Recommendations for Reducing the USE of Fish and Amphibians in Endocrine‐Disruption Testing of Biocides and Plant Protection Products in Europe

Lagadic, Laurent; Bender, Katrin; Burden, Natalie; Salinas, Edward; Weltje, Lennart

doi:10.1002/ieam.4156

Cited by 7 publications

(6 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The current LAGDA design, validation, and implementation have not demonstrated appropriate strength of this assay for use in determing T‐mediated adversity. In addition, the LAGDA is an animal‐intensive assay, using at least 480 animals (excluding a range‐finder and potential repeats; Lagadic et al 2019 ). We have shown that modification of the AMA to a fixed‐stage design improves the performance and interpretation of the assay for assessing thyroid‐related activity.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The Extended Amphibian Metamorphosis Assay: A Thyroid‐Specific and Less Animal‐Intensive Alternative to the Larval Amphibian Growth and Development Assay

Ortego

Olmstead²,

Weltje³

et al. 2021

Enviro Toxic and Chemistry

Self Cite

View full text Add to dashboard Cite

The amphibian metamorphosis assay (AMA; US Environmental Protection Agency [USEPA] test guideline 890.1100 and Organisation for Economic Co-Operation and Development test guideline 231) has been used for more than a decade to assess the potential thyroid-mediated endocrine activity of chemicals. In 2013, in the context of the Endocrine Disruptor Screening Program of the USEPA, a Scientific Advisory Panel reviewed the results from 18 studies and recommended changes to the AMA test guideline, including a modification to a fixed-stage design rather than a fixed-time (i.e., 21-d) design. We describe an extended test design for the AMA (or EAMA) that includes thyroid histopathology and time to metamorphosis (Nieuwkoop-Faber [NF] stage 62), to address both the issues with the fixed-time design and the specific question of thyroid-mediated adversity in a shorter assay than the larval amphibian growth and development assay (LAGDA; Organisation for Economic Co-Operation and Development test guideline 241), using fewer animals and resources. A demonstration study was conducted with the EAMA (up to NF stage 58) using sodium perchlorate. Data analyses and interpretation of the fixed-stage design of the EAMA are more straightforward than the fixed-time design because the fixedstage design avoids confounded morphometric measurements and thyroid histopathology caused by varying developmental stages at test termination. It also results in greater statistical power to detect metamorphic delays than the fixed-time design. By preferentially extending the AMA to NF stage 62, suitable data can be produced to evaluate thyroid-mediated adversity and preclude the need to perform a LAGDA for thyroid mode of action analysis. The LAGDA remains of further interest should investigations of longer term effects related to sexual development modulated though the hypothalamus-pituitary-gonadal axis be necessary. However, reproduction assessment or life cycle testing is currently not addressed in the LAGDA study design. This is better addressed by higher tier studies in fish, which should then include specific thyroid-related endpoints.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Another important consideration is that the EAMA is 3 to 4 times shorter than the LAGDA, thus reducing animal suffering. Also, due to the thorough validation of the AMA, the failure rate of the EAMA is lower than that of the LAGDA (Lagadic et al 2019 ), necessitating fewer repeats.…”

Section: Discussionmentioning

confidence: 99%

The Extended Amphibian Metamorphosis Assay: A Thyroid‐Specific and Less Animal‐Intensive Alternative to the Larval Amphibian Growth and Development Assay

Ortego

Olmstead²,

Weltje³

et al. 2021

Enviro Toxic and Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…These early developmental stage assays are used increasingly to obtain mechanistic endocrine insight. Several assays have been developed including the REACTIV assay (estrogen and/or steroidogenesis), the RADAR assay (androgen and/or steroidogenesis), and the EASZY assay (estrogen; Lagadic et al, 2019). These assays combine the advantages of using organisms (embryos before free feeding) with at least partially competent metabolic systems and molecular tools that provide useful mechanistic data.…”

Section: Assays and Endpoints For The Hpg Axismentioning

confidence: 99%

Current testing programs for pesticides adequately capture endocrine activity and adversity for protection of vertebrate wildlife

Staveley

Freeman

McArdle

et al. 2023

Integr Envir Assess & Manag

Self Cite

View full text Add to dashboard Cite

The toxicity and ecotoxicity of pesticide active ingredients are evaluated by a number of standardized test methods using vertebrate animals. These standard test methods are required under various regulatory programs for the registration of pesticides. Over the past two decades, additional test methods have been developed with endpoints that are responsive to endocrine activity and subsequent adverse effects. This article examines the available test methods and their endpoints that are relevant to an assessment of endocrine-disrupting properties of pesticides. Furthermore, the article highlights how weight-of-evidence approaches should be applied to determine whether an adverse response in (eco)toxicity tests is caused by an endocrine mechanism of action. The large number of endpoints in the current testing paradigms for pesticides make it unlikely that endocrine activity and adversity is being overlooked.

show abstract

“…The authors argue that there is no need for using amphibian testing in endocrine disruptor screening evaluations for thyroid effects if there are mammalian data because there is a high degree of conservation of modes of action on thyroid activity with the mammalian assays. For endocrine activity, especially thyroid activity, fish respond with a sensitivity similar to that of amphibians (mainly X. laevis ; see Weltje et al 2013), and making use of read‐across between mammalian‐based mechanistic data and amphibians is encouraged (Lagadic et al 2019).…”

Section: Biological Read‐across For Eatsmentioning

confidence: 99%

Critical Review of Read‐Across Potential in Testing for Endocrine‐Related Effects in Vertebrate Ecological Receptors

McArdle

Freeman

Staveley

et al. 2020

Enviro Toxic and Chemistry

Self Cite

View full text Add to dashboard Cite

Recent regulatory testing programs have been designed to evaluate whether a chemical has the potential to interact with the endocrine system and could cause adverse effects. Some endocrine pathways are highly conserved among vertebrates, providing a potential to extrapolate data generated for one vertebrate taxonomic group to others (i.e., biological read‐across). To assess the potential for biological read‐across, we reviewed tools and approaches that support species extrapolation for fish, amphibians, birds, and reptiles. For each of the estrogen, androgen, thyroid, and steroidogenesis (EATS) pathways, we considered the pathway conservation across species and the responses of endocrine‐sensitive endpoints. The available data show a high degree of confidence in the conservation of the hypothalamus–pituitary–gonadal axis between fish and mammals and the hypothalamus–pituitary–thyroid axis between amphibians and mammals. Comparatively, there is less empirical evidence for the conservation of other EATS pathways between other taxonomic groups, but this may be due to limited data. Although more information on sensitive pathways and endpoints would be useful, current developments in the use of molecular target sequencing similarity tools and thoughtful application of the adverse outcome pathway concept show promise for further advancement of read‐across approaches for testing EATS pathways in vertebrate ecological receptors. Environ Toxicol Chem 2020;39:739–753. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.

show abstract

Recommendations for Reducing the USE of Fish and Amphibians in Endocrine‐Disruption Testing of Biocides and Plant Protection Products in Europe

Cited by 7 publications

References 10 publications

The Extended Amphibian Metamorphosis Assay: A Thyroid‐Specific and Less Animal‐Intensive Alternative to the Larval Amphibian Growth and Development Assay

The Extended Amphibian Metamorphosis Assay: A Thyroid‐Specific and Less Animal‐Intensive Alternative to the Larval Amphibian Growth and Development Assay

Current testing programs for pesticides adequately capture endocrine activity and adversity for protection of vertebrate wildlife

Critical Review of Read‐Across Potential in Testing for Endocrine‐Related Effects in Vertebrate Ecological Receptors

Contact Info

Product

Resources

About