EPA plan to end animal testing splits scientists

Grimm, David

doi:10.1126/science.365.6459.1231

Cited by 63 publications

(22 citation statements)

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“…Other examples of FFP assays have been pursued with p53 mediated DNA damage (Clewell et al, 2014Adeleye et al, 2015;Clewell and Andersen, 2016), PPARα signaling (Mc-Mullen et al, 2014, 2019 and adipocyte differentiation (Foley et al, 2017;Hartman et al, 2018). Our work with these FFP assays has helped establish criteria for the cellular read-outs to ensure applicability of the results for assessing adversity.…”

Section: Level 3: Fit-for-purpose Assays and Safety Assessmentmentioning

confidence: 99%

“…The original figure (S-1) from the report (NRC, 2007) describing components of the vision had three parts -Chemical Characterization, Toxicity Testing (including both toxicity pathway evaluations and targeted testing) and Dose-Re-to maintain a list of acceptable NAMs. More recently, a US EPA memorandum published in September 2019 officially announced a commitment to reduce its requests for and funding of live mammal studies by 30% by 2025 and to eliminate all live mammal study requests by 2035 (Grimm, 2019).…”

Section: Introductionmentioning

confidence: 99%

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Developing context appropriate toxicity testing approaches using new alternative methods (NAMs)

Andersen¹,

McMullen²,

Phillips³

et al. 2019

ALTEX

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the NAS report, moved forward to outline a broadly collaborative program (Collins et al., 2008) with other United States federal agencies to implement recommendations from the NAS report. A multi-stakeholder program, SEURAT (Safety Evaluation Ultimately Replacing Animal Testing) 1 that focused on implementation of non-animal methods also began in Europe. Following SEURAT, EU-ToxRisk, a large-scale project funded by the European Commission's Horizon 2020 program 2 , is now driving the European research efforts on alternative testing methods.These in vitro and computational technologies, together with application of existing tools to new data streams (e.g., readacross), are collectively referred to as new approach methodologies -NAMs (US EPA, 2018b). The US EPA under the new Toxic Substances Control Act (TSCA) in section 4(h) is required Food for Thought …

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Section: Level 3: Fit-for-purpose Assays and Safety Assessmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Developing context appropriate toxicity testing approaches using new alternative methods (NAMs)

Andersen¹,

McMullen²,

Phillips³

et al. 2019

ALTEX

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show abstract

“…However, because these tests are not on “normal” human cells, their applications are limited ( Perel et al., 2007 ). In addition, the use of animals has become a major issue from the standpoint of animal welfare; in 2019, the U.S. Environmental Protection Agency (EPA) announced that research studies using mammals as well as funding for mammal studies will be cut by 30% by 2025 and abolished by 2035 ( Grimm, 2019 ). To reduce animal studies, new approach methodologies (NAMs) ( Topical Scientific Workshop - New Approach Methodologies in Regulatory Science, 2016 ), which are any technology, methodology, approach, or combination thereof that can be used to provide information on chemical hazard and risk assessment that avoids the use of intact animals ( New Approach Methods Work Plan: Reducing Use of Animals in Chemical Testing, 2016 ), are widely investigated and adopted for the development of new tools for testing pharmaceuticals and other chemicals for potential adverse impacts on human health and ecological endpoints, under the direction of the U.S. EPA and the amended Toxic Substances Control Act (TSCA) for improving regulatory toxicology guidelines to consider the use of toxicity information, computational toxicology and bioinformatics, and high-throughput screening methods and prediction models, prior to animal studies ( Becker, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

StemPanTox: A fast and wide-target drug assessment system for tailor-made safety evaluations using personalized iPS cells

et al. 2022

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“…The influential report from the National Research Council (2007) recommended using in vitro data based on human-derived cells and organoids as initial models for chemical safety assessments. In addition, Europe has already banned the use of whole animal models for cosmetic testing, and the US EPA announced in 2019 that it aims to stop conducting and funding all mammal-based experiments by 2035 ( Regulation, 2016 ; Grimm, 2019 ). Interest in the field of in silico predictive tools has increased to bypass the use of animal models.…”

Section: Introductionmentioning

confidence: 99%

Dynamic Mass Balance Modeling for Chemical Distribution Over Time in In Vitro Systems With Repeated Dosing

et al. 2022

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As toxicologists and risk assessors move away from animal testing and more toward using in vitro models and biological modeling, it is necessary to produce tools to quantify the chemical distribution within the in vitro environment prior to extrapolating in vitro concentrations to human equivalent doses. Although models predicting chemical distribution in vitro have been developed, very little has been done for repeated dosing scenarios, which are common in prolonged experiments where the medium needs to be refreshed. Failure to account for repeated dosing may lead to inaccurate estimations of exposure and introduce bias into subsequent in vitro to in vivo extrapolations. Our objectives were to develop a dynamic mass balance model for repeated dosing in in vitro systems; to evaluate model accuracy against experimental data; and to perform illustrative simulations to assess the impact of repeated doses on predicted cellular concentrations. A novel dynamic in vitro partitioning mass balance model (IV-MBM DP v1.0) was created based on the well-established fugacity approach. We parameterized and applied the dynamic mass balance model to single dose and repeat dosing scenarios, and evaluated the predicted medium and cellular concentrations against available empirical data. We also simulated repeated dosing scenarios for organic chemicals with a range of partitioning properties and compared the in vitro distributions over time. In single dose scenarios, for which only medium concentrations were available, simulated concentrations predicted measured concentrations with coefficients of determination (R2) of 0.85–0.89, mean absolute error within a factor of two and model bias of nearly one. Repeat dose scenario simulations displayed model bias <2 within the cell lysate, and ∼1.5-3 in the medium. The concordance between simulated and available experimental data supports the predictive capacity of the IV-MBM DP v1.0 tool, but further evaluation as empirical data becomes available is warranted, especially for cellular concentrations.

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EPA plan to end animal testing splits scientists

Abstract: Some see nonanimal models as the future, but others worry about health impacts.

Cited by 63 publications

References 0 publications

Developing context appropriate toxicity testing approaches using new alternative methods (NAMs)

Developing context appropriate toxicity testing approaches using new alternative methods (NAMs)

StemPanTox: A fast and wide-target drug assessment system for tailor-made safety evaluations using personalized iPS cells

Dynamic Mass Balance Modeling for Chemical Distribution Over Time in In Vitro Systems With Repeated Dosing

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