ICCVAM Agency Activities
EPA Requests Nominees for TSCA Advisory Committee
EPA requests nominations of scientific experts for ad hoc participation and possible membership on the Toxic Substances Control Act (TSCA) Science Advisory Committee for Chemicals (SACC). The SACC will be conducting peer reviews of EPA’s risk evaluations for the first 10 chemical substances addressed under TSCA. Nominations must be submitted by October 29.
Any person or organization may nominate qualified individuals, and interested individuals may self-nominate. Nominees should have expertise in one or more of the following areas: women’s health; children’s health; genetic variability; disproportionately exposed populations; aging; other susceptible populations; biochemistry; chemistry; epidemiology; human health risk assessment; pathology; physiologically based pharmacokinetic modeling; pharmacology; ecological risk assessment; environmental fate; environmental toxicology; occupational, consumer, and general exposure assessment; toxicology; dose response modeling; environmental engineering; biostatistics; computational toxicology; fiber science; inhalation toxicology; volatile organics; and systematic review.
Update of ToxTutor Available
The National Library of Medicine has updated its online ToxTutor course. ToxTutor is a self-paced tutorial for users of NLM chemical and toxicology databases that covers the key principles of toxicology.
The August 2018 release of ToxTutor adds "The Microbiome" as a new topic, expands content on alternatives to animal testing and human-on-a-chip testing approaches, and includes induced pluripotent stem cells as an emerging approach for toxicity testing. The tutorial has also added more content on adverse outcome pathways and new sections on "Intuitive Toxicology and Risk Communication" (including content on uncertainty) and "Environmental Toxicology, Environmental Health, and One Health."
FIFRA Advisory Panel to Meet in December, Nominations Requested
The scientific advisory panel for the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA SAP) will meet December 4-7 at EPA in Arlington, VA. The FIFRA SAP provides independent scientific advice, recommendations, and information to the EPA Administrator relating to the impact of pesticide regulatory actions on human health and the environment. The upcoming meeting will focus on "Evaluation of a Proposed Approach to Refine the Inhalation Risk Assessment for Point of Contact Toxicity: A Case Study Using a New Approach Methodology." The meeting is open to the public and will be webcast.
EPA seeks nominees to serve as ad hoc members of the FIFRA SAP for this meeting, specifically nominees with expertise in development and implementation of new approach methodologies. Nominations should be submitted by September 7. More information is available in an August 8 Federal Register notice.
Funding Opportunity to Support Alternative Methods Development
EPA is funding research to promote the development and use of alternative test methods and strategies that reduce, refine, or replace vertebrate animal testing. Pertinent research includes approaches such as analog/read-across techniques, mathematical models, and tiered-testing approaches that integrate evidence from multiple sources to help accomplish these goals. Research activities should advance the science underpinning the use of non-vertebrate test methods and develop actionable alternative approaches for developmental toxicity, reproductive toxicity, or ecotoxicity testing.
This opportunity is expected to fund five grants of up to $850,000 each. Eligible institutions include U.S. state, local, and territory governments; federally recognized Indian tribal governments; and public and private nonprofits, hospitals, and academic institutions located in the U.S. Applications are due September 25.
Funding Available for Tissue Chip Models
The National Center for Advancing Translational Sciences (NCATS) has issued funding opportunities to support development of tissue chip technologies.
FDA Webinar on In Silico Medicine August 9
FDA will present a webinar on “What We’re Doing to Advance In Silico Medicine at FDA.” Tina Morrison, Ph.D., chair of FDA’s Modeling and Simulation Working Group and Regulatory Advisor of Computational Modeling for FDA’s Office of Device Evaluation will give an overview of in silico modeling and simulation approaches used by FDA. Her presentation will highlight success stories with simulation and discuss the potential for in silico clinical trials for advancing medical products. The webinar will be presented on Thursday, August 9, from noon-1:00 p.m. EDT. Continuing education credit is available for viewing the webinar.
NICEATM/EPA Project Receives EPA Award
EPA annually recognizes outstanding scientific work of its employees with the Scientific Technological Achievement Awards (STAA). An EPA collaboration with NICEATM, “Using Novel Zebrafish Toxicity Assays to Evaluate a Predictive Model of Development Vascular Toxicity,” has received a Level III STAA, for projects accomplishing an unusually notable research or technological effort.
Small Business Funding Available for Assessing Nanomaterials Toxicity
The National Institute of Environmental Health Sciences (NIEHS) has issued a funding opportunity to support development of technologies to assess exposure of engineered nanomaterials and characterize their effects on biological systems. In particular, this funding opportunity supports development of mid- to high-throughput assays or high-content assays for characterizing the effects of specific nanomaterials on biological pathways, including cytotoxicity, cellular uptake, inflammatory pathways, and oxidative stress in target tissues.
NIEHS intends to fund four or five awards totaling $1 million in 2019. This funding opportunity is open only to U.S. small business concerns. Applicant organizations may submit more than one application, provided that each application is scientifically distinct. Letters of intent are due August 11, with applications due September 11. More information is available on the National Institutes of Health Grants website.
FDA Workshop on Dermal Safety Testing September 10
The U.S. Food and Drug Administration (FDA) is hosting a workshop on human dermal safety testing for topical drug products. Workshop participants will review current approaches to the collection of human data during clinical development of topical drug products. The workshop will also address the impact of human skin toxicity studies on drug labeling and consider alternative approaches to providing information about skin toxicity.
The workshop will be held on September 10 at the FDA White Oak Campus in Silver Spring, Maryland and will also be webcast. Those interested in attending in person or viewing the webcast should register by September 4. More information about the workshop is available on the FDA website. Information for visitors to the FDA White Oak Campus is also available on the FDA website.
FDA Public Hearing on Predictive Toxicology Roadmap September 12
The U.S. Food and Drug Administration (FDA) is holding a public hearing on Wednesday, September 12, 2018 on its Predictive Toxicology Roadmap. The Agency is seeking comments on how to foster the development and evaluation of emerging toxicological methods and new technologies and incorporate them into regulatory review, as applicable.
The public hearing will be held at the FDA White Oak Campus in Silver Spring, Maryland, and will also be webcast. Those wishing to attend in person or view the webcast must register by Wednesday, August 29, 2018.
Read the June 30 Federal Register notice announcing the public hearing and providing instructions on submitting comments.
Physical Scientist Opportunity at Department of Defense
The Defense Threat Reduction Agency in the Department of Defense is seeking a Physical Scientist to plan, implement, and evaluate research and development programs in drug discovery, development, and safety. Applicants must be U.S. citizens and should have (1) experience in drug discovery and development research and (2) relevant knowledge in the areas of chemistry, biology, toxicology, and the U.S. Food and Drug Administration regulatory process. For more information and to apply, visit the USAJobs website. Applications must be submitted by Wednesday, July 4.
EPA Releases Strategic Plan to Promote Alternative Methods
The U.S. Environmental Protection Agency (EPA) has published its Strategic Plan to Promote the Development and Implementation of Alternative Test Methods Within the TSCA Program. The document describes how EPA will promote development and implementation of methods and strategies that reduce, refine, or replace vertebrate animal testing to provide chemical safety information required under the Toxic Substances Control Act (TSCA).
The core components of the plan are (1) identifying, developing, and integrating new approach methodologies (NAMs) for TSCA decisions; (2) building confidence that the NAMs are scientific reliable and relevant for TSCA decisions; and (3) implementing the reliable and relevant NAMs for TSCA decisions.
FDA Issues Guidance on Nonclinical Testing of Cancer Drugs
In a June 18 Federal Register notice, the FDA announced release of a Q&A to help stakeholders interpret international guidance on nonclinical evaluation of cancer drugs. The Q&A includes statements about reduction of animal use or use of in vitro alternatives in these studies. The Q&A is available on the FDA website.
EPA Biologist/Toxicologist Positions Available, Deadlines Next Week
The U.S. Environmental Protection Agency (EPA) has Biologist/Toxicologist positions open in the Risk Assessment Division of the Office of Pollution Prevention and Toxics within the Office of Chemical Safety and Pollution Prevention. Multiple positions are available for each of the following opportunities:
Report Available from BioMed21 Workshop
The June 2017 BioMed21 workshop, co-organized by NICEATM and the Human Toxicology Project Consortium, examined actions needed to implement a human systems-biology approach to understanding disease and improving interventions. The report from the workshop has been published in the journal Drug Discovery Today.
Agenda and Registration Available for Workshop on Rabies Vaccine Testing
A preliminary agenda and registration are available for a workshop on Implementing Non-animal Approaches to Human and Veterinary Vaccine Testing: Achieving Scientific and Regulatory Success for Rabies and Beyond. The workshop will be held October 16-17 at the Natcher Conference Center, National Institutes of Health, Bethesda, Maryland. It is co-organized by NICEATM and the International Alliance for Biological Standardization. The workshop is open to the public, there is no registration charge, and participants may attend in person or view a webcast.
Testing to ensure effectiveness and safety of vaccines often requires the use of large numbers of animals. However, technological advances have led to the development of methods that could reduce or eliminate the need for animal testing. This workshop will bring together scientific and regulatory leaders from government, academia, and industry to develop recommendations to advance alternative methods for human and veterinary rabies vaccine testing. Workshop sessions will also spotlight state-of-the-science animal alternatives for other antigens and future possibilities for advancing animal reduction and replacement initiatives.
NICEATM Requests Information on Technologies for Detection and Measurement of Botulinum Neurotoxin
NICEATM requests available data and information on approaches and/or technologies currently used for detection and measurement of botulinum neurotoxin (BoNT). Submitted information will be used to assess the state of the science and determine technical needs for non-animal test methods used to detect the presence of BoNT and measure potency of BoNT preparations.
Respondents to this request should provide information on any activities relevant to the development or validation of alternatives to in vivo test methods currently used by federal agencies for regulatory and other decision contexts. NICEATM also requests available data from in vivo BoNT tests used for similar applications as the proposed alternative, such as distinguishing between BoNT serotypes in biological matrix samples or measuring the potency of therapeutic BoNT preparations.
The deadline for receipt of the requested information is July 11. More information is available on the NICEATM website.
NIH Releases Strategic Plan for Data Science, Seeks Chief Data Strategist
Storing, managing, standardizing, and publishing the vast amounts of data produced by biomedical research is a critical NIH mission. In support of this effort, NIH has released its first Strategic Plan for Data Science, which provides a roadmap for modernizing the NIH-funded biomedical data science ecosystem.
The strategic plan calls for the appointment of a Chief Data Strategist. This person will guide the development and implementation of NIH’s data-science activities and provide leadership within the broader biomedical research data ecosystem. The vacancy announcement for the Chief Data Strategist is available on the NIH Jobs website. Applications will be reviewed starting July 9 and will be accepted until the position is filled.
FDA Final Guidance on Toxicokinetics Studies Available
In a May 10 Federal Register notice, the U.S. Food and Drug Administration (FDA) announced availability of final guidance on the benefits and limitations of the use of microsampling techniques in toxicokinetics studies. Benefits of these techniques include reducing the numbers of animals needed for these studies.
Workshop on Pyrogen Testing Methods September 18-19
NICEATM is co-organizing a workshop on September 18-19 with the PETA International Science Consortium to discuss non-animal approaches for pyrogen testing. The workshop will be held at NIH in Bethesda, Maryland, and will focus on the use of the monocyte activation test (MAT) as a standalone release test for medical devices. Registration and materials will be posted on the NICEATM website when available.
Pyrogens are substances such as bacteria, fungi, and viruses that can produce fever. Medical products for implantation or injection must be shown to be free of pyrogens before use. This workshop will bring together scientists and regulatory authorities from government and industry to review the MAT and discuss ongoing challenges such as identifying material-mediated and other non-endotoxin pyrogens. Participants will also describe industry experience and use of the MAT and identify any issues to be addressed to enable its implementation.
NICEATM Requests Information on Technologies for Identifying Developmental Toxicants
NICEATM requests available data and information on approaches and/or technologies currently used for identifying potential developmental toxicants. Submitted information will be used to assess the state of the science and determine technical needs for non-animal test methods used to evaluate the potential of chemicals to induce adverse effects in offspring. The deadline for receipt of the requested information is June 15.
Respondents to this request should provide information on any activities relevant to the development or validation of alternatives to in vivo developmental toxicity test methods currently used by federal agencies for regulatory and other decision contexts. NICEATM also requests available data from in vivo developmental studies, human or animal studies, or accidental human exposures, using the same chemicals used to evaluate the alternative developmental toxicity test methods.
NIEHS Webinars to Discuss New Approaches and Methodologies for Chemical Safety Evaluation
The National Institute of Environmental Health Sciences (NIEHS) Superfund Research Program is hosting a webinar series highlighting research that may be useful as new approaches and methodologies for toxicity testing. This series coincides with recent initiatives found in the EPA draft strategic plan discussed above and the Strategic Roadmap for Establishing New Approaches to Evaluate the Safety of Chemicals and Medical Products in the United States.
Session 1, presented on May 14 at 1:00 p.m. EDT, will discuss “Toxicity Testing Strategies and Model Systems.” Speakers will provide an overview of toxicity testing strategies to advance the use of 21st-century science in chemical safety evaluation. Speakers will also describe the pros and cons of model systems such as zebrafish and cell-based assays in hazard identification.
Session 2, on May 23, will focus on “Tools for Assessing Exposure and Toxicity,” and a third session on May 31 will discuss “Modernizing Safety Testing.” More information and links to register for all three webinars are available on the NIEHS website.
Comments on EPA Draft Strategy Due May 11
Comments on a U.S. Environmental Protection Agency (EPA) draft strategy to reduce use of vertebrate animals in chemical testing are due Friday, May 11. The draft strategy and related documents are available at https://www.regulations.gov/ under docket EPA-HQ-OPPT-2017-0559. Comments received will be considered in the Agency's development of the final strategy. The Frank R. Lautenberg Chemical Safety for the 21st Century Act, which amended the Toxic Substances Control Act, mandated development of the strategy, which was released March 7. The announcement of the draft strategy release is available on the EPA website.
EPA Requests Comments on Draft Policy on Skin Sensitization Testing
On April 10, the U.S. Environmental Protection Agency (EPA) released a draft Science Policy to reduce animal use in testing strategies to evaluate chemicals for their ability to cause an allergic reaction, inflammation, or sensitization of the skin. “This draft policy is another step toward achieving EPA's goal of reducing the use of animals and increasing the use of cutting-edge science in chemical testing,” said EPA Administrator Scott Pruitt in an EPA Office of Pesticide Programs news release.
The draft policy is the result of national and international collaboration among ICCVAM, NICEATM, Cosmetics Europe, the European Union Reference Laboratory for Alternatives to Animal Testing, and Health Canada’s Pest Management Regulatory Agency.
SOT-FDA Colloquium on Testing of Food Mixtures March 27
Humans are routinely exposed simultaneously to numerous chemicals in food, yet risk assessments of chemicals in food rely on test data from individual chemicals. A March 27 colloquium sponsored by the Society of Toxicology (SOT) and the U.S. Food and Drug Administration (FDA) will consider whether new testing approaches such as in vitro assays, in silico models, and non-mammalian in vivo models could be used to assess the potential health impacts of exposure to chemical mixtures in food.
“Can Alternatives Inform a Risk Assessment of Mixtures in Food?” will be held from 8:30 a.m. to 1:00 p.m. at the Wiley Auditorium, FDA Center for Food Safety and Applied Nutrition, College Park, Maryland. Preregistration to attend the colloquium in person has closed; walk-in registration is available to U.S. federal employees only. The colloquium will also be webcast.
NEI Sponsors Competition to Develop In Vitro Models
On February 13, the National Eye Institute (NEI), part of the National Institutes of Health, announced the 3-D Retina Organoid Challenge. This $1 million federal prize competition is designed to support development of lab-grown human retinas from stem cells. Organoids developed for the competition will mimic the structure, organization, and function of the human retina, the light-sensitive tissue in the back of the eye.
In the current phase of the challenge, NEI will award up to $100,000 each to as many as six teams whose models best address the challenge’s scientific criteria. Participating teams must designate a captain who is a U.S. citizen or permanent resident. Private entities participating must maintain a primary place of business in the United States. Federal offices or employees are not eligible to participate, and federal funds may not be used to develop submissions. Submission deadline is October 1; winners will be announced in December. Complete challenge details are available on the NEI website.
EPA Releases Strategic Plan
On February 12, the U.S. Environmental Protection Agency (EPA) released its 2018-2022 Strategic Plan. The Strategic Plan states as one of the EPA’s goals, to “Administer the law, as Congress intended, to refocus the Agency on its statutory obligations under the law.” One of the objectives under this goal is to “prioritize robust science”, which includes an intention to “Use ToxCast/Tox21 data to develop high-throughput risk assessments, particularly for chemicals for which adequate risk assessment information has been historically unavailable.”
NIH Requests Comments on Draft Strategic Plan for Data Science
To capitalize on the opportunities presented by advances in data science, the National Institutes of Health (NIH) is developing a Strategic Plan for Data Science. This plan describes NIH’s overarching goals, strategic objectives, and implementation tactics for promoting the modernization of the NIH-funded biomedical data science ecosystem.
NIH published a Request for Information that seeks input from stakeholders, including members of the scientific community, academic institutions, the private sector, health professionals, professional societies, advocacy groups, patient communities, as well as other interested members of the public. Comments in response to the request can be submitted via the NIH Grants website. To ensure consideration, comments must be submitted by April 2.
NIEHS Offers Funding to Small Businesses for Toxicity Screening, Testing, and Modeling
The National Institute of Environmental Health Sciences (NIEHS) is offering funding for small businesses developing technologies of interest to the Tox21 program. These technologies include improved or expanded testing methods for toxicity screening, computational approaches for predictive toxicology, and other technologies such as alternative or improved methods for fixing and preserving tissues. The funding is being offered as part of the 2018 Omnibus Solicitation of the National Institutes of Health (NIH), Centers for Disease Control, and Food and Drug Administration for small business grant applications to support development and commercialization of innovative technologies.
The next application deadline is March 5. Complete information about the grants is available on the NIH Grants website:
More information about these and other NIH grants is available on the NICEATM website.
USDA Issues Updated Guidance on Vaccine Testing Exemptions
The U.S. Department of Agriculture (USDA) Center for Veterinary Biologics recently added Veterinary Services (VS) Memorandum 800.116 Target Animal Safety Testing Exemption to its website. View all USDA VS Memoranda
VS Memorandum No. 800.116, signed in August 2017, replaces an earlier version issued in July 2013. The memorandum provides guidance to licensed firms on requesting an exemption under title 9, Code of Federal Regulations (9 CFR), part 113.4, to target animal safety testing as required for testing of live and inactivated vaccines and antibody products. Such exemptions can reduce animal use in facilities that have documented consistency in manufacturing processes and product safety.
Grants Offer Support for Tissue Chip Development
The National Institutes of Health (NIH) has announced several funding opportunities for research and development of microphysiological systems (MPS; “tissue chips”) for studying human physiology and assessing toxicity and safety of new drugs and other substances. All of these funding opportunities are open to U.S.-based for-profit, non-profit, academic, and government institutions.
Information about these and other funding opportunities for alternative methods development is available on the NICEATM website.
USDA Releases Guidance Documents on Animal Health
The U.S. Department of Agriculture (USDA) administers the Animal Welfare Act, which sets standards for the humane care and treatment of animals used in research. USDA Animal Care has developed two Tech Notes for Animal Welfare Act licensees and registrants to help improve adherence to animal welfare standards.
Publication of the two Tech Notes was announced in a December 15 USDA Animal and Plant Health Inspection Service bulletin. The recent Tech Notes and other publications relevant to animal welfare are available on the USDA Animal Welfare website.
NIDDK Offers Support for Development of Tissue Chips
The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) is establishing a new research consortium "Microphysiological Systems for Modeling Diabetes." This consortium will support the development and validation of human tissue chips that closely mimic the normal physiology of key metabolic tissues, including the pancreatic islet, liver, skeletal muscle, and white adipose tissue. An essential feature of this consortium will be a multidisciplinary approach that brings together basic science experts and physician scientists in stem cell biology, bioengineering, computational biology, pharmacology, liver biology, islet biology, adipose biology, metabolism and diabetes.
To establish the consortium, NIDDK intends to commit up to $3 million per year for Fiscal Years 2018 through 2019, and up to $6 million per year for Fiscal Years 2020 through 2022 to fund 2-3 awards. Eligible institutions include U.S.-based higher education institutions, nonprofits, for-profit organizations, and government entities.
Letters of intent are due February 20, 2018; applications are due March 20, 2018. Complete funding information is available on the NIH Grants website. Helpful information about applying for NIH grants is available on the NICEATM website.
FDA Launches Predictive Toxicology Roadmap
In an article published December 6 on the FDA Voice blog, the U.S. Food and Drug Administration (FDA) announced publication of FDA’s Predictive Toxicology Roadmap for integrating predictive toxicology methods into safety and risk assessments. The Predictive Toxicology Roadmap presents a framework for new or enhanced FDA engagement in the science of toxicology that includes six elements:
FDA will be holding a public workshop as part of its efforts to foster opportunities for sharing ideas, discussing new technologies, and highlighting collaborations to develop and test new methods.
Read the complete blog post, with links to the Predictive Toxicology Roadmap and related activities
Computational Toxicology Communities of Practice Webinar Series
The U.S. Environmental Protection Agency (EPA) will present a webinar titled “High-Throughput H295R Steroidogenesis Assay: Utility as an Alternative and a Statistical Approach to Characterize Effects on Steroidogenesis” on Thursday, December 14, from 11:00 a.m.-noon U.S. Eastern Time. The speaker is Dr. Derik Haggard, ORISE Postdoctoral Fellow with the EPA National Center for Computational Toxicology.
To access the webinar via Adobe Connect, go to the EPA web conferencing website. To listen in via telephone, call (866) 299-3188 (toll-free U.S.) or (706) 758-1822 (international toll number) and use the conference code 9195411522. Those in the Research Triangle Park, North Carolina, area who would like to attend the seminar in person should email Cameron Clark.
This is the latest in EPA’s Computational Toxicology Communities of Practice webinar series. Visit the EPA website for more information about the webinar series and slides and recordings from past webinars.
Workshop Examines Use of New Data Streams in Decision Making
The National Academies of Science, Engineering, and Medicine will present a workshop on Understanding Pathways to a Paradigm Shift in Toxicity Testing and Decision Making on November 20-21 in Washington, DC.
Technological advances have led to new approaches to understanding the toxicity of chemicals in humans. However, many questions remain about whether and how to make the shift to using new data streams as the basis for the wide array of research, policy, and regulatory decisions. This workshop will explore key factors that influence how scientists, policymakers, risk assessors, and regulators incorporate new science into their decisions. John Bucher, Ph.D, Associate Director of the National Toxicology Program and Stanley Barone, Ph.D., Acting Director, Environmental Protection Agency Office of Science Coordination and Policy served on the workshop organizing committee.
The workshop is free and will be webcast. More information and a link to registration are available on the National Academies website.
Webinar Series on Adverse Outcome Pathways
The Superfund Research Program of the National Institute of Environmental Health Sciences (NIEHS) is presenting a webinar series on adverse outcome pathways (AOPs), structured ways to represent biological events leading to adverse health effects. The second webinar in the series will be presented November 29. Presenters will discuss the development of AOPs and how they may be used to support hazard and risk assessment.
The webinar will be hosted on the EPA Contaminated Site Clean-Up Information website; registration is free. More information about the webinar series is available on the NIEHS website. This page has a link to a recording of the first webinar in the series, which introduced the AOP concept.
The webinar series provides background information for an April 2018 workshop on Understanding the Combined Effects of Environmental Chemical and Non-Chemical Stressors: Atherosclerosis as a Model. The workshop is being planned and public comments are welcomed: please visit the NIEHS website for details.
Draft Guidance for Reproductive Toxicity Testing
The U.S. Food and Drug Administration (FDA) has requested comment on draft guidance ICH S5(R3), “Detection of Toxicity to Reproduction for Human Pharmaceuticals.” This document clarifies the qualification and potential use of alternative assays to assess reproductive risk and includes a list of compounds suggested for qualification of assays. FDA recognizes that this list is not complete and is requesting information on potential additional compounds to be added to the list.
The draft guidance ICH S5(R3) is available on the FDA website. An announcement in the November 13 Federal Register includes instructions on submitting comments on the draft guidance. To ensure consideration as the guidance is finalized, comments should be received by February 12, 2018.
Public Meeting on EPA Plan to Promote Alternative Tests November 2
The Frank R. Lautenberg Chemical Safety for the 21st Century Act amended Section 4(h) of the Toxic Substances Control Act (TSCA) to require the U.S. Environmental Protection Agency (EPA) to promote the development and implementation of alternative test methods and strategies to reduce, refine, or replace vertebrate animal testing. The Act requires EPA to develop a Strategic Plan for this purpose by June 22, 2018.
EPA will hold a public meeting on November 2 to obtain input from interested parties and the public on the Agency's development of the Strategic Plan. EPA believes this early feedback will be important in developing a strong Plan. The Agency will consider input from the meeting and from written comments to develop a draft Plan that will be shared with the public for comment.
The meeting will be held from 9:00 a.m.-5:00 p.m. at the Porter Neuroscience Research Center, National Institutes of Health, Bethesda, Maryland. The meeting is open to the public with attendance restricted only by the space available, and will also be webcast. It is being co-organized by EPA and ICCVAM.
Goals and objectives to inform the Strategic Plan are available on the EPA website at and may be used for discussion and comment during the meeting. Interested parties may provide input about the draft Strategic Plan during the meeting. Written comments may be submitted to docket EPA-HQ-OPPT-2017-0559 at www.regulations.gov. The deadline for receipt of written comments is January 1, 2018.
EPA Seeks Input on Endocrine Panel Questions: Webinar November 6
EPA will hold a virtual meeting on November 6 to get public input in advance of a November 28-30 meeting of the Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (FIFRA SAP). Both meetings will focus on the topic of “Continuing Development of Alternative High-Throughput Screens to Determine Endocrine Disruption, focusing on Androgen Receptor, Steroidogenesis, and Thyroid Pathways.”
The FIFRA SAP will meet in person on November 28-30 to discuss high-throughput screens to determine endocrine disruption. The purpose of the November 6 virtual meeting is to get input from the panel and the public on the draft charge questions for the in-person meeting.
Those wishing to make oral comments during the November 6 virtual meeting should register by noon on Wednesday, November 1. Those wishing to listen in on the meeting may register at any time. Written comments on the scope and clarity of the draft charge questions should be submitted to docket EPA-HQ-OPP-2017-0214 on www.regulations.gov by noon, November 1. More information about the FIFRA SAP is available on the EPA website.
SOT and FDA Present Free Webinar October 24
The Society of Toxicology (SOT) and the U.S. Food and Drug Administration (FDA) Center for Food Safety and Applied Nutrition will present a colloquium on October 24 on In Vitro to In Vivo Concordance for Toxicity Prediction and Use in Safety Assessments. This program is the latest in the series SOT FDA Colloquia on Emerging Toxicological Science: Challenges in Food and Ingredient Safety. The October 24 colloquium will feature expert reviews on state-of-the-art in vitro technologies for safety assessment and how they are being utilized.
The colloquium will be held from 8:30 a.m. to 1:00 p.m. at the FDA Wiley Federal Building in College Park, Maryland, and will also be webcast. Registration for either in-person attendance or webcast viewing is free. In-person attendance is available to U.S. federal employees only, and those planning to attend in person must register by October 10. More information is available on the SOT website.
NIEHS Offers Grants for Development of Culture Models
NIEHS is providing grants for development of novel in vitro systems using cells from experimental animal models typically used for toxicology testing. The intent is that these systems will replicate biological responses within the corresponding animal tissues or organs. When developed and validated, these systems will provide information needed to predict toxicity of chemical and drug candidates, enable comparisons with existing in vivo animal toxicity data, serve as newer assays for toxicology testing, and have the potential for reducing the numbers of animals used in toxicology testing.
These grants of up to $150,000 for Phase I awards and up to $1 million for Phase II awards are only available to U.S. small businesses. Applications will be accepted starting December 12, with an application due date of January 12, 2018. Applicants are encouraged to apply early to allow time before the due date to correct errors that may be found in the application. Details about the grants are available on the National Institutes of Health (NIH) website.
New Review Describes Use of AOPs in EPA Screening Program
A review in the September issue of the journal Environmental Health Perspectives describes how the U.S. Environmental Protection Agency (EPA) uses adverse outcome pathway (AOP) and toxicity pathway frameworks in its Endocrine Disruptor Screening Program. The review, co-authored by NICEATM Director Warren Casey, describes how these frameworks help to establish biologically plausible links between endocrine mechanisms and apical responses when those end points are not measured in the same assay.
NTP to Present Webinars on Genomic Dose-response Modeling
An ongoing NTP webinar series focuses on the use of genomic features to assess dose-related response to test article treatment. The first two webinars, presented August 30 and September 1, discuss approaches to genomic dose-response modeling being explored by NTP and the U.S. Army Engineer Research and Development Center, respectively. Webinars to be presented later in September will discuss methods developed at North Carolina State University and the National Center for Advancing Translational Sciences.
The webinars are free and open to the public. More information is available on the NTP website; recordings of past webinars will also be available on this page.
EPA Requests Comment on Candidates for Advisory Panel
The U.S. Environmental Protection Agency (EPA) will hold a meeting of the Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (FIFRA SAP) on November 28-30 in Arlington, Virginia. The FIFRA SAP provides scientific advice, information, and recommendations to the EPA Administrator on pesticides and pesticide-related issues as to the impact of regulatory actions on health and the environment. The November meeting will focus on “Continuing Development of Alternative High-Throughput Screens to Determine Endocrine Disruption, focusing on Androgen Receptor, Steroidogenesis, and Thyroid Pathways.”
A list of ad hoc candidates to serve on the panel at the November meeting has been posted on the EPA website. EPA is accepting comments on the candidates through Thursday, September 7. Comments on panel nominees should be provided to the Designated Federal Official, Dr. Todd Peterson, via email at email@example.com or telephone at (202) 564-6428.
NIH to Hold Small Business Workshop
The National Institutes of Health (NIH) will hold a Multi-Institute Small Business Workshop September 7-8, in New Orleans. This event will inform attendees about the NIH Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) Programs, which provide support for researchers developing new methods for testing of chemicals. The workshop will feature presentations from the National Institute of Environmental Health Sciences and other institutes, and provide detailed guidance for applying to these funding programs and successfully managing an award. Attendees will interact with SBIR/STTR program staff, investors, commercialization experts, and successful entrepreneurs.
Exemptions Help Reduce Live Animal Use in Leptospira Vaccine Potency Testing
Leptospirosis is a transmissible bacterial disease of animals and humans caused by infection with any of the pathogenic members of the genus Leptospira. The organism is shed in the urine and milk of infected animals and may cause symptoms of renal and hepatic disease, which could be fatal. Disease transmission to man and animals is reduced by the vaccination of cattle, swine, and dogs. In light of this, the potency of these vaccines must be tested by law.
In April 2017, the U.S. Department of Agriculture–Animal and Plant Health Inspection Service–Center for Veterinary Biologics (USDA-APHIS-CVB) issued CVB Notice 17-06, “Option to Remove Back-titration Hamsters from In Vivo Potency Tests for Leptospira Serogroups Pomona and Grippotyphosa.” This notice permits the removal of back-titration hamsters when potency testing vaccines containing L. pomona and L. grippotyphosa in accordance with 9 CFR 113 §101-104. This exemption to the codified test can reduce animal use up to 50% for these serogroups. CVB Notice 17-06 along with the 2015 CVB Notice 15-13, “Option to Remove Back-titration Hamsters from In Vivo Potency Tests for Leptospira Serogroups Canicola and Icterohaemorrhagiae” are available on the USDA-APHIS website.
CVB Notice 17-06 is the latest action in a continuing effort by USDA, an ICCVAM member, to reduce the number of hamsters required for potency testing of leptospirosis vaccines. In 2013, APHIS issued Veterinary Services Memorandum No. 800.102, which permitted the use of the in vitro ELISA test developed by CVB as a complete alternative to live animal usage required under 9 CFR 113 §101-104. CVB provides supplemental assay methods for in vitro testing using the ELISA test. All of these documents are available on the NICEATM website.
Small Business Phase II Grants for Alternative Methods Development
The National Institute of Environmental Health Sciences is funding grants to U.S. small businesses for development of medium- to high-throughput assays. Assays developed under these grants should evaluate the effects of toxicants on pluripotent or induced pluripotent cells with respect to cell differentiation and the resulting differentiated cell populations. The ability to incorporate genetic diversity in these assays would be useful. Results from these assays should help identify mechanisms of chemically induced biological activity, prioritize chemicals for more extensive toxicological evaluation, and support more predictive models of in vivo biological response.
Letters of intent for this funding opportunity are due September 4, with applications due October 4.
Full funding announcement on NIH website (posted June 23)
Postdoctoral Fellow Opportunity in Computational Toxicology
A computational toxicology postdoctoral fellowship is available at NIEHS. The successful candidate will develop and apply computational methods, tools, and applications across projects in the areas of computational toxicology, bioinformatics, and computational biology. Candidates should have a Ph.D. in computational biology, computer science, biomedical engineering, bioinformatics, or a related discipline. Programming skills are required, ideally in R and/or Python. Experience in Bayesian modeling, deep belief networks, and the application of computational methods to high throughput screening data are highly desirable. Excellent verbal and written communication skills and the ability to simultaneously work on a variety of diverse projects are essential.
The position is in the Computational Toxicology group in the Biostatistics and Computational Biology Branch of the NIEHS Division of Intramural Research. The Computational Toxicology group is led by NICEATM Deputy Director Nicole Kleinstreuer. To apply, send curriculum vitae including publication list, brief summary of past/current research, and the names of three references to firstname.lastname@example.org.
Small Business Grants Available for Alternative Methods Development
The Department of Health and Human Services has released a new solicitation of Small Business Innovation Research and Small Business Technology Transfer applications for grants funded by the National Institutes of Health and other agencies. Included in this solicitation are funding opportunities for technologies to improve predictivity in toxicology testing offered by the National Institute of Environmental Health Sciences.
More information about the grant solicitation and other funding opportunities is available on the NICEATM website. An informational webinar about the 2017 HHS omnibus grant solicitation will be presented on Thursday, June 29, at 2:00 p.m. EDT.
EPA Announces Meetings, Requests Nominations of Panel Members
The Environmental Protection Agency will hold two meetings of the Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (FIFRA SAP) in the coming months. Both meetings will be held at EPA in Arlington, Virginia. The FIFRA SAP provides scientific advice, information, and recommendations to the EPA Administrator on pesticides and pesticide-related issues impacting health and environmental regulatory actions. EPA is requesting nominations for experts to serve as ad hoc members of the FIFRA SAP for each of these meetings. Nominations for either panel should be submitted by July 21.
The Oct. 24-27 FIFRA SAP meeting will consider and review physiologically based pharmacokinetic modeling to address pharmacokinetic differences between and within species. Nominees to serve on the expert panel for the meeting should have expertise in areas including physiologically based pharmacokinetic modeling, pharmacokinetics, pharmacodynamic modeling, in vitro to in vivo extrapolation, human health risk assessment, neurotoxicity, and exposure assessment.
The Nov. 28-30 FIFRA SAP meeting will consider and review the “Continuing Development of Alternative High-Throughput Screens to Determine Endocrine Disruption, Focusing on Androgen Receptor, Steroidogenesis, and Thyroid Pathways.” Nominees to serve on the expert panel for the meeting should have training and experience in computational model development, high-throughput assay development, biostatistics and performance-based validation, as well as general expertise in toxicology, physiology, biochemistry, endocrinology, and epidemiology.
FDA Reaches Food Safety Agreement with Australia
FDA has signed an arrangement with the Australian Department of Agriculture and Water Resources recognizing that their food safety systems are comparable. This recognition means that the FDA and Australian Department of Agriculture and Water Resources are confident that they can leverage each other’s science-based regulatory systems to ensure food safety, and establishes a framework for regulatory cooperation in a variety of areas ranging from scientific collaboration to outbreak response. FDA has similar agreements with New Zealand and Canada.
FDA Partners with Industry to Develop Organs-on-Chips
On April 11, the U.S. Food and Drug Administration (FDA) announced a multi-year research and development agreement with Emulate, Inc., to evaluate the company’s “Organs-on-Chips” technology in laboratories at the FDA’s Center for Food Safety and Applied Nutrition. The project will focus first on developing a liver chip, but the agreement may expand in the future to kidney, lung, and intestine models. The ultimate goal is to predict how specific organs will respond to potential chemical hazards found in foods, cosmetics, or dietary supplements more precisely than with current methods.
More details about the agreement are available in an FDA blog article by FDA ICCVAM representative Suzanne Fitzpatrick.
New Agency Joins ICCVAM
The National Institute of Standards and Technology has joined ICCVAM. NIST participation will provide ICCVAM with interest and experience in the study of process controls, measurement artifacts, and interlaboratory testing.
ICCVAM was established to facilitate and promote development and regulatory acceptance of new toxicological tests with the potential to replace, reduce, or refine animal use. The expertise within NIST will benefit ICCVAM, especially in the development of validation studies to assess the appropriateness of new test methods for specific purposes. In particular, NIST has experience with cell-based and small model organism assays, which are becoming increasingly important as alternatives for traditional animal tests. NIST also brings to ICCVAM additional expertise in experimental design and statistical analysis.
This event represents the first time ICCVAM has expanded its membership to include a new member agency since its inception in 2000. NIST, which is part of the U.S. Department of Commerce, has been interacting with ICCVAM since 2015. The agency submitted an official request to join ICCVAM in January 2017, which was approved in February by National Institute of Environmental Health Sciences Director Linda Birnbaum.
NICEATM and ICCVAM Activities at SOT
NICEATM and ICCVAM will be participating in two exhibitor-hosted sessions.
In other SOT activities, ICCVAM representatives will serve as co-chairs for five platform sessions, NICEATM scientists are co-authors on 10 poster or platform presentations, and ICCVAM members are co-authors on 18 presentations. Visit the NICEATM webpage summarizing SOT 2017 activities.
NICEATM to Present Webinar Series on Zebrafish Screening
A NICEATM webinar series on “Using Informatics to Improve Data Analysis of Chemical Screening Assays Conducted in Zebrafish” begins on February 2. This three-part webinar series will consider the issues of protocol variability in zebrafish screening studies and how some of these issues might be addressed by implementation of standardized nomenclature systems.
The webinars are free and open to the public, although registration is required to attend. The webinar series is being organized by NICEATM in support of the National Toxicology Program’s Systematic Evaluation of the Application of Zebrafish in Toxicology (SEAZIT) program. A link to registration, details about all webinars, and more information about SEAZIT can be found on the NICEATM website.
Voluntary Pilot Program to Reduce Animal Testing
On December 20, 2016, the U.S. Environmental Protection Agency launched a voluntary pilot program to evaluate the usefulness and acceptability of a mathematical tool that estimates the toxicological classification of a chemical, and published guidance on how pesticide companies can submit data for the program. This program is another step toward EPA’s goal of reducing animal testing by adopting better testing methods, as described in the March 2016 Letter to Stakeholders issued by Office of Pesticide Programs Director Jack Housenger.
The mathematical tool, known as the GHS Mixtures Equation, is used in the Globally Harmonized System of Classification and Labeling of Chemicals (GHS). Use of the GHS Mixtures Equation can reduce animal use for oral and inhalation toxicity studies of pesticide formulations.
To evaluate the GHS Mixtures Equation, EPA requests submission of acute oral and acute inhalation toxicity study data paired with mathematical calculations (GHS Mixtures Equation data) to support the evaluation of pesticide product formulations. EPA expects that the pilot will run for approximately six months but will begin data analysis sooner if enough data is received.
National Toxicology Program Level of Concern Study Phase 2 Recruitment
The National Toxicology Program uses Level of Concern categories to communicate its opinion about whether an environmental substance might cause adverse effects in humans. This study aims to update the Level of Concern categories to better inform and protect public health. If you are a public health professional who is familiar with toxicological risk communication tools, please join this important study and share it with interested colleagues. Eligible participants will be individuals who have a M.S., Ph.D., M.D., or equivalent degree and at least three years of experience in toxicology, epidemiology, risk assessment, or a related field.
NICEATM Research Featured in Special Issue of Reproductive Toxicology
NICEATM Deputy Director Nicole Kleinstreuer is senior author on one article and co-author on a second article to be included in a special issue of Reproductive Toxicology focused on developmental angiogenesis. The articles describe collaborations among NICEATM, the U.S. Environmental Protection Agency, and other investigators to use transgenic zebrafish to test predictions made using adverse outcome pathways on how chemicals can disrupt blood vessel formation during development. Links to the articles by McCollum et al. and Tal et al. are available on the NICEATM publications page.
New Guidance for Testing Pesticides Will Reduce Animal Testing
On November 30, the U.S. Environmental Protection Agency (EPA) published "Guidance for Waiving Acute Dermal Toxicity Tests for Pesticide Formulations and Supporting Retrospective Analysis." The new guidance expands the potential for data waivers for acute dermal studies and includes a policy statement to waive all acute lethality dermal studies for formulated pesticide products. EPA expects this waiver guidance to reduce the use of laboratory animals, potentially up to 2,500 or more each year. The guidance document is available on the EPA website.
AR Pathway Article Named Editors’ Choice
NICEATM Deputy Director Nicole Kleinstreuer is the lead author on a paper describing an androgen receptor pathway model that incorporates 11 high throughput screening assays. “Development and Validation of a Computational Model for Androgen Receptor Activity,” which was published online on November 18 in Chemical Research in Toxicology, has been selected as an ACS Editor’s Choice Article. This selection was based on recommendations by the scientific editors of ACS journals around the world. With this designation, the article becomes open access, meaning it can viewed by anyone regardless of institutional affiliation or subscription status. The article is on the ACS Publications website.
NLM Requests Stakeholder Input for Strategic Plan
In a November 8 Request for Information, the National Library of Medicine announced that it is soliciting stakeholder input as part of its ongoing strategic planning process. The RFI and NLM’s planning process are organized around the role of NLM in these four areas:
The November 8 RFI is intended to obtain public input on goals and priorities for NLM’s next strategic plan. Many NLM stakeholders replied to a similar RFI in 2015 in the context of NLM’s leadership transition and emerging NIH data science priorities. Input provided in 2015 is already under consideration and does not need to be re-submitted.
The deadline for responses to the November 8 RFI is January 9, 2017. More information about the RFI, including how to submit input, is available on the National Institutes of Health Grants website.
Kleinstreuer Receives Lush Cosmetics’ Young Researcher Prize
In a November 2 ceremony, NICEATM Deputy Director Nicole Kleinstreuer received the Lush Cosmetics’ Young Researcher Prize recognizing efforts to eliminate animal use for chemical safety testing. Five researchers in the Americas received the honors presented at Lush Cosmetics headquarters in Vancouver.
Kleinstreuer is the first U.S. federal government employee to receive a Lush Prize. She is also part of a group of U.S. federal employees named as finalists for the Science prize for advancing non-animal approaches to identify endocrine-active substances. Lush Prize winners in this and other categories will be announced later in November.
A list of the 2016 Young Researcher Prize winners from the Americas and more information about the Lush Prize are available on the Lush Prize website. Video summaries of the prize winners’ work are available on the Lush Cosmetics website.
NICEATM Requests Data on Zebrafish Embryo Chemical Screening
NICEATM requests available data and information on zebrafish embryo screening tests and protocol design, including pharmacokinetics measurements. Submitted information will be used to assess the state of the science and determine technical needs for non-animal test methods used to evaluate the potential of chemicals to induce developmental effects in offspring. Respondents to this data request should provide information on any activities relevant to the development or validation of zebrafish embryo screening assays.
NICEATM specifically requests information on efforts to optimize zebrafish embryo screening tests and protocol design including comparisons of (1) zebrafish strains, (2) embryos with and without an intact chorion, and (3) static and static renewal exposures. NICEATM is also interested in developing a better understanding of pharmacokinetics in the zebrafish embryo model and requests available data on chemical uptake.
More information on this data request, including guidelines for data submission, is available on the NICEATM website. The deadline for receipt of the requested information is December 30, 2016.
Resources From the National Library of Medicine: ToxTutor and ALTBIB
The National Library of Medicine has updated its online ToxTutor course. ToxTutor is a self-paced tutorial for users of NLM chemical and toxicology databases that covers the key principles of toxicology. The ToxTutor update incorporates recent advances in the science of toxicology, provides more information on alternatives to animal testing, and features responsive design to support use on mobile devices. ToxTutor is available on the NLM website.
A December 8 NLM webinar will introduce new users to the NLM database ALTBIB: Resources for Alternatives to the Use of Live Vertebrates in Biomedical Research and Testing. The webinar will describe the history, purpose, and scope of ALTBIB, identify key people who work on ALTBIB, and demonstrate the features of the resource. Participants will gain hands-on experience with practice exercises and leave the webinar with a sense of what ALTBIB can and cannot do for animal alternative searches. The webinar is free and open to residents of the United States.
NTP Requests Data on Alternative Methods to Assess Inflammation or Exaggerated Immune Responses
The National Toxicology Program at the National Institute of Environmental Health Sciences requests available data and information on approaches and/or technologies currently used to identify substances with the potential to cause excessive inflammation or exaggerated immune responses leading to tissue injury when swallowed, inhaled, or absorbed through the skin. Submitted information will be used to assess the state of the science and determine technical needs for non-animal test methods that could be used to evaluate the potential of chemicals to induce inflammation and immune-related conditions.
View Federal Register notice announcing the data request
NICEATM Director Participates in Congressional Briefing
NICEATM Director Warren Casey was a panelist for a September 13 Congressional briefing on “Alternatives to Animal Testing: Emerging Uses and Policy Implications.” Casey and other panelists discussed how to use non-animal and alternative toxicology and safety testing methods to better protect consumers and public health while using fewer animals. Topics considered included how to spark research that advances the development and application of alternatives, as well as what policy discussions are required to ensure regulatory frameworks can adapt while realizing the fastest possible innovation. The briefing was organized by the American Chemical Society and the Johns Hopkins Bloomberg School for Public Health, and sponsored by the offices of Representatives Earl Blumenauer (D-OR) and Ken Calvert (R-CA).
Computational Biology Symposium September 16
PLoS Computational Biology is presenting a Computational Biology Symposium on the National Institutes of Health campus on Friday, September 16, from 9:30 a.m.-4:00 p.m. Keynote speakers will include Dr. David J. Lipman of the National Center for Biotechnology Information, Dr. Jennifer Lippincott-Schwartz of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and Dr. Bert Vogelstein of Johns Hopkins Medical Institutes. The agenda also includes two discussion panels comprised of PLoS Computational Biology editors from a range of fields. The morning panel will consider the “Biggest Challenges and Greatest Opportunities in Computational Biology over the Next 10 Years,” while the topic of the afternoon panel is “How Computational Biology Will Affect Human Health.”
The symposium is open to all National Institutes of Health staff and the wider community. Attendance is free and no preregistration is required. More information is available on the PLoS website. The symposium will also be webcast; more information about the webcast is available on the NIH Videocast website.
Comments Requested on Draft Guidance for Toxicokinetics Studies
A U.S. Food and Drug Administration (FDA) notice in the September 8 Federal Register requested comments on draft guidance titled “ICH S3A Guidance: Note for Guidance on Toxicokinetics: The Assessment of Systemic Exposure in Toxicity Studies—Questions and Answers.” The draft guidance facilitates interpretation of the ‘‘S3A Guidance: The Assessment of Systemic Exposure in Toxicity Studies,’’ especially to address the benefit and use of microsampling techniques in main study animals. The Q&A guidance is intended to provide points to consider before incorporating the microsampling method in toxicokinetic studies, and acknowledges the benefits (and some limitations) of the use of microsampling. Comments on the draft guidance are requested by December 7.
Chips in Space
The National Center for Advancing Translational Sciences (NCATS) and the Center for the Advancement of Science in Space are promoting a new program for research on the International Space Station United States National Laboratory (ISS-NL): we’re sending tissue chips to space! This program will leverage recent advances in tissue engineering and microfabrication to create microphysiological systems and organ-on-chip technology platforms to better understand the molecular and cellular basis of human disease in microgravity. Translation of this research to the ISS-NL promises to accelerate the discovery of molecular mechanisms that underlie a range of common human disorders and advance understanding of therapeutic targets and treatments in a reduced fluid shear, microgravity environment that recapitulates cellular and tissue matrices of Earth.
NCATS has published a notice of intent to publish a funding opportunity for this initiative. Grant applications are not currently being solicited, but interested investigators are encouraged to begin developing meaningful collaborations and responsive projects.
Comments Requested on Proposed Amendments to GLP
A Proposed Rule published by the U.S. Food and Drug Administration (FDA) in the August 24 Federal Register describes amendments to the regulations for good laboratory practice (GLP) for nonclinical laboratory studies. The new amendments will require a complete quality system approach, referred to as a GLP Quality System, when safety and toxicity studies support or are intended to support applications or submissions for products regulated by FDA. FDA is proposing additional management responsibilities and standard operating procedures consistent with the proposed requirement for a GLP Quality System. In addition, the testing facility definition will be revised to reflect current practices for the conduct of nonclinical laboratory studies, particularly multisite studies. These proposals are intended to build quality into planning, conducting, and reporting a nonclinical laboratory study and to help ensure data quality and integrity. Comments on the Proposed Rule are due by November 22.
Workshop Report on Carcinogenicity of Mixtures Now Available
An August 2015 workshop sponsored by the National Institute of Environmental Health Sciences evaluated the scientific support for the Low-Dose Mixture Hypothesis of Carcinogenesis and developed a research agenda. A report from this workshop is now available on the Environmental Health Perspectives website. NICEATM Deputy Director Nicole Kleinstreuer, Ph.D., was a breakout group moderator and co-authored the report.
The Low-Dose Mixture Hypothesis of Carcinogenesis suggests that ongoing low-dose exposures to mixtures of commonly encountered environmental chemicals can produce effects in concert that promote carcinogenesis. The workshop report describes the science that supports this novel theory, identifies knowledge gaps, recommends future methodologies, and explores preventative risk assessment and policy decision making that incorporates cancer biology, environmental health science, translational toxicology, and clinical epidemiology. The workshop participants concluded that the theoretical merits of the Low-Dose Carcinogenesis Hypothesis are well founded with clear biological relevance and the premise warrants further investigation.
TSCA Reform Bill Becomes Law, Will Promote Use of Alternatives
A bill signed into law June 22 by President Obama updates the Toxic Substances Control Act (TSCA). The Frank R. Lautenberg Chemical Safety for the 21st Century Act (H.R. 2576) provides the Environmental Protection Agency (EPA) with the authority and a consistent source of funding to evaluate chemicals on the basis of health risks. The new law also includes language that requires EPA to develop a plan to promote the use of alternative methods that reduce, refine, or replace vertebrate animal testing and include in that plan a list of acceptable alternative methods.
The highlights of the Lautenberg Chemical Safety Act were outlined in a blog post by EPA Administrator Gina McCarthy. A news release from the Physicians Committee for Responsible Medicine summarizes aspects of the bill relevant to alternative methods development.
FDA Issues Final Guidance and Presents Webinar on Biological Evaluation of Medical Devices
The Food and Drug Administration (FDA) has issued a final guidance document on the use of International Standard ISO 10993-1, “Biological Evaluation of Medical Devices – Part 1: Evaluation and Testing Within a Risk Management Process.” FDA developed the guidance document to assist industry in preparing applications and notifications on medical devices so that the devices are appropriately evaluated for the potential for adverse reactions.
FDA will present a webinar on the new guidance on July 21 at 1:00 p.m. Eastern Daylight Time. The webinar is open to the public and there is no charge to view.
EPA Releases Training Videos on Data Requirements for Antimicrobials
EPA is releasing five training videos providing guidance on EPA’s 40 CFR Part 158W data requirements for antimicrobial pesticides. These training videos will help the public and the pesticide industry better understand the pesticide registration process and make the process more efficient and transparent. The videos include the 2013 amendments to the data requirements that were made to ensure pesticide risk management decisions are founded on the best available sound science.
Additional videos will be released in the future as they become available. The videos are available on the EPA website.
New Guidance for Testing Pesticides Will Reduce Animal Testing
In a March 17 press release, EPA announced the publication of two guidance documents and initiation of a pilot program, all of which will support its goal to significantly reduce animal use for acute effects testing.
“Process for Establishing & Implementing Alternative Approaches to Traditional In Vivo Acute Toxicity Studies for FIFRA Regulatory Use” describes a transparent, stepwise process for evaluating and implementing alternative methods for the “six-pack studies,” which test for acute oral, dermal, and inhalation toxicity; skin and eye irritation; and skin sensitization. The document includes discussion of three major phases of the evaluation and implementation process, as well as the implications for reporting information required by the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA). Establishment of this process and the clear articulation of the related reporting requirements address challenges associated with adopting alternative methods.
EPA is also requesting comment on draft guidance titled “Retrospective Analysis & Guidance for Waiving Acute Dermal Toxicity Tests for Pesticide Formulations.” This guidance document provides a rationale for waiving all acute dermal toxicity studies for pesticide formulations, and includes a data analysis conducted by the EPA Office of Pesticide Products (OPP) and NICEATM in support of this rationale. EPA is accepting comments on the guidance document until May 16.
Availability of the two documents was announced in an open letter to stakeholders from OPP Director Jack Housenger, who also announced a pilot program to evaluate alternative approaches to classify the toxicity of mixtures. Under the GHS Mixtures Equation Pilot, OPP will accept submission of oral and inhalation toxicity data paired with calculations done in accordance with the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) to support the evaluation of pesticide product formulations.
NICEATM Deputy Director to Receive Teratology Society Award
NICEATM Deputy Director Nicole Kleinstreuer, Ph.D., has been named to receive the 2016 F. Clarke Fraser New Investigator Award from the Teratology Society. This award recognizes an active Teratology Society member that has, within 10 years of completion of training, established a successful independent research career in a field relevant to developmental biology. Kleinstreuer will be presented with her award during the Society’s Annual Meeting in June, at which she will give a plenary presentation about her research.
NICEATM Director Elected to Lead SOT IVAM Specialty Section
NICEATM Director Warren Casey, Ph.D., has been elected Vice President-Elect of the In Vitro and Alternative Methods (IVAM) Specialty Section of the Society of Toxicology (SOT). Casey will serve as Vice President-Elect for 2016-2017 and will then serve subsequent one-year terms as Vice President, President, and Past President of the specialty section.
The SOT IVAM Specialty Section members have expertise or special interest in the application of in vitro techniques to address problems of cellular toxicity, with a special emphasis on product safety evaluation. IVAM interests include the study of cellular processes involved in adverse outcomes of specific organs as well as whole animals, and the development of systems to predict in vivo toxicity for risk assessment purposes. Other topics of interest include in vitro test validation and all aspects of test development and acceptance for individual or regulatory purposes.
EPA and NIH Centers Launch Transform Tox Testing Challenge
U.S. government agencies are offering awards totaling $1 million to improve the relevance and predictivity of data generated from automated technology used for toxicity testing.
In a Jan. 8 press release, the U.S. Environmental Protection Agency (EPA) announced that it is partnering with the National Center for Advancing Translational Sciences and the National Toxicology Program to sponsor the Transform Tox Testing Challenge: Innovating for Metabolism. The challenge calls on innovative thinkers to find new ways to incorporate physiological levels of chemical metabolism into high throughput screening assays. This will help researchers more accurately assess effects of chemicals and better protect human health.
Participating teams will compete in three stages for a total award of $1 million. The first stage, which closes April 8, seeks practical designs that may be fully implemented. Up to ten entries may receive a prize of $10,000 each and an invitation to continue to the second stage, prototype development. The final stage will involve testing by the sponsoring agencies of commercially viable methods or technologies.
The challenge is closed to federal employees acting within the scope of their employment but is open to all other segments of government, industry, academia, or non-governmental organizations.
NICEATM Director Wins SOT Award
NICEATM Director Warren Casey has won the Society of Toxicology (SOT) 2016 Enhancement of Animal Welfare Award. In announcing the award, SOT specifically noted Casey’s efforts to improve the quality of data from traditional animal studies that are used to evaluate new approaches, and his leadership on projects supporting replacement of animal tests with high throughput screening approaches and computational models.
Guidance for Reducing Animal Use for Vaccine Testing
The U.S. Department of Agriculture (USDA) Center for Veterinary Biologics (CVB) recently issued CVB Notice 15-13, Option to Remove Back-titration Hamsters from In Vivo Potency Tests for Leptospira Serogroups Canicola and Icterohaemorrhagiae. The notice describes an exemption from the titration requirement in vaccination-challenge potency assays for Leptospira Serogroups Canicola and Icterohaemorrhagiae. Removal of the back-titration hamsters could reduce animal use by 50% for potency testing on these two fractions. The policy is effective Oct. 8. CVB Notice 15-13 is available on the USDA website.
Database of Rodent Uterotrophic Bioactivity Now Available
An article published October 2 as an advance publication in Environmental Health Perspectives describes curation and evaluation of a database of rodent uterotrophic bioactivity. The uterotrophic assay is a widely accepted in vivo test for identifying chemicals with potential estrogen receptor agonist activity.
The new database, which includes data from studies that adhere to six criteria specified in accepted regulatory test guidelines, is being proposed as a resource both for understanding in vivo outcome variability and for evaluating performance of in vitro alternative assays that measure estrogenic activity. For example, the database was used to validate an approach that could use high-throughput assays and computational methods to replace the uterotrophic assay in the U.S. Environmental Protection Agency’s (EPA’s) Endocrine Disruptor Screening Program (see article in the August Environmental Factor).
Reference: Kleinstreuer NC, Ceger PC, Allen DG, Strickland J, Chang X, Hamm JT, Casey WM. A curated database of rodent uterotrophic bioactivity [published online ahead of print 2 Oct 2015]. Environmental Health Perspectives.
Version 2 of S1500+ Human Gene Set Now Available
NIEHS and National Toxicology Program scientists along with Tox21 partners have developed a list of environmentally responsive genes to be used in toxicogenomics approaches to screening large numbers of chemicals. Genes on the list were identified through both bioinformatics approaches and experimental data establishing certain genes’ importance to responses to toxicity. The recently updated “S1500+” gene list contains approximately 2750 genes that will be used to evaluate transcriptional changes in human cells or tissues in response to chemical exposure. These genes may also be useful for biomarker development and basic research efforts.
Nature Biotechnology Paper Reports Results of Crowdsourcing Challenge
An international study published in Nature Biotechnology presents the combined results of a crowdsourcing initiative to test how well the effects of a toxic compound can be predicted in different people. The study shows that computational methods can be used to predict some toxic effects on populations, although they are not yet sensitive enough to predict such effects in individuals. It also presents algorithms useful for environmental risk assessment.
The community-based challenge, known as the DREAM Toxicogenetics Collaboration, was led and organized by scientists from NIEHS, EMBL-EBI, Sage Bionetworks, IBM, the University of North Carolina, and the NIH’s National Center for Advancing Translational Sciences. Hundreds of computational biologists from all over the world tried their hand at predicting the toxicities of environmental compounds that had potential adverse health effects. One key benefit of the study is that it offers new methodologies for improvements in some areas of hazard evaluation and assessment.
Report Outlines Predictive Toxicology Approach for Defense Applications
The National Academies Press has issued a report on “Application of Modern Toxicology Approaches for Predicting Acute Toxicity for Chemical Defense.” Prepared in response to a request by the U.S. Department of Defense, the report provides a conceptual approach that could be used to evaluate chemicals that could pose threats to deployed personnel. In addition to providing an overview of current computational and high-throughput testing approaches and methods for integrating data and predictions, the report summarizes lessons learned from current high-throughput screening programs and suggests initial steps for investment. The report can be read online or downloaded as a PDF for free.
NIH Invites Comments and Suggestions on a Framework for the NIH-wide Strategic Plan
In order to advance its mission, NIH is developing an NIH-wide Strategic Plan. The goal of this 5-year plan is to outline a vision for biomedical research that ultimately extends healthy life and reduces illness and disability. NIH senior leadership and staff have developed a proposed framework for the Strategic Plan that identifies areas of opportunity across all biomedicine and unifying principles to guide NIH’s support of the biomedical research enterprise. The aim is to pursue crosscutting areas of research that span NIH’s 27 Institutes, Centers, and Offices. The Strategic Plan is due to the Congress in late December 2015.
NIH published a Request for Information (RFI) seeking input from stakeholders throughout the extramural community and the general public regarding the Framework for the 5-year NIHS-wide Strategic Plan on July 22, 2015. Feedback to the RFI may be submitted through the NIH Grants website. Comments are due by August 16.
NIEHS Offers Financial Support for Test Method Development
The National Institute of Environmental Health Sciences (NIEHS) will provide additional support to current federal grantees for validation and commercialization of replacement or reduction alternatives to tests required by U.S. government agencies. These Small Business Innovation Research (SBIR) Phase IIB awards will support further development of non-clinical toxicology tests for use as stand-alone replacements or elements of a weight-of-evidence testing approach. Phase IIB awards will assist small businesses in pursuing the next appropriate milestone(s) necessary to advance promising methods towards U.S. federal agency acceptance and for subsequent commercialization of these test methods for products intended for global markets. Highest priority will be given to supporting development of methods that can serve as stand-alone replacements for animal-based tests currently used or required by U.S. federal agencies.
SBIR Phase IIB awards are available only to U.S. small business concerns that currently receive SBIR/STTR Phase II funding for their projects from NIEHS, other NIH institutes, or other federal agencies. However, note that Phase IIB funding will be offered in three rounds during 2015, 2016, and 2017. If your project does not currently qualify for Phase IIB funding, the funding announcement provides guidelines for future eligibility. Letters of intent for the first round of funding are due October 17, 2015, with applications due November 17, 2015.
EPA Requests Comments on Use of High-Throughput Assays for EDSP
The Environmental Protection Agency (EPA) requests comments on a plan to incorporate validated ToxCast/Tox21 high-throughput assays and an associated computational model as an alternative to three Tier 1 tests used in its Endocrine Disruptor Screening Program (EDSP) to assess estrogenic activity. Described as “groundbreaking” in an EPA press release, the use of high-throughput assays and computational methods will accelerate the pace of screening, decrease costs, and reduce animal testing. The EPA plan was developed and validated by EPA and NICEATM scientists and is described in detail in a paper by Browne et al. in the journal Environmental Science and Technology. Comments on the plan are requested by August 18.
USDA Requests Comments on Petition to Revise Animal Use Reporting Requirements
The Department of Agriculture Animal and Plant Health Inspection Service (USDA APHIS) has received a petition from the National Anti-Vivisection Society (NAVS) to increase the level of detail in information collected from research facilities in their reports on animal use. NAVS is asking that the annual report required under the Animal Welfare Act include more information on how animals are being used for research and experimentation.
APHIS is soliciting comments to help determine what action, if any, to take in response to this request. In particular, APHIS invites responses to the following questions. Comments are requested by August 24.
NIH Updates Solicitation for SBIR/STTR Grant Applications
The NIH has updated the solicitation announcement for SBIR and Small Business Technology Transfer (STTR) grant applications. The NIEHS section has been updated to include a section on “Toxicity Screening, Testing, and Modeling,” which states an interest in “technologies to improve predictivity in toxicology testing to support the goals and initiatives of Tox21.” Specific technologies of interest include (1) physiologically relevant cell-based systems or phylogenetically lower order animal models for toxicity screening, (2) computational approaches for predictive toxicology, and (3) other technologies for enhanced toxicity testing including high-throughput measurement of gene expression, improved methods for fixing and preserving tissues, and real-time in vivo detection of oxygen radicals. The next deadline for applying for SBIR and STTR grants is September 5.
EPA Updates Guidance on Non-Animal Eye Irritation Tests
EPA has updated its guidance document describing a non-animal testing scheme for assessing eye irritation potential of EPA-registered antimicrobial cleaning products. The testing scheme uses the bovine corneal opacity and permeability, EpiOcular, and cytosensor microphysiometer assays to identify antimicrobial cleaning product Toxicity Category I, II, and III eye irritants.
USDA Updates Guidelines for Validation of In Vitro Potency Assays
The CVB recently updated Veterinary Services Memorandum No. 800.112, “Guidelines for Validation of In Vitro Potency Assays.” This memorandum provides guidance concerning the information a manufacturer of veterinary vaccines and other biological products should provide when submitting a new potency assay for consideration by the CVB. These guidelines apply to in vitro assays used to determine the potency of such products, and provide a framework for designing in vitro potency assays and the studies needed to validate those assays. Use of in vitro assays may replace, reduce, or refine animal use for this purpose.
Veterinary Services Memorandum No. 800.112 and other recently published CVB documents are available on the USDA website.
NTP Requests Comments on Human "S1500" Gene Set
NTP requests comments on a set of human genes that have been identified and prioritized as environmentally responsive genes. This set of approximately 1500 "sentinel" genes was developed with input from the scientific community, to be used in toxicogenomics studies to screen human cells or tissues against large numbers of chemicals and evaluate transcriptional changes in response to chemical exposures. The goal is to develop a gene set that (1) is representative of highly diverse gene expression changes reported to date, (2) is capable of predicting the gene expression changes observed across the transcriptome, and (3) covers all major biological pathways.
The current version of the human S1500 gene set can be found on the NTP website. This site will be updated as changes to the list are made. The consensus strategy for selection of an appropriate sentinel gene set can be accessed at the same site. Comments on the gene set should be submitted as Microsoft Word or Excel files to Genelist@niehs.nih.gov by May 15.
FDA Science Forum
The FDA will hold a Science Forum on May 27-28 at their White Oak Campus in Silver Spring, Maryland. The Forum will highlight the FDA’s cutting-edge research, demonstrate how this research informs FDA’s regulatory decision-making, and provide an opportunity for internal and external participants to develop collaborations. The focus of this year’s Forum will be FDA’s eight Regulatory Science priority areas, one of which is “Modernize Toxicology to Enhance Product Safety.”
The Forum is open to FDA staff, FDA collaborators, and the public; you may attend in person or view presentations remotely. There is no registration fee, but in-person and remote attendees must register by May 15, and early registration is recommended for in-person attendees as seating is limited. More information and links to registration forms are available on the FDA website.
Guidance Issued on Photosafety Testing
The FDA has issued guidance document "S10 Photosafety Evaluation of Pharmaceuticals." This guidance outlines details on when photosafety testing is warranted and on possible assessment strategies, including in vitro test methods that might be useful. The purpose of the guidance is to recommend international standards for photosafety assessment and to harmonize such assessments that support human clinical trials and marketing authorization for pharmaceuticals. An announcement of availability of the guidance was published in the January 27 Federal Register.
Workshop on In Vitro Tools and Models for Drug Discovery
A free workshop on “Validation and Qualification of New In Vitro Tools and Models for the Pre-clinical Drug Discovery Process” will be presented at the National Institutes of Health (NIH) on February 12. The workshop is being organized by the National Institute of Biomedical Imaging and Bioengineering (NIBIB) in partnership with the American Institute for Medical and Biological Engineering and the National Center for Advancing Translational Sciences (NCATS). It will be held in the Lister Hill Auditorium on the NIH campus in Bethesda, Maryland. Additional information, agenda, a link to registration, and information on previous workshops in this series can be found on the NIBIB website.
Draft Process Document Available for Comment
A draft EPA document describing a “Process for Establishing and Implementing Alternative Approaches to Traditional In Vivo Acute Toxicity Studies” is now available for comment. The document 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 the Federal Insecticide, Fungicide, and Rodenticide Act. Please submit comments on the document by email to Christopher Schlosser. Comments will be accepted until March 10.
FIFRA Scientific Advisory Panel to Discuss Prioritization of EDSP Chemicals
The U.S. Environmental Protection Agency (EPA) Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Scientific Advisory Panel will meet on December 2–5 at the EPA Conference Center in Arlington, Virginia. The panel will consider and review scientific issues related to endocrine activity and exposure-based prioritization and screening. NICEATM scientists will present their work on assessing bioactivity of chemicals tested in the ToxCast high-throughput screening assays. Read summary of the meeting and the NICEATM presentations in the January Environmental Factor newsletter.
Grants Available for Development of Novel Assays for Screening the Effects of Chemical Toxicants on Cell Differentiation
Small business concerns are invited to submit grant applications to develop medium- to high-throughput assays to evaluate the effects of toxicants on pluripotent or induced pluripotent cells with respect to cell differentiation and the resulting differentiated cell populations. Assays will provide information on mechanisms of chemically-induced biological activity, help to prioritize chemicals for more extensive toxicological evaluation, support more predictive models of in vivo biological response, and potentially inform on the role of genetic diversity in toxicological effects. For more information, please visit the NIH website:
Applications are due February 13, 2015.
Update of Hazardous Substances Data Bank
The Hazardous Substances Data Bank (HSDB), a part of NLM's Toxicology Data Network (TOXNET®), has undergone numerous recent enhancements to its records for chemicals and substances. Examples include the creation of new subheadings in the human and non-human toxicity excerpts to allow users to more efficiently locate data from in vitro and other alternative methods. Coverage includes results from methods validated by ICCVAM and the European Union Reference Laboratory for Alternatives to Animal Testing.
Training Available on Searching for Alternatives
USDA’s Animal Welfare Information Center (AWIC) holds free workshops at the National Agricultural Library to help researchers explore alternatives to procedures that may cause pain or distress to their animals. Training is targeted to principal investigators, IACUC members, administrators of animal use programs, veterinarians, librarians, and other information specialists. The workshops provide an overview of relevant topics and resources, instruction on the use of existing databases and websites, and hands-on practice conducting online database searches.