Reducing the need for animal testing while increasing efficiency in a pesticide regulatory setting: Lessons from the EPA Office of Pesticide Programs’ Hazard and Science Policy Council

Craig, Evisabel A.; Lowe, Kelly; Akerman, Gregory; Dawson, Jeffrey L.; May, Brenda; Reaves, Elissa; Lowit, Anna

doi:10.1016/j.yrtph.2019.104481

Cited by 34 publications

(18 citation statements)

References 1 publication

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“…Although this guidance was developed to address particular toxicity studies, the same general WoE approach is applied by HASPOC when considering the need for other toxicity studies for pesticide regulatory purposes. Between 2012 and 2018, the most common studies requested to be waived were acute and subchronic neurotoxicity, subchronic inhalation, and immunotoxicity studies ( Craig et al, 2019 ). For the acute six-pack studies, the Chemistry and Acute Toxicology Science Advisory Council (CATSAC) was formed to consider bridging proposals and/or waivers using the aforementioned waiving and bridging guidance documents.…”

Section: Pesticides and Plant Protection Productsmentioning

confidence: 99%

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Use of new approach methodologies (NAMs) to meet regulatory requirements for the assessment of industrial chemicals and pesticides for effects on human health

Stucki¹,

et al. 2022

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New approach methodologies (NAMs) are increasingly being used for regulatory decision making by agencies worldwide because of their potential to reliably and efficiently produce information that is fit for purpose while reducing animal use. This article summarizes the ability to use NAMs for the assessment of human health effects of industrial chemicals and pesticides within the United States, Canada, and European Union regulatory frameworks. While all regulations include some flexibility to allow for the use of NAMs, the implementation of this flexibility varies across product type and regulatory scheme. This article provides an overview of various agencies’ guidelines and strategic plans on the use of NAMs, and specific examples of the successful application of NAMs to meet regulatory requirements. It also summarizes intra- and inter-agency collaborations that strengthen scientific, regulatory, and public confidence in NAMs, thereby fostering their global use as reliable and relevant tools for toxicological evaluations. Ultimately, understanding the current regulatory landscape helps inform the scientific community on the steps needed to further advance timely uptake of approaches that best protect human health and the environment.

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Section: Pesticides and Plant Protection Productsmentioning

confidence: 99%

“…For example, following a retrospective analysis, the agency released guidance for waiving acute dermal toxicity tests ( US EPA, OCSPP, and OPP, 2016 ). The progress of HASPOC and CATSAC is continuously tracked and reported on an annual basis ( Craig et al, 2019 ; EPA, 2020a , 2021b ).…”

Section: Pesticides and Plant Protection Productsmentioning

confidence: 99%

Use of new approach methodologies (NAMs) to meet regulatory requirements for the assessment of industrial chemicals and pesticides for effects on human health

Stucki¹,

et al. 2022

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“…The reason that governments do not test, or do not require full testing, for potential toxicological effects is primarily economic (Bottini & Hartung, 2009 ). For example, a full toxicological battery of tests for a pesticide can cost between $8 and $16 million U.S. dollars (Craig et al., 2019 ), while the time required for testing and chemical assessment can take eight years or longer (Krewski et al., 2020 ). Such costs and time requirements pose a major hinderance to innovation in chemical manufacturing and bringing consumer products containing new chemical to market.…”

Section: Introductionmentioning

confidence: 99%

A Framework that Considers the Impacts of Time, Cost, and Uncertainty in the Determination of the Cost Effectiveness of Toxicity‐Testing Methodologies

et al. 2021

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Regulatory agencies are required to evaluate the impacts of thousands of chemicals. Toxicological tests currently used in such evaluations are time-consuming and resource intensive; however, advances in toxicology and related fields are providing new testing methodologies that reduce the cost and time required for testing. The selection of a preferred methodology is challenging because the new methodologies vary in duration and cost, and the data they generate vary in the level of uncertainty. This article presents a framework for performing cost-effectiveness analyses (CEAs) of toxicity tests that account for cost, duration, and uncertainty. This is achieved by using an output metric-the cost per correct regulatory decisionthat reflects the three elements. The framework is demonstrated in two example CEAs, one for a simple decision of risk acceptability and a second, more complex decision, involving the selection of regulatory actions. Each example CEA evaluates five hypothetical toxicitytesting methodologies which differ with respect to cost, time, and uncertainty. The results of the examples indicate that either a fivefold reduction in cost or duration can be a larger driver of the selection of an optimal toxicity-testing methodology than a fivefold reduction in uncertainty. Uncertainty becomes of similar importance to cost and duration when decisionmakers are required to make more complex decisions that require the determination of small differences in risk predictions. The framework presented in this article may provide a useful basis for the identification of cost-effective methods for toxicity testing of large numbers of chemicals.

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“…For new nongenotoxic compounds under development, long-term carcinogenicity studies are currently required by regulatory authorities, although there is movement toward granting waivers to eliminate the need for the long-term bioassay based on MOA considerations (Sistare et al 2011;Craig et al 2019). Potential hepatic effects of chemicals can be screened for in studies of up to 13 weeks duration (Allen et al 2004;Cohen 2010), including effects produced by CAR activators.…”

Section: Differences Between the Effects Of Car And Ppara Activators In Rodent Hepatocytes Compared To Other Speciesmentioning

confidence: 99%

Critical evaluation of the human relevance of the mode of action for rodent liver tumor formation by activators of the constitutive androstane receptor (CAR)

Yamada

Cohen

Lake

2021

Critical Reviews in Toxicology

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Many nongenotoxic chemicals have been shown to produce liver tumors in mice and/or rats by a mode of action (MOA) involving activation of the constitutive androstane receptor (CAR). Studies with phenobarbital (PB) and other compounds have identified the key events for this MOA: CAR activation; increased hepatocellular proliferation; altered foci formation; and ultimately the development of adenomas/carcinomas. In terms of human relevance, the pivotal species difference is that CAR activators are mitogenic agents in mouse and rat hepatocytes, but they do not stimulate increased hepatocellular proliferation in humans. This conclusion is supported by substantial in vitro studies with cultured rodent and human hepatocytes and also by in vivo studies with chimeric mice with human hepatocytes. Examination of the literature reveals many similarities in the hepatic effects and species differences between activators of rodent CAR and the peroxisome proliferator-activated receptor alpha (PPARa), with PPARa activators also not being mitogenic agents in human hepatocytes. Overall, a critical analysis of the available data demonstrates that the established MOA for rodent liver tumor forma-

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Reducing the need for animal testing while increasing efficiency in a pesticide regulatory setting: Lessons from the EPA Office of Pesticide Programs’ Hazard and Science Policy Council

Cited by 34 publications

References 1 publication

Use of new approach methodologies (NAMs) to meet regulatory requirements for the assessment of industrial chemicals and pesticides for effects on human health

Use of new approach methodologies (NAMs) to meet regulatory requirements for the assessment of industrial chemicals and pesticides for effects on human health

A Framework that Considers the Impacts of Time, Cost, and Uncertainty in the Determination of the Cost Effectiveness of Toxicity‐Testing Methodologies

Critical evaluation of the human relevance of the mode of action for rodent liver tumor formation by activators of the constitutive androstane receptor (CAR)

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