By Lynn L. Bergeson and Carla N. Hutton
 
The U.S. Environmental Protection Agency (EPA) will hold training on May 23, 2023, on Generalized Read-Across (GenRA), a publicly available tool that uses an automated approach to make reproducible read-across predictions of toxicity. EPA states that read-across “is a commonly used data gap filling technique whereby endpoint information for one substance is used to predict the same endpoint for another substance, supported by structural or other feature similarities.” According to EPA, while read-across sometimes relies on subjective or expert judgement, use of the GenRA tool could provide more objective and reproducible read-across predictions. Specifically targeted for decision-makers, this training will provide:

• A presentation overview of GenRA’s purpose and scope;
• A demonstration of GenRA’s interface and navigation; and
• Opportunities for participatory learning and engagement.

The virtual training will feature EPA’s Dr. Grace Patlewicz. The training will include a plenary presentation, small group discussions, and a chance to try out GenRA. EPA has divided the training into two parts to accommodate a variety of interests and schedules. Registration for one or both sessions is free but required.

• Session 1 (Presentation and Questions and Answers (Q&A)) 11:00 a.m. - 12:30 p.m. (EDT)

This session will provide an overview of GenRA content and function with opportunities for participation and Q&A.

• Session 2 (Breakout Sessions) 12:30 - 1:30 p.m. (EDT)

This session will break participants into breakout rooms to work on exercises in small groups, aided by facilitators.

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By Lynn L. Bergeson and Carla N. Hutton
 
The U.S. Environmental Protection Agency (EPA) Office of Inspector General (OIG) announced on March 7, 2023, that EPA did not follow the typical intra-agency review and clearance process during the development and publication of the January 2021 perfluorobutane sulfonic acid (PFBS) toxicity assessment. OIG conducted its evaluation to determine whether EPA followed applicable policies and procedures to develop and publish the PFBS toxicity assessment. OIG notes that two weeks after publication, EPA removed the toxicity assessment from its website, citing political interference and Scientific Integrity Policy violations. EPA republished the toxicity assessment in April 2021.
 
According to OIG, EPA did not follow the typical intra-agency review and clearance process during the development and publication of the January 2021 toxicity assessment. OIG states that during final clearance, “a political appointee directed that a last-minute review be conducted of the uncertainty factors used to calculate toxicity values, resulting in a scientific disagreement that caused delay, confusion, and significant changes to the near-final, peer-reviewed work product.” The changes included replacing single toxicity values with “unprecedented toxicity ranges.” Users of the toxicity assessment, including regulated entities cleaning up PFBS contamination, “could have selected a less stringent value within this range, which may have been less costly but also less protective of human health.” While EPA staff expressed scientific integrity concerns about the last-minute review and risks to public health, EPA lacked policies and procedures to address these concerns. According to OIG, without updates to policies and procedures, EPA cannot fulfill its commitment to scientific integrity and information quality.
 
OIG made five recommendations:

• Three to the Assistant Administrator for Research and Development to reduce procedural confusion and strengthen existing policies, procedures, and guidance by clarifying if and when comments expressing scientific disagreement can be expressed; making clear if and when toxicity ranges are acceptable; and using OIG as a resource for high-profile scientific integrity concerns that relate to political interference or that assert risk to human health or the environment;
• One to the Assistant Administrator for Mission Support to update policies and procedures on environmental information quality to require additional quality assurance reviews for EPA products; and
• One to the Deputy Administrator to strengthen EPA’s culture of scientific integrity, transparency, and accountability of political leadership actions when changes occur as a result of policy decisions.

OIG notes that “EPA disagreed with all five recommendations, which remain unresolved.”

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By Lynn L. Bergeson and Carla N. Hutton
 
On February 15, 2023, the U.S. Environmental Protection Agency (EPA) requested nominations for technical experts to serve as Special Government Employees (SGE) on a review panel under the authority of the Board of Scientific Counselors (BOSC), a federal advisory committee to the Office of Research and Development (ORD). 88 Fed. Reg. 9880. EPA states that selected experts will review ORD’s draft documents detailing scientific studies supporting the development of transcriptomic-based toxicity values and their implementation as a new EPA Transcriptomic Assessment Product (ETAP). According to EPA, the ETAP is a proposed ORD assessment product that uses a standardized short-term in vivo study design and data analysis procedures to develop transcriptomic-based toxicity values for data-poor chemicals. Draft documents will be provided in the BOSC docket prior to the meeting for an in-depth evaluation of:

• Literature review and scientific studies supporting the development of transcriptomic points of departure from short-term in vivo studies;
• Derivation of transcriptomic toxicity values for chronic toxicity;
• Incorporation of transcriptomic toxicity values into a new standardized assessment product that is intended for data-poor chemicals; and
• Example application of the ETAP to a data-poor per- and polyfluoroalkyl substance (PFAS).

According to EPA, the review of the draft documents detailing underlying scientific studies and implementation of ETAP by the BOSC is being performed in close coordination with a separate BOSC review of a value-of-information (VOI) analysis comparing the ETAP with traditional human health assessment practices. EPA states that the VOI analysis is intended to evaluate the public health and economic trade-offs associated with the timeliness, uncertainty, and costs of the different toxicity evaluation and assessment approaches.

The review will take place between April and July 2023. Nominations are due March 3, 2023.

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By Lynn L. Bergeson and Carla N. Hutton
 
The U.S. Environmental Protection Agency (EPA) has opened registration for the second ECOTOXicology Knowledgebase (ECOTOX) virtual training on February 7, 2023. ECOTOX is a comprehensive, publicly available tool providing environmental toxicity data on aquatic life, terrestrial plants, and wildlife.  EPA states that the virtual training, which is specifically targeted for decision-makers, will provide:

• An overview of the database content and function;
• Application-oriented use case demonstrations; and
• Opportunities for participatory learning and engagement.

According to EPA, the virtual training will be a live encore of the training offered in May 2022, presenting the same material and featuring expanded opportunity for live interaction in Session 2. Participants may register for one or both sessions; registration is free but required to attend each session.
 
Session 1 (Presentation and Questions and Answers (Q&A))
11:00 a.m.-12:30 p.m. (EST)
This session will provide an overview of the knowledgebase content and function with opportunities for participation and Q&A.
 
Session 2 (Breakout Sessions)
12:30-1:30 p.m. (EST)
This session will break participants into breakout groups to work on case study exercises in small groups, aided by facilitators.

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By Lynn L. Bergeson and Carla N. Hutton
 
The U.S. Environmental Protection Agency (EPA) announced on April 18, 2022, that it will hold a webinar on May 11, 2022, entitled “Data-Driven Solutions to Reducing Animal Use in Ecotoxicity.” Speakers will include:

• Carlie LaLone, Ph.D., EPA Office of Research and Development (ORD), on “The Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) Tool: Extrapolating Knowledge Computationally.” EPA states that regulatory decision-making for chemical safety relies upon toxicity data generated from laboratory test species for the protection of wildlife in the environment. Typically, ecological risk assessments integrate safety factors to account for interspecies variability. According to EPA, the SeqAPASS tool is a more informed way to extrapolate knowledge from model species to other species that does not require the use of animals in toxicity testing and instead uses existing protein sequence knowledge. LaLone will describe EPA’s SeqAPASS tool and its applications for cross-species extrapolation relative to understanding conservation of biology and predicting chemical susceptibility.
   
• Michael Lowit, Ph.D., EPA Office of Pesticide Programs (OPP), on “Exploring Potential Reductions in Fish Testing in a Regulatory Context.” According to EPA, as part of its commitment to reducing animal testing, OPP is conducting retrospective analyses of existing data to evaluate critically which EPA guideline studies form the basis of regulatory decisions. EPA states that the results from these analyses can inform if reductions can be made to the number of animals used without reducing the quality of ecological risk assessments. EPA is currently conducting a retrospective analysis for fish acute toxicity tests, which are used by OPP to assess potential risk to fish species from pesticides. For each pesticide, EPA typically requires in vivo testing of three different fish species. Lowit will focus on the relative sensitivity among species subjected to in vivo fish acute toxicity studies. The results of this analysis will inform whether there is a basis for reducing the number of species while providing sufficient information to support pesticide registration decisions.

The webinar is co-organized by the People for the Ethical Treatment of Animals (PETA) Science Consortium International, EPA, and the Physicians Committee for Responsible Medicine (PCRM). EPA notes that it does not necessarily endorse the views of the speakers. Registration is now open.

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By Lynn L. Bergeson and Carla N. Hutton
 
The U.S. Environmental Protection Agency (EPA) announced on April 8, 2021, that it is releasing an updated toxicity assessment for perfluorobutane sulfonic acid (PFBS), which is a member of the group of per- and polyfluoroalkyl substances (PFAS).  EPA states that this PFBS assessment is part of its commitment to restore scientific integrity to all of the Agency’s actions and increase the amount of research and information available to the public on PFAS.  According to EPA’s announcement, “EPA, federal agencies, states, tribes, and local communities can use the PFBS toxicity assessment, along with specific exposure and other relevant information, to determine if and when it is necessary to take action to address potential health risks associated with human exposures to PFBS under appropriate regulations and statutes.”  EPA notes that the updated assessment “has gone through all appropriate reviews, includes input EPA received from external peer review, upholds the tenants of scientific integrity, was authored by expert career scientists in EPA’s Office of Research and Development, and has not been compromised by political staff -- these were all issues with a version of the assessment that was posted during the previous administration.  The release of today’s PFBS assessment upholds the integrity of EPA’s science, which EPA, states, tribes, and more rely on to make decisions that protect the health of their communities.”
 
According to EPA’s fact sheet on the toxicity assessment, PFBS is a replacement chemical for perfluorooctanesulfonic acid (PFOS), a PFAS that was voluntarily phased out by the primary U.S. manufacturer by 2002.  PFBS has been identified in the environment and consumer products, including surface water, wastewater, drinking water, dust, carpeting and carpet cleaners, and floor wax.  The fact sheet states that the PFBS toxicity assessment is comparable to assessments developed under EPA’s Integrated Risk Information System (IRIS) and Provisional Peer-Reviewed Toxicity Value (PPRTV) Programs in that it provides hazard identification, dose-response information, and toxicity values.  EPA will continue to work with state, tribal, and local partners to provide technical assistance as they consider the final PFBS toxicity values in relevant exposure scenarios.  The fact sheet notes that at this time, EPA does not plan to issue a regulation for PFBS.

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By Lynn L. Bergeson and Carla N. Hutton
 
The U.S. Environmental Protection Agency (EPA) announced on November 10, 2020, that the Integrated Risk Information System (IRIS) Program released the ORD Staff Handbook for Developing IRIS Assessments (IRIS Handbook) for public comment.  EPA states that the IRIS Handbook provides operating procedures for developing IRIS assessments, including problem formulation approaches and methods for conducting systematic review, dose response analysis, and developing toxicity values.  The IRIS Handbook notes that it does not supersede existing EPA guidance and does not serve as guidance for other EPA programs.  EPA will publish a Federal Register notice announcing the beginning of a 90-day public comment period on the IRIS Handbook and on the draft charge questions for reviewers in advance of a National Academies of Sciences, Engineering, and Medicine (NASEM) peer review.  EPA will summarize comments received and provide them to the committee conducting the peer review.  EPA has posted a pre-publication version of the Federal Register notice.

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By Lynn L. Bergeson and Carla N. Hutton
 
The U.S. Environmental Protection Agency (EPA) issued a press release on September 10, 2019, announcing that EPA Administrator Andrew Wheeler signed a directive to prioritize efforts to reduce animal testing.  Administrator Wheeler also announced $4.25 million in funding to five universities to research the development and use of alternative test methods and strategies that reduce, refine, and/or replace vertebrate animal testing.  Administrative Wheeler directs the Office of Chemical Safety and Pollution Prevention (OCSPP) and the Office of Research and Development (ORD) “to prioritize ongoing efforts and to direct existing resources toward additional activities that will demonstrate measurable impacts in the reduction of animal testing while ensuring protection of human health and the environment.”  The directive states that EPA “will reduce its requests for, and [its] funding of, mammal studies by 30 percent by 2025 and eliminate all mammal study requests and funding by 2035.  Any mammal studies requested or funded by the EPA after 2035 will require Administrator approval on a case-by-case basis.”  Administrative Wheeler requests that OCSPP and ORD hold a joint animal conference on new approach methods (NAM), with the first conference to be held in 2019. 
 
Five universities were awarded grants through EPA’s Science to Achieve Results Program.  According to EPA, the research focuses on advancing the development and use of alternative test methods and strategies to reduce, refine, and/or replace vertebrate animal testing.  The grantees are advancing the science of non-vertebrate alternative test methods and strategies in chemical hazard assessment.  The grantees include:

• Johns Hopkins University to develop a human-derived brain model to assess the mechanism by which environmental chemicals might cause developmental neurotoxicity;
   
• Vanderbilt University to test their organ-on-a-chip to study the blood brain barrier and potential brain injury after organophosphate exposure;
   
• Vanderbilt University Medical Center to use their Endo Chip technology to research how preexisting diseases affect cellular responses to environmental toxicants with a focus on reproductive disorders in women;
   
• Oregon State University to develop in vitro test methods for fish species to screen chemicals in complex environmental mixtures; and
   
• University of California Riverside to use human cells to develop a cost-effective end point to characterize potential skeletal embryotoxicants.

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