laboratory space and support from IIVS experts, we will be able to organize workshops to train many more scientists within China on the use of in vitro methods for testing of cosmetics.”
Following the signing ceremony IIVS visited the laboratories of the NIFDC center responsible for the testing of drugs; the National Center for Safety Evaluation of Drugs (NCSED). The center Director, Dr. Wang Jufeng, and staff discussed potential collaborations and uses of in vitro methods in the evaluation of drugs within China.
About NIFDC: NIFDC areas of responsibility cover quality control of pharmaceutical products, biological products, medical devices, food, healthy food, cosmetics, reference standards, laboratory animals, and drug safety evaluation. The Institute for Food and Cosmetics Control (IFCC), an internal institute of NIFDC, is responsible for safety evaluations of food, healthy food and cosmetics.
About IIVS: IIVS is a non-profit laboratory based organization with a mission to advance the use and regulatory acceptance of in vitro testing methods. IIVS provides laboratory testing services to industry as well as training and educational programs. www.iivs.org
Media Contact: Erin Hill - firstname.lastname@example.org
REACH registrants are increasing their use of alternative methods to animal testing, according to a report published by ECHA. However, NGOs say little progress has been made as the number of new animal tests has more than doubled since 2011. The report, The Use of Alternatives to Testing on Animals for the REACH Regulation, shows that by 1 October 2013, ECHA’s database contained information on 7,939 new experimental studies for those endpoints which may involve testing on vertebrate animals. Out of these, 3,052 are in vitro tests, which involves using human cells or tissue, and 4,887 are experiments on animals. Please follow the link above to Chemical Watch to read the full article.
India's CROs Opt for Computer Model Techniques to Test Cosmetics as Ban on Animal Testing Comes into Effect
India’s pre-clinical contract research organisations (CROs) are looking at in vitro test methods and considering the advanced computer modelling techniques as the Indian ban on the use of animal testing comes into effect. With the prohibition of the animal testing by the Union government and the revision of the Drugs and Cosmetics Rules 1945 inserting a new rule after 148-B with 148-C to forbid animal testing for cosmetics, research institutes are utilizing computer models which accurately predict drug reactions, techniques like the 3-dimensional human cell derived skin model, and quantitative structure activity relationships (QSARs) to help to replace the use of guinea pigs and mice in generating safety information. Please read the full article above for additional information.
Nominations are now open and entries are invited in the fields of science, lobbying, training and public awareness, as well as from young scientists. The closing date for nominations is Friday 25th July 2014. Please visit the website above for more information
..." toxicity testing experts from Humane Society International and the Institute for In Vitro Sciences have teamed up to head to China. It's the start of an intensive training program, funded as part of an $80,000 grant from Humane Society International, The Humane Society of the United States and the Human Toxicology Project Consortium. Chinese scientists will be given laboratory-based hands-on training in how to use state-of-the-art in vitro methods such as the BCOP test to assess eye irritation and the 3T3 NRU to measure phototoxicity in cosmetics instead of using live animals." To read the full article, please visit the Huffington Post UK website by following the link above.
The pre-congress workshop will address the industrial and regulatory implementation of integrated testing strategies based on in silico, in chemico and in vitro test methods for the assessment of skin sensitization hazards and potential. For this purpose, lessons learned from other areas will be presented, the definition and regulatory implementation of ITS will be given and examples of advanced strategies available on skin sensitization will be presented by speakers from different horizons (industry, academia, governmental bodies and NGOs). The session will end with round-table discussions to allow for exchanges and constructive discussions between the participants and the invited speakers. For more information, please visit the IIVS event page above.
A policy change, announced in December by the Chinese Food and Drug Administration and to take effect in June, will allow the sale of “non-specialized cosmetics” manufactured in China, such as soap, shampoo and some skin products, without being tested on animals, if they can draw on existing safety data for raw ingredients or perform European Union-validated nonanimal tests. “When the results of risk assessment produce sufficient evidence to guarantee safety, toxicity tests on the finished products may be skipped,” the new rule says. To read the full article, including a quote from IIVS Vice-President Erin Hill, please follow the link above.
"While there are a number of validated and widely-used non-animal methods for assessing a chemical’s potential to cause skin irritation or skin corrosion, the technical challenges of modeling skin sensitization in vitro have proven harder to surmount. But 2013 and early 2014 have seen several important advances, including the first formally EURL ECVAM-validated non-animal sensitization assay." Follow the link above to read the rest of this article on skin sensitization on the AltTox website.
Apply now for the ASCCT travel award! Students and young scientists wishing to attend the 9th World Congress on Alternatives and Animal Use in the Life Sciences in Prague are eligible for a $750 travel award and a 1-year ASCCT membership. Applications are due by May 23rd. Visit the American Society for Cellular and Computational Toxicology to apply.
Scientists in China are being trained in how to use state-of-the-art in vitro methods to test cosmetics instead of using live animals such as rabbits and guinea pigs, as part of an $80,000 grant from Humane Society International, The Humane Society of the United States and the Human Toxicology Project Consortium. China is the first stop on HSI’s Be Cruelty-Free Asia science tour, which will also take in Hong Kong, Japan and Taiwan. Read the rest of the press release on the HSI website.
The Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) will hold a public meeting from 1-4 P.M. EDT Wednesday, June 25, 2014, at the National Institutes of Health Natcher Conference Center in Bethesda, MD. The purpose of this public meeting is to communicate progress on topics of interest to ICCVAM stakeholders and provide stakeholders with an opportunity to comment and ask questions.
The meeting will be open to the public with attendance limited only by the space available. Teleconference access will be available, but participants planning to submit comments are encouraged to attend in person to facilitate interaction. Details of the meeting and information for participants will be published in the Federal Register, posted on the NTP website above.
Travel grants are now available to students and young scientists for attendance at the 9th World Congress on Alternatives to Animal Use in the Life Sciences meeting in Prague, Czech Republic August 24-28. Please visit the website linked above to submit an application for consideration. The deadline for applications is April 30th.
Toxicokinetics (TK) refers to the absorption, distribution, metabolism and excretion (ADME) of chemical substances in the body. TK information is essential in regulatory safety assessment of chemicals. Aspects also include interspecies and route-to-route extrapolation, development of mechanistic understanding of TK processes, and better interpretation of systemic toxicity data.
Hepatic metabolic clearance plays a key role in the transformation and the elimination of chemicals from the human body and in recent times various in vitro methods for human hepatic metabolic clearance/stability have been developed. With the present survey, EURL ECVAM (the European Union Reference Laboratory for Alternatives to Animal Testing) seeks to identify in vitro human hepatic metabolic clearance/stability methods, which can contribute to the development of harmonized standards and associated international TK test guidelines. Click on the "read source" link above to begin filling out the survey for your method.
Deadline - June 30, 2014
Content includes information on a novel assay for determining eye sting, recent training workshops held at IIVS, a synopsis of global outreach activities, publication of a chapter in a new book on reduction of animal use for toxicology testing, and more .
The "Humane Cosmetics Act" (H.R. 4148) was introduced yesterday in the US Congress by Representative Jim Moran, Northern Virginia Democrat, who is Co-Chair of the House Animal Protection Caucus. According to the Humane Society of the United States, this act would 1) Make it unlawful for anyone to conduct or commission cosmetic animal testing in the U.S., and 2) Prohibit selling, offering for sale or transporting any cosmetics in interstate commerce if the final product or any component was developed or manufactured using animal testing. Under The Humane Cosmetics Act, after a one-year phase-in, animal testing would be banned. After a three-year phase-in period, the sale of animal tested cosmetics would be banned. For more information on the bill, please follow the link above.
The 9th World Congress will be held in Prague, the capital of the Czech Republic on August 24–28, 2014. The World Congress on Alternatives and Animal Use in the Life Sciences provides an exceptional forum to underline the importance of both the ethical issues of animal experimentation and the approach to the life sciences in the 21st century.You can find the scientific program linked above. Participants from many countries are encouraged to contribute to the program by submitting abstracts, exhibiting, and registering as an attendee. In the last decade there is much evidence of global acceptance of the 3R principles. WC9 will provide the opportunity to share scientific data and experience in animal use and welfare, to gain knowledge on the 3R policy, and to recognize efficient approaches in education in order to further extend the global progress in the 3Rs and to satisfy the highest scientific criteria. Please follow the link above to view the latest updates on the 9th World Congress.
The KeratinoSens in vitro test method for skin sensitisation testing, developed by Givaudan, has been evaluated by ECVAM. The full recommendation and summary data pdfs can be found by following the link above. In summary, ECVAM found that the Keap1-Nrf2-ARE pathway is relevant for assessing skin sensitization. They recommend that the KeratinoSens assay be used in combination with other assays (such as the Direct Peptide Reactivity Assay) in a Weight of Evidence (WOE) approach or as part of an Integrated Testing Strategy (ITS) for skin sensitization. The assay has good predictive capacity and was shown to be transferable between laboratories. Additional work is recommended by ECVAM to evaluate the assay's ability to relate potency catagories to human data. ECVAM states that "Respecting the provisions of Directive 2010/63/EU (EU, 2010) on the protection of animals used for scientific purposes, before embarking on animal experiments to identify substances with skin sensitisation potential, data from the KeratinoSens test method should be considered in combination with complementary information in order to reduce and possibly avoid animal testing. As provided for in Annex XI (point 1.2) of the REACH Regulation (EC, 2006), data from non-standard testing methods, such as the KeratinoSens, may be used to adapt the standard information requirement in the context of Weight-of-Evidence (WoE) judgments."
Sao Paulo became the first Brazilian state to ban the use of animal testing to determine the safety of cosmetic products and ingredients. The bill, which was signed into law last week, includes specified fines for violations of this law. Please follow the link above to read more on the Cosmetics Design website.
The Alternatives Research and Development Foundation is currently soliciting research proposals for its 2014 Alternatives Research Grant Program. Grants of up to $40,000 are available to support individual projects of scientific merit and feasibility with the potential to significantly reduce or replace laboratory animal use. Preference will be given to projects as U.S. universities and research institutions and projects that use pathway-based approaches.
More information is available on the ARDF website by following the link above . Application deadline for the grants is April 30, 2014.
For the past year Dr. Warren Casey served as Acting Director of the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) within the Division of the National Toxicology Program at the National Institute of Environmental Health Sciences. On January 7th Dr. John Bucher, Associate Director of the National Toxicology Program, Division of the National Toxicology Program/National Institute of Environmental Health Sciences announced that Dr. Casey has agreed to serve as the next permanent Director of NICEATM. IIVS wishes Dr. Casey well with his continued efforts at NICEATM, ICCVAM and ICATM.
Content includes information on an integrated testing strategy for skin sensitization, recent training activities in local Universities and in China, upcoming meetings, and more.
In an effort to make information on NICEATM and ICCVAM activities more easily available to stakeholders, NICEATM has launched a new website. located at . The new NICEATM website resides within the existing National Toxicology Program (NTP) website, reflecting NICEATM's increased involvement in NTP high-throughput screening and other activities. The new NICEATM website condenses summaries of past and current NICEATM and ICCVAM activities into a reduced number of webpages for easier navigation. A section dedicated to ICCVAM processes and activities within the new NICEATM site is located on this site as well. NICEATM Federal and contract support staff will continue to be actively involved in developing and maintaining content for the new NICEATM website. Please visit the new site by following the link above.
The European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) has recommended a cell transformation assay (CTA) for carcinogenicity testing. The in vitro test uses rodent Bhas 42 cells, which change their growing behavior when exposed to carcinogens. EURL ECVAM considers that the CTA can “provide important information on the carcinogenicity potential of substances when used within integrated approaches for assessment and testing”. The recommendation is partly based on the results of a Japanese validation study and was developed in consultation with EU regulators, stakeholders and international partners. Please follow the link above for more information.
The U.S. Environmental Protection Agency (EPA) announced the release of chemical screening data accessible through the new interactive Chemical Safety for Sustainability or iCSS Dashboard. The iCSS Dashboard provides access to data from innovative screening technologies for chemicals that are found in industrial and consumer products, food additives and drugs.
As part of this data release, EPA is announcing the ToxCast Data Challenges, a series of challenges inviting the science and technology community to work with the data and provide solutions for how the new chemical screening data can be used to predict potential health effects. Challenge winners will receive awards for their innovative research ideas. For additional information, please follow the EPA's link above.
GAITHERSBURG, MD, December 16, The Institute for In Vitro Sciences (IIVS), with support from its Industry Council for the Advancement of Regulatory Acceptance of Alternatives (ICARAA), conducted a training course on September 23-27 for in vitro safety testing methods for scientists from China’s NIFDC (National Institutes for Food and Drug Control), a division of the China Food and Drug Administration.
The training was held at the Institute for Food and Cosmetic Control (IFCC) of the National Institutes for Food and Drug Control (NIFDC) in Beijing. The goal of the training was to familiarize NIFDC scientists with the biological relevance, critical techniques and data interpretation of in vitro (non-animal) methods for safety testing. Twenty-eight participants from 18 provincial Institutes for Food and Drug Control, Institutes for Medical Device Control and Institute for Food and Drug Safety Evaluation of NIFDC attended. Lectures and hands-on laboratory sessions focused on methods for eye irritation, skin irritation and sensitization.
Wang Youchun, Vice Director-General of NIFDC spoke at the opening ceremony and emphasized that it is “very necessary to expedite training and research of in vitro cosmetic safety evaluation methods and promote in vitro safety evaluation technology application and academic exchanges in Food and Drug Control systems in order to adapt to the international cosmetics testing technology development and to meet the requirements for actual inspection work.”
The CFDA is currently responsible for the registration and subsequent post market surveillance of cosmetic products. While previous regulations have relied on animal testing, the regulatory and scientific community within China is investigating how existing knowledge of ingredients and in vitro testing could be incorporated into their regulatory framework.
“In vitro methods can provide significant technical advantages over animal models. Our training courses highlight the key technical steps that are necessary to generate relevant and reliable data,” explains Erin Hill, IIVS co-founder and Vice President for Program Development. According to NIFDC participants “the training not only facilitated the application of in vitro test methods in the domestic cosmetic industry, but also laid a solid foundation for the further academic exchange, technical cooperation and personnel training between NIFDC and IIVS.”
EURL ECVAM Releases Recommendations on the Direct Peptide Reactivity Assay (DPRA) for Skin Sensitization Testing
EURL ECVAM has fully endorsed the ECVAM Scientific Advisory Committee's (ESAC) opinion on the ECVAM coordinated validation study of the Direct Peptide Reactivity Assay (DPRA). They have found that information from peptide reactivity assays, such as the DPRA, is relevant for the assessment of the skin sensitization potential of chemicals. The DPRA is transferable to suitably equipped laboratories that are proficient in high performance liquid chromatography (HPLC) analysis, and both the within and between laboratory repeatability was quite high (87% and 75% respectively). Although full review of the assay's predictive capacity was outside the scope of this review, its accuracy of distinguishing between sensitizers and non-sensitizers is 82%. To read EURL ECVAMs' full recommendation, please follow the link above.
The German Federal Ministry of Food, Agriculture and Consumer Protection (BMELV), has awarded the BASF research team with €15,000 for their work in developing and implementing strategies for testing the local toxicity of chemicals without animal experimentation.
BASF research scientists have developed, optimized, and validated animal testing-free methods and strategies that examine substances for skin sensitization, eye irritation and skin irritation. “Not only did we develop these methods, we also validated them, which allows us to use them in our routine testing now,” said Dr. Robert Landsiedel, head of the Short-Term Toxicology Unit at BASF. Together with Dr. Susanne Kolle, head of the laboratory for applied alternative methods, and Dr. Caroline Bauch, who worked on the development of the methods as part of her doctoral thesis, Landsiedel received the prize on behalf of the entire Experimental Toxicology and Ecology team from the hands of Parliamentary Secretary of State at the German Federal Ministry of Food, Agriculture and Consumer Protection, Peter Bleser. “Research contributes greatly to restricting animal experimentation to a minimum. Our goal is to replace as many animal tests as possible by alternative methods,” Bleser explained. Please follow the link above for the complete press release.
The Lush Prize is an initiative which uses resources to bring forward the day when safety testing takes place without the use of animals. The Lush Prize focuses pressure on toxicity testing for consumer products and ingredients in a way which complements the many projects already addressing the use of animals in medical testing. The prizes themselves consist of a £250,000 annual fund that is split between recipients in several categories. IIVS was honored to receive a joint award in the training category for 2012 and was among the groups short listed for the training prize again this year. Please follow the link above to view a list of all of the prize recipients from this year's awards, presented to the winners last week in a ceremony in the UK.
On 14 November, Prof. Bas Blaauboer will be presented with the Willy van Heumen Prize by the Alternatives for Laboratory Animals Stimulus Fund Foundation. The Willy van Heumen Prize is presented every other year by the Alternatives for Laboratory Animal Testing Stimulus Fund Foundation. It is intended for individuals or institutions that have made outstanding achievements in limiting the use of laboratory animal tests and promoting the use of alternatives to animal testing. Prof. Blaauboer is Professor of Alternatives to Animal Testing in Toxicological Risk Assessment at Utrecht University’s Institute for Risk Assessment Sciences. He will receive the Willy van Heumen prize for his entire body of work, involving the 3R’s of laboratory animal testing – replacement, reduction and refinement. For more information, please follow the link above.
The international NC3Rs 3Rs Prize is awarded to highlight an outstanding original contribution to scientific and technological advances in the 3Rs in medical, biological or veterinary sciences published within the last three years. The prize is part of the NC3Rs' commitment to recognize and reward high-quality research which has an impact on the use of animals in the life sciences. Sponsored by GlaxoSmithKline, the prize consists of a grant of £18k, plus a personal award of £2k. Highly-commended entries receive a £4k grant and £1k personal award.
The 3Rs prize is for a piece of primary research published in a peer-reviewed journal in the last three years and is open to any researcher, in academia or industry. The prize is awarded to the principal investigator, research team leader, or other nominated author. The Prize is open to international groups. For further details on eligibility, see the Application Process page. A panel will assess the applications and select the winner based on the quality of the published research and its impact on the 3Rs. The deadline for application is Wednesday, December 11, 2013. For further information on the 3Rs Prize, please contact 3Rsprize@nc3rs.org.uk
Content includes details on an upcoming IIVS skin sensitization webinar, summaries of recent OECD Test Guideline Updates, recent activities in China, upcoming meetings, and more.
IIVS is honored to be short listed among others for The 2013 Lush Prize for outstanding contributions to replacing animal testing. All of the short-listed projects have contributed to advancing animal-free safety testing, through scientific research, training, lobbying or public awareness in 2012. IIVS was a co-recipient of the training award last year. This year's winners will be announced at the Lush Prize Awards which are scheduled to take place in London on November 13th 2013. Please follow the link above to the LUSH prize blog for additional information.
The EPA has launched a new web tool on chemical information called ChemView to improve access to chemical specific information developed by EPA and data submitted under the Toxic Substances Control Act (TSCA). Utilizing flexible search tools the user can access EPA assessments, hazard characterizations and information on safer chemical ingredients. In the months ahead, EPA will be adding additional chemicals, functionality and links. When fully populated, the portal will contain data for thousands of chemicals. EPA has incorporated stakeholder input into the design, and welcomes feedback on the current version of the site, linked above.
The re-elected Labor party government in Australia will commit to a national consultation on ending the importation, manufacture, sale and advertising of cosmetics and cosmetic ingredients which have undergone animal testing. This pledge would bring Australian policy in line with those of other nations such as the EU. To read the full article in Cosmetic Design, please follow the link above.
The animal welfare group, People for the Ethical Treatment of Animals (Peta) International Science Consortium, highlighted the confusion surrounding testing to comply with REACH regulations in a recent post on the AltTox forum. In her posting, Jessica Sandler director of the consortium says, "In our meetings with international corporations we are finding a lot of confusion on this issue and a number of companies are conducting in vivo skin irritation testing for REACH, especially because certain REACH Annexes state that negative in vitro results should be followed up in vivo." Please follow the link above to read the full posting on the AltTox forum and join the discussion if you aren't already registered.
The revised EURL ECVAM search guide titled "Good search practice on animal alternatives : re-edition" has been published and is available as a free download in the EU Bookshop. The EURL ECVAM Search Guide has been specifically developed to inform and support untrained database users to find high quality information on relevant alternative strategies and methods to animal experiments in an easy, yet systematic, efficient and effective way. Encouraged by the success of the first edition in 2012 the JRC has re-published an entirely updated second version
The Humane Society International (HSI) is accepting proposals for grants to prepare an in-depth narrative review of current research approaches to a disease area, critically assessing the value and limitations of animal models in health research and drug discovery (not toxicology) and proposing a new ‘roadmap’ for future research. The goal would be to publish the review in a peer-reviewed scientific journal and to contribute to dissemination of the work. The reviews should include proposals for a new ‘roadmap’ for future research to understand human disease and improve translation to the clinic, based on modern, human-specific models, tools and technologies. The full background and project description are in the attached Request for Proposals document.
Applicants (from academia, industry or the public sector) with a scientific PhD or equivalent and current or recent research and publication experience in an area of human disease, are invited to tender for one of these grants. Full details including the Request for Proposals and Application Form are available online by following this link to the Humane Society's website.
The application process closes at midnight EST on 15 October 2013.
The Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and the National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) work together to promote the development, validation, and regulatory acceptance of new and revised regulatory test methods. In a February 2013 editorial in the journal Environmental Health Perspectives, National Institute of Environmental Health Sciences and NTP Director Linda Birnbaum announced upcoming significant changes to the focus and priorities of both ICCVAM and NICEATM.
A draft document now available on the NTP website, titled “A New Vision and Direction for ICCVAM,” describes the initial steps towards a new strategic direction for ICCVAM. Specifically, this document discusses (1) ICCVAM priority setting and areas for scientific focus for immediate resource investment; (2) plans to improve communications with stakeholders and the public; and (3) exploration of new paradigms for the validation and utilization of alternative toxicological methods.
NICEATM invites public comments on “A New Vision and Direction for ICCVAM.” The document will be discussed at the Sept. 24 meeting of the Scientific Advisory Committee on Alternative Toxicological Methods (SACATM).
Links to “A New Vision and Direction for ICCVAM,” the Environmental Health Perspectives editorial, and the ICCVAM response to the editorial are available on the SACATM Background Materials page under the heading “New ICCVAM Vision and Procedures.” To submit a comment on “A New Vision and Direction for ICCVAM,” go to the NTP page and select the “Submit Comment” link beside the SACATM meeting announcement. Written comments submitted by September 10 will be considered during the discussion of the draft document at the SACATM meeting.
Click here for more information about the SACATM meeting. This page includes links to the Background Materials page, a preliminary meeting agenda, a registration form to attend the meeting, and a webcast that will be available on the day of the meeting.
Second Annual Meeting of the American Society for Cellular and Computational Toxicology
The Future is Here: Practical Application of Emerging Scientific Tools
Oct. 31, 2013, Bethesda, Md. Lister Hill Auditorium, NLM, NIH
• Invited plenaries by Donald E. Ingber, Harvard University, and Thomas Knudsen, U.S. Environmental Protection Agency • Panel discussion • Poster session and talks selected from submitted abstracts • Reception
Poster Abstract Deadline: August 31
To view the agenda, submit an abstract, or register please visit the link above.
The European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) is inviting public comments on its latest recommendations concerning two alternative test methods. The recommendations to be reviewed are for the Direct Peptide Reactivity Assay (DPRA) for skin sensitization and the Cell Transformation Assay (CTA) for predicting the the potential of chemicals to cause cancer. Both of these assays are being presented as useful in integrated testing strategies for safety assessment. The deadline for submission of comments is September 13. Please follow the link above for more information.
Scientists at the National Institute of Agrobiological Societies have developed a layer of cells that they are suspending on an ultra thin collagen sheet to be used to measure the ocular toxicity of chemicals. The new tissue performed similarly to already marketed models according to a study published in Toxicological Sciences. The human corneal epithelium (HCE) model is created by growing HCE-T cells (a HCE-derived cell strain) in a collagen vitrigel membrane chamber. For more information about this new model, please follow the link above to read the full article.
OECD Test Guideline 439 provides an in vitro procedure that may be used for the hazard identification of irritant chemicals (substances and mixtures) in accordance with UN GHS Category 2 (1) (2). In member countries or regions that do not adopt the optional UN GHS Category 3 (mild irritants), this Test Guideline can also be used to identify non-classified chemicals. Therefore, depending on the regulatory framework and the classification system in use, this Test Guideline may be used to determine the skin irritancy of chemicals either as a stand-alone replacement test forin vivo skin irritation testing or as a partial replacement test within a tiered testing strategy (4). For clarification on what this means to you and your skin irritation testing program, please contact us to speak with one of our study directors.
OECD Test Guideline 431 addresses the human health endpoint skin corrosion. It makes use of reconstructed human epidermis (RhE) (obtained from human derived non-transformed epidermal keratinocytes) which closely mimics the histological, morphological, biochemical and physiological properties of the upper parts of the human skin, i.e. the epidermis. This Test Guideline was originally adopted in 2004 and updated in 2013 to include a set of Performance Standards (PS) (Annex 1) for the assessment of similar and modified RhE-based test methods (8), in accordance with the principles of Guidance Document No. 34 (9). Other updates comprise the addition of two test methods, and the possibility to use some of the methods for the sub-categorisation among corrosive chemicals. Please follow the link above to read the full guideline, then contact us to speak to one of our study directors to determine how these updates could affect your testing program.
The Bovine Corneal Opacity and Permeability (BCOP) test method was evaluated by the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), in conjunction with the European Centre for the Validation of Alternative Methods (ECVAM) and the Japanese Center for the Validation of Alternative Methods (JaCVAM), in 2006 and 2010. A new review of the data has been completed and the OECD TG has been updated. The main differences between the original 2009 version and the 2013 updated version concern, but are not limited to: the use of the BCOP test method to identify chemicals not requiring classification according to UN GHS (paragraphs 2 and 7); clarifications on the applicability of the BCOP test method to the testing of alcohols, ketones and solids (paragraphs 6 and 7) and of substances and mixtures (paragraph 8); clarifications on how surfactant substances and surfactant-containing mixtures should be tested (paragraph 28); updates and clarifications regarding the positive controls (paragraphs 39 and 40); an update of the BCOP test method decision criteria (paragraph 47); an update of the study acceptance criteria (paragraph 48); an update to the test report elements (paragraph 49); an update of Annex 1 on definitions; the addition of Annex 2 for the predictive capacity of the BCOP test method under various classification systems; an update of Annex 3 on the list of proficiency chemicals; and an update of Annex 4 on the BCOP corneal holder (paragraph 1) and on the opacitometer (paragraphs 2 and 3). Please follow the link above to read the full guideline. Contact us if you have any questions about how these new modifications could affect your testing program.
The European Union Reference Laboratory for Alternatives to Animal Testing (EURL Ecvam) has chosen 13 in vitro test facilities located across Europe as the first members of the EU Network of Laboratories for the Validation of Alternative Methods (EU-Netval).The EU-Netval is expected to play an important role in translating new tools and techniques resulting from European research initiatives into test methods that could reduce, refine or replace animal testing.To read more, follow the link above to the JRC website.
Please join us for the second annual meeting of the American Society for Cellular and Computational Toxicology on October 31 in the Lister Hill Auditorium on the NIH campus in Bethesda Maryland. A sample agenda can be found here. Follow the link above to be directed to the registration page. Click here for instructions on how to submit and abstract. The abstract submission deadline is August 31st. Authors will be notified by September 20th. Space is limited. A small number of posters will be selected for oral presentations. For additional information, please visit the ASCCT website.
The latest issue of ALTEX is available for download on the Altweb website (link above). This issue includes an article on what clinical studies tell us about pre-clinical testing and several workshop reports from meetings in the field of 3Rs and alternative testing.
A new "artificial skin" product has been launched by global technology company Greiner Bio-One. Their ThinCert cell culture inserts allow human skin cells to be cultured in a thin membrane. This allows them to develop some of the same properties as normal human skin. The ThinCert will be available in a variety of multiwell plate sizes and pore diameters depending on the needs of the customers. Read more about the new product on the Greiner Bio-One website (linked above).
ARDF is pleased to announce that its 2013 Alternatives Research Grant Program has made its selections. ARDF has awarded $200,000 to scientists developing alternative methods in a variety of areas of medical research, testing and education.
Congratulations to awardees:
Patrick D. McMullen, PhD The Hamner Institute for Health Sci ences, Research Triangle Park, NC Characterization and Visualization of Toxicity Pathways from High-Throughput in vitro Screening: An Example with the aryl-hydrocarbon receptor
Gary S. Sayler, PhD University of Tennessee, Knoxville, TN Expressing Bacterial Bioluminescence in Human Cell Lines: Engineering Autobioluminescent Reporter Cells to Screen for Oxidative Stress
Karen H. Watanabe, PhD Oregon Health & Science University, Portland, OR Formulation of a Computational Model for Ovarian Development
L. Ray Whalen, DVM, PhD Colorado St ate University, Fort Collins, CO Support for the Virtual Feline Anatomy and Virtual Equine Anatomy Programs In Development at Colorado State University, College of Veterinary Medicine and Biomedical Sciences
Matthew C. Wright, PhD Newcastle University, Newcastle Up on Tyne, UK An Unlimited Supply of Rat Hepatocytes in vitro - Replacing Animals as Donors
For additional information on this program, please follow the link above.
Principle scientists from the Tox21 project in the US and Europe's SEURAT-1 came together for a 3 day workshop at the European Commission's Joint Research Center in Italy to discuss ways in which they can cooperate and collaborate to advance the field of non-animal safety assessment. The workshop included five sessions examining ToxCast, Tox21 and SEURAT-1 research programs; the chemical inventories used by the three parties; an overview of in vitro assays and test systems that are under development; a review of computational approaches for making toxicology predictions; and how these efforts can be leveraged for use in chemical safety assessment. For more information on this meeting, please read the article linked above.
On July 1st, MatTek began commercial production of EpiOcular tissue in its European lab MatTek In Vitro Life Science Laboratories (IVLSL), located in Bratislava, Slovakia. The facility has been producing EpiDerm tissue since January 2012. According to MatTek, tissues produced in MatTek IVLSL are produced under GMP conditions. Dr. Helena Kandarova serves as director of MatTek IVLSL. For more information on the production of MatTek tissues in Europe, please follow the link above to read the full article or [visit their newly launch website here][http://www.mattek.com/].
The Food and Drug Administration has issued draft guidance on good manufacturing practices (GMPs) for cosmetic products. This document is intended to assist industry and other stakeholders by identifying standards and issues that can affect the quality and safety of cosmetic products.
The new draft guidance updates FDA’s current “Cosmetic Good Manufacturing Guidelines/Inspection Checklist.” Updates include a new section on definitions, which is intended to clarify terms contained in the guidance, and one on documentation, which notes its role in preventing errors and correcting problems that may occur during manufacture.
The guidance also is part of an effort to align international standards on cosmetic manufacturing. FDA participates in this effort through its work with the International Cooperation on Cosmetics Regulation (ICCR). The guidance includes specific recommendations on documentation, recordkeeping, buildings and facilities, equipment, personnel, raw materials, production, internal audits, laboratory controls, handling consumer complaints and reports of adverse events, and conducting recalls. It can be viewed by following the link above.
The LUSH prize consists of £250,000 prize money which will be awarded as five separate prizes of £50,000 in the catagories of: Science, Training, Public Awareness, Young Researcher, Lobbying, and the Black Box prize which is reserved for a major breakthrough in 21st Century Toxicology. For more information on the prize or to make a nomination, please visit the LUSH prize website above.
IIVS was pleased to share the 2012 LUSH prize for training. Click here to view a video of the 2012 LUSH Prize awards dinner.
Former Chairman of Trustees Professor Michael Balls has accepted the title of Honorary Life President of FRAME (Fund for the Replacement of Animals in Medical Experiments). Professor Balls recently resigned from the FRAME Trustees, although he remains honorary editor of the journal ATLA (Alternatives to Laboratory Animals) and of PiLAS (Perspectives in Laboratory Animal Science).
Professor Balls has been associated with FRAME since 1979 and during that time has played a significant part in promoting the Three Rs (Replacement, Reduction and Refinement) to the scientific community. He was instrumental in the drafting and passage through Parliament of the Animals (Scientific Procedures) Act 1986 and has received many awards and honors for his work in the search for alternatives to laboratory animals, both in the UK and overseas. The FRAME Trustees have presented him with a computer and a crystal decanter in honor of his long service.
We wish Professor Balls and FRAME all the best through this transition.
Content includes a press release on the formation of ICARAA, a scientific article on in vitro phototoxicity assays (and our upcoming webinar on the same topic), a synopsis on our recent activities in Vietnam, information about our inhalation toxicity workshop, and much more.
EURL ECVAM Releases Progress Report on the Development, Validation and Regulatory Acceptance of Alternative Methods
The report covers advances made in the field of non-animal testing since 2010, which is the last time a summary report on alternative methods was published by ECVAM. The report addresses all toxicological areas relevant to the Cosmetics Regulation and is intended to supplement the 2013 Commission Communication on the animal testing and marketing ban. EURL ECVAM feels that good progress has been made in the area of local toxicity where the science and methods are more established. Efforts in the areas of reproductive and systemic toxicology and carcinogenicity are still mainly focused on research and development of new alternative methods. Please read the attached full report for additional information.
Addressing the phototoxic potential of individual ingredients and final formulations, especially those that absorb light in the UV/visible ranges and accumulate at the skin, has been a priority in the cosmetics industry; exactly how to address this has been examined using in vitro methods such as the 3T3 Phototoxicity Assay using Neutral Red Uptake (3T3-PT-NRU) Assay and Phototoxicity Assays using a 3-dimensional reconstructed epidermal skin model (3D-PT). These assays can cover the assessment of a variety of chemicals; but sometimes choosing the right assay (or assays) can be challenging. Which assay is best suited for your testing needs or product development goals?
GAITHERSBURG, Md., May 28, 2013 — The Institute for In Vitro Sciences Inc., (IIVS) a world renowned leader in the validation, training, and application of non-animal test methods, announces the formation of ICARAA: Industry Council for the Advancement of Regulatory Acceptance of Alternatives. ICARAA was formed in response to international regulations that still require animal testing to assess the safety of cosmetic and personal care products. “Many companies have been working for decades to eliminate animal testing,” states Dr. Rodger Curren , President of IIVS. “As a non-profit organization with a mission to expand the use and acceptance of in vitro methods, IIVS is well positioned to assist international regulatory agencies in the adoption of such technologies. With the combined support of the industry partners we are able to significantly expand and sharpen our efforts.”
ICARAA activities focus on educational programs that include lectures, laboratory demonstrations, hands-on training and data interpretation. Priority is given to those in vitro tests that have been widely used by the personal care and cosmetic industries and recognized by the OECD. Currently, ICARAA is also working with a major university and a biotechnology company to help increase the number of in vitro testing laboratories in China as well as assist with the development of the technology required to conduct in vitro testing. ICARAA’s overall goal is to facilitate movement away from animal testing by China’s regulatory agencies.
ICARAA is currently comprised of a number of companies including:
British American Tobacco Group Research & Development
The Estee Lauder Companies, Inc.
Mary Kay Inc.
About the Institute for In Vitro Sciences (IIVS)
Founded in 1997 as a non-profit organization, IIVS is recognized as a leading provider of in vitro testing and training services. Rigorous scientific programs coupled with educational and outreach initiates have established IIVS as a global leader in the advancement of alternatives to animal testing. For more information please visit [www.iivs.org].[http://www.iivs.org]
SOURCE Institute for In Vitro Sciences
A bipartisan group of US senators introduced a bill to modernize the Toxic Substances Control Act (TSCA), the principal federal law governing chemicals in commerce. The bill was crafted with additional input from the chemicals industry, environmentalists and other stakeholders. Under current law, the EPA can call for safety testing only after evidence surfaces demonstrating a chemical may be dangerous. As a result, EPA has only been able to require testing for roughly 200 of the more than 84,000 chemicals currently registered in the United States, and has been able to ban only five dangerous substances since TSCA was first enacted in 1976. These shortfalls led the Government Accountability Office (GAO) to identify TSCA as a “high risk” area of the law in 2009.The new bill, titled the Chemical Safety Improvement Act (CSIA) would:
Require Safety Evaluations for All Chemicals: All active chemicals in commerce must be evaluated for safety and labeled as either “high” or “low” priority chemical based on potential risk to human health and the environment. For high priority chemicals, EPA must conduct further safety evaluations.
Protect Public Health from Unsafe Chemicals: If a chemical is found to be unsafe, the Environmental Protection Agency (EPA) has the necessary authority to take action. This can range from labeling requirements to the full phase-out or ban of a chemical.
Prioritize Chemicals for Review: The Environmental Protection Agency will have to transparently assess risk, determine safety, and apply any needed measures to manage risks.
Screen New Chemicals for Safety: New chemicals entering the market must be screened for safety and the EPA is given the authority to prohibit unsafe chemicals from entering the market.
Secure Necessary Health and Safety Information: The legislation allows EPA to secure necessary health and safety information from chemical manufacturers, while directing EPA to rely first on existing information to avoid duplicative testing.
Promote Innovation and Safer Chemistry: This legislation provides clear paths to getting new chemistry on the market and protects trade secrets and intellectual property from disclosure.
Protect Children and Pregnant Women: The legislation requires EPA to evaluate the risks posed to particularly vulnerable populations, such as children and pregnant women, when evaluating the safety of a chemical—a provision not included in existing law.
Give States and Municipalities a Say: States and local governments will have the opportunity to provide input on prioritization, safety assessment and the safety determination processes, requiring timely response from EPA, and the bill establishes a waiver process to allow state regulations or laws to remain in effect when circumstances warrant it.
To read more about this proposed legislation, please follow the link above.
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.
“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.
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.
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.
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.
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!
SUMMARY OF KEY THEMES
There are several plausible in vitro test systems, models, and assay endpoints currently available with the potential to be used for assessing adverse impacts of tobacco product exposure in respiratory tissues. These models and assay endpoints should be further evaluated for their use as hazard assessment tools in a regulatory arena.
Of particular interest are three-dimensional (3D) reconstructed, human, organotypic tissue models of the respiratory airways; these should reduce the need to extrapolate results across species, thus strengthening the relevancy of results.
Standardization of promising test methods should be a high priority.
Relevant reference standards should be developed and made easily available to the research community.
Access to information from non-invasive or minimally invasive clinical studies is needed to bridge the gap between in vitro and in vivo results.
Development of test methods for regulatory purposes is unlikely to be funded through the traditional grant process; more direct funding programs should be developed.
Close communication should be maintained between regulators and the research community to be most efficient in the development of useful in vitro methods to assess relative risk.
A Tiered In Vitro Irritation/Corrosion Testing Strategy for GHS Classification of Pharmaceutical Compunds
Irritation reactions are a frequently reported occupational health hazard. To reduce animal testing, BMS and IIVS have developed a testing strategy using three in vitro assays to assess the irritation/corrosive potential of pharmaceutical compounds (PC) for worker safety. The strategy allows for GHS classification by utilizing the Corrositex® assay for corrosivity (OECD TG 435), the Bovine Corneal Opacity and Permeability (BCOP) assay for ocular irritation (OECD TG 437), and the EpiDerm™ skin irritation test (SIT) for dermal irritation (OECD TG 439). Twenty-five solid PCs were evaluated in this tiered testing strategy. First the pH of each substance was determined. If the pH was ≥11 or ≤2, a Corrositex® assay was conducted. If the compound was negative in the Corrositex® assay or the pH was between 2 - 11, a BCOP assay was performed followed by a SIT assay. Based on their extreme pH, 4 compounds were tested in the Corrositex® assay, which resulted in corrosive predictions (packing group II or III) and thus no further testing was needed. Twenty-two compounds were evaluated in the BCOP assay (both neat and as a 20% dilution), with the higher response used for classification. The results were 5 Category 1 (score>55), and 8 non-irritants (score<3). There were 9 compounds with scores between 3 - 25, which were described as mild irritants on internal BMS hazard communications. Twenty-five compounds were evaluated using the SIT assay and were classified as non-irritants to skin. This is consistent with the BMS historical animal model results showing very low number of PCs as skin irritants. The comparison also confirmed 50% viability as an acceptable cut off for GHS dermal irritation classification. This tiered testing strategy, which replaces the use of animal studies, represents a rational platform that can be utilized for the prediction of ocular and dermal irritation/corrosive potential of PCs.
Using the Novel NociOcular Assay to Predict the Eye Sting Potential of Shampoos and Sunscreen Products
Although several in vitro eye irritation models exist, none have demonstrated the ability to predict eye stinging. The NociOcular assay, a novel neuronal in vitro model with high expression of capsaicin-responsive Transient Receptor Potential Vanilloid type 1 (TRPV1) channels, has been shown to distinguish stinging from non-stinging baby bath products. We sought to evaluate the eye stinging potential of additional surfactant-based products and sunscreen formulations. In the assay, SH-SY5Y neuroblastoma cells are cultured in 96-well plates and exposed to serially diluted test substance and TRPV1 channel activation is measured by acute increases in the intracellular free calcium. In separate wells, cells are treated with the TRPV1 antagonist capsazepine to confirm TRPV1-mediated calcium influx. The positive control, an adult shampoo that contains cocamide MEA, a known stinging ingredient, was the most active surfactant-based test substance evaluated in the assay. The negative control, a baby shampoo, was negative in the NociOcular assay and clinical tests. Four shampoo products demonstrated a range of responses between these controls and were classified as either stinging or non-stinging based on the percentage calcium influx as compared to capsaicin over the dose-response. During pilot studies with sunscreen formulations, several technical challenges arose including insolubility in assay buffers and pipetting the subsequent dilutions onto the cells. In order to achieve greater solubility, alternate solvents composed of detergents along with assay buffers were used. These alternate solvents allowed for increased solubility and dilutions were successfully administered onto the cells. Ten sunscreen formulations were evaluated and ranked according to TRPV-1 response and compared to available consumer experience reviews for eye stinging. Future research aims to assess the accuracy of the predictions for both the shampoos and sunscreen products through clinical data comparison.
The Transient Receptor Potential Vanilloid type 1 (TRPV1) receptor is one of the most well characterized pain-inducing receptors and has been recently identified as a valuable tool to predict eye stinging potential of surfactant based formulations. In this study we sought to predict eye stinging of non-surfactant based cosmetic formulations by studying TRPV1 activity using the NociOcular assay. In the NociOcular assay, TRPV1 expressing neuroblastoma cells are exposed to test substance and TRPV1 activity is measured by acute increases in intracellular calcium. Three of the formulations induced stinging in the human test and were also positive in the NociOcular assay. The other four formulations evaluated were classified as stinging in the human test, but a conclusive determination could not be made in the NociOcular assay as the formulations were not fully soluble in assay buffers. The formulations were also evaluated in the EpiOcularTM assay, an established in vitro model for eye irritation utilized by the cosmetics industry. The EpiocularTM assay results did not correlate with the human sting data. Our data support that the NociOcular assay may be a valuable in vitro tool to predict human eye stinging sensation for cosmetic formulations. Future efforts seeks to further expand the applicability of the assay to product types other than surfactant based formulations.
Investigation of Novel In Vitro Methods for Predicting the Dermal Sensitization Potential of Synthetic Process Intermediates
Skin Sensitization is a critical endpoint in the evaluation of synthetic process intermediates used in the manufacture of active pharmaceutical ingredients. Although the in vivo Local Lymph node assay (LLNA) has been traditionally used to qualitatively and quantitatively assess dermal sensitization, many novel alternative assays have reached an advanced stage of pre-validation and official testing guidelines are expected within the year. In this study we sought to evaluate two alternative assays, the KeratinoSensTM assay and the Direct Peptide Reactivity Assay (DPRA), for the prediction of dermal sensitization of synthetic process intermediates. The KeratinoSensTM assay is a cell-based reporter gene assay which identifies skin sensitizers by measuring the induction of luciferase under the control of the antioxidant response element (ARE) derived from the human AKR1C2 gene. Luciferase induction indicates activation of ARE-dependent genes which are involved in the dermal sensitization mechanism. The DPRA is an in chemico assay which identifies dermal sensitizers based on their reactivity with model peptides. Test substances are incubated with cysteine/lysine containing peptides and the depletion of each peptide is then used to determine the degree of reactivity and dermal sensitization potential. Ten process intermediates have been evaluated in KeratinoSensTM and DPRA and the results have been compared to existing LLNA data on these test substances. Compared to the LLNA data, nine of the ten test substances were identified correctly by the KeratinoSensTM assay; a positive response in either KeratinoSensTM assay or DPRA was considered to be potential sensitizer. Continued evaluation of these alternative assays for assessment of the dermal sensitization potential of synthetic process intermediates will be beneficial in establishing testing strategies to reduce animal testing while providing a useful tool for risk assessments.
Protocol Considerations for Testing Surfactants and Surfactant-based Formulations in the Bovine Corneal Opacity and Permeability Assay
The Bovine Corneal Opacity and Permeability (BCOP) assay is an ex vivo test for predicting ocular irritation. For regulatory classification, OECD Test Guideline (TG) 437 specifies that liquid and solid surfactants may be tested as 10% aqueous dilutions for 10 minutes, although alternate dilutions and exposure times may be conducted with scientific rationale. Guidance Document (GD) No. 160 also presents that solid and concentrated liquid surfactants may be diluted to 10% for testing. 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. Without question, surfactant solids should not be tested using the solid chemical protocol, since overexposure conditions are likely. In the absence of clear guidance from these regulatory documents, we present on the testing of a few common surfactant ingredients (sodium lauryl sulfate, Triton X-100, and benzalkonium chloride), and surfactant-based liquid and solid formulations in BCOP using standard and modified dilutions and exposures to evaluate the impact of these variables. Whereas the opacity values for the non-ionic and anionic surfactants were low, changes in the fluorescein permeability values correlated well to expected surfactant activities in all of the surfactant classes tested. Histopathology was performed to confirm corneal changes. We found that surfactants at very high concentrations may not exhibit dose-related effects, as irritation optima may occur at aqueous concentrations between 10 and 30%. Furthermore, since surfactants induce corneal erosion, we advocate that the fluorescein permeability endpoint in the BCOP assay should be evaluated individually from the In Vitro Irritation Score (IVIS) in a hazard assessment. Accordingly, a framework to guide the testing of surfactants and surfactant-based products is presented. Please contact us for more information on this work at email@example.com.
Toxic Insult to Rat Precision Cut Lung Slices Increases Tissue Cytokine Levels and Activation of Macrophages, and Causes Acute Damage, While Prolonged Insult May Lead to Increased Deposition of Collagen - a Marker of Fibrosis
The use of in vitro or ex vivo models is intended to provide meaningful data that will identify or predict the adverse effects of tissue exposure. Precision-cut lung slices (PCLS) are used as a model that retains the heterogenous population of cells in the native architecture of the organ. The retention of native cells allows the study of the initial, dynamic events (such as inflammation) that occur following a toxic insult prior to overt tissue damage. The purpose of the reported studies was to identify initial inflammatory signals, acute toxicities, as well as markers associated with chronic toxicities of PCLS exposed to a toxic insult as a way to qualify the model for identifying such endpoints. Rat PCLS were exposed to several chemotherapeutics known to cause acute and/or chronic pulmonary damage. Time points for respective endpoints were chosen based on known response times of when relevant endpoints may change. Cytokines and acute toxicity were evaluated during initial days of exposure while activation of macrophages and collagen deposition were evaluated through 4 weeks of culture in other studies. Exposure of PCLS for 24 hours resulted in increased cytokine levels and 72 hour exposure caused overt toxicity, as assessed using tissue protein content and histologically using H&E and ED-1 staining. Long term exposure of PCLS to two agents known to cause fibrosis (bleomycin and carmustine) resulted in elevated numbers of macrophages and also increased collagen deposition. PCLS generate inflammatory cytokine signals and, if levels persist after insult removal, these signals may predict subsequent tissue damage. The expression of adverse markers of chronic exposures (collagen deposition) in PCLS may signify risk of fibrosis. Cytokine responses, macrophage activation, and fibrosis are hallmarks of tobacco related exposures. PCLS may elucidate acute and chronic adverse pulmonary responses when exposed to tobacco products.
Evaluation of a Reconstructed Human Oral Buccal Tissue Model as a Testing Platform for Determining the Oral Irritation Potential of Tobacco Products
There is an increasing need by the tobacco industry to evaluate the irritation and inflammation potential of tobacco products to support product development goals, for sound product stewardship, and likely regulatory safety tests. The use of in vitro human cell and tissue-based test methods to replace in vivo animal models addresses the need for more human-relevant predictive tools, and is consistent with many corporate animal welfare policies. Although monolayer cell-based cytotoxicity and cytokine expression assays have been used, three-dimensional tissue constructs provide distinct advantages since tissue exposures and pharmacokinetics more closely resemble the in vivo events. In this study, we evaluated a reconstructed human oral buccal model for determining the oral irritation of oral tobacco products. A dilution series of tobacco extracts were applied topically onto the EpiOral™ reconstructed human oral buccal model (Cat no. ORL-200) (MatTek Corporation, Ashland, MA) for various exposure times (ranging from 2 to 16 hours) to estimate oral irritation potential based upon reduction in cell viability and the synthesis/release of the inflammatory mediators IL-1α and IL-8. We determined tobacco extract concentration-related increases in cytotoxicity for the highest tobacco extract concentrations. We also found that increases in IL-1α release (up to 19-fold) generally correlated with the cytotoxicity increases. Exposure time related increases in IL-8 release were generally observed in tissues treated with the three lower tobacco extract concentrations where relative viabilities were sufficiently high to allow for secondary cytokine production, but at the highest tobacco extract concentrations IL-8 release were below control levels where cytotoxic effects inhibited the cells’ ability to synthesize proteins. These results demonstrate the utility of reconstructed human epithelial models for evaluating the irritation potential of tobacco products. To expand upon this utility, we propose to apply these general methods for determining cytotoxicity and inflammatory cytokine profiles to evaluating inflammation responses in reconstructed human airway tissue models exposed to combustible tobacco product extracts, particulate matter, and whole smoke.
Preliminary Investigation on Reducing Ocular Irritation Potential of Harsh Ingredients By Increasing Formulation Viscosity
Formulations tested for ocular irritation using the Bovine Corneal Opacity and Permeability (BCOP) assay may be assigned a specific irritation label based on the resulting In Vitro Irritancy Score (IVIS) and specific regulatory guidelines (e.g. OECD, EPA, and CLP) that provide cutoff values for classifications. The ability to reduce ocular irritation by slightly adjusting the physical properties of a formulation is highly desirable. Laboratory investigations found that incrementally changing viscosity using increasing amounts of Carbopol® as a thickening agent reduced ocular irritation when mixed with a 1% NaOH solution in water. Following a 10-minute exposure in the BCOP assay, 1% NaOH was previously classified as a severe ocular irritant (IVIS=161.6). Increasing Carbopol® from 0.25% to 1.25% in a mixture with 1% NaOH decreased the In Vitro score to a range of values between 150.9 and 18.3 and decreased ocular irritation across a range of irritation classifications from severe to mild irritation (n= 3 corneas per treatment). Exposure to 1% Carbopol® alone exhibits minimal irritation (IVIS=1.3) and Carbopol® is consequently not considered to contribute to ocular irritation within the tested mixtures. Histopathology evaluation further supports that exposure to 1% Carbopol® results in damage similar to negative control treated corneas and that epithelial and stromal damage decreases as viscosity increases. Additionally, preliminary findings indicate that when a small amount of thickener is added to a complex formulation containing otherwise harsh ingredients, ocular irritation can be mitigated from a Category I label to a Category II label according to current EPA guidelines applicable to cleaning products making anti-microbial claims. Similarly, increasing the viscosity of a formulation containing more than 3% of a severe ingredient also resulted in a “Not Classified” label according to OECD criteria when it would have received a severe classification if left untested (according to CLP regulations). These results indicate that increasing viscosity may be an effective tool for reducing ocular irritation potential of a formulation. Viscosity, among other physical properties, may therefore be used to inform decision making during product development, ultimately affecting downstream users in such areas as marketing, labeling, packaging and distribution.
Assessing Increased Sensitivity and Variability Issues in an Established In Vitro Phototoxicity Testing Program
The 3T3 Neutral Red Uptake (NRU) Phototoxicity assay is an established in vitro assay used to evaluate the potential phototoxicity hazard of a test chemical. The assay methods and prediction model are described in The Organization for Economic Cooperation and Development (OECD) Test Guideline (TG) 432 “In Vitro 3T3 NRU phototoxicity test”1. IIVS’ routine assay performance is evaluated on the comparison of the positive control, chlorpromazine, and solvent control results to our historical database. Failure to consistently meet acceptance criteria calls for examination of assay performance. High assay sensitivity and low optical density values have contributed to the failure of recent assay results to meet acceptance criteria. Storage conditions, preparation, and manufacturer lot-to-lot consistency of assay reagents (DMSO, chlorpromazine, and neutral red) were evaluated. Variations in positive control or solvent control responses in different DMSO (lot-lot or catalog number). Preparation, storage condition, and filtration methods affected neutral red signal. UVA light source investigated for impacts on irradiance uniformity. Variations in UVA light intensity observed depending on plate placement under the light source. Several variables (reagents and light source) which likely impacted assay performance and may have contributed to increasing assay sensitivity were investigated.