National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/40549

Announcements Sent to the NICEATM News List in 2012


These announcements were originally distributed via the NICEATM News email list. Subscribing to the NICEATM News email list will notify you directly of publication of NICEATM Federal Register notices, availability of ICCVAM reports, notices of upcoming meetings, requests for public comments or data, and other events of interest to our stakeholders.

December 10: U.S. Consumer Product Safety Commission Amends Regulations on Animal Testing Methods

A rule published by the U.S. Consumer Product Safety Commission (CPSC) codifies the statement of policy on animal testing that provides guidance for manufacturers of products subject to the Federal Hazardous Substances Act (FHSA) regarding replacement, reduction, and refinement of animals. Codification of this policy is intended to make CPSC's animal testing policy and test methods recommended by ICCVAM and accepted by CPSC more transparent and accessible to interested parties.

The rule was published December 10, 2012, in the Federal Register (77 FR 73286). The rule includes comments received on the proposal and CPSC responses to the comments. The rule also includes the relevant amendments made to the text of 16 CFR part 1500. The statement of policy is effective January 9, 2013.

Federal Register notice - View notice as webpage

In a related notice, the CPSC announced amendments to its regulations on the CPSC's animal testing methods under the FHSA. The announcement, also published in today's Federal Register (77 FR 73290) includes comments received on the proposed rule and CPSC responses to the comments. The rule also includes revisions to animal testing regulations and explanations of the rationale for the revisions. The rule takes effect January 9, 2013.

Federal Register notice - View notice as webpage

The FHSA (15 U.S.C. 1261-1278) requires appropriate cautionary labeling to alert consumers to the potential hazards that certain hazardous household products may present. These include products that are toxic, corrosive, irritants, flammable, combustible, or strong sensitizers. The changes to the FHSA announced today clarify the criteria used for classification of substances as "highly toxic," "toxic," "corrosive," "irritant," "primary irritant," and "eye irritant." The changes emphasize that the use of in vitro and other alternative test methods, including a weight-of-evidence approach, and prior human experience are recommended over in vivo animal tests wherever possible. Furthermore, the CPSC reiterates its preference for reliable human experience over animal test data.

CPSC has also established a page on its website  regarding ICCVAM recommendations and new developments in test methods that avoid or further reduce or refine animal testing.

According to the ICCVAM Authorization Act, ICCVAM member agencies should promote and encourage the development and use of alternatives to animal test methods for regulatory purposes. Since the establishment of ICCVAM, the CPSC has approved, where applicable, recommendations made by ICCVAM to reduce and refine animal testing applicable to test methods under the FHSA. A table summarizing U.S. and international regulatory acceptance of alternative test methods, which includes methods recommended by ICCVAM applicable to testing under the FHSA, is available on the ICCVAM website.

 

November 6: New Test Guidelines Available for Endocrine Disruptor Testing

The Organisation for Economic Co-operation and Development (OECD) has officially adopted two test guidelines for test methods to identify substances with the potential to affect the function of the endocrine system. Both test guidelines describe in vitro methods that do not use animals, and the tests are appropriate for use in the U.S. Environmental Protection Agency (EPA) Endocrine Disruptor Screening Program.

OECD Test Guideline 457: BG1Luc Estrogen Receptor Transactivation Test Method for Identifying Estrogen Receptor Agonists and Antagonists

OECD Test Guideline 455: Performance-Based Test Guideline for Stably Transfected Transactivation In Vitro Assays to Detect Estrogen Receptor Agonists

Test Guideline 457 describes the BG1Luc estrogen receptor (ER) transactivation (TA) assays to detect ER agonist and antagonists and provides performance standards for each assay. The test guideline was based on data from an international validation study that was coordinated by NICEATM and that included laboratories in the United States, Japan, and Italy.

NICEATM worked closely with the EPA to usher this method through the OECD nomination and adoption process. The adoption of Test Guideline 457 means that these methods may now be used in the 34 member countries of the OECD. In July 2012, the EPA announced its acceptance of the BG1 method as an alternative to the HeLa9903 TA assay in response to a recommendation by ICCVAM.

More about the ICCVAM recommendations on the BG1 Luc ER TA test method

Test Guideline 455 has been updated to include both the BG1 and HeLa9903 methods, and now describes general characteristics of stably transfected transactivation in vitro assays to detect ER agonists. This performance-based test guideline also provides standards for development of new test methods of this type. These standards include a harmonized list of reference chemicals that should be tested during assay development, as well as performance standards that should be met by successful assays.

 

November 5: Report Provides Overview of International Processes for Adoption and Use of Alternatives

The International Cooperation on Cosmetics Regulation (ICCR) has issued a report on "Applicability of Animal Testing Alternatives in Regulatory Frameworks Within ICCR Regions." The report "provides an overview of processes and mechanisms for the use of alternatives in human safety assessments of cosmetic products and ingredients in the four ICCR jurisdictions."

The ICCR is made up of representatives of cosmetic regulatory authorities from the United States, Japan, the European Union, and Canada. The goal of the ICCR framework is to maintain the highest level of global consumer protection while minimizing barriers to international trade.

Recognizing the importance of reducing, refining, and replacing animal use in toxicity testing, ICCR recommended in September 2007 that international cooperation on evaluation, adoption, and use of alternatives be strengthened. This recommendation led to the establishment of the International Cooperation on Alternative Test Methods (ICATM) in 2009. NICEATM and ICCVAM participate in ICATM along with the other ICCR participating governments and the Republic of Korea.

More information about ICCR on the FDA website

 

October 25: New Test Guidelines Available for Eye Safety Testing

The Organisation for Economic Co-operation and Development (OECD) has officially adopted two test guidelines for identification of substances with the potential to cause eye injury. One of these, an updated test guideline for the traditional rabbit eye test, incorporates specific procedures to avoid or minimize animal pain and distress when it necessary to use animals to identify substances with the potential to cause eye injuries. The other test guideline provides a new method to identify substances that may cause serious eye injuries without using animals.

OECD Test Guideline 405: Acute Eye Irritation/Corrosion

OECD Test Guideline 460: Fluorescein Leakage Test Method for Identifying Ocular Corrosives and Severe Irritants

The updated Test Guideline 405 incorporates recommendations made by ICCVAM to U.S. Federal agencies in 2010. After an evaluation of the use of anesthetics, analgesics, and humane endpoints in eye safety testing, ICCVAM recommended that pain management procedures should always be used when it is determined necessary to use the rabbit eye test for regulatory safety assessments.

The ICCVAM recommendations were accepted or endorsed by U.S. Federal agencies in 2011. The adoption of the updated OECD test guideline 405 means that these procedures may now be used in the 34 member countries of the OECD, refining animal use for eye safety testing in many more countries.

The fluorescein leakage (FL) test method can be used to identify ocular corrosives and severe irritants: substances that can cause severe, permanent eye injuries. While it is not a complete replacement for the rabbit eye test, the FL test method can be used as an initial step in a testing strategy to identify water-soluble substances and mixtures that are potential corrosives or severe irritants.

The FL test method was adopted by OECD after being evaluated by the European Union Reference Laboratory for Alternatives to Animal Testing. NICEATM and ICCVAM contributed to the evaluation of the FL test as members of the International Cooperation on Alternative Test Methods.

 

October 4: Page on Alternatives Now Available on the CPSC Website

The U.S. Consumer Product Safety Commission (CPSC) has added a page to its website entitled Recommended Procedures Regarding the CPSC's Policy on Animal Testing . The page summarizes the CPSC policy on animal testing and emphasizes the CPSC's support for the use of existing information and scientifically validated alternatives to animal testing in hazard assessment. The page also lists acceptable alternative methods for acute toxicity testing,  ocular irritation testing, dermal irritation testing, and skin sensitization testing, and provides links to CPSC votes or approvals with respect to animal testing policy.

CPSC is an ICCVAM member agency.  Links to the CPSC website and the new CPSC alternatives page are available on the ICCVAM member agency list page. Links to websites of the other 14 ICCVAM member agencies are also available on this page, as are links to pages on these websites specifically discussing animal testing and alternatives use.

 

September 25: Update Available of National Library of Medicine ALTBIB Portal for Alternatives for Research and Testing

The National Library of Medicine (NLM) ALTBIB portal has been updated. ALTBIB provides access to PubMed®/MEDLINE® citations relevant to alternatives to the use of live vertebrates in biomedical research and testing.

The site’s topics and subtopics are aligned with current approaches. For example, information is provided on in silico, in vitro, and improved (refined) animal testing methods. Strategies that incorporate validated methods and other approaches are also covered.

In addition to the topic area PubMed searches, the ALTBIB portal includes a searchable bibliographic collection on alternatives to animal testing. This collection provides citations from published articles, books,book chapters, and technical reports published from 1980 to 2000. The bibliography features citations concerning methods, tests, assays, and procedures that may prove useful in establishing alternatives to the use of intact vertebrates.

ALTBIB has an extensive collection of links to key organizations providing information on alternatives to animal testing, and provides access to animal alternatives news sources, such as ICCVAM, of which NLM is a member. The portal also offers access to the ICCVAM webpages U.S. and International Acceptance of Alternative Methods, 1998-2012 and Alternative Test Method Project Milestones.

A fact sheet with more information about the ALTBIB portal is available on the NLM website.

 

August 8: USDA Seeks Comments on Draft Proposal on Exemption from Animal Safety Testing for Veterinary Vaccines and Other Biological Products

The U.S. Department of Agriculture (USDA) Center for Veterinary Biologics (CVB) regularly seeks public comment on drafts of proposed guidance documents concerning all aspects of veterinary vaccines production, testing, and distribution. Veterinary Services Memorandum Draft Notice 453, which is currently available for comment, provides for exemption from animal safety testing. The proposed exemption could reduce animal use for testing of veterinary vaccines.

The Draft Notice notes that documentation of product safety and consistency in manufacturing processes may make animal safety testing (as described in various subsections of 9 CFR 113) unnecessary. It presents a process by which manufacturers of testing of veterinary vaccines could obtain an exemption from animal safety testing.

This proposal is consistent with recommendations made by the International Cooperation on Harmonization of Technical Requirements for Registration of Veterinary Products (VICH). The proposal also incorporates recommendations for reduction of animal use made by participants at the September 2010 NICEATM–ICCVAM workshop on alternative methods for vaccine safety and potency testing.

Comments on the draft proposed guidance document should be submitted to the Center for Veterinary Biologics by August 13, 2012.

July 27: U.S. National Institutes of Health Awards Grants to Fund Development of Tissue Chips to Help Predict Drug Safety

The U.S. National Institutes of Health (NIH) has awarded 17 grants aimed at creating 3-D chips with living cells and tissues that accurately model the structure and function of human organs such as the lung, liver and heart.
View July 24th NIH news release 

Once developed, these tissue chips will be tested with compounds known to be safe or toxic in humans. Data from these tests will help identify the most reliable drug safety signals, ultimately advancing research to help predict the safety of potential drugs in a faster, more cost-effective way. The initiative marks the first interagency collaboration launched by the NIH's recently created National Center for Advancing Translational Sciences.

More than 30 percent of promising medications have failed in human clinical trials because they are determined to be toxic despite promising preclinical studies in animal models. Tissue chips, which are a newer human cell-based approach, may enable scientists to predict more accurately how effective a therapeutic candidate would be in clinical studies. Tissue chips merge techniques from the computer industry with modern tissue engineering by combining miniature models of living organ tissues on a transparent microchip. Ranging in size from a quarter to a house key, the chips are lined with living cells and contain features designed to replicate the complex biological functions of specific organs.

NIH's newly funded "Tissue Chip for Drug Screening" initiative is the result of collaborations that focus the resources and ingenuity of the NIH, the Defense Advanced Research Projects Agency, and the U.S. Food and Drug Administration. NIH's Common Fund and the National Institute of Neurological Disorders and Stroke led the trans-NIH efforts to establish the program. The NIH plans to commit up to $70 million to the program over five years.

Tissue chips are an example of innovative tools and methodologies that can be used to identify whether substances are likely to be safe or toxic to humans. In its draft 2013-2017 Five-Year Plan, the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) identifies "Promoting the Application and Translation of Innovative Science and Technology" as one of its core strategies to support the development of predictive alternative test methods. Innovative testing approaches such as tissue chips have the potential to more accurately and efficiently identify substances that may present human health hazards, while reducing and ultimately replacing animal use for this purpose.

Read more about the NIH grants:

July 18: U.S. Food and Drug Administration Issues Guidance Document on Pyrogen and Endotoxins Testing

The U.S. Food and Drug Administration (FDA) has issued guidance on the use of alternatives to the rabbit pyrogen test (RPT) and the bacterial endotoxins test (BET) for detecting pyrogens in pharmaceuticals and other products. “Guidance for Industry – Pyrogen and Endotoxins Testing: Questions and Answers,” issued June 2012, includes guidance regarding the use of alternatives to the RPT or the BET. Firms producing products for which pyrogen testing is required may use alternative methods if they provide advantages in terms of accuracy, sensitivity, precision, selectivity, or adaptability to automation or computerized data reduction, and in other special circumstances. Alternative methods should be subjected to appropriate validation and shown to achieve equivalent or better results compared to the standard method. The document also provides guidance for transitioning from one test method to another.

As examples of alternative assays that may be used, the guidance document cites the recombinant horseshoe crab Factor C assay and monocyte activation type pyrogen tests (MATs). ICCVAM recommended in 2008 that MATs could be considered for use to detect Gram-negative endotoxin in human parenteral drugs on a case-by-case basis, subject to validation for each specific product to demonstrate equivalence to the RPT, in accordance with applicable U.S. Federal regulations. The ICCVAM recommendations were accepted by Federal agencies, including the FDA.

ICCVAM has given a high priority for further discussion to a 2011 nomination to ICCVAM for activities to expand the applicability domain of a MAT that measures IL-1 release from cryopreserved human blood cells to include detection of non-endotoxin pyrogens.

View the FDA guidance on the agency's website 

 

July 12: U.S. Consumer Product Safety Commission Requests Comments on Proposed Amendments to Regulations on Animal Testing Methods

In a Federal Register notice published June 29 (77 FR 38754), the U.S. Consumer Product Safety Commission (CPSC) announced a proposal to amend and update regulations on the CPSC’s animal testing methods under the Federal Hazardous Substance Act (FHSA). The proposed updates reflect CPSC approval of recommendations issued by ICCVAM to reduce and refine animal testing applicable to test methods under the FHSA. In a related notice, the CPSC announced a proposal to amend its regulations (16 CFR 1500) to add a “Statement on Animal Testing Policy” (77 FR 38751).

The FHSA (15 U.S.C. 1261-1278) requires appropriate cautionary labeling to alert consumers to the potential hazards that certain hazardous household products may present. These include products that are toxic, corrosive, irritants, flammable, combustible, or strong sensitizers. The proposed changes to the FHSA clarify the criteria used for classification of substances as “highly toxic,” “toxic,” “corrosive,” “irritant,” “primary irritant,” and “eye irritant.” The proposed changes emphasize that tests using animals are not the only means by which these classification decisions can be made and that CPSC does not require data from animal tests to support these classifications. The proposal also revises sections of the FHSA that discuss methods to be used for testing toxic substances, primary irritant substances, and eye irritants. The proposed revisions clearly recommend consideration of non-animal methods before using animal tests and use of approaches that reduce and refine (enhance animal well-being and lessen or avoid pain and distress) animal use when animal testing is necessary.

According to the ICCVAM Authorization Act, ICCVAM member agencies should promote and encourage the development and use of alternatives to animal test methods for regulatory purposes. Since the establishment of ICCVAM, the CPSC has approved, where applicable, recommendations made by ICCVAM to reduce and refine animal testing applicable to test methods under the FHSA. The CPSC is amending and updating regulations under the FHSA to make the ICCVAM recommendations and the CPSC animal testing policy more accessible and transparent to interested parties. CPSC will also create a page on its website regarding ICCVAM recommendations and new developments in test methods that further reduce or refine animal testing.

A table summarizing U.S. and international regulatory acceptance of alternative test methods, which includes methods recommended by ICCVAM applicable to testing under the FHSA, is available on the ICCVAM website.

The CPSC is accepting comments on its proposals until September 12, 2012. Comments may be submitted on the Regulations.gov website (Docket Numbers CPSC-2012-0036 and CPSC-2012-0037). Comments may also be submitted to the CPSC in writing; please refer to the Federal Register notices (77 FR 38751 or or 77 FR 38754 ) for details.

 

June 29: USDA Issues Guidance Document on the Use of Humane Endpoints and Methods in Animal Testing of Biological Products

The U.S. Department of Agriculture (USDA) Center for Veterinary Biologics (CVB) has issued new guidance on the use of humane endpoints and methods in animal testing of biological products. CVB Notice No. 12-12, issued May 25, 2012, includes specific guidance regarding the use of humane endpoints in biological products testing, including guidance on humane endpoints for the rabies challenge test. The guidance also strongly encourages the use of anesthesia for intracerebral inoculation of mice during rabies vaccine testing, and encourages the use of analgesics in animal studies and potency testing when it can be shown this does not affect the study outcome.

The draft guidance incorporates recommendations for refinement of rabies vaccine testing made by participants at the October 2011 NICEATM–ICCVAM workshop on alternative methods for rabies vaccine potency testing.

View a summary of the Rabies Vaccine Workshop

The new guidance and other notices issued by the CVB are available on the USDA website.

April 10: USDA Seeks Comments on Draft Proposed Guidance Document on the Use of Humane Endpoints and Methods in Animal Testing of Biological Products

The U.S. Department of Agriculture (USDA) Center for Veterinary Biologics (CVB) regularly seeks public comment on drafts of proposed guidance documents concerning all aspects of veterinary vaccines production, testing, and distribution. Draft Notice 465, which is currently available for comment, provides proposed guidance on the use of humane endpoints and methods in animal testing of biological products. The draft document includes specific guidance regarding the use of humane endpoints in biological products testing, including guidance on humane endpoints for the rabies challenge test. The draft guidance also strongly encourages the use of anesthesia for intracerebral inoculation of mice during rabies vaccine testing.

The draft guidance incorporates recommendations for refinement of rabies vaccine testing made by participants at the October 2011 NICEATM–ICCVAM workshop on alternative methods for rabies vaccine potency testing.

View a summary of the Rabies Vaccine Workshop

Comments on the draft proposed guidance document should be submitted to the Center for Veterinary Biologics by April 23, 2012.

NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.